Renal outcomes with sodium-glucose cotransporter 2 inhibitors in Japanese people with grade 3 chronic kidney disease and type 2 diabetes: Analysis of medical administrative databases.

AIM: To evaluate whether sodium-glucose cotransporter 2 inhibitor (SGLT2i) therapy is associated with a reduction of renal events compared with other glucose-lowering drugs (oGLDs) among Japanese people with type 2 diabetes (T2D) and grade 3 (G3) chronic kidney disease (CKD) in a real-world clinical practice setting. MATERIALS AND METHODS: People with T2D who were newly prescribed an SGLT2i or an oGLD from April 2014 to November 2021 (without prior use of index drugs for ≥ 1 year prior to index date) and G3 CKD (estimated glomerular filtration rate [eGFR] ≥ 30 to < 60 mL/min/1.73 m2) were selected from the Medical Data Vision database (MDV-DB) and the Real-World Data database (RWD-DB). SGLT2i and oGLD users were matched (1:1) using propensity score on patient background characteristics. The primary endpoint was a composite of the development of end-stage kidney disease or a sustained decline in eGFR of 50% or more. Hazard ratios (HRs) were estimated using the Cox proportional hazards model. RESULTS: Overall, 3190 (1595 per group) patients in the MDV-DB and 2572 (1286 per group) patients in the RWD-DB were included in the analyses. The composite outcome was significantly lower in the SGLT2i group than in the oGLD group in the MDV-DB (HR 0.49, 95% confidence interval [CI] 0.33 to 0.74, P < 0.001) and in the RWD-DB (HR 0.57, 95% CI 0.37 to 0.88, P = 0.011). CONCLUSIONS: Japanese people with T2D and G3 CKD initiating an SGLT2i had a lower risk of renal events than people initiating an oGLD.

[Utilization of the standard questionnaire in specific health checkups].

Objectives　Interviewing people about their health behaviour in specific health checkups (SHCs) is thought to promote awareness of and help improve such behaviour. The standard questionnaire (SQ) for SHCs consists of 22 items presented in the guidelines of the Ministry of Health, Labour, and Welfare. However, using items other than those necessary for stratification for specific health guidance (SHG) is optional. We believe that clarifying the actual utilization of SQ items could contribute to improving the procedure used for the fourth SHCs and SHG, which will be initiated in 2024.　This study seeks to clarify the actual utilization of the SQ for (1) conducting SHCs, (2) planning, implementing, and evaluating SHG and health programs aimed at preventing lifestyle-related diseases, and (3) planning, implementing, and evaluating the data health plan.Methods　We enrolled 3,179 people from 1,741 departments in charge of national health insurance, 47 Japan Health Insurance Association branches, and 1,391 health insurance societies across all municipalities in Japan. One participant among the study participants was the main person in charge of SHCs and SHG at each facility. We conducted a self-reported survey on the implementation of SHCs and SHG in February 2022. This study was approved by the ethics review board of the institution to which the first author belongs.Results　A total of 1,221 (38.4%) were received. The proportions of valid responses from national health insurance departments, Japan Health Insurance Association branches, and health insurance societies were 816 (46.9%), 47 (100%), and 358 (25.7%), respectively. Over 96% of responders used the group SHCs method, and over 93% of those adopting the individual SHCs method used each of the 22 SQ items. However, 187 (18.2%) responders found it difficult to use the item "If you had the opportunity to receive health guidance for lifestyle improvement, would you take it?" The reason was that the on-request SHG system was misunderstood. Additionally, only approximately 50% of respondents used the SQ to develop, implement, and evaluate their health program.Conclusion　We believe there will be no problem in implementing the SQ even if using all its component items is required. However, the aforementioned item needs to be revised. Methods to encourage health insurers and their supporters to use the SQ for health-related data collection and health program planning should be devised.

Impact of Age on Prognosis in Papillary Thyroid Carcinoma: How Should Age be Incorporated into the Treatment Strategy?

BACKGROUND: Age has been recognized as one of the strong prognostic indicators for thyroid cancer. However, treatment strategies for papillary thyroid cancer (PTC) are usually determined only by the extent of disease progression, without considering the patient's age. The aim of this study was to investigate how the surgical strategy for PTC should take into account patient age. METHODS: To exclude the effect of treatment strategy, 837 patients treated with uniform treatment strategies (hemithyroidectomy without radioiodine therapy) between 1986 and 1995 were the subjects of this study. Using a Cox proportional hazard model, clinical risk factors related to disease-specific survival (DSS), disease-free survival (DFS), and distant metastasis-free survival (DMFS) were analyzed. A receiver-operating characteristic (ROC) curve analysis was performed to identify the optimal cutoff points. RESULTS: Significant risk factors related to DSS and DMFS were age, extrathyroidal extension (ETE), and numbers of metastatic lymph nodes (NMLNs), but age was not significantly related to DFS. The 20-year DSS and DMFS rates were fair in patients without ETE regardless of age or NMLNs. However, in patients with ETE, DSS and DMFS rates were significantly worse in elderly patients than in young patients. ROC curve analysis showed that the optimal cutoff age was 48 years for discriminating DSS in patients with ETE. CONCLUSION: Regardless of age, PTC patients without ETE are candidates for a treatment strategy not using RAI, and more aggressive treatment may be recommended for elderly PTC patients with ETE.

MEK inhibition suppresses metastatic progression of KRAS-mutated gastric cancer.

Metastatic progression of tumors is driven by genetic alterations and tumor-stroma interaction. To elucidate the mechanism underlying the oncogene-induced gastric tumor progression, we have developed an organoid-based model of gastric cancer from GAstric Neoplasia (GAN) mice, which express Wnt1 and the enzymes COX2 and microsomal prostaglandin E synthase 1 in the stomach. Both p53 knockout (GAN-p53KO) organoids and KRASG12V -expressing GAN-p53KO (GAN-KP) organoids were generated by genetic manipulation of GAN mouse-derived tumor (GAN wild-type [WT]) organoids. In contrast with GAN-WT and GAN-p53KO organoids, which manifested Wnt addiction, GAN-KP organoids showed a Wnt-independent phenotype and the ability to proliferate without formation of a Wnt-regulated three-dimensional epithelial architecture. After transplantation in syngeneic mouse stomach, GAN-p53KO cells formed only small tumors, whereas GAN-KP cells gave rise to invasive tumors associated with the development of hypoxia as well as to liver metastasis. Spatial transcriptomics analysis suggested that hypoxia signaling contributes to the metastatic progression of GAN-KP tumors. In particular, such analysis identified a cluster of stromal cells located at the tumor invasive front that expressed genes related to hypoxia signaling, angiogenesis, and cell migration. These cells were also positive for phosphorylated extracellular signal-regulated kinase (ERK), suggesting that mitogen-activated protein kinase (MAPK) signaling promotes development of both tumor and microenvironment. The MEK (MAPK kinase) inhibitor trametinib suppressed the development of GAN-KP gastric tumors, formation of a hypoxic microenvironment, tumor angiogenesis, and liver metastasis. Our findings therefore establish a rationale for application of trametinib to suppress metastatic progression of KRAS-mutated gastric cancer.

Postal reminder with reduced burden of clinic information seeking for equitable participation in general health check-ups: A randomized controlled trial.

High participation rate and low inequality in participation are key to the program success of general health check-ups in Japan. This study examined the effectiveness of a postal reminder including nearest clinic information, compared to the standard postal reminder including details of all local clinics, on participation rate and income-based participation rate in general health checks. This was a single-blind, two-arm, prospective, randomized controlled study conducted at the Fukuoka Branch of Japan Health Insurance Association. Dependents (family members) of insured persons aged 40-69 years were randomly assigned (1:1) to the intervention group that received a tailored postal reminder intervention (showing information on the nearest clinic from each participant's address) or to the control group that received an original template postal reminder (containing just the URL of the website listing all available clinics). Allocation was concealed from participants and service providers of general health check-up. The primary outcome was participation in general health check-ups within 1 month of intervention. Between February 1 and February 10, 2017, 21,017 were randomly assigned to the intervention (n = 10,474) or control (n = 10,543) group. The participation rate in the intervention group was higher than control group (3.2% vs. 2.1%; OR: 1.55, 95% CI: 1.31-1.85, P < 0.001). The intervention effect was estimated to decrease as the income category increased (P for interaction = 0.037). Tailored postal reminders with information on the nearest clinic were able to improve the overall participation rate and reduce income-based inequality in participation for general health check-ups in Japan. Trial registration: UMIN-CTR, UMIN000042509, Registered 26 November 2020 - Retrospectively registered.

Combined thoracoscopic and axillary subcutaneous endoscopic thyroidectomy: a novel approach for cervicomediastinal goiters.

PURPOSE: After our group described the first remote-access thyroidectomy series in 2000, the procedure has been further developed. Although a thoracoscopic approach with a conventional open cervical incision for thyroid goiters with mediastinal extension has been performed at many institutions, remote-access thyroidectomy for cervicomediastinal goiters has not been established. We have performed combined thoracoscopic and axillary subcutaneous endoscopic thyroidectomies (axillo-thoracic endoscopic thyroidectomies). Here, we describe a novel technique for performing a remote-access thyroidectomy for a cervicomediastinal goiter (CMG). PATIENTS AND METHODS: The patients with CMGs who agreed to an axillo-thoracic endoscopic thyroidectomy at one of two hospitals in Japan underwent a remote-access thyroidectomy. RESULTS: We performed the axillo-thoracic endoscopic right or left hemithyroidectomy successfully, but most of the patients did not require the thoracoscopic procedure. None of the patients had complications, and none was converted to an open thyroidectomy. CONCLUSIONS: Most thyroid goiters with substernal extension can be removed by the axillary approach, but some cases require a thoracoscopic approach. The novel approach described herein (axillo-thoracic endoscopic thyroidectomy) enables the safe excision of a CMG with high patient satisfaction for selected patients.

Changes in Drug Utilization After Publication of Clinical Trials and Drug-Related Scandals in Japan: An Interrupted Time Series Analysis, 2005-2017.

BACKGROUND: Breaches of ethics undermine the practice of medicine. In Japan, two major scandals involving clinical research and drug marketing occurred after the publication of clinical trials. To study the effects of those scandals, we evaluated changes in the use of first-generation angiotensin II receptor blockers (ARBs) after publication of relevant clinical trials and also after the subsequent scandals. METHODS: We conducted a quasi-experimental design of an interrupted time series analysis (ITSA) on nationwide monthly drug-market data covering 12 years (2005 to 2017) in Japan. The main outcome was the use of first-generation ARBs (valsartan, candesartan, and losartan). The two exposures were the publication of ARB-related clinical-trial results (October 2006) and subsequent ARB-related scandals involving research and marketing (February 2013). A generalized estimating equation model was fitted for ITSA with a log link, Poisson distribution, robust variance estimators, and seasonality adjustment. RESULTS: The publication of clinical trials was associated with 12% increase in the use of first-generation ARBs in Japan, and the subsequent ARB-related scandals was associated with 19% decrease. The decrease in the use of first-generation ARBs after the scandals was greater than the increase in their use after the publication of clinical-trial results. The net effect of the two exposures was a 9% decrease in the use of first-generation ARBs. CONCLUSIONS: The scandals were associated with decrease in the use of first-generation ARBs, and that decrease was greater than the increase associated with the publication of "successful" clinical trials, making the net effect not zero but negative.

Pregnancy outcome after first trimester exposure to domperidone-An observational cohort study.

AIM: To assess the teratogenic risk of domperidone by comparing the incidence of major malformation with domperidone to a control. METHODS: Pregnancy outcome data were obtained for women at two Japanese facilities that provide counseling on drug use during pregnancy between April 1988 and December 2017. The incidence of major malformation was calculated among infants born to women taking domperidone (n = 519), nonteratogenic drugs (control, n = 1673), or metoclopramide (reference, n = 241) during the first trimester of pregnancy. Using the control group as reference, the crude odds ratio (OR) of the incidence of major malformation in the domperidone and metoclopramide groups was calculated using univariable logistic regression analysis. Adjusted OR was also calculated using multivariable logistic regression analysis adjusted for various other factors. RESULTS: The incidence of major malformation was 2.9% (14/485, 95% confidence interval [CI]: 1.6-4.8) in the domperidone group, 1.7% (27/1554, 95%CI: 1.1-2.5) in the control group, and 3.6% (8/224, 95%CI: 1.6-6.9) in the metoclopramide group. The adjusted multivariable logistic regression analysis showed no significant difference in incidence between the control and domperidone groups (adjusted OR: 1.86 [95%CI: 0.73-4.70], p = 0.191) or between the control and metoclopramide groups (adjusted OR: 2.20 [95%CI: 0.69-6.98], p = 0.183). CONCLUSIONS: This observational cohort study showed that domperidone exposure during the first trimester was not associated with increased risk of major malformation in infants. These results may help alleviate the anxiety of patients who took domperidone during pregnancy.

Extracorporeal membrane oxygenation for the anesthetic management of a patient with severe airway stenosis caused by thyroid carcinoma invasion.

The treatment of a thyroid carcinoma extending into the thoracic cavity with severe airway stenosis is difficult, since there is a risk of acute respiratory decompensation at every stage of anesthesia. Extracorporeal membrane oxygenation (ECMO) is a life support technique for maintaining both the cardiac and respiratory functions. It is used for the management of acute, severe, reversible respiratory or cardiac failure refractory to conventional management. We herein describe the use of ECMO for the anesthetic management of an elderly patient with severe airway stenosis caused by thyroid carcinoma invasion, which underwent total thyroidectomy with the resection of four tracheal rings and end-to-end anastomosis under a median sternotomy. Although the risks and benefits should be carefully weighed before a decision to use ECMO is made, the use of ECMO in the management of general anesthesia may be a rational and effective strategy for maintaining oxygenation.

Lack of a bridge between screening and medical management for hypertension: health screening cohort in Japan.

BACKGROUND: Patient journeys for hypertensive individuals after detection at screening have not been well examined in a general population. Thus, we aimed to assess the medical treatment status and subsequent longitudinal changes in blood pressure in a middle-aged Japanese population. METHODS: We conducted a cohort study using a nationwide Japanese health screening cohort, from April 2014 to March 2019. Among health screening participants aged 40-74 years who had not previously received treatment for hypertension, hypertensive patients were newly identified based on screening results, and their medical treatment status for hypertension during the year following their initial screening was assessed. The main outcomes were longitudinal changes in systolic blood pressure (SBP) and diastolic blood pressure (DBP) over 4 years after initial screening. RESULTS: Of the 153,523 screening participants (mean age = 49.7 years), 16,720 (10.9%) and 4150 (2.7%) were newly detected as having hypertension, with baseline SBP of 140-159 mmHg (grade 1) and ≥ 160 mmHg (grade 2-3), respectively. Among them, 15.9% of the grade 1 hypertensive participants and 36.3% of the grade 2-3 hypertensive participants started receiving medical treatment during the year following initial screening. A linear generalised estimating equation with propensity score matching showed that receiving medical treatment was associated with 5.77 mmHg lower SBP (95% CI - 6.64 to - 4.90) and 3.82 mmHg lower DBP (95% CI - 4.47 to - 3.16) in the grade 1 hypertensive group, and 14.69 mmHg lower SBP (95% CI - 16.35 to - 13.04) and 8.42 mmHg lower DBP (95% CI - 9.49 to - 7.34) in the grade 2-3 hypertensive group. CONCLUSIONS: Health screenings detected hypertension in a substantial percentage of the middle-aged population in this study. However, detection was often followed by insufficient medical treatment and inappropriate blood pressure management. These findings indicate an inadequate link between health screenings and medical treatments in patients with hypertension.

Thyroid and Parathyroid Functions After Pharyngo-Laryngo-Esophagectomy for Cervical Esophageal Cancer.

BACKGROUND: Cervical esophageal cancer (CEC) patients whose larynx function cannot be preserved often undergo chemoradiotherapy, whereas those with residual or recurrent lesions undergo a pharyngo-laryngo-esophagectomy (PLE); however, some need to undergo a pharyngolaryngectomy with total esophagectomy (PLTE) for synchronous or metachronous esophageal cancer. We retrospectively evaluated the relationship between preoperative irradiation (or the extent of esophageal resection) and postoperative endocrine complications in CEC, including hypothyroidism and hypoparathyroidism. METHODS: The cancers of 35 (5.4%) of 678 esophageal cancer patients with esophagectomy treated in 2000-2017 were CECs. We also analyzed the 17 cases of CEC patients who underwent PLE with thyroid lobectomy-11 with irradiation before PLE and 6 without irradiation. Seven patients underwent a PLTE. RESULTS: Hypothyroidism and hypoparathyroidism occurred in 14 and 12 patients, respectively. The hypothyroidism rate was significantly higher in patients with irradiation versus those without irradiation (100% vs. 50%; p = 0.010), and the hypoparathyroidism rate was significantly higher in the PLTE versus non-PLTE patients (100% vs. 50%; p = 0.026). The mean levothyroxine dosage was 1.60 µg/kg/day in the PLE patients post-irradiation. CONCLUSIONS: Irradiation appears to be a risk factor for hypothyroidism after PLE with thyroid lobectomy, while PLTE might have some effect on hypoparathyroidism. Due to vocal function loss, PLE patients may experience symptoms from endocrine complications. Levothyroxine treatment soon after PLE for post-irradiation patients and patients requiring as-needed calcium or vitamin D supplementation based on biochemical hypocalcemia for PLE (especially PLTE), may be effective in preventing symptomatic endocrine complications.

Development of a functional thyroid model based on an organoid culture system.

The low turnover rate of thyroid follicular cells and the lack of a long-term thyroid cell culture system have hampered studies of thyroid carcinogenesis. We have now established a thyroid organoid culture system that supports thyroid cell proliferation in vitro. The established mouse thyroid organoids performed thyroid functions including thyroglobulin synthesis, iodide uptake, and the production and release of thyroid hormone. Furthermore, transplantation of the organoids into recipient mice resulted in the formation of normal thyroid-like tissue capable of iodide uptake and thyroglobulin production in vivo. Finally, forced expression of oncogenic NRAS (NRASQ61R) in thyroid organoids established from p53 knockout mice and transplantation of the manipulated organoids into mouse recipients generated a model of poorly differentiated thyroid cancer. Our findings suggest that this newly developed thyroid organoid culture system is a potential research tool for the study of thyroid physiology and pathology including thyroid cancer.

Clinical Status and Treatment of Liver Metastasis of Differentiated Thyroid Cancer Using Tyrosine Kinase Inhibitors.

BACKGROUND: Treatment of patients with liver metastasis of differentiated thyroid carcinoma (DTC) has not been sufficiently defined, because liver metastasis of DTC has been described mostly as case reports. Additionally, such patients are considered end-of-treatment responders. A relatively new approach using tyrosine kinase inhibitors (TKIs) may provide opportunities to manage systemic metastasis. This study aims to define the clinical features of DTC patients with liver metastasis and evaluate the benefits of TKIs. METHODS: We retrospectively analyzed clinical features of 29 patients (mean age 67.8 years) diagnosed with liver metastasis of DTC at our institution between January 1981 and May 2017. RESULTS: All patients had distant metastasis at other organ sites upon diagnosis of liver metastasis; 41% of them developed new metastasis afterward. Management after diagnosis of liver metastasis comprised palliative care (48%), radioactive iodine therapy (28%), and TKI therapy (24%). The median survival after diagnosis of liver metastasis was only 4.8 months. Survival rates were significantly better in patients with performance statuses between 0 and 2 on the Eastern Cooperative Oncology Group scale at diagnosis of liver metastasis (n = 22, 76%) treated with TKI compared to those who were not (P = 0.017; log-rank test; hazard ratio 0.19). One-year survival rates were 71.4 and 26.7% for patients treated with or without TKI, respectively. CONCLUSIONS: Patients with liver metastasis had poor clinical prognosis. When other distant metastases existed at diagnosis of liver metastasis, TKI therapy was considered an effective therapeutic option for patients with liver metastasis of DTC.

Lenvatinib induces early tumor shrinkage in patients with advanced thyroid carcinoma.

Although advanced thyroid carcinoma patients who cannot be cured by conventional therapy have lacked effective treatment, multitargeted tyrosine kinase inhibitors have recently become available. Phase 3 trials of lenvatinib showed a median time to objective response of 2 (95 % confidence interval (CI) 1.9-3.5) months, demonstrating that shrinks tumors rapidly. The phenomenon of immediate tumor shrink is known as early tumor shrinkage (ETS) which is related to clinical outcome in other malignancies. However, precisely when within 8 weeks lenvatinib starts to affect tumors remains unclear. In tumors near the carotid arteries, trachea, or esophagus, a rapid therapeutic effect can induce fistula formation or arterial bleeding. To prevent such treatment-emergent serious adverse events (SAE), early imaging evaluation seems to be very important. In this study, the point in time when lenvatinib started to shrink tumors was retrospectively investigated. The subjects were 16 patients who started lenvatinib administration between May and August 2015. Tumor size was evaluated by computed tomography (CT) scans frequently within the first 8 weeks according to the Response Evaluation Criteria In Solid Tumors (RECIST) guideline. Initial tumor response was defined as ≥ 10% tumor reduction. Serum thyroglobulin (Tg) level was monitored in 8 differentiated thyroid carcinoma (DTC) without TgAb patients. At the first evaluation, 13 patients (83.3 %) showed tumor reduction and that decreased with time. Thirteen patients (83.3 %) showed >10 % tumor reduction within 8 weeks. In all DTC patients, serum Tg level was markedly decreased. In conclusion, lenvatinib immediately shrinks tumors, the so-called ETS phenomenon. Therefore, careful attention should be paid to fistula formation from the early phase.

Introduction of 2-octyl cyanoacrylate (Dermabond®) for incisional hernia mesh repair.

PURPOSE: We developed a new technique, sutureless mesh fixation, using 2-octyl cyanoacrylate (Dermabond®, a surgical tissue adhesive) for incisional hernia repair. The objective of this article is to introduce the new technique and to examine whether the technique provides sufficient resistance to abdominal pressure. METHODS: We conducted two tests using a porcine model, a traction experiment and artificial pneumoperitoneum test. In the traction experiment, the adherence properties of Dermabond® with mesh and peritoneum were examined using a tissue fragment from a pig. In the artificial pneumoperitoneum test, which used an incisional hernia porcine model, mesh was implanted on the peritoneum in the abdominal cavity with Dermabond®. It was then determined whether sutureless mesh fixation could bear artificial abdominal air pressure. RESULTS: In the traction experiment, Dermabond®, which bonded the mesh to the peritoneum, tolerated pressure up to 2.45 × 103 mmHg. In the artificial pneumoperitoneum test, the mesh was strongly fastened to the peritoneum by means of only Dermabond®, and there was little air circulation even without closing the wound over the mesh. CONCLUSIONS: Sutureless mesh fixation with Dermabond® is technically feasible and promises to provide sufficient resistance to abdominal pressure.

[Advanced lung cancer with recurrence of liver and tracheal metastases responsive to multimodality therapy - a case report].

We report a case of advanced lung cancer with recurrence of liver and tracheal metastases that were responsive to multimodality therapy. The patient was a 77-year-old man who suffered from advanced lung cancer with chronic obstructive pulmonary disease (COPD) and alcohol-induced liver cirrhosis. The primary lung cancer was surgically resected. Eight months after resection of the primary lung cancer, a solitary liver tumor appeared and hepatic resection was performed. Histological findings showed that both the primary lung tumor and the solitary liver tumor were squamous cell carcinoma (SCC). Subsequently, he developed a recurrence in his trachea 8 months after hepatic resection. Radiotherapy, endobronchial argon plasma coagulation (APC), and systemic chemotherapy were administered. The tracheal tumor remained stable without any liver metastasis for 25 months.

Correction: The Usefulness of AirSeal™ Intelligent Flow System in Gas Insufflation Total Endoscopic Thyroidectomy.

[This corrects the article DOI: 10.1007/s12070-022-03257-0.].

Implementation of Guideline-Based HBV Reactivation Management in Patients with Chronic HBV Infections of HBsAg or Resolved HBV Infection Undergoing Immunosuppressive Therapy.

INTRODUCTION: Although patients with HBV have a risk of reactivation after immunosuppressive therapy (IST), the status of their risk management is unclear in Japan. This study aims to describe the proportion of patients who received preventive management of HBV reactivation during ISTs in patients with chronic HBV infection of HBsAg or resolved HBV infection. METHOD: A retrospective cohort study was conducted using the JMDC Japanese claims database from April 2011 to June 2021. Patients with HBV infections of HbsAg who received ISTs or patients who had resolved HBV infections who received ISTs were identified from the database and evaluated for appropriate management to prevent HBV reactivation. RESULTS: In total, 6242 eligible patients were identified. The proportions of patients with appropriate HBV reactivation management, stratified by the HBV reactivation risk level of IST, was 43.1% (276/641) for high-risk, 40.2% (223/555) for intermediate-risk and 14.9% (741/4965) for low-risk patients. When the evaluation period for the outcome calculation was shortened from 360 to 180 days, the proportion for high risk increased to 52.7%. The odds ratios of large hospitals for receiving appropriate management were 2.16 (95% CI 1.12-4.44) in the high-risk, 4.63 (95% CI 2.34-10.25) in the intermediate-risk and 3.60 (95% CI 3.07-4.24) in the low-risk patients. CONCLUSION: HBV reactivation management was tailored according to the reactivation risk associated with IST. However, adherence to HBV reactivation management guidelines was sub-optimal, even among high-risk patients. This is especially the case for ensuring smaller-sized medical institutions, highlighting the need for further educational activities.

The study assesses the implementation of guideline-based management of hepatitis B virus reactivation during immunosuppressive therapy in Japan. The appropriate management of hepatitis B virus treatment involves prophylactic nucleos(t)ide analog (NUC) therapy and regular monitoring of hepatitis B virus DNA. This study aims to assess the extent to which these management practices are implemented in a clinical setting in Japan using a retrospective cohort study using the Japanese Medical Claims Database. The analysis identified 6242 eligible patients and identified whether they received appropriate management to prevent hepatitis B virus reactivation based on the level of risk associated with their immunosuppressive therapy. Based on the guidelines, the proportions of patients receiving appropriate reactivation management were 43.1% for high-risk, 40.2% for intermediate-risk and 14.9% for low-risk immunosuppressive therapy patients. Shortening the evaluation period from 360 to 180 days showed an increase in the proportion of high-risk patients to 52.7%, which indicated the potential challenge for continued monitoring after immunosuppressive therapy administration. The study shows that large hospitals present higher odds of patients receiving appropriate management. Overall, adherence to hepatitis B virus reactivation management guidelines was suboptimal, especially in smaller medical institutions, emphasizing the need for additional educational activities.

Prevalence of multimorbidity and its associations with hospitalisation or death in Japan 2014-2019: a retrospective cohort study using nationwide medical claims data in the middle-aged generation.

OBJECTIVE: To describe the prevalence of multimorbidity and its associations with clinical outcomes across age groups. DESIGN: Retrospective cohort study using nationwide medical claims data. SETTING: Carried out in Japan between April 2014 and March 2019. PARTICIPANTS: N=246 671 Japanese individuals aged 20-74 enrolled in the health insurance were included into the baseline data set for fiscal year (FY) 2014. Of those, N=181 959 individuals were included into the cohort data set spanning FY2014-FY2018. EXPOSURES: Multimorbidity was defined as having ≥2 of 15 chronic conditions according to the International Classification of Diseases 10th Revision codes of the Charlson Comorbidity Index. PRIMARY AND SECONDARY OUTCOMES: Primary outcome: the standardised prevalence of multimorbidity across age groups was evaluated using data from FY2014 and extrapolated to the Japanese total population. SECONDARY OUTCOME: hospitalisation or death events were traced by month using medical claims data and insurer enrolment data. Associations between multimorbidity and 5-year hospitalisation and/or death events across age groups were analysed using a Cox regression model. RESULTS: The standardised prevalence rate of multimorbidity in the nationwide Japanese total population was estimated to 26.1%. The prevalence rate with age was increased, approximately 5% (ages 20-29), 10% (30-39), 20% (40-49), 30% (50-59), 50% (60-69) and 60% (70-74). Compared with individuals aged 20-39 without multimorbidity, those with multimorbidity had a higher incidence of clinical events in any age group (HR=2.43 (95% CI 2.30 to 2.56) in ages 20-39, HR=2.55 (95% CI 2.47 to 2.63) in ages 40-59 and HR=3.41 (95% CI 3.23 to 3.53) in ages ≥60). The difference in the incidence of clinical events between multimorbidity and no multimorbidity was larger than that between age groups. CONCLUSIONS: Multimorbidity is already prevalent in the middle-aged generation and is associated with poor clinical outcomes. These findings underscore the significance of multimorbidity and highlight the urgent need for preventive intervention at the public healthcare level.