Yutaka Matsuyama

Aim: To compare risks of malignancy, opportunistic infections, and venous thromboembolism between the targeted synthetic disease‐modifying antirheumatic drugs (tsDMARDs) and biologic DMARDs (bDMARDs) at the 2nd and 3rd lines of therapy (LOT). Methods: We conducted a cohort study using the National Database of Health Insurance Claims (2013–2021). Patients with rheumatoid arthritis (RA) initiating tsDMARDs or bDMARDs after conventional synthetic DMARDs (csDMARDs) were identified at the 2nd LOT or 3rd LOT. Hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated using Cox models weighted by inverse probability of treatment weighting. Results: Among 498 813 csDMARD initiators, 66 638 and 4177 initiated bDMARDs and tsDMARDs at 2nd LOT; 14 085 and 1757 initiated bDMARDs and tsDMARDs at 3rd LOT. For malignancy, HRs (95% CIs) for tsDMARDs versus bDMARDs were 0.92 (0.60–1.43) at 2nd LOT and 0.94 (0.53–1.65) at 3rd LOT. HRs (95% CIs) for pneumocystis pneumonia (PCP) and deep vein thrombosis (DVT) were as follows: PCP, 0.98 (0.75–1.29) at 2nd LOT and 1.12 (0.81–1.54) at 3rd LOT; DVT, 1.13 (0.64–1.99) at 2nd LOT and 0.96 (0.52–1.78) at 3rd LOT. In contrast, herpes zoster (HZ) risk was consistently higher with tsDMARDs (2nd LOT: HR, 2.61 [95% CI, 2.24–3.05]; 3rd LOT: HR, 2.90 [95% CI, 2.38–3.53]). Conclusions: In the nationwide Japanese cohort, tsDMARDs did not show increased malignancy risk compared to bDMARDs, and PCP risk had no clear difference at 2nd and 3rd LOTs, whereas the risk of HZ was higher with tsDMARDs.

Background and Aim: With Helicobacter pylori ( H. pylori )–naïve adults becoming increasingly common in Japan, the magnitude of their gastric cancer (GC) risk remains uncertain and warrants clarification. Materials and Methods: We conducted a systematic review and meta‐analysis to estimate the screen‐detected prevalence and incidence of GC among H. pylori –naïve individuals in Japan. MEDLINE and EMBASE were searched for studies published between January 2014 and August 2024. Eligible studies included cross‐sectional or cohort designs that confirmed H. pylori –naïve status using ≥1 validated test and reported histologically diagnosed GC. Generalized linear mixed‐effects models were used to derive pooled estimates. Results: Of 652 screened articles, six were included ( n = 248 482; four cohorts, two cross‐sectional). Among these, 96 GC cases were identified. The mean age ranged from 48 to 58 years, with a male proportion between 35% and 60%. The pooled screen‐detected prevalence of GC was 0.029% (95% confidence interval [CI], 0.006–0.137), equivalent to approximately one case per 3500 individuals screened. The pooled incidence from four cohorts (218 000 person‐years) was 1.40 per 10 000 person‐years (95% CI, 0.61–3.23), based on 30 incident cases. Pooled screen‐detected prevalence of invasive GC was 0.015% (95% CI, 0.002–0.094), 80.6% of which were histologically diagnosed as gastric adenocarcinoma of the fundic gland type, an indolent subtype. Conclusions: The screen‐detected prevalence and incidence of GC among H. pylori –naïve individuals were low. The present meta‐analysis provides important baseline data to characterize GC risk among H. pylori –naïve individuals in Japan.

Supplementary Figure from Association between Statins and Incidence of Cancer in Patients with Dyslipidemia Using Large-Scale Health Insurance Claims Data

Background: The World Health Organization has confirmed that Helicobacter pylori is a carcinogen associated with gastric cancer (GC). Although a recent increasing trend in the prevalence of the H. pylori‐naïve status has been reported, the precise values of each generation have not yet been specified. This study aimed to confirm the generational H. pylori‐naïve prevalence in Japan.Materials and Methods: Scientific articles available in PubMed and EMBASE between January 2014 and June 2024 were systematically searched. Publications that specified the generational H. pylori‐naïve prevalence were included in the analysis. Publications that did not describe the prevalence of H. pylori‐naïve individuals and the definition of H. pylori‐eradicated individuals were excluded. A meta‐regression analysis with a logistic mixed effect model was conducted to predict the generational prevalence of the H. pylori‐naïve status. In this model, birth year was incorporated as a spline function to model non‐linear trends, and study differences were included as random effects.Results: A total of 899 publications were identified. After screening, eight publications were included in the final analysis. Nine different study groups comprising 46,704 individuals included in those publications were identified and analyzed. The calculated H. pylori‐naïve prevalence rates among the average cohort were 21.1% for births in 1930, 47.2% for births in 1950, 75.3% for births in 1970, 91.7% for births in 1990, and 97.7% for births in 2010.Conclusions: The H. pylori‐naïve prevalence increased dramatically with more recent birth years and reached a plateau of over 95%, especially after 2000. The current GC screening strategy can be modified based on this finding.

Recent experimental studies have examined the efficacy of statins in preventing cancer, but the findings of clinical studies are inconsistent, and studies on Japanese patients are limited. This study aimed to clarify the association between statins and cancer risk among Japanese patients. We conducted a large population-based retrospective cohort study using the Japanese health insurance claims database, including patients newly diagnosed with dyslipidemia between 2005 and 2015. Patients who were on newly prescribed statins during the study period were designated as statin users. They were matched 1:1 with randomly selected drug nonusers who were not prescribed drugs for dyslipidemia according to age, sex, and year of first diagnosis of dyslipidemia. There were 23,746 patients in each group. The mean duration of follow-up for statin users and drug nonusers was approximately 2 years. Using a Cox proportional hazards model, significant reduction in cancer risk was observed in statin users compared with that in drug nonusers [adjusted HR = 0.84; 95% confidence interval (CI), 0.72–0.97; adjusted for patient background factors]. The results of subgroup analyses suggested that prescribed statins reduced the incidence of cancer of the digestive organs (adjusted HR = 0.79; 95% CI, 0.63–0.99) as well as reduced cancer risk in patients with nonsmokers (adjusted HR = 0.78, 95% CI = 0.65–0.92). Our results suggest that statin use may reduce cancer risk in patients with dyslipidemia.Prevention Relevance:This study clarified the relationship between statin use and cancer risk in patients with dyslipidemia. Our study will contribute to medicine selection in patients with hypercholesterolemia level.See related Spotlight, p. 1

Recent experimental studies have examined the efficacy of statins in preventing cancer, but the findings of clinical studies are inconsistent, and studies on Japanese patients are limited. This study aimed to clarify the association between statins and cancer risk among Japanese patients. We conducted a large population-based retrospective cohort study using the Japanese health insurance claims database, including patients newly diagnosed with dyslipidemia between 2005 and 2015. Patients who were on newly prescribed statins during the study period were designated as statin users. They were matched 1:1 with randomly selected drug nonusers who were not prescribed drugs for dyslipidemia according to age, sex, and year of first diagnosis of dyslipidemia. There were 23,746 patients in each group. The mean duration of follow-up for statin users and drug nonusers was approximately 2 years. Using a Cox proportional hazards model, significant reduction in cancer risk was observed in statin users compared with that in drug nonusers [adjusted HR = 0.84; 95% confidence interval (CI), 0.72–0.97; adjusted for patient background factors]. The results of subgroup analyses suggested that prescribed statins reduced the incidence of cancer of the digestive organs (adjusted HR = 0.79; 95% CI, 0.63–0.99) as well as reduced cancer risk in patients with nonsmokers (adjusted HR = 0.78, 95% CI = 0.65–0.92). Our results suggest that statin use may reduce cancer risk in patients with dyslipidemia.Prevention Relevance:This study clarified the relationship between statin use and cancer risk in patients with dyslipidemia. Our study will contribute to medicine selection in patients with hypercholesterolemia level.See related Spotlight, p. 1

Supplementary Figure from Association between Statins and Incidence of Cancer in Patients with Dyslipidemia Using Large-Scale Health Insurance Claims Data

Background: Prevention of perinatal depression beginning from the antenatal period is essential. Therefore, this study aimed to investigate the effectiveness of recently developed internet‐delivered cognitive behavioral therapy (iCBT) for preventing the onset of a major depressive episode (MDE) in the third trimester and at 3 months postpartum.Methods: This is a two‐arm, parallel‐group, general‐information controlled, randomized controlled trial. Participants were 5017 pregnant women at 16–20 weeks' gestation without MDE at baseline. They were randomly assigned to an iCBT (intervention; n = 2509) or general‐information (control; n = 2508) group, stratified by psychological distress at baseline. The primary outcomes were the numbers of new MDE onsets, measured using the World Health Organization Composite International Diagnostic Interview 3.0, at 32 weeks' gestation and at 3 months postpartum.Results: New MDE onset was reported by 59 participants (2.35%) in the intervention group and 73 (2.91%) in the control group during follow‐up. Compared with the control group, the hazard ratio (HR) of MDE in the intervention group was 0.85 (95% CI 0.61–1.20), which was not significantly different. Among participants who scored between 5 and 8 on K6 at baseline, 10 (1.37%) in the intervention group reported new onset of MDE, compared with 28 (3.81%) in the control group, and the HR of MDE was 0.38 (95%CI 0.19–0.79).Conclusions: No intervention effect was found for iCBT in preventing new onset of perinatal MDE. iCBT might prevent perinatal depression only among pregnant women with subthreshold depressive symptoms. Trial registration: UMIN000038190.

Recent experimental studies have examined the efficacy of statins in preventing cancer, but the findings of clinical studies are inconsistent, and studies on Japanese patients are limited. This study aimed to clarify the association between statins and cancer risk among Japanese patients. We conducted a large population-based retrospective cohort study using the Japanese health insurance claims database, including patients newly diagnosed with dyslipidemia between 2005 and 2015. Patients who were on newly prescribed statins during the study period were designated as statin users. They were matched 1:1 with randomly selected drug nonusers who were not prescribed drugs for dyslipidemia according to age, sex, and year of first diagnosis of dyslipidemia. There were 23,746 patients in each group. The mean duration of follow-up for statin users and drug nonusers was approximately 2 years. Using a Cox proportional hazards model, significant reduction in cancer risk was observed in statin users compared with that in drug nonusers [adjusted HR = 0.84; 95% confidence interval (CI), 0.72–0.97; adjusted for patient background factors]. The results of subgroup analyses suggested that prescribed statins reduced the incidence of cancer of the digestive organs (adjusted HR = 0.79; 95% CI, 0.63–0.99) as well as reduced cancer risk in patients with nonsmokers (adjusted HR = 0.78, 95% CI = 0.65–0.92). Our results suggest that statin use may reduce cancer risk in patients with dyslipidemia. Prevention Relevance: This study clarified the relationship between statin use and cancer risk in patients with dyslipidemia. Our study will contribute to medicine selection in patients with hypercholesterolemia level. See related Spotlight, p. 1