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Introduction: We aimed to comprehensively compile placebo-controlled trials on the efficacy and safety of romosozumab (210 mg, subcutaneously, once monthly) in postmenopausal women and men with osteoporosis. Materials and methods: PubMed, Google Scholar, and ClinicalTrials.gov were searched for relevant placebo-controlled trials (as of January 1, 2024). Percent change in bone mineral density (BMD), falls, fractures, and adverse events (AEs) after drug administration were collected. Risk ratios (RRs) and mean differences (MDs) with 95% confidence intervals (CIs) were calculated. Results: Six trials (7990 patients; follow-up period, 6–12 months) were included. Compared with placebo, romosozumab significantly increased lumbar spine BMD (MD = 12.69; 95% CI 11.10–14.29), total hip BMD (MD = 4.42; 95% CI 3.03–5.80), and femoral neck BMD (MD = 3.99; 95% CI 2.42–5.57) at 12 months. Romosozumab significantly decreased falls (RR = 0.80; 95% CI 0.68–0.93) and major osteoporotic fractures (RR = 0.37; 95% CI 0.25–0.54), but increased injection-site reactions (RR = 1.83; 95% CI 1.46–2.30) within 12 months. No significant differences were observed in other AEs (including cardiovascular AEs) within 12 months. Conclusion: Romosozumab treatment resulted in a significant BMD gain, reduced falls and major osteoporotic fractures. It was generally well-tolerated, including the cardiovascular aspects. However, clinicians should consider the occurrence of minor AEs (e.g., injection-site reactions). [ABSTRACT FROM AUTHOR]

Background and Objective: Several associations between diabetes mellitus and delirium have been reported; however, they have been inconsistent, and evidence on the effects of antidiabetic medications on delirium is also limited. This study aimed to investigate whether the use of antidiabetic drugs is a risk factor for delirium development. Methods: Using the Japanese Adverse Event Reporting Database, we analyzed 662,899 reports between 2004 and 2022. Reporting odds ratios (RORs) and 95% confidence intervals (CIs) for delirium associated with diabetes and using each antidiabetic medication were calculated after adjusting for potential confounders. Results: Overall, 8892 of the reports analyzed were associated with delirium. A comparison of the incidence of delirium between patients with and without diabetes showed no significant difference, with 1.34% in patients without diabetes and 1.37% in those with diabetes. In each antidiabetic medication, signals for delirium were detected for sulfonylurea (crude ROR, 1.35; 95% CI 1.21–1.51) and insulin (crude ROR, 1.28; 95% CI 1.13–1.44). These results were maintained even after adjusting for factors with potential confounders (sulfonylurea: adjusted ROR, 1.75; 95% CI 1.54–2.00, insulin: adjusted ROR, 1.35; 95% CI 1.20–1.54). Conclusions: Our results suggest no association between diabetes and delirium; however, using sulfonylurea and insulin may be associated with delirium development. Nonetheless, these findings should be validated in future studies. [ABSTRACT FROM AUTHOR]

Background: Antiepileptic drugs may cause delirium, and the risk may vary with each drug. However, related studies have provided inconsistent results. Aim: The aim of this study was to investigate whether the use of antiepileptic drugs is a risk factor for delirium development. Method: Using the Japanese Adverse Drug Event Report database, we analysed 573,316 reports pertaining to the period from 2004 to 2020. Reporting odds ratios and 95% confidence intervals of delirium associated with use of antiepileptic drugs were calculated after adjusting for potential confounders. Furthermore, for each antiepileptic drug, we performed an analysis stratified based on older age and benzodiazepine receptor agonist usage. Results: There were 27,439 reports of antiepileptic drug-related adverse events. Of these, 191 reports were associated with antiepileptic drugs and delirium (crude reporting odds ratio [cROR], 1.66; 95% confidence interval [CI], 1.43–1.93). The use of lacosamide (adjusted reporting odds ratio [aROR], 2.44; 95% CI, 1.24–4.80), lamotrigine (aROR, 1.54; 95% CI, 1.05–2.26), levetiracetam (aROR, 1.91; 95% CI, 1.35–2.71), and valproic acid (aROR, 1.49; 95% CI, 1.16–1.91) was related to a significantly higher reporting odds ratio for delirium, even after adjustment for possible confounding factors. However, when used in combination with benzodiazepine receptor agonists, none of the antiepileptic drugs were found to be associated with delirium. Conclusion: Our study's findings suggest that antiepileptic drug usage may be associated with delirium development. [ABSTRACT FROM AUTHOR]

Aims: Hemoglobin A1c (HbA1c) levels are widely employed to diagnose diabetes. However, estimates of the heritability of HbA1c and glucose levels are different. Therefore, we explored HbA1c- and blood glucose-associated loci in a non-diabetic Japanese population. Methods: We conducted a two-stage genome-wide association study (GWAS) on variants associated with HbA1c and blood glucose levels in a Japanese population. In the initial stage, data of 4911 participants of the Japan Multi-Institutional Collaborative Cohort (J-MICC) were subjected to discovery analysis. In the second stage, two datasets from the Tohoku Medical Megabank project, with 8175 and 40,519 participants, were used for the replication study. Association of the imputed variants with HbA1c and blood glucose levels was determined via linear regression analyses adjusted for age, sex, body mass index (BMI), smoking, and genetic principal components (PC1–PC10). Moreover, we performed a BMI-stratified GWAS on HbA1c levels in the J-MICC. The discovery analysis and BMI-stratified GWAS results were validated with re-analyses of normalized HbA1c levels adjusted for site in addition to the above, and blood glucose adjusted for fasting time as an additional covariate. Results: Genetic variants associated with HbA1c levels were identified in KCNQ1 and TMC6. None of the genetic variants associated with blood glucose levels in the discovery analysis were replicated. Association of rs2299620 in KCNQ1 with HbA1c levels showed heterogeneity between individuals with BMI ≥ 25 kg/m2 and BMI < 25 kg/m2. Conclusions: The variant rs2299620 in KCNQ1 might affect HbA1c levels differentially based on BMI grouping in the Japanese population. [ABSTRACT FROM AUTHOR]

Background/objectives: Low-carbohydrate diets (LCD) are useful for weight reduction, and 50-55% carbohydrate consumption is associated with minimal risk. Genetic differences were related to nutritional consumption, food preferences, and dietary patterns, but whether particular genetic differences in individuals influence LCD adherence is unknown.Subjects/methods: We conducted a GWAS on adherence to LCD utilizing 14,076 participants from the Japan Multi-Institutional Collaborative Cohort study. We used a previously validated semiquantitative food frequency questionnaire to estimate food consumption. Association of the imputed variants with the LCD score by Halton et al. we used linear regression analysis adjusting for sex, age, total dietary energy consumption, and components 1 to 10 by principal component analysis. We repeated the analysis with adjustment for alcohol consumption (g/day) in addition to the above-described variables.Results: Men and women combined analysis without adjustment for alcohol consumption; we found 395 variants on chromosome 12 associated with the LCD score having P values <5 × 10-8. A conditional analysis with the addition of the dosage data of rs671 on chromosome 12 as a covariate, P values for all 395 SNPs on chromosome 12 turned out to be insignificant. In the analysis with additional adjustment for alcohol consumption, we did not identify any SNPs associated with the LCD score.Conclusion: We found rs671 was inversely associated with adherence to LCD, but that was strongly confounded by alcohol consumption. [ABSTRACT FROM AUTHOR]

Background/objectives: Individual eating habits may be influenced by genetic factors, in addition to environmental factors. Previous studies suggested that adherence to Japanese food patterns was associated with a decreased risk of all-cause and cardiovascular disease mortality. We conducted a genome-wide association study (GWAS) in a Japanese population to find genetic variations that affect adherence to a Japanese food pattern.Subjects/methods: We analyzed GWAS data using 14,079 participants from the Japan Multi-Institutional Collaborative Cohort study. We made a Japanese food score based on six food groups. Association of the imputed variants with the Japanese food score was performed by linear regression analysis with adjustments for age, sex, total energy intake, alcohol intake (g/day), and principal components 1-10 omitting variants in the major histocompatibility region.Results: We found one SNP in the 14q11.2 locus that was significantly associated with the Japanese food score with P values <5 × 10-8. Functional annotation revealed that the expression levels of two genes (BCL2L2, SLC22A17) were significantly inversely associated with this SNP. These genes are known to be related to olfaction and obesity.Conclusion: We found a new SNP that was associated with the Japanese food score in a Japanese population. This SNP is inversely associated with genes link to olfaction and obesity. [ABSTRACT FROM AUTHOR]

Background/objective: Although benefits of fish consumption for health are well known, a significant percentage of individuals dislike eating fish. Fish consumption may be influenced by genetic factors in addition to environmental factors. We conducted a genome-wide association study (GWAS) to find genetic variations that affect fish consumption in a Japanese population.Methods: We performed a two-stage GWAS on fish consumption using 13,739 discovery samples from the Japan Multi-Institutional Collaborative Cohort study, and 2845 replication samples from the other population. We used a semi-quantitative food frequency questionnaire to estimate food intake. Association of the imputed variants with fish consumption was analyzed by separate linear regression models per variant, with adjustments for age, sex, energy intake, principal component analysis components 1-10, and alcohol intake (g/day). We also performed conditional analysis.Results: We found 27 single nucleotide polymorphisms (SNPs) located in 12q24 and 14q32.12 that were associated with fish consumption. The 19 SNPs were located at 11 genes including six lead SNPs at the BRAP, ACAD10, ALDH2, NAA25, and HECTD4 regions on 12q24.12-13, and CCDC197 region on 14q32.12. In replication samples, all five SNPs located on chromosome 12 were replicated successfully, but the one on chromosome 14 was not. Conditional analyses revealed that the five lead variants in chromosome 12 were in fact the same signal.Conclusion: We found that new SNPs in the 12q24 locus were related to fish intake in two Japanese populations. The associations between SNPs on chromosome 12 and fish intake were strongly confounded by drinking status. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to investigate independent relationships of daily non-exercise life activity and leisure-time exercise volume and intensity with the prevalence of metabolic syndrome and its traits in Japanese adults. Methods: Data of 24,625 eligible subjects (12,709 men, 11,916 women) who participated in the baseline survey of the Japan Multi-Institutional Collaborative Cohort (J-MICC) Study were analyzed. Information about lifestyle characteristics was obtained from a questionnaire. Logistic regression analyses were performed to evaluate the independent associations of daily life activity as well as leisure-time exercise volume and intensity with the prevalence of metabolic syndrome and its traits by sex. Results: Male subjects with higher daily life activity as well as with higher leisure-time exercise volume had a lower prevalence of metabolic syndrome, independently with each other. Female subjects with higher daily life activity also had a lower prevalence of metabolic syndrome. Particularly, male and female subjects with the highest daily life activity quartile showed considerably low odds ratios of 0.66 (95% CI, 0.53–0.81) and 0.64 (0.52–0.79), respectively, for low HDL-cholesterol even after the adjustment for BMI compared with the first quartile. Meanwhile, male subjects with the higher leisure-time exercise showed a quite lower prevalence of elevated triglycerides. Higher moderate-intensity exercise was more intensely associated with a lower prevalence of metabolic syndrome and some of its traits in both sexes. Conclusions: Our results suggest that higher daily life activity and higher moderate-intensity exercise may be independently associated with a lower risk of metabolic syndrome in Japanese adults. [ABSTRACT FROM AUTHOR]

Background: Perceived stress and coping strategies may influence the risk of cardiovascular disease through their possible association with inflammation, but data remain controversial for perceived stress or scanty for coping strategies. Purpose: We examined the associations of perceived stress and coping strategies with serum high-sensitivity C-reactive protein (CRP) in a Japanese general population. Methods: This cross-sectional study included 2,971 men and 4,902 women aged 40-69 years who were enrolled between 2005 and 2007. Subjects with possible inflammation-related disease, CRP levels ≥3,000 ng/mL, or currently used analgesics or lipid-lowering drugs were excluded. Analyses were performed by gender with adjustment for lifestyle, socioeconomic, and psychosocial factors. Results: Unexpectedly, elevated perceived stress was significantly associated with lower CRP levels in men ( P < 0.001) but not in women ( P = 0.90) after adjustment for age and covariates. Among five items of coping strategies evaluated, 'disengagement' showed a significant inverse association with CRP in men only ( P = 0.027). In addition, a possible interaction between 'emotional support seeking' and perceived stress on CRP was detected in men ( P = 0.021); 'emotional support seeking' was associated with lower CRP at the high stress level only ( P = 0.028). Conclusions: Both perceived stress and coping strategies may be associated with systemic inflammation in Japanese men, yet caution must be exercised before accepting the stress-inflammation-disease pathway. [ABSTRACT FROM AUTHOR]