Background: The association between chronic lipopolysaccharide exposure and the development of metabolic syndrome (MetS) is unclear. In this study we examined the association between serum lipopolysaccharide-binding protein (LBP) levels, an indicator of lipopolysaccharide exposure, and the development of MetS in a general Japanese population.

Methods: 1,869 community-dwelling Japanese individuals aged ≥40 years without MetS at baseline examination in 2002–2003 were followed up by repeated examination in 2007–2008. MetS was defined according to the Japanese criteria. Serum LBP levels were classified into quartiles (quartiles 1–4: 2.20–9.56, 9.57–10.78, 10.79–12.18, and 12.19–24.34 µg/mL, respectively). Odds ratios (ORs) for developing MetS were calculated using a logistic regression model.

Results: At the follow-up survey, 159 participants had developed MetS. Higher serum LBP levels were associated with greater risk of developing MetS after multivariable adjustment for age, sex, smoking, drinking, and exercise habits (OR [95% confidence interval] for quartiles 1–4: 1.00 [reference], 2.92 [1.59–5.37], 3.48 [1.91–6.35], and 3.86 [2.12–7.03], respectively; P for trend <0.001). After additional adjustment for homeostasis model assessment of insulin resistance, this association was attenuated but remained significant (P for trend = 0.007). On the other hand, no significant association was observed after additional adjustment for serum high-sensitivity C-reactive protein (P for trend = 0.07).

Conclusion: In the general Japanese population, our findings suggest that higher serum LBP levels are associated with elevated risk of developing MetS. Low-grade endotoxemia could play a role in the development of MetS through systemic chronic inflammation and insulin resistance.

Background: Despite the widespread practice of Japanese traditional Kampo medicine, the characteristics of patients receiving various Kampo formulations have not been documented in detail. We applied a machine learning model to a health insurance claims database to identify the factors associated with the use of Kampo formulations.

Methods: A 10% sample of enrollees of the JMDC Claims Database in 2018 and 2019 was used to create the training and testing sets, respectively. Logistic regression analyses with lasso regularization were performed in the training set to construct models with prescriptions of 10 commonly used Kampo formulations in 1 year as the dependent variable and data of the preceding year as independent variables. Models were applied to the testing set to calculate the C-statistics. Additionally, the performance of simplified scores using 10 or 5 variables were evaluated.

Results: There were 338,924 and 399,174 enrollees in the training and testing sets, respectively. The commonly prescribed Kampo formulations included kakkonto, bakumondoto, and shoseityuto. Based on the lasso models, the C-statistics ranged from 0.643 (maoto) to 0.888 (tokishakuyakusan). The models identified both the common determinants of different Kampo formulations and the specific characteristics associated with particular Kampo formulations. The simplified scores were slightly inferior to full models.

Conclusion: Lasso regression models showed good performance for explaining various Kampo prescriptions from claims data. The models identified the characteristics associated with Kampo formulation use.

Background: Psychological stress can cause various mental and physical health problems. The previous results on stress and oral health are inconsistent, possibly because of the narrow stress measurements. We aimed to examine the association between a broader range of stressful life events and oral health among workers.

Methods: This cross-sectional study analyzed anonymous individual data from a national survey in Japan. Data on stressful life events, oral health problems which are one or more of tooth pain, gum swelling/bleeding, and difficulty chewing, and covariates were obtained using a self-reported questionnaire. Covariates used included gender, age group, and disease under treatment. Logistic regression analysis was used to estimate the association between stressful life events and oral health problems. We then estimated the causal treatment effects of stress using the augmented inverse-probability weighting (AIPW) method.

Results: Among the 274,881 subjects, 152,850 men (55.6%) and 122,031 women (44.4%) with a mean age of 47.0 (standard deviation, 14.4) years, 4.0% reported oral health problems, with a prevalence of 2.1% among those without any stress. The prevalence increased with stress score, reaching 15.4% for those with the maximum stress score. The adjusted odds ratio of this group compared to those without any stress was 9.2 (95% confidence interval [CI], 8.2–10.3). The estimated prevalence of oral health problems by the AIPW analysis was 2.2% (95% CI, 2.1–2.3%) for those without any stress and 14.4% (95% CI, 12.1–16.7%) for those with the maximum stress scores.

Conclusion: There was a clear dose-response association between stressful life events and oral health problems.

Purpose: Although examining the dose-response curves of physical activity (PA) and sitting time with health-related outcomes is an important research agenda, the results for older Japanese adults are extremely limited. We examined the dose-response associations of PA and sitting time with all-cause mortality among older Japanese.

Methods: Initially, 8,069 non-disabled residents (4,073 men; 3,996 women) aged 65–84 years of Ota City, Japan, were analyzed. Moderate-to-vigorous PA (MVPA) and sitting time were evaluated using the International Physical Activity Questionnaire-Short Form. Multivariate-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) of MVPA and sitting time for all-cause mortality were calculated, and the dose-response curves were examined using restricted cubic splines (RCS).

Results: During 4.1 years of follow-up, 458 participants (5.7%; 331 men and 127 women) died. Compared with the low MVPA (<600 metabolic equivalents [METs]·minutes/week) group, HR for mortality gradually reduced in moderate (600–3,000 METs·minutes/week) and high (>3,000 METs·minutes/week) MVPA groups (moderate: HR 0.66; 95% CI, 0.54–0.82; high: HR 0.58; 95% CI, 0.45–0.75; P < 0.001 for trend). RCS showed that the HR for mortality reduced linearly up to approximately 2,000 METs·minutes/week of MVPA, and maximal risk reduction was seen at approximately 3,000–4,500 METs·minutes/week of MVPA. No significant dose-response association of sitting time with mortality was observed.

Conclusion: Higher MVPA levels reduced all-cause mortality risk, in a significant inverse non-linear dose-response manner. Sitting time was not significantly associated with all-cause mortality. It is important to disseminate the significance of even a slight increase in the MVPA for reducing mortality risk.

Background: The neurological prognosis of asphyxia is poor and the effect of advanced airway management (AAM) in the prehospital setting remains unclear. This study aimed to evaluate the association between AAM with adrenaline injection and prognosis in adult patients with asystole asphyxia out-of-hospital cardiac arrest (OHCA).

Methods: This study assessed all-Japan Utstein cohort registry data between January 1, 2013 and December 31, 2019. We used propensity score matching analyses before logistic regression analysis to evaluate the effect of AAM on favorable neurological outcome.

Results: There were 879,057 OHCA cases, including 70,299 cases of asphyxia OHCAs. We extracted the data of 13,642 cases provided with adrenaline injection by emergency medical service. We divided 7,945 asphyxia OHCA cases in asystole into 5,592 and 2,353 with and without AAM, respectively. After 1:1 propensity score matching, 2,338 asphyxia OHCA cases with AAM were matched with 2,338 cases without AAM. Favorable neurological outcome was not significantly different between the AAM and no AAM groups (adjusted odds ratio [OR] 1.1; 95% confidence interval [CI], 0.5–2.5). However, the return of spontaneous circulation (ROSC) (adjusted OR 1.7; 95% CI, 1.5–1.9) and 1-month survival (adjusted OR 1.5; 95% CI, 1.1–1.9) were improved in the AAM group.

Conclusion: AAM with adrenaline injection for patients with asphyxia OHCA in asystole was associated with improved ROSC and 1-month survival rate but showed no differences in neurologically favorable outcome. Further prospective studies may comprehensively evaluate the effect of AAM for patients with asphyxia.

Background: The logistic regression analysis proposed by Schouten et al (Stat Med. 1993;12:1733–1745) has been a standard method in current statistical analysis of case-cohort studies, and it enables effective estimation of risk ratios from selected subsamples, with adjustment of potential confounding factors. Schouten et al (1993) also proposed the standard error estimate of the risk ratio estimator can be calculated using the robust variance estimator, and this method has been widely adopted.

Methods and Results: The robust variance estimator does not account for the duplications of case and subcohort samples and generally has certain bias (ie, inaccurate confidence intervals and P-values are possibly obtained). To address the invalid statistical inference problem, we provide an alternative bootstrap-based valid variance estimator. Through simulation studies, the bootstrap method consistently provided more precise confidence intervals compared with those provided using the robust variance method, while retaining adequate coverage probabilities.

Conclusion: The robust variance estimator has certain bias, and inadequate conclusions might be deduced from the resultant statistical analyses. The proposed bootstrap variance estimator can provide more accurate and precise interval estimates. The bootstrap method would be an alternative effective approach in practice to provide accurate evidence.

Background: We sought to establish a prospective hospital-based cohort, featuring detailed multidimensional data of trauma patients with active follow-ups, which can be a reliable data source for all studies focusing on the effects or underlying mechanistic pathways of environmental and biological factors on multiple interested trauma-related outcomes, particularly the incidence and trajectory of trauma-related psychopathology, in a Chinese population.

Methods: The China Severe Trauma Cohort (CSTC) enrolled all traumatized individuals aged 12 to 80 years admitted to the Trauma Center of West China Hospital between March 1^st, 2020 and July 8^th, 2022. The bio-sample and detailed questionnaire data were collected at recruitment, and phone/internet follow-ups were scheduled at 1, 3, 6, and 12 months after the baseline. Long-term health outcomes are planned to be obtained from administrative databases through data linkage.

Results: A total of 2,500 trauma patients were enrolled (response rate = 87.1%) with an average age of 46.01 years, and most of the participants were males (62.6%). The proportions of participants with blood and fecal sample collected at baseline were 93.8% and 66.3%, respectively. As of August 31^st, 2022, the follow-up rate was 90.0%, 77.0%, 76.5%, and 89.0% for 1-, 3-, 6-, and 12-month follow-ups, respectively. Fall/wrench (47.6%) and traffic accident (26.2%) were the top causes of current trauma. The most common psychopathology at recruitment was sleep disturbance (39.4%), followed by depression (22.6%), anxiety (18.2%), and acute stress reaction (7.8%), all of which showed recovering trajectories during the follow-up period, particularly the first 3 months after baseline.

Conclusion: CSTC provides a platform with multidimensional data to study both short-term and long-term trauma-related health consequences, prompting early identification and intervention for individuals with high risk of health decline after trauma exposures.