Tooth loss is a risk factor for increased mortality; however, the underlying mechanism remains unclear. This study aimed to evaluate the mediating effect of weight change on the relationship between ...tooth loss and mortality risk. This was a 10-y follow-up prospective cohort study using the data from the Japan Gerontological Evaluation Study (JAGES). The participants were independent older adults aged ≥65 y at baseline and were followed up from 2010 to 2020. The incidence of death in 2013 and 2020, incidence of >5% weight loss/gain in 2010 and 2013, and the number of remaining teeth in 2010 were used as the outcome, mediator, and explanatory variables, respectively. We conducted causal mediation analysis by fitting the Cox proportional hazard model, including possible confounders. Hazard ratios (HRs) and 95% confidence intervals (95% CIs) of the total effect (TE), natural indirect effect (NIE), and proportion mediated (PM) were estimated. Among the 34,510 participants, the mean age was 72.6 (SD = 5.4) y, and 47.6% were men. From 2013 to 2020, 14.0% of the participants (n = 4,825) died, 60.5% (n = 20,871) had 0 to 19 remaining teeth, and 17.2% (n = 5,927) and 8.4% (n = 2,907) experienced >5% weight loss and gain, respectively. The mortality rate was 0.016 per person-year among those with ≥20 remaining teeth and 0.027 per person-year among those with 0 to 19 remaining teeth. Weight loss of >5% significantly mediated the association between tooth loss and higher mortality risk (TE: HR, 1.28 95% CI, 1.16 to 1.40; NIE: HR, 1.03 95% CI, 1.02 to 1.04; PM, 13.1%); however, we observed a slight mediating effect for >5% weight gain (NIE: HR, 1.003 95%CI, 1.0001 to 1.01; PM, 1.3%). The present study suggests that a clinically meaningful level of weight loss mediated the association between tooth loss and increased risk of mortality among independent older adults.
Acceleration of particles from the interaction of ultraintense laser pulses up to 5×10^{21} W cm^{-2} with thin foils is investigated experimentally. The electron beam parameters varied with ...decreasing spot size, not just laser intensity, resulting in reduced temperatures and divergence. In particular, the temperature saturated due to insufficient acceleration length in the tightly focused spot. These dependencies affected the sheath-accelerated protons, which showed poorer spot-size scaling than widely used scaling laws. It is therefore shown that maximizing laser intensity by using very small foci has reducing returns for some applications.
Tooth loss is prevalent in older adults and associated with functional capacity decline. Studies on the susceptibility of some individuals to the effects of tooth loss are lacking. This study aimed ...to investigate the heterogeneity of the association between tooth loss and higher-level functional capacity in older Japanese individuals employing a machine learning approach. This is a prospective cohort study using the data of adults aged ≥65 y in Japan (N = 16,553). Higher-level functional capacity, comprising instrumental independence, intellectual activity, and social role, was evaluated using the Tokyo Metropolitan Institute of Gerontology Index of Competence (TMIG-IC). The scale ranged from 0 (lowest function) to 13 (highest function). Doubly robust targeted maximum likelihood estimation was used to estimate the population-average association between tooth loss (having <20 natural teeth) and TMIG-IC total score after 6 y. The heterogeneity of the association was evaluated by estimating conditional average treatment effects (CATEs) using the causal forest algorithm. The result showed that tooth loss was statistically significantly associated with lower TMIG-IC total scores (population-average effect: −0.14; 95% confidence interval, −0.18 to −0.09). The causal forest analysis revealed the heterogeneous associations between tooth loss and lower TMIG-IC total score after 6 y (median of estimated CATEs = −0.13; interquartile range = 0.12). The high-impact subgroup (i.e., individuals with estimated CATEs of the bottom 10%) were significantly more likely to be older and male, had a lower socioeconomic status, did not have a partner, and had poor health conditions compared with the low-impact subgroup (i.e., individuals with estimated CATEs of the top 10%). This study found that heterogeneity exists in the association between tooth loss and lower scores on functional capacity. Implementing tooth loss prevention policy and clinical measures, especially among vulnerable subpopulations significantly affected by tooth loss, may reduce its burden more effectively.
Some modifiable risk factors for dementia are closely related to oral health. Although eating and speaking abilities are fundamental oral functions, limited studies have focused on the effect of ...malnutrition and lack of social interaction between oral health and dementia. We investigated the mediating effects of nutritional and social factors on the association between the number of teeth and the incidence of dementia. This 6-y cohort study used data from the Japan Gerontological Evaluation Study targeting older adults aged 65 y and above. The number of teeth (exposure) and covariates in 2010 (baseline survey), mediators (weight loss, vegetable and fruit intake, homeboundness, social network) in 2013, and the onset of dementia (outcome) between 2013 and 2016 were obtained. The Karlson–Holm–Breen mediation method was applied. A total of 35,744 participants were included (54.0% women). The mean age at baseline was 73.1 ± 5.5 y for men and 73.2 ± 5.5 y for women. A total of 1,776 participants (5.0%) had dementia during the follow-up period. There was a significant total effect of the number of teeth on the onset of dementia (hazard ratio, 1.14; 95% CI, 1.01–1.28). Controlling for nutritional and social mediators, the effect of the number of teeth was reduced to 1.10 (95% CI, 0.98–1.25), leaving an indirect effect of 1.03 (95% CI, 1.02–1.04). In the sex-stratified analysis, the proportion mediated by weight loss was 6.35% for men and 4.07% for women. The proportions mediated by vegetable and fruit intake and homeboundness were 4.44% and 4.83% for men and 8.45% and 0.93% for women, respectively. Furthermore, the proportion mediated by social networks was 13.79% for men and 4.00% for women. Tooth loss was associated with the onset of dementia. Nutritional and social factors partially mediated this association.
Aim
To assess the efficacy, safety and dose–response relationship of once‐daily teneligliptin, a novel dipeptidyl peptidase‐4 inhibitor, in Japanese patients with type 2 diabetes mellitus (T2DM) ...inadequately controlled with diet and exercise.
Methods
In this randomized, double‐blind, placebo‐controlled, parallel‐group study, patients (n = 324) were randomized to receive teneligliptin 10, 20 or 40 mg, or placebo, once daily before breakfast for 12 weeks. The primary endpoint was the change in haemoglobin (Hb)A1c from baseline to week 12.
Results
All teneligliptin‐treated groups showed significantly greater reductions in HbA1c and fasting plasma glucose (FPG) than did the placebo group. The differences between the teneligliptin 10, 20 or 40 mg groups and the placebo group for the change in HbA1c were −0.9 least‐squares (LS) mean; 95% confidence interval: −1.0, −0.7, −0.9 (−1.1, −0.7) and −1.0 (−1.2, −0.9)%, respectively (all, p < 0.001). The respective LS means for FPG were −17.8 (−23.4, −12.1), −16.9 (−22.6, −11.2) and −20.0 (−25.7, −14.3) mg/dl (all, p < 0.001). There were no significant differences in HbA1c among the three doses of teneligliptin. The incidence of adverse events and adverse drug reactions was similar in each group. The incidence of hypoglycaemia was not significantly different among the four groups.
Conclusions
Treatment with teneligliptin for 12 weeks provided significant and clinically meaningful reductions in HbA1c and FPG across the dose range studied and was generally well tolerated in Japanese patients with T2DM.
Despite their prevalence and burdens, oral diseases are neglected in universal health coverage. In Japan, a 30% copayment (out of pocket) by the user and a 70% contribution by Japan’s universal ...health insurance (JUHI) are required for dental and medical services. From the age of 70 y, an additional 10% is offered by JUHI (copayment, 20%; JUHI, 80%). This study aimed to investigate the effect of cost on dental service use among older adults under the current JUHI system. A regression discontinuity quasi-experimental method was used to investigate the causal effect of the JUHI discount policy on dental visits based on cross-sectional data. Data were derived from the 2016 Japan Gerontological Evaluation Study. This analysis contained 7,161 participants who used JUHI, were aged 68 to 73 y, and responded to questions regarding past dental visits. Analyses were controlled for age, sex, number of teeth, and equalized household income. Mean ± SD age was 72.1 ± 0.79 y for the discount-eligible group and 68.9 ± 0.78 y for the noneligible group. During the past 12 mo, significantly more discount-eligible participants had visited dental services than noneligible participants (66.0% vs. 62.1% for treatment visits, 57.7% vs. 53.1% for checkups). After controlling for covariates, the effect of discount eligibility was significant on dental treatment visits (odds ratio OR, 1.36; 95% CI, 1.32 to 1.40) and dental checkups (OR, 1.49; 95% CI, 1.44 to 1.54) in the regression discontinuity analysis. Similar findings were observed in triangular kernel-weighted models (OR, 1.38 95% CI, 1.34 to 1.44; OR, 1.52 95% CI, 1.47 to 1.56, respectively). JUHI copayment discount policy increases oral health service utilization among older Japanese. The price elasticity for dental checkup visits appears to be higher than for dental treatment visits. Hence, reforming the universal health coverage system to improve the affordability of relatively inexpensive preventive care could increase dental service utilization in Japan.
Aims
To assess the efficacy and safety of teneligliptin in combination with glimepiride in Japanese patients with type 2 diabetes mellitus (T2DM) inadequately controlled with glimepiride monotherapy.
...Methods
In the initial 12‐week, double‐blind, placebo‐controlled, parallel‐group period, 194 patients haemoglobin A1c (HbA1c): 8.4 ± 0.8%; fasting plasma glucose (FPG): 164.2 ± 28.1 mg/dl were randomized to either teneligliptin 20 mg or placebo once daily while continuing stable glimepiride therapy. This randomized period was then followed by a 40‐week, open‐label period, where all patients received teneligliptin once daily. The primary endpoint was the change in HbA1c from baseline to week 12.
Results
Teneligliptin reduced HbA1c significantly compared with placebo at week 12. The placebo‐subtracted change in HbA1c was −1.0 ± 0.1% least‐squares (LS) mean ± s.e., p < 0.001. Teneligliptin also significantly reduced FPG and 2‐h postprandial glucose (PPG) as compared with placebo at week 12; the placebo‐subtracted changes were −27.1 ± 3.2 and −49.1 ± 6.2 mg/dl (LS mean ± s.e., both p < 0.001), respectively. The blood glucose‐lowering effects were sustained throughout the 40‐week open‐label period. The incidence rates of adverse events and adverse drug reactions, including hypoglycaemia, during the double‐blind randomized period were similar in both groups. Therefore, teneligliptin was generally well tolerated when used in combination with glimepiride.
Conclusions
The addition of teneligliptin was effective and generally well tolerated in Japanese patients with T2DM inadequately controlled with glimepiride monotherapy. The improvements in glycaemic control were maintained for up to 52 weeks.
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