Perivascular leukocyte clusters are essential for efficient activation of effector T cells in the skin.

It remains largely unclear how antigen-presenting cells (APCs) encounter effector or memory T cells efficiently in the periphery. Here we used a mouse contact hypersensitivity (CHS) model to show that upon epicutaneous antigen challenge, dendritic cells (DCs) formed clusters with effector T cells in dermal perivascular areas to promote in situ proliferation and activation of skin T cells in a manner dependent on antigen and the integrin LFA-1. We found that DCs accumulated in perivascular areas and that DC clustering was abrogated by depletion of macrophages. Treatment with interleukin 1α (IL-1α) induced production of the chemokine CXCL2 by dermal macrophages, and DC clustering was suppressed by blockade of either the receptor for IL-1 (IL-1R) or the receptor for CXCL2 (CXCR2). Our findings suggest that the dermal leukocyte cluster is an essential structure for elicitating acquired cutaneous immunity.

Duration of effectiveness of the COVID-19 vaccine in Japan: a retrospective cohort study using large-scale population-based registry data.

BACKGROUND: Most evidence of the waning of vaccine effectiveness is limited to a relatively short period after vaccination. METHODS: Data obtained from a linked database of healthcare administrative claims and vaccination records maintained by the municipality of a city in the Kanto region of Japan were used in this study. The study period extended from April 1, 2020, to December 31, 2022. The duration of the effectiveness of the COVID-19 vaccine was analyzed using a time-dependent piecewise Cox proportional hazard model using the age, sex and history of cancer, diabetes, chronic obstructive pulmonary disease, asthma, chronic kidney disease, and cardiovascular disease as covariates. RESULTS: Among the 174,757 eligible individuals, 14,416 (8.3%) were diagnosed with COVID-19 and 936 (0.54%) were hospitalized for COVID-19. Multivariate analysis based on the time-dependent Cox regression model with reference of non-vaccine group revealed a lower incidence of COVID-19 in the one-dose group (hazard ratio, 0.76 [95% confidence interval, 0.63-0.91]), two-dose (0.89 [0.85-0.93]), three-dose (0.80 [0.76-0.85]), four-dose (0.93 [0.88-1.00]), and five-dose (0.72 [0.62-0.84]) groups. A lower incidence of COVID-19-related hospitalization was observed in the one-dose group (0.42 [0.21-0.81]), two-dose (0.44 [0.35-0.56]), three-dose (0.38 [0.30-0.47]), four-dose (0.20 [0.14-0.28]), and five-dose (0.11 [0.014-0.86]) groups. Multivariable analyses based on the time-dependent piecewise Cox proportional hazard model with reference of non-vaccine group revealed significant preventive effects of the vaccine for 4 months for the incidence of COVID-19 and ≥ 6 months for hospitalization. CONCLUSIONS: Vaccine effectiveness showed gradual attenuation with time after vaccination; however, protective effects against the incidence of COVID-19 and hospitalization were maintained for 4 months and ≥ 6 months, respectively. These results may aid in formulating routine vaccination plans after the COVID-19 pandemic.

Machine Learning-based Models for Outpatient Prescription of Kampo Formulations: An Analysis of a Health Insurance Claims Database.

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.

Effect of periodontal therapy on glycaemic control in type 2 diabetes.

AIM: This study aimed to elucidate the impact of periodontal therapy on glycaemic control in individuals with type 2 diabetes and various baseline blood glucose levels using a large-scale claims database from Japan. MATERIALS AND METHODS: Using the JMDC Claims Database, we identified individuals with type 2 diabetes who underwent health check-ups in the fiscal years 2018 or 2019 and were followed up until the next year's health check-up. We conducted a weighted cohort analysis using stabilized inverse probability weights for treatment and censoring to estimate the effect of periodontal therapy on changes in haemoglobin A1c levels within a year. Analysis was done for different baseline haemoglobin A1c categories: 6.5%-6.9%, 7.0%-7.9% and ≥8.0%. RESULTS: Of the 4279 insured persons included in the study, 957 received periodontal therapy. Overall, there was a tendency towards improved glycaemic control among those who received periodontal therapy. Participants with baseline haemoglobin A1c levels of 7.0%-7.9% who received periodontal therapy exhibited significantly better glycaemic control compared with those without dental visits (difference; -0.094 [95% confidence interval: -0.181 to -0.007]). CONCLUSIONS: Periodontal therapy may improve glycaemic control in individuals with diabetes, especially in those with haemoglobin A1c levels ≥7.0%.

"Association between perinatal mood disorders of parents and child health outcomes".

PURPOSE: Perinatal mood disorders affect both parents, impacting their children negatively. Little is known on the association between parental perinatal mood disorders and pediatric outcomes in Japan considering relevant covariates. Our objective was to investigate the association between paternal and maternal perinatal mood disorders and adverse physical and psychological child outcomes by the age of 36 months, adjusting for covariates such as the child's sex, age of parent at child's birth, perinatal mood disorders of the other parent, and perinatal antidepressant use. METHODS: We identified parents in the JMDC Claims Database in Japan from 2012 to 2020. Perinatal mood disorders were defined using International Classification of Diseases, 10th codes for mood disorders during the perinatal period combined with psychiatric treatment codes. We evaluated the association between parental perinatal mood disorders and pediatric adverse outcomes by the age of 36 months using Cox proportional hazard models adjusted for the covariates. RESULTS: Of the 116,423 father-mother-child triads, 2.8% of fathers and 2.3% of mothers had perinatal mood disorders. Paternal perinatal mood disorders were not significantly associated with adverse child outcomes. After adjusting for paternal perinatal mood disorders and antidepressant use, maternal perinatal mood disorders were associated with delayed motor development, language development disorders, autism spectrum disorders, and behavioral and emotional disorders (adjusted hazard ratio [95% confidence interval]: 1.65 [1.01-2.69], 2.26 [1.36-3.75], 4.16 [2.64-6.55], and 6.12 [1.35-27.81], respectively). CONCLUSIONS: Paternal perinatal mood disorders were not associated with adverse child outcomes in this population. Maternal perinatal mood disorders were associated with multiple child outcomes.

Exploring the influence of a financial incentive scheme on early mobilization and rehabilitation in ICU patients: an interrupted time-series analysis.

BACKGROUND: Clinical guidelines recommend early mobilization and rehabilitation (EMR) for patients who are critically ill. However, various barriers impede its implementation in real-world clinical settings. In 2018, the Japanese universal healthcare coverage system announced a unique financial incentive scheme to facilitate EMR for patients in intensive care units (ICU). This study evaluated whether such an incentive improved patients' activities of daily living (ADL) and reduced their hospital length of stay (LOS). METHODS: Using the national inpatient database in Japan, we identified patients admitted to the ICU, who stayed over 48 hours between April 2017 and March 2019. The financial incentive required medical institutions to form a multidisciplinary team approach for EMR, development and periodic review of the standardized rehabilitation protocol, starting rehabilitation within 2 days of ICU admission. The incentive amounted to 34.6 United States Dollars per patient per day with limit 14 days, structured as a per diem payment. Hospitals were not mandated to provide detailed information on individual rehabilitation for government, and the insurer made payments directly to the hospitals based on their claims. Exposure was the introduction of the financial incentive defined as the first day of claim by each hospital. We conducted an interrupted time-series analysis to assess the impact of the financial incentive scheme. Multivariable radon-effects regression and Tobit regression analysis were performed with random intercept for the hospital of admission. RESULTS: A total of 33,568 patients were deemed eligible. We confirmed that the basic assumption of ITS was fulfilled. The financial incentive was associated with an improvement in the Barthel index at discharge (0.44 points change in trend per month; 95% confidence interval = 0.20-0.68) and shorter hospital LOS (- 0.66 days change in trend per month; 95% confidence interval = - 0.88 - -0.44). The sensitivity and subgroup analyses showed consistent results. CONCLUSIONS: The study suggests a potential association between the financial incentive for EMR in ICU patients and improved outcomes. This incentive scheme may provide a unique solution to EMR barrier in practice, however, caution is warranted in interpreting these findings due to recent changes in ICU care practices.

Infiltration and local differentiation of bone marrow-derived integrinß7-positive mast cell progenitors in atopic dermatitis-like skin.

BACKGROUND: Mast cells (MCs) are tissue-resident cells with various immunologic functions. MCs are increased in atopic dermatitis (AD) skin and can contribute to the inflammation. Although skin MCs are inducible from bone marrow (BM) cells in vitro, they are maintained locally by self-proliferation in the steady state in vivo. However, how skin MCs are increased in AD skin, including the infiltration of BM-derived MC progenitors (MCps) and their differentiation, remains unclear. OBJECTIVE: We sought to identify and characterize BM-derived MCps in AD skin. METHODS: BM-derived MCps in AD skin were analyzed by flow cytometry using BM-chimeric mice and parabiosis in an MC903-induced AD model. BM-derived MCps in AD-like skin were compared with resident MCs for gene expression by RNA- sequencing analysis. RESULTS: We observed local proliferation of resident MCs and an increase in BM-derived MCs in AD-like skin. BM-derived MCs in the skin were derived from circulating MCps and were distinguishable from resident MCs by integrinß7. RNA- sequence analysis showed that integrinß7+ MCs (BM-derived MCps) in the skin shared the characteristics of both mucosal-type MCs and connective tissue-type MCs, and increased the expression of genes related to MCp migration. BM-derived MCps proliferated in situ, gradually lost the integrinß7 expression, and acquired connective tissue-type MC phenotypes during the remission phase of inflammation. CONCLUSIONS: BM-derived integrinß7+ MCps migrate to AD-like skin and contribute to the maintenance of skin MCs.

Comparative Effectiveness of BNT162b2 and mRNA-1273 Booster Dose After BNT162b2 Primary Vaccination Against the Omicron Variants: A Retrospective Cohort Study Using Large-Scale Population-Based Registries in Japan.

BACKGROUND: Direct comparative effectiveness of booster doses of BNT162b2 and mRNA-1273 after BNT162b2 primary vaccination is unknown. METHODS: We investigated comparative effectiveness of BNT162b2 and mRNA-1273 booster dose using data from registry systems for vaccination and coronavirus disease 2019 (COVID-19) infection in a local city in Japan. We followed participants aged ≥16 years who completed the BNT162b2 primary vaccination between 22 November 2021, and 15 April 2022. We collected information on age, sex, vaccination status, vaccine type, and infection status. Age was categorized as 16-44, 45-64, 65-84, and ≥85 years. Vaccine effectiveness for mRNA-1273 and no booster vaccination against BNT162b2 was estimated using age-stratified Cox regression adjusted for age, sex, and days since the second vaccination. The estimated hazard ratios for mRNA-1273 and no booster vaccinations were integrated separately using random effects meta-analyses. RESULTS: During the study period, we identified 62 586 (40.4%), 51 490 (33.2%), and 40 849 (26.4%) participants who received BNT162b2, mRNA-1273, and no booster dose, respectively. The median age was 69, 71, and 47 years for BNT162b2, mRNA-1273, and no booster dose, respectively. The integrated hazard ratio with reference to BNT162b2 was 1.72 for no booster vaccination and 0.62 for mRNA-1273. The comparative effectiveness of mRNA-1273 was similar across age categories. CONCLUSIONS: Both homologous and heterologous vaccinations are effective against Omicron variants. In the head-to-head comparison, the effect was stronger in people who received heterologous vaccination than in those who received homologous vaccination. These findings may help improve logistics and decision making in future vaccination programs.

Ocular Adverse Events after Coronavirus Disease 2019 mRNA Vaccination: Matched Cohort and Self-Controlled Case Series Studies Using a Large Database.

PURPOSE: To investigate the risk of ocular adverse events after Coronavirus Disease 2019 (COVID-19) mRNA vaccination. DESIGN: Matched cohort and self-controlled case series (SCCS) studies. PARTICIPANTS: We used a population-based database of medical claims and vaccination records in a large Japanese city. In the matched cohort study, we identified individuals who received COVID-19 vaccination (BNT162b2) from February 2021 to September 2021. One control was selected from nonvaccinated individuals by matching time, date of birth, sex, Charlson comorbidity index, and the enrollment period for health insurance. In the SCCS study, we analyzed individuals who developed ocular adverse events. METHODS: In the matched cohort study, we applied the Kaplan-Meier estimator to estimate the cumulative incidence of ocular adverse events over 21 days after the first dose and 84 days after the second dose. In the SCCS method, we used conditional Poisson regression to estimate the incidence rate ratio (IRR) of ocular adverse events during the risk periods (0-21 days after the first dose and 0-84 days after the second dose) compared with the remaining periods. MAIN OUTCOME MEASURES: Composite outcome of uveitis, scleritis, retinal vein occlusion (RVO), and optic neuritis. RESULTS: There were 99 718 pairs eligible for the matched cohort study after the first dose (mean age, 69.3 years; male, 44%). The vaccinated and control groups developed 29 and 21 events, respectively, over 21 days after the first dose, and 79 and 28 events, respectively, over 84 days after the second dose. The differences in cumulative incidence (reference, the control group) were 2.9 (95% confidence interval, -14.5 to 19.1) events/100 000 persons and 51.3 (16.2-84.3) events/100 000 persons, respectively, for the first and second doses. The SCCS study showed the IRRs of 0.89 (0.62-1.28) and 0.89 (0.71-1.11) for the first and second doses, respectively. CONCLUSIONS: The matched cohort analysis found an increased risk for the composite outcome after the second dose; however, the SCCS analysis showed no increased risk. Considering that the SCCS can cancel out time-invariant confounders, the current results suggest that COVID-19 vaccination is unlikely to causally increase the risk of ocular adverse events. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Effectiveness of vaccination on influenza-related critical illnesses in the elderly population.

OBJECTIVES: The prevention of serious influenza-related severe conditions due to influenza is important, particularly in elderly patients, age is a risk factor for death resulting from influenza-related respiratory diseases. The aim of the present study was to investigate the association of influenza vaccination with severe condition requiring critical care and death in elderly people, using vaccine records and healthcare administrative claims data in a Japanese city. RESULTS: Among 5608 patients aged ≥65 years diagnosed with influenza, we identified 96 patients who had received invasive mechanical ventilation or died. Thereafter, we matched 384 controls with the cases. The cases were less vaccinated than the controls (37.5% vs. 56.0%, P < 0.01). In the multivariate analysis, influenza vaccination was associated with a lower proportion of the composite outcome (odds ratio, 0.35; 95% confidence interval, 0.21-0.60). In patients aged ≥80 years old and those with cardiovascular disease, influenza vaccination was associated with low composite outcomes. CONCLUSIONS: Influenza vaccination was associated with reduced proportions of receiving invasive mechanical ventilation or influenza-related mortality, particularly in those aged ≥80 years old.

Comparison of bleeding complications after pediatric kidney biopsy between intravenous sedation and general anesthesia: a nationwide cohort study.

BACKGROUND: An increasing number of studies are evaluating the safety of intravenous sedation compared with that of general anesthesia; however, data on bleeding complications after pediatric percutaneous renal biopsy performed under intravenous sedation or general anesthesia are lacking. We aimed to examine differences in bleeding complications between intravenous sedation and general anesthesia in pediatric patients. METHODS: Data of pediatric patients aged ≤ 15 years undergoing percutaneous kidney biopsy for kidney disease between July 2007 and March 2019 were retrieved from a national inpatient database in Japan. We examined differences in bleeding complications after renal biopsy performed under intravenous sedation, defined by the absence of the record of general anesthesia with intubation but by the presence of intravenous sedation during biopsy, and general anesthesia, defined by the presence of the record of general anesthesia with intubation during biopsy, among pediatric patients admitted for percutaneous renal biopsy. We performed binomial regression using overlap weights based on propensity scores for patients receiving intravenous sedation. Analyses stratified by age or sex, a sensitivity analysis using generalized estimating equations considering cluster effects by hospital among a propensity score-matched cohort, and another sensitivity analysis using the instrumental variable method were performed to confirm the robustness of the results. RESULTS: We identified 6,560 biopsies performed in 5,999 children aged 1-15 years from 328 hospitals and 178 events. Only three severe complications and no death were observed. No significant difference in the proportion of bleeding complications was observed between procedures performed under intravenous sedation and those performed under general anesthesia (unadjusted proportions, 2.8% and 2.3%; adjusted proportions, 2.5% and 2.2%), with an unadjusted relative risk of 1.21 (95% confidence interval, 0.80-1.81) and adjusted relative risk of 1.13 (95% confidence interval, 0.74-1.73). Both age- and sex-stratified analyses yielded similar results. The analysis using generalized estimating equation and the instrumental variable method showed relative risks of 0.95 (95% confidence interval, 0.48-1.88) and 1.18 (95% confidence interval, 0.74-1.89), respectively. CONCLUSION: This retrospective cohort study using a national database revealed that the risk of biopsy-related bleeding was comparable between intravenous sedation and general anesthesia during pediatric percutaneous kidney biopsy, suggesting that intravenous sedation alone and general anesthesia may have a similar bleeding risk in pediatric percutaneous kidney biopsies.

Association between better night-shift nurse staffing and surgical outcomes: A retrospective cohort study using a nationwide inpatient database in Japan.

INTRODUCTION: Although many studies have investigated the relationship between patient outcomes and the level of nurse staffing, little is known about the association between increased night-shift nurse staffing and patient outcomes. In the Japanese universal health insurance system, a new scheme of additional financial incentives for acute care hospitals was launched in 2012 to increase the number of nurses during the night shift in general wards. The objective of this study was to investigate whether an additional financial incentive to increase night-shift nurse staffing in general wards was associated with better patient outcomes. DESIGN: Adoption of the above-mentioned scheme of additional financial incentives was used as a natural experiment, and the difference-in-differences method was conducted to evaluate the effect of the scheme. The study was performed using a nationwide inpatient database and hospital information in Japan. METHODS: To conduct a difference-in-differences analysis, first, hospitals with and without increased night-shift nurse staffing were matched using propensity score matching. A patient-level difference-in-differences analysis was then conducted. The intervention group comprised the hospitals that adopted the new scheme of additional financial incentives. The outcome measures were in-hospital mortality, failure to rescue, and length of hospital stay. RESULTS: Subjects were 403,971 adult patients who underwent planned major surgeries in Japanese acute care hospitals from April 2012 to March 2018. The adjusted difference-in-differences estimates were not significant for in-hospital mortality (odds ratio: 0.83; 95% confidence interval: 0.68 to 1.01; p = 0.07) or failure to rescue (odds ratio: 0.92; 95% confidence interval: 0.73 to 1.14; p = 0.44). The adjusted difference-in-differences estimate for length of hospital stay was significant (percent change: -3.2%; 95% confidence interval: -6.1 to -0.3%; p = 0.029), indicating that the adoption of the scheme was associated with a decreased length of hospital stay. CONCLUSIONS: Increased night-shift nurse staffing was not associated with a decrease in in-hospital mortality or failure to rescue, but it was associated with a reduction in the length of hospital stay. It may be necessary to consider changes in policy content to make the policy more effective. The findings of this study are potentially useful for medical policymakers considering nurse staffing to decrease the length of stay, which may decrease costs. CLINICAL RELEVANCE: This study showed that increased night-shift nurse staffing was not associated with a decrease in in-hospital mortality or failure to rescue, but it was associated with a reduction in the length of hospital stay. The examination of the effectiveness of increasing nurse staffing during a specific shift in acute care hospitals is potentially useful for health policymakers worldwide in their considerations of future nurse staffing policies.

Major complications after percutaneous biopsy of native or transplanted liver in pediatric patients: a nationwide inpatient database study in Japan.

AIM: Although major complication rates following percutaneous liver biopsy (PLB) have been reported to be higher in children than in adults, scarce data are available regarding pediatric patients stratified by native and transplanted liver. We aimed to assess the factors associated with major complications after percutaneous biopsy of native or transplanted liver using a nationwide inpatient database. METHODS: Using the Japanese Diagnosis Procedure Combination database, we retrospectively identified pediatric patients who underwent PLB between 2010 and 2018. We described major complication rates and analyzed factors associated with major complications following PLB, stratified by native and transplanted liver. RESULTS: We identified 3584 pediatric PLBs among 1732 patients from 239 hospitals throughout Japan during the study period, including 1310 in the native liver and 2274 in the transplanted liver. Major complications following PLB were observed in 0.5% (n = 18) of the total cases; PLB in the transplanted liver had major complications less frequently than those in the native liver (0.2% vs. 1.0%, p = 0.002). The occurrence of major complications was associated with younger age, liver cancers, unscheduled admission, anemia or coagulation disorders in cases with native liver, while it was associated with younger age alone in cases with transplanted liver. CONCLUSIONS: The present study, using a nationwide database, found that major complications occurred more frequently in pediatric cases with native liver and identified several factors associated with its major complications.

Trends in prophylactic antibiotic use for tooth extraction from 2015 to 2018 in Japan: An analysis using a health insurance claims database.

INTRODUCTION: To describe patterns in antibiotic prophylaxis for tooth extraction following the 2016 Japanese National Action Plan on Antimicrobial Resistance. METHODS: Using a health insurance claims database, we retrospectively identified tooth extraction visits by patients aged ≥18 years from September 2015 to August 2018 and classified patients as undergoing extraction of a fully impacted or horizontally impacted mandibular wisdom tooth, being at risk of infective endocarditis or surgical site infection, or being at low risk. Antibiotic use and type of antibiotics prescribed on the day of tooth extraction were evaluated across the study period, with stratification by tooth extraction category and facility type (hospital or dental clinic). RESULTS: We identified 662,435 patients with tooth extraction. The mean age was 42.7 years, and 57% were male. Twelve percent underwent wisdom tooth extraction, 32% were high risk, and 10% visited hospitals. The proportion of antibiotic use was 83% overall and 82% among low-risk patients. This proportion remained similar throughout the study period. A shift from third-generation cephalosporins to amoxicillin was observed from 2015 to 2018: the proportion prescribed third-generation cephalosporins decreased from 58% to 34% in hospitals and from 57% to 56% in clinics, and the proportion prescribed amoxicillin increased from 16% to 37% in hospitals and from 6% to 10% in clinics. CONCLUSIONS: The pattern of prophylactic antibiotic use for tooth extraction gradually changed after the initiation of the National Action Plan. Further efforts are required to reduce potentially inappropriate prescriptions for low-risk patients, especially in dental clinics.

Amoxicillin vs third-generation cephalosporin for infection prophylaxis after third molar extraction.

OBJECTIVES: Although amoxicillin is the first-line prophylactic drug for impacted mandibular third molar extraction, third-generation cephalosporins are widely prescribed in Japan. The lack of real-world evidence may be one reason for this inappropriate use. We evaluated differences in the incidence of surgical site infection between amoxicillin and third-generation cephalosporins for impacted mandibular third molar extraction. METHODS: Using the JMDC Claims Database, we identified dental visits with fully or horizontally impacted mandibular third molar extraction from April 2015 to March 2020. One-to-one propensity-score matching was conducted between amoxicillin and third-generation cephalosporin groups. The incidence of surgical site infection following extraction was compared in the matched pairs using McNemar's test. RESULTS: We identified 109,266 dental visits, including 39,514 (36.2%) patients who received amoxicillin and 69,752 (63.8%) patients who received third-generation cephalosporins. In the 39,514 matched pairs, the incidence of surgical site infection was 3.5% (n = 1399) for amoxicillin group and 3.7% (n = 1467) for third-generation cephalosporin group (p = 0.003). CONCLUSIONS: Amoxicillin was associated with a lower incidence of surgical site infection after impacted mandibular third molar extraction compared with third-generation cephalosporins. This result supports current guidelines and strengthens the importance of disseminating and implementing antimicrobial resistance control in dentistry.

Impact of body mass index on in-hospital mortality in older patients hospitalized for bacterial pneumonia with non-dialysis-dependent chronic kidney disease.

BACKGROUND: Low body mass index (BMI) in older individuals with decreased kidney function is important because of its association with poor prognosis and frailty. Herein, we aimed to clarify the association between BMI and in-hospital mortality among older patients with non-dialysis-dependent chronic kidney disease (CKD) stratified by kidney function. METHODS: Using data from the Medical Vision Database, this multicentre cohort study included people aged ≥ 60 years with an estimated glomerular filtration rate of < 60 ml/min/1.73 m2 but without dialysis dependency, hospitalised for bacterial pneumonia during 2014-2019. We compared the risk of in-hospital death between patients with BMI categories based on the quartiles (low, medium-low, medium-high, and high) setting medium-high BMI as a reference. We further assessed the association with BMI using a cubic spline, setting BMI as a nonlinear continuous variable and a BMI of 22 kg/m2 as a reference. We also evaluated the association between BMI and kidney function using a generalised additive model adjusted for interaction terms between nonlinear continuous BMI and kidney function. RESULTS: We obtained data for 3,952 patients, with 350 (8.9%) in-hospital deaths. When compared with medium-high BMI, low BMI was associated with an increased risk of death and longer hospital stay, whereas the other two categories were comparable. Models using a cubic spline showing an association between BMI and in-hospital death showed an L-shaped curve; BMI < 22.0 kg/m2 was associated with an increased risk for mortality, and at a BMI of 18.5 kg/m2, the odds ratio was 1.43 with a 95% confidence interval of 1.26-1.61 when compared with a BMI of 22.0 kg/m2. Analysis of the interactive effects of kidney function using the generalised additive model showed that a protective association of high BMI tapered along with decreased kidney function. CONCLUSIONS: This cohort study suggests not only that lower BMI and low kidney function are associated with in-hospital mortality independently but also that the protective effects of high BMI weaken as kidney function decreases via the analysis of the interaction terms. This study highlights the necessity for the prevention of underweight and demonstrates the interaction between BMI and kidney function in older patients with non-dialysis-dependent CKD.

Prevalence, Incidence Rate, and Risk Factors of Medication-Related Osteonecrosis of the Jaw in Patients With Osteoporosis and Cancer: A Nationwide Population-Based Study in Japan.

PURPOSE: Medication-related osteonecrosis of the jaw (MRONJ) is a rare but severe adverse event of antiresorptive agents. However, the precise prevalence and factors associated with the development of MRONJ remain unknown. The present study was performed to describe the prevalence, incidence rate, and risk factors of developing MRONJ. METHODS: We conducted a population-based retrospective cohort study using the National Database of Health Insurance, an administrative claims database of all patients in Japan. We identified patients who newly began using antiresorptive drugs from April 2015 to December 2018. The primary outcome was the development of MRONJ. We calculated the prevalence and incidence rate of MRONJ and performed a time-dependent Cox proportional hazard regression analysis to examine risk factors for developing MRONJ. RESULTS: We identified 2,819,310 patients who newly used antiresorptive drugs during the study period. Of these patients, 2,664,104 (94.5%) had osteoporosis and 155,206 had cancer. Among the patients with osteoporosis, 1,603 (0.06%) developed MRONJ; the incidence rate was 22.9 per 100,000 person-years. Among the patients with cancer, 2,274 (1.47%) developed MRONJ; the incidence rate was 1,231.7 per 100,000 person-years. The occurrence of MRONJ was associated with poor oral conditions (including tooth extraction), age, male sex, drug type, concomitant drug use, comorbidities, cancer type, and geographic location. CONCLUSIONS: The overall prevalence and incidence rate were low, but they were still higher than those in previous studies. Poor oral conditions were more closely related to the development of MRONJ than other factors. These findings suggest that improving poor oral hygiene may be essential to prevent MRONJ.

Dental characteristics associated with methamphetamine use: analysis using forensic autopsy data.

BACKGROUND: Little is known regarding the oral conditions in nonelderly methamphetamine users, such as the presence of dental caries and periodontitis. We aimed the oral conditions between methamphetamine users and non-users stratified by age groups. METHODS: In this cross-sectional study, computed tomography images were obtained from 3,338 decedents at two forensic medicine departments in Japan. Decedents aged > 20 or ≤ 64 years were included in the study and categorised into methamphetamine-detected (MA) and undetected (control) groups based on toxicological examinations. Decedents in the MA and control groups were matched for age and sex in a 1:4 ratio. The matched pairs were further categorised into young adults (20-44 years) and middle-aged adults (45-64 years). Oral characteristics, including the decayed, missing, and filled teeth (DMFT) index; periodontitis; distributional patterns of each tooth condition; and occlusal status, were compared between the MA and control groups for each age category. Among 3,338 decedents, 37 young and 55 middle-aged adults in the MA group were matched with 148 and 220 adults in the control group, respectively. RESULTS: In the young adult group, methamphetamine use was significantly associated with higher DMFT index (mean [standard deviation], 14.2 [7.6] vs 11.0 [6.1]; p = 0.007), smaller number of filled teeth (2.8 [2.9] vs 5.3 [4.0]; p = 0.001), higher proportion of periodontitis (39.0% vs 6.8%; p < 0.001), and lower proportion of occlusal support (54.1% vs 81.1%; p = 0.001). Young adult methamphetamine users tended to have untreated decayed canines and molars and missing molars. These findings were similar to those in middle-aged adults except the tendency to have missing maxillary incisors. CONCLUSIONS: Nonelderly methamphetamine users had distinctive oral characteristics that may help screen for methamphetamine abuse through dental examinations.

Treatment of latent tuberculosis infection in patients receiving biologic agents.

INTRODUCTION: Treatment of latent tuberculosis infection is recommended in patients receiving biologics. However, evidence is weak regarding the efficacy of treatment regimens in this population, and the real-world practice pattern has not been elucidated. METHODS: Using a large-scale health insurance claims database in Japan, we identified patients who started treatment of immune-mediated inflammatory diseases with tumor necrosis factor inhibitors or other biologics. Treatment with isoniazid within 12 months of starting a biologic was summarized to evaluate the duration of treatment for latent tuberculosis infection and the time between start of isoniazid and initiation of a biologic. RESULTS: Among 2064 patients starting biologics, 10% received treatment for latent tuberculosis infection with isoniazid. Among the patients with biologics and isoniazid, isoniazid was started in the same month as initiating biologics or 1 month before in 82%. In addition to the recommended 6- and 9-month treatments, 20% of patients were receiving isoniazid at 12 months after starting treatment and 20% received a prescription for 350 days or more. CONCLUSIONS: In patients starting biologics, treatment for latent tuberculosis infection was provided for different durations, including not only the recommended periods but also longer periods. Research on safety and effectiveness of the treatment in this population is necessary.

Validity of diagnoses and procedures in Japanese dental claims data.

BACKGROUND: Dental claims data have been used for epidemiological studies without establishing the validity of the recorded diagnoses or procedures. The present study aimed to examine the accuracy of diagnoses, procedures, operation time, and the number of teeth recorded in dental claims data. METHODS: We reviewed the charts of 200 patients who visited and 100 patients who were hospitalized in the Department of General Dentistry, Orthodontics, and Oral and Maxillofacial Surgery in an academic hospital between August 2012 and December 2017. The sensitivity and specificity of the dental claims data for five diseases and 15 procedures were evaluated. We assessed the difference in the number of teeth and duration of general anesthesia between claims data and chart reviews. RESULTS: Sensitivity was more than 86% for six out of seven diagnoses except for pericoronitis (67%). Specificity ranged from 72% (periodontal disease) to 100% (oral cancer for inpatient). The sensitivity of procedures ranged from 10% (scaling for inpatient) to 100%, and the specificity ranged from 6% (food intake on the day of the surgery) to 100%. The mean (standard deviation [SD]) number of teeth in the chart review was 22.6 (6.8), and in the dental claims was 21.6 (8.6). The mean (SD) operation time was 171.2 (120.3) minutes, while the duration of general anesthesia was 270.9 (171.3) minutes. CONCLUSIONS: The present study is the first study to validate dental claims data, and indicates the extent of usefulness of each diagnosis and procedure for future dental research using administrative data.