Association between mRNA COVID-19 vaccine boosters and mortality in Japan: The VENUS study.

Although previous studies have shown no increased mortality risk after the primary series of COVID-19 mRNA vaccines, reports on booster doses are lacking. This study aimed to evaluate mortality risk after the mRNA vaccine boosters in addition to the primary series. This nested case-control study included two age-specific cohorts (18-64 and ≥65 years as of February 1, 2021) in two municipalities. All deaths were identified and matched five controls for each case at each date of death (index date) with risk set sampling according to municipality, age, and sex. The adjusted odds ratios (aORs) and 95% confidence intervals (CIs) for mRNA vaccines (first to fifth doses) were estimated by comparing with no vaccination within 21 and 42 days before the index date using a conditional logistic regression model. The 18-64-years cohort comprised 431 cases (mean age, 57.0 years; men, 58.2%) and 2,155 controls (mean age, 56.0; men, 58.2%), whereas the ≥65-years cohort comprised 12,166 cases (84.0; 50.2%) and 60,830 controls (84.0, 50.2%). The aORs (95% CI) in 0-21 days after the third and fourth doses in the 18-64-years cohort were 0.62 (0.24, 1.62) and 0.38 (0.08, 1.84), respectively. The aORs (95% CI) after the third to fifth doses in the ≥65 years cohort were 0.36 (0.31, 0.43), 0.30 (0.25, 0.37), and 0.26 (0.20, 0.33), respectively. In conclusion, booster doses of mRNA vaccines do not increase mortality risk. These findings could help subsequent vaccine campaigns and alleviate vaccine hesitancy.

Validity of claims-based definition of number of remaining teeth in Japan: Results from the Longevity Improvement and Fair Evidence Study.

BACKGROUND: Secondary healthcare data use has been increasing in the dental research field. The validity of the number of remaining teeth assessed from Japanese dental claims data has been reported in several studies, but has not been tested in the general population in Japan. OBJECTIVES: To evaluate the validity of the number of remaining teeth assessed from Japanese dental claims data and assess its predictability against subsequent health deterioration. METHODS: We used the claims data of residents of a municipality that implemented oral health screening programs. Using the number of teeth in the screening records as the reference standard, we assessed the validity of the claims-based number of teeth by calculating the mean differences. In addition, we assessed the association between the claims-based number of teeth and pneumococcal disease (PD) or Alzheimer's disease (AD) in adults aged ≥65 years using Cox proportional hazards analyses. RESULTS: Of the 10,154 participants, the mean number of teeth assessed from the claims data was 20.9, that in the screening records was 20.5, and their mean difference was 0.5. During the 3-year follow-up, PD or AD onset was observed in 10.4% (3,212/30,838) and 5.3% (1,589/30,207) of participants, respectively. Compared with participants with ≥20 teeth, those with 1-9 teeth had a 1.29 (95% confidence interval [CI]: 1.17-1.43) or 1.19 (95% CI: 1.04-1.36) times higher risk of developing PD or AD, respectively. CONCLUSION: High validity of the claims-based number of teeth was observed. In addition, the claims-based number of teeth was associated with the risk of PD and AD.

Investigating the epidemiology and outbreaks of scabies in Japanese households, residential care facilities, and hospitals using claims data: the Longevity Improvement & Fair Evidence (LIFE) study.

Objectives: This study aimed to characterize the epidemiology of scabies and its outbreaks in Japanese households, residential care facilities (RCFs), and hospitals using claims data. Methods: This descriptive epidemiological study was conducted using claims data from eight municipalities in Japan. Scabies cases were identified using a combination of recorded diagnoses and administered medications. The study period was from April 2015 to March 2019. Outbreaks were defined as ≥2 cases of scabies occurring within a calendar month at a single household, RCF, or hospital. Results: We identified 857 scabies cases for analysis. The annual prevalence of scabies ranged from 40 to 67 per 100,000 beneficiaries. The annual attack rate of scabies was found to be highest in RCFs (21 per 1000 RCFs), followed by hospitals (11 per 1000 hospitals) and households (0.25 per 1000 households). The annual outbreak attack rate was also highest in RCFs (4.0 per 1000 RCFs), followed by hospitals (1.6 per 1000 hospitals) and household (0.027 per household). The patterns of outbreaks varied widely among the RCFs. Conclusions: The study showcases the potential of claims data for detecting infectious disease outbreaks, which could provide valuable insight for the future management and prevention of scabies. Infection control of scabies in RCFs is crucial in aging societies.

Incidence of post-COVID psychiatric disorders according to the periods of SARS-CoV-2 variant dominance: The LIFE study.

This retrospective cohort study examined the incidence of post-COVID psychiatric disorders in older adults according to hospitalization status and SARS-CoV-2 variant period in Japan. Claims data, COVID-19 case-related information, and vaccination records were obtained from three Japanese municipalities. We identified individuals aged ≥65 years who had COVID-19 or other respiratory tract infection (RTI) between March 2021 and December 2022. Participants were categorized into non-hospitalized and hospitalized patients, and the study period was divided into the Alpha (March to May 2021), Delta (June to December 2021), Omicron BA.1/BA.2 (January to June 2022), and Omicron BA.5 (July to December 2022) periods. Modified Poisson regression analyses were performed to estimate the incidence rate ratios (IRRs) for the occurrence of psychiatric disorders (organic mental disorders, psychotic disorders, mood disorders, anxiety disorders, and insomnia) three months after COVID-19 (reference: other RTI). For overall psychiatric disorders, we analyzed 19,489 non-hospitalized patients (COVID-19: 6,728, Other RTI: 12,761) and 2925 hospitalized patients (COVID-19: 1,036, Other RTI: 1889). When compared with other RTI cases, COVID-19 cases had significantly lower IRRs for overall psychiatric disorders in both non-hospitalized (IRR: 0.59, P < 0.001) and hospitalized cases (IRR: 0. 83, P = 0.045) during the Omicron BA.1/BA.2 period, but only in non-hospitalized cases (IRR: 0.45, P < 0.001) during the Omicron BA.5 period. The incidences of the individual post-COVID psychiatric disorders varied according to disorder type, hospitalization status, and SARS-CoV-2 variant period. These findings provide a foundation for further research to explore these variations and improve the provision of psychiatric care in future epidemics.

Changes in the utilization of outpatient and visiting dental care and per-attendance care cost by age groups during COVID-19 pandemic waves in Japan: A time-series analysis from LIFE study.

BACKGROUND: The influence of the coronavirus disease (COVID-19) pandemic on dental care utilization may have differed according to individual characteristics or type of dental care provision. This study aimed to evaluate the changes in dental care utilization and per-attendance costs by age group and type of dental care during the COVID-19 pandemic in Japan. METHODS: This time-series study used healthcare insurance claims data from 01/07/2019 to 09/27/2021 (143 weeks) from nine municipalities in Japan. Dental care utilization rate per week and average dental care cost per attendance by age groups (0-19y/20-64y/65-74y/≥ 75y) and types of dental care (outpatient/visiting) were used as outcome variables. COVID-19 pandemic waves in Japan were used as predictors: 1st (03/23/2020-05/17/2020), 2nd (06/22/2020-09/27/2020), 3rd (10/26/2020-02/21/2021), 4th (02/22/2021-06/07/2021), and 5th (07/05/2021-09/13/2021) waves. Fixed effect models were employed to estimate the proportional changes. RESULTS: In the fixed effect model, we observed large declines in dental care utilization during the 1st (17.0-22.0%) and 2nd waves (3.0-13.0%) compared to the non-pandemic wave period in all age groups. In contrast, the average dental care cost per attendance increased in all age groups by 5.2-8.6% during the 1st wave. CONCLUSIONS: During the initial wave of the COVID-19 pandemic in Japan, dental care utilization decreased in all age groups, whereas the average dental care cost per attendance increased. The COVID-19 pandemic may have changed the dental care provision pattern towards less frequent and more concentrated dental care to avoid the risk of infection.

Impact of Concurrent Visual and Hearing Impairment on Incident Alzheimer's Disease: The LIFE Study.

Background: The prevalence of Alzheimer's disease (AD) is increasing in Japan due to population aging. The association between sensory impairment and incident AD remains unclear. Objective: This study aimed to investigate the impact of sensory impairment on incident AD. Methods: We analyzed residents of five municipalities participating in the Longevity Improvement & Fair Evidence (LIFE) Study. The participants comprised individuals who had newly applied for long-term care needs certification between 2017 and 2022 and had no cognitive impairment upon application or AD diagnosis within the preceding six months. Participants were classified according to sensory impairment status: visual impairment (VI), hearing impairment (HI), neither sensory impairment (NSI), and dual sensory impairment (DSI). The month succeeding the certification application was set as the index month, and the interval from that month until AD onset was assessed. Multivariable Cox proportional hazards analysis was performed to calculate the risk of AD onset according to sensory impairment status while adjusting for sex, age, dependence level, self-reliance level, and comorbidities. Results: Among 14,186 participants, we identified 1,194 (8.4%) who developed AD over a median follow-up period of 22.6 months. VI and HI only were not associated with incident AD. However, DSI conferred a significantly higher risk (HR: 1.6, CI: 1.1-2.2, p = 0.008) of AD onset than NSI. Conclusions: Individuals with concurrent DSI have a higher risk of developing AD than those with single or NSI. Preventing and treating sensory impairment may not only improve functional outcomes, but could also help to reduce the future risk of AD.

Associations between COVID-19 vaccination and incident psychiatric disorders after breakthrough SARS-CoV-2 infection: The VENUS Study.

BACKGROUND: The associations between COVID-19 vaccination and post-COVID psychiatric disorders are unclear. Furthermore, it is uncertain if these associations differ depending on the dominant SARS-CoV-2 variant at the time of infection. This retrospective cohort study aimed to clarify the associations between COVID-19 vaccination and incident psychiatric disorders after breakthrough infection according to the different variant periods in Japan. METHODS: Medical claims data, COVID-19 case-related information, and vaccination records were collected from three Japanese municipalities. The study population comprised public insurance enrollees aged ≥65 years who developed COVID-19 between June 2021 and December 2022. The study exposure was each participant's vaccination status 14 days before infection, and the outcomes were the occurrence of psychiatric disorders within three months of infection. Multivariable logistic regression analyses were performed to calculate the odds ratios (ORs) and 95 % confidence intervals (CIs) of vaccination for the occurrence of psychiatric disorders. Analyses were conducted for the Delta period (June to December 2021), Omicron BA.1/BA.2 period (January to June 2022), and Omicron BA.5 period (July to December 2022). RESULTS: We analyzed 270 participants (vaccinated: 149) in the Delta period, 2,963 participants (vaccinated: 2,699) in the Omicron BA.1/BA.2 period, and 7,723 participants (vaccinated: 7,159) in the Omicron BA.5 period. During the Delta period, vaccinated participants had significantly lower odds for psychotic disorders (OR: 0.23, 95 % CI: 0.06-0.88, P = 0.032) than unvaccinated participants. During the Omicron BA.5 period, vaccinated participants had significantly lower odds for organic mental disorders (OR: 0.54, 95 % CI: 0.30-0.95, P = 0.033), psychotic disorders (OR: 0.31, 95 % CI: 0.19-0.53, P < 0.001), mood disorders (OR: 0.53, 95 % CI: 0.29-0.99, P = 0.046), and insomnia (OR: 0.48, 95 % CI: 0.32-0.72, P < 0.001) than unvaccinated participants. There were no significant differences in psychiatric disorders between the vaccinated and unvaccinated groups during the Omicron BA.1/BA.2 period. CONCLUSIONS: This is the first study to demonstrate that the associations between COVID-19 vaccination and post-COVID psychiatric disorders vary among the different variant periods. Future studies on these associations should be conducted with consideration to the prevalent circulating variants.

The age-specific impact of COVID-19 vaccination on medical expenditures and hospitalization duration after breakthrough infection: The Vaccine Effectiveness, Networking, and Universal Safety (VENUS) Study.

OBJECTIVES: Although COVID-19 no longer constitutes a Public Health Emergency of International Concern, vaccination remains an important tool for reducing disease burden and mitigating future outbreaks. However, little is known about the impact of vaccination on medical expenditures and hospitalization duration after breakthrough infection. This study aimed to examine this impact during the Delta wave in Japan. METHODS: This retrospective study was conducted using medical care claims data, vaccination records, and COVID-19-related information. COVID-19 cases in three municipalities were categorized into two age groups: 20-64 years and ≥65 years. For each group, we constructed linear regression models with a generalized estimating equation. We calculated the risk ratios (RRs) and 95% confidence intervals (CIs) of COVID-19 vaccination for total medical expenditures and hospitalization duration after adjusting for sex, comorbidities, and municipality. RESULTS: We analyzed 618 cases aged 20-64 years (mean age: 38.4 years, women: 45.1%) and 208 cases aged ≥65 years (76.4 years, 53.8%). The RRs (95% CIs) of vaccination for total medical expenditures were 0.53 (0.44-0.64) in the 20-64 years age group and 0.51 (0.39-0.66) in the ≥65 years age group. Next, the RRs (95% CIs) of vaccination for hospitalization duration were 0.59 (0.42-0.83) in the 20-64 years age group and 0.69 (0.49-0.98) in the ≥65 years age group. CONCLUSIONS: COVID-19 vaccination was associated with lower total medical expenditures and hospitalization duration after breakthrough infection, with a more pronounced effect in older persons.

Medication adherence and associated factors in newly diagnosed hypertensive patients in Japan: the LIFE study.

Hypertension is the leading cardiovascular risk factor worldwide. However, in Japan, only 30% of patients have their blood pressure controlled under 140/90 mmHg, and nonadherence to antihypertensives is thought to be a reason for the poor control of hypertension. We therefore sought to assess the adherence to hypertension treatment and to evaluate factors influencing patients' adherence in a large, representative sample of the Japanese population. To this end, we analyzed claims data from the LIFE Study database, which includes 112 506 Japanese adults with newly diagnosed hypertension. Medication adherence was measured for a year postdiagnosis using the proportion of days covered (PDC) method. Factors associated with adherence to antihypertensives were also assessed. Among the total 112 506 hypertensive patients, the nonadherence rate (PDC ≤ 80%) for antihypertensives during the first year after initiation of the treatment was 26.2%. Younger age [31-35 years: odds ratio (OR), 0.15; 95% confidence interval (95% CI), 0.12-0.19 compared with 71-74-year-old patients], male gender, monotherapy, and diuretics use [OR, 0.87; 95% CI, 0.82-0.91 compared with angiotensin II receptor blockers (ARBs)] were associated with poor adherence in the present study. Cancer comorbidity (OR, 0.84; 95% CI, 0.79-0.91 compared with no comorbidity), prescription at a hospital, and living in a medium-sized to regional city were also associated with poor adherence. Our present findings showing the current status of adherence to antihypertensive medications and its associated factors using claims data in Japan should help to improve adherence to antihypertensives and blood pressure control.

Association between regular physical activity and pneumonia-related hospitalization according to pneumococcal vaccination status: The VENUS study.

BACKGROUND: Little is known about the impact of physical activity (PA) and PPSV23 vaccination on pneumonia-related hospitalizations. This study examined the association between regular PA and pneumonia-related hospitalization according to PPSV23 vaccination status in older adults. METHODS: This retrospective cohort study was conducted using health checkup data, medical care claims data, and vaccination records from two Japanese municipalities. Residents aged ≥65 years who had undergone a health checkup between April 2016 and March 2021 were categorized into a PPSV23 vaccinated or unvaccinated cohort. Each cohort was further divided into a PA group and no PA group. The hazard ratio (HR) of PA for pneumonia-related hospitalization was calculated for each cohort while adjusting for sex, age, comorbidities, and metabolic syndrome. RESULTS: The vaccinated cohort comprised 16,295 participants (no PA: 5,139, PA: 11,156), and the unvaccinated cohort comprised 7,998 participants (no PA: 2,671, PA: 5,327). In the vaccinated cohort, the PA group had a significantly lower hazard for pneumonia-related hospitalization than the no PA group (adjusted HR: 0.58, P = 0.004). However, PA was not associated with pneumonia-related hospitalization in the unvaccinated cohort (adjusted HR: 0.70, P = 0.270). CONCLUSIONS: PA can reduce the risk of pneumonia-related hospitalization in vaccinated persons. Interventions that increase both vaccination rates and PA habits may help to reduce these hospitalizations in older adults.

Bivalent mRNA vaccine effectiveness against COVID-19 among older adults in Japan: a test-negative study from the VENUS study.

BACKGROUND: Bivalent COVID-19 vaccines have been implemented worldwide since the booster vaccination campaigns of autumn of 2022, but little is known about their effectiveness. Thus, this study holistically evaluated the effectiveness of bivalent vaccines against infection in older adults in Japan. METHODS: We adopted the test-negative design using COVID-19 test data of individuals, aged ≥ 65 years, residing in three municipalities in Japan, who underwent tests in medical institutions between October 1 and December 30, 2022. Logistic regression analyses were conducted to estimate the odds of testing positive according to vaccination status. Vaccine effectiveness was defined as (1 - odds ratio) × 100%. RESULTS: A total of 3,908 positive and 16,090 negative results were included in the analyses. Receiving a bivalent dose in addition to ≥ 2 monovalent doses was 33.6% (95% confidence interval [CI]: 20.8, 44.3%) more effective than receiving no vaccination, and 18.2% (95% CI: 9.4, 26.0%) more effective than receiving ≥ 2 monovalent doses but not receiving a bivalent vaccination. In addition, the effectiveness peaked at 14-20 days after administration and then gradually declined over time. Furthermore, a bivalent booster dose provided 18.6% (95% CI: 9.9, 26.5%) additional protection among those vaccinated with ≥ 2 monovalent doses, in the absence of a previous infection history. However, we did not find sufficient evidence of effectiveness of bivalent vaccines among previously infected older adults. CONCLUSIONS: Bivalent vaccines are effective against COVID-19 infections among older adults without a history of infection.

Pneumococcal vaccination coverage and vaccination-related factors among older adults in Japan: LIFE Study.

PURPOSE: To investigate individual and environmental vaccination-related factors among the older adults in Japan, using administrative data. METHODS: We conducted a cohort study and included people who reached the relevant age (≥65 years) for routine pneumococcal vaccination of older adults between April 2015 and March 2020. Monthly data of residents in the two municipalities from April 2014 to March 2020 and vaccination records from April 2015 to March 2020 were used. We defined five cohorts according to the year in which routine vaccinations were available. Each cohort was followed for a total of two years, with the first year being the "baseline period" and second year being the "vaccine follow-up period." Pneumococcal vaccination data was extracted from vaccination records at "first dose." Age, sex, socioeconomic status, comorbidities, hospital visit history, hospitalization history, Specific Health Check-ups participation, and information on contracted hospitals for pneumococcal vaccination were used as covariates. A multivariate logistic regression model was used to investigate the relationship between pneumococcal vaccination and vaccination-related factors. Odds ratios (OR) and 95 % confidence intervals (95 % CI) were calculated. RESULTS: Analysis included 17,991 patients. Vaccination coverage was 33.6 % for all subjects. Multivariate analysis found the following as significant vaccination-related factors: female (OR: 1.18, 95 % CI: 1.11-1.26), not low income (1.76, 1.17-2.76), hospital visits: ≥once/month (1.27, 1.19-1.35), and Specific Health Check-ups participation (2.10, 1.95-2.27). No significant results were found for hospitals that contracted pneumococcal vaccination. CONCLUSIONS: Individual factors, such as sex and Specific Health Check-ups participation, were found to be important factors affecting pneumococcal vaccination among older adults in Japan. Environmental factors, such as the characteristics of residential areas, should be evaluated in further investigations.

Immune thrombocytopenic purpura and Guillain-Barré syndrome after 23-valent pneumococcal polysaccharide vaccination in Japan: The vaccine effectiveness, networking, and universal safety (VENUS) study.

BACKGROUND: To address the lack of an active vaccine safety surveillance system in Japan, the Vaccine Effectiveness, Networking, and Universal Safety (VENUS) study was initiated in 2021 as a pilot system using existing health insurance claims data and vaccination records. METHODS: This study evaluated the value of the VENUS study by assessing the incidence of immune thrombocytopenic purpura (ITP) and Guillain-Barré syndrome (GBS) following vaccination with the 23-valent pneumococcal polysaccharide vaccine (PPSV23) using a self-controlled case series (SCCS) design. RESULTS: Incidence rate ratios for ITP during 28-day and 42-day risk periods were 0.89 (95% confidence interval [CI], 0.12-6.4), and 0.58 (95% CI, 0.081-4.2), respectively. Neither was statistically significant. Incidence rate ratios could not be estimated for GBS due to the limited sample size. CONCLUSION: The VENUS study can provide valuable insights to facilitate the establishment of an advanced vaccine monitoring system in Japan.

Association of anticholinergic drug exposure with the risk of dementia among older adults in Japan: The LIFE Study.

OBJECTIVES: Several studies have investigated that anticholinergic drugs cause cognitive impairment. However, the risk of dementia associated with anticholinergics has not been extensively investigated in the super-aging society of Japan. We conducted this study to assess the association between anticholinergic drugs and the risk of dementia in older adults in Japan. METHODS: This nested case-control study used data from the Longevity Improvement & Fair Evidence Study, which includes claim data in Japan from 2014 to 2020. We included 66,478 cases of diagnosed dementia and 328,919 matched controls aged ≥65 years, matched by age, sex, municipality, and cohort entry year. Primary exposure was the total cumulative anticholinergic drugs prescribed from cohort entry date to event date or matched index date, which was the total standardized daily doses for each patient, calculated by adding the total dose of different types of anticholinergic drugs in each prescription, divided by the World Health Organization-defined daily dose values. Odds ratios for dementia associated with cumulative exposure to anticholinergic drugs were calculated using conditional logistic regression adjusted for confounding variables. RESULTS: The mean (standard deviation) age at index date was 84.3 (6.9), and the percentage of women was 62.1%. From cohort entry date to event date or matched index date, 18.8% of the case patients and 13.7% of the controls were prescribed at least one anticholinergic drug. In the multivariable-adjusted model, individuals with anticholinergic drugs prescribed had significantly higher odds of being diagnosed with dementia (adjusted odds ratio, 1.50 [95% confidence interval, 1.47-1.54]). Among specific types of anticholinergic drugs, a significant increase in risk was observed with the use of antidepressants, antiparkinsonian drugs, antipsychotics, and bladder antimuscarinics in a fully multivariable-adjusted model. CONCLUSIONS: Several types of anticholinergic drugs used by older adults in Japan are associated with an increased risk of dementia. These findings suggest that the underlying risks should be considered alongside the benefits of prescribing anticholinergic drugs to this population.

Association between seasonal influenza vaccination and antimicrobial use in Japan from the 2015-16 to 2020-21 seasons: from the VENUS study.

BACKGROUND: Seasonal influenza vaccination might be considered an antimicrobial resistance (AMR) countermeasure because it can reduce unnecessary antimicrobial use for acute respiratory infection by mitigating the burden of such diseases. OBJECTIVES: To examine the association between seasonal influenza vaccination and antimicrobial use (AMU) in Japan at the community level and to examine the impact of influenza vaccination on the frequency of unnecessary antimicrobial prescription for upper respiratory infection. METHODS: For patients who visited any healthcare facility in one of the 23 wards of Tokyo, Japan, due to upper respiratory infection and who were aged 65 years or older, we extracted data from the Vaccine Effectiveness, Networking, and Universal Safety (VENUS) study database, which includes all claims data and vaccination records from the 2015-16 to 2020-21 seasons. We used the average treatment effect (ATE) with 1:1 propensity score matching to examine the association of vaccination status with frequency of antibiotic prescription, frequency of healthcare facility consultation, risk of admission and risk of death in the follow-up period of the same season (from 1 January to 31 March). RESULTS: In total, 244 642 people were enrolled. Matched data included 101 734 people in each of the unvaccinated and vaccinated groups. The ATE of vaccination was -0.004 (95% CI -0.006 to -0.002) for the frequency of antibiotic prescription, -0.005 (-0.007 to -0.004) for the frequency of healthcare facility consultation, -0.001 (-0.002 to -0.001) for the risk of admission and 0.00 (0.00 to 0.00) for the risk of death. CONCLUSIONS: Our results suggest that seasonal influenza vaccination is associated with lower frequencies of unnecessary antibiotic prescription and of healthcare facility consultation.

Bivalent Vaccine Effectiveness Among Adults Aged ≥65 Years During the BA.5-Predominant Period in Japan: The VENUS Study.

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron BA.5 became prevalent in July 2022 in Japan. Bivalent messenger RNA (mRNA) vaccines were approved as booster doses for individuals who received the primary series or booster dose by monovalent vaccines. We aimed to assess the effectiveness of bivalent vaccines in Japanese adults aged ≥65 years. Methods: We conducted a population-based cohort study using data collected from January 2019 to February 2023 in Japan. We included individuals aged ≥65 years in a municipality who received the first or second booster dose of monovalent mRNA vaccines. We estimated the effectiveness of the second or third booster dose of bivalent mRNA vaccines during the Omicron BA.5-predominant period (July-December 2022), compared with ≥90 days after the booster dose of monovalent vaccines. We used a Cox proportional hazard regression model with vaccination status as a time-dependent covariate. Results: A total of 81 977 individuals aged ≥65 years (mean [standard deviation] age, 78.3 [7.4] years; 33 487 male [40.8%]) were included in the study cohort. Among them, 57 396 were vaccinated with the second or third dose of bivalent vaccines (BA.1 or BA.4/5). The effectiveness against coronavirus disease 2019 (COVID-19) was estimated to be 57.9% (95% confidence interval, 52.7%-62.5%) for ≥14 days after the second or third bivalent booster dose, compared with 90 days after the first or second monovalent booster dose. Conclusions: The study showed that the bivalent mRNA vaccines as the second and third doses would provide protection against COVID-19 among adults ≥65 years in Japan.

Effectiveness of BNT162b2 against infection, symptomatic infection, and hospitalization among older adults aged ≥65 years during the Delta variant predominance in Japan: The VENUS Study.

BACKGROUND: We evaluated the effectiveness of the BNT162b2 vaccine against infection, symptomatic infection, and hospitalization in older people during the Delta-predominant period (July 1 to September 30, 2021). METHODS: We performed a population-based cohort study in an older adult population aged ≥65 years using data from the Vaccine Effectiveness, Networking, and Universal Safety Study conducted from January 1, 2019, to September 30, 2021, in Japan. We matched BNT162b2 vaccinated and unvaccinated individuals in a 1:1 ratio on the date of vaccination of the vaccinated individual. We evaluated the effectiveness of the vaccine against infection, symptomatic infection, and COVID-19-related hospitalization by comparing the vaccinated and unvaccinated groups. We estimated the risk ratio and risk difference using the Kaplan-Meier method with inverse probability weighting. The vaccine effectiveness was calculated as (1 - risk ratio) × 100%. RESULTS: The study included 203,574 matched pairs aged ≥65 years. At 7 days after the second dose, the vaccine effectiveness (95% confidence interval) of BNT162b2 against infection, symptomatic infection, and hospitalization was 78.1% (65.2 to 87.8%), 79.1% (64.6 to 88.9%), and 93.5% (83.7 to 100%), respectively. CONCLUSIONS: BNT162b2 was highly effective against infection, symptomatic infection, and hospitalization in Japan's older adult population aged ≥65 years during the Delta-predominant period.

Disease Burden and Progression in Patients with New-Onset Mild Cognitive Impairment and Alzheimer's Disease Identified from Japanese Claims Data: Evidence from the LIFE Study.

BACKGROUND: Accurate epidemiological data on mild cognitive impairment (MCI) and Alzheimer's disease (AD) can inform the development of prevention and control measures, but there is a lack of such data in Japan. OBJECTIVE: To investigate the disease burden and progression in patients with new-onset MCI or AD in Japan. METHODS: Using claims data, this multi-region cohort study was conducted on new-onset MCI and AD patients in 17 municipalities from 2014 to 2021. To characterize the patients, we investigated their age, comorbidities, and long-term care (LTC) needs levels at disease onset according to region type (urban, suburban, or rural). Disease burden was examined using health care expenditures and LTC expenditures, which were estimated for 1, 2, and 3 years after disease onset. Kaplan-Meier curves were plotted for AD progression in new-onset MCI patients and death in new-onset AD patients. RESULTS: We analyzed 3,391 MCI patients and 58,922 AD patients. In MCI and AD patients, health care expenditures were high in the first year ($13,035 and $15,858, respectively), but had declined by the third year ($8,278 and $10,414, respectively). In contrast, LTC expenditures (daily living support) steadily increased over the 3-year period (MCI patients: $1,767 to $3,712, AD patients: $6,932 to $9,484). In the third year after disease onset, 30.9% of MCI patients developed AD and 23.3% of AD patients had died. CONCLUSIONS: This provides an important first look at the disease burden and progression of MCI and AD in Japan, which are high-priority diseases for a rapidly aging population.

Multiregional Population-Based Cohort Study for Evaluation of the Association Between Herpes Zoster and mRNA Vaccinations for Severe Acute Respiratory Syndrome Coronavirus-2: The VENUS Study.

Background: This study was performed to assess the increased risk of herpes zoster (HZ) associated with mRNA vaccines for coronavirus disease 2019. Methods: This population-based cohort study was conducted in 4 municipalities in Japan. Individuals covered under public health insurance systems without a history of HZ were followed from October 1, 2020 to November 30, 2021. Incidence rates of HZ within 28 days of BNT162b2 or mRNA-1273 vaccination were compared. Adjusted incidence rate ratios (IRR) and 95% confidence intervals (CI) were estimated using a Poisson regression model, including vaccination status as a time-dependent covariate. Subgroup analyses by sex, age, and municipality were also conducted. Results: A total of 339 548 individuals (median age, 74 years) were identified. During follow up, 296 242 individuals (87.2%) completed the primary series, among whom 289 213 and 7019 individuals received homologous BNT162b2 and mRNA-1273 vaccines, respectively. The adjusted IRRs of the first and second BNT162b2 vaccinations were 1.05 (95% CI, 0.84-1.32) and 1.09 (95% CI, 0.90-1.32), respectively. No cases of HZ were observed after mRNA-1273 vaccination. In subgroup analysis, the adjusted IRR of the second BNT162b2 vaccination was 2.94 (95% CI, 1.41-6.13) in individuals aged <50 years old. Conclusions: No increased risk of HZ was found after BNT162b2 vaccination in the overall study population. However, an increased risk was observed in the younger subgroup.

Effectiveness of COVID-19 vaccines against infection in Japan: A test-negative study from the VENUS study.

BACKGROUND: Although the effectiveness of coronavirus disease 2019 (COVID-19) vaccines is a crucial public health concern, evidence from Western Pacific countries is limited, including Japan. This study aimed to estimate the COVID-19 vaccines effectiveness (VE) against infection during the Delta variant predominance (July-September 2021) in Japan. METHODS: We performed a test-negative study using COVID-19 test data of ≥20-year-old residents in four municipalities who were tested in medical institutions between July 1 and September 30, 2021. We extracted COVID-19 test data from healthcare claims data, and the vaccination status at the testing date was ascertained using the Vaccination Record System data. Confirmed positive cases were identified using data from the national system for COVID-19, Health Center Real-time Information-sharing System on COVID-19. Logistic regression analyses were conducted to estimate the odds of testing positive according to vaccination status. VE was calculated as (1 - odds ratio) × 100%. RESULTS: This study included 530 positive and 15,650 negative results. Adjusted manufacturer-unspecified VE was 4.1% (95% confidence interval [CI], -36.5-32.6) at 0-13 days after the first dose, 45.2% (95% CI, 13.4-65.3) at ≥14 days after the first dose, 85.2% (95% CI, 69.9-92.7) at 0-13 days after the second dose, and 79.6% (95% CI, 72.6-84.8) at ≥14 days after the second dose. In addition, the VE after the second dose was highest at 14-34 days after the dose (VE, 89.1%; 95% CI, 80.5-93.9). CONCLUSIONS: High real-world effectiveness of COVID-19 vaccines, especially two doses, against infection during the Delta variant predominance in Japan was confirmed.