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An increased risk of fracture has been reported in older adults taking hypnotics. However, few studies have reported the comparative safety of hypnotics with different mechanisms of action. We examined the risk of fracture in older adults initiating suvorexant compared to those initiating Z-drugs.We conducted a retrospective cohort study using a claims database within a longevity improvement and fair evidence (LIFE) study in Japan (1.5 million beneficiaries). People aged ≥65 years were included in this study. Exposure was defined as the initiation of either suvorexant or Z-drugs (eszopiclone, zolpidem, or zopiclone). The evaluated outcomes were hip fracture and all-cause fracture requiring hospitalization. We used inverse probability of treatment weights to adjust for confounding and followed the incidence of the outcome for three different periods: 30, 90, and 365 days. Cox proportional hazards models were fitted to the weighted population to estimate hazard ratios (HRs). Sensitivity analyses were performed with narrowed outcome definitions and inverse probability of censoring weights.We identified 16,148 suvorexant new users and 54,327 Z-drugs new users. During the 30-day follow-up, 21 (16.6 events per 1000 person-years) and 53 hip fractures (12.2 events per 1000 person-years) were identified among suvorexant and Z-drugs new users, respectively (HR: 1.01, 95% confidence interval [CI]: 0.58-1.76). The analysis for all-cause fracture showed an HR of 1.03 (95% CI: 0.78-1.36). Extended follow-up (90 and 365 days) showed similar results for both outcomes. Sensitivity analyses showed consistent results except for an increased risk of all-cause fracture requiring surgery (HR: 1.41, 95% CI: 0.87-2.29) during the 30-day follow-up.This is the first study to show that suvorexant has a generally comparable risk of fracture as compared to Z-drugs. Further research is needed to investigate the potential short-term increased risk of all-cause fracture requiring surgery among suvorexant initiators.

Japan currently lacks a data platform that can support quantitative assessments of the causal relationships between vaccines and adverse events. This study describes the development and application of the Vaccine Effectiveness, Networking, and Universal Safety (VENUS) Study to facilitate such assessments.A database was created by linking public insurance enrollees' claims data with vaccination records acquired from participating municipalities. To provide an overview of the study data, we produced descriptive statistics of sex, age, and vaccinations. We also conducted a pilot study using the database to assess influenza vaccine safety during the 2018/2019 season among older persons (≥65 years) residing in a single municipality.Our database was created using data from approximately 1.12 million individuals in 7 municipalities between 2013 and 2020. The data during fiscal year 2018 included 853,016 individuals (male: 363,079, female: 489,937) with a median age of 70 years (interquartile range: 52-79). We obtained information on 17 vaccine types, including the pneumococcal vaccine and influenza vaccine. In the pilot study, we analyzed 48,723 vaccinated persons matched with 48,723 unvaccinated persons. The only adverse event that occurred in both groups was Bell's palsy, which had an adjusted incidence rate ratio of 1.21 (95 % confidence interval: 0.48-3.07).The VENUS Study is Japan's first healthcare data platform that enables comparative assessments of vaccinated and unvaccinated persons in large samples covering all age groups. Efforts are underway to increase the number of participating municipalities and to generate evidence on vaccine effectiveness and safety.

Background To assess the increased risk of herpes zoster (HZ) associated with mRNA vaccines for COVID-19. Methods This population-based cohort study was conducted in four municipalities in Japan. Individuals covered under public health insurance systems without a history of HZ were followed up 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 7,019 individuals received homologous BNT162b2 and mRNA-1273 vaccines, respectively. The adjusted IRRs (95% CI) of the first and second BNT162b2 vaccinations were 1.05 (0.84, 1.32) and 1.09 (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 (1.41, 6.13) in individuals aged Conclusion 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.

Background: Donepezil is frequently used to treat Alzheimer’s disease (AD) symptoms but is associated with early discontinuation. Determining the persistence rates of anti-dementia drug use after donepezil initiation may inform the development and improvement of treatment strategies, but there is little evidence from Japan. Objective: To determine anti-dementia drug persistence following donepezil initiation among AD patients in Japan using insurance claims data. Methods: Insurance claims data for AD patients with newly prescribed donepezil were obtained from 17 municipalities between April 2014 and October 2021. Anti-dementia drug persistence was defined as a gap of ≤60 days between the last donepezil prescription and a subsequent prescription of donepezil, another cholinesterase inhibitor, or memantine. Cox proportional hazards models were used to analyze the association between care needs levels and discontinuation. Results: We analyzed 20,474 AD patients (mean age±standard deviation: 82.2±6.3 years, women: 65.7%). The persistence rates were 89.1% at 30 days, 79.4% at 90 days, 72.6% at 180 days, 64.5% at 360 days, and 58.3% at 540 days after initiation. Among the care needs levels, the hazard ratio (95% confidence interval) for discontinuation was 1.01 (0.94–1.07) for patients with support needs, 1.12 (1.06–1.18) for patients with low long-term care needs, and 1.31 (1.21–1.40) for patients with moderate-to-high long-term care needs relative to independent patients. Conclusion: Japanese AD patients demonstrated low anti-dementia drug persistence rates that were similar to those of other countries. Higher long-term care needs were associated with discontinuation. Further measures are needed to improve drug persistence in AD patients.

Background Vaccine effectiveness against the severe acute respiratory syndrome coronavirus 2 Omicron BA.2 sublineage in Japan is unknown. We assessed the effectiveness of a third dose of COVID-19 mRNA vaccine compared with that of 2 doses. Methods We performed a population-based cohort study using a municipality database located in the Chubu region of Japan during the Omicron BA.1- and BA.2-predominant periods (January 1–March 31, 2022 and April 1–27, 2022, respectively). We included residents aged ≥16 years who received a second vaccine dose at ≥14 days before the start of each period, regardless of the third dose. We compared the data at 14 days after the second and third dose and at 2-week intervals from 14 days to 10 weeks after the third dose using a Cox regression model. Vaccine effectiveness was defined as (1 – hazard ratio) × 100 (%). Results In total, 295 705 and 288 184 individuals were included in the BA.1- and BA.2-predominant periods, respectively. The effectiveness of a third dose against infection was 62.4% and 48.1% in the BA.1- and BA.2-predominant periods, respectively. Vaccine effectiveness at 2–3 weeks and ≥10 weeks after the third dose decreased from 63.6% (95% confidence interval [CI], 56.4–69.5%) to 52.9% (95% CI, 41.1–62.3%) and from 54.5% (95% CI, 3.0–78.7%) to 40.1% (95% CI, 15.1–57.7%) in the BA.1- and BA.2-predominant periods, respectively. Conclusions A third dose was moderately effective against BA.1 and BA.2 sublineages, but its effectiveness decreased by approximately 10% age points from 2–3 weeks to ≥10 weeks after the third vaccination.

BackgroundCharacterising the psychiatric sequelae of coronavirus disease 2019 (COVID-19) can inform the development of long-term treatment strategies. However, few studies have examined these sequelae at different time points after COVID-19 infection.AimsThe study aimed to investigate the incidences and risks of acute and delayed psychiatric sequelae in patients hospitalised with COVID-19 in Japan.MethodsThis retrospective cohort study was conducted using a database comprising healthcare claims data from public health insurance enrollees residing in a Japanese city. We analysed a primary cohort comprising patients hospitalised with COVID-19 between March 2020 and July 2021 and two control cohorts comprising patients hospitalised with influenza or other respiratory tract infections (RTI) during the same period. We calculated the incidences of acute (1–3 months after infection) and delayed (4–6 months after infection) psychiatric sequelae. These sequelae were identified using diagnosis codes and categorised as mood/anxiety/psychotic disorder, mood disorder, anxiety disorder, psychotic disorder or insomnia. Multivariable logistic regression models were used to estimate the odds ratios (ORs) of psychiatric sequelae occurrence after COVID-19 infection compared with influenza and other RTI.ResultsThe study population with acute psychiatric sequela consisted of 662 patients with COVID-19, 644 patients with influenza, and 7369 patients with RTI who could be followed for 3 months; the study population with delayed psychiatric sequelae consisted of 371 patients with COVID-19, 546 patients with influenza, and 5397 patients with RTI who could be followed for 6 months. In the analysis of acute psychiatric sequelae, COVID-19 had significantly higher odds of mood/anxiety/psychotic disorder (OR: 1.39, p=0.026), psychotic disorder (OR: 2.13, pConclusionsCOVID-19 was generally associated with an increased risk of psychiatric sequelae occurring within 3 months after infection, but had a lower risk of new psychiatric sequelae developing 4–6 months after infection.

The effect of raising insurance co-payment rates on healthcare service utilization in Japan remains unclear. In this study, we utilized patient-level long-term care (LTC) insurance claims data to analyze these effects.Claims data were obtained on individuals certified as requiring LTC in City A and City B, Fukuoka Prefecture, Japan during August 2014-July 2016. Individuals whose LTC insurance co-payment rate increased from 10% to 20% in August 2015 were regarded as high-income individuals; individuals whose co-payment rate remained at 10% were regarded as non-high-income individuals. We examined the changes in LTC service utilization between high-income individuals and non-high-income individuals during the study period. Monthly LTC insurance charges were analyzed to evaluate service utilization. We created monthly panel data for the study participants, and quantified the differences in LTC service utilization before and after August 2015 between the high-income and non-high-income groups. Care needs levels and age were included as covariates in a fixed-effects model.The sample comprised 7711 individuals (1000 high-income individuals and 6711 non-high-income individuals) in City A and 647 individuals (84 high-income individuals and 563 non-high-income individuals) in City B. After adjusting for care needs levels and age, the co-payment rate increase was associated with reductions in monthly LTC insurance charges of $34.3 (P 0.001) in City A and $91.0 (P = 0.022) in City B.The increase in co-payment rate for high-income individuals in August 2015 negatively affected their utilization of LTC services. Geriatr Gerontol Int ••; ••: ••-•• Geriatr Gerontol Int 2020; ••: ••-••.

Background: Alzheimer’s disease (AD) can increase both medical care and long-term care (LTC) costs, but the latter are frequently neglected in estimates of AD’s economic burden. Objective: To elucidate the economic burden of new AD cases in Japan by estimating patient-level medical care and LTC expenditures over 3 years using a longitudinal database. Methods: The study was performed using monthly claims data from residents of 6 municipalities in Japan. We identified patients with new AD diagnoses between April 2015 and March 2016 with 3 years of follow-up data. Medical care and LTC expenditures were estimated from 1 year before onset until 3 years after onset. To quantify the additional AD-attributable expenditures, AD patients were matched with non-AD controls using propensity scores, and their differences in expenditures were calculated. Results: After propensity score matching, the AD group and non-AD group each comprised 1748 individuals for analysis (AD group: mean age±standard deviation, 81.9±7.6 years; women, 66.0%). The total additional expenditures peaked at $1398 in the first month, followed by $1192 and $1031 in the second and third months, respectively. The additional LTC expenditures increased substantially 3 months after AD onset ($227), and gradually increased thereafter. These additional LTC expenditures eventually exceeded the additional medical care expenditures in the second year after AD onset. Conclusion: Although total AD-attributable expenditures peaked just after disease onset, the impact of LTC on these expenditures rose over time. Failure to include LTC expenditures would severely underestimate the economic burden of AD.

Objective We aimed to ascertain the degree of influence of income disparity among older people with newly developed dementia on the probability and duration of stay in a hospital or long-term care facility and the degree of influence on medical expenses for hospitalization and care costs. Methods This was a retrospective cohort study. Study participants included 12 829 individuals aged 75 years or older not diagnosed with dementia between April 2012 and March 2013 but newly diagnosed with dementia between April 2013 and March 2014. Participants were categorized according to income. We evaluated the associations of income with the probability and duration of stay in a hospital or long-term care facility and the costs for hospitalization and care. Results In the adjusted analyses, high-income individuals had a lower probability of admission to a hospital or long-term care facility than middle- and high-income individuals. In all hospitals, low-income individuals had the longest duration of stay, but in long-term care facilities, income categories varied by facility type. Medical expenses for hospitalization and care costs were highest in the low-income group. Conclusion Income category affects the probability and duration of stay in the hospital or a long-term care facility, as well as expenses for hospitalization and care. It is necessary to consider a policy to enable low-income older patients with dementia to continue living at home.

Six complexes, Ni(medach)(dike)X, have been newly obtained, where medach = N-methyl-1,4-diazacycloheptane, dike = a β-diketonate such as benzoylacetonate (bzac), dibenzoylmethanate (dibm), X = BPh 4 - , NO 3 - or dike: Ni(medach)(bzac)(NO3) (1a), Ni(medach)(dibm)(NO3) (2a), Ni(medach)(bzac)(BPh4) (1b), Ni(medach)(dibm)(BPh4) (2b), Ni(medach)(bzac)2 (1c), Ni(medach)(dibm)2 (2c). X-ray single crystal structures of the complexes 1a, 2a, 1b and 2c have been determined and the structures of the complexes Ni(medach)(acac)(NO3) (3a) and Ni(medach)(acac)BPh4 (3b) (acac = acetylacetonate), reported previously, have also been clarified. In the cases of the tetraphenylborate and the nitrate complexes, two types of solvatochromism due to the donor and the acceptor interactions were observed in organic solvents. These spectral behaviors will be discussed in relation to the complex geometry and the donor and acceptor properties of the solvents, and also compared to those of the corresponding complexes containing a linear diamine such as N,N,N′,N′-tetramethylethylenediamine (tmen), Ni(tmen)(dike)X.

Mixed copper(II) chelates, [Cu(trop/hino)(tmen)]B(C 6 H 5 ) 4 , were prepared with a tropolonato or hinokitiolato ligands (trop/hino) and N , N , N ′, N ′-tetramethylethylenediamine (tmen). These chelates were, as expected, quite similar to the corresponding acetylacetonato analog [Cu(acac)(tmen)]B(C 6 H 5 ) 4 , being fairly soluble in a large number of solvents and remarkably solvatochromic in them. They were also useful as excellent Lewis basicity indicators in solution because their d–d bands continuously shift to red in wider ranges with increasing DN (donor number) of solvent. The examination on addition of various anions to these solvatochromic systems led to a quantitative view of the competition between solvent molecule and anion for coordination to metal center.

Three mixed-ligand copper (II) complexes containing the rigid bidentate nitrogen ligand bis[N-(2,4,6-trimethylphenyl)imino]acenaphthene (abbr. 2,4,6-Me3C6H2-BIAN) and β-diketonate (dike) ligands are reported and characterized. These complexes namely, [Cu(dike)(2,4,6-Me3C6H2-BIAN)]ClO4 {where dike=acac (acetylacetonate), bzac (benzoylacetonate) or (dibm) dibenzoylmethanate}have been synthesized and characterized by elemental analysis, spectroscopic, magnetic and molar conductance measurements. In addition to their high solubility in various organic solvents, these three complexes show a color change on going from one solvent to another, that is, strong solvatochromism of their solutions. The observed solvatochromism is mainly due to the solute–solvent interaction between the chelate cation and the solvent molecules. Reported also are the X-ray crystal structures of the free 2,4,6-Me3C6H2-BIAN ligand and the [Cu(acac)(2,4,6-Me3C6H2-BIAN)]ClO4 complex.

The thermochromic behaviour of various coordination compounds in solution is discussed, with a special focus on cyclic diamine chelates. Thermally induced spin-crossover phenomena of iron(II) complexes are also considered. The solvatochromic behaviour of mixed-ligand complexes is presented in detail.

We reported that recovery from total intravenous anesthesia with propofol was delayed in hepatectomy patients, and the hazard ratio was half against controls. This study was designed to evaluate recovery from sevoflurane anesthesia in patients for hepatectomy.Sixteen patients receiving hepatectomy and 17 patients receiving other epigastric surgeries (controls) were anesthetized with sevoflurane. Fentanyl was injected repeatedly to insure maintenance of the effect-site concentration of 2.0 ng x ml(-1). Propofol was administered for induction of general anesthesia, and then inhaled sevoflurane was titrated to maintain a Bispectral Index (BIS) value between 40 and 50. The intervals to emergence and extubation after sevoflurane discontinuation, and the predicted fentanyl concentrations were recorded.The amount of sevoflurane and concentration of fentanyl in hepatectomy were similar to those in controls. The extubation time was longer in hepatectomy patients than in control subjects, and the hazard ratio was half against controls.Recovery from anesthesia with sevoflurane was delayed in hepatectomy, and the hazard ratios were half against controls. We speculate that the influence of hepatectomy caused delay of recovery from anesthesia in hepatectomy patients.

Liver dysfunction has major impacts on the pharmacokinetics and pharmacodynamics of anesthetics. This study was designed to evaluate propofol concentrations during and at the end of total intravenous anesthesia (TIVA) for hepatectomy.Fifty patients receiving hepatectomy (n = 25) or other epigastric surgeries (controls, n = 25) were anesthetized with TIVA. Fentanyl was injected repeatedly to insure maintenance of the effect-site concentration in the 2.0 to 2.5 ng x ml(-1) range with off line computer similation program. Propofol was administered with target-controlled infusion at the initial target concentration of 3.0 mcg x kg(-1), and then titrated to maintain bispectral index (BIS) values between 40 and 50. The intervals after propofol discontinuation to emergence and extubation and the predicted propofol and fentanyl concentrations were recorded. Propofol concentrations at emergence were measured with blood sample in eight cases.The propofol dose in hepatectomy patients as well as both measured and predicted concentrations of propofol at extubation, were lower than in control patients. The extubation time was longer in hepatectomy than in control subjects.Recovery from TIVA is delayed in hepatectomy patients. We speculate that this is attributable to altered pharmacodynamics in these patients.

The thermochromic behaviour of various coordination compounds in solution is discussed, with a special focus on cyclic diamine chelates. Thermally induced spin-crossover phenomena of iron(II) complexes are also considered. The solvatochromic behaviour of mixed-ligand complexes is presented in detail.