Prevalence of and Risk Factors for Post-COVID-19 Condition during Omicron BA.5-Dominant Wave, Japan.

The increased risk for post-COVID-19 condition after the Omicron-dominant wave remains unclear. This population-based study included 25,911 persons in Japan 20-69 years of age with confirmed SARS-CoV-2 infection enrolled in the established registry system during July-August 2022 and 25,911 age- and sex-matched noninfected controls who used a self-reported questionnaire in January-February 2023. We compared prevalence and age- and sex-adjusted odds ratios of persistent COVID-19 symptoms (lasting ≥2 months). We evaluated factors associated with post-COVID-19 condition by comparing cases with and without post-COVID-19 condition. We analyzed 14,710 (8,392 cases and 6,318 controls) of 18,183 respondents. Post-COVID-19 condition proportion among cases was 11.8%, higher by 6.3% than 5.5% persistent symptoms among controls. Female sex, underlying medical conditions, mild to moderate acute COVID-19, and vaccination were associated with post-COVID-19 condition. Approximately 12% had post-COVID-19 condition during the Omicron-dominant wave, indicating the need for longer follow-up.

Risk factors for post-coronavirus disease condition in the Alpha-, Delta-, and Omicron-dominant waves among adults in Japan: A population-based matched case-control study.

Vaccination is associated with a reduced risk of post-coronavirus disease (COVID-19) condition (PCC). Here, risk factors including vaccination for PCC in the Omicron-dominant waves among Japanese adults were investigated. This was a registry-based matched case-control study of individuals aged 18-79 years diagnosed with COVID-19 registered in a National database between March 2021 and April 2022 and matched noninfected individuals living in Yao City, Japan. A self-administered questionnaire was used to assess persistent symptoms and their risk factors. The COVID-19 vaccination status was obtained from the Vaccination Registry. PCC risk factors were analyzed using logistic regression after adjusting for potential confounding factors. Overall, 4185 infected (cases) and 3382 noninfected (controls) individuals were included in the analysis. The mean ages and proportions of women were 44.7 years and 60.2% and 45.5 years and 60.7% for cases and controls, respectively. A total of 3805 (90.9%) participants had asymptomatic or mild acute symptoms at the median (range) follow-up of 271 (185-605) days. The prevalence of PCC was 15.0% for cases while that of persistent symptoms was 4.4% for controls; among the cases, it was 27.0% in the Alpha- and Delta-dominant waves and 12.8% in the Omicron-dominant wave. Female sex, comorbidities, and hospitalization were positively associated with PCC. One or more vaccine doses of vaccination were inversely associated with PCC; the inverse association was stronger in the Alpha- and Delta-dominant waves (adjusted odds ratio [aOR]: 0.29, 95% confidence interval [CI]: 0.12-0.73) than in the Omicron-dominant wave (aOR: 0.79, 95% CI: 0.59-1.07).

Efficacy and safety of dexamethasone sparing for the prevention of nausea and vomiting associated with highly emetogenic risk antineoplastic agents: a systematic review and meta-analysis of the Clinical Practice Guidelines for Antiemesis 2023 from the Japan Society of Clinical Oncology.

BACKGROUND: Chemotherapy-induced nausea and vomiting (CINV) are common side effects, classified according to timing and severity. Conventional agents such as dexamethasone are effective but have various side effects. For moderately emetogenic chemotherapy, dexamethasone-sparing antiemetic therapies have been developed to minimize these side effects. This systematic review evaluated the efficacy and safety of dexamethasone-sparing antiemetic therapy for highly emetogenic chemotherapy (HEC). METHODS: We performed a thorough literature search for studies related to dexamethasone-sparing antiemetic therapy with neurokinin-1 antagonists (NK1RA) for HEC using the PubMed, Cochrane Library, and Ichushi-Web databases. A qualitative analysis of the combined data was performed and risk differences with confidence intervals were calculated. RESULTS: Two reviewers independently assessed the 425 records and 12 full-text articles were evaluated for eligibility. Two studies were included in the qualitative and meta-analyses. These studies included anthracycline-cyclophosphamide (AC) regimens and cisplatin-based regimens, with palonosetron as the serotonin receptor antagonist. In the two studies, no difference was found in the prevention of vomiting (delayed complete response). However, non-inferiority was not demonstrated in the subgroup that received cisplatin-containing regimens. Delayed complete control showed different results for nausea prevention; however, there was no significant difference in the meta-analysis. Only one report has shown non-inferiority for delayed total control. Although the strength of evidence for individual outcomes varied, there was no difference in the duration of dexamethasone administration. CONCLUSIONS: This systematic review and meta-analysis revealed that dexamethasone-sparing antiemetic therapy with NK1RA and palonosetron can be used to prevent CINV in HEC, limited to AC combination therapy.

Non-pharmacological treatments for anticipatory nausea and vomiting during chemotherapy: a systematic review and meta-analysis of the Clinical Practice Guidelines for Antiemesis 2023.

BACKGROUND: Anticipatory chemotherapy-induced nausea and vomiting (CINV) is a conditioned response influenced by the severity and duration of previous emetic responses to chemotherapy. We aimed to evaluate the efficacy of non-pharmacologic interventions for anticipatory CINV among patients with cancer. METHODS: We conducted a systematic search in databases, including PubMed, the Cochrane Library, CINAHL, and Ichushi-Web, from January 1, 1990, to December 31, 2020. Randomized controlled trials, non-randomized designs, observational studies, or case-control studies that utilized non-pharmacological therapies were included. The primary outcomes were anticipatory CINV, with an additional investigation into adverse events and the costs of therapies. The risk-of-bias for each study was assessed using the Cochrane risk-of-bias tool, and meta-analysis was performed using Revman 5.4 software. RESULTS: Of the 107 studies identified, six met the inclusion criteria. Three types of non-pharmacological treatments were identified: systematic desensitization (n = 2), hypnotherapy (n = 2), and yoga therapy (n = 2). Among them, systematic desensitization significantly improved anticipatory CINV as compared to that in the control group (nausea: risk ratio [RR] = 0.60, 95% confidence interval [CI] = 0.49-0.72, p < 0.00001; vomiting: RR = 0.54, 95% CI = 0.32-0.91, p = 0.02). However, heterogeneity in outcome measures precluded meta-analysis for hypnotherapy and yoga. Additionally, most selected studies had a high or unclear risk of bias, and adverse events were not consistently reported. CONCLUSIONS: Our findings suggest that systematic desensitization may effectively reduce anticipatory CINV. However, further research is warranted before implementation in clinical settings.

Hospitalizations for Ambulatory Care Sensitive Conditions in a Large City of Japan: a Descriptive Analysis Using Claims Data.

BACKGROUND: Hospitalization for ambulatory care sensitive conditions (ACSCs) is an indicator of the quality of primary care in different health systems. In Japan, where patients can choose any healthcare facility with universal health coverage (UHC), data on these admissions are unknown. OBJECTIVE: To describe the current situation of ACSC admissions in a city of Japan. DESIGN: Retrospective observational study using claims data. PARTICIPANTS: Beneficiaries aged 0-74 years of the National Health Insurance (NHI) program in a large city in the Greater Tokyo Area. We extracted ACSC admissions from all inpatient claims between April 2013 and March 2017. MAIN MEASURES: We calculated age- and sex-specific annual ACSC admission rates for three categories: acute, chronic, and vaccine-preventable. We estimated the age-adjusted admission rates by ACSC category according to administrative districts and rate ratios using Poisson regression models. We also estimated medical expenditures and lengths of stay for ACSC admissions. KEY RESULTS: Of 91,350 hospitalization episodes, we identified 7666 (8.4%) that were ACSC admissions. Males had higher annual ACSC admission rates than females (p < 0.001), especially for chronic ACSCs. Admission rates were lowest in those aged 15-39 years and higher in the youngest (0-4 years) and oldest (70-74 years) age groups. Age-adjusted chronic ACSC admission rates were lower in a newly developed area (rate ratio [RR]: 0.79, 95% confidence interval [CI]: 0.71-0.87) and higher in a residential area (RR: 1.14, 95% CI: 1.04-1.24) than in the center of the city. Total medical expenditures for all ACSC admissions accounted for 5.8% of the total inpatient expenditures of NHI in the city. CONCLUSIONS: ACSC admission rates in Japan were higher for males than for females and showed a U-shaped trend in terms of age, as in other countries with UHC, and deferred by region. This study provided possible factors to reduce ACSC admissions.

Out-of-pocket payment and patients' treatment choice for assisted reproductive technology by household income: a conjoint analysis using an online social research panel in Japan.

BACKGROUND: Economic disparities affect access to assisted reproductive technology (ART) treatment in many countries. At the time of this survey, Japan provided partial reimbursement for ART treatment only for those in low- or middle-income classes due to limited governmental budgets. However, the optimal level of financial support by income class remains unclear. METHODS: We conducted a conjoint analysis of ART in Japan in January 2020. We recruited 824 women with fertility problems aged 25 to 44 years via an online social research panel. They completed a questionnaire of 16 hypothetical scenarios measuring six relevant ART attributes (i.e., out-of-pocket payment, pregnancy rate, risk of adverse effects, number of visits to outpatient clinics, consultation hours and kindness of staff) and their relations to treatment choice. RESULTS: Mixed-effect logistic regression models showed that all six attributes significantly influenced treatment preferences, with participants valuing out-of-pocket payment the most, followed by pregnancy rates and kindness of staff. Significant interactions occurred between high household income (≥ 8 million JPY) and high out-of-pocket payment (≥ 500,000 JPY). However, the average marginal probability of the highest-income patients (i.e., ≥ 10 million JPY, ineligible for the subsidy) receiving ART treatment at the average cost of 400,000 JPY was 47%, compared to 56 - 61% of other income participants, who opted to receive ART at an average cost of 100,000 JPY after a 300,000 JPY subsidy. CONCLUSION: Our results suggest that out-of-pocket payment is the primary determinant in patients' decision to opt for ART treatment. High-income patients were more likely to choose treatment, even at a high cost, but their income-based ineligibility for government financial support might discourage some from receiving treatment.

Acute exacerbation of rheumatoid arthritis-associated interstitial lung disease: clinical features and prognosis.

OBJECTIVES: RA-associated interstitial lung disease (RA-ILD) is commonly associated with acute exacerbations (ILD-AE). This study examined the clinical characteristics and risk factors of ILD-AE and mortality of RA-ILD. METHODS: We retrospectively collected data on 165 RA-ILD patients who visited or were admitted to our hospital between January 2007 and December 2019. We compared the clinical characteristics of patients who did and did not develop ILD-AE and identified variables significantly associated with ILD-AE. We also compared the admission characteristics of those who survived and those who died after admission for ILD-AE. ILD-AE was defined using previously proposed criteria, modified slightly for application to RA-ILD. RESULTS: The mean patient age was 73.6 years (s.d. 9.7) and 97 (71.9%) patients were female. Thirty (22.2%) patients developed ILD-AE, 13 (43.3%) of whom died. In univariate analyses, neither the usual interstitial pneumonia (UIP) pattern nor MTX was associated with ILD-AE. In multivariate analyses, the UIP pattern was significantly associated with ILD-AE [odds ratio (OR) 2.55 (95% CI 1.05, 6.20), P = 0.038]. In the Cox proportional hazards model, the UIP pattern [hazard ratio (HR) 4.67 (95% CI 1.02, 21.45), P = 0.048] was significantly associated with death, while MTX use [HR 0.16 (95% CI 0.04, 0.72), P = 0.016] was significantly associated with survival. CONCLUSION: Our data suggest that the UIP pattern is related to ILD-AE. Furthermore, both the UIP pattern and non-use of MTX might be related to death from ILD-AE in RA-ILD.

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.

Household income and medical help-seeking for fertility problems among a representative population in Japan.

BACKGROUND: Fertility treatments help many infertile couples to have children. However, disparities exist in access to fertility tests and treatments. We investigated the association between household income and medical help-seeking for fertility in Japan. METHODS: We conducted a cross-sectional study using nationally representative data from the National Fertility Survey 2015. Respondents were 6598 married women younger than 50 years old. The primary outcome was medical help-seeking for fertility among those who experienced fertility problems. Multiple logistic regression models were used to assess the association between household income and medical help-seeking, adjusting for age, length of marriage, educational level, employment status, number of children, childbearing desires, living with parents, and region of residence. RESULTS: Among 2253 (34%) women who experienced fertility problems, 1154 (51%) sought medical help. The proportion of help-seekers increased linearly from 43% in the low-income group (< 4 million Japanese yen [JPY]) to 59% in the high-income group (≥ 8 million JPY) (P for trend < 0.001). Respondents with upper-middle (6-8 million JPY) or high household income were more likely to seek medical help, compared to those with low household income: adjusted odds ratio [aOR] 1.37 (95% confidence interval [CI]: 1.00-1.86) and aOR 1.78 (95% CI: 1.29-2.47), respectively. CONCLUSIONS: We found that higher household income was associated with a higher probability of seeking medical help among Japanese women who experienced fertility problem. Along with policy discussion about additional financial support, further studies from societal, cultural, or psychological views are required.

Fertility treatments have helped millions of people to have a child. Although financial factors are known to play an important role in the decision to use fertility treatments, no previous studies have investigated how socioeconomic factors affect medical help-seeking for fertility in Japan. Therefore, we assessed the association between household income and medical help-seeking among couples with fertility problems in Japan, using nationally representative data from the National Fertility Survey 2015. Of the 6598 respondents (married women under 50 years old), one-third (2253) reported worrying about fertility problems, and half of those women (1154) sought medical help for fertility-related issues. The proportion of help-seekers was highest (59%) among those with high household income and lowest (43%) among those with low household income with a significant linear trend. Even after accounting for age, length of marriage, educational level, employment status, and other possibly related factors, those with higher household income were more likely to seek medical help for fertility tests and treatments. Japan provides various sources of financial support for fertility-related care, such as health insurance coverage for tests and early-stage treatments and partial subsidies for assisted reproductive technology treatments. However, the results indicate that further policy discussion about additional financial support and further studies focusing on barriers to care in Japan could help improve the situations for those with fertility problems.

Association between spatial access and hospitalization for ambulatory care sensitive conditions: A retrospective cohort study using claims data.

Background: Hospitalization for ambulatory care sensitive conditions (ACSCs) is potentially preventable with timely and effective primary care but may increase owing to poor access. Spatial access inequalities exist between Japan and other countries. This retrospective cohort study examined the association between admission for ACSC and spatial accessibility to primary care. Methods: We used claims data and spatial data of 50-74 years-old beneficiaries of the National Health Insurance program in a large city in Japan from April 2013-March 2014 and followed them until March 2015. We used a multilevel Poisson regression model to assess the association between the number of ACSC admissions, the distance to the nearest clinic, and the number of physicians in a given area, adjusting for age, gender, comorbidities, number of visits, and household income. Results: Among 126,666 eligible beneficiaries (mean age 65.8 years, 54% were women), 1,793 (1.4%) were hospitalized for ACSCs. The ACSC admission rate was significantly higher in those with a distance to the nearest clinic of >1 km than in those with <0.3 km (incident rate ratio [IRR] 1.32, 95% confidence interval [CI] 1.03-1.69). In the stratified analyses, a longer distance to the nearest clinic was associated with higher ACSC admission rates among women (≥0.3 km and <0.5 km: IRR 1.48, 95% CI 1.01-2.17; ≥0.5 km and <1 km: IRR 1.74, 95% CI 1.19-2.56; >1 km: IRR 1.98, 95% CI 1.29-3.03, respectively) and those aged ≥65 years (≥0.3 km and <0.5 km: IRR 1.38, 95% CI 1.07-1.79; ≥0.5 km and <1 km: IRR 1.38, 95% CI 1.06-1.80; >1 km: IRR 1.48, 95% CI 1.10-1.98). Conclusion: Unfavorable spatial access was associated with ACSC admissions, particularly among women and older adults.

Literature Review of Studies Using the National Database of the Health Insurance Claims of Japan (NDB): Limitations and Strategies in Using the NDB for Research.

The use of the National Database of Health Insurance Claims and Specific Health Checkups of Japan (NDB) for research has increased over time. Researchers need to understand the characteristics of the data to generate quality-assured evidence from the NDB. In this review, we mapped and characterized the limitations and related strategies using the NDB for research based on the descriptions of published NDB studies. To find studies that used Japanese healthcare claims data, we searched MEDLINE, EMBASE, and Ichushi-Web up to June 2023. Additionally, we hand-searched the NDB data publication list from the Ministry of Health, Labour and Welfare (2017-2023). We abstracted data based on the NDB data type, research themes, age of the study sample or population, targeted disease, and the limitations and strategies in the NDB studies. Ultimately, 267 studies were included. Overall, the most common research theme was describing and estimating the prescriptions and treatment patterns (125 studies, 46.8%). There was a variation in the frequency of themes according to the type of NDB data. We identified the following categories of limitations: (1) lack of information on confounders/covariates, outcomes, and other clinical content, (2) limitations regarding patients not included in the NDB, (3) misclassification of data, (4) lack of unique identifiers and register of beneficiaries, and (5) others. Although the included studies noted several limitations of using the NDB for research, they also provided some strategies to address them. Organizing the limitations of NDB in research and the related strategies across research fields can help support high-quality NDB studies.

In-Hospital Deaths From Ambulatory Care-Sensitive Conditions Before and During the COVID-19 Pandemic in Japan.

Importance: The COVID-19 pandemic may have played a role in the deterioration of access to medical care for ambulatory care-sensitive conditions (ACSCs). Objective: To ascertain whether the number of in-hospital deaths and in-hospital mortality rate associated with ACSC changed after the declaration of the COVID-19 national state of emergency in Japan. Design, Setting, and Participants: This cohort study used a difference-in-differences design to compare outcomes for ACSC in the period before (January 1, 2015, to December 31, 2019) vs the period after (January 1, 2020, to December 31, 2020) Japan declared a national state of emergency for the COVID-19 pandemic. Analyses used discharge summary data from 242 acute care hospitals across Japan. The sample comprised unscheduled hospitalizations of patients with ACSC during the study period (January 1, 2015, to December 31, 2020). Data analyses were performed between August 16 and December 7, 2022. Exposure: The declaration of the COVID-19 national state of emergency announced by the Japanese government in April 2020 was considered to be an exogenous shock. Main Outcomes and Measures: Primary outcomes were the ACSC-associated number of in-hospital deaths, number of hospitalizations, and in-hospital mortality rate. Results: A total of 28 321 ACSC-related hospitalizations were observed involving 15 318 males (54.1%), with a median (IQR) age of 76 (58-85) years. The number of in-hospital deaths was 2117 (7.5%). The number of hospitalizations decreased overall (incidence rate ratio [IRR], 0.84; 95% CI, 0.75-0.94), for chronic conditions (IRR, 0.84; 95% CI, 0.77-0.92), and for vaccine-preventable conditions (IRR, 0.58; 95% CI, 0.44-0.76). However, in-hospital deaths (IRR, 1.66; 95% CI, 1.15-2.39) and in-hospital deaths within 24 hours of hospital arrival (IRR, 7.27 × 106; 95% CI, 1.83 × 106 to 2.89 × 107) increased for acute conditions. The in-hospital mortality rate increased for acute conditions (IRR, 1.71; 95% CI, 1.16-2.54), and the 24-hour in-hospital mortality rates also increased overall (IRR, 1.87; 95% CI, 1.19-2.96), for acute conditions (IRR, 2.15 × 106; 95% CI, 5.25 × 105 to 8.79 × 106), and for vaccine-preventable conditions (IRR, 4.64; 95% CI, 1.28-16.77). Conclusions and Relevance: This cohort study found that in Japan, the number of in-hospital deaths increased after the declaration of the COVID-19 national state of emergency in 2020, particularly for acute ACSC and deaths within 24 hours of hospital admission. This finding suggests that access to good-quality primary care and inpatient care for patients with acute ACSC may have been compromised during the pandemic.

Tuberculosis screening and management of latent tuberculosis infection prior to biologic treatment in patients with immune-mediated inflammatory diseases: A longitudinal population-based analysis using claims data.

BACKGROUND AND AIM: Screening for tuberculosis before treating with biologic agents is recommended in patients with immune-mediated inflammatory diseases (IMIDs). We conducted this study to identify adherence to the recommended practice in a real-world setting in Japan. METHODS: We used a community-based insurance claims database in a city in the Greater Tokyo Area in Japan. Between July 2012 and January 2019, we enrolled patients with IMIDs in the age range 15 to 74 years who had initiated biologic therapy. Tuberculosis screening was defined as (a) interferon-γ release assay and/or a tuberculin skin test (IGRA/TST) and (b) IGRA/TST and X-ray and/or CT scan (X-ray/CT) within 2 months before starting biologic agents. We analyzed the proportions of patients who underwent tuberculosis screening and their association with the patient- and treatment-related factors and treatment for latent tuberculosis infection (LTBI). RESULTS: Of 421 patients presumed to have initiated biologic therapy, 202 (48%) underwent IGRA/TST and 169 (40%) underwent IGRA/TST and X-ray/CT. Patients aged 65 to 74 years were more likely to undergo tuberculosis screening than those aged 45 to 64 years. Compared to infliximab, IGRA/TST was less frequently performed in patients treated with etanercept, adalimumab, golimumab, abatacept, and tocilizumab. Treatment for LTBI was provided to 67 (16%) patients. Proportions of patients receiving LTBI treatment did not significantly differ according to the screening status. CONCLUSION: There was low adherence to the recommendations for tuberculosis screening and prophylactic treatment before biologic therapy. It is necessary to continue alerting clinical practitioners to the importance of screening for tuberculosis and treatment for LTBI.