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BACKGROUND: Evaluating the selective pressure of antimicrobials on bacteria is important for promoting antimicrobial stewardship programs (ASPs). The aim of this study was to assess the selective pressure of antimicrobials by evaluating their use (carbapenem [CBP] and CBP-sparing therapy) over time and the detection status of CBP-resistant organisms using multicenter data. METHODS: Among the facilities whose data were registered in the Japan Surveillance for Infection Prevention and Healthcare Epidemiology from 2017 to 2020, those that had data on the use of CBP and CBP-sparing therapy (fluoroquinolones [FQs], cefmetazole [CMZ], piperacillin-tazobactam [PIP/TAZ], ampicillin-sulbactam [ABPC/SBT], ceftriaxone/cefotaxime [CTRX/CTX], CAZ (ceftazidime), cefepime [CFPM], and aminoglycosides [AGs]) as well as on CBP-resistant Enterobacterales (CRE) and CBP-resistant Pseudomonas aeruginosa (CRPA) detection were included. Alcohol-based hand rubbing (ABHR) usage was also analyzed. Regression analyses, including multivariable regression analysis, were performed to evaluate trends. The association of antimicrobial use density (AUD) with CRE and CRPA detection rates was evaluated. RESULTS: In 28 facilities nationwide, CBP, FQ, CAZ, AG, and PIP/TAZ use decreased over the 3-year period, whereas the use of CMZ, ABPC/SBT, CTRX/CTX, CFPM, and ABHR as well as the rates of CRE and CRPA detection increased. The average AUD did not significantly correlate with CRE and CRPA detection rates. The multivariable regression analysis did not reveal any significant correlation between each AUD or ABHR and CRE or CRPA detection. CONCLUSION: CBP and ABHR use showed a decreasing and an increasing trend, respectively, while CRPA and CRE detection rates exhibited a gradual increase. The considerably low CRE and CRPA detection rates suggest that slight differences in numbers may have been observed as excessive trend changes. Further investigation is warranted to evaluate selective pressure while considering the characteristics of ASP and the mechanisms underlying resistance.
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Antibacterianos , Gestão de Antimicrobianos , Japão/epidemiologia , Humanos , Antibacterianos/uso terapêutico , Carbapenêmicos/uso terapêutico , Carbapenêmicos/farmacologia , Monitoramento Epidemiológico , Pseudomonas aeruginosa/efeitos dos fármacos , Farmacorresistência Bacteriana , Enterobacteriaceae/efeitos dos fármacos , Enterobacteriaceae/isolamento & purificaçãoRESUMO
Antimicrobial resistance (AMR) has emerged and spread globally. Recent studies have also reported the presence of antimicrobials in a wide variety of aquatic environments. Conducting a nationwide monitoring survey of AMR in the environment to elucidate its status and to assess its impact on ecosystems and human health is of social importance. In this study, we developed a novel high-throughput analysis (HTA) system based on a 96-well plate solid-phase extraction (SPE), using automated pipetting and an SPE pre-treatment system. The effectiveness of the system as an HTA for antimicrobials in environmental water was verified by comparing it with a conventional manual analytical system in a domestic hospital over a period of two years and four months. The results of the manual analysis and HTA using a combination of automated pipetting and SPE systems were generally consistent, and no statistically significant difference was observed (p > 0.05) between the two systems. The agreement ratios between the measured concentrations based on the conventional and HTA methods were positively correlated with a correlation coefficient of r = 0.99. These results indicate that HTA, which combines automated pipetting and an SPE pre-treatment system for rapid, high-volume analysis, can be used as an effective approach for understanding the environmental contamination of antimicrobials at multiple sites. To the best of our knowledge, this is the first report to present the accuracy and agreement between concentrations based on a manual analysis and those measured using HTA in hospital wastewater. These findings contribute to a comprehensive understanding of antimicrobials in aquatic environments and assess the ecological and human health risks associated with antimicrobials and antimicrobial-resistant bacteria to maintain the safety of aquatic environments.
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INTRODUCTION: Comprehensive evidence about the burden of infectious diseases in the Western Pacific Region is scarce. We thus examined the disease burden of infectious diseases in Japan in terms of disability-adjusted life years (DALYs). METHODS: We extracted national claims data from Japan's universal health insurance system to estimate the burden of disease for selected infections between 2015 and 2020 using DALYs. The mortality rate, disability duration and severity weight of each disease were estimated based on national data and literature reviews. RESULTS: Disease burden per 100,000 population was 1307.0 in 2015 and 972.1 in 2020 for bloodstream infections (BSI), 796.5 DALYs in 2015 and 498.9 DALYs in 2020 for pneumonia, 171.5 in 2015 and 149.4 in 2020 for meningitis and 11.6 in 2015 and 11.4 in 2020 for urinary tract infections (UTI). Only surgical site infections (SSI) showed a slightly increasing trend over the 5-year period, from 2.2 in 2015 to 2.8 in 2020. CONCLUSIONS: Our results showed that the disease burden of the five major infectious diseases was higher in Japan than in other countries. However, while the burden of SSI increased, the burden of pneumonia, meningitis, BSI and UTI gradually decreased year on year. The possible causes of the decreased morbidity should be examined in future work.
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BACKGROUND: This study aimed to develop and validate claims-based algorithms for identifying hospitalized patients with coronavirus disease (COVID-19) and the disease severity. METHODS: We used claims data including all patients at the National Center for Global and Medicine Hospital between January 1, 2020, and December 31, 2021. The claims-based algorithms for three statuses with COVID-19 (hospitalizations, moderate or higher status, and severe status) were developed using diagnosis codes (ICD-10 code: U07.1, B34.2) and relevant medical procedure code. True cases were determined using the COVID-19 inpatient registry and electronic health records. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated for each algorithm at 6-month intervals. RESULTS: Of the 75,711 total patients, number of true cases was 1,192 for hospitalizations, 622 for moderate or higher status, and 55 for severe status. The diagnosis code-only algorithm for hospitalization had sensitivities 90.4% to 94.9% and PPVs 9.3% to 19.4%. Among the algorithms consisting of both diagnosis codes and procedure codes, high sensitivity and PPV were observed during the following periods; 93.9% and 97.1% for hospitalization (January-June 2021), 90.4% and 87.5% for moderate or higher status (July-December 2021), and 92.3% and 85.7% for severe status (July-December 2020), respectively. Almost all algorithms had specificities and NPVs of approximately 99%. CONCLUSIONS: The diagnosis code-only algorithm for COVID-19 hospitalization showed low validity throughout the study period. The algorithms for hospitalizations, moderate or higher status, and severe status with COVID-19, consisting of both diagnosis codes and procedure codes, showed high validity in some periods.
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Monitoring antibiotic-resistant bacteria (ARB) and understanding the effects of antimicrobial drugs on the human microbiome and resistome are crucial for public health. However, no study has investigated the association between antimicrobial treatment and the microbiome-resistome relationship in long-term care facilities, where residents act as reservoirs of ARB but are not included in the national surveillance for ARB. We conducted shotgun metagenome sequencing of oral and stool samples from long-term care facility residents and explored the effects of antimicrobial treatment on the human microbiome and resistome using two types of comparisons: cross-sectional comparisons based on antimicrobial treatment history in the past 6 months and within-subject comparisons between stool samples before, during and 2-4 weeks after treatment using a single antimicrobial drug. Cross-sectional analysis revealed two characteristics in the group with a history of antimicrobial treatment: the archaeon Methanobrevibacter was the only taxon that significantly increased in abundance, and the total abundance of antimicrobial resistance genes (ARGs) was also significantly higher. Within-subject comparisons showed that taxonomic diversity did not decrease during treatment, suggesting that the effect of the prescription of a single antimicrobial drug in usual clinical treatment on the gut microbiota is likely to be smaller than previously thought, even among very elderly people. Additional analysis of the detection limit of ARGs revealed that they could not be detected when contig coverage was <2.0. This study is the first to report the effects of usual antimicrobial treatments on the microbiome and resistome of long-term care facility residents.
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Anti-Infecciosos , Microbiota , Idoso , Humanos , Antagonistas de Receptores de Angiotensina , Estudos Transversais , Assistência de Longa Duração , Inibidores da Enzima Conversora de Angiotensina , DNA , Análise de Sequência de DNARESUMO
BACKGROUND: The cumulative antibiogram is essential to guide empirical therapy for infectious diseases and monitor the trend of antimicrobial resistance. However, the status of antibiogram generation at medical institutions in Japan is uncertain. METHODS: A web-based questionnaire survey was conducted in February 2023 on the status of antibiogram preparation among facilities participating in the Japan Surveillance for Infection Prevention and Healthcare Epidemiology (J-SIPHE), an infection control surveillance system in Japan. RESULTS: The questionnaire collection rate was 19.6% (379/1931). Of all facilities, 47% (178/379) performed microbiological tests mainly in-house, while 53% (201/379) performed microbiological tests mainly outsourced. Of all facilities, 78% (296/379) prepared antibiograms. Of those without antibiograms, 33% (27/83) were considering the development in the future. Some facilities cited staff shortage as a barrier to preparing antibiograms. Of the 214 facilities with antibiograms that could use the J-SIPHE system to prepare antibiograms, 19% (41/214) were using the J-SIPHE system to prepare their antibiograms. CONCLUSIONS: One-quarter of the facilities that responded to the survey had not prepared antibiograms. Technical support for surveillance and awareness activity for using cumulative antibiograms might promote antibiogram preparation in Japan, which may improve antimicrobial stewardship and antimicrobial resistance measures.
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Antibacterianos , Hospitais , Humanos , Antibacterianos/uso terapêutico , Japão/epidemiologia , Testes de Sensibilidade Microbiana , Atenção à SaúdeRESUMO
BACKGROUND: To date, few studies from the Asian region have reported the effectiveness of messenger ribonucleic acid coronavirus disease 2019 (COVID-19) vaccines against disease progression and death after hospitalization. METHODS: We evaluated the data from the COVID-19 registry in Japan during the delta- and omicron-dominant phases. A propensity score-matched cohort study was conducted between the incompletely (0-1 dose) and fully (2 doses) vaccinated groups during the delta-dominant phase and among the incompletely, fully, and booster (3 doses) vaccinated groups during the omicron-dominant phase. RESULTS: In the delta-dominant phase, 411 pairs were matched. The fully vaccinated group showed a significantly lower oxygen supplementation rate (24.1 % vs. 41.1 %, p < 0.001) but little difference in the mortality rate (2.2 % vs. 2.9 %, p = 0.66). In the omicron-dominant phase, 1494 pairs from the incompletely and fully vaccinated groups, and 425 pairs from the fully and booster vaccinated groups were matched. Full vaccination reduced both the oxygen supplementation rate (18.6 % vs 25.7 %, p < 0.001) and mortality rate (0.7 % vs 2.3 %, p < 0.001). Booster vaccination showed little difference in either the rate of oxygen supplementation (21.2 % vs. 24.7 %, p = 0.25) or mortality (1.2 % vs. 2.6 %, p = 0.21) compared with full vaccination. CONCLUSIONS: Full vaccination reduced disease severity during the delta- and omicron-dominant phases; booster vaccination did not further enhance the protective effects against disease progression during the omicron-dominant phase compared to full vaccination. Future vaccine strategies and policy decisions should consider preventing infection or disease progression in the target population, as well as the characteristics of the dominant variant in that phase.
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COVID-19 , Humanos , COVID-19/prevenção & controle , Japão/epidemiologia , Estudos de Coortes , Pontuação de Propensão , Dados de Saúde Coletados Rotineiramente , Gravidade do Paciente , Vacinas contra COVID-19 , Progressão da Doença , RNA Mensageiro , VacinaçãoRESUMO
BACKGROUND: The severity of coronavirus disease 2019 (COVID-19) infections has led to the development of several therapeutic agents, with tocilizumab becoming increasingly used to treat patients with COVID-19-related pneumonia. This study compared the use of tocilizumab treatment with the standard of care (SOC) to determine its efficacy against severe COVID-19-related pneumonia in Japan. METHODS: This retrospective cohort study was designed to evaluate the efficacy of tocilizumab in two different databases: the JA42434 single-arm study and COVID-19 Registry Japan (COVIREGI-JP), with a synthetic control group from the COVIREGI-JP cohort as a benchmark for the tocilizumab group. The study's primary objective was to evaluate the efficacy of tocilizumab in treating severe COVID-19-related pneumonia compared to the SOC among patients included in the above two databases. The SOC group was extracted as the synthetic control group using exact matching and a propensity score matching in sequence per subject. As a secondary objective, the efficacy of tocilizumab compared to the SOC was evaluated exclusively among patients included in the COVIREGI-JP database. In each objective, the primary endpoint was defined as the time to discharge or the status of awaiting discharge. RESULTS: For the primary endpoint, the hazard ratio (HR) of the tocilizumab group against the SOC group was 1.070 (95% confidence interval [CI]: 0.565-2.028). The median time from Study Day 1 to discharge or the state of awaiting discharge was 15 days in the tocilizumab group and 16 days in the SOC group. The HRs for the secondary endpoints, namely, time to improvement in the clinical state, time to clinical failure, and time to recovery, were 1.112 (95% CI: 0.596-2.075), 0.628 (95% CI: 0.202-1.953), and 1.019 (95% CI: 0.555-1.871), respectively. Similarly, the HR of the primary endpoint for the secondary objective was 0.846 (95% CI: 0.582-1.230). CONCLUSIONS: Tocilizumab did not demonstrate a positive effect on time to discharge or the state of awaiting discharge. Furthermore, no statistically significant differences in other clinical outcomes, such as time to improvement in the clinical state, time to clinical failure, and time to recovery, were observed among the groups.
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COVID-19 , Humanos , SARS-CoV-2 , Estudos Retrospectivos , Dados de Saúde Coletados Rotineiramente , Resultado do Tratamento , Tratamento Farmacológico da COVID-19RESUMO
Objectives: Dexamethasone's (DEXA) beneficial effect on survival when administered to critically ill patients with coronavirus disease 2019 (COVID-19) has been documented in randomized trials and meta-analyses. Here, we conducted this study to clarify the association between time from COVID-19 onset to steroid initiation and mortality and to examine the factors underlying these results.Methods: This was a multicenter, retrospective, observational study of patients enrolled in the Japanese COVID-19 Registry from January 1, 2020, to April 30, 2021. Demographic and clinical factors were extracted from patient records. Patients diagnosed with COVID-19 using polymerase chain reaction, loop-mediated isothermal amplification, or antigen tests were included. Patients aged <18 years, pregnant, with a history of chronic obstructive pulmonary disease or steroid or immunosuppressive drug use, transferred to another hospital, or with an unknown symptom onset were excluded.Results and Conclusion: The analysis included 3692 patients (men, 64.1%; median age, 68 years). Unadjusted comparisons of mortality groups showed significant differences in demographic and clinical characteristics; patients with early dexamethasone initiation had more risk factors for severe disease and significantly higher mortality than did patients with delayed initiation (13.3% vs 7.9%, p < .001). No significant differences were found in intubation rates or duration, length of hospitalization, or time from intubation to death. Multivariate analyses showed significant differences from symptom onset to steroid administration, with an adjusted odds ratio of 0.7 (p = .05) for patients who received steroids for ≥8 days. Early steroid administration to COVID-19 patients was associated with increased mortality, suggesting a subset with early severe disease and high mortality and/or adverse effects of early steroid administration.
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COVID-19 , Masculino , Humanos , Idoso , SARS-CoV-2 , Estudos Retrospectivos , Esteroides , Dexametasona/uso terapêuticoRESUMO
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.
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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.
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INTRODUCTION: The latest therapeutic drug monitoring guidelines for vancomycin (VCM) recommend that area under the concentration-time curve is estimated based on model-informed precision dosing and used to evaluate efficacy and safety. Therefore, we predicted VCM concentrations in individual methicillin-resistant Staphylococcus aureus-infected patients using existing a physiologically based pharmacokinetic (PBPK) model and 1- and 2-compartment population pharmacokinetic (PPK) models and confirmed and verified the accuracy of the PBPK model in estimating VCM concentrations with the PPK model. METHODS: The subjects of the study are 20 patients, and the predicted concentrations were evaluated by comparing the observed and predicted trough and peak values of VCM concentrations for individual patients. RESULTS: The results showed good correlation between the observed and predicted trough and peak concentrations of VCM was observed generally in the PBPK model, R2 values of 0.72, 0.62, and 0.40 with trough values of 0.49, 0.40, and 0.34 with peak values for PBPK model, 1-compartment, and 2-compartment model, respectively. CONCLUSIONS: Although the performance of the PBPK model is not as predictive as the PPK model, generally similar predictive trends were obtained, suggesting that it may be a valuable tool for rapid and accurate prediction of AUC for VCM.
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INTRODUCTION: Antimicrobial resistance (AMR) is a major global health threat. While antimicrobial consumption (AMC) in Japan substantially decreased after implementation of the AMR National Action Plan, the disease burden due to AMR seems to be unchanged. The main objective of this study is to examine the relationship between AMC and the disease burden due to AMR in Japan. METHODS: We estimated the annual population-standardized AMC from 2015 to 2021 using defined daily doses (DDDs) per 1000 inhabitants per day (DIDs) and the disease burden due to bloodstream infections caused by nine major antimicrobial-resistant bacteria (AMR-BSIs) from 2015 to 2021 using disability-adjusted life years (DALYs). We then examined the correlation between AMC and DALYs using Spearman's rank correlation coefficient and cross-correlation function. Spearman's [Formula: see text] > 0.7 was considered to indicate a strong correlation. RESULTS: The sales amounts of third-generation cephalosporins, fluoroquinolones, and macrolides were 3.82 DIDs, 2.71 DIDs, and 4.59 DIDs, respectively, in 2015, but 2.11, 1.48, and 2.72 in 2021. This corresponded to reductions of 44.8%, 45.4%, and 40.7% during the study period. DALYs due to AMR-BSIs were 164.7 per 100,000 population in 2015 but 195.2 per 100,000 in 2021. Spearman's rank correlation coefficients between AMC and DALYs were - 0.37 (total antibiotics), - 0.50 (oral antibiotics), - 0.43 (third-generation cephalosporins), - 0.5 (fluoroquin,olones) and - 0.5 (macrolides). No obvious cross-correlations were found. CONCLUSIONS: Our results reveal that changes in AMC are not associated with DALYs caused by AMR-BSIs. AMR countermeasures besides efforts to reduce inappropriate AMC might be necessary to mitigate the disease burden due to AMR.
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Clinical efficacy of remdesivir in children with COVID-19 is unclear. This propensity-score-matched retrospective cohort study of children with COVID-19 showed that the rate of patients achieving defervescence on Day 4 was higher in the remdesivir group than in the non-remdesivir group, but was not statistically different (86.7% vs 73.3%, P = 0.333).
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COVID-19 , Humanos , Criança , SARS-CoV-2 , Estudos Retrospectivos , Antivirais/uso terapêutico , Tratamento Farmacológico da COVID-19 , Resultado do Tratamento , Alanina/uso terapêuticoRESUMO
BACKGROUND: Infectious diseases are treated based on clinical guidelines, which usually require a large amount of data and time to formulate. Therefore, various treatments are tried and used in the early stages of epidemics of emerging and reemerging infectious diseases. In this study, we focused on two drugs for coronavirus disease 2019 (COVID-19) treatment, i.e., steroids and favipiravir, and analyzed the changes in treatment trends by region. METHODS: This was a retrospective study of cases from the COVID-19 Registry Japan. The proportion of patients who received steroids and favipiravir was calculated on a monthly and pandemic wave basis, and the trend of drug administration by region was estimated using logistic curves. RESULTS: The effect of wave on steroid administration was as high as 2.75 [2.60, 2.90], indicating a rapid increase in the proportion of steroid administration. The odds ratios for Hokuriku and Hokkaido were 0.49 [0.35, 0.68] and 0.55 [0.43, 0.71], respectively, indicating that steroids were less likely administered in these regions. For favipiravir, the effect of timing was 0.43 [0.41, 0.46], denoting a decreasing trend. On the other hand, the odds ratio was very high in some regions, such as Hokkaido (6.66 [5.24, 8.48]), indicating that the administration trend varied by region. CONCLUSIONS: The increase in the proportion of steroid use showed the same trend nationwide, although the rate of increase differed, confirming that the use of drugs with proven efficacy was spreading rapidly and that effective treatment was available nationwide. However, the results suggest that drugs such as favipiravir, which were initially expected to be effective, may continue to be administered. Registry studies include larger populations than clinical trials and enable real-time monitoring of medication status and trends. Further use of registry studies for treatment standardization is expected in the future.
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COVID-19 , Humanos , SARS-CoV-2 , Estudos Retrospectivos , Tratamento Farmacológico da COVID-19 , Antivirais/uso terapêutico , Resultado do Tratamento , Esteroides/uso terapêuticoRESUMO
Background: The mortality rates of coronavirus disease 2019 (COVID-19) have been changed across the epidemiological waves. The aim was to investigate the differences in mortality rates of COVID-19 patients in Japan across the 6 epidemiological waves stratified by age group and Coronavirus Clinical Characterisation Consortium (4C) mortality score risk group. Methods: A total of 56 986 COVID-19 patients in the COVID-19 Registry Japan from 2 March 2020 to 1 February 2022 were enrolled. These patients were categorized into 4 risk groups based on their 4C mortality score. Mortality rates of each risk group were calculated separately for different age groups: 18-64, 65-74, 75-89, and ≥90â years. In addition, mortality rates across the wave periods were calculated separately in 2 age groups: <75 and ≥75â years. All calculated mortality rates were compared with reported data from the United Kingdom (UK) during the early epidemic. Results: The mortality rates of patients in Japan were significantly lower than in the UK across the board, with the exception of patients aged ≥90â years at very high risk. The mortality rates of patients aged ≥75â years at very high risk in the fourth and fifth wave periods showed no significant differences from those in the UK, whereas those in the sixth wave period were significantly lower in all age groups and in all risk groups. Conclusions: The present analysis showed that COVID-19 patients had a lower mortality rate in the most recent sixth wave period, even among patients ≥75â years old at very high risk.
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AIMS/INTRODUCTION: To assess the association of undiagnosed diabetes mellitus and its acute-to-chronic glycemic ratio with clinical outcome in patients hospitalized with coronavirus disease 2019 (COVID-19) using a large-scale nationwide registry in Japan. MATERIALS AND METHODS: Overall, 4,747 patients were included between July 2021 and January 2022. We evaluated blood glucose and glycated hemoglobin levels at admission, and calculated the acute-to-chronic glycemic ratio for each non-diabetes mellitus, undiagnosed diabetes mellitus and pre-existing diabetes mellitus group. The primary composite outcome comprised in-hospital mortality, invasive mechanical ventilation, extracorporeal membrane oxygenation support, intensive care unit admission and transfer to a more advanced medical facility. RESULTS: Compared with the non-diabetes mellitus group, the undiagnosed diabetes mellitus group was significantly associated with a worse COVID-19 outcome (odds ratio 2.18, 95% confidence interval 1.50-3.18). In patients with undiagnosed diabetes mellitus, the 3rd tertile of the acute-to-chronic glycemic ratio was linked with a worse COVID-19 outcome compared with the 1st tertile (odds ratio 3.33, 95% confidence interval 1.43-7.77), whereas glycated hemoglobin levels were not; among patients with pre-existing diabetes mellitus, glycated hemoglobin levels were linked with a worse outcome. CONCLUSIONS: Among patients with undiagnosed diabetes mellitus with COVID-19, the magnitude of elevation of blood glucose from chronic to acute levels is associated with worse outcomes.
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COVID-19 , Diabetes Mellitus , Humanos , Glicemia , COVID-19/complicações , COVID-19/diagnóstico , COVID-19/epidemiologia , Hemoglobinas Glicadas , Estudos Retrospectivos , Estudos de Coortes , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/epidemiologiaRESUMO
BACKGROUND: Prioritization for novel coronavirus disease 2019 (COVID-19)-related health policies usually considers age and certain other characteristics, but sex is rarely included, despite the higher risk of severe disease in men. The aim of this study was to compare the impact of sex and age on the severity of COVID-19 by estimating the age difference in years for which the risk for men versus women is the same. METHODS: We analyzed 23,414 Japanese COVID-19 inpatients aged 20-89 years (13,360 men and 10,054 women). We graded the severity of COVID-19 (0 to 5) according to the most intensive treatment required during hospitalization. The risk of grade 2/3/4/5 (non-invasive positive pressure ventilation/invasive mechanical ventilation/extracorporeal membrane oxygenation/death), grade 3/4/5, and separately grade 5 was analyzed using a multiple logistic regression model. RESULTS: The odds ratio (OR) of grades 2/3/4/5, 3/4/5 (primary outcome), and 5 for men relative to women was 2.76 (95% CI, 2.44-3.12), 2.78 (95% CI, 2.42-3.19), and 2.60 (95% CI, 2.23-3.03), respectively, after adjustment for age and date of admission. These risks for men were equivalent to those for women 14.1 (95% CI, 12.3-15.8), 11.2 (95% CI, 9.7-12.8), and 7.5 (95% CI, 6.3-8.7) years older, respectively. CONCLUSION: The risks of worse COVID-19 prognosis (grades 3/4/5) in men were equivalent to those of women 11.2 years older. Reanalyzing data extracted from four previous studies also revealed a large impact of sex difference on the severity of COVID-19. We should pay more attention to sex differences to predict the risk of COVID-19 severity and to formulate public health policy accordingly.
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COVID-19 , Feminino , Humanos , Masculino , COVID-19/epidemiologia , Caracteres Sexuais , SARS-CoV-2 , Japão/epidemiologia , Prognóstico , Hospitalização , Estudos RetrospectivosRESUMO
BACKGROUND: Information regarding effects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant strains on clinical manifestations and outcomes of coronavirus disease 2019 (COVID-19) in pregnant women is limited. METHODS: A retrospective observational study was conducted using the data from the nationwide COVID-19 registry in Japan. We identified pregnant patients with symptomatic COVID-19 hospitalized during the study period. The Delta and Omicron variants of concern (VOC) predominant periods were defined as August 1 to December 31, 2021 and January 1 to May 31, 2022, respectively. Clinical characteristics were compared between the patients in the Delta and Omicron VOC periods. In addition, logistic regression analysis was performed to identify risk factors for developing moderate-to-severe COVID-19. RESULTS: During the study period, 310 symptomatic COVID-19 cases of pregnant women were identified; 111 and 199 patients were hospitalized during the Delta and Omicron VOC periods, respectively. Runny nose and sore throat were more common, and fatigue, dysgeusia, and olfactory dysfunction were less common manifestations observed in the Omicron VOC period. In the multivariable logistic regression analysis, onset during the later stage of pregnancy (OR: 2.08 [1.24-3.71]) and onset during the Delta VOC period (OR: 2.25 [1.08-4.90]) were independently associated with moderate-to-severe COVID-19, whereas two doses of SARS-CoV-2 vaccine were protective against developing moderate-to-severe COVID-19 (OR: 0.34 [0.13-0.84]). CONCLUSIONS: Clinical manifestations of COVID-19 in pregnant women differed between the Delta and Omicron VOC periods. SARS-CoV-2 vaccination was still effective in preventing severe COVID-19 throughout the Delta and Omicron VOC periods.
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COVID-19 , Complicações Infecciosas na Gravidez , Humanos , Feminino , Gravidez , Gestantes , COVID-19/epidemiologia , Vacinas contra COVID-19 , SARS-CoV-2 , Complicações Infecciosas na Gravidez/epidemiologiaRESUMO
The impact of the COVID-19 pandemic on the incidence of microbial infections and other metrics related to antimicrobial resistance (AMR) has not yet been fully described. Using data from Japan Surveillance for Infection Prevention and Healthcare Epidemiology (J-SIPHE), a national surveillance database system that routinely collects clinical and epidemiological data on microbial infections, infection control practices, antimicrobial use, and AMR emergence from participating institutions in Japan, we assessed the temporal changes in AMR-related metrics before and after the start of the COVID-19 pandemic. We found that an apparent decrease in the incidence of microbial infections in 2020 compared with 2019 may have been driven primarily by a reduction in bed occupancy, although the incidence showed a constant or even slightly increasing trend after adjusting for bed occupancy. Meanwhile, we found that the incidence of Streptococcus pneumoniae dramatically decreased from April 2020 onward, probably due to stringent non-pharmaceutical interventions against COVID-19. Antimicrobial use showed a weak increasing trend, while the use of hand sanitiser at the included medical institutions increased by about 50% in 2020 compared with 2019.