Ustekinumab effectiveness in Crohn's disease with lesions in the intestines.

Ustekinumab is prescribed for the treatment of patients with steroid-resistant moderate to severe Crohn's disease. We investigated its clinical outcome in patients with small and large intestinal lesions. Patients who were newly administered ustekinumab between March 2014 and December 2020 at Hamamatsu University Hospital were included in the study. The primary endpoint was Crohn's disease activity index score at baseline and weeks 8, 24, and 48 after the initiation of treatment, and secondary endpoints were albumin, hemoglobin, and C-reactive protein at these time points. Ustekinumab treatment retention was examined in both groups; the 2 groups were compared using the Friedman test, Mann-Whitney U test, or Fisher exact test. Overall, Crohn's disease activity index scores improved between baseline and 48 weeks, but the difference was not significant. However, there was a significant improvement between baseline and 48 weeks in patients with lesions in the small intestine only. Overall, patients showed significant improvement in albumin levels between baseline and 48 weeks but not in C-reactive protein or hemoglobin levels. When limited to patients with lesions in the small intestine, albumin and hemoglobin levels showed significant improvement. Both types showed high rates of treatment retention, although there was no significant difference. Ustekinumab appears to be a safe and effective treatment option that may be particularly effective in patients with lesions in the small intestine only.

Urine oxygenation predicts COVID-19 risk.

Since February, 2023, the omicron variant has accounted for essentially all new coronavirus infections in Japan. If future infections involve mutant strains with the same level of infectivity and virulence as omicron, the government's basic policy will be to prevent the spread of infection, without compromising socioeconomic activities. Objectives include protecting pregnant women and elderly persons, and focusing on citizens requiring hospitalization and those at risk of serious illness, without imposing new social restrictions. Although the government tries to raise public awareness through education, most people affected by COVID-19 stay at home, and by the time patients become aware of the seriousness of their disease, it has often reached moderate or higher severity. In this review, we discuss why this situation persists even though the disease seems to have become milder with the shift from the delta variant to omicron. We also propose a pathophysiological method to determine the risk of severe illness. This assessment can be made at home in the early stages of COVID-19 infection, using urine analysis. Applicability of this method to drug discovery and development is also discussed.

High diagnostic accuracy of quantitative SARS-CoV-2 spike-binding-IgG assay and correlation with in vitro viral neutralizing activity.

Background: Antibody testing can easily evaluate the clinical status of patients, aid in the diagnosis of multisystem inflammatory syndrome, and monitor the immunity level in the population. However, the applicability of serological tests in detecting antibodies against the severe acute respiratory syndrome 2 (SARS-CoV-2) spike-binding protein remains limited. This study aimed to quantify both serum-derived neutralizing immunoglobulin-G (IgG) antibody activity and the amount of anti-SARS-CoV-2 Spike-IgG (S-IgG) in convalescent sera/plasmas and evaluate the direct correlation between the in vitro IgG-EC50 values and S-IgG values. Methods: We evaluated the neutralizing activity of purified IgG (IgG-EC50), quantified S-IgG in the serum/plasma of consecutive COVID-19 convalescent individuals using a cell-based virus-neutralizing assay, and determined the correlation between IgG-EC50 and S-IgG. In addition, we evaluated rational cut-off values using the receiver operating characteristic (ROC) curve and calculated the sensitivity and specificity of the quantitative S-IgG assay for moderate and high IgG-EC50. Results: A high correlation was observed between S-IgG and IgG-EC50 with a Spearman's ρ value of -0.748 (95 % confidence interval [CI]: -0.804-0.678). Using an IgG-EC50 of 50 µg/mL and 20 µg/mL as the cut-off values for moderate and high in vitro neutralizing activity, respectively, the Youden's index values of 287.5 binding antibody units (BAU)/mL and 454.1 BAU/mL determined from the ROC curve showed the highest diagnostic accuracy, with Kappa values of 0.884 (95 % CI: 0.823-0.946) and 0.920 (95 % CI: 0.681-0.979), respectively. Conclusions: Quantitative S-IgG tests are a useful and convenient tool for estimating in vitro virus-neutralizing activity, with a high correlation with IgG-EC50 when the rational cut-off value is carefully determined.

Albumin change predicts failure in ulcerative colitis treated with adalimumab.

Anti-tumor necrosis factor (TNF) -α antibodies, including infliximab (IFX), adalimumab (ADA), and golimumab, which were the first biologic therapeutic agents, have a crucial position in advanced therapy for ulcerative colitis (UC). We aimed to investigate serum albumin (Alb) change as a prognostic factor for the therapeutic effect of ADA in UC. Thirty-four patients with UC treated with ADA were enrolled in this study and were divided into failure and non-failure groups. Biological data, such as Alb were compared between the two groups. Thirteen patients showed failure within six months. Examination of the biological data showed a significant difference between the two groups only in the week 2/week 0 Alb ratio. In receiver-operating characteristic (ROC) curve analysis to predict failure, the cut-off value of week 2/week 0 Alb ratio was 1.00, and the area under the curve was 0.868 (95% confidence interval: 0.738-0.999). In addition, in the sub-group analysis of only clinically active patients, the week 2/week 0 Alb ratio of the non-failure group was significantly higher than that of the failure group, and the cut-off-value in ROC analysis was 1.00. Week 2/week 0 Alb ratio ≤ 1 predicts failure within six months of ADA for UC.

Real-world effectiveness of full and booster mRNA vaccination for coronavirus disease 2019 against disease severity during the delta- and omicron-dominant phases: A propensity score-matched cohort study using the nationwide registry data in Japan.

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.

Factors Associated with Geographical Variability of Antimicrobial Use in Japan.

INTRODUCTION: Evidence regarding the factors affecting the geographical variation of antimicrobial use (AMU) is relatively scarce. This study aimed to evaluate factors potentially associated with geographical variability of AMU per day per 1000 habitants in the 47 prefectures of Japan. METHODS: This is an observational ecological study using the Japanese national database in 2019. The outcome was the defined daily doses per 1000 inhabitants per day by prefecture. Multivariable negative binomial regression analysis was conducted using patient- and physician-level variables. RESULTS: The study included 605,391,054 defined daily doses of AMU in 2019 from the 47 prefectures. In the multivariable negative binomial regression analyses for the outcome of total AMU, the proportion of female individuals (adjusted rate ratio [aRR] 1.04 [1.01-1.08] per 1% increase, p = 0.021), the proportion of upper secondary graduates going to further education (aRR 1.01 [1.00-1.01] per 1% increase, p = 0.005), and the annual number of diagnoses related to upper respiratory infections (URIs) per 1000 inhabitants per day (aRR 1.21 [1.10-1.34], p < 0.001) were significantly correlated with total AMU. CONCLUSIONS: In this ecological study, the variability of total AMU by Japanese prefecture was associated with the proportion of female individuals, education level, and the number of URI diagnoses per population. The results suggest the potential need for additional stewardship efforts to reduce unnecessary antimicrobial prescriptions for URI.

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.

Trends of participants in convalescent plasma donation for COVID-19 in Japan as the pandemic evolved.

Background: We aimed to investigate chronological changes in the characteristics of participants in a coronavirus disease 2019 convalescent plasma donation study that may benefit optimal collection methods in the future. Methods: Data from a convalescent plasma donation study from April 30, 2020 to November 5, 2021 were collected and analyzed. After August 23, 2021, an interim analysis of factors linked to higher antibody titers led us to restrict our participant recruitment criteria to participants who were within 4 months of disease onset and to patients who were otherwise most likely to have sufficiently high antibody titers. Overall, 1299 samples from 1179 patients were analyzed. Results: Over the duration of the study, 35.9% of the samples were deemed eligible for convalescent plasma collection. The overall eligibility rate initially declined, dipping to <20% after one year. During this period, the proportion of enrolled samples from patients who had severe illness also declined, and the proportion of samples from participants who were >120 days post disease onset increased. After the addition of days from onset and vaccination status to our participant recruitment criteria, the eligibility rate improved significantly. Conclusions: As outbreaks of emerging infectious disease occur, it is desirable to construct and implement a scheme for convalescent plasma donation promptly and to monitor the eligibility rate over time. If it declines, promptly analyze and resolve the associated factors. Additionally, vaccine development and infection prevalence are likely to influence the effective recruitment of participants with high antibody titers.

Characteristics of preventive intervention acceptance for international travel among clients aged 60 years and older from a Japanese multicenter pretravel consultation registry.

OBJECTIVES: Pretravel consultation (PTC) is important for older adults owing to health problems associated with overseas travel. Although older adults in Japan, their PTC characteristics are less known. This study aimed to investigate the epidemiology of clients aged ≥ 60 years based on data from the Japan Pre-travel Consultation Registry (J-PRECOR). METHODS: Clients aged ≥ 60 years who visited J-PRECOR cooperative hospitals from February 1, 2018, to May 31, 2022, were included. The primary endpoint was a comparison of prescriptions for vaccines for hepatitis A, tetanus toxoid, and malaria prophylaxis in travelers to high-risk malaria countries in yellow fever vaccination (YFV)-available facilities with and without YFV. RESULTS: In total, 1000 clients (median age: 67 years) were included. Although 523 clients were immunized with YFV, only 38.6% of the 961 unimmunized clients were vaccinated with the tetanus toxoid-containing vaccine. Malaria chemoprophylaxis was prescribed to 25.7% of clients traveling for ≤55 days. At YFV-capable institutes, 557 clients traveling to yellow fever risk countries took PTC, 474 of whom received YFV and 83 were unvaccinated. Lower age (odds rate 0.85 per 1 year; 95% CI 0.80-0.90) and lower hepatitis A vaccination rate (0.29; 95% CI 0.14-0.63) were significantly associated with YFV. CONCLUSIONS: Preventive interventions other than YFV should be offered to older adults.

Evaluation of potential rabies exposure among Japanese international travelers: A retrospective descriptive study.

BACKGROUND: Although Japan has been a rabies-free country for >50 years, a few cases have been reported among people traveling abroad. This study aimed to investigate animal exposure among Japanese travelers using the Japanese Registry for Infectious Diseases from Abroad (J-RIDA). METHOD: In this retrospective analysis, we examined Japanese overseas travelers with animal exposure, as included the J-RIDA database, reported from October 1, 2017, to October 31, 2019, with a focus on pre-exposure prophylaxis (PrEP) administration and the animals to which the patients were exposed. RESULTS: Among the 322 cases included in the analysis, 19 (5.9%) patients received PrEP and 303 did not. The most common purpose of travel was a non-package tour (n = 175, 54.3%). Most trips (n = 213, 66.1%) were to a single country for <2 weeks. Most patients (n = 286, 87.9%) traveled to countries with a rabies risk. The majority of patients with and without PrEP were injured in rabies-risk countries [n = 270 (89.1%) for non-PrEP and n = 16 (84.2%) for PrEP]. Animals associated with injuries included dogs (55.0%), cats (25.5%), and monkeys (15.5%). Most patients were classified as World Health Organization Category II/III for contact with suspected rabid animals (39.5% and 44.1% for categories II and III, respectively) and had exposure within 5 days of travel. Southeast Asia (n = 180, 55.9%) was the most common region in which travelers were exposed to animals. CONCLUSIONS: Japanese overseas travelers had contact with animals that could possibly transmit the rabies virus, even on short trips. Promoting pre-travel consultation and increasing awareness of the potential for rabies exposure are important for prevention of rabies among Japanese international travelers.

Assessing the efficacy of health countermeasures on arrival time of infectious diseases.

Public health measures to control the international spread of infectious diseases include strengthening quarantines and sealing borders. Although these measures are effective in delaying the importation of infectious diseases, they also have a significant economic impact by stopping the flow of people and goods. The arrival time of infectious diseases is often used to assess quarantine effectiveness. Although the arrival time is highly dependent on the number of infected cases in the endemic country, direct comparisons have not yet been made. Therefore, this study derives an explicit relationship between the number of infected cases and arrival time. Transmission behavior is stochastic, and deterministic models are not always realistic. In this study, random differential equations, which are differential equations with stochastic processes, were used to describe the dynamics of infection in an endemic country. Furthermore, the flow of travelers from the endemic country was described in terms of survival time, and the arrival time in each country was calculated. A scenario in which PCR kits were distributed between endemic and disease-free countries was also considered, and the impact of different distribution rates on arrival time was evaluated. The simulation results showed that increasing the distribution of PCR kits in the endemic country was more effective in delaying arrival times than using PCR kits in quarantine in disease-free countries. It was also found that increasing the proportion of identified infected persons in the endemic country, leading to isolation, was more important and effective in delaying arrival times than increasing the number of PCR tests.

Intrahepatic cholangiocarcinoma in patients with primary sclerosing cholangitis and ulcerative colitis: Two case reports.

BACKGROUND: Primary sclerosing cholangitis (PSC) is an extraintestinal manifestation of ulcerative colitis (UC). PSC is a well-known risk factor for intrahepatic cholangiocarcinoma (ICC), and ICC is known to have a poor prognosis. CASE SUMMARY: We present two cases of ICC in patients with PSC associated with UC. In the first case, a tumor was found by magnetic resonance imaging (MRI) in the liver of a patient with PSC and UC who presented to our hospital with right-sided rib pain. The second patient was asymptomatic, but we unexpectedly detected two liver tumors in an MRI performed to evaluate bile duct stenosis associated with PSC. ICC was strongly suspected by computed tomography and MRI in both cases, and surgery was performed, but unfortunately, the first patient died of ICC recurrence 16 mo postoperatively, and the second patient died of liver failure 14 mo postoperatively. CONCLUSION: Careful follow-up of patients with UC and PSC with imaging and blood tests is necessary for early detection of ICC.

Clinical efficacy of remdesivir for COVID-19 in children: A propensity-score-matched analysis.

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).

Investigation of oral macrolide prescriptions in Japan using a retrospective claims database, 2013-2018.

Macrolide usage in Japan exceeds that in Europe and the United States. Investigating the actual conditions in which macrolides are used is important for identifying further interventions for appropriate antimicrobial use; however, this situation has not been evaluated in Japan. Therefore, we aimed to clarify the number of macrolide prescriptions and their changes before and after implementation of the Antimicrobial Resistance (AMR) Action Plan. In addition, we also investigated the names of diseases for which macrolides have been prescribed and the number of days of prescription. A retrospective observational study was conducted using JMDC claims data from January 2013 to December 2018. The proportion of all oral antimicrobials and macrolides used during this period and the diseases for which macrolides were used in the 3 years before and after the AMR Action Plan were determined separately for acute (< 14 prescription days) and chronic (> 14 prescription days) diseases. The number of prescriptions for macrolides constituted approximately 30% of those for all oral antimicrobials; of these, clarithromycin accounted for approximately 60%. Most prescriptions for acute diseases were for common cold, whereas allergic and dermatological diseases were included among chronic diseases. The names of these illnesses did not change before and after the AMR Action Plan. Overall, these results indicate that appropriate macrolide use involves a review of their use for common cold along with appropriate evaluation of their long-term use for skin and allergic diseases. They also indicate the need for further fact-finding studies and ongoing AMR measures.

Tin(II)-Based Metal-Organic Frameworks Enabling Efficient, Selective Reduction of CO2 to Formate under Visible Light.

Certain metal complexes are known as high-performance CO2 reduction photocatalysts driven by visible light. However, most of them rely on rare, precious metals as principal components, and integrating the functions of light absorption and catalysis into a single molecular unit based on abundant metals remains a challenge. Metal-organic frameworks (MOFs), which can be regarded as intermediate compounds between molecules and inorganic solids, are potential platforms for the construction of a simple photocatalytic system composed only of Earth-abundant nontoxic elements. In this work, we report that a tin-based MOF enables the conversion of CO2 into formic acid with a record high apparent quantum yield (9.8 % at 400 nm) and >99 % selectivity without the need for any additional photosensitizer or catalyst. This work highlights a new MOF with strong potential for photocatalytic CO2 reduction driven by solar energy.

Urinary L-Type Fatty Acid-Binding Protein Predicts Oxygen Demand of COVID-19 in Initially Mild Cases.

Early detection of illness trajectory in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infected patients is crucial for patients and healthcare workers. An effective, noninvasive approach, with simple measurement for decision-making, is necessary in a pandemic to discriminate between high- and low-risk patients, even though both groups may exhibit mild symptoms in the beginning. OBJECTIVES: To predict COVID-19 disease severity within 10 days, distinguishing cases that will progress to moderate or severe versus mild, patient urinary L-type fatty acid-binding protein (L-FABP) was assayed within 4 days of receiving a diagnosis. The study also examined whether L-FABP point of care (POC) test is helpful in risk screening. DESIGN: Symptomatic subjects who tested positive for SARS-CoV-2 and were hospitalized were prospectively enrolled at the National Center for Global Health and Medicine (NCGM), Yamanashi Prefectural Central Hospital (YPCH), and Sinai Hospital in Maryland. The outcome of each case was evaluated 7 days after admission and the diagnostic performance of L-FABP was assessed. SETTING AND PARTICIPANTS: Subjects were treated for COVID-19 at public healthcare centers in Japan from January 31, 2020, to January 31, 2021, to NCGM, YPCH, and at Sinai Hospital in Baltimore, MD, during the same period. MAIN OUTCOMES AND MEASURES: The primary outcome was to determine whether urinary L-FABP within 48 hours of admission can predict the patient's severity of COVID-19 1 week later. We obtained demographic data, information on clinical symptoms, radiographic images, and laboratory data. RESULTS: Diagnostic performance was assessed using receiver operating characteristic analysis. Of the 224 participants in the study, 173 initially had a mild form of COVID-19. The area under the curve (AUC) for a severe outcome was 93.5%. L-FABP POC risk prediction of a severe outcome had an AUC of 88.9%. CONCLUSIONS AND RELEVANCE: Urinary L-FABP can predict patient risk of COVID-19 illness severity. L-FABP POC is implementable for patient management. (ClinicalTrials.gov number, NCT04681040).

Characteristics of hospitalized COVID-19 patients with other respiratory pathogens identified by rapid diagnostic test.

Rapid diagnostic tests (RDTs) significantly impact disease treatment strategy. In Japan, information on the use of RDTs for patients with COVID-19 is limited. Here, we aimed to investigate the RDT implementation rate, pathogen detection rate, and clinical characteristics of patients positive for other pathogens by using COVIREGI-JP, a national registry of hospitalized patients with COVID-19. A total of 42,309 COVID-19 patients were included. For immunochromatographic testing, influenza was the most common (n = 2881 [6.8%]), followed by Mycoplasma pneumoniae (n = 2129 [5%]) and group A streptococcus (GAS) (n = 372 [0.9%]). Urine antigen testing was performed for 5524 (13.1%) patients for S. pneumoniae and for 5326 patients (12.6%) for L. pneumophila. The completion rate of M. pneumonia loop-mediated isothermal amplification (LAMP) testing was low (n = 97 [0.2%]). FilmArray RP was performed in 372 (0.9%) patients; 1.2% (36/2881) of patients were positive for influenza, 0.9% (2/223) for the respiratory syncytial virus (RSV), 9.6% (205/2129) for M. pneumoniae, and 7.3% (27/372) for GAS. The positivity rate for urine antigen testing was 3.3% (183/5524) for S. pneumoniae and 0.2% (13/5326) for L. pneumophila. The positivity rate for LAMP test was 5.2% (5/97) for M. pneumoniae. Five of 372 patients (1.3%) had positive FilmArray RP, with human enterovirus being the most frequently detected (1.3%, 5/372). The characteristics of patients with and without RDTs submission and positive and negative results differed for each pathogen. RDTs remain an important diagnostic tool in patients with COVID-19 in whom coinfection with other pathogens needs to be tested based on clinical evaluation.

Effects of population age structure on parenteral antimicrobial use estimations.

Antimicrobial use (AMU) is conventionally reported as unadjusted defined daily doses (DDDs) or population-adjusted DDDs per 1000 inhabitants per day (DID). DID is frequently used to monitor national AMU trends, this metric does not intrinsically take temporal changes in population age structure into account. We examined the effects of population age structure on DID estimates of parenteral AMU in Japan, and predicted future trends in DDDs based on population projections. Parenteral AMU data from 2013 to 2018 were acquired from a national claims database. We assessed temporal trends in parenteral AMU by age group (children aged < 15 years, working-age persons aged 15-64 years, and older persons aged ≥ 65 years) using both DID and DDDs. In addition, we modeled DDD predictions based on age-specific population projections from 2019 to 2030. DID values for older persons were 8.08-10.15 times and 5.43-5.63 times higher than in children and working-age persons, respectively. DID was stable, but DDDs increased in older persons. The prediction models showed that DDDs will continue to increase until 2030 if DID remains steady or decreases. DID estimates were skewed by the older population. More rigorous antimicrobial stewardship efforts targeting geriatric care are needed to counter the aging-associated increase in AMU.

Statistical Analysis of Mortality Rates of Coronavirus Disease 2019 (COVID-19) Patients in Japan Across the 4C Mortality Score Risk Groups, Age Groups, and Epidemiological Waves: A Report From the Nationwide COVID-19 Cohort.

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 ≥90 years. In addition, mortality rates across the wave periods were calculated separately in 2 age groups: <75 and ≥75 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 ≥90 years at very high risk. The mortality rates of patients aged ≥75 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 ≥75 years old at very high risk.

Regional trends in the use of steroids and favipiravir for COVID-19 treatment.

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.