Vitamin D deficiency during the coronavirus disease 2019 (COVID-19) pandemic among healthcare workers.

BACKGROUND & AIMS: Vitamin D deficiency is a common nutritional problem worldwide that may have worsened during the coronavirus disease 2019 (COVID-19) pandemic. The present study sought to examine the prevalence and correlates of vitamin D deficiency among healthcare workers three years after the start of the COVID-19 pandemic. METHODS: Participants comprised 2543 staff members from a medical research institute, who completed a questionnaire and donated blood samples in June 2023. 25-hydroxyvitamin D (25[OH]D) levels were measured using an electrochemiluminescence immunoassay. Logistic regression was used to calculate the odds ratio and its 95% confidence interval while adjusting for covariates. RESULTS: The proportions of participants with vitamin D insufficiency (25[OH]D 20-29 ng/mL) and deficiency (25[OH]D < 20 ng/mL) were 44.9% and 45.9%, respectively. In a multivariable-adjusted model, factors associated with a higher prevalence of vitamin D deficiency included younger age, female sex, fewer hours of daytime outdoor physical activity during leisure time (without regular use of sunscreen), lower intake of fatty fish, no use of vitamin D supplements, smoking, and no alcohol consumption. Occupational factors, including shift work, were not independently associated with vitamin D deficiency. CONCLUSIONS: Our results suggest that vitamin D insufficiency and deficiency are highly prevalent among healthcare workers. Health education regarding lifestyle modifications for this occupational group are warranted to improve their vitamin D status in the COVID-19 era.

Bloodstream infections in the elderly Japanese population: Current reality and countermeasures.

We reviewed bloodstream infections in the elderly in Japan, referring to data recently reported from the National Center for Global Health and Medicine in Tokyo. We divided the locations of bloodstream infections into Hospital-onset (HO), healthcare-associated (HCA), and CA (community-acquired), as the elderly reside in different places. The study focused on the fact that the general condition and underlying diseases of the elderly differ by age group. And thus, we divided them into three groups: Pre-old (65-74 years), Old (75-89 years), and Super-old (≥ 90 years), and compared their characteristics of bloodstream infections. HO bacteremia was most common in the pre-old group. On the other hand, HCA bloodstream infections tended to increase as the population aged, and it was most prevalent in super-old group. According to the study results, early intervention through infectious diseases (ID) consultation may improve the prognosis of bloodstream infections even in the elderly. Since the rate of ID consultation is lower in the super-old group than in other groups, this group may be a significant target. In conclusion, a study of a cohort of elderly patients with bloodstream infections in Japan indicates that bloodstream infections in patients over 65 years is not uniform.

Pyelonephritis due to Escherichia coli in the older population in Japan: Impacts on activities of daily living and medical costs.

This study aimed to investigate differences in Activities of Daily Living (ADL), at admission and discharge, as well as the medical costs of pyelonephritis in older adults in Japan. Patients hospitalized for pyelonephritis between January 1, 2013 and March 31, 2019, were retrospectively enrolled. The inclusion criteria were urine culture within 48 h of admission with > 104 colony-forming units/mL of Escherichia coli and symptoms of pyelonephritis. Patients were divided into Young (20-64 years), Pre-old (65-74 years), Old (75-84 years), and Super-old (≥ 85 years). ADL and medical costs were compared. Finally, 393 patients were included: 112 (28.5%) were Young, 72 (18.3%) were Pre-old, 130 (33.1 %) were Old, and 79 (20.1%) were Super-old between January 1, 2013, and March 31, 2019. The median differences between Barthel Index (BI) scores, which indicates ADL, at admission and discharge were 0, 0, 25, and 23 in each age group, respectively (p < 0.001). No significant differences existed between the groups aged ≥ 65. Median medical costs were $3,368, $4,894, $5,372, and $6,078 for each age group, respectively (p < 0.001). Medical costs per day did not differ significantly between the groups (p = 0.163). Pyelonephritis due to E. coli in patients aged ≥ 75 is associated with a decline in ADL, longer hospital stays, and higher medical costs compared to that in young patients. Pre-old patients did not have lower ADL; however, they tended to have longer hospital stays and higher medical costs.

Development and validation of claims-based algorithms for identifying hospitalized patients with COVID-19 and their severity in 2020 and 2021.

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.

How Much More Efficient Are Adaptive Platform Trials Than Multiple Stand-Alone Trials? A Comprehensive Simulation Study for Streamlining Drug Development During a Pandemic.

With the coronavirus disease 2019 (COVID-19) pandemic, there is growing interest in utilizing adaptive platform clinical trials (APTs), in which multiple drugs are compared with a single common control group, such as a placebo or standard-of-care group. APTs evaluate several drugs for one disease and accept additions or exclusions of drugs as the trials progress; however, little is known about the efficiency of APTs over multiple stand-alone trials. In this study, we simulated the total development period, total sample size, and statistical operating characteristics of APTs and multiple stand-alone trials in drug development settings for hospitalized patients with COVID-19. Simulation studies using selected scenarios reconfirmed several findings regarding the efficiency of APTs. The APTs without staggered addition of drugs showed a shorter total development period than stand-alone trials, but the difference rapidly diminished if patient's enrollment was accelerated during the trials owing to the spread of infection. APTs with staggered addition of drugs still have the possibility of reducing the total development period compared with multiple stand-alone trials in some cases. Our study demonstrated that APTs could improve efficiency relative to multiple stand-alone trials regarding the total development period and total sample size without undermining statistical validity; however, this improvement varies depending on the speed of patient enrollment, sample size, presence/absence of family-wise error rate adjustment, allocation ratio between drug and placebo groups, and interval of staggered addition of drugs. Given the complexity of planning and implementing APT, the decision to implement APT during a pandemic must be made carefully.

Molecular Epidemiology of Escherichia coli Resistant to Carbapenems, Fluoroquinolones, and Aminoglycosides Isolated from One of the Largest Hospitals in Vietnam in 2014-2019.

Introduction: Multidrug-resistant (MDR) Gram-negative bacilli including carbapenem-resistant Gram-negative Enterobacteriaceae (CRE) threaten global health. Little is known, however, about the distribution of antimicrobial resistance genes in MDR isolated from patients in Vietnamese hospitals. In this study, we collected MDR Escherichia coli, defined as E. coli resistance against all fluoroquinolones, aminoglycosides, and carbapenems. Aim: This study was designed to clarify the molecular epidemiology of Escherichia coli isolates resistant to carbapenems, fluoroquinolones, and aminoglycosides isolated from patients admitted to one of the largest hospitals in Vietnam in 2014-2019 based on both whole-genome sequencing (WGS) and phenotypic data. Methodology. Sixty-seven Vietnamese isolates screened by drug resistance by the disk test were subjected to WGS, and their sequences were analyzed to determine their multilocus sequence type (MLST), O-types, H-types, distribution of drug resistance genes, plasmid types, pathogenicity islands (PIs), virulence factor distribution, and phylogenetic evolution using the WGS data. Results: Among the STs detected, ST410 was relatively dominant. Dominant O-types and H-types were O102 and H9 and showed some links, such as those between O102 and H8. The most dominant plasmid type and carbapenemase type were 4 and NDM-5, respectively. MLST, O-types, H-types, plasmid types, and types of carbapenemases were very heterogeneous among the isolates, with no clear correlation between them. Dominant plasmid type carrying drug resistance gene was IncQ1_1. The percentage of isolates positive for drug resistance genes, such as anti-beta-lactams and aminoglycosides, was relatively high because the isolates screened were resistant to carbapenems, fluoroquinolones, and aminoglycosides. Conclusions: MDR E. coli isolates isolated at a high-volume Vietnamese hospital were very heterogeneous, suggesting that they were acquired from different sources, including nosocomial infection, animals, and water. Eradication of MDR E. coli from hospitals and other clinical environments is very challenging because a single measure may be ineffective.

Micafungin-breakthrough Coniochaeta hoffmannii (Lecythophora hoffmannii) fungemia following cord blood transplant in a patient with acute myeloid leukemia successfully treated with voriconazole.

Phaeohyphomycosis is caused by dematiaceous (pigmented) fungi. Most phaeohyphomycosis is non-invasive infections, however, they can lead to invasive infections, including fungemia and disseminated disease, particularly in severely immunocompromised patients. Invasive phaeohyphomycosis has recently emerged, however, the treatment strategy was not determined because of the intrinsic resistance to antifungals and the lack of clinical experience. Here, we describe a novel case of echinocandin-breakthrough Coniochaeta hoffmannii (Lecythophora hoffmannii) fungemia after hematopoietic stem cell transplantation, which was identified using matrix-assisted laser desorption ionization time-of-flight mass spectrometry and ribosomal RNA sequencing. The patient was a female in her 40s who had acute myeloid leukemia refractory to chemotherapy before progressing to cord blood transplantation. Before developing fungemia, the patient was administered multiple broad-spectrum antibiotics and micafungin for recurrent infections and prophylaxis. Clinical and microbiological responses to liposomal amphotericin B were poor but improved after replacement to voriconazole and engraftment. A literature review of the previously reported cases with C. hoffmannii human infections imply that disruption of the cutaneous/mucosal barrier and the use of antimicrobial agents, both antibiotics and antifungals, could incite C. hoffmannii invasive infections.

Epidemiology of post-COVID conditions beyond 3 years and factors associated with their persistence longer than 2 years: A cross-sectional study.

OBJECTIVE: This study aimed to investigate the epidemiology of post-coronavirus disease 2019 (COVID-19) conditions (PCCs) beyond 3 years and identify factors associated with their persistence longer than 2 years. STUDY DESIGN: Cross-sectional questionnaire-based survey. METHODS: We surveyed patients who had recovered from COVID-19 and visited our institution from February 2020 to November 2021. Demographic and clinical data and information on the presence and duration of PCCs were obtained. We identified factors associated with the persistence of PCCs longer than 2 years using multivariate linear regression analyses. RESULTS: Among 935 patients surveyed, 407 completed the survey. Among them, 360 patients had mild disease in the acute phase. The proportions of participants with at least one symptom at 1, 2, and 3 years after symptom onset or COVID-19 diagnosis were 33.2%, 29.8%, and 5.7%, respectively. The numbers of participants with and without any residual symptoms 2 years after the onset of COVID-19 were 87 and 193, respectively. After multivariate adjustment, persistence of PCCs longer than 2 years was associated with lower body mass index, presence of any underlying medical conditions, and number of symptoms lasting for more than 1 month ≥ 5. CONCLUSIONS: The prevalence of PCCs decreased 2 years after symptom onset or COVID-19 diagnosis. We also identified factors associated with PCC persistence longer than 2 years, which could help primary care physicians and patients with PCCs predict the duration of PCCs and better understand their natural history, thus reducing patients' anxiety about their duration.

Unfractionated Heparin Safety in COVID-19: Incidence and Risks of Bleeding Complications in Japan.

AIM: Several studies have shown the efficacy and safety of low-molecular-weight heparin use in coronavirus disease 2019 (COVID-19), but that of unfractionated heparin (UFH) has not been investigated. We investigated the prevalence of bleeding complications during UFH administration, its impact on mortality, and the risk factors of bleeding outcomes associated with UFH. METHODS: This retrospective cohort study was conducted at a single-center tertiary care hospital, including hospitalized patients with COVID-19. The primary outcomes were measured as the prevalence of bleeding complications during hospitalization, and the secondary outcomes were thromboembolic events and 60-day mortality rates. Logistic regression analysis and propensity score matching were used to assess risk factors for bleeding complications and their impact on mortality. RESULTS: Among 1035 included patients, 516 patients were treated with UFH. Twelve (2.3%) patients in the UFH group experienced major bleeding. The prevalence of major bleeding in patients treated with therapeutic-dose UFH was 9.2%. Logistic regression analysis showed that age ≥ 60 years (adjusted odds ratio [aOR], 3.89; 95% confidence interval [CI], 1.01-15.0; P＜.05) and COVID-19 severity (aOR, 35.9; 95% CI, 4.57-282; P ＜.05) were associated with major bleeding complications. After propensity score matching, 11 major and 11 non-major bleeding cases (including minor bleeding) were matched. The 60-day cumulative mortality rate between the two groups did not differ significantly (P=.13, log-rank test). CONCLUSIONS: The incidence of major bleeding in COVID-19 patients using therapeutic-dose UFH was relatively high. Critical COVID-19 and older age were risk factors for bleeding complications.

Coffee and green tea consumption with the risk of COVID-19 among the vaccine recipients in Japan: a prospective study.

BACKGROUND: While coffee and green tea have been suggested to have immunoprotective effects, it remains elusive whether they can decrease the risk of COVID-19. OBJECTIVE: We prospectively examined the association between coffee and green tea consumption and the risk of COVID-19 among mRNA vaccine recipients during the epidemic of the Omicron variant. METHOD: Participants were 2,110 staff (aged 18 to 76 years) of a large medical facility in Tokyo, who attended a serosurvey in June 2022, predominatly received ≥3 doses of vaccine, and were followed for COVID-19 until December 2022. Coffee and green tea consumption was ascertained via a questionnaire. COVID-19 was identified through the in-house registry. Cox proportional hazards model was used to estimate the hazard ratios (HRs) of COVID-19 across the categories of beverage consumption. RESULT: During 6 months of follow-up, 225 (10.6%) cases of COVID-19 were identified. Contrary to the expectation, higher consumption of coffee was associated with a significant increase in the risk of COVID-19; multivariable-adjusted HRs (95% CI) was 1.00, 0.92 (0.62-1.35), 1.48 (0.99-2.22), and 1.82 (1.20-2.76) for <1 cup/day, 1 cup/day, 2 cups/day, and ≥3 cups/day, respectively (p trend=0.003). Green tea consumption was not significantly associated with the risk of COVID-19. The association with coffee was attenuated if serologically detected infection was added to the cases. CONCLUSION: In a cohort of Japanese hospital staff who received COVID-19 vaccine, higher consumption of coffee was associated with an increased risk of COVID-19 during the epidemic of the Omicron variant. There was no evidence of a significant association between green tea consumption and COVID-19 risk.

Improving diagnostic accuracy of blood culture-positive cases in a cancer center via an antimicrobial stewardship program and infectious disease consultations.

The direct impact of antimicrobial stewardship programs (ASP) and infectious disease (ID) consultations on patients' clinical diagnoses remains unknown. We assessed their influence on improving the diagnostic accuracy of blood culture-positive inpatients at a Japanese cancer center. Our single-center, retrospective observational study was conducted from April 1, 2018 to March 31, 2022 to evaluate two phases: pre-intervention (notification of antimicrobials by the infection control team) and post-intervention (ASP implementation and ID consultation service establishment). There were 42,514 inpatients: 22,096 during the pre-intervention and 20,418 during the intervention periods. A total of 939 blood culture-positive episodes (pre-intervention, n = 434; post-intervention, n = 505) were analyzed. During the pre-intervention period, 28.1% of the patients had an unknown diagnosis, which decreased significantly to 1.2% post-intervention. Furthermore, hepatobiliary tract and other infections increased significantly post-intervention, and the mortality rate due to Staphylococcus aureus infection decreased from 28.6% pre-intervention to 10.4% post-intervention. The trend and level of the total number of culture specimens submitted per 1000 patient days for all culture specimens increased significantly post-intervention. Notably, the two-set rate of monthly blood cultures increased significantly. In conclusion, improving the overall diagnostic process with ASP and ID consultations at cancer centers could lead to the optimization of patient care.

Efficacy and Safety of 5-Day Oral Ensitrelvir for Patients With Mild to Moderate COVID-19: The SCORPIO-SR Randomized Clinical Trial.

Importance: Treatment options for COVID-19 are warranted irrespective of the presence of risk factors for severe disease. Objective: To assess the efficacy and safety of ensitrelvir in patients with mild to moderate COVID-19. Design, Setting, and Participants: This phase 3 part of a phase 2/3, double-blind, placebo-controlled randomized clinical trial was conducted from February 10 to July 10, 2022, with a 28-day follow-up period, at 92 institutions in Japan, Vietnam, and South Korea. Patients (aged 12 to <70 years) with mild to moderate COVID-19 within 120 hours of positive viral test results were studied. Interventions: Patients were randomized (1:1:1) to receive 125 mg of once-daily ensitrelvir (375 mg on day 1), 250 mg of once-daily ensitrelvir (750 mg on day 1), or placebo for 5 days. Main Outcomes and Measures: The primary end point was the time to resolution of the composite of 5 characteristic symptoms of SARS-CoV-2 Omicron infection, assessed using a Peto-Prentice generalized Wilcoxon test stratified by vaccination history. Virologic efficacy and safety were also assessed. Results: A total of 1821 patients were randomized, of whom 1030 (347 in the 125-mg ensitrelvir group, 340 in the 250-mg ensitrelvir group, and 343 in the placebo group) were randomized in less than 72 hours of disease onset (primary analysis population). The mean (SD) age in this population was 35.2 (12.3) years, and 552 (53.6%) were men. A significant difference was observed between the 125-mg ensitrelvir group and the placebo group (P = .04 with a Peto-Prentice generalized Wilcoxon test). The difference in median time was approximately 1 day between the 125-mg ensitrelvir group and the placebo group (167.9 vs 192.2 hours; difference, -24.3 hours; 95% CI, -78.7 to 11.7 hours). Adverse events were observed in 267 of 604 patients (44.2%) in the 125-mg ensitrelvir group, 321 of 599 patients (53.6%) in the 250-mg ensitrelvir group, and 150 of 605 patients (24.8%) in the placebo group, which included a decrease in high-density lipoprotein level (188 [31.1%] in the 125-mg ensitrelvir group, 231 [38.6%] in the 250-mg ensitrelvir group, and 23 [3.8%] in the placebo group). No treatment-related serious adverse events were reported. Conclusions and Relevance: In this randomized clinical trial, 125-mg ensitrelvir treatment reduced the time to resolution of the 5 typical COVID-19 symptoms compared with placebo in patients treated in less than 72 hours of disease onset; the absolute difference in median time to resolution was approximately 1 day. Ensitrelvir demonstrated clinical and antiviral efficacy without new safety concerns. Generalizability to populations outside Asia should be confirmed. Trial Registration: Japan Registry of Clinical Trials Identifier: jRCT2031210350.

Mpox Neutralizing Antibody Response to LC16m8 Vaccine in Healthy Adults.

Mpox Neutralizing Antibody Response to LC16m8 VaccineIn this study of 50 healthy volunteers in Japan, a smallpox vaccine (LC16m8) exhibited a robust neutralizing antibody response against two strains of the mpox virus. With a 94% "take" rate by day 14, seroconversion rates on day 28 were 72 and 70% against the Zr599 and Liberia strains, respectively, decreasing to 30% for both on day 168; no serious adverse events occurred.

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.

Relapse of toxocariasis after completion of four-week treatment with albendazole.

Food-borne toxocariasis caused by the consumption of raw meat or liver has occasionally been reported from East Asia. We treated a 38-year-old Japanese man who was infected with Toxocara in China and underwent a four-week treatment with albendazole. The liver and lung lesions disappeared after the treatment, suggesting that the treatment was successful. One month after the end of the treatment, the patient relapsed, and albendazole was administered again for eight weeks. The patient has remained relapse-free for one year. Although toxocariasis can heal spontaneously, in some cases, such as the present case, the disease relapses even after long-term treatment. In conclusion, different durations of treatment are recommended by various guidelines, and the duration of treatment needs to be modified with each case, considering the response to the treatment.

Successful management of persistent COVID-19 using combination antiviral therapy (nirmatrelvir/ritonavir and remdesivir) and intravenous immunoglobulin transfusion in an immunocompromised host who had received CD20 depleting therapy for follicular lymphoma.

The management of persistent symptomatic coronavirus disease 2019 (COVID-19) infections in immunocompromised patients remains unclear. Here, we present the first case of successful antiviral therapy (nirmatrelvir/ritonavir and remdesivir) in combination with intravenous immunoglobulin (IVIg) in a patient who had received CD20 depleting therapy for follicular lymphoma and experienced recurrent COVID-19 relapses. After the patient received IVIg treatment, the viral load decreased without recurrence. Subsequently, it was found that the anti-spike antibody titer in the administered immunoglobulin was high at 9528.0 binding antibody units/mL. Our case highlights the potential of combination therapy with selective IVIg and antiviral drugs for relapsed immunocompromised COVID-19 patients who have received CD20 depleting therapy.

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.

Trends in Implementation of Loading Dose of Voriconazole from 2010 to 2019 and Influencing Factors of Loading Dose Based on a Japanese Administrative Claim Database: A Retrospective Cohort Study.

A loading dose of voriconazole (VRCZ) is recommended to increase its blood concentration at an early stage. However, the trends in the implementation of the loading dose in VRCZ in Japan has not yet been clarified. In addition, although pharmacists play many important roles in antimicrobial stewardship, the effect of pharmacist intervention on the implementation of a loading dose of VRCZ has not yet been reported. Therefore, this study aimed to clarify the implementation of loading dose of VRCZ and the influencing factors of loading dose. This study used an administrative claims database that included patients who received injectable VRCZ between 2010 and 2019. The implementation of loading doses in the VRCZ was evaluated annually. Multivariate logistic regression analysis was performed to identify the factors influencing loading dose. Overall, 2197 patients were included. The implementation rate of the loading dose remained below 65% throughout the study period. Among medical fees that can be calculated through pharmacist intervention, only the infection prevention and control premium significantly increased the implementation of loading dose of VRCZ (odds ratio: 1.587, 95% confidence interval: 1.053-2.392). In conclusion, antifungal stewardship may have been promoted at medical institutions that established infection prevention and control. In the future, pharmacists will need to intervene more actively from the beginning of VRCZ administration.