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[This corrects the article DOI: 10.3389/fimmu.2025.1624095.].

•Assessed the physical compatibility of reduced glutathione for injection with 44 intravenous drugs during simulated Y-site administration.•Found reduced glutathione for injection to be physically incompatible with 11 of 44 intravenous drugs over a 4-hour period.•Observed immediate formation of a flocculent mixture when combined with acyclovir.•Detected an immediate Tyndall effect when mixed with diazepam, dexmedetomidine hydrochloride, and other intravenous drugs. Reduced glutathione (GSH) is extensively used in clinical therapeutics due to its antioxidative and cytoprotective properties. It is essential in the management of various chronic and acute conditions and serves as an adjunct therapy in oncology. Despite its widespread use, the physical compatibility of GSH with other intravenous drugs during Y-site administration has not been thoroughly investigated, posing risks such as reduced efficacy and adverse reactions. This study fills this critical gap by examining the physical compatibility of GSH with 44 commonly used intravenous drugs in simulated Y-site administration with 0.9% sodium chloride injection (NS) and 5% dextrose injection, aiming to enhance patient safety and clinical outcomes. Simulated Y-site administration was conducted in vitro by mixing 24 mg/mL of GSH with equal volumes of 44 diluted intravenous drugs. Physical compatibility was assessed by observing visual changes, checking for the Tyndall effect, measuring turbidity, and monitoring pH levels at 0, 0.5, 1, 2, and 4 hours post-mixing. Physical compatibility was defined as the absence of color changes, gas evolution, particulate formation, and the Tyndall effect within 4 hours, with turbidity changes of less than 0.5 nephelometric turbidity units from baseline and pH variations of less than 10% from initial values. GSH exhibited physical incompatibility with 11 of the 44 intravenous drugs evaluated, while it remained compatible with 33 drugs over 4 hours. This study reveals that while GSH is physically compatible with the majority of tested intravenous drugs, incompatibilities with 11 drugs under simulated Y-site conditions necessitate rigorous compatibility testing prior to co-administration in clinical settings. These findings emphasize the importance of such testing to prevent potential treatment failures and adverse effects. Further research is needed to explore chemical stability and therapeutic efficacy in clinical settings, ensuring the safe and effective use of GSH in medical treatments.

Background In China, enterovirus 71 (EV71) is the major etiological agents of hand foot mouth disease that poses severe risks to children’s health. Since 2015, three inactivated EV71 vaccines have been approved for use. Previous studies indicated the high willingness of EV71 vaccination in eastern China. However, few studies have assessed coverage and utilization patterns of EV71 vaccine in China. Methods Children born during 2012–2018 were sampled and their records were abstracted from Ningbo childhood immunization information management system. Descriptive statistics characterized the study population and assessed coverage and timeliness for EV71 vaccination. Simultaneous administration patterns as well as type of EV71 vaccine used were also evaluated. Bivariate and multivariable analysis was used to examine the relationship of socio-demographic characteristics with vaccination coverage and timeliness. Results Of 716,178 children living in Ningbo. One hundred seventy-two thousand two hundred thirty-six received EV71 vaccine with a coverage rate of 24.05% and only 8.61% received vaccination timely. 21.97% of children received the complete two dose EV71 series but only 6.49% completed timely. Vaccination coverage and timeliness increased significantly from 2012 birth cohort to 2018 birth cohort. Relatively higher coverage and timeliness were observed in resident children, Inner districts, high socioeconomic areas and large-scaled immunization clinics. Of 329,569 doses of EV71 vaccine, only 5853(1.78%) doses were administered at the same day as other vaccines. Conclusions There is a need for increasing EV71 vaccination coverage and timeliness as well as eliminating disparities among different populations. Our study highlights the importance of simultaneous administration to increasing coverage and timeliness of EV71 vaccination.

The inactivated quadrivalent influenza vaccine (IIV4) and the 23-valent pneumococcal polysaccharide vaccine (PPSV23) are widely administered. However, there was limited clinical evidence on the immunogenicity and safety of administration of the two vaccines in individuals with chronic diseases, especially concerning simultaneous administration. A total of 480 participants aged ≥60 years were randomly assigned to receive simultaneous or separate administration of IIV4 and PPSV23 and categorized into the Chronic Disease group or Healthy group based on their baseline health status. Blood samples were drawn before and 28 days after each vaccination to test the antibodies against all four influenza virus strains and 23 pneumococcus serotypes. The geometric mean titer ratios (Chronic Disease group/Healthy group) of influenza antibodies ranged from 1.04 to 1.37 in the whole population and from 1.02 to 1.39 in the simultaneous administration population. The geometric mean concentration ratios of pneumococcal antibodies ranged from 0.87 to 1.12 in the whole population and from 0.97 to 1.33 in the simultaneous administration population. All ratios met the criteria for non-inferiority. The rate of adverse events was 0.96% in the Chronic Disease group and 1.47% in the Healthy group, with most events being mild (grade 1). No serious adverse events were observed. The immunogenicity and safety profiles of IIV4 and PPSV23, particularly when administered simultaneously, in individuals with chronic diseases were comparable to those in healthy individuals, supporting the vaccination strategy of IIV4 and PPSV23 in chronic disease population.

To evaluate the immunogenicity and safety of simultaneous administration of the enterovirus 71 (EV71) vaccine with the measles and rubella (MR) combined vaccine. In this phase 4, randomized, open-label and noninferiority study, a total of 680 infants aged 8 months were enrolled and assigned to the simultaneous administration group (infants received the first dose of EV71 vaccine and MR vaccine on Day 0, and the second dose of EV71 vaccine on Day 28), or the separate administration groups (EV71 group: infants received two doses of EV71 vaccine on Day 0 and Day 28, respectively; MR group: infants received MR vaccine on Day 0). Blood sample was obtained on Day 0 and Day 56 to measure antibody responses to each of the antigens in terms of antibody titer or concentration, respectively. Local and systemic adverse reactions (ARs) and other adverse events (AEs) following each dose were monitored and compared among groups. After vaccination, simultaneous administration group showed similar seroconversion rates of antibody against EV71(97.9%), measles (97.4%), and rubella (94.3%) compared to EV71 group (99.6% for anti-EV71) or MR group (98.4% for anti-measles and 98.9% for anti-rubella, respectively). Noninferiority was demonstrated for all antibodies as the lower limits of two-sided 97.5% confidence intervals (CIs) of the difference in seroconversion rates between simultaneous administration group and separate administration groups were above the predefined margin of −10%. Additionally, the adverse reaction rates were comparable among groups (54.4% in the simultaneous group versus 43.9% in the MR group versus 52.6% in the EV71 group). Antibody responses induced by simultaneous administration of EV71 vaccine with MR vaccine were robust and noninferior to those by single administration alone. Like the previous findings by single administration alone, simultaneous administration demonstrated comparable reactogenicity and safety profiles.

This case–control study investigated immune thrombocytopenic purpura (ITP) risk following live, inactivated, and simultaneous vaccination, with a focus on infants aged < 2 years. We matched case patients with ITP to one or two control patients with other diseases by institution, hospital visit timing, sex, and age. We calculated McNemar’s pairwise odds ratios (ORs [95% confidence interval]) with 114 case–control pairs. The case group had 27 (44%) males and 22 (35%) infants, and the control group included 49 (43%) males and 42 (37%) infants. For all age groups, the McNemar’s OR for ITP occurrence was 1.80 (0.54–6.84, p = 0.64) for all vaccines. Among infants, these were 1.50 (0.17–18.0, p = 0.50) for all vaccines, 2.00 (0.29–22.1, p = 0.67) for live vaccines, and 1.00 (0.01–78.5, p = 0.50) for inactivated vaccines. Sex-adjusted common ORs for simultaneous vaccination were 1.52 (0.45–5.21, p = 0.71) for all vaccines, 1.83 (0.44–7.59, p = 0.40) for inactivated vaccines only, and 1.36 (0.29–6.30, p = 0.69) for mixed live and inactivated vaccines. In infants, these were 1.95 (0.44–8.72, p = 0.38), 1.41 (0.29–6.94, p = 0.67) and 2.85 (0.43–18.9, p = 0.28), respectively. These limited data suggest no significant ITP risk following vaccinations or simultaneous vaccination in any age group, including infants.

This study tested the hypothesis that the immunogenicity and safety of the simultaneous administration of enterovirus 71 (EV71) vaccine (dose 1) with recombinant hepatitis B vaccine (HepB) on day 1 and EV71 vaccine (dose 2) with group A meningococcal polysaccharide vaccine (MenA) on day 30 is not inferior to separate administration of each vaccine. The study was designed as a randomized, open-label, noninferiority trial. A total of 775 healthy infants aged 6 months were randomly assigned in a ratio of 1:1:1 to receive simultaneous administration of EV71 vaccine (dose 1) and HepB on day 1 and EV71 vaccine (dose 2) and MenA on day 30 (the SI group); administration of doses 1 and 2 of EV71 vaccine on days 1 and 30, respectively (the SE1 group); or administration of HepB and MenA on days 1 and 30, respectively (the SE2 group). According to the per protocol set, antibody responses against EV71, hepatitis B virus (HBV), and group A meningococcal polysaccharide were similar regardless of administration schedule. With the non-inferiority margin setting at 10%, the seroconversion rates of the three pathogens in the SI group (100% [98.25, 100], 44.84% [38.20, 51.63] and 27.83% [21.91, 34.38]) were not inferior to those in SE1 or SE2 group (100% [98.31, 100], 44.35% [37.82, 51.02] and 29.17% [23.20, 35.72], respectively). Frequencies of adverse reactions to each vaccination regimen were comparable (60.62% in the SI group vs 52.33% in the SE1 group and 56.98% in the SE2 group; P = .16). Simultaneous administration of combined EV71 vaccine with HepB and MenA has noninferior immunogenicity and safety, compared with separate administration of these vaccines. NCT03274102.

•Implement simultaneous administration of recommended childhood vaccines.•Evaluate potentially achievable vaccination coverage for 4+DTaP, 4+PCV, Hib-FS.•Potentially achievable vaccination coverage might increase significantly, P<0.001.•Potentially achievable coverage would achieve the 90% target across the USA.•In the USA, 51% of the states could reach the 90% target for the 3 vaccine series. Routine administration of all age-appropriate doses of vaccines during the same visit is recommended for children by the National Vaccine Advisory Committee (NVAC) and the Advisory Committee on Immunization Practices (ACIP). Evaluate the potentially achievable vaccination coverage for ≥4 doses of diphtheria and tetanus toxoids and acellular pertussis vaccine (4+DTaP), ≥4 doses of pneumococcal conjugate vaccine (4+PCV), and the full series of Haemophilus influenzae type b vaccine (Hib-FS) with simultaneous administration of all recommended childhood vaccines. Compare the potentially achievable vaccination coverage to the reported vaccination coverage for calendar years 2001 through 2013; by state in the United States and by selected socio-demographic factors in 2013. The potentially achievable vaccination coverage was defined as the coverage possible for the recommended 4+DTaP, 4+PCV, and Hib-FS if missed opportunities for simultaneous administration of all age-appropriate doses of vaccines for children had been eliminated. Compared to the reported vaccination coverage, the potentially achievable vaccination coverage for 4+DTaP, 4+PCV, and Hib-FS could have increased significantly (P<0.001), the vaccination coverage would have achieved the 90% target of Healthy People 2020 for the three vaccines beginning in 2005, 2008, and 2011 respectively. In 2013, the potentially achievable vaccination coverage increased significantly across all selected socio-demographic factors, potentially achievable vaccination coverage would have reached the 90% target for more than 51% of the states in the United States. The findings in this study suggest that fully utilization of all opportunities for simultaneous administration of all age-eligible childhood doses of vaccines during the same vaccination visit is a critical strategy for achieving the vaccination coverage target of Healthy People 2020. Encouraging providers to deliver all recommended vaccines that are due at each visit by implementing client reminder and recall systems might decrease missed opportunities for simultaneous administration of childhood vaccines.

Background: The aim of this study was to investigate the immunogenicity and safety of the enterovirus 71 vaccine (EV71 vaccine) administered alone or simultaneously. Methods: A multi-center, open-label, randomized controlled trial was performed involving 1080 healthy infants aged 6 months or 8 months from Shandong, Shanxi, Shaanxi, and Hunan provinces. These infants were divided into four simultaneous administration groups and EV71 vaccine separate administration group. Blood samples were collected from the infants before the first vaccination and after the completion of the vaccination. This trial was registered in the Clinical Trials Registry (NCT03519568). Results: A total of 895 were included in the per-protocol analysis. The seroconversion rates of antibodies against EV71 in four simultaneous administration groups (98.44% (189/192), 94.57% (122/129), 99.47% (187/188) and 98.45% (190/193)) were non-inferior to EV71 vaccine separate administration group (97.93% [189/193]) respectively. Fever was the most common adverse event, the pairwise comparison tests showed no difference in the incidence rate of solicited, systemic or local adverse events. Three serious adverse events related to the vaccination were reported. Conclusions: The evidence of immunogenicity and safety supports that the EV71 vaccine administered simultaneously with vaccines need to be administered during the same period of time recommended in China.

•Missed opportunities for simultaneous administration of the fourth dose of DTaP.•Prevalence rates vary 5.7–9.0% in years, and 3.3–22.9% in domains.•Timeliness of the first 3 doses of DTaP are significant and modifiable risk factors.•Adjusted prevalence ratios are 1.7, 1.6, 3.2 respectively and all P-value<0.01. Simultaneous administration of all age-appropriate doses of vaccines is an effective strategy for raising vaccination coverage. Vaccination coverage for ≥4 dose of DTaP (diphtheria, tetanus toxoids, and acellular pertussis vaccine) among children 19–35months in the United States has not reached the Healthy People 2020 target of 90%. Risk factors for missed opportunities for simultaneous administration of the fourth dose of DTaP have not been investigated. A missed opportunity for simultaneous administration of the fourth dose of DTaP is defined as the failure to administer an age-eligible fourth dose of DTaP, and during the same age-eligible period for the fourth dose of DTaP other recommended and age-appropriate doses of vaccines are given to children. This study used 2001–2014 National Immunization Survey data to describe the trend in missed opportunities for simultaneous administration of the fourth dose of DTaP from 2001 through 2014, assess the prevalence of children who missed opportunities for simultaneous administration of the fourth dose of DTaP by selected factors, and recognize significant risk factors for missed opportunities for simultaneous administration of the fourth dose of DTaP. From 2001 to 2014, the prevalence of missed opportunities for simultaneous administration of the fourth dose of DTaP among children 19–35months in the United States ranged from 5.7% to 9.0%; across 13 factors considered, the prevalence of missed opportunities varied from 3.3% to 22.9%. Children who were late in receiving the first to third dose of DTaP had significantly higher prevalence of missed opportunities for simultaneous administration of the fourth dose of DTaP than children who received these doses on-time, with adjusted prevalence ratios for late vs. on-time of 1.7, 1.6, and 3.2, and all P-value<0.01. Improving on-time vaccination of the third dose of DTaP could substantially reduce missed opportunities for simultaneous administration of the fourth dose of DTaP.