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Data Availability | The datasets generated and/or analysed during the current study are available from the corresponding author on reasonable request. | PMC10173559 | ||
Declarations | PMC10173559 | |||
Competing interests | The authors declare that they have no competing interests | PMC10173559 | ||
Ethics approval and consent to participate | This study was reviewed and approved by the Makerere University School of Public Health’s Research and Ethics Committee (Protocol #: 825) and cleared by the Uganda National Council for Science and Technology (UNCST). All participants provided written informed consent prior to participation in the study. All study procedures were performed in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. | PMC10173559 | ||
Consent for publication | Not applicable. | PMC10173559 | ||
References | PMC10173559 | |||
Subject terms | PD-L1-positive esophageal squamous cell carcinoma, ESCC | OESOPHAGEAL SQUAMOUS CELL CARCINOMA | First-line systemic therapeutic options for advanced esophageal squamous cell carcinoma (ESCC) are limited. In this multicenter, double-blind phase 3 trial, a total of 551 patients with previously untreated, locally advanced or metastatic ESCC and PD-L1 combined positive score of ≥1 were randomized (2:1) to receive serplulimab (an anti-PD-1 antibody; 3 mg/kg) or placebo (on day 1), plus cisplatin (50 mg/mThe combination of anti-PD-1 treatment with cisplatin and 5-fluorouracil in patients with previously untreated, PD-L1-positive esophageal squamous cell carcinoma improved progression-free survival and overall survival. | PMC9941045 |
Main | esophageal cancer, death, ESCC | OESOPHAGEAL CANCER, ESOPHAGEAL SQUAMOUS CELL CARCINOMA | Esophageal squamous cell carcinoma (ESCC) is the predominant histological subtype of esophageal cancer and accounts for approximately 84% of all esophageal cancer casesSystemic chemotherapy remains the backbone of treatment of unresectable or metastatic ESCC. Although 5-fluorouracil (5-FU) or paclitaxel plus cisplatin has been widely used in the first-line setting, programmed cell death protein 1 (PD-1) inhibitors in combination with chemotherapy showed improved efficacy compared with chemotherapy alone in phase 3 trialsAdvances in immunotherapy have uncovered programmed cell death protein ligand 1 (PD-L1) as a potential therapeutic target and biomarker for patients with ESCC. PD-L1 overexpression was observed in up to 40% of ESCCSerplulimab (HLX10) is a fully humanized, selective immunoglobulin G4 monoclonal antibody against PD-1 receptor | PMC9941045 |
Results | PMC9941045 | |||
Patients and treatment | A total of 976 patients were screened between 19 June 2019 and 17 December 2021, and 551 of them were randomly assigned to serplulimab plus chemotherapy ( | PMC9941045 | ||
Efficacy | DISEASE PROGRESSION | At the data cutoff date, 219 (60%) patients in the serplulimab plus chemotherapy group and 129 (70%) in the placebo plus chemotherapy group had disease progression or had died. At the time of this final PFS analysis, serplulimab plus chemotherapy met the criteria for superiority in prolonging PFS over placebo plus chemotherapy. The median PFS assessed by the blinded independent radiological review committee (IRRC) was 5.8 months (95% confidence interval (CI), 5.7–6.9 months) in the serplulimab plus chemotherapy group and 5.3 months (95% CI, 4.3–5.6 months) in the placebo plus chemotherapy group (stratified hazard ratio (HR), 0.60; 95% CI, 0.48–0.75; | PMC9941045 | |
Discussion | esophageal cancer, tumor, death, ESCC, treatment-related adverse | TUMOR, OESOPHAGEAL CANCER, ADVERSE EVENTS, SOLID TUMORS, MICROSATELLITE INSTABILITY, SECONDARY, LUNG METASTASES, CPS, METASTASES | In this double-blind, placebo-controlled, randomized phase 3 study, we evaluated the efficacy and safety of first-line serplulimab plus chemotherapy versus placebo plus chemotherapy in patients with locally advanced or metastatic, PD-L1-positive (CPS ≥ 1) ESCC. In our prespecified final analysis for PFS and interim analysis for OS, the addition of serplulimab to cisplatin and 5-FU chemotherapy resulted in a significant improvement in both efficacy endpoints. In addition, the safety profile of serplulimab plus chemotherapy was manageable. Other planned secondary endpoints that were not reported in this manuscript but that will be reported in the future are PFS, ORR and DOR assessed by IRRC and by investigators based on immune-response evaluation criteria in solid tumors (iRECIST), pharmacokinetics and immunogenicity of serplulimab, quality-of-life assessment, the relationship between efficacy and microsatellite instability and the relationship between efficacy and tumor mutation burden. In this study, we demonstrate an improvement in survival with the addition of PD-1 blockade to chemotherapy administered every 2 weeks in a solely PD-L1-positive population with advanced ESCC.Anti-PD-1 antibodies have changed the systemic treatment of advanced esophageal cancer in recent years. In the first-line setting, results from five previous phase 3 studies showed that PD-1 inhibitors plus chemotherapy provided significant improvement in OS over chemotherapy alone in patients with advanced ESCCCisplatin plus 5-FU is commonly adopted in the first-line treatment of advanced ESCC, and different schedules for drug delivery exist for this combination. The dose intensities of cisplatin and 5-FU in our 2-week schedule were similar to those in the KEYNOTE-590 and CHECKMATE-648 trials, which used the same chemotherapy backboneThe expression of PD-L1, assessed with the 22C3, 28-8 or SP263 antibodies, has been considered a potential biomarker for efficacy in patients with advanced ESCC treated with anti-PD-1 antibodiesSerplulimab combined with cisplatin and 5-FU delivered every 2 weeks was well tolerated in our trial. The incidences of grade 3 or higher treatment-related adverse events, serious adverse events and adverse events leading to death were similar between the two treatment groups. A higher incidence of treatment-related adverse events leading to treatment discontinuation was observed in patients treated with serplulimab plus chemotherapy; this was probably related to the immune-related adverse events induced by serplulimab and a longer treatment duration in this group. Similar findings have also been reported in other controlled trials of PD-1 inhibitors in combination with chemotherapy in patients with ESCCOur study had some limitations. First, we included only patients from China; however, our results might be extrapolated to patients with ESCC outside China, as no differences were noted in terms of survival between Asian and non-Asian patients in the CHECKMATE-648 study. In addition, the presence of liver or lung metastases at baseline was not considered in stratification. These common visceral metastases are representative of tumor burden and may affect treatment outcomes. Furthermore, biomarkers other than PD-L1 expression were not investigated in our current analysis.In conclusion, first-line serplulimab in combination with chemotherapy significantly improved PFS and OS in patients with previously untreated, PD-L1-positive, locally advanced or metastatic ESCC, compared with chemotherapy alone, with a manageable safety profile. | PMC9941045 |
Methods | PMC9941045 | |||
Ethics statement | Cancer Center/Cancer | The study was performed in accordance with the Declaration of Helsinki and the International Conference on Harmonisation Good Clinical Practice guidelines. The study protocol was approved by the institutional review boards or ethics committees of all participating centers (the ethics committee of the leading clinical center was the Ethics Committee of National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College). All patients provided written informed consent before participating in the study. Patients received compensation as described in detail in the informed consent form. | PMC9941045 | |
Study design and participants | ASTRUM-007 was a randomized, placebo-controlled, double-blind, phase 3 clinical study conducted at 70 hospitals in China (Supplementary Table | PMC9941045 | ||
Randomization and masking | CPS, DISEASE | Eligible patients were randomly assigned (2:1) using an integrated web response system to receive serplulimab plus chemotherapy or placebo plus chemotherapy. Randomization was stratified by PD-L1 expression level (CPS ≥ 10 versus CPS < 10), age (≥65 years versus <65 years) and disease status (locally advanced versus distantly metastatic). Patients, investigators and the sponsor’s study team were masked to group assignment. | PMC9941045 | |
Procedures | Cancer | ADVERSE EVENT, ADVERSE EVENT, CANCER | Patients received serplulimab or placebo (3 mg kgTumor imaging was scheduled once every 6 weeks for 48 weeks from randomization and every 12 weeks thereafter. Response was assessed according to RECIST v1.1 by the blinded IRRC and the investigators locally. During follow-up, patients were contacted every 12 weeks to assess survival. Adverse events and laboratory abnormalities were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (v.4.03). Additional details regarding the study treatments, including dose interruptions and modifications, are provided in the study protocol. | PMC9941045 |
Outcomes | death | DISEASE PROGRESSION | The dual primary endpoints were PFS (time from randomization to first disease progression or death) assessed by the IRRC in accordance with RECIST v1.1 and OS (time from randomization to death due to any cause). Secondary endpoints included IRRC-assessed PFS using iRECIST | PMC9941045 |
Statistical analysis | REGRESSION, EVENTS | The planned sample size was 540 patients, with 339 PFS events and 388 OS events needed to achieve a power of 80% to show an HR of 0.68 for PFS at a one-sided α level of 0.005 and an HR of 0.73 for OS at a one-sided α level of 0.02 for comparison between the serplulimab plus chemotherapy group and the placebo plus chemotherapy group. The primary efficacy analyses were conducted in the ITT population. All randomized patients who received at least one dose of study medication were included in the analysis of safety. The Kaplan–Meier method was used to estimate OS, PFS and DOR. The reverse Kaplan–Meier method was used to estimate the median follow-up duration. Between-group differences in OS and PFS were assessed using the stratified log-rank test and the Cox proportional hazards model. The Schoenfeld residual test was planned to check the proportional hazard assumption. Differences in ORR were assessed using the Cochran–Mantel–Haenszel test and logistic regression.The statistical analysis plan specified one interim analysis and a final analysis of OS. The interim analysis of OS was planned to be performed during the final analysis of PFS, when approximately 339 IRRC-assessed PFS events had been observed in the ITT population.The protocol prespecified two primary hypotheses that were tested in parallel: (1) the superiority of serplulimab plus chemotherapy over placebo plus chemotherapy for PFS (assessed by the IRRC in accordance with RECIST v1.1) in all randomized patients; and (2) the superiority of serplulimab plus chemotherapy over placebo plus chemotherapy for OS in all randomized patients. The study was considered successful if serplulimab plus chemotherapy was superior to placebo plus chemotherapy for any primary endpoint. The threshold for statistical significance was 0.01 (two-sided) for the final log-rank analysis of PFS and 0.01 (two-sided) for the interim log-rank analysis of OS (adjusted according to the actual 266 OS events and O’Brien–Fleming-like α-spending function). An O’Brien–Fleming-like α-spending function (Lan–DeMets approximation) was used to control the overall type I error rate. The significance level for each analysis could be modified based on the actual number of PFS and OS events reached at the analytical time point.The independent data monitoring committee confirmed that the study met the specified efficacy endpoints after reviewing the results of the final analysis of PFS and the interim analysis of OS conducted by an unblinded external statistician. The trial is continuing in order to evaluate outcomes with additional follow-up. All data reported here are based on the interim analysis, with a data cutoff date of 15 April 2022. The statistical analysis plan is available in the Supplementary Information. Sample size calculation and statistical analyses were done using SAS (v9.4). This trial is registered with ClinicalTrials.gov (NCT03958890). | PMC9941045 | |
Reporting summary | Further information on research design is available in the | PMC9941045 | ||
Online content | Any methods, additional references, Nature Portfolio reporting summaries, source data, extended data, supplementary information, acknowledgements, peer review information; details of author contributions and competing interests; and statements of data and code availability are available at 10.1038/s41591-022-02179-2. | PMC9941045 | ||
Supplementary information |
Supplementary Table 1, study protocol and statistical analysis plan.Reporting Summary | PMC9941045 | ||
Extended data | PMC9941045 | |||
Extended data | is available for this paper at 10.1038/s41591-022-02179-2. | PMC9941045 | ||
Supplementary information | The online version contains supplementary material available at 10.1038/s41591-022-02179-2. | PMC9941045 | ||
Acknowledgements | This study was funded by Shanghai Henlius Biotech, Inc. We thank the patients, their families and the study personnel involved in this trial. We thank the clinical study team (clinical operations, Lu Luo, Guiyu Yang and Haoyu Yu; statistics, Xiao Qi and Jianchen Cheng) and Wenjie Zhang from Shanghai Henlius Biotech, Inc, for their support in study execution, study design, data acquisition, statistical analyses and manuscript revisions. We thank Shiqi Zhong and Chen Hu from Shanghai Henlius Biotech, Inc. for their assistance in writing this manuscript. The study was designed by the lead principal investigator (J.H.) and Shanghai Henlius Biotech, Inc. Shanghai Henlius Biotech, Inc. contributed to data collection and data interpretation in collaboration with all investigators, funded data analyses and participated in manuscript preparation with all authors. | PMC9941045 | ||
Author contributions | J.H. and Q.W. contributed to the conception, design and planning of the study. All authors contributed to the acquisition of data. B.Z., J.H., Y.S. and Q.W. contributed to the writing of the manuscript, and all authors contributed to critical review and revision of the manuscript. J.H. had full access to all of the data in the study and had final responsibility for the decision to submit for publication. | PMC9941045 | ||
Peer review | PMC9941045 | |||
Data availability | huangjingwg@163.com, Cancer | CANCER | All requests for data will be reviewed by the leading clinical site (National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College) and the sponsor (Shanghai Henlius Biotech, Inc) to verify whether the request is subject to any intellectual property or confidentiality obligations. Requests for access to the patient-level data from this study can be submitted via email to J.H. (huangjingwg@163.com) with detailed proposals for use of information, and responses to such requests can be expected within 1 month. A signed data access agreement with the sponsor is required before accessing shared data. | PMC9941045 |
Code availability | No custom code was used for statistical analysis in this study. | PMC9941045 | ||
Competing interests | ONCOLOGY | Y.K., J.L., Q.W. and J.Z. are employees of Shanghai Henlius Biotech, Inc. J.H. has served a consulting or advisory role for Merck Sharp & Dohme Oncology and Roche. All other authors declare no competing interests. | PMC9941045 | |
References | PMC9941045 | |||
Introduction | Edited by: Mrinmoy Sanyal, Stanford University, United StatesReviewed by: Lei Li, Oracle, Australia; Larry Ellingsworth, Novavax, Inc., United States†These authors have contributed equally to this workThe SARS-CoV-2 Omicron variant has become the dominant SARS-CoV-2 variant and exhibits immune escape to current COVID-19 vaccines, the further boosting strategies are required. | PMC10585368 | ||
Methods | ADENOVIRUS | We have conducted a non-randomized, open-label and parallel-controlled phase 4 trial to evaluate the magnitude and longevity of immune responses to booster vaccination with intramuscular adenovirus vectored vaccine (Ad5-nCoV), aerosolized Ad5-nCoV, a recombinant protein subunit vaccine (ZF2001) or homologous inactivated vaccine (CoronaVac) in those who received two doses of inactivated COVID-19 vaccines. | PMC10585368 | |
Results | SARS-CoV-2-specific mucosal IgA | The aerosolized Ad5-nCoV induced the most robust and long-lasting neutralizing activity against Omicron variant and IFNg T-cell response among all the boosters, with a distinct mucosal immune response. SARS-CoV-2-specific mucosal IgA response was substantially generated in subjects boosted with the aerosolized Ad5-nCoV at day 14 post-vaccination. At month 6, participants boosted with the aerosolized Ad5-nCoV had remarkably higher median titer and seroconversion of the Omicron BA.4/5-specific neutralizing antibody than those who received other boosters. | PMC10585368 | |
Discussion | Our findings suggest that aerosolized Ad5-nCoV may provide an efficient alternative in response to the spread of the Omicron BA.4/5 variant. | PMC10585368 | ||
Clinical trial registration | PMC10585368 | |||
Introduction | More than 6.8 million people have died from COVID-19 worldwide since the start of the pandemic (More than 100 countries worldwide have already issued recommendations on booster or additional vaccination (In China, seven COVID-19 vaccines have been authorized for use, including five inactivated vaccines, an adenovirus-vectored vaccine (Ad5-nCoV, Convidecia) and a recombinant protein subunit vaccine (ZF2001, Zifivax). These vaccines have been shown to be efficacious in preventing mild to severe COVID-19 (Booster vaccination strategies based on inactivated vaccine priming have been well studied, and heterologous vaccination regimens induce immune responses that are superior to those induced by homologous regimens (To optimize the booster vaccination regimen in persons who have received two doses of inactivated vaccines in China, we performed a head-to-head immunological comparison of the COVID-19 vaccines available in China, including intramuscular Ad5-nCoV, aerosolized Ad5-nCoV, a recombinant protein subunit vaccine (ZF2001) and homologous CoronaVac booster administration in inactivated vaccine-primed recipients who were vaccinated 6 months prior. | PMC10585368 | ||
Materials and methods | PMC10585368 | |||
Study design | This study was a non-randomized, open-label and parallel-controlled phase 4 trial (ChiCTR2200057278). 904 eligible participants were randomly assigned to four groups using computer-generated random numbers in SPSS, to receive one dose of Ad5-nCoV via intramuscular injection (Ad5-nCoV-IM, 5×10 | PMC10585368 | ||
Vaccines | All COVID-19 vaccines in this study were developed based on the SARS-CoV-2 wild-type strain (Wuhan-Hu-1 strain) isolated in December 2019. Ad5-nCoV (Convidecia) is a replication-defective human type 5 adenovirus-vectored vaccine, encoding the full-length Spike gene of the Wuhan-Hu-1 strain (YP_009724390) ( | PMC10585368 | ||
RBD-binding IgG assay | SECONDARY | RBD-binding IgG antibodies in the heat-inactivated human serum samples and the culture supernatant of PBMCs stimulated for 4 days with R848 + IL-2 were detected with an RBD-binding IgG ELISA kit (Beijing, Kewei). Briefly, diluted samples and a reference standard were added in duplicate to rSARS-CoV-2 RBD-precoated wells and incubated for 30 min at 37°C. The microplates were washed, and a horseradish peroxidase (HRP)-conjugated goat anti-human IgG secondary antibody was added to bind the RBD-bound human antibodies. After 30 min of incubation, the microplates were washed, and TMB chromogenic substrate was added to generate a colorimetric signal for 10 min. A stop solution was added to stop color development, and the signal was read on a microplate reader. The total anti-RBD IgG antibody levels were quantitated in ELISA units (EU) ml | PMC10585368 | |
Coronavirus-specific saliva IgA assay | IgA | CORONAVIRUS | Saliva samples were collected by centrifugation after having each subject spit about 2 mL of saliva into a disposable saliva sample collector (HUAXIA Medical Equipment). Coronavirus-specific IgA was tested with a SARS-CoV-2 specific (COVID-19 Coronavirus Panel 2) Mesoscale Discovery (MSD) immunoassay. According to the manufacturer’s instructions, plates were blocked, washed, and incubated with diluted saliva samples. After incubation with the detection antibody, plates were read on a Meso QuickPlex instrument. IgA concentrations were showed in arbitrary units (AU) per ml as calculated from a standard curve supplied with the kit. To minimize the variability of mucosal sampling, saliva samples were normalized via an enzyme-linked immunosorbent assay for quantitative detection of human IgA using a commercial kit (Invitrogen) as described previously ( | PMC10585368 |
Pseudotype-based neutralization assays | The generation of SARS-CoV-2 Pseudoviruses was performed using the human immunodeficiency virus (HIV) pseudotyped virus production system (Neutralizing activity in each sample was measured with a serial dilution approach as Nie et al. reported ( | PMC10585368 | ||
RBD-ACE2 competitive binding assay | RBD | VIRUS | The RBD neutralizing antibody against the different SARS-CoV-2 variants was evaluated using a commercial ELISA kit (Vazyme) by a surrogate virus neutralization test (sVNT). Sera are serially diluted by 3-fold from 1:5 to 1:1215 or 1:10935 with horseradish peroxidase-labeled recombinant RBD (HRP-RBD) protein and incubated at 37 °C for 30 minutes. HRP-RBD without the serum were added in duplicated in each plate as the negative control. Then 100 μl of dilution mixture was transferred to the corresponding wells of microplate that precoated hACE2 protein. After the incubation at 37 °C for 20 minutes, each well was washed with 350μl of wash buffer for 4 times. 100 μl of TMB substrate was added and incubated for 15 minutes at 37 °C and 100 μl of stop solution was used to stop the reaction, immediately followed by the plate reading at 450nm. The antibody titer was calculated as the reciprocal of the dilution for which the OD value was reduced by 50% of that of the negative control (IC | PMC10585368 |
Spike-specific IgG ELISpot assays | Spike-specific IgG ELISpot assays were performed on R848- and IL-2-activated PBMCs with a human IgG ELISpot Kit (Mabtech). Briefly, fresh PBMCs were activated with a mixture of R848 at 1 μg ml | PMC10585368 | ||
IFNγ ELISpot assays | STERILE | IFNγ ELISpot assays were performed with fresh PBMCs and a human IFNγ ELISpot Kit (Mabtech) following the manufacturer’s instructions. Tests were performed in duplicate. The precoated ELISpot plates were washed with sterile PBS and blocked with RPMI 1640 medium containing 10% fetal bovine serum and 1× penicillin–streptomycin solution (Gibco) for at least 30 min at room temperature. Fresh PBMCs were added at 2 × 10 | PMC10585368 | |
Statistical analysis | All analyses of participant samples were conducted using GraphPad Prism 8.0.2 or SAS 9.4. Levels of antibodies against SARS-CoV-2 are presented as the median concentration or median titer with IQR. Spike-specific IgG spots and IFNγ responses are depicted as the median with IQR. Categorical data were analyzed by the χ | PMC10585368 | ||
Results | PMC10585368 | |||
Baseline characteristics of the participants | In this study, 904 subjects who received two doses of inactivated vaccine 6 months prior were assigned to 4 groups for booster vaccination (Trial profile.Baseline characteristics of the participants.Data are n (%) or median. Seropositivity for neutralizing antibody against SARS-CoV-2 from a subset of participants in each group before receiving a booster vaccination at day 0 is defined as a detectable neutralizing antibody titer ≥ 1:30. | PMC10585368 | ||
SARS-CoV-2-specific serum IgG and mucosal IgA responses | Concentrations of anti-SARS-CoV-2 IgG and IgA antibodies were assessed before and after the boost. (Wild-type SARS-CoV-2 RBD-specific binding antibody responses. The level of saliva IgA at day 0 and 14 after boost was also measured to evaluate the mucosal immune response induced by different vaccines. An obvious increase in IgA response to spike at day 14 was observed in intramuscular Ad5-nCoV (2.68-fold, p<0.001), aerosolized Ad5-nCoV (2.59-fold, p<0.001) and ZF2001 (1.33-fold, p=0.0027) recipients compared with that in CoronaVac recipients (These data suggest that heterologous boosting with Ad5-nCoV via different routes can elicit significantly higher RBD-specific IgG levels than ZF2001 or CoronaVac, and the aerosolized Ad5-nCoV induced a distinct mucosal immune response. | PMC10585368 | ||
Pseudotyped SARS-CoV-2 neutralizing antibody responses | Before booster vaccination, only 6.3%~11.8% of participants had a weak wild-type pseudovirus neutralizing antibody (PNAb) titer. Generation of PNAb against wild-type SARS-CoV-2 was significantly increased after booster vaccination in all groups (Pseudotyped SARS-CoV-2 neutralizing antibody responses. Similar kinetics were observed for the PNAb response against the Omicron BA.1 variant (The neutralization activity against new-emerging Omicron subvariants including BA.4/5, BQ.1.1, XBB and CH.1.1 was further evaluated ( | PMC10585368 | ||
SARS-COV-2 surrogate virus neutralization antibody response | The breadth and magnitude of neutralizing antibody responses to various SARS-CoV-2 variants were investigated via an SARS-CoV-2 Surrogate Virus Neutralization Test (sVNT) based on the RBD-ACE2 competitive binding assay. In all the groups, the better antibody responses were against wild-type strain, Alpha and Delta variants, and the worst were against Omicron variants. Ad5-nCoV-IH booster vaccination elicited most potent cross-reactivity neutralizing antibody responses in wild-type, Alpha, Beta, Delta, Omicron BA.1, BA.2 and BA.4/5 variants, followed with Ad5-nCoV-IM, ZF2001 and CoronaVac booster vaccination at day 28 and month 6 post-vaccination (SARS-CoV-2 sVNT neutralizing antibody responses. | PMC10585368 | ||
Spike-specific IgG B-cell responses | To further investigate the ability of the boosters to induce antigen-specific B-cell responses, spike-specific IgG spots were detected at baseline and at 28 days and 6 months after booster vaccination in R848-activated peripheral blood mononuclear cells (PBMCs) (Wild-type SARS-CoV-2 spike-specific IgG B-cell responses. | PMC10585368 | ||
Spike-specific IFNγ responses | Spike-specific IFNγ responses were detected at days 0, 14, 28 and month 6 after booster vaccination to determine the T-cell responses (SARS-CoV-2 spike-specific IFNγ ELISpot responses. | PMC10585368 | ||
Discussion | T-cell immunity, infection, dimer vaccine | INFECTION | In China, where more than 95% of individuals vaccinated against COVID-19 received inactivated vaccines, we evaluated the immunogenicity of homologous and heterologous boosters in adults who received prime vaccination with two doses of the inactivated COVID-19 vaccine approximately 6 months prior. Both homologous and heterologous booster vaccination led to an increase in levels of spike RBD-specific binding antibodies, neutralizing antibodies, the B-cell response and T-cell responses from day 14 after booster vaccination, but these increases were highest in participants who received heterologous regimens with an adenovirus-based COVID-19 vaccine.Booster vaccination with the Ad5-nCoV vaccine induced a superior T-cell response and neutralizing antibody responses compared to those induced by the homologous inactivated vaccine booster or heterologous recombinant protein vaccine booster, regardless of whether intramuscular injection or aerosol inhalation was used (The durability of the humoral response is crucial for COVID-19 vaccines. In our study, participants who received two-dose of CoronaVac 6 months ago showed a low seropositivity rate for neutralizing antibodies against SARS-CoV-2, which is similar to other findings (The highly transmissible Omicron variant severely impairs the neutralizing activity of priming two-dose COVID vaccines, with a more than 10-fold reduction compared to that with the wild-type strain (T-cell immunity is required for viral clearance and supports the generation and maintenance of high-affinity antibodies (In the present study, intramuscular or aerosolized Ad5-nCoV-induced neutralizing antibodies and T-cell responses after booster vaccination were significantly higher than those from the recombinant RBD dimer vaccine ZF2001. However, ZF2001 booster vaccination induced 2-fold more neutralizing antibodies than the homologous inactivated vaccine booster. Low cellular responses were detected with the aluminum-adjuvanted recombinant protein and inactivated COVID-19 vaccine. In the case of ChAdOx1 nCoV-19 and BNT162b1-primed vaccination, the immune responses upon booster vaccination with the recombinant protein vaccine (NVX-CoV2373) were also inferior to those upon administration of the adenovirus-vectored boosters, including neutralizing antibodies and cellular immune responses (So far, few studies have reported the longevity of antibody response to the Omicron variant boosted by SARS-CoV-2 vaccines. Immune recall by a homologous 3rd dose of mRNA vaccine in COVID-naive vaccinees greatly enhanced great and stable Omicron-specific antibody response (There are some limitations to this study. First, this study only evaluated the immune response of different boosters in young male subjects, although similar results have been observed in subjects of different ages and sexes (In summary, in the face of waning immunity and the circulation of SARS-CoV-2 variants, the mucosal IgA, neutralizing antibody and T-cell responses were boosted most efficiently with aerosolized Ad5-nCoV in those who received inactivated vaccines as initial doses. Aerosolized Ad5-nCoV booster probably provides a new tool against infection and transmission of the SARS-CoV-2 Omicron variant. | PMC10585368 |
Data availability statement | The original contributions presented in the study are included in the article/ | PMC10585368 | ||
Ethics statement | The studies involving humans were approved by the Ethics Committee of 305 Hospital of PLA. The studies were conducted in accordance with the local legislation and institutional requirements. The participants provided their written informed consent to participate in this study. | PMC10585368 | ||
Author contributions | MH, ZHZ | RECRUITMENT | YS is the principal investigator of this trial. WC, LH, YWL, and KL designed the trials and the study protocol. ZZ and SW drafted the manuscript. WC and LH contributed to critical review and revising of the report. ZZ, SW, YWL, and KL contributed to data interpretation and revising the manuscript. SW led laboratory analyses. SW, ZZ, PF, XS, YW, ZHZ, JX, YL, YHL, MH, GZ, SL, YZ, FS, YY and XFZ were responsible for laboratory analyses. BW was responsible for statistical analysis. TZ and JLZ contributed to study supervision. XWZ, JS, JZ, KF, PWL, PL, and ZQ led and participated in site work, including recruitment, follow-up and data collection. All authors contributed to the article and approved the submitted version. | PMC10585368 |
Conflict of interest | TZ is the employee of CanSino Biologics and has stock options in CanSino Biologics.The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. | PMC10585368 | ||
Publisher’s note | All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher. | PMC10585368 | ||
Supplementary material | REGRESSION | The Supplementary Material for this article can be found online at: RBD-specific IgG reverse cumulative distribution curves. Reverse cumulative distribution curves denote the percentage of participants in each group that reach a different level of antibody concentration at days 0, 7, 14, 28 and months 3 and 6 after the booster.Click here for additional data file.Seroconversion of PNAb response against wild-type SARS-CoV-2 and Omicron variants. Click here for additional data file.Correlation between PNAb and RBD-specific IgG antibodies. Click here for additional data file.Comparison of PNAb titers between wild-type SARS-CoV-2 and the Omicron BA.1 and BA.4/5. Click here for additional data file.Correlates of sVNT NAb titers and PNAb titers. Spearman’s correlation and linear regression (diagonal lines) analyses were performed for each group with log-transformed data of the indicated sVNT NAb titers and PNAb titers at day 28 Click here for additional data file. | PMC10585368 | |
References | PMC10585368 | |||
Background | SECONDARY, HOLIDAY | Emerging evidence suggests that children’s fatness increases and fitness declines at a greater rate during the summer holiday period, compared with the school year. The aim of this study was to compare rates of change in fitness and fatness over the in-term and summer holiday periods among Australian schoolchildren. A secondary aim was to explore whether rates of change differed according to the child’s sex, socio-economic status (SES), pubertal status and weight status. | PMC10601165 | |
Methods | HOLIDAY | Children (n = 381) initially in Grade 4 (age 9) were recruited for this 2-year longitudinal study. Fatness (% body fat, BMI z-score, waist-to-height ratio) and fitness (20-m shuttle run and standing broad jump) were measured at the start and end of two consecutive years. Rates of change were calculated for the two in-school periods (Grades 4 and 5) and for the summer holiday period. Rates of change in fatness and fitness between in-school and holiday periods were compared, and differences in rates of change according to sex, socio-economic status, and weight status were explored. | PMC10601165 | |
Results | overweight | HOLIDAYS | During the holidays, percentage body fat increased at a greater rate (annualised rate of change [RoC]: +3.9 vs. Grade 4 and + 4.7 vs. Grade 5), and aerobic fitness declined at a greater rate (RoC − 4.7 vs. Grade 4 and − 4.4 vs. Grade 5), than during the in-school periods. There were no differences in rates of change for BMI z-score, waist-to-height ratio or standing broad jump. Body fatness increased faster in the holidays (relative to the in-school period) in children who are overweight and from low-SES families. Aerobic fitness declined more rapidly in the holidays in children who are overweight. | PMC10601165 |
Conclusion | HOLIDAY | This study highlights that during the summer holiday period, children experience greater increases in fatness and declines in fitness, with children who live with low-SES families and are overweight being more affected. The findings suggest the need for targeted interventions during this period to address these negative health trends. | PMC10601165 | |
Trial registration | Australia New Zealand Clinical Trials Registry, identifier ACTRN12618002008202. Retrospectively registered on 14 December 2018. | PMC10601165 | ||
Supplementary Information | The online version contains supplementary material available at 10.1186/s12889-023-17009-4. | PMC10601165 | ||
Keywords | PMC10601165 | |||
Background | HOLIDAYS, SECONDARY, HOLIDAY | Physical fitness and body composition play a crucial role in the overall health and wellbeing of children [Recent research suggests that increases in fatness and declines in aerobic fitness in children occur at a greater rate during the school summer holiday period compared to the school year [The “Structured Days Hypothesis” [The aim of this study was to describe and compare rates of change in children’s fitness and fatness over the in-school and summer holiday periods in Australia, a southern hemisphere country with relatively short summer holidays (6 weeks) and relatively few summer camp offerings. A secondary aim was to explore whether rates of change differed according to the child’s sex, socio-economic status (SES), pubertal status and weight status. | PMC10601165 | |
Materials and methods | PMC10601165 | |||
Participants | The participants in this study were drawn from the | PMC10601165 | ||
Measures | The dependent variables were measures of fatness (percentage body fat, Body Mass Index (BMI) z-score and waist-to-height ratio) and fitness (maximal aerobic power, standing broad jump). Each child’s height was measured using a Seca 213 stadiometer (Seca, Hamburg, Germany), and weight and percentage body fat (The Pubertal status was measured using The Pubertal Development Scale [ | PMC10601165 | ||
Bias | Numerous efforts were made to minimise study biases. In particular, a randomised stratified sampling methodology was used. Outcomes were gathered using high-quality tools and protocols with established reliability and validity. Research personnel were thoroughly trained, and participant retention was maximised through the use of multiple reminders and follow ups and a yearly incentive for participants to remain engaged in the study. | PMC10601165 | ||
Sample size justification | Full details of the power calculation are provided in the study protocol [ | PMC10601165 | ||
Analysis | HOLIDAY | Figure
Schematic of data treatment to extrapolate the rates of change in fatness and fitness across Grade 4, Grade 5 and the holiday period. Outcomes (here, estimated VOMulti-level models were carried out in R [ | PMC10601165 | |
Results | overweight | HOLIDAYS, HOLIDAY | Participant characteristics are shown in Table
Participant characteristicsData are shown for the outcome with the largest sample size (n = 156 for SBJ)BMI = Body Mass Index; SES = socio-economic statusTable
Observed rates of change (means, SDs) for fatness and fitness outcomes across the study timepoints.%BF = percentage body fat; ∆T1-start = annualised rate of changed from T1 to start of holidays; ∆Start-End = annualised rate of change from start to end of holidays; ∆End-T5 = annualised rate of change from end of holidays to T5; SBJ = standing broad jump (cm); T1 = timepoint 1 (February-April); T5 = timepoint 5 (November-December); V̇O
Visualisation of the observed rates of change in fatness and fitness across Grade 4, Grade 5 and the holiday period. Filled symbols represent measured values and empty symbols extrapolated valuesPercentage body fat increased at a faster rate during the holidays than during the in-school periods. The rate of increase in %BF was significantly higher in the holidays than in the Grade 5 school year (by + 4.7%BF/year; p = 0.030; Table
Annualised rates of change in fatness and fitness metrics during the holiday periods compared to in-school periodsThe table depicts the differences in annualised rates of change (and 95% CIs) during the holiday period compared to the two in-school periods (School Year Grade 4 and School Year Grade 5). For example, during the holiday period, body fat percentage increased at a rate of 4.7%BF/year more than during Grade 5.BF = percentage body fat; SBJ = standing broad jump (cm); V̇OWe next explored whether differences in rates of change (holidays vs. school years) varied according to socio-demographic characteristics (sex, SES, pubertal status, weight status; Table
Comparative annuaslised rates of change in fatness and fitness metrics by socio-demographic categories: holiday vs. in-school periodsThe table delineates the variations in annualised rates of change (accompanied by 95% CIs) during the holiday period, contrasted against the Grade 4 and Grade 5 in-school periods, segmented by socio-demographic categories. For instance, in the context of body fat percentage (%BF), the rate of change during the holidays compared to the Grade 5 in-school period was notably higher (p = 0.020) in overweight children by + 11.9%BF/year when compared to normal-weight children (who serve as the reference category). In terms of Socioeconomic Status (SES), a 1 SD increase in the SES z-score was associated with a decrease of 9.4%BF/year in the rate of change in %BF during holidays versus the Grade 5 in-school period.Models were mutually adjusted for all covariates, and random intercepts were used to account for nesting of observations within participants, within schools, within study waves. Note: p < 0.05 shown in boldfaceAbbreviations: SES = socioeconomic status; Wt status = weight status; %BF = percentage body fat; SBJ = standing broad jump (cm); V̇O | PMC10601165 |
Sex | Sex did not moderate differences in rates of change for any outcome. | PMC10601165 | ||
Socio-economic status | HOLIDAYS | SES moderated differences in the rate of change in %BF and zBMI. Overall, children from lower SES families showed greater increases in fatness over the holidays compared to children from higher SES families. Every 1 SD increase in SES was associated with a 7.5%BF/year greater difference in the rate of change during the in-school period in Grade 4 compared to the holidays (p = 0.045), and a 9.4%BF/year greater difference for Grade 5. Similarly, a 1 SD increase in SES was associated with a 0.9 SD/year greater relative difference in rates of change in zBMI in Grade 5 vs. the holidays (p = 0.040), although the relative difference of + 0.7 SD/year was not significant for Grade 4. Socio-economic status did not moderate differences in the rates of change of Waist:Ht%, SBJ, or V̇O | PMC10601165 | |
Pubertal status | HOLIDAYS, HOLIDAY | Pubertal status moderated differences in rates of change in all fatness measures. Children who were early pubertal in Grade 4 showed relatively lower increases in all fatness measures over the holidays compared to children who were mid-pubertal (p = 0.023–0.046). In Grade 5, these differences were similar but did not reach statistical significance. Children who were pre-pubertal, however, showed relatively faster declines in aerobic fitness during the holiday periods compared to children who were mid-pubertal (p = 0.027–0.029). Pubertal status did not moderate differences in rates of change in SBJ performance. | PMC10601165 | |
Weight status | overweight | OBESE, HOLIDAY | Weight status moderated differences in rates of change in %BF. Compared to children of normal-weight, children who were overweight (but not obese) increased %BF relatively faster in the holiday periods than in both in-school periods (p = 0.020–0.027). The corresponding rate of decline in aerobic fitness for children who were overweight (but not obese) was higher in the holiday period (p = 0.010–0.013). Weight status did not moderate differences in the rates of change of zBMI, Waist:Ht% or SBJ. | PMC10601165 |
Discussion | PMC10601165 | |||
Main findings | weight gain, overweight, adiposity | HOLIDAYS, HOLIDAY, ADIPOSITY | The focus of this study was to compare rates of change in children’s fitness and fatness between in-school and summer holiday periods, and to explore whether differences in rates of change in these outcomes were moderated by sex, SES, pubertal status, or weight status. During the holiday period, there was a significant increase in the rate of change of percentage body fat and a significant increase in the rate of decline of aerobic fitness, indicating differential increases in fatness and decreases in fitness in the holiday period. However, there were no differences in rates of change for BMI z-score, waist-to-height ratio, or standing broad jump. Some differences in rates of change in fitness and fatness were moderated by socio-demographic characteristics. In general, children who were overweight and from lower-SES families exhibited relatively faster increases in fatness and declines in fitness in the holidays compared to the in-school period.The study’s finding of summer holiday weight gain is generally consistent with previous studies [Few previous studies have examined whether summer holiday weight gain and fitness losses differ according to sociodemographic and anthropometric characteristics [Similar to Moreno et al. [Interestingly, patterns for summertime changes in fatness and fitness were not consistent for the various markers. Generally speaking, results were significant when fatness was considered based on %BF (and mostly consistent based on zBMI), but not when considered based on waist:height. It is likely that %BF measured by bioimpedance is a more sensitive measure of adiposity than zBMI and waist:height. Furthermore, it is possible that changes in body shape associated with puberty may have contributed to the lack of significant findings for the waist:height variable.Similarly, clear fitness losses were apparent in V̇OIt is interesting to consider that the significant increases in percentage body fat and decreases in aerobic fitness may even be directly related. Given that the 20mSRT is performed under gravity where children carry their entire body mass, a holiday-related increase in BMI should reduce 20mSRT performance. Fat mass per se does not affect aerobic fitness but increased fat mass could reduce 20mSRT performance and our estimate of V̇O | PMC10601165 |
Strengths and limitations | HOLIDAYS, HOLIDAY | Key strengths of the current study are its longitudinal design spanning two school years. Furthermore, it used the highest quality measures of fatness and fitness possible for collection in a school setting. Relatively few studies of children’s summer holiday fatness and fitness have been conducted outside the US, and none in the southern hemisphere or in countries with relatively short summer holidays, meaning this study makes a highly valuable contribution to the international literature.Limitations must also be acknowledged. The COVID-19 pandemic commenced approximately halfway through data collection. This led to some data loss (because some schools wouldn’t permit data collection visits to go ahead) and also likely contributed to participant dropout, which was considerable. This is likely to have negatively affected the study’s power, and may also impact the generalisability of findings. Finally, we chose to study children across Year 4 and 5 on the basis that they were older enough to reliably complete fitness tests, and so that the likelihood of them changing schools would be minimised (children attending government schools in South Australia transition to high school at the end of Year 6, though a considerable portion choose to transition to private schools for high school, with many transitioning at the end of Year 5). However, we acknowledge that children’s bodies change rapidly at this age, which may make it harder to detect summer-holiday-related changes in fatness and fitness. Changes across the 2-year period are overlaid on expected age-related changes in growth and development. At this age, %BF increases on average by 0.3–0.8% p.a [ | PMC10601165 | |
Implications | weight gain | HOLIDAYS, HOLIDAY | If the holiday environment leads to increases in fatness and decreases in aerobic fitness, there are potential policy implications. Interventions targeted at the holiday period (such as summer camps and programs which offer a mix of physical and learning activities), at the home environment, or at effectively extending the in-school environment (such as shortening the holiday period) may provide the structured day needed to prevent weight gain and losses in aerobic fitness. Further, many sporting competitions stop during the summer holidays (e.g., netball, basketball) while others (e.g., little athletics) have a short Christmas-New Year break. Perhaps an emphasis on moderate-to-vigorous aerobic activities like swimming, bike riding, running, and dancing, as recommended in national physical activity guidelines, may help minimise holiday-related declines in aerobic fitness, particularly while competitive sports are in a hiatus.There is accumulating evidence that interventions of this sort of structured programming have been effective in North America and Europe, where summer camps are common [Family-based interventions are difficult during the holiday diaspora, but a recent systematic review [ | PMC10601165 |
Conclusion | overweight | HOLIDAY | In summary, this study provides important insights into the differential rates of change in children’s fitness and fatness during in-school and summer holiday periods. Our findings suggest that during the holiday period, there is a significant increase in the rate of change of percentage body fat and a significant decline in fitness. Furthermore, we found that socio-demographic characteristics such as SES and weight status moderated the rates of change in fitness and fatness, with children who were overweight and from lower-SES families exhibiting relatively faster increases in fatness and declines in fitness during the holiday period compared to the in-school period. These findings have important implications for policymakers and public health practitioners, highlighting the need for targeted interventions to address the summer holiday deficits in children’s fitness and fatness, particularly among low-SES and overweight populations. Overall, this study contributes to the international literature on children’s summer holiday fatness and fitness, and underscores the importance of longitudinal studies using high-quality measures of fitness and fatness in school settings. | PMC10601165 |
Acknowledgements | Not applicable. | PMC10601165 | ||
Authors’ contributions | CM | HOLIDAYS | TO and CM developed the concept for this study. TO, CM, DD, FF, GT & RG obtained funding for the original Life on Holidays study. TO, CM, EE & AM drafted the manuscript. DD performed the analysis. All authors have read and approved the final version of the manuscript and agree with the order of presentation of the authors. | PMC10601165 |
Funding | CM | HOLIDAYS | The life on Holidays study was funded by the National Health and Medical Research Council [grant number APP1143379] (2018–2022). The funding body played no role in the design, collection, analysis and interpretation of data or in writing the manuscript. AW is supported by NHMRC Project Grant APP143379 (2018–2022). CM is funded by a Medical Research Future Fund Investigator Grant (GNT1193862). DD is supported by an Australian National Health and Medical Research Council (NHMRC) Early Career Fellowship APP1162166 and by the Centre of Research Excellence in Driving Global Investment in Adolescent Health funded by NHMRC APP1171981. AM is supported by the Centre of Research Excellence in Driving Global Investment in Adolescent Health funded by NHMRC APP1171981. FF is supported by an Australian Defence Science and Technology Group research grant (MyIP: 9275) and an iMOVE Australia CRC research grant (6 − 002). AM is supported by an Australian Government Research Training Program (RTP) grant and the Centre of Research Excellence in Driving Global Investment in Adolescent Health funded by NHMRC APP1171981. EE is supported by an RTP grant. | PMC10601165 |
Data Availability | Data analysed during this study will be made available upon reasonable request to the corresponding author Carol Maher by emailing her at carol.maher@unisa.edu.au. | PMC10601165 | ||
Declarations | PMC10601165 | |||
Competing interests | The authors declare no competing interests. | PMC10601165 | ||
Ethics approval and consent to participate | Ethical approval was obtained from the University of South Australia Human Research Ethics Committee, Adelaide, Australia (200980), the South Australian Department of Education and Child Development (2008-0055) and the Adelaide Catholic Education Centre (201820). All methods were carried out in accordance with relevant guidelines and regulations. Principals and parents provided written informed consent, and children provided verbal assent on each measurement occasion. | PMC10601165 | ||
Consent for publication | Not applicable. | PMC10601165 | ||
References | PMC10601165 | |||
Keywords | ChiCTR2000039383, pain, fractures, diaphragmatic paralysis, hemidiaphragmatic paresis | The sensory innervation of the clavicle is complex, and the best regional block technology for clavicular surgery has yet to be determined. The purpose of this study was to compare the application of ultrasound-guided superficial cervical plexus block combined with clavipectoral fascial plane block verses interscalene brachial plexus block in clavicular surgery. Fifty patients undergoing internal fixation surgery for elective clavicle fractures were randomly divided into two groups (n = 25 for each group): group I and group II. Superficial cervical plexus block combined with clavipectoral fascial plane block was used in group I, and superficial cervical plexus block combined with interscalene brachial plexus block was used in group II. The primary outcome measure was the duration of analgesia. The duration of analgesia in group I was significantly longer than that in group II (P < 0.05). The modified Bromage scale function score in group II was lower than that in group I (P < 0.01). There was no significant difference in the skin acupuncture pain score 30 min after block and visual analog scale (VAS) scores at 6 and 12 h after surgery. However, the 24 h VAS score in group I was lower than that in group II (P < 0.05). The incidence of diaphragmatic paralysis was significantly increased in group II (P < 0.01). Ultrasound-guided superficial cervical plexus block combined with clavipectoral fascial plane block can be used for clavicular surgery. It has a long postoperative analgesia time, can retain the motor function of the involved upper limb and does not cause hemidiaphragmatic paresis.Clinical trial number and registry URL: Clinical Trials.gov; Trial registration number: ChiCTR2000039383; Date of registration: 25 October 2020. | PMC10371927 | |
Introduction | upper limb muscle strength, fracture, clavicular fracture, Clavicular fracture, clavicle fracture, nausea, vomiting | ADVERSE REACTIONS, LARYNGEAL SPASM, COMPLICATIONS | Clavicular fracture is the most common injury in the shoulder, particularly in young men. It mainly occurs due to sports or traffic accidents, especially in the middle of the clavicle. Better functional results can be obtained by surgical treatment. General anaesthesia can be used during surgery, but there is a risk of nausea, vomiting, aspiration and laryngeal spasm during endotracheal intubation and extubation. Furthermore, the cost of anaesthesia increases the economic burden of patients. Regional anaesthesia can meet the requirements of satisfactory operation, avoid many complications in general and provide good postoperative analgesia [It is well known that the skin above the clavicle is innervated by the supraclavicular nerve. However, sensory innervation of the clavicle itself is controversial [Therefore, many scholars have attempted to use different regional nerve block techniques to meet the needs of clavicle fracture surgery. Clavipectoral fascial plane block (CPB) is a new regional nerve block proposed by Valdés in 2017 and can be used in anaesthesia and postoperative analgesia for clavicle fracture surgery. There is a very clear relationship between the pectoral fascia, which covers the anterior surface of the pectoralis major muscle, and the investing layer of the deep cervical fascia, which envelops the sternocleidomastoid muscle. Since Valdés proposed using CPB for clavicle fracture surgery in 2017, many scholars have reported relevant cases [Therefore, we designed this single-centre, double-blind, randomized controlled trial study. We performed clavicular surgery with ultrasound-guided SCPB combined with CPB or ISBP to explore the effects of two regional block techniques on anaesthesia, postoperative analgesia, upper limb muscle strength and adverse reactions in clavicular fracture surgery. | PMC10371927 |
Materials and methods | PMC10371927 | |||
Study design and participants | cardio-cerebrovascular diseases, abnormal blood coagulation, allergy, fractures, hypertension | RESPIRATORY INSUFFICIENCY, ALLERGY, CORONARY HEART DISEASE, HEART FAILURE, HYPERTENSION, OBSTRUCTIVE EMPHYSEMA, PUNCTURE SITE INFECTION | This is a single-centre double-blind, randomized controlled trial of 50 patients with American Society of Anaesthesiologists (ASA) I-II at our hospital (Teaching Hospital, Residency training Hospital). This study was performed in line with the principles of the Declaration of Helsinki. Hospital ethics committee approval was obtained before starting patient enrolment (No: 2020-462). Written informed consent was obtained from all participants. The trial was registered prior to patient enrolment at the Chinese Clinical Trial Registry on 25 October 2020 (ChiCTR2000039383).The subjects were patients with unilateral clavicle fractures who underwent elective internal fixation of clavicle fractures in our hospital. The patients were randomly divided into two groups: patients with SCPB and CPB were included in group I, and patients with SCPB and ISBP were included in group II. There were 25 patients in each group. An anaesthesiologist (who did not participate in the other steps) was responsible for recruiting patients and determining random grouping with the use of random-number tables. On the day of operation, a nurse anaesthetist (who was blinded to the scope of the study) opened the envelope, determined the grouping of patients and was responsible for the preparation of regional anaesthesia drugs. The second anaesthesiologist (who was blinded to the patient group allocation) was responsible for the regional anaesthesia operation. The second nurse anaesthetist (who was blinded for patient group allocation) was responsible for evaluating the scale, recording research data and postoperative follow-up. The exclusion criteria were as follows: (1) cardio-cerebrovascular diseases (history of heart failure, poor control of hypertension, coronary heart disease and cerebrovascular history); (2) respiratory insufficiency (bilateral rib fractures, obstructive emphysema, etc.); (3) abnormal blood coagulation; (4) puncture site infection; (5) continuous use of analgesics for the last 3 months; and (6) allergy to local anaesthetics. All data were collected from Neusoft and MedicalSystem Technology. | PMC10371927 |
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