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METHODS
PMC10640691
Study Design and Participants
This was a phase 3, randomized, open-label, multicenter clinical trial conducted in the US. Eligible adults were randomly assigned (1:1) to receive coadministration of a booster dose (50 µg) of mRNA-1273 and the first dose of RZV (RZV1) (Coad group), or the mRNA-1273 booster followed 2 weeks later by RZV1 (Sequential [...
PMC10640691
Randomization
Participants were stratified by age (50–59, 60–69, ≥70 years) and centrally randomized to either the Seq or Coad group. The randomization system allocated a participant identification number and provided the treatment number to be administered.
PMC10640691
Objectives
The primary objectives were (1) to demonstrate noninferiority in terms of humoral immunogenicity of 2 doses of RZV when RZV1 was coadministered with an mRNA-1273 booster dose compared to RZV1 administered 2 weeks after mRNA-1273; and (2) to demonstrate noninferiority in terms of humoral immunogenicity of a booster dose...
PMC10640691
Study Interventions and Procedures
immune-mediated diseases
ADVERSE EVENTS
The composition of RZV and mRNA-1273 is provided in the Anti-gE antibodies were measured using an enzyme-linked immunosorbent assay at GSK [Solicited local and systemic adverse events (AEs) with onset within 7 days after each vaccination were recorded using electronic diaries. Unsolicited AEs were recorded for 30 days ...
PMC10640691
Statistical Analysis
EVENT
The exposed set included all participants who received at least 1 dose of a study vaccine. The per-protocol set (PPS) included study participants who met eligibility criteria, received all vaccinations according to their random assignment, complied with protocol-defined procedures, did not receive prohibited medication...
PMC10640691
RESULTS
PMC10640691
Participants
zoster
ZOSTER
The study was conducted between 7 October 2021 and 29 August 2022 at 47 sites in the US. From a total of 545 participants randomized, 539 were vaccinated (exposed set; 272 in the Seq and 267 in the Coad group), and 91.2% in the Seq and 92.6% in the Coad group completed the study (Participant flow. The Seq group receive...
PMC10640691
Immunogenicity Results
zoster, Zoster Vaccine
ZOSTER
Noninferiority of the humoral immune response to the gE and S antigens was demonstrated according to the protocol-specified criteria. For the PPS, the adjusted GMC ratio (Seq over Coad) was 1.01 (95% CI, .89–1.13) for anti-gE antibodies 1 month post-RZV2 (Analysis of Anti–Glycoprotein E Antibody Responses 1 Month After...
PMC10640691
Safety Results
pulmonary embolism, myalgia, fatigue, hyperlipidemia, cutaneous vasculitis, headache
ADVERSE EVENTS, HYPERLIPIDEMIA, CUTANEOUS VASCULITIS, PULMONARY EMBOLISM
The frequency of any or grade 3 intensity solicited local AEs post–mRNA-1273 or post-RZV1 were similar in both study groups (Percentage of solicited local and systemic adverse events reported per participant after the mRNA-1273 and first RZV vaccinations (exposed set). The Seq group received the mRNA-1273 booster dose ...
PMC10640691
DISCUSSION
This is the first clinical study to evaluate the safety and immunogenicity of the mRNA-1273 COVID-19 vaccine booster when coadministered with RZV or when administered sequentially. As with sequential administration, coadministration elicited robust anti-gE and anti-S antibody responses, with MGIs exceeding 34-fold and ...
PMC10640691
Supplementary Data
PMC10640691
Supplementary Material
Click here for additional data file.
PMC10640691
Trademark Statement
Shingrix is a trademark owned by or licensed to GSK and Spikevax is a trademark of Moderna.
PMC10640691
Notes
PMC10640691
Plain Language Statement
COVID-19 disease
Booster vaccinations against COVID-19 disease are likely to be necessary for the foreseeable future. Doctors and patients are interested to know whether COVID-19 booster vaccines can be given at the same time as other vaccines in adults. The results of our study showed that an mRNA-based COVID-19 booster vaccine could...
PMC10640691
References
PMC10640691
Background
LISB
Ultrasound-guided low interscalene brachial plexus block (LISB) can provide satisfactory anesthesia for surgery at or below the elbow. However, the anesthesia effect of ultrasound-guided middle interscalene brachial plexus block (MISB) has not been fully investigated. We hypothesized that MISB provides a non-inferior a...
PMC9808947
Methods
A total of 82 patients with ASA I-III (18–65 years) scheduled for elective surgery at or below the elbow were randomized to the MISB group or the LISB group equally, located 1/2 or 2/3 of the caudal distance from C6 to the clavicle. Both groups were administered 15 mL 0.5% ropivacaine at the lower part of the brachial ...
PMC9808947
Results
SECONDARY
For the primary outcome, 92.3% in the MISB group experienced successful anesthesia compared to 94.6% in the LISB group [difference: –2.3%, 95% confidence interval (CI) –13.4% to 8.8%], exceeding the predefined non-inferiority margin -15%. For the secondary outcomes, the incidence of pleura suppression for the first inj...
PMC9808947
Conclusions
MISB provides a non-inferior anesthesia effect to LISB for surgery at or below the elbow.
PMC9808947
Trial registration
Chinese Clinical Trial Register (identifier: ChiCTR2100054196).
PMC9808947
Keywords
PMC9808947
Key points
LISB
PNEUMOTHORAX
We proposed the middle interscalene brachial plexus block (MISB) for the first time and assessed its efficacy for the sensory and motor block.MISB provides a non-inferior anesthesia effect to low interscalene brachial plexus block (LISB) for surgery at or below the elbow.MISB may be considered a valuable alternative f...
PMC9808947
Introduction
trauma
The classic interscalene brachial plexus block (CISB) was performed at the C6 level in the cricoid cartilage, which has evident advantages such as not requiring moving the patient's arm or forearm in the case of trauma or abnormality, a better anesthesia effect for upper limb and shoulder surgery, and easy to learn [
PMC9808947
Materials and methods
PMC9808947
Ethics
Ethic for this randomized, prospective, observer-blinded clinical study was approved by the Medical Ethics Committee of the third affiliated hospital of Chongqing Medical University (president Fei Hao), China 2/12/2021, approval number 2021/35. The study protocol was registered with the Chinese registry of clinical tr...
PMC9808947
Patients
allergic reaction, toxicity, edema, impaired neurological function, pain, infection, psychiatric
ALLERGIC REACTION, EDEMA, DYSFUNCTION, INFECTION, COAGULATION DISORDER
Inclusion criteria were patients aged 18 to 65 years; American Society of Anesthesiologists classification (ASA) I–III; ability to express pain; and patients undergoing elective surgery at or below the elbow. Exclusion criteria were patients who had neck tissue abnormality, infection, or edema; impaired neurological f...
PMC9808947
Randomization and blinding
On the day of surgery, consented patients were randomly assigned to the LISB or MISB group (1:1) using SPSS 25.0 software (Statistical Program for Social Sciences, SPSS Inc., Chicago, Illinois, USA) by C.-M.G. who was not involved in the study. Allocation anonymity was ensured by enclosing assignments in sealed, opaque...
PMC9808947
Intervention technique
LISB
INFILTRATION
Venous access was established after arrival in the operating room without any premedication before anesthesia. During the same time, the vital signs of the patients were monitored every three minutes using a non-invasive blood pressure parameter, pulse oximeter, and electrocardiogram. Patients were kept supine with the...
PMC9808947
Perioperative analgesia and management
shoulder abduction, paralysis
PARTIAL PARALYSIS, COLD
Data on age, sex, weight, height, BMI, surgical site, and ASA classification were collected. The anesthesia effects were defined as below: "success ", the surgery was performed under the block with or without additional sufentanil and propofol intravenously administered at a maximum usage of 10 ug or 2 mg/kg, respecti...
PMC9808947
Magnetic resonance imaging of the brachial plexus
Magnetic resonance imaging was performed immediately after surgery on a 1.5 T magnet (Siemens Aera MR, Germany) to observe the diffusion of the local anesthetics. MRI examination consents were obtained from the two patients of the corresponding group. The patient in the supine and head advanced position was placed in ...
PMC9808947
Outcome measures
toxicity, dyspnea, hoarseness, nausea, vomiting
HORNER SYNDROME, PNEUMOTHORAX
The primary outcome was the anesthesia success rate with a non-inferiority test. Secondary outcomes included: incidence of suppression of the pleura when administering the first injection; the sensory and motor blockade scores of all branch nerves at 5 min, 15 min, and the end of surgery; evaluation of the motor respon...
PMC9808947
Sample size and statistical analysis
LISB
This study was designed to compare the non-inferiority of the anesthesia success rate in MISB and LISB undergoing surgery at or below the elbow. Previous studies reported that the success rate of low interscalene brachial plexus block anesthesia for surgery at or near the elbow was approximately 95% when opiates and mi...
PMC9808947
Results
PMC9808947
Patient characteristics
SD, fifty-four
MAY
One hundred fifty-four consecutive patients were assessed for eligibility between January 2022 and May 2022. Of these, 59 patients did not meet the inclusion criteria and 13 refused to participate. The remaining 82 patients were randomized into the LISB (Consort flow study diagram. Note: MISB = middle interscalene brac...
PMC9808947
Primary outcome
The anesthesia success rate was 92.3% in the MISB group and 94.6% in the LISB group. The mean difference in the anesthesia success rate between the two groups was –2.3%, with a 95% confidence interval (CI) of –13.4% to 8.8%. With the non-inferiority margin set at − 15%, MISB was confirmed to provide a non-inferior anes...
PMC9808947
Secondary outcomes
inferior sensory blockade, paralysis
PARTIAL PARALYSIS, SECONDARY, COLD
For the incidences of suppression of the pleura when administering the first volume of local anesthetics, 3 patients (7.7%) in the MISB group showed significantly less than 17 patients (45.9%) in the LISB group (Comparison of the primary and secondary outcomes between the two groups35/2(94.6%/ 5.4%)36/3(92.3%/ 7.7%)Not...
PMC9808947
Acknowledgements
We thank the patients for their participation in this study.
PMC9808947
Author’s contributions
Yang Zhao: Conceptualization, Formal analysis, Funding acquisition, Writing original draft, Software, Validation. Shiming Qin: Methodology, Project administration, Data curation, Software, writing original draft. Xue Yang: Methodology, Project administration, Software, Supervision. Chongmei Gao: Methodology, Investigat...
PMC9808947
Funding
This study was supported by the Project of North Sichuan Medical College (NO. CBY21-QA42) and Innovation Project of Guangxi Graduate Education (NO. YCBZ2022091).
PMC9808947
Availability of data and materials
The data used and/or analyzed during the current study are also available from the corresponding author upon reasonable request.
PMC9808947
Declarations
PMC9808947
Ethics approval and consent to participate
This randomized, prospective, observer-blinded clinical study was registered with the Chinese registry of clinical trials at
PMC9808947
Consent for publication
Not applicable.
PMC9808947
Competing interests
The authors declare no competing interests.
PMC9808947
References
PMC9808947
1. Introduction
psychiatric, PMS
DISORDER, PREMENSTRUAL SYNDROME (PMS), PMS, SECONDARY, COMPLICATIONS
Premenstrual syndrome (PMS) continues to impact the health outcomes and emotional well-being of reproductive-age women, globally. Several studies have provided conflicting evidence concerning the role of dietary approaches in improving PMS symptoms. Accordingly, this study aimed to evaluate the possible influence of a ...
PMC10742710
2. Materials and Methods
SECONDARY, PMS
This is a prospective, open-label, randomized controlled trial of two parallel groups. It was conducted in two randomly selected secondary schools in Al Seeb Willayah, in Muscat region. The consecutive sampling approach was used to recruit the study participants. Candidates who qualified for the initial eligibility cri...
PMC10742710
2.1. Inclusion and Exclusion Criteria
anxiety disorder, PMDD, psychiatric, post-traumatic stress disorder, premenstrual dysphoric disorder, depression, psychotic disorders, diabetes
DISORDER, PMS, DIABETES
Adolescents who were in grade 10 or 11, aged 16 years or above, and had regular menstrual cycles were included in this study. Exclusion criteria included those who were known to have a psychiatric disorder (such as depression, generalized anxiety disorder, post-traumatic stress disorder, psychotic disorders), and diabe...
PMC10742710
2.2. Sample Size
PMS
The sample size for the primary outcome was calculated based on the difference in mean DRSP scores for a two-group parallel clinical trial with equal allocation. The acceptable effect at which superiority could be declared if there was a decrease in the summary DRSP score of six on the DRSP tool in the intervention gro...
PMC10742710
2.3. Recruitment and Randomization
SECONDARY, RECRUITMENT
Consecutive sampling was used for the recruitment stage. Cluster randomization of the schools was carried out to minimize the contamination anticipated from recruiting subjects from the same school. Notably, the study was conducted in two randomly selected secondary schools in Al Seeb Wilayat in Muscat region. The part...
PMC10742710
2.4. Treatment Protocol
FBDs
Participants in the intervention group received individual face-to-face dietary consultations with a well-experienced clinical dietician, who evaluated the overall nutritional status of the participants, followed by an explanation of the concept of a healthy diet, including a discussion on the six food groups essential...
PMC10742710
2.5. Assessment Approach
THYROID DISEASE, PMS
At baseline, the sociodemographic questionnaire was administered to both study groups, which included basic sociodemographic features such as age, and chronic conditions such as thyroid disease, medication use, smoking, alcohol status and substance use. The dietitian evaluated the dietary habits of participants in both...
PMC10742710
2.6. Statistical Analysis
SECONDARY
The trial was reported using the intention-to-treat analysis method. The difference in the DRSP scores (primary outcome) and PSS scores (secondary outcomes) from baseline to the end of the intervention was compared between the randomized groups using analysis of covariance (ANCOVA), and differences in scores reported a...
PMC10742710
4. Discussion
premenstrual syndrome
PREMENSTRUAL SYNDROME, PATHOLOGY, PMS
Our study revealed no significant association between healthy and well-balanced dietary intake and symptoms of premenstrual syndrome based on the daily record of severity of problems questionnaire (DRSP). Additionally, no significant association was found between a healthy diet in adolescents with premenstrual syndrome...
PMC10742710
4.1. Limitations
This study has some limitations. First, the small sample size impacts the generalizability of the findings. In addition, the lack of blinding, despite the study’s randomized controlled design, increased the risk of selection bias. Moreover, the use of self-reported questionnaires might have further impacted the reliabi...
PMC10742710
4.2. Recommendations
PMS
In spite of a variety of cross-sectional studies evaluating the relationships between PMS and dietary patterns, the paucity of evidence to date has substantiated the need for further prospective randomized studies with larger sample sizes to understand the potential factors impacting the PMS manifestations. These rando...
PMC10742710
5. Conclusions
PMS
PMS
The overall findings from this study revealed a nonsignificant association between healthy balanced diet, motivational follow-ups, and PMS symptom improvements. Although our research did not find statistically significant results supporting the effectiveness of dietary modifications and motivational support as treatmen...
PMC10742710
Supplementary Materials
The following supporting information can be downloaded at: Click here for additional data file.
PMC10742710
Author Contributions
M.H.A.K. contributed to the conceptualization, methodology, investigation, resources, writing—original draft, project administration, funding acquisition, and supervision. Z.A.B. contributed to the conceptualization, methodology, investigation, resources, writing—original draft, project administration, funding acquisit...
PMC10742710
Institutional Review Board Statement
Ethical approval for this study was obtained from the Directorate General of Planning and Studies, Ministry of Health, Oman (MoH/CSR/20/23884). Additionally, the trial is registered with the WHO/Iranian Registry of Clinical Trials # IRCT20201129049526N1.
PMC10742710
Informed Consent Statement
Informed consent was obtained from all subjects involved in the study.
PMC10742710
Data Availability Statement
Data supporting the reported results can be provided by the corresponding authors upon request.
PMC10742710
Conflicts of Interest
The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.
PMC10742710
References
Flow chart.Baseline characteristics.24 h recall analysis of participants in the intervention group at pre-intervention period, and at weeks 1, 4, and 8 at post-intervention period.Analysis of Covariance (ANCOVA) of subsections and total scores of the Daily Record of Severity of Problems questionnaire (DRSP).* Change fr...
PMC10742710
Background/Objectives
Trauma
PATHOLOGY
The Adjunctive Steroid Combination in Ocular Trauma (ASCOT) trial is a unique pragmatic, multi-centre, patient and assessor masked, randomised controlled trial. We evaluate the clinical characteristics and pathology of this large trial cohort of patients with open globe injuries undergoing vitreoretinal surgery, includ...
PMC10220025
Subjects/Methods
Diabetic Retinopathy, trauma
REGRESSION, DIABETIC RETINOPATHY
We (i) summarise demographics, injury history and ocular history of the 280 participants recruited into the ASCOT trial using descriptive statistics; (ii) analyse the national and seasonal variation across England and Scotland in these participant characteristics; and (iii) explore the associations between participant ...
PMC10220025
Results
hyphaemia, presenting vision, haemorrhaging
HYPHAEMIA, SCAR, LENS
The majority of participants with open globe penetrating injuries were of white ethnicity (233, 84%), male (246, 88%), with a median age of 43 years (IQR 30–55 years). There was considerable variability in presenting visual acuity with 75% unable to read any letters on the ETDRS chart, whilst the median ETDRS letter sc...
PMC10220025
Conclusion
PATHOLOGY
The ASCOT trial provides valuable insights into the spectrum of pathology of patients with open globe eye injuries undergoing vitreoretinal surgery. The identified causes of injury and clinical presentation of the cases will help in training and resource planning to deal with these often challenging surgical cases.
PMC10220025
Trial registration
EudraCT No. 014-002193-37. HTA Project 12/35/64.
PMC10220025
Subject terms
PMC10220025
Introduction
vitreous humour, visual loss, monocular blindness, traumatic, monocular visual impairment, ocular trauma, injuries, trauma
LOSS OF VISION, OPTIC NERVE, RETINA
Ocular trauma is a leading cause of monocular visual impairment and monocular blindness worldwide [Frequently the posterior segment of the eye, comprising the vitreous humour, retina, choroid, and optic nerve, is affected by injuries that result in visual loss and to prevent severe loss of vision, posterior segment (vi...
PMC10220025
Subjects and methods
Full details of the ASCOT study design have been published [
PMC10220025
Data collection and outcomes
Diabetic Retinopathy, trauma
DIABETIC RETINOPATHY
In this report, we analyse participant baseline demographics, trauma history and ocular history including baseline biomicroscopic ocular exam results prior to surgery. The baseline eye exam included the Early Treatment Diabetic Retinopathy Study (ETDRS) letter score measured using the standard validated ETDRS chart at ...
PMC10220025
Statistical analysis
vision, lens, zero/very low vision, hyphaemia, trauma
ENDOPHTHALMITIS, RECRUITMENT, RETINAL DETACHMENT, LENS, MACULAR DISEASE, VITREOUS HAEMORRHAGE, REGRESSION, SCARRING, HYPHAEMIA
The target sample size for ASCOT was 300 patients (150 per arm) over a 3-and-a-half-year recruitment period. As actual recruitment rate was slower than projected, the recruitment period was extended to a total of 75 months; 280 eligible patients were recruited and all are included within this analysis.Baseline characte...
PMC10220025
Results
PMC10220025
Regional variability
rupture, ocular co-morbidities, injuries, corneal injury
LOW VISION
The majority (148, 53%) of ASCOT participants were recruited from hospitals in London, a quarter came from the Midlands & Northern England (70, 25%), 55 (20%) were recruited in Southern England and 7 from Scotland (3%). London had a higher proportion of Black, Asian and Minority Ethnic (BAME) participants (24%) than an...
PMC10220025
Seasonal variation
ocular injuries, injuries
RECRUITMENT
The dates of ocular injuries were investigated for seasonal trends. Only injuries from 2014 were included as the date of injury was not collected accurately prior to this time, resulting in 255 participants included within this analysis. The most common month for injury was April and injuries in April were consistently...
PMC10220025
Seasonal variation in the number of ocular injuries.
ocular injuries, injuries
Number of injuries shown by year (represented by different colours) and month.Workplace incidents and interpersonal violence accounted for the majority of ocular injuries and there were fluctuations in the months these injuries occurred (see Fig. 
PMC10220025
Causes of ocular injuries.
injuries
Proportion of injuries (as a percentage) by cause of injury (workplace, road traffic accident, interpersonal violence, sports injury and other) and month of injury.
PMC10220025
Discussion
detachments, iris abnormalities, cataract, Vitreous haemorrhage, ocular trauma, vitreous haemorrhage, retinal detachment, glaucoma, hyphaema, ocular co-morbidities, injuries, trauma
SCAR, POOR VISION, CATARACT, VITREOUS HAEMORRHAGE, ENDOPHTHALMITIS, MACULAR DISEASE, PATHOLOGY, DETACHMENTS, EYE DISEASE, RECRUITMENT, CORNEA, VITREOUS HAEMORRHAGE, RETINAL DETACHMENT, SCARRING, EYE, RECRUITMENT, LENS, HYPHAEMA, OPACITIES, GLAUCOMA, ANTERIOR
The ASCOT study was a prospective randomised controlled trial designed to test the efficacy of intraocular and periocular triamcinolone given at the time of vitrectomy surgery in cases of open globe injury. It recruited nationally in the UK from 27 sites. The baseline data therefore represents the cases considered suit...
PMC10220025
Conclusion
rupture, injuries
OPACITIES, PATHOLOGY
The ASCOT study provides detailed clinical data on an extensive cohort of patients with open globe penetrating injuries undergoing vitreoretinal surgery. Although not a comprehensive epidemiological study, this study provides valuable insights into the spectrum of pathology encountered by vitreoretinal surgeons. We hav...
PMC10220025
Summary
PMC10220025
What was known before
monocular visual impairment, Trauma, blindness, trauma
BLINDNESS
Ocular trauma is a leading cause of monocular visual impairment and blindness worldwide, affecting 55 million people every year.Ocular trauma is a serious health problem that has extensive, variable, physical and psychological impacts on patients and their relatives.The primary aim of the Adjunctive Steroid Combinatio...
PMC10220025
What this study adds
rupture
OPACITIES
Common settings for open globe injury for the ASCOT cohort include the workplace and through interpersonal violence, with a trend in seasonal variation.There is considerable variability in presenting visual acuity for patients with open globe eye injuries undergoing vitreoretinal surgery.Clinical presentations of case...
PMC10220025
Supplementary information
The online version contains supplementary material available at 10.1038/s41433-022-02206-z.
PMC10220025
Acknowledgements
Authors contributing to this paper are supported by the United Kingdom Clinical Research Collaboration-registered King’s Clinical Trials Unit at King’s Health Partners. We thank Beverley White-Alao and staff in the wider KCTU who supported the electronic data capture and randomisation systems and data management for th...
PMC10220025
Author contributions
CM
DC is the chief investigator for ASCOT. SC, GP, VC, CB and DC wrote the statistical analysis plan for this manuscript. SC, GP and VC conducted the statistical analysis for this manuscript. SC, GP and DC wrote the first draft of the manuscript. SC, GP, VC, PB, MZ, EC, SS, CB and DC interpreted the data and critically re...
PMC10220025
Funding
NIHR300593, Cancer
CANCER
The ASCOT trial is funded by a project grant from the National Institute for Health Research Health Technology Assessment (HTA) programme (HTA 12/35/64). CB’s post is part funded by the National Institute for Health Research (NIHR) Biomedical Research Centre at The Royal Marsden NHS Foundation Trust and the Institute o...
PMC10220025
Data availability
The datasets generated and analysed during the current study are available from the corresponding author on reasonable request.
PMC10220025
Competing interests
The authors declare no competing interests.
PMC10220025
References
PMC10220025
Background
There is some initial evidence suggesting that mindsets about the adequacy and health consequences of one’s physical activity (
PMC9909519
Objective
This research examined how wearable fitness trackers and meta-mindset interventions influence AAMs, affect, behavior, and health.
PMC9909519
Methods
A total of 162 community-dwelling adults were recruited via flyers and web-based platforms (ie, Craigslist and Nextdoor; final sample size after attrition or exclusion of 45 participants). Participants received an Apple Watch (Apple Inc) to wear for 5 weeks, which was equipped with an app that recorded step count and c...
PMC9909519
Results
Participants receiving accurate step counts perceived their activity as more adequate and healthier, adopted a healthier diet, and experienced improved mental health (Patient-Reported Outcomes Measurement Information System [PROMIS]-29) and aerobic capacity but also reduced functional health (PROMIS-29; compared with t...
PMC9909519
Conclusions
AAMs––induced by trackers or adopted deliberately––can influence affect, behavior, and health independently of actual physical activity.
PMC9909519
Trial Registration
ClinicalTrials.gov NCT03939572; https://www.clinicaltrials.gov/ct2/show/NCT03939572
PMC9909519
Introduction
PMC9909519