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Ancillary and post -trial care | GHD | GHD | Indemnity arrangements for the GHD Reversal Trial will be undertaken by the sponsor University College London. University College London holds insurance against claims from participants for injury caused by their participation in the clinical trial. Full insurance and indemnity details are given in the study protocol. | PMC10440873 |
Confidentiality and data protection | Personal data recorded on all documents will be regarded as strictly confidential and will be handled and stored in accordance with the Data Protection Act 2018 and Regulation (EU) 2016/679 (General Data Protection Regulation). Full details are given in the current study protocol. | PMC10440873 | ||
Regulatory aspects | The trial will be conducted in compliance with the approved protocol, UK Policy Framework for Health and Social Care Research 2017, Regulation (EU) No. 536/2014 (Clinical Trial Safety Reporting requirements), the Data Protection Act 2018, and Regulation (EU) 2016/679 (General Data Protection Regulation) and the principles of Good Clinical Practice as defined by the European Good Clinical Practice (GCP) Directive and laid down in UK law by the Medicines for Human Use (Clinical Trials) Regulations (2004) and subsequent amendments thereof. In Austria, the trial will be conducted in compliance with the protocol, the relevant Austrian regulatory bodies’ rules and EU relevant regulations in that member state.The study is sponsored by the University College London (UCL), reference number: 108048.EudraCT number: 2020–001006-39.ISRCTN12552768IRAS reference number: 281209. | PMC10440873 | ||
Discussion and potential impact | GHD | ADVERSE EFFECTS, GHD | Five previous studies have demonstrated reversal of GHD (mean 49%; range 19–95%) with earlier re-testing, before or during puberty [Assuming that GH discontinuation will be non-inferior to GH continuation, the expected impact of the study will be:A change in inter/national guidance on GH therapy in I-GHDImproved QoL, fewer injections and clinic visits, diagnostic certainty, and earlier discharge from care for reversed GHD patientsReduce health care costs, with savings estimated at £2 million per year in the UK alone, and potentially hundreds of millions worldwide, every year. In turn, such huge cost savings will benefit patients with other conditions needing expensive therapies, particularly in resource-limited countries.Reduce the risk of long-term potential adverse effects | PMC10440873 |
Trial status | RECRUITMENT, RECRUITMENT | Publication based on Protocol V2.0, 8 April 2022. At the time of publication, several study sites are open to recruitment, but no patients have yet been recruited into the study. Recruitment is estimated to take three and a half years. A list of study sites can be found on the study website: | PMC10440873 | |
Acknowledgements | PIsWolfgang | We would like to thank the NIHR HTA for funding the study. We are also most grateful for the support of the sponsor, University College London, and the University of Birmingham Clinical Trials Unit and the Child Growth Foundation. We would like to thank our DMC and TSC members and the principal investigators (PI) at our study sites. We are particularly grateful to our future study participants and their parents.DMEC members:Professor Ken Ong, Cambridge University Hospitals NHS Foundation Trust (Chair)Dr Malcolm Donaldson, University of GlasgowDr Victoria Harris, University of OxfordProfessor Mohamad Maghnie, University of GenovaTSC members:John Gregory, previously Cardiff University (Chair)Peter Auguste, University of WarwickGerhard Binder, previously Universitätsklinik für Kinder und Jugendmedizin TübingenCarrol Gambol, Director, Liverpool Clinical TrialsLaura Roy, Child Growth FoundationUK PIsPoonam Dhamaraj, Alder Hey Children's NHS Foundation TrustEvelien Gevers, Barts Health NHS TrustVrinda Saraff, Birmingham Women's and Children's NHS Foundation TrustMehul Dattani, Great Ormond Street Hospital for Children NHS Foundation TrustPeter Clayton, Manchester University NHS Foundation TrustTabitha Randell, Nottingham University Hospitals NHS TrustTalat Mushtaq, Leeds Teaching Hospitals NHS TrustTimothy Cheetham, Newcastle Upon Tyne Hospitals NHS Foundation TrustJustin Davies, University Hospital Southampton NHS Foundation TrustNoina Abid, Belfast Health & Social Care TrustRanna El Khairi, University College London Hospitals Children NHS Foundation TrustAustrian PIsWolfgang Högler, Johannes Kepler University LinzKlaus Kapelari, Universitätsklinikum InnsbruckElena Gottardi-Butturini, Uniklinikum SalzburgElke Reiterer-Fröhlich, LKH-Univ. Klinikum GrazWalter Bonfig, Klinikum Wels-Grieskirchen | PMC10440873 | |
Authors’ contributions | EB drafted the manuscript and managed the co-ordination of the study. WH conceived of the study, led in its design and co-ordination, and contributed to the writing of the manuscript. MD led in the co-ordination of the study, contributed to the study design, and contributed to the writing of the manuscript. CC participated in the design of the study and its statistical analysis. RW co-ordinated the statistical aspects of the trial. RO participated in the design of the study and led on health economic component of the study. JM participated in the design of the study and led on the qualitative research component of the study. AK and CH managed the co-ordination of the trial. LR provided vital personal and public involvement input to the study. All authors read and approved the final manuscript. | PMC10440873 | ||
Funding | Funding body: National Institute for Health Research Health Technology Assessment programme: NIHR127468.The views expressed in this publication are those of the author(s) and not necessarily those of the NHS, the National Institute for Health Research, Health Education England or the Department of Health and Social Care. The funder had no role with respect to trial design; collection, management, analysis, and interpretation of data; writing of the report; and the decision to submit the report for publication. | PMC10440873 | ||
Declarations | PMC10440873 | |||
Competing interests | Mehul Dattani and Wolfgang Högler have both received travel support, lecture fees and consultation fees from companies marketing growth hormone over the last few years.Jonathan Mathers, Elizabeth Brettell, Carole Cummins, Rebecca Woolley, Laura Roy, Adam Khan Charmaine Hunt and Raymond Oppong have no conflicts of interest. | PMC10440873 | ||
References | PMC10440873 | |||
Background | The practical training course of internal medicine of traditional Chinese medicine (PTC-IMTCM) is primarily based on traditional case teaching, which can be stressful for teachers. The use of virtual standardized patient (VSP) applications could be an alternative; however, there is limited evidence regarding their feasibility and effectiveness. | PMC10551797 | ||
Objective | This study aimed to build a VSP-TCM application according to the characteristics of PTC-IMTCM and the needs of students and to compare its efficacy with that of traditional teaching in improving TCM clinical competence among students. | PMC10551797 | ||
Methods | A prequestionnaire investigation was conducted before the course, and a VSP-TCM system was developed based on the results of the questionnaire. A randomized controlled trial was then conducted between February 26, 2020, and August 20, 2021. A total of 84 medical students were included and were divided into 2 groups: an observation group, trained with VSP-TCM (n=42, 50%), and a control group, trained with traditional academic training (n=42, 50%). Formative and summative assessments were conducted to evaluate teaching effectiveness. After completing the course, the students were administered a questionnaire to self-assess their satisfaction with the course. A questionnaire was also administered to 15 teachers to uncover their perspectives on VSP-TCM. | PMC10551797 | ||
Results | All participants completed the study. In the formative assessment, the VSP-TCM group performed better in medical interviewing ability (mean 7.19, SD 0.63, vs mean 6.83, SD 0.81; | PMC10551797 | ||
Conclusions | VSP-TCM enhances students’ TCM clinical competence and dialectical thinking and improves their ability to work autonomously. Moreover, the VSP-TCM system is feasible, practical, and cost-effective and thus merits further promotion in TCM education. | PMC10551797 | ||
Introduction | TCM | Clinical practice is the most crucial experience for undergraduate medical students [An alternative training approach could be the use of virtual standardized patient (VSP) programs, which use computerized characters for SP encounters [Traditional Chinese medicine (TCM) is a comprehensive medical system that emphasizes the holistic concept of harmony between humans and nature. Its core principle is to maintain the balance between yin and yang, promote the circulation of qi and blood, and coordinate the different functions of various organs of the body. TCM clinical skills, such as inspection, auscultation and olfaction, palpation, and inquiry, are usually used to assess an individual’s overall health status. TCM practitioners often adopt various therapeutic methods to treat patients, such as herbal medicine, acupuncture, moxibustion, and However, using SPs in TCM education has several limitations; therefore, VSPs present a viable alternative. In the past, VSPs have not been used in TCM education due to technical limitations and the lack of promotion and traditional view. With the implementation of education informatization, an education reform, VSP programs have become more mature and widely acknowledged [In 2019, we formally established the VSP-TCM system and cultivated the first batch of students trained using TCM-VSP. Subsequently, we integrated the VSP-TCM system into the PTC-IMTCM course and conducted training in VSP-TCM mode. In this study, we conducted a multifaceted analysis to compare the effects of VSP-TCM and traditional academic training on students’ clinical competence. We hypothesized that medical students who receive VSP-TCM training would achieve greater progress in clinical competency than those who receive traditional academic training. Our findings are expected to provide a reduced-cost and high-efficiency training mode in TCM medical education. | PMC10551797 | |
Methods | PMC10551797 | |||
Study Design | First, we conducted a questionnaire investigation to gain the perspectives of TCM students who have taken the PTC-IMTCM course. The final version of the VSP-TCM system was designed and developed based on the characteristics of TCM and the results of the questionnaire investigation [Flow diagram of the study. PTC-IMTCM: practical training course of internal medicine of traditional Chinese medicine; VSP-TCM: virtual standardized patient of traditional Chinese medicine; TCM: traditional Chinese medicine; Mini-CEX: mini-clinical evaluation exercise. | PMC10551797 | ||
Ethical Considerations | The study was approved by the Ethics Committee of Chengdu University of Traditional Chinese Medicine (CDUTCM; approval no. 25382) and adhered to the principles of the Declaration of Helsinki. Curriculum planning adhered to the guidelines set by the “Undergraduate Medical Education Standards - Traditional Chinese Medicine” issued by the National Advisory Committee on Higher Traditional Chinese Medicine Education of the Ministry of Education [ | PMC10551797 | ||
Development of the VSP-TCM System | PMC10551797 | |||
Prequestionnaire Investigation | A questionnaire was administered to 1628 medical students who had taken the PTC-IMTCM course. The questionnaire was formulated based on the characteristics and teaching objectives of the course, which included basic information, learning methods, learning habits, learning interests, and acceptance and demand for VSP-TCM. Students who had completed the course were chosen as survey subjects over those who did not complete it, because the former were more familiar with the contents and teaching methods of the course. They could also provide better feedback on course improvement. The results of the questionnaire were used to design the detailed functions and modules of the VSP-TCM system. | PMC10551797 | ||
Design of the VSP-TCM System | DISEASES | The teaching goal of VSP-TCM is to enhance the clinical competence of TCM students. We constructed a case database that included diseases that met the requirements of the latest version of the physician qualification examination outlines. The included diseases were all foundational. Subsequently, we developed an intelligent human-computer interaction environment where users could send instructions by text or voice, such as “What is the main reason for your coming to see a doctor this time?” The VSP-TCM system responded to the user’s commands and simulated a clinical diagnosis, including history taking, physical examination, auxiliary examination, diagnosis and differential diagnosis, and treatment. The VSP-TCM system also summarized the systematic knowledge and evaluated the user’s performance in real time.We collaborated with Shanghai Dream Road Digital Technology Co. Ltd. to complete the development of the VSP-TCM system. Autodesk Maya was used for scene and character modeling, and Adobe Animate CC technology was used for program synthesis. Microsoft Windows 7 or higher was used as the computer operating system, and Microsoft Internet Explorer 8.0 or higher was used as the browser. When using the system, the students wore headsets with microphones (Lenovo). | PMC10551797 | |
User Flow of the VSP-TCM System | The operation procedures of the VSP-TCM system (Operation procedures of the VSP-TCM system. | PMC10551797 | ||
Protocol of the Course | PMC10551797 | |||
Participants | The participants were recruited offline from 112 TCM (5+3 integration) sophomores enrolled in the CDUTCM in 2019. Based on previous studies, a minimum sample size of 78 was required [ | PMC10551797 | ||
Inclusion and Exclusion Criteria | TCM (5+3 integration) students in their second year at the CDUTCM were included. The exclusion criteria were as follows: participants who (1) had received VSP or SP training; (2) had taken courses related to IMTCM, such as PTC-IMTCM and reception and clinical thinking skills; and (3) failed to adhere to the study schedule or withdrew from the study. | PMC10551797 | ||
Randomization and Blinding | Using computer-generated randomization, the participants were randomly assigned to either a VSP-TCM group or a control group in a 1:1 ratio. The randomization was performed by individuals who were not in contact with the participants. The participants, staff, and investigators were blinded to the training assignments. Data analysis was deferred until all data were collected by investigators who were blinded to the outcomes. | PMC10551797 | ||
Teacher Training and Eligibility | coin toss | Teachers in the course group underwent standardized training 1 month before the course started. The standardized training planning was set based on the “Eight-Year Undergraduate Talent Training Guide of Traditional Chinese Medicine” issued by the CDUTCM. Subsequently, experienced clinical experts were invited to assess the teachers’ qualifications. Finally, we selected 2 teachers who were closely matched in terms of age, sex, teaching experience, and teaching style. Using a random coin toss, they were then assigned to either the VSP-TCM group or the control group. | PMC10551797 | |
Training Interventions and Data Collection | DISEASE, PATHOGENESIS, SYNDROME | PTC-IMTCM was conducted in the second semester of the sophomore year (36 class hours, 3 class hours/week, a total of 12 weeks). Both groups had the same teaching materials, such as Microsoft PowerPoint presentations and textbooks. The VSP-TCM group received 36 class hours of VSP-TCM training. The teaching methods were as follows: (1) The teacher discussed the fundamentals of the disease, including etiology, pathogenesis, diagnosis, differential diagnosis, syndrome differentiation and treatment, and key points of history collection; (2) students logged into the VSP-TCM system, selected a disease to practice, and entered the simulated medical scene; (3) students completed the diagnosis and treatment with a VSP, following the process shown in The control group received 36 class hours of traditional academic training, which included teacher teaching and group discussion. Specifically, the teaching methods were as follows: (1) The teacher discussed the fundamentals of the disease and syndrome, similar to the VSP-TCM group; (2) students were randomly assigned to several study groups; (3) students discussed the case provided by the teacher, made a diagnosis, and suggested treatments for the disease within the specified time frame; (4) the teacher evaluated the answers and provided feedback to the students; and (5) students voluntarily completed after-school exercises and recorded their learning time.This study was initiated on February 26, 2020, and concluded on August 20, 2021. From the start of the study to March 2021, staff not involved in the study conducted a prequestionnaire investigation and gathered data on the participants’ performance in basic TCM and WM courses. Next, the 13-week PTC-IMTCM course was conducted from April 1 to July 10, 2021 (first 12 weeks, training; 13th week, evaluation). Finally, investigators who did not take part in the study collected and analyzed the data by August 20, 2021. | PMC10551797 | |
Evaluation of Training Effectiveness | PMC10551797 | |||
Formative Evaluation | The mini-clinical evaluation exercise (mini-CEX), a tool developed by the American College of Internal Medicine in 1995 based on the traditional clinical evaluation exercise, has teaching functions and was used to assess the residents’ clinical ability [ | PMC10551797 | ||
Summative Assessment | SYNDROME | After the course, students were given 1 week to review for the assessment, and the summative assessment was conducted on a day in week 13. The summative assessment was divided into online and offline assessments. Students completed the systematic knowledge test of PTC-IMTCM online before entering the clinical skill center of the CDUTCM for the offline assessment. The offline assessment included the following steps: (1) collecting the medical history from OSPs, (2) medical writing, and (3) syndrome differentiation and treatment. | PMC10551797 | |
Online Systematic Knowledge Test | TCM | SYNDROME | After the course, students completed an objective and standardized online case-based examination. They had 90 minutes to complete 6 cases. For the first 5 cases, there were 5 multiple-choice questions in each case, and students were required to select the right diagnosis, syndrome, treatment principle, treatment method, and prescription. Each multiple-choice question was worth 2 points. The sixth case was a case analysis question. Students were required to provide a TCM diagnosis (5 points), syndrome differentiation (5 points), a syndrome differentiation basis (15 points), treatment (5 points), a prescription (5 points), and prescription analysis (15 points) for the patient in the case. The examination had a total score of 100. | PMC10551797 |
Offline Clinical Skill Test | Following the online examination, students proceeded to the clinical skill center of the CDUTCM for a 45-minute offline clinical skill test. For this test, we used previously developed offline clinical skill assessment methods [ | PMC10551797 | ||
Scores for the Application of TCM Technology | TCM | In the assessment process, a TCM professional who was not part of the research team and did not participate in activities such as teaching and proposition scored the students’ clinical skills using a pre-established checklist. The checklist included the following items: introduction (4 points), chief complaint (8 points), current medical history (30 points), past medical history (12 points), personal medical history (12 points), family medical history (8 points), physical examination and 4 TCM examinations (16 points), and summary (10 points). | PMC10551797 | |
Scores for Written Medical Records | TCM | The medical writing checklist included the following items: general information (3 points), chief complaint (5 points), current medical history (30 points), past medical history (10 points), personal medical history (10 points), family medical history (6 points), physical examination (20 points), and 4 TCM examinations (16 points). Individual item scores were calculated and processed. | PMC10551797 | |
Scores for TCM Syndrome Differentiation and Therapeutic Regimen | TCM syndrome, TCM | SYNDROME | The following were items were included in the checklist for TCM treatment based on syndrome differentiation: TCM diagnosis (6 points); basis for TCM diagnosis (6 points); WM diagnosis (6 points); basis for WM diagnosis (14 points); TCM syndrome type (10 points); analysis of TCM syndrome differentiation (24 points); TCM treatment method (8 points); formula (8 points); medication, administration method, and corresponding dosage (14 points); and medical advice (4 points). The examination was scored using predetermined standards. | PMC10551797 |
OSP Real-Time Assessment Scores | Following each interaction, OSPs used the Arizona Clinical Interviewing Rating (ACIR) scale to assess students’ interpersonal communication and interview skills. The ACIR scale is a 20-item scale, with points ranging from 1 to 5 points, with 5 being the highest [ | PMC10551797 | ||
Postcourse Feedback Questionnaire | A previous study’s [ | PMC10551797 | ||
Statistical Analysis | A blinded research analyst conducted the test. The intraclass correlation coefficient (ICC) was calculated to determine the consistency of the Mini-CEX scores. Statistical analysis was conducted using SPSS 25.0 (IBM). Continuous variables were expressed as the mean (SD) and categorical variables as a frequency or percentage. The Kolmogorov-Smirnov test was used to determine the normality of all the data. When data had a normal distribution, the independent-samples | PMC10551797 | ||
Results | PMC10551797 | |||
Evaluation of Training Effectiveness | PMC10551797 | |||
Summative Assessment | PMC10551797 | |||
Online Systematic Knowledge Test | After 12 weeks of the course, the VSP-TCM group mastered the systematic knowledge of the course better than the control group (Scores of summative assessment (* | PMC10551797 | ||
Offline Clinical Skill Test | PMC10551797 | |||
Scores for the Application of TCM Technology | The VSP-TCM group outperformed the control group in receiving VSP-TCM. The VSP-TCM group performed better in the application of TCM skills (mean 87.86, SD 3.04, vs mean 86.19, SD 3.08; t | PMC10551797 | ||
Scores for Written Medical Records | VSP-TCM did not provide the expected benefits in improving students’ ability to write medical records. The VSP-TCM group scored lower than the control group (mean 75.07, SD 3.61, vs mean 75.71, SD 2.86; t | PMC10551797 | ||
Scores for TCM Syndrome Differentiation and Therapeutic Regimen | TCM syndrome | SYNDROME | VSP-TCM effectively improved core TCM skills, including syndrome differentiation and treatment. The VSP-TCM group had higher scores for TCM syndrome differentiation and treatment than the control group (mean 90.93, SD 2.42, vs mean 89.60, SD 2.86; U=636, | PMC10551797 |
Real-Time Assessment Scores From OSPs | VSP-TCM had a satisfactory effect on improving students’ interpersonal communication and interview skills. The real-time evaluation score from OSPs for the VSP-TCM group was significantly higher than the control group (mean 90.67, SD 4.52, vs mean 88.24, SD 4.56; U=618.5, | PMC10551797 | ||
Discussion | PMC10551797 | |||
Principal Findings | TCM | DISEASES, SYNDROMES, SYNDROME | This study demonstrated that compared with traditional academic training, VSP-TCM significantly improves abilities in medical interviewing, clinical judgment, TCM technology application, and systematic knowledge among TCM students. The VSP-TCM system enabled TCM education to be more efficient and less stressful for teachers. It was also helpful for reforming the course and achieving the goal of training applied talents.IMTCM is a core course that helps students learn how to diagnose and treat patients using TCM technology in the real world [This randomized controlled trial compared the teaching efficacy of VSP-TCM in the PTC-IMTCM course and traditional academic training for 3 months. The findings supported the merits of VSP-TCM; students faced less stress in the simulative clinic, allowing them to devote more time to learning. Through repeated practice within a safe environment, they gradually became familiar with the diagnosis and treatment process, in line with the findings of a previous study [VSP-TCM significantly improved 2 core TCM skills, the ability to collect medical history and the syndrome differentiation and treatment ability. Students’ mastery of the content, logic, and communication skills of inquiry reflected the improvement in their ability to collect medical history. More than 85% of students in the experimental group agreed that VSP-TCM effectively helped them improve their interpersonal communication skills, as opposed to less than 67% in the control group. The real-time evaluation of offline clinical skills from OSPs also indicated that VSP-TCM can significantly improve students’ competence. Given that a solid command of theoretical knowledge guarantees clinical ability, students in the experimental group performed better on the OSKT than the control group, indicating improvement in their theoretical knowledge. This may be attributed to 2 unique advantages of VSP-TCM: repeatability and real-time feedback. Students could better remember the content and logic of medical history collection due to repeatability. In addition, real-time feedback offered students valuable insights into the overall quality of their performance and identified areas that needed further improvement [Overall, the postcourse feedback questionnaire showed that both groups were satisfied with the course. The course had positive teaching efficacy and achieved the teaching objectives. VSP-TCM promoted the development of TCM thinking and critical thinking. It also strengthened students’ clinical skills, self-study ability, and comprehensive ability to help them become qualified future doctors. Interestingly, although VSP-TCM improved students’ clinical skills, they did not have a high confidence level in solving clinical problems. This may be because the students had not yet officially begun their clinical work, which was unfamiliar to them. Furthermore, students believed that VSP-TCM did not significantly improve their medical writing ability, which contradicted our assumption. This may be because VSP-TCM automatically records and displays all operations of students, with easy access to clinical data. Consequently, the students did not develop the awareness and habit of taking notes during medical interviews. This gave us a preliminary idea for improving VSP-TCM. In addition, teachers’ perspectives on the VSP-TCM system indicated that it could be a good teaching tool, which could improve teaching efficacy and partly reduce the teaching pressure on teachers. However, the system should be more consistent with the characteristics of TCM, such as simulating patients with different syndromes instead of diseases.VSP-TCM is cost-effective, which is an outstanding advantage. According to our previous experience, OSP and SSP systems incur substantial costs in terms of human resources and materials [ | PMC10551797 |
Limitations | Although the findings of this study are positive, it has some limitations that should be acknowledged. First, in this prospective study, we only evaluated the clinical skills of students during and after the course, with no long-term follow-up. We were unaware of how VSP-TCM maintained the trainees’ competence. Second, VSP-TCM cannot convey some physical signs of real patients. For example, TCM-specific pulse conditions can only be displayed through images, preventing trainees from gaining real clinical experience in pulse diagnosis [ | PMC10551797 | ||
Conclusion | HY, JGYB2019008 | This randomized controlled trial demonstrated the feasibility of VSP-TCM in improving the clinical competence of medical students. VSP-TCM may be a replacement for OSPs and SSPs in universities with limited expenditure. VSP-TCM deserves more attention and promotion. Therefore, future studies aiming to improve VSP-TCM systems that can effectively enhance the clinical abilities of medical students are warranted.This study was funded by grants JGYB2019008 (HY) from the Teaching Reform Project of the Chengdu University of Traditional Chinese Medicine (CDUTCM); CDUTCM-2020 no. 140 (BL) from the Promotion Plan for Young Teachers of the CDUTCM; 2022ZLGC40 (BL) from the Special Project of Education and Teaching Research Center of the CDUTCM; JYJX202211 (YZ) and JYJX202215 (JZ) from the Education and Teaching Reform Research Project of clinical medical school of CDUTCM; S202210633021 (XX) from the Innovation Training Project of the CDUTCM; and ky-2022004 (XX) from the Scientific, Practice, and Innovation Project of the CDUTCM.Authors' Contributions: HY, XX, and XW contributed to this paper equally and share first authorship. XX, JZ, and YZ had full access to all the data in the study and take accountability for data integrity and the accuracy of data analysis. YZ, BL, and JZ concepted and designed the study. XX, XF, and YL obtained and analyzed data. HY, XX, XW, and JZ drafted and revised the manuscript. XX and QD performed the statistical analysis. HY, XX, and BL obtained funding.Conflicts of Interest: None declared.Modified mini-clinical evaluation exercise (mini-CEX) and the flow of formative evaluation.Consolidated Standards of Reporting Trials of Electronic and Mobile Health Applications and Online Telehealth (CONSORT-eHEALTH) checklist (V 1.6.1). | PMC10551797 | |
Abbreviations | Arizona Clinical Interviewing RatingChengdu University of Traditional Chinese Medicineintraclass correlation coefficientinternal medicine of traditional Chinese medicinemini-clinical evaluation exerciseonline systematic knowledge testoccupational standardized patientpractical training course of internal medicine of traditional Chinese medicinestandardized patientstudent standardized patienttraditional Chinese medicinevirtual standardized patientWestern medicine | PMC10551797 | ||
Data Availability | The “Eight-Year Undergraduate Talent Training Guide of Traditional Chinese Medicine” issued by the Chengdu University of Traditional Chinese Medicine is available upon reasonable request. | PMC10551797 | ||
1. Introduction | bleeding, hematological abnormalities, TPO-RAs, thrombocytopenia, cirrhosis, hepatocellular carcinoma, transfusion-associated, CLD | CHRONIC LIVER DISEASE, BLEEDING, THROMBOCYTOPENIA, ADVERSE EVENTS, THROMBOCYTOPENIA, CIRRHOSIS, HEPATOCELLULAR CARCINOMA, PORTAL VEIN THROMBOSIS, CLD, CHRONIC LIVER DISEASE | The phase 4 observational cohort study assessed the effectiveness and safety of the thrombopoietin receptor agonist avatrombopag in patients with chronic liver disease (CLD) and thrombocytopenia undergoing a procedure. Patients with CLD may have thrombocytopenia, increasing the risk of periprocedural bleeding. Prophylactic platelet transfusions used to reduce this risk have limitations including lack of efficacy and transfusion-associated reactions. Prophylactic thrombopoietin receptor agonists have been shown to increase platelet counts and decrease platelet transfusions. Effectiveness was assessed by change from baseline in platelet count and proportion of patients needing a platelet transfusion. Safety was assessed by monitoring adverse events (AEs). Of 50 patients enrolled, 48 were unique patients and 2 patients were enrolled twice for separate procedures. The mean (standard deviation) change in platelet count from baseline to procedure day was 41.1 × 10Chronic liver disease (CLD) is associated with hematological abnormalities,Thrombocytopenia in patients with CLD is nearly always linked to cirrhosis,Invasive surgical and therapeutic procedures, such as liver biopsies, variceal band ligation, or percutaneous procedures for hepatocellular carcinoma are common in patients with CLD.Prophylactic platelet transfusion is commonly used to improve thrombocytopenia in patients with CLD,Given the drawbacks of traditional treatments, focus has shifted to the use of thrombopoietin receptor agonists (TPO-RAs), which interact with the thrombopoietin receptor on megakaryocytes resulting in an increase in platelet production.Recent meta-analyses indicated that the use of TPO-RAs prior to procedures results in increased platelet counts and decreased incidence of platelet transfusions, compared with placebo, whilst having no significant effect on the rate of portal vein thrombosis.This phase 4 observational cohort study was designed to assess the real-world effectiveness, safety, and treatment patterns of avatrombopag in patients with thrombocytopenia associated with CLD undergoing a procedure. | PMC10553023 |
2. Materials and methods | PMC10553023 | |||
2.1. Study design | MAY | This was a phase 4, multicenter, observational cohort study (NCT03554759) conducted from July 2018 to January 2019. The study planned to enroll a total of 500 subjects from sites in the USA after avatrombopag was approved for this indication by the FDA in May 2018.Data were collected prospectively or retrospectively from information routinely recorded in a patient’s medical records and from laboratory data. Visits, examinations, laboratory tests, or procedures were not mandated or recommended as part of this study. The duration of patient participation and collection of clinical data was up to 6 weeks from the initial (baseline) visit or data were extracted from an approximately 6-week window of patient visits. Data were entered into the electronic data capture system based on patient visits occurring within approximately 7 calendar days of their first avatrombopag use (baseline visit), during any visits while taking avatrombopag (treatment period), on procedure day, on discharge day (if applicable) and for any visit performed up to 30 days post-procedure (follow-up period). | PMC10553023 | |
2.2. Inclusion criteria | CLD, thrombocytopenia | THROMBOCYTOPENIA, CLD | All patients enrolled were ≥ 18 years, had thrombocytopenia associated with CLD and were planned to undergo, or underwent, treatment with avatrombopag prior to a procedure. For retrospective enrollment (patients enrolled and consented after procedure day) patients must have had, at a minimum, a platelet count from approximately 7 days prior to starting avatrombopag and a platelet count on the procedure day, to enable evaluation of study endpoints. All patients provided written informed consent and there were no exclusion criteria for participation in this observational study, including no exclusion of patients for concomitant medications before or during the study. | PMC10553023 |
2.3. Treatment | Avatrombopag was taken orally and doses were determined by the treating physician in conjunction with the FDA-approved US prescribing information. | PMC10553023 | ||
2.4. Effectiveness analysis | The effectiveness of avatrombopag was assessed by the change from baseline in platelet count on procedure day and the proportion of patients who received a platelet transfusion after the baseline visit and up to 7 days post-procedure day. The effectiveness of avatrombopag was also assessed by subgroup analyses of the change in platelet count from baseline to procedure day by baseline platelet count group and Child–Turcotte–Pugh (CTP) Grade.Additional ad hoc analyses, not prespecified in the final statistical analysis plan, were also performed. These included a responder analysis based on patients achieving platelet count ≥ 50 × 10 | PMC10553023 | ||
2.5. Safety analysis | death, bleeding, congenital anomaly, blood loss, thrombotic | THROMBOEMBOLIC EVENT, BLEEDING, ADVERSE EVENTS, BLOOD LOSS, EVENT, EVENTS, COMPLICATIONS | The safety of avatrombopag was assessed by recording adverse events (AEs). These were reported by the patient or, when appropriate, by a caregiver, surrogate, or the patient’s legally authorized representative, and/or collected from data recorded in the patient’s medical record. The severity of each AE was recorded, with mild AEs defined as transient, requiring minimal treatment or intervention and not interfering with daily living; moderate AEs defined as being alleviated with specific therapeutic intervention causing some impairment to daily activities and discomfort but posing no significant or permanent risk of harm; and serious AEs defined as AEs resulting in death, a threat to life, hospitalization (even if admitted and discharged on the same day, although an emergency room attendance that did not result in admission was not included), or prolongation of existing hospitalization, a persistent or significant disability, a congenital anomaly, or a requirement for medical or surgical intervention to prevent any of the aforementioned criteria.AEs were deemed to be treatment-emergent AEs (TEAEs) or serious TEAEs when the time course between the administration of avatrombopag and the occurrence or worsening of the AE was consistent with a causal relationship and no other cause (concomitant drugs, therapies, complications, etc) could be identified. The AEs of special interest were defined as thromboembolic events (any thrombotic or embolic event, whether arterial or venous) and bleeding events (any clinically significant blood loss). | PMC10553023 |
2.6. Statistical analysis | The sample size for this study was based on clinical, rather than statistical rationale, and was considered adequate to address the study objective, which was to observe the treatment patterns and effects of avatrombopag in real-world practice. This objective was neither related to the testing of a specific hypothesis, nor to the precision of a particular estimate. The analysis population and the safety population analyzed were defined as all enrolled patients. The analysis of effectiveness endpoints was descriptive and based on data entered in the electronic case report form for enrolled patients. A 95% exact confidence interval (CI) (using the Clopper–Pearson method) was performed for the proportion of patients who received a platelet transfusion after the baseline visit and up to 7 calendar days following procedure day. | PMC10553023 | ||
3. Results | PMC10553023 | |||
3.1. Patient population | autoimmune hepatitis, primary biliary cholangitis, biliary cirrhosis, acid-related disorders, liver cancer, hepatoportal sclerosis, hepatic cirrhosis, hepatocellular carcinoma, CLD | AUTOIMMUNE HEPATITIS, BILIARY CIRRHOSIS, PRIMARY BILIARY CHOLANGITIS, LIVER CANCER, CRYPTOGENIC CIRRHOSIS, HEPATIC CIRRHOSIS, HEPATOCELLULAR CARCINOMA, CIRRHOSIS OF THE LIVER, PRIMARY SCLEROSING CHOLANGITIS, CLD | This phase 4 observational registry study was conducted at 43 sites in the USA and was terminated by the sponsor, due to enrollment challenges, prior to completing the planned enrollments. When terminated, 29 of the 43 active sites had screened a total of 65 patients, and 25 of the sites had enrolled a total of 50 patients. Of these 50 patients, 48 were unique patients with 2 patients having been reenrolled into the study and received 2 regimens of avatrombopag for separate procedures, as allowed by the protocol.The overall mean (standard deviation [SD]) age was 61.2 (8.28) years with a higher proportion of males (56%) than females. The enrolled patients had a mean (SD) CTP Grade of 6.7 (1.55) (n = 38) and were of predominantly white racial heritage; full demographics and baseline characteristics are shown in Table Demographics and baseline characteristics.Percentages are based on the number of enrolled patients.SD = standard deviation.Patients may be counted in more than one category.Other etiology of CLD included cryptogenic cirrhosis (n = 4), autoimmune hepatitis (n = 3), hepatic cirrhosis (n = 2), primary sclerosing cholangitis (n = 1), biliary cirrhosis (n = 1), primary biliary cholangitis (n = 1), hepatoportal sclerosis (n = 1) and cirrhosis of the liver (n = 1).Barcelona clinic liver cancer Grade for hepatocellular carcinoma included: Grade 0 (n = 1), Grade A (n = 2), Grade B (n = 1) and unknown (n = 1).All patients completed a 5-day course of once-daily avatrombopag, with 1 (2%) receiving 20 mg (off-label), 27 (54%) receiving 40 mg, and 22 (44%) receiving 60 mg. All patients received at least 1 concomitant medication during the study, which included medications administered during the procedure (41 [82%] receiving a concomitant medication on procedure day) and for the treatment of AEs. Most concomitant medications were within the pharmacological subclasses of anesthetics and drugs for acid-related disorders. | PMC10553023 |
3.2. Types of procedures | umbilical hernia, right inguinal hernia | SECONDARY | Procedures that occurred during the study could be defined as either the primary procedure or the secondary procedure when multiple procedures occurred at the same time. The most common procedure was upper gastrointestinal (GI) endoscopy (56% [n = 28] of primary procedures and 4% [n = 2] of secondary procedures). Of the 7 procedures classified as “other,” 2 were right inguinal hernia repairs, 1 cervical epidural injection, 1 right L3 to L4 microdiscectomy and 1 endometrial curette (all primary), and 1 umbilical hernia repair and 1 sigmoidoscopy (secondary) (Table Surgical procedures.Total percentages sum to > 100% as both primary and secondary procedures are listed.GI = gastrointestinal.One patient received avatrombopag treatment and completed the study but did not have a procedure performed (the planned procedure was canceled).Secondary procedures were performed at the same time as the primary procedure. | PMC10553023 |
3.3. Effectiveness analysis | Treatment with avatrombopag resulted in an increased platelet count, with a mean (SD) change in platelet count from baseline to procedure day (days 8 to 15 after the first dose of avatrombopag, n = 38) of 41.1 × 10Platelet count by study visit. Treatment is defined as the day of initiation of avatrombopag up to and including the day before procedure day. For patients who did not have a platelet count assessment on the day of the procedure, but rather had a platelet count assessed the day prior to the procedure, the platelet count assessed the day prior to the procedure was summarized as a procedure platelet count. N = number, SD = standard deviation.Platelet count at baseline and procedure day by baseline platelet count. For patients who did not have a platelet count assessment on the day of the procedure, but rather had a platelet count assessed the day prior to the procedure, the platelet count assessed the day prior to the procedure was summarized as a procedure platelet count. N = number, SD = standard deviation.The proportion of patients not requiring a platelet transfusion after baseline and up to 7 calendar days following procedure day was 98% (n = 49; 95% CI: 89.4%–99.9%). One patient with a baseline platelet count of 34 × 10 | PMC10553023 | ||
3.4. Additional effectiveness analysis | cirrhosis | CIRRHOSIS | A subgroup analysis by the severity of cirrhosis, using reported CTP Grade at baseline, was performed. The change in platelet count from baseline to procedure day, within each CTP Grade, was consistent with the overall analysis (Fig. Platelet count at baseline and procedure day by Child–Turcotte–Pugh Grade. Baseline CTP Grade B and C groups were combined due to the small sample size (Grade B: baseline n = 11, procedure n = 10; Grade C: baseline n = 3, procedure n = 2). For patients who did not have a platelet count assessment on the day of the procedure, but rather had a platelet count assessed the day prior to the procedure, the platelet count assessed the day prior to the procedure was summarized as a procedure platelet count. CTP = Child–Turcotte–Pugh Grade, SD = standard deviation. | PMC10553023 |
3.5. Responder analysis | A responder analysis (patients achieving a platelet count of ≥ 50 × 10When evaluated by baseline platelet count cohort, 9 of 18 patients with a baseline platelet count < 40 × 10 | PMC10553023 | ||
3.6. Safety analysis | bleeding, TEAEs, pyrexia, deaths, TEAE | ADVERSE EVENTS, EVENTS, BLEEDING, ADVERSE EVENT | All enrolled patients received 5 days of once-daily exposure to avatrombopag with no significant safety issues observed. No deaths occurred and 5 serious AEs were reported in 2 (4%) patients, with none considered related to avatrombopag treatment. The majority of patients had TEAEs that were mild (n = 3 [6%]) or moderate (n = 3 [6%]), with 1 (2%) severe TEAE of pyrexia; none led to discontinuation or were considered related to avatrombopag (Table Overview of treatment-emergent adverse events.TEAE = treatment-emergent adverse event.Two mild bleeding events were reported, with both considered unrelated to avatrombopag by the investigator. One patient, prescribed 60 mg avatrombopag, had a baseline platelet count of 36 × 10 | PMC10553023 |
4. Discussion | bleeding, TPO-RAs, thrombocytopenia, cirrhosis, TEAEs, CLD | THROMBOCYTOPENIA, BLEEDING, CIRRHOSIS, CLD | The objective of this phase 4 study was to collect real-world data on the ability of avatrombopag to increase platelet counts and reduce the need for platelet transfusions or rescue procedures for bleeding in patients with CLD scheduled to undergo a procedure. Avatrombopag was effective and well tolerated by all patients, with the mean platelet count nearly doubling by procedure day and only 1 patient (2%) requiring a platelet transfusion.The progression of CLD frequently results in cirrhosis,The advent of TPO-RAs has resulted in a new treatment management strategy to allow procedures that carry a risk of periprocedural bleeding to be managed safely in this vulnerable patient population.In this study, avatrombopag consistently increased platelet counts in patients with CLD and thrombocytopenia. The mean (SD) baseline platelet count in this study was 46.9 × 10Avatrombopag was also found to reduce the need for platelet transfusions in this patient population. Forty-nine out of 50 enrolled patients did not require a platelet transfusion after the baseline visit and up to 7 days following procedure day (98%; 95% CI: 89.4%–99.9%), and no patients required a rescue procedure for bleeding during the study period. Although direct comparisons cannot be made due to the heterogeneity of patient populations and study designs, the proportion of patients not requiring a platelet transfusion was higher than that in the phase 3 ADAPT studies,Similar efficacy results were recently reported in a real-world retrospective study of avatrombopag in patients with CLD scheduled to undergo a procedure (n = 29), which had similar patient population demographics and in which the most common procedure was upper GI endoscopy with planned esophageal band ligation (86%).Our study provides limited initial data on the safety and effectiveness of avatrombopag in patients with baseline platelet counts greater than those previously evaluated in the phase 3 ADAPT studies. Increasing platelet counts in patients with baseline platelet counts ≥ 50 × 10The use of avatrombopag could facilitate invasive procedures that would otherwise be postponed or not performed due to the severity of the patient’s thrombocytopenia. In the real-world setting, patients with CLD require diverse interventions and severe thrombocytopenia can exclude these patients from life-saving procedures such as percutaneous radio-frequency ablation in malignant lesions.The safety profile observed in this study is comparable to the pooled phase 3 ADAPT data and similar to the reported safety of lusutrombopag.The TEAEs identified in this study were similar for all doses of avatrombopag taken and do not suggest any new or unexpected safety concerns compared to the 2 large, multicenter, phase 3 ADAPT studies. The safety and effectiveness profiles did not differ in the 2 patients who received 2 subsequent courses of treatment with avatrombopag for separate procedures, in line with data published for lusutrombopag, | PMC10553023 |
4.1. Challenges and limitations | TPO-RAs | THROMBOCYTOPENIA | A limitation of this study is the small sample size that limits the conclusions, especially those regarding observations drawn from subgroups of patients. Nonexperimental observational studies typically involve a more diverse group of patients than experimental and interventional clinical studies and more accurately reflect real-world medical practice. Future larger real-world studies should help to elucidate the potential use of TPO-RAs prior to procedure in this challenging patient population. Further evidence may allow for shift in the risk/benefit calculation for more invasive procedures in patients with CLD-associated thrombocytopenia. | PMC10553023 |
5. Conclusion | CLD, bleeding | THROMBOCYTOPENIA, BLEEDING, CLD | The results of this real-world study indicate that avatrombopag is effective in a patient population with CLD of diverse etiologies and severity. Importantly, avatrombopag was well tolerated and effective in increasing platelet counts, allowing procedures to be performed with greater confidence. The limited data presented in this study also suggest that avatrombopag is suitable for repeated use and can be used to prevent periprocedural bleeding in surgical interventions not previously studied. In a real-world setting in patients with CLD and thrombocytopenia, treatment with avatrombopag consistently increased platelet counts to nearly double the baseline platelet count by the day of the procedure and reduced the need for platelet transfusions. | PMC10553023 |
Supplementary Material | PMC10553023 | |||
Abbreviations: | thrombocytopenia, chronic liver disease | THROMBOCYTOPENIA, MITCHELL, CHRONIC LIVER DISEASE | adverse eventsconfidence intervalchronic liver diseaseChild–Turcotte–Pughelectronic case report formfood and drug administrationgastrointestinalstandard deviationtreatment-emergent AEsthrombopoietin receptor agonistThe datasets generated during and/or analyzed during the current study are not publicly available, but are available from the corresponding author on reasonable request.Supplemental Digital Content is available for this article.Brian Jamieson is an employee of Sobi, Inc. and was an employee of Dova Pharmaceuticals, a Sobi company. Mitchell L. Shiffman has received fees for participating in advisor meetings with AbbVie, Exelexis, Gilead, HepQuagnt, Intercept and Intra-Sana and discloses grant support from Celgene, CymaBay, Durect, Enanta, Galectin, Genfit, Gilead, HepQuant, Hamni, High Tide, Intercept, Madrigal, Mirum, Novo Nordisk, Pliant, and Viking. Mitchell L. Shiffman has also received speaker fees from AbbVie, Gilead, Genentech, Intercept, Intra-Sana, Mallinkrodt. Sanjaya K. Satapathy has served as a speaker for Intercept, Alexion, Dova, as an advisory board member for Gilead, Intercept, Bayer and has received research funding from Novartis, Fibronostics Gilead, Biotest, Genfit, Conatus, Intercept, Shire, Exact Sciences, Eananta, Dova, Bayer. Sanjaya K. Satapathy is an employee of Northwell Health. The study was funded by Dova Pharmaceuticals, a Sobi company. Medical writing and editorial support, funded by Sobi, was provided by Catherine Hoare, PhD, Bioscript Group, Macclesfield, UK.The authors have no conflicts of interest to disclose.How to cite this article: Satapathy SK, Sundaram V, Shiffman ML, Jamieson BD. Real-world use of avatrombopag in patients with chronic liver disease and thrombocytopenia undergoing a procedure. Medicine 2023;102:40(e35208). | PMC10553023 |
References | PMC10553023 | |||
Aims | hip arthroplasty | Robot-assisted total hip arthroplasty (rTHA) boasts superior accuracy in implant placement, but there is a lack of effective assessment in perioperative management in the context of enhanced recovery after surgery (ERAS). This study aimed to compare the effectiveness and safety of rTHA versus conventional total hip arthroplasty (cTHA) in ERAS-managed patients. | PMC10506298 | |
Methods | blood loss, pain | BLOOD LOSS, POSTOPERATIVE COMPLICATIONS | In this prospective trial, a total of 60 eligible patients aged between 18 and 80 years were randomly divided into two groups to undergo either rTHA or cTHA. The primary outcomes included blood loss parameters. Secondary outcomes were the duration of the operation, surgical time, WOMAC pain score, WOMAC stiffness score, WOMAC physical function score, Harris score, and postoperative complications. | PMC10506298 |
Results | SEVERE ANEMIA | The study cohort analyzed 59 eligible participants, 30 of whom underwent rTHA and 29 of whom underwent cTHA. Analysis could not be conducted for one patient due to severe anemia. Notably, the cTHA group had a significantly shorter surgical time than the rTHA group (69.49 ± 18.97 vs. 104.20 ± 19.63 min, | PMC10506298 | |
Conclusions | blood loss, pain | BLOOD LOSS, COMPLICATIONS | Despite the longer surgical time, rTHA did not negatively affect blood loss, pain, or functional recovery or lead to an increased risk of complications in ERAS-managed patients, suggesting that rTHA can be safely and effectively incorporated into an ERAS program for primary THA. | PMC10506298 |
Keywords | PMC10506298 | |||
Introduction | blood loss, end-stage hip joint diseases, THA, pain | BLOOD LOSS, COMPLICATIONS | Total hip arthroplasty (THA) is widely considered one of the most successful surgical procedures in the twentieth century and a common approach in treating end-stage hip joint diseases [Robot-assisted THA is a relatively new technology that has shown great clinical prospects [In this prospective trial, we aimed to compare perioperative blood loss, pain, functional recovery, and complications between rTHA and cTHA. Through the analysis of these outcomes, we hope to determine the effectiveness and safety of robot-assisted THA in ERAS programs. | PMC10506298 |
Materials and methods | PMC10506298 | |||
Patients | neuromuscular dysfunction, dysplasia, hip arthroplasty, infection, bony ankylosis, hip deformity | DYSPLASIA, WEST, INFECTION, DISEASES, ANKYLOSING SPONDYLITIS | The Ethics Committee on Clinical Trials of West China Hospital of Sichuan University approved this single-center, prospective trial (HX-IRB-AF-12-V4.0) involving participants aged 18–80 years. All patients provided written informed consent. Exclusion criteria included neuromuscular dysfunction, active infection lesions, severe hip deformity, hip dysplasia with Crowe grade 3 or 4, ankylosing spondylitis patients with bony ankylosis or severe stiffness, bilateral hip arthroplasty, severe internal and surgical diseases, weak physique, and poor expected compliance. A total of 67 patients were scheduled to undergo primary THA, 4 were ineligible, and 3 declined participation (Fig. Consort (consolidated standards of reporting trials) flow diagram showing the process for incorporating participants through robotic arm-assisted total hip arthroplasty (rTHA) vs conventional total hip arthroplasty (cTHA) | PMC10506298 |
Sample size calculation | bleeding | BLEEDING | This study was designed as a randomized controlled trial to assess non-inferiority. The experimental group consisted of patients undergoing rTHA, while the control group comprised patients undergoing cTHA. The primary outcome measure was the total amount of bleeding in the study participants. Based on the findings from our preliminary experiment, there was a difference of 115 between the experimental and control groups. With a bilateral α level of 0.05 and a power (1 − | PMC10506298 |
Surgical procedure and perioperative management | blood loss, thrombosis, THA, pain | BLOOD LOSS, THROMBOSIS | Patients underwent either conventional THA or robotic arm-assisted THA. The rTHA was operated with a single semiactive surgical robot (YUANHUA-THA) whose surgical procedures were described in the technical manuals provided by the manufacturer. All patients were administered the standard ERAS protocol in our hospital including tranexamic acid (TXA) for blood loss prevention, pain management techniques, thrombosis prevention measures, and functional rehabilitation. Specifically, patients were prescribed a twice-daily dose of 200 mg celecoxib from admission until 14 days after discharge. As part of our TXA protocol, patients received 2 g of intravenous TXA 30 min before the incision, followed by 1 g of intravenous TXA at 3 and 6 h after the surgery. Prior to TXA administration, all patients received 5 mg of dexamethasone intravenously. For thrombosis prevention, low molecular weight heparin (enoxaparin) in 0.2 ml was administered 8 h after the surgery and increased to 0.4 ml per day on subsequent days until discharge. Patients were then prescribed apixaban for two weeks. | PMC10506298 |
Clinical outcomes | bleeding, blood loss, intraoperative blood loss, numbness, anemia, dislocation, infection, dysuria, hypokalemia, arthralgia | PULMONARY EMBOLISM, BLEEDING, POSTOPERATIVE COMPLICATIONS, BLOOD LOSS, DEEP VEIN THROMBOSIS, HYPOPROTEINEMIA, ANEMIA, INFECTION, SECONDARY, INTRAOPERATIVE BLOOD LOSS, COMPLICATIONS | The primary outcome was assessed by measuring various parameters related to blood loss, as blood management was a very crucial component of ERAS. Objective indicators such as total blood loss, intraoperative blood loss, drainage volume, blood transfusion volume, and hidden blood loss were measured. The theoretical bleeding volume of each patient was determined by Gross's formula [The secondary outcomes were measured based on several parameters, such as the duration of the operation, surgical time, WOMAC score, Harris score, and postoperative complications. These outcomes were evaluated on admission, every day from postoperative days (PODs) 1–3, the day of discharge, and one and three months after surgery. Postsurgical complications, such as anemia, hypoproteinemia, hypokalemia, arthralgia, superficial infection, dysuria, numbness of lower limbs, dislocation, deep vein thrombosis, and pulmonary embolism, were monitored. | PMC10506298 |
Statistical analysis | Means and standard deviations were used for quantitative variables, and percentages were used for qualitative variables. Independent sample | PMC10506298 | ||
Acknowledgements | We would like to thank the surgeons, nurses, and research staff at our joint center for their support. | PMC10506298 | ||
Author contributions | HPL and HCS drafted the work and provided critical revision for important intellectual content. HPL, QX, and HX performed data collection, analysis, and interpretation. QZ, LYL, and TFY participated in final approval of the version to be published. DW and ZKZ contributed to the conception and design of the study, and revised the manuscript. All authors read and approved the final manuscript. | PMC10506298 | ||
Funding | This study was supported by the Key Research & Development Program of the Science & Technology Department of Sichuan Province (2021YFS0125), and the Regional Innovation & Cooperation Program of the Science &Technology Department of Sichuan Province (2021YFQ0028). The funders had no role in study design, data collection, data analysis, decision to publish, or preparation of the manuscript. | PMC10506298 | ||
Declarations | PMC10506298 | |||
Ethical approval and consent for participants | WEST | This trial received approval from the Ethics Committee on Clinical Trials at West China Hospital of Sichuan University (HX-IRB-AF-12-V4.0). Prior to their participation, all patients provided written informed consent. A statement of the location where the work was performed: The work was performed in Department of Orthopaedic surgery, West China Hospital, Sichuan University. | PMC10506298 | |
Competing interests | No conflict of interest exits in the submission of this manuscript, and manuscript is approved. | PMC10506298 | ||
References | PMC10506298 | |||
Rationale | PREMATURE BIRTH | Premature birth is an independent predictor of long-term cardiovascular risk. Individuals affected are reported to have a lower rate of | PMC10161761 | |
Objectives | The primary objective was to determine whether the | PMC10161761 | ||
Methods | Fifty-two preterm-born and 151 term-born participants were randomly assigned (1:1) to 16 weeks of aerobic exercise training ( | PMC10161761 | ||
Measurements and Main Results | term-born | For term-born participants, | PMC10161761 |
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