| BackgroundThe use of traditional Chinese medicine(TCM)in the treatment of osteonecrosis of the femoral head(ONFH)has been recommended in the relevant Western medical consensus and guidelines,and the advantages of curative effect in the early and middle stages have also been gradually recognized.However,due to the confusion and different standards of the evaluation method of TCM in the treatment of ONFH,The therapeutic effects reported in different literatures may get opposite results,and there is a lack of consistent and systematic evaluation method of the therapeutic effect.This further leads to low repeatability of clinical and scientific research,difficulty in horizontal comparison of therapeutic effects and reduce data utilization between the original researches,which is not conducive to the evidence-based development of TCM and provides high-quality evidence for evidence decision-making.The concept of core outcome set(COS)can effectively solve the problem of the selection of outcomes for efficacy evaluation in clinical practice,which standardizes the set of minimum outcome indicators that must be measured for specific diseases.it can not only effectively simplify the design of the trial scheme,reduce the risk of bias in the implementation process,but also enhance the practicability of clinical research and improve the quality of the transformation from original research to evidence decision-making.Based on this,we introduce the concept of COS into the evaluation of the efficacy of TCM in the treatment of ONFH,and carry out the construction of the COS of TCM clinical research on ONFH,and form a clinically feasible evaluation method of therapeutic effect and carry out clinical verification on its reliability,validity and responsiveness,aiming at standardizing the evaluation of therapeutic effect of TCM on ONFH,and improving the quality of data utilization of original research and transformation to evidence decision-making.Objective1 To establish a method for evaluating the efficacy of TCM in the treatment of ONFH based on the concept of "the most important,standardized and consensus" of COS.2 To verify the clinical evaluation outcome of the therapeutic effect evaluation method,through the cross-sectional and prospective follow-up study.3 To verify the radiological imaging evaluation outcome of the therapeutic effect evaluation method by cross-sectional study and retrospective study.Methods1 Through the systematic evaluation of the literature,we searched the clinical trial study of osteonecrosis of the femoral head in the Chinese and English databases from 2015 to 2017,extracted the outcome index from the original literature and standardized expression according to the relevant terms;at the same time,classify the outcomes according to the categories of outcomes to form a list;Delphi questionnaires were designed,and the importance of outcomes were evaluated,screened and concentrated through two rounds of Delphi physicians' questionnaire and one round of patients' questionnaire.At the same time,the opinions and views of key stakeholders on the selection of outcomes of TCM in the treatment of ONFH were obtained.Finally,through the face-to-face consensus meeting,the final outcomes and measurement methods which finally constitute the COS weredetermined,and form the therapeutic effect evaluation method of TCM in the treatment of ONFH.2 Through cross-sectional and prospective follow-up study,231 patients with ONFH were voluntarily treated with TCM from September 2018 to December 2019.The scores of this method,Harris hip score(HHS)and the time required for the measurement of the two methods were collected before and 3 months after treatment.These data were used to verify the validity,responsiveness and feasibility of clinical evaluation outcome.3 The verification of the radiological imaging evaluation outcome was divided into two parts:(1)Consistency verification:through the cross-sectional study,the X-rays of 231 patients(231 hips)included from September 2018 to December 2019 were collected and sampled equidistant,6 orthopedic surgeons were selected to verify the consistency between observers and the retest consistency.(2)Dynamic observation:the X-ray images of the patients who had received total hip arthroplasty(THA)from 2018 to 2019 and were treated with hip preservation for at least 2 years were dynamically observed.A senior professional physician scored the changes of the morphology,necrotic area and degree of osteoarthritis of the femoral head.The aim was to observe its dynamic changes and to explore the relationship between X-ray images before replacement and THA.Results1 Establishment of a method for evaluating the therapeutic effect of TCM on ONFH based on COS1.1 Form the original outcome listIn this study,a total of 11697 literatures were searched in Chinese and English databases,3828 repetitive literatures were removed,and 1207 literatures were read by reading titles and abstracts,excluding reviews,medical records,animal experiments and other non-compliant literatures.finally,411 studies that meet the requirements were included.The 149 outcomes extracted were classified according to symptoms and signs,long-term outcome,quality of life,radiological imaging evaluation,safety events,evaluation of TCM syndrome,satisfaction evaluation,physical and chemical parameters,hospitalization time and surgical evaluation.Then,the original outcome list was formed,and the Delphi questionnaires for clinicians and patients were designed according to the original list.1.2 Delphi Survey of key stakeholder groups.Two rounds of clinician questionnaires:round 1,a total of 73 questionnaires were distributed and 67 were recovered,with a response rate of 91.8%.Each outcome was evaluated by the 9-point Likert score system.27 outcomes with an average importance score ?4 were fed back to the experts,including visual analogue scale(VAS),joint range of motion,walking distance,the morphology of femoral head on X-ray,THA rate,harris hip score,radiological imaging stabilization rate(comprehensive X-ray,CT and MRI),femoral head survival time,necrotic area on MRI,necrotic area on X-ray,degree of osteoarthritis on X-ray,TCM syndrome score,claudication,walking ability,SF-36 score,ARCO staging change,bone mineral density,adverse reactions,total cholesterol,triglyceride,bone marrow edema on MRI,harris hip score excellent rate,complications,plasma viscosity,total effective rate,osteoblast count and osteoclast count.The coefficient of variation(CV)of 20 outcomes were more than 15%,indicating that the divergence of experts evaluation were relatively high.The coordination coefficient of experts was 0.255(?2=495.411,P<0.000),indicating that the score of the outcomes were not consistent.Before the beginning of round 2,fed back the results of round 1,referred to the expert opinion,adjusted the questionnaire structure,and continued the investigation.A total of 73 questionnaires were sent out and 60 were recovered,with a response rate of 82.2%.According to the principle that 50%of experts considered the outcome very important(7-9 points)and the mean importance score ?7 points,a total of 8 outcomes entered the consensus meeting as potential core outcomes,including VAS score,joint range of motion,walking distance,the morphology of femoral head on X-ray,THA rate,necrotic area on X-ray,degree of osteoarthritis on X-ray and TCM syndrome score.Among them,the coefficient of variation(CV)were less than 15%,indicating that the discreteness of the experts were small,and the coordination coefficient of the expert was 0.504(X2=237.995,P<0.000),and the consistency was good.A total of 103 patients were investigated by questionnaire,and the top 10 outcome indicators included pain,joint activity,walking distance,lameness,imaging findings,up and down stairs,joint deformities,wearing shoes and socks,daily life and crutches.1.3 Consensus meeting to determine the therapeutic effect evaluation methodThere are two rounds of consensus meetings.In round 1 six outcomes were selected to form the COS:VAS score,joint range of motion,walking distance,the morphology of femoral head on X-ray,necrotic area on X-ray and degree of osteoarthritis on X-ray;round 2 determined the measurement standard and scoring method,and formed the therapeutic effect evaluation method,including clinical evaluation outcome and the radiological imaging evaluation outcome.The clinical outcome included VAS score(0-10 points,coefficient 0.5),flexion degree(0-10 points,coefficient 0.3)and walking distance(0.10 points,coefficient 0.2),a total of 10 points,the higher the score,the more serious the clinical symptoms and signs.X-ray was used to evaluate the radiological imaging evaluation outcome.The evaluation included the morphology of the femoral head(collapse degree measurement,0-3 points,coefficient 1),necrotic area(cystic range measurement,0-3 points,coefficient 1)and the occurrence degree of osteoarthritis(K-L grade measurement,0-4 points,coefficient 1),a total of 10 points,the higher the score,the more serious the imaging manifestation representing of ONFH.2 Verification of clinical evaluation outcomeA total of 231 patients with ONFH without auxiliary tools treated by TCM from September 2018 to December 2019 were included.Among them,148 cases were unilateral,83 cases were bilateral and one side was stable without symptoms,151 males and 80 females,with an average course of 31.87 ± 41.51 months and an age of 45.24 ± 13.64 years.2.1 Validity test.Compared with Harris hip score,the spearman correlation coefficients between flexion score of clinical evaluation outcome and joint range of motion score of Harris hip score before and after treatment were-0.644 and-0.768,indicating that there was a strong negative correlation between them;The spearman correlation coefficients of walking distance score and Harris joint function score were-0.825 and-0.753 before and after treatment,which indicates that they have strong negative correlation.The correlation coefficients between the total score of clinical evaluation indicator and Harris score were-0.782 and-0.767 before and after treatment and the correlation coefficients with VAS score were 0.663 and 0.768 respectively.This showed that the total score had a strong negative correlation with Harris score and a strong positive correlation with VAS score before and after treatment,with good validity.2.2 Reaction test.By comparing the scores of walking distance,VAS score,the degree of flexion and the total score before and after treatment,After treatment,walking distance score decreased,walking distance increased(p<0.000);VAS score decreased,pain relieved(p<0.000),flexion score decreased,flexion degree increased,joint range of motion increased(p<0.000).The total score decreased and the overall symptoms and signs were significantly improved(p<0.000).Harris hip scores of pain,joint function,range of motion and total score were significantly improved after treatment(p<0.000),indicated that the symptoms and signs of the patients were significantly improved,and the two scores showed consistent changes.The VAS score,the degree of flexion and the total score of clinical evaluation outcome were calculated to calculate the change value,the effect size(ES)and standardized response mean(SRM)before and after treatment.The results showed that the amount of effect was 2.43,0.86 and 1.96 respectively,and the mean of standardized response was 2.01,0.91 and 2.12,respectively.Both the sub-item and the total score of clinical evaluation indicator had a good degree of reaction.3 Verification of the radiological imaging evaluation outcome3.1 Reliability verification.After isometric sampling of unilateral hip X-ray images of 231 cases of ONFH from September 2018 to December 2019,47 X-ray images were obtained and numbered.Six orthopedic physicians evaluated the images separately after training.The Kendall's W coefficients for the morphology of the femoral head,necrotic area and degree of osteoarthritis among different physicians are 0.864,0.714 and 0.727 respectively,indicating that there were high consistency among different physicians.Six orthopedic physicians evaluated the same batch of X-ray images after 2 weeks.Statistics showed that the weighted kappa values repeatedly measured by the same physician for the three indicators of the morphology of the femoral head,necrotic area and degree of osteoarthritis are all above 0.7,which also had high consistency.3.2 Dynamic observation of the radiological imaging evaluation outcomeThe X-ray images of 20 hips of patients with ONFH who received THA in our department from 2018 to 2019 and had received hip preservation treatment for at least 2 years were scored,retrospectively.The collapse degree of the morphology of the femoral head was more serious(p<0.000).The scope of cystic degeneration of osteonecrosis of the femoral head decreased(p<0.000),and the severity of osteoarthritis gradually increased(p<0.000).Before THA,the average total score of the last images evaluation was 5.95±0.887,the average morphology was 2.85±0.366,the average necrotic area was 0.15±0.366,and the average degree of osteoarthritis was 2.95±0.759,which indicated that the general image collapse was more than 4mm,there was almost no cystic area and osteoarthritis occurred in grade 3 and above,it is suggested that THA should be considered from radiological imaging.Conclusions1 Based on the concept of COS,a method for evaluating the efficacy of TCM in the treatment of ONFH was established,which was divided into clinical evaluation outcome and radiological imaging evaluation outcome.clinical evaluation outcome included VAS score,flexion degree and walking distance;hip X-ray images was used for radiological imaging evaluation outcome,including the morphology of the femoral head,necrotic area and the degree of osteoarthritis.2 Through the cross-sectional and prospective follow-up study,it is proved that the clinical evaluation outcome has good validity and reaction between each sub-item and total score,the operation time is short,and the selection of outcome indicator and weight coefficient are reasonable.It is suggested to be used as an intermediate outcome to evaluate the therapeutic effect at short-term or short measurement time points.3 After repeated measurements among different observers and the same observer,the contents of the radiological imaging evaluation outcome shows a high consistency,which proved that it is accurate and reliable to evaluate the efficacy of TCM in the treatment of ONFH.And from the perspective of imaging,it provides an objective basis for the selection of THA.Therefore,it is suggested that it should be used as a secondary end point outcome for dynamic observation or for the evaluation of curative effect in a longer observation period. |
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