Evidence-based Research On Integrated Chinese And Western Medicine In Convalescence From Corona Virus Disease-2019

Background More than 758 million confirmed Corona Virus Disease-2019(COVID-19)globally up to February 2023,which has posed a huge burden to society and economic development.Post-COVID-19 symptoms involve the respiratory system,cardiovascular system and musculoskeletal system,etc.Earlier,comprehensive and safe rehabilitation can relieve symptoms,promote functional recovery,improve quality of life and help to return to normal life and work.It is necessary and important to analyse the research status,hotspots and development trends,to assess the quality of current relevant evidence,and to develop an evidence-based practice guideline for the management of convalescence patients by integrated Chinese and Western medicine,which can provide evidence support and decision basis.Objectives(1)To understand and analyse the research status,hotspots and development trends on rehabilitation for COVID-19;(2)to assess the current evidence quality on rehabilitation for COVID-19 in both Chinese and Western medicine;(3)to develop an evidence-based practice guideline for the management of COVID-19 by integrated Chinese and Western medicine among convalescence patients.Methods(1)Bibliometric and visualization: “COVID-19” and “rehabilitation” were used to search for publications in English and Chinese related to the rehabilitation of COVID-19 in Pub Med and Chinese Biomedical Literature Database.The results were selected based on inclusion and exclusion criteria.Microsoft Office Excel 2019 and VOSviewer 1.6.10,Cite Space 6.1.R6,Bibliometri X were used for descriptive analysis and to generate visualized maps.It analysed research trends in publications of relevant research,drew cooperative network relationships between countries/regions,and authors,developed a map of co-cited references,and sorted out information on institutions and journals.Keywords were analysed on frequency and clusters.It provided a clear and intuitive overview of the current research status,hotspots and trends in the rehabilitation of COVID-19.(2)Evidence quality evaluation: 9 common databases were searched systematically,including China National Knowledge Infrastructure,Wanfang database,Chinese Biomedical Literature Database,VIP database,Pub Med,Cochrane Library,EMBASE,Web of Science and PEDro database.Research on various rehabilitation treatments for COVID-19,both Chinese and Western medicine,were included.Randomised controlled trials,cohort studies,and systematic reviews/meta-analyses were assessed separately using the risk of bias tool recommended by the Cochrane Handbook 5.1.0(Ro B-1),Newcastle-Ottawa scale(NOS),and A Measure Tool to Assess Systematic Reviews-2(AMSTAR-2).It helped comprehensively to sort out the quality status of research evidence on rehabilitation of COVID-19 and to provide evidence basis on application.(3)Clinical practice guideline development: The guideline was been developed based on the World Health Organization handbook for Guideline Development and Guidelines for the Development/Revision of Clinical Treatment Guidelines in China(2022 Edition).It was initiated by the Rehabilitation Medicine Committee of the Chinese Association of Integrative Medicine and Gansu Rehabilitation Medicine Association.Evidence-based Medicine Centre of Lanzhou University,WHO Collaborating Centre for Guideline Implementation and Knowledge Translation,Gansu Provincial Centre for Medical Guideline Industry Technology and Gansu Provincial Hospital of Traditional Chinese Medicine provided methodological guidance.Guideline working groups were established,including a steering committee,a consensus expert panel,an external review expert panel,an academic secretary and an evidence evaluation panel.The guidelines were registered on the International Guidelines Registration and Transparency Platform(Registration No.PREPARE-2023CN164).A questionnaire survey was conducted to investigate the prevalence of COVID-19 and the prevalence and severity of symptoms among convalescent people,using Numerical Rating Scale(0-10,with 0 being no symptoms and 10 being very severe symptoms)to identify the clinical concerns.Electronic databases were searched systematically for evidence.The quality of evidence was evaluated using respective tools and the results were synthesised to produce a body of evidence.The Grade of Recommendation,Assessment,Development,and Evaluation of Evidence(GRADE)tool was used to grade the credibility of the body of evidence.Initial recommendations were established based on the body of evidence with relevant published guidelines and expert consensus.The strength of the recommendations was determined also using the GRADE tool.A Delphi questionnaire and evidence summary was sent to consensus experts to reach a consensus.The final recommendations were determined by the Delphi results with the steering committee’s suggestions.The full text of the guideline was written following the Guidelines for Research and Evaluation(AGREE II)and Reporting Items for Practice Guidelines in Healthcare(RIGHT).The manuscript was published with the approval of external reviewers.Results(1)Bibliometric and visualization: Pub Med and the Chinese Biomedical Literature Database were searched and 622 studies(421 in English and 201 in Chinese)related to the rehabilitation treatment of COVID-19 were included after the screening.The annual number of English-language studies was highest in 2021(N=167)and that of Chinese studies was highest in 2020(N=112).It then declined each year after getting to the peak.59 countries/regions participated in the publication of relevant English-language literature,with the top three participating countries being China(N=93),the United States(N=84)and Italy(N=44);the United Kingdom had the highest total number of citations(N=1760),followed by Italy(N=1284)and China(N=850).Hubei Province(N=38)was the region with the highest number of publications in Chinese,followed by Beijing(N=29)and Guangdong Province(N=18).A total of 942 institutions were involved in the publication of English-language literature related to the rehabilitation of COVID-19,with the highest number of articles published by Shandong University of Traditional Chinese Medicine(N=15),followed by IRCCS Istituti Clinici Scientifici Maugeri in Italy(N=10),Sichuan University(N=7),Università del Piemonte Orientale in Italy(N=7)and Universidade de S?o Paulo in Brazil(N=7).217 institutions were involved in Chinese research.Hubei Provincial Hospital of Traditional Chinese Medicine has the most publications(N=14),followed by Hubei University of Traditional Chinese Medicine(N=12),Hospital of Chengdu University of Traditional Chinese Medicine(N=8)and Chinese Academy of Traditional Chinese Medicine(N=8).There were 2364 authors and 1065 authors involved in publications related to the rehabilitation of COVID-19 in English or Chinese,respectively.Calculating based on Price’s law,authors with at least 3 articles in English or 2 articles in Chinese were identified as core authors in this field.45 core authors in English and 123 core authors in Chinese were identified.Professor Michele Vitacca has the highest number of publications in English from Italy(N=8);the highest number of articles published in Chinese is by Professor Suofang Shi from Jiangsu Provincial Hospital of Traditional Chinese Medicine(N=6).The most cited English-language research paper was "Physiotherapy management for COVID-19 in the acute hospital setting: clinical practice recommendations" by Peter Thomas et al.published in Journal of physiotherapy in April 2020.167 English-language journals and 107 Chinese-language journals have published related research.Most English-language journals specialised in rehabilitation medicine and therapy,with the highest number of articles published in Medicine(N=55);followed by International Journal of Environmental Research and Public Health(N=29)and Physical Therapy(N=20).Chinese journals were mainly related to Chinese medicine and rehabilitation.The highest number of publications was in Chinese Acupuncture & Moxibustion and World Latest Medicine Information(N=11),followed by Chinese Manipulation and Rehabilitation Medicine(N=8).Among the journals with more than 5 articles,only Chinese Acupuncture & Moxibustion was included in the Chinese Science Citation Database.After data cleaning,888 English keywords were obtained.The keyword with the highest frequency was "COVID-19"(N=263),followed by "rehabilitation"(N=132)and "SARS-Co V-2"(N=58).The keywords can be divided and summarized into five clusters and research hotspots,including functional status and rehabilitation assessment,post-COVID-19 syndrome,cardiopulmonary function and rehabilitation,telerehabilitation and exercise,and early rehabilitation treatment for severe and critical patients.365 keywords were obtained in the Chinese research."Corona Virus Disease-2019" was the keyword with the highest frequency(N=183).The second and third were "convalescence period"(N=73)and "respiratory rehabilitation"(N=19).The research hotspots can be summarised into five clusters,including pattern identification,Chinese physical therapy rehabilitation(including acupuncture and moxibustion),exercise rehabilitation therapy,sleep and psychologicalrelated symptoms and treatment,and Chinese medicine rehabilitation therapy.(2)Evidence quality evaluation: 9 databases were searched to obtain research evidence on integrated rehabilitation of COVID-19.159 studies were finally selected,including122 randomised controlled trials,12 cohort studies and 25 systematic reviews/metaanalyses.The risk of bias of the included 122 randomised controlled trials was assessed by the Ro B-1 tool.78 studies(63.93%)used a low risk of bias random sequence generation method such as random number lists.43 studies(35.25%)used websites or opaque sealed envelopes to conceal group allocation.20 studies(16.39%)described blinding of patients and intervention implementers.35 studies(28.69%)described blinding of outcome measurers.90 studies(73.77%)completed follow-ups of all participants or had a follow-up rate of more than 90%.117 studies(95.90%)reported all important expected outcomes.90 studies(73.77%)reported other biases,such as funding sources and potential conflicts of interest.NOS was used to evaluate the study quality of 12 cohort studies,of which three studies(25.00%)were of high quality(scores 6-9),eight studies(67.00%)were of moderate quality(scores 3-6)and one study(8.00%)was of low quality(scores 0-2).8 studies(66.67%)selected exposure groups that were truly or largely representative of the community population.11 studies(91.67%)selected control groups from the same population.11 studies(91.67%)had reliable methods to identify exposure factors.None of the studies had outcome indicators to be observed at the start of the study.8 studies(66.67%)controlled for age and other the most important factors related to population comparability,six of these(50.00%)also controlled for other confounding factors.7 studies(58.33%)used independent and reliable outcome indicators.4 studies(33.33%)followed up with the population,and three of these studies(25.00%)had a complete follow-up or missed follow-up rate of less than 10%.The methodological quality of the 25 included systematic reviews/meta-analyses was assessed using the AMSTAR-2 tool,with 11studies(44.00%)being of high quality(11-16 scores),9 studies(36.00%)being of moderate quality(5-10.5 scores)and 5 studies(20.00%)being of low quality(0-4.5scores).The highest score was 13.5 and the lowest was 2.23 studies(92.00%)constructed research questions and inclusion criteria based on population,intervention,control,and outcome.18 studies(72.00%)developed and published a study plan.3studies(12.00%)explained the reasons for the choice of study type.22 studies(88.00%)used a partially comprehensive or comprehensive search strategy.17 studies(68.00%)used repeatable methods for the data screening and extraction process.19 studies(76.00%)provided a list of reasons for excluding studies,of which 4(16.00%)provided an additional list of checklists.23 studies(92.00%)provided basic or detailed information on included studies.21 studies(84.00%)chose an appropriate risk of bias assessment tool.2 studies(8.00%)planned to report or reported on the funding of included studies.14 studies(56.00%)did not perform a meta-analysis.9 studies(36.00%)chose a reasonable method of data synthesis.9 studies(36.00%)considered the impact of single-study risk of bias in performing the meta-analysis.8 studies(32.00%)considered the effect of individual study risk of bias in the interpretation and discussion of results.15 studies(60.00%)provided a reasonable explanation and discussion of the heterogeneity between studies included in the study.10 studies(40.00%)considered or analysed the effect of publication bias.All studies(25,100%)reported funding status or conflicts of interest.(3)Clinical practice guideline development: Conflicts of interest of people involved in the development of the guidelines were managed.Based on the results of the questionnaire survey,combined the prevalence of common symptoms with the severity scores,11 preliminary clinical concerns were identified.These symptoms and dysfunctions included cough and other pharyngeal discomforts,fatigue,lung function descend,sleep disturbance,nasal congestion and runny nose,loss of appetite,chilliness,abnormal taste and smell,muscle pain and headache.The search and screen of relevant research evidence,guidelines and expert consensus for clinical concerns resulted in the inclusion of 82 randomised controlled trials,14 observational studies,4 systematic reviews/Meta analyses and 10 guidelines and expert consensus.27 preliminary recommendations were formed.17 consensus experts reached a Delphi consensus on23 recommendations.The recommendations were divided,revised,supplemented and collated by combining expert suggestions and the steering committee’s comments.Finally,9 clinical topics and 33 recommendations for evidence-based practice guidelines were developed.The recommended protocols include western rehabilitation interventions,traditional Chinese rehabilitation,Chinese herbal medicine,Chinese physiotherapy and traditional exercises.The preliminary manuscript was reviewed by external reviewers.The language and expression of the guidelines were revised and improved according to the comments of the external experts,resulting in the final version of the guidelines.Conclusion(1)The number of published studies related to COVID-19 rehabilitation treatment in both English and Chinese showed a decreasing trend.The high-producing countries/regions have established some cooperation networks with others,and the number of articles published may be related to the severity of the epidemic.The cooperation between institutions and authors was mainly within the same institution.Some cross-institutional cooperation has been formed between authors of Chinese studies,but the international cooperation of both Chinese and English studies needs to be strengthened.The academic influence of journals publishing English studies was higher than that publishing in Chinese.The hotspots of English studies focused on function assessment,cardiopulmonary rehabilitation,remote rehabilitation,exercise,and early treatment of severe or critical infected patients.While Chinese studies mainly focused on identification and classification,use of Chinese medicine,physiotherapy and rehabilitation of Chinese medicine and traditional exercises,and psychological discomfort of patients.(2)The results of the quality evaluation of the COVID-19 evidence related to Chinese and Western medicine rehabilitation treatment showed that the overall risk of bias in the included randomised controlled trials was high,with the risk of bias mainly arising from allocation concealment and the implementation of blinding.On these items,the Chinese studies had a significantly higher risk of bias than the English studies.In addition,the Chinese studies also needed further improvement in the generation of randomised sequences and the reporting of other bias controls.The quality of the included cohort studies was good.Improvements were needed in the comparability between groups and in the design and completeness of the follow-up.The quality of the included systematic reviews/Meta-analyses was good.However,the included studies were all in English with no Chinese studies meeting the inclusion criteria.Improvements were required in several items,including using a more comprehensive search strategy,increasing the emphasis on the rationale and list of excluded studies,considering to focus on the funded status of the included studies and the impact of the risk of bias of individual studies when interpreting the discussion results.(3)Evidence-based Practice Guidelines on Integrated Chinese Medicine Management of Common Disorders in Convalescence of COVID-19 is an evidence-based practice guideline focused on selected clinical concerns and followed World Health Organization handbook for Guideline Development and Guidelines for the Development/Revision of Clinical Treatment Guidelines in China(2022 Edition).The publication of the guideline will provide decision support and guidance for the management of convalescence COVID-19 people.However,due to the lack of highquality systematic evaluation/meta-analysis,recommendations of the guideline were formed based on direct research evidence and expert consensus issued by the State Administration of Traditional Chinese Medicine,the Chinese Academy of Traditional Chinese Medicine and other institutions or organizations.More high quality research evidence,including randomized controlled trials and systematic reviews/meta-analyses,focused on convalescent patients of COVID-19 are appealed to provide basis on the guideline update.