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      Constraint-Induced Movement Therapy Combined With Botulinum Toxin for Post-stroke Spasticity: A Systematic Review and Meta-Analysis

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          Abstract

          Stroke is considered one of the main causes of adult disability and the second most serious cause of death worldwide. The combination of botulinum toxin type A (BTX) with rehabilitation techniques such as modified constraint-induced movement therapy (mCIMT) has emerged as a highly efficient intervention for stroke patients to start synchronized motor function along with spasticity reduction. The current systematic review and meta-analysis were conducted in order to evaluate the available literature about the safety and efficacy of constraint-induced movement therapy (CIMT) combined with BTX in stroke patients with upper limb spasticity.

          Searches were conducted on WoS (Web of Science), Ovid, EBSCO-ASC&BSC, and PubMed for identifying relevant literature published from 2000-2020. Randomized Controlled Trials (RCTs) and Quasi-experimental studies were considered for inclusion. Rayyan (systematic review tool) QCRI (Qatar Computing Research Institute) was used for independent screening of the studies by two reviewers. For risk of bias and study quality assessment, Cochrane risk of bias tool (RoB 2) and Physiotherapy Evidence Database (PEDro) scales were used. Cochrane review manager was used to carry out the meta-analyses of the included studies.

          The search resulted in a total of 13065 references, of which 4967 were duplicates. After the title, abstract and full-text screening, two RCTs were deemed eligible for inclusion. Both the RCTs scored 8 on PEDro and were level evidence. The studies were heterogeneous. The findings of this meta-analysis in all the three joints post-stroke spasticity assessed on modified Ashworth scale (MAS) at four weeks post-injection aren’t statistically significant (elbow P-value 0.74, wrist P-value 0.57, fingers P-value 0.42), however, according to one of the included studies the therapeutic efficacy of the combination of BTX-mCIMT injection assessed at four weeks post-injection in wrist and finger flexors was promising. 

          The effectiveness of BTX-CIMT combination over conventional therapy (CT) for improving post-stroke spasticity still needs to be explored with long-term, multicenter rigorously designed RCTs having a good sample size. However, the BTX-CIMT combination is promising for enhancing motor function recovery and improving activities of daily living (ADLs).

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          Most cited references26

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          Rayyan—a web and mobile app for systematic reviews

          Background Synthesis of multiple randomized controlled trials (RCTs) in a systematic review can summarize the effects of individual outcomes and provide numerical answers about the effectiveness of interventions. Filtering of searches is time consuming, and no single method fulfills the principal requirements of speed with accuracy. Automation of systematic reviews is driven by a necessity to expedite the availability of current best evidence for policy and clinical decision-making. We developed Rayyan (http://rayyan.qcri.org), a free web and mobile app, that helps expedite the initial screening of abstracts and titles using a process of semi-automation while incorporating a high level of usability. For the beta testing phase, we used two published Cochrane reviews in which included studies had been selected manually. Their searches, with 1030 records and 273 records, were uploaded to Rayyan. Different features of Rayyan were tested using these two reviews. We also conducted a survey of Rayyan’s users and collected feedback through a built-in feature. Results Pilot testing of Rayyan focused on usability, accuracy against manual methods, and the added value of the prediction feature. The “taster” review (273 records) allowed a quick overview of Rayyan for early comments on usability. The second review (1030 records) required several iterations to identify the previously identified 11 trials. The “suggestions” and “hints,” based on the “prediction model,” appeared as testing progressed beyond five included studies. Post rollout user experiences and a reflexive response by the developers enabled real-time modifications and improvements. The survey respondents reported 40% average time savings when using Rayyan compared to others tools, with 34% of the respondents reporting more than 50% time savings. In addition, around 75% of the respondents mentioned that screening and labeling studies as well as collaborating on reviews to be the two most important features of Rayyan. As of November 2016, Rayyan users exceed 2000 from over 60 countries conducting hundreds of reviews totaling more than 1.6M citations. Feedback from users, obtained mostly through the app web site and a recent survey, has highlighted the ease in exploration of searches, the time saved, and simplicity in sharing and comparing include-exclude decisions. The strongest features of the app, identified and reported in user feedback, were its ability to help in screening and collaboration as well as the time savings it affords to users. Conclusions Rayyan is responsive and intuitive in use with significant potential to lighten the load of reviewers.
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            Reliability of the PEDro scale for rating quality of randomized controlled trials.

            Assessment of the quality of randomized controlled trials (RCTs) is common practice in systematic reviews. However, the reliability of data obtained with most quality assessment scales has not been established. This report describes 2 studies designed to investigate the reliability of data obtained with the Physiotherapy Evidence Database (PEDro) scale developed to rate the quality of RCTs evaluating physical therapist interventions. In the first study, 11 raters independently rated 25 RCTs randomly selected from the PEDro database. In the second study, 2 raters rated 120 RCTs randomly selected from the PEDro database, and disagreements were resolved by a third rater; this generated a set of individual rater and consensus ratings. The process was repeated by independent raters to create a second set of individual and consensus ratings. Reliability of ratings of PEDro scale items was calculated using multirater kappas, and reliability of the total (summed) score was calculated using intraclass correlation coefficients (ICC [1,1]). The kappa value for each of the 11 items ranged from.36 to.80 for individual assessors and from.50 to.79 for consensus ratings generated by groups of 2 or 3 raters. The ICC for the total score was.56 (95% confidence interval=.47-.65) for ratings by individuals, and the ICC for consensus ratings was.68 (95% confidence interval=.57-.76). The reliability of ratings of PEDro scale items varied from "fair" to "substantial," and the reliability of the total PEDro score was "fair" to "good."
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              Practical meta-analysis

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                Author and article information

                Journal
                Cureus
                Cureus
                2168-8184
                Cureus
                Cureus (Palo Alto (CA) )
                2168-8184
                1 September 2021
                September 2021
                : 13
                : 9
                : e17645
                Affiliations
                [1 ] Department of Rehabilitation Medicine and Physical Therapy, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, CHN
                [2 ] Department of Rehabilitation Medicine and Physical Therapy, First Hospital of Jilin University, Jilin University, Changchun, CHN
                [3 ] Department of Physical Therapy, Albaath University, Homs, SYR
                [4 ] Department of Orthopedic Surgery, Al-Assad University Hospital, Damascus University, Damascus, SYR
                [5 ] Physical Medicine, Rheumatology and Rehabilitation, Tanta University Hospitals & Faculty of Medicine, Tanta University, Tanta, EGY
                [6 ] Department of Rheumatology, Assiut University Hospital, Assiut, EGY
                [7 ] Immunohematology Cellular Therapy, Medical School Oujda / Mohammed VI University Hospital of Oujda, Oujda, MAR
                [8 ] Physical Medicine and Rehabilitation, National Taiwan University Hospital Bei-Hu Branch, Taipei, TWN
                [9 ] Department of Physical Medicine and Rehabilitation, National Taiwan University Hospital, Bei-Hu Branch, Taipei, TWN
                [10 ] Pain Management, Whipps Cross Hospital Barts Health National Health Service (NHS), London, GBR
                [11 ] Medical-Geriatric Department, Rheumatology, University Hospital Azienda Ospedaliero Universitaria (AOU) Careggi, Florence, ITA
                [12 ] King Abdullah University Hospital, Jordan University of Science and Technology, Amman, JOR
                [13 ] Anesthesia and Pain Medicine, Cleveland Clinic, Abu Dhabi, ARE
                [14 ] Research, Paolo Procacci Foundation, Roma, ITA
                Author notes
                Article
                10.7759/cureus.17645
                8486367
                34646693
                a89a0b78-097a-4db5-8ed7-78d55e244e35
                Copyright © 2021, Nasb et al.

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 13 July 2021
                : 30 August 2021
                Funding
                Paolo Procacci Foundation, a non-profit organization, has supported the publication of this research.
                Categories
                Neurology
                Pain Management
                Physical Medicine & Rehabilitation

                botulinum toxin,cimt,mcimt,neuroplasticity,rehabilitation,spasticity,stroke

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