The Cochrane Handbook was used to decide over the methodological approach in the present study (17), and the findings will be reported using the recommended methods and checklist of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) (18). The protocol is formed according to the guidelines of PRISMA (21). In order to improve the validity of the results and also to decrease the inconsistencies in the process, the protocol is then registered as PROSPERO( International Prospective Register of Systematic Reviews).
The following criteria will be used in order to include or exclude initial studies.
Types of studies:
In this systematic review, we will include studies only if they address the effect of early rehabilitation or early inpatient rehabilitation or early comprehensive rehabilitation in traumatic brain injury in randomized clinical trials (RCTs) and controlled clinical trials (CCTs; quasi-randomized and quasi-experimental designs with comparative controls – controlled before and-after studies, experimental, before and after studies), prospective and retrospective cohort studies, and case control studies which are published in English. We will also exclude the following studies: qualitative, mixed method, descriptive, cross-sectional studies, editorial, case report, and anecdotal report.
Types of Participants:
We will include patients (both male and female) with mild to severe TBI who are older than 16 years of age and patient who have received early rehabilitation interventions in hospital.
We will exclude studies if: patients are admitted to hospital due to neurological conditions (e.g., stroke, multiple sclerosis, amyotrophic lateral sclerosis, brain tumor, spinal cord injury, neuromuscular diseases, substance abuse disorders), or trauma that could limit rehabilitation (e.g., major trauma, fractures, joint replacement) and studies on community or home rehabilitation, and outpatients.
Intervention group includes all the patients whose early rehabilitation interventions procedure begins within the first 35 days after hospitalization in ICU or Neurological Ward. Such early rehabilitation interventions should start after the stability of vital signs, intracranial pressure, and cerebral perfusion pressure and should last for at least one hour a day. The rehabilitation team consists of at least two experts including nurses, physiotherapists, occupational therapists, speech therapists, dieticians, and medical social workers. Such interventions should take at least half an hour per day based on the patients’ needs.
Patients in the control group receive routine care or any interventions except for early rehabilitation interventions. Besides, the types of control groups will be included in the data extraction section.
Searching strategy in the PubMed database is as follows:
(rehabilitation[ti] OR habilitation[ti] OR "Early intervention*" OR "Early mobili*" OR "Early therap*" OR "Early ambulation" OR vertical OR "early exercis*" OR "tilt table" OR "out of bed" )AND ("brain injury" OR (injur* AND brain) OR ("brain injury" AND diffuse[ti]) OR "diffuse brain injury"[ti] OR (injury[ti] AND "diffuse Brain"[ti]) OR ("brain injury"[ti] AND focal[ti]) OR "focal brain injury"[ti] OR (injury[ti] AND "focal brain"[ti]) OR "focal brain injuries"[ti] OR ("brain injury"[ti] AND "trauma*"[ti]) OR (injury[ti] AND "traumatic brain"[ti]) OR (injury[ti] AND brain[ti] AND traumatic[ti]) OR "traumatic encephalopathy"[ti] OR (trauma[ti] AND brain[ti]) OR "brain trauma"[ti] OR "traumatic brain injury"[ti] OR (encephalopathy[ti] AND traumatic[ti]) OR "traumatic encephalopathies"[ti] OR TBI[ti] OR "brain laceration"[ti] OR (laceration[ti] AND brain[ti]) OR "brain contusion"[ti] OR (contusion[ti] AND brain[ti]) OR "cortical contusion"[ti] OR (contusion[ti] AND cortical[ti]) OR (encephalopathy[ti] AND "post-concussive"[ti]) OR (encephalopathy[ti] AND "post concussive"[ti]) OR "post-concussive encephalopathy"[ti] OR "post concussive encephalopathy"[ti] OR (encephalopathy[ti] AND post-traumatic[ti]) OR (encephalopathy[ti] AND "post traumatic"[ti]) OR "post-traumatic encephalopathy"[ti] OR "post traumatic encephalopathy"[ti] OR "Acute Brain Injury"[ti] OR ("Brain Injury"[ti] AND Acute[ti]) OR (injury[ti] AND "acute brain"[ti]) OR "mild traumatic brain injury"[ti] OR (injury[ti] AND brain[ti] AND "traumatic mild"[ti])) AND (1990/01/01:2019/12/31[dp].
Sources of Primary Research:
We will search the following electronic databases using a strategy developed by the researchers based on the medical subject headings pertaining to each database. PubMed, EMBASE, CINAHL, AMED, Psych INFO, the Cochrane Library, Scopus, Web of Science, Clinical trials.gov, WHO International Clinical Trials Registry Platform (ICTRP), IFPMA Clinical Trials Portal, Current Controlled Trials, Scielo and LILACS, ProQuest dissertations and theses are used to retrieve primary studies published from 1990 to 2019. Gray Literature was identified by additional hand-searching of the reference lists of the review articles on early rehabilitation in TBI patient. This ensured that the literature review was relevant and comprehensive. We will search Gray Literatures such as conference paper based on Scopus and thesis in ProQuest dissertations. We will conduct hand-searching 2 key journals based on Scopus.
Methods of the review
Selection of studies:
The initial screening of titles will be performed by two independent reviewers (RB and ME). Disagreements will be resolved by consensus. The citations are classified as eligible, uncertain about eligibility, or excluded and stored in an Excel spreadsheet. Abstracts of references considered relevant based on the title will then be checked by two independent reviewers (RB and ME). The full text articles of eligible and uncertain about eligibility citations are retrieved and reviewed. If, after reviewing the full text version of the article, eligibility is not clear or there is missing information, the authors will be contacted by email. When there is no response, a reminder email is sent at two week intervals. After three unsuccessful attempts at contact, the decision will be made based on the information available.
In a second selection phase, two independent reviewers (RB, ME) will confirm the eligibility of the studies by reviewing the full text of the selected studies. A third party (HK) will consider all discrepancies not resolved by discussion in the course of the two selection phases and make a final decision about eligibility. A kappa statistic and the percent agreement will be used to calculate inter-rater agreement in both selection phases.
The data will be extracted by two reviewers in a standardized way and according to the general information, the features of the study, the primary and secondary outcomes and also the results. Disagreements will be resolved by consensus. Otherwise, another researcher will be asked to make the final decision. The data points will be obtained using Get Data Graph Digitizer following the data extraction from the graph (www.getdata-graph-digitizer.com).
Risk of biased assessment:
The PEDro scale is used to assess the methodological quality of randomized clinical trial on the included studies (19). The new castle Ottawa will be used to assess risks of bias in non-randomized studies (20). A risk of bias table will be generated with the principal biases and the methodological quality of the studies.
At first, the frequency of all types of early rehabilitation interventions for TBI patients will be listed. And then, the number and percentage of each frequency will be provided. All the studies included in this systematic review will be reported within a form referring to the study characteristics and the types of the studies.
Initially, a narrative synthesis method will be used in order to evaluate the effectiveness of such intervention on functional outcomes so as to describe the results of the present study. Then, all the included studies will be reported in a narrative form and a table of specifications for key features of these studies (study characteristics, interventions, starting time and intervention time, the sample size, sampling method, study setting, statistical methods, expected outcomes and other necessary information) will be presented as well.
Afterwards, meta-analysis will be conducted when possible. The tau-squared and I2 will be used to measure the statistical heterogeneity among the studies. Where P <0.10 and also I2 is larger than 50%, the results show a high level of statistical heterogeneity. If the homogeneity of the features of the studies is approved, they will be categorized into different groups and meta-analysis of the pooled data will be performed as well. All analyses will be conducted using STATA software. In the end, two independent experts will assess the quality of the present systematic review according to the Preferred Reporting Items for Systematic Reviews and using Meta-Analyses (PRISMA) guidelines.