Management of traumatic brain injury in India: A protocol for systematic review and meta-analysis

1.1 Rationale

Traumatic brain injury (TBI) and its aftermath are thought to be a global health concern nowadays. They significantly affect patient function, quality of life, and social impact globally. Traumatic brain injury (TBI) can cause a variety of long-term problems, including headaches, erratic sleep patterns, psychosis, mood, behavioural, and anxiety disorders, and psychosis.⁵ In the coming years, there will likely be a rise in the incidence of traumatic brain injury (TBI) due to the increased use of motor vehicles, which is a major cause of traffic accidents and TBI development. There are projections that indicate both global population growth and density will contribute to this in-crease. As of 2018, an estimated 69 million people had suffered traumatic brain injury (TBI), with the majority of these cases occurring as a result of traffic accidents, which have a particularly serious effect in low- and middle-income countries (LMICs).⁶

The prevention of traumatic brain injury (TBI) has focused on treatment strategies that lessen the injury’s immediate to moderate-term effects in addition to surveillance systems and programs for the purpose of preventing TBI. These methods include pharmacological treatment with steroids, muscle relaxants, anticonvulsants, antidepressants, stimulants, anti-anxiety drugs, and more, as well as rehabilitation therapy.⁷ Treatment for traumatic brain injury (TBI) that enhances long-term functionality and quality of life by promoting neurological regeneration, restoration, and repair is more well-established than the modalities mentioned above. Novel approaches to treating a range of diseases, including traumatic brain injury (TBI), have been made possible by biotechnology breakthroughs such as platelet-rich plasma (PRP). Platelet-rich preparations, such as platelet-rich plasma (PRP), are essentially the platelet-rich fraction of blood obtained by centrifuging fresh blood. They have the potential to accelerate healing, stimulate bone and tissue regeneration, and improve bone density.⁸ Apart from the previously mentioned potential advantages, PRP is inexpensive, non-invasive, adaptable, has a simple preparation process, and has an excellent biosafety profile.

Apart from its ability to reduce inflammation, platelet-derived growth factor (PDGF), insulin-like growth factor 1 (IGF-1), transforming growth factor-N (TGF-β), endothelial growth factor (EGF), and vascular endothelial growth factor (VEGF) are among the growth factors that PRP can inhibit and stimulate locally. In addition to promoting vascularization and collagen synthesis, the growth factors mentioned above are also responsible for stimulating keratinocyte proliferation and attracting local fibroblasts and stem cells.^9,10

1.2 Aims of the study

Primary aim: To assess the management of TBI in India.

Secondary aim:

Protocol

2.1 The population of study

Patients with traumatic brain injury(ies), regardless of age or gender.

2.2 Period of study

From January 2024 to February 14, 2024.

2.3 Inclusion criteria

All randomized controlled trials (RCTs), non-randomized con-trolled clinical trials, observational studies, case-control and prospective cohort studies describing the management of traumatic brain injury. Only articles reported in English will be included.

2.4 Exclusion criteria

Case series, case reports, abstract-only articles, letters to the editor, conference proceedings, review articles, articles with missing data in other languages, and those reporting animal studies will be excluded. Studies describing the management of traumatic brain injury and other disease conditions in animals will al-so be excluded.

2.5 Information source and Search Strategy

Articles for our study will be sourced from PubMed, EMBASE, SCOPUS, Web of Science, and Cochrane Central.

2.5.1 Search strategy

(“manage”[All Fields] OR “managed”[All Fields] OR “management s”[All Fields] OR “managements”[All Fields] OR “manager”[All Fields] OR “manager s”[All Fields] OR “managers”[All Fields] OR “manages”[All Fields] OR “managing”[All Fields] OR “managment”[All Fields] OR “organization and administration”[MeSH Terms] OR (“organization”[All Fields] AND “administration”[All Fields]) OR “organization and administration”[All Fields] OR “management”[All Fields] OR “disease manage-ment”[MeSH Terms] OR (“disease”[All Fields] AND “management”[All Fields]) OR “disease management”[All Fields]) AND (“brain injuries, traumatic”[MeSH Terms] OR (“brain”[All Fields] AND “injuries”[All Fields] AND “traumatic”[All Fields]) OR "trau-matic brain injuries”[All Fields] OR (“traumatic”[All Fields] AND “brain”[All Fields] AND “injury”[All Fields]) OR “traumatic brain injury”[All Fields]) AND (“india”[MeSH Terms] OR “india”[All Fields] OR “india s”[All Fields] OR “indias”[All Fields]) AND (“systematic review”[Publication Type] OR “systematic reviews as topic”[MeSH Terms] OR “systematic review”[All Fields]) AND (“meta analysis”[Publication Type] OR “meta analysis as topic”[MeSH Terms] OR “meta analysis”[All Fields])

2.5.2 Translations

Management: “manage”[All Fields] OR “managed”[All Fields] OR “management’s”[All Fields] OR “managements”[All Fields] OR “manager”[All Fields] OR “manager’s”[All Fields] OR “managers”[All Fields] OR “manages”[All Fields] OR “managing”[All Fields] OR “managment”[All Fields] OR “organization and administration”[MeSH Terms] OR (“organization”[All Fields] AND “administration”[All Fields]) OR “organization and administration”[All Fields] OR “management”[All Fields] OR “disease manage-ment”[MeSH Terms] OR (“disease”[All Fields] AND “management”[All Fields]) OR “disease management”[All Fields]

Traumatic Brain Injury: “brain injuries, traumatic”[MeSH Terms] OR (“brain”[All Fields] AND “injuries”[All Fields] AND “traumatic”[All Fields]) OR “traumatic brain in-juries”[All Fields] OR (“traumatic”[All Fields] AND “brain”[All Fields] AND “injury”[All Fields]) OR “traumatic brain injury”[All Fields]

India: “india”[MeSH Terms] OR “india”[All Fields] OR “india’s”[All Fields] OR “indias”[All Fields]

Systematic Review: “systematic review”[Publication Type] OR “systematic reviews as topic”[MeSH Terms] OR “systematic review”[All Fields]

Meta-analysis: “meta-analysis”[Publication Type] OR “meta-analysis as topic”[MeSH Terms] OR “meta-analysis”[All Fields]

Search results from PubMed on 11/02/2024 at 09:23:08 have been shown in Table 1.

3.1 Study selection

Two independent reviewers who are blinded will perform a preliminary screening of titles and abstracts after downloading and uploading the database literature search result to Rayyan (ref). This will help to avoid duplication of studies. Any disagreements that arise will be discussed and settled by the review team; if an agreement cannot be reached, an independent author will act as an arbitrator.

The selected papers will then go through a second round of full-text screening to ensure they meet our inclusion requirements, followed by a final screening to assess bi-as risk. Using a PRISMA flow diagram, this study selection procedure will be illustrated.

3.2 Data extraction

There will be two steps in the data extraction process. We will perform a preliminary pilot extraction. The process will entail the authors selecting ten (10) articles at random and extracting data from them according to the goals and study outcomes. The purpose of the pilot phase is to verify the consistency of the extraction process and identify any unclear or missing data. Once the pilot phase is over, a meeting of the authors will take place to decide on the right data to extract. The primary data extraction phase, which comes next, will involve a detailed review of the studies that satisfy the eligibility requirements in order to extract established data.

3.3 Charting the data

This section explains how the data for this systematic review and meta-analysis will be recorded and charted in order to guarantee openness and the reproducibility of the procedures involved.

In order to chart the data and find answers to our research questions and study objectives, the following procedures will be followed:

3.3.1 Data extraction: A standardized extraction form will be used to extract the important data from each study that is part of the review. This data extraction will com-prise the following: the year of publication, the study design, the sample size, the severity of traumatic brain injury, the drug dosage (such as propranolol or platelet rich plasma, etc), the timing and duration, the outcome measures, and the main conclusions. At least two separate reviewers will handle the extraction process in order to guarantee accuracy and minimize bias.

3.3.2 Data organization: Tabulated and standardized data format will be used to arrange the extracted data in order to facilitate comparison and analysis. We’ll use readily readable tables and graphs created by applications such as Microsoft Excel.

3.3.3 Statistical analysis: The I2 statistic will be used to determine the homogeneity be-tween the studies. A fixed-effects model will be used in the meta-analysis if the results indicate a low level of heterogeneity (I² <50%), and a random-effects model will be used in the case of high heterogeneity (I² >50%).

3.3.4 Assessment of heterogeneity: Using suitable statistical tests, such as the chi squared or I2 statistic, heterogeneity will be evaluated to make sure that variable results from various studies are taken into account when performing statistical analysis.

3.3.5 Analysing and synthesizing the drug’s neuroprotective effects: Results from all of the studies on the neuroprotective effects of propranolol in the treatment of traumatic brain injury will be examined. Its effects on synaptic plasticity, neuronal regeneration, lowering neuronal damage, neuroinflammation, and oxidative stress are among these.

3.3.6 Tabular and graphical representation: We will use clear tables and accurate graphical representations, such as forest plots, to present the collected data for the synthesized outcome measures. This procedure will make understanding the specific study results and the overall meta-analysis results easier.

3.3.7 Quality assessment: Every study will undergo an independent evaluation to identify any potential sources of bias using the Cochrane risk-of-bias tool and overall study quality. We’ll assess the evidence’s quality using the GRADE method.

We will be able to fully comprehend the role of propranolol in treating traumatic brain injury (TBI), pinpoint knowledge gaps, and produce tangible evidence to direct clinical practice and future research by adhering to this strict and impartial system of data charting.

4.1 Study status

Once this protocol is thoroughly peer reviewed by 2 peer reviewers the authors will start writing the review article keeping in mind the insights of the reviewers. Hence, the status of the article is the protocol

5.1 Risk of bias individual studies

Using the Newcastle-Ottawa Scale (NOS), a method for estimating the risk of bias in observational studies, three authors will separately evaluate the quality of the studies. Research that receive a NOS score of 4 or higher will be deemed to have minimal bias risk and will be incorporated into reviews and meta-analyses.

5.2 Data synthesis

Numerous studies have looked into the management of traumatic brain injury (TBI) using platelet rich plasma, propranolol etc. Regarding propranolol, these studies have demonstrated that giving low-dose propranolol to TBI patients at an early stage can shorten their hospital stay and mortality rate. Propranolol improves cerebral per-fusion by lowering sympathetic discharge and catecholamine release associated with paroxysmal sympathetic hyperactivity. It does this by lowering tachycardia, hypertension, hyperthermia, cerebral oedema, metabolism, and hypoxia. Propranolol can cross the blood-brain barrier. More investigation is required to completely comprehend propranolol’s neuroprotective mechanisms in traumatic brain injury and to establish the best dosage and administration guidelines.

5.3 Subgroup analysis

To reduce the possibility of bias in the event that there is a lot of heterogeneity, we will categorize the results and perform a pooled subgroup analysis.

5.4 Patient and public involvement

Since we are using previously published studies, no patients will be involved in this study.

5.5 Strength of body of evidence

The validity and applicability of the evidence that has been compiled from this review will be evaluated using the Grading of Recommendation, Assessment, Development and Evaluation (GRADE) algorithm.

5.6 Ethics and dissemination:

Because it is a novel method of assessing the volume of literature on the topic, this systematic review of published articles on “management of traumatic brain injury in India" will not need ethical approval because it is a secondary analysis. The Cochrane Handbook for systematic reviews and meta-analyses of diagnostic test accuracy guide-lines will be adhered to in this study.¹¹ In order to protect human subjects and ensure responsible research practices, we have followed ethical principles and guidelines during the conduct of this study. First off, the data in this review originate from pub-lished, publicly accessible literature, suggesting that the authors of the original studies have already gotten informed consent. Our privacy policies protect patients’ and their families’ identity and we never gather personally identifiable information.¹²

We will follow PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) guidelines to ensure that our findings are comprehensible, thorough, and repeatable. In order to maintain scientific rigor, we make an effort to reduce bias and maintain transparency throughout the planning, gathering, analyzing, interpreting, and reporting of our review.¹³ In order to do this, we will adhere to a predetermined protocol that is listed in the International Prospective Register of Systematic Reviews (PROSPERO), which specifies the goals, qualifying requirements, search approach, synthesis techniques, and scheduled analyses.¹⁴ Publication of our review to enable clinicians, researchers, and policymakers to critically evaluate and apply the findings.¹⁵ Additionally, we offer an assessment of the risk of bias and a summary of findings table that employs GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) to aid readers in understanding the calibre and potency of the evidence.¹⁶

As part of the dissemination strategy, we plan to submit our study to a peer-reviewed journal in the field of neurology and neurosciences, providing open access to ensure a wider reach and impact of our findings. We also aim to present the results in conferences and meetings, targeting not only academics but also healthcare professionals, policymakers, and patient advocacy groups who can use our findings to in-form the improvement of paediatric traumatic brain injury care in LMICs.¹⁷

Ultimately, this section on Ethics and Dissemination highlights our dedication to carrying out a transparent and morally sound systematic review and meta-analysis that can support better clinical practices and policies to enhance patient outcomes and quality of life, as well as the evidence-based management of pediatric traumatic brain injury patients in LMICs.

5.7 Limitations

It may be necessary to address certain significant limitations despite the meticulous procedures employed in this systematic review and meta-analysis. First and fore-most, there may be a bias in the publications that are published because studies with significant findings are more likely to be published than those with smaller findings.

Furthermore, because we limited our search to English-language publications, we might have missed relevant research that was only available in other languages. Furthermore, there is a chance that some of the included studies in the systematic review were biased, which could affect our study’s results.