Systematic Review Procedures for the World Health Organization (WHO) Evidence Syntheses on Benefits and Harms of Structured and Standardized Education/Advice, Structured Exercise Programs, Transcutaneous Electrical Nerve Stimulation (TENS), and Needling Therapies for the Management of Chronic Low Back Pain in Adults.

As commissioned by the WHO, we updated and expanded the scope of four systematic reviews to inform its (in development) clinical practice guideline for the management of CPLBP in adults, including older adults. Methodological details and results of each review are described in the respective articles in this series. In the last article of this series, we discuss methodological considerations, clinical implications and recommendations for future research.

Systematic Review to Inform a World Health Organization (WHO) Clinical Practice Guideline: Benefits and Harms of Structured Exercise Programs for Chronic Primary Low Back Pain in Adults.

PURPOSE: Evaluate benefits and harms of structured exercise programs for chronic primary low back pain (CPLBP) in adults to inform a World Health Organization (WHO) standard clinical guideline. METHODS: We searched for randomized controlled trials (RCTs) in electronic databases (inception to 17 May 2022). Eligible RCTs targeted structured exercise programs compared to placebo/sham, usual care, or no intervention (including comparison interventions where the attributable effect of exercise could be isolated). We extracted outcomes, appraised risk of bias, conducted meta-analyses where appropriate, and assessed certainty of evidence using GRADE. RESULTS: We screened 2503 records (after initial screening through Cochrane RCT Classifier and Cochrane Crowd) and 398 full text RCTs. Thirteen RCTs rated with overall low or unclear risk of bias were synthesized. Assessing individual exercise types (predominantly very low certainty evidence), pain reduction was associated with aerobic exercise and Pilates vs. no intervention, and motor control exercise vs. sham. Improved function was associated with mixed exercise vs. usual care, and Pilates vs. no intervention. Temporary increased minor pain was associated with mixed exercise vs. no intervention, and yoga vs. usual care. Little to no difference was found for other comparisons and outcomes. When pooling exercise types, exercise vs. no intervention probably reduces pain in adults (8 RCTs, SMD = - 0.33, 95% CI - 0.58 to - 0.08) and functional limitations in adults and older adults (8 RCTs, SMD = - 0.31, 95% CI - 0.57 to - 0.05) (moderate certainty evidence). CONCLUSIONS: With moderate certainty, structured exercise programs probably reduce pain and functional limitations in adults and older people with CPLBP.

Improving Rehabilitation Research to Optimize Care and Outcomes for People with Chronic Primary Low Back Pain: Methodological and Reporting Recommendations from a WHO Systematic Review Series.

Chronic primary low back pain (CPLBP) is a prevalent and disabling condition that often requires rehabilitation interventions to improve function and alleviate pain. This paper aims to advance future research, including systematic reviews and randomized controlled trials (RCTs), on CPLBP management. We provide methodological and reporting recommendations derived from our conducted systematic reviews, offering practical guidance for conducting robust research on the effectiveness of rehabilitation interventions for CPLBP. Our systematic reviews contributed to the development of a WHO clinical guideline for CPLBP. Based on our experience, we have identified methodological issues and recommendations, which are compiled in a comprehensive table and discussed systematically within established frameworks for reporting and critically appraising RCTs. In conclusion, embracing the complexity of CPLBP involves recognizing its multifactorial nature and diverse contexts and planning for varying treatment responses. By embracing this complexity and emphasizing methodological rigor, research in the field can be improved, potentially leading to better care and outcomes for individuals with CPLBP.

Systematic Review to Inform a World Health Organization (WHO) Clinical Practice Guideline: Benefits and Harms of Transcutaneous Electrical Nerve Stimulation (TENS) for Chronic Primary Low Back Pain in Adults.

PURPOSE: To evaluate benefits and harms of transcutaneous electrical nerve stimulation (TENS) for chronic primary low back pain (CPLBP) in adults to inform a World Health Organization (WHO) standard clinical guideline. METHODS: We searched for randomized controlled trials (RCTs) from various electronic databases from July 1, 2007 to March 9, 2022. Eligible RCTs targeted TENS compared to placebo/sham, usual care, no intervention, or interventions with isolated TENS effects (i.e., combined TENS with treatment B versus treatment B alone) in adults with CPLBP. We extracted outcomes requested by the WHO Guideline Development Group, appraised the risk of bias, conducted meta-analyses where appropriate, and graded the certainty of evidence using GRADE. RESULTS: Seventeen RCTs (adults, n = 1027; adults ≥ 60 years, n = 28) out of 2010 records and 89 full text RCTs screened were included. The evidence suggested that TENS resulted in a marginal reduction in pain compared to sham (9 RCTs) in the immediate term (2 weeks) (mean difference (MD) = -0.90, 95% confidence interval -1.54 to -0.26), and a reduction in pain catastrophizing in the short term (3 months) with TENS versus no intervention or interventions with TENS specific effects (1 RCT) (MD = -11.20, 95% CI -17.88 to -3.52). For other outcomes, little or no difference was found between TENS and the comparison interventions. The certainty of the evidence for all outcomes was very low. CONCLUSIONS: Based on very low certainty evidence, TENS resulted in brief and marginal reductions in pain (not deemed clinically important) and a short-term reduction in pain catastrophizing in adults with CPLBP, while little to no differences were found for other outcomes.

Systematic Review to Inform a World Health Organization (WHO) Clinical Practice Guideline: Benefits and Harms of Needling Therapies for Chronic Primary Low Back Pain in Adults.

PURPOSE: Evaluate benefits and harms of needling therapies (NT) for chronic primary low back pain (CPLBP) in adults to inform a World Health Organization (WHO) standard clinical guideline. METHODS: Electronic databases were searched for randomized controlled trials (RCTs) assessing NT compared with placebo/sham, usual care, or no intervention (comparing interventions where the attributable effect could be isolated). We conducted meta-analyses where indicated and graded the certainty of evidence. RESULTS: We screened 1831 citations and 109 full text RCTs, yeilding 37 RCTs. The certainty of evidence was low or very low across all included outcomes. There was little or no difference between NT and comparisons across most outcomes; there may be some benefits for certain outcomes. Compared with sham, NT improved health-related quality of life (HRQoL) (physical) (2 RCTs; SMD = 0.20, 95%CI 0.07; 0.32) at 6 months. Compared with no intervention, NT reduced pain at 2 weeks (21 RCTs; MD = - 1.21, 95%CI - 1.50; - 0.92) and 3 months (9 RCTs; MD = - 1.56, 95%CI - 2.80; - 0.95); and reduced functional limitations at 2 weeks (19 RCTs; SMD = - 1.39, 95%CI - 2.00; - 0.77) and 3 months (8 RCTs; SMD = - 0.57, 95%CI - 0.92; - 0.22). In older adults, NT reduced functional limitations at 2 weeks (SMD = - 1.10, 95%CI - 1.71; - 0.48) and 3 months (SMD = - 1.04, 95%CI - 1.66; - 0.43). Compared with usual care, NT reduced pain (MD = - 1.35, 95%CI - 1.86; - 0.84) and functional limitations (MD = - 2.55, 95%CI - 3.70; - 1.40) at 3 months. CONCLUSION: Based on low to very low certainty evidence, adults with CPLBP experienced some benefits in pain, functioning, or HRQoL with NT; however, evidence showed little to no differences for other outcomes.

Systematic Review to Inform a World Health Organization (WHO) Clinical Practice Guideline: Benefits and Harms of Structured and Standardized Education or Advice for Chronic Primary low back pain in Adults.

PURPOSE: Evaluate benefits and harms of education/advice for chronic primary low back pain (CPLBP) in adults to inform a World Health Organization (WHO) standard clinical guideline. METHODS: Electronic databases were searched for randomized controlled trials (RCTs) assessing education/advice compared with placebo/sham, usual care, or no intervention (including comparison interventions where the attributable effect of education/advice could be isolated). We conducted meta-analyses and graded the certainty of evidence. RESULTS: We screened 2514 citations and 86 full text RCTs and included 15 RCTs. Most outcomes were assessed 3 to 6 months post-intervention. Compared with no intervention, education/advice improved pain (10 RCTs, MD = -1.1, 95% CI -1.63 to -0.56), function (10 RCTs, SMD = -0.51, 95% CI -0.89 to -0.12), physical health-related quality of life (HRQoL) (2 RCTs, MD = 24.27, 95% CI 12.93 to 35.61), fear avoidance (5 RCTs, SMD = -1.4, 95% CI -2.51 to -0.29), depression (1 RCT; MD = 2.10, 95% CI 1.05 to 3.15), and self-efficacy (1 RCT; MD = 4.4, 95% CI 2.77 to 6.03). Education/advice conferred less benefit than sham Kinesio taping for improving fear avoidance regarding physical activity (1 RCT, MD = 5.41, 95% CI 0.28 to 10.54). Compared with usual care, education/advice improved pain (1 RCT, MD = -2.10, 95% CI -3.13 to -1.07) and function (1 RCT, MD = -7.80, 95% CI -14.28 to -1.32). There was little or no difference between education/advice and comparisons for other outcomes. For all outcomes, the certainty of evidence was very low. CONCLUSION: Education/advice in adults with CPLBP was associated with improvements in pain, function, HRQoL, and psychological outcomes, but with very low certainty.

Are Nonpharmacologic Interventions Delivered Through Synchronous Telehealth as Effective and Safe as In-Person Interventions for the Management of Patients With Nonacute Musculoskeletal Conditions? A Systematic Rapid Review.

OBJECTIVE: To determine whether nonpharmacologic interventions delivered through synchronous telehealth are as effective and safe compared with in-person interventions for the management of patients with musculoskeletal conditions in improving pain, functioning, self-reported recovery, psychological outcomes, or health-related quality of life using rapid review methods. DATA SOURCES: We searched MEDLINE, CINAHL, Embase, and Cochrane Central Register of Controlled Trials from 2010 to August 2020 for randomized controlled trials (RCTs) published in English or French; we updated our search in January 2021. STUDY SELECTION: One reviewer screened citations in 2 phases (phase 1: title/abstract; phase 2: full-text) selecting RCTs comparing synchronous telehealth with in-person care for the management of musculoskeletal conditions. A random 10% sample was screened by 2 independent reviewers with minimum 95% agreement prior to full screening. One reviewer critically appraised and one reviewer validated appraisal for eligible RCTs. DATA EXTRACTION: One author extracted participant characteristics, setting, sample size, interventions, comparisons, follow-up period, and outcome data. A second author validated data extraction. DATA SYNTHESIS: We summarized the findings narratively. Low- to moderate-quality evidence suggests that synchronous telehealth (ie, videoconference or telephone calls) alone or in combination with in-person care leads to similar outcomes as in-person care alone for nonspecific low back pain, generalized osteoarthritis, hip or knee osteoarthritis, and nonacute headaches in adults. CONCLUSIONS: Synchronous telehealth may be an option for the management of nonacute musculoskeletal conditions in adults. However, our results may not be generalizable to rural or low socioeconomic populations. Future research should investigate the outcomes associated the use of new technologies, such as videoconference.

Exploring clinician perceptions of a care pathway for the management of shoulder pain: a qualitative study.

BACKGROUND: Clinical care pathways may be useful tools to improve the quality of healthcare by facilitating the translation of evidence into practice. Our study is situated within a larger project, whereby end-users co-developed a care pathway for the management of shoulder pain. In this study, we explored end-user perceptions of the usefulness and practicality of implementing a care pathway to manage shoulder pain. We also solicited feedback for the pathway's improvement. METHODS: We conducted a qualitative study using a transcendental phenomenological approach seen through a constructivist lens. Clinicians recorded themselves interacting with the care pathway while working through a clinical case. Clinicians described their thoughts and movements aloud as they completed the activity. Second, we conducted individual semi-structured interviews to discuss the usefulness and practicality of pathway implementation. Interview transcripts were coded independently by reviewers. Transcript codes and associated quotes were grouped into themes. Themes were sequenced and linked creating a 'web' of thematic connections. Summary statements were developed to synthesize the overall essence of the phenomena. RESULTS: Nine clinicians participated. Participants included eight chiropractors and one medical physician. We found that clinicians believed the care pathway could be useful at various levels, including education (students, interns), for early career clinicians, for engaging patients, facilitating interprofessional communication, and as a reminder of information for certain, less familiar conditions. When discussing the practicality of implementing the care pathway into practice settings, clinicians expressed that agreement with the care pathway and its recommendations may influence its acceptability among clinicians. Additionally, integrating recommendations into practice may be a skill requirement included into clinical training. Clinicians described the importance of opinion leaders in the acceptability of new evidence. Various difficulties with the replicability of interventions into clinical care was also discussed. In general, clinicians suggested the layout of the care pathway was manageable, and there was sufficient information for clinical decision-making. Clinicians also made several recommendations for improvement. CONCLUSIONS: End-user involvement and collaboration provides tangible instruction to improve care pathways themselves, their implementation strategies and helps to support and strengthen future research for overcoming individual, systemic and contextual barriers.

Exploring clinicians' experiences and perceptions of end-user roles in knowledge development: a qualitative study.

BACKGROUND: End-user involvement in developing evidence-based tools for clinical practice may result in increased uptake and improved patient outcomes. Understanding end-user experiences and perceptions about the co-production of knowledge is useful to further the science of integrated knowledge translation (iKT) - a strategy for accelerating the uptake and impact of research. Our study had two main objectives: (1) explore end-user (clinician) experiences of co-producing an evidence-based practice tool; and (2) describe end-user perceptions in knowledge development. METHODS: We used a qualitative study design. We conducted semi-structured interviews with clinicians and used a transcendental phenomenological approach to analyze themes/phenomena. In addition, we explored the interrelated themes between the thematic maps of each objective. RESULTS: Four themes emerged from clinicians' experiences in co-producing the practice tool: ease/convenience of participating, need for support and encouragement, understanding the value of participating, and individual skillsets yield meaningful contributions. Stakeholder roles in knowledge tool development and improving dissemination of evidence and knowledge tools were themes that related to clinician perceptions in knowledge development. The review of interrelated thematic maps depicts an intertwined relationship between stakeholders and dissemination. CONCLUSIONS: End-users provide invaluable insight and perspective into the development of evidence-based clinical tools. Exploring the experiences and perceptions of end-users may support future research endeavours involving iKT, such as the co-production of clinical resources, potentially improving uptake and patient health outcomes.

A conceptual framework for prognostic research.

BACKGROUND: Prognostic research has many important purposes, including (i) describing the natural history and clinical course of health conditions, (ii) investigating variables associated with health outcomes of interest, (iii) estimating an individual's probability of developing different outcomes, (iv) investigating the clinical application of prediction models, and (v) investigating determinants of recovery that can inform the development of interventions to improve patient outcomes. But much prognostic research has been poorly conducted and interpreted, indicating that a number of conceptual areas are often misunderstood. Recent initiatives to improve this include the Prognosis Research Strategy (PROGRESS) and the Transparent Reporting of a multivariable prediction model for Individual Prognosis or Diagnosis (TRIPOD) Statement. In this paper, we aim to show how different categories of prognostic research relate to each other, to differentiate exploratory and confirmatory studies, discuss moderators and mediators, and to show how important it is to understand study designs and the differences between prediction and causation. MAIN TEXT: We propose that there are four main objectives of prognostic studies - description, association, prediction and causation. By causation, we mean the effect of prediction and decision rules on outcomes as determined by intervention studies and the investigation of whether a prognostic factor is a determinant of outcome (on the causal pathway). These either fall under the umbrella of exploratory (description, association, and prediction model development) or confirmatory (prediction model external validation and investigation of causation). Including considerations of causation within a prognostic framework provides a more comprehensive roadmap of how different types of studies conceptually relate to each other, and better clarity about appropriate model performance measures and the inferences that can be drawn from different types of prognostic studies. We also propose definitions of 'candidate prognostic factors', 'prognostic factors', 'prognostic determinants (causal)' and 'prognostic markers (non-causal)'. Furthermore, we address common conceptual misunderstandings related to study design, analysis, and interpretation of multivariable models from the perspectives of association, prediction and causation. CONCLUSION: This paper uses a framework to clarify some concepts in prognostic research that remain poorly understood and implemented, to stimulate discussion about how prognostic studies can be strengthened and appropriately interpreted.

Epidemiology of Isolated Versus Nonisolated Mild Traumatic Brain Injury Treated in Emergency Departments in the United States, 2006-2012: Sociodemographic Characteristics.

OBJECTIVES: To describe the frequencies and rates of mild traumatic brain injury (mTBI) emergency department (ED) visits, analyze the trend across the years, and compare sociodemographic characteristics of visits by mTBI type (ie, mTBI as the only injury, or present along with other injuries). DESIGN: Population-based descriptive study using data from the Nationwide Emergency Department Sample (2006-2012). METHODS: Joinpoint regression was used to calculate the average annual percent changes of mTBI incidence rates. Characteristics between isolated and nonisolated visits were compared, and the odds ratios were reported. RESULTS: The rate per 100 000 population of mTBI ED visits in the United States increased significantly from 569.4 (in 2006) to 807.9 (in 2012). The highest rates were observed in 0- to 4-year-olds, followed by male 15- to 24-year-olds and females 65 years and older; the lowest rates were among 45- to 64-year-olds. The majority (70%) of all visits were nonisolated and occurred more frequently in residents of metropolitan areas. Falls were the leading external cause. Most visits were privately insured or covered by Medicare/Medicaid, and the injury occurred on weekdays in predominantly metropolitan hospitals in the South region. CONCLUSIONS: The burden of mTBI in US EDs is high. Most mTBI ED visits present with other injuries. Awareness of sociodemographic factors associated with nonisolated mTBI may help improve diagnosis in US EDs. This information has implications for resource planning and mTBI screening in EDs.

Is Sex an Indicator of Prognosis After Mild Traumatic Brain Injury: A Systematic Analysis of the Findings of the World Health Organization Collaborating Centre Task Force on Mild Traumatic Brain Injury and the International Collaboration on Mild Traumatic Brain Injury Prognosis.

OBJECTIVE: To determine sex differences in the recovery and prognosis after mild traumatic brain injury (MTBI) in adults and children. DATA SOURCES: We analyzed all scientifically admissible primary studies in the World Health Organization (WHO) (n=120) and International Collaboration on Mild Traumatic Brain Injury Prognosis (ICoMP) (n=101) systematic reviews regarding prognosis of MTBI for sex-stratified findings. They searched MEDLINE and other databases from 1980 through 2000 (WHO) and 2001 through 2012 (ICoMP) for published, peer-reviewed reports in English and other languages. STUDY SELECTION: We selected controlled trials and cohort and case-control studies that assessed the effect of sex on outcomes after MTBI. DATA EXTRACTION: Data from the eligible studies from both systematic reviews combined (n=14, 7%) were extracted into evidence tables. DATA SYNTHESIS: Prognostic information relating to sex was prioritized according to design as exploratory or confirmatory, and a best-evidence synthesis was conducted. After MTBI, females may have a higher risk of epilepsy (children, young adults) and suicide, and use more health care services; males may be at higher risk for schizophrenia. Most studies did not find a sex difference for postconcussion symptoms in children and adults. No sex difference was found for risk of dementia and primary brain tumor, return to work, or posttraumatic stress syndrome. CONCLUSIONS: Sex is not a well-studied prognostic indicator for recovery after MTBI, but small sex differences were found for some outcomes. More well-designed studies are needed that report outcomes according to sex and control for potential confounders.

Healthy and productive workers: using intervention mapping to design a workplace health promotion and wellness program to improve presenteeism.

BACKGROUND: Presenteeism is a growing problem in developed countries mostly due to an aging workforce. The economic costs related to presenteeism exceed those of absenteeism and employer health costs. Employers are implementing workplace health promotion and wellness programs to improve health among workers and reduce presenteeism. How best to design, integrate and deliver these programs are unknown. The main purpose of this study was to use an intervention mapping approach to develop a workplace health promotion and wellness program aimed at reducing presenteeism. METHODS: We partnered with a large international financial services company and used a qualitative synthesis based on an intervention mapping methodology. Evidence from systematic reviews and key articles on reducing presenteeism and implementing health promotion programs was combined with theoretical models for changing behavior and stakeholder experience. This was then systematically operationalized into a program using discussion groups and consensus among experts and stakeholders. RESULTS: The top health problem impacting our workplace partner was mental health. Depression and stress were the first and second highest cause of productivity loss respectively. A multi-pronged program with detailed action steps was developed and directed at key stakeholders and health conditions. For mental health, regular sharing focus groups, social networking, monthly personal stories from leadership using webinars and multi-media communications, expert-led workshops, lunch and learn sessions and manager and employee training were part of a comprehensive program. Comprehensive, specific and multi-pronged strategies were developed and aimed at encouraging healthy behaviours that impact presenteeism such as regular exercise, proper nutrition, adequate sleep, smoking cessation, socialization and work-life balance. Limitations of the intervention mapping process included high resource and time requirements, the lack of external input and viewpoints skewed towards middle and upper management, and using secondary workplace data of unknown validity and reliability. CONCLUSIONS: In general, intervention mapping was a useful method to develop a workplace health promotion and wellness program aimed at reducing presenteeism. The methodology provided a step-by-step process to unravel a complex problem. The process compelled participants to think critically, collaboratively and in nontraditional ways.

Systematic search and review procedures: results of the International Collaboration on Mild Traumatic Brain Injury Prognosis.

OBJECTIVES: To update the last best-evidence synthesis conducted by the World Health Organization Collaborating Centre for Neurotrauma, Prevention, Management and Rehabilitation in 2002; and to describe the course, identify prognostic factors, determine long-term sequelae, identify effects of interventions for mild traumatic brain injury (MTBI), identify knowledge gaps in the literature, and make recommendations for future research. DATA SOURCES: MEDLINE, Embase, PsycINFO, Cumulative Index to Nursing and Allied Health, and SPORTDiscus were searched between 2001 and 2012. Inclusion criteria included published peer-reviewed articles in English and 5 other languages. References were also identified from relevant reviews and meta-analyses and the bibliographies of eligible articles. STUDY SELECTION: Controlled trials and cohort and case-control studies were selected according to predefined inclusion/exclusion criteria. Studies had to have at least 30 MTBI cases and assess outcomes relevant to prognosis after MTBI. DATA EXTRACTION: Eligible studies were critically appraised using modified Scottish Intercollegiate Guidelines Network (SIGN) criteria. Two reviewers independently reviewed each study and extracted data from accepted articles (ie, with a low risk of bias) into evidence tables. DATA SYNTHESIS: The evidence was synthesized qualitatively according to modified SIGN criteria and prioritized according to design as exploratory or confirmatory. The evidence was organized into separate articles according to population (eg, adults, children, and athletes) and outcomes (eg, risk of dementia after MTBI). CONCLUSIONS: After 77,914 records were screened, 299 articles were eligible and reviewed. Of these, 101 (34%) were accepted as scientifically admissible and form the basis of our findings, which are organized into 10 articles in this supplement. These reviews present the best available evidence on MTBI prognosis, but more research is needed.

Psychosocial consequences of mild traumatic brain injury in children: results of a systematic review by the International Collaboration on Mild Traumatic Brain Injury Prognosis.

OBJECTIVE: To synthesize the best available evidence regarding psychosocial consequences of mild traumatic brain injury (MTBI) in children. DATA SOURCES: MEDLINE, Embase, CINAHL, PsycINFO, and SPORTDiscus were searched (2001-2012). Inclusion criteria included published peer-reviewed reports in English, French, Norwegian, Spanish, Swedish, and Danish. References were also identified from relevant reviews and meta-analyses, and the bibliographies of eligible articles. STUDY SELECTION: This article presents an update of a previous review with a much larger scope, of which this topic is a small subset of the questions addressed by that review. Controlled trials and cohort and case-control studies were selected according to predefined criteria. Two independent reviewers used modified Scottish Intercollegiate Guidelines Network criteria to critically appraise eligible studies. A total of 77,914 records were screened; 101 of these articles were deemed scientifically admissible, of which 6 investigated the psychosocial consequences of MTBI in children. DATA EXTRACTION: Two reviewers independently extracted data from accepted studies into evidence tables. DATA SYNTHESIS: We conducted a best-evidence synthesis by linking our conclusions to the evidence tables. Most accepted studies were exploratory rather than confirmatory. Preliminary evidence suggests that most children recover within 3 months post-MTBI. After 1 year, the prevalence of postconcussion symptoms and syndrome is similar between children with MTBI and children with orthopedic injuries. The functional status of children with MTBI improves over a 30-month follow-up period, but further research is needed to investigate the possibility that children with MTBI experience greater rates of psychiatric illness during the 3 years after their injury. CONCLUSIONS: The prognosis of MTBI is favorable in children. Most appear to recover functionally from a physical and psychological perspective. However, future research should investigate the risk for psychiatric illness.

Systematic review of prognosis after mild traumatic brain injury in the military: results of the International Collaboration on Mild Traumatic Brain Injury Prognosis.

OBJECTIVE: The World Health Organization Collaborating Centre Task Force on Mild Traumatic Brain Injury (MTBI) published its findings on the prognosis of MTBI in 2004. This is an update of that review with a focus on deployed military personnel. DATA SOURCES: Relevant literature published between January 2001 and February 2012 listed in MEDLINE and 4 other databases. STUDY SELECTION: Controlled trials and cohort and case-control studies were selected according to predefined criteria. After 77,914 titles and abstracts were screened, 13 articles were rated eligible for this review and 3 (23%) with a low risk of bias were accepted. Two independent reviewers critically appraised eligible studies using a modification of the Scottish Intercollegiate Guidelines Network criteria. DATA EXTRACTION: The reviewers independently extracted data from eligible studies and produced evidence tables. DATA SYNTHESIS: The evidence was synthesized qualitatively and presented in evidence tables. Our findings are based on 3 studies of U.S. military personnel who were deployed in Iraq or Afghanistan. We found that military personnel with MTBI report posttraumatic stress disorder and postconcussive symptoms. In addition, reporting of postconcussive symptoms differed on the basis of levels of combat stress the individuals experienced. The evidence suggests a slight decline in neurocognitive function after MTBI, but this decline was in the normal range of brain functioning. CONCLUSIONS: We found limited evidence that combat stress, posttraumatic stress disorder, and postconcussive symptoms affect recovery and prognosis of MTBI in military personnel. Additional high-quality research is needed to fully assess the prognosis of MTBI in military personnel.

Introduction to the findings of the International Collaboration on Mild Traumatic Brain Injury Prognosis: what is a prognostic study?

Prognostic studies of mild traumatic brain injury (MTBI) can serve many purposes. First, they are used to describe paths and outcomes of patients with MTBI. Second, they provide information on which characteristics are associated with the occurrence of outcomes. Third, they provide insight into the causation of poor or favorable course of the disease. Finally, they can assess how differences in the probability of outcomes can help predict the course of patients. In this article, we summarize methodologic principles used by the International Collaboration on MTBI Prognosis to appraise the prognostic literature. Differentiating prognostic factors (causally linked with outcome), prognostic markers (associated but not causally), and predictors is important to guide interventions, public health policy, and research. Ideally, prognostic studies need a clear statement of the type of question (hypothesis-generating descriptive, exploration of possible prognostic variables, confirmatory modeling of prognosis); a cohort study design with standardized follow-up of a representative population of patients with MTBI; a standardized data collection using reliable and accurate tools to capture clinically, biologically, psychologically, or socially relevant variables and outcomes; and an analysis of data based on survival methods. Interpretation of prognostic studies should consider biases related to differential inclusion of nonrepresentative samples of patients, poor measurements of outcomes, and poor control for confounders. Transferring prognostic results into clinical practice should be based on estimates of the predictive performance of models and on a demonstration that patient outcomes can be improved by the use of prediction rules.

Systematic review of the clinical course, natural history, and prognosis for pediatric mild traumatic brain injury: results of the International Collaboration on Mild Traumatic Brain Injury Prognosis.

OBJECTIVE: To synthesize the best available evidence on prognosis after pediatric mild traumatic brain injury (MTBI). DATA SOURCES: We searched MEDLINE, Embase, PsycINFO, CINAHL, and SPORTDiscus (2001-2012), as well as reference lists of eligible articles, and relevant systematic reviews and meta-analyses. STUDY SELECTION: Controlled trials and cohort and case-control studies were selected according to predefined criteria. Studies had to have a minimum of 30 MTBI pediatric cases. After 77,914 records were screened for the entire review, 299 studies were eligible and assessed for scientific rigor. DATA EXTRACTION: Eligible studies were critically appraised using the Scottish Intercollegiate Guidelines Network (SIGN) criteria. Two reviewers independently reviewed each study and extracted data from accepted articles into evidence tables. DATA SYNTHESIS: Evidence from 25 accepted articles was synthesized qualitatively according to SIGN criteria, and prognostic information was prioritized according to design as exploratory or confirmatory. Most studies show that postconcussion symptoms and cognitive deficits resolve over time. Limited evidence suggests that postconcussion symptoms may persist in those with lower cognitive ability and intracranial pathology on neuroimaging. Preliminary evidence suggests that the risk of epilepsy is increased for up to 10 years after MTBI; however, there is insufficient high-quality evidence at this time to support this link. CONCLUSIONS: Common post-MTBI symptoms and deficits in children are not specific to MTBI and appear to resolve with time; however, limited evidence suggests that children with intracranial pathology on imaging may experience persisting symptoms or deficits. Well-designed, long-term studies are needed to confirm these findings.

Systematic review of the risk of Parkinson's disease after mild traumatic brain injury: results of the International Collaboration on Mild Traumatic Brain Injury Prognosis.

OBJECTIVE: To synthesize the best available evidence on the risk of Parkinson's disease (PD) after mild traumatic brain injury (MTBI). DATA SOURCES: MEDLINE and other databases were searched (1990-2012) with terms including "craniocerebral trauma" and "parkinsonian disorders." Reference lists of eligible articles and relevant systematic reviews and meta-analyses were also searched. STUDY SELECTION: Controlled clinical trials, cohort studies, and case-control studies were selected according to predefined criteria. Studies had to have a minimum of 30 concussion cases. DATA EXTRACTION: Eligible studies were critically appraised using a modification of the Scottish Intercollegiate Guidelines Network criteria. Two reviewers independently reviewed and extracted data from accepted studies into evidence tables. DATA SYNTHESIS: Evidence was synthesized qualitatively according to modified Scottish Intercollegiate Guidelines Network criteria. Sixty-five studies were eligible and reviewed, and 5 of these with a low risk of bias were accepted as scientifically admissible and form the basis of our findings. Among these admissible studies, the definitions of MTBI were highly heterogeneous. One study found a significant positive association between MTBI and PD (odds ratio, 1.5; 95% confidence interval, 1.4-1.7). The estimated odds ratio decreased with increasing latency between MTBI and PD diagnosis, which suggests reverse causality. The other 4 studies did not find a significant association. CONCLUSIONS: The best available evidence argues against an important causal association between MTBI and PD. There are few high-quality studies on this topic. Prospective studies of long duration would address the limitations of recall of head injury and the possibility of reverse causation.