Utility of Acute and Subacute Blood Biomarkers to Assist Diagnosis in CT-Negative Isolated Mild Traumatic Brain Injury.

BACKGROUND AND OBJECTIVES: Blood biomarkers glial fibrillary acidic protein (GFAP) and ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) have recently been Food and Drug Administration approved as predictors of intracranial lesions on CT after mild traumatic brain injury (mTBI). However, most cases with mTBI are CT negative, and no biomarkers are approved to assist diagnosis in these individuals. In this study, we aimed to determine the optimal combination of blood biomarkers to assist mTBI diagnosis in otherwise healthy adults younger than 50 years presenting to an emergency department within 6 hours of injury. To further understand the utility of biomarkers, we assessed how biological sex, presence or absence of loss of consciousness and/or post-traumatic amnesia (LOC/PTA), and delayed presentation affected classification performance. METHODS: Blood samples, symptom questionnaires, and cognitive tests were prospectively conducted for participants with mTBI recruited from The Alfred Hospital Level 1 Emergency & Trauma Center and uninjured controls. Follow-up testing was conducted at 7 days. Simoa quantified plasma GFAP, UCH-L1, tau, neurofilament light chain (NfL), interleukin (IL)-6, and IL-1ß. Area under the receiver operating characteristic (AUC) analysis assessed classification accuracy for diagnosed mTBI, and logistic regression models identified optimal biomarker combinations. RESULTS: Plasma IL-6 (AUC 0.91, 95% CI 0.86-0.96), GFAP (AUC 0.85, 95% CI 0.78-0.93), and UCH-L1 (AUC 0.79, 95% CI 0.70-0.88) best differentiated mTBI (n = 74) from controls (n = 44) acutely (<6 hours), with NfL (AUC 0.81, 95% CI 0.72-0.90) the only marker to have such utility subacutely (7 days). Biomarker performance was similar between sexes and for participants with and without LOC/PTA, with the exception at 7 days, where GFAP and IL-6 retained some utility in female participants (GFAP: AUC 0.71, 95% CI 0.55-0.88; IL-6: AUC 0.71, 95% CI 0.55-0.87) and in those with LOC/PTA (GFAP: AUC 0.73, 95% CI 0.59-0.86; IL-6: AUC 0.71, 95% CI 0.57-0.84). Acute IL-6 (R 2 = 0.50, 95% CI 0.34-0.64) outperformed GFAP and UCH-L1 combined (R 2 = 0.35, 95% CI 0.17-0.50), with the best acute model featuring GFAP and IL-6 (R 2 = 0.54, 95% CI 0.34-0.68). DISCUSSION: These findings indicate that adding IL-6 to a panel of brain-specific proteins such as GFAP and UCH-L1 might assist in the acute diagnosis of mTBI in adults younger than 50 years. Multiple markers had high classification accuracy in participants without LOC/PTA. When compared with the best-performing acute markers, subacute measures of plasma NfL resulted in minimal reduction in classification accuracy. Future studies will investigate the optimal time frame over which plasma IL-6 might assist diagnostic decisions and how extracranial trauma affects utility.

MicroRNA biomarkers for diagnosis of mild traumatic brain injury and prediction of persistent symptoms: A prospective cohort study.

The diagnosis of mild traumatic brain injury (mTBI) and early identification of patients who have persistent symptoms remains challenging. Symptoms are variably reported, and tests for cognitive impairment require specific expertise. The aim of this study was to assess the ability of plasma micro-ribonucleic acid (miRNA) biomarkers to distinguish between patients with mTBI and healthy controls. A secondary aim was to assess whether miRNA biomarker levels on the day of injury could predict persistent symptoms on day 7. Injured patients presented to an adult, tertiary referral hospital emergency department and were diagnosed with isolated mTBI (n = 75). Venous blood samples were collected within 6 h of injury. Symptom severity was assessed using the Rivermead Post-Concussion Symptom Questionnaire (RPQ) on the day of injury and at 7 days post-injury. The comparator group (n = 44) were healthy controls without any injury, who had bloods sampled and symptom severity assessed at the same time-point. Patients after mTBI reported higher symptom severity and had worse cognitive performance than the control group. Plasma miR423-3p levels were significantly higher among mTBI patients acutely post-injury compared to healthy controls and provided moderate discriminative ability (AUROC 0.67; 95 %CI: 0.57-0.77). None of the assessed miRNA biomarkers predicted persistent symptoms at 7 days. Plasma miR423-3p levels measured within 6 h of injury can discriminate for mTBI compared to healthy controls, with potential utility for screening after head injury or as an adjunct to the diagnosis of mTBI. Acute plasma miRNA levels did not predict patients who reported persistent symptoms at 7 days.

Perceived Utility of Intracranial Pressure Monitoring in Traumatic Brain Injury: A Seattle International Brain Injury Consensus Conference Consensus-Based Analysis and Recommendations.

BACKGROUND: Intracranial pressure (ICP) monitoring is widely practiced, but the indications are incompletely developed, and guidelines are poorly followed. OBJECTIVE: To study the monitoring practices of an established expert panel (the clinical working group from the Seattle International Brain Injury Consensus Conference effort) to examine the match between monitoring guidelines and their clinical decision-making and offer guidance for clinicians considering monitor insertion. METHODS: We polled the 42 Seattle International Brain Injury Consensus Conference panel members' ICP monitoring decisions for virtual patients, using matrices of presenting signs (Glasgow Coma Scale [GCS] total or GCS motor, pupillary examination, and computed tomography diagnosis). Monitor insertion decisions were yes, no, or unsure (traffic light approach). We analyzed their responses for weighting of the presenting signs in decision-making using univariate regression. RESULTS: Heatmaps constructed from the choices of 41 panel members revealed wider ICP monitor use than predicted by guidelines. Clinical examination (GCS) was by far the most important characteristic and differed from guidelines in being nonlinear. The modified Marshall computed tomography classification was second and pupils third. We constructed a heatmap and listed the main clinical determinants representing 80% ICP monitor insertion consensus for our recommendations. CONCLUSION: Candidacy for ICP monitoring exceeds published indicators for monitor insertion, suggesting the clinical perception that the value of ICP data is greater than simply detecting and monitoring severe intracranial hypertension. Monitor insertion heatmaps are offered as potential guidance for ICP monitor insertion and to stimulate research into what actually drives monitor insertion in unconstrained, real-world conditions.

Prognostication and Goals of Care Decisions in Severe Traumatic Brain Injury: A Survey of The Seattle International Severe Traumatic Brain Injury Consensus Conference Working Group.

Abstract Best practice guidelines have advanced severe traumatic brain injury (TBI) care; however, there is little that currently informs goals of care decisions and processes despite their importance and frequency. Panelists from the Seattle International severe traumatic Brain Injury Consensus Conference (SIBICC) participated in a survey consisting of 24 questions. Questions queried use of prognostic calculators, variability in and responsibility for goals of care decisions, and acceptability of neurological outcomes, as well as putative means of improving decisions that might limit care. A total of 97.6% of the 42 SIBICC panelists completed the survey. Responses to most questions were highly variable. Overall, panelists reported infrequent use of prognostic calculators, and observed variability in patient prognostication and goals of care decisions. They felt that it would be beneficial for physicians to improve consensus on what constitutes an acceptable neurological outcome as well as what chance of achieving that outcome is acceptable. Panelists felt that the public should help to define what constitutes a good outcome and expressed some support for a "nihilism guard." More than 50% of panelists felt that if it was certain to be permanent, a vegetative state or lower severe disability would justify a withdrawal of care decision, whereas 15% felt that upper severe disability justified such a decision. Whether conceptualizing an ideal or existing prognostic calculator to predict death or an unacceptable outcome, on average a 64-69% chance of a poor outcome was felt to justify treatment withdrawal. These results demonstrate important variability in goals of care decision making and a desire to reduce this variability. Our panel of recognized TBI experts opined on the neurological outcomes and chances of those outcomes that might prompt consideration of care withdrawal; however, imprecision of prognostication and existing prognostication tools is a significant impediment to standardizing the approach to care-limiting decisions.

Padded Headgear in Junior and Youth Australian Football: Player Insights From a National Survey.

OBJECTIVES: To investigate beliefs and factors associated with padded headgear (HG) use in junior (<13 years) and youth (≥13 years) Australian football. DESIGN: Online survey. SETTING: Junior and youth athletes in Australia. PARTICIPANTS: Australian football players aged U8 to U18. ASSESSMENT OF VARIABLES: Survey questions regarding demographics, HG use, concussion history, beliefs about HG, and risk-taking propensity. MAIN OUTCOME MEASURES: Rates of padded HG use, and beliefs associated with HG use. RESULTS: A total of 735 players (including 190, 25.9% female) representing 206 clubs participated. Headgear was worn by 315 players (42.9%; 95% CI: 39.3-46.4). Most (59.5%) HG users wore it for games only and wore it voluntarily (59.7%), as opposed to being mandated to do so. Junior players were more likely than youth players to agree to feeling safer ( P < 0.001) and being able to play harder while wearing HG ( P < 0.001). Median responses were "disagree" on preferring to risk an injury than wear HG, and on experienced players not needing to wear HG. Beliefs did not differ between males and females. Headgear use was associated with players belonging to a club where HG was mandated for other age groups (OR 16.10; 95% CI: 7.71-33.62, P < 0.001), youth players (OR 2.79; 95% CI: 1.93-3.93, P < 0.001), and female players (OR 1.57; 95% CI: 1.07-2.30, P = 0.019). CONCLUSIONS: Club HG culture, older age and being female were prominent variables associated with voluntary HG use. Players reported believing that HG offers protection. The rate of voluntary and mandated HG use identified is at odds with current scientific evidence that does not support HG as effective concussion prevention.

A Randomized Controlled Trial of the Prevent Alcohol and Risk-Related Trauma in Youth Program in Reducing Alcohol-Related Harms in Young Naval Trainees.

BACKGROUND: The aim of this study was to test whether participation in an alcohol risk reduction program known as Prevent Alcohol and Risk-Related Trauma in Youth (P.A.R.T.Y.) is effective in reducing the prevalence of risky drinking at 12 months' post-intervention in a sample of Royal Australian Navy (RAN) trainees. METHODS: A non-blinded randomized controlled trial of 952 RAN trainees comparing two forms of P.A.R.T.Y. plus RAN annual alcohol and other drug awareness training with annual alcohol and other drugs awareness training only (Control). Participants were screened at baseline and at 12-month follow-up using the Alcohol Use Disorders Identification Test (AUDIT). Participants were randomized to one of three arms: (1) in-hospital P.A.R.T.Y program, (2) on-base P.A.R.T.Y. program, or (3) control.The primary outcome measure was the percentage of participants reporting an AUDIT score of 8 or above at 12 months in each group. A secondary outcome considered was reports of alcohol-related incidents in the 12-month follow-up. RESULTS: There was no difference in the risk of reporting an AUDIT score of 8 or above in either the in-hospital (Relative Risk (RR) 0.96, 95% CI: 0.75-1.23; P = .75) or on-base (RR 1.11, 95% CI: 0.89-1.369; P = 0.35) intervention groups, compared to the control group. Compared to the on-base group, there was no difference in the risk of reporting an AUDIT score of 8 or above in the in-hospital group (RR 1.16, 95% CI: 0.90-1.48; P = .24). The rate of reporting an alcohol-related incident was not different for the in-hospital (Hazard Ratio (HR) 0.60, 95% CI: 0.27-1.33; P = .21) or on-base (HR 0.50, 95% CI: 0.21-1.16; P = .11) intervention groups when compared to the control group. CONCLUSION: Participation in either an on-base or an in-hospital P.A.R.T.Y. program did not affect the proportion of naval trainee participants screening positive for risky drinking on the AUDIT.

The Impact of Major Military War Campaigns on Neurosurgery: Informetric Data and Time-Trend Analysis.

BACKGROUND: Given the neurotrauma that soldiers might face during wars, a byproduct of such devastating neurosurgical conditions can be novel data, which can act as a catalyst for potentially paradigm-shifting research. We aimed to identify the impact of major U.S. military campaigns on military neurosurgery literature across defined time periods. METHODS: A comprehensive Elsevier's Scopus database search was performed to capture all published and indexed studies from 1915 to 2021 relevant to military neurosurgery. A discrete set of validated informetric metadata parameters were extracted and analyzed using productivity analysis, citation analysis, keyword analysis, text mining, content analysis, and collaboration network mapping. RESULTS: Our search yielded 2216 documents. Annual scientific production since 1915 grew at a compounded rate of 6.1% per year, with the most significant increases during U.S. military campaigns (coefficient = 42.9, P < 0.001) and following the introduction of the Department of Defense Trauma Registry in 2007 (coefficient = 114.5; P < 0.001). Each war had a direct influence on military neurosurgery literature growth (P < 0.05), with the most prominent following the Afghanistan war. The journals with the most publications on military neurosurgery were Military Medicine (n = 168) and Journal of Head Trauma. The topmost cited author was Hoge et al. (N = 2083), while the topmost cited country was the United States (N = 1098). CONCLUSIONS: Since World War II, the military has contributed significant historical developments to neurosurgery, the most prominent being after the Iraq and Afghanistan wars and the introduction of the Department of Defense Trauma Registry.

The legacy of Renaissance surgeon Giovanni Andrea Dalla Croce on the history of military surgery and neurosurgery.

Giovanni Andrea Dalla Croce was a Venetian physician who lived in the 16th century and was famous for his treatment of wounds, which was surprisingly modern. He was the military surgeon of the Venetian Republic's naval fleet. In 1537, he published the Chirurgiae universalis opus absolutum (The absolute work on universal surgery) in Latin, then expanded and translated into vernacular Italian and published in 1574 with the title Cirugia universale e perfetta di tutte le parti pertinenti all'ottimo chirurgo (Universal and perfect surgery of all the parts necessary for the optimal surgeon). This monumental work was a comprehensive handbook of surgery, medicine, and the treatment of many kinds of wounds with techniques to be used on the battlefield. It is also notable for the inclusion of illustrations of various weapons and projectiles, for the most comprehensive description and illustrations of surgical instruments at that time, and for the first illustrations of a surgeon performing trephination of the skull in an operating room. Dalla Croce also considered the writings of his surgical forebears in formulating his own ideas. Dalla Croce was a leader of traumatology, a universal surgeon who exemplified the erudite Renaissance man, and left a tremendous legacy to military surgery of the 16th century and beyond.

Rationale and Methods for Updated Guidelines for the Management of Penetrating Traumatic Brain Injury.

Penetrating traumatic brain injury (pTBI) affects civilian and military populations resulting in significant morbidity, mortality, and healthcare costs. No up-to-date and evidence-based guidelines exist to assist modern medical and surgical management of these complex injuries. A preliminary literature search revealed a need for updated guidelines, supported by the Brain Trauma Foundation. Methodologists experienced in TBI guidelines were recruited to support project development alongside two cochairs and a diverse steering committee. An expert multi-disciplinary workgroup was established and vetted to inform key clinical questions, to perform an evidence review and the development of recommendations relevant to pTBI. The methodological approach for the project was finalized. The development of up-to-date evidence- and consensus-based clinical care guidelines and algorithms for pTBI will provide critical guidance to care providers in the pre-hospital and emergent, medical, and surgical settings.

The Impact of Preinjury Antiplatelet and Anticoagulant Use on Elderly Patients with Moderate or Severe Traumatic Brain Injury Following Traumatic Acute Subdural Hematoma.

BACKGROUND: Although it is often assumed that preinjury anticoagulant (AC) or antiplatelet (AP) use is associated with poorer outcomes among those with acute subdural hematoma (aSDH), previous studies have had varied results. This study examines the impact of preinjury AC and AP therapy on aSDH thickness, 30-day mortality, and extended Glasgow Outcome Scale at 6 months in elderly patients (aged ≥65). METHODS: A level 1 trauma center registry was interrogated to identify consecutive elderly patients who presented with moderate or severe traumatic brain injury (TBI) and associated traumatic aSDH between the first of January 2013 and the first of January 2018. Relevant demographic, clinical, and radiological data were retrieved from institutional medical records. The 3 primary outcome measures were aSDH thickness on initial computed tomography scan, 30-day mortality, and unfavorable outcome at 6 months (extended Glasgow Outcome Scale). RESULTS: One hundred thirty-two elderly patients were admitted with moderate or severe TBI and traumatic aSDH. The mean (±SD) age was 78.39 (±7.87) years, and a majority of patients (59.8%, n = 79) were male. There was a statistically significant difference in mean aSDH thickness, but there were no significant differences in 30-day mortality (P = 0.732) and unfavorable outcome between the AP, AC, combined AP and AC, and no antithrombotic exposure groups (P = 0.342). CONCLUSIONS: Further studies with larger sample sizes are necessary to confirm these observations, but our findings do not support the preconceived notion in clinical practice that antithrombotic use is associated with poor outcomes in elderly patients with moderate or severe TBI.

The role of tranexamic acid in traumatic brain injury.

Evidence from recent trials evaluating efficacy of antifibrinolytic agents in the context of traumatic brain injury may lead to changes in the management of patients with traumatic brain injury. Tranexamic acid (TXA) reduces the proteolytic action of plasmin on fibrin clots, resulting in an inhibition of fibrinolysis and stabilisation of established blood clots. There has been significant interest in use of the drug as a therapeutic agent in the context of severe haemorrhage; however, considerable controversies regarding its efficacy remain. A number of trials have demonstrated a small but significant decrease in mortality following its administration, but the results have been somewhat inconsistent and may not be generalisable. The results of the CRASH-3 trial were that there was no statistical difference in the number of traumatic brain injury related deaths (18.5% with TXA and 19.8% with placebo; relative risk [RR] 0·94; 95% confidence interval [CI] 0·86-1·02). Nonetheless, there was a subgroup of patients for whom TXA appeared to provide benefit, and this was in patients with mild and moderate injury (with a Glasgow Coma Score > 8). This is potentially a very important finding that may have huge potential implications; however, we believe it does not currently provide indisputable evidence to support the administration of TXA to all patients with TBI. Further work is required to better define the subset of patients who may benefit as well as to evaluate the long-term functional benefit in order to determine which types of severe traumatic brain injury patients would derive more benefits than harms from TXA.

An initial Glasgow Coma Scale score of 8 or less does not define severe brain injury.

The wide-spread use of an initial 'Glasgow Coma Scale (GCS) 8 or less' to define and dichotomise 'severe' from 'mild' or 'moderate' traumatic brain injury (TBI) is an out-dated research heuristic that has become an epidemiological convenience transfixing clinical care. Triaging based on GCS can delay the care of patients who have rapidly evolving injuries. Sole reliance on the initial GCS can therefore provide a false sense of security to caregivers and fail to provide timely care for patients presenting with GCS greater than 8. Nearly 50 years after the development of the GCS - and the resultant misplaced clinical and statistical definitions - TBI remains a heterogeneous entity, in which 'best practice' and 'prognoses' are poorly stratified by GCS alone. There is an urgent need for a paradigm shift towards more effective initial assessment of TBI.

Neurotrauma, COVID and the rationing of intensive care: an ethical approach.

The advent of the COVID-19 pandemic with its extreme pressure on resources and intensive care beds has prompted many healthcare providers to consider more fully the potentially futile nature of some treatments and how resources might be better managed. This is especially relevant in the context of neurosurgery which is highly resource dependent in terms of technology, funding, and manpower and it may be difficult to balance fair, equitable and sustainable resource allocation, especially in circumstances where those healthcare resources become limited or completely exhausted. Indeed, it may be necessary to consider limiting the availability of certain neurosurgical services or perhaps reconsider the utility or otherwise of performing procedures that commit very restricted resources, such as intensive care beds, to patients who are arguably receiving limited long-term benefit. In these circumstances, the decision-making paradigm is challenging and there are several ethically disparate viewpoints that need to be reconciled. These include but are not limited to, Futility, Utilitarianism and the Rule of rescue.

Visible Signs of Concussion and Cognitive Screening in Community Sports.

Video surveillance and detection of players with visible signs of concussion by experienced medical staff facilitates rapid on-field screening of suspected concussion in professional sports. This method, however has not been validated in community sports where video footage is unavailable. This study aimed to explore the utility of visible signs of concussion to identify players with decrements in performance on concussion screening measures. In this observational prospective cohort study, personnel with basic training observed live matches across a season (60 matches) of community male and female Australian football for signs of concussion outlined in the community-based Head Injury Assessment form (HIAf). Players identified to have positive signs of concussion (CoSign+) following an impact were compared with players without signs (CoSign-). Outcome measures, the Sport Concussion Assessment Tool (SCAT3) and Cogstate, were administered at baseline and post-match. CoSign+ (n = 22) and CoSign- (n = 61) groups were similar with respect to age, sex, education, baseline mood, and medical history. CoSign+ players exhibited worse orientation, concentration, and recall, and slower reaction time in attention and working memory tasks. Comparing individual change from baseline to post-match assessment revealed 100% (95% confidence interval [CI]: 84-100%) of CoSign+ players demonstrated clinically significant deficits on SCAT3 or Cogstate tasks, compared with 59% (95% CI: 46-71%) of CoSign- players. All CoSign+ players observed to have a blank/vacant look demonstrated clinically significant decline on the Standardized Assessment of Concussion (SAC). Detection of visible signs of concussion represents a rapid, real-time method for screening players suspected of concussion in community sports where video technology and medical personnel are rarely present. Consistent with community guidelines, it is recommended that all CoSign+ players be immediately removed from play for further concussion screening.

The association of padded headgear with concussion and injury risk in junior Australian football: A prospective cohort study.

OBJECTIVES: To assess whether padded headgear was associated with incidence of suspected sports-related concussion, non-sports-related concussion head injury, and injuries to other body regions in junior Australian football. DESIGN: Prospective cohort injury surveillance. METHODS: There were 400 junior players (42.5% female) enrolled across two seasons. Suspected sports-related concussion was defined by detection of observable signs on the field and medical assessment or missed match(es) due to suspected sports-related concussion. Non-sports-related concussion head injury and injuries to other body regions were defined as those that received medical assessment or resulted in a missed match. RESULTS: There were 20 teams monitored over 258 matches. 204 players (2484 player hours) wore mandated headgear throughout the season and 196 (2246 player hours) did not. The incidence rate of suspected sports-related concussion was 3.17 (95% confidence interval: 3.04-3.30) per 1000 player-hours and no differences were observed between males and females (risk ratio 1.11; 95% confidence interval: 0.40-3.06). Headgear use was not associated with suspected sports-related concussion (risk ratio 1.09; 95% confidence interval: 0.41-2.97), non-sports-related concussion head injury (risk ratio 0.27; 95% confidence interval: 0.06-1.31), or injuries to other body regions (risk ratio 1.41; 95% confidence interval: 0.79-2.53). CONCLUSIONS: Headgear use was not associated with reduced risk of suspected sports-related concussion, non-sports-related concussion head injury or injuries to other body regions. There was no difference in the rate of suspected sports-related concussion in female compared to male players, however, rates of non-sports-related concussion head injury and injuries to other body regions were higher in male players.

Micro-RNA levels and symptom profile after mild traumatic brain injury: A longitudinal cohort study.

Micro riboneucleic acids (miRNAs) may be transcribed after brain injury and be detectable in plasma. This study aimed to assess the discriminative ability of seven miRNAs in plasma to differentiate between patients with mild traumatic brain injury (mTBI) and healthy controls. Changes in miRNA levels over 28 days were compared to changes in self-reported symptom profile. This was a prospective cohort study with longitudinal measurements of miRNA levels and symptom self-report. The Rivermead Post-Concussion Symptom Questionnaire (RPQ) was used to determine symptom severity. Mean normalised expression ratios (NER) of miRNAs at day 0 between mTBI and healthy controls were compared. An analysis of response profiles compared the response over time of miRNA species with RPQ symptom severity. miRNA levels of subjects who were defined to have "recovered" on Day 7 and 28 were compared to "non-recovered" subjects. There were 28 mTBI patients and 30 healthy controls included for analysis. Symptom severity was significantly higher on the day of injury among mTBI subjects (p < 0.001), and miRNA 32-5p levels were also higher (p = 0.009). Change of miRNA levels were similar to RPQ change at Day 7, but significantly different at Day 28. Differences were observed among miRNA levels of recovered subjects. This study demonstrated differences in miRNA levels among mTBI subjects compared to healthy controls and different miRNA levels among those who had recovered compared to those reporting symptoms. The change in profiles of miRNAs was different to symptom severity, suggesting that the two measures reflect different aspects of brain injury and recovery.

Is antibiotic treatment effective in the management of chronic low back pain with disc herniation? Study protocol for a randomised controlled trial.

BACKGROUND: There has been immense interest and debate regarding the effectiveness of antibiotic treatment for chronic low back pain. Two randomised controlled trials have examined the efficacy of antibiotics for chronic low back pain with disc herniation and Modic changes, but have reported conflicting results. The aim of this double-blind, randomised, placebo-controlled trial is to determine the efficacy of antibiotic treatment in a broader patient subgroup of chronic low back pain with disc herniation and investigate whether the presence of Modic changes predicts response to antibiotic therapy. METHODS: One hundred and seventy individuals with chronic low back pain will be recruited through hospital and private medical and allied health clinics; advertising in national, community and social media; and posting of flyers in community locations. They will be randomly allocated to receive either amoxicillin-clavulanate (500 mg/125 mg) twice per day for 90 days or placebo. The primary outcome measure of pain intensity will be assessed using the Low Back Pain Rating scale and a 100-mm visual analogue scale at 12 months. Secondary measures of self-reported low back disability and work absence and hindrance will also be examined, and an economic analysis will be conducted. Intention-to-treat analyses will be performed. DISCUSSION: There is uncertainty about whether antibiotic treatment is effective for chronic low back pain and, if effective, which patient subgroup is most likely to respond. We will conduct a clinical trial to investigate the efficacy of antibiotics compared with placebo in individuals with chronic low back pain and a disc herniation. Our findings will provide high-quality evidence to assist in answering these questions. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12615000958583 . Registered on 11 September 2015.