Frequency of fatigue and its changes in the first 6 months after traumatic brain injury: results from the CENTER-TBI study

Abstract Background Fatigue is one of the most commonly reported subjective symptoms following traumatic brain injury (TBI). The aims were to assess frequency of fatigue over the first 6 months after TBI, and examine whether fatigue changes could be predicted by demographic characteristics, injury severity and comorbidities. Methods Patients with acute TBI admitted to 65 trauma centers were enrolled in the study Collaborative European NeuroTrauma Effectiveness Research in TBI (CENTER-TBI). Subjective fatigue was measured by single item on the Rivermead Post-Concussion Symptoms Questionnaire (RPQ), administered at baseline, three and 6 months postinjury. Patients were categorized by clinical care pathway: admitted to an emergency room (ER), a ward (ADM) or an intensive care unit (ICU). Injury severity, preinjury somatic- and psychiatric conditions, depressive and sleep problems were registered at baseline. For prediction of fatigue changes, descriptive statistics and mixed effect logistic regression analysis are reported. Results Fatigue was experienced by 47% of patients at baseline, 48% at 3 months and 46% at 6 months. Patients admitted to ICU had a higher probability of experiencing fatigue than those in ER and ADM strata. Females and individuals with lower age, higher education, more severe intracranial injury, preinjury somatic and psychiatric conditions, sleep disturbance and feeling depressed postinjury had a higher probability of fatigue. Conclusion A high and stable frequency of fatigue was found during the first 6 months after TBI. Specific socio-demographic factors, comorbidities and injury severity characteristics were predictors of fatigue in this study.

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Systemic inflammation alters the neuroinflammatory response: a prospective clinical trial in traumatic brain injury

Journal of Neuroinflammation ◽

10.1186/s12974-021-02264-2 ◽

2021 ◽

Vol 18 (1) ◽

Author(s):

Philipp Lassarén ◽

Caroline Lindblad ◽

Arvid Frostell ◽

Keri L. H. Carpenter ◽

Mathew R. Guilfoyle ◽

...

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

Information Content ◽

Systemic Inflammation ◽

Injury Severity ◽

Extracellular Fluid ◽

Clinical Infection ◽

Mixed Effect ◽

Markers Of Inflammation ◽

Arterial Blood

Abstract Background Neuroinflammation following traumatic brain injury (TBI) has been shown to be associated with secondary injury development; however, how systemic inflammatory mediators affect this is not fully understood. The aim of this study was to see how systemic inflammation affects markers of neuroinflammation, if this inflammatory response had a temporal correlation between compartments and how different compartments differ in cytokine composition. Methods TBI patients recruited to a previous randomised controlled trial studying the effects of the drug anakinra (Kineret®), a human recombinant interleukin-1 receptor antagonist (rhIL1ra), were used (n = 10 treatment arm, n = 10 control arm). Cytokine concentrations were measured in arterial and jugular venous samples twice a day, as well as in microdialysis-extracted brain extracellular fluid (ECF) following pooling every 6 h. C-reactive protein level (CRP), white blood cell count (WBC), temperature and confirmed systemic clinical infection were used as systemic markers of inflammation. Principal component analyses, linear mixed-effect models, cross-correlations and multiple factor analyses were used. Results Jugular and arterial blood held similar cytokine information content, but brain-ECF was markedly different. No clear arterial to jugular gradient could be seen. No substantial delayed temporal associations between blood and brain compartments were detected. The development of a systemic clinical infection resulted in a significant decrease of IL1-ra, G-CSF, PDGF-ABBB, MIP-1b and RANTES (p < 0.05, respectively) in brain-ECF, even if adjusting for injury severity and demographic factors, while an increase in several cytokines could be seen in arterial blood. Conclusions Systemic inflammation, and infection in particular, alters cytokine levels with different patterns seen in brain and in blood. Cerebral inflammatory monitoring provides independent information from arterial and jugular samples, which both demonstrate similar information content. These findings could present potential new treatment options in severe TBI patients, but novel prospective trials are warranted to confirm these associations. Graphical abstract

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Systemic Inflammation Alters The Neuroinflammatory Response: A Prospective Clinical Trial In Traumatic Brain Injury

10.21203/rs.3.rs-345717/v2 ◽

2021 ◽

Author(s):

Philipp Lassarén ◽

Caroline Lindblad ◽

Arvid Frostell ◽

Keri LH Carpenter ◽

Mathew R Guilfoyle ◽

...

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

Information Content ◽

Systemic Inflammation ◽

Injury Severity ◽

Extracellular Fluid ◽

Clinical Infection ◽

Mixed Effect ◽

Markers Of Inflammation ◽

Arterial Blood

Abstract Background: Neuroinflammation following traumatic brain injury (TBI) has been shown to be associated with secondary injury development, however how systemic inflammatory mediators affect this is not fully understood. The aim of this study was to see how systemic inflammation affects markers of neuroinflammation, if this inflammatory response had a temporal correlation between compartments and how different compartments differ in cytokine composition.Methods: TBI patients recruited to a previous randomized controlled trial studying the effects of the drug anakinra (Kineret®), a human recombinant interleukin-1 receptor antagonist (rhIL1ra), were used (n=10 treatment arm, n=10 control arm). Cytokine concentrations were measured in arterial and jugular venous samples twice a day, as well as in microdialysis-extracted brain extracellular fluid (ECF) following pooling every 6 hours. C-reactive protein level (CRP), white blood cell count (WBC), temperature and confirmed systemic clinical infection were used as systemic markers of inflammation. Principal component analyses, linear mixed-effect models, cross-correlations and multiple factor analyses were used.Results: Jugular and arterial blood held similar cytokine information content, but brain-ECF was markedly different. No clear arterial to jugular gradient could be seen. No substantial delayed temporal associations between blood and brain compartments were detected. The development of a systemic clinical infection resulted in a significant decrease of IL1-ra, G-CSF, PDGF-ABBB, MIP-1b and RANTES (p<0.05, respectively) in brain-ECF, even if adjusting for injury severity and demographic factors, while an increase in several cytokines could be seen in arterial blood. Conclusions: Systemic inflammation, and infection in particular, alters cytokine levels with different patterns seen in brain and in blood. Cerebral inflammatory monitoring provides independent information from arterial and jugular samples, which both demonstrate similar information content. These findings could present potential new treatment options in severe TBI patients, and stresses the need of adequate monitoring of inflammatory markers.

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We Finally Learnt to Demand: Consumers’ Access to Rehabilitation Following Traumatic Brain Injury

Brain Impairment ◽

10.1017/brimp.2013.32 ◽

2013 ◽

Vol 14 (3) ◽

pp. 436-449 ◽

Cited By ~ 2

Author(s):

Anna Copley ◽

Lindy McAllister ◽

Linda Wilson

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

Care Pathway ◽

Clinical Care ◽

Standards Of Care ◽

Outpatient Rehabilitation ◽

Research Approach ◽

Access To Services ◽

Care Guidelines ◽

Delivery Of Services

Clinical care guidelines exist internationally recommending the appropriate standards of care for adults following brain injury. These guidelines recommend a care pathway including acute, inpatient and outpatient rehabilitation and community-based care. However, if and how these guidelines are implemented is largely unknown. The aim of this study was to explore the recollected continuum of care experienced by 202 adults with moderate to severe traumatic brain injury (TBI) in Victoria, Australia. The experiences of participants in this study were investigated using a mixed methods research approach (surveys and in-depth interviews). The results indicated that only 20% of participants in this study recollected receiving care in line with recommendations made in clinical care guidelines. Reasons they identified for their problematic access to services included: a lack of information about the services available, the absence of an advocate and services being restricted by limited funding. The findings of this study indicate that while guidelines provide recommendations regarding standards of care and can serve as a benchmark to improve the quality of services, they do not ensure the equitable delivery of services. Clinicians using these guidelines need to be aware of the factors that restrict clients’ access to services and take these into account when planning the delivery of services.

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One-year costs of intensive care in pediatric patients with traumatic brain injury

Journal of Neurosurgery Pediatrics ◽

10.3171/2020.6.peds20189 ◽

2021 ◽

Vol 27 (1) ◽

pp. 79-86

Author(s):

Era D. Mikkonen ◽

Markus B. Skrifvars ◽

Matti Reinikainen ◽

Stepani Bendel ◽

Ruut Laitio ◽

...

Keyword(s):

Traumatic Brain Injury ◽

Intensive Care ◽

Brain Injury ◽

Social Security ◽

Functional Outcome ◽

Injury Severity ◽

Pediatric Population ◽

Favorable Outcome ◽

Index Hospitalization ◽

Pediatric Tbi

OBJECTIVETraumatic brain injury (TBI) is a major cause of death and disability in the pediatric population. The authors assessed 1-year costs of intensive care in pediatric TBI patients.METHODSIn this retrospective multicenter cohort study of four academic ICUs in Finland, the authors used the Finnish Intensive Care Consortium database to identify children aged 0–17 years treated for TBI in ICUs between 2003 and 2013. The authors reviewed all patient health records and head CT scans for admission, treatment, and follow-up data. Patient outcomes included functional outcome (favorable outcome defined as a Glasgow Outcome Scale score of 4–5) and death within 6 months. Costs included those for the index hospitalization, rehabilitation, and social security up to 1 year after injury. To assess costs, the authors calculated the effective cost per favorable outcome (ECPFO).RESULTSIn total, 293 patients were included, of whom 61% had moderate to severe TBI (Glasgow Coma Scale [GCS] score 3–12) and 40% were ≥ 13 years of age. Of all patients, 82% had a favorable outcome and 9% died within 6 months of injury. The mean cost per patient was €48,719 ($54,557) (95% CI €41,326–€56,112). The index hospitalization accounted for 66%, rehabilitation costs for 27%, and social security costs for 7% of total healthcare costs. The ECPFO was €59,727 ($66,884) (95% CI €52,335–€67,120). A higher ECPFO was observed among patients with clinical and treatment-related variables indicative of parenchymal swelling and high intracranial pressure. Lower ECPFO was observed among patients with higher admission GCS scores and those who had epidural hematomas.CONCLUSIONSGreater injury severity increases ECPFO and is associated with higher postdischarge costs in pediatric TBI patients. In this pediatric cohort, over two-thirds of all resources were spent on patients with favorable functional outcome, indicating appropriate resource allocation.

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Retrospective Review and Proof of Concept of Asia’s First Mobile Stroke Unit Experience in Kovai Medical Center and Hospital

Journal of Stroke Medicine ◽

10.1177/2516608520968418 ◽

2020 ◽

Vol 3 (2) ◽

pp. 116-123

Author(s):

Mathew Cherian ◽

Pankaj Mehta ◽

Shriram Varadharajan ◽

Santosh Poyyamozhi ◽

Elango Swamiappan ◽

...

Keyword(s):

Acute Stroke ◽

Retrospective Review ◽

Stroke Unit ◽

Care Pathway ◽

Clinical Care ◽

Stroke Care ◽

First Year ◽

Proof Of Concept ◽

Mobile Stroke Unit ◽

Clinical Care Pathway

Background: We review our initial experience of India’s and Asia’s first mobile stroke unit (MSU) following the completion of its first year of operation. We outline the clinical care pathway integrating the MSU services using a case example taking readers along our clinical care workflow while highlighting the challenges faced in organizing and optimizing such services in India. Methods: Retrospective review of data collected for all patients from March 2018 to February 2019 transported and treated within the MSU during the first year of its operation. Recent case example is reviewed highlighting complete comprehensive acute clinical care pathway from prehospital MSU services to advanced endovascular treatment with focus on challenges faced in developing nation for stroke care. Results: The MSU was dispatched and utilized for 14 patients with clinical symptoms of acute stroke. These patients were predominantly males (64%) with median age of 59 years. Ischemic stroke was seen in 7 patients, hemorrhagic in 6, and 1 patient was classified as stroke mimic. Intravenous tissue plasminogen activator was administered to 3 patients within MSU. Most of the patients’ treatment was initiated within 2 h of symptom onset and with the median time of patient contact (rendezvous) following stroke being 55 mins. Conclusion: Retrospective review of Asia’s first MSU reveals its proof of concept in India. Although the number of patients availing treatment in MSU is low as compared to elsewhere in the world, increased public awareness with active government support including subsidizing treatment costs could accelerate development of optimal prehospital acute stroke care policy in India.

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Canadian Nationwide Survey on Pediatric Malnutrition Management in Tertiary Hospitals

Nutrients ◽

10.3390/nu13082635 ◽

2021 ◽

Vol 13 (8) ◽

pp. 2635

Author(s):

Koen Huysentruyt ◽

Kim Brunet-Wood ◽

Robert Bandsma ◽

Leah Gramlich ◽

Bonnie Fleming-Carroll ◽

...

Keyword(s):

Health Care Professionals ◽

Care Pathway ◽

Clinical Care ◽

Tertiary Care ◽

Nationwide Survey ◽

Nutritional Screening ◽

Pediatric Hospitals ◽

Adoption And Implementation ◽

Clinical Care Pathway

Background: Disease-associated malnutrition (DAM) is common in hospitalized children. This survey aimed to assess current in-hospital practices for clinical care of pediatric DAM in Canada. Methods: An electronic survey was sent to all 15 tertiary pediatric hospitals in Canada and addressed all pillars of malnutrition care: screening, assessment, treatment, monitoring and follow-up. Results: Responses of 120 health care professionals were used from all 15 hospitals; 57.5% were medical doctors (MDs), 26.7% registered dietitians (RDs) and 15.8% nurses (RNs). An overarching protocol for prevention, detection and intervention of pediatric malnutrition was present or “a work in progress”, according to 9.6% of respondents. Routine nutritional screening on admission was sometimes or always performed, according to 58.8%, although the modality differed among hospitals and profession. For children with poor nutritional status, lack of nutritional follow-up after discharge was reported by 48.5%. Conclusions: The presence of a standardized protocol for the clinical assessment and management of DAM is uncommon in pediatric tertiary care hospitals in Canada. Routine nutritional screening upon admission has not been widely adopted. Moreover, ongoing nutritional care of malnourished children after discharge seems cumbersome. These findings call for the adoption and implementation of a uniform clinical care pathway for malnutrition among pediatric hospitals.

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Altered speech patterns in subjects with post-traumatic headache due to mild traumatic brain injury

The Journal of Headache and Pain ◽

10.1186/s10194-021-01296-6 ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Catherine D. Chong ◽

Jianwei Zhang ◽

Jing Li ◽

Teresa Wu ◽

Gina Dumkrieger ◽

...

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

Speech Production ◽

Mild Traumatic Brain Injury ◽

Mobile Application ◽

Speaking Rate ◽

Mixed Effect ◽

Effect Model ◽

Vowel Space ◽

Post Traumatic

Abstract Background/objective Changes in speech can be detected objectively before and during migraine attacks. The goal of this study was to interrogate whether speech changes can be detected in subjects with post-traumatic headache (PTH) attributed to mild traumatic brain injury (mTBI) and whether there are within-subject changes in speech during headaches compared to the headache-free state. Methods Using a series of speech elicitation tasks uploaded via a mobile application, PTH subjects and healthy controls (HC) provided speech samples once every 3 days, over a period of 12 weeks. The following speech parameters were assessed: vowel space area, vowel articulation precision, consonant articulation precision, average pitch, pitch variance, speaking rate and pause rate. Speech samples of subjects with PTH were compared to HC. To assess speech changes associated with PTH, speech samples of subjects during headache were compared to speech samples when subjects were headache-free. All analyses were conducted using a mixed-effect model design. Results Longitudinal speech samples were collected from nineteen subjects with PTH (mean age = 42.5, SD = 13.7) who were an average of 14 days (SD = 32.2) from their mTBI at the time of enrollment and thirty-one HC (mean age = 38.7, SD = 12.5). Regardless of headache presence or absence, PTH subjects had longer pause rates and reductions in vowel and consonant articulation precision relative to HC. On days when speech was collected during a headache, there were longer pause rates, slower sentence speaking rates and less precise consonant articulation compared to the speech production of HC. During headache, PTH subjects had slower speaking rates yet more precise vowel articulation compared to when they were headache-free. Conclusions Compared to HC, subjects with acute PTH demonstrate altered speech as measured by objective features of speech production. For individuals with PTH, speech production may have been more effortful resulting in slower speaking rates and more precise vowel articulation during headache vs. when they were headache-free, suggesting that speech alterations were related to PTH and not solely due to the underlying mTBI.

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The role of salivary vesicles as a potential inflammatory biomarker to detect traumatic brain injury in mixed martial artists

Scientific Reports ◽

10.1038/s41598-021-87180-4 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Rani Matuk ◽

Mandy Pereira ◽

Janette Baird ◽

Mark Dooner ◽

Yan Cheng ◽

...

Keyword(s):

Gene Expression ◽

Traumatic Brain Injury ◽

Brain Injury ◽

Head Injury ◽

Injury Severity ◽

Expression Profiles ◽

High Impact ◽

Impact Mechanism ◽

Inflammatory Biomarker ◽

Potential Biomarker

AbstractTraumatic brain injury (TBI) is of significant concern in the realm of high impact contact sports, including mixed martial arts (MMA). Extracellular vesicles (EVs) travel between the brain and oral cavity and may be isolated from salivary samples as a noninvasive biomarker of TBI. Salivary EVs may highlight acute neurocognitive or neuropathological changes, which may be particularly useful as a biomarker in high impact sports. Pre and post-fight samples of saliva were isolated from 8 MMA fighters and 7 from controls. Real-time PCR of salivary EVs was done using the TaqMan Human Inflammatory array. Gene expression profiles were compared pre-fight to post-fight as well as pre-fight to controls. Largest signals were noted for fighters sustaining a loss by technical knockout (higher impact mechanism of injury) or a full match culminating in referee decision (longer length of fight), while smaller signals were noted for fighters winning by joint or choke submission (lower impact mechanism as well as less time). A correlation was observed between absolute gene information signals and fight related markers of head injury severity. Gene expression was also significantly different in MMA fighters pre-fight compared to controls. Our findings suggest that salivary EVs as a potential biomarker in the acute period following head injury to identify injury severity and can help elucidate pathophysiological processes involved in TBI.

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Optimizing Outcomes After Cleft Palate Repair: Design and Implementation of a Perioperative Clinical Care Pathway

The Cleft Palate-Craniofacial Journal ◽

10.1177/10556656211017409 ◽

2021 ◽

pp. 105566562110174

Author(s):

Thomas R. Cawthorn ◽

Anna R. Todd ◽

Nina Hardcastle ◽

Adam O. Spencer ◽

A. Robertson Harrop ◽

...

Keyword(s):

Length Of Stay ◽

Cleft Palate ◽

Care Pathway ◽

Clinical Care ◽

Oral Intake ◽

Opioid Consumption ◽

Complication Rates ◽

Cleft Palate Repair ◽

Palate Repair ◽

Clinical Care Pathway

Objective: To evaluate the development process and clinical impact of implementing a standardized perioperative clinical care pathway for cleft palate repair. Design: Medical records of patients undergoing primary cleft palate repair prior to pathway implementation were retrospectively reviewed as a historical control group (N = 40). The historical cohort was compared to a prospectively collected group of patients who were treated according to the pathway (N = 40). Patients: Healthy, nonsyndromic infants undergoing primary cleft palate repair at a tertiary care pediatric hospital. Interventions: A novel, standardized pathway was created through an iterative process, combining literature review with expert opinion and discussions with institutional stakeholders. The pathway integrated multimodal analgesia throughout the perioperative course and included intraoperative bilateral maxillary nerve blocks. Perioperative protocols for preoperative fasting, case timing, antiemetics, intravenous fluid management, and postoperative diet advancement were standardized. Main Outcome Measures: Primary outcomes include: (1) length of hospital stay, (2) cumulative opioid consumption, (3) oral intake postoperatively. Results: Patients treated according to the pathway had shorter mean length of stay (31 vs 57 hours, P < .001), decreased cumulative morphine consumption (77 vs 727 μg/kg, P < .001), shorter time to initiate oral intake (9.3 vs 22 hours, P = .01), and greater volume of oral intake in first 24 hours postoperatively (379 vs 171 mL, P < .001). There were no differences in total anesthesia time, total surgical time, or complication rates between the control and treatment groups. Conclusions: Implementation of a standardized perioperative clinical care pathway for primary cleft palate repair is safe, feasible, and associated with reduced length of stay, reduced opioid consumption, and improved oral intake postoperatively.

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Increase in recruitment upon integration of trial into a clinical care pathway: an observational study

BMJ Open Respiratory Research ◽

10.1136/bmjresp-2021-000967 ◽

2021 ◽

Vol 8 (1) ◽

pp. e000967

Author(s):

Kay Por Yip ◽

Simon Gompertz ◽

Catherine Snelson ◽

Jeremy Willson ◽

Shyam Madathil ◽

...

Keyword(s):

Clinical Trial ◽

Hospital Admissions ◽

Care Pathway ◽

Clinical Care ◽

Intensive Therapy ◽

Respiratory Support ◽

Trial Recruitment ◽

Recruitment Process ◽

Support Unit ◽

Clinical Care Pathway

IntroductionMany respiratory clinical trials fail to reach their recruitment target and this problem exacerbates existing funding issues. Integration of the clinical trial recruitment process into a clinical care pathway (CCP) may represent an effective way to significantly increase recruitment numbers.MethodsA respiratory support unit and a CCP for escalation of patients with severe COVID-19 were established on 11 January 2021. The recruitment process for the Randomised Evaluation of COVID-19 Therapy-Respiratory Support trial was integrated into the CCP on the same date. Recruitment data for the trial were collected before and after integration into the CCP.ResultsOn integration of the recruitment process into a CCP, there was a significant increase in recruitment numbers. Fifty patients were recruited over 266 days before this process occurred whereas 108 patients were recruited over 49 days after this process. There was a statistically significant increase in both the proportion of recruited patients relative to the number of COVID-19 hospital admissions (change from 2.8% to 9.1%, p<0.0001) and intensive therapy unit admissions (change from 17.8% to 50.2%, p<0.001) over the same period, showing that this increase in recruitment was independent of COVID-19 prevalence.DiscussionIntegrating the trial recruitment process into a CCP can significantly boost recruitment numbers. This represents an innovative model that can be used to maximise recruitment without impacting on the financial and labour costs associated with the running of a respiratory clinical trial.

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