Elevated risk of venous thromboembolism among post-traumatic brain injury patients requiring pharmaceutical immobilization.
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SUBMITTER: Zhang M
PROVIDER: S-EPMC8253589 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:The aims of this study are to describe the use of pharmaceutical venous thromboembolism (pVTE) prophylaxis in patients with traumatic brain injury (TBI) in Europe and study the association of pVTE prophylaxis with outcome. We included 2006 patients ≥18 years of age admitted to the intensive care unit from the CENTER-TBI study. VTE events were recorded based on clinical symptoms. Variation between 54 centers in pVTE prophylaxis use was assessed with a multi-variate random-effect model and quantified with the median odds ratio (MOR). The association between pVTE prophylaxis and outcome (Glasgow Outcome Scale-Extended at 6 months) was assessed at center level with an instrumental variable analysis and at patient level with a multi-variate proportional odds regression analysis and a propensity-matched analysis. A time-dependent Cox survival regression analysis was conducted to determine the effect of pVTE prophylaxis on survival during hospital stay. The association between VTE prophylaxis and computed tomography (CT) progression was assessed with a logistic regression analysis. Overall, 56 patients (2%) had a VTE during hospital stay. The majority, 1279 patients (64%), received pVTE prophylaxis, with substantial between-center variation (MOR, 2.7; p < 0.001). A moderate association with improved outcome was found at center level (odds ratio [OR], 1.2 [0.7-2.1]) and patient level (multi-variate adjusted OR, 1.4 [1.1-1.7], and propensity adjusted OR, 1.5 [1.1-2.0]), with similar results in subgroup analyses. Survival was higher with the use of pVTE prophylaxis (p < 0.001). We found no clear effect on CT progression (OR, 0.9; CI [0.6-1.2]). Overall, practice policies for pVTE prophylaxis vary substantially between European centers, whereas pVTE prophylaxis may contribute to improved outcome. Trial registration number is NCT02210221 at ClinicalTrials.gov, registered on August 6, 2014 (first patient enrollment on December 19, 2014).
| S-EPMC8804253 | biostudies-literature
Project description:BackgroundVenous thromboembolism chemoprophylaxis (VTE-CHEMO) is often delayed in patients with traumatic brain injury because of the concern for intracranial hemorrhage (ICH) progression. We hypothesize that (1) late time to VTE-CHEMO (≥48 h) is associated with higher incidence of VTE, and (2) VTE-CHEMO use does not correlate with ICH progression.Materials and methodsThis is a multiinstitutional retrospective study of patients with traumatic brain injury admitted between 2014 and 2016. Inclusion criteria were head Abbreviated Injury Code ≥2, ICH present on initial head computed tomography, and two or more head computed tomography scans after admission. The primary outcome was VTE, and the secondary outcome was ICH progression. Patients were classified as receiving VTE-CHEMO early (<48 h) or late (≥48 h). Multivariable analysis with Cox proportional hazards regression was performed.ResultsOverall, 1803 patients were included. Patients with VTE (n = 137) were more likely to have spinal cord injury, blunt cerebrovascular injury, pelvic or femur fractures, and missed VTE-CHEMO doses. After multivariable regression, body mass index >30 (hazard ratio [HR], 1.05; P = 0.002), Injury Severity Score (HR, 1.004; P < 0.001), pelvic or femur fractures (HR, 1.05; P < 0.0001), spinal cord injury (HR, 1.28; P = 0.02), and missed VTE-CHEMO doses (HR, 1.08; P = 0.01) were significant predictors of VTE. In those who required neurosurgery, late VTE-CHEMO predicted VTE (HR, 1.21; P = 0.0001). Overall, 32% patients experienced ICH progression, which did not correlate with VTE-CHEMO use or timing.ConclusionsThis multicenter study highlights benefits from early VTE-CHEMO and identifies high-risk groups who may benefit from more aggressive prophylaxis. These data also emphasize risk to patients by withholding VTE-CHEMO.
| S-EPMC8480540 | biostudies-literature
Project description:ImportanceThere is a lack of evidence regarding the effectiveness and safety of pharmacologic venous thromboembolism (VTE) prophylaxis among patients who undergo neurosurgical interventions for traumatic brain injury (TBI).ObjectiveTo measure the association between timing of VTE prophylaxis after urgent neurosurgical intervention for TBI and thromboembolic and intracranial complications.Design, setting, and participantsThis retrospective cohort study included adult patients (aged ≥16 years) who underwent urgent neurosurgical interventions (craniotomy/craniectomy or intracranial monitor/drain insertion within 24 hours after admission) for TBI at level 1 and 2 trauma centers participating in the American College of Surgeons Trauma Quality Improvement Program between January 1, 2012, and December 31, 2016. Data were analyzed from January to August 2020.ExposuresTiming of pharmacologic VTE prophylaxis initiation after urgent neurosurgical intervention (prophylaxis delay) measured in days (24-hour periods).Main outcomes and measuresThe primary outcome was VTE (deep vein thrombosis or pulmonary embolism). Secondary outcomes were repeated neurosurgery (neurosurgical reintervention after initiation of VTE prophylaxis) and mortality. Hierarchical logistic regression models were used to evaluate the association between prophylaxis delay and each outcome at the patient level and were adjusted for patient baseline and injury characteristics.ResultsThe study included 4951 patients (3676 [74%] male; median age, 50 years [IQR, 31-64 years]) who underwent urgent neurosurgical intervention for TBI at 304 trauma centers. The median prophylaxis delay was 3 days (IQR, 1-5 days). After adjustment for patient baseline and injury characteristics, prophylaxis delay was associated with increased odds of VTE (adjusted odds ratio [aOR], 1.08 per day; 95% CI, 1.04-1.12). Earlier initiation of prophylaxis was associated with increased risk of repeated neurosurgery. During the first 3 days, each additional day of prophylaxis delay was associated with a 28% decrease in odds of repeated neurosurgery (aOR, 0.72 per day; 95% CI, 0.59-0.88). After 3 days, each additional day of prophylaxis delay was associated with an additional 15% decrease in odds of repeated neurosurgery (aOR, 0.85 per day; 95% CI, 0.80-0.90). Earlier prophylaxis was associated with greater mortality among patients who initially underwent intracranial monitor/drain procedures, such that each additional day of prophylaxis delay was associated with decreased odds of death (aOR, 0.94 per day; 95% CI, 0.89-0.99).Conclusions and relevanceIn this cohort study of patients who underwent urgent neurosurgical interventions for TBI, early pharmacologic VTE prophylaxis was associated with reduced risk of thromboembolism. However, earlier initiation of prophylaxis was associated with increased risk of repeated neurosurgery. These findings suggest that although timely initiation of prophylaxis should be prioritized, caution should be used particularly during the first 3 days after the index procedure, when this risk appears to be highest.
| S-EPMC8674806 | biostudies-literature
Project description:Traumatic brain injury (TBI) is associated with increased risk for psychological and substance use disorders. The study aim is to determine incidence and risk factors for persistent opioid prescription after hospitalization for TBI. Electronic medical records of patients age ≥ 18 admitted to a neuroscience intensive care unit between January 2013 and February 2017 for an intracranial injury were retrospectively reviewed. Primary outcome was opioid use through 12 months post-hospital discharge. A total of 298 patients with complete data were included in the analysis. The prevalence of opioid use among preadmission opioid users was 48 (87%), 36 (69%) and 22 (56%) at 1, 6 and 12-months post-discharge, respectively. In the opioid naïve group, 69 (41%), 24 (23%) and 17 (19%) were prescribed opioids at 1, 6 and 12 months, respectively. Preadmission opioid use (OR 324.8, 95% CI 23.1-16907.5, p = 0.0004) and higher opioid requirements during hospitalization (OR 4.5, 95% CI 1.8-16.3, p = 0.006) were independently associated with an increased risk of being prescribed opioids 12 months post-discharge. These factors may be used to identify and target at-risk patients for intervention.
| S-EPMC6880998 | biostudies-literature
Project description:Venous thromboembolism (VTE) is a common, multi-causal disease with potentially serious short- and long-term complications. In clinical practice, there is a need for improved plasma biomarker-based tools for VTE diagnosis and risk prediction. We use multiplex proteomics profiling to screen plasma from patients with suspected acute VTE, and several case-control studies for VTE, to identify Complement Factor H Related Protein 5 (CFHR5), a regulator of the alternative pathway of complement activation, as a novel VTE associated plasma biomarker. In plasma, higher CFHR5 levels are associated with increased thrombin generation potential and recombinant CFHR5 enhanced platelet activation in vitro. GWAS analysis of ~52,000 participants identifies six loci associated with CFHR5 plasma levels, but Mendelian randomization do not demonstrate causality between CFHR5 and VTE. Our results indicate an important role for the regulation of the alternative pathway of complement activation in VTE and that CFHR5 represents a potential diagnostic and/or risk predictive plasma biomarker.
2023-03-25 | PXD040913 | Pride
Project description:Essentials Thromboprophylaxis after lower limb injury is often based on complex risk stratification. Our systematic review identified variables predicting venous thromboembolism (VTE) in this group. Age and injury type were commonly reported to increase the odds of VTE (odds ratio 1.5-3.48). We found limited evidence to support the use of other risk factors within prediction models. SUMMARY: Background Patients immobilized after lower limb injury are at risk of venous thromboembolism (VTE). There is international variation in the use of thromboprophylaxis for such patients. Risk-based strategies have been adopted to aid decision making in many settings. The accuracy of these strategies is unclear. Objectives A systematic review was undertaken to identify all individual patient-identifiable risk factors linked to any VTE outcome following lower limb immobilization. Methods Several electronic databases were searched from inception to May 2017. Any studies that included a measurement of VTE as a patient outcome in adults requiring temporary immobilization (e.g. leg cast or brace in an ambulatory setting) for an isolated lower limb injury and reported risk factor variables were included. Descriptive statistics and thematic analysis were used to synthesize the evidence. Results Our database search returned 4771 citations, of which 15 studies reporting outcome data on 80 678 patients were eligible for analysis. Risk-factor associations were reported through regression analyses, non-parametric tests and descriptive statistics. All studies were assessed as at moderate or serious risk of bias using the ROBINS-I risk of bias tool. Advancing age and injury type were the only individual risk factors demonstrating a reproducible association with increased symptomatic and/or asymptomatic VTE rates. Several risk factors currently used in scoring tools did not appear to be robustly evaluated for subsequent association with VTE within these studies. Conclusions Clinicians should be aware of the limited evidence to support individual risk factors in guiding thromboprophylaxis use for this patient cohort.
| S-EPMC6392108 | biostudies-literature
Project description:Post-traumatic headaches (PTHs) are associated with mild traumatic brain injuries (mTBI) and may predict the persistence of concussion symptoms. Altered brain networks implicated in brain injury and the affective components of headache-related pain may underlie the resolution of PTH. This is a hypothesis-generating investigation to evaluate the extent to which pain symptom reporting and functional brain changes are different in a cohort of young mTBI patients with resolved (PTH-R) and persistent (PTH-P) post-traumatic headache symptoms relative to healthy controls. This was a cross-sectional investigation involving 59 participants between the ages of 12-24 (PTH-P, n = 21; PTH-R, n = 18; healthy control, n = 20). Participants had no significant history of pre-existing headaches, chronic pain, or psychiatric neurological conditions. The primary outcome was resting-state functional connectivity (RS-Fc) alterations between cohorts. Secondary outcomes were self-reported pain-related symptoms. Elevated scores were reported for fear of pain in both PTH cohorts. Using a false discovery rate of p = 0.05, the PTH-P cohort showed altered connectivity relative to healthy controls in brain regions such as the frontal, temporal, and cerebellar regions, as well as sub-cortical regions including the amygdala and accumbens. The PTH-R cohort showed altered RS-Fc between cerebellar and temporal lobe sub-regions. Our results indicate that a core network of brain regions implicated in the affective pain response are functionally altered in PTH cohorts. Results should be interpreted given limitations on sample size and multiple comparisons. Despite the resolution of symptoms, persons who experience PTH may experience ongoing functional brain abnormalities, which may underlie symptom chronification.
| S-EPMC8165471 | biostudies-literature
Project description:BACKGROUND:Thromboprophylaxis has the potential to reduce venous thromboembolism (VTE) following lower limb immobilization resulting from injury. OBJECTIVES:We aimed to estimate the effectiveness of thromboprophylaxis, compare different agents, and identify any factors associated with effectiveness. METHODS:We undertook a systematic review and network meta-analysis (NMA) of randomized trials reporting VTE or bleeding outcomes that compared thromboprophylactic agents with each other or to no pharmacological prophylaxis, for this indication. An NMA was undertaken for each outcome or agent used, and a series of study-level network meta-regressions examined whether population characteristics, type of injury, treatment of injury, or duration of thromboprophylaxis were associated with treatment effect. RESULTS:Data from 6857 participants across 13 randomized trials showed that, compared with no treatment, low molecular weight heparin (LMWH) reduced the risk of any VTE (odds ratio [OR]: 0.52; 95% credible interval [CrI]: 0.37-0.71), clinically detected deep vein thrombosis (DVT) (OR: 0.39; 95% CrI: 0.12-0.94) and pulmonary embolism (PE) (OR: 0.16; 95% CrI: 0.01-0.74), whereas fondaparinux reduced the risk of any VTE (OR: 0.13; 95% CrI: 0.05-0.30) and clinically detected DVT (OR: 0.10; 95% CrI: 0.01-0.86), with inconclusive results for PE (OR: 0.40; 95% CrI: 0.01-7.53). CONCLUSIONS:Thromboprophylaxis with either fondaparinux or LMWH appears to reduce the odds of both asymptomatic and clinically detected VTE in people with temporary lower limb immobilization following an injury. Treatment effects vary by outcome and are not always conclusive. We were unable to identify any treatment effect modifiers other than thromboprophylactic agent used.
| S-EPMC7028118 | biostudies-literature
Project description:Recently, age-related timing dissociation between the superficial and deep venous systems has been observed; this was particularly pronounced in patients with normal pressure hydrocephalus, suggesting a common mechanism of ventriculomegaly. Establishing the relationship between venous drainage and ventricular enlargement would be clinically relevant and could provide insight into the mechanisms underlying brain ageing. To investigate a possible link between venous drainage and ventriculomegaly in both normal ageing and pathological conditions, we compared 225 healthy subjects (137 males and 88 females) and 71 traumatic brain injury patients of varying ages (53 males and 18 females) using MRI-based volumetry and a novel perfusion-timing analysis. Volumetry, focusing on the CSF space, revealed that the sulcal space and ventricular size presented different lifespan profiles with age; the latter presented a quadratic, rather than linear, pattern of increase. The venous timing shift slightly preceded this change, supporting a role for venous drainage in ventriculomegaly. In traumatic brain injury, a small but significant disease effect, similar to idiopathic normal pressure hydrocephalus, was found in venous timing, but it tended to decrease with age at injury, suggesting an overlapping mechanism with normal ageing. Structural bias due to, or a direct causative role of ventriculomegaly was unlikely to play a dominant role, because of the low correlation between venous timing and ventricular size after adjustment for age in both patients and controls. Since post-traumatic hydrocephalus can be asymptomatic and occasionally overlooked, the observation suggested a link between venous drainage and CSF accumulation. Thus, hydrocephalus, involving venous insufficiency, may be a part of normal ageing, can be detected non-invasively, and is potentially treatable. Further investigation into the clinical application of this new marker of venous function is therefore warranted.
| S-EPMC7296851 | biostudies-literature
Project description:The long-term effects of mild TBI (mTBI) are not well understood, and there is an ongoing debate about whether there are sex differences in outcomes following mTBI. This study examined i) symptom burden and functional outcomes at 8-years post-injury in males and females following mTBI; ii) sex differences in outcomes at 8-years post-injury for those aged <45 years and ≥45 years and; iii) sex differences in outcomes for single and repetitive TBI. Adults (≥16 years at injury) identified as part of a population-based TBI incidence study (BIONIC) who experienced mTBI 8-years ago (N = 151) and a TBI-free sample (N = 151) completed self-report measures of symptoms and symptom burden (Rivermead Post-Concussion Symptom Questionnaire, Hospital Anxiety and Depression Scale, Post-traumatic Stress Disorder Checklist), and functional outcomes (Participation Assessments with Recombined Tools, Work Limitations Questionnaire). The mTBI group reported significantly greater post-concussion symptoms compared to the TBI-free group (F(1,298) = 26.84, p<.01, ηp2 = .08). Females with mTBI were twice as likely to exceed clinical cut-offs for post-concussive (X2 (1)>5.2, p<.05, V>.19) and PTSD symptoms (X2(1) = 6.10, p = .014, V = .20) compared to the other groups, and reported their health had the greatest impact on time-related work demands (F(1,171) = 4.36, p = .04, ηp2 = .03. There was no interaction between sex and age on outcomes. The repetitive mTBI group reported significantly greater post-concussion symptoms (F(1,147) = 9.80, p<.01, ηp2 = .06) compared to the single mTBI group. Twice the proportion of women with repetitive mTBI exceeded the clinical cut-offs for post-concussive (X2(1)>6.90, p<.01, V>.30), anxiety (X2(1)>3.95, p<.05, V>.23) and PTSD symptoms (X2(1)>5.11, p<.02, V>.26) compared with males with repetitive TBI or women with single TBI. Thus, at 8-years post-mTBI, people continued to report a high symptom burden. Women with mTBI, particularly those with a history of repetitive mTBI, had the greatest symptom burden and were most likely to have symptoms of clinical significance. When treating mTBI it is important to assess TBI history, particularly in women. This may help identify those at greatest risk of poor long-term outcomes to direct early treatment and intervention.
| S-EPMC9140230 | biostudies-literature