Dataset Information

Prognostic factors for recovery of health status after injury: a prospective multicentre cohort study.

ABSTRACT:

Objectives

To determine prognostic factors for health status and recovery patterns during the first 2?years after injury in the clinical trauma population.

Design

A prospective longitudinal cohort study.

Setting

Ten participating hospitals in Brabant, the Netherlands.

Participants

Injured adult patients admitted to a hospital between August 2015 and November 2016 were followed: 4883 (50%) patients participated.

Main outcome measures

Primary outcome was health status, measured with the EuroQol-5-dimensions-3-levels (EQ-5D), including a cognition item and the EuroQol Visual Analogue Scale. Health status was collected at 1 week, 1, 3, 6, 12 and 24 months after injury. Potential prognostic factors were based on literature and clinical experience (eg, age, sex, pre-injury frailty (Groningen Frailty Index), pre-injury EQ-5D).

Results

Health status increased mainly during the first 6?months after injury with a mean EQ-5D utility score at 1 week of 0.49 and 0.79 at 24 months. The dimensions mobility, pain/discomfort and usual activities improved up to 2 years after injury. Lower pre-injury health status, frailty and longer length of stay at the hospital were important prognostic factors for poor recovery. Spine injury, lower and upper extremity injury showed to be prognostic factors for problems after injury. Traumatic brain injury was a prognostic factor for cognitive problems.

Conclusion

This study contributes to the increase in knowledge of health recovery after injury. It could be a starting point to develop prediction models for specific injury classifications and implementation of personalised medicine.

Trial registration number

NCT02508675.

SUBMITTER: de Munter L

PROVIDER: S-EPMC7789437 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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Publications

Prognostic factors for recovery of health status after injury: a prospective multicentre cohort study.

de Munter Leonie L Polinder Suzanne S Havermans Roos J M RJM Steyerberg Ewout W EW de Jongh Mariska A C MAC

BMJ open 20210106 1

<h4>Objectives</h4>To determine prognostic factors for health status and recovery patterns during the first 2 years after injury in the clinical trauma population.<h4>Design</h4>A prospective longitudinal cohort study.<h4>Setting</h4>Ten participating hospitals in Brabant, the Netherlands.<h4>Participants</h4>Injured adult patients admitted to a hospital between August 2015 and November 2016 were followed: 4883 (50%) patients participated.<h4>Main outcome measures</h4>Primary outcome was health ...[more]

PMID: 33408198

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Project description:Introduction: Brain plasticity, synaptic regeneration and neuroinflammation are crucial mechanisms that play important roles in the recovery from acute brain injuries, such as aneurysmal subarachnoid hemorrhage (aSAH), ischemic stroke (IS), and traumatic brain injury (TBI). The p75 neurotrophic receptor (p75NTR) is a significant receptor that modulates brain plasticity, neuroinflammation and apoptosis, making it an interesting target for therapeutic interventions. However, despite the progress made in understanding the molecular mechanisms involved in brain plasticity and neuroinflammation, there are still significant knowledge gaps in identifying protein biomarkers and microRNAs (miRNAs) associated with different types of acute brain injuries. Addressing these gaps will be critical in advancing our understanding of the underlying mechanisms involved in brain injury and developing effective therapies or prognostic strategies for recovery. Hypotheses: We hypothesized that changes in serum levels of p75NTR and its linked neuroinflammatory signaling proteins could predict recovery from acute brain injuries, regardless of injury type. Differentially expressed (DE) circulating miRNAs following acute brain injuries may regulate studied protein targets and overall injury outcome. Methods: A prospective cohort of 74 patients with ischemic stroke (n=30), aneurysmal subarachnoid hemorrhage (n=31), and traumatic brain injury (n=13) was evaluated. Serum samples were collected at two time points after the injury (early at 1.9 ± 1.0 days and late at 5.9 ± 2.2 days) and outcome evaluation was performed after three months. Six proteins were measured using ELISAs: p75NTR, NGF, sortilin, IL1, TNF, and cyclophilin A. A 2-tailed 2-sample t-test, univariate, and multivariate linear discriminant analysis (LDA) was used to compare serum molecules between patients with favorable (modified Rankin Scale (mRS) 0-3) and unfavorable outcome (mRS 4-6). Additionally, circulating miRNAs were extracted from the samples (n=48, early and late) and DE miRNAs were identified using DESeq2. The miRNA putative target genes were predicted and LDA was performed using the normalized expression values of identified DE miRNAs. Results: In this study, p75NTR (p < 0.01) and IL1 (p < 0.05) were found to be independently associated with outcome among the six circulating protein biomarkers studied. Combinatory LDA analysis of all six biomarkers showed significant predictive value for favorable outcome (OR 2.95 (1.46-5.98); area under the curve (AUC)= 71.2%, 95% CI = (0.590-0.833), p = 0.003). Temporal alterations of miRNA expression were observed in the aSAH, TBI, and IS groups (p<0.05, FDR corrected). Twenty-three common miRNAs were identified that differentiated favorable and unfavorable outcome (p<0.05) in all three groups. LDA of four identified miRNAs with predicted targets to studied proteins showed high predictive accuracy (OR (95% CI) 11.7 (2.39-226)); AUC = 94.1%, 95% CI = (0.849 - 1.00), p = 0.016). Conclusions This study indicates that assessing serum levels of p75NTR and its mechanistically linked proteins can predict recovery outcome in patients with different types of acute brain injuries. The combined miRNA and protein biomarker models demonstrated accurate outcome prediction across diverse injury types, implying the presence of a common recovery mechanism. DE miRNAs were found to target the studied molecules, suggesting a potential mechanistical role in recovery. The identified common miRNAs may provide new targets for mechanistic validation in disease models. Further investigation is warranted to validate and explore the potential of these proteins and miRNAs in prognostication and as therapeutic targets for enhancing recovery from acute brain injuries.

Project description:Background: Poststroke cognitive impairment (PSCI) has been increasingly recognized in patients, but some stroke survivors appear to show cognitive improvement beyond the acute stage. The risk factors associated with cognitive recovery after spontaneous intracerebral hemorrhage (ICH) onset have not yet been sufficiently investigated in prospective studies. Objective: We aimed to identify the trajectory of post-ICH cognitive impairment and the association of potential prognostic factors with follow-up cognitive recovery beyond early PSCI. Methods: In this stroke center-based cohort study, 141 consecutive dementia-free patients with spontaneous ICH were included and underwent Montreal Cognitive Assessment (MoCA) evaluation for cognitive function at baseline (within 2 weeks of ICH onset) and the shortened MoCA (short-MoCA) at a 6-month follow-up. To explore the prognostic factors associated with trajectory of cognition after an ICH onset, we adjusted for demographic and vascular risk factors, using multivariate logistic regression analysis. Results: Of the 141 ICH patients, approximately three quarters (106/141) were diagnosed with early PSCI (MoCA score <26) within 2 weeks of ICH onset. The multiple logistic regression indicated independent positive associations between risk of early PSCI and dominant-hemisphere hemorrhage [odd's ratio (OR): 8.845 (3.347-23.371); P < 0.001], mean corpuscular volume (MCV) [OR: 1.079 (1.002-1.162); P = 0.043], admission systolic blood pressure (sBP) [OR: 1.021 (1.005-1.038); P = 0.012]. Furthermore, 36% (33/90) of ICH survivors who had early PSCI exhibited cognitive recovery at the 6-month follow-up. After examining potential predictors through multiple linear regression based on stepwise, there were independent negative associations between cognitive recovery and dominant hemisphere hemorrhage [OR: 6.955 (1.604-30.162); P < 0.01], lobar ICH [OR: 8.363 (1.479-47.290); P = 0.016], years of education ? 9 [OR: 5.145 (1.254-21.105); P = 0.023], and MCV [OR: 1.660 (1.171-2.354); P = 0.004]. Baseline cognitive performance in the domains of visuospatial/executive function, attention, orientation, and language showed positive correlations with cognitive improvement (P < 0.05). Conclusion: In this cohort study of dementia-free survivors of ICH, our results show that one in three early PSCI survivors exhibit cognitive recovery, in relation to dominant-hemisphere hematoma, lobar ICH, educational history, and MCV levels. Future clinical trials including ICH survivors with cognitive dysfunction should assess these factors.

Project description:BackgroundMortality rates are high among hospitalized patients with COVID-19, especially in those intubated on the ICU. Insight in pathways associated with unfavourable outcome may lead to new treatment strategies.MethodsWe performed a prospective cohort study of patients with COVID-19 admitted to general ward or ICU who underwent serial blood sampling. To provide insight in the pathways involved in disease progression, associations were estimated between outcome risk and serial measurements of 64 biomarkers in potential important pathways of COVID-19 infection (inflammation, tissue damage, complement system, coagulation and fibrinolysis) using joint models combining Cox regression and linear mixed-effects models. For patients admitted to the general ward, the primary outcome was admission to the ICU or mortality (unfavourable outcome). For patients admitted to the ICU, the primary outcome was 12-week mortality.FindingsA total of 219 patients were included: 136 (62%) on the ward and 119 patients (54%) on the ICU; 36 patients (26%) were included in both cohorts because they were transferred from general ward to ICU. On the general ward, 54 of 136 patients (40%) had an unfavourable outcome and 31 (23%) patients died. On the ICU, 54 out of 119 patients (45%) died. Unfavourable outcome on the general ward was associated with changes in concentrations of IL-6, IL-8, IL-10, soluble Receptor for Advanced Glycation End Products (sRAGE), vascular cell adhesion molecule 1 (VCAM-1) and Pentraxin-3. Death on the ICU was associated with changes in IL-6, IL-8, IL-10, sRAGE, VCAM-1, Pentraxin-3, urokinase-type plasminogen activator receptor, IL-1-receptor antagonist, CD14, procalcitonin, tumor necrosis factor alfa, tissue factor, complement component 5a, Growth arrest-specific 6, angiopoietin 2, and lactoferrin. Pathway analysis showed that unfavourable outcome on the ward was mainly driven by chemotaxis and interleukin production, whereas death on ICU was associated with a variety of pathways including chemotaxis, cell-cell adhesion, innate host response mechanisms, including the complement system, viral life cycle regulation, angiogenesis, wound healing and response to corticosteroids.InterpretationClinical deterioration in patients with severe COVID-19 involves multiple pathways, including chemotaxis and interleukin production, but also endothelial dysfunction, the complement system, and immunothrombosis. Prognostic markers showed considerable overlap between general ward and ICU patients, but we identified distinct differences between groups that should be considered in the development and timing of interventional therapies in COVID-19.FundingAmsterdam UMC, Amsterdam UMC Corona Fund, and Dr. C.J. Vaillant Fonds.

Project description:INTRODUCTION:Survival after trauma has considerably improved. This warrants research on non-fatal outcome. We aimed to identify characteristics associated with both short and long-term health status (HS) after trauma and to describe the recovery patterns of HS and psychological outcomes during 24 months of follow-up. METHODS:Hospitalized patients with all types of injuries were included. Data were collected at 1 week 1, 3, 6, 12, and 24 months post-trauma. HS was assessed with the EuroQol-5D-3L (EQ-5D-3L) and the Health Utilities Index Mark 2 and 3 (HUI2/3). For the screening of symptoms of post-traumatic stress, anxiety and depression, the Impact of Event Scale (IES) and the Hospital Anxiety and Depression Scale (HADS) subscale anxiety (HADSA) and subscale depression (HADSD) were used. Recovery patterns of HS and psychological outcomes were examined with linear mixed model analyses. RESULTS:A total of 4,883 patients participated (median age 68 (Interquartile range 53-80); 50% response rate). The mean (Standard Deviation (SD)) pre-injury EQ-5D-3L score was 0.85 (0.23). One week post-trauma, mean (SD) EQ-5D-3L, HUI2 and HUI3 scores were 0.49 (0.32), 0.61 (0.22) and 0.38 (0.31), respectively. These scores significantly improved to 0.77 (0.26), 0.77 (0.21) and 0.62 (0.35), respectively, at 24 months. Most recovery occurred up until 3 months. At long-term follow-up, patients of higher age, with comorbidities, longer hospital stay, lower extremity fracture and spine injury showed lower HS. The mean (SD) scores of the IES, HADSA and HADSD were respectively 14.80 (15.80), 4.92 (3.98) and 5.00 (4.28), respectively, at 1 week post-trauma and slightly improved over 24 months post-trauma to 10.35 (14.72), 4.31 (3.76) and 3.62 (3.87), respectively. DISCUSSION:HS and psychological symptoms improved over time and most improvements occurred within 3 months post-trauma. The effects of severity and type of injury faded out over time. Patients frequently reported symptoms of post-traumatic stress. TRIAL REGISTRATION:ClinicalTrials.gov identifier: NCT02508675.

Dataset Information

Prognostic factors for recovery of health status after injury: a prospective multicentre cohort study.

Objectives

Design

Setting

Participants

Main outcome measures

Results

Conclusion

Trial registration number

Publications

Prognostic factors for recovery of health status after injury: a prospective multicentre cohort study.

Similar Datasets

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