Ultra-Early and Short-Term Tranexamic Acid Treatment in Patients With Good- and Poor-Grade Aneurysmal Subarachnoid Hemorrhage.

BACKGROUND AND OBJECTIVES: The results of the ULTRA trial showed that ultra-early and short-term treatment with tranexamic acid (TXA) does not improve clinical outcome after aneurysmal subarachnoid hemorrhage (aSAH). Possibly, the lack of a beneficial effect in all patients with aSAH is masked by antagonistic effects of TXA in certain subgroups. In this post hoc subgroup analysis, we investigated the effect of TXA on clinical outcome in patients with good-grade and poor-grade aSAH. METHODS: The ULTRA trial was a multicenter, prospective, randomized, controlled, open-label trial with blinded outcome assessment. Participants received ultra-early and short-term TXA in addition to usual care or usual care only. This post hoc subgroup analysis included only ULTRA participants with confirmed aSAH and available World Federation of Neurosurgical Societies (WFNS) grade on admission. Patients were categorized into those with good-grade (WFNS 1-3) and poor-grade (WFNS 4-5) aSAH. The primary outcome was clinical outcome assessed by the modified Rankin scale (mRS). Odds ratios (ORs) and adjusted ORs (aORs) with 95% CIs were calculated using ordinal regression analyses. Analyses were performed using the as-treated principle. In all patients with aSAH, no significant effect modification of TXA on clinical outcome was observed for admission WFNS grade (p = 0.10). RESULTS: Of the 812 ULTRA participants, 473 patients had (58%; N = 232 TXA, N = 241 usual care) good-grade and 339 (42%; N = 162 TXA, N = 176 usual care) patients had poor-grade aSAH. In patients with good-grade aSAH, the TXA group had worse clinical outcomes (OR: 0.67, 95% CI 0.48-0.94, aOR 0.68, 95% CI 0.48-0.94) compared with the usual care group. In patients with poor-grade aSAH, clinical outcomes were comparable between treatment groups (OR: 1.04, 95% CI 0.70-1.55, aOR 1.05, 95% CI 0.70-1.56). DISCUSSION: This post hoc subgroup analysis provides another important argument against the use of TXA treatment in patients with aSAH, by showing worse clinical outcomes in patients with good-grade aSAH treated with TXA and no clinical benefit of TXA in patients with poor-grade aSAH, compared with patients treated with usual care. TRIAL REGISTRATION INFORMATION: ClinicalTrials.gov (NCT02684812; submission date February 18, 2016, first patient enrollment on July 24, 2013). CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that tranexamic acid, given for <24 hours within the first 24 hours, does not improve the 6-month outcome in good-grade or poor initial-grade aneurysmal SAH.

Safety and efficacy of active blood-pressure reduction to the recommended thresholds for intravenous thrombolysis in patients with acute ischaemic stroke in the Netherlands (TRUTH): a prospective, observational, cluster-based, parallel-group study.

BACKGROUND: Intravenous thrombolysis is contraindicated in patients with ischaemic stroke with blood pressure higher than 185/110 mm Hg. Prevailing guidelines recommend to actively lower blood pressure with intravenous antihypertensive agents to allow for thrombolysis; however, there is no robust evidence for this strategy. Because rapid declines in blood pressure can also adversely affect clinical outcomes, several Dutch stroke centres use a conservative strategy that does not involve the reduction of blood pressure. We aimed to compare the clinical outcomes of both strategies. METHODS: Thrombolysis and Uncontrolled Hypertension (TRUTH) was a prospective, observational, cluster-based, parallel-group study conducted across 37 stroke centres in the Netherlands. Participating centres had to strictly adhere to an active blood-pressure-lowering strategy or to a non-lowering strategy. Eligible participants were adults (≥18 years) with ischaemic stroke who had blood pressure higher than 185/110 mm Hg but were otherwise eligible for intravenous thrombolysis. The primary outcome was functional status at 90 days, measured using the modified Rankin Scale and assessed through telephone interviews by trained research nurses. Secondary outcomes were symptomatic intracranial haemorrhage, the proportion of patients treated with intravenous thrombolysis, and door-to-needle time. All ordinal logistic regression analyses were adjusted for age, sex, stroke severity, endovascular thrombectomy, and baseline imbalances as fixed-effect variables and centre as a random-effect variable to account for the clustered design. Analyses were done according to the intention-to-treat principle, whereby all patients were analysed according to the treatment strategy of the participating centre at which they were treated. FINDINGS: Recruitment began on Jan 1, 2015, and was prematurely halted because of a declining inclusion rate and insufficient funding on Jan 5, 2022. Between these dates, we recruited 853 patients from 27 centres that followed an active blood-pressure-lowering strategy and 199 patients from ten centres that followed a non-lowering strategy. Baseline characteristics of participants from the two groups were similar. The 90-day mRS score was missing for 15 patients. The adjusted odds ratio (aOR) for a shift towards a worse 90-day functional outcome was 1·27 (95% CI 0·96-1·68) for active blood-pressure reduction compared with no active blood-pressure reduction. 798 (94%) of 853 patients in the active blood-pressure-lowering group were treated with intravenous thrombolysis, with a median door-to-needle time of 35 min (IQR 25-52), compared with 104 (52%) of 199 patients treated in the non-lowering group with a median time of 47 min (29-78). 42 (5%) of 852 patients in the active blood-pressure-lowering group had a symptomatic intracranial haemorrhage compared with six (3%) of 199 of those in the non-lowering group (aOR 1·28 [95% CI 0·62-2·62]). INTERPRETATION: Insufficient evidence was available to establish a difference between an active blood-pressure-lowering strategy-in which antihypertensive agents were administered to reduce blood pressure below 185/110 mm Hg-and a non-lowering strategy for the functional outcomes of patients with ischaemic stroke, despite higher intravenous thrombolysis rates and shorter door-to-needle times among those in the active blood-pressure-lowering group. Randomised controlled trials are needed to inform the use of an active blood-pressure-lowering strategy. FUNDING: Fonds NutsOhra.

Emergency Department Risk Factors for Post-Concussion Syndrome After Mild Traumatic Brain Injury: A Systematic Review.

Approximately 16% of patients with mild traumatic brain injury (mTBI) develop a post-concussion syndrome (PCS) with persistent physical, neurological, and behavioral complaints. PCS has a great impact on a patient's quality of life, often decreases the ability to return to work, and henceforth has a great economic impact. Recent studies suggest that early treatment can greatly improve prognosis and prevent long-term effects in these patients. However, early recognition of patients at high risk of PCS remains difficult. The objective of this systematic review is to assess risk factors associated with the development of PCS, primarily aimed at the group of non-hospitalized patients who were seen with mTBI at the emergency department (ED). We searched PubMed/MEDLINE, Cochrane Library and EMBASE on September 23, 2022, for prospective studies that assessed the risk factors for the development of PCS. Exclusion criteria were: retrospective studies; > 20% computed tomography (CT) abnormalities, <18 years of age, follow-up <4 weeks, severe trauma, and study population <100 patients. The search strategy identified 1628 articles, of which 17 studies met eligibility criteria. Risk factors found in this systematic review are pre-existing psychiatric history, headache at the ED, neurological symptoms at the ED, female sex, CT abnormalities, pre-existent sleeping problems, and neck pain at the ED. This systematic review identified seven risk factors for development of PCS in patients with mTBI. Future research should assess if implementation of these risk factors into a risk stratification tool will assist the emergency physician in the identification of patients at high risk of PCS.

Clinical value of S100B in detecting intracranial injury in elderly patients with mild traumatic brain injury.

OBJECTIVE: The biomarker S100B is a sensitive biomarker to detect traumatic intracranial injury in patients mild traumatic brain injury (mTBI). Higher blood values of S100B, resulting in lower specificity and decreased head computed tomography (CT) reduction has been regarded as one of shortcomings in patients over 65 years of age. The purpose of this study was to assess the accuracy of plasma S100B to detect intracranial injury in elderly patients with mTBI. METHODS: A posthoc analysis was performed of a larger prospective cohort study. Previous recorded patient variables and plasma values of S100B from patients with mTBI who presented to the Emergency Department (ED) within 6 h of injury, underwent a head CT and had a blood sample drawn as part of their routine clinical care, were partitioned at 65 years of age. Sensitivity, specificity, negative predictive value, and positive predictive value of plasma S100B for predicting traumatic intracranial lesions on head CT, with a cut-off set at 0.105 µg/L, were calculated. Results were compared with data from an additional systematic review on the accuracy of S100B to detect intracranial injury in elderly patients with mTBI. RESULTS: Data of 240 patients (48.4 %) of 65 years or older were analyzed. Sensitivity and NPV of S100B were 89 % and 86 % respectively, which is lower than among younger patients (both 97 %). The specificity decreased stepwise with older age: 22 %, 18 %, and 5 % for the age groups 65-74, 75-84, and ≥ 85 years old, respectively. The meta-analysis comprised 4 studies and the current study with data from 2166 patients. Pooled data estimated the sensitivity of s100B as 97.4 % (95 % CI 83.3-100 %) and specificity as 17.3 % (95 % CI 9.5-29.3 %) to detect intracranial injury in elderly patients with mTBI. CONCLUSION: The biomarker S100B at the routine threshold has a limited clinical value in the management of elderly mTBI patients mainly due to a poor specificity leading to only a small decrease in head CTs. Alternate cut-off values and combining several plasma biomarkers with clinical variables may be useful strategies to increase the accuracy of S100B in (subgroups of) elderly mTBI patients.

Dexamethasone versus Surgery for Chronic Subdural Hematoma.

BACKGROUND: The role of glucocorticoids without surgical evacuation in the treatment of chronic subdural hematoma is unclear. METHODS: In this multicenter, open-label, controlled, noninferiority trial, we randomly assigned symptomatic patients with chronic subdural hematoma in a 1:1 ratio to a 19-day tapering course of dexamethasone or to burr-hole drainage. The primary end point was the functional outcome at 3 months after randomization, as assessed by the score on the modified Rankin scale (range, 0 [no symptoms] to 6 [death]). Noninferiority was defined by a lower limit of the 95% confidence interval of the odds ratio for a better functional outcome with dexamethasone than with surgery of 0.9 or more. Secondary end points included scores on the Markwalder Grading Scale of symptom severity and on the Extended Glasgow Outcome Scale. RESULTS: From September 2016 through February 2021, we enrolled 252 patients of a planned sample size of 420; 127 were assigned to the dexamethasone group and 125 to the surgery group. The mean age of the patients was 74 years, and 77% were men. The trial was terminated early by the data and safety monitoring board owing to safety and outcome concerns in the dexamethasone group. The adjusted common odds ratio for a lower (better) score on the modified Rankin scale at 3 months with dexamethasone than with surgery was 0.55 (95% confidence interval, 0.34 to 0.90), which failed to show noninferiority of dexamethasone. The scores on the Markwalder Grading Scale and Extended Glasgow Outcome Scale were generally supportive of the results of the primary analysis. Complications occurred in 59% of the patients in the dexamethasone group and 32% of those in the surgery group, and additional surgery was performed in 55% and 6%, respectively. CONCLUSIONS: In a trial that involved patients with chronic subdural hematoma and that was stopped early, dexamethasone treatment was not found to be noninferior to burr-hole drainage with respect to functional outcomes and was associated with more complications and a greater likelihood of later surgery. (Funded by the Netherlands Organization for Health Research and Development and others; DECSA EudraCT number, 2015-001563-39.).

Increasing incidence of ED-visits and admissions due to traumatic brain injury among elderly patients in the Netherlands, 2011-2020.

BACKGROUND AND IMPORTANCE: Traumatic brain injury (TBI) is a leading cause of disability and mortality worldwide. Nowadays the highest combined incidence of TBI-related emergency department (ED) visits, hospitalizations and deaths occurs in older adults. Knowledge of the changing patterns of epidemiology is essential to identify targets to enhance prevention and management of TBI. OBJECTIVE: To examine time trends of ED visits, admissions, and mortality for TBI comparing non-elderly and elderly people (aged ≥ 65 years) in the Netherlands from 2011 to 2020. DESIGN: We conducted a retrospective observational, longitudinal study of TBI using data from the Dutch Injury Surveillance System (DISS) and Statistics Netherlands from 2011 to 2020. OUTCOME MEASURE AND ANALYSIS: The main outcome measures were TBI-related ED visits, hospitalizations, and mortality. Temporal trends in population-based incidence rates were evaluated using Poisson regression. We compared patients under 65 years and patients aged 65 years or older. MAIN RESULTS: From 2011 to 2020, absolute numbers of TBI related ED visits increased by 244%, and hospital admissions and mortality showed an almost twofold increase in patients aged 65 years and older. The incidence of TBI-related ED visits and hospital admission increased also in elderly adults, with 156% and 51% respectively, whereas the mortality remained stable. In contrast, overall rates of ED visits, admissions, and mortality, and causes for TBI did not change in patients younger than 65 years during the study period. CONCLUSION: This trend analysis shows a significant increase of ED-visits and hospital admission for TBI in elderly adults from 2011 to 2020, whereas the mortality remained stable. This increase cannot be explained by the aging of the Dutch population alone, but might be related to comorbidities, causes of injury, and referral policy. These findings strengthen the development of strategies to prevent TBI and improve the organization of acute care necessary to reduce the impact and burden of TBI in elderly adults and on healthcare and society.

Clinical response following hypertension induction for clinical delayed cerebral ischemia following subarachnoid hemorrhage: A retrospective, multicenter, cohort study.

BACKGROUND: Hypertension induction (HTI) is often used for treating delayed cerebral ischemia (DCI) following aneurysmal subarachnoid hemorrhage (aSAH); however, high-quality studies on its efficacy are lacking. We studied immediate and 3-/6-month clinical efficacy of HTI in aSAH patients with clinical DCI. METHODS: A retrospective, multicenter, comparative, observational cohort study in aSAH patients with clinical deterioration due to DCI, admitted to three tertiary referral hospitals in the Netherlands from 2015 to 2019. Two hospitals used a strategy of HTI (HTI group) and one hospital had no such strategy (control group). We calculated adjusted relative risks (aRR) using Poisson regression analyses for the two primary (clinical improvement of DCI symptoms at days 1 and 5 after DCI onset) and secondary outcomes (DCI-related cerebral infarction, in-hospital mortality, and poor clinical outcome [modified Rankin Scale 4-6] assessed at 3 or 6 months), using the intention-to-treat principle. We also performed as-treated and per-protocol analyses. RESULTS: The aRR for clinical improvement on day 1 after DCI in the HTI group was 1.63 (95% CI 1.17-2.27) and at day 5 after DCI 1.04 (95% CI 0.84-1.29). Secondary outcomes were comparable between the groups. The as-treated and per-protocol analyses yielded similar results. CONCLUSIONS: No clinical benefit of HTI is observed 5 days after DCI due to spontaneous reversal of DCI symptoms in patients treated without HTI. The 3-/6-month clinical outcome was similar for both groups. Therefore, these data suggest that one may consider to not apply HTI in aSAH patients with clinical DCI.

Evaluation of Clinical Characteristics and CT Decision Rules in Elderly Patients with Minor Head Injury: A Prospective Multicenter Cohort Study.

Age is variably described as a minor or major risk factor for traumatic intracranial lesions after head injury. However, at present, no specific CT decision rule is available for elderly patients with minor head injury (MHI). The aims of this prospective multicenter cohort study were to assess the performance of existing CT decision rules for elderly MHI patients and to compare the clinical and CT characteristics of elderly patients with the younger MHI population. Thirty-day mortality between two age groups (cutoff ≥ 60 years), along with clinical and CT characteristics, was evaluated with four CT decision rules: the National Institute for Health and Care Excellence (NICE) guideline, the Canadian CT Head Rule (CCHR), the New Orleans Criteria (NOC), and the CT Head Injury Patients (CHIP) rule. Of the 5517 MHI patients included, 2310 were aged ≥ 60 years. Elderly patients experienced loss of consciousness (17% vs. 32%) and posttraumatic amnesia (23% vs. 31%) less often, but intracranial lesions (13% vs. 10%), neurological deterioration (1.8% vs. 0.2%), and 30-day mortality (2.0% vs. 0.1%) were more frequent than in younger patients (all p < 0.001). Elderly patients with age as their only risk factor showed intracranial lesions in 5% (NOC and CHIP) to 8% (CCHR and NICE) of cases. The sensitivity of decision rules in the elderly patients was 60% (CCHR) to 97% (NOC) when age was excluded as a risk factor. Current risk factors considered when evaluating elderly patients show lower sensitivity to identify intracranial abnormalities, despite more frequent intracranial lesions. Until age-specific CT decision rules are developed, it is advisable to scan every elderly patient with an MHI.

The cognitive status of chronic subdural hematoma patients after treatment: an exploratory study.

OBJECTIVE: Chronic subdural hematoma (CSDH) is a common neurological condition, often affecting the elderly. Cognitive impairment is frequently observed at presentation. However, the course and longer term aspects of the cognitive status of CSDH patients are unknown. In this study, we aim to explore the cognitive status of CSDH patients after treatment. METHODS: An exploratory study in which CSDH patients were assessed 3 months after treatment and compared to healthy controls. A total of 56 CSDH patients (age 72.1 SD ± 10.8 years with 43 [77%] males) and 60 healthy controls were included (age 67.5 ± SD 4.8 with 34 [57%] males). Cognitive testing was performed using the Telephonic Interview of Cognitive Status-modified (TICS-m), a 12-item questionnaire in which a total of 50 points can be obtained on several cognitive domains. RESULTS: Median time between treatment and cognitive testing was 93 days (range 76-139). TICS-m scores of CSDH patients were significantly lower than healthy controls, after adjusting for age and sex: mean score 34.6 (95% CI: 33.6-35.9) vs. 39.6 (95% CI: 38.5-40.7), p value < 0.001. More than half (54%) of CSDH patients have cognitive scores at follow-up that correspond with cognitive impairment. CONCLUSION: A large number of CSDH patients show significantly worse cognitive status 3 months after treatment compared to healthy controls. This finding underlines the importance of increased awareness for impaired cognition after CSDH. Further research on this topic is warranted.

Biomarker S100B in plasma a screening tool for mild traumatic brain injury in an emergency department.

INTRODUCTION: A computerized tomography (CT) scan is an effective test for detecting traumatic intracranial findings after mild traumatic brain injury (mTBI). However, a head CT is costly, and can only be performed in a hospital. OBJECTIVE: To determine if the addition of plasma S100B to clinical guidelines could lead to a more selective scanning strategy without compromising safety. METHODS: We conducted a single center prospective cohort study at the emergency department. Patients (≥16 years) who received head CT and had a blood draw were included. The primary outcome was the accuracy of plasma S100B to predict the presence of any traumatic intracranial lesion on head CT. RESULTS: We included 495 patients, out of the 74 patients who had traumatic intracranial lesions, 5 patients had a plasma S100B level below the cutoff value of 0.105 ug/L. For the detection of traumatic intracranial injury, S100B had a sensitivity of 0.932 , a specificity of 0.157, a negative predictive value of 0.930, and a positive predictive value of 0.163. CONCLUSIONS: Among patients undergoing guideline-based CT scan for mTBI, the use of S100B, would results in a further decrease (14.8%) of CT scans but at a cost of missed injury, without clinical consequence, on CT.

Change in Hematoma Size after Dexamethasone Therapy in Chronic Subdural Hematoma Subtypes: A Prospective Study in Symptomatic Patients.

The main treatment strategy for chronic subdural hematoma is surgical intervention. When a conservative pharmacological approach is considered in symptomatic patients, mainly dexamethasone therapy is applied. Recent trials revealed dexamethasone therapy to be an ineffective treatment in symptomatic patients with chronic subdural hematoma. Whether the efficacy of dexamethasone therapy differs in radiological hematoma subtypes is unknown. The aim of this substudy was to identify which hematoma subtype might be favorable for dexamethasone therapy. As part of a randomized controlled trial, symptomatic chronic subdural hematoma patients received 19-days dexamethasone therapy. The primary outcome measure was the change in hematoma size as measured on follow-up computed tomography (CT) after 2 weeks of dexamethasone in six hematoma (architectural and density) subtypes: homogeneous total, laminar, separated and trabecular architecture types, and hematoma without hyperdense components (homogeneous hypodense, isodense) and with hyperdense components (homogeneous hyperdense, mixed density). We analyzed hematoma thickness, midline shift, and volume using multi-variable linear regression adjusting for age, sex and baseline value of the specific radiological parameter. From September 2016 until February 2021, 85 patients were included with a total of 114 chronic subdural hematoma. The mean age was 76 years and 25% were women. Larger decrease in hematoma thickness and midline shift was revealed in hematoma without hyperdense components compared with hematoma with hyperdense components (adjusted [adj.] b -2.2 mm, 95% confidence interval [CI] -4.1 to -0.3 and adj. b -1.3 mm, 95% CI -2.7 to 0.0 respectively). Additional surgery was performed in 57% of patients with the highest observed rate (81%) in separated hematoma. Largest hematoma reduction and better clinical improvement was observed in chronic subdural hematoma without hyperdense components after dexamethasone therapy. Evaluation of these parameters can be part of an individualized treatment strategy.

Diagnostic Accuracy of Clinical Signs and Biochemical Parameters for External Ventricular CSF Catheter-Associated Infection.

Background and Objectives: Few prospective well-designed diagnostic accuracy studies have been performed to study the parameters of infection in patients suspected for external ventricular catheter-associated infection. Our objective was to analyze the diagnostic accuracy of clinical characteristics and biochemical and microbiological parameters in diagnosing external ventricular CSF catheter-associated infection. Methods: From 2014 to 2017, we performed a single-center cohort study in consecutive patients at the intensive care unit who required an external ventricular CSF catheter in the Hague, the Netherlands. CSF was sampled and analyzed daily. Ventricular catheter-associated infection was defined according to the 2017 Infectious Diseases Society of America's Clinical Practice Guidelines. We compared clinical characteristics and biochemical parameters between patients with and without infection from 3 days before to 3 days after the day the CSF sample was collected that grew bacteria. Results: A total of 103 patients were included of whom 15 developed a catheter-associated infection (15%). The median day cultures were positive was 3 days after CSF collection (interquartile range [IQR] +2 to +4). On day 0, none of the tests could differentiate between patients with and without infection. The CSF leukocyte count was increased in patients with ventricular catheter-associated infection as compared with patients without on days +2 and +3. The difference was most prominent on day +2 (1,703 × 106/L [IQR 480-6,296] vs 80 × 106/L [IQR 27-251]; p < 0.001; area under the curve [AUC] 0.87 [95% confidence interval (CI) 0.71-1.00]). Sensitivity for the CSF leukocyte count at a cutoff level >1,000 × 106/L was 67% (95% CI 30-93), and specificity was 100% (95% CI 90-100); the positive predictive value was 100%, and the negative predictive value was 92% (95% CI 83-97). The percentage of polymorphonuclear cells (PMNs) was higher in patients with infection on days +1 and +2 (day +2 89% [IQR 78-94] vs 59% [IQR 39-75]; p < 0.01; AUC 0.91 [95% CI 0.81-1.0]). Discussion: An elevated CSF leukocyte count and increased percentage of PMNs are the strongest indicators for external catheter-associated infections on the days before culture positivity. New CSF markers of drain-associated infection should be studied to enable earlier diagnosis and treatment in patients with an infection and reduce antibiotic treatment in those with no infection. Classification of Evidence: This study provides Class I evidence that in individuals requiring an external ventricular CSF catheter, an elevated CSF leukocyte count and an increased percentage of PMNs are the strongest indicators of catheter-associated infections in the days before CSF culture positivity.

Tranexamic Acid After Aneurysmal Subarachnoid Hemorrhage: Post-Hoc Analysis of the ULTRA Trial.

BACKGROUND AND OBJECTIVES: The ULTRA-trial showed that ultra-early and short-term tranexamic acid treatment after subarachnoid hemorrhage did not improve clinical outcome at six months. An expected proportion of the included patients had non-aneurysmal subarachnoid hemorrhage In this post-hoc study, we will investigate whether ultra-early and short-term tranexamic acid treatment in patients with aneurysmal subarachnoid hemorrhage improves clinical outcome at six months. METHODS: The ULTRA-trial is a multicenter, prospective, randomized, controlled, open-label trial with blinded outcome assessment, conducted between July 24, 2013 and January 20, 2020. After confirmation of subarachnoid hemorrhage on non-contrast computer tomography, patients were allocated to either ultra-early and short-term tranexamic acid treatment with usual care, or usual care only. In this post-hoc analysis, we included all ULTRA-participants with a confirmed aneurysm on CT angiography and/or digital subtraction angiography. The primary endpoint was clinical outcome at six months, assessed by the modified Rankin Scale, dichotomized into good (0-3) and poor (4-6) outcome. RESULTS: Of the 813 ULTRA-trial patients who had an aneurysmal subarachnoid hemorrhage, 409 (50%) were assigned to the tranexamic acid group and 404 (50%) to the control group. In the intention-to-treat analysis, 233 of 405 (58%) patients in the tranexamic acid group and 238 of 399 (60%) patients in the control group had a good clinical outcome (adjusted odds ratio (aOR) 0·92; 95% confidence interval (C.I.) 0·69 to 1·24). None of the secondary outcomes showed significant differences between the treatment groups: excellent clinical outcome (mRS 0-2) aOR 0.76, 95% C.I. 0.57-1.03, all-cause mortality at 30 days aOR 0.91, 95% C.I. 0.65-1.28), all-cause mortality at six months aOR 1.10 (95% C.I. 0.80-1.52). DISCUSSION: Ultra-early and short-term tranexamic acid treatment did not improve clinical outcome at six months in patients with aneurysmal subarachnoid hemorrhage and therefore, cannot be recommended. TRIAL REGISTRATION: ClinicalTrials.gov (NCT02684812; submission date February 18, 2016, first patient enrollment on July 24th, 2013). CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that tranexamic acid does not improve outcomes in patients presenting with aneurysmal subarachnoid hemorrhage.

Mortality after chronic subdural hematoma is associated with frailty.

PURPOSE: Chronic subdural hematoma (CSDH) is a common neurological disease often affecting the elderly. Long-term excess mortality for patients after CSDH has been suggested but causes of death are unknown. We hypothesize that excess mortality of CSDH patients is related to frailty. In this article, we describe mortality rates and causes of death of CSDH patients compared with the general population and assess the association of frailty with mortality. METHODS: A cohort study in which consecutive CSDH patients were compared to the general population regarding mortality rates. Furthermore, the association of six frailty indicators (cognitive problems, frequent falling, unable to live independently, unable to perform daily self-care, use of benzodiazepines or psychotropic drugs, and number of medications) with mortality was assessed. RESULTS: A total of 1307 CSDH patients were included, with a mean age of 73.7 (SD ± 11.4) years and 958 (73%) were male. Median follow-up was 56 months (range: 0-213). Compared with controls CSDH patients had a hazard ratio for mortality of 1.34 (95% CI: 1.2-1.5). CSDH patients more often died from cardiovascular diseases (37% vs. 30%) and falls (7.2% vs. 3.7%). Among CSDH patients frequent falling (HR 1.3; 95% CI: 1.0-1.7), inability to live independently (HR 1.4, 95% CI: 1.1-1.8), inability to perform daily self-care (HR 1.5; 95% CI: 1.1-1.9), and number of medications used (HR 1.0; 95% CI: 1.0-1.1) were independently associated with mortality. CONCLUSIONS: CSDH patients have higher mortality rates than the general population. Frailty in CSDH patients is associated with higher mortality risk. More attention for the frailty of CSDH patients is warranted.

[What were the consequences of the COVID-19 pandemic on trauma care in the Netherlands?] / Hoe nadelig was het effect van de covid-19-pandemie op de traumazorg?

The COVID-19 pandemic changed daily practice in a number of ways. In a recent article it was shown that mortality in multitrauma patients with mild to moderate head injury, was higher compared to pre-COVID-19 mortality. The authors describe possible mechanisms for this higher mortality, for instance scarcity of IC beds and changes in Intensive care unit admissions. However, the study only showed mortality data, not the complete range of possible outcomes. In multitrauma patients, mere survival is not necessarily a good outcome. It would be very interesting to know whether the increased mortality is a accompanied by a lower proportion of patients who need daily care. If that is the case, then the conclusion of the authors that the COVID-19 pandemic leads to worse outcomes needs to be nuanced.

Update of the CHIP (CT in Head Injury Patients) decision rule for patients with minor head injury based on a multicenter consecutive case series.

OBJECTIVE: To update the existing CHIP (CT in Head Injury Patients) decision rule for detection of (intra)cranial findings in adult patients following minor head injury (MHI). METHODS: The study is a prospective multicenter cohort study in the Netherlands. Consecutive MHI patients of 16 years and older were included. Primary outcome was any (intra)cranial traumatic finding on computed tomography (CT). Secondary outcomes were any potential neurosurgical lesion and neurosurgical intervention. The CHIP model was validated and subsequently updated and revised. Diagnostic performance was assessed by calculating the c-statistic. RESULTS: Among 4557 included patients 3742 received a CT (82%). In 383 patients (8.4%) a traumatic finding was present on CT. A potential neurosurgical lesion was found in 73 patients (1.6%) with 26 (0.6%) patients that actually had neurosurgery or died as a result of traumatic brain injury. The original CHIP underestimated the risk of traumatic (intra)cranial findings in low-predicted-risk groups, while in high-predicted-risk groups the risk was overestimated. The c-statistic of the original CHIP model was 0.72 (95% CI 0.69-0.74) and it would have missed two potential neurosurgical lesions and one patient that underwent neurosurgery. The updated model performed similar to the original model regarding traumatic (intra)cranial findings (c-statistic 0.77 95% CI 0.74-0.79, after crossvalidation c-statistic 0.73). The updated CHIP had the same CT rate as the original CHIP (75%) and a similar sensitivity (92 versus 93%) and specificity (both 27%) for any traumatic (intra)cranial finding. However, the updated CHIP would not have missed any (potential) neurosurgical lesions and had a higher sensitivity for (potential) neurosurgical lesions or death as a result of traumatic brain injury (100% versus 96%). CONCLUSIONS: Use of the updated CHIP decision rule is a good alternative to current decision rules for patients with MHI. In contrast to the original CHIP the update identified all patients with (potential) neurosurgical lesions without increasing CT rate.

External validation of prognostic models predicting outcome after chronic subdural hematoma.

BACKGROUND: Several prognostic models for outcomes after chronic subdural hematoma (CSDH) treatment have been published in recent years. However, these models are not sufficiently validated for use in daily clinical practice. We aimed to assess the performance of existing prediction models for outcomes in patients diagnosed with CSDH. METHODS: We systematically searched relevant literature databases up to February 2021 to identify prognostic models for outcome prediction in patients diagnosed with CSDH. For the external validation of prognostic models, we used a retrospective database, containing data of 2384 patients from three Dutch regions. Prognostic models were included if they predicted either mortality, hematoma recurrence, functional outcome, or quality of life. Models were excluded when predictors were absent in our database or available for < 150 patients in our database. We assessed calibration, and discrimination (quantified by the concordance index C) of the included prognostic models in our retrospective database. RESULTS: We identified 1680 original publications of which 1656 were excluded based on title or abstract, mostly because they did not concern CSDH or did not define a prognostic model. Out of 18 identified models, three could be externally validated in our retrospective database: a model for 30-day mortality in 1656 patients, a model for 2 months, and another for 3-month hematoma recurrence both in 1733 patients. The models overestimated the proportion of patients with these outcomes by 11% (15% predicted vs. 4% observed), 1% (10% vs. 9%), and 2% (11% vs. 9%), respectively. Their discriminative ability was poor to modest (C of 0.70 [0.63-0.77]; 0.46 [0.35-0.56]; 0.59 [0.51-0.66], respectively). CONCLUSIONS: None of the examined models showed good predictive performance for outcomes after CSDH treatment in our dataset. This study confirms the difficulty in predicting outcomes after CSDH and emphasizes the heterogeneity of CSDH patients. The importance of developing high-quality models by using unified predictors and relevant outcome measures and appropriate modeling strategies is warranted.

Dutch injection versus surgery trial in patients with carpal tunnel syndrome (DISTRICTS): protocol of a randomised controlled trial comparing two treatment strategies.

INTRODUCTION: Carpal tunnel syndrome (CTS) is the most common peripheral neuropathy. The optimal treatment strategy is still unknown. The objective of the Dutch Injection versus Surgery TRIal in patients with CTS (DISTRICTS) is to investigate if initial surgery of CTS results in a better clinical outcome and is more cost-effective when compared with initial treatment with corticosteroid injection. METHODS AND ANALYSIS: The DISTRICTS is an ongoing multicenter, open-label randomised controlled trial. Participants with CTS are randomised to treatment with surgery or with a corticosteroid injection. If needed, any additional treatments after this first treatment are allowed and these are not dictated by the study protocol. The primary outcome is the difference between the groups in the proportion of participants recovered at 18 months. Recovery is defined as having no or mild symptoms as measured with the 6-item carpal tunnel symptoms scale. Secondary outcome measurements are among others: time to recovery, hand function, patient satisfaction, quality of life, additional treatments, adverse events, and use of care and health-related costs. ETHICS AND DISSEMINATION: The study was approved by the Medical Ethical Committee of the Amsterdam University Medical Centers (study number 2017-171). Study results will be disseminated in peer-reviewed journals and conferences. TRIAL REGISTRATION NUMBER: ISRCTN Registry: 13164336.

Pathophysiology of transient neurological deficit in patients with chronic subdural hematoma: A systematic review.

Patients with chronic subdural hematoma (CSDH) can have transient neurological deficits deficit (TND) mimicking transient ischemic attacks. The prevalence of TNDs in CSDH varies between 1%-24%, depending on TND definition. Despite this high prevalence the pathophysiology of TND in CSDH is not clear in many cases. In this systematic review, we aim to unravel the responsible mechanism. Pubmed and Embase were searched for all articles concerning the pathophysiology of TND as a presenting symptom in patients with CSDH. There were no publication date restrictions for the articles in the search. Two reviewers independently selected studies for inclusion and subsequently extracted the necessary data. Out of 316 identified references, 15 met the inclusion criteria. Several articles mentioned multiple pathophysiological mechanisms. One of the proposed etiologies of TND was epileptic activity, stated by three articles. In contrast, three different studies stated that seizures are unlikely to cause TND. Five papers suggested that obstruction of blood flow, caused by the hematoma or subsequent swelling, might be the cause. Six articles made no definite statement on the responsible pathophysiological mechanism of TND. Different mechanisms have been proposed to be the cause of TNDs in patients with CSDH. Based on this review, the exact pathophysiology of TND remains unclear. We suggest that future studies on this topic should incorporate MRI of the brain (with diffusion-weighted imaging) and EEG, to provide better insight into TND pathophysiology. The knowledge resulting from future studies might contribute to better understanding of TND and optimal treatment in CSDH.

Surgery After Primary Dexamethasone Treatment for Patients with Chronic Subdural Hematoma-A Retrospective Study.

BACKGROUND: We aimed to quantify the need for additional surgery in patients with chronic subdural hematoma (CSDH) primarily treated with dexamethasone and to identify patient characteristics associated with additional surgery. METHODS: Data were retrospectively collected from 283 patients with CSDH, primarily treated with dexamethasone, in 3 hospitals from 2008 to 2018. Primary outcome was the need for additional surgery. The association between baseline characteristics and additional surgery was analyzed with univariable and multivariable logistic regression analysis and presented as adjusted odds ratios (aOR). RESULTS: In total, 283 patients with CSDH were included: 146 patients (51.6%) received 1 dexamethasone course (DXM group), 30 patients (10.6%) received 2 dexamethasone courses (DXM-DXM group), and 107 patients (37.8%) received additional surgery (DXM-SURG group). Patients who underwent surgery more often had a Markwalder Grading Scale of 2 (as compared with 1, aOR 2.05; 95% confidence interval [CI] 0.90-4.65), used statins (aOR 2.09; 95% CI 1.01-4.33), had a larger midline shift (aOR 1.10 per mm; 95% CI 1.01-1.21) and had larger hematoma thickness (aOR 1.16 per mm; 95% CI 1.09-1.23), had a bilateral hematoma (aOR 1.85; 95% CI 0.90-3.79), and had a separated hematoma (as compared with homogeneous, aOR 1.77; 95% CI 0.72-4.38). Antithrombotics (aOR 0.45; 95% CI 0.21-0.95) and trabecular hematoma (as compared with homogeneous, aOR 0.31; 95% CI 0.12-0.77) were associated with a lower likelihood of surgery. CONCLUSIONS: More than one-third of patients with CSDH primarily treated with dexamethasone received additional surgery. These patients were more severely affected amongst others with larger hematomas.