Risk of Intracranial Complications in Minor Head Injury:The Role of Loss of Consciousness and Post-Traumatic Amnesia in a Multi-Center Observational Study

Various guidelines for minor head injury focus on patients with a Glasgow Coma Scale (GCS) score of 13-15 and loss of consciousness (LOC) or post-traumatic amnesia (PTA), while clinical management for patients without LOC or PTA is often unclear. We aimed to investigate the effect of presence and absence of LOC or PTA on intracranial complications in minor head injury. A prospective multi-center cohort study of all patients with blunt head injury and GCS score of 15 was conducted at six Dutch centers between 2015 and 2017. Five centers used the national guideline and one center used a local guideline-both based on the CT in Head Injury Patients (CHIP) prediction model-to identify patients in need of a computed tomography (CT) scan. We studied the presence of traumatic findings and neurosurgical interventions in patients with and without LOC or PTA. In addition, we assessed the association of LOC and PTA with traumatic findings with logistic regression analysis and the additional predictive value of LOC and PTA compared with other risk factors in the CHIP model. Of 3914 patients, 2249 (58%) experienced neither LOC nor PTA and in 305 (8%) LOC and PTA was unknown. Traumatic findings were present in 153 of 1360 patients (11%) with LOC or PTA and in 67 of 2249 patients (3%) without LOC and PTA. Five patients without LOC and PTA had potential neurosurgical lesions and one patient underwent a neurosurgical intervention. LOC and PTA were strongly associated with traumatic findings on CT, with adjusted odds ratios of 2.9 (95% confidence interval [CI] 2.2-3.8) and 3.5 (95% CI 2.7-4.6), respectively. To conclude, patients who had minor head injury with neither LOC nor PTA are at risk of intracranial complications. Clinical guidelines should include clinical management for patients without LOC and PTA, and they should include LOC and PTA as separate risk factors rather than as diagnostic selection criteria

Development of prognostic models for Health-Related Quality of Life following traumatic brain injury

Background Traumatic brain injury (TBI) is a leading cause of impairments affecting Health-Related Quality of Life (HRQoL). We aimed to identify predictors of and develop prognostic models for HRQoL following TBI. Methods We used data from the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) Core study, including patients with a clinical diagnosis of TBI and an indication for computed tomography presenting within 24 h of injury. The primary outcome measures were the SF-36v2 physical (PCS) and mental (MCS) health component summary scores and the Quality of Life after Traumatic Brain Injury (QOLIBRI) total score 6 months post injury. We considered 16 patient and injury characteristics in linear regression analyses. Model performance was expressed as proportion of variance explained (R2) and corrected for optimism with bootstrap procedures. Results 2666 Adult patients completed the HRQoL questionnaires. Most were mild TBI patients (74%). The strongest predictors for PCS were Glasgow Coma Scale, major extracranial injury, and pre-injury health status, while MCS and QOLIBRI were mainly related to pre-injury mental health problems, level of education, and type of employment. R2 of the full models was 19% for PCS, 9% for MCS, and 13% for the QOLIBRI. In a subset of patients following predominantly mild TBI (N = 436), including 2 week HRQoL assessment improved model performance substantially (R2 PCS 15% to 37%, MCS 12% to 36%, and QOLIBRI 10% to 48%). Conclusion Medical and injury-related characteristics are of greatest importance for the prediction of PCS, whereas patient-related characteristics are more important for the prediction of MCS and the QOLIBRI following TBI.Output Status: Forthcoming/Available Onlin

National Institutes of Health Stroke Scale An Alternative Primary Outcome Measure for Trials of Acute Treatment for Ischemic Stroke

Background and Purpose- The modified Rankin Scale (mRS) at 3 months is the most commonly used primary outcome measure in stroke treatment trials, but it lacks specificity and requires long-term follow-up interviews, which consume time and resources. An alternative may be the National Institutes of Health Stroke Scale (NIHSS), early after stroke. Our aim was to evaluate whether the NIHSS assessed within 1 week after treatment could serve as a primary outcome measure for trials of acute treatment for ischemic stroke. Methods- We used data from 2 randomized controlled trials of endovascular treatment for ischemic stroke: the positive MR CLEAN (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands; N=500) and the neutral IMS (Interventional Management of Stroke) III trial (N=656). We used a causal mediation model, with linear and ordinal logistic regression adjusted for confounders, to evaluate the NIHSS 24 hours and 5 to 7 days after endovascular treatment as primary outcome measures (instead of the mRS at 3 months) in both trials. Patients who had died before the NIHSS was assessed received the maximum score of 42. NIHSS+1 was then log10-transformed. Results- In both trials, there was a significant correlation between the NIHSS at 24 hours and 5 to 7 days and the mRS. In MR CLEAN, we found a significant effect of endovascular treatment on the mRS and on the NIHSS at 24 hours and 5 to 7 days. After adjustment for NIHSS at 24 hours and 5 to 7 days, the effect of endovascular treatment on the mRS decreased from common odds ratio 1.68 (95% CI, 1.22-2.32) to respectively 1.36 (95% CI, 0.97-1.91) and 1.24 (95% CI, 0.87-1.79), indicating that treatment effect on the mRS is in large part mediated by the NIHSS. In the IMS III trial there was no treatment effect on the NIHSS at 24 hours and 5 to 7 days, corresponding with the absence of a treatment effect on the mRS. Conclusions- The NIHSS within 1 week satisfies the requirements for a surrogate end point and may be used as a primary outcome measure in trials of acute treatment for ischemic stroke, particularly in phase II(b) trials. This could reduce stroke-outcome assessment to its essentials (ie, neurological deficit), and reduce trial duration and costs. Whether and under which conditions it could be used in phase III trials requires a debate in the field with all parties. Clinical Trial Registration- URL: http://www.isrctn.com. Unique identifier: ISRCTN10888758; https://www.clinicaltrials.gov. Unique identifier: NCT00359424.</p

National Institutes of Health Stroke Scale: An Alternative Primary Outcome Measure for Trials of Acute Treatment for Ischemic Stroke

Background and Purpose- The modified Rankin Scale (mRS) at 3 months is the most commonly used primary outcome measure in stroke treatment trials, but it lacks specificity and requires long-term follow-up interviews, which consume time and resources. An alternative may be the National Institutes of Health Stroke Scale (NIHSS), early after stroke. Our aim was to evaluate whether the NIHSS assessed within 1 week after treatment could serve as a primary outcome measure for trials of acute treatment for ischemic stroke. Methods- We used data from 2 randomized controlled trials of endovascular treatment for ischemic stroke: the positive MR CLEAN (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands; N=500) and the neutral IMS (Interventional Management of Stroke) III trial (N=656). We used a causal mediation model, with linear and ordinal logistic regression adjusted for confounders, to evaluate the NIHSS 24 hours and 5 to 7 days after endovascular treatment as primary outcome measures (instead of the mRS at 3 months) in both trials. Patients who had died before the NIHSS was assessed received the maximum score of 42. NIHSS+1 was then log10-transformed. Results- In both trials, there was a significant correlation between the NIHSS at 24 hours and 5 to 7 days and the mRS. In MR CLEAN, we found a significant effect of endovascular treatment on the mRS and on the NIHSS at 24 hours and 5 to 7 days. After adjustment for NIHSS at 24 hours and 5 to 7 days, the effect of endovascular treatment on the mRS decreased from common odds ratio 1.68 (95% CI, 1.22-2.32) to respectively 1.36 (95% CI, 0.97-1.91) and 1.24 (95% CI, 0.87-1.79), indicating that treatment effect on the mRS is in large part mediated by the NIHSS. In the IMS III trial there was no treatment effect on the NIHSS at 24 hours and 5 to 7 days, corresponding with the absence of a treatment effect on the mRS. Conclusions- The NIHSS within 1 week satisfies the requirements for a surrogate end point and may be used as a primary outcome measure in trials of acute treatment for ischemic stroke, particularly in phase II(b) trials. This could reduce stroke-outcome assessment to its essentials (ie, neurological deficit), and reduce trial duration and costs. Whether and under which conditions it could be used in phase III trials requires a debate in the field with all parties. Clinical Trial Registration- URL: http://www.isrctn.com. Unique identifier: ISRCTN10888758; https://www.clinicaltrials.gov. Unique identifier: NCT00359424

Predictors of Mortality in Patients with Advanced Cancer—A Systematic Review and Meta-Analysis

To timely initiate advance care planning in patients with advanced cancer, physicians should identify patients with limited life expectancy. We aimed to identify predictors of mortality. To identify the relevant literature, we searched Embase, MEDLINE, Cochrane Central, Web of Science, and PubMed databases between January 2000–April 2020. Identified studies were assessed on risk-of-bias with a modified QUIPS tool. The main outcomes were predictors and prediction models of mortality within a period of 3–24 months. We included predictors that were studied in ≥2 cancer types in a meta-analysis using a fixed or random-effects model and summarized the discriminative ability of models. We included 68 studies (ranging from 42 to 66,112 patients), of which 24 were low risk-of-bias, and 39 were included in the meta-analysis. Using a fixed-effects model, the predictors of mortality were: the surprise question, performance status, cognitive impairment, (sub)cutaneous metastases, body mass index, comorbidity, serum albumin, and hemoglobin. Using a random-effects model, predictors were: disease stage IV (hazard ratio [HR] 7.58; 95% confidence interval [CI] 4.00–14.36), lung cancer (HR 2.51; 95% CI 1.24–5.06), ECOG performance status 1+ (HR 2.03; 95% CI 1.44–2.86) and 2+ (HR 4.06; 95% CI 2.36–6.98), age (HR 1.20; 95% CI 1.05–1.38), male sex (HR 1.24; 95% CI 1.14–1.36), and Charlson comorbidity score 3+ (HR 1.60; 95% CI 1.11–2.32). Thirteen studies reported on prediction models consisting of different sets of predictors with mostly moderate discriminative ability. To conclude, we identified reasonably accurate non-tumor specific predictors of mortality. Those predictors could guide in developing a more accurate prediction model and in selecting patients for advance care planning

Predictors of mortality in chronic obstructive pulmonary disease: a systematic review and meta-analysis

Background: Better insight in patients’ prognosis can help physicians to timely initiate advance care planning (ACP) discussions with patients with chronic obstructive pulmonary disease (COPD). We aimed to identify predictors of mortality. Methods: We systematically searched databases Embase, PubMed, MEDLINE, Web of Science, and Cochrane Central in April 2020. Papers reporting on predictors or prognostic models for mortality at 3 months and up to 24 months were assessed on risk-of-bias. We performed a meta-analysis with a fixed or random-effects model, and evaluated the discriminative ability of multivariable prognostic models. Results: We included 42 studies (49–418,251 patients); 18 studies were included in the meta-analysis. Significant predictors of mortality within 3–24 months in the random-effects model were: previous hospitalization for acute exacerbation (hazard ratio [HR] 1.97; 95% confidence interval [CI] 1.32–2.95), hospital readmission within 30 days (HR 5.01; 95% CI 2.16–11.63), cardiovascular comorbidity (HR 1.89; 95% CI 1.25–2.87), age (HR 1.48; 95% CI 1.38–1.59), male sex (HR 1.68; 95% CI 1.38–1.59), and long-term oxygen therapy (HR 1.74; 95% CI 1.10–2.73). Nineteen previously developed multicomponent prognostic models, as examined in 11 studies, mostly had moderate discriminate ability. Conclusion: Identified predictors of mortality may aid physicians in selecting COPD patients who may benefit from ACP. However, better discriminative ability of prognostic models or development of a new prognostic model is needed for further large-scale implementation. Registration: PROSPERO (CRD42016038494), https://www.crd.york.ac.uk/prospero/

Prediction of 60-Day Case Fatality After Aneurysmal Subarachnoid Hemorrhage : External Validation of a Prediction Model

OBJECTIVE:: External validation of prognostic models is crucial but rarely done. Our aim was to externally validate a prognostic model to predict 60-day case fatality after aneurysmal subarachnoid hemorrhage developed from the International Subarachnoid Aneurysm Trial in a retrospective unselected cohort of subarachnoid hemorrhage patients. DESIGN:: The model’s predictors were age, aneurysm size, Fisher grade, and World Federation of Neurological Surgeons grade. Two versions of the model were validated: one with World Federation of Neurological Surgeons grade scored at admission and the other with World Federation of Neurological Surgeons grade at treatment decision. The outcome was 60-day case fatality. Performance of the model was assessed by studying discrimination, expressed by the area under the receiver operating characteristic curve, and calibration. SETTING:: University hospital. PATIENTS:: We analyzed data from 307 consecutive aneurysmal subarachnoid hemorrhage patients admitted between 2007 and 2011 (validation cohort). INTERVENTIONS:: None. MEASUREMENTS AND MAIN RESULTS:: The observed 60-day case fatality rate was 30.6%. Discrimination was good, and differed between the model with World Federation of Neurological Surgeons grade at treatment decision (area under the receiver operating characteristic curve, 0.89) and at admission (area under the receiver operating characteristic curve, 0.82). Mean predicted probabilities were lower than observed: 17.0% (model with World Federation of Neurological Surgeons grade at admission) and 17.7% (model with World Federation of Neurological Surgeons grade at treatment decision). CONCLUSIONS:: The model discriminated well between patients who died or survived within 60 days. In addition, we found that using World Federation of Neurological Surgeons grade at moment of treatment decision of the ruptured aneurysm improved model performance. However, since predicted probabilities were much lower than observed probabilities, the International Subarachnoid Aneurysm Trial prediction model needs to be adapted to be used in clinical practice

Prediction of 60-Day Case Fatality After Aneurysmal Subarachnoid Hemorrhage : External Validation of a Prediction Model

OBJECTIVE:: External validation of prognostic models is crucial but rarely done. Our aim was to externally validate a prognostic model to predict 60-day case fatality after aneurysmal subarachnoid hemorrhage developed from the International Subarachnoid Aneurysm Trial in a retrospective unselected cohort of subarachnoid hemorrhage patients. DESIGN:: The model’s predictors were age, aneurysm size, Fisher grade, and World Federation of Neurological Surgeons grade. Two versions of the model were validated: one with World Federation of Neurological Surgeons grade scored at admission and the other with World Federation of Neurological Surgeons grade at treatment decision. The outcome was 60-day case fatality. Performance of the model was assessed by studying discrimination, expressed by the area under the receiver operating characteristic curve, and calibration. SETTING:: University hospital. PATIENTS:: We analyzed data from 307 consecutive aneurysmal subarachnoid hemorrhage patients admitted between 2007 and 2011 (validation cohort). INTERVENTIONS:: None. MEASUREMENTS AND MAIN RESULTS:: The observed 60-day case fatality rate was 30.6%. Discrimination was good, and differed between the model with World Federation of Neurological Surgeons grade at treatment decision (area under the receiver operating characteristic curve, 0.89) and at admission (area under the receiver operating characteristic curve, 0.82). Mean predicted probabilities were lower than observed: 17.0% (model with World Federation of Neurological Surgeons grade at admission) and 17.7% (model with World Federation of Neurological Surgeons grade at treatment decision). CONCLUSIONS:: The model discriminated well between patients who died or survived within 60 days. In addition, we found that using World Federation of Neurological Surgeons grade at moment of treatment decision of the ruptured aneurysm improved model performance. However, since predicted probabilities were much lower than observed probabilities, the International Subarachnoid Aneurysm Trial prediction model needs to be adapted to be used in clinical practice

Early Circulating Lactate and Glucose Levels After Aneurysmal Subarachnoid Hemorrhage Correlate With Poor Outcome and Delayed Cerebral lschemia: A Two-Center Cohort Study

Objective: In critically ill patients, elevated blood lactate at admission is associated with poor outcome, but after aneurysmal subarachnoid hemorrhage, this has not been investigated. We studied the association between early circulating lactate and glucose with delayed cerebral ischemia and poor outcome. Lactate and glucose were both studied, hypothesizing that both may be increased due to sympathetic activation after subarachnoid hemorrhage similar to critically ill patients. Design: Retrospective cohort study. Setting: ICUs of two academic hospitals in the Netherlands. Patients: Patients with aneurysmal subarachnoid hemorrhage admitted to the ICU within 24 hours after the bleed surviving beyond 48 hours after ICU admission and who had at least one lactate measurement within 24 hours after admission. Interventions: None. Measurements and Main Results: In 285 patients, maximal lactate and glucose levels within the first 24 hours after admission were determined. Early lactate and glucose were related with delayed cerebral ischemia related infarction and poor outcome (a modified Rankin Scale score of 4, 5, or death at 3 mo). Delayed cerebral ischemia occurred in 84 patients (29%), and 106 patients (390%) had poor outcome. Multivariable analyses were performed with adjustment of established predictors for delayed cerebral ischemia and outcome: age, sex, World Federation of Neurological Surgeons grade at admission and Hijdra sum scores. Early lactate and glucose were strongly related (Spearman p = 0.55; p <0.001). Lactate and glucose were both independently associated with delayed cerebral ischemia and poor outcome in multivariable analyses with either lactate or glucose as covariates. When both lactate and glucose were included, only glucose showed an independent association with delayed cerebral ischemia (odds ratio, 1.14; 95% CI, 1.01-1.28) and only lactate showed an independent association with poor outcome (odds ratio, 1.42; 95% CI, 1.11-1.81). Conclusions: Early lactate and glucose levels after aneurysmal subarachnoid hemorrhage are associated with delayed cerebral ischemia and poor outcome, suggesting that they may be considered in conjunction with other parameters for future prognostic models