Prompt closure versus gradual weaning of external ventricular drain for hydrocephalus following aneurysmal subarachnoid haemorrhage: a statistical analysis plan for the DRAIN randomised clinical trial.

BACKGROUND: Insertion of an external ventricular drain (EVD) is a first-line treatment of acute hydrocephalus caused by aneurysmal subarachnoid haemorrhage (aSAH). Once the patient is clinically stable, the EVD is either removed or replaced by a permanent internal shunt. The optimal strategy for cessation of the EVD is unknown. Prompt closure carries a risk of acute hydrocephalus or redundant shunt implantations, whereas gradual weaning may increase the risk of EVD-related infections. METHODS: DRAIN (Danish RAndomised Trial of External Ventricular Drainage Cessation IN Aneurysmal Subarachnoid Haemorrhage) is an international multicentre randomised clinical trial comparing prompt closure versus gradual weaning of the EVD after aSAH. The primary outcome is a composite of VP-shunt implantation, all-cause mortality, or EVD-related infection. Secondary outcomes are serious adverse events excluding mortality and health-related quality of life (EQ-5D-5L). Exploratory outcomes are modified Rankin Scale, Fatigue Severity Scale, Glasgow Outcome Scale Extended, and length of stay in the neurointensive care unit and hospital. Outcome assessment will be performed 6 months after ictus. Based on the sample size calculation (event proportion 80% in the gradual weaning group, relative risk reduction 20%, alpha 5%, power 80%), 122 participants are required in each intervention group. Outcome assessment for the primary outcome, statistical analyses, and conclusion drawing will be blinded. Two independent statistical analyses and reports will be tracked using a version control system, and both will be published. Based on the final statistical report, the blinded steering group will formulate two abstracts. CONCLUSION: We present a pre-defined statistical analysis plan for the randomised DRAIN trial, which limits bias, p-hacking, and data-driven interpretations. This statistical analysis plan is accompanied by tables with simulated data, which increases transparency and reproducibility. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03948256. Registered on May 13, 2019.

Time from injury to acute surgery for patients with traumatic cervical spinal cord injury in South-East Norway.

Background: The recommended treatment for cervical spinal cord injury (cSCI) is surgical decompression and stabilization within 24 h after injury. The aims of the study were to estimate our institutional compliance with this recommendation and identify potential factors associated with surgical delay. Methods: Population-based retrospective database study of patients operated for cSCI in 2015-2022 within the South-East Norway Health Region (3.1 million inhabitants). Data extracted were demographics, injury description, management timeline, place of primary triage [local hospital (LH) or neurotrauma center (NTC)]. Main outcome variables were: (1) time from injury to surgery at NTC, (2) time from injury to admission NTC, and (3) time from admission NTC to surgery. Results: We found 243 cSCI patients having acute neck surgery. Their median age was 63 years (IQR 47-74 years), 77% were male, 48% were ≥65 years old. Primary triage at an LH occurred in 150/243 (62%). The median time from injury to acute surgery was 27.8 h (IQR 15.4-61.9 h), and 47% had surgery within 24 h. The median time from injury to NTC admission was 5.6 h (IQR 1.9-19.4 h), and 67% of the patients were admitted to the NTC within 12 h. Significant factors associated with increased time from injury to NTC admission were transfer via LH, severe preinjury comorbidities, less severe cSCI, time of injury other than night, absence of multiple injuries. The median time from NTC admission to surgery was 16.7 h (IQR 9.5-31.0 h), and 70% had surgery within 24 h. Significant factors associated with increased time from NTC admission to surgery were increasing age and non-translational injury morphology. Conclusion: Less than half of the patients with cSCI were operated on within the recommended 24 h time frame after injury. To increase the fraction of early surgery, we suggest the following: (1) patients with clinical suspicion of cSCI should be transported directly to the NTC from the scene of the accident, (2) MRI should be performed only at the NTC, (3) at the NTC, surgery should commence on the same calendar day as arrival or as the first operation the following day.

Decreasing incidence of cervical spine fractures in patients with ankylosing spondylitis: a population-based study in Southeast Norway.

BACKGROUND CONTEXT: Individuals diagnosed with ankylosing spondylitis (AS) face an increased risk of spine fractures, specifically cervical spine fractures (CS-Fxs). In the past two decades, biological disease-modifying antirheumatic drugs (bDMARDs) have provided considerable relief from pain and an enhanced sense of wellbeing for a large segment of AS patients. Despite these improvements, it remains unclear whether extended use of bDMARDs can indeed reduce the risk of spine fractures. PURPOSE: In this study, we aimed to investigate the evolving patterns and epidemiology of traumatic CS-Fxs in both AS and non-AS populations. We hypothesized that the risk of CS-Fxs among AS patients would show a decreasing trend over time, while the risk among non-AS patients would remain constant. STUDY DESIGN/SETTING: Retrospective cohort study based on a prospective database. PATIENT SAMPLE: A total of 3,598 consecutive patients with CS-Fxs were treated at Oslo University Hospital over an 8-year period. OUTCOME MEASURES: CS-Fxs in AS patients were contrasted with non-AS-related CS-Fxs in terms of temporal trends, age, sex, injury mechanism, associated cervical spinal cord injury (cSCI), need for surgical fixation, and 30-day mortality. METHODS: Data regarding all CS-Fxs diagnosed between 2015 and 2022 were extracted from the Southeast Norway population-based quality control database for traumatic CS-Fxs. Categorical data were summarized using frequencies, and continuous data were summarized using medians. The Wilcoxon rank-sum test was used to compare continuous variables, and the chi-squared test and Fischer exact test were used to compare categorical variables. To investigate the trend in the incidence of fractures, two different Poisson models were fitted with the number of non-AS and AS fractures as dependent variables and the year as the explanatory variable. RESULTS: Over an 8-year period, we registered 3,622 CS-Fxs in 3598 patients, with AS patients accounting for 125 of these fractures. Relative to their non-AS counterparts, AS patients presented a 9-fold and 8-fold higher risk of initial and subsequent CS-Fxs, respectively. We observed a declining trend in AS-related CS-Fxs with an annual linear decrease of 8.4% (p=.026), whereas non-AS-related CS-Fxs showed an annual linear increase of 3.7% (p<.001). AS patients sustaining CS-Fxs were typically older (median age 70 vs 63 years), predominantly male (89% vs 67%), and more frequently experienced injuries due to falls (82% vs 57%). They also exhibited a higher prevalence of subaxial CS-Fxs (91% vs 62%), fewer C0-C2 CS-Fxs (14% vs 44%), a higher rate of associated cSCI (21% vs 11%), and a greater tendency for surgical fixation (66% vs 21%). We observed a 30-day mortality rate of 11% in AS patients and 5.4% in non-AS patients (p=.005). CONCLUSIONS: The results of this study confirm the elevated risk of CS-Fxs among AS patients, although this risk appears to show a decreasing trend. The most plausible explanation for this risk reduction is the widespread application of bDMARDs.

Prompt closure versus gradual weaning of external ventricular drainage for hydrocephalus following aneurysmal subarachnoid haemorrhage: Protocol for the DRAIN randomised clinical trial.

BACKGROUND: Aneurysmal subarachnoid haemorrhage (aSAH) is a life-threatening disease caused by rupture of an intracranial aneurysm. A common complication following aSAH is hydrocephalus, for which placement of an external ventricular drain (EVD) is an important first-line treatment. Once the patient is clinically stable, the EVD is either removed or replaced by a ventriculoperitoneal shunt. The optimal strategy for cessation of EVD treatment is, however, unknown. Gradual weaning may increase the risk of EVD-related infection, whereas prompt closure carries a risk of acute hydrocephalus and redundant shunt implantations. We designed a randomised clinical trial comparing the two commonly used strategies for cessation of EVD treatment in patients with aSAH. METHODS: DRAIN is an international multi-centre randomised clinical trial with a parallel group design comparing gradual weaning versus prompt closure of EVD treatment in patients with aSAH. Participants are randomised to either gradual weaning which comprises a multi-step increase of resistance over days, or prompt closure of the EVD. The primary outcome is a composite outcome of VP-shunt implantation, all-cause mortality, or ventriculostomy-related infection. Secondary outcomes are serious adverse events excluding mortality, functional outcome (modified Rankin scale), health-related quality of life (EQ-5D) and Fatigue Severity Scale (FSS). Outcome assessment will be performed 6 months after ictus. Based on the sample size calculation (event proportion 80% in the gradual weaning group, relative risk reduction 20%, type I error 5%, power 80%), 122 patients are needed in each intervention group. Outcome assessment for the primary outcome, statistical analyses and conclusion drawing will be blinded. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03948256.

Bilateral calcification of the optic nerve sheath: A diagnostic dilemma.

PURPOSE: To present a case of symptomatic optic nerve sheath calcification and highlight clues and pitfalls for the final diagnosis: bilateral optic nerve sheath meningioma. OBSERVATIONS: A 48-year-old man presented with painless vision loss in his left eye and findings consistent with left optic nerve atrophy. Magnetic resonance imaging (MRI) displayed thinning of the left optic nerve without contrast-enhancement or evidence of compressive lesions. A supplementary computed tomography angiography (CTA) exposed scattered dural calcification, which included the optic nerves. This was regarded as an incidental finding. The initial diagnosis was ischemic optic neuropathy. Over the next two years, the vision loss in the left eye progressed. A CT of the orbits revealed extensive calcification surrounding both optic nerves. A second MRI was unchanged in comparison to the first MRI. The diagnosis was changed to idiopathic duro-optic calcification. The vision in the left eye further declined over another two years. Consecutive optical coherence tomography measurements of the peripapillary retinal nerve fiber layer suggested bilateral progressive thinning. A third MRI displayed progression of tubular contrast-enhancement surrounding the optic nerves. On the basis of this finding, the patient was finally diagnosed with a bilateral optic nerve sheath meningioma and received external beam radiotherapy. CONCLUSION AND IMPORTANCE: It is crucial to differentiate an optic nerve sheath meningioma from idiopathic calcification of the optic nerve. In the present case the initial MRI did not detect optic nerve sheath abnormalities. To better demonstrate characteristic calcification, additional CT imaging should be considered when a bilateral optic nerve sheath meningioma is suspected.

Traumatic brain injury-the effects of patient age on treatment intensity and mortality.

BACKGROUND: Ageing is associated with worse treatment outcome after traumatic brain injury (TBI). This association may lead to a self-fulfilling prophecy that affects treatment efficacy. The aim of the current study was to evaluate the role of treatment bias in patient outcomes by studying the intensity of diagnostic procedures, treatment, and overall 30-day mortality in different age groups of patients with TBI. METHODS: Included in this study was consecutively admitted patients with TBI, aged ≥ 15 years, with a cerebral CT showing intracranial signs of trauma, during the time-period between 2015-2018. Data were extracted from our prospective quality control registry for admitted TBI patients. As a measure of management intensity in different age groups, we made a composite score, where placement of intracranial pressure monitor, ventilator treatment, and evacuation of intracranial mass lesion each gave one point. Uni- and multivariate survival analyses were performed using logistic multinomial regression. RESULTS: A total of 1,571 patients with TBI fulfilled the inclusion criteria. The median age was 58 years (range 15-98), 70% were men, and 39% were ≥ 65 years. Head injury severity was mild in 706 patients (45%), moderate in 437 (28%), and severe in 428 (27%). Increasing age was associated with less management intensity, as measured using the composite score, irrespective of head injury severity. Multivariate analyses showed that the following parameters had a significant association with an increased risk of death within 30 days of trauma: increasing age, severe comorbidities, severe TBI, Rotterdam CT-score ≥ 3, and low management intensity. CONCLUSION: The present study indicates that the management intensity of hospitalised patients with TBI decreased with advanced age and that low management intensity was associated with an increased risk of 30-day mortality. This suggests that the high mortality among elderly TBI patients may have an element of treatment bias and could in the future be limited with a more aggressive management regime.