Feasibility of Hidden Markov Models for the Description of Time-Varying Physiologic State After Severe Traumatic Brain Injury.

OBJECTIVES: Continuous assessment of physiology after traumatic brain injury is essential to prevent secondary brain insults. The present work aims at the development of a method for detecting physiologic states associated with the outcome from time-series physiologic measurements using a hidden Markov model. DESIGN: Unsupervised clustering of hourly values of intracranial pressure/cerebral perfusion pressure, the compensatory reserve index, and autoregulation status was attempted using a hidden Markov model. A ternary state variable was learned to classify the patient's physiologic state at any point in time into three categories ("good," "intermediate," or "poor") and determined the physiologic parameters associated with each state. SETTING: The proposed hidden Markov model was trained and applied on a large dataset (28,939 hr of data) using a stratified 20-fold cross-validation. PATIENTS: The data were collected from 379 traumatic brain injury patients admitted to Addenbrooke's Hospital, Cambridge between 2002 and 2016. INTERVENTIONS: Retrospective observational analysis. MEASUREMENTS AND MAIN RESULTS: Unsupervised training of the hidden Markov model yielded states characterized by intracranial pressure, cerebral perfusion pressure, compensatory reserve index, and autoregulation status that were physiologically plausible. The resulting classifier retained a dose-dependent prognostic ability. Dynamic analysis suggested that the hidden Markov model was stable over short periods of time consistent with typical timescales for traumatic brain injury pathogenesis. CONCLUSIONS: To our knowledge, this is the first application of unsupervised learning to multidimensional time-series traumatic brain injury physiology. We demonstrated that clustering using a hidden Markov model can reduce a complex set of physiologic variables to a simple sequence of clinically plausible time-sensitive physiologic states while retaining prognostic information in a dose-dependent manner. Such states may provide a more natural and parsimonious basis for triggering intervention decisions

Modelling of Brain Deformation After Decompressive Craniectomy.

Hyperelastic finite element models, with either an idealized cylindrical geometry or with realistic craniectomy geometries, were used to explore clinical issues relating to decompressive craniectomy. The potential damage in the brain tissue was estimated by calculating the volume of material exceeding a critical shear strain. Results from the idealized model showed how the potentially damaged volume of brain tissue increased with an increasing volume of brain tissue herniating from the skull cavity and with a reduction in craniectomy area. For a given herniated volume, there was a critical craniectomy diameter where the volume exceeding a critical shear strain fell to zero. The effects of details at the craniectomy edge, specifically a fillet radius and a chamfer on the bone margin, were found to be relatively slight, assuming that the dura is retained to provide effective protection. The location in the brain associated with volume expansion and details of the material modeling were found to have a relatively modest effect on the predicted damage volume. The volume of highly sheared material in the realistic models of the craniectomy varied roughly in line with differences in the craniectomy area.TLF acknowledges funding from the Engineering and Physical Sciences Research Council (EPSRC). BW is supported by the Studienstiftung des deutschen Volkes, the Max Weber-Programm and the Stiftung Maximilianeum. AGK is supported by a Royal College of Surgeons of England Research Fellowship (funded by the Freemasons and the Rosetrees Trust), a National Institute of Health Research (NIHR) Academic Clinical Fellowship and a Raymond and Beverly Sackler Studentship. PJH is supported by a NIHR Research Professorship and the NIHR Cambridge Biomedical Research Centre.This is the final version of the article. It first appeared from Springer via http://dx.doi.org/10.1007/s10439-016-1666-

Survival Trends After Surgery for Acute Subdural Hematoma in Adults Over a 20-year Period.

OBJECTIVE: We sought to determine 30-day survival trends and prognostic factors following surgery for acute subdural hematomas (ASDHs) in England and Wales over a 20-year period. SUMMARY OF BACKGROUND DATA: ASDHs are still considered the most lethal type of traumatic brain injury. It remains unclear whether the adjusted odds of survival have improved significantly over time. METHODS: Using the Trauma Audit and Research Network (TARN) database, we analyzed ASDH cases in the adult population (>16 yrs) treated surgically between 1994 and 2013. Two thousand four hundred ninety-eight eligible cases were identified. Univariable and multiple logistic regression analyses were performed, using multiple imputation for missing data. RESULTS: The cohort was 74% male with a median age of 48.9 years. Over half of patients were comatose at presentation (53%). Mechanism of injury was due to a fall (2 m 24%), road traffic collision (25%), and other (17%). Thirty-six per cent of patients presented with polytrauma. Gross survival increased from 59% in 1994 to 1998 to 73% in 2009 to 2013. Under multivariable analysis, variables independently associated with survival were year of injury, Glasgow Coma Scale, Injury Severity Score, age, and pupil reactivity. The time interval from injury to craniotomy and direct admission to a neurosurgical unit were not found to be significant prognostic factors. CONCLUSIONS: A significant improvement in survival over the last 20 years was observed after controlling for multiple prognostic factors. Prospective trials and cohort studies are expected to elucidate the distribution of functional outcome in survivors.AGK is supported by a Royal College of Surgeons of England Research Fellowship, a National Institute for Health Research (NIHR) Academic Clinical Fellowship, and a Raymond and Beverly Sackler Studentship. PJH is supported by a NIHR Research Professorship and the NIHR Cambridge Biomedical Research Centre.This is the author accepted manuscript. It is currently under an indefinite embargo pending publication by Wolters Kluwer

Observations on the Cerebral Effects of Refractory Intracranial Hypertension After Severe Traumatic Brain Injury

Funder: Woolf Fisher TrustAbstract: Background: Raised intracranial pressure (ICP) is a prominent cause of morbidity and mortality after severe traumatic brain injury (TBI). However, in the clinical setting, little is known about the cerebral physiological response to severe and prolonged increases in ICP. Methods: Thirty-three severe TBI patients from a single center who developed severe refractory intracranial hypertension (ICP > 40 mm Hg for longer than 1 h) with ICP, arterial blood pressure, and brain tissue oxygenation (PBTO2) monitoring (subcohort, n = 9) were selected for retrospective review. Secondary parameters reflecting autoregulation (including pressure reactivity index—PRx, which was available in 24 cases), cerebrospinal compensatory reserve (RAP), and ICP pulse amplitude were calculated. Results: PRx deteriorated from 0.06 ± 0.26 a.u. at baseline levels of ICP to 0.57 ± 0.24 a.u. (p 50 mm Hg). In 4 cases, PRx was impaired (> 0.25 a.u.) before ICP was raised above 25 mm Hg. Concurrently, PBTO2 decreased from 27.3 ± 7.32 mm Hg at baseline ICP to 12.68 ± 7.09 mm Hg at high levels of ICP (p < 0.001). The pulse amplitude of the ICP waveform increased with increasing ICP but showed an ‘upper breakpoint’—whereby further increases in ICP lead to decreases in pulse amplitude—in 6 out of the 33 patients. Discussion: Severe intracranial hypertension after TBI leads to decreased brain oxygenation, impaired pressure reactivity, and changes in the pulse amplitude of ICP. Impaired pressure reactivity may denote increased risk of developing refractory intracranial hypertension in some patients

Integration of paper microfluidic sensors into contact lenses for tear fluid analysis

In this article, using the integration of paper microfluidics within laser-inscribed commercial contact lenses, we demonstrate the multiplexed detection of clinically relevant analytes including hydrogen ions, proteins, glucose, nitrites and l-ascorbic acid, all sampled directly from model tears. In vitro measurements involved the optimization of colorimetric assays, with readouts collected, stored and analyzed using a bespoke Tears Diagnostics smartphone application prototype. We demonstrate the potential of the device to perform discrete measurements either for medical diagnosis or disease screening in the clinic or at the point-of-care (PoC), with future applications including monitoring of ocular infections, uveitis, diabetes, keratopathies and assessing oxidative stress

Activation of Hepatic Lipase Expression by Oleic Acid: Possible Involvement of USF1

Polyunsaturated fatty acids affect gene expression mainly through peroxisome proliferator-activated receptors (PPARs) and sterol regulatory element binding proteins (SREBPs), but how monounsaturated fatty acids affect gene expression is poorly understood. In HepG2 cells, oleate supplementation has been shown to increase secretion of hepatic lipase (HL). We hypothesized that oleate affects HL gene expression at the transcriptional level. To test this, we studied the effect of oleate on HL promoter activity using HepG2 cells and the proximal HL promoter region (700 bp). Oleate increased HL expression and promoter activity 1.3–2.1 fold and reduced SREBP activity by 50%. Downregulation of SREBP activity by incubation with cholesterol+25-hydroxycholesterol had no effect on HL promoter activity. Overexpression of SREBP2, but not SREBP1, reduced HL promoter activity, which was effected mainly through the USF1 binding site at -307/-312. Oleate increased the nuclear abundance of USF1 protein 2.7 ± 0.6 fold, while USF1 levels were reduced by SREBP2 overexpression. We conclude that oleate increases HL gene expression via USF1. USF1 may be an additional fatty acid sensor in liver cells

Decompressive craniectomy following traumatic brain injury: developing the evidence base.

In the context of traumatic brain injury (TBI), decompressive craniectomy (DC) is used as part of tiered therapeutic protocols for patients with intracranial hypertension (secondary or protocol-driven DC). In addition, the bone flap can be left out when evacuating a mass lesion, usually an acute subdural haematoma (ASDH), in the acute phase (primary DC). Even though, the principle of "opening the skull" in order to control brain oedema and raised intracranial pressure has been practised since the beginning of the 20th century, the last 20 years have been marked by efforts to develop the evidence base with the conduct of randomised trials. This article discusses the merits and challenges of this approach and provides an overview of randomised trials of DC following TBI. An update on the RESCUEicp study, a randomised trial of DC versus advanced medical management (including barbiturates) for severe and refractory post-traumatic intracranial hypertension is provided. In addition, the rationale for the RESCUE-ASDH study, the first randomised trial of primary DC versus craniotomy for adult head-injured patients with an ASDH, is presented.The RESCUEicp study is funded by the Efficacy and Mechanism Evaluation (EME) Programme, an MRC and National Institute for Health Research (NIHR) partnership (project number 09/800/16). The views expressed in this publication are those of the authors and not necessarily those of the MRC, NHS, NIHR or the Department of Health. The RESCUE-ASDH study is funded by the NIHR Health Technology Assessment programme (project number 12/35/57). The views and opinions expressed herein are those of the authors and do not necessarily reflect those of the Health Technology Assessment programme, NIHR, NHS or the Department of Health.This is the final version of the article. It first appeared from Taylor & Francis via https://doi.org/10.3109/02688697.2016.115965

Cost-effectiveness of craniotomy versus decompressive craniectomy for UK patients with traumatic acute subdural haematoma

Objective To estimate the cost-effectiveness of craniotomy, compared with decompressive craniectomy (DC) in UK patients undergoing evacuation of acute subdural haematoma (ASDH). Design Economic evaluation undertaken using health resource use and outcome data from the 12-month multicentre, pragmatic, parallel-group, randomised, Randomised Evaluation of Surgery with Craniectomy for Patients Undergoing Evacuation-ASDH trial. Setting UK secondary care. Participants 248 UK patients undergoing surgery for traumatic ASDH were randomised to craniotomy (N=126) or DC (N=122). Interventions Surgical evacuation via craniotomy (bone flap replaced) or DC (bone flap left out with a view to replace later: cranioplasty surgery). Main outcome measures In the base-case analysis, costs were estimated from a National Health Service and Personal Social Services perspective. Outcomes were assessed via the quality-adjusted life-years (QALY) derived from the EuroQoL 5-Dimension 5-Level questionnaire (cost-utility analysis) and the Extended Glasgow Outcome Scale (GOSE) (cost-effectiveness analysis). Multiple imputation and regression analyses were conducted to estimate the mean incremental cost and effect of craniotomy compared with DC. The most cost-effective option was selected, irrespective of the level of statistical significance as is argued by economists. Results In the cost-utility analysis, the mean incremental cost of craniotomy compared with DC was estimated to be −£5520 (95% CI −£18 060 to £7020) with a mean QALY gain of 0.093 (95% CI 0.029 to 0.156). In the cost-effectiveness analysis, the mean incremental cost was estimated to be −£4536 (95% CI −£17 374 to £8301) with an OR of 1.682 (95% CI 0.995 to 2.842) for a favourable outcome on the GOSE. Conclusions In a UK population with traumatic ASDH, craniotomy was estimated to be cost-effective compared with DC: craniotomy was estimated to have a lower mean cost, higher mean QALY gain and higher probability of a more favourable outcome on the GOSE (though not all estimated differences between the two approaches were statistically significant). Ethics Ethical approval for the trial was obtained from the North West—Haydock Research Ethics Committee in the UK on 17 July 2014 (14/NW/1076). Trial registration number ISRCTN87370545

Decompressive craniectomy versus craniotomy for acute subdural hematoma

BACKGROUND: Traumatic acute subdural hematomas frequently warrant surgical evacuation by means of a craniotomy (bone flap replaced) or decompressive craniectomy (bone flap not replaced). Craniectomy may prevent intracranial hypertension, but whether it is associated with better outcomes is unclear. METHODS: We conducted a trial in which patients undergoing surgery for traumatic acute subdural hematoma were randomly assigned to undergo craniotomy or decompressive craniectomy. An inclusion criterion was a bone flap with an anteroposterior diameter of 11 cm or more. The primary outcome was the rating on the Extended Glasgow Outcome Scale (GOSE) (an 8-point scale, ranging from death to “upper good recovery” [no injury-related problems]) at 12 months. Secondary outcomes included the GOSE rating at 6 months and quality of life as assessed by the EuroQol Group 5-Dimension 5-Level questionnaire (EQ-5D-5L). RESULTS: A total of 228 patients were assigned to the craniotomy group and 222 to the decompressive craniectomy group. The median diameter of the bone flap was 13 cm (interquartile range, 12 to 14) in both groups. The common odds ratio for the differences across GOSE ratings at 12 months was 0.85 (95% confidence interval, 0.60 to 1.18; P=0.32). Results were similar at 6 months. At 12 months, death had occurred in 30.2% of the patients in the craniotomy group and in 32.2% of those in the craniectomy group; a vegetative state occurred in 2.3% and 2.8%, respectively, and a lower or upper good recovery occurred in 25.6% and 19.9%. EQ-5D-5L scores were similar in the two groups at 12 months. Additional cranial surgery within 2 weeks after randomization was performed in 14.6% of the craniotomy group and in 6.9% of the craniectomy group. Wound complications occurred in 3.9% of the craniotomy group and in 12.2% of the craniectomy group. CONCLUSIONS: Among patients with traumatic acute subdural hematoma who underwent craniotomy or decompressive craniectomy, disability and quality-of-life outcomes were similar with the two approaches. Additional surgery was performed in a higher proportion of the craniotomy group, but more wound complications occurred in the craniectomy group. (Funded by the National Institute for Health and Care Research; RESCUE-ASDH ISRCTN Registry number, ISRCTN87370545.

Traumatic brain injury: integrated approaches to improve prevention, clinical care, and research

No abstract available