Comparison of several prognostic tools in traumatic brain injury including S100B.

PRIMARY OBJECTIVE: To identify which tool (a model, a biomarker or a combination of these) has better prognostic strength in traumatic brain injury (TBI). DESIGN AND METHODS: Data of 100 patients were analysed. TBI prognostic model B, constructed in Trauma Audit and Research Network (TARN), was run on the dataset and then S100B was added to this model. Another model was developed containing only S100B and, subsequently, other important predictors were added to assess the enhancement of the predictive power. The outcome measures were survival and favourable outcome. RESULTS: No difference between performance of the prognostic model or S100B in isolation is observed. Addition of S100B to the prognostic model improves the performance (e.g. AUC, R(2) Nagelkerke and classification accuracy of TARN model B to predict survival increase respectively from 0.66, 0.11 and 70% to 0.77, 0.25 and 75%). Similarly, the predictive power of S100B increases by adding other predictors (e.g. AUC (0.69 vs. 0.79), R(2) Nagelkerke (0.15 vs. 0.30) and classification accuracy (73% vs. 77%) for survival prediction). CONCLUSION: A better prognostic tool than those currently available may be a combination of clinical predictors with a biomarker.

Influence of acute fasting on pain tolerance in healthy subjects: a randomised crossover study.

Background: Although chronic pain and obesity are global health crises with substantial healthcare costs, little is known about the relationship between pain perception and eating behaviours. Food consumption has been reported to provide an analgesic effect by the release of neurotransmitters modulating the pain network. However, whether short-term (acute) fasting affects pain perception remains unclear. Purpose: This study aimed to investigate the effect of acute fasting on pain perception and whether attention and mood changes drove the observed changes. Patients and methods: The cold pressor test (CPT) was used to investigate the pain tolerance of 25 healthy participants in both non-fasting and 12-h fasting sessions. They were randomised to either session with a crossover to the other after at least 24 h, with the experimenter blinded to the sessions. The pain tolerance was measured using a Stroop task in both attentive and distracted states. The Profile of Mood States (POMS) questionnaire was used to capture the mood, and a 10-point hunger scale was used to measure hunger. Mixed-effects models were used to investigate the influence of fasting and distraction on pain perception, accounting for the repeated measures. Results: Fasting reduced CPT pain tolerance, with fasting participants twice as likely to withdraw their hands early (hazard ratio = 2.4, 95% CI: 1.3-4.5). Though men tolerated CPT pain longer than women, there was no evidence that men responded to fasting differently than women (p = 0.9). In addition, no evidence supporting that fasting affected attention or mood was found. Nonetheless, it increased hunger scores by 2.7 points on a 10-point scale (95% CI: 1.2-4.2) and decreased blood glucose concentration levels by 0.51 mmol/L (95% CI: 0.19-0.84). Conclusion: Acute fasting reduces pain tolerance in the healthy participants, and this effect is independent of gender and attention or mood changes.

Morning and evening salivary cortisol levels in patients with chronic widespread pain and those at high risk.

BACKGROUND: Hypothalamic-Pituitary-Adrenal (HPA) axis dysregulation has been implicated in chronic widespread pain (CWP); the hallmark of fibromyalgia (FM). This is the first study to compare HPA axis changes in individuals with CWP and those at high risk of symptom development. METHODS: We sought to determine differences in morning and evening salivary cortisol levels in FM (n = 19), those at-risk (n = 20) and pain-free controls (n = 17). Risk factors included non-CWP pain, somatic symptoms, illness behaviour and sleep disturbance. We conducted the study in the absence of centrally acting medication, to address limitations of previous research. RESULTS: Repeated measures ANOVA revealed significant main effects of group (p = 0.003), and time of day (p = 0.002), with no significant interaction. Cortisol levels were higher in FM (p = 0.027) and at-risk (p = 0.003) groups, compared to controls, but there was no significant difference between FM and at-risk groups. The main effect of group remained significant with sleep problems (p = 0.021) and life events (p = 0.007), but was not significant with anxiety (p = 0.076) or depression (p = 0.098) scores as covariates. With sleep problems as a covariate, cortisol levels remained significantly higher only in the at-risk group (p = 0.017). CONCLUSIONS: This study indicates elevated salivary cortisol in FM and those at high risk, and identifies anxiety, depression and sleep problems as potential contributing factors. The results shed light on the dynamic relationship between stress, mood and sleep disorders and the brain's resilience to pain. SIGNIFICANCE: This study examines neurobiological changes in chronic widespread pain and high risk individuals. One strength of the study is the absence of centrally acting medication. We found high salivary cortisol common to Fibromyalgia and those at risk and identified contributing factors. Our results offer insight into the early mechanistic changes underlying Fibromyalgia development and open up possibilities for early diagnosis and prevention.

Individuals with chronic pain have the same response to placebo analgesia as healthy controls in terms of magnitude and reproducibility.

It is unclear whether a diagnosis of chronic pain is associated with an increase or decrease in the placebo response. The aim of this study was to use an experimental placebo conditioning paradigm to test whether expectancy for pain relief impacts on acute pain perception in individuals with a chronic pain diagnosis of osteoarthritis (OA) or fibromyalgia (FM), compared to healthy individuals (HIs). An inert cream was applied to the dominant forearm of participants (60 OA, 79 FM, and 98 HI), randomly assigned to either a placebo or control group. In both groups, an inactive cream was applied to the dominant forearm. The placebo group was told this may or may not be a local anaesthetic cream, whereas the control group was told the cream was inactive. Laser pain was delivered, and numerical pain intensity ratings collected before, during, and after cream application, along with expectation of pain relief and anxiety. The procedure was repeated 2 weeks later to assess reproducibility. There was a significant reduction in pain in the placebo group, independent of clinical diagnosis. Diagnostic groups (OA, FM, and HI) did not differ in their magnitude of placebo analgesia or expectancy of pain relief. The results were similar in the repeat session. The results demonstrate that individuals with chronic pain respond to experimental placebo analgesia in a similar and reproducible manner as HIs, despite higher levels of psychological comorbidity. This has implications for using placebo analgesia in the treatment of chronic pain.

Predicting outcome after severe traumatic brain injury using the serum S100B biomarker: results using a single (24h) time-point.

BACKGROUND AND OBJECTIVES: In recent years, biochemical markers have been employed to predict the outcome of patients with traumatic brain injury (TBI). In mild TBI, S100B has shown the most promise as a marker of outcome. The objective of this study in patients with severe TBI was to: show the range of serum S100B levels during the acute phase after trauma: determine if S100B has potential to discriminate favourable from unfavourable outcome in patients with similar brain injury severity scores and to establish an S100B 'cut-off' predictive for death. METHODS: All patients with severe TBI, admitted to this neurointensive care unit within 24h of injury were eligible for inclusion in the study. One serum blood sample was obtained from each patient at the 24h post-injury time-point. S100B levels were measured using enzyme-linked immunosorbent assay. Injuries were coded using an internationally recognised injury severity scoring system (ISS). Three-month follow-up was undertaken with outcome assessed using the Glasgow outcome score (GOS). RESULTS: One hundred patients were recruited. Serum S100B levels ranged from 0.08 to 12.62microgL(-1) S100B levels were significantly higher in patients with a GOS of 1 (death) 2 and 3 (unfavourable outcome) compared with those with GOS 4 and 5 (good recovery). In this study a cut-off point of 0.53microgL(-1) has sensitivity of >80% and specificity of 60% to predict unfavourable outcome and 49% to predict death. CONCLUSION: In 100 patients studied with similar brain injury severity scores, serum S100B measured at the 24-h time-point after injury is significantly associated with outcome but a cut-off 0.53microgL(-1) does not have good prognostic performance.

Infra-red thermometry: the reliability of tympanic and temporal artery readings for predicting brain temperature after severe traumatic brain injury.

INTRODUCTION: Temperature measurement is important during routine neurocritical care especially as differences between brain and systemic temperatures have been observed. The purpose of the study was to determine if infra-red temporal artery thermometry provides a better estimate of brain temperature than tympanic membrane temperature for patients with severe traumatic brain injury. METHODS: Brain parenchyma, tympanic membrane and temporal artery temperatures were recorded every 15-30 min for five hours during the first seven days after admission. RESULTS: Twenty patients aged 17-76 years were recruited. Brain and tympanic membrane temperature differences ranged from -0.8 degrees C to 2.5 degrees C (mean 0.9 degrees C). Brain and temporal artery temperature differences ranged from -0.7 degrees C to 1.5 degrees C (mean 0.3 degrees C). Tympanic membrane temperature differed from brain temperature by an average of 0.58 degrees C more than temporal artery temperature measurements (95% CI 0.31 degrees C to 0.85 degrees C, P < 0.0001). CONCLUSIONS: At temperatures within the normal to febrile range, temporal artery temperature is closer to brain temperature than is tympanic membrane temperature.

The effect of spontaneous alterations in brain temperature on outcome: a prospective observational cohort study in patients with severe traumatic brain injury.

There are few prospective studies reporting the effect of spontaneous temperature changes on outcome after severe traumatic brain injury (TBI). Where studies have been conducted, results are based on systemic rather than brain temperature per se. However, body temperature is not a reliable surrogate for brain temperature. Consequently, the effect of brain temperature changes on outcome in the acute phase after TBI is not clear. Continuous intraparenchymal brain temperature was measured in consecutive admissions of severe TBI patients during the course of the first 5 days of admission to the intensive care unit (ICU). Patients received minimal temperature altering therapy during their ICU stay. Logistic regression was used to explore the relationship between the initial, the 24-h mean, and the 48-h mean brain temperature with outcome for mortality at 30 days and outcome at 3 months. Multifactorial analysis was performed to account for potential confounders. At the 24-h time point, brain temperature within the range of 36.5°C to 38°C was associated with a lower probability of death (10-20%). Brain temperature outside of this range was associated with a higher probability of death and poor 3-month neurological outcome. After adjusting for other predictors of outcome, low brain temperature was independently associated with a worse outcome. Lower brain temperatures (below 37°C) are independently associated with a higher mortality rate after severe TBI. The results suggest that, contrary to current opinion, temperatures within the normal to moderate fever range during the acute post-TBI period do not impose an additional risk for a poor outcome after severe TBI.

Brain temperature and outcome after severe traumatic brain injury.

INTRODUCTION: In humans, raised body temperature is linked to poor outcome after brain injury. Because deviations between brain and body temperature have been reported after severe traumatic brain injury (TBI), the aim of this study was to explore the relationship between initial and mean brain temperature and survival at 3 months. METHODS: Intraparenchymal temperature was measured 3 - 4 cm within white matter. Logistic regression was used to explore linear and quadratic relationships between initial and average brain temperature and survival at 3 months. RESULTS: In 36 patients, initial brain temperatures ranged from 33.5 to 39.2 degrees C (median 37.4 degrees C). There was no evidence of an association between initial brain temperature and risk of death, either linear (odds ratio [OR] 95% confidence interval [CI] = 1.3 [0.68 to 2.5], p = 0.42) or quadratic ( p = 0.26). Assuming a linear relationship, patients with higher mean brain temperatures were less likely to die: OR (95% CI) for death per 1 degrees C was 0.31 (0.09 to 1.1), p = 0.06. However, by fitting the quadratic relationship, there was a suggestion that both high and low temperatures were associated with increased risk of death: p = 0.06. CONCLUSION: Initial brain temperature measured shortly after admission did not predict outcome. There is a suggestion that patients with "middle range" temperatures were less likely to die.