A bump in the night: a 15-year retrospective analysis of urgent inpatient and emergency CT reporting out of hours in a tertiary referral centre.

AIM: To assess the impact on specialty trainee (ST) experience of out-of-hours (OOH) working, focusing on what might be improved with both patient safety and staff wellbeing in mind. MATERIALS AND METHODS: The number of acute computed tomography (CT) examinations reported OOH over the last 15 years (2007-2021) at Oxford University Hospitals NHS Foundation Trust was analysed. Qualitative data from the radiology STs participating in the acute OOH rotas were obtained using questionnaires during winter months in 2019 and 2021, before and after the introduction of an OOH CT outsourcing service in 2020. RESULTS: Overnight acute CT has increased over 10-fold over the last decade to almost 50 CT examinations in 2021, and similar increases were observed during evening and weekend shifts. The option to outsource acute CT on an ad hoc basis was introduced in 2020 to manage the increase in demand. This resulted in a statistically significant improvement in the STs' level of reported satisfaction for OOH shifts (p<0.018), despite significantly increased perception of how busy the shifts were (p<0.035). CONCLUSION: OOH acute CT reporting at Oxford NHS Foundation Trust has increased dramatically over the previous 15 years. Working patterns and resources have changed incrementally to absorb this increase in demand, most recently with the option for outsourcing at times of peak demand. The trend for increasing OOH CT demand has considerable implications for future resource planning.

Hippocampal Blood Flow Is Increased After 20 min of Moderate-Intensity Exercise.

Long-term exercise interventions have been shown to be a potent trigger for both neurogenesis and vascular plasticity. However, little is known about the underlying temporal dynamics and specifically when exercise-induced vascular adaptations first occur, which is vital for therapeutic applications. In this study, we investigated whether a single session of moderate-intensity exercise was sufficient to induce changes in the cerebral vasculature. We employed arterial spin labeling magnetic resonance imaging to measure global and regional cerebral blood flow (CBF) before and after 20 min of cycling. The blood vessels' ability to dilate, measured by cerebrovascular reactivity (CVR) to CO2 inhalation, was measured at baseline and 25-min postexercise. Our data showed that CBF was selectively increased by 10-12% in the hippocampus 15, 40, and 60 min after exercise cessation, whereas CVR to CO2 was unchanged in all regions. The absence of a corresponding change in hippocampal CVR suggests that the immediate and transient hippocampal adaptations observed after exercise are not driven by a mechanical vascular change and more likely represents an adaptive metabolic change, providing a framework for exploring the therapeutic potential of exercise-induced plasticity (neural, vascular, or both) in clinical and aged populations.

Calibrated fMRI for mapping absolute CMRO2: Practicalities and prospects.

Functional magnetic resonance imaging (fMRI) is an essential workhorse of modern neuroscience, providing valuable insight into the functional organisation of the brain. The physiological mechanisms underlying the blood oxygenation level dependent (BOLD) effect are complex and preclude a straightforward interpretation of the signal. However, by employing appropriate calibration of the BOLD signal, quantitative measurements can be made of important physiological parameters including the absolute rate of cerebral metabolic oxygen consumption or oxygen metabolism (CMRO2) and oxygen extraction (OEF). The ability to map such fundamental parameters has the potential to greatly expand the utility of fMRI and to broaden its scope of application in clinical research and clinical practice. In this review article we discuss some of the practical issues related to the calibrated-fMRI approach to the measurement of CMRO2. We give an overview of the necessary precautions to ensure high quality data acquisition, and explore some of the pitfalls and challenges that must be considered as it is applied and interpreted in a widening array of diseases and research questions.

Dual-calibrated fMRI measurement of absolute cerebral metabolic rate of oxygen consumption and effective oxygen diffusivity.

Dual-calibrated fMRI is a multi-parametric technique that allows for the quantification of the resting oxygen extraction fraction (OEF), the absolute rate of cerebral metabolic oxygen consumption (CMRO2), cerebral vascular reactivity (CVR) and baseline perfusion (CBF). It combines measurements of arterial spin labelling (ASL) and blood oxygenation level dependent (BOLD) signal changes during hypercapnic and hyperoxic gas challenges. Here we propose an extension to this methodology that permits the simultaneous quantification of the effective oxygen diffusivity of the capillary network (DC). The effective oxygen diffusivity has the scope to be an informative biomarker and useful adjunct to CMRO2, potentially providing a non-invasive metric of microvascular health, which is known to be disturbed in a range of neurological diseases. We demonstrate the new method in a cohort of healthy volunteers (n = 19) both at rest and during visual stimulation. The effective oxygen diffusivity was found to be highly correlated with CMRO2 during rest and activation, consistent with previous PET observations of a strong correlation between metabolic oxygen demand and effective diffusivity. The increase in effective diffusivity during functional activation was found to be consistent with previously reported increases in capillary blood volume, supporting the notion that measured oxygen diffusivity is sensitive to microvascular physiology.

Patterns of Growth and Decline in Lung Function in Persistent Childhood Asthma.

BACKGROUND: Tracking longitudinal measurements of growth and decline in lung function in patients with persistent childhood asthma may reveal links between asthma and subsequent chronic airflow obstruction. METHODS: We classified children with asthma according to four characteristic patterns of lung-function growth and decline on the basis of graphs showing forced expiratory volume in 1 second (FEV1), representing spirometric measurements performed from childhood into adulthood. Risk factors associated with abnormal patterns were also examined. To define normal values, we used FEV1 values from participants in the National Health and Nutrition Examination Survey who did not have asthma. RESULTS: Of the 684 study participants, 170 (25%) had a normal pattern of lung-function growth without early decline, and 514 (75%) had abnormal patterns: 176 (26%) had reduced growth and an early decline, 160 (23%) had reduced growth only, and 178 (26%) had normal growth and an early decline. Lower baseline values for FEV1, smaller bronchodilator response, airway hyperresponsiveness at baseline, and male sex were associated with reduced growth (P<0.001 for all comparisons). At the last spirometric measurement (mean [±SD] age, 26.0±1.8 years), 73 participants (11%) met Global Initiative for Chronic Obstructive Lung Disease spirometric criteria for lung-function impairment that was consistent with chronic obstructive pulmonary disease (COPD); these participants were more likely to have a reduced pattern of growth than a normal pattern (18% vs. 3%, P<0.001). CONCLUSIONS: Childhood impairment of lung function and male sex were the most significant predictors of abnormal longitudinal patterns of lung-function growth and decline. Children with persistent asthma and reduced growth of lung function are at increased risk for fixed airflow obstruction and possibly COPD in early adulthood. (Funded by the Parker B. Francis Foundation and others; ClinicalTrials.gov number, NCT00000575.).

Effect of obesity on sinonasal disease in asthma.

OBJECTIVE: Sinonasal disease can contribute to poor asthma control. There are reports that link obesity with an increased prevalence of sinonasal disease, but no studies evaluating the severity of sinonasal disease in obese asthmatics, and how this impacts asthma control. The purpose of the current study was to determine if obesity is associated with increased severity of sinonasal disease, and/or affects response to nasal corticosteroid treatment in asthma. METHODS: This study included 236 adults participating in a 24-week randomized, double-masked, placebo-controlled study of nasal mometasone for the treatment of poorly controlled asthma. Sinonasal disease severity was assessed using validated questionnaires, and compared in participants of differing BMIs. Eosinophilic inflammation was assessed using markers in nasal lavage, serum and exhaled nitric oxide. Response to treatment was compared in different BMI groups. RESULTS: Obesity had no effect on the severity of sinonasal disease symptoms in asthmatics (Sino-Nasal Outcome Test 22 (SNOT 22) score [mean ± SD] 35.4 ± 18.5, 40.2 ± 22.8, and 39.1 ± 21.7, p = 0.43, in lean, overweight and obese participants), nor on nasal, bronchial or systemic markers of allergic inflammation. Nasal steroids had some limited effects on symptoms, lung function and inflammatory markers in lean participants, but no detectable effect was found in obese patients. CONCLUSIONS: Obesity does not affect severity of sinonasal disease in patients with asthma; the association of sinonasal disease symptoms with increased asthma severity and markers of Type 2 inflammation are consistent across all BMI groups. The response of obese patients to nasal corticosteroids requires further study.

A forward modelling approach for the estimation of oxygen extraction fraction by calibrated fMRI.

The measurement of the absolute rate of cerebral metabolic oxygen consumption (CMRO2) is likely to offer a valuable biomarker in many brain diseases and could prove to be important in our understanding of neural function. As such there is significant interest in developing robust MRI techniques that can quantify CMRO2 non-invasively. One potential MRI method for the measurement of CMRO2 is via the combination of fMRI and cerebral blood flow (CBF) data acquired during periods of hypercapnic and hyperoxic challenges. This method is based on the combination of two, previously independent, signal calibration techniques. As such analysis of the data has been approached in a stepwise manner, feeding the results of one calibration experiment into the next. Analysing the data in this manner can result in unstable estimates of the output parameter (CMRO2), due to the propagation of errors along the analysis pipeline. Here we present a forward modelling approach that estimates all the model parameters in a one-step solution. The method is implemented using a regularized non-linear least squares approach to provide a robust and computationally efficient solution. The proposed framework is compared with previous analytical approaches using modelling studies and in vivo acquisitions in healthy volunteers (n=10). The stability of parameter estimates is demonstrated to be superior to previous methods (both in vivo and in simulation). In vivo estimates made with the proposed framework also show better agreement with expected physiological variation, demonstrating a strong negative correlation between baseline CBF and oxygen extraction fraction. It is anticipated that the proposed analysis framework will increase the reliability of absolute CMRO2 measurements made with calibrated BOLD.

Can a simple test of functional capacity add to the clinical assessment of diabetes?

AIM: To identify impairment in functional capacity associated with complicated and non-complicated diabetes using the 6-min walk distance test. METHODS: We enrolled 111 adults, aged ≥40 years, with Type 2 diabetes from a hospital facility and 150 healthy control subjects of similar age and sex from a community site in Lima, Peru. All participants completed a 6-min walk test. RESULTS: The mean age of the 261 participants was 58.3 years, and 43.3% were male. Among those with diabetes, 67 (60%) had non-complicated diabetes and 44 (40%) had complications such as peripheral neuropathy, retinopathy or nephropathy. The mean unadjusted 6-min walk distances were 376 m and 394 m in adults with and without diabetes complications, respectively, vs 469 m in control subjects (P<0.001). In multivariable regression, the subjects with diabetes complications walked 84 m less far (95% CI -104 to -63 m) and those without complications walked 60 m less far (-77 to -42 m) than did control subjects. When using HbA1c level as a covariate in multivariable regression, participants walked 13 m less far (-16.9 to -9.9 m) for each % increase in HbA1c . CONCLUSIONS: The subjects with diabetes had lower functional capacity compared with healthy control subjects with similar characteristics. Differences in 6-min walk distance were even apparent in the subjects without diabetes complications. Potential mechanisms that could explain this finding are early cardiovascular disease or deconditioning.

Chronic exposure to biomass fuel smoke and markers of endothelial inflammation.

Indoor smoke exposure may affect cardiovascular disease (CVD) risk via lung-mediated inflammation, oxidative stress, and endothelial inflammation. We sought to explore the association between indoor smoke exposure from burning biomass fuels and a selected group of markers for endothelial inflammation. We compared serum concentrations of amyloid A protein, E-selectin, soluble intercellular adhesion molecule 1 (ICAM-1) and VCAM-1, von Willebrand factor (vWF), and high-sensitivity C-reactive protein (hs-CRP) in 228 biomass-exposed vs. 228 non-exposed participants living in Puno, Peru. Average age was 56 years (s.d. = 13), average BMI was 26.5 kg/m(2) (s.d. = 4.4), 48% were male, 59.4% completed high school, and 2% reported a physician diagnosis of CVD. In unadjusted analysis, serum levels of soluble ICAM-1 (330 vs. 302 ng/ml; P < 0.001), soluble VCAM-1 (403 vs. 362 ng/ml; P < 0.001), and E-selectin (54.2 vs. 52.7 ng/ml; P = 0.05) were increased in biomass-exposed vs. non-exposed participants, respectively, whereas serum levels of vWF (1148 vs. 1311 mU/ml; P < 0.001) and hs-CRP (2.56 vs. 3.12 mg/l; P < 0.001) were decreased, respectively. In adjusted analyses, chronic exposure to biomass fuels remained positively associated with serum levels of soluble ICAM-1 (P = 0.03) and VCAM-1 (P = 0.05) and E-selectin (P = 0.05), and remained negatively associated with serum levels of vWF (P = 0.02) and hs-CRP (P < 0.001). Daily exposure to biomass fuel smoke was associated with important differences in specific biomarkers of endothelial inflammation and may help explain accelerated atherosclerosis among those who are chronically exposed.

Prevalence and risk factors for allergic rhinitis in two resource-limited settings in Peru with disparate degrees of urbanization.

BACKGROUND: Allergic rhinitis is a disease with a high global disease burden, but risk factors that contribute to this condition are not well understood. OBJECTIVE: To assess the prevalence and risk factors of allergic rhinitis in two Peruvian populations with disparate degrees of urbanization. METHODS: We conducted a population-based, cross-sectional study on 1441 children aged 13-15 years at enrollment (mean age 14.9 years, 51% boys) to investigate the prevalence of allergic disease. We used a standardized, Spanish validated questionnaire to determine the prevalence of allergic rhinitis and asked about sociodemographics and family history of allergies. Children also underwent spirometry, exhaled nitric oxide, allergy skin testing to 10 common household allergens and provided a blood sample for measurement of 25OH vitamin D and total serum IgE. RESULTS: Overall prevalence of allergic rhinitis was 18% (95% CI 16% to 20%). When stratified by site, the prevalence of allergic rhinitis was 23% Lima vs. 13% in Tumbes (P < 0.001); however, this difference was no longer significant after controlling for subject-specific factors (P = 0.95). There was a strong association with other allergic diseases: 53% of children with asthma had allergic rhinitis vs. 15% in those without asthma (P < 0.001) and 42% of children with eczema vs. 17% of those without eczema (P < 0.001). Important risk factors for allergic rhinitis were parental rhinitis (adjusted OR = 3.0, 95% CI 1.9-4.7 for 1 parent and adjusted OR = 4.4, 95% CI 1.5-13.7 for 2 parents); allergic sensitization to common household aeroallergens (1.6, 1.1-2.3); being overweight (1.5, 1.0-2.3); exhaled nitric oxide ≥ 20 ppb (1.9, 1.3-2.7); and total serum IgE ≥ 95th percentile (2.4, 1.2-4.8). Population attributable risk of important factors for allergic rhinitis were 25% for high exhaled nitric oxide, 22% for allergic sensitization to common household aeroallergens, 22% for paternal rhinitis, 10% for being overweight and 7% for an elevated total serum IgE. CONCLUSION AND CLINICAL RELEVANCE: Allergic rhinitis was prevalent in both settings, and important risk factors include elevated exhaled nitric oxide, allergic sensitization to common household aeroallergens, parental rhinitis, being overweight and high total serum IgE. When considering subject-specific factors, the difference in prevalence between the urban and rural settings became non-important.

25-hydroxy vitamin D levels are associated with childhood asthma in a population-based study in Peru.

BACKGROUND: Vitamin D deficiency may be associated with an increased risk of asthma. OBJECTIVE: We studied the association between 25-hydroxy (25-OH) vitamin D deficiency and asthma prevalence in two Peruvian populations close to the equator but with disparate degrees of urbanization. METHODS: We conducted a population-based study in 1441 children in two communities in Peru, of which 1134 (79%) provided a blood sample for 25-OH vitamin D analysis. RESULTS: In these 1134 children, mean age was 14.8 years; 52% were boys; asthma and atopy prevalence was 12% in Lima vs. 3% in Tumbes (P < 0.001) and 59% in Lima vs. 41% in Tumbes (P < 0.001), respectively; and, mean 25-OH vitamin D level was 20.8 ng/mL in Lima vs. 30.1 ng/mL in Tumbes (P < 0.001). Prevalence of 25-OH vitamin D deficiency (< 20 ng/mL) was 47% in Lima vs. 7% in Tumbes (P < 0.001). In multi-variable logistic regression, we found that lower 25-OH vitamin D levels were associated with an increased odds of asthma (OR = 1.7 per each 10 ng/mL decrease in 25-OH vitamin D levels, 95% CI 1.2-2.6; P < 0.01). In stratified analyses, the association between lower 25-OH vitamin D levels and asthma was limited to children with atopy (OR = 2.2, 95% CI 1.3-3.6) and not in those without atopy (OR = 0.9, 95% CI 0.5-2.0). We did not find associations between 25-OH vitamin D levels and other clinical biomarkers for asthma, including exhaled nitric oxide, total serum IgE and pulmonary function. CONCLUSION AND CLINICAL RELEVANCE: Both asthma and 25-OH vitamin D deficiency were common among children living in Lima (latitude = 12.0 °S) but not among those in Tumbes (3.6 °S). The relationship between 25-OH vitamin D deficiency and asthma was similar in both sites and was limited among children with atopy. Future supplementation trials may need to consider stratification by atopy at the time of design.

The pathways for intelligible speech: multivariate and univariate perspectives.

An anterior pathway, concerned with extracting meaning from sound, has been identified in nonhuman primates. An analogous pathway has been suggested in humans, but controversy exists concerning the degree of lateralization and the precise location where responses to intelligible speech emerge. We have demonstrated that the left anterior superior temporal sulcus (STS) responds preferentially to intelligible speech (Scott SK, Blank CC, Rosen S, Wise RJS. 2000. Identification of a pathway for intelligible speech in the left temporal lobe. Brain. 123:2400-2406.). A functional magnetic resonance imaging study in Cerebral Cortex used equivalent stimuli and univariate and multivariate analyses to argue for the greater importance of bilateral posterior when compared with the left anterior STS in responding to intelligible speech (Okada K, Rong F, Venezia J, Matchin W, Hsieh IH, Saberi K, Serences JT,Hickok G. 2010. Hierarchical organization of human auditory cortex: evidence from acoustic invariance in the response to intelligible speech. 20: 2486-2495.). Here, we also replicate our original study, demonstrating that the left anterior STS exhibits the strongest univariate response and, in decoding using the bilateral temporal cortex, contains the most informative voxels showing an increased response to intelligible speech. In contrast, in classifications using local "searchlights" and a whole brain analysis, we find greater classification accuracy in posterior rather than anterior temporal regions. Thus, we show that the precise nature of the multivariate analysis used will emphasize different response profiles associated with complex sound to speech processing.

Understanding the contribution of neural and physiological signal variation to the low repeatability of emotion-induced BOLD responses.

Previous studies have reported low repeatability of BOLD activation measures during emotion processing tasks. It is not clear, however, whether low repeatability is a result of changes in the underlying neural signal over time, or due to insufficient reliability of the acquired BOLD signal caused by noise contamination. The aim of this study was to investigate the influence of "cleaning" the BOLD signal, by correcting for physiological noise and for differences in BOLD responsiveness, on measures of repeatability. Fifteen healthy volunteers were scanned on two different occasions, performing an emotion provocation task with faces (neutral, 50% fearful, 100% fearful) followed by a breath-hold paradigm to provide a marker of BOLD responsiveness. Repeatability of signal distribution (spatial repeatability) and repeatability of signal amplitude within two regions of interest (amygdala and fusiform gyrus) were estimated by calculating the intraclass correlation coefficient (ICC). Significant repeatability of signal amplitude was only found within the right amygdala during the perception of 50% fearful faces, but disappeared when physiological noise correction was performed. Spatial repeatability was higher within the fusiform gyrus than within the amygdala, and better at the group level than at the participant level. Neither physiological noise correction, nor consideration of BOLD responsiveness, assessed through the breath-holding, increased repeatability. The findings lead to the conclusion that low repeatability of BOLD response amplitude to emotional faces is more likely to be explained by the lack of stability in the underlying neural signal than by physiological noise contamination. Furthermore, reported repeatability might be a result of repeatability of task-correlated physiological variation rather than neural activity. This means that the emotion paradigm used in this study might not be useful for studies that require the BOLD response to be a stable measure of emotional processing, for example in the context of biomarkers.

Pharmacogenetics of asthma controller treatment.

The interpatient variability in response to asthma controllers is significant and associates with pharmacogenomic variability. The goal of the present study was to identify novel variants that associate with response to common asthma controllers: fluticasone, combination of fluticasone + salmeterol and montelukast with single nucleotide polymorphisms (SNPs) in ß2-adrenergic receptor, corticosteroid and leukotriene pathway candidate genes. Participants in a large clinical trial of step-down strategies volunteered for this pharmacogenetic study. A total of 169 SNPs in 26 candidate genes were genotyped in 189 Caucasian participants with asthma who took either fluticasone (100 µg bid), fluticasone propionate (100 µg) + salmeterol (50 µg) (FP/Salm) or montelukast (5 or 10 mg) each night for 16 weeks. Primary outcomes were the slopes of plots of Asthma Control Questionnaire (ACQ) scores versus time following randomization; and the percent change in percent predicted FEV1 (ΔFEV1%pred) from enrollment to the end of the study. Associations between SNPs and outcomes were analyzed using general linear models. False discovery rate and Bonferroni corrections were used to correct for multiple comparisons. In all, 16 SNPs in seven genes were significantly associated with outcomes. For FP/Salm, three SNPs in CHRM2 associated with ACQ slope (P=2.8 × 10⁻5), and rs1461496 in HSPA8 associated with ΔFEV1%pred. For fluticasone, five SNPs in CRHR1 (P=1.9 × 10⁻4), and three SNPs in COL2A1 associated with ACQ slope and ΔFEV1%pred, respectively. For montelukast, four SNPs in CHRM2 associated with ΔFEV1%pred and predicted an opposite effect compared with fluticasone (P=9 × 10⁻³). The present study indentified several novel SNPs that associate with response to common asthma controllers, and support further pharmacogenomic study and the use of genetic variants to personalize asthma treatment.

ALOX5 polymorphism associates with increased leukotriene production and reduced lung function and asthma control in children with poorly controlled asthma.

BACKGROUND: Identification of risk factors for reduced asthma control could improve the understanding and treatment of asthma. A promoter polymorphism in the 5-lipoxygenase gene affects gene expression and response to asthma therapy, but its impact on disease control remains unclear. OBJECTIVE: We sought to determine if the ALOX5 promoter SP1 tandem repeat polymorphism was associated with changes in cysteinyl leukotriene production, lung function, airway inflammation and asthma control score. METHODS: We analysed 270 children, 6- to 17-years old, with poorly controlled asthma enrolled in a 6-month clinical trial (NCT00604851). In secondary analysis, we associated the ALOX5 promoter SP1 tandem repeat polymorphism genotype (rs59439148) with asthma outcomes using both additive and recessive genetic models. We evaluated FEV1 percent predicted, symptom control, exhaled nitric oxide and urinary LTE4 levels. RESULTS: Of all children, 14.8% (40/270) (and 28% (38/135) of African Americans) carried two non-5-repeat variant alleles of rs59439148. Children who were homozygous for variant alleles had significantly higher urinary LTE4 levels (38 vs. 30 nmol/mol creatinine, P = 0.0134), significantly worse FEV1% predicted (84 vs. 91, P = 0.017) and a trend towards worse asthma control. FEV1% predicted values were significantly negatively correlated with urinary LTE4 (r = -0.192, P = 0.009). CONCLUSION AND CLINICAL RELEVANCE: Carrying two copies of a minor variant ALOX5 promoter SP1 tandem repeat allele contributes to increased cysLT exposure as determined by urinary LTE4 levels, reduced lung function and potentially worse asthma control. ALOX5 promoter SP1 tandem repeat genotype may be a risk factor for worse asthma outcomes.

Outcomes of traumatic brain injury patients in an adult intensive care unit of a South African regional hospital, without on-site neurosurgical service: A retrospective quantitative study on the neurological improvement at discharge.

Background: Traumatic brain injury (TBI) is a major cause of mortality and disability. The South African (SA) province of Kwazulu-Natal faces challenges in providing appropriate care for TBI patients owing to limited resources and delayed access to healthcare services. We aimed to assess the outcomes of patients with TBI who were treated at a hospital without a neurosurgical unit (NSU). Objectives: The primary objective was to compare the Glasgow Coma Scale (GCS) scores at admission and discharge from the intensive care unit (ICU) for patients with TBI receiving neuroprotection. Secondary objectives included analysing demographics and identifying predictive factors associated with GCS score improvement. Methods: This retrospective study analysed data from the already established ICU Integrated Critical Care Electronic Database. Data on patient demographics, mechanisms of injury and GCS scores were collected and analysed. Results: The analysis included 95 TBI patients, most of whom were young males. Interpersonal violence and transport-related trauma were the main causes of injury among patients. Approximately 63% of patients had a GCS score improvement >1 upon discharge from the ICU. Patients who received >12 hours of neuroprotection in the emergency department had significantly lower rates of improvement. Conclusion: Sixty-three percent of TBI patients had improved GCS scores by >1 on discharge from the ICU, but outcomes varied. Delayed ICU admission from the emergency department of >12 hours might contribute to worse outcomes. Timely neuroprotection, improved access to neurosurgical care and better understanding of the factors affecting outcomes are needed. Contribution of the study: This study explores the outcomes of patients with TBI admitted to a non-neurosurgical ICU. Factors contributing to a worse outcome are identified, highlighting the need for adequate numbers of ICU beds and prompt admission from the emergency department.

Implications for psychedelic-assisted psychotherapy: functional magnetic resonance imaging study with psilocybin.

BACKGROUND: Psilocybin is a classic psychedelic drug that has a history of use in psychotherapy. One of the rationales for its use was that it aids emotional insight by lowering psychological defences. AIMS: To test the hypothesis that psilocybin facilitates access to personal memories and emotions by comparing subjective and neural responses to positive autobiographical memories under psilocybin and placebo. METHOD: Ten healthy participants received two functional magnetic resonance imaging scans (2 mg intravenous psilocybin v. intravenous saline), separated by approximately 7 days, during which they viewed two different sets of 15 positive autobiographical memory cues. Participants viewed each cue for 6 s and then closed their eyes for 16 s and imagined re-experiencing the event. Activations during this recollection period were compared with an equivalent period of eyes-closed rest. We split the recollection period into an early phase (first 8 s) and a late phase (last 8 s) for analysis. RESULTS: Robust activations to the memories were seen in limbic and striatal regions in the early phase and the medial prefrontal cortex in the late phase in both conditions (P<0.001, whole brain cluster correction), but there were additional visual and other sensory cortical activations in the late phase under psilocybin that were absent under placebo. Ratings of memory vividness and visual imagery were significantly higher after psilocybin (P<0.05) and there was a significant positive correlation between vividness and subjective well-being at follow-up (P<0.01). CONCLUSIONS: Evidence that psilocybin enhances autobiographical recollection implies that it may be useful in psychotherapy either as a tool to facilitate the recall of salient memories or to reverse negative cognitive biases.

Taking into account latency, amplitude, and morphology: improved estimation of single-trial ERPs by wavelet filtering and multiple linear regression.

Across-trial averaging is a widely used approach to enhance the signal-to-noise ratio (SNR) of event-related potentials (ERPs). However, across-trial variability of ERP latency and amplitude may contain physiologically relevant information that is lost by across-trial averaging. Hence, we aimed to develop a novel method that uses 1) wavelet filtering (WF) to enhance the SNR of ERPs and 2) a multiple linear regression with a dispersion term (MLR(d)) that takes into account shape distortions to estimate the single-trial latency and amplitude of ERP peaks. Using simulated ERP data sets containing different levels of noise, we provide evidence that, compared with other approaches, the proposed WF+MLR(d) method yields the most accurate estimate of single-trial ERP features. When applied to a real laser-evoked potential data set, the WF+MLR(d) approach provides reliable estimation of single-trial latency, amplitude, and morphology of ERPs and thereby allows performing meaningful correlations at single-trial level. We obtained three main findings. First, WF significantly enhances the SNR of single-trial ERPs. Second, MLR(d) effectively captures and measures the variability in the morphology of single-trial ERPs, thus providing an accurate and unbiased estimate of their peak latency and amplitude. Third, intensity of pain perception significantly correlates with the single-trial estimates of N2 and P2 amplitude. These results indicate that WF+MLR(d) can be used to explore the dynamics between different ERP features, behavioral variables, and other neuroimaging measures of brain activity, thus providing new insights into the functional significance of the different brain processes underlying the brain responses to sensory stimuli.

The minimal important difference of exercise tests in severe COPD.

Our aim was to determine the minimal important difference (MID) for 6-min walk distance (6MWD) and maximal cycle exercise capacity (MCEC) in patients with severe chronic obstructive pulmonary disease (COPD). 1,218 patients enrolled in the National Emphysema Treatment Trial completed exercise tests before and after 4-6 weeks of pre-trial rehabilitation, and 6 months after randomisation to surgery or medical care. The St George's Respiratory Questionnaire (domain and total scores) and University of California San Diego Shortness of Breath Questionnaire (total score) served as anchors for anchor-based MID estimates. In order to calculate distribution-based estimates, we used the standard error of measurement, Cohen's effect size and the empirical rule effect size. Anchor-based estimates for the 6MWD were 18.9 m (95% CI 18.1-20.1 m), 24.2 m (95% CI 23.4-25.4 m), 24.6 m (95% CI 23.4-25.7 m) and 26.4 m (95% CI 25.4-27.4 m), which were similar to distribution-based MID estimates of 25.7, 26.8 and 30.6 m. For MCEC, anchor-based estimates for the MID were 2.2 W (95% CI 2.0-2.4 W), 3.2 W (95% CI 3.0-3.4 W), 3.2 W (95% CI 3.0-3.4 W) and 3.3 W (95% CI 3.0-3.5 W), while distribution-based estimates were 5.3 and 5.5 W. We suggest a MID of 26 ± 2 m for 6MWD and 4 ± 1 W for MCEC for patients with severe COPD.

Supplementation with vitamin A early in life and subsequent risk of asthma.

Animal models suggest that vitamin A deficiency affects lung development adversely and promotes airway hyperresponsiveness, and may predispose to an increased risk of asthma. We examined the long-term effects of vitamin A supplementation early in life on later asthma risk. In 2006-2008, we revisited participants from two cohorts in rural Nepal who were enrolled in randomised trials of vitamin A supplementation. The first cohort received vitamin A or placebo for <16 months during their pre-school years (1989-1991). The second cohort was born to mothers who received vitamin A, ß-carotene or placebo before, during and after pregnancy (1994-1997). At follow-up, we asked about asthma symptoms and performed spirometry. Out of 6,421 subjects eligible to participate, 5,430 (85%) responded to our respiratory survey. Wheezing prevalence during the previous year was 4.8% in participants aged 9-13 yrs and 6.6% in participants aged 14-23 yrs. We found no differences between the vitamin A supplemented and placebo groups from either trial in the prevalence of lifetime or current asthma and wheeze or in spirometric indices of obstruction (p ≥ 0.12 for all comparisons). Vitamin A supplementation early in life was not associated with a decreased risk of asthma in an area with chronic vitamin A deficiency.