Community based rehabilitation after severe traumatic brain injury: a randomised controlled trial

Objective: Evaluation of multidisciplinary community based outreach rehabilitation after severe traumatic brain injury (TBI). Methods: A randomised controlled trial compared outreach treatment (mean of two sessions a week for 27.3 (SD 19.1) weeks) in community settings such as participants' homes, day centres, or workplaces, with provision of written information detailing alternative resources. Follow up for an average of 24.8 months after initial allocation was by a blinded independent assessor. Participants were aged 16–65, had sustained severe TBI between 3 months and 20 years previously, and had no other neurological conditions. Of 110 initially allocated, 48 outreach and 46 information participants were successfully followed up. Primary outcome measures (Barthel index (BI) and the brain injury community rehabilitation outcome-39 (BICRO-39)) focused on levels of activity and participation. Secondary measures were the functional independence measure and the functional assessment measure (FIM+FAM) and, in a subgroup of 46 participants, the hospital anxiety and depression scale. Analyses were non-parametric. Results: outreach participants were significantly more likely to show gains on the BI and the BICRO-39 total score and self organisation and psychological wellbeing subscales. There were likewise strong trends (p<0.10) for BICRO personal care and mobility, and on the FIM+FAM for personal care and cognitive functions. Differential improvements were not seen for indices of socialising, productive employment, anxiety, or depression. Median changes on individual subscales were small, reflecting the diversity of the clinical population; however, 40% of outreach but only 20% of information participants made a clinically significant improvement of 2+ points on at least one BICRO-39 scale. Time since injury was unrelated to the magnitude of gains. Conclusions: This is the first RCT of multidisciplinary community rehabilitation after severe TBI, and suggests that even years after injury it can yield benefits which outlive the active treatment period

A double-blind placebo controlled experimental study of nicotine: II - Effects on response inhibition and executive functioning

Rationale: Smokers may show abnormal functioning in prefrontal cortex during acute abstinence, reflecting deficient activity in mesocorticolimbic circuitry. Cognitive correlates of this putatively include impaired response inhibition and other aspects of executive functioning. Objectives: To investigate whether inhibitory control and other executive functions in smokers are impaired during acute abstinence relative to post-nicotine. Methods: 145 smokers were tested twice following overnight abstinence, once after nicotine and once after placebo lozenges (order counterbalanced, double-blind), on: an antisaccade task; a Continuous Performance Task (CPT); a delayed response Spatial Working Memory (SWM) task; and a verbal fluency test. Results: Compared with placebo, nicotine was associated with better inhibitory control on the antisaccade task and fewer impulsive responses to filler stimuli (motor errors) on the CPT; at the first assessment only, nicotine also reduced impulsive responses to ‘catch’ stimuli on the CPT. However, it did not affect CPT response bias (an index of impulsive vs. cautious decision-making), spatial working memory, or verbal fluency. Conclusions: Smoking abstinence appears to be associated with difficulty in inhibiting prepotent motor responses, and nicotine to attenuate this difficulty. However, more ‘cognitive’ forms of inhibitory control (e.g. decision-making) and the other aspects of executive function tested here appear to be unaffected

The development of a brief self-report questionnaire to measure 'recent' Rash Impulsivity: A preliminary investigation of its validity and association with recent alcohol consumption

Background: Traditionally, impulsivity has been regarded as a stable trait. However, a series of longitudinal and behavioural laboratory studies has found that impulsivity can fluctuate within individuals, suggesting that it has a state as well as a trait manifestation. Whilst existing impulsivity questionnaires tap the former, there is no self-report instrument to assess recent fluctuations in impulsivity. Research aims and design. The present study set out to develop and undertake preliminary validation of a measure of 'recent' impulsivity, focusing in particular on Rash Impulsivity. Part of the construct validation of the resulting Recent Rash Impulsivity Scale (RRIS) entailed examining its association with recent alcohol intake, since there are well-documented reciprocal relationships between alcohol consumption and inhibitory control. In developing the RRIS, items from existing trait impulsivity questionnaires were converted into a 'previous two weeks' format. The pilot RRIS was then administered, along with a parallel trait version (Trait Rash Impulsivity Scale; TRIS) and a well-established trait impulsivity measure (the BIS-11; Patton, Stanford & Barratt, 1995), to two cohorts of first-year undergraduates aged 17 to 25 (N = 240), on two occasions one month apart. Information about habitual and recent alcohol intake was also gathered. Results: Factor analyses on both the RRIS and TRIS identified two factors: 'Cognitive Impulsivity' (CogImp) and 'Motor Impulsivity' (MotImp). Consistent with the RRIS being sensitive to fluctuations in impulsivity, it was found that, as predicted: i) the RRIS was somewhat less strongly correlated than the TRIS with an established trait measure (the BIS-11; Patton et al., 1995); ii) the test-retest stability of 'Total' scores (CogImp and MotImp) was weaker for the RRIS than the TRIS; iii) there was evidence that the RRIS MotImp and Total scales were more strongly predicted by recent alcohol intake than were their trait equivalents; and iv) the RRIS CogImp and Total scales correlated more strongly with their trait equivalents in participants whose alcohol consumption had remained stable recently (relative to their habitual intake), compared to those whose consumption had recently changed. Conclusions: These data suggest that transient changes in impulsivity can be assessed via self-report, and that the RRIS is sensitive to recent changes in alcohol intake. Subject to a more intensive and detailed validation, it is thus promising as a tool for tapping and characterising fluctuations in behavioural control and for exploring a range of factors to which this might be associated

Relapse to smoking during unaided cessation: clinical, cognitive, and motivational predictors

Rationale: Neurobiological models of addiction suggest that abnormalities of brain reward circuitry distort salience attribution and inhibitory control processes, which in turn contribute to high relapse rates. Objectives: To determine whether impairments of salience attribution and inhibitory control predict relapse in a pharmacologically unaided attempt at smoking cessation. Methods: 141 smokers were assessed on indices of nicotine consumption / dependence (e.g. the FTND, cigarettes per day, salivary cotinine), and three trait impulsivity measures. After overnight abstinence they completed experimental tests of cue reactivity, attentional bias to smoking cues, response to financial reward, motor impulsiveness, and response inhibition (antisaccades). They then started a quit attempt with follow-up after 7 days, 1 month, and 3 months; abstinence was verified via salivary cotinine levels ≤ 20ng/ml. Results: Relapse rates at each point were 52.5%, 64% and 76.3%. The strongest predictor was pre-cessation salivary cotinine; other smoking / dependence indices did not explain additional outcome variance and neither did trait impulsivity. All experimental indices except responsivity to financial reward significantly predicted one week outcome. Salivary cotinine, attentional bias to smoking cues and antisaccade errors explained unique as well as shared variance. At one and three months, salivary cotinine, motor impulsiveness and cue reactivity were all individually predictive; the effects of salivary cotinine and motor impulsiveness were additive. Conclusions: These data provide some support for the involvement of abnormal cognitive and motivational processes in sustaining smoking dependence and suggest that they might be a focus of interventions, especially in the early stages of cessation

White matter damage and cognitive impairment after traumatic brain injury

White matter disruption is an important determinant of cognitive impairment after brain injury, but conventional neuroimaging underestimates its extent. In contrast, diffusion tensor imaging provides a validated and sensitive way of identifying the impact of axonal injury. The relationship between cognitive impairment after traumatic brain injury and white matter damage is likely to be complex. We applied a flexible technique—tract-based spatial statistics—to explore whether damage to specific white matter tracts is associated with particular patterns of cognitive impairment. The commonly affected domains of memory, executive function and information processing speed were investigated in 28 patients in the post-acute / chronic phase following traumatic brain injury and in 26 age-matched controls. Analysis of fractional anisotropy and diffusivity maps revealed widespread differences in white matter integrity between the groups. Patients showed large areas of reduced fractional anisotropy, as well as increased mean and axial diffusivities, compared with controls, despite the small amounts of cortical and white matter damage visible on standard imaging. A stratified analysis based on the presence or absence of microbleeds (a marker of diffuse axonal injury) revealed diffusion tensor imaging to be more sensitive than gradient-echo imaging to white matter damage. The location of white matter abnormality predicted cognitive function to some extent. The structure of the fornices was correlated with associative learning and memory across both patient and control groups, whilst the structure of frontal lobe connections showed relationships with executive function that differed in the two groups. These results highlight the complexity of the relationships between white matter structure and cognition. Although widespread and, sometimes, chronic abnormalities of white matter are identifiable following traumatic brain injury, the impact of these changes on cognitive function is likely to depend on damage to key pathways that link nodes in the distributed brain networks supporting high-level cognitive functions

Gender, age and the MBA: An analysis of extrinsic and intrinsic career benefits

Against the background of an earlier UK study, this paper presents the findings of a Canadian based survey of career benefits from the MBA. Results indicate firstly that gender and age interact to influence perceptions of career outcomes (young men gain most in terms of extrinsic benefits of career change and pay), and secondly that both men and women gain intrinsic benefits from the MBA. However, intrinsic benefits vary by gender: men in the study were more likely to say they gained confidence from having a fuller skill set while women were more likely to say they gained confidence from feelings of self worth; men emphasised how they had learned to give up control while women argued that they had gained a ‘voice’ in the organization. The role of the MBA in career self- management and the acquisition of key skills are examined as well as the implications for the design of programmes in meeting the varied need of men and women in different age groups

Prehospital critical care for out-of-hospital cardiac arrest: An observational study examining survival and a stakeholder-focused cost analysis

© 2016 The Author(s). Background: Survival rates from out-of-hospital cardiac arrest (OHCA) remain low, despite remarkable efforts to improve care. A number of ambulance services in the United Kingdom (UK) have developed prehospital critical care teams (CCTs) which attend critically ill patients, including OHCA. However, current scientific evidence describing CCTs attending OHCA is sparse and research to date has not demonstrated clear benefits from this model of care. Methods: This prospective, observational study will describe the effect of CCTs on survival from OHCA, when compared to advanced-life-support (ALS), the current standard of prehospital care in the UK. In addition, we will describe the association between individual critical care interventions and survival, and also the costs of CCTs for OHCA. To examine the effect of CCTs on survival from OHCA, we will use routine Utstein variables data already collected in a number of UK ambulance trusts. We will use propensity score matching to adjust for imbalances between the CCT and ALS groups. The primary outcome will be survival to hospital discharge, with the secondary outcome of survival to hospital admission. We will record the critical care interventions delivered during CCT attendance at OHCA. We will describe frequencies and aim to use multiple logistic regression to examine possible associations with survival. Finally, we will undertake a stakeholder-focused cost analysis of CCTs for OHCA. This will utilise a previously published Emergency Medical Services (EMS) cost analysis toolkit and will take into account the costs incurred from use of a helicopter and the proportion of these costs currently covered by charities in the UK. Discussion: Prehospital critical care for OHCA is not universally available in many EMS. In the UK, it is variable and largely funded through public donations to charities. If this study demonstrates benefit from CCTs at an acceptable cost to the public or EMS commissioners, it will provide a rationale to increase funding and service provision. If no clinical benefit is found, the public and charities providing these services can consider concentrating their efforts on other areas of prehospital care. Trial registration: ISRCTN registry ID ISRCTN18375201

How moving home influences appliance ownership: a Passivhaus case study

Low carbon dwellings shift the focus to electricity consumption and appliances by significantly lowering space heating energy consumption. Using a UK Passivhaus (low carbon) case study, interviews and pre/post-move-in appliance audits were employed to investigate how moving home can change the appliance requirements of appliance-using practices. Changes in appliance ownership were due to differences in how appliance-using practices (e.g. cooking, laundering, homemaking) were being performed. Existing/new appliances complemented/conflicted with a new home on the basis of whether the social meanings of specific appliance-using practices (e.g. stylishness, convenience, thermal comfort, cleanliness) could be met. This was evident, when moving home more generally, by households buying new modern appliances and managing spatial constraints. More specifically, regarding Passivhaus, hosting and homemaking practices were performed in ways that met thermal comfort expectations, in addition to appliance purchasing also being influenced by a fear that the Passivhaus technologies could fail. Whilst skills and competences were needed to perform appliance-using practices, these were less prominent in influencing appliance ownership changes. Conclusions include reflections on how the elements of appliance-using practices change when moving home, as well as what adhering to building standards could mean for the standardisation of appliance-using practices and domestic life more generally

Association of Liver Injury From Specific Drugs, or Groups of Drugs, With Polymorphisms in HLA and Other Genes in a Genome-Wide Association Study

BACKGROUND & AIMS: We performed a genome-wide association study (GWAS) to identify genetic risk factors for drug-induced liver injury (DILI) from licensed drugs without previously reported genetic risk factors. METHODS: We performed a GWAS of 862 persons with DILI and 10,588 population-matched controls. The first set of cases was recruited before May 2009 in Europe (n = 137) and the United States (n = 274). The second set of cases were identified from May 2009 through May 2013 from international collaborative studies performed in Europe, the United States, and South America. For the GWAS, we included only cases with patients of European ancestry associated with a particular drug (but not flucloxacillin or amoxicillin-clavulanate). We used DNA samples from all subjects to analyze HLA genes and single nucleotide polymorphisms. After the discovery analysis was concluded, we validated our findings using data from 283 European patients with diagnosis of DILI associated with various drugs. RESULTS: We associated DILI with rs114577328 (a proxy for A*33:01 a HLA class I allele; odds ratio [OR], 2.7; 95% confidence interval [CI], 1.9-3.8; P = 2.4 × 10-8) and with rs72631567 on chromosome 2 (OR, 2.0; 95% CI, 1.6-2.5; P = 9.7 × 10-9). The association with A*33:01 was mediated by large effects for terbinafine-, fenofibrate-, and ticlopidine-related DILI. The variant on chromosome 2 was associated with DILI from a variety of drugs. Further phenotypic analysis indicated that the association between DILI and A*33:01 was significant genome wide for cholestatic and mixed DILI, but not for hepatocellular DILI; the polymorphism on chromosome 2 was associated with cholestatic and mixed DILI as well as hepatocellular DILI. We identified an association between rs28521457 (within the lipopolysaccharide-responsive vesicle trafficking, beach and anchor containing gene) and only hepatocellular DILI (OR, 2.1; 95% CI, 1.6-2.7; P = 4.8 × 10-9). We did not associate any specific drug classes with genetic polymorphisms, except for statin-associated DILI, which was associated with rs116561224 on chromosome 18 (OR, 5.4; 95% CI, 3.0-9.5; P = 7.1 × 10-9). We validated the association between A*33:01 terbinafine- and sertraline-induced DILI. We could not validate the association between DILI and rs72631567, rs28521457, or rs116561224. CONCLUSIONS: In a GWAS of persons of European descent with DILI, we associated HLA-A*33:01 with DILI due to terbinafine and possibly fenofibrate and ticlopidine. We identified polymorphisms that appear to be associated with DILI from statins, as well as 2 non-drug-specific risk factors

Association of Liver Injury From Specific Drugs, or Groups of Drugs, With Polymorphisms in HLA and Other Genes in a Genome-Wide Association Study

BACKGROUND & AIMS: We performed a genome-wide association study (GWAS) to identify genetic risk factors for druginduced liver injury (DILI) from licensed drugs without previously reported genetic risk factors. METHODS: We performed a GWAS of 862 persons with DILI and 10,588 population-matched controls. The first set of cases was recruited before May 2009 in Europe (n = 137) and the United States (n = 274). The second set of cases were identified from May 2009 through May 2013 from international collaborative studies performed in Europe, the United States, and South America. For the GWAS, we included only cases with patients of European ancestry associated with a particular drug (but not flucloxacillin or amoxicillin-clavulanate). We used DNA samples from all subjects to analyze HLA genes and single nucleotide polymorphisms. After the discovery analysis was concluded, we validated our findings using data from 283 European patients with diagnosis of DILI associated with various drugs. RESULTS: We associated DILI with rs114577328 (a proxy for A* 33: 01 a HLA class I allele; odds ratio [OR], 2.7; 95% confidence interval [CI], 1.9 - 3.8; P = 2.4 x 10(-8)) and with rs72631567 on chromosome 2 (OR, 2.0; 95% CI, 1.6 - 2.5; P = 9.7 x 10(-9)). The association with A* 33: 01 was mediated by large effects for terbinafine-, fenofibrate-, and ticlopidine-related DILI. The variant on chromosome 2 was associated with DILI from a variety of drugs. Further phenotypic analysis indicated that the association between DILI and A* 33: 01 was significant genome wide for cholestatic and mixed DILI, but not for hepatocellular DILI; the polymorphism on chromosome 2 was associated with cholestatic and mixed DILI as well as hepatocellular DILI. We identified an association between rs28521457 (within the lipopolysaccharide-responsive vesicle trafficking, beach and anchor containing gene) and only hepatocellular DILI (OR, 2.1; 95% CI, 1.6 - 2.7; P = 4.8 x 10(-9)). We did not associate any specific drug classes with genetic polymorphisms, except for statin-associated DILI, which was associated with rs116561224 on chromosome 18 (OR, 5.4; 95% CI, 3.0 - 9.5; P = 7.1 x 10(-9)). We validated the association between A* 33: 01 terbinafine-and sertraline-induced DILI. We could not validate the association between DILI and rs72631567, rs28521457, or rs116561224. CONCLUSIONS: In a GWAS of persons of European descent with DILI, we associated HLA-A* 33: 01 with DILI due to terbinafine and possibly fenofibrate and ticlopidine. We identified polymorphisms that appear to be associated with DILI from statins, as well as 2 non-drug-specific risk factors.Peer reviewe