Assessment of cognitive symptoms in prodromal and early Huntington disease

The Functional Rating Scale Taskforce for pre-Huntington Disease (FuRST-pHD) is a multinational, multidisciplinary initiative with the goal of developing a data-driven, comprehensive, psychometrically sound, rating scale for assessing symptoms and functional ability in prodromal and early Huntington disease (HD) gene expansion carriers. The process involves input from numerous sources to identify relevant symptom domains, including HD individuals, caregivers, and experts from a variety of fields, as well as knowledge gained from the analysis of data from ongoing large-scale studies in HD using existing clinical scales. This is an iterative process in which an ongoing series of field tests in prodromal (prHD) and early HD individuals provides the team with data on which to make decisions regarding which questions should undergo further development or testing and which should be excluded. We report here the development and assessment of the first iteration of interview questions aimed to assess cognitive symptoms in prHD and early HD individuals.

Cognitive follow up of a small cohort of Huntington's disease patients over a 5 year period

A small group of patients with manifest Huntington's disease (HD) were followed longitudinally to assess cognitive decline in relation to time from disease diagnosis. This article looks at performance on a range of computerised and pencil and paper cognitive tasks in patients 5 years post diagnosis, who were assessed annually for a 5 year follow up period. The almost universal cognitive decline reported in other longitudinal studies of HD was not replicated in this study. It was proposed that longitudinal follow up in HD is complicated by the varying degree to which different tasks are able to withstand repeated administration; a finding which would have significant implications on study design in future trials of cognitive enhansing interventions.

A pharmacist-led information technology intervention for medication errors (PINCER): a multicentre, cluster randomised, controlled trial and cost-effectiveness analysis

Background: Medication errors are common in primary care and are associated with considerable risk of patient harm. We tested whether a pharmacist-led, information technology-based intervention was more effective than simple feedback in reducing the number of patients at risk of measures related to hazardous prescribing and inadequate blood-test monitoring of medicines 6 months after the intervention. Methods: In this pragmatic, cluster randomised trial general practices in the UK were stratified by research site and list size, and randomly assigned by a web-based randomisation service in block sizes of two or four to one of two groups. The practices were allocated to either computer-generated simple feedback for at-risk patients (control) or a pharmacist-led information technology intervention (PINCER), composed of feedback, educational outreach, and dedicated support. The allocation was masked to general practices, patients, pharmacists, researchers, and statisticians. Primary outcomes were the proportions of patients at 6 months after the intervention who had had any of three clinically important errors: non-selective non-steroidal anti-inflammatory drugs (NSAIDs) prescribed to those with a history of peptic ulcer without co-prescription of a proton-pump inhibitor; β blockers prescribed to those with a history of asthma; long-term prescription of angiotensin converting enzyme (ACE) inhibitor or loop diuretics to those 75 years or older without assessment of urea and electrolytes in the preceding 15 months. The cost per error avoided was estimated by incremental cost-eff ectiveness analysis. This study is registered with Controlled-Trials.com, number ISRCTN21785299. Findings: 72 general practices with a combined list size of 480 942 patients were randomised. At 6 months’ follow-up, patients in the PINCER group were significantly less likely to have been prescribed a non-selective NSAID if they had a history of peptic ulcer without gastroprotection (OR 0∙58, 95% CI 0∙38–0∙89); a β blocker if they had asthma (0∙73, 0∙58–0∙91); or an ACE inhibitor or loop diuretic without appropriate monitoring (0∙51, 0∙34–0∙78). PINCER has a 95% probability of being cost eff ective if the decision-maker’s ceiling willingness to pay reaches £75 per error avoided at 6 months. Interpretation: The PINCER intervention is an effective method for reducing a range of medication errors in general practices with computerised clinical records. Funding: Patient Safety Research Portfolio, Department of Health, England.

Investigating the prevalence and causes of prescribing errors in general practice: the PRACtICe Study

Aim: To determine the prevalence and nature of prescribing errors in general practice; to explore the causes, and to identify defences against error. Methods: 1) Systematic reviews; 2) Retrospective review of unique medication items prescribed over a 12 month period to a 2% sample of patients from 15 general practices in England; 3) Interviews with 34 prescribers regarding 70 potential errors; 15 root cause analyses, and six focus groups involving 46 primary health care team members Results: The study involved examination of 6,048 unique prescription items for 1,777 patients. Prescribing or monitoring errors were detected for one in eight patients, involving around one in 20 of all prescription items. The vast majority of the errors were of mild to moderate severity, with one in 550 items being associated with a severe error. The following factors were associated with increased risk of prescribing or monitoring errors: male gender, age less than 15 years or greater than 64 years, number of unique medication items prescribed, and being prescribed preparations in the following therapeutic areas: cardiovascular, infections, malignant disease and immunosuppression, musculoskeletal, eye, ENT and skin. Prescribing or monitoring errors were not associated with the grade of GP or whether prescriptions were issued as acute or repeat items. A wide range of underlying causes of error were identified relating to the prescriber, patient, the team, the working environment, the task, the computer system and the primary/secondary care interface. Many defences against error were also identified, including strategies employed by individual prescribers and primary care teams, and making best use of health information technology. Conclusion: Prescribing errors in general practices are common, although severe errors are unusual. Many factors increase the risk of error. Strategies for reducing the prevalence of error should focus on GP training, continuing professional development for GPs, clinical governance, effective use of clinical computer systems, and improving safety systems within general practices and at the interface with secondary care.

The impact of North Atlantic sea surface temperature errors on the simulation of North Atlantic European region climate

Current state-of-the-art climate models fail to capture accurately the path of the Gulf Stream and North Atlantic Current. This leads to a warm bias near the North American coast, where the modelled Gulf Stream separates from the coast further north, and a cold anomaly to the east of the Grand Banks of Newfoundland, where the North Atlantic Current remains too zonal in this region. Using an atmosphere-only model forced with the sea surface temperature (SST) biases in the North Atlantic, we consider the impact they have on the mean state and the variability in the North Atlantic European region in winter. Our results show that the SST errors produce a mean sea-level pressure response that is similar in magnitude and pattern to the atmospheric circulation errors in the coupled climate model. The work also suggests that errors in the coupled model storm tracks and North Atlantic Oscillation, compared to reanalysis data, can also be explained partly by these SST errors. Our results suggest that both the error in the Gulf Stream separation location and the path of the North Atlantic Current around the Grand Banks play important roles in affecting the atmospheric circulation. Reducing these coupled model errors could improve significantly the representation of the large-scale atmospheric circulation of the North Atlantic and European region.

Breakdown of hydrostatic balance at convective scales in the forecast errors in the Met Office Unified Model

For data assimilation in numerical weather prediction, the initial forecast-error covariance matrix Pf is required. For variational assimilation it is particularly important to prescribe an accurate initial matrix Pf, since Pf is either static (in the 3D-Var case) or constant at the beginning of each assimilation window (in the 4D-Var case). At large scales the atmospheric flow is well approximated by hydrostatic balance and this balance is strongly enforced in the initial matrix Pf used in operational variational assimilation systems such as that of the Met Office. However, at convective scales this balance does not necessarily hold any more. Here we examine the extent to which hydrostatic balance is valid in the vertical forecast-error covariances for high-resolution models in order to determine whether there is a need to relax this balance constraint in convective-scale data assimilation. We use the Met Office Global and Regional Ensemble Prediction System (MOGREPS) and a 1.5 km resolution version of the Unified Model for a case study characterized by the presence of convective activity. An ensemble of high-resolution forecasts valid up to three hours after the onset of convection is produced. We show that at 1.5 km resolution hydrostatic balance does not hold for forecast errors in regions of convection. This indicates that in the presence of convection hydrostatic balance should not be enforced in the covariance matrix used for variational data assimilation at this scale. The results show the need to investigate covariance models that may be better suited for convective-scale data assimilation. Finally, we give a measure of the balance present in the forecast perturbations as a function of the horizontal scale (from 3–90 km) using a set of diagnostics. Copyright © 2012 Royal Meteorological Society and British Crown Copyright, the Met Office

Individual differences in brain structure underpin empathizing–systemizing cognitive styles in male adults

Individual differences in cognitive style can be characterized along two dimensions: ‘systemizing’ (S, the drive to analyze or build ‘rule-based’ systems) and ‘empathizing’ (E, the drive to identify another's mental state and respond to this with an appropriate emotion). Discrepancies between these two dimensions in one direction (S > E) or the other (E > S) are associated with sex differences in cognition: on average more males show an S > E cognitive style, while on average more females show an E > S profile. The neurobiological basis of these different profiles remains unknown. Since individuals may be typical or atypical for their sex, it is important to move away from the study of sex differences and towards the study of differences in cognitive style. Using structural magnetic resonance imaging we examined how neuroanatomy varies as a function of the discrepancy between E and S in 88 adult males from the general population. Selecting just males allows us to study discrepant E-S profiles in a pure way, unconfounded by other factors related to sex and gender. An increasing S > E profile was associated with increased gray matter volume in cingulate and dorsal medial prefrontal areas which have been implicated in processes related to cognitive control, monitoring, error detection, and probabilistic inference. An increasing E > S profile was associated with larger hypothalamic and ventral basal ganglia regions which have been implicated in neuroendocrine control, motivation and reward. These results suggest an underlying neuroanatomical basis linked to the discrepancy between these two important dimensions of individual differences in cognitive style.

Cognitive, affective and behavioural characteristics of mothers with anxiety disorders in the context of child anxiety disorder

Parental emotional distress, particularly high maternal anxiety, is one of the most consistent predictors of child anxiety treatment outcome. In order to identify the cognitive, affective and behavioural parenting characteristics of mothers of children with anxiety disorders who themselves have an anxiety disorder, we assessed the expectations and appraisals of 88 mothers of anxious children (44 not anxious (NONANX) and 44 with a current anxiety disorder (ANX)) before and after interacting with their 7-12 year old children. There were no observed differences in anxiety and avoidance among children of ANX and NONANX mothers, but, compared to NONANX mothers, ANX mothers held more negative expectations and differed on observations of intrusiveness, expressed anxiety, warmth and the quality of the relationship. Associations were moderated by the degree to which children expressed anxiety during the tasks. Maternal reported negative emotions during the task significantly mediated the association between maternal anxiety status and the observed quality of the relationship. These findings suggest that maternal anxiety disorder is associated with reduced tolerance of children’s negative emotions. This may interfere with the maintenance of a positive, supportive mother-child interaction under conditions of stress, and as such impede optimum treatment outcomes. The findings identify potential cognitive, affective and behavioural targets to improve treatment outcomes for children with anxiety disorders in the context of a current maternal anxiety disorder.

Does training improve understanding of core concepts in cognitive behaviour therapy by people with intellectual disabilities? A randomized experiment

Background. People with intellectual disabilities (ID) experience similar or even higher rates of mental health problems than the general population and there is a need to develop appropriate treatments. Cognitive behaviour therapy (CBT) is effective for a wide range of disorders in the general population. However, there is some evidence that people with ID may lack the cognitive skills needed to take part in CBT. Aims. To test if people with ID can learn skills required for CBT, specifically the ability to distinguish between thoughts, feelings, and behaviours and to link thoughts and feelings (cognitive mediation). Method. A randomized independent groups design was used to examine the effect of training in CBT on two tasks measuring CBT skills. Thirty-four adults with ID were randomly allocated to the experimental condition ðN ¼ 18Þ or to the control condition ðN ¼ 16Þ. CBT skills were assessed blind at baseline and after the intervention. Results. The training led to significant improvements in participants’ ability to link thoughts and feelings, and this skill was generalized to new material. There was no effect of training on participants’ ability to distinguish amongst thoughts, feelings, and behaviours. People with ID can, therefore, learn some skills required for CBT. This implies that preparatory training for CBT might be useful for people with ID. The results might be applicable to other groups who find aspects of CBT difficult.

Cognitive behaviour therapy for low self-esteem: A preliminary randomized controlled trial in a primary care setting

Background and Objectives Low self-esteem (LSE) is associated with psychiatric disorder, and is distressing and debilitating in its own right. Hence, it is frequent target for treatment in cognitive behavioural interventions, yet it has rarely been the primary focus for intervention. This paper reports on a preliminary randomized controlled trial of cognitive behaviour therapy (CBT) for LSE using Fennell’s (1997) cognitive conceptualisation and transdiagnostic treatment approach ( [Fennell, 1997] and [Fennell, 1999]). Methods Twenty-two participants were randomly allocated to either immediate treatment (IT) (n = 11) or to a waitlist condition (WL) (n = 11). Treatment consisted of 10 sessions of individual CBT accompanied by workbooks. Participants allocated to the WL condition received the CBT intervention once the waitlist period was completed and all participants were followed up 11 weeks after completing CBT. Results The IT group showed significantly better functioning than the WL group on measures of LSE, overall functioning and depression and had fewer psychiatric diagnoses at the end of treatment. The WL group showed the same pattern of response to CBT as the group who had received CBT immediately. All treatment gains were maintained at follow-up assessment. Limitations The sample size is small and consists mainly of women with a high level of educational attainment and the follow-up period was relatively short. Conclusions These preliminary findings suggest that a focused, brief CBT intervention can be effective in treating LSE and associated symptoms and diagnoses in a clinically representative group of individuals with a range of different and co-morbid disorders.

Landscape, regional and global estimates of nitrogen flux from land to sea: errors and uncertainties

Regional to global scale modelling of N flux from land to ocean has progressed to date through the development of simple empirical models representing bulk N flux rates from large watersheds, regions, or continents on the basis of a limited selection of model parameters. Watershed scale N flux modelling has developed a range of physically-based approaches ranging from models where N flux rates are predicted through a physical representation of the processes involved, through to catchment scale models which provide a simplified representation of true systems behaviour. Generally, these watershed scale models describe within their structure the dominant process controls on N flux at the catchment or watershed scale, and take into account variations in the extent to which these processes control N flux rates as a function of landscape sensitivity to N cycling and export. This paper addresses the nature of the errors and uncertainties inherent in existing regional to global scale models, and the nature of error propagation associated with upscaling from small catchment to regional scale through a suite of spatial aggregation and conceptual lumping experiments conducted on a validated watershed scale model, the export coefficient model. Results from the analysis support the findings of other researchers developing macroscale models in allied research fields. Conclusions from the study confirm that reliable and accurate regional scale N flux modelling needs to take account of the heterogeneity of landscapes and the impact that this has on N cycling processes within homogenous landscape units.

Neural correlates of true and false memory in mild cognitive impairment

The goal of this research was to investigate the changes in neural processing in mild cognitive impairment. We measured phase synchrony, amplitudes, and event-related potentials in veridical and false memory to determine whether these differed in participants with mild cognitive impairment compared with typical, age-matched controls. Empirical mode decomposition phase locking analysis was used to assess synchrony, which is the first time this analysis technique has been applied in a complex cognitive task such as memory processing. The technique allowed assessment of changes in frontal and parietal cortex connectivity over time during a memory task, without a priori selection of frequency ranges, which has been shown previously to influence synchrony detection. Phase synchrony differed significantly in its timing and degree between participant groups in the theta and alpha frequency ranges. Timing differences suggested greater dependence on gist memory in the presence of mild cognitive impairment. The group with mild cognitive impairment had significantly more frontal theta phase locking than the controls in the absence of a significant behavioural difference in the task, providing new evidence for compensatory processing in the former group. Both groups showed greater frontal phase locking during false than true memory, suggesting increased searching when no actual memory trace was found. Significant inter-group differences in frontal alpha phase locking provided support for a role for lower and upper alpha oscillations in memory processing. Finally, fronto-parietal interaction was significantly reduced in the group with mild cognitive impairment, supporting the notion that mild cognitive impairment could represent an early stage in Alzheimer’s disease, which has been described as a ‘disconnection syndrome’.