Identification of patients for clinical risk assessment by prediction of cardiovascular risk using default risk factor values

Abstract Background To identify high risk patients without cardiovascular disease requires assessment of risk factors. Primary care providers must therefore determine which patients without cardiovascular disease should be highest priority for cardiovascular risk assessment. One approach is to prioritise patients for assessment using a prior estimate of their cardiovascular risk. This prior estimate of cardiovascular risk is derived from risk factor data that are routinely held in electronic medical records, with unknown blood pressure and cholesterol levels replaced by default values derived from national survey data. This paper analyses the test characteristics of using such a strategy for identification of high risk patients. Methods Prior estimates of Framingham cardiovascular risk were derived in a population obtained from the Health Survey for England 2003. Receiver operating characteristics curves were constructed for using a prior estimate of cardiovascular risk to identify patients at greater than 20% ten-year cardiovascular risk. This was compared to strategies using age, or diabetic and antihypertensive treatment status to identify high risk patients. Results The area under the curve for a prior estimate of cardiovascular risk calculated using minimum data (0.933, 95% CI: 0.925 to 0.941) is significantly greater than for a selection strategy based on age (0.892, 95% CI: 0.882 to 0.902), or diabetic and hypertensive status (0.608, 95% CI: 0.584 to 0.632). Conclusion Using routine data held on primary care databases it is possible to identify a population at high risk of cardiovascular disease. Information technology to help primary care prioritise patients for cardiovascular disease prevention may improve the efficiency of cardiovascular risk assessment.</p

The Sandwell Project: A controlled evaluation of a programme of targeted screening for prevention of cardiovascular disease in primary care

<p>Abstract</p> <p>Background</p> <p>A pilot cardiovascular disease prevention project was implemented in the inner-city West Midlands. It was evaluated by comparing its effectiveness to a control group where full implementation was delayed by a year.</p> <p>Methods</p> <p>Cardiovascular risk factor data were extracted on all untreated patients 35 to 74 years old from electronic medical databases in six general practices. A best estimate of ten-year CVD risk cardiovascular risk was calculated on all patients using the extracted risk factor data. Default risk-factor values were used for all missing risk factor data. High risk patients were thus identified. In four practices a project nurse systematically invited, assessed and referred high risk patients for treatment. Two control practices were provided with a list of their high risk patients. The outcomes were the proportions of untreated high-risk patients who were assessed, identified as eligible for treatment and treated under two strategies for identifying and treating such patients in primary care.</p> <p>Results</p> <p>Of all high-risk patients suitable for inclusion in the project, 40.6% (95% CI: 36.7 to 45.7%) of patients in intervention practices were started on treatment were started on at least one treatment, compared to 12.7% (95% CI: 9.8% to 16.1%) in control practices.</p> <p>Conclusion</p> <p>A strategy using electronic primary care records to identify high risk patients for CVD prevention works best with a process for acting on information, ensuring patients are invited, assessed and treated.</p

Impaired Interoceptive Accuracy in Semantic Variant Primary Progressive Aphasia

Background: Interoception (the perception of internal bodily sensations) is strongly linked to emotional experience and sensitivity to the emotions of others in healthy subjects. Interoceptive impairment may contribute to the profound socioemotional symptoms that characterize frontotemporal dementia (FTD) syndromes, but remains poorly defined. Methods: Patients representing all major FTD syndromes and healthy age-matched controls performed a heartbeat counting task as a measure of interoceptive accuracy. In addition, patients had volumetric MRI for voxel-based morphometric analysis, and their caregivers completed a questionnaire assessing patients’ daily-life sensitivity to the emotions of others. Results: Interoceptive accuracy was impaired in patients with semantic variant primary progressive aphasia relative to healthy age-matched individuals, but not in behavioral variant frontotemporal dementia and nonfluent variant primary progressive aphasia. Impaired interoceptive accuracy correlated with reduced daily-life emotional sensitivity across the patient cohort, and with atrophy of right insula, cingulate, and amygdala on voxel-based morphometry in the impaired semantic variant group, delineating a network previously shown to support interoceptive processing in the healthy brain. Conclusion: Interoception is a promising novel paradigm for defining mechanisms of reduced emotional reactivity, empathy, and self-awareness in neurodegenerative syndromes and may yield objective measures for these complex symptoms

Simulating hemispatial neglect with virtual reality

<p>Abstract</p> <p>Background</p> <p>Hemispatial neglect is a cognitive disorder defined as a lack of attention for stimuli contra-lateral to the brain lesion. The assessment is traditionally done with basic pencil and paper tests and the rehabilitation programs are generally not well adapted. We propose a virtual reality system featuring an eye-tracking device for a better characterization of the neglect that will lead to new rehabilitation techniques.</p> <p>Methods</p> <p>This paper presents a comparison of eye-gaze patterns of healthy subjects, patients and healthy simulated patients on a virtual line bisection test. The task was also executed with a reduced visual field condition hoping that fewer stimuli would limit the neglect.</p> <p>Results</p> <p>We found that patients and healthy simulated patients had similar eye-gaze patterns. However, while the reduced visual field condition had no effect on the healthy simulated patients, it actually had a negative impact on the patients. We discuss the reasons for these differences and how they relate to the limitations of the neglect simulation.</p> <p>Conclusion</p> <p>We argue that with some improvements the technique could be used to determine the potential of new rehabilitation techniques and also help the rehabilitation staff or the patient's relatives to better understand the neglect condition.</p

Gender equality and girls education: Investigating frameworks, disjunctures and meanings of quality education

The article draws on qualitative educational research across a diversity of low-income countries to examine the gendered inequalities in education as complex, multi-faceted and situated rather than a series of barriers to be overcome through linear input–output processes focused on isolated dimensions of quality. It argues that frameworks for thinking about educational quality often result in analyses of gender inequalities that are fragmented and incomplete. However, by considering education quality more broadly as a terrain of quality it investigates questions of educational transitions, teacher supply and community participation, and develops understandings of how education is experienced by learners and teachers in their gendered lives and their teaching practices. By taking an approach based on theories of human development the article identifies dynamics of power underpinning gender inequalities in the literature and played out in diverse contexts and influenced by social, cultural and historical contexts. The review and discussion indicate that attaining gender equitable quality education requires recognition and understanding of the ways in which inequalities intersect and interrelate in order to seek out multi-faceted strategies that address not only different dimensions of girls’ and women’s lives, but understand gendered relationships and structurally entrenched inequalities between women and men, girls and boys

Altered Time Awareness in Dementia

Our awareness of time, specifically of longer intervals spanning hours, days, months, and years, is critical for ensuring our sense of self-continuity. Disrupted time awareness over such intervals is a clinical feature in a number of frontotemporal dementia syndromes and Alzheimer's disease, but has not been studied and compared systematically in these diseases. We used a semi-structured caregiver survey to capture time-related behavioral alterations in 71 patients representing all major sporadic and genetic syndromes of frontotemporal dementia, in comparison to 28 patients with typical Alzheimer's disease and nine with logopenic aphasia, and 32 healthy older individuals. Survey items pertained to apparent difficulties ordering past personal events or estimating time intervals between events, temporal rigidity and clockwatching, and propensity to relive past events. We used a logistic regression model including diagnosis, age, gender, and disease severity as regressors to compare the proportions of individuals exhibiting each temporal awareness symptom between diagnostic groups. Gray matter associations of altered time awareness were assessed using voxel-based morphometry. All patient groups were significantly more prone to exhibit temporal awareness symptoms than healthy older individuals. Clinical syndromic signatures were identified. While patients with typical and logopenic Alzheimer's disease most frequently exhibited disturbed event ordering or interval estimation, patients with semantic dementia were most prone to temporal rigidity and clockwatching and those with behavioral variant frontotemporal dementia commonly exhibited all these temporal symptoms as well as a propensity to relive past events. On voxel-based morphometry, the tendency to relive past events was associated with relative preservation of a distributed left-sided temporo-parietal gray matter network including hippocampus. These findings reveal a rich and complex picture of disturbed temporal awareness in major dementia syndromes, with stratification of frontotemporal dementia syndromes from Alzheimer's disease. This is the first study to assess symptoms of altered temporal awareness across frontotemporal dementia syndromes and provides a motivation for future work directed to the development of validated clinical questionnaires, analysis of underlying neurobiological mechanisms and design of interventions

Laughter as a paradigm of socio-emotional signal processing in dementia

Laughter is a fundamental communicative signal in our relations with other people and is used to convey a diverse repertoire of social and emotional information. It is therefore potentially a useful probe of impaired socio-emotional signal processing in neurodegenerative diseases. Here we investigated the cognitive and affective processing of laughter in forty-seven patients representing all major syndromes of frontotemporal dementia, a disease spectrum characterised by severe socio-emotional dysfunction (twenty-two with behavioural variant frontotemporal dementia, twelve with semantic variant primary progressive aphasia, thirteen with nonfluent-agrammatic variant primary progressive aphasia), in relation to fifteen patients with typical amnestic Alzheimer’s disease and twenty healthy age-matched individuals. We assessed cognitive labelling (identification) and valence rating (affective evaluation) of samples of spontaneous (mirthful and hostile) and volitional (posed) laughter versus two auditory control conditions (a synthetic laughter-like stimulus and spoken numbers). Neuroanatomical associations of laughter processing were assessed using voxel-based morphometry of patients’ brain MR images. While all dementia syndromes were associated with impaired identification of laughter subtypes relative to healthy controls, this was significantly more severe overall in frontotemporal dementia than in Alzheimer’s disease and particularly in the behavioural and semantic variants, which also showed abnormal affective evaluation of laughter. Over the patient cohort, laughter identification accuracy was correlated with measures of daily-life socio-emotional functioning. Certain striking syndromic signatures emerged, including enhanced liking for hostile laughter in behavioural variant frontotemporal dementia, impaired processing of synthetic laughter in the nonfluent-agrammatic variant (consistent with a generic complex auditory perceptual deficit) and enhanced liking for numbers (‘numerophilia’) in the semantic variant. Across the patient cohort, overall laughter identification accuracy correlated with regional grey matter in a core network encompassing inferior frontal and cingulo-insular cortices; and more specific correlates of laughter identification accuracy were delineated in cortical regions mediating affective disambiguation (identification of hostile and posed laughter in orbitofrontal cortex) and authenticity (social intent) decoding (identification of mirthful and posed laughter in anteromedial prefrontal cortex) (all p<0.05 after correction for multiple voxel-wise comparisons over the whole brain). These findings reveal a rich diversity of cognitive and affective laughter phenotypes in canonical dementia syndromes and suggest that laughter is an informative probe of neural mechanisms underpinning socio-emotional dysfunction in neurodegenerative disease

Altered phobic reactions in frontotemporal dementia: a behavioural and neuroanatomical analysis

Introduction: Abnormal behavioural and physiological reactivity to emotional stimuli is a hallmark of frontotemporal dementia (FTD), particularly the behavioural variant (bvFTD). As part of this repertoire, altered phobic responses have been reported in some patients with FTD but are poorly characterised. Methods: We collected data (based on caregiver reports) concerning the prevalence and nature of any behavioural changes related to specific phobias in a cohort of patients representing canonical syndromes of FTD and Alzheimer’s disease (AD), relative to healthy older controls. Neuroanatomical correlates of altered phobic reactivity were assessed using voxel-based morphometry. Results: 46 patients with bvFTD, 20 with semantic variant primary progressive aphasia, 25 with non-fluent variant primary progressive aphasia, 29 with AD and 55 healthy age-matched individuals participated. Changes in specific phobia were significantly more prevalent in the combined FTD cohort (15.4% of cases) and in the bvFTD group (17.4%) compared both to healthy controls (3.6%) and patients with AD (3.5%). Attenuation of phobic reactivity was reported for individuals in all participant groups, however new phobias developed only in the FTD cohort. Altered phobic reactivity was significantly associated with relative preservation of grey matter in left posterior middle temporal gyrus, right temporo-occipital junction and right anterior cingulate gyrus, brain regions previously implicated in contextual decoding, salience processing and reward valuation. Conclusion: Altered phobic reactivity is a relatively common issue in patients with FTD, particularly bvFTD. This novel paradigm of strong fear experience has broad implications: clinically, for diagnosis and patient well-being; and neurobiologically, for our understanding of the pathophysiology of aversive sensory signal processing in FTD and the neural mechanisms of fear more generally

Integrin αvβ6-specific therapy for pancreatic cancer developed from foot-and-mouth-disease virus

GOALS OF INVESTIGATION: The 5-year survival rate for pancreatic ductal adenocarcinoma (PDAC) has remained at <5% for decades because no effective therapies have been identified. Integrin αvβ6 is overexpressed in most PDAC and represents a promising therapeutic target. Thus, we attempted to develop an αvβ6-specific peptide-drug conjugate (PDC) for therapy of PDAC. METHODOLOGY: We conjugated the DNA-binding pyrrolobenzodiazepine (PBD)-based payload SG3249 (tesirine) to an αvβ6-specific 20mer peptide from the VP1 coat protein of foot-and-mouth-disease virus (FMDV) (forming conjugate SG3299) or to a non-targeting peptide (forming conjugate SG3511). PDCs were tested for specificity and toxicity on αvβ6-negative versus-positive PDAC cells, patient-derived cell lines from tumor xenografts, and on two different in vivo models of PDAC. Immunohistochemical analyses were performed to establish therapeutic mechanism. RESULTS: The αvβ6-targeted PDC SG3299 was significantly more toxic (up to 78-fold) for αvβ6-expressing versus αvβ6-negative PDAC cell lines in vitro, and achieved significantly higher toxicity at equal dose than the non-targeted PDC SG3511 (up to 15-fold better). Moreover, SG3299 eliminated established (100mm3) Capan-1 PDAC human xenografts, extending the lifespan of mice significantly (P=0.005). Immunohistochemistry revealed SG3299 induced DNA damage and apoptosis (increased γH2AX and cleaved caspase 3, respectively) associated with significant reductions in proliferation (Ki67), β6 expression and PDAC tumour growth. CONCLUSION: The FMDV-peptide drug conjugate SG3299 showed αvβ6-selectivity in vitro and in vivo and can specifically eliminate αvβ6-positive cancers, providing a promising new molecular- specific therapy for pancreatic cancer

Dimensions of Children's Health Beliefs

Health beliefs interviews were conducted with 250 children aged 6-17 years. A factor analysis of the items resulted in six correlated fac tors which were interpreted as 1) specific health concerns, 2)general health concerns, 3) perceived parental concern, 4) perceived general susceptibility, 5) perceived susceptibility to specific conditions, and 6) perceived seriousness of and susceptibility to disease. Factor scores were computed and two-way analyses of variance (by age and sex of child) were conducted on six sets of factor scores. No significant sex differences or sex by age in teraction effects were noted. Younger children scored significantly higher on "specific health concerns"and "perceived general susceptibility,"while older children scored significantly higher on "perceived parental concern. " Tests of differences among variances showed a tendency for the variability to be greater among younger children. The results are interpreted as pro viding partial support for a model of children's health beliefs and as a basis for further operationalization of concepts which are central to an understand ing of motivated health behavior. Implications for practice are discussed.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/66657/2/10.1177_109019818000700304.pd