Health state values for the HUI 2 descriptive system: results from a UK survey

This paper reports the results of a study to estimate a statistical health state valuation model for a revised version of the Health Utilities Index Mark 2, using Standard Gamble health state preference data. A sample of 51 health states were valued by a sample of the 198 members of the UK general population. Models are estimated for predicting health state valuations for all 8,000 states defined by the revised HUI2. The recommended model produces logical and significant coefficients for all levels of all dimensions in the HUI2. These coefficients appear to be robust across model specifications. This model performs well in predicting the observed health state values within the valuation sample and for a separate validation sample of health states. However, there are concerns over large prediction errors for two health states in the valuation sample. These problems must be balanced against concerns over the validity of using the VAS based health state valuation data of the original HUI2 valuation model.HUI2

Factors affecting patients' trust and confidence in GPs: evidence from the English national GP patient survey.

OBJECTIVES: Patients' trust in general practitioners (GPs) is fundamental to effective clinical encounters. Associations between patients' trust and their perceptions of communication within the consultation have been identified, but the influence of patients' demographic characteristics on these associations is unknown. We aimed to investigate the relative contribution of the patient's age, gender and ethnicity in any association between patients' ratings of interpersonal aspects of the consultation and their confidence and trust in the doctor. DESIGN: Secondary analysis of English national GP patient survey data (2009). SETTING: Primary Care, England, UK. PARTICIPANTS: Data from year 3 of the GP patient survey: 5 660 217 questionnaires sent to patients aged 18 and over, registered with a GP in England for at least 6 months; overall response rate was 42% after adjustment for sampling design. OUTCOME MEASURES: We used binary logistic regression analysis to investigate patients' reported confidence and trust in the GP, analysing ratings of 7 interpersonal aspects of the consultation, controlling for patients' sociodemographic characteristics. Further modelling examined moderating effects of age, gender and ethnicity on the relative importance of these 7 predictors. RESULTS: Among 1.5 million respondents (adjusted response rate 42%), the sense of 'being taken seriously' had the strongest association with confidence and trust. The relative importance of the 7 interpersonal aspects of care was similar for men and women. Non-white patients accorded higher priority to being given enough time than did white patients. Involvement in decisions regarding their care was more strongly associated with reports of confidence and trust for older patients than for younger patients. CONCLUSIONS: Associations between patients' ratings of interpersonal aspects of care and their confidence and trust in their GP are influenced by patients' demographic characteristics. Taking account of these findings could inform patient-centred service design and delivery and potentially enhance patients' confidence and trust in their doctor

GABAergic nerve terminals decrease in the substantia nigra following hemitransections of the striatonigral and pallidonigral pathways.

Glutamic acid decarboxylase (GAD), the enzyme that synthesizes the neurotransmitter, GABA, was immunocytochemically localized in axon terminals as well as in small and medium-sized neurons of the rat substantia nigra. The pattern formed by GAD-containing axon terminals with the dendrites and somata of neurons in the substantia nigra was altered following ipsilateral hemitransections of the striatonigral and pallidonigral pathways. A marked reduction of GAD-positive terminals occurred throughout this brain region, but the ventral fifth of the pars reticulata showed a nearly normal pattern of GAD-positive axon terminals. The results of this investigation are consistent with results from biochemical studies which have indicated that the striatonigral and/or pallidonigral pathways are GABAergic. In addition, these results suggest that the residual GABAergic terminals remaining after hemitransection are derived from intrinsic neurons of the substantia nigra

Glue ear, hearing loss and IQ:an association moderated by the child's home environment

BACKGROUND: Glue ear or otitis media with effusion (OME) is common in children and may be associated with hearing loss (HL). For most children it has no long lasting effects on cognitive development but it is unclear whether there are subgroups at higher risk of sequelae. OBJECTIVES: To examine the association between a score comprising the number of times a child had OME and HL (OME/HL score) in the first four/five years of life and IQ at age 4 and 8. To examine whether any association between OME/HL and IQ is moderated by socioeconomic, child or family factors. METHODS: Prospective, longitudinal cohort study: the Avon Longitudinal Study of Parents and Children (ALSPAC). 1155 children tested using tympanometry on up to nine occasions and hearing for speech (word recognition) on up to three occasions between age 8 months and 5 years. An OME/HL score was created and associations with IQ at ages 4 and 8 were examined. Potential moderators included a measure of the child's cognitive stimulation at home (HOME score). RESULTS: For the whole sample at age 4 the group with the highest 10% OME/HL scores had performance IQ 5 points lower [95% CI -9, -1] and verbal IQ 6 points lower [95% CI -10, -3] than the unaffected group. By age 8 the evidence for group differences was weak. There were significant interactions between OME/HL and the HOME score: those with high OME/HL scores and low 18 month HOME scores had lower IQ at age 4 and 8 than those with high OME/HL scores and high HOME scores. Adjusted mean differences ranged from 5 to 8 IQ points at age 4 and 8. CONCLUSIONS: The cognitive development of children from homes with lower levels of cognitive stimulation is susceptible to the effects of glue ear and hearing loss

Inhibitory, GABAergic nerve terminals decrease at sites of focal epilepsy.

Using an immunocytochemical method for the localization of the gamma-aminobutyric acid (GABA) synthesizing enzyme, glutamic acid decarboxylase (GAD), we have observed GABAergic nerve terminals distributed throughout all layers of normal monkey sensorimotor cortex. These terminals displayed ultrastructural characteristics that suggested that they arose from aspinous and sparsely spinous stellate neurons. In monkeys (Macaca mulatta and M. fascicularis) made epileptic by cortical application of alumina gel, a highly significant numerical decrease of GAD-positive nerve terminals occurred at sites of seizure foci indicating a functional loss of GABAergic inhibitory synapses. A loss of such inhibition at seizure foci could lead to epileptic activity of cortical pyramidal neurons

Differences in prefrontal blood oxygenation during an acute multitasking stressor in ecstasy polydrug users

Background: Cognitive deficits are well documented in ecstasy (MDMA) users with such deficits being taken as evidence of dysregulation of the 5HT system. More recently neuroimaging has been used to corroborate these deficits. The present study aimed to assess multitasking performance in ecstasy polydrug users, polydrug users and drug naïve individuals. It was predicted that ecstasy polydrug users would perform worse than nonusers on the behavioural measure and this would be supported by difference in cortical blood oxygenation. Methods: Twenty ecstasy-polydrug users, 17 polydrug users and 19 drug naïve individuals took part. On day 1 drug use history was taken and questionnaire measures were completed. On day 2, participants completed a 20 minute multitasking stressor while brain blood oxygenation was measured using functional near infrared spectroscopy (fNIRS). Results: There were no significant differences between the 3 groups on the subscales of the multitasking stressor. In addition, there were no significant differences on self-report measures of perceived workload (NASA – TLX). In terms of mood, ecstasy users were significantly less calm and less relaxed compared to drug-naïve controls. There were also significant differences at 3 voxels on the fNIRS indicating decreased blood oxygenation in ecstasy users compared to drug naïve controls at V2 (left DLPFC), V14 and V16 (right DLPFC), and compared to polydrug controls at V14. Conclusions: The results of the present study provide support for changes in brain activation during performance of demanding tasks in ecstasy polydrug users, which could be related to cerebral vasoconstriction

Immunocytochemical localization of glutamate decarboxylase in rat substantia nigra

l-Glutamate decarboxylase (GAD, EC 4.1.1.15), the enzyme which catalyzes the α-decarboxylase of l-glutamate to form γ-aminobutyric acid (GABA), was localized both light and electron microscopically in rat substantia nigra by an immunoperoxidase method. Large amounts of GAD-positive reaction product were seen throughout the substantia nigra in light microscopic preparations, and it appeared to be localized in punctate structures that were apposed to dendrites and somata. Electron microscopic studies revealed that most of the axon terminals in the substantia nigra were filled with GAD-positive reaction product and formed both axodendritic and axosomatic synapses. Many dendrites were extensively surrounded by GAD-positive terminals which most commonly formed symmetric synaptic junctions, although some formed asymmetric synaptic junctions. The results of this investigation are consistent with biochemical, pharmacological and physiological data which have indicated that neurons of the neostriatum and globus pallidus exert a GABA-mediated, postsynaptic inhibition upon the neurons of the substantia nigra. These findings provide another example in the vertebrate central nervous system where Golgi I projection neurons are inhibitory and use GABA as their neurotransmitter. © 1976

Cadaveric Spinal Surgery Simulation: A Comparison of Cadaver Types

Study Design: Single-blinded study. Objective: To assess the suitability of three types of cadaver for simulating pedicle screw insertion and establish if there is an ideal. Methods: Three types of cadaver-Thiel-embalmed, Crosado-embalmed, and formaldehyde-embalmed-were draped and the spines exposed. Experienced surgeons were asked to place pedicle screws in each cadaver and give written questionnaire feedback using a modified Likert scale. Soft tissue and bony properties were assessed, along with the role of simulation in spinal surgery training. Results: The Thiel cadaver rated highest for soft tissue feel and appearance with a median score of 6 for both (range 2 to 7). The Crosado cadaver rated highest for bony feel, with a median score of 6 (range 2 to 7). The formaldehyde cadaver rated lowest for all categories with median scores of 2, 2.5, and 3.5, respectively. All surgeons felt pedicle screw insertion should be learned in a simulated setting using human cadavers. Conclusion: Thiel and Crosado cadavers both offered lifelike simulation of pedicle screw insertion, with each having advantages depending on whether the focus is on soft tissue approach or technical aspects of bony screw insertion. Both cadaver types offer the advantage of long life span, unlike fresh frozen tissue, which means cadavers can be used multiple times, thus reducing the costs

Electrophysiological Evidence of Atypical Processing Underlying Mental Set Shifting in Ecstasy Polydrug and Polydrug Users

Executive functioning deficits are reported in ecstasy users. However research into mental set switching has been equivocal, with behavioural studies suggesting the function is preserved. The current study sought to address the issue of switching deficits in ecstasy users by combining behavioural performance with electrophysiological correlates (EEG). Twenty ecstasy polydrug users, 20 non-ecstasy polydrug users and 20 drug naive controls were recruited. Participants completed questionnaires about their drug use, sleep quality, fluid intelligence and current mood state. Each participant completed a mental set switching task (the number-letter task) whilst EEG measures were recorded. ANOVA revealed no between group differences on performance of the task, however a regression suggested that ecstasy use was a significant predictor for performance, after controlling for cannabis use. Mixed ANOVA revealed a significant effect of group on the P3, with significant differences between both drug groups and naives. There was also an interaction between electrode and group on the P2 component, with ecstasy users differing from both other groups. On the P3 component the results suggest a reduction in positivity at parieto-occipital electrodes for drug users compared to controls. Furthermore a significant increase in negativity in ecstasy users compared to control groups could be observed in several occipito-parietal electrodes at an N2 component as well as observable atypicalities in early processing (P2) displayed by ecstasy users and polydrug controls. The present study provides evidence of atypical processing of attentional shifting in ecstasy and polydrug users. Deficits in this executive function could reflect cognitive inflexibility and paucity of rapid behavioural adjustment, which may be problematic in real world situations. Keywords: Ecstasy; cannabis; executive function; stimulants; cannabis

Glutamate decarboxylase localization in neurons of the olfactory bulb.

Glutamate decarboxylase (GAD), the enzyme that synthesizes the neurotransmitter gamma-aminobutyric acid (GABA), has been localized in the rat olfactory bulb by immunocytochemical methods with both light and electron microscopy. The light microscopic results demonstrated GAD-positive puncta concentrated in the external plexiform layer and in the glomeruli of the glomerular layer. In addition, GAD-positive reaction product stained the dentrites and somata of granule and periglomerular cells. The electron microscopic observations confirmed the presence of GAD-positive reaction product within granule and periglomerular somata and dendrites. In electron micrographs of the external plexiform layer, the gemmules which arise from the distal dentrites of granule cells were also observed to be filled with reaction product, and these structures corresponded in size and location to the puncta observed in light microscopic preparations. The gemmules were observed to form reciprocal dendrodentritic synaptic junctions with mitral cell dentrites which lacked reaction product. In the glomeruli, GAD-positive reaction product was observed in the dentritic shafts and gemmules of periglomerular cells which also formed reciprocal dendrodentritic synaptic contacts with mitral/tufted cell dentrites. The localization of GAD in known inhibitory neurons of the olfactory bulb supports the case that these local circuit neurons use GABA as their neurotransmitter. The present study demonstrates that GAD molecules located within certain neuronal somata and dentrites can be visualized with antisera prepared against GAD that was purified from synaptosomal fractions of mouse brains. This finding suggests that the lack of GAD staining within somata and dentrites of GABA-ergic neurons noted in previous studies of the cerebellum and spinal cord was probably due to low GAD concentrations, rather than to antigenic differences among GAD molecules located in different portions of the neuron. A striking differences among GAD molecules located in different portions of the neuron. A striking difference between the granule and periglomerular neurons of the olfactory bulb and the neurons of the cerebellum and spinal cord is that the former have presynaptic dentrites while the latter do not. Since GAD-positive reaction product can be detected in the somata and dentrites of GABA-ergic neurons which have presynaptic dentrites, it is suggested that these neurons may differ from other GABA-ergic neurons with respect to either transport or metabolism of GAD