First evidence for a pharmacist-led anticoagulant clinic in a medicare part A long term care environment.

Anticoagulation risks in older adult, long-term care patients are known to be high, especially in those with frequent transitions between care environments. Introduction of collaborative practice agreements (CPA) in specific settings is encouraged in the United States and has provided an additional option for the care of medically challenging patients. The aim of this study was to investigate the time in therapeutic range (TTR) in a Medicare Part A sponsored long-term care environment managed by pharmacists through a collaborative practice agreement in South-Central Appalachia. A retrospective review of all warfarin patient admissions from a large long-term care pharmacy's anticoagulant clinic was conducted for residents over an 18-month period. For all patients (n = 104), the overall TTR was 46.7% (INR 43% in range). Average management duration was 19.5 days per patient. Further studies are required to optimize CPA and transition strategies for complex, advanced age warfarin patients.

Prescription drug abuse: a comparison of prescriber and pharmacist perspectives.

This study compared perceptions of prescribers and pharmacists (N = 89) regarding multiple aspects of prescription drug abuse. Questionnaires were developed to assess perceptions regarding the prevalence of prescription drug abuse, self-perceived communication competence, and additional communication and prescription drug abuse domains. Pharmacists perceived a larger percentage of patients (41%) to be abusing opioid pain relievers as compared with their prescriber colleagues (17%). Both prescribers and pharmacists indicated improvements in prescriber-pharmacist communication would serve to deter prescription drug abuse. Self-efficacy beliefs for detecting and discussing prescription drug abuse with patients were low for both cohorts. Implications and limitations are noted. Year of data collection: 2012 SETTING: Rural Appalachia Data Collection Instruments: Prescriber- and pharmacist-specific survey instruments Data Analysis Techniques: Independent samples t-test; Mann-Whitney U test.

Advancing pharmacy technician training and practice models in the United States: Historical perspectives, workforce development needs, and future opportunities.

The United States healthcare system faces immense challenges related to cost, quality, and access. As the pharmacy profession addresses these challenges by shifting toward a practice model centered around direct patient care clinical services, a competent and capable technician workforce is needed to support the roles of pharmacists. Until recently, little focus has been paid to pharmacy technicians or their role as they relate to practice model change. With ongoing pharmacist practice transformation, an approach that ensures uniform technician education, training, registration, and certification is vital to support a practice model designed to transform medication management across the continuum of care. The purpose of this commentary is three-fold: to review the history of pharmacy technician training and practice, discuss current and future technician practice models, and examine workforce development implications.

pH-Dependent cis --> trans isomerization rates for azobenzene dyes in aqueous solution.

Azobenzenes can function as molecular switches driven by their unusual cis <--> trans photoisomerization properties. The stability of an azobenzene-based switch depends on its rate of thermal relaxation, which is known to depend on the solvent environment, but few kinetic studies in aqueous media have been reported. We use nanosecond UV laser flash photolysis-transient absorption spectroscopy to measure thermal cis --> trans isomerization rates for mono- and disubstituted p-aminoazobenzenes and p-hydroxyazobenzenes in water at 23 degrees C over the pH range of 4 to 11. Observed absorption transients are fit to first-order relaxation rate constants between 10(5) and 10(1) s(-1), which is generally much faster than in nonpolar solvents, and the relaxation rates vary systematically and predictably with pH as the equilibrium shifts to ionized forms of the dyes that isomerize much more rapidly. Acid ionization constants for these dyes determined from our kinetic mechanism are compared with the pH dependence of their equilibrium UV-vis spectra. New kinetics results may enable pH control of azobenzene-based molecular switching times.

A behavioural and functional neuroimaging investigation into the effects of nicotine on sensorimotor gating in healthy subjects and persons with schizophrenia.

RATIONALE: Schizophrenia patients display an excessive rate of smoking compared to the general population. Nicotine increases acoustic prepulse inhibition (PPI) in animals as well as healthy humans, suggesting that smoking may provide a way of restoring deficient sensorimotor gating in schizophrenia. No previous study has examined the neural mechanisms of the effect of nicotine on PPI in humans. OBJECTIVES: To investigate whether nicotine enhances tactile PPI in healthy subjects and patients with schizophrenia employing a double-blind, placebo-controlled, cross-over design and, if so, what are the neural correlates of nicotine-induced modulation of PPI. MATERIALS AND METHODS: In experiment 1, 12 healthy smokers, 12 healthy non-smokers and nine smoking schizophrenia patients underwent testing for tactile PPI on two occasions, 14 days apart, once after receiving (subcutaneously) 12 microg/kg body weight of nicotine and once after receiving saline (placebo). In experiment 2, six healthy subjects and five schizophrenia patients of the original sample (all male smokers) underwent functional magnetic resonance imaging (fMRI) under the same drug conditions and the same tactile PPI paradigm as in experiment 1. RESULTS: Nicotine enhanced PPI in both groups. A comparison of patterns of brain activation on nicotine vs placebo conditions showed increased activation of limbic regions and striatum in both groups after nicotine administration. Subsequent correlational analyses demonstrated that the PPI-enhancing effect of nicotine was related to increased hippocampal activity in both groups. CONCLUSIONS: Nicotine enhances tactile PPI in both healthy and schizophrenia groups. Our preliminary fMRI findings reveal that this effect is modulated by increased limbic activity.

Evidence against functionalism from neuroimaging of the alien colour effect in synaesthesia.

Coloured hearing synaesthetes experience colours to heard words, as confirmed by reliability of self-report, psychophysical testing and functional neuroimaging data. Some also describe the 'alien colour effect' (ACE): in response to colour names, they experience colours different from those named. We have previously reported that the ACE slows colour naming in a Stroop task, reflecting cognitive interference from synaesthetically induced colours, which depends upon their being consciously experienced. It has been proposed that the hippocampus mediates such consciously experienced conflict. Consistent with this hypothesis, we now report that, in functional magnetic resonance imaging of the Stroop task, hippocampal activation differentiates synaesthetes with the ACE from those without it and from non-synaesthete controls. These findings confirm the reality of coloured hearing synaesthesia and the ACE, phenomena which pose major challenges to the dominant contemporary account of mental states, functionalism. Reductive functionalism identifies types of mental states with causal roles: relations to inputs, outputs and other states. However, conscious mental states, such as experiences of colour, are distinguished by their qualitative properties or qualia. If functionalism is applied to conscious mental states, it identifies the qualitative type of an experience with its causal role or function. This entails both that experiences with disparate qualitative properties cannot have the same functional properties, and that experiences with disparate functional properties cannot have the same qualitative properties. Challenges to functionalism have often denied the first entailment. Here, we challenge the second entailment on empirical grounds. In coloured hearing synaesthesia, colour qualia are associated with both hearing words and seeing surfaces; and, in the ACE, these two functions act in opposition to one another. Whatever its merits as an account of other mental states, reductive functionalism cannot be the correct account of conscious experiences.

Personality predicts brain responses to cognitive demands.

Eysenck (1981) proposed that the personality dimension of introversion- extraversion (E) reflects individual differences in a cortical arousal system modulated by reticulothalamic- cortical pathways: it is chronically more active in introverts relative to extraverts and influences cognitive performance in interaction with task parameters. A circuit with connections to this system, including the dorsolateral prefrontal cortex (DLPFC) and anterior cingulate (AC) cortex, has been identified in studies applying functional magnetic resonance imaging (fMRI) to a broad range of cognitive tasks. We examined the influence of E, assessed with the Eysenck Personality Questionnaire-Revised (Eysenck and Eysenck, 1991), in fMRI activity during an "n-back" task involving four memory loads (0-, 1-, 2-, and 3-back) and a rest condition in healthy men. To confirm the specificity of E effects, we also examined the effects of neuroticism and psychoticism (P) scores. We observed that, as predicted by Eysenck's model, the higher the E score, the greater the change in fMRI signal from rest to the 3-back condition in the DLPFC and AC. In addition, E scores were negatively associated with resting fMRI signals in the thalamus and Broca's area extending to Wernicke's area, supporting the hypothesized (negative) relationship between E and resting arousal. P scores negatively correlated with resting fMRI signal in the globus pallidus-putamen, extending previous findings of a negative relationship of schizotypy to striatal activity seen with older neuroimaging modalities to fMRI. These observations suggest that individual differences affect brain responses during cognitive activity and at rest and provide evidence for the hypothesized neurobiological basis of personality.

Disruption of learned irrelevance in acute schizophrenia in a novel continuous within-subject paradigm suitable for fMRI.

Learned irrelevance (LIrr) is closely related to latent inhibition (LI). In LI a to-be-conditioned stimulus (CS) is prexposed alone prior to the opportunity to learn an association between the CS and an unconditioned stimulus (UCS). In LIrr preexposure consists of intermixed presentations of both CS and UCS in a random relationship to each other. In both paradigms preexposure leads in normal subjects to reduced or retarded learning of the CS-UCS association. Acute schizophrenics fail to show LI. LI is usually demonstrated as a one-off, between-groups difference in trials to learning, so posing problems for neuroimaging. We have developed a novel, continuous, within-subject paradigm in which normal subjects show robust and repeated LIrr. We show that this paradigm is suitable for functional magnetic resonance imaging (fMRI) and gives rise, in normal subjects, to activation in the hippocampal formation, consistent with data from animal experiments on LI. We also report, consistent with previous studies of LI, loss (indeed, significant reversal) of LIrr in acute (first 2 weeks of current psychotic episode) schizophrenics. Chronic schizophrenics failed to demonstrate learning, precluding measurement in this group of LIrr. These findings establish the likely value of the new paradigm for neuroimaging studies of attentional dysfunction in acute schizophrenia.

Task instructions modulate neural responses to fearful facial expressions.

BACKGROUND: The amygdala, hippocampus, ventral, and dorsal prefrontal cortices have been demonstrated to be involved in the response to fearful facial expressions. Little is known, however, about the effect of task instructions upon the intensity of responses within these regions to fear-inducing stimuli. METHODS: Using functional magnetic resonance imaging, we examined neural responses to alternating, 30-sec blocks of fearful and neutral expressions in nine right-handed male volunteers during three different 5-min conditions: 1) passive viewing; 2) performance of a gender-decision task, with no explicit judgment of facial emotion; 3) performance of an emotionality judgment task - an explicitly emotional task. RESULTS: There was a significant effect of task upon activation within the left hippocampus and the left inferior occipital gyrus, and upon the magnitude of response within the left hippocampus, with maximal activation in these regions occurring during passive viewing, and minimal during performance of the explicit task. Performance of the gender-decision and explicit tasks, but not passive viewing, was also associated with activation within ventral frontal cortex. CONCLUSIONS: Neural responses to fearful facial expressions are modulated by task instructions.

Procedural learning in schizophrenia: a functional magnetic resonance imaging investigation.

Procedural learning (PL) is a type of rule-based learning in which performance facilitation occurs with practice on task without the need for conscious awareness. Schizophrenic patients have often (though not invariably) been found to show impaired PL. We performed functional magnetic resonance imaging (fMRI) during a blocked, periodic sequence-learning task with groups of: (i) healthy subjects, and (ii) schizophrenic patients on conventional antipsychotics. Healthy subjects showed significant PL, but patients did not. In healthy subjects, PL was associated with increased activation in the striatum, thalamus, cerebellum, precuneus, medial frontal lobe, and cingulate gyrus. The power of activation in the thalamus, striatum, precuneus, cingulate gyrus and BA 6 was related to the magnitude of PL in these subjects. No regions, except the anterior inferior gyrus, were significantly activated in patients. The caudate nucleus, thalamus, precuneus, and sensorimotor regions were activated significantly differently between the two groups. The findings demonstrate the involvement of the striatum, cerebellum, thalamus, cingulate gyrus, precuneus, and sensorimotor regions in PL. Further fMRI studies of PL in normal subjects treated with conventional antipsychotics, drug naïve patients, and patients given atypical antipsychotics would help to clarify the roles of schizophrenic disease processes and antipsychotic medication in impaired PL and associated brain abnormalities in schizophrenia.

The partial reinforcement extinction effect in humans: effects of schizophrenia, schizotypy and low doses of amphetamine.

The partial reinforcement extinction effect (PREE) was studied in human subjects. It has been suggested that the PREE depends on neural mechanisms critical to the cognitive dysfunction which underlines acute schizophrenia. We therefore predicted that the PREE should be reduced, through decreased resistance to extinction in the partial reinforcement (PR) condition, in various types of individual: (a) healthy volunteers given low doses of oral amphetamine; (b) those in the acute (but not chronic) phase of a schizophrenic illness and; (c) healthy volunteers with high scores on personality measures of schizotypy. Despite obtaining robust demonstrations of PREE in all experiments, none of these predictions were confirmed. A single, low dose, of amphetamine had no effect on either continuous reinforcement (CR) or partial reinforcement (PR). Acute and chronic schizophrenic patients showed a reduced PREE compared to controls. However this was due to increased resistance to extinction in the CR groups. Finally, high schizotypy scores were associated with greater PREE, attributable to both decreased extinction in the CR condition and increased extinction in the PR condition. The results of these experiments on human PREE provide no support that PREE is a valid paradigm with which to explore the cognitive dysfunction underlying schizophrenia.

A demonstration of within-subjects latent inhibition in the human: limitations and advantages.

The magnitude of latent inhibition (LI) (a retardation of associative learning due to prior exposure to the conditioning stimulus) was measured in healthy volunteers using both a within- and a between-subjects version of the task. Reliable LI was demonstrated for the within-subjects paradigm (using a design that fully counter-balanced stimulus of pre-exposure) but the magnitude of the effect was smaller than for the between-subjects version. Measures of schizotypal personality were found to be associated with reduced LI for the between-subjects task, but not for the within-subjects task. We hypothesised that for the within-subjects task learning about the first stimulus-consequence association (usually that for the not pre-exposed (NPE) stimulus) primes learning about the second stimulus, thus reducing the effect of pre-exposure and restricting the range of LI scores. In turn, this restricted range of LI scores does not allow subtle differences on schizotypal personality dimensions to reveal their effect using this within-subjects paradigm. In conclusion, a within-subjects LI task has been developed which is not open to explanation in terms of differences in stimulus salience. However, the limited range of pre-exposure scores in the current within-subject paradigm may severely limit it is use as an indicator of subtle performance changes.

Allocentric spatial memory activation of the hippocampal formation measured with fMRI.

Hippocampal activation was investigated, comparing allocentric and egocentric spatial memory. Healthy participants were immersed in a virtual reality circular arena, with pattern-rendered walls. In a viewpoint-independent task, they moved toward a pole, which was then removed. They were relocated to another position and had to move to the prior location of the pole. For viewpoint-dependent memory, the participants were not moved to a new starting point, but the patterns were rotated to prevent them from indicating the final position. Hippocampal and parahippocampal activation were found in the viewpoint-independent memory encoding phase. Viewpoint-dependent memory did not result in such activation. These results suggest differential activation of the hippocampal formation during allocentric encoding, in partial support of the spatial mapping hypothesis as applied to humans.

Learned fear, emotional reactivity and fear of heights: a factor analytic map from a large F(2) intercross of Roman rat strains.

Anxiety-related behaviours were evaluated across various tests in a 800 F(2)-intercross of the Roman high- and low-avoidance inbred rats. These tests either evoke unlearned (open field [OF]; plus-maze [PM]; hole-board [HB]; spontaneous activity [A]; and acoustic startle reflex [ASR]) or learned (classical fear conditioning [CFC]; and shuttlebox avoidance conditioning [SAC]), anxious/fearful responses. Using factor analysis (oblique rotation), we obtained a six-fold solution with 14 variables derived from all tests. These six factors represented SAC, CFC, PM anxiety, PM and OF activity, ASR anxiety, plus a mixed whole of anxious and activity variables (from OF and A), respectively. In searching for a smaller number of meaningful factors, we applied a three-factor solution that coherently corresponded with differentiated facets of fearfulness, rather than with the tests. Results showed that (1) measures of SAC and CFC strongly loaded onto Factor 1, labelled as "Learned Fear"; (2) a blend of almost all variables loaded onto Factor 2, called "Emotional Reactivity"; and (3) open arm behaviour in the PM loaded onto Factor 3, called "Fear of Heights." After discussing limitations of this apparently consistent behavioural map of anxiety, we advance some connections between those factors with quantitative trait loci candidates (genetic markers) as detected in the same sample.

Fearfulness and sex in F2 Roman rats: males display more fear though both sexes share the same fearfulness traits.

The pattern of sex differences in a large sample (about 400 for each sex) of F2-generation rats, derived from inbred Roman high- and low-avoidance strains differing in fearfulness and brain functioning, was investigated. We obtained measures from responses to a battery of novel/threatening tests [open field (OF), plus maze (PM), hole board (HB), activity (A), and acoustic startle reflex (ASR)] as well as learned fear paradigms [classical fear conditioning (CFC) and shuttlebox avoidance conditioning (SAC)]. The results showed that almost all behaviors assessed fit with a pattern of unidirectional sex effects characterized by male rats as being more fearful than females: males defecated more than females in the OF, PM, HB, ASR, and CFC; ambulated less in the OF, PM, A, and SAC; showed more self-grooming in PM and HB; explored the open arms of the PM and the holes of the HB less; displayed enhanced ASR; and showed poorer performance in the SAC task. We applied two factor analyses to each sex showing that, in general, they shared a common three-factor structure: a Learned Fear Factor comprising SAC and CFC responding, a Fear of Heights/Open Spaces Factor with the highest loadings for open arm behavior in the PM, and an Emotional Reactivity Factor, mainly grouping defecations, ambulation, and self-grooming. These results indicate that the essential components of fearful behavior are similar for both sexes in an inbred but genetically heterogeneous population.

Neural correlates of tactile prepulse inhibition: a functional MRI study in normal and schizophrenic subjects.

Prepulse inhibition (PPI) of the startle reflex refers to the ability of a weak prestimulus, the prepulse, to inhibit the response to a closely following strong sensory stimulus, the pulse. PPI is found to be deficient in a number of psychiatric and neurological disorders associated with abnormalities at some level in the limbic and cortico-pallido-striato-thalamic circuitry. We applied whole-brain functional magnetic resonance imaging to elucidate the neural correlates of PPI using airpuff stimuli as both the prepulse and the pulse in groups of (i) healthy subjects and (ii) schizophrenic patients. Cerebral activation during prepulse-plus-pulse stimuli with stimulus-onset asynchronies of 120 ms was contrasted with activation during pulse-alone stimuli. In healthy subjects, PPI was associated with increased activation bilaterally in the striatum extending to hippocampus and thalamus, right inferior frontal gyrus and bilateral inferior parietal lobe/supramarginal gyrus, and with decreased activation in the right cerebellum and left medial occipital lobe. All activated regions showed significantly greater response in healthy subjects than schizophrenic patients, who also showed a trend for lower PPI. The findings demonstrate involvement of the striatum, hippocampus, thalamus, and frontal and parietal cortical regions in PPI. Dysfunctions in any of these regions may underlie observations of reduced PPI in schizophrenia.

The use and misuse of prescription stimulants as "cognitive enhancers" by students at one academic health sciences center.

PURPOSE: Prescription stimulant use as "cognitive enhancers" has been described among undergraduate college students. However, the use of prescription stimulants among future health care professionals is not well characterized. This study was designed to determine the prevalence of prescription stimulant misuse among students at an academic health sciences center. METHOD: Electronic surveys were e-mailed to 621 medical, pharmacy, and respiratory therapy students at East Tennessee State University for four consecutive weeks in fall 2011. Completing the survey was voluntary and anonymous. Surveys asked about reasons for, frequency of, and side effects of nonprescription misuse of prescription stimulants. Given the sensitive material, an opportunity to win one of ten $50 gift cards was used as an incentive. RESULTS: Three hundred seventy-two (59.9%) students completed the survey from three disciplines (47.6% medical, 70.5% pharmacy, and 57.6% respiratory therapy). Overall, 11.3% of responders admitted to misusing prescription stimulants. There was more misuse by respiratory therapy students, although this was not statistically significant (10.9% medicine, 9.7% pharmacy, 26.3% respiratory therapy; P = .087). Reasons for prescription stimulant misuse included to enhance alertness/energy (65.9%), to improve academic performance (56.7%), to experiment (18.2%), and to use recreationally/get high (4.5%). CONCLUSIONS: Prescription stimulant misuse was prevalent among participating students, but further research is needed to describe prevalence among future health care workers more generally. The implications and consequences of such misuse require further study across professions with emphasis on investigating issues of academic dishonesty (e.g., "cognitive enhancement"), educational quality, and patient safety or health care quality.