Patient- and practice-related determinants of emergency department length of stay for patients with psychiatric illness.

STUDY OBJECTIVE: To identify patient and clinical management factors related to emergency department (ED) length of stay for psychiatric patients. METHODS: This was a prospective study of 1,092 adults treated at one of 5 EDs between June 2008 and May 2009. Regression analyses were used to identify factors associated with ED length of stay and its 4 subcomponents. Secondary analyses considered patients discharged to home and those who were admitted or transferred separately. RESULTS: The overall mean ED length of stay was 11.5 hours (median 8.2 hours). ED length of stay varied by discharge disposition, with patients discharged to home staying 8.6 hours (95% confidence interval 7.7 to 9.5 hours) and patients transferred to a hospital outside the system of care staying 15 hours (95% confidence interval 12.7 to 17.6 hours) on average. Older age and being uninsured were associated with increased ED length of stay, whereas race, sex, and homelessness had no association. Patients with a positive toxicology screen result for alcohol stayed an average of 6.2 hours longer than patients without toxicology screens, an effect observed primarily in the periods before disposition decision. Diagnostic imaging was associated with an average 3.2-hour greater length of stay, prolonging both early and late components of the ED stay. Restraint use had a similar effect, leading to a length of stay 4.2 hours longer than that of patients not requiring restraints. CONCLUSION: Psychiatric patients spent more than 11 hours in the ED on average when seeking care. The need for hospitalization, restraint use, and the completion of diagnostic imaging had the greatest effect on postassessment boarding time, whereas the presence of alcohol on toxicology screening led to delays earlier in the ED stay. Identification and sharing of best practices associated with each of these factors would provide an opportunity for improvement in ED care for this population.

Measuring outcomes in adult outpatient psychiatry.

Despite growing pressure for accountability, mental health professionals continue to debate the value of routinely measuring treatment outcomes. This paper sought to move the outcomes measurement debate forward by reviewing some of the current limitations in outcomes methodology and by providing initial strategies to address them. Using these strategies, we evaluated outcomes for a large diagnostically diverse group of adult outpatients receiving treatment as usual (TAU) within an academic medical centre. Initial self-report and clinician-rated assessments were obtained from 5546 patients, and follow-up data were obtained from 1572 (28%) patients. Using the subset of patients with the follow-up data, we determined treatment effect sizes, rates of reliable improvement (and deterioration) and rates of clinically significant improvement for all patients and for specific diagnostic groups (depression, anxiety, substance abuse, mood disorders not otherwise specified, bipolar and psychotic conditions). TAU outcomes for depression and anxiety were also compared with benchmarks derived from the randomized controlled trial literature. Lastly, the impact of patient or sample characteristics on outcome was explored. Overall, these findings generally support the benefit of TAU over no treatment while also highlighting both the utility and limitations inherent in the current approaches to evaluating treatment outcomes. Suggestions for improving outcomes measurement are provided.

The oversight of autonomous artificial intelligence: lessons from nurse practitioners as physician extenders.

The development of autonomous artificial intelligence (A-AI) products in health care raises novel regulatory challenges, including how to ensure their safety and efficacy in real-world settings. Supplementing a device-centered regulatory scheme with a regulatory scheme that considers A-AI products as a 'physician extender' may improve the real-world monitoring of these technologies and produce other benefits, such as increased access to the services offered by these products. In this article, we review the three approaches to the oversight of nurse practitioners, one type of physician extender, in the USA and extrapolate these approaches to produce a framework for the oversight of A-AI products. Under the framework, the US Food and Drug Administration would evaluate A-AI products and determine whether they are allowed to operate independently of physician oversight; required to operate under some physician oversight via a 'collaborative protocol' model; or required to operate under direct physician oversight via a 'supervisory protocol' model.

Hospital variability in emergency department length of stay for adult patients receiving psychiatric consultation: a prospective study.

STUDY OBJECTIVE: We ascertain the components of emergency department (ED) length of stay for adult patients receiving psychiatric evaluation and to examine their variability across 5 hospitals within a health care system. METHODS: This was a prospective study of 1,092 adults treated between June 2008 and May 2009. Research staff abstracted length of stay and clinical information from the medical records. Clinicians completed a time log for each patient contact. Main outcomes were median times for the overall ED length of stay and its 4 components, or time from triage to request for psychiatric evaluation, request to start of psychiatric evaluation, start to completion of psychiatric evaluation with a disposition decision, and disposition decision to discharge from the ED. RESULTS: The overall median length of stay was more than 8 hours. Median times for the components were 1.8 hours from triage to request, 15 minutes from request to start of psychiatric evaluation, 75 minutes from start of psychiatric evaluation to disposition decision, and nearly 3 hours from disposition decision to ED discharge. The median disposition decision to discharge time was substantially shorter for patients who went home (40 minutes) than for patients who were admitted (2.5 hours) or transferred for psychiatric admission at other facilities (6.3 hours). When adjustments for patient and clinical factors were made, differences in ED length of stay persisted between hospitals. CONCLUSION: ED length of stay for psychiatric patients varied greatly between hospitals, highlighting differences in the organization of psychiatric services and inpatient bed availability. Findings may not generalize to other settings or populations.

MTHFR 677C --> T genotype disrupts prefrontal function in schizophrenia through an interaction with COMT 158Val --> Met.

Understanding how risk genes cumulatively impair brain function in schizophrenia could provide critical insights into its pathophysiology. Working memory impairment in schizophrenia has been associated with abnormal dopamine signaling in the prefrontal cortex, which is likely under complex genetic control. The catechol-O-methyltransferase (COMT) 158Val --> Met polymorphism (rs4680), which affects the availability of prefrontal dopamine signaling, consistently stratifies prefrontal activation during working memory performance. However, the low-dopamine COMT 158Val allele does not confer increased risk for schizophrenia, and its effects on prefrontal function are not specific to the disorder. In the setting of other genetic variants influencing prefrontal dopamine signaling, COMT 158Val --> Met genotype may exert disease-specific effects. A second polymorphism, methylenetetrahydrofolate reductase (MTHFR) 677C --> T (rs1801133), has been associated with overall schizophrenia risk and executive function impairment in patients, and may influence dopamine signaling through mechanisms upstream of COMT effects. We found that the hypofunctional 677T variant was associated with decreased working memory load-dependent activation in the prefrontal and insular cortices in 79 schizophrenia patients, but not in 75 demographically matched healthy controls. Further, significant MTHFR x COMT genotype interactions were observed, which differed by diagnostic group: Reduced prefrontal activation was associated with the 677T and 158Val alleles in patients, but with 677C/C and 158Met/Met genotype in controls. These findings are consistent with epistatic effects of the COMT and MTHFR polymorphisms on prefrontal dopamine signaling, and suggest that in schizophrenia patients, the MTHFR 677T allele exacerbates prefrontal dopamine deficiency. The findings also suggest the importance of weighing COMT effects on prefrontal function within the context of MTHFR genotype.

Aberrant frontoparietal function during recognition memory in schizophrenia: a multimodal neuroimaging investigation.

Prefrontal-parietal networks are essential to many cognitive processes, including the ability to differentiate new from previously presented items. As patients with schizophrenia exhibit structural abnormalities in these areas along with well documented decrements in recognition memory, we hypothesized that these patients would demonstrate memory-related abnormalities in prefrontal and parietal physiology as measured by both functional magnetic resonance imaging and magnetoencephalography (MEG). Medicated outpatients with schizophrenia (n = 18) and age-matched healthy control subjects (n = 18) performed an old-new recognition memory task while physiological data were obtained. Whereas controls exhibited strong, bilateral activation of prefrontal and posterior parietal regions during successful identification of old versus new items, patients exhibited greatly attenuated activation of the right prefrontal and parietal cortices. However, within the patient group, there was strong correlation between memory performance and activation of these right-sided regions as well as a tight correlation between old-new effect-related activations in frontal and parietal regions, a pattern not seen in control subjects. Using MEG, control subjects-but not patients-exhibited a sequential pattern of old > new activity in the left posterior parietal cortex and then right prefrontal cortex; however, patients uniquely exhibited old > new activity in right temporal cortex. Collectively, these findings point to markedly different distributions of regional specialization necessary to complete the old-new item recognition task in patients versus controls. Inefficient utilization of prefrontal-parietal networks, with compensatory activation in temporal regions, may thus contribute to deficient old-new item recognition in schizophrenia.

The effects of transdermal nicotine on cognition in nonsmokers with schizophrenia and nonpsychiatric controls.

Abundant evidence indicates that the neuronal nicotinic acetylcholine receptor (nAChR) system is integral to regulation of attentional processes and is dysregulated in schizophrenia. Nicotinic agonists may have potential for the treatment of cognitive impairment in this disease. This study investigated the effects of transdermal nicotine on attention in individuals with schizophrenia (n=28) and healthy controls (n=32). All participants were nonsmokers in order to eliminate confounding effects of nicotine withdrawal and reinstatement that may occur in the study of smokers. Subjects received 14 mg transdermal nicotine and identical placebo in a randomized, placebo-controlled, crossover design. A cognitive battery was conducted before and 3 h after each patch application. The primary outcome measure was performance on the Continuous Performance Test Identical Pairs (CPT-IP) Version. Nicotine significantly improved the performance on the CPT-IP as measured by hit reaction time, hit reaction time standard deviation and random errors in both groups. In addition, nicotine reduced commission errors on the CPT-IP and improved the performance on a Card Stroop task to a greater extent in those with schizophrenia vs controls. In summary, nicotine improved attentional performance in both groups and was associated with greater improvements in inhibition of impulsive responses in subjects with schizophrenia. These results confirm previous findings that a single dose of nicotine improves attention and suggest that nicotine may specifically improve response inhibition in nonsmokers with schizophrenia.

Effects of transdermal nicotine on episodic memory in non-smokers with and without schizophrenia.

RATIONALE: Nicotinic agonists may improve attention and memory in humans and may ameliorate some cognitive deficits associated with neuropsychiatric disorders such as schizophrenia. MATERIALS AND METHODS: We investigated the effects of a single dose of nicotine on episodic memory performance in 10 adults with schizophrenia and 12 healthy controls. Participants were nonsmokers in order to avoid confounding effects of nicotine withdrawal and reinstatement on memory. At each of two study visits, participants performed a test of episodic memory before and 4 h after application of a 14-mg transdermal nicotine (or identical placebo) patch in counterbalanced order. RESULTS: Compared with placebo, nicotine treatment was associated with more rapid and accurate recognition of novel items. There was a trend for a treatment by diagnosis interaction, such that the effect of nicotine to reduce false alarms was stronger in the schizophrenia than the control group. There was no effect of nicotine on accuracy or reaction time for identification of previously viewed items. CONCLUSIONS: These data suggest that nicotine improves novelty detection in non-smokers, an effect that may be more pronounced in non-smokers with schizophrenia. Because memory deficits are associated with functional impairment in schizophrenia and because impaired novelty detection has been linked to the positive symptoms of schizophrenia, study of the effects of chronic nicotinic agonist treatment on novelty detection may be warranted.

Distinguishing familiarity-based from source-based memory performance in patients with schizophrenia.

BACKGROUND: There is substantial current interest in the cognitive deficits associated with schizophrenia, particularly those in the realm of memory. Yet the exact nature of these deficits remains a matter of some debate. This study sought to examine performance on two distinct aspects of memory performance: familiarity-based and source-based memory processes. METHODS: Eighteen medicated outpatients with schizophrenia and eighteen healthy adult control subjects performed an external source memory task. Key measures included the ability to distinguish old (previously experienced) items from new items, the ability to correctly identify the source (male voice or female voice) of previously experienced items, and the reaction time associated with these responses. RESULTS: Patients with schizophrenia showed an impaired ability to distinguish old from new items, but intact performance in correctly identifying the source of items recognized as old. Whereas control subjects showed a rapid response to items deemed unfamiliar, particularly in rejecting novel items, these responses were slowed in patients with schizophrenia. This was not attributable to a generalized diminution in processing speed, as reaction times to correctly recognized old items (regardless of source accuracy) did not differ between the two groups. CONCLUSIONS: Patients with schizophrenia demonstrated impaired familiarity-based and intact source-based memory performance. In addition, the reaction time for novelty detection, an important component of familiarity-based memory, was significantly delayed in patients compared to controls, while the response times for source-based decisions were completely overlapping. Considered together, these findings suggest a deficit in the familiarity-based aspect of episodic memory in at least some patients with schizophrenia.

Auditory stimulus repetition effects on cortical hemoglobin oxygenation: a near-infrared spectroscopy investigation.

The cortical response to repeated sensory stimuli plateaus (or declines) as repetition frequencies increase beyond 2-8 Hz. This study examined the underlying changes in cortical oxygenated and deoxygenated hemoglobin associated with this phenomenon using near-infrared spectroscopy. The optical signal was measured from 11 healthy volunteers listening to noise-burst trains presented at 2, 10, and 35 Hz. In a bilateral region consistent with the posterior superior temporal gyrus there was an inverse relationship between deoxyhemoglobin concentration change and stimulus frequency: greatest at 2 Hz, intermediate at 10 Hz, and smallest at 35 Hz. These findings provide preliminary support for a relationship between the perceptual characteristics of auditory stimuli and modulation of cortical oxygenation as measured via an emerging neuromonitoring technique.

No evidence for a differential deficit of reality monitoring in schizophrenia: a meta-analysis of the associative memory literature.

INTRODUCTION: Patients with schizophrenia exhibit deficits in memory performance, particularly when required to bind together disparate items (associative memory). Yet the literature on associative memory is decidedly mixed, with some studies showing large deficits and other showing none. METHODS: The aims of this meta-analysis were to determine an overall effect size for the associative memory deficit in patients with schizophrenia and to examine two potential moderating variables related to this impairment: the nature of the memory being tested (pair vs. source recognition) and the inclusion or exclusion of novel items as part of the recognition test. RESULTS: We found that the mean effect sizes were large for pair recognition (r=.50) and medium for source recognition (r=.29), with a significant difference between the two recognition types. Contrary to a priori hypotheses, there were no differences in the effect sizes across the various types of source memory (i.e., internal, external, or reality monitoring). There was, however, a significant difference in the effect sizes between those studies that included novel items as part of the memory test (r=.26) and those that did not (r=.44). CONCLUSION: These findings suggest that the associative memory deficit in schizophrenia is not specific to self/other distinctions, but is rather a more global effect seen across testing conditions. In addition, memory tests that do not include new items appear to maximise this effect, perhaps by removing a potential response outlet for subjects who lack confidence in the accuracy of their memory performance.

Interactive effects of COMT Val108/158Met and MTHFR C677T on executive function in schizophrenia.

Schizophrenia is characterized by heritable deficits in executive function. Two common, functional polymorphisms, catechol-O-methyltransferase (COMT) Val108/158Met and methylenetetrahydrofolate reductase (MTHFR) C677T, have separately been associated with executive function performance in schizophrenia. Given the closely related biochemistry of MTHFR and COMT, it is plausible that the T and Val alleles act synergistically to impair executive function. This investigation of 185 outpatients with schizophrenia examined the interactive effects of these two polymorphisms on Wisconsin Card Sorting Task (WCST) performance. Two WCST measures consistently associated with schizophrenia, perseverative errors and inability to generate categories, were contrasted among compound COMT-MTHFR genotype groups. Individuals homozygous for the COMT Val allele who also carried at least one copy of the MTHFR T allele exhibited a significantly higher percentage of perseverative errors than patients in the other genotype groups. While the T allele also exerted a negative effect on category generation, COMT genotype did not contribute to category performance. It is plausible that cumulative effects of the MTHFR T and COMT Val alleles on intracellular methylation profiles and prefrontal dopamine transmission underlie their interactive effect on perseverative errors.

Trends in Medicare Part B Spending on Discarded Drugs, 2017-2020.

This cross-sectional study quantifies trends in discarded drug spending since the onset of mandated reporting.

Measuring the impact of medical research: moving from outputs to outcomes.

Billions of dollars are spent every year to support medical research, with a substantial percentage coming from charitable foundations. To justify these expenditures, some measure of the return on investment would be useful, particularly one aligned with the intended ultimate outcome of this scientific effort: the amelioration of disease. The current mode of reporting on the success of medical research is output based, with an emphasis on measurable productivity. This approach falls short in many respects and may be contributing to the well-described efficacy-effectiveness gap in clinical care. The author argues for an outcomes-based approach and describes the steps involved, using an adaptation of the logic model. A shift in focus to the outcomes of our work would provide our founders with clearer mission-central return-on-investment feedback, would make explicit the benefits of science to an increasingly skeptical public, and would serve as a compass to guide the scientific community in playing a more prominent role in reducing the efficacy-effectiveness gap. While acknowledging the enormous complexity involved with the implementation of this approach on a large scale, the author hopes that this essay will encourage some initial steps toward this aim and stimulate further discussion of this concept.

Effects of the methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism on executive function in schizophrenia.

BACKGROUND: The methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism has been associated with both overall schizophrenia risk and severity of negative symptoms. This study examined whether schizophrenia patients homozygous for the risk allele (T/T) exhibit greater impairment in executive function, and determined the extent to which MTHFR's effects on negative symptoms underlie this relationship. METHODS: 200 outpatients with chronic schizophrenia were evaluated with the Verbal Fluency Test (VFT), Wisconsin Card Sort Test (WCST), and California Verbal Learning Test (CVLT). Performance was stratified by MTHFR C667T genotype. Path analysis determined the extent to which MTHFR effects on negative symptoms mediated the relationship between genotype and cognitive measures. RESULTS: T/T subjects exhibited significantly greater deficits on the VFT and had more difficulty achieving the first category on the WCST. Genotype groups did not differ in CVLT performance. C677T effects on negative symptoms contributed to, but did not fully account for, genotype effects on VFT. Negative symptoms did not mediate WCST performance. CONCLUSIONS: MTHFR C677T genotype contributes to certain executive function deficits in schizophrenia. These deficits remained significant when taking into account mediating effects of negative symptoms. Although the intermediate mechanisms for C677T effects remain uncertain, these results suggest that MTHFR-related cognitive impairment and negative symptoms reflect differing neural substrates.

Fronto-hippocampal function during temporal context monitoring in schizophrenia.

BACKGROUND: Patients with schizophrenia have difficulty using contextual information to recall the source of information. Given the importance of the hippocampus and prefrontal cortex (PFC) in this type of memory, we hypothesized that this cognitive deficit stemmed from aberrant fronto-hippocampal activation during memory retrieval. METHODS: Patients with schizophrenia (n = 16) and age-matched comparison subjects (n = 16) underwent functional magnetic resonance imaging while performing a verbal memory task that requires intact use of temporal context. Blood oxygen-level dependent (BOLD) signal during correct memory decisions was compared between the two groups with statistical parametric mapping. RESULTS: Contrary to our hypotheses, patients with schizophrenia demonstrated nearly identical memory performance to that of the comparison subjects. Despite this, there were significant between-group BOLD signal differences, including a pattern of task-dependent hypofrontality or hyperfrontality. In addition, whereas the highest-performing subset of the comparison group demonstrated robust modulation of hippocampal activity, this pattern was not seen in the highest-performing patients with schizophrenia. CONCLUSIONS: Despite memory performance similar to that of comparison subjects, patients with schizophrenia activated different neural pathways to achieve this success. This might reflect underlying neuropathology in fronto-hippocampal circuitry, the use of an alternate cognitive strategy to accomplish task performance, or both.

Increased medial temporal lobe activation during the passive viewing of emotional and neutral facial expressions in schizophrenia.

INTRODUCTION: Patients with schizophrenia show deficits in facial affect and facial identity recognition and exhibit structural and neurophysiological abnormalities in brain regions known to mediate these processes. Functional neuroimaging studies of neural responses to emotional facial expressions in schizophrenia have reported both increases and decreases in medial temporal lobe (MTL) activity in schizophrenia. Some of this variability may be related to the tasks performed and the baseline conditions used. Here we tested whether MTL responses to human faces in schizophrenia are abnormal when unconstrained by a cognitive task and measured relative to a low-level baseline (fixation) condition. METHODS: 15 patients with schizophrenia and 16 healthy control subjects underwent functional magnetic resonance imaging (fMRI) while passively viewing human faces displaying fearful, happy, and neutral emotional expressions. RESULTS: Relative to control subjects, the patients demonstrated (1) significantly greater activation of the left hippocampus while viewing all three facial expressions and (2) increased right amygdala activation during the initial presentation of fearful and neutral facial expressions. CONCLUSIONS: In schizophrenia, hippocampal and amygdala activity is elevated during the passive viewing of human faces.

Hippocampal and parahippocampal volumes in schizophrenia: a structural MRI study.

Smaller medial temporal lobe volume is a frequent finding in studies of patients with schizophrenia, but the relative contributions of the hippocampus and three surrounding cortical regions (entorhinal cortex, perirhinal cortex, and parahippocampal cortex) are poorly understood. We tested the hypothesis that the volumes of medial temporal lobe regions are selectively changed in schizophrenia. We studied 19 male patients with schizophrenia and 19 age-matched male control subjects. Hippocampal and cortical volumes were estimated using a three-dimensional morphometric protocol for the analysis of high-resolution structural magnetic resonance images, and repeated measures ANOVA was used to test for region-specific differences. Patients had smaller overall medial temporal lobe volumes compared to controls. The volume difference was not specific for either region or hemisphere. The finding of smaller medial temporal lobe volumes in the absence of regional specificity has important implications for studying the functional role of the hippocampus and surrounding cortical regions in schizophrenia.

Neuroimaging-genetic paradigms: a new approach to investigate the pathophysiology and treatment of cognitive deficits in schizophrenia.

Cognitive impairment is a prominent and debilitating feature of schizophrenia. Genetic predisposition likely accounts for a large proportion of these cognitive deficits. Direct associations between candidate genes and cognitive dysfunction have been difficult to establish, however, largely due to the subtle effects of these genes on observable behavior. Neuroimaging techniques can provide a sensitive means to bridge the neurobiology of genes and behavior. Here we illustrate the use of neuroimaging-genetics paradigms to elaborate the relationship between genes and cognitive dysfunction in schizophrenia. After reviewing principles important for the selection of genes, neuroimaging techniques, and subjects, we describe how imaging-genetics investigations have helped clarify the contribution of five candidate genes (COMT, GRM3, G72, DISC1, and BDNF) to cognitive deficits in schizophrenia. The potential of this approach for improving patient care will depend on its ability to predict outcomes with greater accuracy and sensitivity than current clinical measures.