Delirium Phenotype by Age and Sex in a Pooled Data Set of Adult Patients.

The authors aimed to evaluate whether the clinical phenotype of delirium differs if dichotomized either by sex or age (cutoff age, 65 years old) in a pooled sample of 406 nondemented adult patients with delirium as defined by DSM-IV criteria. Delirium characteristics were measured with the Delirium Rating Scale-Revised-98 (DRS-R-98). DRS-R-98 items were subgrouped to represent subscores representing the three core domains of delirium (cognitive, higher-order thinking, and circadian), noncore accessory symptoms (psychotic and affective), and diagnostic characteristics (temporal onset, fluctuation, and physical disorder). The authors compared means of the DRS-R-98 subscores and medians of individual items. Exploratory factor analyses evaluated delirium characteristics for each subgroup for each of the four groups-male, female, nongeriatric, and geriatric-while taking into account active medical diagnoses. Males had higher scores on motor agitation and affective lability (behavioral), whereas females had a higher frequency of hypoactive delirium. Delirium had a two-factor structure that emerged in all four study groups, and all its core domains loaded (i.e., correlated together) onto some of these two factors and with circadian domain correlating with accessory symptoms. Although the influence of a variety of active diagnoses on delirium was small and complex, traumatic brain injury had a clear influence on cognitive domain and abrupt onset. Age had a mild influence over delirium characteristics for both males and females. In conclusion, the authors confirmed a two-factor structure for delirium phenomenology, regardless of age and sex, with few significant differences between etiological groups.

Confirmatory Factor Analysis of the Delirium Rating Scale Revised-98 (DRS-R98).

Principal components analysis applied to the Delirium Rating Scale-Revised-98 contributes to understanding the delirium construct. Using a multisite pooled international delirium database, the authors applied confirmatory factor analysis to Delirium Rating Scale-Revised-98 scores from 859 adult patients evaluated by delirium experts (delirium, N=516; nondelirium, N=343). Confirmatory factor analysis found all diagnostic features and core symptoms (cognitive, language, thought process, sleep-wake cycle, motor retardation), except motor agitation, loaded onto factor 1. Motor agitation loaded onto factor 2 with noncore symptoms (delusions, affective lability, and perceptual disturbances). Factor 1 loading supports delirium as a single construct, but when accompanied by psychosis, motor agitation's role may not be solely as a circadian activity indicator.

Three core domains of delirium validated using exploratory and confirmatory factor analyses.

OBJECTIVE: To confirm the existence of the proposed three-core symptom domains in delirium by analyzing a dataset of nondemented adults using selected core symptoms as measured by the Delirium Rating Scale-Revised-98 (DRS-R98) scale. METHODS: Exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) of proposed delirium core symptoms were conducted in a pooled international dataset of 592 delirious and nondelirious patients using DSM-IV criteria from 14 studies with comparable methodologies. Using DRS-R98 categorization, 445 had either subsyndromal or full delirium and comprised the delirium group. The dataset was divided into three independent random subsamples to perform a stepwise analysis. First we performed EFA in 100 cases to delineate latent factor loadings of DRS-R98 items selected to represent the three-core domains (circadian, higher level thinking, and cognitive). These items were then assessed using CFA-modeling (n = 246) followed by a CFA-validation (n = 246). Reliability and goodness of fit of these two CFA were assessed statistically. RESULTS: DRS-R98 items representing the proposed delirium core symptoms loaded onto one factor in the EFA, supporting their core nature. The two CFA confirmed the nature of this core factor as comprising three core domains where DRS-R98 items each loaded with high values (>0.7) onto their corresponding core domain (circadian, higher level thinking, and cognitive) with good fit and reliability. Attention was DRS-R98 item with the highest loading in CFA, followed by thought process, and then by sleep-wake cycle and motor behavior. CONCLUSIONS: Our EFA and CFA confirm and validate the proposed three-core domains of delirium, where symptoms were highly related to the domain that they were hypothesized to represent. These domains are consistent with delirium being a state of impaired consciousness, and should be considered necessary to assess whether in clinical or research settings.

Delusions and Hallucinations Are Associated With Greater Severity of Delirium.

BACKGROUND: The 3 core domains of delirium (cognitive, higher level thinking, circadian) do not include the less common noncore psychotic symptoms. However, psychosis might inform about perturbations of neural circuitry, outcomes, or suggest tailored clinical management. OBJECTIVE: We assessed relationships between psychosis and other characteristics of delirium in patients without dementia or antipsychotics treatment. METHODS: Cross-sectional analysis of 366 adults with delirium per the Delirium Rating Scale Revised-98, whose items distinguish hallucinations and delusions from other types of misperceptions and abnormal thought content, assessed during the preceding 24 hours to capture symptom severity fluctuation. The relationship of psychosis with other delirium characteristics was assessed using bivariate comparisons and analysis of variance as appropriate for groups with no psychosis and any psychosis (hallucinations and/or delusions), and subgroups with only hallucinations, only delusions, or both. A discriminant logistic model assessed variables associated with presence of any psychotic features versus none. RESULTS: Delirium with any psychotic features occurred in 44.5% (163 of 366). Of the 366, 119 (32.5%) had only hallucinations (Hall), 14 (3.8%) had only delusions (Del), and 30 (8.2%) had both (Both). In the psychotic group (n = 163), 73.0% were Hall, 8.6% Del, and 18.4% Both. All psychotic patient groupings had significantly greater delirium severity on the Delirium Rating Scale Revised-98. Delusions and hallucinations were discordant for occurring together. The discriminant model found increased odds of having psychosis as 3 symptom severities increased (visuospatial ability, thought process, and sleep-wake cycle) where these each represented a delirium core domain. The noncore symptom of lability of affect had high odds ratio for psychosis, while motor retardation reduced odds of psychosis in this model. CONCLUSIONS: Consistent with prior reports, psychosis occurred in less than half of delirious patients with delusions being infrequent, and an association with affective lability was found. Given that previous functional magnetic resonance imaging research found a correlation between neural network dysconnectivity with greater severity of delirium, psychotic symptoms might be a clinical marker for greater underlying cerebral cortical neural circuitry dysfunction.

Urinary Dysfunctions and Post-Void Residual Urine in Typical and Atypical Parkinson Diseases.

BACKGROUND: Urinary dysfunction is relatively common, however, is often underestimated and diagnosed by subjective questionnaires in patients with Parkinsonism. OBJECTIVE: To determine the correlation between subjective urinary dysfunction and post-void residual urine volume in patients with Parkinson's disease (PD), multiple system atrophy (MSA) and progressive supranuclear palsy (PSP), and to assess the relationship between clinical characteristics and subjective or objective urinary dysfunction. METHODS: A total of 196 patients with de novo Parkinsonism without urological and gynecological disorders were included. For all subjects, data were collected on sonographic post-void residual urine volume and urinary symptoms. All patients were also assessed on motor symptom severity, cognitive and affective measurements, other nonmotor symptoms, 39-item Parkinson's Disease Questionnaire, and renal functions. RESULTS: Seventeen out of 196 parkinsonian patients showed abnormal post-void residual urine volumes, with ≥100 ml. The MSA group showed significantly higher post-void residual urine volume compared to the PD and PSP groups. Symptoms of the sense of incomplete emptying, weak urine stream, and nocturia were strongly correlated with post-void residual urine volume. Post-void residual urine volume was positively related to autonomic symptoms, other non-motor symptoms, patient activities of daily living, and negatively related to renal function. CONCLUSION: Increased post-void residual urine volumes were observed in small portion of early drug-naïve Parkinsonian patients, especially in MSA. Post-void residual urine volume was significantly related to subjective urinary and other autonomic dysfunctions. Voiding dysfunction is associated with not only end organ damage, but also other nonmotor dysfunctions and patient activities of daily living.

Dissociation of emotional decision-making from cognitive decision-making in chronic schizophrenia.

Recent studies have examined the decision-making ability of schizophrenic patients using the Iowa Gambling Task (IGT). These studies, however, were restricted to the assessment of emotional decision-making. Decision-making depends on cognitive functions as well as on emotion. The purpose of this study was to examine the performance of schizophrenic patients on the IGT and the Game of Dice Task (GDT), a decision-making task with explicit rules for gains and losses. In addition, it was intended to test whether poor performance on IGT is attributable to impairments in reversal learning within the schizophrenia group using the Simple Reversal Learning Task (SRLT), which is sensitive to measure the deficit of reversal learning following ventromedial prefrontal cortex damage. A group of 23 stable schizophrenic patients and 28 control subjects performed computerized versions of the IGT, GDT, SRLT and Wisconsin Card Sorting Test (WCST). While schizophrenic patients performed poorly on the IGT relative to normal controls, there was no significant difference between the two groups on GDT performance. The performance of the schizophrenia group on the SRLT was poorer than that of controls, but was not related to IGT performance. These data suggest that schizophrenic patients have impaired emotional decision-making but intact cognitive decision-making, suggesting that these two processes of decision-making are different. Furthermore, the impairments in reversal learning did not contribute to poor performance on the IGT in schizophrenia. Therefore, schizophrenic patients have difficulty in making decisions under ambiguous and uncertain situations whereas they make choices easily in clear and unequivocal ones. The emotional decision-making deficits in schizophrenia might be attributable more to another mechanism such as a somatic marker hypothesis than to an impairment in reversal learning.

Risperidone in combination with mood stabilizers for acute mania: a multicentre, open study.

The primary aims of this study were (i) a replication of the effectiveness and tolerability of risperidone in the treatment of patients with acute mania in a very large cohort in a naturalistic treatment setting and (ii) to extend the data on the effect and tolerability of risperidone in the treatment of patients with acute mania to an Asian population. A total of 909 patients fulfilling DSM-IV criteria of bipolar disorder (current manic and hypomanic episode) entered this large, open, multicentre study. The Young Mania Rating Scale (YMRS), Clinical Global Impression (CGI) and Simpson-Angus Rating Scale (SARS) were measured at baseline and weeks 1, 3 and 6, for the assessment of effectiveness and extrapyramidal symptoms. This study showed a statistically significant reduction of scores on the YMRS and CGI-severity (mean change=-23.5+/-11.8, P<0.0001; mean change=-2.7+/-1.5, P<0.0001, respectively) from baseline to endpoint (week 6). The number of patients with a 50% reduction or more in the YMRS and CGI-severity scores was 693 (77.8%) and 630 (70.7%) at endpoint, respectively. There were no statistically significant increments of scores on SARS. Risperidone was generally well tolerated. The present larger open study indicates that risperidone add-on therapy is effective and tolerable in treatment of bipolar disorder, replicating results in various controlled and uncontrolled studies from Western countries.

Phenotype of subsyndromal delirium using pooled multicultural Delirium Rating Scale--Revised-98 data.

OBJECTIVE: There is no consensus definition for the phenotype of subsyndromal delirium (SSD), a subthreshold state to full delirium. Without an a priori definition we applied advanced analytic techniques to discern SSD. METHOD: We pooled Delirium Rating Scale-Revised-98 (DRS-R98) data from 859 DSM-IV diagnosed nondemented delirious adults and nondelirious controls collected by investigators in 7 countries. Discriminant analyses defined an SSD group that was then compared to Nondelirium and Delirium groups. RESULTS: SSD (n=138) had intermediate DRS-R98 item severities between Delirium (n=497) and Nondelirium (n=224) groups, where groups significantly differed on all DRS-R98 items (ANOVA p<.001) except delusions. Discriminant analysis found SSD phenomenologically closer to Delirium than Nondelirium. Using full multinomial logistical regression, SSD was distinguished from Nondelirium by temporal onset, sleep-wake cycle, perceptual disturbances, motor retardation, delusion, affective lability, and all cognitive items; SSD was similar to Delirium in thought process, language, motor agitation or retardation, sleep-wake cycle, all cognitive items, fluctuation and physical disorder. The multivariate model correctly classified 94.2% of Nondelirium, 75.4% of SSD and 97.2% of Delirium subjects. Binary logistic regression of six core domain symptoms (sleep-wake cycle, thought process, language, attention, orientation, and visuospatial ability) together were found as highly differentiating of SSD from Nondelirium, which correctly classified almost 80% of SDD. CONCLUSIONS: SSD is intermediate in severity between nondelirious controls and full syndromal delirium, but its phenotype is more like delirium. Core domain delirium symptoms present at milder severity in SSD should be evaluated further for utility in detecting and managing SSD, preventing delirium, and possible inclusion in DSM-V.

Korean version of the delirium rating scale-revised-98: reliability and validity.

OBJECTIVE: The aims of the present study were 1) to standardize the validity and reliability of the Korean version of Delirium Rating Scale-Revised-98 (DRS-R98-K) and 2) to establish the optimum cut-off value, sensitivity, and specificity for discriminating delirium from other non-delirious psychiatric conditions. METHODS: Using DSM-IV criteria, 157 subjects (69 delirium, 29 dementia, 32 schizophrenia, and 27 other psychiatric patients) were enrolled. Subjects were evaluated using DRS-R98-K, DRS-K, Mini-Mental State Examination (MMSE-K), and Clinical Global Impression-Severity (CGI-S) scale. RESULTS: DRS-R98-K total and severity scores showed high correlations with DRS-K. They were significantly different across all groups (p=0.000). However, neither MMSE-K nor CGI-S distinguished delirium from dementia. All DRS-R98-K diagnostic items (#14-16) and items #1 and 2 significantly discriminated delirium from dementia. Cronbach's alpha coefficient revealed high internal consistency for DRS-R98-K total (r=0.91) and severity (r=0.89) scales. Interrater reliability (ICC between 0.96 and 1) was very high. Using receiver operating characteristic analysis, the area under the curve of DRS-R98-K total score was 0.948 between the delirium group and all other groups and 0.873 between the delirium and dementia groups. The best cut-off scores in DRS-R98-K total score were 18.5 and 19.5 between the delirium and the other three groups and 20.5 between the delirium and dementia groups. CONCLUSION: We demonstrated that DRS-R98-K is a valid and reliable instrument for assessing delirium severity and diagnosis and discriminating delirium from dementia and other psychiatric disorders in Korean patients.

Current use of depression rating scales in mental health setting.

OBJECTIVE: This study was to investigate the current use of depression rating scales by psychiatrists and clinical psychologists in Korea. METHODS: The questionnaires from many psychiatrists and clinical psychologists were included in the analysis. The questionnaire was composed of items about examining the percentage of patients clinically using depression rating scales, reasons for not use of them, the degree of satisfaction, the perceived agreement rate between the result of depression rating scales and doctor's clinical interview in the evaluation of patients with depressive symptoms. Data were analyzed by χ(2) and independent t-test. RESULTS: The clinical use of depression rating scales was more frequent in the psychologists than in the psychiatrists. The purposes for using depression rating scales were assessed into six areas, there was no significant difference in between two groups, and both groups pointed out their purpose as rating of severity and screening. The reasons for not using scales were that their interview may be sufficient for diagnosis and assessment of depressive patients and they are not familiar with the use of depression rating scales. The psychiatrists usually prefer the Beck Depression Inventory (BDI), Hamilton Depression Rating Scale and Symptom Checklist 90-Revision (SCL-90-R) in order of frequency, and the clinical psychologists are more likely to use the BDI, Minnesota Multiphasic Personality Inventory and SCL-90-R. Overall rate of satisfaction in the use of the scales was 67.29±14.45% and overall perceived agreement rate was 70.89±16.45%. CONCLUSION: Currently used depression rating scales at the clinical practice were not various. Therefore, to heighten clinicians' utility of these depression rating scales measures, either educational efforts or advertisements, or both, will be necessary to spread them wildly.

Effectiveness and tolerability of long-acting risperidone: A 9-month open-label extension of a 12-week switching study from oral antipsychotics.

Objectives. The aim of this non-randomized, single-arm, multi-center, 9-month extension study was to evaluate the maintained efficacy and tolerability of long-acting risperidone injection when we switched to it from previous oral antipsychotics in symptomatically stable patients with schizophrenia or other psychotic disorders. Methods. A total of 98 patients who had completed a previous 12-week acute phase study were included. Efficacy and tolerability were assessed with the Positive and Negative Syndrome Scale (PANSS), Clinical Global Impression (CGI), Global Assessment of Functioning (GAF), and Extrapyramidal Symptom Rating Scale (ESRS). Results. The remission rate of 77.6% (76/98) at baseline and 57.1% (56/98) at the end of the study. Of patients who were in remission at baseline, 65.8% (50/76) maintained their remission state until the end. The symptom worsening rate was relatively low (11.1%), and there was no aggravation in mean PANSS total and subscale scores. Spontaneous treatment-emergent adverse events (TEAE) were reported by 21 (21.4%) patients, and most commonly reported adverse events were extrapyramidal symptoms (N=6, 6.1%) and insomnia (N=4, 4.1%). Extrapyramidal symptoms were significantly improved. Conclusions. Switching to long-acting risperidone injection from oral antipsychotics was a safe and well-tolerated strategy for maintaining clinical stability in symptomatically stable patients with schizophrenia.

Long-term patient monitoring for clozapine-induced agranulocytosis and neutropenia in Korea: when is it safe to discontinue CPMS?

OBJECTIVES: This study documents the incidences of agranulocytosis and neutropenia, and the patterns of incidence of the side effects of long-term clozapine treatment in order to determine an appropriate time to stop the Clozaril Patient Monitoring System (CPMS). METHODS: Hematological, demographic, and other data from the CPMS for 6782 patients who took clozapine for the past 11 years in the Republic of Korea has been analyzed. RESULTS: Twenty-nine (53.7%) of fifty-four agranulocytosis cases occurred within the first 18 weeks. The cumulative incidence of agranulocytosis was 1.64% between 6 and 11 years and the crude incidence was 0.8%. Neutropenia occurred in 697 patients, and 365 (52.4%) of these cases occurred within the first 18 weeks. The cumulative incidence of neutropenia was 19.8% between 8 and 11 years, and the crude incidence was 10.3%. There were no cases of agranulocytosis or neutropenia after the 9th year of clozapine treatment. CONCLUSIONS: The incidence of agranulocytosis in the Republic of Korea was similar to those in the rest of the world. While agranulocytosis began several years after clozapine treatment, long-term monitoring of white blood cells is necessary. We suggest that the CPMS should be stopped or less frequently after the 9th year of treatment.