Validation of the delirium diagnostic tool-provisional (DDT-Pro) in geriatric medical inpatients with diagnostic permutations of the 3Ds with and without delirium.

OBJECTIVE: Validations of brief delirium tools have not included analysis of psychiatric disorders comorbidities or control groups. We validated the Delirium Diagnostic Tool-Provisional (DDT-Pro) in 422 geriatric inpatients with high incidence of depression and/or dementia. METHODS: Cross-sectional study using two delirium reference standards, DSM-5-TR and Delirium Rating Scale-Revised-98 (DRS-R98). We assessed concurrent and construct DDT-Pro validity too. RESULTS: There were 117 (27.7%) delirium cases using DDT-Pro, 104 (24.6%) per DSM-5-TR and 93 (22.0%) per DRS-R98; 133 patients (31.5%) had depression and 105 (24.9%) dementia, some comorbid with delirium. DDT-Pro accuracy (AUC under ROC curve) ranges were 88.3-95.9% vs DSM-5-TR and 92.7-95.0% vs DRS-R98 for whole sample and four diagnostic groups, without statistical differences. DDT-Pro ≤6 had the most balanced sensitivity-specificity for delirium diagnosis against both DSM-5-TR and DRS-R98 with similar specificity but higher sensitivity for DRS-R98 than DSM-5-TR delirium, with the highest values in patients with depression and dementia (≥92% sensitivity, ≥81% specificity). Positive and negative likelihood ratios support diagnostic strength. Concurrent validity was high reflected by significant correlations (p < 0.001) of DDT-Pro total and item scores with DRS-R98 and Delirium Frontal Index scores, highest in groups with comorbid depression and/or dementia. The DDT-Pro represented a single construct for delirium demonstrated by one factor with high item loadings and high internal consistency reliability of its items. CONCLUSIONS: The DDT-Pro demonstrated strong performance metrics in general hospital elderly inpatients with preexisting depression and/or dementia, which is unique among brief delirium tools. Its optimized cutoff score was the same as in other populations.

Practical Application of a Battery of Brief Tools to Evaluate Geriatric Medical Inpatients for the Three Ds.

OBJECTIVE: The investigators aimed to identify the clinical characteristics of patients with or without delirium and preexisting depression, dementia, both, or neither by using validated tools easily administered in clinical practice. METHODS: In this cross-sectional prospective observational study conducted in Medellín, Colombia, 200 geriatric inpatients were evaluated with the Delirium Diagnostic Tool-Provisional (DDT-Pro), Informant Questionnaire on Cognitive Decline in the Elderly, Hachinski Ischemic Scale, Cornell Scale for Depression in Dementia, and Charlson Comorbidity Index-short form. Delirium motor subtype, mortality, and length of hospital stay were assessed. RESULTS: The study included 134 patients without delirium (67%), 14 with delirium only (7%), 16 with delirium and dementia (8%), 13 with delirium and depression (7%), and 23 with delirium, dementia, and depression (the three Ds) (12%). Prevalence rates of dementia (59%) and depression (55%) among 66 patients with delirium were higher than prevalence rates among patients without delirium (13% and 28%, respectively), suggesting that both conditions are risk factors. Main medical diagnoses, mortality, and dementia type did not differ among groups. Motor subtypes were similar among delirium groups. Patients in the delirium groups, except those in the delirium and depression group, were older than patients without delirium. Medical burden was highest among the patients with delirium and dementia and those with all three conditions. Delirium and dementia were more severe when comorbid with each other. Depression was most severe among patients with delirium and depression. Patients with all three conditions had a longer length of hospital stay than those without delirium. CONCLUSIONS: Using brief tools to detect dementia and depression in conjunction with the DDT-Pro to assess delirium diagnosis and severity is feasible and enables a more in-depth evaluation of elderly hospitalized patients. Because previous longitudinal research suggests that these comorbid conditions influence prognosis following a delirium episode, better identification of the three Ds offers proactive interventional opportunities. Depression is an underrecognized risk factor for delirium.

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.

Variables associated with concordance or discordance for delirium diagnosis between referring and consulting physicians at a Tertiary Hospital in Colombia: Prospective observational study.

Delirium is an acute state of impaired consciousness and a medical urgency. Its broad range of alterations in mental status make diagnosis challenging. Awareness and accurate provisional diagnosis by nonpsychiatric clinicians are important for prompt management. Because delirium symptoms overlap and mimic other neuropsychiatric conditions, a referral to a consultant psychiatrist is often needed. The aim of this study was to determine the discriminating variables that are associated with concordance or discordance for a DSM-5 delirium diagnosis made by the consultation/liaison (C/L) psychiatrist as compared to the referral diagnosis/reasons given by the referring physicians for inpatients from a Tertiary Hospital in a Latin-American country. Prospective study of a cohort of 399 consecutive patients admitted to any ward of a university hospital in Medellin-Colombia and referred by a specialist physician to the C/L Psychiatry service. Analyses for diagnostic concordance used a nested sample of 140 cases diagnosed with delirium by the psychiatrist. Two multivariate logistic models were run, for delirium diagnosis concordance and discordance between the referring physician and C/L psychiatrist. The referral diagnosis was concordant with that of Psychiatry in 90/140 patients in 64.3%, with 35.7% discordance. Increasing age (OR = 1.024) and internal medicine ward (OR = 3.0) were significantly related (Wald statistic P < .05) to concordance in the multivariate analysis whose model accuracy was 68.6%. Trauma/orthopedics ward (OR = 5.7) and SARS-CoV-2 infection (OR = 3.8) were important contributors to the model fit though not significant. Accuracy of the discordance model was 70.7%, where central nervous system (CNS) disorder (OR = 6.1) and referrals from ICU (OR = 4.9), surgery (OR = 4.6), neurology/neurosurgery (OR = 5.1) and another consultant (OR = 4.7) were significantly related (Wald statistic P < .05), while metabolic/endocrine disorder (OR = 2.7) was important for model fit, but not significant. Concordance for delirium diagnosis was higher from services where education, guidelines and working relationships with C/L Psychiatry could have contributed beneficially whereas, surprisingly, CNS disorders and neurology/neurosurgery services had higher discordance, as well as the ICU. Routine use of brief sensitive delirium assessment tools such as the DDT-Pro could enhance provisional delirium diagnosis.

Etiologies of Delirium in Consecutive COVID-19 Inpatients and the Relationship Between Severity of Delirium and COVID-19 in a Prospective Study With Follow-Up.

OBJECTIVE: The investigators aimed to describe delirium etiologies and clinical characteristics, as well as the relationship between COVID-19 and delirium severities, at baseline and follow-up after delirium improvement among patients with SARS-CoV-2 infection. METHODS: A longitudinal study of 20 consecutive critically ill, delirious COVID-19 inpatients, assessed with the Charlson Comorbidity Index-Short Form (CCI-SF), COVID-19 Clinical Severity Scale (CCSS), Delirium Etiology Checklist, Delirium Motor Subtype Scale-4, and Delirium Diagnostic Tool-Provisional (DDT-Pro), was conducted. Correlational analysis of delirium severity (DDT-Pro) with each measure of clinical severity (CCI-SF and CCSS) and comparison of baseline DDT-Pro scores between patients who were living and those who were deceased at follow-up were conducted. RESULTS: Participants were 50-90 years old (male, 75%; hypertension, 60%). The prevalence of preexisting medical comorbidities (CCI-SF) was low and not correlated with delirium severity (p=0.193). Eighteen patients were on mechanical or high-flow noninvasive ventilation at baseline in the intensive care unit (ICU; CCSS scores 2-4). Delirium severity (DDT-Pro scores 0-6) correlated with COVID-19 severity (0.459, p=0.021). Delirium motor subtype was hyperactive in 75% of patients. There were three to four etiologies for delirium in each patient, most commonly organ insufficiency (100%), systemic infection (100%), and metabolic and endocrine disturbances (95%). The baseline DDT-Pro score was ≤4 for five (25%) patients who died before the final assessment, with a trend of being lower than that for survivors (χ2=3.398, p=0.065). CONCLUSIONS: Among inpatients with COVID-19, at least three different etiological categories were identified for delirium. ICU staff treating patients with severe cases of COVID-19 should anticipate a greater severity of delirium. Although multivariate analyses with larger study samples are needed, more severe delirium may herald greater risk of death among COVID-19 patients.

How do delirium motor subtypes differ in phenomenology and contributory aetiology? a cross-sectional, multisite study of liaison psychiatry and palliative care patients.

OBJECTIVES: To investigate whether delirium motor subtypes differ in terms of phenomenology and contributory aetiology. DESIGN: Cross-sectional study. SETTING: International study incorporating data from Ireland and India across palliative care, old age liaison psychiatry and general adult liaison psychiatry settings. PARTICIPANTS: 1757 patients diagnosed with delirium using criteria from the Diagnostic and Statistical Manual of Mental Disorders, Fourth edition (DSM IV). PRIMARY AND SECONDARY OUTCOME MEASURES: Hyperactive, mixed and hypoactive delirium subtypes were identified using the abbreviated version of the Delirium Motor Subtype Scale. Phenomenology was assessed using the Delirium Rating Scale Revised. Contributory aetiologies were assessed using the Delirium Aetiology Checklist (DEC), with a score >2 indicating that the aetiology was likely or definitely contributory. RESULTS: Hypoactive delirium was associated with dementia, cerebrovascular and systemic infection aetiologies (p<0.001) and had a lower overall burden of delirium symptoms than the other motor subtypes. Hyperactive delirium was associated with younger age, drug withdrawal and the DEC category other systemic aetiologies (p<0.001). Mixed delirium showed the greatest symptom burden and was more often associated with drug intoxication and metabolic disturbance (p<0.001). All three delirium motor subtypes had similar levels of impairment in attention and visuospatial functioning but differed significantly when compared with no subtype (p<0.001). CONCLUSIONS: This study indicates a pattern of aetiology and symptomatology of delirium motor subtypes across a large international sample that had previously been lacking. It serves to improve our understanding of this complex condition and has implications in terms of early detection and management of delirium.

Validation of the Delirium Diagnostic Tool-Provisional (DDT-Pro) in a skilled nursing facility and comparison to the 4 'A's test (4AT).

OBJECTIVE: To validate the Delirium Diagnostic Tool (DDT-Pro) in a SNF and compare its performance to the 4 A's Test (4AT) in real life conditions. METHODS: Prospective cross-sectional study of 262 consecutively admitted adults to a SNF, independently assessed by psychiatrists using DSM-5 delirium criteria and by geriatricians using the DDT-Pro (0-9 points) and 4AT (0-12 points). RESULTS: 141 (53.8%) participants had dementia and 79 (30.1%) had delirium. DDT-Pro and 4AT were moderately correlated (-0.59). Accuracies against DSM-5 diagnosis ranged from 80 to 85% and were comparable between tools regardless of dementia. Recommended delirium cutoff for the DDT-Pro (≤6) had 77.2% sensitivity, 84% specificity, and NPV = 89.5% and 4AT (≥4) had 54.4% sensitivity and 92.9% specificity, with lower specificity in the dementia subsample. DDT-Pro sensitivity increased (84.8%) at ≤7cutoff. Sensitivity and specificity of all DDT-Pro and 2/4 4AT items displayed gradients along severity levels, but two dichotomously rated 4AT items had low positivity. The tools had low concordance (p < 0.05) for delirium positivity. CONCLUSIONS: DDT-Pro is valid to detect delirium in SNF population where simple, structured tools with high sensitivity are needed. DDT-Pro items assess the three core domains of delirium as a continuous measure and may have advantages over the 4AT.

Discriminant Performance of Dysexecutive and Frontal Release Signs for Delirium in Patients With High Dementia Prevalence: Implications for Neural Network Impairment.

BACKGROUND: Prevalence of signs of abnormal executive function (EF) and primitive reflexes (PR) with delirium in older hospitalized patients with or without comorbid dementia has not been reported. OBJECTIVE: To describe prevalence of signs of EF deficits and PR in older inpatients and their discriminant value for delirium while accounting for dementia. METHODS: Participants were evaluated for delirium using the Diagnostic and Statistical Manual of Mental Disorders 5th edition and the Delirium Rating Scale Revised-98, dementia using Informant Questionnaire on Cognitive Decline in the Elderly, and signs of PR (n = 5) and EF deficits (n = 3) using bedside neuropsychiatric examination. Three indices (PR, EF, and Combined) and 4 diagnostic groups were created for correlational and discriminant analyses. RESULTS: Correlations of indices were higher with the Delirium Rating Scale Revised-98 than with the Informant Questionnaire on Cognitive Decline in the Elderly and even higher in those with dementia, especially the Combined index (Delirium Frontal Index). Among individual signs, glabellar and Simple Luria Hand Sequence were most common in delirium and the best for delirium discrimination irrespective of dementia status. The Combined index had about 80% sensitivity and specificity at the ≥2 cutoff in the whole cohort (positive and negative predictive values and likelihood ratios: PPV 50.0%, NPV 93.8%, +LR 3.82, -LR 0.25). The Combined index also had the best performance on discriminating delirium in dementia patients at the ≥3 cutoff, with about 80% for both sensitivity and specificity. CONCLUSIONS: PR and EF deficit signs are consistent with reduced neural network integration during delirium, even worse in those with dementia whose baseline structural injury impairs network connectivity with frontal regions. We recommend simple bedside assessment of PR and EF signs to help assess for delirium as an indicator of cerebral cortical neural network impairment in older persons.

Delirium diagnostic tool-provisional (DDT-Pro) scores in delirium, subsyndromal delirium and no delirium.

OBJECTIVE: To evaluate whether the Delirium Diagnostic Tool-Provisional (DDT-Pro), a 0-9 point scale with three items each representing symptoms from delirium's three core domains, differentiates subsyndromal delirium (SSD) from delirium and no delirium. METHODS: We applied cluster analyses of DDT-Pro scores from 200 consecutive inpatients using three reference standards for delirium diagnosis to determine DDT-Pro cutoff values for delirium, SSD and no delirium groups. Clinical validators and DDT-Pro item scores were compared among groups. RESULTS: DDT-Pro SSD range was 6-7 (n = 54), with no delirium having higher scores (n = 98) and delirium lower (n = 48). Dementia prevalence in the SSD group (40.7%) was intermediate between no delirium (20.4%) and delirium (66.7%). SSD and delirium groups were more affected than no delirium regarding medical comorbidities, hospital stay (no delirium <1 week, SSD and delirium >1 week) and mortality (SSD = 7.4%, delirium = 18.8%, no delirium = 1%). Values for motor subtypes, frontal lobe signs, and DRS-R98 in the SSD group were intermediate between no delirium and delirium, as well as for the DDT-Pro items (all p < 0.05). CONCLUSIONS: All DDT-Pro items, which represent the three delirium core domains, are important for SSD diagnosis. Patients scoring in the SSD 6-7 range have significant clinical and prognostic features and deserve clinical attention.

Validation of the Delirium Diagnostic Tool-Provisional (DDT-Pro) With Medical Inpatients and Comparison With the Confusion Assessment Method Algorithm.

OBJECTIVE: Delirium remains underdetected as a result of its broad constellation of symptoms and the inadequate neuropsychiatric expertise of most medical-surgical clinicians. Brief, accurate tools are needed to enhance detection. METHODS: The authors extended validation of the Delirium Diagnostic Tool-Provisional (DDT-Pro), originally validated in a study of inpatients with traumatic brain injury for diagnosis of delirium by nonexpert clinicians, for 200 general medical inpatients in Colombia. The three structured, quantitatively rated items in DDT-Pro represent the three core delirium domains. RESULTS: High interrater reliability between physician and nurse (0.873) administrators, internal consistency (>0.81), and content validity were found. Compared with independent reference standard diagnosis with DSM-5 or the Delirium Rating Scale-Revised-98, the area under the receiver operating characteristic (ROC) curve (global diagnostic accuracy) range was 93.8%-96.3%. ROC analysis revealed the same cutoff score (≤6) as that for the original study, with somewhat lower sensitivities of 88.0%-90.0% and specificities of 85.3%-81.2% (independent expert physician or nurse ratings). Even when rated by a trained expert physician, the original version of the Confusion Assessment Method algorithm (CAM-A) performed moderately, with lower sensitivities (61.8%-70.0%) than the DDT-Pro (88.0%-100%) and somewhat higher specificities (84.8%-95.3% versus 67.4%-86.7%), with values depending on dementia status, reference standard, and rater type. Accuracies for the DDT-Pro and CAM-A were comparable (DDT-Pro: 83.0%-87.5% versus CAM-A: 87.5%-88.5%), although lower in the dementia subgroup, especially for CAM-A. However, these tools were significantly discordant, especially in negative cases, which suggests that they do not detect diagnosis of patients in the same way. CONCLUSIONS: The DDT-Pro had high validity and reliability in provisional delirium diagnosis by physicians and nonexpert clinicians, although further validation is warranted before widespread use can be recommended.

Distinguishing characteristics of delirium in a skilled nursing facility in Spain: Influence of baseline cognitive status.

OBJECTIVE: Mild cognitive impairment (MCI) and dementia (DEM) are prevalent in skilled nursing facilities (SNFs), confounding delirium detection. We report characteristics of delirium in an SNF to ascertain distinguishing features for delirium diagnosis, despite challenges of comorbidity with MCI and DEM. METHODS: Cross-sectional study of 200 consecutive patients from an SNF in Catalunya, Spain, assessed within the first 24 to 48 admission hours by independent experts with Spanish-Informant Questionnaire on Cognitive Decline in the Elderly (for MCI-DEM), Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) delirium criteria, and Delirium Rating Scale Revised-98 (DRS-R98) for delirium phenomenology. Delirium characteristics were modeled in successive steps, according to the presence of delirium and MCI-DEM, with analysis of variance (ANOVA), receiver operator characteristic analyses, and conditional logistic regression. RESULTS: The final model produced symptoms that represented each of the three delirium core domains (ie, cognitive, higher order thinking, and circadian). The DRS-R98 items rated these symptoms as moderate-severe attention/vigilance, mild-severe language, and moderate-severe sleep-wake cycle alterations. The delirium discriminant accuracy of the three symptoms together was high: 84.6% in the MCI-DEM group to 92.8% in the No MCI-DEM group. CONCLUSIONS: Impairments of attention, language, and sleep-wake cycle indicate delirium in SNF patients regardless of the underlying MCI-DEM status. Because delirium is underdetected in SNFs, where nursing staff/patient ratios are low, brief simple tools that measure these symptoms could potentially enhance delirium detection.

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.

Sleep-wake cycle disturbances in elderly acute general medical inpatients: Longitudinal relationship to delirium and dementia.

INTRODUCTION: Sleep disturbances in elderly medical inpatients are common, but their relationship to delirium and dementia has not been studied. METHODS: Sleep and delirium status were assessed daily for a week in 145 consecutive newly admitted elderly acute general hospital patients using the Delirium Rating Scale-Revised-98 (DRS-R98), Diagnostic and Statistical Manual 5, and Richards-Campbell Sleep Quality Scale measures. The longitudinal relationship between DRS-R98 and Richards-Campbell Sleep Quality Scale sleep scores and delirium, also with dementia as a covariate, was evaluated using generalized estimating equation logistic regression. RESULTS: The cohort was divided into delirium only, dementia only, comorbid delirium-dementia, and no-delirium/no-dementia subgroups. Mean age of total group was 80 ± 6.3, 48% were female, and 31 (21%) had dementia, 29 had delirium at admission (20%), and 27 (18.5%) experienced incident delirium. Mild sleep disturbance (DRS-R98 sleep item score ≥1) occurred for at least 1 day in all groups, whereas moderate sleep disturbance (score ≥2) occurred in significantly more of the prevalent delirium-only (81%; n = 17) cases than incident delirium-only (46%; n = 13) cases (P < .001). There were more cases with DRS-R98 sleep item scores ≥2 (P < .001) in the delirium-only group compared with the other subgroups. Severity of sleep-wake cycle disturbance over time was significantly associated with Diagnostic and Statistical Manual 5 delirium status but not with age, sex, or dementia (P < .001). CONCLUSIONS: Observer-rated more severe sleep-wake cycle disturbances are highly associated with delirium irrespective of dementia status, consistent with being a core feature of delirium. Monitoring for altered sleep-wake cycle patterns may be a simple way to improve delirium detection.

Subsyndromal delirium compared with delirium, dementia, and subjects without delirium or dementia in elderly general hospital admissions and nursing home residents.

INTRODUCTION: Subsyndromal delirium (SSD) complicates diagnosis of delirium and dementia, although there is little research comparing their symptom profiles. METHODS: Cross-sectional study of 400 elderly patients' admission to a general hospital or nursing home diagnosed with delirium, SSD, dementia, or no-delirium/no-dementia (NDND). Symptom profiles were assessed using the Delirium Rating Scale-Revised-98 (DRS-R98). RESULTS: Twenty percent patients had delirium, 19.3% had SSD, 29.8% had dementia-only, and 31% had NDND. Eighty-one percent of subsyndromal and 76% of delirium groups had comorbid dementia. DRS-R98 scores showed ascending severity from NDND < dementia-only < SSD < delirium. DRS-R98 scores for items evaluating the three core symptom domains (cognitive, higher-order thinking, and circadian) distinguished SSD from delirium and both from nondelirium groups. DRS-R98 profiles were essentially the same in delirium and SSD subgroups with or without dementia, although total scale scores were generally higher when in comorbid subgroups. DISCUSSION: SSD shared characteristic core domain symptoms with delirium, which distinguished each from nondelirium groups, although severity was intermediate in the subsyndromal group. Delirium core symptoms overshadowed the dementia phenotype when comorbid. Milder disturbances of delirium core domain symptoms are highly suggestive of SSD.

Efficacy and Safety of Atomoxetine Hydrochloride in Asian Adults With ADHD.

OBJECTIVE: The efficacy and safety of atomoxetine was assessed in adult ADHD patients from Japan, Korea, and Taiwan in this first placebo-controlled Asian clinical study in adults of an ADHD medication. METHOD: Atomoxetine was compared with placebo (195 atomoxetine, 196 placebo) over 10 weeks. The change from baseline to endpoint and changes over time in the Conners' Adult ADHD Rating Scale-Investigator Rated: Screening Version total score (CAARS-Inv: SV total score) were assessed along with changes in quality of life (QoL) and executive function. RESULTS: Atomoxetine treatment resulted in a mean reduction of -14.3 (placebo, -8.8) in CAARS-Inv: SV total score and a steady increase of between-group differences from Week 2. Improvements in QoL and executive functioning were also observed. Treatment-emergent adverse events leading to discontinuation were infrequent (atomoxetine: 5.2%, placebo: 1.5%). CONCLUSION: Atomoxetine was tolerable and effective in improving QoL and executive function as well as ameliorating core ADHD symptoms in adult Asian patients.

Delirium diagnosis defined by cluster analysis of symptoms versus diagnosis by DSM and ICD criteria: diagnostic accuracy study.

BACKGROUND: Information on validity and reliability of delirium criteria is necessary for clinicians, researchers, and further developments of DSM or ICD. We compare four DSM and ICD delirium diagnostic criteria versions, which were developed by consensus of experts, with a phenomenology-based natural diagnosis delineated using cluster analysis of delirium features in a sample with a high prevalence of dementia. We also measured inter-rater reliability of each system when applied by two evaluators from distinct disciplines. METHODS: Cross-sectional analysis of 200 consecutive patients admitted to a skilled nursing facility, independently assessed within 24-48 h after admission with the Delirium Rating Scale-Revised-98 (DRS-R98) and for DSM-III-R, DSM-IV, DSM-5, and ICD-10 criteria for delirium. Cluster analysis (CA) delineated natural delirium and nondelirium reference groups using DRS-R98 items and then diagnostic systems' performance were evaluated against the CA-defined groups using logistic regression and crosstabs for discriminant analysis (sensitivity, specificity, percentage of subjects correctly classified by each diagnostic system and their individual criteria, and performance for each system when excluding each individual criterion are reported). Kappa Index (K) was used to report inter-rater reliability for delirium diagnostic systems and their individual criteria. RESULTS: 117 (58.5 %) patients had preexisting dementia according to the Informant Questionnaire on Cognitive Decline in the Elderly. CA delineated 49 delirium subjects and 151 nondelirium. Against these CA groups, delirium diagnosis accuracy was highest using DSM-III-R (87.5 %) followed closely by DSM-IV (86.0 %), ICD-10 (85.5 %) and DSM-5 (84.5 %). ICD-10 had the highest specificity (96.0 %) but lowest sensitivity (53.1 %). DSM-III-R had the best sensitivity (81.6 %) and the best sensitivity-specificity balance. DSM-5 had the highest inter-rater reliability (K =0.73) while DSM-III-R criteria were the least reliable. CONCLUSIONS: Using our CA-defined, phenomenologically-based delirium designations as the reference standard, we found performance discordance among four diagnostic systems when tested in subjects where comorbid dementia was prevalent. The most complex diagnostic systems have higher accuracy and the newer DSM-5 have higher reliability. Our novel phenomenological approach to designing a delirium reference standard may be preferred to guide revisions of diagnostic systems in the future.

Comparison of diagnostic classification systems for delirium with new research criteria that incorporate the three core domains.

OBJECTIVE: Diagnostic classification systems do not incorporate phenomenological research findings about the three core symptom domains of delirium (Attentional/Cognitive, Circadian, Higher Level Thinking). We evaluated classification performances of novel Trzepacz, Meagher, and Franco research diagnostic criteria (TMF) that incorporate those domains and ICD-10, DSM-III-R, DSM-IV, and DSM-5. METHODS: Primary data analysis of 641 patients with mixed neuropsychiatric profiles. Delirium (n=429) and nondelirium (n=212) reference standard groups were identified using cluster analysis of symptoms assessed using the Delirium Rating Scale-Revised-98. Accuracy, sensitivity, specificity, positive and negative predictive values (PPV, NPV), and likelihood ratios (LR+, LR-) are reported. RESULTS: TMF criteria had high sensitivity and specificity (87.4% and 89.2%), more balanced than DSM-III-R (100% and 31.6%), DSM-IV (97.7% and 74.1%), DSM-5 (97.7% and 72.6%), and ICD-10 (66.2% and 100%). PPV of DSM-III-R, DSM-IV, and DSM-5 were <90.0%, while PPV for ICD-10 and TMF were >90%. ICD-10 had the lowest NPV (59.4%). TMF had the highest LR+ (8.06) and DSM-III-R the lowest LR- (0.0). Overall, values for DSM-IV and DSM-5 were similar, whereas for ICD-10 and DSM-III-R were inverse of each other. In the pre-existing cognitive impairment/dementia subsample (n=128), TMF retained its highest LR+ though specificity (58.3%) became less well balanced with sensitivity (87.9%), which still exceeded that of DSM. CONCLUSIONS: TMF research diagnostic criteria performed well, with more balanced sensitivity and specificity and the highest likelihood ratio for delirium identification. Reflecting the three core domains of delirium, TMF criteria may have advantages in biological research where delineation of this syndrome is important.

Comparison of cognitive and neuropsychiatric profiles in hospitalised elderly medical patients with delirium, dementia and comorbid delirium-dementia.

OBJECTIVES: Differentiation of delirium and dementia is a key diagnostic challenge but there has been limited study of features that distinguish these conditions. We examined neuropsychiatric and neuropsychological symptoms in elderly medical inpatients to identify features that distinguish major neurocognitive disorders. SETTING: University teaching hospital in Ireland. PARTICIPANTS AND MEASURES: 176 consecutive elderly medical inpatients (mean age 80.6 ± 7.0 years (range 60-96); 85 males (48%)) referred to a psychiatry for later life consultation-liaison service with Diagnostic and Statistical Manual of Mental Disorders (DSM) IV delirium, dementia, comorbid delirium-dementia and cognitively intact controls. Participants were assessed cross-sectionally with comparison of scores (including individual items) for the Revised Delirium Rating Scale (DRS-R98), Cognitive Test for Delirium (CTD) and Neuropsychiatric Inventory (NPI-Q). RESULTS: The frequency of neurocognitive diagnoses was delirium (n=50), dementia (n=32), comorbid delirium-dementia (n=62) and cognitively intact patients (n=32). Both delirium and comorbid delirium-dementia groups scored higher than the dementia group for DRS-R98 and CTD total scores, but all three neurocognitively impaired groups scored similarly in respect of total NPI-Q scores. For individual DRS-R98 items, delirium groups were distinguished from dementia groups by a range of non-cognitive symptoms, but only for impaired attention of the cognitive items. For the CTD, attention (p=0.002) and vigilance (p=0.01) distinguished between delirium and dementia. No individual CTD item distinguished between comorbid delirium-dementia and delirium. For the NPI-Q, there were no differences between the three neurocognitively impaired groups for any individual item severity. CONCLUSIONS: The neurocognitive profile of delirium is similar with or without comorbid dementia and differs from dementia without delirium. Simple tests of attention and vigilance can help to distinguish between delirium and other presentations. The NPI-Q does not readily distinguish between neuropsychiatric disturbances in delirium versus dementia. Cases of suspected behavioural and psychological symptoms of dementia should be carefully assessed for possible delirium.