Attention! A good bedside test for delirium?

peer-reviewedBackground Routine delirium screening could improve delirium detection, but it remains unclear as to which screening tool is most suitable. We tested the diagnostic accuracy of the following screening methods (either individually or in combination) in the detection of delirium: MOTYB (months of the year backwards); SSF (Spatial Span Forwards); evidence of subjective or objective 'confusion'.Methods We performed a cross-sectional study of general hospital adult inpatients in a large tertiary referral hospital. Screening tests were performed by junior medical trainees. Subsequently, two independent formal delirium assessments were performed: first, the Confusion Assessment Method (CAM) followed by the Delirium Rating Scale-Revised 98 (DRS-R98). DSM-IV (Diagnostic and Statistical Manual of Mental Disorders, fourth edition) criteria were used to assign delirium diagnosis. Sensitivity and specificity ratios with 95% CIs were calculated for each screening method.Results 265 patients were included. The most precise screening method overall was achieved by simultaneously performing MOTYB and assessing for subjective/objective confusion (sensitivity 93.8%, 95% CI 82.8 to 98.6; specificity 84.7%, 95% CI 79.2 to 89.2). In older patients, MOTYB alone was most accurate, whereas in younger patients, a simultaneous combination of SSF (cutoff 4) with either MOTYB or assessment of subjective/objective confusion was best. In every case, addition of the CAM as a second-line screening step to improve specificity resulted in considerable loss in sensitivity.Conclusions Our results suggest that simple attention tests may be useful in delirium screening. MOTYB used alone was the most accurate screening test in older people.PUBLISHEDpeer-reviewe

Florbetapir positron emission tomography and cerebrospinal fluid biomarkers

BACKGROUND: We evaluated the relationship between florbetapir-F18 positron emission tomography (FBP PET) and cerebrospinal fluid (CSF) biomarkers. METHODS: Alzheimer's Disease Neuroimaging Initiative-Grand Opportunity and Alzheimer's Disease Neuroimaging Initiative 2 (GO/2) healthy control (HC), mild cognitive impairment (MCI), and Alzheimer's disease (AD) dementia subjects with clinical measures and CSF collected ±90 days of FBP PET data were analyzed using correlation and logistic regression. RESULTS: In HC and MCI subjects, FBP PET anterior and posterior cingulate and composite standard uptake value ratios correlated with CSF amyloid beta (Aβ1-42) and tau/Aβ1-42 ratios. Using logistic regression, Aβ1-42, total tau (t-tau), phosphorylated tau181P (p-tau), and FBP PET composite each differentiated HC versus AD. Aβ1-42 and t-tau distinguished MCI versus AD, without additional contribution by FBP PET. Total tau and p-tau added discriminative power to FBP PET when classifying HC versus AD. CONCLUSION: Based on cross-sectional diagnostic groups, both amyloid and tau measures distinguish healthy from demented subjects. Longitudinal analyses are needed

Relationship between atomoxetine plasma concentration, treatment response and tolerability in attention-deficit/hyperactivity disorder and comorbid oppositional defiant disorder

The purpose of this study was to examine whether atomoxetine plasma concentration predicts attention-deficit/hyperactivity disorder (ADHD) or oppositional defiant disorder (ODD) response. This post-hoc analysis assessed the relationship between atomoxetine plasma concentration and ADHD and ODD symptoms in patients (with ADHD and comorbid ODD) aged 6–12 years. Patients were randomly assigned to atomoxetine 1.2 mg/kg/day (n = 156) or placebo (n = 70) for 8 weeks (Study Period II). At the end of 8 weeks, ODD non-remitters (score >9 on the SNAP-IV ODD subscale and CGI-I > 2) with atomoxetine plasma concentration <800 ng/ml at 2 weeks were re-randomized to either atomoxetine 1.2 mg/kg/day or 2.4 mg/kg/day for an additional 4 weeks (Study Period III). ODD remitters and non-remitters with plasma atomoxetine ≥800 ng/ml remained on 1.2 mg/kg/day atomoxetine for 4 weeks. Patients who received atomoxetine, completed Study Period II, and entered Study Period III were included in these analyses. All the groups demonstrated improvement on the SNAP-IV ODD and ADHD-combined subscales (P < .001). At the end of Study Periods II and III, ODD and ADHD improvement was significantly greater in the remitter group compared with the non-remitter groups. Symptom improvement was numerically greater in the non-remitter (2.4 mg/kg/day compared with the non-remitter 1.2 mg/kg/day) group. Atomoxetine plasma concentration was not indicative of ODD and ADHD improvement after 12 weeks of treatment. ADHD and ODD symptoms improved in all the groups with longer duration on atomoxetine. Results suggest atomoxetine plasma concentration does not predict ODD and ADHD symptom improvement. However, a higher atomoxetine dose may benefit some patients

Association between Serum IGF-I levels and Postoperative Delirium in Elderly Subjects Undergoing Elective Knee Arthroplasty.

Evidence is mixed for an association between serum insulin-like growth factor-I (IGF-I) levels and postoperative delirium (POD). The current study assessed preoperative serum IGF-I levels as a predictor of incident delirium in non-demented elderly elective knee arthroplasty patients. Preoperative serum levels of total IGF-I were measured using a commercially available Human IGF-I ELISA kit. POD incidence and severity were determined using DSM-IV criteria and the Delirium Rating Scale-Revised-98 (DRS-R98), respectively. Median IGF-I levels in delirious (62.6 ng/ml) and non-delirious groups (65.9 ng/ml) were not significantly different (p = 0.141). The ratio (95% CI) of geometric means, D/ND, was 0.86 (0.70, 1.06). The Hodges-Lehmann median difference estimate was 7.23 ng/mL with 95% confidence interval (−2.32, 19.9). In multivariate logistic regression analysis IGF-I level was not a significant predictor of incident POD after correcting for medical comorbidities. IGF-I levels did not correlate wit

Improving delirium care in the intensive care unit: The design of a pragmatic study

<p>Abstract</p> <p>Background</p> <p>Delirium prevalence in the intensive care unit (ICU) is high. Numerous psychotropic agents are used to manage delirium in the ICU with limited data regarding their efficacy or harms.</p> <p>Methods/Design</p> <p>This is a randomized controlled trial of 428 patients aged 18 and older suffering from delirium and admitted to the ICU of Wishard Memorial Hospital in Indianapolis. Subjects assigned to the intervention group will receive a multicomponent pharmacological management protocol for delirium (PMD) and those assigned to the control group will receive no change in their usual ICU care. The primary outcomes of the trial are (1) delirium severity as measured by the Delirium Rating Scale revised-98 (DRS-R-98) and (2) delirium duration as determined by the Confusion Assessment Method for the ICU (CAM-ICU). The PMD protocol targets the three neurotransmitter systems thought to be compromised in delirious patients: dopamine, acetylcholine, and gamma-aminobutyric acid. The PMD protocol will target the reduction of anticholinergic medications and benzodiazepines, and introduce a low-dose of haloperidol at 0.5-1 mg for 7 days. The protocol will be delivered by a combination of computer (artificial intelligence) and pharmacist (human intelligence) decision support system to increase adherence to the PMD protocol.</p> <p>Discussion</p> <p>The proposed study will evaluate the content and the delivery process of a multicomponent pharmacological management program for delirium in the ICU.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov: <a href="http://www.clinicaltrials.gov/ct2/show/NCT00842608">NCT00842608</a></p

Clinical use of amyloid-positron emission tomography neuroimaging: Practical and bioethical considerations

Until recently, estimation of β-amyloid plaque density as a key element for identifying Alzheimer's disease (AD) pathology as the cause of cognitive impairment was only possible at autopsy. Now with amyloid-positron emission tomography (amyloid-PET) neuroimaging, this AD hallmark can be detected antemortem. Practitioners and patients need to better understand potential diagnostic benefits and limitations of amyloid-PET and the complex practical, ethical, and social implications surrounding this new technology. To complement the practical considerations, Eli Lilly and Company sponsored a Bioethics Advisory Board to discuss ethical issues that might arise from clinical use of amyloid-PET neuroimaging with patients being evaluated for causes of cognitive decline. To best address the multifaceted issues associated with amyloid-PET neuroimaging, we recommend this technology be used only by experienced imaging and treating physicians in appropriately selected patients and only in the context of a comprehensive clinical evaluation with adequate explanations before and after the scan

Validation of the 4AT tool for delirium assessment in specialist palliative care settings: protocol of a prospective diagnostic test accuracy study [version 1; peer review: 2 approved]

BACKGROUND: Delirium is a serious and distressing neuropsychiatric condition, which is prevalent across all palliative care settings. Hypoactive delirium is particularly common, but difficult to recognize, partly due to overlapping symptoms with depression and dementia. Delirium screening tools can lead to earlier identification and hence better management of patients. The 4AT (4 ‘A’s Test) is a brief tool for delirium detection, designed for use in clinical practice. It has been validated in 17 studies in over 3,700 patients. The test is currently used in specialist palliative care units, but has not been validated in this setting. The aim of the study is to determine the diagnostic accuracy of the 4AT for delirium detection against a reference standard, in hospice inpatients. METHODS: 240 participants will be recruited from the inpatient units of two hospices in Scotland. If a patient lacks capacity to consent, agreement will be sought from a legal proxy. Each participant will complete the 4AT and a reference standard assessment based on the diagnostic delirium criteria in the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5). This will be supplemented by tests of cognition and attention, including reverse days of the week, counting down from 20 to 1, Vigilance 'A', the Observational Scale for Level of Arousal, the modified Richmond Agitation Sedation Scale and the Delirium Rating Scale-Revised-98. The assessments will be conducted in a randomized order by two independent clinicians, who will be blinded to the results until both are complete. Primary outcomes will be the sensitivity and specificity of the 4AT in detecting delirium. DISCUSSION: The findings will inform clinical practice regarding delirium assessment in palliative care settings. TRIAL REGISTRATION: ISRCTN ISRCTN97417474 (21/02/2020)

The Mini-Mental State Examination (MMSE) as a diagnostic and screening test for delirium: Systematic review and meta-analysis

Objective: To analyse the evidence concerning the accuracy of the Mini-Mental State Examination (MMSE) as a diagnostic and screening test for the presence of delirium in adults. Method: Two authors searched MEDLINE, PsychINFO and EMBASE from inception till 3/2014. Articles were included that investigated the diagnostic validity of the MMSE to detect delirium against standardised criteria. A diagnostic validity meta-analysis was conducted. Results: Thirteen studies were included representing 2017 patients in medical settings of whom 29.4% had delirium. The meta-analysis revealed the MMSE had an overall sensitivity and specificity estimate of 84.1% and 73.0%, but this was 81.1% and 82.8% in a subgroup analysis involving robust high quality studies. Sensitivity was unchanged but specificity was 68.4% (95% CI = 50.9% to 83.5%) in studies using a predefined cut-off of < 24 to signify a case. In high-risk samples where delirium was present in 25% of patients, then the Positive predictive value and Negative predictive value would be 50.9% (48.3% - 66.2%) and 93.2% (90.0% - 96.5%). Conclusion: The MMSE cannot be recommended as a case-finding confirmatory test of delirium, but may be used as an initial screen to rule out high scorers who are unlikely to have delirium with approximately 93% accuracy