DeltaScan for the Assessment of Acute Encephalopathy and Delirium in ICU and non-ICU Patients, a Prospective Cross-Sectional Multicenter Validation Study.

OBJECTIVES: To measure the diagnostic accuracy of DeltaScan: a portable real-time brain state monitor for identifying delirium, a manifestation of acute encephalopathy (AE) detectable by polymorphic delta activity (PDA) in single-channel electroencephalograms (EEGs). DESIGN: Prospective cross-sectional study. SETTING: Six Intensive Care Units (ICU's) and 17 non-ICU departments, including a psychiatric department across 10 Dutch hospitals. PARTICIPANTS: 494 patients, median age 75 (IQR:64-87), 53% male, 46% in ICUs, 29% delirious. MEASUREMENTS: DeltaScan recorded 4-minute EEGs, using an algorithm to select the first 96 seconds of artifact-free data for PDA detection. This algorithm was trained and calibrated on two independent datasets. METHODS: Initial validation of the algorithm for AE involved comparing its output with an expert EEG panel's visual inspection. The primary objective was to assess DeltaScan's accuracy in identifying delirium against a delirium expert panel's consensus. RESULTS: DeltaScan had a 99% success rate, rejecting 6 of the 494 EEG's due to artifacts. Performance showed and an Area Under the Receiver Operating Characteristic Curve (AUC) of 0.86 (95% CI: 0.83-0.90) for AE (sensitivity: 0.75, 95%CI=0.68-0.81, specificity: 0.87 95%CI=0.83-0.91. The AUC was 0.71 for delirium (95%CI=0.66-0.75, sensitivity: 0.61 95%CI=0.52-0.69, specificity: 72, 95%CI=0.67-0.77). Our validation aim was an NPV for delirium above 0.80 which proved to be 0.82 (95%CI: 0.77-0.86). Among 84 non-delirious psychiatric patients, DeltaScan differentiated delirium from other disorders with a 94% (95%CI: 87-98%) specificity. CONCLUSIONS: DeltaScan can diagnose AE at bedside and shows a clear relationship with clinical delirium. Further research is required to explore its role in predicting delirium-related outcomes.

Successful treatment of severe, treatment resistant GHB withdrawal through thiopental-coma.

BACKGROUND: In patients with gamma-hydroxybutyrate (GHB) use disorder (GUD), withdrawal can have a fulminant course with rapid progression of severe, potentially life-threatening complications. Case: We present a 45-year old man with severe GHB withdrawal, resistant to conventional treatment with pharmaceutical GHB, high doses of benzodiazepines and baclofen. GHB withdrawal finally responded to thiopental-induced coma therapy, with burst suppression pattern on electroencephalography (EEG). The patient fully recovered, without withdrawal or residual neuropsychiatric symptoms. Discussion: To our knowledge, this is the first case report in which barbiturates were used to induce a coma to treat severe, treatment resistant GHB withdrawal. This case suggests barbiturate coma therapy might be considered in severe GHB withdrawal which does not respond to conventional treatment.

Behavior and cognitive functioning in Witteveen-Kolk syndrome.

Witteveen-Kolk syndrome (WITKOS) is a rare neurodevelopmental disorder characterized by developmental delay/intellectual disability, facial dysmorphisms, and short stature. The syndrome is caused by loss of function of switch-insensitive 3 transcription regulator family member A (SIN3A). Regarding behavioral functioning, Autism Spectrum Disorders (ASD), obsessive-compulsive behaviors, as well as Attention-Deficit/Hyperactivity Disorder symptoms (ADHD) have been suggested. The present study explores various aspects of neurocognitive functioning in five individuals (age range 10-23) with WITKOS. Medical records and results of extensive neuropsychological assessment are used to describe developmental trajectories and neurocognitive profiles. Systematic analysis of medical records displays developmental difficulties described as ASD or ADHD in childhood, sleep problems and internalizing problems during adolescence. Results of cognitive assessments indicate profoundly disabled (n = 1), mildly disabled (n = 2), borderline (n = 1), and average (n = 1) levels of intelligence. Furthermore, results indicate weaknesses in speed of information processing/sustained attention in all participants, and difficulties in planning and maintaining overview in three participants. Furthermore, parent reports of behavioral functioning primarily suggest problems in social functioning. Implications of both cognitive problems and social-emotional vulnerabilities for counseling are discussed and supplemented with suggestions for interventions.

Performance and validation of two ICU delirium assessment and severity tools; a prospective observational study.

BACKGROUND: The clinical statistical performance of the Confusion Assessment Method Intensive Care Unit (CAM-ICU, including CAM-ICU-7) and Intensive Care Delirium Screening Checklist (ICDSC) have rarely been studied. Additionally, delirium severity is often not measured due to a lack of validation of delirium assessment tools. OBJECTIVE: The aim was to determine the statistical performance of both delirium assessment tools in daily practice, and the correlation with the gold standard Delirium Rating Scale (DRS)-R98, for delirium severity. RESEARCH METHOD: CAM-ICU-7 and ICDSC, performed by nurses were compared with the DRS-R98 assessed by delirium experts, twice weekly. Within a time-window of one hour all assessments were independently performed. DESIGN: A prospective observational study performed between October and December 2020. MAIN OUTCOME MEASURES: Sensitivity, specificity, positive and negative predictive value of both tools was determined. The correlation between DRS-R98 and CAM-ICU-7 and ICDSC was used for validation of delirium severity. RESULTS: In total, 104 CAM-ICU-7 and 105 ICDSC assessments in 86 patients were compared with the DRS-R98. For the CAM-ICU-7 and ICDSC, respectively, the sensitivity was 90% and 95%, the specificity was 92.4% and 92.3%. The positive predictive value was 0.76 and 0.80, and negative predictive value was 0.77 and 0.97. Correlation of the CAM-ICU-7 score and ICDSC score with the DRS-R98 score was 0.74 (95% CI 0.64-0.81) and 0.70 (95%CI 0.59-0.79; both p < 0.001), respectively. CONCLUSION: Both CAM-ICU-7 and ICDSC demonstrated good statistical performance and correlated well with the delirium severity tool DRS-R98. IMPLICATIONS FOR CLINICAL PRACTICE: Nurses can either use the CAM-ICU(-7) or the ICDSC in their practice, both are accurate in delirium diagnosis. Total CAM-ICU-7 and ICDSC score reflects delirium severity well; the higher the score, the more severe the delirium. This enables nurses to gauge the impact of their interventions and enhance the well-being of patients experiencing delirium by minimizing distressing occurrences.

Neural basis of recollection in first-episode major depression.

BACKGROUND: Patients with major depressive disorder (MDD) display impairments in recollection, which have been explained by both hippocampal and prefrontal dysfunction. Here, we used an event-related fMRI design, to dissociate hippocampal and prefrontal contributions to the neural processes involved in recollection success and recollection attempt early in the course of MDD. METHODS: To disentangle state- and trait-effects of depression, we included 20 medication-naive patients with a first depressive episode, 20 medication-free patients recovered from a first episode, and 20 matched, healthy controls in an event-related fMRI study using a source recollection paradigm. RESULTS: Group comparisons revealed that during the acute state of depression there is an increase in left prefrontal activity related to recollection attempt, while there were no differences in neural correlates of successful recollection. CONCLUSIONS: Our results indicate that in the early course of depression, depressive state is associated with increased left prefrontal activation during the attempt to recollect source information suggesting an increased need for executive control during recollection in MDD. In this sample of first-episode MDD patients we found no evidence for hippocampal dysfunction.

Improved neurocognitive functions correlate with reduced inflammatory burden in atrial fibrillation patients treated with intensive cholesterol lowering therapy.

BACKGROUND: Atrial fibrillation (AF) is associated with increased mortality and morbidity, including risk for cerebral macro- and microinfarctions and cognitive decline, even in the presence of adequate oral anticoagulation. AF is strongly related to increased inflammatory activity whereby anti-inflammatory agents can reduce the risk of new or recurrent AF. However, it is not known whether anti-inflammatory therapy can also modify the deterioration of neurocognitive function in older patients with AF. In the present study, older patients with AF were treated with intensive lipid-lowering therapy with atorvastatin 40 mg and ezetimibe 10 mg, or placebo. We examined the relationship between neurocognitive functions and inflammatory burden. FINDINGS: Analysis of inflammatory markers revealed significant reductions in high sensitivity C-reactive protein (hs-CRP), fibroblast growth factor (FGF), granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-1 receptor antagonist (IL-1RA), interleukin (IL)-9, IL-13 and IL-17, and interferon-γ (IFNγ) in the treatment group compared to placebo. Reduction in plasma concentration of IL-1RA, IL-2, IL-9 and IL-12, and macrophage inflammatory protein-1ß (MIP-1ß) correlated significantly with improvement in the neurocognitive functions memory and speed. Loss of volume in amygdala and hippocampus, as determined by magnetic resonance imaging (MRI), was reduced in the treatment arm, statistically significant for left amygdala. CONCLUSIONS: Anti-inflammatory therapy through intensive lipid-lowering treatment with atorvastatin 40 mg and ezetimibe 10 mg can modify the deterioration of neurocognitive function, and the loss of volume in certain cerebral areas in older patients with AF. TRIAL REGISTRATION ClinicalTrials.gov: NCT00449410.

[Prevention of delirium in the Intensive Care Unit]. / Preventie van delier op de intensive care.

Delirium is highly prevalent in the Intensive Care Unit (ICU) and is strongly associated with negative patient outcomes. We aimed to present an overview of the effectiveness of non-pharmacological and pharmacological interventions to prevent delirium in ICU patients. Multicomponent non-pharmacological interventions are proven effective in the prevention of delirium. These interventions are aimed at multiple domains, including re-orientation, providing a safe and healing environment, cognitive stimulation, mobilization and family engagement. A special type of multicomponent intervention is the ''A-F bundle'', comprising both non-pharmacological and pharmacological interventions. Multicomponent non-pharmacological interventions and the ''A-F bundle'' are recommended. There is insufficient evidence for the effectiveness of pharmacological prophylaxis using antipsychotics, dexmedetomidine, melatonin or thiamin, except for delirium due to substance withdrawal. Therefore, pharmacological interventions should be aimed at minimizing delirogenousmedication (especially benzodiazepines and opiates), adequate pain management and the prevention of deep and continuous sedation.

Measuring Adaptive Behavior in Patients with Mendelian Neurodevelopmental Disorders. Comparison of ABAS-3 and Dutch Vineland Scales.

Objective: Several instruments are available for measuring (aspects of) adaptive functioning, but knowledge is lacking about which is best to use to monitor patients with etiologically homogeneous neurodevelopmental disorders. In this study we compare the use of the Vineland-Z and ABAS-3 adaptive behavior scales in such a specific group. Method: Of patients with a molecularly confirmed diagnosis of Kleefstra syndrome, 34 were assessed with both the Vineland-Z and ABAS-3 of which 12 (35,3%) males and 22 (64,7%) females. Raw scores and developmental ages were calculated and a comparison between the instruments was done via correlation analysis. Results: Biological age ranged from 12 to 50 years old (median age of 23,1 ± 9,6 years). Pearson r correlation analyses show that the Vineland-Z and ABAS-3 assessments are highly interchangeable in this population. However, there are practical issues which require attention: (i) the use of ABAS-3 needs several versions to cover the whole adaptive spectrum, and (ii) the Vineland-Z discriminates more at the lower end of the adaptive functioning spectrum compared to the ABAS-3, but less at the higher end. An ideal instrument for this specific purpose is not yet available. Conclusions: We recommend that either the Vineland-Z, with modification of the dated items, the abridged version of the Vineland III, or a merge of the 0-4/517 ABAS-3 versions would work best to assess the entire spectrum of adaptive functioning adequately.

The Delirium Interview as a new reference standard in studies on delirium assessment tools.

BACKGROUND: The reference standard in studies on delirium assessment tools is usually based on the clinical judgment of only one delirium expert and may be concise, unstandardized, or not specified at all. This multicenter study investigated the performance of the Delirium Interview, a new reference standard for studies on delirium assessment tools allowing classification of delirium based on written reports. METHODS: We tested the diagnostic accuracy of our standardized Delirium Interview by comparing delirium assessments of the reported results with live assessments. Our reference, the live assessment, was performed by two delirium experts and one well-trained researcher who registered the results. Their delirium assessment was compared to the majority vote of three other independent delirium experts who judged the rapportage of the Delirium Interview. Our total pool consisted of 13 delirium experts with an average of 13 ± 8 years of experience. RESULTS: We included 98 patients (62% male, mean age 69 ± 12 years), of whom 56 (57%) intensive care units (ICUs) patients, 22 (39%) patients with a Richmond Agitation Sedation Scale (RASS) < 0 and 26 (27%) non-verbal assessments. The overall prevalence of delirium was 28%. The Delirium Interview had a sensitivity of 89% (95% confidence interval [CI]: 71%-98%) and specificity of 82% (95% CI: 71%-90%), compared to the diagnosis of an independent panel of two delirium experts and one researcher who examined the patients themselves. Negative and positive predictive values were 95% (95% CI: 86%-0.99%), respectively, 66% (95% CI: 49%-80%). Stratification into ICU and non-ICU patients yielded similar results. CONCLUSION: The Delirium Interview is a feasible reference method for large study cohorts evaluating delirium assessment tools since experts could assess delirium with high accuracy without seeing the patient at the bedside.

Development of the Tilburg Pregnancy Distress Scale: the TPDS.

BACKGROUND: Pregnant women with high levels of stress, depression and/or anxiety are at increased risk for adverse perinatal outcomes and impaired neurologic and emotional development of the offspring. Pregnancy specific instruments to measure psychological functioning during gestation are scarce and do not define items based on in-depth interviews of pregnant and recently delivered women. The current study developed a pregnancy specific scale that measures psychological functioning using in-depth interviews. METHODS: Three focus groups were formed to discuss issues most relevant to pregnancy distress; 22 candidate items were derived for pilot testing (study I, n = 419) its psychometric properties by means of explorative factor analyses (EFA). This resulted in a 17-item TPDS which was further explored by confirmatory factor analyses (CFA) and concurrent and construct validity assessment (study II, n = 454). RESULTS: EFA in study I suggested a two component solution (negative affect (NA) and partner involvement (PI)). CFA in study II resulted in a higher order model of the NA subscale into three more subscales: NA regarding confinement, delivery and general health. TPDS, EPDS and GAD-7 were all significantly correlated. CONCLUSIONS: The TPDS constitutes a valid and user friendly instrument to assess pregnancy distress. In addition to its proven ability to pick up pregnancy specific negative affect it also includes an important sub-scale measuring perceived partner involvement.

Factors associated with a persistent delirium in the intensive care unit: A retrospective cohort study.

PURPOSE: To explore differences between ICU patients with persistent delirium (PD), non-persistent delirium (NPD) and no delirium (ND), and to determine factors associated with PD. MATERIALS AND METHODS: Retrospective cohort study including all ICU adults admitted for ≥12 h (January 2015-February 2020), assessable for delirium and followed during their entire hospitalization. PD was defined as ≥14 days of delirium. Factors associated with PD were determined using multivariable logistic regression analysis. RESULTS: Out of 10,295 patients, 3138 (30.5%) had delirium, and 284 (2.8%) had PD. As compared to NPD (n = 2854, 27.7%) and ND (n = 7157, 69.5%), PD patients were older, sicker, more physically restrained, longer comatose and mechanically ventilated, had a longer ICU and hospital stay, more ICU readmissions and a higher mortality rate. Factors associated with PD were age (adjusted odds ratio [aOR] 1.03; 95% confidence interval [CI] 1.02-1.04); emergency surgical (aOR 1.84; 95%CI 1.26-2.68) and medical (aOR 1.57; 95%CI 1.12-2.21) referral, mean Sequential Organ Failure Assessment (SOFA) score before delirium onset (aOR 1.18; 95%CI 1.13-1.24) and use of physical restraints (aOR 5.02; 95%CI 3.09-8.15). CONCLUSIONS: Patients with persistent delirium differ in several characteristics and had worse short-term outcomes. Physical restraints were the most strongly associated with PD.

Associations Between Maternal Depression, Antidepressant Use During Pregnancy, and Adverse Pregnancy Outcomes: An Individual Participant Data Meta-analysis.

OBJECTIVE: To evaluate the associations of depressive symptoms and antidepressant use during pregnancy with the risks of preterm birth, low birth weight, small for gestational age (SGA), and low Apgar scores. DATA SOURCES: MEDLINE, EMBASE, ClinicalTrials.gov, and PsycINFO up to June 2016. METHODS OF STUDY SELECTION: Data were sought from studies examining associations of depression, depressive symptoms, or use of antidepressants during pregnancy with gestational age, birth weight, SGA, or Apgar scores. Authors shared the raw data of their studies for incorporation into this individual participant data meta-analysis. TABULATION, INTEGRATION, AND RESULTS: We performed one-stage random-effects meta-analyses to estimate odds ratios (ORs) with 95% CIs. The 215 eligible articles resulted in 402,375 women derived from 27 study databases. Increased risks were observed for preterm birth among women with a clinical diagnosis of depression during pregnancy irrespective of antidepressant use (OR 1.6, 95% CI 1.2-2.1) and among women with depression who did not use antidepressants (OR 2.2, 95% CI 1.7-3.0), as well as for low Apgar scores in the former (OR 1.5, 95% CI 1.3-1.7), but not the latter group. Selective serotonin reuptake inhibitor (SSRI) use was associated with preterm birth among women who used antidepressants with or without restriction to women with depressive symptoms or a diagnosis of depression (OR 1.6, 95% CI 1.0-2.5 and OR 1.9, 95% CI 1.2-2.8, respectively), as well as with low Apgar scores among women in the latter group (OR 1.7, 95% CI 1.1-2.8). CONCLUSION: Depressive symptoms or a clinical diagnosis of depression during pregnancy are associated with preterm birth and low Apgar scores, even without exposure to antidepressants. However, SSRIs may be independently associated with preterm birth and low Apgar scores. SYSTEMATIC REVIEW REGISTRATION: PROSPERO, CRD42016035711.

Delayed complications after severe clozapine intoxication: a case report. The pharmacokinetic profile of clozapine and it's important role in the course of symptoms.

Clozapine intoxications have a varied clinical presentation and may have severe complications. Management and treatment guidelines rarely highlight the risks of delayed clinical presentations. We present the case of a 50-year-old man showing severe complications 15 hours after intoxication with 4200 mg clozapine. Treatment consisted of strict monitoring, including vital support and regular clozapine blood levels. Clinical presentations may be delayed up to 5 days after intoxication, for which strict monitoring of clinical symptoms and vital functions during this period is of major importance. We discuss the clinical course of clozapine intoxication, the value of sampling clozapine blood levels and provide an overview of the current treatment guidelines, which we suggest to update to include the management of delayed complications.

Epidemiological evaluation of the Patient Health Questionnaire-2 in a pregnant population.

INTRODUCTION: The Patient Health Questionnaire-2 (PHQ-2) is a commonly used 2-item screening tool for depressive symptoms among pregnant women in primary care settings. However, its validity has not been assessed for large-scale epidemiological studies. Therefore, the aim of this study was to provide an epidemiological evaluation of the PHQ-2 among pregnant women. METHOD: A total of 3033 pregnant women participating in the PRegnancy and Infant DEvelopment Study completed the PHQ-2 as well as the Hospital Anxiety Depression Scale-Depression (HADS-D) or the Edinburgh Depression Scale (EDS) three times throughout pregnancy. The validity of the PHQ-2 was assessed with the HADS-D/EDS as reference standard. RESULTS: Sensitivity and specificity of the PHQ-2 were 69-84% and 79-84%, respectively. The positive predictive values (range 19-26%) were substantially lower than the negative predictive values (96-99%). CONCLUSION: Despite the relatively high number of false-positive screens, initial screening for depression by two questions only may enhance routine evaluation of depressive symptoms among pregnant women.

[Pseudologia fantastica. Recognition and treatment of pathological lying]. / Pseudologica fantastica: herkenning en behandeling van pathologisch liegen.

Although a clear definition of pseudologia fantastica cannot be found in the literature, there is consensus that this condition differs quantitatively and qualitatively from 'normal lying'. We discuss recognition of pseudologia fantastica based on 2 patients who presented with suicidal ideations at the casualty department following a traumatic event. Early recognition is important in order to break the pattern of lying, to restrict the use of medical resources and, finally, to act in accordance with the general principle of 'primum-non-nocere'. Although a psychiatric diagnostic workup might be worthwhile, it remains difficult to engage these patients for psychiatric treatment.