Delirium Rating Scale Research Articles

The 4AT, a rapid delirium detection tool for use in hospice inpatient units: Findings from a validation study

Background: Delirium is a serious neuropsychiatric syndrome with adverse outcomes, which is common but often undiagnosed in terminally ill people. The 4 ‘A’s test or 4AT (www.the4AT.com), a brief delirium detection tool, is widely used in general settings, but validation studies in terminally ill people are lacking. Aim: To determine the diagnostic accuracy of the 4AT in detecting delirium in terminally ill people, who are hospice inpatients. Design: A diagnostic test accuracy study in which participants underwent the 4AT and a reference standard based on the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders. The reference standard was informed by Delirium Rating Scale Revised-98 and tests assessing arousal and attention. Assessments were conducted in random order by pairs of independent raters, blinded to the results of the other assessment. Setting/participants: Two hospice inpatient units in Scotland, UK. Participants were 148 hospice inpatients aged ⩾18 years. Results: A total of 137 participants completed both assessments. Three participants had an indeterminate reference standard diagnosis and were excluded, yielding a final sample of 134. Mean age was 70.3 (SD = 10.6) years. About 33% (44/134) had reference standard delirium. The 4AT had a sensitivity of 89% (95% CI 79%–98%) and a specificity of 94% (95% CI 90%–99%). The area under the receiver operating characteristic curve was 0.97 (95% CI 0.94–1). Conclusion: The results of this validation study support use of the 4AT as a delirium detection tool in hospice inpatients, and add to the literature evaluating methods of delirium detection in palliative care settings. Trial registry: ISCRTN 97417474.

Increased IgA-mediated responses to the gut paracellular pathway and blood-brain barrier proteins predict delirium due to hip fracture in older adults.

Delirium is accompanied by immune response system activation, which may, in theory, cause a breakdown of the gut barrier and blood-brain barrier (BBB). Some results suggest that the BBB is compromised in delirium, but there is no data regarding the gut barrier. This study investigates whether delirium is associated with impaired BBB and gut barriers in elderly adults undergoing hip fracture surgery. We recruited 59 older adults and measured peak Delirium Rating Scale (DRS) scores 2-3 days after surgery, and assessed plasma IgG/IgA levels (using ELISA techniques) for zonulin, occludin, claudin-6, β-catenin, actin (indicating damage to the gut paracellular pathway), claudin-5 and S100B (reflecting BBB damage), bacterial cytolethal distending toxin (CDT), LPS-binding protein (LBP), lipopolysaccharides (LPS), Porphyromonas gingivalis, and Helicobacter pylori. Results from univariate analyses showed that delirium is linked to increased IgA responses to all the self-epitopes and antigens listed above, except for LPS. Part of the variance (between 45-48.3%) in the peak DRS score measured 2-3 days post-surgery was explained by independent effects of IgA directed to LPS and LBP (or bacterial CDT), baseline DRS scores, and previous mild stroke. Increased IgA reactivity to the paracellular pathway and BBB proteins and bacterial antigens is significantly associated with the activation of M1 macrophage, T helper-1, and 17 cytokine profiles. Heightened bacterial translocation, disruption of the tight and adherens junctions of the gut and BBB barriers, elevated CDT and LPS load in the bloodstream, and aberrations in cell-cell interactions may be risk factors for delirium.

Spanish transcultural adaptation of the 4AT score for the evaluation of delirium in the emergency department: a prospective diagnostic test accuracy study

BackgroundDelirium is one of the most common adverse events in older people during hospitalization, especially in the emergency department. Reliable, easy-to-use instruments are necessary to properly manage delirium in this setting. This study aims to evaluate the diagnostic validity of the Spanish version of the 4 ‘A’s Test (4AT) in the ED.MethodsA diagnostic accuracy study was conducted in patients over 65 years old admitted to the Emergency Department who did not have a formal diagnosis of dementia or a severe mental health disorder. Face and content validity were evaluated by an expert panel. Emergency nurses performed the evaluation with 4AT, whilst blinded and trained researchers assessed patients with the Revised Delirium Rating Scale as the gold standard. The content validity index, sensitivity, specificity, positive and negative predictive values, likelihood ratios, Youden’s Index and ROC curves were calculated to evaluate the diagnostic accuracy of the instrument.ResultsOf 393 eligible patients, 380 were finally analyzed. Content validity yielded a median content validity index of 4 (interquartile range: 0). The Spanish 4AT sensitivity (95.83%; 95% ECI: 78.9–99.9%), specificity (92.98%; 95% CI: 89.8–95.4%), positive predictive value (47.92%) and negative predictive value (99.7%) were satisfactory. Youden’s index was 0.89. Positive likelihood ratio was 13.65, and negative likelihood ratio 0.045. The area under the curve was 0.97.ConclusionsThe Spanish version of the 4AT for use in the Emergency Departments is easy-to-use and applicable. The validation results indicate that it is a valid instrument with sufficient predictive validity to identify patients at risk of delirium in the Emergency Departments. Moreover, it is a tool that facilitates the management of an adverse event that is associated with increased mortality and morbidity.

Efficacy and Safety of Risperidone in Patients With Delirium: The RIDDLE Pilot Study.

The cornerstone treatment of delirium is to assess and treat its underlying causes and prevent further complications. Drug therapy may be necessary to control agitation and behavioral symptoms associated with delirium. The aim of this pilot study was to evaluate the feasibility of a randomized placebo controlled trial to evaluate the efficacy and safety of risperidone in the treatment of delirium. This was a randomized double-blinded placebo-controlled trial. Patients were enrolled in the study if they were hospitalized and 65 years or older and had a diagnosis of delirium. Delirium Rating Scale revised 98 was used to determine delirium and motor agitation. A total of 14 participants with 57% being men and having a mean age of 86 years were included. There were no statistically significant differences between the risperidone and placebo group for the Delirium Rating Scale revised 98 score. There were no severe adverse reactions reported in the study, and no patients discontinued the study for adverse reactions. Risperidone at low doses (1 mg daily or less) was well tolerated for the treatment of delirium. Future large-scale trials are needed to evaluate the safety and efficacy of risperidone in the treatment of delirium. This pilot study taught us that the phase 2 RIsperDone DELirium trial will need a multicenter design with more research personnel to increase the number of participants enrolled.

Sleep Disruptions in Hospitalized Adults Sustaining a Traumatic Brain Injury: A Scoping Review.

Adults sustaining a traumatic brain injury (TBI) are at risk of sleep disturbances during their recovery, including when such an injury requires hospitalization. However, the sleep-wake profile, and internal and external factors that may interfere with sleep initiation/maintenance in hospitalized TBI patients are poorly understood. This review aimed to: (1) identify/summarize the existing evidence regarding sleep and sleep measurements in TBI adults receiving around-the-clock care in a hospital or during inpatient rehabilitation, and (2) identify internal/external factors linked to poor sleep in this context. A scoping review was conducted in accordance with the PRISMA Scoping Review Extension guidelines. A search was conducted in MEDLINE, PsycINFO, CINAHL, and Web of Science databases. Thirty relevant studies were identified. The most common sleep variables that were put forth in the studies to characterize sleep during hospitalization were nighttime sleep time (mean = 6.5 hours; range: 5.2-8.9 hours), wake after sleep onset (87.1 minutes; range: 30.4-180 minutes), and sleep efficiency (mean = 72.9%; range: 33%-96%) using mainly actigraphy, polysomnography, and questionnaires (eg, the sleep-wake disturbance item of the Delirium Rating Scale or the Pittsburgh Sleep Quality Index). Twenty-four studies (80%) suggested that hospitalized TBI patients do not get sufficient nighttime sleep, based on the general recommendations for adults (7-9 hours per night). Sleep disruptions during hospitalization were found to be associated to several internal factors including TBI severity, cognitive status, and analgesia intake. External and modifiable factors, such as noise, light, and patient care, were consistently associated with sleep disruptions in this context. Although the literature on sleep disturbances in hospitalized TBI patients has been increasing in recent years, many gaps in knowledge remain, including phenotypes and risk factors. Identifying these factors could help clinicians better understand the multiple sources of TBI patients' sleep difficulties and intervene accordingly.

The Validity and Applicability of the Revised Delirium Rating Scale (DRS-R98) for Delirium Severity Assessment in a Critical Care Setting.

Delirium is a neuropsychiatric syndrome common in critical illness. Worsening delirium severity is associated with poorer clinical outcomes, yet its assessment remains under-reported with most severity assessment tools not validated for critical care. The DRS-R98 is a widely applied and validated tool. The aim of this project is to report the validation and utility of the DRS-R98 in critical illness. This prospective, cohort study was conducted in adults with delirium admitted to a critical care unit and predicted to stay for ≥ 24 h. We excluded patients with severe neurological or communication barriers that would have interfered with the DRS-R98 assessment. Patients were screened using a delirium detection algorithm and the Confusion Assessment Method for the Intensive Care Unit. Eligible patient informations were collected and reported to qualified assessor/s before visiting clinical areas, confirming delirium presence and undertaking DRS- R98 assessments. To assess the tool's construct validity, an intensivist completed the Clinical Global Impression-Scale (CGI-S). To calculate the inter-rater reliability (IRR) a subset of patients were simultaneously evaluated by two assessors. We assessed 22 patients, 73% were male, with a median age of 65 years (IQR14). The DRS -R98 mean (SD) severity score was 24 (+/-7.7), total scale was 29 (+/18.0), and CGI-S 3.5 (+/11.5). Assessment duration was 90 min (+/-55) and 15 min (+/-5) for record data extraction and clinical assessment respectively. The CGI-S significantly correlated with DRS-R98 severity (r = 0.626) and total (r = 0.628) scales. The DRS-R98 Cronbach's alpha was 0.896 for severity scale and 0.886 for total scale. The inter-rater reliability (IRR) was assessed in six patients and reported an inter-correlation coefficient of 0.505 (p = 0.124) and 0.565 (p = 0.93) for the severity and total scale respectively. In critical care, the Delirium Rating Scale R98 had good construct validity, excellent internal consistency, and moderate inter-rater reliability.

The Association between Electroencephalography with Auditory Steady-State Response and Postoperative Delirium.

Delirium is a disorder of consciousness and a risk factor for cognitive dysfunction and poor prognosis. We hypothesized that preoperative gamma activities would be linked to postoperative delirium. We enrolled 71 subjects for elective surgery and recorded auditory steady-state response (ASSR) by electroencephalography (EEG) before the surgery and examined postoperative delirium with DSM-5. The EEG data were analyzed for baseline power, and ASSR evoked power (EP) and phase-locking factor (PLF) within the gamma range. Postoperative delirium was found in 18 patients (delirium group) but not in 53 patients (non-delirium group). There were no significant differences in the 40-Hz EP or PLF between the two groups. The baseline gamma activity negatively correlated with the 40-Hz PLF in the non-delirium group (ρ = -0.444, p < 0.01). The correlation between baseline gamma activity and 40-Hz EP was not significant in either the delirium or non-delirium group. In all patients, both preoperative PLF and EP had no significant correlations with the Delirium Rating Scale Revised-98 and the Memorial Delirium Assessment Measure at the post-operation, respectively. The disruption of the neurophysiological relationship between baseline gamma activity before sound stimuli and the PLF of the 40-Hz ASSR may be one of the potential neurophysiological indicators associated with postoperative delirium.

Reactivity to neural tissue epitopes, aquaporin 4 and heat shock protein 60 is associated with activated immune-inflammatory pathways and the onset of delirium following hip fracture surgery.

Activation of the immune-inflammatory response system (IRS) and a deficiency in the compensatory immunoregulatory system (CIRS), neuronal injuries, and alterations in the glutamate receptor (GlutaR), aquaporin-4 (AQP4) and heat shock protein 60 (HSP60) are involved in delirium. Increased serum levels of neurofilament protein (NFP), glial fibrillary acidic protein (GFAP) and myelin basic protein (MBP) are biomarkers of neuronal injury. This investigation delineates whether elevated IgA/IgG reactivity against those self-antigens is associated with delirium severity and IRS activation. We measured peak Delirium Rating Scale (DRS) scores on days 2 and 3 following surgery in 59 hip fractured older adults, and IgA and IgG antibody levels against MBP, NFP, GFAP and myelin oligodendrocyte glycoprotein (MOG), metabotropic glutamate receptors mGluRs 1 and 5, N-Methyl-D-Aspartate receptor (NMDAR) GLU1 (NR1) and GLU2 (NR2), APQ4 and HSP60. The IgA antibody levels against those self-antigens, especially GFAP, MBP and HSP60, strongly predict peak DRS scores on days 2 and 3 post-surgery. IgA reactivity against NMDAR and baseline DRS scores explained 40.6% of the variance in peak DRS scores, while IgA against NMDAR, IgG against MBP and age explained 29.1% of the variance in the IRS/CIRS ratio. There was no correlation between DRS scores and IgG directed against other self-antigens. Increased IgA levels against neuronal self-antigens, AQP4 and HSP60 are risk factors for delirium. Polyreactive antibody-associated breakdown of immune tolerance, IRS activation and injuries in the neuronal cytoskeleton, oligodendrocytes, astrocytes, glial cells, and myelin sheath are involved in the pathophysiology of delirium.

Contribution of intraoperative electroencephalogram suppression to frailty-associated postoperative delirium: mediation analysis of a prospective surgical cohort

BackgroundFrailty is a risk factor for postoperative delirium (POD), and has led to preoperative interventions that have reduced, but not eliminated, the risk. We hypothesised that EEG suppression, another risk factor for POD, mediates some of the frailty risk for POD. MethodsA prospective cohort study enrolled patients aged 65 yr or older, scheduled for noncardiac surgery under total intravenous anaesthesia. Frailty was assessed using the FRAIL scale. Cumulative duration of EEG suppression, defined as an amplitude between –5 and 5 μV for >0.5 s during anaesthesia, was measured. POD was diagnosed by either confusion assessment method (CAM), CAM-ICU, or medical records. The severity of POD was assessed using the Delirium Rating Scale – Revised-98 (DRS). Mediation analysis was used to estimate the relationships between frailty, EEG suppression, and severity of POD. ResultsAmong 252 enrolled patients, 51 were robust, 129 were prefrail, and 72 were frail. Patients classified as frail had higher duration of EEG suppression than either the robust (19 vs 0.57 s, P<0.001) or prefrail groups (19 vs 3.22 s, P<0.001). Peak delirium score was higher in the frail group than either the robust (17 vs 15, P<0.001) or prefrail groups (17 vs 16, P=0.007). EEG suppression time mediated 24.2% of the frailty–DRS scores association. ConclusionEEG suppression time mediated a statistically significant portion of the frailty–POD association in older noncardiac surgery patients. Trials directed at reducing EEG suppression time could result in intraoperative interventions to reduce POD in frail patients. Clinical trial registrationChiCTR2000041092 (Chinese Clinical Trial Registry).

Proton pump inhibitors-induced psychiatric symptoms

ABSTRACT Proton pump inhibitors are widely used in cure of digestive tract diseases and drug-induced psychiatric symptoms are rare. In this study, we aim to investigate the presentations, diagnostic approaches, treatments and prognosis. We present one case of proton pump inhibitors-induced motor hallucination underwent drug withdrawal and recovery subsequently. Delirium Rating Scale and Hamilton Anxiety Scale examinations showed transient delirium and anxiety. Proton pump inhibitors-induced psychiatric symptoms are benign and affect patients’ prognosis. No standard treatment exists, and the strategies contain discontinuing proton pump inhibitors and/or antipsychotics drugs. Overall prognosis is usually good and recurrence seems to be rare.

Delirium due to hip fracture is associated with activated immune-inflammatory pathways and a reduction in negative immunoregulatory mechanisms

BackgroundThe objectives of this study were to delineate whether delirium in older adults is associated with activation of the immune-inflammatory response system (IRS) as indicated by activation of M1, T helper (Th)1, and Th17 profiles, and/or by reduced activities of the compensatory immunoregulatory system (CIRS), including Th2 and T regulatory profiles.MethodsWe recruited 65 older adult patients with a low energy impact hip fracture who underwent hip fracture operation. The CAM-ICU and the Delirium Rating Scale, Revised-98-Thai version (DRS-R-98) were assessed pre-operatively and 1, 2 and 3 days after surgery. Blood samples (day 1 and 2) post-surgery were assayed for cytokines/chemokines using a MultiPlex assay and the neutrophil/lymphocyte ratio.ResultsWe found that delirium and/or the DRS-R-98 score were associated with IRS activation as indicated by activated M1, Th1, Th17 and T cell growth profiles and by attenuated CIRS functions. The most important IRS biomarkers were CXCL8, interleukin (IL)-6, and tumor necrosis factor-α, and the most important CIRS biomarkers were IL-4 and soluble IL-1 receptor antagonist. We found that 42.5% of the variance in the actual changes in the DRS-R-98 score (averaged from day 1 to day 3) was explained by T cell growth factors, baseline DRS-R-98 scores and age. An increase in the NLR reflects overall IRS, M1, Th1, Th17, and Th2 activation.ConclusionsPost-hip surgery delirium is associated with activated IRS pathways and appears especially in patients with lowered CIRS functions.

Early Intervention of Perioperative Delirium in Older Patients (&gt;60 years) with Hip Fracture: A Randomized Controlled Study

ObjectiveTo explore the effect of early intervention for perioperative delirium in older (> 60 years) hip fracture patients.MethodsThis prospective study enrolled hip fracture patients aged ≥60 years who were admitted into our hospital between July 2011 and August 2019. Hip fractures were classified according to the Arbeitsgemeinschaft für Osteo‐synthesefragen (AO) classification. This study included patients with isolated hip fracture and excluded patients with pathological or peri prosthetic fracture or patients with multiple traumatic injuries and high‐energy trauma. They were randomized to receive conventional orthopedic care group (n = 65) or comprehensive orthopedic care group including preoperative psychological counseling and preventative risperidone (n = 63). Daily assessment was based on patient interview with the CAM‐CR, and delirium was diagnosed by the Delirium Rating Scale (DRS‐R‐98). The rate, severity and duration of perioperative delirium and the length of postoperative stay were analyzed.ResultsTotally 200 patients were screened for eligibility. Twenty patients were excluded due to alcohol abuse and 40 were excluded because of brain lesions on head CT. In addition, 12 patients were excluded because of impaired cognition. Finally 128 patients were enrolled. Their mean age was 75.3 ± 2.2 years for the comprehensive orthopedic care group and 73.5 ± 6.1 years for the conventional orthopedic care group, and 53.9% of the patients were female. Sixty‐eight (53.1%) patients had intertrochanteric fracture, 39.8% patients had femoral head fracture, and 7.0% patients had subtrochanteric fracture. In addition, 58.6% patients underwent internal fixation and 41.4% patients received arthroplasty. In this study, 63 patients were randomized to the comprehensive orthopedic care group and 65 patients to the conventional orthopedic care group. The two groups were comparable in demographic and baseline characteristics (P > 0.05). The rate of perioperative delirium was significantly lower in the comprehensive care group vs the conventional care group (15.9% vs. 30.8%; P < 0.05). The comprehensive care group had significantly reduced length of postoperative hospital stay vs the conventional care group (11.3 ± 2.5 days vs. 14.2 ± 2.2 days, P < 0.01). The mean DRS‐R‐98 score was 7.1 ± 2.7 for the comprehensive care group, and was significantly lower than that of the conventional orthopedic care group (11.2 ± 3.0; P < 0.05).ConclusionsOur early intervention may reduce the incidence of perioperative delirium in elderly hip fracture patients (>60 years).

Safety and Effectiveness of Perospirone in Comparison to Risperidone for Treatment of Delirium in Patients with Advanced Cancer: A Multicenter Prospective Observational Study in Real-World Psycho-Oncology Settings.

The clinical benefit of perospirone for treatment of delirium in patients with advanced cancer is not sufficiently clear. The objective of this study was to compare the safety and effectiveness of perospirone to those of risperidone for the treatment of delirium in patients with advanced cancer. This is a secondary analysis of a multicenter prospective observational study in nine psycho-oncology consultation services in Japan. The study used the Delirium Rating Scale (DRS) Revised-98 to measure effectiveness and the CTCAE (Common Terminology Criteria for Adverse Events) version 4 to assess safety. Data from 16 patients who received perospirone and 53 patients who received risperidone were analyzed. The mean age was 70 years in the perospirone group and 73 years in the risperidone group. Both groups showed a significant decrease in the total score of DRS-R-98 after three days of treatment (perospirone: 11.7 (7.9-15.4) to 7.0 (3.3-10.7), difference -4.7, effect size=0.72, p=0.003; risperidone: 15.5 (13.6-17.4) to 12.2 (10.1-14.2), difference -3.3, effect size=0.55, p=0.00). The risperidone group showed significant improvements in sleep-wake cycle disturbance, orientation, attention, and visuospatial ability. In the perospirone group, there was a significant improvement of sleep-wake cycle disturbance. The median daily dose of perospirone was 4 mg/day. There were fewer episodes of somnolence as an adverse event in the perospirone group. Low-dose perospirone was thus found to be effective for the treatment of delirium in patients with advanced cancer and may be associated with fewer episodes of over-sedation as an adverse event.

Delirium in COVID-19 and post-liver transplant patients: an observational study

Objective Delirium is a major complication in hospitalised patients. This study aimed to compare the mortality trends of patients with delirium according to the underlying physical condition. Methods Hospitalised patients diagnosed with delirium by the Modena Consultation-Liaison Psychiatry Service (Italy) during 2020 were enrolled. Three groups were identified: COVID; after orthotopic liver transplant (OLT); other conditions. The full medical records were screened to retrieve socio-demographic and clinical data. INTERMED score and Delirium Rating Scale were used to retrospectively rate bio-social-complexity and delirium severity. Early (20 days) and end of study (31st January 2021) mortality were ascertained for each subject. Results A total of 103 patients were enrolled. Patients hospitalised for COVID showed higher INTERMED scores (two-tailed t-test, p = 0.019) and higher 20-day mortality (HR = 3.68, p = 0.014). When considering a 1-year follow-up, the main predictor of mortality was patients’ age in all three subgroups (HR = 1.06; p = 0.003). Conclusion Our results suggest that patients hospitalised for COVID-19 with delirium showed higher bio-psycho-social complexity and higher short-term mortality, regardless of the severity of delirium. OLT patients showed lower mortality and bio-psycho-social complexity, despite being still considered as ‘complex’, according to the INTERMED score. Future research should focus on understanding the underlying mechanisms in the relationship between delirium and mortality. Key points Patients hospitalised for COVID-19 with delirium were found at risk of higher short-term mortality and higher bio-psycho-social complexity. OLT patients showed lower overall mortality and lower bio-psycho-social complexity than the other two groups, despite being still in the ‘complex’ range according to the INTERMED score. Future research should assess the areas of impact of delirium in patients affected by COVID-19, considering short- and long-term outcomes.

Management of Psychiatric Disorders in Patients with Respiratory Diseases.

Management of Psychiatric Disorders in Patients with Respiratory Diseases.

Management of Psychiatric Disorders with HIV and Dermatological Disorders.

Management of Psychiatric Disorders with HIV and Dermatological Disorders.

Screening and Assessment Tools for Measuring Delirium in Patients with Cancer in Hospice and Palliative Care: A Systematic Review.

This study reviewed screening and assessment tools that are used to measure delirium in patients with cancer in hospice and palliative care settings and examined their psychometric properties. Four databases were searched for studies using related search terms (delirium, tools, palliative care, cancer, and others). The inclusion criteria were a) studies that included screening/assessment tools for measuring delirium in cancer patients receiving hospice/palliative care, and b) studies published in English or Korean. The exclusion criteria were a) studies that were conducted in an intensive care setting, and b) case studies, qualitative studies, systematic reviews, or meta-analyses. Out of the 81 studies identified, only 10 examined the psychometric properties of tools for measuring delirium, and 8 tools were ultimately identified. The psychometric properties of the Memorial Delirium Assessment Scale (MDAS) were the most frequently examined (n=5), and the MDAS showed good reliability, concurrent validity, and diagnostic accuracy. The Delirium Rating Scale had good reliability and diagnostic accuracy. The Delirium Rating Scale-Revised 98 also showed good reliability and structural validity, but its diagnostic performance was not examined in hospice/palliative care settings. The Nursing Delirium Screening Scale showed relatively low diagnostic accuracy. The MDAS showed evidence of being a valid assessment tool for assessing delirium in patients with cancer in palliative care. Few studies examined the diagnostic performance of delirium tools. Therefore, further studies are needed to examine the diagnostic performance of screening/assessment tools for the optimal detection of delirium in patients with cancer in hospice/palliative care.

A decision tree prediction model for a short-term outcome of delirium in patients with advanced cancer receiving pharmacological interventions: A secondary analysis of a multicenter and prospective observational study (Phase-R).

There is no widely used prognostic model for delirium in patients with advanced cancer. The present study aimed to develop a decision tree prediction model for a short-term outcome. This is a secondary analysis of a multicenter and prospective observational study conducted at 9 psycho-oncology consultation services and 14 inpatient palliative care units in Japan. We used records of patients with advanced cancer receiving pharmacological interventions with a baseline Delirium Rating Scale Revised-98 (DRS-R98) severity score of ≥10. A DRS-R98 severity score of <10 on day 3 was defined as the study outcome. The dataset was randomly split into the training and test dataset. A decision tree model was developed using the training dataset and potential predictors. The area under the curve (AUC) of the receiver operating characteristic curve was measured both in 5-fold cross-validation and in the independent test dataset. Finally, the model was visualized using the whole dataset. Altogether, 668 records were included, of which 141 had a DRS-R98 severity score of <10 on day 3. The model achieved an average AUC of 0.698 in 5-fold cross-validation and 0.718 (95% confidence interval, 0.627-0.810) in the test dataset. The baseline DRS-R98 severity score (cutoff of 15), hypoxia, and dehydration were the important predictors, in this order. We developed an easy-to-use prediction model for the short-term outcome of delirium in patients with advanced cancer receiving pharmacological interventions. The baseline severity of delirium and precipitating factors of delirium were important for prediction.

Immune, Blood Cell, and Blood Gas Biomarkers of Delirium in Elderly Individuals with Hip Fracture Surgery

Background: Postoperative delirium in elderly people with hip fracture is associated with various adverse clinical outcomes. Nevertheless, the pathophysiological processes underpinning delirium have remained elusive. Objectives: The aim of this study was to explore the associations between delirium and its features and immune-inflammatory and blood gas biomarkers. Methods: In this prospective study, we examined 65 patients who underwent a hip fracture surgery and assessed the Confusion Assessment Method for the Intensive Care Unit, Richmond Agitation-Sedation Scale (RASS), and Delirium Rating Scale Revised-98 (DRS-R-98) before and during 4 days after the surgery. Complete blood count and venous blood gas markers were obtained at the same time points. Results: Delirium was observed in 19 patients and was accompanied by significantly increased pO₂, number of white blood cells, neutrophil percentage, and neutrophil/lymphocyte ratio, and lower mean platelet volume (MPV) after adjusting for age, central nervous system (CNS) disease, blood loss during surgery, sleep disorders, and body mass index. The severity of delirium was associated with lowered number of platelets and MPV. Psychomotor disorders were associated with lower bicarbonate levels. The requirement of physical restraint of the patients was predicted by increased percentages of neutrophils and lymphocytes. Prior CNS disease was together with these biomarkers a significant predictor of delirium and severity of delirium. Conclusion: Delirium and psychomotor disorders following hip fracture and surgery may be caused by immune-inflammatory and oxidative stress pathways probably attributable to an aseptic inflammatory process.

A randomized double-blind placebo-controlled trial of intravenous thiamine for prevention of delirium following allogeneic hematopoietic stem cell transplantation

ObjectiveTo determine if high dose intravenous (IV) thiamine can prevent delirium during hospitalization following allogeneic HSCT. Secondarily, we evaluated the effects of high dose IV thiamine on thiamine levels and explored risk factors for delirium. MethodsRandomized, double-blind, placebo-controlled trial in patients undergoing allogeneic HSCT at a U.S. academic medical center between October 2017 and March 2020. 64 participants were randomized 1:1 to thiamine 200 mg IV three times daily for 7 days or placebo. We used the Delirium Rating Scale to assess for delirium. Delirium incidence was compared between groups using the chi-square test. Group differences in time to onset and duration of delirium were compared using the Kaplan-Meier method. Fisher's Exact and Wilcoxon Rank Sum tests were used to examine associations between pre-transplantation variables and delirium. Results61 participants were analyzed. Delirium incidence (25% vs. 21%, Chi-square (df = 1) = 0.12, p = 0.73), time to onset, duration, and severity were not different between study arms. Immediately following the intervention, thiamine levels were higher in the thiamine arm (275 vs. 73 nmol/L, t-test (df = 57) = 13.63, p < 0.0001), but not predictive of delirium. Variables associated with delirium in our sample included disease severity, corticosteroid exposure, infection, and pre-transplantation markers of nutrition. ConclusionHigh dose IV thiamine did not prevent delirium in patients receiving allogeneic HSCT. Given the multiple contributors to delirium in this population, further research regarding the efficacy of multicomponent interventions may be needed.Trial Registration: Clinical Trials NCT03263442.Funding: Rising Tide Foundation for Clinical Cancer Research.