Memorial Delirium Assessment Scale Research Articles

The relationship between intraoperative hypothermia and postoperative delirium: The PNDRFAP study.

Our study aimed to investigate the correlation between intraoperative hypothermia and postoperative delirium (POD) in patients undergoing general anesthesia for gastrointestinal surgery. The study comprised 750 participants from the Perioperative Neurocognitive Disorder Risk Factor and Prognosis (PNDRFAP) study database, which ultimately screened 510 individuals in the final analysis. Preoperative cognitive function was evaluated using the Mini-Mental State Examination (MMSE). The occurrence of POD was determined using the Confusion Assessment Method, and the severity of POD was evaluated using the Memorial Delirium Assessment Scale. Logistic regression was employed to scrutinize the association between intraoperative hypothermia and the incidence of POD, and the sensitivity analysis was conducted by introducing adjusted confounding variables. Decision curves and a nomogram model were utilized to assess the predictive efficacy of intraoperative hypothermia for POD. Mediation analysis involving 10,000 bootstrapped iterations was employed to appraise the suggested mediating effect of numeric rating scale (NRS) scores at 24 and 48h post-surgeries. The receiver-operating characteristic (ROC) was utilized to evaluate the effectiveness of intraoperative hypothermia in predicting POD. In the PNDRFAP study, the occurrence of POD was notably higher in the intraoperative hypothermia group (62.2%) compared to the intraoperative normal body temperature group (9.8%), with an overall POD incidence of 17.6%. Logistic regression analysis, adjusted for various confounding factors (age [40-90], gender, education, MMSE, smoking history, drinking history, hypertension, diabetes, and the presence of cardiovascular heart disease), demonstrated that intraoperative hypothermia significantly increased the risk of POD (OR=4.879, 95% CI=3.020-7.882, p<.001). Mediation analyses revealed that the relationship between intraoperative hypothermia and POD was partially mediated by NRS 24h after surgery, accounting for 14.09% of the association (p=.002). The area under the curve of the ROC curve was 0.685, which confirmed that intraoperative hypothermia could predict POD occurrence to a certain extent. Decision curve and nomogram analyses, conducted using the R package, further substantiated the predictive efficacy of intraoperative hypothermia on POD. Intraoperative hypothermia may increase the risk of POD, and this association may be partially mediated by NRS scores 24h after surgery.

Physical activity may a probably protective factor for postoperative delirium: the PNDABLE study.

This study aims to explore the relationship between physical activity (PA) and postoperative delirium (POD). We selected 400 patients from the Perioperative Neurocognitive Disorder and Biomarkers Lifestyle (PNDABLE) database, and the patients in the PNDABLE database were sampled and tested Alzheimer's biomarkers. The diagnosis of POD was made using the Confusion Assessment Scale (CAM) and the severity was assessed using Memorial Delirium Assessment Scale (MDAS). Mini-Mental State Examination (MMSE) scale was used to detect the mental state of the patients. Enzyme-linked immunosorbent assay (ELISA) was used to detect the level of preoperative cerebrospinal fluid (CSF) biomarkers, such as amyloid β plaque 42 (Aβ42), total tau protein (T-tau), and phosphorylated tau protein (P-tau). Logistic regression, sensitivity analysis, and post hoc analysis were used to explore the relationship between risk and protective factors on POD. We used the mediating effect to explore whether PA mediates the occurrence of POD through CSF biomarkers. The incidence of POD was 17.5%. According to our research, the consequence prompted that PA might be the protective factor for POD [odds ratio (OR): 0.336, 95% confidence interval (95 CI) 0.206-0.548, P < 0.001]. The result of logistic regression revealed that CSF biomarker Aβ42 (OR: 0.997, 95 CI 0.996-0.999, P < 0.001) might be a protective factor against POD, and the T-tau (OR: 1.006, 95 CI 1.003-1.009, P = 0.001) and P-tau (OR: 1.039, 95 CI 1.018-1.059, P < 0.001) might risk factors for POD. Sensitivity analysis confirmed the correlation between PA and CSF biomarkers in the patients with POD. Mediation effect analysis showed that PA may reduce the occurrence of POD partly through CSF biomarkers, such as Aβ42 (proportion: 11%, P < 0.05), T-tau (proportion: 13%, P < 0.05), and P-tau (proportion: 12%, P < 0.05). Physical activity is probably a protective factor for POD and may exert a mediating effect through CSF biomarkers.

Melatonin does not reduce delirium severity in hospitalized older adults: Results of a randomized placebo-controlled trial.

Delirium is common in older inpatients, causing distress, cognitive decline, and death. Current therapies are unsatisfactory, limited by lack of efficacy and adverse effects. There is an urgent need for effective delirium treatment. Sleep wake cycle is disturbed in delirium; endogenous Melatonin is perturbed, and exogenous Melatonin is a safe and effective medication for sleep disorders. This study aims to determine the effect of oral Melatonin 5 mg immediate release (IR) nightly for five nights on the severity of delirium in older (≥65 years) medical inpatients. This was a double-blinded, randomized controlled trial in general internal medicine units of a tertiary teaching hospital. Older inpatients with Confusion Assessment Method positive, hyperactive or mixed delirium within 48 h of admission or onset of in-hospital delirium were included. The primary outcome was change in delirium severity measured with the Memorial Delirium Assessment Scale (MDAS). A previous pilot trial showed 120 participants randomized 1:1 to Melatonin or Placebo would provide 90% power to demonstrate a 3-point reduction in the MDAS. One hundred and twenty participants were randomized, 61 to Melatonin 5 mg and 59 to Placebo. The medication was well tolerated. The mean MDAS improvement was 4.9 (SD 7.6) in the Melatonin group and 5.4 (SD 7.2) in the Placebo group, p-value 0.42, a non-significant difference. A post-hoc analysis showed length of stay (LOS) was shorter in the intervention group (median 9 days [Interquartile Range (IQR) 4, 12] vs. Placebo group 10 [IQR 6, 16] p-value = 0.033, Wilcoxon Rank Sum test). This trial does not support the hypothesis that Melatonin reduces the severity of delirium. This may be due to no effect of Melatonin, a smaller effect than anticipated, an effect not captured on a multidimensional delirium assessment scale, or a type II statistical error. Melatonin may improve LOS; this hypothesis should be studied.

Relationship between preoperative neutrophil-to-lymphocyte ratio and postoperative delirium: The PNDABLE and the PNDRFAP cohort studies.

In this study, the relationship between preoperative neutrophil-to-lymphocyte ratio (NLR) and Alzheimer-related biomarkers in cerebrospinal fluid (CSF) was investigated to determine whether high NLR is a potential risk factor for postoperative delirium (POD) and to evaluate its predictive efficacy. We selected 1000 patients from the perioperative neurocognitive disorder risk factor and prognosis (PNDRFAP) database and 999 patients from the perioperative neurocognitive disorder and biomarker lifestyle (PNDABLE) database. Patients in the PNDABLE database have been measured for Alzheimer-related biomarkers in CSF (Aβ40 , Aβ42 , P-tau, and tau protein). Mini-mental state examination was used to assess the preoperative mental status of patients. POD was diagnosed using the confusion assessment method and assessed for severity using the memorial delirium assessment scale. Logistic regression analysis was utilized to explore the association of preoperative NLR with POD. What's more, we also performed sensitivity analysis by adding corrected confounders, and the results were almost unchanged. Spearman's rank correlation was used to determine the associations between NLR and Alzheimer-related biomarkers. Mediation analyses with 10,000 bootstrapped iterations were used to explore the mediation effects. Finally, we use decision curves and the nomogram model to evaluate the efficacy of preoperative NLR in predicting POD; we also performed external validation using data from Qilu Hospital. Logistic regression results showed that an elevated preoperative NLR was a risk factor for the development of POD in patients (PNDRFAP: OR=1.067, 95% CI 1.020-1.116; PNDABLE: OR=1.182, 95% CI 1.048-1.335, p<.05). Spearman's rank correlation analysis showed a positive but weak correlation between NLR and P-tau/T-tau (R=.065). The mediating effect results indicate that NLR likely mediates the occurrence of POD through elevated tau protein levels (proportion: 47.47%). The results of the box plots showed statistically significant NLR and CSF biomarkers between the POD and non-POD (NPOD) groups (p<.05), with higher NLR, P-tau, and T-tau in the POD group than in the NPOD group. In contrast, the NPOD group had higher Aβ42 levels compared to the POD group. In addition, we used R package to plot the decision curve and nomogram both suggesting a good predictive effect of preoperative NLR on the occurrence of POD. Elevated preoperative NLR levels may be a risk factor for POD and likely mediate the development of POD through elevated P-tau/T-tau levels.

Daytime dysfunction may be associated with postoperative delirium in patients undergoing total hip/knee replacement: The PNDABLE study.

Postoperative delirium (POD) is a usual complication after total hip/knee replacement, which may be affected by sleep characteristics. However, up to now, preoperative sleep characteristics have not been evaluated as risk factors of POD. The relationship between self-reported sleep characteristics and POD in patients has been investigated in this study. We recruited 495 cognitively intact individuals in the final analysis from the Perioperative Neurocognitive Disorder and Biomarker Lifestyle study. Sleep characteristics were tested by the Pittsburgh Sleep Quality Index (PSQI). Mini-mental state examination was applied to assess preoperative mental status of patients. Postoperatively, we used confusion assessment method and memorial delirium assessment scale to evaluate the incidence of POD and POD severity, respectively. The cerebrospinal fluid (CSF) levels of T-tau, P-tau, Aβ40, and Aβ42 were detected by enzyme-linked immune-sorbent assay before the operation. Logistic regression, multiple linear regression, and mediation effects were performed to analyze the relationship between self-reported sleep characteristics and POD. POD was detected in 11.31% (56/495) of the patients, with logistic regression analysis showing that daytime dysfunction, P-tau, and T-tau were risk factors of POD, and Aβ42 was a protective factor of POD. Multiple linear regression analysis confirmed that daytime dysfunction was positively correlated with P-tau in patients with POD. Meanwhile, compared to the patients with no postoperative delirium, the CSF levels of P- and T-tau were higher in patients with POD. Furthermore, mediation analysis showed that it was probable that daytime dysfunction mediated POD through P-tau (proportion: 12.90%) partially. Daytime dysfunction is a risk factor of POD preoperatively. To sum up, CSF P-tau protein might partially mediate the influence of daytime dysfunction on POD. This study was registered at Chinese Clinical Trial Registry (ChiCTR2000033439).

Switching to Intravenous Methadone in Advanced Cancer Patients: A Retrospective Analysis.

Information about opioid switching to intravenous methadone is lacking. The aim of this study was to assess the outcome of opioid switching to intravenous methadone (IV-ME) in patients admitted to an acute supportive/palliative care unit (ASPCU). The secondary outcome was to assess the conversion ratio from IV-ME to oral methadone at time of hospital discharge. We retrieved from the pharmacy registry the list of patients who were prescribed IV-ME during their ASPCU admission for a period of 47 months. Poor analgesia with previous opioids and/or adverse effects were the main indications for opioid switching. IV-ME was titrated until acceptable analgesia was achieved. The effective dose was multiplied by three to establish the intravenous daily dose, given as a continuous infusion. Doses were then changed according to the clinical needs. Once the patient was stabilized, IV-ME dose was converted to oral methadone, by using an initial ratio of 1:1.2. Further dose changes were made according to clinical needs until stabilization, before patients' discharge. Information about patients' characteristics, pain scores on the Edmonton Symptom Assessment Scale (ESAS), Memorial Delirium Assessment Scale (MDAS), Cut-down, Annoyed, Guilty, Eye-opener (CAGE) questionnaire, previous opioids and their doses, expressed as oral morphine equivalents (OME), were recorded. The effective bolus of IV-ME, initial daily infusion rate, and oral methadone doses were assessed, and conversion ratios calculated. Forty-one patients were taken into consideration for the study. The mean effective bolus of IV-ME titrated for achieving acceptable analgesia was 9 mg (range 5-15 mg). The mean daily continuous infusion rate of IV-ME was 27.6 mg/day (SD 21). The mean daily dose of oral methadone at time of discharge was 46.8 mg/day (SD 43). Discharge occurred within a median of seven days (range 6-9) after admission. Previous opioid (OME)/IV-ME, oral-IV-ME, and previous opioid (OME)/oral methadone were 6.25, 1.7, and 3.7, respectively. IV-ME dose titration followed by intravenous infusion allowed a rapid pain control in few minutes in patients with severe pain intensity, not responsive to previous opioids. Conversion to oral route was successful and facilitated home discharge. Further studies should be performed to confirm these preliminary results.

The Confusion Assessment Method Could Be More Accurate than the Memorial Delirium Assessment Scale for Diagnosing Delirium in Older Cancer Patients: An Exploratory Study.

Older people with cancer carry a high risk of delirium, an underdiagnosed syndrome due to its diagnostic complexity and often subtle presentation. Tools based on the Diagnostic and Statistical Manual of Mental Disorders (DSM) are available to different health professionals. Our aim is to assess the prevalence of delirium in older people with cancer in an inpatient unit and the accuracy of the Confusion Assessment Method (CAM) and Memorial Delirium Assessment Scale (MDAS). This exploratory, cross-sectional study included people aged 65 years or older with a diagnosis of cancer and admitted to the medical oncology unit from June 2021 to December 2022. The diagnostic accuracy of CAM and MDAS was analyzed against the gold standard medical diagnosis based on DSM-5 criteria by two medical oncologists. The cutoff point for the MDAS was determined using a receiver-operating characteristics (ROC) curve. Among the 75 included patients (mean age 71.6 years, standard deviation 4.1; 52% males), the prevalence of delirium was 62.7%. The most prevalent types of cancer in patients with delirium were hematological and lung cancer. The scale with the highest diagnostic accuracy was the CAM, with a sensitivity of 100% and specificity of 86%, followed by the MDAS, with a sensitivity of 88% and specificity of 30%. The presence of cognitive impairment hindered the detection of delirium. The CAM scale was more accurate than the MDAS pre-existing cognitive impairment in our sample. Further studies are needed to analyze the diagnostic accuracy of delirium tools in older populations with cancer and in the presence of cognitive impairment.

Alcohol consumption may be associated with postoperative delirium in the elderly: the PNDABLE study

ObjectivesThis study aimed to reveal the relationship between alcohol consumption and Postoperative delirium (POD) in the elderly.MethodsWe selected 252 patients from the Perioperative Neurocognitive Disorder And Biomarker Lifestyle (PNDABLE ) study. Patients in the PNDABLE database have been measured for Alzheimer-related biomarkers in CSF (Aβ40, Aβ42, P-tau, and tau protein). Mini-Mental State Examination (MMSE) was used to assess the preoperative mental status of patients. POD was diagnosed using the Confusion Assessment Method (CAM) and assessed for severity using the Memorial Delirium Assessment Scale (MDAS). Logistic regression analysis was utilized to explore the association of alcohol consumption with POD. Linear regression analysis was used to study the relationship between alcohol consumption and CSF biomarkers. Mediation analyses with 10,000 bootstrapped iterations were used to explore the mediation effects. Finally, we constructed the receiver operating characteristic (ROC) curve and the nomogram model to evaluate the efficacy of alcohol consumption and CSF biomarkers in predicting POD. ResultThe incidence of POD was 17.5%. Logistic regression showed that alcohol consumption (OR = 1.016, 95%CI 1.009–1.024, P < 0.001) is a risk factor for POD. What’s more, Aβ42 is a protective factor for POD (OR = 0.993, 95%CI 0.989–0.997, P < 0.05), and P-Tau was a risk factor for POD (OR = 1.093, 95%CI 1.022–1.168, P < 0.05). Linear regression analysis revealed that alcohol consumption was negatively associated with CSF Aβ42 (β = -0.638, P < 0.001) in POD patients. Mediation analyses showed that alcohol consumption is likely to partially mediate POD through Aβ42 (proportion:14.21%). ROC curve showed that alcohol consumption (AUC = 0.904; P < 0.001) exhibited a relatively better discriminatory ability in POD prediction compared to Aβ42 (AUC = 0.798; P < 0.001). The calibration curve indicated a good nomogram prediction (P = 0.797).ConclusionAlcohol consumption is a risk factor for POD (particularly for those with > 24 g a day on average) in the elderly, and contributes to POD through the mediation of Aβ42.

A single preoperative low-dose dexamethasone may reduce the incidence and severity of postoperative delirium in the geriatric intertrochanteric fracture patients with internal fixation surgery: an exploratory analysis of a randomized, placebo-controlled trial

ObjectivePostoperative delirium (POD) is a common complication along with poor prognosis in geriatric intertrochanteric fracture (ITF) patients. However, the prevention and treatment of POD remain unclear. Previous studies have confirmed that POD is essentially a consequence of neuro-inflammatory responses. Dexamethasone is a glucocorticoid with comprehensive anti-inflammatory effects, while a high dose of dexamethasone correlates with many side effects or even adverse consequences. Thus, this prospective study aims to discuss whether a single preoperative low-dose dexamethasone can reduce the impact of POD on geriatric ITF patients with internal fixation surgery.MethodsBetween June 2020 and October 2022, there were 219 consecutive ITF patients assessed in our department. Of the 219 ITF patients, 160 cases who met the inclusion and exclusion criteria were finally enrolled and randomly allocated to the dexamethasone group and the placebo group (80 geriatric ITF patients in each group) in this prospective study. The patients in the dexamethasone group received intravenous 10 mg (2 ml) dexamethasone while the patients in the placebo group received intravenous 2 ml saline in 30 min before being sent to the operating room, respectively. The baseline characteristics, surgical information, incidence and severity of POD as the efficacy-related outcomes, and infection events and hyperglycemia as safety-related outcomes (adverse events), were collected and analyzed between the two groups. The severity of POD was evaluated by Memorial Delirium Assessment Scale (MDAS) score.ResultsThere were no differences in baseline characteristics and surgical information between the dexamethasone group and the placebo group. The dexamethasone group had a lower incidence of POD than the placebo group within the first 5 days after surgery [(9/80, 11.3% vs. 21/80, 26.3%, RR = 0.83, 95% CI 0.71–0.97, P = 0.015]. The dexamethasone group had lower MDAS scores (Mean ± SD) than the placebo group [13.2 ± 1.0 (range 11 to 15) vs. 15.48 ± 2.9 (range 9 to 20), P = 0.011, effect size = 0.514]. There were no differences in infection events and hyperglycemia between the two groups.ConclusionsA single preoperative low-dose dexamethasone may reduce the incidence and severity of POD in geriatric ITF patients with internal fixation surgery.Trial registration: ChiCTR2200055281.

Accuracy of Delirium Screening Tools in Older People with Cancer-A Systematic Review.

The increase in life expectancy worldwide has led to a larger population of older people, which in turn entails a rising prevalence of cancer. One of the main complications of cancer is delirium, especially in advanced stages. To determine which delirium screening instrument is the most accurate in older people with cancer. A systematic review was designed. A literature search was performed in MEDLINE, EBSCO and SCOPUS; additional records were identified by handsearching. Selection criteria were studies involving people with cancer and a mean sample age of 60 years or older, assessing delirium, and reporting the metric properties of the assessment instrument. Studies with post-surgical patients and substance abuse delirium were excluded. From 2001 to 2021, 14 eligible studies evaluated 13 different assessment tools, reporting an incidence of delirium ranging from 14.3% to 68.3%. The Delirium Observation Screening Scale (DOSS) showed the best metric properties, followed by the Nursing Delirium Screening Scale (NuDESC), Confusion Assessment Method (CAM) and Memorial Delirium Assessment Scale (MDAS). Only two studies were considered to be at low risk of bias using the QUADAS-2 Tool. No study exclusively examined this population group. Screening tools for delirium are heterogeneous for older people with cancer, and there is a need to analyze metric properties exclusively in the older population. Registered on PROSPERO ID: CRD42022303530.

Preoperative cerebrospinal fluid biomarkers may be associated with postoperative delirium in patients undergoing knee/hip arthroplasty: the PNDABLE study

BackgroundIn the global aging population, the incidence of postoperative delirium (POD) is increasing. Therefore, finding its effective predictive tools becomes crucial. We aimed to identify potential Cerebrospinal fluid (CSF)biomarkers for POD.MethodsA total of 825 patients undergoing knee/hip arthroplasty under combined spinal-epidural anesthesia were selected. The patients were aged 40 to 90 years with American Society of Anesthesiologists physical status I~II. The Mini-Mental State Examination was completed 1 day before the operation. CSF was extracted after successful spinal-epidural combined puncture, and α-synuclein (α-syn), amyloid beta40 (Aβ40), amyloid beta42 (Aβ42), t-Tau, phosphorylated Tau (p-Tau), progranulin (PGRN) and soluble triggering receptor expressed on myeloid cells 2 (sTREM2) in the CSF were measured by enzyme-linked immunosorbent assays (ELISA). The patient’s operation time, anesthesia time, intraoperative blood loss and fluid input were also recorded. After the operation, the occurrence rate and severity of POD were determined by the Confusion Assessment Method and the Memorial Delirium Assessment Scale (MDAS), respectively. Patients were categorized into POD group and non-POD group. Logistic regression analysis was performed on the indicators with statistically significant differences, and the area under the ROC curve (AUC) was used to estimate the predictive accuracy of the biomarkers for POD.ResultsA total of 92 patients developed POD and the incidence of POD was 11.15%. The results of the multivariable logistic regression showed that CSF t-Tau (P = 0.004, OR = 1.006, 95%CI 1.002~1.009) and α-syn (P = 0.004, OR = 1.001, 95%CI 1.000~1.001) were positively associated with the occurrence rate of POD, while Aβ42 (P < 0.001, OR = 0.989, 95%CI 0.986~0.993), CSF PGRN (P = 0.002, OR = 0.999, 95%CI 0.999~1.000), Aβ42/ t-Tau (P < 0.001, OR = 0.181, 95%CI 0.102~0.319) and Aβ42/p-Tau (P < 0.001, OR = 0.617, 95%CI 0.526~0.725) were inversely proportional to the occurrence of POD. ROC curve analysis indicated that Aβ42/t-Tau (AUC = 0.823), CSF Aβ42 (AUC = 0.813), Aβ42/p-Tau (AUC = 0.810), α-syn (AUC = 0.644) and PGRN (AUC = 0.638) could predict the occurrence rate of POD. The combination of all these biomarkers showed a greater AUC(0.896) than using any of them alone.ConclusionsCSF Aβ42, PGRN, α-syn, Aβ42/t-Tau and Aβ42/p-Tau might be associated with the occurrence rate of POD in patients undergoing knee/hip arthroplasty.Trial registrationClinical Registration No. ChiCTR2000033439.

Live and recorded music interventions for management of delirium symptoms in acute geriatric patients: Protocol for a randomized feasibility trial

ABSTRACT Introduction Delirium is an acute alteration in attention, awareness, arousal, and cognition, precipitated by a sudden illness and highly prevalent in older, frail and acutely hospitalized patients. It is associated with poor outcomes, and few effective treatment alternatives. Non-pharmacological interventions and music show promising effects, warranting further research. This pilot randomized repeated measures trial aims to test feasibility of the trial methodology, acceptability, fidelity and safety of the music interventions, suitability of the effect-outcomes. and preliminary effectiveness. Method Acute geriatric patients with delirium or subsyndromal delirium will be randomized to Preferred Recorded Music (n = 30) or Preferred Live Music (n = 30), delivered for 30 minutes, over three consecutive days. Planned feasibility outcomes will comprise recruitment rate, retention and attrition rates, percentage of adherence, deviations rates, and success of treatment fidelity. Clinical outcomes will include: (a) trajectory of delirium symptoms: level of arousal as assessed by Observational Scale of Level of Arousal (OSLA) and modified Richmond Agitation Sedation Scale (mRASS); attention, assessed using backwards tests and digit span tests; orientation and short-term memory, assessed using recall tasks and orientation questions from Memorial Delirium Assessment Scale, (b) duration of delirium, (c) length of hospital stay, and (d) use of PRN medication (benzodiazepines and antipsychotics). Discussion The trial will provide results needed to design a subsequent sufficiently powered RCT, informing on the expected recruitment, feasibility and acceptability of the interventions and assessments and preliminary effectiveness

Extremes of baseline cognitive function determine the severity of delirium: a population study.

Although delirium is a significant clinical and public health problem, little is understood about how specific vulnerabilities underlie the severity of its presentation. Our objective was to quantify the relationship between baseline cognition and subsequent delirium severity. We prospectively investigated a population-representative sample of 1510 individuals aged ≥70 years, of whom 209 (13.6%) were hospitalized across 371 episodes (1999 person-days assessment). Baseline cognitive function was assessed using the modified Telephone Interview for Cognitive Status, supplemented by verbal fluency measures. We estimated the relationship between baseline cognition and delirium severity [Memorial Delirium Assessment Scale (MDAS)] and abnormal arousal (Observational Scale of Level of Arousal), adjusted by age, sex, frailty and illness severity. We conducted further analyses examining presentations to specific hospital settings and common precipitating aetiologies. The median time from baseline cognitive assessment to admission was 289 days (interquartile range 130 to 47 days). In admitted patients, delirium was present on at least 1 day in 45% of admission episodes. The average number of days with delirium (consecutively positive assessments) was 3.9 days. Elective admissions accounted for 88 bed days (4.4%). In emergency (but not elective) admissions, we found a non-linear U-shaped relationship between baseline global cognition and delirium severity using restricted cubic splines. Participants with baseline cognition 2 standard deviations below average (z-score = -2) had a mean MDAS score of 14 points (95% CI 10 to 19). Similarly, those with baseline cognition z-score = + 2 had a mean MDAS score of 7.9 points (95% CI 4.9 to 11). Individuals with average baseline cognition had the lowest MDAS scores. The association between baseline cognition and abnormal arousal followed a comparable pattern. C-reactive protein ≥20 mg/l and serum sodium <125 mM/l were associated with more severe delirium. Baseline cognition is a critical determinant of the severity of delirium and associated changes in arousal. Emergency admissions with lowest and highest baseline cognition who develop delirium should receive enhanced clinical attention.

Subjective cognitive decline may mediate the occurrence of postoperative delirium by P-tau undergoing total hip replacement: The PNDABLE study.

We again investigated the relationship between subjective cognitive decline (SCD) and postoperative delirium (POD) with a larger sample queue. We also determined whether SCD could cause the occurrence of POD through cerebrospinal fluid (CSF) biomarkers. A prospective, observational cohort study was implemented in the Qingdao Municipal Hospital Affiliated with Qingdao University. This study recruited 1,471 qualified patients affiliated with the Perioperative Neurocognitive Disorder And Biomarker Lifestyle (PNDABLE) study scheduled for total hip replacement under combined spinal and epidural anesthesia from June 2020 to May 2022. The Mini-Mental State Examination (MMSE) and the Montreal Cognitive Assessment (MoCA) were used to assess the cognitive level of the patients the day before surgery. Pittsburgh sleeps quality index (PSQI) scale was used to assess sleep status. Patients were divided into the SCD group and the non-SCD (NSCD) group based on the Subjective Cognitive Decline Scale (SCDS). CSF was collected after a successful spinal-epidural combined puncture, and amyloid-β40 (Aβ40), amyloid-β42 (Aβ42), total tau (T-tau), and phosphorylated tau (P-Tau) in CSF were analyzed by enzyme-linked immunosorbent assays. After the surgery, the incidence of POD was determined by the Confusion Assessment Scale (CAM), and Memorial Delirium Assessment Scale (MDAS) score was used to determine the severity of POD. Logistic regression and sensitivity analyses were performed to determine the relationship between CSF biomarkers, SCD, and POD. The mediating effect was used to analyze the function of specific CSF biomarkers in the relationship between SCD and POD. The risk factors of SCD were also separately verified by logistic regression and sensitivity analysis models. The total incidence rate of POD was 19.60% (n = 225/1148), which was 29.3% (n = 120/409) in the SCD group and 14.2% (n = 105/739) in the NSCD group. We comprehensively considered the effect of covariates such as age, hypertension, and diabetes. Multivariate logistic regression analysis showed that SCD (OR = 1.467, 95%CI: 1.015-2.120, p = 0.042) and P-tau (OR = 1.046, 95%CI: 1.028-1.063, p < 0.001) were risk factors for POD. The sensitivity analysis results were consistent with the above results. Mediation analysis showed that the relationship between SCD and POD was partially mediated by P-tau, which accounted for 31.25% (P-tau, IE = 4.279 × 10-2, p < 0.001). For SCD, the results of logistic regression analysis models showed that age (OR = 1.035, 95% CI: 1.020-1.049, p < 0.001), higher preoperative PSQI score (OR = 1.047, 95%CI: 1.014-1.080, p = 0.005), and P-tau (OR = 1.015, 95%CI: 1.002-1.028, p = 0.021) were risk factors for SCD, and subsequent sensitivity analysis confirmed this result after adjustment for ASA grade, height, and weight. Patients with SCD are more likely to develop POD undergoing total hip replacement, and SCD can mediate the occurrence of POD via P-tau. This study was registered at China Clinical Trial Registry (Chictr2000033439).

Potential value of cerebrospinal fluid α-synuclein in the identification of postoperative delirium undergoing knee/hip arthroplasty: The perioperative neurocognitive disorder and biomarker lifestyle study.

Postoperative delirium (POD) is a common postoperative complication, which may be associated with α-synuclein (α-syn). The purpose of this study was to explore the association between the expression level of α-syn in cerebrospinal fluid (CSF) and POD. We conducted a prospective observational cohort study, which involved in 740 participants (mean age of 61.86 years, range 40-90 years; 40% female) from the Perioperative Neurocognitive Disorder And Biomarker Lifestyle (PNDABLE) study in the final analysis. POD was diagnosed using the Confusion Assessment Scale (CAM), and its severity was measured using the Memorial Delirium Assessment Scale (MDAS). Enzyme-linked immune-sorbent assay (ELISA) was used to detect the concentrations of α-syn, Aβ40, Aβ42, T-tau, and P-tau in CSF. The incidence of POD was 11.22% (83/740). The logistic regression analysis showed that the increased concentrations of CSF α-syn (OR = 1.005, 95%CI 1.004-1.006, P < 0.001), P-tau (OR = 1.093, 95%CI 1.071-1.115, P < 0.001), and T-tau (OR = 1.008, 95%CI 1.006-1.009, P < 0.001) were risk factors of POD. Linear regression showed that CSF α-syn had positive correlations with P-tau (β = 0.480, P < 0.001), T-tau (β = 0.334, P < 0.001), while negative correlations with Aβ40 (β = -0.378 P < 0.001), Aβ42 (β = -0.800, P = 0.001) in POD patients. Mediation analyses showed the association between α-syn and POD was partially mediated by tau pathologies (proportion: 16-17%). CSF α-syn is one of the preoperative risk factors for POD, which may be mediated through tau pathologies. [www.ClinicalTrials.gov], identifier [ChiCTR20 00033439].

Potential value of preoperative fasting blood glucose levels in the identification of postoperative delirium in non-diabetic older patients undergoing total hip replacement: The perioperative neurocognitive disorder and biomarker lifestyle study.

BackgroundPostoperative delirium (POD) is a common complication after total hip replacement. This study aims to explore the relationship between preoperative fasting blood glucose (FBG) levels and POD in non-diabetic older patients undergoing total hip replacement.Materials and methodsThis study included a total of 625 patients undergoing elective total hip replacement under combined spinal and epidural anesthesia from the PNDABLE study. The relationship between POD and preoperative FBG was analyzed by using the logistic regression model. The associations of FBG with individual cerebrospinal fluid (CSF) biomarkers were detected by using the multivariable linear regression model controlling for age, gender, and education level. The mediation effects were explored by mediation analyses with 5,000 bootstrap iterations, while sensitivity analysis was used to test the reliability and stability of the results. The receiver operating characteristic (ROC) curve and the nomogram model were applied to evaluate the efficacy of FBG and POD-related CSF biomarkers in predicting POD. POD assessment was performed two times daily by a trained anesthesiologist at 9:00–10:00 am and 2:00–3:00 pm on postoperative days 1–7 or before the patients were discharged from the hospital. POD was defined by the Confusion Assessment Method (CAM), and POD severity was measured using the Memorial Delirium Assessment Scale (MDAS). Enzyme-linked immunosorbent assay (ELISA) was used to measure CSF Aβ40, Aβ42, T-tau, and P-tau levels.ResultsPOD was detected in 10.2% (60/588) of the patients. Logistic regression analysis showed that after adjusting for age and education level, the increased levels of FBG (OR 1.427, 95% CI 1.117–1.824, P = 0.004), CSF P-tau (OR 1.039, 95% CI 1.019–1.060, P < 0.001), and CSF T-tau (OR 1.013, 95% CI 1.009–1.018, P < 0.001) were risk factors for POD, and the increased level of CSF Aβ42 (OR 0.996, 95% CI 0.994–0.998, P = 0.001) was a protective factor for POD. Multivariable linear regression models showed that when adjusting for age, gender, and education level, in the POD group, higher preoperative FBG levels were negatively correlated with the CSF Aβ42 level (β = −0.290, P = 0.028) and positively correlated with CSF P-tau (β = 0.384, P = 0.004) and T-tau (β = 0.447, P < 0.001). In the non-POD group, a higher preoperative FBG was not related to CSF biomarkers. Mediated effect analysis showed that CSF T-tau (proportion = 17.1%) had an apparent mediation effect on the relationship between FBG and POD. Sensitivity analysis revealed that the results from the logistic regression and multivariable linear regression models were consistent with previous results.ConclusionIncreased preoperative FBG was a risk factor for POD in older patients without T2DM, and T-tau might mediate the relationship between FBG and POD.

The relationship between mild cognitive impairment and postoperative delirium undergoing total knee arthroplasty: The PNDABLE study.

BackgroundPatients undergoing surgery are at a higher risk of developing postoperative delirium (POD) as a result of anesthesia and surgical procedures. This study examined the association between POD and mild cognitive impairment (MCI) and whether MCI influences POD through the core pathology of POD.MethodsWe enrolled Chinese Han patients undergoing unilateral total knee arthroplasty (aged 50–90, weighing 50–80 kg, and using ASAI-II), combined with epidural anesthesia between October 2020 and June 2021. All the participants were assessed using Winblad's criteria for diagnosing MCI on pre-operation and using the Confusion Assessment Method (CAM) and the Memorial Delirium Assessment Scale (MDAS) postoperative 1–7 days (or before discharge) for diagnosing POD by an anesthesiologist. Cerebrospinal fluid (CSF) biomarkers of POD were measured by enzyme-linked immunosorbent assay (ELISA). To examine the mechanism by which POD pathologies affect cognition, causal mediation analyses were performed.ResultsPOD incidence was 20.2%, including 32.5% in the MCI group and 12.4% in the non-mild cognitive impairment (NMCI) group. The MCI and CSF levels of T-tau and P-tau were risk factors, and the CSF levels of Aβ42, Aβ42/ T-tau, and Aβ42/ P-tau were protective factors in POD (p < 0.05). Part of the effects of MCI on cognition can be attributed to amyloid pathology and tau.ConclusionMCI may be a reasonably good prognostic factor in POD development. Overall, amyloid pathology and tau protein might partially mediate the influence of MCI on POD.Clinical trial registrationwww.clinicaltrials.gov, identifier: ChiCTR2000033439.

"Triple Threat" Conditions Predict Mortality Among Patients With Advanced Cancer Who Present to the Emergency Department

BackgroundDelirium, poor performance status, and dyspnea predict short survival in the palliative care setting. ObjectiveOur goal was to determine whether these three conditions, which we refer to as a “triple threat,” also predict mortality among patients with advanced cancers in the emergency department (ED). MethodsThe study sample included 243 randomly selected, clinically stable patients with advanced cancer who presented to our ED. The analysis included patients who had delirium (Memorial Delirium Assessment Scale score ≥ 7), poor performance status (Eastern Cooperative Oncology Group performance status score of 3 or 4), or dyspnea as a presenting symptom. We obtained survival data from medical records. We calculated predicted probability of dying within 30 days and association with number of symptoms after the ED visit using logistic regression analysis. ResultsTwenty-eight patients died within 30 days after presenting to the ED. Death within 30 days occurred in 36% (16 of 44) of patients with delirium, 28% (17 of 61) of patients with poor performance status, and 14% (7 of 50) of patients with dyspnea, with a predicted probability of 30-day mortality of 0.38 (95% confidence interval [CI] 0.25–0.53), 0.28 (95% CI 0.18–0.40), and 0.15 (95% CI 0.07–0.29), respectively. The predicted probability of death within 30 days for patients with two or three of the conditions was 0.49 (95% CI 0.34–0.66) vs. 0.05 (95% CI 0.02–0.09) for patients with none or one of the conditions. ConclusionsPatients with advanced cancers who present to the ED and have at least two triple threat conditions have a high probability of death within 30 days.

The effect of neostigmine on postoperative delirium after colon carcinoma surgery: a randomized, double-blind, controlled trial

BackgroundPostoperative delirium (POD) is a critical complication in patients accepting colon carcinoma surgery. Neostigmine, as a cholinesterase inhibitor, can enhance the transmission of cholinergic transmitters in synaptic space, and play an important role in maintaining the normal level of cognition, attention and consciousness. The objective of this study was to investigate the effect of neostigmine on POD and clinical prognosis.MethodsA randomized, double-blind controlled trial was implemented in Qingdao Municipal Hospital Affiliated to Qingdao University. A total of 454 patients aged 40 to 90 years old accepted colon carcinoma surgery were enrolled between June 7, 2020, and June 7, 2021, with final follow-up on December 8, 2021. Patients were randomly assigned to two groups: the neostigmine group (group N) and the placebo group (group P), the patients in group N were injected with 0.04 mg/kg neostigmine and 0.02 mg/kg atropine intravenously. The primary endpoint was the incidence of POD, researchers evaluated the occurrence of POD by the Confusion Assessment Method (CAM) twice daily (at 10 a.m. and 2 p.m.) during the first 7 postoperative days, POD severity was assessed by the Memorial Delirium Assessment Scale (MDAS). The secondary endpoints were the extubating time, postanesthesia care unit (PACU) time, the incidence of various postoperative complications, length of hospital stays, and 6 months postoperative mortality.ResultsThe incidence of POD was 20.20% (81/401), including 19.39% (38/196) in group N and 20.98% (43/205) in group P. There was no significant statistical significance in the incidence of POD between group N and group P (P > 0.05); Compared to group P, the extubating time and PACU time in group N were significantly reduced (P < 0.001), the incidence of postoperative pulmonary complications (POPCs) decreased significantly in group N (P < 0.05), while no significant differences were observed in postoperative hospital stay and mortality in 6 months between the two groups (P > 0.05).ConclusionFor patients accepted colon carcinoma surgery, neostigmine did not significantly reduce the incidence of POD, postoperative mortality and postoperative hospital stay, while it indeed reduced the extubating time, PACU time and the incidence of POPCs.Trial registrationThe randomized, double-blind, controlled trial was registered retrospectively at www.chictr.org.cn on 07/06/2020 (ChiCTR2000033639).

Lower Preoperative Verbal Memory Performance Is Associated with Delirium after Coronary Artery Bypass Graft Surgery: A Prospective Cohort Study.

Cognitive impairment constitutes one of the major risk factors of delirium after coronary artery bypass graft (CABG) surgery; however, it is unclear whether only patients with global cognitive decline are at increased risk for delirium or if individuals with preserved global cognitive functions but impairments in specific cognitive domains are also more vulnerable to developing delirium. Thus, this study aimed to analyze the neurocognitive status of patients scheduled for CABG surgery with the use of an advanced computerized cognitive battery (CNS Vital Signs) and to investigate possible associations between impaired performance in selective cognitive areas and the risk of postoperative delirium development. The study enrolled 127 participants with a median age of 67years (IQR: 63-71). Postoperative delirium developed in 32 (25%) patients.Before surgery, the patients were screened for global cognitive impairment with the use of the Mini-Mental State Examination Test, and the individuals were asked to perform the CNS Vital Signs battery to investigate 12 specific cognitive domains. The Confusion Assessment Method and the Memorial Delirium Assessment Scale were used to screen for a diagnosis of delirium postoperatively. In multivariate models, a lower score of verbal memory-assessed preoperatively was independently associated with the risk of postoperative delirium development. Other independent predictors of delirium included more advanced age, gender female, depression, postoperative pyrexia, and the presence of extracorporeal circulation. As decreased verbal memory constitutes an independent risk factor for postoperative delirium, a verbal memory test may be a useful predictor of postoperative delirium development.