Modification in ICU Design May Affect Delirium and Circadian Melatonin: A Proof of Concept Pilot Study.

OBJECTIVES: Nonpharmacologic delirium management is recommended by current guidelines, but studies on the impact of ICU design are still limited. The study's primary purpose was to determine if a multicomponent change in room design prevents ICU delirium. Second, the influence of lighting conditions on serum melatonin was assessed. DESIGN: Prospective observational cohort pilot study. SETTING: The new design concept was established in two two-bed ICU rooms of a university hospital. Besides modifications aimed at stress relief, it includes a new dynamic lighting system. PATIENTS: Seventy-four adult critically ill patients on mechanical ventilation with an expected ICU length of stay of at least 48 hours, treated in modified or standard rooms. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The clinical examination included a prospective assessment for depth of sedation, delirium, and pain every 8 hours using validated scores. Blood samples for serum melatonin profiles were collected every 4 hours for a maximum of three 24-hour periods. Seventy-four patients were included in the analysis. Seventy-six percent ( n = 28) of patients in the standard rooms developed delirium compared with 46% of patients ( n = 17) in the modified rooms ( p = 0.017). Patients in standard rooms (vs. modified rooms) had a 2.3-fold higher delirium severity (odds ratio = 2.292; 95% CI, 1.582-3.321; p < 0.0001). Light intensity, calculated using the measure of circadian effective irradiance, significantly influenced the course of serum melatonin ( p < 0.0001). Significant interactions ( p < 0.001) revealed that differences in serum melatonin between patients in standard and modified rooms were not the same over time but varied in specific periods of time. CONCLUSIONS: Modifications in ICU room design may influence the incidence and severity of delirium. Dedicated light therapy could potentially influence delirium outcomes by modulating circadian melatonin levels.

Effectiveness of sleep interventions to reduce delirium in critically ill patients: A systematic review and meta-analysis.

PURPOSE: To analyze the effectiveness of sleep interventions in reducing the incidence and duration of delirium in the ICU. MATERIALS AND METHODS: We searched the PubMed, Embase, CINAHL, Web of Science, Scopus, and Cochrane databases for relevant randomized controlled trials from inception to August 2022. Literature screening, data extraction, and quality assessment were performed independently by two investigators. Data from the included studies were analyzed using Stata and TSA software. RESULTS: Fifteen randomized controlled trials were eligible. Meta-analysis showed that the sleep intervention was associated with a reduced incidence of delirium in the ICU (RR = 0.73, 95% CI = 0.58 to 0.93, p < 0.001) compared to the control group. The results of the trial sequence analysis further confirm that sleep interventions are effective in reducing the occurrence of delirium. Pooled data from the three dexmedetomidine trials showed significant differences in the incidence of ICU delirium between groups (RR = 0.43, 95% CI = 0.32 to 0.59, p < 0.001). The respective pooled results of other sleep interventions (e.g., light therapy, earplugs, melatonin, and multicomponent nonpharmacologic treatments) did not find a significant effect on reducing the incidence and duration of ICU delirium (p > 0.05). CONCLUSIONS: The current evidence suggests that non-pharmacological sleep interventions are not effective in preventing delirium in ICU patients. However, limited by the number and quality of included studies, future well-designed multicenter randomized controlled trials are still needed to validate the results of this study.

Deficient vitamin B12 levels are associated with increased delirium incidence in critically ill patients.

BACKGROUND & AIMS: In intensive care unit (ICU) patients, deficiency of vitamin B12 (cobalamin) occur often and may be associated with significant neurologic syndromes. Therefore, this study aimed to investigate the association between cobalamin (cbl) serum levels and the incidence of delirium in ICU patients. METHODS: In this multi-center, cross-sectional clinical study, adult patients with GCS (Glasgow Coma Scale) ≥ 8 and RASS (The Richmond Agitation-Sedation Scale) ≥ -3, without a history of mood disorders before ICU admission, were eligible for inclusion. After informed consent was obtained, clinical and biochemical characteristics of eligible patients were recorded on the first day and then daily during follow-up for seven days or until delirium was developed. The CAM-ICU tool was used to evaluate delirium. Moreover, the cbl level was measured at the end of the study to assess its association with the incidence of delirium. RESULTS: Among 560 patients screened for eligibility, 152 could be analyzed. Logistic regression results indicated a high cbl level (>900 pg/ml) was independently associated with lower delirium incidence (P < 0.001). Further analysis revealed that the delirium rate was significantly higher in patients with deficient and sufficient cbl compared to the high cbl group (P = 0.002 and 0.017, respectively). In addition, surgical and medical patients and pre-deliric scores were negatively associated with high cbl (P = 0.006, 0.003, and 0.031, respectively). CONCLUSIONS: We have shown that deficient and sufficient compared to the high cbl group were significantly associated with a higher delirium incidence in critically ill patients. Further controlled clinical studies are required to evaluate the safety and efficacy of high-dose cbl to prevent delirium in critically ill patients.

Safety of baclofen versus tizanidine for older adults with musculoskeletal pain.

BACKGROUND: Baclofen and tizanidine are both muscle relaxants that carry the risk for neuropsychiatric events in older adults but there is a lack of data directly comparing their safety. This study aimed to investigate the relative risk between these two medications in causing injury and delirium in older adults. METHODS: This was a retrospective cohort study that was completed in an integrated healthcare system in the United States and included patients aged 65 years or older who started baclofen or tizanidine for the treatment of musculoskeletal pain from January 2016 through December 2018. Outcomes included new incidence of injury (concussion, contusion, dislocation, fall, fracture, or other injuries) and delirium. The cohort was followed from the initiation of therapy until the first occurrence of any of the following events: end of the index drug exposure, end of health plan membership, death, or the study end date of December 31st, 2019. Descriptive statistics were used to compare baseline patient characteristics between baclofen and tizanidine treatment groups. Cox proportional hazards model was used to calculate adjusted hazard ratios (HRs) with 95% confidence intervals. RESULTS: The final study cohort included 12,101 and 6,027 older adults in the baclofen and tizanidine group respectively (mean age 72.2 ± 6.2 years old, 59% female). Older adults newly started on baclofen had a greater risk of injury (HR = 1.54, 95% CI = 1.21-1.96, P = < 0.001) and delirium (HR = 3.33, 95% CI = 2.11-5.26, p = <0.001) compared to those started on tizanidine. CONCLUSION: The results of this study suggest that baclofen is associated with higher incidences of injury and delirium compared to tizanidine when used for the treatment of musculoskeletal pain. Future studies should investigate if these risks are dose-related and include a comparison group not exposed to either drug.

Hypomagnesemia and incident delirium in hospitalized older persons.

BACKGROUND: Altered serum magnesium (Mg) levels in older persons have been hypothesized to have a role in predicting hospitalization and mortality. Hypomagnesemia and delirium are frequent problems in older patients, but no study has evaluated such an association in acute geriatric setting. AIMS: We investigated the impact of hypomagnesemia on the incidence of delirium in an acute geriatric setting. METHODS: This retrospective study was conducted on 209 older hospitalized patients. All subjects underwent a comprehensive geriatric assessment. Mg was measured in serum by routine laboratory methods. The presence of incident delirium was determined by the 4AT screening tool. A logistic regression model was used to assess the association between serum Mg and delirium controlling for multiple covariates. RESULTS: 209 patients (77.9% women) were included in the study. The mean age of the participants was 85.7 ± 6.50 years (range 65-100). 27 subjects (12.9%) developed delirium during the hospitalization, with no difference between genders. Subjects with delirium had lower serum magnesium levels than those without (1.88 ± 0.34 versus 2.04 ± 0.28; p = 0.009). Delirium risk was significantly higher in patients with lower serum magnesium levels (OR 5.80 95% CI 1.450-23.222; p = 0.013), independent of multiple covariates. CONCLUSION: Our data show that low serum Mg level is a good predictor of incident delirium in acute geriatric settings. Present findings have relevant implications for clinical management, highlighting the need for analyzing Mg concentration carefully. Whether Mg supplementation in patients with hypomagnesemia could lead to delirium prevention and/or control needs further investigation.

The effect of taurine supplementation on delirium post liver transplantation: A randomized controlled trial.

BACKGROUND & AIMS: Delirium is a prevalent complication of liver transplantation (LT). It may enhance the risk of morbidity and mortality. Taurine is considered to have antioxidant and neuroprotective activities. The aim of this study was to evaluate taurine supplementation effect on post-LT delirium. METHODS: Patients older than 18 years old who had received LT in Abu-Ali Sina transplantation center in Shiraz, Iran from September 2020 to June 2021, were enrolled in this double-blinded randomized clinical trial. Exclusion criteria was known hypersensitivity to taurine, pregnancy or breast-feeding and death within 72 h post-LT. Patients were randomly divided into two groups, each received 2 g/day placebo or taurine from the first day post-LT for 30 days. Delirium was assessed using Confusion Assessment Method-Intensive Care Unit (CAM-ICU). Mortality and rejection rates and length of Intensive Transplantation Unit (ITU) and hospital stays were evaluated within one month after transplantation. RESULTS: Two hundred and seven patients were divided into two groups. Twenty-eight and 23 patients were excluded due to their refuse to participate in the study and death within 72 h post-LT, respectively. Delirium rate within the first month was 23.08% and was significantly lower in taurine group (9.46%) compared with placebo (35.36%, P = 0.012). Length of ITU stay was significantly higher among delirious patients (P = 0.015) in this analysis. CONCLUSION: we reached to the result that taurine can prevent post-LT delirium, dramatically. Placebo receiving and longer stay in ITU were the only independent risk factors in this trial. REGISTRATION NUMBER OF CLINICAL TRIAL: The study was registered at the Iranian Registry of Clinical Trials (IRCT20200312046755N1; http://www.irct.ir/).

The Preventive Effect of Transcutaneous Electrical Acupoint Stimulation on Postoperative Delirium in Elderly Patients with Time Factors: A Randomized Trial.

Objectives: There is currently no exact and effective treatment for postoperative delirium (POD). The purpose of this study was to observe the effect of transcutaneous electrical acupoint stimulation (TEAS) before surgery and during surgery in elderly patients with POD. Materials and Methods: A total of 90 patients were randomly divided into three groups: a preoperative TEAS group (group E1), an intraoperative TEAS group (group E2), and a control group (group C). In group E1, TEAS was applied at the Shenting, Baihui, bilateral Neiguan, and Hegu points for 30 min 1 day before surgery and before the induction of anesthesia. In group E2, TEAS was applied during surgery. In group C, electrodes were applied to the points just cited, but no electric stimulation was administered. The incidence of delirium was assessed within 5 days after surgery, and the plasma concentration of propofol at bispectral index (BIS) = 50 was recorded. Blood samples were collected to measure neuron-specific enolation (NSE), tumor necrosis factor-α (TNF-α), and interleukin (IL)-1ß 1 day before surgery and 1 and 5 days after surgery. Results: The incidence of delirium in group E1 was decreased in comparison with group C and group E1 (both p < 0.05). The propofol plasma concentration at BIS = 50 in group E1 was also decreased in comparison with group C and group E2 (both p < 0.05). Compared with group C, the concentrations of NSE, TNF-α, and IL-1ß in plasma were decreased in group E1 and group E2 1 and 5 days after surgery (both p < 0.05), and the concentrations of NSE and IL-1ß in plasma in group E1 were decreased 1 and 5 days after surgery in comparison with group E2. Conclusion: The TEAS can reduce the dosage of propofol required during surgery and the occurrence of delirium after surgery. Its mechanism may be related to inhibiting inflammation response and alleviating brain injury. Compared with intraoperative application, the effect of preconditioning with TEAS before surgery is better. Clinical Trial Registration: ChiCTR-INR-17012501. Date of registration: August 29, 2017.

Habitual tea consumption and postoperative delirium after total hip/knee arthroplasty in elderly patients: The PNDABLE study.

PURPOSE: To clarify the effects of habitual tea consumption on postoperative delirium (POD) in elderly patients undergoing total hip/knee arthroplasty. PATIENTS AND METHODS: A prospective cohort study was carried out at Qingdao Municipal Hospital Affiliated to Qingdao University between June 2020 and June 2021. A total of 332 patients aged 65-85 years undergoing total hip/knee arthroplasty under combined spinal and epidural anesthesia were enrolled from the Perioperative Neurocognitive Disorder and Biomarker Lifestyle (PNDABLE) study in the final analysis, consisting of 168 patients with habitual tea consumption and 164 patients with infrequent tea consumption. The primary endpoint was the effects of habitual tea consumption on POD and the incidence of POD, which was assessed by the Confusion Assessment Method (CAM) twice daily during the first 7 postoperative days, and POD severity was measured by the Memorial Delirium Assessment Scale (MDAS). The secondary endpoints were the concentrations of caffeine and tea polyphenols in plasma and cerebrospinal fluid (CSF), which were detected by the enzyme-linked immunosorbent assay. RESULTS: POD occurred in 61 of 332 patients (18.37%), among whom 19 had habitual tea consumption (5.72%) and 42 had infrequent tea consumption (12.65%). Habitual tea consumption (odds ratio [OR] = 0.370, 95% confidence interval [CI]: 0.205-0.670, P = .001) was significantly associated with POD in the logistic analysis, and then after adjusting for age and American Society of Anesthesiologists (ASA) physical status (OR = 0.353, 95% CI: 0.190-0.655, P = .001). Furthermore, caffeine in T0 plasma (OR = 0.834, 95% CI: 0.752-0.924, P = .001), T1 plasma (OR = 0.818, 95% CI: 0.738-0.908, P < .001), and CSF (OR = 0.899, 95% CI: 0.820-0.984, P = .022) and tea polyphenols in T0 plasma (OR = 0.541, 95% CI: 0.416-0.704, P < .001), T1 plasma (OR = 0.477, 95% CI: 0.359-0.633, P < .001), and CSF (OR = 0.526, 95% CI: 0.397-0.696, P < .001) were associated with POD after adjusting for age and ASA physical status. CONCLUSION: Habitual tea consumption may be associated with a lower incidence of POD in elderly patients.

Regional anesthesia techniques and postoperative delirium: systematic review and meta-analysis.

INTRODUCTION: Postoperative delirium is a frequent occurrence in the elderly surgical population. As a comprehensive list of predictive factors remains unknown, an opioid-sparing approach incorporating regional anesthesia techniques has been suggested to decrease its incidence. Due to the lack of conclusive evidence on the topic, we conducted a systematic review and meta-analysis to investigate the potential impact of regional anesthesia and analgesia on postoperative delirium. EVIDENCE ACQUISITION: PubMed, Embase, and the Cochrane central register of Controlled trials (CENTRAL) databases were searched for randomized trials comparing regional anesthesia or analgesia to systemic treatments in patients having any type of surgery. This systematic review and meta-analysis followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. We pooled the results separately for each of these two applications by random effects modelling. Grading of Recommendations Assessment, Development and Evaluation (GRADE) system was used to evaluate the certainty of evidence and strength of conclusions. EVIDENCE SYNTHESIS: Eighteen trials (3361 subjects) were included. Using regional techniques for surgical anesthesia failed to reduce the risk of postoperative delirium, with a relative risk (RR) of 1.21 (95% CI: 0.79 to 1.85); P=0.3800. In contrast, regional analgesia reduced the relative risk of perioperative delirium by a RR of 0.53 (95% CI: 0.42 to 0.68; P<0.0001), when compared to systemic analgesia. Post-hoc subgroup analysis for hip fracture surgery yielded similar findings. CONCLUSIONS: These results show that postoperative delirium may be decreased when regional techniques are used in the postoperative period as an analgesic strategy. Intraoperative regional anesthesia alone may not decrease postoperative delirium since there are other factors that may influence this outcome.

Preoperative Vitamin D Deficiency Is Associated With Postoperative Delirium in Critically Ill Patients.

INTRODUCTION: Postoperative delirium is common, with a reported incidence of 11% to 80% in critically ill patients. Delirium is an independent prognostic factor for poor hospital outcomes. Low vitamin D concentrations are associated with a decline in cognitive function. We therefore tested the hypothesis that low preoperative serum 25-hydroxyvitamin D [25(OH)D] concentrations are associated with postoperative delirium in critically ill patients. METHOD: We conducted a retrospective analysis of adults in a surgical intensive care unit for at least 48 hours immediately after non-cardiac and non-neurosurgical operations at Cleveland Clinic between 2013 and 2018. Delirium was assessed by trained nurses using CAM-ICU twice daily for the initial 5 postoperative days. Any positive value was considered evidence of delirium. We assessed the association between 25(OH)D concentrations within a year before surgery and the incidence of postoperative delirium using logistic regression, adjusted for potential confounders. A linear spline term with a knot at 30 ng/ml, the threshold for normal 25(OH)D concentration, was added to accommodate a nonlinear relationship between 25(OH)D concentrations and delirium. RESULTS: We included 632 patients, who had a mean (SD) 25(OH)D concentration of 25 (15) ng/ml; 55% (346/632) experienced delirium. We observed an adjusted odds ratio of 1.4 (95% CI: [1.1, 1.8], P = 0.01) for delirium per 10 ng/ml decrease in 25(OH)D concentrations when patients' 25(OH)D concentrations were less than 30 ng/ml. In patients whose 25(OH)D concentrations were at least 30 ng/ml, the adjusted odds ratio was 0.9 (95% CI: [0.7, 1.1], P = 0.36). CONCLUSION: Preoperative 25(OH)D concentrations are associated with postoperative delirium in patients whose concentrations are below the normal threshold, but not at concentrations ≥30 ng/ml. A trial will be needed to determine whether the relationship is causal, and whether vitamin D supplementation before surgery might reduce the incidence of delirium.

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

OBJECTIVE: To 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. METHODS: Randomized, 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. RESULTS: 61 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. CONCLUSION: High 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.

"SQiD, the Single Question in Delirium; can a single question help clinicians to detect delirium in hospitalised cancer patients?" running heading Single Question in Delirium" (Bcan-D-20-01665).

AIM: A serious syndrome for cancer in-patients, delirium risk increases with age and medical acuity. Screening tools exist but detection is frequently delayed or missed. We test the 'Single Question in Delirium' (SQiD), in comparison to psychiatrist clinical interview. METHODS: Inpatients in two comprehensive cancer centres were prospectively screened. Clinical staff asked informants to respond to the SQiD: "Do you feel that [patient's name] has been more confused lately?". The primary endpoint was negative predictive value (NPV) of the SQiD versus psychiatrist diagnosis (Diagnostic and Statistics Manual criteria). Secondary endpoints included: NPV of the Confusion Assessment Method (CAM), sensitivity, specificity and Cohen's Kappa coefficient. RESULTS: Between May 2012 and July 2015, the SQiD plus CAM was applied to 122 patients; 73 had the SQiD and psychiatrist interview. Median age was 65 yrs. (interquartile range 54-74), 46% were female; median length of hospital stay was 12 days (5-18 days). Major cancer types were lung (19%), gastric or other upper GI (15%) and breast (14%). 70% of participants had stage 4 cancer. Diagnostic values were similar between the SQiD (NPV = 74, 95% CI 67-81; kappa = 0.32) and CAM (NPV = 72, 95% CI 67-77, kappa = 0.32), compared with psychiatrist interview. Overall the CAM identified only a small number of delirious cases but all were true positives. The specificity of the SQiD was 87% (74-95) The SQiD had higher sensitivity than CAM (44% [95% CI 41-80] vs 26% [10-48]). CONCLUSION: The SQiD, administered by bedside clinical staff, was feasible and its psychometric properties are now better understood. The SQiD can contribute to delirium detection and clinical care for hospitalised cancer patients.

Intravenous Iron in a Prehabilitation Program for Older Surgical Patients: Prospective Cohort Study.

BACKGROUND: Older patients often have iron deficiency anemia before surgery, which can be effectively treated with intravenous iron supplementation (IVIS). Anemia and blood transfusions are associated with an increased risk of delirium. The aim of this research was to assess the effectiveness and safety of using IVIS in a prehabilitation program. MATERIAL AND METHODS: Patients ≥70 y who underwent abdominal surgery between November 2015 and June 2018 were included in this single-center prospective cohort study. All patients were prehabilitated; however, only anemic patients received a single dose of 1000 mg intravenous iron (ferric carboxymaltose) to increase preoperative hemoglobin levels (IVIS group). Nonanemic patients received standard care (SC). The hemoglobin levels (primary outcome) were assessed at the outpatient clinic visit, at admission, and at discharge. Secondary outcomes were postoperative delirium, postoperative anemia, blood transfusion, complications other than delirium, and length of hospital stay. All outcomes were compared between the IVIS group and SC group. RESULTS: Of all patients (n = 248), 97 anemic patients received IVIS (39%). Of the anemic patients, 50 patients (52%) had iron deficiency. Initial differences in hemoglobin concentrations between the IVIS group and SC group at T1 and T2 (7.2 versus 8.8; P < 0.001 and 7.4 versus 8.6; P = 0.023, respectively) were no longer present at discharge (6.6 versus 7.2; P = 0.35). No statistically significant differences were observed for all secondary outcomes between the IVIS group and the SC group. No infusion-related adverse events occurred. CONCLUSIONS: Adding IVIS to prehabilitation programs is safe and diminishes differences in these concentrations between preoperatively anemic and nonanemic patients. IVIS may be worthwhile as an additional component of prehabilitation programs. Results merit further investigation.

Yokukansan for Treatment of Preoperative Anxiety and Prevention of Postoperative Delirium in Cancer Patients Undergoing Highly Invasive Surgery. J-SUPPORT 1605 (ProD Study): A Randomized, Double-Blind, Placebo-Controlled Trial.

CONTEXT: No standard preventive or therapeutic methods have been established for preoperative anxiety and postoperative delirium in patients with cancer. OBJECTIVES: To clarify the therapeutic effect of yokukansan for perioperative psychiatric symptoms in patients with cancer as well as to confirm its safety profile. METHODS: This is a randomized, double-blind, and placebo-controlled trial conducted at a single center in Tokyo, Japan. About 195 patients with cancer scheduled to undergo tumor resection took one packet of the study drug, which was administered orally. Coprimary outcomes were change in preoperative anxiety assessed with the Hospital Anxiety and Depression Scale-Anxiety and incidence of postoperative delirium assessed with the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. Interim analysis was performed with one-third (n = 74) of the target number of registered patients. RESULTS: Because this trial was canceled based on the results of the interim analysis and the protocol treatment was discontinued in patients who were already registered, conclusions were based on the full analysis set of 160 participants. There were no significant differences between groups in the change of mean Hospital Anxiety and Depression Scale-Anxiety score (intervention group [SD] 0.4 [3.0] vs. placebo group 0.5 [3.0]; P = 0.796) or the incidence of postoperative delirium (32% vs. 30%; P = 0.798). There were no serious adverse events in either group. CONCLUSION: In patients with cancer undergoing highly invasive surgeries, yokukansan demonstrated no significant efficacy for the treatment of preoperative anxiety or the prevention of postoperative delirium. Yokukansan is already used in daily practice in Japan, but we should be careful with its future use.

Design of a randomized placebo controlled trial of high dose intravenous thiamine for the prevention of delirium in allogeneic hematopoietic stem cell transplantation.

BACKGROUND: Delirium is a highly prevalent and preventable neuropsychiatric condition with major health consequences. Thiamine deficiency is a well-established cause of delirium in those with chronic, severe alcoholism, but there remains an underappreciation of its significance in non-alcoholic populations, including patients with cancer. Treatment of suspected thiamine-related mental status changes with high dose intravenous (IV) thiamine has preliminary evidence for improving a variety of cognitive symptoms in oncology inpatient settings but has never been studied for the prevention of delirium in any population. OBJECTIVES: The primary objective of this clinical trial is to determine if high dose IV thiamine can prevent delirium in patients receiving allogeneic hematopoietic stem cell transplantation (HSCT) for treatment of cancer. Secondary objectives are to determine if thiamine status is predictive of delirium onset and if high dose IV thiamine can attenuate the deleterious impact of delirium on health-related quality of life (HRQOL), functional status, and long-term neuropsychiatric outcomes. METHODS: In this phase II study, we are recruiting 60 patients undergoing allogeneic HSCT, randomizing them to treatment with high dose IV thiamine (n = 30) versus placebo (n = 30), and systematically evaluating all participants for delirium and related comorbidities. We use the Delirium Rating Scale to measure the severity and duration of delirium during hospitalization for HSCT. We obtain thiamine levels weekly during the transplantation hospitalization. We assess HRQOL, functional status, depression, post-traumatic stress symptoms, and cognitive function prior to and at one, three, and six months after transplantation.

Predisposing and precipitating risk factors for delirium in palliative care patients.

OBJECTIVE: Delirium is a common complication in palliative care patients, especially in the terminal phase of the illness. To date, evidence regarding risk factors and prognostic outcomes of delirium in this vulnerable population remains sparse. METHOD: In this prospective observational cohort study at a tertiary care center, 410 palliative care patients were included. Simple and multiple logistic regression models were used to identify associations between predisposing and precipitating factors and delirium in palliative care patients. RESULTS: The prevalence of delirium in this palliative care cohort was 55.9% and reached 93% in the terminally ill. Delirium was associated with prolonged hospitalization (p < 0.001), increased care requirements (p < 0.001) and health care costs (p < 0.001), requirement for institutionalization (OR 0.11; CI 0.069-0.171; p < 0.001), and increased mortality (OR 18.29; CI 8.918-37.530; p < 0.001). Predisposing factors for delirium were male gender (OR 2.19; CI 1.251-3.841; p < 0.01), frailty (OR 15.28; CI 5.885-39.665; p < 0.001), hearing (OR 3.52; CI 1.721-7.210; p < 0.001), visual impairment (OR 3.15; CI 1.765-5.607; p < 0.001), and neoplastic brain disease (OR 3.63; CI 1.033-12.771; p < 0.05). Precipitating factors for delirium were acute renal failure (OR 6.79; CI 1.062-43.405; p < 0.05) and pressure sores (OR 3.66; CI 1.102-12.149; p < 0.05). SIGNIFICANCE OF RESULTS: Our study identified several predisposing and precipitating risk factors for delirium in palliative care patients, some of which can be targeted early and modified to reduce symptom burden.

Comparison of combined lumbar and sacral plexus block with sedation versus general anaesthesia on postoperative outcomes in elderly patients undergoing hip fracture surgery (CLSB-HIPELD): study protocol for a prospective, multicentre, randomised controlled trial.

INTRODUCTION: Hip fracture in elderly people is a global public health problem, with substantial associated mortality and disability. Nearly all patients with hip fracture undergo surgical treatment, but optimal anaesthesia for hip fracture surgery in elderly patients is still inconclusive. Ultrasound-guided combined lumbar and sacral plexus block has been widely used in hip fracture surgery in recent years, especially for some high-risk patients. However, it is not clear whether it can improve the postoperative outcomes of elderly patients with hip fracture. METHOD AND ANALYSIS: This research project is a two-arm, parallel, multicentre, prospective randomised controlled trail. A total of 1086 patients aged 75 and older scheduled for hip fracture surgery in five clinical trial centres of China will be randomised in a 1:1 ratio to receive either combined lumbar and sacral plexus block plus sedation or general anaesthesia. The primary outcome will be the postoperative 1-year all-cause mortality. The secondary outcomes will be the incidence of postoperative complications, high-sensitivity cardiac troponin T, early mobility after surgery, postoperative Visual Analogue Scale pain scores, postoperative delirium, length of stay in intensive care unit and hospital, cost-effective outcomes, Barthel Index and incidence of adverse events after discharge. Assessments will be conducted in four steps: preoperative, intraoperative, in-hospital data collection and post-discharge telephone follow-up. ETHICS AND DISSEMINATION: This study has been supported by Shanghai Municipal Commission of Health and Family Planning Foundation for Key Developing Disciplines (2015ZB0103) and approved by the Ethics Committee of Shanghai Sixth People's Hospital [No: 2016-28-(2)]. At the time of manuscript submission, the protocol version is V.1.6 (March 2nd, 2018) with one subsequent approved amendment. Results will be disseminated via an international peer-reviewed publication. TRIAL REGISTRATION NUMBER: NCT03318133.

Bach to the Basics: Implementation and Impact of a Postoperative, Inpatient Personalized Music Program for Older Adults.

PURPOSE: Music as an intervention to mitigate pain and anxiety has been well studied in the perioperative period. We present a quality improvement (QI) report describing implementation and evaluation of a postoperative, inpatient personalized music program for older adults undergoing elective surgeries. DESIGN: We embedded this program in an existing interdisciplinary perioperative care program, with an outpatient and an inpatient component, at an academic institution. METHODS: We describe our initial QI steps, highlight critical lessons learned from this behavioral intervention, and discuss high yield areas to focus on future implementation efforts. FINDINGS: Rapid cycle improvement was an effective method to monitor QI measures. Participants in our program perceived improved mood and pain control, were satisfied with their experience, and had lower rates of incident delirium. CONCLUSIONS: This program offers perioperative teams, especially frontline nursing staff, an inexpensive, patient-centered tool to optimize postoperative pain and anxiety. We believe that it can be easily replicated at a variety of hospital systems.

The effectiveness of non-pharmacological interventions in reducing the incidence and duration of delirium in critically ill patients: a systematic review and meta-analysis.

PURPOSE: To evaluate the effect of non-pharmacological interventions versus standard care on incidence and duration of delirium in critically ill patients. METHODS: We searched electronic and grey literature for randomised clinical trials up to March 2018. Two reviewers independently screened, selected and extracted data. Meta-analysis was undertaken using random effects modelling. RESULTS: We identified 15 trials (2812 participants). Eleven trials reported incidence of delirium. Pooled data from four trials of bright light therapy showed no significant effect between groups (n = 829 participants, RR 0.45, 99% CI 0.10-2.13, P = 0.19, very low quality evidence). Seven trials of various individual interventions also failed to report any significant effects. A total of eight trials reported duration of delirium. Pooled data from two trials of multicomponent physical therapy showed no significant effect [n = 404 participants, MD (days) - 0.65, 99% CI - 2.73 to 1.44, P = 0.42, low quality of evidence]. Four trials of various individual interventions also reported no significant effects. A trial of family voice reorientation showed a beneficial effect [n = 30, MD (days) - 1.30, 99% CI - 2.41 to - 0.19, P = 0.003, very low quality evidence]. CONCLUSIONS: Current evidence does not support the use of non-pharmacological interventions in reducing incidence and duration of delirium in critically ill patients. Future research should consider well-designed and well-described multicomponent interventions and include adequately defined outcome measures.

Combined effects of four major geriatric syndromes on adverse outcomes based on Korean National Health Insurance claims data.

AIM: Geriatric syndromes are common among older individuals, and can affect their health and quality of life. The present study aimed to determine if combinations of geriatric syndromes affected adverse outcomes among older Koreans. METHODS: Korean national health insurance data were collected for a cohort of 5 058 720 individuals who were aged ≥65 years in 2008. The same data source was used to follow these individuals until 2015. Diagnostic codes were used to assess four major geriatric syndromes (delirium, fall-related fractures, incontinence and pressure ulcers) and adverse outcomes (mortality and nursing home institutionalization). RESULTS: The prevalence of geriatric syndromes was 0.3% for delirium, 3.49% for fall-related fractures, 1.08% for incontinence and 0.82% for pressure ulcers. All four geriatric syndromes were associated with increased risks of institutionalization (adjusted hazard ratio [aHR] 2.18, 95% CI 2.08-2.17 for delirium; aHR 1.59, 95% CI 1.58-1.60 for fall-related fractures; aHR 1.43, 95% CI 1.41-1.44 for incontinence; and aHR 2.51, 95% CI 2.47-2.55 for pressure ulcers) and increased risks of mortality (aHR 2.13, 95% CI 2.08-2.17 for delirium; aHR 1.41, 95% CI 1.40-1.42 for fall-related fractures; aHR 1.09, 95% CI 1.07-1.10 for incontinence; and aHR 3.23, 95% CI 3.20-3.27 for pressure ulcers). The aHR for institutionalization were 1.64 (95% CI 1.63-1.65) for one geriatric syndrome, 2.40 (95% CI 2.35-2.44) for two coexisting geriatric syndromes and 2.56 (95% CI 2.35-2.74) for three coexisting geriatric syndromes. The aHR for mortality were 1.52 (95% CI 1.51-1.53) for one geriatric syndrome, 2.36 (95% CI 2.32-2.40) for two coexisting geriatric syndromes and 2.90 (95% CI 2.72-3.09) for three coexisting geriatric syndromes. CONCLUSIONS: Delirium, fall-related fractures, incontinence and pressure ulcers were associated with increased risks of institutionalization and mortality. The magnitude of these risks increased with increasing numbers of coexisting geriatric syndromes. Geriatr Gerontol Int 2018; 18: 1463-1468.