Intranasal vitamin B12 administration in elderly patients: A randomized controlled comparison of two dosage regimens.

AIM: Vitamin B12 deficiency is common in the elderly population. Standard treatment via intramuscular injections, however, has several disadvantages. Safer and more convenient dosage forms such as intranasal are therefore being explored. This study compares the effects of two intranasal vitamin B12 dosage regimens in elderly vitamin B12-deficient patients. METHODS: Sixty patients ≥65 years were randomly assigned to either a loading dose (daily administration for 14 days followed by weekly administration) or a no loading dose (administration every 3 days) regimen for 90 days. Each dose contained 1000 µg cobalamin. Total vitamin B12, holotranscoblamin (holoTC), methylmalonic acid (MMA) and total homocysteine (tHcy) levels in serum were measured on days 0, 7, 14, 30, 60 and 90. RESULTS: Both dosage regimens resulted in a rapid increase of vitamin B12 and holoTC concentrations and normalization of initial high, MMA and tHcy concentrations. The loading dose regimen resulted in the fastest and greatest increase to a median vitamin B12 of 1090 pmol/L (reference 350-650 pmol/L) concentration after 14 days. Following weekly administration, B12 rapidly decreased to a median concentration of 530 pmol/L after 90 days. The no loading dose regimen resulted in a steady increase to a median vitamin B12 of 717 pmol/L after 90 days. CONCLUSIONS: Intranasal vitamin B12 administration is an effective and suitable way to replenish and sustain vitamin B12 levels in elderly patients.

Deficits in geriatric assessment are important in relation to fatigue in older patients with Inflammatory Bowel Disease.

BACKGROUND: No previous study has investigated fatigue in older patients with Inflammatory Bowel Disease (IBD). AIMS: To describe the prevalence of fatigue in older patients and compare it to the prevalence in younger patients with IBD, and to determine factors associated with fatigue. METHODS: A prospective, multicenter cohort study, including older- (≥ 65 years) and younger patients with IBD (18-64 years). A geriatric assessment was performed in older patients to measure deficits in geriatric assessment (DiG). Fatigue was defined by one item from the short Inflammatory Bowel Disease Questionnaire. Active disease was defined as the presence of clinical or biochemical disease activity. RESULTS: Fatigue prevalence in the 405 older patients varied between 45.4% (71/155) in active disease to 23.6% (60/250) in remission. Fatigue prevalence in 155 younger patients was 59.5% (47/79) and 57.4% (89/155), respectively. Female sex, clinical disease activity, use of immunomodulators and presence of DiG were associated with fatigue in older patients with IBD. CONCLUSIONS: Fatigue prevalence is lower in older patients with IBD compared to younger patients with IBD, but increases when active disease is present. Clinicians should be aware that fatigue is a relevant symptom in older patients with IBD, as it is associated with DiG.

Recipe for primary prevention of delirium in hospitalized older patients.

Delirium is an acute fluctuating syndrome characterized by a change in consciousness, perception, orientation, cognition, sleep-wake rhythm, psychomotor skills, and the mood and feelings of a patient. Delirium and delirium prevention remain a challenge for healthcare professionals, especially nurses who form the basis of patient care. It also causes distress for patients, their caregivers and healthcare professionals. However, delirium is preventable in 30-40% of cases. The aim of this article is to summarize the delirium risk models, delirium screening tools, and (non-pharmacological) delirium prevention strategies. A literature search of review articles supplemented by original articles published in PubMed, Cinahl, and Cochrane between 1 January 2000 and 31 December 2020 was carried out. Among the older patients, delirium is a common condition with major consequences in terms of mortality and morbidity, but prevention is possible. Despite the fact that delirium risk models, delirium screening scales and non-pharmacological prevention are available for the development of a hospital delirium prevention programme, such a programme is still not commonly used on a daily basis.

The effect of the anticholinergic burden on duration and severity of delirium in older hip-surgery patients with and without haloperidol prophylaxis: A post hoc analysis.

BACKGROUND: Anticholinergic acting drugs have been associated with delirium in older patients. OBJECTIVE: To examine the association between the anticholinergic burden (ACB) and the duration and severity of delirium in older hip-surgery patients with or without haloperidol prophylaxis. METHODS: Older patients with a postoperative delirium following hip surgery from a randomized controlled trial investigating the effects of haloperidol prophylaxis on delirium incidence were included in this study. The ACB was quantified using two different tools, the Anticholinergic Drug Scale and an Expert Panel. Using linear regression, the association between the ACB and delirium was analyzed. RESULTS: Overall delirium duration and severity were not significantly associated with the ACB. Also, no statistically significant differences were found in delirium duration or severity between the placebo and haloperidol treatment groups for the ACB groups. The protective effect of haloperidol on delirium duration and severity however tended to be present in patients with no or a low ACB but not or to a lesser extent in patients with an intermediate to high ACB. CONCLUSIONS: The ACB was not significantly associated with delirium duration or severity. Haloperidol prophylaxis tended to shorten delirium duration and decrease delirium severity in patients with no or a low ACB. To further explore the influence of anticholinergic acting drugs on delirium duration and severity and the effect of concomitant haloperidol use, additional research with a higher haloperidol dose, a larger study population, and ACB quantification taking drug exposure into account is warranted.

Development and validation of the delirium risk assessment score (DRAS).

PURPOSE: Development and validation of a delirium risk assessment score. Predisposing risk factors for delirium were used, which are easily assessed at hospital admission without additional clinical or laboratory testing. METHODS: A systematic literature search identified ten risk factors: acute admission, alcohol use > 4 units/day, cognitive impairment, ADL impairment, age > 75 years, earlier delirium, hearing/vision problems, number of medication ≥ 5, number of morbidities > 2 and male. The DRAS was developed in a mixed patient population (N = 842) by the use of univariate and multivariate analyses and -2 log-likelihood calculation to weigh the risk factors. Based on the sensitivity and specificity, a cutoff score was calculated. The validation was performed in 3 cohorts (N = 408, N = 186, N = 365). In cohort 3, the DRAS was compared (AUC, sensitivity and specificity) to 3 instruments (Inouye, Kalisvaart, VMS rules). RESULTS: The delirium incidence was 31.8%, 20.3%, 15.6% and 15.1%. All risk factors were independently predictive for delirium, except male. The multivariate analyses excluded morbidities. The final DRAS consists of 8 items; acute admission, cognitive impairment, alcohol use (3 points), ADLimpairment/mobilityproblems (2 points), higher age, earlier delirium, hearing/vision problems, and medication (1 point). The total score is 15 points and at a cut-of score of 5 or higher the patient is at risk of developing a delirium. The cutoff was at 5 or more points, AUC: 0.76 (95% CI 0.72-0.79), sensitivity 0.77, specificity 0.60. Validation cohorts AUC was 0.75 (95% CI 0.96-0.81), 0.76 (95% CI 0.70-0.83) and 0.78 (95% CI 0.70-0.87), sensitivity 0.71, 0.67 and 0.89 and specificity 0.70, 0.72 and 0.60. The comparison revealed the highest AUC for the DRAS. CONCLUSION: Based on an admission interview, the delirium risk can be easily evaluated using the DRAS shortlist score of predisposing risk factors for delirium in older inpatients.

Communicating uncertainties when disclosing diagnostic test results for (Alzheimer's) dementia in the memory clinic: The ABIDE project.

BACKGROUND: The development of novel diagnostics enables increasingly earlier diagnosis of Alzheimer's disease (AD). Timely diagnosis may benefit patients by reducing their uncertainty regarding the cause of symptoms, yet does not always provide patients with the desired certainty. OBJECTIVE: To examine, using both quantitative and qualitative methods, uncertainty communicated by memory clinic clinicians in post-diagnostic testing consultations with patients and their caregivers. METHODS: First, we identified all uncertainty expressions of 22 clinicians in audiotaped post-diagnostic testing consultations with 78 patients. Second, we statistically explored relationships between patient/clinician characteristics and uncertainty expressions. Third, the transcribed uncertainty expressions were qualitatively analysed, determining the topic to which they pertained, their source and initiator/elicitor (clinicians/patients/caregivers). RESULTS: Within 57/78 (73%) consultations, clinicians expressed in total 115 uncertainties, of which 37% elicited by the patient or caregiver. No apparent relationships were found between patient/clinician characteristics and whether or not, and how often clinicians expressed uncertainty. Uncertainty expressions pertained to ten different topics, most frequently patient's diagnosis and symptom progression. Expressed uncertainty was mostly related to the unpredictability of the future and limits to available knowledge. DISCUSSION AND CONCLUSIONS: The majority of clinicians openly discussed the limits of scientific knowledge and diagnostic testing with patients and caregivers in the dementia context. Noticeably, clinicians did not discuss uncertainty in about one quarter of consultations. More evidence is needed on the beneficial and/or harmful effects on patients of discussing uncertainty with them. This knowledge can be used to support clinicians to optimally convey uncertainty and facilitate patients' uncertainty management.

Postoperative continuous-flow cryocompression therapy in the acute recovery phase of hip fracture surgery-A randomized controlled clinical trial.

BACKGROUND: The acute recovery phase after hip fracture surgery is often complicated by severe pain, postoperative blood loss with subsequent transfusion, and delirium. Prevalent comorbidity in hip fracture patients limit the use of opioid-based analgesic therapies, yielding a high risk for inferior pain treatment. Postoperative cryotherapy is suggested to provide an analgesic effect, and to reduce postoperative blood loss. In this prospective, open-label, parallel, multicentre, randomized controlled, clinical trial, we aimed to determine the efficacy of continuous-flow cryocompression therapy (CFCT) in the acute recovery phase after hip fracture surgery. METHODS: Patients with an intra or extracapsular hip fracture scheduled for surgery were included. Subjects were allocated to receive postoperative CFCT or usual care. The primary endpoint was numeric rating scale (NRS) pain the first 72 postoperative hours. Secondly, analgesic use; postoperative haemoglobin change and transfusion incidence; functional outcome; length of stay; delirium incidence; location of rehabilitation; patient-reported health outcome; complications and feasibility were assessed. RESULTS: Sixty-one subjects in the control group, and 64 subjects in the CFCT group were analysed. Within the CFCT group, post treatment NRS pain declined 0.31 (p=0.07) at 24h, 0.28 (p=0.07) at 48h, and 0.47 (p=0.002) at 72h relative to pre treatment NRS pain. Sensitivity analysis at 72h showed that NRS pain was 0.92 lower in the CFCT group when compared to the control group (1.50 vs. 2.42; p=0.03). Postoperative analgesic use was comparable between groups. Between postoperative day one and three haemoglobin declined 0.29mmol/l in the CFCT group and 0.51mmol/l in controls (p=0.06), and transfusion incidence was comparable. The timed up and go test and length of stay were also comparable between both groups. Complications, amongst delirium and cryotherapy-related adverse events were not statistically significantly different. Discharge locations did not differ between groups. At outpatient follow-up subjects did not differ in patient-reported health outcome scores. Subjects rated CFCT satisfaction with an average of 7.1 out of 10 points. CONCLUSIONS: No evidence was recorded to suggest that CFCT has an added value in the acute recovery phase after hip fracture surgery. If patients complete the CFCT treatment schedule, a mild analgesic effect is observed at 72h.

The efficacy of continuous-flow cryo and cyclic compression therapy after hip fracture surgery on postoperative pain: design of a prospective, open-label, parallel, multicenter, randomized controlled, clinical trial.

BACKGROUND: The number of hip fractures and resulting post-surgical outcome are a major public health concern and the incidence is expected to increase significantly. The acute recovery phase after hip fracture surgery in elder patients is often complicated by severe pain, high morphine consumption, perioperative blood loss with subsequent transfusion and delirium. Postoperative continuous-flow cryocompression therapy is suggested to minimize these complications and to attenuate the inflammatory reaction that the traumatic fracture and subsequent surgical trauma encompass. Based on a pilot study in patients undergoing total hip arthroplasty for osteoarthritis, it is anticipated that patients treated with continuous-flow cryocompression therapy will have less pain, less morphine consumption and lower decrease of postoperative hemoglobin levels. These factors are associated with a shorter hospital stay and better long-term (functional) outcome. METHODS/DESIGN: One hundred and sixty patients with an intra or extracapsular hip fracture scheduled for internal fixation (intramedullary hip nail, dynamic hip screw or cannulated screws) or prosthesis surgery (total hip or hemiarthroplasty) will be included in this prospective, open-label, parallel, multicenter, randomized controlled, clinical superiority trial. Patients will be allocated to two treatment arms: group 'A' will be treated with continuous-flow cryocompression therapy and compared to group 'B' that will receive standard care. Routine use of drains and/or compressive bandages is allowed in both groups. The primary objective of this study is to compare acute pain the first 72 h postoperative, measured with numeric rating scale for pain. Secondary objectives are: (non-) morphine analgesic use; adjusted postoperative hemoglobin level; transfusion incidence; incidence, duration and severity of delirium and use of psychotropic medication; length of stay; location and duration of rehabilitation; functional outcome; short-term patient-reported health outcome; general and cryotherapy related complications and feasibility. DISCUSSION: This is the first randomized controlled trial that will assess the analgesic efficiacy of continuous-flow cryocompression therapy in the acute recovery phase after hip fracture surgery. TRIAL REGISTRATION: www.trialregister.nl, NTR4152 (23(rd) of August 2013).

Effect of administration route on the pharmacokinetics of cobalamin in elderly patients: a randomized controlled trial.

BACKGROUND: The gold standard for cobalamin deficiency treatment is administration of cobalamin by intramuscular injection. The injection is painful and inconvenient, particularly for elderly persons. Cobalamin might also be administered intranasally. Previous studies do not provide insight into the pharmacokinetics of intranasal cobalamin administration in comparison with cobalamin injection. AIM: To quantify the pharmacokinetics of intranasally and intramuscularly administered cobalamin to determine if intranasal administration might be an alternative for intramuscular administration. METHODS: Ten inpatients and outpatients of a geriatrics unit were recruited and randomly assigned to receive a single dose of 1000 µg cobalamin administered either by intranasal spray or intramuscular injection (5 per group). Inclusion criteria were written informed consent, age >65 years, and a cobalamin serum concentration <200 pmol/L. Total cobalamin serum concentrations were determined 10 times within 48 hours after administration. The differences in Cmax, Tmax, and AUC0-48 h per administration route were statistically compared using ANOVA. RESULTS: The average Cmax was 1 nmol/L after intranasal and 38.5 nmol/L after intramuscular administration. The average Tmax for intranasal and intramuscular administration was 42 minutes versus 342 minutes, respectively, and the AUC0-48 h was 1.3 µmol/L/min versus 45.4 µmol/L/min, respectively. These values also differed significantly (P<0.05). The estimated bioavailability of the intranasal administration was 2%. CONCLUSIONS: The pharmacokinetics of intranasal and intramuscular cobalamin administration in elderly, cobalamin-deficient patients differ significantly. However, the estimated 2% bioavailability of cobalamin after intranasal administration makes intranasal cobalamin administration a potentially interesting administration route for elderly patients. Netherlands Trial Registry identifier: NTR 3005.

Preoperative cerebrospinal fluid cytokine levels and the risk of postoperative delirium in elderly hip fracture patients.

BACKGROUND: Aging and neurodegenerative disease predispose to delirium and are both associated with increased activity of the innate immune system resulting in an imbalance between pro- and anti-inflammatory mediators in the brain. We examined whether hip fracture patients who develop postoperative delirium have altered levels of inflammatory mediators in cerebrospinal fluid (CSF) prior to surgery. METHODS: Patients were 75 years and older and admitted for surgical repair of an acute hip fracture. CSF samples were collected preoperatively. In an exploratory study, we measured 42 cytokines and chemokines by multiplex analysis. We compared CSF levels between patients with and without postoperative delirium and examined the association between CSF cytokine levels and delirium severity. Delirium was diagnosed with the Confusion Assessment Method; severity of delirium was measured with the Delirium Rating Scale Revised-98. Mann-Whitney U tests or Student t-tests were used for between-group comparisons and the Spearman correlation coefficient was used for correlation analyses. RESULTS: Sixty-one patients were included, of whom 23 patients (37.7%) developed postsurgical delirium. Concentrations of Fms-like tyrosine kinase-3 (P=0.021), Interleukin-1 receptor antagonist (P=0.032) and Interleukin-6 (P=0.005) were significantly lower in patients who developed delirium postoperatively. CONCLUSIONS: Our findings fit the hypothesis that delirium after surgery results from a dysfunctional neuroinflammatory response: stressing the role of reduced levels of anti-inflammatory mediators in this process. TRIAL REGISTRATION: The Effect of Taurine on Morbidity and Mortality in the Elderly Hip Fracture Patient. REGISTRATION NUMBER: NCT00497978. Local ethical protocol number: NL16222.094.07.

The neuropsychological sequelae of delirium in elderly patients with hip fracture three months after hospital discharge.

BACKGROUND: Delirium is a risk factor for long-term cognitive impairment and dementia. Yet, the nature of these cognitive deficits is unknown as is the extent to which the persistence of delirium symptoms and presence of depression at follow-up may account for the association between delirium and cognitive impairment at follow-up. We hypothesized that inattention, as an important sign of persistent delirium and/or depression, is an important feature of the cognitive profile three months after hospital discharge of patients who experienced in-hospital delirium. METHODS: This was a prospective cohort study. Fifty-three patients aged 75 years and older were admitted for surgical repair of acute hip fracture. Before the surgery, baseline characteristics, depressive symptomatology, and global cognitive performance were documented. The presence of delirium was assessed daily during hospital admission and three months after hospital discharge when patients underwent neuropsychological assessment. RESULTS: Of 27 patients with in-hospital delirium, 5 were still delirious after three months. Patients with in-hospital delirium (but free of delirium at follow-up) showed poorer performance than patients without in-hospital delirium on tests of global cognition and episodic memory, even after adjustment for age, gender, and baseline cognitive impairment. In contrast, no differences were found on tests of attention. Patients with in-hospital delirium showed an increase of depressive symptoms after three months. However, delirium remained associated with poor performance on a range of neuropsychological tests among patients with few or no signs of depression at follow-up. CONCLUSION: Elderly hip fracture patients with in-hospital delirium experience impairments in global cognition and episodic memory three months after hospital discharge. Our results suggest that inattention, as a cardinal sign of persistent delirium or depressive symptomatology at follow-up, cannot fully account for the poor cognitive outcome associated with delirium.

Anesthesia and postoperative delirium in older adults undergoing hip surgery.

OBJECTIVES: To examine the effects of general anesthesia on the risk of incident postoperative delirium in older adults undergoing hip surgery. DESIGN: Secondary analysis of haloperidol prophylaxis for delirium clinical trial data. Predefined risk factors for delirium were assessed prior to surgery. Primary outcome was postoperative delirium. Study outcome was compared across patient groups who received either general or regional anesthesia, and for individuals receiving various perioperative medications (benzodiazepines, anticholinergics, and opioids), using multivariable logistic regression after controlling for potential confounders. Subgroup analyses based on baseline cognitive impairment and delirium risk were also undertaken. SETTING: Large medical school-affiliated general hospital in Alkmaar, the Netherlands. PARTICIPANTS: Five hundred twenty-six adults aged 70 and older undergoing hip surgery. MEASUREMENTS: The primary outcome was the incidence of postoperative delirium (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, and Confusion Assessment Method criteria). RESULTS: Sixty participants (11.4%) had incident postoperative delirium. One hundred eighty-nine (35.9%) received general anesthesia, 18 (9.5%) of whom developed postoperative delirium, and 337 (64.1%) received regional anesthesia, 42 (12.5%) of whom developed postoperative delirium (adjusted odds ratio=0.81, 95% confidence interval=0.43-1.52, P=.51). Results were stratified for baseline cognitive impairment, age, acute admission, perioperative medication and other delirium risk factors. Delirium was not independently associated with specific drugs or the medication classes opioids, benzodiazepines, and anticholinergics. CONCLUSION: General anesthesia has no distinct effect on incident postoperative delirium in older adults undergoing hip surgery. This also holds for individuals suffering from cognitive impairment or who are otherwise at risk for postoperative delirium. Perioperative use of narcotics, benzodiazepines, and anticholinergic agents was not associated with incident delirium in this cohort of older adults undergoing hip surgery.

Cerebrospinal fluid ß-amyloid and tau are not associated with risk of delirium: a prospective cohort study in older adults with hip fracture.

OBJECTIVES: To examine the association between cerebrospinal fluid (CSF) ß-amyloid (Aß1-42), tau, and hyperphosphorylated tau (Ptau) and risk of delirium in older adults with hip fracture. DESIGN: Prospective cohort study. SETTING: University-affiliated general hospital in Alkmaar, the Netherlands. PARTICIPANTS: Seventy-six participants aged 75 and older admitted for surgical repair of acute hip fracture. MEASUREMENTS: Presurgical baseline screening and assessment included the Informant Questionnaire on Cognitive Decline-short form (IQCODE-N), Mini-Mental State Examination, standardized Snellen test for visual impairment, Geriatric Depression Scale, Barthel Index (BI), and Lawton Instrumental Activity of Daily Living (IADL) scale. The number of medical comorbidities and medications at home, American Society of Anesthesiologists score, and Acute Physiology and Chronic Health Evaluation II score were determined according to chart review. Delirium was diagnosed using the Confusion Assessment Method. CSF was collected at the onset of spinal anesthesia. RESULTS: Postoperative delirium occurred in 30 (39.5%) participants. Participants with delirium were older, showed more signs of cognitive decline, were more dependent at home in activity of daily living and IADL functioning, and used more medications before admission. Preoperative CSF Aß1-42, tau, and Ptau levels were not significantly different in participants who did and did not develop delirium during subsequent hospitalization. In contrast, prefracture cognitive decline (IQCODE-N) was significantly related to delirium (odds ratio=9.43, 95% confidence interval=2.45-36.31). CONCLUSION: Cognitive impairment predisposes to delirium, but in this study, postoperative delirium was not associated with baseline CSF Aß1-42, tau, and Ptau levels. These findings suggest that CSF markers for plaque and tangle formation are not strongly associated with delirium risk in older adults with hip fracture.

Mortality associated with delirium after hip-surgery: a 2-year follow-up study.

BACKGROUND: delirium after hip-surgery is associated with poor outcome. Few studies examined the mortality risk associated with delirium in elderly hip-surgery patients after 1 year or more. Aim of this study was to examine the hazard risk associated with delirium in elderly hip-surgery patients at 2-year follow-up, controlling for baseline risk factors and interaction effects. METHODS: this is a secondary analysis based on data from a controlled clinical trial evaluating efficacy of haloperidol prophylaxis for delirium conducted in a large medical school-affiliated general hospital in Alkmaar, The Netherlands. Randomised and non-randomised patients (n = 603) were followed-up for 2 years. Predefined risk factors and other potential risk factors for delirium were assessed prior to surgery. Primary outcome was time of death during the follow-up period. Cox proportional hazards were estimated and compared across patients who had postoperative delirium during hospitalisation and those who did not. RESULTS: a total of 90/603 patients (14.9%) died during the study period and 74/603 (12.3%) had postoperative delirium. Incidence of delirium was higher in patients who died (32.2%) compared with those who survived (8.8%). The interaction effect of delirium by illness severity on mortality was significant after adjusting for predefined delirium risk factors and other potential covariates including study intervention (adjusted Hazard risk = 1.05, 95% CI 1.02-1.08). A total of 14/27 delirium patients who were severely ill on admission died during follow-up versus 15/47 delirium patients who were not (RR 1.63 CI 0.93-2.83). CONCLUSIONS: delirium does not independently predict mortality at 2-year follow-up in elderly hip-surgery patients. However, outcome from delirium is particularly poor when other risk factors are present.

Delirium in elderly patients and the risk of postdischarge mortality, institutionalization, and dementia: a meta-analysis.

CONTEXT: Delirium is a common and serious complication in elderly patients. Evidence suggests that delirium is associated with long-term poor outcome but delirium often occurs in individuals with more severe underlying disease. OBJECTIVE: To assess the association between delirium in elderly patients and long-term poor outcome, defined as mortality, institutionalization, or dementia, while controlling for important confounders. DATA SOURCES: A systematic search of studies published between January 1981 and April 2010 was conducted using the databases of MEDLINE, EMBASE, PsycINFO, and CINAHL. STUDY SELECTION: Observational studies of elderly patients with delirium as a study variable and data on mortality, institutionalization, or dementia after a minimum follow-up of 3 months, and published in the English or Dutch language. Titles, abstracts, and articles were reviewed independently by 2 of the authors. Of 2939 references in the original search, 51 relevant articles were identified. DATA EXTRACTION: Information on study design, characteristics of the study population, and outcome were extracted. Quality of studies was assessed based on elements of the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) checklist for cohort studies. DATA SYNTHESIS: The primary analyses included only high-quality studies with statistical control for age, sex, comorbid illness or illness severity, and baseline dementia. Pooled-effect estimates were calculated with random-effects models. The primary analysis with adjusted hazard ratios (HRs) showed that delirium is associated with an increased risk of death compared with controls after an average follow-up of 22.7 months (7 studies; 271/714 patients [38.0%] with delirium, 616/2243 controls [27.5%]; HR, 1.95 [95% confidence interval {CI}, 1.51-2.52]; I(2), 44.0%). Moreover, patients who had experienced delirium were also at increased risk of institutionalization (7 studies; average follow-up, 14.6 months; 176/527 patients [33.4%] with delirium and 219/2052 controls [10.7%]; odds ratio [OR], 2.41 [95% CI, 1.77-3.29]; I(2), 0%) and dementia (2 studies; average follow-up, 4.1 years; 35/56 patients [62.5%] with delirium and 15/185 controls [8.1%]; OR, 12.52 [95% CI, 1.86-84.21]; I(2), 52.4%). The sensitivity, trim-and-fill, and secondary analyses with unadjusted high-quality risk estimates stratified according to the study characteristics confirmed the robustness of these results. CONCLUSION: This meta-analysis provides evidence that delirium in elderly patients is associated with poor outcome independent of important confounders, such as age, sex, comorbid illness or illness severity, and baseline dementia.

Long-term cognitive outcome of delirium in elderly hip surgery patients. A prospective matched controlled study over two and a half years.

OBJECTIVE: To study the outcome of delirium in elderly hip surgery patients. DESIGN: Prospective matched controlled cohort study. Hip surgery patients (n = 112) aged 70 years and older, who participated in a controlled clinical trial of haloperidol prophylaxis for delirium, were followed for an average of 30 months after discharge. Patients with a diagnosis of dementia or mild cognitive impairment (MCI) were identified using psychiatric interviews. Proportions of patients with dementia/MCI were compared across patients who had postoperative delirium and selected control patients matched for preoperatively assessed risk factors who had not developed delirium during index hospitalization. Other outcomes were mortality rate and rate of institutionalization. RESULTS: During the follow-up period, 54.9% of delirium patients had died compared to 34.1% of the controls (relative risk = 1.6, 95% CI = 1.0-2.6). Dementia or MCI was diagnosed in 77.8% of the surviving patients with postoperative delirium and in 40.9% of control patients (relative risk = 1.9, 95% CI = 1.1-3.3). Half of the patients with delirium were institutionalized at follow-up compared to 28.6% of the controls (relative risk = 1.8, 95% CI = 0.9-3.4). CONCLUSION: The risk of dementia or MCI at follow-up is almost doubled in elderly hip surgery patients with postoperative delirium compared with at-risk patients without delirium. Delirium may indicate underlying dementia.

Pre-operative inflammatory markers and the risk of postoperative delirium in elderly patients.

OBJECTIVE: Pathophysiological mechanisms leading to delirium are not clear. Age is a known risk factor and hypothesised to be accompanied by a low-grade inflammatory state. Previous studies have shown an association between delirium and circulating proinflammatory markers in acutely ill and postoperative patients. In light of the ageing/inflammation theory, we investigated the association of these markers with delirium in not acutely ill, elderly patients. METHODS: In a prospective nested case-control study levels of C-reactive protein (CRP), interleukin 6 (Il-6), insulin growth factor 1 (IGF-1) were measured pre-operatively in elderly patients admitted for hip-surgery. These levels were compared between patients who later developed a post-operative delirium and patients who did not. Patients were matched for age and disease severity. RESULTS: Eighteen patients who developed delirium post-operatively were matched with 50 controls. Median APACHE-scores were below 16 in both groups. Pre-operative serum concentrations of CRP, Il-6 and IGF-1 did not differ between groups. IL-6 levels were associated with a measure of cognitive impairment. CONCLUSION: In the present study no relationship was found between levels of pre-operative circulating pro-inflammatory markers and post-operative delirium in elderly patients, who were free from acute or severe disease.

Reasons for psychiatric consultation referrals in Dutch nursing home patients with dementia: a comparison with normative data on prevalence of neuropsychiatric symptoms.

OBJECTIVE: To study psychiatric consultation referrals of nursing home patients with dementia and to compare referral reasons with normative data on prevalence of neuropsychiatric symptoms. METHODS: This is part of a cross-sectional study of 787 patients residing in 14 nursing homes in the Netherlands. Nursing home physicians (NHP) noted the primary reasons for psychiatric consultation according to the Neuropsychiatric Inventory items and two extra domains. Patients were subsequently assessed by an old-age psychiatrist. Eligible patients were those that had dementia. Reasons for referral were compared with independent data on prevalence of neuropsychiatric symptoms in nursing home patients with dementia. RESULTS: A total of 325/787 (41.3%) patients had dementia. Agitation, disinhibition and aberrant motor behaviour were frequent reasons for referral (>25%). Psychotic symptoms, apathy and eating behaviour changes were infrequent reasons (<10%) for seeking consultation. Agitation and disinhibition were more often primary reasons for consultation than would have been expected based on normative prevalence estimates of these symptoms. In contrast, delusions, euphoria, apathy, irritability and eating behaviour changes were less often reasons for referral compared with prevalence estimates. CONCLUSIONS: This study is the first to examine psychiatric consultation for dementia patients in Dutch nursing home. Large differences exist between referral reasons and normative data on symptom prevalence. Specialized mental health service was provided for the agitated and disinhibited patient in particular. Chances are that this is at the expense of the apathetic, retarded and quietly 'not causing any trouble' patient.

Early symptoms in the prodromal phase of delirium: a prospective cohort study in elderly patients undergoing hip surgery.

OBJECTIVES: The authors investigated prodromal delirium symptoms in elderly patients undergoing hip surgery. METHODS: This was a prospective cohort study in the setting of a large medical school-affiliated general hospital in Alkmaar, The Netherlands. Participants were patients undergoing hip surgery aged 70 and older at risk for delirium. Before surgery, patients were randomized to low-dose prophylactic haloperidol treatment or placebo. Daily assessments were based on patient interviews with the Mini-Mental State Examination and Digit Span test. The Delirium Rating Scale-Revised (DRS-R-98) was used to measure early symptoms during the prodromal phase before the onset of delirium. RESULTS: Data of 66 patients with delirium were compared with those of 35 at-risk patients who did not develop delirium: 14 of 66 patients (21%) had delirium on the day of surgery or early the day after, 32 of 66 (48%) on the second day, 14 of 66 on the third, and six of 66 (9%) on the fourth. The average DRS-R-98 total scores on day -4 to day -1 before delirium were 1.9 for the comparison group patients and 5.0, 4.3, 5.8, and 10.7 for patients with postoperative delirium. Multivariate analysis showed that the early symptoms memory impairments, incoherence, disorientation, and underlying somatic illness predict delirium. CONCLUSIONS: Most elderly patients undergoing hip surgery with postoperative delirium already have early symptoms in the prodromal phase of delirium. These findings are potentially useful for screening purposes and for optimizing prevention strategies targeted at reducing the incidence of postoperative delirium.