Leiv Otto Watne

The effect of a pre- and postoperative orthogeriatric service on cognitive function in patients with hip fracture: randomized controlled trial (Oslo Orthogeriatric Trial).

BackgroundDelirium is a common complication in patients with hip fractures and is associated with an increased risk of subsequent dementia. The aim of this trial was to evaluate the effect of a pre- and postoperative orthogeriatric service on the prevention of delirium and longer-term cognitive decline.MethodsThis was a single-center, prospective, randomized controlled trial in which patients with hip fracture were randomized to treatment in an acute geriatric ward or standard orthopedic ward. Inclusion and randomization took place in the Emergency Department at Oslo University hospital. The key intervention in the acute geriatric ward was Comprehensive Geriatric Assessment including daily interdisciplinary meetings. Primary outcome was cognitive function four months after surgery measured using a composite outcome incorporating the Clinical Dementia Rating Scale (CDR) and the 10 words learning and recalls tasks from the Consortium to Establish a Registry for Alzheimer’s Disease battery (CERAD). Secondary outcomes were pre- and postoperative delirium, delirium severity and duration, mortality and mobility (measured by the Short Physical Performance Battery (SPPB)). Patients were assessed four and twelve months after surgery by evaluators blind to allocation.ResultsA total of 329 patients were included. There was no significant difference in cognitive function four months after surgery between patients treated in the acute geriatric and the orthopedic wards (mean 54.7 versus 52.9, 95% confidence interval for the difference -5.9 to 9.5; P = 0.65). There was also no significant difference in delirium rates (49% versus 53%, P = 0.51) or four month mortality (17% versus 15%, P = 0.50) between the intervention and the control group. In a pre-planned sub-group analysis, participants living in their own home at baseline who were randomized to orthogeriatric care had better mobility four months after surgery compared with patients randomized to the orthopedic ward, measured with SPPB (median 6 versus 4, 95% confidence interval for the median difference 0 to 2; P = 0.04).ConclusionsPre- and postoperative orthogeriatric care given in an acute geriatric ward was not effective in reducing delirium or long-term cognitive impairment in patients with hip fracture. The intervention had, however, a positive effect on mobility in patients not admitted from nursing homes.Trial registrationClinicalTrials.gov NCT01009268 Registered November 5, 2009

The effect of a pre- and post-operative orthogeriatric service on cognitive function in patients with hip fracture. The protocol of the Oslo Orthogeriatrics Trial

BackgroundHip fractures mainly affect older people. It is associated with high morbidity and mortality, and in particular a high frequency of delirium. Incident delirium following hip fracture is associated with an increased risk of dementia in the following months, but it is still not firmly established whether this is an association or a causal relationship. Orthogeriatric units vary with respect to content and timing of the intervention. One main effect of orthogeriatric care may be the prevention of delirium, especially if preoperative and postoperative care are provided. Thus, the aim of Oslo Orthogeriatric Trial, is to assess whether combined preoperative and postoperative orthogeriatric care can reduce the incidence of delirium and improve cognition following hip fracture.Methods/designInclusion and randomisation will take place in the Emergency Department, as soon as possible after admission. All patients with proximal femur fractures are eligible, irrespective of age, pre-fracture function and accommodation, except if the fracture is caused by a high energy trauma or the patient is terminally ill. The intervention is pre-and post-operative orthogeriatric care delivered on a dedicated acute geriatric ward. The primary outcome measure is a composite endpoint combining the Clinical Dementia Rating Scale (CDR) and the 10 word memory task at four months after surgery. Secondary outcomes comprise incident delirium, length of stay, cognition, mobility, place of residence, activities of daily living and mortality, measured at 4 and 12 months after surgery. We have included 332 patients in the period 17th September 2009 to 5th January 2012.DiscussionOur choice of outcome measures and our emphasis of orthogeriatric care in the preoperative as well as the postoperative phase will enable us to provide new knowledge on the impact of orthogeriatric care on cognition.Trials registrationClinicalTrials.gov NCT01009268

Vitamin K1 and 25(OH)D are independently and synergistically associated with a risk for hip fracture in an elderly population: A case control study

BACKGROUND & AIMS The incidence of hip fractures in Oslo is among the highest in the world. Vitamin D, as well as vitamin K, may play an important role in bone metabolism. We examined if vitamin K1 and 25(OH)D were associated with an increased risk of hip fracture, and whether the possible synergistic effect of these two micronutrients is mediated through bone turnover markers. METHODS Blood was drawn for vitamin K1, 25(OH)D, and the bone turnover marker osteocalcin upon admission for hip fracture and in healthy controls. RESULTS Vitamin K1 and 25(OH)D were independently associated with a risk of hip fracture. The adjusted odds ratio (95% CI) per ng/ml increase in vitamin K1 was 0.07 (0.02-0.32), and that per nmol/L increase in 25(OH)D was 0.96 (0.95-0.98). There was a significant interaction between 25(OH)D and vitamin K1 (p < 0.001), and a significant correlation between total osteocalcin and vitamin K1 and 25(OH)D (rho = 0.18, p = 0.01; rho = 0.20, p = 0.01, respectively). CONCLUSIONS Vitamin K1 and 25(OH)D are lower in hip fracture patients compared with controls. Vitamin K1 and 25(OH)D are independently and synergistically associated with the risk of hip fracture when adjusting for confounders. Intervention studies should include both vitamins.

Anticholinergic Activity in Cerebrospinal Fluid and Serum in Individuals with Hip Fracture with and without Delirium

To examine whether anticholinergic activity (AA) in cerebrospinal fluid (CSF) and serum is associated with risk of delirium in individuals with hip fracture.

Delirium is a risk factor for further cognitive decline in cognitively impaired hip fracture patients

BACKGROUND Delirium is a risk factor for dementia in cognitively intact patients. Whether an episode of delirium accelerates cognitive decline in patients with known dementia, is less explored. METHODS This is a prospective follow-up study of 287 hip fracture patients with pre-fracture cognitive impairment. During the hospitalization, the patients were screened daily for delirium using the Confusion Assessment Method. Pre-fracture cognitive impairment was defined as a score of 3.44 or higher on the pre-fracture Informant Questionnaire on Cognitive Decline in the Elderly Short Form (IQCODE-SF). At follow-up after 4-6 months, the caregivers rated cognitive changes emerging after the fracture using the IQCODE-SF, and the patients were tested with the Mini Mental State Examination (MMSE). A sub-group of the patients had a pre-fracture MMSE score which was used to calculate the yearly decline on the MMSE in patients with and without delirium. RESULTS 201 of the 287 patients developed delirium in the acute phase. In linear regression analysis, delirium was a significant and independent predictor of a more prominent cognitive decline at follow-up measured by the IQCODE-SF questionnaire (p=0.002). Among patients having a pre-fracture MMSE score, the patients developing delirium had a median (IQR) yearly decline of 2.4 points (1.1-3.9), compared to 1.0 points (0-1.9) in the group without delirium (p=0.001, Mann-Whitney test). CONCLUSIONS Hip fracture patients with pre-fracture dementia run a higher risk of developing delirium. Delirium superimposed on dementia is a significant predictor of an accelerated further cognitive decline.

Associations Between Delirium and Preoperative Cerebrospinal Fluid C-Reactive Protein, Interleukin-6, and Interleukin-6 Receptor in Individuals with Acute Hip Fracture

To examine whether delirium in individuals with hip fracture is associated with high C‐reactive protein (CRP), interleukin‐6 (IL‐6), and soluble IL‐6 receptor (sIL‐6R) levels in the cerebrospinal fluid (CSF).

Perioperative hemodynamics and risk for delirium and new onset dementia in hip fracture patients; A prospective follow-up study

Background Delirium is common in hip fracture patients and many risk factors have been identified. Controversy exists regarding the possible impact of intraoperative control of blood pressure upon acute (delirium) and long term (dementia) cognitive decline. We explored possible associations between perioperative hemodynamic changes, use of vasopressor drugs, risk of delirium and risk of new-onset dementia. Methods Prospective follow-up study of 696 hip fracture patients, assessed for delirium pre- and postoperatively, using the Confusion Assessment Method. Pre-fracture cognitive function was assessed using the Informant Questionnaire of Cognitive Decline in the Elderly and by consensus diagnosis. The presence of new-onset dementia was determined at follow-up evaluation at six or twelve months after surgery. Blood pressure was recorded at admission, perioperatively and postoperatively. Results Preoperative delirium was present in 149 of 536 (28%) assessable patients, and 124 of 387 (32%) developed delirium postoperatively (incident delirium). The following risk factors for incident delirium in patients without pre-fracture cognitive impairment were identified: low body mass index, low level of functioning, severity of physical illness, and receipt of ≥ 2 blood transfusions. New-onset dementia was diagnosed at follow-up in 26 of 213 (12%) patients, associated with severity of physical illness, delirium, receipt of vasopressor drugs perioperatively and high mean arterial pressure postoperatively. Conclusion Risk factors for incident delirium seem to differ according to pre-fracture cognitive status. The use of vasopressors during surgery and/or postoperative hypertension is associated with new-onset dementia after hip fracture.

Preclinical Amyloid-β and Axonal Degeneration Pathology in Delirium.

BACKGROUND The clinical relevance of brain β-amyloidosis in older adults without dementia is not established. As delirium and dementia are strongly related, studies on patients with delirium may give pathophysiological clues. OBJECTIVE To determine whether the Alzheimers disease (AD) cerebrospinal fluid (CSF) biomarkers amyloid-β 1-42 (Aβ42), total tau (T-tau), and phosphorylated tau (P-tau) are associated with delirium in hip fracture patients with and without dementia. METHODS CSF was collected in conjunction to spinal anesthesia in 129 patients. Delirium was assessed using the Confusion Assessment Method once daily in all patients, both pre- and postoperatively. The diagnosis of dementia at admission was based upon clinical consensus. CSF levels of Aβ42, T-tau, and P-tau were analyzed. RESULTS In patients without dementia, we found lower CSF Aβ42 levels (median, 310 ng/L versus 489 ng/L, p = 0.006), higher T-tau levels (median, 505 ng/L versus 351 ng/L, p = 0.02), but no change in P-tau in patients who developed delirium (n = 16) compared to those who remained lucid (n = 49). Delirious patients also had lower ratios of Aβ42 to T-tau (p < 0.001) and P-tau (p = 0.001) relative to those without delirium. CSF Aβ42 and T-tau remained significantly associated with delirium status in adjusted analyses. In patients with dementia, CSF biomarker levels did not differ between those with (n = 54) and without delirium (n = 10). CONCLUSION The reduction in CSF Aβ42, indicating β-amyloidosis, and increase in T-tau, indicating neurodegeneration, in hip fracture patients without dementia developing delirium indicates that preclinical AD brain pathology is clinically relevant and possibly plays a role in delirium pathophysiology.

CSF biomarkers in delirium: A systematic review

In recent years, there has been a blossoming of studies examining cerebrospinal fluid (CSF) as a method of studying the pathophysiology of delirium. We systematically reviewed the literature for CSF studies in delirium and provide here a summary of the implications for our understanding of delirium pathophysiology. We also summarise the methods used for CSF analysis and discuss challenges and implications for future studies.

Decreases in heart rate variability are associated with postoperative complications in hip fracture patients

Background To explore relevant associations between deviations in linear and nonlinear heart rate variability (HRV) scores, and short-term morbidity and mortality in patients undergoing hip-surgery after a fracture. Methods 165 patients with hip fractures being admitted for surgery at two hospitals were included in a prospective cohort study. A short-term ECG was recorded within 24 hours of arrival. 15 patients had to be excluded due to insufficient quality of the ECG recordings. 150 patients were included in the final analysis. Linear parameters were calculated in time domain: standard deviation of NN intervals (SDNN), root mean square of successive differences (rMSSD); and frequency domain: Total Power (TP), High Frequency Power (HF), Low Frequency Power (LF), Very Low Frequency Power (VLF), and the ratio of LF/HF. Postoperative outcome was evaluated at the time of discharge. This included occurrence of pneumonia, overall infection rate, stroke, myocardial infarction, and all-cause mortality. Results Patients experiencing complications had significantly lower rMSSD (p = 0.04), and TP (p = 0.03) preoperatively. Postoperative infections were predicted by decreased VLF preoperatively (p = 0.04). There was a significant association between pneumonia and LF/HF<1 (p = 0.03). The likelihood ratio to develop pneumonia when LF/HF < 1 was 6,1. Conclusion HRV seems to reflect the general frailty of the patient with hip fracture and might be used to identify patients in need of increased surveillance or prophylactic treatment.