Long-Term Outcomes of Invasive vs Conservative Strategies for Older Patients With Non-ST-Segment Elevation Acute Coronary Syndromes.

BACKGROUND: Non-ST-segment elevation acute coronary syndrome (NSTE-ACS) is a frequent cause of hospital admission in older people, but clinical trials targeting this population are scarce. OBJECTIVES: The After Eighty Study assessed the effect of an invasive vs a conservative treatment strategy in a very old population with NSTE-ACS. METHODS: Between 2010 and 2014, the investigators randomized 457 patients with NSTE-ACS aged ≥80 years (mean age 85 years) to an invasive strategy involving early coronary angiography with immediate evaluation for revascularization and optimal medical therapy or to a conservative strategy (ie, optimal medical therapy). The primary endpoint was a composite of myocardial infarction, need for urgent revascularization, stroke, and death. The long-term outcomes are presented. RESULTS: After a median follow up of 5.3 years, the invasive strategy was superior to the conservative strategy in the reduction of the primary endpoint (incidence rate ratio: 0.76; 95% CI: 0.63-0.93; P = 0.0057). The invasive strategy demonstrated a significant gain in event-free survival of 276 days (95% CI: 151-400 days; P = 0.0001) at 5 years and 337 days (95% CI: 123-550 days; P = 0.0001) at 10 years. These results were consistent across subgroups of patients with respect to major cardiovascular prognostic factors. CONCLUSIONS: In patients aged ≥80 years with NSTE-ACS, the invasive strategy was superior to the conservative strategy in the reduction of composite events and demonstrated a significant gain in event-free survival. (The After Eighty Study: a randomized controlled trial; NCT01255540).

Guideline-Recommended Time Less Than 90 Minutes From ECG to Primary Percutaneous Coronary Intervention for ST-Segment-Elevation Myocardial Infarction Is Associated with Major Survival Benefits, Especially in Octogenarians: A Contemporary Report in 11 226 Patients from NORIC.

Background Using contemporary data from NORIC (Norwegian Registry of Invasive Cardiology) we investigated the predictive value of patient age and time from ECG diagnosis to sheath insertion (ECG-2-sheath) in primary percutaneous coronary intervention for ST-segment-elevation myocardial infarction (STEMI). Methods and Results Data from 11 226 patients collected from all centers offering 24/7/365 primary percutaneous coronary intervention service were explored. For patients aged <80 years the mortality rates were 5.6% and 7.6% at 30 days and 1 year, respectively. For octogenarians the corresponding rates were 15.0% and 24.2%. The Cox hazard ratio was 2.02 (1.93-2.11, P value <0.0001) per 10 years of patient age. Time from ECG-2-sheath was significantly associated with mortality with a 3.6% increase per 30 minutes of time. Using achievement of time goal <90 minutes in patients aged >80 years and mortality at 30 days, mortality was 10.5% and 17.7% for <90 or ≥90 minutes, respectively. The number needed to prevent 1 death was 39 in the whole population and 14 in the elderly. Restricted mean survival gains during median 938 days of follow-up in patients with ECG-2-sheath time <90 minutes were 24 and 76 days for patients aged <80 and ≥80 years, respectively. Conclusions Time from ECG-diagnosis to sheath insertion is strongly correlated with mortality. This applies especially to octogenarians who derive the most in terms of absolute mortality reduction. Registration URL: https://helsedata.no/en/forvaltere/norwegian-institute-of-public-health/norwegian-registry-of-invasive-cardiology/.

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.

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.

Is there a role for monocyte chemoattractant protein-1 in delirium? Novel observations in elderly hip fracture patients.

BACKGROUND: Delirium is common, associated with poor outcome, but its pathophysiology remains obscure. The aim of the present study was to study a possible role of monocyte chemoattractant protein-1 (MCP-1) in the development of delirium. FINDINGS: A prospective cohort of 19 hip fracture patients (median age 83 years) were screened for delirium daily by validated methods. MCP-1 was measured on arrival and postoperatively. The number of patients with a raise in MCP-1 was statistically significantly higher in the group with delirium in the postoperative phase compared to the no-delirium group (5/6 vs. 1/7, p = .03). CONCLUSIONS: MCP-1 might play a role in the development of delirium.

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

BACKGROUND: Delirium 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. METHODS: This 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. RESULTS: A 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). CONCLUSIONS: Pre- 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 REGISTRATION: ClinicalTrials.gov NCT01009268 Registered November 5, 2009.

Anticholinergic activity in cerebrospinal fluid and serum in individuals with hip fracture with and without delirium.

OBJECTIVES: To examine whether anticholinergic activity (AA) in cerebrospinal fluid (CSF) and serum is associated with risk of delirium in individuals with hip fracture. DESIGN: Prospective cohort study. SETTING: Two university hospitals in Oslo, Norway, and Edinburgh, UK. PARTICIPANTS: Individuals admitted with acute hip fracture (N = 151). MEASUREMENTS: Participants were assessed daily for delirium using the Confusion Assessment Method (preoperatively and postoperative days 1-5 (all) or until discharge (participants with delirium)). Prefracture cognitive function was assessed using the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE). Serum was collected preoperatively and CSF at the onset of spinal anesthesia. AA in serum (SAA) and CSF samples was determined according to a muscarinic radio receptor bioassay. The association between AA measures and delirium was evaluated using logistic multivariate analyses. RESULTS: Fifty-two (54%) of the participants in Oslo and 20 (39%) in Edinburgh developed delirium. There was no statistically significant difference in AA between participants with and without delirium in Oslo (serum: 7.02 vs 6.08 pmol/mL, P = .54; CSF: 0.39 vs 0.48 pmol/mL, P = .26) or in Edinburgh (serum: 1.35 vs 1.62 pmol/mL, P = .76; CSF: 0.36 vs 0.31 pmol/mL, P = .93). Nor was there any difference in SAA (Oslo, P = .74; Edinburgh, P = .51) or CSF AA (Oslo, P = .21; Edinburgh, P = .93) when participants were subdivided into prevalent, incident, subsyndromal, and never delirium. Stratifying participants according to prefracture cognitive status (IQCODE) gave the same results. CONCLUSION: This is the first study of AA in CSF of individuals with and without delirium. The study does not support the hypothesis that central (CSF) or peripheral (serum) AA is an important mechanism of delirium in individuals with hip fracture.

Delirium is a risk factor for institutionalization and functional decline in older hip fracture patients.

OBJECTIVES: The risk of institutionalization and functional decline is substantial after a hip fracture. However, previous research has not established the extent to which delirium plays a contributory role. METHODS: Using a prospective design, we studied 207 hip fracture patients aged 65 and older, home-dwelling before the fracture. Patients were screened daily for delirium using the Confusion Assessment Method. Proxy information on pre-fracture cognitive function and function in activities of daily living (ADL) was obtained using the Informant Questionnaire on Cognitive Decline in the Elderly, 16-item version, and the Barthel ADL Index. After 6months, the patients' functions in ADL measured by the Barthel ADL Index and place of living were registered. RESULTS: Delirium was present in 80 patients (39%) during the hospital stay. After 6months, 33 (16%) were institutionalized. Delirium and lower Barthel ADL Index score were the main risk factors for institutionalization with an adjusted odds ratio (AOR) of 5.50 (95% CI=1.77-17.11) and 0.54 (95% CI=0.40-0.74) respectively. In patients able to return to their private home, the independent risk factors for functional decline were higher age (B=0.053, 95% CI=0.003-0.102) and delirium (B=0.768, 95% CI=0.039-1.497). CONCLUSIONS: At 6month follow-up, delirium constitutes an independent risk factor for institutionalization and functional decline in hip fracture patients living at home prior to the fracture.

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.

BACKGROUND: Hip 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/DESIGN: Inclusion 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. DISCUSSION: Our 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 REGISTRATION: ClinicalTrials.gov NCT01009268.

Delirium is an important predictor of incident dementia among elderly hip fracture patients.

BACKGROUND: Delirium is believed to constitute a risk factor for dementia, but previous research has failed to satisfactorily take account of the patients' preexisting level of cognitive functioning. METHODS: A prospective 6-month follow-up of 106 elderly hip fracture patients free from prefracture dementia. Delirium was assessed by the Confusion Assessment Method. Caregivers described the patients' prefracture cognition by the Informant Questionnaire on Cognitive Decline in the Elderly, Short Form (IQCODE-SF). Cognition was measured after 6 months, using 5 validated cognitive tests. An expert panel assessed each case as to whether the diagnostic criteria for dementia according to the DSM-IV were fulfilled at baseline and after 6 months. RESULTS: 29/106 patients (27%) developed delirium in the acute phase. In the delirious group, 11/29 (38%) fulfilled the criteria of dementia after 6 months, compared to 5/77 (7%) in the group without delirium (p < 0.001; χ(2) test). Delirium was the strongest predictor of dementia after 6 months (adjusted odds ratio: 10.5; 95% CI: 1.6-70.3). IQCODE-SF score was a nonsignificant risk factor for incident dementia. CONCLUSION: In hip fracture patients free from prefracture dementia, delirium constitutes the main predictor of dementia 6 months later, adjusted for prefracture cognitive decline measured by the IQCODE-SF.

Delirium is not associated with mortality in elderly hip fracture patients.

BACKGROUND: The relationship between delirium and mortality remains obscure. The aims of this study were to investigate the effect of delirium and the interaction between delirium and chronic cognitive impairment on mortality in elderly hip fracture patients. METHODS: This is a prospective observational study, including 331 hip fracture patients. Information on comorbidity, medications and clinical findings was collected at the time of fracture. Information on cause and time of death was obtained from the Norwegian Cause of Death Register. Patients were screened for delirium by the Confusion Assessment Method. RESULTS: Delirium was not associated with mortality when adjusting for the severity of chronic cognitive impairment, measured by the Infor- mant Questionnaire on Cognitive Decline in the Elderly (IQCODE). Estimated by Kaplan-Meier plots, delirium in patients with dementia was significantly associated with an increased risk of death from stroke (p = 0.004) and dementia (p ≤ 0.001). CONCLUSIONS: No association between delirium and mortality was demonstrated when adjusting for the IQCODE score, but delirium in patients with prefracture dementia was associated with an increased risk of death from stroke and dementia. The effect of delirium on the cause of death might be explained by an aggravation of an ongoing neuro-inflammation.

Medical treatment predicts mortality after hip fracture.

BACKGROUND: The mortality after hip fracture has remained high and stable the past 50 years despite improved surgical treatment. The aim of this study was to identify medications and medical factors associated with mortality after hip fracture. METHODS: This is a prospective observational study with median observation time of 21 months. Three hundred and sixty-four patients, mean age 83.4 years and 75.8% women, were enrolled. Information on comorbidity, medications, surgery, and clinical findings were collected at the time of fracture. Information on cause and time of death was obtained from the Norwegian Cause of Death Register. RESULTS: Six risk factors and one protective factor were identified by Cox proportional hazards model adjusted for propensity score: the use of diuretics (adjusted hazard ratio [HR] = 4.03, 95% confidence interval [CI] = 2.13-7.64), history of coronary heart disease (CHD) (HR = 2.61, CI = 1.37-4.98), male sex (HR = 2.32, CI = 1.27-4.24), Barthel Index < or = 18/20 (HR = 2.48, CI = 1.23-5.01), heart rate > 100 on admission (HR = 2.47, CI = 1.18-5.14), body mass index < or = 20 (HR = 1.94, CI = 1.13-3.34), and the use of statins (HR = 0.23, CI = 0.08-0.68). Patients using diuretics had increased risk of death from all causes, including death from CHD, chronic obstructive pulmonary disease, and falls or other accidents. CONCLUSIONS: The use of diuretics is the strongest predictor of mortality, followed by CHD at the time of fracture, whereas the use of statins is associated with improved survival. Future research is needed to evaluate whether improved diagnosis and management of CHD and congestive heart failure among hip fracture patients would improve survival.

Risk factors for preoperative and postoperative delirium in elderly patients with hip fracture.

OBJECTIVES: To evaluate risk factors for preoperative and postoperative delirium. DESIGN: Prospective cohort study. SETTING: Departments of orthopedic surgery in two Norwegian hospitals. PARTICIPANTS: Three hundred sixty-four patients with and without cognitive impairment, aged 65 and older. MEASUREMENTS: Patients were screened daily for delirium using the Confusion Assessment Method. Established risk factors and risk factors regarded as clinically important according to expert opinion were explored in univariate analyses. Variables associated with the outcomes (P<.05) were entered into multivariate logistic regression models. RESULTS: Delirium was present in 50 of 237 (21.1%) assessable patients preoperatively, whereas 68 of 187 (36.4%) patients developed delirium postoperatively (incident delirium). Multivariate logistic regression identified four risk factors for preoperative delirium: cognitive impairment (adjusted odds ratio (AOR)=4.7, 95% confidence interval (CI)=1.9-11.3), indoor injury (AOR=3.6, 95% CI=1.1-12.2), fever (AOR=3.4, 95% CI=1.5-7.7), and preoperative waiting time (AOR=1.05, 95% CI=1.0-1.1 per hour). Cognitive impairment (AOR=2.9, 95% CI=1.4-6.2), indoor injury (AOR=2.9, 95% CI=1.1-6.3), and body mass index (BMI) less than 20.0 (AOR=2.9, 95% CI=1.3-6.7) were independent and statistically significant risk factors for postoperative delirium. CONCLUSION: Time from admission to operation is a risk factor for preoperative delirium, whereas low BMI is an important risk factor for postoperative delirium in hip fracture patients. Cognitive impairment and indoor injury are independent risk factors for preoperative and postoperative delirium.