Person: Inouye, Sharon
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Inouye
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Sharon
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Inouye, Sharon
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Publication The Short-Term and Long-Term Relationship Between Delirium and Cognitive Trajectory in Older Surgical Patients(Wiley, 2016-07) Inouye, Sharon; Marcantonio, Edward; Kosar, Cyrus M.; Tommet, Douglas; Schmitt, Eva M.; Travison, Thomas; Saczynski, Jane S.; Ngo, Long; Alsop, David; Jones, Richard N.INTRODUCTION Since the relationship between delirium and long-term cognitive decline has not been well-explored, we evaluated this association in a prospective study. METHODS SAGES is an on-going study involving 560 adults age 70+ without dementia scheduled for major surgery. Delirium was assessed daily in the postoperative period using the Confusion Assessment Method. General Cognitive Performance (GCP) and the Informant Questionnaire for Cognitive Decline in the Elderly (IQCODE) were assessed preoperatively then repeatedly out to 36 months. RESULTS On average, patients with post-operative delirium had significantly lower preoperative cognitive performance, greater immediate (1 month) impairment, equivalent recovery at 2 months, and significantly greater long-term cognitive decline relative to the non-delirium group. Proxy reports corroborated the clinical significance of the long-term cognitive decline in delirious patients. DISCUSSION Cognitive decline following surgery is biphasic and accelerated among persons with delirium. The pace of long-term decline is similar to that seen with Mild Cognitive Impairment.Publication Association Between Hospital Readmission and Acute and Sustained Delays in Functional Recovery During 18 Months After Elective Surgery: The Successful Aging after Elective Surgery Study(Wiley, 2017-01) Pisani, Margaret A.; Albuquerque, Asha; Marcantonio, Edward; Jones, Richard N.; Gou, Ray Yun; Fong, Tamara; Schmitt, Eva M.; Tommet, Douglas; Isaza Aizpurua, Ilean I.; Alsop, David; Inouye, Sharon; Travison, ThomasObjectives: To examine the effect of hospital readmission on functional recovery after elective surgery in older adults. Design: Prospective cohort of individuals aged 70 and older undergoing elective surgery, enrolled from June 2010 to August 2013. Setting: Two academic medical centers. Participants: Community-dwelling older adults (N = 566; mean age ± standard deviation 77 ± 5) undergoing major elective surgery and expected to be admitted for at least 3 days. Measurements: Readmission was assessed in multiple interviews with participants and family members over 18 months and validated against medical record review. Physical function was assessed according to ability to perform instrumental activities of daily living (IADLs) and activities of daily living (ADL), Medical Outcomes Study 12-item Short-Form Survey Physical Component Summary score, and a standardized functional composite. Results: Two hundred fifty-five (45%) participants experienced 503 readmissions. Readmissions were associated with delays in functional recovery in all measures of physical function. Having two or more readmissions over 18 months was associated with persistent and significantly greater risk of IADL dependence (relative risk (RR) = 1.8, 95% confidence interval (CI) = 1.5-2.3) and ADL dependence (RR = 3.3, 95% CI = 1.7-6.4). Degree of functional impairment increased progressively with number of readmissions. Readmissions within 2 months resulted in delayed functional recovery to baseline by 18 months, and readmissions between 12 and 18 months after surgery resulted in loss of functional recovery previously achieved. Conclusion: Readmission after elective surgery may contribute to delays in functional recovery and persistent functional deficits in older adults.Publication Alzheimer's-Related Cortical Atrophy Is Associated With Postoperative Delirium Severity in Persons Without Dementia(Elsevier BV, 2017-11) Racine, Annie M.; Fong, Tamara; Travison, Thomas; Jones, Richard N.; Gou, Yun; Vasunilashorn, Sarinnapha; Marcantonio, Edward; Alsop, David; Inouye, Sharon; Dickerson, BradfordPatients with dementia due to Alzheimer’s disease (AD) have increased risk of developing delirium. This study investigated the relationship between a magnetic resonance imaging (MRI)-derived biomarker associated with preclinical AD and postoperative delirium. Participants were older adults (≥70 years) without dementia who underwent preoperative MRI and elective surgery. Delirium incidence and severity were evaluated daily during hospitalization. Cortical thickness was averaged across a published set of a priori brain regions to derive a measure known as the “AD signature.” Logistic and linear regression was used, respectively, to test whether the AD signature was associated with delirium incidence in the entire sample (N=145) or with the severity of delirium among those who developed delirium (N=32). Thinner cortex in the AD signature did not predict incidence of delirium (odds ratio=1.15, p=.38), but was associated with greater delirium severity among those who developed delirium (b=−1.2, p=.014). These results suggest that thinner cortices, perhaps reflecting underlying neurodegeneration due to preclinical AD, may serve as a vulnerability factor that increases severity once delirium occurs.Publication Systemic Inflammation Impairs Attention and Cognitive Flexibility but Not Associative Learning in Aged Rats: Possible Implications for Delirium(Frontiers Media S.A., 2014) Culley, Deborah; Snayd, Mary; Baxter, Mark G.; Xie, Zhongcong; Lee, In Ho; Rudolph, James; Inouye, Sharon; Marcantonio, Edward; Crosby, GregoryDelirium is a common and morbid condition in elderly hospitalized patients. Its pathophysiology is poorly understood but inflammation has been implicated based on a clinical association with systemic infection and surgery and preclinical data showing that systemic inflammation adversely affects hippocampus-dependent memory. However, clinical manifestations and imaging studies point to abnormalities not in the hippocampus but in cortical circuits. We therefore tested the hypothesis that systemic inflammation impairs prefrontal cortex function by assessing attention and executive function in aged animals. Aged (24-month-old) Fischer-344 rats received a single intraperitoneal injection of lipopolysaccharide (LPS; 50 μg/kg) or saline and were tested on the attentional set-shifting task (AST), an index of integrity of the prefrontal cortex, on days 1–3 post-injection. Plasma and frontal cortex concentrations of the cytokine TNFα and the chemokine CCL2 were measured by ELISA in separate groups of identically treated, age-matched rats. LPS selectively impaired reversal learning and attentional shifts without affecting discrimination learning in the AST, indicating a deficit in attention and cognitive flexibility but not learning globally. LPS increased plasma TNFα and CCL2 acutely but this resolved within 24–48 h. TNFα in the frontal cortex did not change whereas CCL2 increased nearly threefold 2 h after LPS but normalized by the time behavioral testing started 24 h later. Together, our data indicate that systemic inflammation selectively impairs attention and executive function in aged rodents and that the cognitive deficit is independent of concurrent changes in frontal cortical TNFα and CCL2. Because inattention is a prominent feature of clinical delirium, our data support a role for inflammation in the pathogenesis of this clinical syndrome and suggest this animal model could be useful for studying that relationship further.Publication Developing and implementing an integrated delirium prevention system of care: a theory driven, participatory research study(BioMed Central, 2013) Godfrey, Mary; Smith, Jane; Green, John; Cheater, Francine; Inouye, Sharon; Young, John BBackground: Delirium is a common complication for older people in hospital. Evidence suggests that delirium incidence in hospital may be reduced by about a third through a multi-component intervention targeted at known modifiable risk factors. We describe the research design and conceptual framework underpinning it that informed the development of a novel delirium prevention system of care for acute hospital wards. Particular focus of the study was on developing an implementation process aimed at embedding practice change within routine care delivery. Methods: We adopted a participatory action research approach involving staff, volunteers, and patient and carer representatives in three northern NHS Trusts in England. We employed Normalization Process Theory to explore knowledge and ward practices on delirium and delirium prevention. We established a Development Team in each Trust comprising senior and frontline staff from selected wards, and others with a potential role or interest in delirium prevention. Data collection included facilitated workshops, relevant documents/records, qualitative one-to-one interviews and focus groups with multiple stakeholders and observation of ward practices. We used grounded theory strategies in analysing and synthesising data. Results: Awareness of delirium was variable among staff with no attention on delirium prevention at any level; delirium prevention was typically neither understood nor perceived as meaningful. The busy, chaotic and challenging ward life rhythm focused primarily on diagnostics, clinical observations and treatment. Ward practices pertinent to delirium prevention were undertaken inconsistently. Staff welcomed the possibility of volunteers being engaged in delirium prevention work, but existing systems for volunteer support were viewed as a barrier. Our evolving conception of an integrated model of delirium prevention presented major implementation challenges flowing from minimal understanding of delirium prevention and securing engagement of volunteers alongside practice change. The resulting Prevention of Delirium (POD) Programme combines a multi-component delirium prevention and implementation process, incorporating systems and mechanisms to introduce and embed delirium prevention into routine ward practices. Conclusions: Although our substantive interest was in delirium prevention, the conceptual and methodological strategies pursued have implications for implementing and sustaining practice and service improvements more broadly. Study registration ISRCTN65924234Publication Prevention of delirium (POD) for older people in hospital: study protocol for a randomised controlled feasibility trial(BioMed Central, 2015) Young, John; Cheater, Francine; Collinson, Michelle; Fletcher, Marie; Forster, Anne; Godfrey, Mary; Green, John; Anwar, Shamaila; Hartley, Suzanne; Hulme, Claire; Inouye, Sharon; Meads, David; Santorelli, Gillian; Siddiqi, Najma; Smith, Jane; Teale, Elizabeth; Farrin, Amanda JBackground: Delirium is the most frequent complication among older people following hospitalisation. Delirium may be prevented in about one-third of patients using a multicomponent intervention. However, in the United Kingdom, the National Health Service has no routine delirium prevention care systems. We have developed the Prevention of Delirium Programme, a multicomponent delirium prevention intervention and implementation process. We have successfully carried out a pilot study to test the feasibility and acceptability of implementation of the programme. We are now undertaking preliminary testing of the programme. Methods/Design The Prevention of Delirium Study is a multicentre, cluster randomised feasibility study designed to explore the potential effectiveness and cost-effectiveness of the Prevention of Delirium Programme. Sixteen elderly care medicine and orthopaedic/trauma wards in eight National Health Service acute hospitals will be randomised to receive the Prevention of Delirium Programme or usual care. Patients will be eligible for the trial if they have been admitted to a participating ward and are aged 65 years or over. The primary objectives of the study are to provide a preliminary estimate of the effectiveness of the Prevention of Delirium Programme as measured by the incidence of new onset delirium, assess the variability of the incidence of new-onset delirium, estimate the intracluster correlation coefficient and likely cluster size, assess barriers to the delivery of the Prevention of Delirium Programme system of care, assess compliance with the Prevention of Delirium Programme system of care, estimate recruitment and follow-up rates, assess the degree of contamination due to between-ward staff movements, and investigate differences in financial costs and benefits between the Prevention of Delirium Programme system of care and standard practice. Secondary objectives are to investigate differences in the number, severity and length of delirium episodes (including persistent delirium); length of stay in hospital; in-hospital mortality; destination at discharge; health-related quality of life and health resource use; physical and social independence; anxiety and depression; and patient experience. Discussion This feasibility study will be used to gather data to inform the design of a future definitive randomised controlled trial. Trial registration ISRCTN01187372. Registered 13 March 2014.Publication Phenomenological Subtypes of Delirium in Older Persons: Patterns, Prevalence, and Prognosis(Elsevier BV, 2009) Yang, Frances Margaret; Marcantonio, Edward; Inouye, Sharon; Kiely, Dan K.; Rudolph, James; Fearing, Michael A.; Jones, Richard NormanPublication Persistent Delirium Predicts Greater Mortality(Wiley-Blackwell, 2009) Kiely, Dan K.; Marcantonio, Edward; Inouye, Sharon; Shaffer, Michele L.; Bergmann, Margaret A.; Yang, Frances Margaret; Fearing, Michael A.; Jones, Richard NormanOBJECTIVES: To examine the association between persistent delirium and 1-year mortality in newly admitted post-acute care (PAC) facility patients with delirium who were followed regardless of residence. DESIGN: Observational cohort study. SETTING: Eight greater-Boston skilled nursing facilities specializing in PAC. PARTICIPANTS: Four hundred twelve PAC patients with delirium at admission after an acute hospitalization. MEASUREMENTS: Assessments were done at baseline and four follow-up times: 2, 4, 12, and 26 weeks. Delirium, defined using the Confusion Assessment Method, was assessed, as were factors used as covariates in analyses: age, sex, comorbidity, functional status, and dementia. The outcome was 1-year mortality determined according to the National Death Index and corroborated using medical record and proxy telephone interview. RESULTS: Nearly one-third of subjects remained delirious at 6 months. Cumulative 1-year mortality was 39%. Independent of age, sex, comorbidity, functional status, and dementia, subjects with persistent delirium were 2.9 (95% confidence interval=1.9–4.4) times as likely to die during the 1-year follow-up as subjects whose delirium resolved. This association remained strong and significant in groups with and without dementia. Additionally, when delirium resolved, the risk of death diminished thereafter. CONCLUSION: In patients who were delirious at the time of PAC admission, persistent delirium was a significant independent predictor of 1-year mortality.Publication Derivation and Validation of a Preoperative Prediction Rule for Delirium After Cardiac Surgery(Ovid Technologies (Wolters Kluwer Health), 2008) Rudolph, James; Jones, Richard Norman; Levkoff, Sue; Rockett, C.; Inouye, Sharon; Sellke, F. W.; Khuri, S. F.; Lipsitz, Lewis; Ramlawi, B.; Levitsky, Sidney; Marcantonio, EdwardBackground— Delirium is a common outcome after cardiac surgery. Delirium prediction rules identify patients at risk for delirium who may benefit from targeted prevention strategies, early identification, and treatment of underlying causes. The purpose of the present prospective study was to develop a prediction rule for delirium in a cardiac surgery cohort and to validate it in an independent cohort. Methods and Results— Prospectively, cardiac surgery patients ≥60 years of age were enrolled in a derivation sample (n=122) and then a validation sample (n=109). Beginning on the second postoperative day, patients underwent a standardized daily delirium assessment, and delirium was diagnosed according to the confusion assessment method. Delirium occurred in 63 (52%) of the derivation cohort patients. Multivariable analysis identified 4 variables independently associated with delirium: prior stroke or transient ischemic attack, Mini Mental State Examination score, abnormal serum albumin, and the Geriatric Depression Scale. Points were assigned to each variable: Mini Mental State Examination ≤23 received 2 points, and Mini Mental State Examination score of 24 to 27 received 1 point; Geriatric Depression Scale >4, prior stroke/transient ischemic attack, and abnormal albumin received 1 point each. In the derivation sample, the cumulative incidence of delirium for point levels of 0, 1, 2, and ≥3 was 19%, 47%, 63%, and 86%, respectively (C statistic, 0.74). The corresponding incidence of delirium in the validation sample was 18%, 43%, 60%, and 87%, respectively (C statistic, 0.75). Conclusions— Delirium occurs frequently after cardiac surgery. Using 4 preoperative characteristics, clinicians can determine cardiac surgery patients’ risk for delirium. Patients at higher delirium risk could be candidates for close postoperative monitoring and interventions to prevent delirium.Publication Benzodiazepine and Opioid Use and the Duration of Intensive Care Unit Delirium in an Older Population*(Ovid Technologies (Wolters Kluwer Health), 2009) Inouye, Sharon; Pisani, Margaret; Murphy, Terrence; Araujo, Katy; Slattum, Patricia; Van Ness, PeterObjective: There is a high prevalence of delirium in older medical intensive care unit (ICU) patients and delirium is associated with adverse outcomes. We need to identify modifiable risk factors for delirium, such as medication use, in the ICU. The objective of this study was to examine the impact of benzodiazepine or opioid use on the duration of ICU delirium in an older medical population. Design: Prospective cohort study. Setting: Fourteen-bed medical intensive care unit in an urban university teaching hospital. Patients: 304 consecutive admissions age 60 and older. Interventions: None. Main Outcome Measurements: The main outcome measure was duration of ICU delirium, specifically the first episode of ICU delirium. Patients were assessed daily for delirium with the Confusion Assessment Method for the ICU and a validated chart review method. Our main predictor was receiving benzodiazepines or opioids during ICU stay. A multivariable model was developed using Poisson rate regression. Results: Delirium occurred in 239 of 304 patients (79%). The median duration of ICU delirium was 3 days with a range of 1–33 days. In a multivariable regression model, receipt of a benzodiazepine or opioid (rate ratio [RR] 1.64, 95% confidence interval [CI] 1.27–2.10) was associated with increased delirium duration. Other variables associated with delirium duration in this analysis include preexisting dementia (RR 1.19, 95% CI 1.07–1.33), receipt of haloperidol (RR 1.35, 95% CI 1.21–1.50), and severity of illness (RR 1.01, 95% CI 1.00–1.02). Conclusions: The use of benzodiazepines or opioids in the ICU is associated with longer duration of a first episode of delirium. Receipt of these medications may represent modifiable risk factors for delirium. Clinicians caring for ICU patients should carefully evaluate the need for benzodiazepines, opioids, and haloperidol.