Publications

BACKGROUND: Cognitive impairment is a well-recognized risk factor for delirium. Our goal was to determine whether the level of cognitive performance across the nondemented cognitive ability spectrum is correlated with delirium risk and to gauge the importance of cognition relative to other known risk factors for delirium.

METHODS: The Successful Aging after Elective Surgery study enrolled 566 adults aged ≥70 years scheduled for major surgery. Patients were assessed preoperatively and daily during hospitalization for the occurrence of delirium using the Confusion Assessment Method. Cognitive function was assessed preoperatively with an 11-test neuropsychological battery combined into a composite score for general cognitive performance (GCP). We examined the risk for delirium attributable to GCP, as well as demographic factors, vocabulary ability, and informant-rated cognitive decline, and compared the strength of association with risk factors identified in a previously published delirium prediction rule for delirium.

RESULTS: Delirium occurred in 135 (24%) patients. Lower GCP score was strongly and linearly predictive of delirium risk (relative risk = 2.0 per each half standard deviation difference in GCP score, 95% confidence interval, 1.5-2.5). This effect was not attenuated by statistical adjustment for demographics, vocabulary ability, and informant-rated cognitive decline. The effect was stronger than, and largely independent from, both standard delirium risk factors and comorbidity.

CONCLUSION: Risk of delirium is linearly and strongly related to presurgical cognitive performance level even at levels above the population median, which would be considered unimpaired.

BACKGROUND: Frailty assessment may inform surgical risk and prognosis not captured by conventional surgical risk scores.

PURPOSE: To evaluate the evidence for various frailty instruments used to predict mortality, functional status, or major adverse cardiovascular and cerebrovascular events (MACCEs) in older adults undergoing cardiac surgical procedures.

DATA SOURCES: MEDLINE and EMBASE (without language restrictions), from their inception to 2 May 2016.

STUDY SELECTION: Cohort studies evaluating the association between frailty and mortality or functional status at 6 months or later in patients aged 60 years or older undergoing major or minimally invasive cardiac surgical procedures.

DATA EXTRACTION: 2 reviewers independently extracted study data and assessed study quality.

DATA SYNTHESIS: Mobility, disability, and nutrition were frequently assessed domains of frailty in both types of procedures. In patients undergoing major procedures (n = 18 388; 8 studies), 9 frailty instruments were evaluated. There was moderate-quality evidence to assess mobility or disability and very-low- to low-quality evidence for using a multicomponent instrument to predict mortality or MACCEs. No studies examined functional status. In patients undergoing minimally invasive procedures (n = 5177; 17 studies), 13 frailty instruments were evaluated. There was moderate- to high-quality evidence for assessing mobility to predict mortality or functional status. Several multicomponent instruments predicted mortality, functional status, or MACCEs, but the quality of evidence was low to moderate. Multicomponent instruments that measure different frailty domains seemed to outperform single-component ones.

LIMITATION: Heterogeneity of frailty assessment, limited generalizability of multicomponent frailty instruments, few validated frailty instruments, and potential publication bias.

CONCLUSION: Frailty status, assessed by mobility, disability, and nutritional status, may predict mortality at 6 months or later after major cardiac surgical procedures and functional decline after minimally invasive cardiac surgery.

PRIMARY FUNDING SOURCE: National Institute on Aging and National Heart, Lung, and Blood Institute.

OBJECTIVES: To apply the Frailty Phenotype (FP) and Frailty Index (FI) before major elective orthopedic surgery to categorize frailty status and assess associations with postoperative outcomes.

DESIGN: Prospective cohort study.

SETTING: Two tertiary hospitals in Boston, Massachusetts.

PARTICIPANTS: Individuals aged 70 and older undergoing scheduled orthopedic surgery enrolled in the Successful Aging after Elective Surgery (SAGES) Study (N = 415).

MEASUREMENTS: Preoperative evaluation included assessment of frailty using the FP and FI. The weighted kappa statistic was used to determine concordance between the two frailty measures and multivariable modeling to determine associations between each measure and postoperative complications, postoperative length of stay (LOS) of longer than 5 days, discharge to postacute institutional care (PAC), and 300 day readmission.

RESULTS: Frailty was highly prevalent (FP, 35%; FI, 41%). There was moderate concordance between the FP and FI (κ = 0.42, 95% confidence interval (CI) 0.36-0.49). When using the FP, being prefrail predicted greater risk of complications (relative risk (RR) = 1.6, 95% CI = 1.1-2.1) and discharge to PAC (RR = 1.8, 95% CI = 1.2-2.9) than being robust, and being frail predicted more complications (RR = 1.7, 95% CI = 1.1-2.1), LOS longer than 5 days (RR = 3.1, 95% CI = 1.1-8.8), and discharge to PAC (RR = 2.3 95% CI = 1.4-3.7). When using FI, being prefrail predicted LOS longer than 5 days (RR = 2.1, 95% CI = 1.0-4.8) and discharge to PAC (RR = 1.5, 95% CI = 1.4-2.1), as did being frail (RR = 1.9, 95% CI = 1.4-2.5; RR = 3.1, 95% CI = 1.4-6.8, respectively). The other outcomes were not significantly associated with frailty status.

CONCLUSION: FP and FI predict postoperative outcomes after major elective orthopedic surgery and should be considered for preoperative risk stratification.

PURPOSE: Accurate risk assessment is necessary for decision-making around breast cancer prevention. We aimed to develop a breast cancer prediction model for postmenopausal women that would take into account their individualized competing risk of non-breast cancer death.

METHODS: We included 73,066 women who completed the 2004 Nurses' Health Study (NHS) questionnaire (all ≥57 years) and followed participants until May 2014. We considered 17 breast cancer risk factors (health behaviors, demographics, family history, reproductive factors) and 7 risk factors for non-breast cancer death (comorbidities, functional dependency) and mammography use. We used competing risk regression to identify factors independently associated with breast cancer. We validated the final model by examining calibration (expected-to-observed ratio of breast cancer incidence, E/O) and discrimination (c-statistic) using 74,887 subjects from the Women's Health Initiative Extension Study (WHI-ES; all were ≥55 years and followed for 5 years).

RESULTS: Within 5 years, 1.8 % of NHS participants were diagnosed with breast cancer (vs. 2.0 % in WHI-ES, p = 0.02), and 6.6 % experienced non-breast cancer death (vs. 5.2 % in WHI-ES, p < 0.001). Using a model selection procedure which incorporated the Akaike Information Criterion, c-statistic, statistical significance, and clinical judgement, our final model included 9 breast cancer risk factors, 5 comorbidities, functional dependency, and mammography use. The model's c-statistic was 0.61 (95 % CI [0.60-0.63]) in NHS and 0.57 (0.55-0.58) in WHI-ES. On average, our model under predicted breast cancer in WHI-ES (E/O 0.92 [0.88-0.97]).

CONCLUSIONS: We developed a novel prediction model that factors in postmenopausal women's individualized competing risks of non-breast cancer death when estimating breast cancer risk.

INTRODUCTION: Hip fractures occur 1.6 million times each year worldwide, with substantial associated mortality and losses of independence. At present, anaesthesia care for hip fracture surgery varies widely within and between countries, with general anaesthesia and spinal anaesthesia representing the 2 most common approaches. Limited randomised evidence exists regarding potential short-term or long-term differences in outcomes between patients receiving spinal or general anaesthesia for hip fracture surgery.

METHODS: The REGAIN trial (Regional vs General Anesthesia for Promoting Independence after Hip Fracture) is an international, multicentre, pragmatic randomised controlled trial. 1600 previously ambulatory patients aged 50 and older will be randomly allocated to receive either general or spinal anaesthesia for hip fracture surgery. The primary outcome is a composite of death or new inability to walk 10 feet or across a room at 60 days after randomisation, which will be assessed via telephone interview by staff who are blinded to treatment assignment. Secondary outcomes will be assessed by in-person assessment and medical record review for in-hospital end points (delirium; major inpatient medical complications and mortality; acute postoperative pain; patient satisfaction; length of stay) and by telephone interview for 60-day, 180-day and 365-day end points (mortality; disability-free survival; chronic pain; return to the prefracture residence; need for new assistive devices for ambulation; cognitive impairment).

ETHICS AND DISSEMINATION: The REGAIN trial has been approved by the ethics boards of all participating sites. Recruitment began in February 2016 and will continue until the end of 2019. Dissemination plans include presentations at scientific conferences, scientific publications, stakeholder engagement efforts and presentation to the public via lay media outlets.

TRIAL REGISTRATION NUMBER: NCT02507505, Pre-results.

OBJECTIVE: Obesity is associated with an increased risk of osteoarthritis (OA) of the knee. Emerging evidence suggests that adipokines, substances produced by adipose tissue, may play a role in the development of knee OA. The aim of this study was to determine whether the inflammatory adipokine leptin partially mediates the relationship between body mass index (BMI) and knee OA.

METHODS: We used baseline data from 653 participants who were 70 years of age or older in the population-based Maintenance of Balance, Independent Living, Intellect, and Zest in the Elderly Boston Study. Height and weight were measured, and participants were assessed for knee OA using clinical criteria. Serum leptin was measured using a microsphere-based assay.

RESULTS: The average BMI and the average serum leptin level were 27.5 kg/m(2) and 589 pM, respectively; the prevalence of knee OA was 24.7%. In regression models adjusted for covariates, we found that a 5-kg/m(2) increase in BMI was associated with 32% increased odds of knee OA (odds ratio [OR] 1.32, 95% confidence interval [95% CI] 1.10, 1.58); a 200-pM increase in serum leptin levels was associated with 11% increased odds of knee OA (OR 1.11, 95% CI 1.05, 1.17). The ratio of the standardized coefficients for the indirect:total effect calculated using the product-of-coefficients method was 0.49, suggesting that approximately half of the total effect of BMI on knee OA may be mediated by serum leptin. The estimated 95% CIs for the mediated effect suggest that this effect is statistically significant. Similarly, mediation analysis using a counterfactual approach suggested that the effect of leptin mediation was statistically significant.

CONCLUSION: We found that almost half of the association between elevated BMI and knee OA could be explained by the inflammatory adipokine leptin.

As part of the Choosing Wisely Campaign, the Society of Hospital Medicine identified reducing inappropriate use of acid-suppressive medication for stress ulcer prophylaxis as 1 of 5 key opportunities to improve the value of care for hospitalized patients. We designed a computerized clinical decision support intervention to reduce use of acid-suppressive medication for stress ulcer prophylaxis in hospitalized patients outside of the intensive care unit at an academic medical center. Using quasiexperimental interrupted time series analysis, we found that the decision support intervention resulted in a significant reduction in use of acid-suppressive medication with stress ulcer prophylaxis selected as the only indication, a nonsignificant reduction in overall use, and no change in use on discharge. We found low rates of use of acid-suppressive medication for the purpose of stress ulcer prophylaxis even before the intervention, and continuing preadmission medication was the most commonly selected indication throughout the study. Our results suggest that attention should be focused on both the inpatient and outpatient settings when designing future initiatives to improve the appropriateness of acid-suppressive medication use.

BACKGROUND: Difficulties with performance of functional activities may result from cognitive and/or physical impairments. To date, there has not been a clear delineation of the physical and cognitive demands of activities of daily living.

OBJECTIVES: To quantify the relative physical and cognitive demands required to complete typical functional activities in older adults.

DESIGN: Expert panel survey.

SETTING: Web-based platform.

PARTICIPANTS: Eleven experts from 8 academic medical centers and 300 community-dwelling elderly adults age 70 and older scheduled for elective noncardiac surgery from 2 academic medical centers.

METHODS: Sum scores of expert ratings were calculated and then validated against objective data collected from a prospective longitudinal study.

MAIN OUTCOME MEASUREMENTS: Correlation between expert ratings and objective neuropsychologic tests (memory, language, complex attention) and physical measures (gait speed and grip strength) for performance-based tasks.

RESULTS: Managing money, self-administering medications, using the telephone, and preparing meals were rated as requiring significantly more cognitive demand, whereas walking and transferring, moderately strenuous activities, and climbing stairs were assessed as more physically demanding. Largely cognitive activities correlated with objective neuropsychologic performance (r = 0.13-0.23, P < .05) and largely physical activities correlated with physical performance (r = 0.15-0.46, P < .05).

CONCLUSIONS: Quantifying the degree of cognitive and/or physical demand for completing a specific task adds an additional dimension to standard measures of functional assessment. This additional information may significantly influence decisions about rehabilitation, postacute care needs, treatment plans, and caregiver education.

Postoperative delirium is a common complication in older people and is associated with increased mortality, morbidity, institutionalization, and caregiver burden. Although delirium is an acute confusional state characterized by global impairments in attention and cognition, it has been implicated in permanent cognitive impairment and dementia. The pathogenesis of delirium and the mechanisms leading to these disabling consequences remain unclear. The present study is the first to address the potential predisposing role of brain morphologic changes toward postoperative delirium in a large prospective cohort of patients undergoing elective surgery using state-of-the-art magnetic resonance imaging (MRI) techniques conducted before admission. We investigated the association of MRI-derived quantitative measures of white-matter damage, global brain, and hippocampal volume with the incidence and severity of delirium. Presurgical white-matter hyperintensities (WMHs), whole brain, and hippocampal volume were measured in 146 consecutively enrolled subjects, ≥70 years old, without dementia who were undergoing elective surgery. These 3 presurgical MRI indices were tested as predictors of incidence and severity of subsequent delirium. Out of 146 subjects, 32 (22%) developed delirium. We found no statistically significant differences in WMH, whole brain, or hippocampal volume between subjects with and without delirium. Both unadjusted and adjusted (age, gender, vascular comorbidity, and general cognitive performance) regression analyses demonstrated no statistically significant association between any of the MRI measures with respect to delirium incidence or severity. In persons without dementia, preexisting cerebral WMHs, general and hippocampal atrophy may not predispose to postoperative delirium or worsen its severity.