Publications

2015

Fick DM, Inouye SK, Guess J, et al. Preliminary development of an ultrabrief two-item bedside test for delirium.. Journal of hospital medicine. 2015;10(10):645-50. doi:10.1002/jhm.2418

BACKGROUND: Delirium is common, morbid, and costly, yet is greatly under-recognized among hospitalized older adults.

OBJECTIVE: To identify the best single and pair of mental status test items that predict the presence of delirium.

DESIGN, SETTING: Diagnostic test evaluation study that enrolled medicine inpatients aged 75 years or older at an academic medical center.

METHODS: Patients underwent a clinical reference standard assessment involving a patient interview, medical record review, and interviews with family members and nurses to determine the presence or absence of Diagnostic and Statistical Manual of Mental Disorders, 4th Edition defined delirium. Participants also underwent the three-dimensional Confusion Assessment Method (3D-CAM), a brief, validated assessment for delirium. Individual items and pairs of items from the 3D-CAM were evaluated to determine sensitivity and specificity relative to the reference standard delirium diagnosis.

RESULTS: Of the 201 participants (mean age 84 years, 62% female), 42 (21%) had delirium based on the clinical reference standard. The single item with the best test characteristics was "months of the year backwards" with a sensitivity of 83% (95% confidence interval [CI]: 69%-93%) and specificity of 69% (95% CI: 61%-76%). The best 2-item screen was the combination of "months of the year backwards" and "what is the day of the week?" with a sensitivity of 93% (95% CI: 81%-99%) and specificity of 64% (95% CI: 56%-70%).

CONCLUSIONS: We identified a single item with >80% and pair of items with >90% sensitivity for delirium. If validated prospectively, these items will serve as an initial innovative screening step for delirium identification in hospitalized older adults.

Wu Y, Shi Z, Wang M, et al. Different MMSE Score Is Associated with Postoperative Delirium in Young-Old and Old-Old Adults.. PloS one. 2015;10(10):e0139879. doi:10.1371/journal.pone.0139879

BACKGROUND: Postoperative delirium is one of the most common postoperative complications in geriatric patients. Mini-mental state examination (MMSE) assesses cognitive function in patients and is associated with postoperative delirium. However, whether there is an age-dependent relationship between preoperative MMSE score and postoperative delirium remains unknown.

METHODS: We therefore set out to investigate the association between preoperative MMSE score and postoperative delirium in young-old (≤80 year-old, 75.46±4.69 years, 27.0% male, n = 63) and old-old (>80 year-old, 84.51±3.46 years, 20.9% male, n = 67) participants, who had repairs of hip fractures under general anesthesia. The Confusion Assessment Method and Memorial Delirium Assessment Scale were administrated before surgery, and on the first, second and fourth days after surgery, to assess the incidence and severity of the delirium, respectively. A receiver operating characteristic curve analysis was used to calculate the optimal cutoff score of MMSE in predicting postoperative delirium.

RESULTS: Thirty-four (26.2%) of 130 patients (80.12±6.12 years, 23.8% male) developed postoperative delirium. Preoperative MMSE scores were negatively associated with higher incidences and greater severity of postoperative delirium. The optimal cutoff scores of MMSE associated with postoperative delirium for young-old and old-old participants were 18.4 and 21.4, with a sensitivity of 60% and 83.8%, and a specificity of 92.5% and 62.8%, respectively.

CONCLUSION: The data demonstrated the optimal cutoff score of MMSE associated with postoperative delirium in young-old adults might be lower than that in old-old adults. Pending further investigation, these findings suggest that the association between preoperative MMSE score and postoperative delirium is age-dependent.

Saczynski JS, Inouye SK, Guess J, et al. The Montreal Cognitive Assessment: Creating a Crosswalk with the Mini-Mental State Examination.. Journal of the American Geriatrics Society. 2015;63(11):2370-4. doi:10.1111/jgs.13710

OBJECTIVES: To establish Montreal Cognitive Assessment (MoCA) scores that correspond to well-established cut-points on the Mini-Mental State Examination (MMSE).

DESIGN: Cross-sectional observational study.

SETTING: General medical service of a large teaching hospital.

PARTICIPANTS: Individuals aged 75 and older (N = 199; mean age 84, 63% female).

MEASUREMENTS: The MoCA (range 0-30) and the MMSE (range 0-30) were administered within 2 hours of each other. The Abbreviated MoCA (A-MoCA; range 0-22) was calculated from the full MoCA. Scores from the three tests were analyzed using equipercentile equating, a statistical method for determining comparable scores on different tests of a similar construct by estimating percentile equivalents.

RESULTS: MoCA scores were lower (mean 19.3 ± 5.8) than MMSE scored (mean 24.1 ± 6.6). Traditional MMSE cut-points of 27 for mild cognitive impairment and 23 for dementia corresponded to MoCA scores of 23 and 17, respectively.

CONCLUSION: Scores on the full and abbreviated versions of the MoCA can be linked directly to the MMSE. The MoCA may be more sensitive to changes in cognitive performance at higher levels of functioning.

Schmitt EM, Saczynski JS, Kosar CM, et al. The Successful Aging after Elective Surgery (SAGES) Study: Cohort Description and Data Quality Procedures.. Journal of the American Geriatrics Society. 2015;63(12):2463-2471. doi:10.1111/jgs.13793

BACKGROUND/OBJECTIVES: Delirium is the most common complication of major elective surgery in older patients. The Successful Aging after Elective Surgery (SAGES) study was designed to examine novel risk factors and long-term outcomes associated with delirium. This report describes the cohort, quality assurance procedures, and results.

DESIGN: Long-term prospective cohort study.

SETTING: Three academic medical centers.

PARTICIPANTS: A total of 566 patients age 70 and older without recognized dementia scheduled for elective major surgery.

MEASUREMENTS: Participants were assessed preoperatively, daily during hospitalization, and at variable monthly intervals for up to 36 months post-discharge. Delirium was assessed in hospital by trained study staff. Study outcomes included cognitive and physical function. Novel risk factors for delirium were assessed including genetic and plasma biomarkers, neuroimaging markers, and cognitive reserve markers. Interrater reliability (kappa and weighted kappa) was assessed for key variables in 119 of the patient interviews.

RESULTS: Participants were an average of 77 years old and 58% were female. The majority of patients (81%) were undergoing orthopedic surgery and 24% developed delirium post-operatively. Over 95% of eligible patients were followed for 18 months. There was >99% capture of key study outcomes (cognitive and functional status) at every study interview and interrater reliability was high (weighted kappas for delirium = 0.92 and for overall cognitive and functional outcomes = 0.94 -1.0). Completion rates for plasma biomarkers (4 timepoints) were 95%-99% and for neuroimaging (one year follow-up) was 86%.

CONCLUSION: The SAGES study will contribute to the understanding of novel risk factors, pathophysiology and long-term outcomes of delirium. This manuscript describes the cohort and data quality procedures, and will serve as a reference source for future studies based on SAGES.

2014

Herzig SJ, Rothberg MB, Cheung M, Ngo LH, Marcantonio ER. Opioid utilization and opioid-related adverse events in nonsurgical patients in US hospitals.. Journal of hospital medicine. 2014;9(2):73-81. doi:10.1002/jhm.2102

BACKGROUND: Recent studies in the outpatient setting have demonstrated high rates of opioid prescribing and overdose-related deaths. Prescribing practices in hospitalized patients are unexamined.

OBJECTIVE: To investigate patterns and predictors of opioid utilization in nonsurgical admissions to US hospitals, variation in use, and the association between hospital-level use and rates of severe opioid-related adverse events.

DESIGN, SETTING, AND PATIENTS: Adult nonsurgical admissions to 286 US hospitals.

MEASUREMENTS: Opioid exposure and severe opioid-related adverse events during hospitalization, defined using hospital charges and International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes.

RESULTS: Of 1.14 million admissions, opioids were used in 51%. The mean ± standard deviation daily dose received in oral morphine equivalents was 68 ± 185 mg; 23% of exposed received a total daily dose of ≥100 mg oral morphine equivalents. Opioid-prescribing rates ranged from 5% in the lowest-prescribing hospital to 72% in the highest-prescribing hospital (mean, 51% ± 10%). After adjusting for patient characteristics, the adjusted opioid-prescribing rates ranged from 33% to 64% (mean, 50% ± standard deviation 4%). Among exposed, 0.60% experienced severe opioid-related adverse events. Hospitals with higher opioid-prescribing rates had higher adjusted relative risk of a severe opioid-related adverse event per patient exposed (relative risk: 1.23 [1.14-1.33] for highest-prescribing compared with lowest-prescribing quartile).

CONCLUSIONS: The majority of hospitalized nonsurgical patients were exposed to opioids, often at high doses. Hospitals that used opioids most frequently had increased adjusted risk of a severe opioid-related adverse event per patient exposed. Interventions to standardize and enhance the safety of opioid prescribing in hospitalized patients should be investigated.

Schonberg MA, Kistler CE, Nekhlyudov L, et al. Evaluation of a Mammography Screening Decision Aid for Women Aged 75 and Older: Protocol for a Cluster-randomized Controlled Trial.. Journal of clinical trials. 2014;4:191.

PURPOSE: There is insufficient evidence to recommend mammography for women >75 years. Guidelines recommend that older women be informed of the uncertainty of benefit and potential for harm, especially for women with short life expectancy. However, few older women are informed of harms of screening and many with short life expectancy are screened. Therefore, we aim to test whether a mammography screening decision aid (DA) for women >75 years affects their use of mammography, particularly for women with <10 year life expectancy.

METHODS/DESIGN: The DA is a self-administered pamphlet that includes information on screening outcomes, tailored information on breast cancer risk, health, life expectancy, and competing mortality risks, and includes a values clarification exercise. We are conducting a large cluster randomized controlled trial (RCT) of the DA with the primary care provider (PCP) as the unit of randomization to evaluate its efficacy. We plan to recruit 550 women 75-89 years from 100 PCPs to receive either the mammography DA or a pamphlet on home safety for older adults (control arm) before a visit with their PCP, depending on their PCP's randomization assignment. The primary outcome is receipt of mammography screening assessed through chart abstraction. Secondary outcomes include effect of the DA on older women's screening intentions, knowledge, and decisional conflict, and on documented discussions about mammography by their PCPs. We will recruit women from 5 Boston-based primary care practices (3 community-based internal medicine practices and 2 academic practices), and 2 North Carolina-based academic primary care practices.

DISCUSSION: It is essential that we test the DA in a large RCT to determine if it is efficacious and to substantiate the need for broad translation into clinical practice. Our DA has the potential to improve health care utilization and care in a manner dictated by patient preferences.

Schonberg MA, Hamel MB, Davis RB, et al. Development and evaluation of a decision aid on mammography screening for women 75 years and older.. JAMA internal medicine. 2014;174(3):417-24. doi:10.1001/jamainternmed.2013.13639

IMPORTANCE: Guidelines recommend that women 75 years and older should be informed of the benefits and risks of mammography before being screened. However, few are adequately informed.

OBJECTIVES: To develop and evaluate a mammography screening decision aid (DA) for women 75 years and older.

DESIGN: We designed the DA using international standards. Between July 14, 2010, and April 10, 2012, participants completed a pretest survey and read the DA before an appointment with their primary care physician. They completed a posttest survey after their appointment. Medical records were reviewed for follow-up information.

SETTING AND PARTICIPANTS: Boston, Massachusetts, academic primary care practice. Eligible women were aged 75 to 89 years, English speaking, had not had a mammogram in 9 months but had been screened within the past 3 years, and did not have a history of dementia or invasive or noninvasive breast cancer. Of 84 women approached, 27 declined to participate, 12 were unable to complete the study for logistical reasons, and 45 participated.

INTERVENTIONS: The DA includes information on breast cancer risk, life expectancy, competing mortality risks, possible outcomes of screening, and a values clarification exercise.

MAIN OUTCOMES AND MEASURES: Knowledge of the benefits and risks of screening, decisional conflict, and screening intentions; documentation in the medical record of a discussion of the risks and benefits of mammography with a primary care physician within 6 months; and the receipt of screening within 15 months. We used the Wilcoxon signed rank test and McNemar test to compare pretest-posttest information.

RESULTS: The median age of participants was 79 years, 69% (31 of 45) were of non-Hispanic white race/ethnicity, and 60% (27 of 45) had attended at least some college. Comparison of posttest results with pretest results demonstrated 2 findings. First, knowledge of the benefits and risks of screening improved (P < .001). Second, fewer participants intended to be screened (56% [25 of 45] afterward compared with 82% [37 of 45] before, P = .03). Decisional conflict declined but not significantly (P = .10). In the following 6 months, 53% (24 of 45) of participants had a primary care physician note that documented the discussion of the risks and benefits of screening compared with 11% (5 of 45) in the previous 5 years (P < .001). While 84% (36 of 43) had been screened within 2 years of participating, 60% (26 of 43) were screened within 15 months after participating (≥ 2 years since their last mammogram) (P = .01). Overall, 93% (42 of 45) found the DA helpful.

CONCLUSIONS AND RELEVANCE: A DA may improve older women's decision making about mammography screening.

Xu Z, Dong Y, Wang H, et al. Age-dependent postoperative cognitive impairment and Alzheimer-related neuropathology in mice.. Scientific reports. 2014;4:3766. doi:10.1038/srep03766

Post-operative cognitive dysfunction (POCD) is associated with increased cost of care, morbidity, and mortality. However, its pathogenesis remains largely to be determined. Specifically, it is unknown why elderly patients are more likely to develop POCD and whether POCD is dependent on general anesthesia. We therefore set out to investigate the effects of peripheral surgery on the cognition and Alzheimer-related neuropathology in mice with different ages. Abdominal surgery under local anesthesia was established in the mice. The surgery induced post-operative elevation in brain β-amyloid (Aβ) levels and cognitive impairment in the 18 month-old wild-type and 9 month-old Alzheimer's disease transgenic mice, but not the 9 month-old wild-type mice. The Aβ accumulation likely resulted from elevation of beta-site amyloid precursor protein cleaving enzyme and phosphorylated eukaryotic translation initiation factor 2α. γ-Secretase inhibitor compound E ameliorated the surgery-induced brain Aβ accumulation and cognitive impairment in the 18 month-old mice. These data suggested that the peripheral surgery was able to induce cognitive impairment independent of general anesthesia, and that the combination of peripheral surgery with aging- or Alzheimer gene mutation-associated Aβ accumulation was needed for the POCD to occur. These findings would likely promote more research to investigate the pathogenesis of POCD.