Publications

2009

Schonberg MA, Marcantonio ER, Hamel MB. Perceptions of physician recommendations for joint replacement surgery in older patients with severe hip or knee osteoarthritis. Journal of the American Geriatrics Society. 2009;57(1):82-8. doi:10.1111/j.1532-5415.2008.02082.x

OBJECTIVES: To exfamine patient perceptions of physician discussions and recommendations about total joint arthroplasty (TJA).

DESIGN: Prospective cohort study.

SETTING: One large academic medical center and four community affiliates in Boston.

PARTICIPANTS: One hundred seventy-four patients aged 65 and older with severe osteoarthritis of the hip or knee for at least 6 months not controlled with medications.

MEASUREMENTS: Patient perceptions of primary care physicians' (PCPs) and orthopedists' communication about TJA were assessed at baseline for all patients and at 12 months for those who did not undergo surgery.

RESULTS: Of the 174 patients, 49 were aged 80 and older, 82% were non-Hispanic white, and 69% had knee osteoarthritis. Eighty-seven percent of individuals with baseline interviews and a PCP (142/163) reported that they had discussed their hip or knee arthritis with their PCP at baseline, and 26% (42/163) reported that their PCP discussed TJA as a treatment option. Of the 128 patients who saw an orthopedist, 65% reported that their orthopedist recommended TJA. Only 29% (51/174) of patients underwent TJA. Those who reported discussing TJA with their PCP at baseline were more likely to undergo TJA (P<.01). Thirty-six percent (44/123) of the patients who did not undergo TJA reported that their PCP discussed surgery as a treatment option at baseline or at 12month follow-up.

CONCLUSION: Patients with severe osteoarthritis of their hip or knee who report discussing TJA as a treatment option with their PCP are more likely to undergo TJA within the next year, but few older adults report having these discussions. Improvement is needed in communication between PCPs and patients about TJA.

Rudolph JL, Jones RN, Levkoff SE, et al. Derivation and validation of a preoperative prediction rule for delirium after cardiac surgery. Circulation. 2009;119(2):229-36. doi:10.1161/CIRCULATIONAHA.108.795260

BACKGROUND: 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 > or =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 < or =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 > or =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.

Schonberg MA, Silliman RA, Marcantonio ER. Weighing the benefits and burdens of mammography screening among women age 80 years or older. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2009;27(11):1774-80. doi:10.1200/JCO.2008.19.9877

PURPOSE: To examine outcomes of mammography screening among women > or = 80 years to inform decision making.

PATIENTS AND METHODS: We conducted a cohort study of 2,011 women without a history of breast cancer who were age > or = 80 years between 1994 and 2004 and who received care at one academic primary care clinic or two community health centers in Boston, MA. Medical record data were abstracted on all screening and diagnostic mammograms, breast ultrasounds and biopsies performed, all breast cancers diagnosed through December 31, 2006, and on sociodemographics. Date and cause of death were confirmed using the National Death Index.

RESULTS: The majority of patients (78.6%) were non-Hispanic white and 51.4% (n = 1,034) had been screened with mammography since age 80 years. Among women who were screened, eight were diagnosed with ductal carcinoma in situ, 16 with early stage disease (1.5%), two with late stage disease, and one died as a result of breast cancer. Many (110; 11%) experienced a false-positive screening mammogram that led to 19 benign breast biopsies, eight refused work-up, and three experienced a false-negative screening mammogram; 97 were screened within 2 years of their death from other causes. There were no significant differences in the rate, stage, recurrence rate, or deaths due to breast cancer between women who were screened and those who were not screened.

CONCLUSION: The majority of women > or = 80 years are screened with mammography yet few benefit. Meanwhile, 12.5% experience a burden from screening. The data from this study can be used to inform elderly women's decision making and potentially lead to more rational use of screening.

Kiely DK, Marcantonio ER, Inouye SK, et al. Persistent delirium predicts greater mortality. Journal of the American Geriatrics Society. 2009;57(1):55-61. doi:10.1111/j.1532-5415.2008.02092.x

OBJECTIVES: To examine the association between persistent delirium and 1-year mortality in newly admitted postacute 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 51.9-4.4) 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.

Dong Y, Zhang G, Zhang B, et al. The common inhalational anesthetic sevoflurane induces apoptosis and increases beta-amyloid protein levels. Archives of neurology. 2009;66(5):620-31. doi:10.1001/archneurol.2009.48

OBJECTIVE: To assess the effects of sevoflurane, the most commonly used inhalation anesthetic, on apoptosis and beta-amyloid protein (Abeta) levels in vitro and in vivo. Subjects Naive mice, H4 human neuroglioma cells, and H4 human neuroglioma cells stably transfected to express full-length amyloid precursor protein.

INTERVENTIONS: Human H4 neuroglioma cells stably transfected to express full-length amyloid precursor protein were exposed to 4.1% sevoflurane for 6 hours. Mice received 2.5% sevoflurane for 2 hours. Caspase-3 activation, apoptosis, and Abeta levels were assessed.

RESULTS: Sevoflurane induced apoptosis and elevated levels of beta-site amyloid precursor protein-cleaving enzyme and Abeta in vitro and in vivo. The caspase inhibitor Z-VAD decreased the effects of sevoflurane on apoptosis and Abeta. Sevoflurane-induced caspase-3 activation was attenuated by the gamma-secretase inhibitor L-685,458 and was potentiated by Abeta. These results suggest that sevoflurane induces caspase activation which, in turn, enhances beta-site amyloid precursor protein-cleaving enzyme and Abeta levels. Increased Abeta levels then induce further rounds of apoptosis.

CONCLUSIONS: These results suggest that inhalational anesthetic sevoflurane may promote Alzheimer disease neuropathogenesis. If confirmed in human subjects, it may be prudent to caution against the use of sevoflurane as an anesthetic, especially in those suspected of possessing excessive levels of cerebral Abeta.

Yang FM, Marcantonio ER, Inouye SK, et al. Phenomenological subtypes of delirium in older persons: patterns, prevalence, and prognosis. Psychosomatics. 2009;50(3):248-54. doi:10.1176/appi.psy.50.3.248

BACKGROUND: Delirium is an acute confusional state that is common, preventable, and life-threatening.

OBJECTIVE: The authors investigated the phenomenology of delirium severity as measured with the Memorial Delirium Assessment Scale among 441 older patients (age 65 and older) admitted with delirium in post-acute care.

METHODS: Using latent class analysis, they identified four classes of psychomotor-severity subtypes of delirium: 1) hypoactive/mild; 2) hypoactive/severe; 3) mixed, with hyperactive features/severe; and 4) normal/mild.

RESULTS: Among those with dementia (N=166), the hypoactive/mild class was associated with a higher risk of mortality. Among those without dementia (N=275), greater severity was associated with mortality, regardless of psychomotor features, when compared with the normal/mild class.

CONCLUSION: The data suggest that instruments measuring delirium severity and psychomotor features provide important prognostic information and should be integrated into the assessment of delirium.

Herzig SJ, Howell MD, Ngo LH, Marcantonio ER. Acid-suppressive medication use and the risk for hospital-acquired pneumonia. JAMA. 2009;301(20):2120-8. doi:10.1001/jama.2009.722

CONTEXT: The use of acid-suppressive medication has been steadily increasing, particularly in the inpatient setting, despite lack of an accepted indication in the majority of these patients.

OBJECTIVE: To examine the association between acid-suppressive medication and hospital-acquired pneumonia.

DESIGN, SETTING, AND PATIENTS: Prospective pharmacoepidemiologic cohort study. All patients who were admitted to a large, urban, academic medical center in Boston, Massachusetts, from January 2004 through December 2007; at least 18 years of age; and hospitalized for 3 or more days were eligible for inclusion. Admissions with time spent in the intensive care unit were excluded. Acid-suppressive medication use was defined as any order for a proton-pump inhibitor or histamine(2) receptor antagonist. Traditional and propensity-matched multivariable logistic regression were used to control for confounders.

MAIN OUTCOME MEASURE: Incidence of hospital-acquired pneumonia, defined via codes from the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM), in patients exposed and unexposed to acid-suppressive medication.

RESULTS: The final cohort comprised 63 878 admissions. Acid-suppressive medication was ordered in 52% of admissions and hospital-acquired pneumonia occurred in 2219 admissions (3.5%). The unadjusted incidence of hospital-acquired pneumonia was higher in the group exposed to acid-suppressive medication than in the unexposed group (4.9% vs 2.0%; odds ratio [OR], 2.6; 95% confidence interval [CI], 2.3-2.8). Using multivariable logistic regression, the adjusted OR of hospital-acquired pneumonia in the group exposed to acid-suppressive medication was 1.3 (95% CI, 1.1-1.4). The matched propensity-score analyses yielded identical results. The association was significant for proton-pump inhibitors (OR, 1.3; 95% CI, 1.1-1.4) but not for histamine(2) receptor antagonists (OR, 1.2; 95% CI, 0.98-1.4).

CONCLUSIONS: In this large, hospital-based pharmacoepidemiologic cohort, acid-suppressive medication use was associated with 30% increased odds of hospital-acquired pneumonia. In subset analyses, statistically significant risk was demonstrated only for proton-pump inhibitor use.

Schonberg MA, Davis RB, McCarthy EP, Marcantonio ER. Index to predict 5-year mortality of community-dwelling adults aged 65 and older using data from the National Health Interview Survey. Journal of general internal medicine. 2009;24(10):1115-22. doi:10.1007/s11606-009-1073-y

BACKGROUND: Prognostic information is becoming increasingly important for clinical decision-making.

OBJECTIVE: To develop and validate an index to predict 5-year mortality among community-dwelling older adults.

DESIGN AND PARTICIPANTS: A total of 24,115 individuals aged >65 who responded to the 1997-2000 National Health Interview Survey (NHIS) with follow-up through 31 December 2002 from the National Death Index; 16,077 were randomly selected for the development cohort and 8,038 for the validation cohort.

MEASUREMENTS: 39 risk factors (functional measures, illnesses, behaviors, demographics) were included in a multivariable Cox proportional hazards model to determine factors independently associated with mortality. Risk scores were calculated for participants using points derived from the final model's beta coefficients. To evaluate external validity, we compared survival by quintile of risk between the development and validation cohorts.

RESULTS: Seventeen percent of participants had died by the end of the study. The final model included 11 variables: age (1 point for 70-74 up to 7 points for >85); male: 3 points; BMI <25: 2 points; perceived health (good: 1 point, fair/poor: 2 points); emphysema: 2 points; cancer: 2 points; diabetes: 2 points; dependent in instrumental activities of daily living: 2 points; difficulty walking: 3 points; smoker-former: 1 point, smoker-current: 3 points; past year hospitalizations-one: 1 point, >2: 3 points. We observed close agreement between 5-year mortality in the two cohorts; which ranged from 5% in the lowest risk quintile to 50% in the highest risk quintile in the validation cohort.

CONCLUSIONS: This validated mortality index can be used to account for participant life expectancy in analyses using NHIS data.

Fong TG, Fearing MA, Jones RN, et al. Telephone interview for cognitive status: Creating a crosswalk with the Mini-Mental State Examination. Alzheimer’s & dementia : the journal of the Alzheimer’s Association. 2009;5(6):492-7. doi:10.1016/j.jalz.2009.02.007

BACKGROUND: Brief cognitive screening measures are valuable tools for both research and clinical applications. The most widely used instrument, the Mini-Mental State Examination (MMSE), is limited in that it must be administered face-to-face, cannot be used in participants with visual or motor impairments, and is protected by copyright. Screening instruments such as the Telephone Interview for Cognitive Status (TICS) were developed to provide a valid alternative, with comparable cut-point scores to rate global cognitive function.

METHODS: The MMSE, TICS-30, and TICS-40 scores from 746 community-dwelling elders who participated in the Aging, Demographics, and Memory Study (ADAMS) were analyzed with equipercentile equating, a statistical process of determining comparable scores based on percentile equivalents for different forms of an examination.

RESULTS: Scores from the MMSE and TICS-30 and TICS-40 corresponded well, and clinically relevant cut-point scores were determined. For example, an MMSE score of 23 is equivalent to 17 and 20 on the TICS-30 and TICS-40, respectively.

CONCLUSIONS: These findings indicate that TICS and MMSE scores can be linked directly. Clinically relevant and important MMSE cut points and the respective ADAMS TICS-30 and TICS-40 cut-point scores are included, to identify the degree of cognitive impairment among respondents with any type of cognitive disorder. These results will help in the widespread application of TICS in both research and clinical practice.

Eamranond PP, Wee CC, Legedza ATR, Marcantonio ER, Leveille SG. Acculturation and cardiovascular risk factor control among Hispanic adults in the United States. Public health reports (Washington, D.C. : 1974). 2009;124(6):818-24.

OBJECTIVES: We sought to determine whether low acculturation, based on language measures, leads to disparities in cardiovascular risk factor control in U.S. Hispanic adults.

METHODS: We studied 4729 Hispanic adults aged 18 to 85 years from the National Health and Nutrition Examination Survey, 1999-2004. We examined the association between acculturation and control of low-density lipoprotein (LDL) cholesterol, blood pressure, and hemoglobin A1c based on national guidelines among participants with hypercholesterolemia, hypertension, and diabetes, respectively. We used weighted logistic regression adjusting for age, gender, and education. We then examined health insurance, having a usual source of care, body mass index, fat intake, and leisure-time physical activity as potential mediators.

RESULTS: Among participants with hypercholesterolemia, Hispanic adults with low acculturation were significantly more likely to have poorly controlled LDL cholesterol than Hispanic adults with high acculturation after multivariable adjustment (odds ratio [OR] = 3.4, 95% confidence interval [CI] 1.2, 9.5). Insurance status mildly attenuated the difference in LDL cholesterol control. After adjusting for diet and physical activity, the magnitude of the association increased. Other covariates had little influence on the observed relationship. Among those with diabetes and hypertension, we did not observe statistically significant associations between low acculturation and control of hemoglobin A1c (OR = 0.5, 95% CI 0.2, 1.2), and blood pressure (OR = 1.1, 95% CI 0.6, 1.7), respectively.

CONCLUSIONS: Low levels of acculturation may be associated with increased risk of inadequate LDL cholesterol control among Hispanic adults with hypercholesterolemia. Further studies should examine the mechanisms by which low acculturation might adversely impact lipid control among Hispanic adults in the U.S.