Sarah D. Berry

Competing Risk of Death: An Important Consideration in Studies of Older Adults

Clinical studies often face the difficult problem of how to account for participants who die without experiencing the study outcome of interest. In a geriatric population with considerable comorbidities, the competing risk of death is especially high. Traditional approaches to describe risk of disease include Kaplan‐Meier survival analysis and Cox proportional hazards regression, but these methods can overestimate risk of disease by failing to account for the competing risk of death. This report discusses traditional survival analysis and competing risk analysis as used to estimate risk of disease in geriatric studies. Furthermore, it illustrates a competing risk approach to estimate risk of second hip fracture in the Framingham Osteoporosis Study and compares the results with traditional survival analysis. In this example, survival analysis overestimated the 5‐year risk of second hip fracture by 37% and the 10‐year risk by 75% compared with competing risk estimates. In studies of older individuals in which a substantial number of participants die during a long follow‐up, the cumulative incidence competing risk estimate and competing risk regression should be used to determine incidence and effect estimates. Use of a competing risk approach is critical to accurately determining disease risk for elderly individuals and therefore best inform clinical decision‐making.

Indoor and outdoor falls in older adults are different: the maintenance of balance, independent living, intellect, and Zest in the Elderly of Boston Study.

OBJECTIVES: To identify risk factors for indoor and outdoor falls.

Dementia Medications and Risk of Falls, Syncope, and Related Adverse Events: Meta-Analysis of Randomized Controlled Trials

OBJECTIVES: To evaluate the effect of cholinesterase inhibitors (ChEIs) and memantine on the risk of falls, syncope, and related events, defined as fracture and accidental injury.

Nonbenzodiazepine sleep medication use and hip fractures in nursing home residents

IMPORTANCE It is important to understand the relationship between sleep medication use and injurious falls in nursing home residents. OBJECTIVE To conduct a case-crossover study to estimate the association between nonbenzodiazepine hypnotic drug use (zolpidem tartrate, eszopiclone, or zaleplon) and the risk for hip fracture among a nationwide sample of long-stay nursing home residents, overall and stratified by individual and facility-level characteristics. DESIGN AND SETTING Case-crossover study performed in an academic research setting. PARTICIPANTS The study participants included 15,528 long-stay US nursing home residents 50 years or older with a hip fracture documented in Medicare Part A and Part D fee-for-service claims between July 1, 2007, and December 31, 2008. MAIN OUTCOME MEASURES Odds ratios (ORs) of hip fracture were estimated using conditional logistic regression models by comparing the exposure to nonbenzodiazepine hypnotic drugs during the 0 to 29 days before the hip fracture (hazard period) with the exposure during the 60 to 89 and 120 to 149 days before the hip fracture (control periods). Analyses were stratified by individual and facility-level characteristics. RESULTS Among the study participants, 1715 (11.0%) were dispensed a nonbenzodiazepine hypnotic drug before the hip fracture, with 927 exposure-discordant pairs included in the analyses. The mean (SD) age of participants was 81.0 (9.7) years, and 77.6% were female. The risk for hip fracture was elevated among users of a nonbenzodiazepine hypnotic drug (OR, 1.66; 95% CI, 1.45-1.90). The association between nonbenzodiazepine hypnotic drug use and hip fracture was somes greater in new users (OR, 2.20; 95% CI, 1.76-2.74) and in residents with mild vs moderate to severe impairment in cognition (OR, 1.86 vs 1.43; P = .06), with moderate vs total or severe functional impairment (OR, 1.71 vs 1.16; P = .11), with limited vs full assistance required with transfers (OR, 2.02 vs 1.43; P = .02), or in a facility with fewer Medicaid beds (OR, 1.90 vs 1.46; P = .05). CONCLUSIONS AND RELEVANCE The risk for hip fracture is elevated among nursing home residents using a nonbenzodiazepine hypnotic drug. New users and residents having mild to moderate cognitive impairment or requiring limited assistance with transfers may be most vulnerable to the use of these drugs. Caution should be exercised when prescribing sleep medications to nursing home residents.

Survival of Aged Nursing Home Residents With Hip Fracture

BACKGROUND Little is known about mortality in nursing home residents with hip fracture. This study examined the effect of pre-fracture characteristics, hospital complications, and post-fracture complications on mortality in residents with hip fracture. METHODS This is a retrospective cohort study of 195 long-term care residents (153 women, 42 men) with hip fracture (1999-2006) followed for mortality until June 30, 2007. Pre-fracture characteristics (age, sex, cognition, functional status, comorbidities, body mass index), hospital complications (acute myocardial infarction, congestive heart failure, delirium, infection) and 6-month complications (delirium, pneumonia, pressure ulcer, urinary tract infection [UTI]) were evaluated as potential predictors of mortality. RESULTS During a median follow-up of 1.4 years, 150 participants (76.9%) died. Male residents were nearly twice as likely to die compared with female residents (hazard ratio [HR] = 1.9, 95% confidence interval [CI] 1.2-3.0). Other pre-fracture characteristics associated with increased mortality included older age (HR per 5 years = 1.3, 95% CI 1.1-1.6), low functional status (HR = 1.7, 95% CI 1.0-3.0), anemia (HR = 1.6, 95% CI 1.1-2.5), and coronary artery disease (HR = 2.0, 95% CI 1.3-2.9). Mortality was 70% greater among residents with a pressure ulcer or pneumonia within 6 months of hip fracture (pressure ulcer, HR = 1.7, 95% CI 1.2-2.6; pneumonia, HR = 1.7, 95% CI 1.1-2.7). Individual hospital complications and post-fracture delirium and UTI were not significant predictors of mortality. CONCLUSIONS In addition to pre-fracture characteristics, potentially modifiable post-fracture complications including pressure ulcer and pneumonia were associated with increased mortality in nursing home residents with hip fracture. Prevention strategies to reduce pressure ulcers and pneumonia may help reduce mortality in this frail population.

Reevaluating the implications of recurrent falls in older adults: location changes the inference

To compare characteristics of indoor and outdoor recurrent fallers and explore some implications for clinical practice, in which a fall risk assessment for all recurrent fallers has been recommended.

Subsequent Fracture in Nursing Home Residents with a Hip Fracture: A Competing Risks Approach

OBJECTIVES: To determine the incidence and predictors of subsequent fracture in nursing home residents with a hip fracture, accounting for the competing risk of death.

Metabolic proteomics of the liver and mammary gland during lactation

The liver and the mammary gland have complementary metabolic roles during lactation. Glucose synthesized by the liver is released into the circulation and is taken up by the mammary gland where major metabolic products of glucose include milk sugar (lactose) and the glycerol backbone of milk fat (triglycerides). Hepatic synthesis of glucose is often accompanied by β-oxidation in that organ to provide energy for glucose synthesis, while mammary gland synthesizes rather than oxidizes fat during lactation. We have therefore compared enzyme abundances between the liver and mammary gland of lactating Friesian cows where metabolic output is well established. Quantitative differences in protein amount were assessed using two-dimensional differential in-gel electrophoresis. As predicted, the abundances of enzymes catalysing gluconeogenesis and β-oxidation were greatest in the liver, and enzyme abundances in mammary tissue were consistent with fat synthesis rather than β-oxidation.

Antidepressant Prescriptions: An Acute Window for Falls in the Nursing Home

BACKGROUND Although many studies have implicated antidepressants as a risk factor for falls, it is not clear if risk accrues with duration of use or if there are acute risks associated with initiation of the prescription. We conducted a case-crossover study of nursing home residents with a fall to determine the effect of an antidepressant change (defined as the new prescription of an antidepressant or increasing the dose of a previously used antidepressant) on fall risk. METHODS Among 1,181 nursing home fallers, we compared the frequency of antidepressant changes during the hazard period (1-7 days before the fall) with the frequency of antidepressant changes during the control period (8-14 days before the fall). Odds ratios were estimated using conditional logistic regression models. Results were estimated for non-selective serotonin reuptake inhibitors (SSRI) and SSRI prescriptions, separately. RESULTS Mean age was 88 years, and 71% were females. Seventy participants experienced an antidepressant change during the hazard and/or control periods. The maximum effect of falling occurred within 2 days of a non-SSRI change (odds ratio: 4.7, 95% confidence interval, 1.3-16.2). The effect on falling was no longer significant at 5 days (odds ratio: 1.9, 95% confidence interval, 0.9-4.0). No association was found between SSRI changes and falls. CONCLUSIONS Nursing home residents are at high risk of falls during the days following a new prescription or increased dose of a non-SSRI antidepressant. Increased surveillance should occur, particularly during the first 48 hours, in an effort to decrease falls.

New loop diuretic prescriptions may be an acute risk factor for falls in the nursing home

Although chronic use of diuretics has been implicated as a risk factor for falls, it is unknown whether changes in diuretic drugs are associated with an acutely elevated risk of falls. We evaluated the relationship between change in a diuretic prescription (new prescription or increased dose) and the occurrence of documented falls among nursing home residents.