Cathleen S. Colón-Emeric

Zoledronic Acid and Clinical Fractures and Mortality after Hip Fracture

BACKGROUND Mortality is increased after a hip fracture, and strategies that improve outcomes are needed. METHODS In this randomized, double-blind, placebo-controlled trial, 1065 patients were assigned to receive yearly intravenous zoledronic acid (at a dose of 5 mg), and 1062 patients were assigned to receive placebo. The infusions were first administered within 90 days after surgical repair of a hip fracture. All patients (mean age, 74.5 years) received supplemental vitamin D and calcium. The median follow-up was 1.9 years. The primary end point was a new clinical fracture. RESULTS The rates of any new clinical fracture were 8.6% in the zoledronic acid group and 13.9% in the placebo group, a 35% risk reduction with zoledronic acid (P=0.001); the respective rates of a new clinical vertebral fracture were 1.7% and 3.8% (P=0.02), and the respective rates of new nonvertebral fractures were 7.6% and 10.7% (P=0.03). In the safety analysis, 101 of 1054 patients in the zoledronic acid group (9.6%) and 141 of 1057 patients in the placebo group (13.3%) died, a reduction of 28% in deaths from any cause in the zoledronic acid group (P=0.01). The most frequent adverse events in patients receiving zoledronic acid were pyrexia, myalgia, and bone and musculoskeletal pain. No cases of osteonecrosis of the jaw were reported, and no adverse effects on the healing of fractures were noted. The rates of renal and cardiovascular adverse events, including atrial fibrillation and stroke, were similar in the two groups. CONCLUSIONS An annual infusion of zoledronic acid within 90 days after repair of a low-trauma hip fracture was associated with a reduction in the rate of new clinical fractures and with improved survival. (ClinicalTrials.gov number, NCT00046254 [ClinicalTrials.gov].).

Inpatient medication reconciliation at admission and discharge: A retrospective cohort study of age and other risk factors for medication discrepancies.

BACKGROUND Medication discrepancies are unintended differences between medication regimens (ie, between a patients home regimen and medications prescribed on admission to the hospital). OBJECTIVE The goal of this study was to describe the incidence, drug classes, and probable importance of hospital admission medication discrepancies and discharge regimen differences, and to determine whether factors such as age and specific hospital services were associated with greater frequency of medication discrepancies and differences. METHODS This was a retrospective cohort study of a random sample of adult patients admitted to the general medicine, cardiology, or general surgery services of a tertiary care academic teaching hospital between July 1, 2006, and August 31, 2006. A chart review was performed to collect the following information: patient demographic characteristics, comorbid conditions, number of preadmission medications, discrepant medications identified by the hospitals reconciliation process, reasons for the discrepancies, and discharge medications that differed from the home regimen. Potentially high-risk discrepancies and differences were identified by determining if the medications were included on either the Institute for Safe Medication Practices high-alert list or the North Carolina Narrow Therapeutic Index list. Univariate and multivariate logistic regression analyses were used to identify factors associated with medication discrepancies and differences. RESULTS Of the 205 patients (mean age, 59.9 years; 116 men, 89 women; 60% white) included in the study, 27 did not have any medications recorded on admission. Of the 178 patients who did have medications listed, 41 had >or=1 discrepancy identified by the reconciliation process on admission (23%; 95% CI, 17-29); 19% (95% CI, 11-31) of these medications were considered to be potentially high risk. In the multivariate logistic regression model, age (odds ratio [OR] per 5-year increase = 1.16; 95% CI, 1.01-1.33; P = 0.035), presence of high-risk medications on admission (OR = 76.68; 95% CI, 9.13-643.76; P < 0.001), and general surgery service (OR = 3.31; 95% CI, 1.40-7.87; P < 0.007) were associated with a higher proportion of patients with discrepancies on admission. At discharge, 196 patients (96% [95% CI, 93<98]) had >or=1 medication change from their home regimen, with 1102 total differences for 205 patients. Less than half (44% [95% CI, 37-51]) of these patients were explicitly alerted at discharge to new medications or dose changes; 12% (95% CI, 7-18) were given written instructions to stop taking discontinued home medications. Cardiovascular drugs were the most frequent class involved at both admission (31%) and discharge (27%) in medication discrepancies or differences. CONCLUSIONS Medication discrepancies on admission and medication differences at discharge were prevalent for adult patients admitted to the general medicine, cardiology, and general surgery services in this academic teaching hospital. Medication reconciliation processes have a high potential to identify clinically important discrepancies for all patients.

Extraskeletal effects of vitamin D in older adults: cardiovascular disease, mortality, mood, and cognition.

BACKGROUND Vitamin D insufficiency is prevalent among older adults and may be associated with higher risk for cardiovascular (CV) disease, mortality, depression, and cognitive deficits. OBJECTIVE The aim of this article was to review published observational and experimental studies that explored the association between vitamin D insufficiency and CV disease, mortality, mood, and cognition with an emphasis on older adults. METHODS PubMed and Web of Science databases were searched for English-language articles from January 1966 through June 2009 relating to vitamin D, using the following MeSH terms: aged, vitamin D deficiency, physiopathology, drug therapy, cardiovascular diseases, blood pressure, mortality, delirium, dementia, cognitive disorders, depression, depressive disorder, seasonal affective disorder, mental disorders, and vitamin D/therapeutic use. Publications had to include patients > or =65 years of age who had > or =1 recorded measurement of 25-hydroxyvitamin D (25[OH]D) or were receiving vitamin D supplementation. All case-control, cohort, and randomized studies were reviewed. RESULTS Forty-two case-control, cohort, and randomized trials were identified and included in the review. Based on these publications, the prevalence of vitamin D insufficiency (25[OH]D concentration <30 ng/mL) in communitydwelling older adults (> or =65 years of age) ranged from 40% to 100%. Epidemiologic data and several small randomized trials found a potential association between vitamin D deficiency (25[OH]D concentration <10 ng/mL) and CV disease, including hypertension and ischemic heart disease. Although subgroup analyses of data from the Womens Health Initiative Randomized Trial (the largest randomized, placebo-controlled trial of vitamin D plus calcium therapy) did not find reductions in blood pressure, myocardial infarction, or CV disease-related deaths, intervention contamination limited the findings. Observational studies and a meta-analysis of randomized controlled trials found a mortality benefit associated with higher serum 25(OH)D concentrations or vitamin D(2) or D(3) supplementation (mean dose, 528 IU/d). Observational and small randomized trials found a potential benefit of sunlight or vitamin D on symptoms of depression and cognition, but the findings were limited by methodologic problems. CONCLUSIONS Vitamin D insufficiency appears to be highly prevalent among older adults. Evidence from epidemiologic studies and small clinical trials suggests an association between 25(OH)D concentrations and systolic blood pressure, risk for CV disease-related deaths, symptoms of depression, cognitive deficits, and mortality. The Womens Health Initiative Randomized Trial did not find a benefit of vitamin D supplementation on blood pressure, myocardial infarction, or mortality in postmenopausal women.

Potential mediators of the mortality reduction with zoledronic acid after hip fracture

Zoledronic acid reduces the risk of death by 28% after hip fracture, but the mechanisms are not known. This exploratory analysis sought to identify potential pathways for the reduction in mortality with zoledronic acid after hip fracture. This was a retrospective analysis of a randomized, controlled trial. Patients with recent hip fracture (n = 2111) were treated with zoledronic acid or placebo infusion yearly, as well as calcium and vitamin D supplementation. Causes of death were adjudicated by a blinded central review committee. Baseline comorbidities, events occurring during the study period, including subsequent fracture, change in bone density, infections, cardiovascular events, arrhythmias, and falls, were included in multivariable analyses. In a model adjusted for baseline risk factors, zoledronic acid reduced the risk of death by 25% [95% confidence interval (CI) 0.58–0.97). The effect was consistent across most subgroups. Subsequent fractures were significantly associated with death (hazard ratio 1.72, 95% CI 1.17–2.51) but explained only 8% of the zoledronic acid effect. Adjusting for acute events occurring during follow‐up eliminated the death benefit, and zoledronic acid–treated subjects were less likely to die from pneumonia (interaction p = .04) and arrhythmias (interaction p = .02) than placebo‐treated subjects. Only 8% of zoledronic acids death benefit is due to a reduction in secondary fractures. Zoledronic acid may have an effect on cardiovascular events and pneumonia. Further studies of zoledronic acid in other acute illnesses may be warranted. Copyright

Antifracture efficacy and reduction of mortality in relation to timing of the first dose of zoledronic acid after hip fracture.

Annual infusions of zoledronic acid (5 mg) significantly reduced the risk of vertebral, hip, and nonvertebral fractures in a study of postmenopausal women with osteoporosis and significantly reduced clinical fractures and all‐cause mortality in another study of women and men who had recently undergone surgical repair of hip fracture. In this analysis, we examined whether timing of the first infusion of zoledronic acid study drug after hip fracture repair influenced the antifracture efficacy and mortality benefit observed in the study. A total of 2127 patients (1065 on active treatment and 1062 on placebo; mean age, 75 yr; 76% women and 24% men) were administered zoledronic acid or placebo within 90 days after surgical repair of an osteoporotic hip fracture and annually thereafter, with a median follow‐up time of 1.9 yr. Median time to first dose after the incident hip fracture surgery was ∼6 wk. Posthoc analyses were performed by dividing the study population into 2‐wk intervals (calculated from time of first infusion in relation to surgical repair) to examine effects on BMD, fracture, and mortality. Analysis by 2‐wk intervals showed a significant total hip BMD response and a consistent reduction of overall clinical fractures and mortality in patients receiving the first dose 2‐wk or later after surgical repair. Clinical fracture subgroups (vertebral, nonvertebral, and hip) were also reduced, albeit with more variation and 95% CIs crossing 1 at most time points. We concluded that administration of zoledronic acid to patients suffering a low‐trauma hip fracture 2 wk or later after surgical repair increases hip BMD, induces significant reductions in the risk of subsequent clinical vertebral, nonvertebral, and hip fractures, and reduces mortality.

Nurse assistant mental models, sensemaking, care actions, and consequences for nursing home residents

In a nursing home case study using observation and interview data, the authors described two mental models that guided certified nurse assistants (CNAs) in resident care. The Golden Rule guided CNAs to respond to residents as they would want someone to do for them. Mother wit guided CNAs to treat residents as they would treat their own children. These mental models engendered self-control and affection but also led to actions such as infantilization and misinterpretations about potentially undiagnosed conditions such as depression or pain. Furthermore, the authors found that CNAs were isolated from clinicians; little resident information was exchanged. They suggest ways to alter CNA mental models to give them a better basis for action and strategies for connecting CNAs and clinical professionals to improve information flow about residents. Study results highlight a critical need for registered nurses (RNs) to be involved in frontline care.

Efficacy and Safety of a Once-Yearly Intravenous Zoledronic Acid 5 mg for Fracture Prevention in Elderly Postmenopausal Women with Osteoporosis Aged 75 and Older

OBJECTIVES: To determine the efficacy of once‐yearly intravenous zoledronic acid (ZOL) 5 mg in reducing risk of clinical vertebral, nonvertebral, and any clinical fractures in elderly osteoporotic postmenopausal women.

A Review of the Effect of Anticonvulsant Medications on Bone Mineral Density and Fracture Risk

BACKGROUND Osteoporosis and seizure disorders are common diagnoses in older adults and often occur concomitantly. OBJECTIVE The goal of this review was to discuss the current hypothesis for the pathogenesis of anticonvulsant-induced bone density loss and the evidence regarding the risk for osteoporosis and fractures in older individuals. METHODS A review of the literature was performed, searching in MEDLINE and CINAHL for articles published between 1990 and October 2009 with the following search terms: anticonvulsant OR antiepileptic; AND osteoporosis OR bone density OR fracture OR absorptiometry, photon. Studies within the pediatric population, cross-sectional studies, and studies whose results were published in a language other than English were excluded. RESULTS A search of the published literature yielded >300 results, of which 24 met the inclusion and exclusion criteria and were included in this review. Hepatic enzyme induction by certain anticonvulsant medications appears to contribute to increased metabolism of 25-hydroxyvitamin D to inactive metabolites, which results in metabolic bone disease. There is increasing evidence that anticonvulsant use is associated with a higher risk of osteoporosis and clinical fractures, especially among older agents such as phenobarbital, carbamazepine, phenytoin, and valproate. Several observational studies suggest a class effect among anticonvulsant agents, associated with clinically significant reductions in bone mineral density and fracture risk. The use of anticonvulsant medications increases the odds of fracture by 1.2 to 2.4 times. However, only 2 large-scale observational studies have specifically examined the risk among those aged >65 years. This review also identified a randomized controlled trial whose results suggest that supplementation with high-dose vitamin D may be associated with increased bone mineral density in patients taking anticonvulsant medications. However, no randomized controlled trials investigating therapeutic agents to prevent fracture in this population were identified. Consequently, there are no formal practice guidelines for the monitoring, prevention, and management of bone disease among those taking anticonvulsants. CONCLUSIONS Observational studies suggest an association between use of anticonvulsant medications, reduced bone mineral density, and increased fracture risk. Randomized clinical trials are needed to guide the management of bone disease among those who use anticonvulsants.

Barriers to and Facilitators of Clinical Practice Guideline Use in Nursing Homes

OBJECTIVES: To identify barriers to and facilitators of the diffusion of clinical practice guidelines (CPGs) and clinical protocols in nursing homes (NHs).

Can historical and functional risk factors be used to predict fractures in community-dwelling older adults? development and validation of a clinical tool.

Abstract: The objectives of the study were: (1) to evaluate the contribution of impaired functional status, cognition and medication to fracture risk; (2) to determine whether risk factor profiles differ between regionally and socially diverse populations; and (3) to develop and validate a simple fracture prediction instrument for use in older adults using easily obtainable clinical information. A prospective population-based cohort study with 6–10 years of follow-up was carried out: the Duke and Iowa Established Populations for the Epidemiologic Study of the Elderly (EPESE), with in-person interviews in North Carolina and Iowa. The participants were community-dwelling men and women aged 65 years or over without a history of previous fracture at the baseline interview (n = 7654). The measurements were potential risk factors for osteoporosis and falls including: demographic factors, co-morbidities, medications, functional status measures, and physical measures. These were examined for association with self-reported subsequent hip fractures and fractures at any site using survival analysis. The resulting multivariable model was simplified and validated in a separate cohort. Test operating characteristics at 3 years were estimated using logistic regression. There were a total of 842 fractures in both cohorts including 382 hip fractures. Significant risk factors for all subsequent fractures and/or hip fracture in the developmental cohort included female sex (relative hazard 1.9–2.3), lowest quartile of body mass index (1.3), Caucasian race (2.1–2.8), one or more Rosow–Breslau physical function impairments (1.8–2.1), age over 75 years (2.1), history of stroke (1.9), cognitive impairment (2.2), one or more impairments in the activities of daily living (1.5) and anti-seizure medication use (2.0). Three predicitive models were highly significantly correlated with subsequent fractures with c-statistics in the developmental cohort at 3 and 6 years of 0.640–0.789. A simple count of risk factors had similar discriminative ability to the full model with a linear 35–65% increase in hazard of all fractures and hip fracture for each additional risk factor. In the validation cohort, the above variables were less potent predictors of fracture with only sex, body mass index and Rosow–Breslau impairment achieving significance. The predictive models including risk factor count remained significant in the validation set although the discriminative ability of the model was poor, with c-statistics of 0.574–0.749. Although there is no cut-point where fracture risk dramatically increases, patients can be counselled that there is a linear 77% increase in risk of hip fracture, and 29% increase in any fracture risk, with each additional risk factor they possess. Functional status impairment is an important predictor of fracture in older community-dwelling adults. The contribution of risk factors to fracture risk may differ between distinct populations.