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1.  Antihypertensive Medications and Serious Fall Injuries in a Nationally Representative Sample of Older Adults 
JAMA internal medicine  2014;174(4):588-595.
The effect of serious injuries, such as hip fracture and head injury, on mortality and function is comparable to that of cardiovascular events. Concerns have been raised about the risk of fall injuries in older adults taking antihypertensive medications. The low risk of fall injuries reported in clinical trials of healthy older adults may not reflect the risk in older adults with multiple chronic conditions.
To determine whether antihypertensive medication use was associated with experiencing a serious fall injury in a nationally representative sample of older adults.
Competing risk analysis as performed with propensity score adjustment and matching in the nationally representative Medicare Current Beneficiary Survey cohort during a 3-year follow-up through 2009. Participants included 4961 community-living adults older than 70 years with hypertension.
Antihypertensive medication intensity based on the standardized daily dose for each antihypertensive medication class that participants used.
Serious fall injuries, including hip and other major fractures, traumatic brain injuries, and joint dislocations, ascertained through Centers for Medicare & Medicaid Services claims.
Of the 4961 participants, 14.1% received no antihypertensive medications; 54.6% were in the moderate-intensity and 31.3% in the high-intensity antihypertensive groups. During follow-up, 446 participants (9.0%) experienced serious fall injuries, and 837 (16.9%) died. The adjusted hazard ratios for serious fall injury were 1.40 (95% CI, 1.03–1.90) in the moderate-intensity and 1.28 (95% CI, 0.91–1.80) in the high-intensity antihypertensive groups compared with nonusers. Although the difference in adjusted hazard ratios across the groups did not reach statistical significance, results were similar in the propensity score–matched subcohort. Among 503 participants with a previous fall injury, the adjusted hazard ratios were 2.17 (95% CI, 0.98–4.80) for the moderate-intensity and 2.31 (95% CI, 1.01–5.29) for the high-intensity antihypertensive groups.
Antihypertensive medications were associated with an increased risk of serious fall injuries, particularly among those with previous fall injuries. The potential harms vs benefits of antihypertensive medications should be weighed in deciding to continue treatment with antihypertensive medications in older adults with multiple chronic conditions.
PMCID: PMC4136657  PMID: 24567036
3.  Effect of a Restorative Model of Posthospital Home Care on Hospital Readmissions 
To compare readmissions of Medicare recipients of usual home care and a matched group of recipients of a restorative model of home care.
Quasiexperimental; matched and unmatched.
Community, home care.
Seven hundred seventy individuals receiving care from a large home care agency after hospitalization.
A restorative care model based on principles adapted from geriatric medicine, nursing, rehabilitation, goal attainment, chronic care management, and behavioral change theory.
Hospital readmission, length of home care episode.
Among the matched pairs, 13.2% of participants who received restorative care were readmitted to an acute hospital during the episode of home care, versus 17.6% of those who received usual care. Individuals receiving the restorative model of home care were 32% less likely to be readmitted than those receiving usual care (conditional odds ratio = 0.68, 95% confidence interval = 0.43–1.08). The mean length of home care episodes was 20.3 ± 14.8 days in the restorative care group and 29.1 ± 31.7 days in the usual care group (P < .001). Results were similar in unmatched analyses.
Although statistical significance was marginal, results suggest that the restorative care model offers an effective approach to reducing the occurrence of avoidable readmissions. It was previously shown that the restorative model of home care was associated with better functional recovery, fewer emergency department visits, and shorter episodes of home care. This model could be incorporated into usual home care practices and care delivery redesign.
PMCID: PMC4083654  PMID: 22860756
readmissions; restorative care; home care
4.  Effect of Co-existing Chronic Obstructive Pulmonary Disease and Cognitive Impairment on Health Outcomes in Older Adults 
To determine the extent to which the co-occurrence of chronic obstructive pulmonary disease (COPD) and cognitive impairment affect adverse health outcomes in older adults.
Multi-center longitudinal cohort study.
California, Pennsylvania, Maryland, and North Carolina.
Three thousand ninety-three community-dwelling adults aged ≥65 from the Cardiovascular Health Study. Four hundred thirty-one participants had chronic obstructive pulmonary disease (COPD) at study baseline.
Follow-up began at the second CHS visit and continued for three years. Spirometric criteria for airflow limitation served to establish COPD, using the Lambda-Mu-Sigma method, which accounts for age-related changes in lung function. Cognitive impairment was evaluated by the modified Mini Mental State Exam and claims data. Outcomes were respiratory-related and all-cause hospitalizations and death.
Participants with co-existing COPD and cognitive impairment had the highest rates of respiratory-related (adjusted hazard ratio [HR]=4.10, 95%CI=1.86–9.05) and all-cause hospitalizations (HR= 1.34, 95%CI=1.00–1.80) and death (HR=2.29, 95%CI=1.18–4.45). In particular, individuals with both conditions had a 48% higher rate of all-cause hospitalizations (adjusted synergy index [SI]=1.48, 95%CI=0.19–11.31) and nearly a three-fold higher rate of death (SI=2.74, 95%CI=0.43–17.32) than the sum of risks for each respective outcome associated with having COPD or cognitive impairment alone. However, tests for interaction were not statistically significant for the presence of synergism between both conditions relative to any of the outcomes. Therefore, we cannot conclude that the combined effect of COPD and cognitive impairment is greater than additive.
Co-existing COPD and cognitive impairment have an additive effect on respiratory-related and all-cause hospitalizations and death. Optimizing outcomes in older adults with COPD and cognitive impairment will require that we determine how to improve concurrent management of both conditions.
PMCID: PMC3470752  PMID: 23035917
Chronic obstructive pulmonary disease; cognitive impairment; health outcomes; hospitalizations; disability; death
5.  Yield of Diagnostic Tests in Evaluating Syncopal Episodes in Older Patients 
Archives of internal medicine  2009;169(14):1299-1305.
Syncopal episodes are common among older adults; etiologies range from benign to life-threatening. We determined the frequency, yield, and costs of tests obtained to evaluate older persons with syncope. We also calculated the cost per test yield and determined whether the San Francisco Syncope Rule (SFSR) improved test yield.
Review of 2,106 consecutive patients 65 years and older admitted following a syncopal episode.
Electrocardiograms (99%), telemetry (95%), cardiac enzymes (95%), and head computed tomography (CT) (63%) were the most frequently obtained tests. Cardiac enzymes, CTs, echocardiograms, carotid ultrasounds, and electroencephalography all affected diagnosis or management in <5% of cases and helped determine etiology of syncope < 2% of the time. Postural blood pressure, performed in only 38% of episodes, had the highest yield with respect to affecting diagnosis (18-26%) or management (25-30%) and determining etiology of the syncopal episode (15-21%). The cost per test affecting diagnosis or management was highest for electroencephalography ($32,973), CT ($24,881), and cardiac enzymes ($22,397) and lowest for postural blood pressure ($17-$20). The yields and costs for cardiac tests were better among patients meeting, than not meeting, SFSR. For example, the cost per cardiac enzymes affecting diagnosis or management was $10,331 in those meeting, versus $111,518 in those not meeting, the SFSR.
Many unnecessary tests are obtained to evaluate syncope. Selecting tests based on history and examination and prioritizing less expensive and higher yield tests would ensure a more informed and cost-effective approach to evaluating older patients with syncope.
PMCID: PMC3752785  PMID: 19636031
6.  The Patient Who Falls 
Falls are common health events that cause discomfort and disability for older adults and stress for caregivers. Using the case of an older man who has experienced multiple falls and a hip fracture, this article, which focuses on community-living older adults, addresses the consequences and etiology of falls; summarizes the evidence on predisposing factors and effective interventions; and discusses how to translate this evidence into patient care. Previous falls; strength, gait, and balance impairments; and medications are the strongest risk factors for falling. Effective single interventions include exercise and physical therapy, cataract surgery, and medication reduction. Evidence suggests that the most effective strategy for reducing the rate of falling in community-living older adults may be intervening on multiple risk factors. Vitamin D has the strongest clinical trial evidence of benefit for preventing fractures among older men at risk. Issues involved in incorporating these evidence-based fall prevention interventions into outpatient practice are discussed, as are the trade-offs inherent in managing older patients at risk of falling. While challenges and barriers exist, fall prevention strategies can be incorporated into clinical practice.
PMCID: PMC3740370  PMID: 20085954
7.  Contribution of Individual Diseases to Death in Older Adults with Multiple Diseases 
To determine empirically the diseases contributing most commonly and strongly to death in older adults, accounting for coexisting diseases.
United States
Twenty two thousand eight hundred ninety Medicare Current Beneficiary Survey participants, a national representative sample of Medicare beneficiaries, enrolled during 2002 – 2006.
Chronic and acute diseases were ascertained from Medicare claims data. Diseases contributing to death during follow-up were identified empirically via regression models among all diseases with a frequency of ≥ 1% and hazard ratio for death of > 1. The additive contributions of these diseases, adjusting for co-existing diseases, were calculated using a longitudinal extension of average attributable fraction; 95% confidence intervals were estimated from bootstrapping.
Fifteen diseases and acute events contributed significantly to death, together accounting for nearly 70% of death. Heart failure (20.0%), dementia (13.6%), chronic lower respiratory disease (12.4%), and pneumonia (5.3%) made the largest contributions to death. Cancers, including lung, colorectal, lymphoma, and head and neck, together contributed to 5.6% of death. The other disease and events included acute kidney injury, stroke, septicemia, liver disease, myocardial infarction, and unintentional injuries.
The extent of the contribution of some diseases such as dementia and respiratory disease to death in older adults may be underappreciated, while the contribution of other diseases may be overestimated, with methods that focus on determining a single underlying cause. Current conceptualization of a single underlying cause may not account adequately for the contribution to death of coexisting diseases experienced by older adults.
PMCID: PMC3419332  PMID: 22734792
death; coexisting diseases; multiple chronic conditions
8.  Making Prevention Recommendations Relevant for an Aging Population 
Annals of internal medicine  2010;153(12):843-844.
PMCID: PMC3705956  PMID: 21173418
9.  Development of a Tool for Eliciting Patient Priority from Among Competing Cardiovascular Disease, Medication-Symptoms, and Fall Injury Outcomes 
To develop a choice task for eliciting priorities in the face of competing cardiovascular disease (CVD) outcomes, medication-related symptoms, and fall injuries.
Conjoint analysis.
Senior housing site.
Convenience sample of 15 senior housing residents for the pretest, 13 residents for the pilot test.
The final task included 11 sets of choices. In each, one option optimized the risk of one or two of the three outcomes at the expense of the other(s); the second option did the reverse. Relative importance scores for CVD, fall injury, and medication-symptom outcomes were calculated. Reliability was assessed for two administrations using intraclass correlations (ICCs). Wilcoxon rank sum tests were used to evaluate order effects.
The ICCs between choice task administrations were 0.70 for fall injuries, 0.73 for medication symptoms, and 0.56 for CVD outcomes. The ICCs with removal of two outliers were 0.84, 0.72, and 0.84, respectively. Whether CVD or fall injuries appeared first had no effect on scores.
Preliminary evidence of comprehensibility and reliability supports using the choice task to determine whether individuals’ priorities differ in the face of competing outcomes.
PMCID: PMC3703614  PMID: 18266842
patient priorities; competing health outcomes; clinical decision-making
10.  Trends in Fall-Related Traumatic Brain Injury among Older Persons in Connecticut from 2000–2007 
Anecdotal evidence suggests a rising trend in the occurrence of fall-related traumatic brain injuries (FR-TBI) among persons ≥ 70 years. To document this apparent trend on a more substantive basis, this report longitudinally describes overall and age-stratified rates of three outcomes attributed to FR-TBI among persons ≥ 70 years: emergency department visits (ED), hospitalizations, and terminal hospitalizations.
Eight years (2000–2007) of observational data from emergency departments and acute care hospitals serving a non-randomly selected, densely populated region in southern Connecticut, U.S.
From 2000–2007 among persons 70 years and older, overall rates of FR-TBI visits to emergency departments more than doubled while corresponding rates of hospitalization and terminal hospitalization rose 58% each. The point estimate of growth in the rate of ED in the oldest stratum was nearly triple that of the younger stratum whereas point estimates of growth in rates of hospitalization and terminal hospitalization were nearly four times higher. Total Medicare costs for ED visits increased nearly four-fold while corresponding costs for hospitalizations and terminal hospitalizations rose by 64% and 76%. The most common discharge diagnoses for ED and hospitalization were unspecified head injury and intracranial hemorrhage.
The rapid rise in rates of FR-TBI and associated Medicare costs underscore the urgent need to prevent this burgeoning source of human suffering and health care utilization. We believe the rise in rates is at least partially due to a greater public awareness of the outcome that has been facilitated by increasing use of diagnostic imaging in the ED and hospital.
PMCID: PMC4280829  PMID: 25558438
Connecticut collaboration for fall prevention; Fall-related traumatic brain injury; Hospitalization; Emergency department; Anticoagulation therapy
11.  Contribution of Multiple Chronic Conditions to Universal Health Outcomes 
To determine the relative effect of five chronic conditions on four representative universal health outcomes.
Cardiovascular Health Study.
Five thousand two hundred and ninety-eight community-living participants aged 65 and older.
Multiple regression and Cox models were used to determine the effect of heart failure (HF), chronic obstructive pulmonary disease (COPD), osteoarthritis, depression, and cognitive impairment on self-rated health, 12 basic and instrumental activities of daily living (ADLs and IADLs), six-item symptom burden scale, and death.
Each condition adversely affected self-rated health (P<.001) and ADLs and IADLs (P<.001). For example, persons with HF performed 0.70 ± 0.08 fewer ADLs and IADLs than those without; persons with depression and persons with cognitive impairment performed 0.59 ± 0.04 and 0.58 ± 0.06 fewer activities, respectively, than those without these conditions. Depression, HF, COPD, and osteoarthritis were associated with 1.18 ± 0.04, 0.40 ± 0.08, 0.40 ± 0.05, and 0.57 ± 0.03 more symptoms, respectively, in individuals with these conditions than in those without. HF (hazard ratio (HR) = 2.84, 95% confidence interval (CI) = 1.97–4.10), COPD (2.62, 95% CI = 1.94–3.53), cognitive impairment (2.05, 95% CI = 1.47–2.85), and depression (1.47, 95% CI = 1.08–2.01) were each associated with death within 2 years. Several paired combinations of conditions had synergistic effects on ADLs and IADLs. For example, individuals with HF plus depression performed 2.0 fewer activities than persons with neither condition, versus the 1.3 fewer activities expected from adding the effects of the two conditions together.
Universal health outcomes may provide a common metric for measuring the effects of multiple conditions and their treatments. The varying effects of the conditions across universal outcomes could inform care priorities.
PMCID: PMC3622699  PMID: 21883118
multiple chronic conditions; patient-reported outcomes; universal health outcomes
12.  Hospitalization Rates and In-Hospital Mortality Among Centenarians 
Archives of internal medicine  2012;172(15):1179-1180.
PMCID: PMC4241633  PMID: 22710863
13.  Design and rationale of the comprehensive evaluation of risk factors in older patients with AMI (SILVER-AMI) study 
While older adults (age 75 and over) represent a large and growing proportion of patients with acute myocardial infarction (AMI), they have traditionally been under-represented in cardiovascular studies. Although chronological age confers an increased risk for adverse outcomes, our current understanding of the heterogeneity of this risk is limited. The Comprehensive Evaluation of Risk Factors in Older Patients with AMI (SILVER-AMI) study was designed to address this gap in knowledge by evaluating risk factors (including geriatric impairments, such as muscle weakness and cognitive impairments) for hospital readmission, mortality, and health status decline among older adults hospitalized for AMI.
SILVER-AMI is a prospective cohort study that is enrolling 3000 older adults hospitalized for AMI from a recruitment network of approximately 70 community and academic hospitals across the United States. Participants undergo a comprehensive in-hospital assessment that includes clinical characteristics, geriatric impairments, and health status measures. Detailed medical record abstraction complements the assessment with diagnostic study results, in-hospital procedures, and medications. Participants are subsequently followed for six months to determine hospital readmission, mortality, and health status decline. Multivariable regression will be used to develop risk models for these three outcomes.
SILVER-AMI will fill critical gaps in our understanding of AMI in older patients. By incorporating geriatric impairments into our understanding of post-AMI outcomes, we aim to create a more personalized assessment of risk and identify potential targets for interventions.
Trial registration
Trial registration number: NCT01755052.
PMCID: PMC4239317  PMID: 25370536
Acute myocardial infarction; Aging; Hospital readmission; Health status
14.  Health Outcome Priorities Among Competing Cardiovascular, Fall Injury, and Medication-Related Symptom Outcomes 
To determine the priority that older adults with coexisting hypertension and fall risk give to optimizing cardiovascular outcomes versus fall- and medication symptom-related outcomes.
One hundred twenty-three cognitively intact persons aged 70 and older with hypertension and fall risk.
Discrete choice task was used to elicit the relative importance placed on reducing the risk of three outcomes: cardiovascular events, serious fall injuries, and medication symptoms. Risk estimates with and without antihypertensive medications were obtained from the literature. Participants chose between 11 pairs of options that displayed lower risks for one or two outcomes and a higher risk for the other outcome(s), versus the reverse. Results were used to calculate relative importance scores for the three outcomes. These scores, which sum to 100, reflect the relative priority participants placed on the difference between the risk estimates of each outcome.
Sixty-two participants (50.4%) placed greater importance on reducing risk of cardiovascular events than reducing risk of the combination of fall injuries and medication symptoms; 61 participants did the converse. A lower percentage of participants with chronic obstructive pulmonary disease (P =.02), unsteadiness (P =.02), functional dependency (P =.04), lower cognition (P =.02) and depressive symptoms (P =.03) prioritized cardiovascular outcomes over fall injuries and medication symptoms than did participants without these characteristics.
Interindividual variability in the face of competing outcomes supports individualizing decision-making to individual priorities. In the current example, this may mean forgoing antihypertensive medications or compromising on blood pressure reduction for some individuals.
PMCID: PMC3494099  PMID: 18662210
competing outcomes; fall injuries; hypertension; patient priorities
15.  Association Between Treatment or Usual Care Region and Hospitalization for Fall-Related Traumatic Brain Injury in the Connecticut Collaboration for Fall Prevention 
Most traumatic brain injuries among older persons in the U.S. are attributed to falls. Efforts to prevent falls may also plausibly reduce the incidence of TBIs and resultant costs.
To evaluate the association between the treatment or usual care region of the Connecticut Collaboration for Fall Prevention (CCFP), a clinical intervention for prevention of falls, and the rate of hospitalization for fall-related traumatic brain injury (FR-TBI) among persons ≥ 70 years. The Medicare charges of FR-TBI hospitalizations are also described.
Using a quasi-experimental design, rates of hospitalization for FR-TBI were recorded over an eight year period (2000–2007) in two distinct geographic regions (treatment and usual care) chosen for their similarity in characteristics associated with occurrence of falls.
Over 200,000 persons, 70 years and older, residing in two geographical regions in Connecticut.
Clinicians in the treatment region translated research protocols from Yale FICSIT, a successful fall prevention randomized clinical trial, into discipline- and site-specific fall prevention procedures for integration into their clinical practices.
The rate of hospitalization for fall-related traumatic brain injury among persons 70 years and older
Relative to the usual care region, CCFP’s treatment region exhibited lower rates of hospitalization for FR-TBI; RR= 0.84 with 95% credible interval (0.72 – 0.99).
The significantly lower rate of hospitalization for FR-TBI in CCFP’s treatment region suggests that the engagement of practicing clinicians in the implementation of evidence-based fall-prevention practices may reduce hospitalizations for FR-TBI.
PMCID: PMC3801219  PMID: 24083593
Connecticut Collaboration for Fall Prevention; fall-related traumatic brain injury; hospitalization; Bayesian; spatial model
16.  Effect of chronic disease-related symptoms and impairments on universal health outcomes in older adults 
To determine the extent to which disease-related symptoms and impairments, which constitute measures of disease severity or targets of therapy, account for the associations between chronic diseases and universal health outcomes.
Cardiovascular Health Study (CHS) and Health ABC.
5,654 CHS, and 2,706 Health ABC, members.
Diseases included heart failure (HF), chronic obstructive pulmonary disease (COPD), osteoarthritis, and cognitive impairment. The universal health outcomes included self-rated health, basic and instrumental activities of daily living (BADLs-IADLs), and death. Disease-related symptoms/impairments included HF symptoms and ejection fraction (EF) for HF; Dyspnea Scale and FEV1 for COPD; joint pain for osteoarthritis, and executive function for cognitive impairment.
The diseases were associated with the universal health outcomes (p<0.001) except osteoarthritis with death (both cohorts) and cognitive impairment with self-rated health (Health ABC). Symptoms/impairments accounted for ≥30% of each disease’s effect on the universal health outcomes. In CHS, for example, HF, compared with no HF, was associated with one fewer (0.918) BADLs-IADL performed without difficulty; 27% of this effect was accounted for by HF symptoms, only 5% by EF. The hazard ratio for death with HF was 6.5 (95% CI, 4.7, 8.9) with 40% accounted for by EF and only 14% by HF symptoms.
Disease-related symptoms/impairments accounted for much of the significant associations between the 4 chronic diseases and the universal health outcomes. Results support considering universal health outcomes as common metrics across diseases in clinical decision-making, perhaps by targeting the disease-related symptoms/impairments that contribute most strongly to the effect of the disease on the universal health outcomes.
PMCID: PMC3287052  PMID: 21883120
chronic diseases; universal health outcomes; patient-reported outcomes; clinical decision-making
17.  Association Between Combined Interleukin-6 and C-Reactive Protein Levels and Pulmonary Function in Older Women: Results from the Women’s Health and Aging Studies I and II 
To determine whether combined higher interleukin-6 (IL-6) and C-reactive protein (CRP) levels are associated with lower pulmonary function levels in older women, accounting for chronic inflammatory diseases, physical function, and other factors associated with inflammation.
Cross-sectional study using data from two prospective cohorts.
Baltimore, Maryland.
Eight hundred forty disabled and 332 higher-functioning community-dwelling women aged 65 and older from the Women’s Health and Aging Studies (WHAS) I and II, respectively.
IL-6 and CRP, combined according to their tertile concentrations, and pulmonary function measures, assessed according to forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC).
In WHAS I and II, similar dose-response trends were observed between combined higher IL-6 and CRP levels and lower pulmonary function levels. In WHAS I (disabled women), the combined highest IL-6 and CRP levels were associated with the lowest levels of FEV1 (mean 137.0 mL, 95% confidence interval (CI) = 128.4–145.7 mL) and FVC (mean 191.7 mL, 95% CI = 180.4–202.9 mL). Similarly, in WHAS II (higher-functioning women), the combined highest IL-6 and CRP levels were associated with the lowest levels of FEV1 (mean 158.3 mL, 95% CI = 146.3–170.4 mL) and FVC (mean 224.2 mL, 95% CI = 209.9–238.5 mL).
Combined elevations in IL-6 and CRP were associated with the lowest pulmonary function levels in older women. These findings suggest that high IL-6 and CRP levels may be an indication of prevalent impaired pulmonary function. Future studies should determine whether measurement of IL-6 and CRP could enhance current methods of monitoring respiratory diseases beyond that provided by pulmonary function measures.
PMCID: PMC4050638  PMID: 21226682
pulmonary function; inflammation; older women
18.  Effect of β-Blockers on Cardiac and Pulmonary Events and Death in Older Adults With Cardiovascular Disease and Chronic Obstructive Pulmonary Disease 
Medical care  2014;52(0 3):S45-S51.
In older adults with multiple conditions, medications may not impart the same benefits seen in patients who are younger or without multimorbidity. Furthermore, medications given for one condition may adversely affect other outcomes. β-Blocker use with coexisting cardiovascular disease (CVD) and chronic obstructive pulmonary disease (COPD) is such a situation.
To determine the effect of β-blocker use on cardiac and pulmonary outcomes and mortality in older adults with coexisting COPD and CVD.
Design, Setting, Participants
The study included 1062 participants who were members of the 2004–2007 Medicare Current Beneficiary Survey cohorts, a nationally representative sample of Medicare beneficiaries. Study criteria included age over 65 years plus coexisting CVD and COPD/asthma. Follow-up occurred through 2009. We determined the association between β-blocker use and the outcomes with propensity score-adjusted and covariate-adjusted Cox proportional hazards.
Main Outcome Measures
The 3 outcomes were major cardiac events, pulmonary events, and all-cause mortality.
Half of the participants used β-blockers. During follow-up, 179 participants experienced a major cardiac event; 389 participants experienced a major pulmonary event; and 255 participants died. Each participant could have experienced any ≥1 of these events. The hazard ratio for β-blocker use was 1.18 [95% confidence interval (CI), 0.85–1.62] for cardiac events, 0.91 (95% CI, 0.73–1.12) for pulmonary events, and 0.87 (95% CI, 0.67–1.13) for death.
In this population of older adults, β-blockers did not seem to affect occurrence of cardiac or pulmonary events or death in those with CVD and COPD.
PMCID: PMC4050644  PMID: 24561758
multiple chronic conditions; multimorbidity; chronic obstructive pulmonary disease; cardiovascular disease; β-blocker; cardiac events; pulmonary events; COPD; CVD; coronary artery disease
20.  Anti-Hypertensive Medications and Cardiovascular Events in Older Adults with Multiple Chronic Conditions 
PLoS ONE  2014;9(3):e90733.
Randomized trials of anti-hypertensive treatment demonstrating reduced risk of cardiovascular events in older adults included participants with less comorbidity than clinical populations. Whether these results generalize to all older adults, most of whom have multiple chronic conditions, is uncertain.
To determine the association between anti-hypertensive medications and CV events and mortality in a nationally representative population of older adults.
Competing risk analysis with propensity score adjustment and matching in the Medicare Current Beneficiary Survey cohort over three-year follow-up through 2010.
Participants and Setting
4,961 community-living participants with hypertension.
Anti-hypertensive medication intensity, based on standardized daily dose for each anti-hypertensive medication class participants used.
Main Outcomes and Measures
Cardiovascular events (myocardial infarction, unstable angina, cardiac revascularization, stroke, and hospitalizations for heart failure) and mortality.
Of 4,961 participants, 14.1% received no anti-hypertensives; 54.6% received moderate, and 31.3% received high, anti-hypertensive intensity. During follow-up, 1,247 participants (25.1%) experienced cardiovascular events; 837 participants (16.9%) died. Of deaths, 430 (51.4%) occurred in participants who experienced cardiovascular events during follow-up. In the propensity score adjusted cohort, after adjusting for propensity score and other covariates, neither moderate (adjusted hazard ratio, 1.08 [95% CI, 0.89–1.32]) nor high (1.16 [0.94–1.43]) anti-hypertensive intensity was associated with experiencing cardiovascular events. The hazard ratio for death among all participants was 0.79 [0.65–0.97] in the moderate, and 0.72 [0.58–0.91] in the high intensity groups compared with those receiving no anti-hypertensives. Among participants who experienced cardiovascular events, the hazard ratio for death was 0.65 [0.48–0.87] and 0.58 [0.42–0.80] in the moderate and high intensity groups, respectively. Results were similar in the propensity score-matched subcohort.
Conclusions and Relevance
In this nationally representative cohort of older adults, anti-hypertensive treatment was associated with reduced mortality but not cardiovascular events. Whether RCT results generalize to older adults with multiple chronic conditions remains uncertain.
PMCID: PMC3948696  PMID: 24614535
21.  Potential Therapeutic Competition in Community-Living Older Adults in the U.S.: Use of Medications That May Adversely Affect a Coexisting Condition 
PLoS ONE  2014;9(2):e89447.
The 75% of older adults with multiple chronic conditions are at risk of therapeutic competition (i.e. treatment for one condition may adversely affect a coexisting condition). The objective was to determine the prevalence of potential therapeutic competition in community-living older adults.
Cross-sectional descriptive study of a representative sample of 5,815 community-living adults 65 and older in the U.S, enrolled 2007–2009. The 14 most common chronic conditions treated with at least one medication were ascertained from Medicare claims. Medication classes recommended in national disease guidelines for these conditions and used by ≥2% of participants were identified from in-person interviews conducted 2008–2010. Criteria for potential therapeutic competition included: 1), well-acknowledged adverse medication effect; 2) mention in disease guidelines; or 3) report in a systematic review or two studies published since 2000. Outcomes included prevalence of situations of potential therapeutic competition and frequency of use of the medication in individuals with and without the competing condition.
Of 27 medication classes, 15 (55.5%) recommended for one study condition may adversely affect other study conditions. Among 91 possible pairs of study chronic conditions, 25 (27.5%) have at least one potential therapeutic competition. Among participants, 1,313 (22.6%) received at least one medication that may worsen a coexisting condition; 753 (13%) had multiple pairs of such competing conditions. For example, among 846 participants with hypertension and COPD, 16.2% used a nonselective beta-blocker. In only 6 of 37 cases (16.2%) of potential therapeutic competition were those with the competing condition less likely to receive the medication than those without the competing condition.
One fifth of older Americans receive medications that may adversely affect coexisting conditions. Determining clinical outcomes in these situations is a research and clinical priority. Effects on coexisting conditions should be considered when prescribing medications.
PMCID: PMC3934884  PMID: 24586786
22.  Acute Decompensated Heart Failure Is Routinely Treated as a Cardiopulmonary Syndrome  
PLoS ONE  2013;8(10):e78222.
Heart failure as recognized and treated in typical practice may represent a complex condition that defies discrete categorizations. To illuminate this complexity, we examined treatment strategies for patients hospitalized and treated for decompensated heart failure. We focused on the receipt of medications appropriate for other acute conditions associated with shortness of breath including acute asthma, pneumonia, and exacerbated chronic obstructive pulmonary disease.
Methods and Results
Using Premier Perspective®, we studied adults hospitalized with a principal discharge diagnosis of heart failure and evidence of acute heart failure treatment from 2009-2010 at 370 US hospitals. We determined treatment with acute respiratory therapies during the initial 2 days of hospitalization and daily during hospital days 3-5. We also calculated adjusted odds of in-hospital death, admission to the intensive care unit, and late intubation (intubation after hospital day 2). Among 164,494 heart failure hospitalizations, 53% received acute respiratory therapies during the first 2 hospital days: 37% received short-acting inhaled bronchodilators, 33% received antibiotics, and 10% received high-dose corticosteroids. Of these 87,319 hospitalizations, over 60% continued receiving respiratory therapies after hospital day 2. Respiratory treatment was more frequent among the 60,690 hospitalizations with chronic lung disease. Treatment with acute respiratory therapy during the first 2 hospital days was associated with higher adjusted odds of all adverse outcomes.
Acute respiratory therapy is administered to more than half of patients hospitalized with and treated for decompensated heart failure. Heart failure is therefore regularly treated as a broader cardiopulmonary syndrome rather than as a singular cardiac condition.
PMCID: PMC3824040  PMID: 24250751
23.  A Method for Partitioning the Attributable Fraction of Multiple Time-Dependent Coexisting Risk Factors for an Adverse Health Outcome 
American journal of public health  2012;103(1):177-182.
We decomposed the total effect of coexisting diseases on a timed occurrence of an adverse outcome into additive effects from individual diseases.
In a cohort of older adults enrolled in the Precipitating Events Project in New Haven County, Connecticut, we assessed a longitudinal extension of the average attributable fraction method (LE-AAF) to estimate the additive and order-free contributions of multiple diseases to the timed occurrence of a health outcome, with right censoring, which may be useful when relationships among diseases are complex. We partitioned the contribution to death into additive LE-AAFs for multiple diseases.
The onset of heart failure and acute episodes of pneumonia during follow-up contributed the most to death, with the overall LE-AAFs equal to 13.0% and 12.1%, respectively. The contribution of preexisting diseases decreased over the years, with a trend of increasing contribution from new onset of diseases.
LE-AAF can be useful for determining the additive and order-free contribution of individual time-varying diseases to a time-to-event outcome.
PMCID: PMC3518339  PMID: 22515873
24.  Assessing the Impact of Screening Colonoscopy on Mortality in the Medicare Population 
Journal of General Internal Medicine  2011;26(12):1441-1449.
Some have recommended against routine screening for colorectal cancer (CRC) among patients ≥75 years of age, while others have suggested that screening colonoscopy (SC) is less beneficial for women than men. We estimated the expected benefits (decreased mortality from CRC) and harms (SC-related mortality) of SC based on sex, age, and comorbidity.
To stratify older patients according to expected benefits and harms of SC based on sex, age, and comorbidity.
Retrospective study using Medicare claims data.
Medicare beneficiaries 67–94 years old with and without CRC.
Main Measures
Life expectancy, CRC- and colonoscopy-attributable mortality rates across strata of sex, age, and comorbidity, pay-off time (i.e. the minimum time until benefits from SC exceeded harms), and life-years saved for every 100,000 SC.
Key Results
Increasing age and comorbidity were associated with lower CRC-attributable mortality. Due to shorter life expectancy and CRC-attributable mortality, the benefits associated with SC were substantially lower among patients with greater comorbidity. Among men aged 75–79 years with no comorbidity, the number of life-years saved was 459 per 100,000 SC, while men aged 67–69 with ≥3 comorbidities had 81 life-years saved per 100,000 SC. There was no evidence that SC was less effective in women. Among men and women 75–79 with no comorbidity, number of life-years saved was 459 and 509 per 100,000 SC, respectively; among patients with ≥3 comorbidities, there was no benefit for either men or women.
Although the effectiveness of SC was equivalent for men and women, there was substantial variation in SC effectiveness within age groups, arguing against screening recommendations based solely on age.
PMCID: PMC3235614  PMID: 21842323
screening colonoscopy; colorectal cancer screening; medicare
25.  Assessing Multiple Medication Use With Probabilities of Benefits and Harms 
Journal of aging and health  2008;20(6):694-709.
A quantitative framework to assess harms and benefits of candidate medications in the context of drugs that a patient is already taking is proposed.
Probabilities of harms and benefits of a given medication are averaged to yield a utility value. The utility values of all medications under consideration are combined as a geometric mean to yield an overall measure of favorability. The grouping of medications yielding the highest favorability value is chosen.
Five examples of choosing between widely used candidate medications demonstrate the feasibility of the proposed framework.
The framework proposed provides a simple method for considering the trade-offs involved in prescribing multiple medications. It can be adapted to include additional parameters representing severity of condition, prioritization of outcomes, patient preferences, dosages, and medication interactions. Inconsistent reporting in the medical literature of data about benefits and harms of medications, dosages, and interactions constitutes its primary limitation.
PMCID: PMC3477770  PMID: 18625759
adverse effect; utility function; aging; trade-offs; multiple medications

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