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Anecdotal observation suggests that older patients in medical intensive care units receive higher doses of psychoactive medications during evening shifts than day and night shifts.
To determine the dosing patterns and total doses of fentanyl, lorazepam, and haloperidol according to nursing shift in a cohort of older patients in a medical intensive care unit.
The sample consisted of 309 patients 60 years and older admitted to the medical intensive care unit at Yale-New Haven Hospital, New Haven, Connecticut. Data on time, dosage, and route of administration of the drugs were collected. Data were analyzed by using a Bayesian random effects Poisson model adjusted for individual heterogeneity, excess zero doses, and important clinical covariates.
Mean age of the patients was 75 years; 58% received fentanyl, 55% received lorazepam, and 32% received haloperidol. Although dosing with fentanyl did not differ according to shift, doses of both lorazepam and haloperidol were higher during the evening shifts (4 pm to midnight) than during the day or night shifts. Compared with women, men received higher doses of both haloperidol and lorazepam and variability between shifts was greater.
In this longitudinal, observational sample of older patients, data indicated a positive association between dose levels of lorazepam and haloperidol during the evening nursing shifts relative to other shifts. Further investigation is needed to determine potential causes and to evaluate the impact on outcomes of sleep deprivation and delirium.
PMCID: PMC4309662  PMID: 23996429
2.  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
3.  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
4.  Integration of Fall Prevention into State Policy in Connecticut 
The Gerontologist  2012;53(3):508-515.
Purpose of Study: To describe the ongoing efforts of the Connecticut Collaboration for Fall Prevention (CCFP) to move evidence regarding fall prevention into clinical practice and state policy. Methods: A university-based team developed methods of networking with existing statewide organizations to influence clinical practice and state policy. Results: We describe steps taken that led to funding and legislation of fall prevention efforts in the state of Connecticut. We summarize CCFP’s direct outreach by tabulating the educational sessions delivered and the numbers and types of clinical care providers that were trained. Community organizations that had sustained clinical practices incorporating evidence-based fall prevention were subsequently funded through mini-grants to develop innovative interventional activities. These mini-grants targeted specific subpopulations of older persons at high risk for falls. Implications: Building collaborative relationships with existing stakeholders and care providers throughout the state, CCFP continues to facilitate the integration of evidence-based fall prevention into clinical practice and state-funded policy using strategies that may be useful to others.
PMCID: PMC3635855  PMID: 23042690
Polypharmacy; Connecticut Collaboration for Fall Prevention; Balance training; Visiting nurse association; Fall prevention
5.  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
6.  A Repeated Trajectory Class Model for Intensive Longitudinal Categorical Outcome 
Statistics in medicine  2014;33(15):2645-2664.
This paper presents a novel repeated latent class model for a longitudinal response that is frequently measured as in our prospective study of older adults with monthly data on activities of daily living (ADL) for more than ten years. The proposed method is especially useful when the longitudinal response is measured much more frequently than other relevant covariates. The repeated trajectory classes represent distinct temporal patterns of the longitudinal response wherein an individual’s membership in the trajectory classes may renew or change over time. Within a trajectory class, the longitudinal response is modeled by a class-specific generalized linear mixed model. Effectively, an individual may remain in a trajectory class or switch to another as the class membership predictors are updated periodically over time. The identification of a common set of trajectory classes allows changes among the temporal patterns to be distinguished from local fluctuations in the response. An informative event such as death is jointly modeled by class-specific probability of the event through shared random effects. We do not impose the conditional independence assumption given the classes. The method is illustrated by analyzing the change over time in ADL trajectory class among 754 older adults with 70500 person-months of follow-up in the Precipitating Events Project. We also investigate the impact of jointly modeling the class-specific probability of the event on the parameter estimates in a simulation study. The primary contribution of our paper is the periodic updating of trajectory classes for a longitudinal categorical response without assuming conditional independence.
PMCID: PMC4145078  PMID: 24519416
joint model; intensive longitudinal data; longitudinal categorical data; shared random effects; repeated latent class; trajectory class
7.  Functional Trajectories Among Older Persons Before and After Critical Illness 
JAMA internal medicine  2015;175(4):523-529.
Little is known about functional trajectories of older persons in the year before and after admission to the intensive care unit (ICU) or how pre-ICU functional trajectories affect post-ICU functional trajectories and death.
To characterize functional trajectories in the year before and after ICU admission and to evaluate the associations among pre-ICU functional trajectories and post-ICU functional trajectories, short-term mortality, and long-term mortality.
Prospective cohort study of 754 community-dwelling persons 70 years or older, conducted between March 23, 1998, and December 31, 2012, in greater New Haven, Connecticut. The analytic sample included 291 participants who had at least 1 admission to an ICU through December 2011.
Functional trajectories in the year before and after an ICU admission based on 13 basic, instrumental, and mobility activities. Additional outcomes included short-term (30 day) and long-term (1 year) mortality.
The mean (SD) age of participants was 83.7 (5.5) years. Three distinct pre-ICU functional trajectories identified were minimal disability (29.6%), mild to moderate disability (44.0%), and severe disability (26.5%). Seventy participants (24.1%) experienced early death, defined as death in the hospital (50 participants [17.2%]) or death after hospital discharge but within 30 days of admission (20 participants [6.9%]). Among the remaining 221 participants, 3 distinct post-ICU functional trajectories identified were minimal disability (20.8%), mild to moderate disability (28.1%), and severe disability (51.1%). More than half of the participants (53.4%) experienced functional decline or early death after critical illness. The pre-ICU functional trajectories of mild to moderate disability and severe disability were associated with more than double (adjusted hazard ratio [HR], 2.41; 95%CI, 1.29–4.50) and triple (adjusted HR, 3.84; 95%CI, 1.84–8.03) the risk of death within 1 year of ICU admission, respectively. Other factors associated with 1-year mortality included ICU length of stay (adjusted HR, 1.03; 95%CI, 1.00–1.05), mechanical ventilation (adjusted HR, 2.89; 95%CI, 1.91–4.37), and shock (adjusted HR, 2.68; 95%CI, 1.63–4.38).
Among older persons with critical illness, more than half died within 1 month or experienced significant functional decline over the following year, with particularly poor outcomes in those who had high levels of premorbid disability. These results may help to inform discussions about prognosis and goals of care before and during critical illness.
PMCID: PMC4467795  PMID: 25665067
8.  Mortality of Hospitalized Patients with Pleural Effusions 
Each year in the United States an estimated 1.5 million people develop pleural effusions and approximately 178,000 thoracenteses (12%) are performed. While it has been established that malignant effusions are associated with increased mortality, the association between mortality and all-cause pleural effusions in a medical population has not been previously evaluated. Our objective was to evaluate associations between 30-day and 12-month all-cause mortality among patients with a pleural effusion.
All patients admitted to the medical service at Yale-New Haven Hospital during March 2011 were screened for pleural effusion. Pleural effusions were documented by the attending radiologist and the medical record was reviewed for admitting diagnosis, severity of illness and whether a thoracenteses was performed. The outcomes were 30-day and 12-month mortality after identification of the pleural effusion.
One-hundred and four patients admitted to the medical service had pleural effusions documented by the attending radiologist. At 30-days, 15% of these patients had died and by 12-months mortality had increased to 32%. Eleven (10.6%) of the 104 patients underwent a thoracenteses. Severity of illness and malignancy were associated with 30-day mortality. For 12-month mortality, associations were found with age, severity of illness, malignancy, and diagnosis of pulmonary disease. Although sample size precluded statistical significance with mortality, the hazard ratio for thoracenteses and 30-day mortality was protective, suggesting a possible short term survival benefit.
In hospitalized medical patients with a pleural effusion, age, severity of illness and malignancy or pulmonary disease were associated with higher 12-month mortality. Thoracenteses may provide a protective effect in the first 30 days, but larger studies are needed to detect a short-term survival benefit. The presence of a pleural effusion indicates a high risk of death, with 15% of patients dying within 30 days and 32% dead within one-year of hospital admission.
PMCID: PMC4428160  PMID: 25977841
Pleural effusion; Thoracenteses; Mortality
9.  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
JAMA internal medicine  2013;173(19):10.1001/jamainternmed.2013.9063.
Although a serious fall injury is often a devastating event, little is known about the course of disability (i.e. functional trajectories) prior to a serious fall injury or the relationship between these trajectories and those that follow the fall.
To identify distinct sets of functional trajectories in the year immediately before and after a serious fall injury, to evaluate the relationship between the pre-fall and post-fall trajectories, and to determine whether these results differed based on the type of injury.
Design, Setting, and Participants
Prospective cohort study conducted in greater New Haven, Connecticut, from March 1998 to June 2012 of 754 community-living persons aged 70 or older who were initially nondisabled in their basic activities of daily living. Of the 130 participants who subsequently sustained a serious fall injury, 62 had a hip fracture and 68 had another fall-related injury leading to hospitalization.
Main Outcome Measures
Functional trajectories, based on 13 basic, instrumental and mobility activities that were assessed during monthly interviews, were identified in the year before and after the serious fall injury, respectively.
Before the fall, five distinct trajectories were identified: no disability (n=16, 12.3%), mild disability (n=34, 26.2%), moderate disability (n=34, 26.2%), progressive disability (n=23, 17.7%), and severe disability (n=23, 17.7%). After the fall, four distinct trajectories were identified: rapid recovery (n=12, 9.2%), gradual recovery (n=35, 26.9%), little recovery (n=26, 20.0%), and no recovery (n=57, 43.8%). For both hip fractures and other serious fall injuries, the probabilities of the post-fall trajectories were greatly influenced by the pre-fall trajectories, such that rapid recovery was observed only among persons who had no disability or mild disability, and a substantive recovery, defined as rapid or gradual, was highly unlikely among those who had progressive or severe disability. The post-fall trajectories were consistently worse for hip fractures than for the other serious injuries.
Conclusions and Relevance
The functional trajectories before and after a serious fall injury are quite varied, but highly interconnected, suggesting that the likelihood of recovery is greatly constrained by the pre-fall trajectory.
PMCID: PMC3812391  PMID: 23958741
11.  The Safety of Thoracentesis in Patients with Uncorrected Bleeding Risk 
Background: Thoracentesis is commonly performed to evaluate pleural effusions. Many medications (warfarin, heparin, clopidogrel) or physiological factors (elevated International Normalized Ratio [INR], thrombocytopenia, uremia) increase the risk for bleeding. Frequently these medications are withheld or transfusions are performed to normalize physiological parameters before a procedure. The safety of performing thoracentesis without correction of these bleeding risks has not been prospectively evaluated.
Methods: This prospective observational cohort study enrolled 312 patients who underwent thoracentesis. All patients were evaluated for the presence of risk factors for bleeding. Hematocrit levels were obtained pre- and postprocedure, and the occurrence of postprocedural hemothorax was evaluated.
Measurements and Main Results: Thoracenteses were performed in 312 patients, 42% of whom had a risk for bleeding. Elevated INR, secondary to liver disease or warfarin, and renal disease were the two most common etiologies for bleeding risk, although many patients had multiple potential bleeding risks. There was no significant difference in pre- and postprocedural hematocrit levels in patients with a bleeding risk when compared with patients with no bleeding risk. No patient developed a hemothorax as a result of the thoracentesis.
Conclusions: This single-center, observational study suggests that thoracentesis may be safely performed without prior correction of coagulopathy, thrombocytopenia, or medication-induced bleeding risk. This may reduce the morbidity associated with transfusions or withholding of medications.
PMCID: PMC3960907  PMID: 23952852
pleural effusion; pleural cavity; thoracentesis; coagulopathy
12.  Association of Injurious Falls With Disability Outcomes and Nursing Home Admissions in Community-Living Older Persons 
American Journal of Epidemiology  2013;178(3):418-425.
Little is known about the deleterious effects of injurious falls relative to those of other disabling conditions or whether these effects are driven largely by hip fractures. From a cohort of 754 community-living elders of New Haven, Connecticut, we matched 122 hospitalizations for an injurious fall (59 hip-fracture and 63 other fall-related injuries) to 241 non–fall-related hospitalizations. Participants (mean age: 85.7 years) were evaluated monthly for disability in 13 activities and admission to a nursing home from 1998 to 2010. For both hip-fracture and other fall-related injuries, the disability scores were significantly greater during each of the first 6 months after hospitalization than for the non–fall-related admissions, with adjusted risk ratios at 6 months of 1.5 (95% confidence interval (CI): 1.3, 1.7) for hip fracture and 1.4 (95% CI: 1.2, 1.6) for other fall-related injuries. The likelihood of having a long-term nursing home admission was considerably greater after hospitalization for a hip fracture and other fall-related injury than for a non–fall-related reason, with adjusted odds ratios of 3.3 (95% CI: 1.3, 8.3) and 3.2 (95% CI: 1.3, 7.8), respectively. Relative to other conditions leading to hospitalization, hip-fracture and other fall-related injuries are associated with worse disability outcomes and a higher likelihood of long-term nursing home admissions.
PMCID: PMC3816345  PMID: 23548756
accidental falls; activities of daily living; aged; cohort studies; nursing homes
13.  Restricting Symptoms in the Last Year of Life 
JAMA internal medicine  2013;173(16):1534-1540.
Freedom from symptoms is an important determinant of a good death, but little is known about symptom occurrence during the last year of life.
To evaluate the monthly occurrence of physical and psychological symptoms leading to restrictions in daily activities (ie, restricting symptoms) among older persons during the last year of life and to determine the associations of demographic and clinical factors with symptom occurrence.
Prospective cohort study. Comprehensive assessments were completed every 18 months, and monthly interviews were conducted to assess the presence of restricting symptoms. Of 1002 nondisabled community-dwelling individuals 70 years or older in greater New Haven, Connecticut, eligible to participate, 754 agreed and were enrolled between 1998 and 1999.
The primary outcome was the monthly occurrence of restricting symptoms as a dichotomous outcome. The monthly mean count of restricting symptoms was a secondary outcome.
Among the 491 participants who died after their first interview and before June 30, 2011, mean age at death was 85.8 years, 61.9% were women, and 9.0% were nonwhite. The mean number of comorbid conditions was 2.4, and 73.1% had multimorbidity. The monthly occurrence of restricting symptoms was fairly constant from 12 months before death (20.4%) until 5 months before death (27.4%), when it began to increase rapidly, reaching 57.2% in the month before death. In multivariable analysis, age younger than 85 years (odds ratio [OR], 1.30 [95% CI, 1.07–1.57]), multimorbidity (OR, 1.38 [95% CI, 1.09–1.75]), and proximity to time of death (OR, 1.14 per month [95% CI, 1.11–1.16]) were significantly associated with the monthly occurrence of restricting symptoms. Participants who died of cancer had higher monthly symptom occurrence (OR, 1.80 [95% CI, 1.03–3.14]) than participants who died of sudden death, although this difference was only marginally significant (P = .04). Symptom burden did not otherwise differ substantially according to condition leading to death.
Restricting symptoms are common during the last year of life, increasing substantially approximately 5 months before death. Our results highlight the importance of assessing and managing symptoms in older patients, particularly those with multimorbidity.
PMCID: PMC4041035  PMID: 23836056
14.  Validation of a handoff assessment tool: the Handoff CEX 
Journal of clinical nursing  2012;22(0):1477-1486.
Aims and objectives
Test the feasibility and validity of a handoff evaluation tool for nurses.
No validated tools exist to assess the quality of handoff communication during change of shift.
Prospective cohort study.
A standardised tool, the Handoff CEX, was developed based on the mini-CEX. The tool consisted of seven domains scored on a 1–9 scale. Nurse educators observed shift-to-shift handoff reports among nurses and evaluated both the provider and recipient of the report. Nurses participating in the report simultaneously evaluated each other as part of their handoff.
Ninety-eight evaluations were obtained from 25 reports. Scores ranged from 3–9 in all domains except communication and setting (4–9). Experienced (>five years) nurses received significantly higher mean scores than inexperienced (≤five years) nurses in all domains except setting and professionalism. Mean overall score for experienced nurses was 7·9 vs 6·9 for inexperienced nurses. External observers gave significantly lower scores than peer evaluators in all domains except setting. Mean overall score by external observers was 7·1 vs. 8·1 by peer evaluators. Participants were very satisfied with the evaluation (mean score 8·1).
A brief, structured handoff evaluation tool was designed that was well-received by participants, was felt to be easy to use without training, provided data about a wide range of communication competencies and discriminated well between experienced and inexperienced clinicians.
Relevance to clinical practice
This tool may be useful for educators, supervisors and practicing nurses to provide training, ongoing assessment and feedback to improve the quality of handoff.
PMCID: PMC3504166  PMID: 22671983
communication; evaluation; handover; nurses; nursing; nursing education; transfer of care
15.  Association Between Indicators of Disability Burden and Subsequent Depression Among Older Persons 
Disability is associated with depression in older persons, yet the effect of disability burden on the likelihood of being depressed is uncertain.
A total of 754 community-living persons, aged ≥70, underwent monthly assessments in four essential activities of daily living and assessments of depression (yes/no) every 18 months for up to 108 months. Within each 18-month person-interval, participants’ disability burden was operationalized as none or any, and according to severity (none, mild, or severe) and chronicity (none, nonchronic, or chronic) given the highest level of severity or chronicity experienced during a given 18-month interval, respectively. A variable combining severity and chronicity (none, nonchronic mild, nonchronic severe, chronic–mild, or chronic–severe) was also created. Using generalized estimating equations, we evaluated the association between each indicator of disability burden and subsequent depression.
Participants who had any versus no disability during the previous 18 months were 65% more likely to experience subsequent depression (OR = 1.65; 95% confidence interval [CI] 1.34, 2.02). Quantifying severity (mild disability vs. none, OR = 1.43; 95% CI: 1.15, 1.79; severe disability vs. none, OR = 2.07; 95% CI 1.56, 2.74) and chronicity (nonchronic disability vs. none, OR = 1.44; 95% CI 1.13, 1.83; chronic disability vs. none, OR = 1.96; 95% CI 1.50, 2.55) indicated increasingly stronger associations with subsequent depression, with the highest likelihood of subsequent depression (OR = 2.42; 95% CI 1.78, 3.30) observed among participants with chronic–severe disability.
Quantifying the magnitude of disability burden, particularly on the basis of severity and chronicity, provides additional information regarding the likelihood of experiencing subsequent depression among older persons.
PMCID: PMC3605908  PMID: 22967459
Aging; Disability; Depression; Depressive symptoms; Prospective studies.
16.  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
17.  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
19.  Multivariate Graphical Methods Provide an Insightful Way to Formulate Explanatory Hypotheses from Limited Categorical Data 
Journal of Clinical Epidemiology  2011;65(2):179-188.
Graphical methods for generating explanatory hypotheses from limited categorical data are described and illustrated.
Study Design and Setting
Univariate, bivariate, multivariate, and multiplicative graphical methods were applied to clinical data regarding very ill older persons. The data to which these methods were applied were limited as to their nature (e.g., nominal categorical data) or quality (e.g., data subject to measurement error and missing values). Such limitations make confirmatory inference problematic but might still allow for meaningful generation of new explanatory hypotheses in some cases.
A striking feature of the graphical results from this study’s major illustrative application was that Post-Traumatic Stress Disorder (PTSD) following Intensive Care Unit (ICU) discharge occurred rarely and nearly always co-occurred with two or more other mental health conditions. These results suggest the explanatory hypothesis that PTSD in this context is less attributable to single traumatic causes than to acute illnesses contributing to a cascade of mental health decrements.
Illustrative applications of a sequence of graphical procedures yield more informative and less abstract representations of limited data than do descriptive statistics alone, and by doing so, they aid in the formulation of explanatory hypotheses.
PMCID: PMC3250573  PMID: 21889310
graphical methods; multivariate data; older patients; logic; critical care
20.  Bayesian Time-Series Analysis of a Repeated-Measures Poisson Outcome With Excess Zeroes 
American Journal of Epidemiology  2011;174(11):1230-1237.
In this article, the authors demonstrate a time-series analysis based on a hierarchical Bayesian model of a Poisson outcome with an excessive number of zeroes. The motivating example for this analysis comes from the intensive care unit (ICU) of an urban university teaching hospital (New Haven, Connecticut, 2002–2004). Studies of medication use among older patients in the ICU are complicated by statistical factors such as an excessive number of zero doses, periodicity, and within-person autocorrelation. Whereas time-series techniques adjust for autocorrelation and periodicity in outcome measurements, Bayesian analysis provides greater precision for small samples and the flexibility to conduct posterior predictive simulations. By applying elements of time-series analysis within both frequentist and Bayesian frameworks, the authors evaluate differences in shift-based dosing of medication in a medical ICU. From a small sample and with adjustment for excess zeroes, linear trend, autocorrelation, and clinical covariates, both frequentist and Bayesian models provide evidence of a significant association between a specific nursing shift and dosing level of a sedative medication. Furthermore, the posterior distributions from a Bayesian random-effects Poisson model permit posterior predictive simulations of related results that are potentially difficult to model.
PMCID: PMC3254157  PMID: 22025357
autocorrelation; Bayes theorem; models, statistical; periodicity; time series
21.  College Graduation Rates for Minority Students in a Selective Technical University: Will Participation in a Summer Bridge Program Contribute to Success? 
There are many approaches to solving the problem of underrepresentation of some racial and ethnic groups and women in scientific and technical disciplines. Here, the authors evaluate the association of a summer bridge program with the graduation rate of underrepresented minority (URM) students at a selective technical university. They demonstrate that this 5-week program prior to the fall of the 1st year contains elements reported as vital for successful student retention. Using multivariable survival analysis, they show that for URM students entering as fall-semester freshmen, relative to their nonparticipating peers, participation in this accelerated summer bridge program is associated with higher likelihood of graduation. The longitudinal panel data include more than 2,200 URM students.
PMCID: PMC3489281  PMID: 23136456
persistence; retention; underrepresented minority; survival analysis; STEM; bridge program
22.  An examination of effect estimation in factorial and standardly-tailored designs 
Many clinical trials are designed to test an intervention arm against a control arm wherein all subjects are equally eligible for all interventional components. Factorial designs have extended this to test multiple intervention components and their interactions. A newer design referred to as a ‘standardly-tailored’ design, is a multicomponent interventional trial that applies individual interventional components to modify risk factors identified a priori and tests whether health outcomes differ between treatment arms. Standardly-tailored designs do not require that all subjects be eligible for every interventional component. Although standardly-tailored designs yield an estimate for the net effect of the multicomponent intervention, it has not yet been shown if they permit separate, unbiased estimation of individual component effects. The ability to estimate the most potent interventional components has direct bearing on conducting second stage translational research.
We present statistical issues related to the estimation of individual component effects in trials of geriatric conditions using factorial and standardly-tailored designs. The medical community is interested in second stage translational research involving the transfer of results from a randomized clinical trial to a community setting. Before such research is undertaken, main effects and synergistic and or antagonistic interactions between them should be identified. Knowledge of the relative strength and direction of the effects of the individual components and their interactions facilitates the successful transfer of clinically significant findings and may potentially reduce the number of interventional components needed. Therefore the current inability of the standardly-tailored design to provide unbiased estimates of individual interventional components is a serious limitation in their applicability to second stage translational research.
We discuss estimation of individual component effects from the family of factorial designs and this limitation for standardly-tailored designs. We use the phrase ‘factorial designs’ to describe full-factorial designs and their derivatives including the fractional factorial, partial factorial, incomplete factorial and modified reciprocal designs. We suggest two potential directions for designing multicomponent interventions to facilitate unbiased estimates of individual interventional components.
Full factorial designs and their variants are the most common multicomponent trial design described in the literature and differ meaningfully from standardly-tailored designs. Factorial and standardly-tailored designs result in similar estimates of net effect with different levels of precision. Unbiased estimation of individual component effects from a standardly-tailored design will require new methodology.
Although clinically relevant in geriatrics, previous applications of standardly-tailored designs have not provided unbiased estimates of the effects of individual interventional components.
Future directions to estimate individual component effects from standardly-tailored designs include applying D-optimal designs and creating independent linear combinations of risk factors analogous to factor analysis.
Methods are needed to extract unbiased estimates of the effects of individual interventional components from standardly-tailored designs.
PMCID: PMC3477845  PMID: 18375650
23.  Effect of Dissemination of Evidence in Reducing Injuries from Falls 
The New England journal of medicine  2008;359(3):252-261.
Falling is a common and morbid condition among elderly persons. Effective strategies to prevent falls have been identified but are underutilized.
Using a nonrandomized design, we compared rates of injuries from falls in a region of Connecticut where clinicians had been exposed to interventions to change clinical practice (intervention region) and in a region where clinicians had not been exposed to such interventions (usual-care region). The interventions encouraged primary care clinicians and staff members involved in home care, outpatient rehabilitation, and senior centers to adopt effective risk assessments and strategies for the prevention of falls (e.g., medication reduction and balance and gait training). The outcomes were rates of serious fall-related injuries (hip and other fractures, head injuries, and joint dislocations) and fall-related use of medical services per 1000 person-years among persons who were 70 years of age or older. The interventions occurred from 2001 to 2004, and the evaluations took place from 2004 to 2006.
Before the interventions, the adjusted rates of serious fall-related injuries (per 1000 person-years) were 31.2 in the usual-care region and 31.9 in the intervention region. During the evaluation period, the adjusted rates were 31.4 and 28.6, respectively (adjusted rate ratio, 0.91; 95% Bayesian credibility interval, 0.88 to 0.94). Between the preintervention period and the evaluation period, the rate of fall-related use of medical services increased from 68.1 to 83.3 per 1000 person-years in the usual-care region and from 70.7 to 74.2 in the intervention region (adjusted rate ratio, 0.89; 95% credibility interval, 0.86 to 0.92). The percentages of clinicians who received intervention visits ranged from 62% (131 of 212 primary care offices) to 100% (26 of 26 home care agencies).
Dissemination of evidence about fall prevention, coupled with interventions to change clinical practice, may reduce fall-related injuries in elderly persons.
PMCID: PMC3472807  PMID: 18635430
We determined the association between clinically significant depressive symptoms, often referred to as depression, and subsequent transitions between no disability, mild disability, severe disability, and death.
Prospective cohort study.
General community in greater New Haven, Connecticut, from March 23, 1998, to December 31, 2008.
Seven-hundred fifty four persons, aged 70 years or older.
Monthly assessments of disability in essential activities of daily living and assessments of depressive symptoms every 18 months using a short-form of the Center for Epidemiologic Studies of Depression Scale for up to 129 months.
Depressed participants were more likely than those who were non-depressed to transition from a state of no disability to mild (HR= 1.52; 95% CI 1.25, 1.85) and severe disability (HR=1.57; 95% CI 1.22, 2.01), and from a state of mild disability to severe disability (HR=1.33; 95% CI 1.06, 1.65); and were less likely to transition from a state of mild disability to no disability (HR=0.69; 95% CI 0.57, 0.85) and from a state of severe disability to no disability (HR=0.50; 95% CI 0.31, 0.79).
Depressive symptoms are associated with transitions into and out of disabled states, and with increased likelihood of transitioning from mild to severe disability. More broadly, our findings underscore the complexity of the relationship between depressive symptoms and disability. Future work is needed to evaluate the likely reciprocal relationship between depression and functional transitions in older persons.
PMCID: PMC3164788  PMID: 21873834
Depression; Depressive symptoms; Disability; Prospective studies
Annals of Internal Medicine  2012;156(2):131-140.
Relatively little is known about why older persons develop long-term disability in community mobility.
To identify the risk factors and precipitants for long-term disability in walking ¼ mile and driving a car, respectively.
Prospective cohort study from March 1998 to December 2009.
Greater New Haven, Connecticut.
641 persons, 70+ years, who were active drivers or nondisabled in walking ¼ mile. Persons who were physically frail were oversampled.
Candidate risk factors were assessed every 18 months. Disability in community mobility and exposure to potential precipitants, which included illnesses/injuries leading to hospitalization or restricted activity, respectively, were assessed every month. Disability lasting ≥6 consecutive months was considered long term.
318 (56.0%) and 269 (53.1%) participants developed long-term disability in walking and driving, respectively. Seven risk factors were independently associated with walking disability, while eight were associated with driving disability; the strongest associations for each outcome were found for older age and lower score on the Short Physical Performance Battery. The effects of the precipitants on long-term disability were large, with multivariable hazard ratios for each outcome greater than 6 for hospitalization and 2.4 for restricted activity. The largest differences in absolute risk were generally observed for participants who had a specific risk factor and were subsequently hospitalized.
The observed associations may not be causal. The severity of precipitants was not assessed. The effect of the precipitants may have been underestimated because their exposure after the initial onset of disability was not evaluated.
Long-term disability in community mobility is common among older persons. Multiple risk factors, together with subsequent precipitants, greatly increase the likelihood of developing long-term mobility disability.
Primary Funding Source
National Institute on Aging.
PMCID: PMC3278794  PMID: 22250144

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