Spirometric Criteria for Chronic Obstructive Pulmonary Disease in Clinical Trials of Pharmacotherapy.

Clinical trials of pharmacotherapy in chronic obstructive pulmonary disease (COPD) often include older persons with moderate-to-severe airflow-obstruction, as defined by the Global Initiative for chronic Obstructive Lung Disease (GOLD). In this context, spirometric airflow-obstruction establishes COPD. Because GOLD misidentifies COPD and its severity in older persons, we set out to apply more age-appropriate spirometric criteria from the Global Lung function Initiative (GLI) in a prior clinical trial of COPD pharmacotherapy, specifically the Towards a Revolution in COPD Health (TORCH) trial - N = 6,112, mean age 65 years. In the TORCH trial, which enrolled GOLD-defined moderate COPD (26.2%, n = 1,200) and GOLD-defined severe COPD (73.8%, n = 4,511), the GLI reclassification yielded a higher frequency of severe COPD (89.6%, n = 5,474), the inclusion of restrictive-pattern (6.9%, n = 420) and, in turn, a very low frequency of moderate COPD (3.5%, n = 212). These GLI reclassification results suggest that GOLD-based enrollment criteria for the TORCH trial may have assembled a cohort that was: 1) less likely to respond to COPD pharmacotherapy, given the greater representation of severe COPD, very minor representation of moderate COPD, and inclusion of a non-obstructive spirometric impairment (restrictive-pattern); and 2) more likely to have medication-related adverse events, given the inappropriate use of COPD pharmacotherapy in misidentified COPD (restrictive-pattern). We therefore propose that future clinical trials of COPD pharmacotherapy should consider GLI criteria for defining COPD, including a greater representation of GLI-defined moderate COPD.

Factors Associated with Functional Recovery among Older Intensive Care Unit Survivors.

RATIONALE: Most of the 1.4 million older adults who survive the intensive care unit (ICU) annually in the United States face increased disability, but little is known about those who achieve functional recovery. OBJECTIVES: Our objectives were twofold: to evaluate the incidence and time to recovery of premorbid function within 6 months of a critical illness and to identify independent predictors of functional recovery among older ICU survivors. METHODS: Potential participants included 754 persons aged 70 years or older who were evaluated monthly in 13 functional activities (1998-2012). The analytic sample included 218 ICU admissions from 186 ICU survivors. Functional recovery was defined as returning to a disability count less than or equal to the pre-ICU disability count within 6 months. Twenty-one potential predictors were evaluated for their associations with recovery. MEASUREMENTS AND MAIN RESULTS: Functional recovery was observed for 114 (52.3%) of the 218 admissions. In multivariable analysis, higher body mass index (hazard ratio [HR], 1.07; 95% confidence interval [CI], 1.03-1.12) and greater functional self-efficacy (HR, 1.05; 95% CI, 1.02-1.08), a measure of confidence in performing various activities, were associated with recovery, whereas pre-ICU impairment in hearing (HR, 0.38; 95% CI, 0.22-0.66) and vision (HR, 0.59; 95% CI, 0.37-0.95) were associated with a lack of recovery. CONCLUSIONS: Among older adults who survived an ICU admission with increased disability, pre-ICU hearing and vision impairment were strongly associated with poor functional recovery within 6 months, whereas higher body mass index and functional self-efficacy were associated with recovery. Future research is needed to evaluate whether interventions targeting these factors improve functional outcomes among older ICU survivors.

Development and validation of a prediction model for persistent functional impairment among older ICU survivors.

BACKGROUND: Critical illness often leads to persistent functional impairment among older Intensive Care Unit (ICU) survivors. Identification of high-risk survivors prior to discharge from their ICU hospitalization can facilitate targeting for restorative interventions after discharge, potentially improving the likelihood of functional recovery. Our objective was to develop and validate a prediction model for persistent functional impairment among older adults in the year after an ICU hospitalization. METHODS: The analytic sample included community-living participants enrolled in the National Health and Aging Trends Study 2011 cohort who survived an ICU hospitalization through December 2017 and had a follow-up interview within 1 year. Persistent functional impairment was defined as failure to recover to the pre-ICU level of function within 12 months of discharge from an ICU hospitalization. We used Bayesian model averaging to identify the final predictors from a comprehensive set of 17 factors. Discrimination and calibration were assessed using area-under-the-curve (AUC) and calibration plots. RESULTS: The development cohort included 456 ICU admissions (2,654,685 survey-weighted admissions) and the validation cohort included 227 ICU admissions (1,350,082 survey-weighted admissions). In the development cohort, the median age was 81.0 years (interquartile range [IQR] 76.0, 86.0) and 231 (50.7%) participants were women; demographic characteristics were comparable in the validation cohort. The rates of persistent functional impairment were 49.3% (development) and 50.2% (validation). The final model included age, pre-ICU disability, probable dementia, frailty, prior hospitalizations, vision impairment, depressive symptoms, and hospital length of stay. The model demonstrated good discrimination (AUC 71%, 95% confidence interval [CI] 0.66-0.76) and good calibration. When applied to the validation cohort, the model demonstrated comparable discrimination (AUC 72%, 95% CI 0.66-0.78) and good calibration. CONCLUSIONS: Application of the model prior to discharge from an ICU hospitalization may identify older adults at the highest risk of persistent functional impairment in the subsequent year, thereby facilitating targeted interventions and follow-up.

A Longitudinal Analysis of Functional Disability, Recovery, and Nursing Home Utilization After Hospitalization for Ambulatory Care Sensitive Conditions Among Community-Living Older Persons.

BACKGROUND/OBJECTIVE: Hospitalizations for ambulatory care sensitive conditions (ACSCs) are considered potentially preventable. With little known about the functional outcomes of older persons after ACSC-related hospitalizations, our objectives were to describe: (1) the 6-month course of postdischarge functional disability, (2) the cumulative monthly probability of functional recovery, and (3) the cumulative monthly probability of incident nursing home (NH) admission. METHODS: The analytic sample included 251 ACSC-related hospitalizations from a cohort of 754 nondisabled, community-living persons aged 70 years and older who were interviewed monthly for up to 19 years. Patient-reported disability scores in basic, instrumental, and mobility activities ranged from 0 to 13. Functional recovery was defined as returning within 6 months of discharge to a total disability score less than or equal to that immediately preceding hospitalization. RESULTS: The mean age was 85.1 years, and the mean disability score was 5.4 in the month prior to the ACSC-related hospitalization. After the ACSC-related hospitalization, total disability scores peaked at month 1 and improved modestly over the next 5 months, but remained greater than the pre-hospitalization score. Functional recovery was achieved by 70% of patients, and incident NH admission was experienced by 50% within 6 months after the 251 ACSC-related hospitalizations. CONCLUSIONS: During the 6 months after an ACSC-related hospitalization, older persons exhibited total disability scores that were higher than those immediately preceding hospitalization, with 3 of 10 not achieving functional recovery and half experiencing incident NH admission. These findings provide evidence that older persons experience clinically meaningful adverse patient-reported outcomes after ACSC-related hospitalizations.

Disability and Recovery After Hospitalization for Medical Illness Among Community-Living Older Persons: A Prospective Cohort Study.

OBJECTIVES: To determine for each basic, instrumental, and mobility activity after hospitalization for acute medical illness: (1) disability prevalence immediately before and monthly for 6 months after hospitalization; (2) disability incidence 1 month after hospitalization; and (3) recovery time from incident disability during months 2 to 6 after hospitalization. DESIGN: Prospective cohort study. SETTING: New Haven, Connecticut. PARTICIPANTS: A total of 515 community-living persons, mean age 82.7 years, hospitalized for acute noncritical medical illness and alive within 1 month of hospital discharge. MEASUREMENTS: Disability was defined monthly for each basic (bathing, dressing, walking, transferring), instrumental (shopping, housework, meal preparation, taking medications, managing finances), and mobility activity (walking a quarter mile, climbing flight of stairs, lifting/carrying 10 pounds, driving) if help was needed to perform the activity or if a car was not driven in the prior month. RESULTS: Disability was common 1 and 6 months after hospitalization for activities frequently involved in leaving the home to access care including walking a quarter mile (prevalence 65% and 53%, respectively) and driving (65% and 61%). Disability was also common for activities involved in self-managing chronic health conditions including meal preparation (53% and 41%) and taking medications (41% and 31%). New disability was common and often prolonged. For example, 43% had new disability walking a quarter mile, and 30% had new disability taking medications, with mean recovery time of 1.9 months and 1.7 months, respectively. Findings were similar for the subgroup of persons residing at home (ie, not in a nursing home) at the first monthly follow-up interview after hospitalization. CONCLUSION: Disability in specific functional activities important to leaving home to access care and self-managing health conditions is common, often new, and present for prolonged time periods after hospitalization for acute medical illness. Post-discharge care should support patients through extended periods of vulnerability beyond the immediate transitional period. J Am Geriatr Soc 68:486-495, 2020.

Re-evaluation of the Uplift Clinical Trial Using Age-Appropriate Spirometric Criteria.

BACKGROUND: The clinical trial of tiotropium in COPD, UPLIFT, enrolled adults with a mean age of 65 years and moderate-to-severe airflow obstruction, based on criteria from the Global Initiative for Chronic Obstructive Lung Disease (GOLD). For the UPLIFT cohort, however, GOLD-based criteria are not age-appropriate. RESEARCH QUESTION: Will the use of more age-appropriate criteria for airflow obstruction from the Global Lung Function Initiative (GLI) modify the spirometric classification of the UPLIFT cohort and, in turn, the mortality effect of tiotropium in COPD? STUDY DESIGN AND METHODS: Baseline spirometric classifications were first cross-tabulated by GLI- and GOLD-based criteria. Next, in GLI- and GOLD-based airflow obstruction, modified intention-to-treat analyses evaluated differences in time to death over 4 years, comparing tiotropium vs placebo. Because treatment response may differ by COPD severity, the mortality effect also was evaluated within stratum defined by GLI- and GOLD-based moderate and severe airflow obstruction. RESULTS: Of 5,898 participants with GOLD-based airflow-obstruction, staged as moderate in 2,739 (46.4%) and severe in 3,156 (53.5%), GLI-based criteria established airflow obstruction in 5,750 (97.5%), staged as moderate in 795 (13.5%) and severe in 4,947 (83.9%). Relative to placebo, tiotropium yielded statistically nonsignificant adjusted hazard ratios (adjHRs) (95% CI) for death of 0.91 (0.80-1.04) and 0.91 (0.79-1.03) in GLI- and GOLD-based airflow obstruction, respectively. However, statistically significant effect modification was observed, but only in GLI-based moderate and severe airflow-obstruction, with tiotropium yielding adjHRs for death of 0.53 (0.34-0.81) and 0.99 (0.86-1.13), respectively. The P value for interaction was .007. INTERPRETATION: Mortality reduction by tiotropium was only statistically significant in GLI-based moderate airflow-obstruction, a group that was underrepresented in UPLIFT because of severity misclassification by the original GOLD-based enrollment criteria.

Diffusing capacity in normal-for-age spirometry and spirometric impairments, using reference equations from the global lung function initiative.

BACKGROUND: Reference equations from the Global Lung Function Initiative (GLI) are now available for both spirometry and diffusion. However, respiratory phenotypes defined by GLI-based measures of diffusion have not yet been evaluated in GLI-based normal-for-age spirometry or spirometric impairments. METHODS: We evaluated cross-sectional data from 2100 Caucasians, aged 40-85 years. GLI-based spirometric categories included normal-for-age and the impairments of restrictive-pattern and three-level severity of airflow-obstruction (mild, moderate, severe). GLI-based diffusion included diffusing capacity of the lung for carbon monoxide (DLCO) and measured components of alveolar volume (VA) and transfer coefficient (KCO): DLCO = [VA]x[KCO]. Using multivariable regression models, adjusted odds ratios (adjORs) for DLCO, VA, and KCO < lower limit of normal (LLN) were calculated for spirometric impairments, relative to normal-for-age spirometry. RESULTS: Relative to normal-for-age spirometry, the restrictive-pattern increased the adjORs (95% confidence intervals) for DLCO and VA < LLN-4.61 (3.62, 5.85) and 15.53 (11.8, 20.4), respectively, but not for KCO < LLN-1.02 (0.79, 1.33). Also relative to normal-for-age spirometry, airflow-obstruction from mild to severe increased the adjORs for DLCO < LLN-from 1.22 (0.80, 1.86) to 6.63 (4.91, 8.95), for VA < LLN-from 1.37 (0.85, 2.18) to 7.01 (5.20, 9.43), and for KCO < LLN-from 2.04 (1.33, 3.14) to 3.03 (2.29, 3.99). Notably, in normal-for-age spirometry, 34.5%, 19.7%, and 25.3% of participants had DLCO, VA, or KCO < LLN, respectively. CONCLUSION: Abnormal diffusion is most prevalent in spirometric impairments but also occurs in normal-for-age spirometry. These results further inform the respiratory phenotypes of GLI-based spirometric categories and, in turn, the spirometric evaluation of respiratory disease.

Re-evaluation of combination therapy in chronic obstructive pulmonary disease (COPD).

BACKGROUND: Clinical trials of COPD pharmacotherapy typically involve aging populations with moderate-to-severe COPD, but the latter is often diagnosed by spirometric criteria that are not age-appropriate across the continuum of lung function. We have therefore re-evaluated the clinical effect of combination therapy (salmeterol plus fluticasone) in moderate-to-severe COPD, using more age-appropriate spirometric criteria from the Global Lung Function Initiative (GLI) and trial data from Towards a Revolution in COPD Health (TORCH). METHODS: Of the 6112 TORCH participants, 5688 (93.1%) had GLI-based moderate-to-severe COPD (mean age 64.8 years). The primary outcome was all-cause mortality and the primary comparison was combination therapy vs. placebo. Secondary outcomes included COPD and cardiovascular (CV) mortality and pneumonia. A modified intention-to-treat analysis evaluated differences in time-to-event over a three-year period, using Cox proportional hazards models with statistical significance at p < 0.010 (acknowledging repeated significance testing). RESULTS: Relative to placebo, combination therapy yielded a statistically non-significant reduction in all-cause mortality-adjusted hazard ratio [adjHR] 0.78 (95% confidence interval [CI]: 0.64, 0.95), p = 0.012. Relative to placebo, combination therapy also yielded statistically non-significant reductions in COPD and CV mortality-adjHR 0.75 (95% CI: 0.55, 1.02), p = 0.068 and adjHR 0.76 (95% CI: 0.53, 1.09), p = 0.135, respectively. In contrast, combination therapy yielded a statistically significant increased risk of pneumonia, relative to placebo-adjHR 1.80 (95% CI: 1.46, 2.21), p < 0.001. CONCLUSION: In GLI-based moderate-to-severe COPD, combination therapy yields a statistically significant increased risk of pneumonia but the reductions in mortality are not statistically significant, although could potentially be clinically meaningful.

The Competing Risk of Death in Longitudinal Geriatric Outcomes.

OBJECTIVES: To address the competing risk of death in longitudinal studies of older persons, we demonstrate sensitivity analyses that evaluate robustness of associations between exposures and three outcome types: dichotomous, count, and time to event. DESIGN: A secondary analysis of data from a prospective cohort study. SETTING: Community-based data from the Precipitating Events Project in New Haven, CT. PARTICIPANTS: Persons 70 years and older who were initially community dwelling and without disability in the four basic activities of daily living (N = 754). MEASUREMENTS: Missing outcome values from decedents were multiply imputed under different scenarios. Three outcomes were examined: dichotomous fall-related hospitalization (FRH); a count (0-13) of total disability in each of the 6 months after discharge; and days to functional recovery among those whose disability worsened in the hospital. Each outcome had a different exposure: for dichotomous, indicators of being overweight or obese; for count, frailty from the Fried phenotype (0-5, where not frail = 0, prefrail = 1-2, and frail = 3-5); for days to recovery, vision impairment. RESULTS: For FRH, being overweight or obese lost significance when decedents were kept in the risk pool without outcome events for over 10 years. For disability count and time to recovery, with follow-up of 6 months, exposures only lost significance under highly implausible clinical scenarios. CONCLUSION: This method facilitates evaluation of potential bias from the competing risk of death in longitudinal studies for nondeath outcomes that are not necessarily time to event. Results suggest that death introduces substantive bias when long-term follow-up results in cumulatively high levels of mortality. J Am Geriatr Soc 67:357-362, 2019.

Bayesian Model Averaging for Selection of a Risk Prediction Model for Death within Thirty Days of Discharge: The SILVER-AMI Study.

We describe a selection process for a multivariable risk prediction model of death within 30 days of hospital discharge in the SILVER-AMI study. This large, multi-site observational study included observational data from 2000 persons 75 years and older hospitalized for acute myocardial infarction (AMI) from 94 community and academic hospitals across the United States and featured a large number of candidate variables from demographic, cardiac, and geriatric domains, whose missing values were multiply imputed prior to model selection. Our objective was to demonstrate that Bayesian Model Averaging (BMA) represents a viable model selection approach in this context. BMA was compared to three other backward-selection approaches: Akaike information criterion, Bayesian information criterion, and traditional p-value. Traditional backward-selection was used to choose 20 candidate variables from the initial, larger pool of five imputations. Models were subsequently chosen from those candidates using the four approaches on each of 10 imputations. With average posterior effect probability ≥ 50% as the selection criterion, BMA chose the most parsimonious model with four variables, with average C statistic of 78%, good calibration, optimism of 1.3%, and heuristic shrinkage of 0.93. These findings illustrate the utility and flexibility of using BMA for selecting a multivariable risk prediction model from many candidates over multiply imputed datasets.

Pre-Intensive Care Unit Cognitive Status, Subsequent Disability, and New Nursing Home Admission among Critically Ill Older Adults.

RATIONALE: Cognitive impairment is common among older adults, yet little is known about the association of pre-intensive care unit cognitive status with outcomes relevant to older adults maintaining independence after a critical illness. OBJECTIVES: To evaluate whether pre-intensive care unit cognitive status is associated with post-intensive care unit disability, new nursing home admission, and mortality after a critical illness among older adults. METHODS: In this prospective cohort study, 754 persons aged 70 years or more were monitored from March 1998 to December 2013 with monthly assessments of disability. Cognitive status was assessed every 18 months, using the Mini-Mental State Examination (range, 0-30), with scores classified as 28 or higher (cognitively intact), 24-27 (minimal impairment), and less than 24 (moderate impairment). The primary outcome was disability count (range, 0-13), assessed monthly over 6 months after an intensive care unit stay. The secondary outcomes were incident nursing home admission and time to death after intensive care unit admission. The analytic sample included 391 intensive care unit admissions. RESULTS: The mean age was 83.5 years. The prevalence of moderate impairment, minimal impairment, and intact cognition (the comparison group) was 17.3, 46.2, and 36.5%, respectively. In the multivariable analysis, moderate impairment was associated with nearly a 20% increase in disability over the 6-month follow-up period (adjusted relative risk, 1.19; 95% confidence interval, 1.04-1.36), and minimal impairment was associated with a 16% increase in post-intensive care unit disability (adjusted relative risk, 1.16; 95% confidence interval, 1.02-1.32). Moderate impairment was associated with more than double the likelihood of a new nursing home admission (adjusted odds ratio, 2.37; 95% confidence interval, 1.01-5.55). Survival differed significantly across the three cognitive groups (log-rank P = 0.002), but neither moderate impairment (adjusted hazard ratio, 1.19; 95% confidence interval, 0.65-2.19) nor minimal impairment (adjusted hazard ratio, 1.00; 95% confidence interval, 0.61-1.62) was significantly associated with mortality in the multivariable analysis. CONCLUSIONS: Among older adults, any impairment (even minimal) in pre-intensive care unit cognitive status was associated with an increase in post-intensive care unit disability over the 6 months after a critical illness; moderate cognitive impairment doubled the likelihood of a new nursing home admission. Pre-intensive care unit cognitive impairment was not associated with mortality from intensive care unit admission through 6 months of follow-up. Pre-intensive care unit cognitive status may provide prognostic information about the likelihood of older adults maintaining independence after a critical illness.

The Association of Frailty With Post-ICU Disability, Nursing Home Admission, and Mortality: A Longitudinal Study.

BACKGROUND: Frailty is a strong indicator of vulnerability among older persons, but its association with ICU outcomes has not been evaluated prospectively (ie, with objective measurements obtained prior to ICU admission). Our objective was to prospectively evaluate the relationship between frailty and post-ICU disability, incident nursing home admission, and death. METHODS: The parent cohort included 754 adults aged ≥ 70 years, who were evaluated monthly for disability in 13 functional activities and every 18 months for frailty (1998-2014). Frailty was assessed using the Fried index, where frailty, prefrailty, and nonfrailty were defined, respectively, as at least three, one or two, and zero criteria (of five). The analytic sample included 391 ICU admissions. RESULTS: The mean age was 84.0 years. Frailty and prefrailty were present prior to 213 (54.5%) and 140 (35.8%) of the 391 admissions, respectively. Relative to nonfrailty, frailty was associated with 41% greater disability over the 6 months following a critical illness (adjusted risk ratio, 1.41; 95% CI, 1.12-1.78); prefrailty conferred 28% greater disability (adjusted risk ratio, 1.28; 95% CI, 1.01-1.63). Frailty (odds ratio, 3.52; 95% CI, 1.23-10.08), but not prefrailty (odds ratio, 2.01; 95% CI, 0.77-5.24), was associated with increased nursing home admission. Each one-point increase in frailty count (range, 0-5) was associated with double the likelihood of death (hazard ratio, 2.00; 95% CI, 1.33-3.00) through 6 months of follow-up. CONCLUSIONS: Pre-ICU frailty status was associated with increased post-ICU disability and new nursing home admission among ICU survivors, and death among all admissions. Pre-ICU frailty status may provide prognostic information about outcomes after a critical illness.

Depressive symptoms and the risk of incident delirium in older hospitalized adults.

OBJECTIVES: To determine whether specific subsets of symptoms from the Geriatric Depression Scale (GDS), assessed at hospital admission, were associated with the incidence of delirium. DESIGN: Secondary analysis of a prospective cohort study of patients from the Delirium Prevention Trial. SETTING: General medicine service at Yale New Haven Hospital, March 25, 1995, through March 18, 1998. PARTICIPANTS: Four hundred sixteen patients aged 70 and older who were at intermediate or high risk for delirium and were not taking antidepressants at hospital admission. MEASUREMENTS: Depressive symptoms were assessed GDS, and daily assessments of delirium were obtained using the Confusion Assessment Method. RESULTS: Of the 416 patients in the analysis sample, 36 (8.6%) developed delirium within the first 5 days of hospitalization. Patients who developed delirium reported 5.7 depressive symptoms on average, whereas patients without delirium reported an average of 4.2 symptoms. Using a Cox proportional hazards model, it was found that depressive symptoms assessing dysphoric mood and hopelessness were predictive of incident delirium, controlling for measures of physical and mental health. In contrast, symptoms of withdrawal, apathy, and vigor were not significantly associated with delirium. CONCLUSION: These findings suggest that assessing symptoms of dysphoric mood and hopelessness could help identify patients at risk for incident delirium. Future studies should evaluate whether nonpharmacological treatment for these symptoms reduces the risk of delirium.

Spirometry, Static Lung Volumes, and Diffusing Capacity.

BACKGROUND: Spirometric Z-scores from the Global Lung Initiative (GLI) rigorously account for age-related changes in lung function and are thus age-appropriate when establishing spirometric impairments, including a restrictive pattern and air-flow obstruction. However, GLI-defined spirometric impairments have not yet been evaluated regarding associations with static lung volumes (total lung capacity [TLC], functional residual capacity [FRC], and residual volume [RV]) and gas exchange (diffusing capacity). METHODS: We performed a retrospective review of pulmonary function tests in subjects ≥40 y old (mean age 64.6 y), including pre-bronchodilator measures for: spirometry (n = 2,586), static lung volumes by helium dilution with inspiratory capacity maneuver (n = 2,586), and hemoglobin-adjusted single-breath diffusing capacity (n = 2,508). Using multivariable linear regression, adjusted least-squares means (adjLSMeans) were calculated for TLC, FRC, RV, and hemoglobin-adjusted single-breath diffusing capacity. The adjLSMeans were expressed with and without height-cubed standardization and stratified by GLI-defined spirometry, including normal (n = 1,251), restrictive pattern (n = 663), and air-flow obstruction (mild, [n = 128]; moderate, [n = 150]; and severe, [n = 394]). RESULTS: Relative to normal spirometry, restrictive-pattern had lower adjLSMeans for TLC, FRC, RV, and hemoglobin-adjusted single-breath diffusing capacity (P ≤ .001). Conversely, relative to normal spirometry, mild, moderate, and severe air-flow obstruction had higher adjLSMeans for FRC and RV (P < .001). However, only mild and moderate air-flow obstruction had higher adjLSMeans for TLC (P < .001), while only moderate and severe air-flow obstruction had higher adjLSMeans for RV/TLC (P < .001) and lower adjLSMeans for hemoglobin-adjusted single-breath diffusing capacity (P < .001). Notably, TLC (calculated as FRC + inspiratory capacity) was not increased in severe air-flow obstruction (P ≥ .11) because inspiratory capacity decreased with increasing air-flow obstruction (P < .001), thus opposing the increased FRC (P < .001). Finally, P values were similar whether adjLSMeans were height-cubed standardized. CONCLUSIONS: A GLI-defined spirometric restrictive pattern is strongly associated with a restrictive ventilatory defect (decreased TLC, FRC, and RV), while GLI-defined spirometric air-flow obstruction is strongly associated with hyperinflation (increased FRC) and air trapping (increased RV and RV/TLC). Both spirometric impairments were strongly associated with impaired gas exchange (decreased hemoglobin-adjusted single-breath diffusing capacity).

Older adults discharged from the hospital with delirium: 1-year outcomes.

OBJECTIVES: To compare 1-year institutionalization and mortality rates of patients who were delirious at discharge, patients whose delirium resolved by discharge, and patients who were never delirious in the hospital. DESIGN: Secondary analysis of prospective cohort data from the Delirium Prevention Trial. SETTING: General medicine service at Yale New Haven Hospital, March 25, 1995, through March 18, 1998, with follow-up interviews completed in 2000. PARTICIPANTS: Four hundred thirty-three patients aged 70 and older who were not delirious at admission. MEASUREMENTS: Patients underwent daily assessments of delirium from admission to discharge using the Confusion Assessment Method. Nursing home placement and mortality were determined at 1-year follow up. RESULTS: Of the 433 study patients, 24 (5.5%) had delirium at discharge, 31 (7.2%) had delirium that resolved during hospitalization, and 378 (87.3%) were never delirious. After 1 year of follow-up, 20 of 24 (83.3%) patients discharged with delirium, 21 of 31 (67.7%) patients whose delirium resolved, and 157 of 378 (41.5%) patients who were never delirious were admitted to a nursing home or died. Compared with patients who were never delirious, patients with delirium at discharge had a multivariable adjusted hazard ratio (HR) of 2.64 (95% confidence interval (CI)=1.60-4.35) for nursing home placement or mortality, whereas resolved cases had a HR of 1.53 (95% CI=0.96-2.43). CONCLUSION: Delirium at discharge is associated with a high rate of nursing home placement and mortality over a 1-year follow-up period. Interventions to increase detection of delirium and improvements in transitional care may help reduce these negative outcomes.

Premature death associated with delirium at 1-year follow-up.

BACKGROUND: While previous studies have demonstrated the increased mortality risk associated with delirium, little is known about the mortality time course. The objective of this study is to estimate the fraction of a year of life lost associated with delirium at 1-year follow-up. METHODS: Hospitalized patients 70 years and older who participated in a previous controlled clinical trial of a delirium prevention intervention at an academic medical center from March 25, 1995, through March 18, 1998, were followed up for 1 year after discharge, and patients who died were identified, along with the date of death. The adjusted number of days survived were estimated using a 2-step regression model approach and compared across patients who developed delirium during hospitalization and those who did not develop delirium. RESULTS: After adjusting for pertinent covariates (age, sex, functional status, and comorbidity), patients with delirium survived 274 days, compared with 321 days for patients without delirium, representing a difference of 13% of a year (hazard ratio, 1.62; P<.001). Results were confirmed with a separate binomial regression analysis. CONCLUSIONS: Patients who experienced delirium during hospitalization had a 62% increased risk of mortality and lost an average of 13% of a year of life compared with patients without delirium. Although delirium is an acute condition, it is associated with multiple long-term sequelae that extend beyond the hospital setting, including premature mortality.

Consequences of preventing delirium in hospitalized older adults on nursing home costs.

OBJECTIVES: To determine whether costs of long-term nursing home (NH) care for patients who received a multicomponent targeted intervention (MTI) to prevent delirium while hospitalized were less than for those who did not receive the intervention. DESIGN: Longitudinal follow-up from a randomized trial. SETTING: Posthospital discharge settings: community-based care and NHs. PARTICIPANTS: Eight hundred one hospitalized patients aged 70 and older. MEASUREMENTS: Patients were followed for 1 year after discharge, and measures of NH service use and costs were constructed. Total long-term NH costs were estimated using a two-part regression model and compared across intervention and control groups. RESULTS: Of the 400 patients in the intervention group and 401 patients in the matched control group, 153 (38%) and 148 (37%), respectively, were admitted to a NH during the year, and 54 (13%) and 51 (13%), respectively, were long-term NH patients. The MTI had no effect on the likelihood of receiving long-term NH care, but of patients receiving long-term NH care, those in the MTI group had significantly lower total costs, shorter length of stay and lower cost per survival day. Adjusted total costs were $50,881 per long-term NH patient in the MTI group and $60,327 in the control group, a savings of 15.7% (P=.01). CONCLUSION: Active methods to prevent delirium are associated with a 15.7% decrease in long-term NH costs. Shorter length of stay of patients receiving long-term NH services was the primary source of these savings.

Functional trajectories among older persons before and after critical illness.

IMPORTANCE: 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. OBJECTIVES: 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. DESIGN, SETTING, AND PARTICIPANTS: 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. MAIN OUTCOMES AND MEASURES: 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. RESULTS: 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). CONCLUSIONS AND RELEVANCE: 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.

Trends in Fall-Related Traumatic Brain Injury among Older Persons in Connecticut from 2000-2007.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.