Pathways from physical frailty to activity limitation in older people: Identifying moderators and mediators in the English Longitudinal Study of Ageing.

Physical frailty increases the risk of future activity limitation, which in turn, compromises independent living of older people and limits their healthspan. Thus, we seek to identify moderators and mediators of the effect of physical frailty on activity limitation change in older people, including gender- and age-specific effects. In a longitudinal study using data from waves 2, 4, and 6 of the English Longitudinal Study of Ageing, unique physical frailty factor scores of 4638 respondents aged 65 to 89years are obtained from confirmatory factor analysis of physical frailty, which is specified by three indicators, namely slowness, weakness, and exhaustion. Using a series of autoregressive cross-lagged models, we estimate the effect of physical frailty factor score on activity limitation change, including its moderation by social conditions, and indirect effects through physical and psychological conditions. We find that the effect of physical frailty on activity limitation change is significantly stronger with older age, while it has significant indirect effects through low physical activity, depressive symptoms, and cognitive impairment. In turn, indirect effects of physical frailty through low physical activity and cognitive impairment are stronger with older age. Sensitivity analyses suggest that these effects vary in their robustness to unmeasured confounding. We conclude that low physical activity, depressive symptoms, and cognitive impairment are potentially modifiable mediators on pathways from physical frailty to activity limitation in older people, including those who are very old. This evidence offers support for population-level interventions that target these conditions, to mitigate the effect of physical frailty on activity limitation, and thereby enhance healthspan.

Multidimensional predictors of physical frailty in older people: identifying how and for whom they exert their effects.

Physical frailty in older people is an escalating health and social challenge. We investigate its physical, psychological, and social predictors, including how and for whom these conditions exert their effects. For 4638 respondents aged 65-89 years from wave 2 of the English Longitudinal Study of Ageing, we examine prediction of future physical frailty by physical, psychological, and social conditions using latent growth curve analysis with multiple indicators. In addition, we explore their indirect effects through disease and physiologic decline, and repeat these analyses after stratification by gender, age group, and selected conditions which are possible moderators. We find that chronic disease, allostatic load, low physical activity, depressive symptoms, cognitive impairment, and poor social support all predict future physical frailty. Furthermore, chronic disease and allostatic load mediate the effects of low physical activity, depressive symptoms, and cognitive impairment on future physical frailty. Finally, although poor social integration is not a predictor of future physical frailty, this condition moderates the indirect effect of poor social support through chronic disease by rendering it stronger. By virtue of their roles as predictor, mediator, or moderator on pathways to physical frailty, chronic disease, allostatic load, low physical activity, cognitive impairment, depressive symptoms, poor social support, and poor social integration are potentially modifiable target conditions for population-level health and social interventions to reduce future physical frailty in older people.

Developing physical frailty specifications for investigation of frailty pathways in older people.

Different frailty definitions are suitable for different purposes. When investigating its key multidimensional predictors and effects, narrower definitions of frailty that exclude these elements may be more desirable. For this purpose, candidate physical frailty specifications are constructed and then evaluated on their construct and concurrent validity. For 4638 participants aged 65 to 89 years from wave 2 (2004) of the English Longitudinal Study of Ageing, confirmatory factor analysis is performed to create physical frailty specifications with four indicators (slowness, weakness, exhaustion, and weight loss) and with three indicators (slowness, weakness, and either exhaustion or weight loss). Using derived factor scores, their convergent, discriminant, and concurrent validity are compared. For specifications with four indicators and with three indicators including exhaustion, slowness contributes dominantly to the physical frailty factor. However, with three indicators including weight loss, weakness contributes most. Where represented, weight loss only contributes minimally. Higher factor scores are significantly associated with chronic diseases, functional impairment, and poor self-rated health, although less so for the third specification. Factor scores for the first two specifications have low correlation with psychological and social frailty while those for the third have negligible correlation. Factor scores increase with higher Frailty Index although again less so for the third specification. Minor differences are seen across gender. On account of their convergent, discriminatory, and concurrent validity, physical frailty specifications with four indicators and with three indicators including exhaustion hold promise for use in investigation of frailty pathways involving multidimensional predictors and effects.

Hemoglobin Level and Hospital Mortality Among ICU Patients With Cardiac Disease Who Received Transfusions.

BACKGROUND: There is a paucity of randomized clinical trial data on the use of red blood cell (RBC) transfusion in critically ill patients, specifically in the setting of cardiac disease. OBJECTIVES: This study examined how hemoglobin (Hgb) level and cardiac disease modify the relationship of RBC transfusion with hospital mortality. The aim was to estimate the Hgb level threshold below which transfusion would be associated with reduced hospital mortality. METHODS: We performed secondary data analyses of Veterans Affairs intensive care unit (ICU) episodes across 5 years. Logistic regression quantified the effect of transfusion on hospital mortality while adjusting for nadir Hgb level, demographic characteristics, admission information, comorbid conditions, and ICU admission diagnoses. RESULTS: Among 258,826 ICU episodes, 12.4% involved transfusions. Hospital death occurred in 11.6%. Without comorbid heart disease, transfusion was associated with decreased adjusted hospital mortality when Hgb was approximately <7.7 g/dl, but transfusion increased mortality above this Hgb level. Corresponding Hgb level thresholds were approximately 8.7 g/dl when comorbid heart disease was present and approximately 10 g/dl when the ICU admission diagnosis was acute myocardial infarction (AMI). Sensitivity analysis using additional adjustment for selected blood tests in a subgroup of 182,792 ICU episodes lowered these thresholds by approximately 1 g/dl. CONCLUSIONS: Transfusion of critically ill patients was associated with reduced hospital mortality when Hgb level was <8 to 9 g/dl in the presence of comorbid heart disease. This Hgb level threshold for transfusion was 9 to 10 g/dl when AMI was the ICU admission diagnosis.

Short-term mortality among older persons hospitalized for pneumonia: influence of baseline patient characteristics beyond severity of illness.

BACKGROUND: Although severity of illness indices such as pneumonia severity index (PSI) are good predictors of short-term mortality for community-acquired pneumonia (CAP) and healthcare-associated pneumonia (HCAP), other patient factors may have added prognostic value. OBJECTIVE: To identify patient factors beyond the PSI which explain 30-day mortality among older persons hospitalized with CAP and HCAP. DESIGN: Retrospective cohort study. SETTING: Three acute care hospitals in Singapore in 2007. PATIENTS: Hospitalized adults aged 65 years or older who have primary International Classification of Diseases, 9th revision, Clinical Modification (ICD-9-CM) codes 480 to 486 with clinical and radiological features of pneumonia. INTERVENTIONS: None. MEASUREMENTS: Thirty-day mortality, PSI class, demographic and clinical features, comorbid conditions, functional status, selected laboratory tests, and chest radiographic findings. RESULTS: Among 1607 patients included, 890 (55.4%) had CAP and 717 (44.6%) had HCAP. After adjustment for PSI class in logistic regression analyses, pre-morbid ambulation impairment (odds ratio [OR] 2.61, 95% confidence interval [CI] 1.98 to 3.45), hospitalization in the prior 30 days (OR 1.93, 95% CI 1.38 to 2.71), and absence of cough and purulent sputum (OR 1.47, 95% CI 1.14 to 1.90) were all significantly associated with 30-day mortality. These associations remained constant when CAP and HCAP were analyzed separately. CONCLUSIONS: Recent hospitalization, pre-morbid ambulation impairment, and atypical presentation were independently associated with higher 30-day mortality among older persons hospitalized for pneumonia, after adjusting for severity of illness. These factors could be considered in addition to PSI when performing risk stratification and adjustment in this setting.

Patient factors associated with transfusion practices in Veterans Affairs intensive care units: implications for further research.

PURPOSE: We sought to describe how patient characteristics influence the frequency of red blood cell (RBC) transfusions among critically ill patients after taking into account hemoglobin (Hgb) level. METHODS: This was a retrospective cohort study using secondary analysis of administrative data of Veterans Affairs intensive care unit (ICU) admissions. The outcome of interest was RBC transfusion during the first 30 days of ICU admission. Besides Hgb level, explanatory variables included demographics, admission-related information, comorbid conditions, ICU admission diagnosis, and selected laboratory test results. Logistic regression modeling quantified associations between explanatory variables and transfusion. RESULTS: For 259 281 ICU admissions from 2001 to 2005, the overall incidence of RBC transfusion was 12.5%. Increased age, male gender, admission for acute myocardial infarction (AMI), and comorbid heart disease were independently associated with transfusion. Compared with admission for reference diagnoses, transfusions were more likely for admissions for AMI, unstable angina, and congestive heart failure only at Hgb levels below 11, 9, and 6 g/dL, respectively. CONCLUSIONS: Intensive care unit patients admitted for AMI, unstable angina, and congestive heart-failure had higher likelihood of receiving RBC transfusions below specific Hgb levels varying from 6 to 11 g/dL. Further research is needed to determine how these transfusion practices influence outcomes.