Virginia Towle

Age-associated decrease in TLR function in primary human dendritic cells predicts influenza vaccine response.

We evaluated TLR function in primary human dendritic cells (DCs) from 104 young (age 21–30 y) and older (≥65 y) individuals. We used multicolor flow cytometry and intracellular cytokine staining of myeloid DCs (mDCs) and plasmacytoid DCs (pDCs) and found substantial decreases in older compared with young individuals in TNF-α, IL-6, and/or IL-12 (p40) production in mDCs and in TNF-α and IFN-α production in pDCs in response to TLR1/2, TLR2/6, TLR3, TLR5, and TLR8 engagement in mDCs and TLR7 and TLR9 in pDCs. These differences were highly significant after adjustment for heterogeneity between young and older groups (e.g., gender, race, body mass index, number of comorbid medical conditions) using mixed-effect statistical modeling. Studies of surface and intracellular expression of TLR proteins and of TLR gene expression in purified mDCs and pDCs revealed potential contributions for both transcriptional and posttranscriptional mechanisms in these age-associated effects. Moreover, intracellular cytokine production in the absence of TLR ligand stimulation was elevated in cells from older compared with young individuals, suggesting a dysregulation of cytokine production that may limit further activation by TLR engagement. Our results provide evidence for immunosenescence in DCs; notably, defects in cytokine production were strongly associated with poor Ab response to influenza immunization, a functional consequence of impaired TLR function in the aging innate immune response.

Health Outcome Prioritization as a Tool for Decision Making Among Older Persons With Multiple Chronic Conditions

Older persons with multiple chronic conditions are at substantial risk for unintended adverse outcomes, such as medication adverse events. Less severe adverse events are commonly referred to as “side effects,” implying that they are secondary to disease-specific benefits. However, patients consider these adverse events to be important outcomes in their own right.1 Such findings suggest that all possible benefits and harms resulting from different treatment options be considered as competing outcomes, among which older persons with multiple chronic conditions face trade-offs. When treatments involve trade-offs, the best option depends upon patients’ preferences. The challenge for older persons with multiple conditions is that these trade-offs encompass both many different specific diseases and non disease-specific health domains.2 One approach to this challenge is to consider treatment in terms of its effects on a set of universal, cross-disease outcomes and to use older persons’ prioritization of these outcomes as an assessment of preferences. These outcomes, examples of which include length of life, physical and cognitive function, and symptoms, include basic domains recognized to be the key components of health.3 The goal of this study was to explore the use of a simple to tool to elicit older persons’ health outcome priorities.

Health Outcomes Associated with Polypharmacy in Community‐Dwelling Older Adults: A Systematic Review

To summarize evidence regarding the health outcomes associated with polypharmacy, defined as number of prescribed medications, in older community‐dwelling persons.

Cognitive Impairment in Older Adults with Heart Failure: Prevalence, Documentation, and Impact on Outcomes

BACKGROUND Despite the fact that 80% of patients with heart failure are aged more than 65 years, recognition of cognitive impairment by physicians in this population has received relatively little attention. The current study evaluated physician documentation (as a measure of recognition) of cognitive impairment at the time of discharge in a cohort of older adults hospitalized for heart failure. METHODS We performed a prospective cohort study of older adults hospitalized with a primary diagnosis of heart failure. Cognitive status was evaluated with the Folstein Mini-Mental State Examination at the time of hospitalization. A score of 21 to 24 was used to indicate mild cognitive impairment, and a score of ≤20 was used to indicate moderate to severe impairment. To evaluate physician documentation of cognitive impairment, we used a standardized form with a targeted keyword strategy to review hospital discharge summaries. We calculated the proportion of patients with cognitive impairment documented as such by physicians and compared characteristics between groups with and without documented cognitive impairment. We then analyzed the association of cognitive impairment and documentation of cognitive impairment with 6-month mortality or readmission using Cox proportional hazards regression. RESULTS A total of 282 patients completed the cognitive assessment. Their mean age was 80 years of age, 18.8% were nonwhite, and 53.2% were female. Cognitive impairment was present in 132 of 282 patients (46.8% overall; 25.2% mild, 21.6% moderate-severe). Among those with cognitive impairment, 30 of 132 (22.7%) were documented as such by physicians. Compared with patients whose cognitive impairment was documented by physicians, those whose impairment was not documented were younger (81.3 vs 85.2 years, P<.05) and had less severe impairment (median Mini-Mental State Examination score 22.0 vs 18.0, P<.01). After multivariable adjustment, patients whose cognitive impairment was not documented were significantly more likely to experience 6-month mortality or hospital readmission than patients without cognitive impairment. CONCLUSIONS Cognitive impairment is common in older adults hospitalized for heart failure, yet it is frequently not documented by physicians. Implementation of strategies to improve recognition and documentation of cognitive impairment may improve the care of these patients, particularly at the time of hospital discharge.

Clinical Features to Identify Urinary Tract Infection in Nursing Home Residents: A Cohort Study

OBJECTIVES: To identify clinical features associated with bacteriuria plus pyuria in noncatheterized nursing home residents with clinically suspected urinary tract infection (UTI).

Risk adjustment for older hospitalized persons: A comparison of two methods of data collection for the Charlson index

To compare Charlson indices based on chart data and ICD-9 data for agreement overall and on rating specific comorbid conditions, and to compare mortality risks associated with these indices. Prospective cohort study. Six general medicine wards at Yale-New Haven Hospital. 524 consecutive patients who had no clinical evidence of delirium at enrollment, admitted between November 6, 1989 and July 31, 1991, aged 70 years or older. Death within 1 year of the index hospital admission date. Scores using the chart-based data were significantly higher than those using ICD-9 data. About half of the individual conditions showed fair-to-good agreement between the two scores, whereas the other half showed poor agreement. A comparison of mortality prediction indicated that the weightings assigned to individual comorbidities differed substantially from those used in Charlsons original index. While mortality prediction of each individual index was comparable, the ICD-9 and chart indices contributed independently to mortality prediction in the presence of the other. Low agreement between Charlson scores based on the two methods of data collection and their cumulative contribution to mortality prediction suggest that these indices may include different information. Our results suggest that the original Charlson index may not provide optimal risk adjustment for elderly general medicine samples. We suggest development of an empirically-derived index of comorbid conditions and weights may be warranted for older general medical patients.

Yale Children's Inventory (YCI): An instrument to assess children with attentional deficits and learning disabilities I. Scale development and psychometric properties

The Yale Childrens Inventory (YCI), a parent based rating scale, and the scales derived from it have been developed to identify and measure multiple dimensions of learning disabilities with particular emphasis on attentional deficits. Scale construction was based on factor analytic procedures. Measures of internal consistency, test retest reliability, and coefficients of congruence support the reliability and stability of the 11 scales. A discriminant function classified normal and learning disabled children with a relatively high rate of accuracy. The relationship and content of the three relevant YCI scales were compared to the DSM-III diagnostic categories for ADD. As operationalized, DSM-III criteria for hyperactivity formed a cohesive factor, while criteria for attention and impulsivity were not distinguishable from each other since they loaded together on a single factor. In contrast, the equivalent YCI scales for attention, impulsivity, and hyperactivity were found to be distinct.

What does the medical record reveal about Functional status? A comparison of medical record and interview data

OBJECTIVE: Functional status measures are potent independent predictors of hospital outcomes and mortality. The study objective was to compare medical record with interview data for functional status.SUBJECTS AND METHODS: Subjects were 525 medical patients, aged 70 years or older, hospitalized at an academic medical center. Patient interviews determined status for 7 basic activities of daily living (BADLs) and 7 instrumental activities of daily living (IADLs). Medical records were reviewed to assess documentation of BADLs and IADLs.RESULTS: Most medical records contained no documentation of individual BADLs and IADLs (61% to 98% of records lacking documentation), with the exception of walking (24% of medical records lacking documentation). Impairment prevalence was lower in medical records than at interview for all BADLs and IADLs, and agreement between interview and medical record was poor (κ<0.40 for individual BADLs and IADLs). Sensitivity of the medical record for BADL and IADL impairment was poor (range 95% to 44%), using the interview as a reference standard. Sensitivity and specificity of the medical record for detection of BADL and IADL impairment changed substantially when records with nondocumentation of functional status were excluded or were assumed to be equivalent to independence.CONCLUSIONS: The results suggest that the medical record is a poor source of data on many functional status measures, and that assuming that nondocumentation of functional status is equivalent to independence may be unwarranted. Given the prognostic importance of functional status measures, the results highlight the importance of developing reliable and efficient means of obtaining functional status information on hospitalized older patients.

Nursing home practitioner survey of diagnostic criteria for urinary tract infections.

Objectives: To identify clinical and laboratory criteria used by nursing home practitioners for diagnosis and treatment of urinary tract infections (UTIs) in nursing home residents. To determine practitioner knowledge of the most commonly used consensus criteria (i.e., McGeer criteria) for UTIs.

Antimicrobial Susceptibility of Bacteria Isolated from Urine Samples Obtained from Nursing Home Residents

In our study of nursing home residents with clinically suspected urinary tract infection who did not require the use of an indwelling catheter, we identified bacteria isolated from urine samples, the resistance patterns of these isolated bacteria, and the antibiotic therapy prescribed to the residents. Escherichia coli, the predominant organism isolated, frequently was resistant to commonly prescribed oral antibiotics. Trimethoprim-sulfamethoxazole remains the best empiric antimicrobial therapy for a urinary tract infection, but nitrofurantoin should be considered if E. coli is identified.