Background
Despite the fact that 80% of patients with heart failure are over age 65, recognition of cognitive impairment by physicians in this population has received relatively little attention. The purpose of our study was to evaluate physician documentation (as a measure of recognition) of cognitive impairment at 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 (MMSE) at the time of hospitalization. A score of 21–24 was used to indicate mild cognitive impairment, and a score of ≤20 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 132/282 patients (46.8% overall; 25.2% mild, 21.6% moderate-severe). Among those with cognitive impairment, 30/132 (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 years vs. 85.2 years, P<0.05) and had less severe impairment (median MMSE score 22.0 vs. 18.0, P<0.01). 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 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.
Germline mutations in the human breast cancer susceptibility genes BRCA1 and BRCA2 account for the majority of hereditary breast and ovarian cancer. In spite of the large number of sequence variants identified in BRCA1 and BRCA2 mutation analyses, many of these genetic alterations are still classified as variants of unknown significance (VUS). In this study, we evaluated 12 BRCA1/2 intronic variants in order to differentiate their pathogenic or polymorphic effects on the mRNA splicing process. We detected the existence of aberrant splicing in three BRCA1 variants (c.301-2delA/IVS6-2delA, c.441+1G>A/IVS7+1G>A, and c.4986+6T>G/IVS16+6T>G) and two BRCA2 variants (c.8487+1G>A/IVS19+1G>A and c.8632-2A>G/IVS20-2A>G). All but one of the aberrant transcripts arise from mutations affecting the conserved splice acceptor or donor sequences and all would be predicted to result in expression of truncated BRCA1 or BRCA2 proteins. However, we demonstrated that four of these splice-site mutations (i.e., c.301-2delA, c.441+1G>A, c.4986+6T>G, and c.8632-2A>G) with premature termination codons were highly unstable and were unlikely to encode for abundant expression of a mutant protein. Three variants of BRCA1 (c.212+3A>G/IVS5+3A>G, c.593+8A>G/IVS9+8A>G, and c.4986-20A>G/IVS16-20A>G) and four variants of BRCA2 (c.516-19C>T/IVS6-19C>T, c.7976-4_7976_3delTT/IVS17-4delTT, c.8487+19A>G/IVS19+19A>G, and c.9256- 18C>A/IVS24- 18C>A) in our studies show no effects on the normal splicing process, and they are considered to be benign polymorphic alterations. Our studies help to clarify the aberrant splicing in BRCA1 and BRCA2 as well as provide information that can be used clinically to help counsel breast/ovarian cancer prone families.
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