Yield of Diagnostic Tests in the Evaluation of Syncopal Episodes in Older Patients

ABSTRACT: YIELD OF DIAGNOSTIC TESTS IN THE EVALUATION OF SYNCOPAL EPISODES IN OLDER PATIENTS Mallika L. Mendu, Gail McAvay, Rachel Lampert, Jonathan Stoehr, Mary E. Tinetti, Department of Internal Medicine, Department of Epidemiology and Public Health Yale University, School of Medicine, New Haven, CT Syncopal episodes are common among older adults; etiologies range from benign to life-threatening. We determined the frequency, yield, and costs of tests obtained to evaluate older persons with syncope. We also calculated the cost per test yield and determined whether the San Francisco Syncope Rule (SFSR) improved test yield. Review of 2,106 consecutive patients 65 years and older admitted following a syncopal episode. Electrocardiograms (99%), telemetry (95%), cardiac enzymes (95%), and head computed tomography (CT) (63%) were the most frequently obtained tests. Cardiac enzymes, CTs, echocardiograms, carotid ultrasounds, and electroencephalography all affected diagnosis or management in \u3c5% of cases and helped determine etiology of syncope \u3c 2% of the time. Postural blood pressure, performed in only 38% of episodes, had the highest yield with respect to affecting diagnosis (18-26%) or management (25-30%) and determining etiology of the syncopal episode (15-21%). The cost per test affecting diagnosis or management was highest for electroencephalography ($32,973), CT ($24,881), and cardiac enzymes ($22,397) and lowest for postural blood pressure ($17-$20). The yields and costs for cardiac tests were better among patients meeting, than not meeting, SFSR. For example, the cost per cardiac enzymes affecting diagnosis or management was$10,331 in those meeting, versus $111,518 in those not meeting, the SFSR. Many unnecessary tests are obtained to evaluate syncope. Selecting tests based on history and examination and prioritizing less expensive and higher yield tests would ensure a more informed and cost-effective approach to evaluating older patients with syncope

Plasmalogen Deficiency: A Risk Factor for Dementias and Potential Treatment Target

Altered lipid metabolism is implicated in the risk of sporadic Alzheimer’s disease (AD) and related dementias (ADRD); however, the precise mechanisms accounting for findings from observational studies remains to be fully elucidated. Plasmalogens are a subclass of integral membrane phospholipids with unique properties that appear to play important roles relevant to the pathophysiology of AD and ADRD, including vesicle fusion necessary for synaptic neurotransmitter release, modulation of membrane fluidity and microdomain dynamics, membrane antioxidant functions, and neuroprotection. Like the more familiar phosphatides, plasmalogens are synthesized on a 3-carbon glycerol backbone; however, they differ from phosphatides by the presence of a vinyl ether linkage at the 1st (sn1) glycerol carbon atom in place of the acyl ester linkage present at sn1 in phosphatides, and at sn2 in both lipid subclasses. Plasmalogens bearing the omega-3 fatty acid docosahexaenoic acid (DHA), a key component of fish oils, are the most abundant plasmalogen species in cerebral cortex membranes. Circulating plasmalogen levels are decreased in older individuals, and are further decreased in AD and Mild Cognitive Impairment (MCI). In addition, reduced indices of plasmalogen biosynthesis and/or remodeling are significantly correlated with elevated cerebrospinal fluid (CSF) concentrations of total tau, which is a biomarker of AD and certain other neurodegenerative diseases. This correlation suggests a functional relationship between reduced plasmalogen availability and neurodegeneration. Endogenous plasmalogen synthesis requires the integrity of peroxisomes for the attachment of an alkyl side chain to the sn1 glycerol carbon. Decreased peroxisome function may be a key factor underlying the decrease in circulating plasmalogens with aging and with neurodegenerative diseases such as AD and ADRD. Preclinical data indicate that oral administration of a precursor phospholipid compound, DHA-containing alkyl-diacylglycerol, or DHA-AAG, can increase circulating DHA-containing plasmalogens in a peroxisome-independent manner, as conversion to plasmalogens from this precursor requires only the endoplasmic reticulum. We present here data showing that: 1) oral administration of a single dose of DHA-AAG at 100mg/kg to 6 (4M/2F) healthy subjects aged 23-56 increased circulating plasmalogen levels by 80% within 24 hours; and 2) daily oral administration of DHA-AAG to 22 persons (11M/11F), aged 37-84 (mean= 69) yr, with mild to moderate cognitive impairment [CDR: 0.5 (N=14); 1 (N=4); 2 (N = 4)] on an ascending-dose schedule of 1.0 ml/day for 30 days, followed by 2.0 ml/day for 60 days, followed by 4.0 ml for 30 days, increased serum DHA plasmalogens by \u3e 2-fold by the end of the treatment period. DHA-AAG was well-tolerated by both groups of individuals in these 2 studies. These findings suggest that DHA-AAG may be a useful agent for correcting plasmalogen deficiency associated with aging and aging-associated cognitive disorders. Future studies will examine the effect of plasmalogen repletion with DHA-AAG on cerebrospinal fluid plasmalogen concentrations, and effects on cognitive function and other clinical outcomes

Estimated GFR With Cystatin C and Creatinine in Clinical Practice: A Retrospective Cohort StudyPlain-Language Summary

Rationale &amp; Objective: Estimation of glomerular filtration rate (eGFR) and staging of chronic kidney disease (CKD) are essential to guide management. Although creatinine is routinely used, a recent national task force recommended the use of cystatin C for confirmation. The objective of this study was to examine the following parameters: (1) how cystatin C correlates with creatinine eGFR; (2) how it indicates differences in CKD staging; and (3) how it may affect kidney care delivery. Study Design: Retrospective observational cohort study. Setting &amp; Participants: 1,783 inpatients and outpatients who had cystatin C and creatinine levels drawn within 24 hours at Brigham Health-affiliated clinical laboratories. Predictors: Serum creatinine levels, basic clinical/sociodemographic variables, and reasons for ordering cystatin C from a structured partial chart review. Analytical Approach: Univariate and multivariable linear and logistic regression. Results: Cystatin C-based eGFR was very strongly correlated with creatinine-based eGFR (Spearman correlation ρ = 0.83). Cystatin C eGFR resulted in a change to a later CKD stage in 27%, an earlier stage in 7%, and no change in 66% of patients. Black race was associated with a lower likelihood of change to a later stage (OR, 0.53; 95% CI [0.36, 0.75]; P < 0.001), whereas age (OR per year OR, 1.03; 95% CI [1.02, 1.04]; P < 0.001) and Elixhauser score (OR per point OR, 1.22; 95% CI [1.10, 1.36]; P < 0.001) were associated with a higher likelihood of change to a later stage. Limitations: Single center, no direct measurement of clearance for comparison, and inconsistent self-identification of race/ethnicity. Conclusions: Cystatin C eGFR correlates strongly with creatinine eGFR but can have a substantial effect on CKD staging. As cystatin C is adopted, clinicians must be informed on this impact

Excessive diagnostic testing in acute kidney injury

Background: The patterns, performance characteristics, and yield of diagnostic tests ordered for the evaluation of acute kidney injury (AKI) have not been rigorously evaluated. Methods: We characterized the frequency of AKI diagnostic testing for urine, blood, radiology, and pathology tests in all adult inpatients who were admitted with or developed AKI (N = 4903 patients with 5731 AKI episodes) during a single calendar year. We assessed the frequency of abnormal test results overall and by AKI stage. We manually reviewed electronic medical records to evaluate the diagnostic yield of selected urine, blood, and radiology tests. Diagnostic yield of urine and blood tests was determined based on whether an abnormal test affected AKI diagnosis or management, whereas diagnostic yield of radiology tests was based on whether an abnormal test resulted in a procedural intervention. In sensitivity analyses we also evaluated appropriateness of testing using prespecified criteria. Results: Frequency of testing increased with higher AKI stage for nearly all diagnostic tests, whereas frequency of detecting an abnormal result increased for some, but not all, tests. Frequency of detecting an abnormal result was highly variable across tests, ranging from 0 % for anti-glomerular basement membrane testing to 71 % for urine protein testing. Many of the tests evaluated had low diagnostic yield. In particular, selected urine and blood tests were unlikely to impact AKI diagnosis or management, whereas radiology tests had greater clinical utility. Conclusions: In patients with AKI, many of the diagnostic tests performed, even when positive or abnormal, may have limited clinical utility