Background:Antinuclear Antibody (ANA) testing forms the basis on which many rheumatological diseases are subsequently diagnosed. ANA testing quantifies the dilution of plasma to produce the titer and staining pattern and this can be a part of an ANA order set that reflexively cascades to sub-serology if positive. Studies have shown that a low titer ANA may potentially translate into an erroneous diagnosis: if one estimates a 1 percent prevalence of ANA associated disease in the general population then 30% of those individuals would have a false positive result of ANA detected at 1:40 titer [1]. We theorized that there is no need for several methods to coexist within a single inpatient hospital setting especially since diagnostic value of staining patterns alone is limited.Objectives:To compare the utility and yield of “ANA screening reflex to profile” (ARP) and “ANA reflex to titer” (ART) order sets in the inpatient setting of a community tertiary care hospital. We aim to identify the appropriateness of the ANA testing ordered including cost-effectiveness of ordering ARP over ART in order to implement the identified quality measures towards improving utilization of ANA testing.Methods:We identified all inpatient ANA reflex testing orders performed at Community Regional Medical Center, Fresno, California completed between 11/2018 till 07/2019. This included ART and ARP orders with 6 sub-serologies: SSA, SSB, dsDNA, Smith, Scl-70 and U1RNP. A Health Information Management report was generated which included patient’s age, gender, length of hospital stay, dates of testing ordered, principal diagnosis and type of ANA testing ordered. Descriptive statistics were computed and analyzed.Results:We reviewed a total of 1,012 ANA lab orders performed between 11/01/2018 until 07/30/2019 performed on 700 patients. According to the laboratory standard using Immunofluorescence Assay, an ANA titer starting from 1:40 is reported as positive. Out of the 1,012 tests, 334 tests were positive i.e. 33%. The ART order by itself contributed to 29.9% of the positive testing while ARP formed 70% of the positive testing. 56 of the 910 ARP (6%) performed had one or more sub-serology antibody positive while in 178 ARP orders (20%) only the ANA titer was positive with negative serology. The most common sub-serology antibody noted positive was dsDNA forming 54% of the positive serology results. Multiple testing was noted with 218 orders of ARP and ART being ordered on the same patient within the same week, which shows 21.5% of ANA lab orders were repetitive. Length of stay was noted to be more than 3 days for 89% of the patients who had repetitive testing, majority of those tests (99%) on the same day by the same medical provider. It cost $5.0 for an ART order that resulted negative and $5.0 for an ARP panel that resulted negative. It cost $10.0 for those patients who had both ART and ARP ordered with negative results. A positive ART result added $12.0 additional to the cost of each positive ANA profile ($67.36) when both tests were ordered together.Conclusion:Our study findings reflect the need for using higher yield ANA testing that has been standardized. It demonstrated that physicians ordering the testing were not familiar with the ART vs. ARP, and the laboratory orders needed to be re-structured. We removed the ART from the inpatient Electronic Medical Record i.e. Epic system so that only the ARP order remained. This would prevent repetitive testing and reduce healthcare costs through reduction by at least $12.0 per positive ANA result and may also translate into reduced length of hospital stay. We were able to add Centromere Antibody (Ab) to the ANA profile sub serologies to standardize it further as it is an important part of Scleroderma diagnosis.References:[1]Range of antinuclear antibodies in “healthy” individuals. AU, Tan EM, et al. Arthritis Rheum. 1997; 40(9):1601Disclosure of Interests:None declared
Background:The functions of the complement system are to protect the host against infection, clearance of immune complexes, and regulate adaptive immunity after activation by C-reactive protein (CRP) or foreign cells.1C3 and C4 may increase up to 50 percent of baseline values as part of the acute-phase response, which is an expected host response for infection and injury.2Objectives:We aimed to examine the correlation between elevated C3/C4 levels and the underlying causes (infectious vs. non-infectious) of fever (subjective and/or objective) in adults admitted to Community Regional Medical Center (CRMC).Methods:This is a retrospective study of C3/C4 level that was ordered in adult patients who were admitted to CRMC in April 1st, 2018 to September 30th, 2018 with fever. This was also analyzed in comparison to elevated lactic acid, erythrocyte sedimentation rate (ESR), and CRP level.Results:Complement levels were ordered in 210 patients admitted to CRMC medicine or intensive care units. Among these patients, 28.09% (59/210) were diagnosed with various infectious diseases confirmed by gold standard methods (cultures, serology tests, computerized tomography, or magnetic resonance imaging), regardless of fever status during admission.About 26.6% (56/210) had subjective or objective (temperature greater than100.4 F or above), and52of them had complement levels (C3/C4) ordered with resulted in either normal or elevated. Within these52patients, lactic acid, ESR, and CRP were ordered in33,28,25of them respectively.Table 1.Elevated C3/C4 level vs. normal C3/C4 level in detecting infection in fever patients when tested against gold standards.Patients with infectious disease diagnosisPatients without infectious disease diagnosisElevated C3 or C4 or both (screen test +)137Positive predictive value (PPV)=13/20=65%Both normal C3 and C4 (screen test -)824Negative predictive value (NPV)=15/32=48.9%Sensitivity=13/21=61.9%Specificity=24/31=77.4%Table 2.Sensitivity, specificity, PPV, NPV, likelihood ratio positive (LR+), and likelihood ratio negative (LR-) among C3/C4, lactic acid, ESR, CRPI/CRPH in detecting infection in patient with feverC3/C4 (N=52)Lactic Acid(N=33)ESR(N=28)CRPI/CRPH(N=25)Sensitivity61.9%50%90%100%Specificity77.4%91.3%11.1%11.8%PPV65%71.4%36%34.8%NPV48.9%80.8%66.6%100%LR+2.75.71.01.1LR -0.490.550.90Conclusion:Complement levels can be used as a rapid screening test to guide infection consideration as it correctly identified 61.9 % of febrile patients with infection, and 77.4% who didn’t have an infection. A positive screening test in itself still requires further investigation in the causes of fever to confirm the diagnosis since the PPV is 65%. With the NPV of 48.9%, a negative screening test is still not reassuring that the febrile patient doesn’t have an infection. Our study demonstrated the potential utilization of the elevated complement level as an inflammatory marker for infectious etiology of fever, as it has better LR+ when compares to ESR and CRP with similar turnaround time.This study helps educate providers to acknowledge the fact that complement level does not have to be limited to be used on autoimmune related disorders only. Further large pool studies will be necessary to further investigate the role of complement levels as part of the screening test in a patient with fever.References:[1]Walport. MJ. Complement. Second of two parts. N Engl J Med.2001 Apr 12; 344(15):1140-4. DOI: 10.1056/NEJM200104123441506[2]Wen L, Atkinson JP, Giclas PC. Clinical and laboratory evaluation of complement deficiency. J Allergy Clin Immunol. 2004;113(4):585. DOI: 10.1016/j.jaci.2004.02.003Characters from table content:731Disclosure of Interests:None declared
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