Sensitivity For Identification Of Patients Research Articles

Treatment changes in hemophilia A with chromogenic factor VIII assay implementation

BackgroundThe one-stage assay (OSA) and the chromogenic assay (CSA) are 2 factor VIII (FVIII) assays used for the diagnosis and classification of hemophilia A. Discrepancies between the 2 assays exist in approximately one-third of patients with mild hemophilia A. ObjectivesThe objectives of this study were to report the proportion of patients with mild or moderate hemophilia A and OSA-CSA discrepancies and to report the observed changes in treatment approach prompted by the presence of assay discrepancy. The study aimed to identify OSA:CSA ratio associated with the highest sensitivity for identification of patients in whom modification of treatment approach may be recommended. MethodsThis is a retrospective cohort study including adult (>18-year-old) patients with mild or moderate hemophilia A who were followed up at the Adult British Columbia Hemophilia Program between January 2013 and March 2019. ResultsA total of 75 patients with mild and 23 with moderate hemophilia A based on baseline OSA were included. Overall, 52% of study patients had OSA-CSA discrepancies, and change in treatment approach was observed in 27% of patients with OSA-CSA discrepancy. The OSA:CSA ratio of 1.8 to 3.5 demonstrated the highest area under the receiver operating characteristics curve and sensitivity for identification of patients in which modification of treatment approach may be recommended (AUC 0.75; sensitivity 71%). ConclusionIn our population, OSA-CSA discrepancy was observed in 52% of patients with mild or moderate hemophilia A, and the treatment approach in 27% of these patients had to be modified.

Dickkopf-1 Is a Biomarker for Systemic Lupus Erythematosus and Active Lupus Nephritis.

An early diagnosis of lupus nephritis (LN) has an important clinical implication in guiding treatments of systemic lupus erythematosus (SLE) in clinical settings. In this study, the concentrations of Wnt-3A, Frizzled-8 (FZD-8), and Dickkopf-1 (DKK-1) of Wnt signaling, as well as their diagnostic values for accessing LN, were evaluated by ELISA in sera and urine of 111 SLE patients (31 with LN and 80 without LN) and 70 healthy cohorts. Significantly more abundances of DKK-1 protein were determined in both of sera and urine of SLE patients compared to healthy cohorts (p < 0.0001); in particular the serum DKK-1 concentration was even higher in LN-SLE patients relative to non-LN SLE subjects (p < 0.0001). Intriguingly, concentrations of above examined proteins in SLE patients showed no correlation between serum and urine. Moreover, a combination of DKK-1 with anti-dsDNA and/or levels of complement C3 and C4 could not increase the specificity and/or sensitivity for identification of patients with LN diseases, but both ROC curve and multiple-factor nonconditional logistic regression analysis showed that serum DKK-1 was considered better positive biomarker for identification of LN in SLE patients. These results imply that serum and/or urine DKK-1 may be a valuable and independent biomarker for identification of SLE patients with LN.

Diagnostic precision of PET imaging and functional MRI in disorders of consciousness: a clinical validation study

Bedside clinical examinations can have high rates of misdiagnosis of unresponsive wakefulness syndrome (vegetative state) or minimally conscious state. The diagnostic and prognostic usefulness of neuroimaging-based approaches has not been established in a clinical setting. We did a validation study of two neuroimaging-based diagnostic methods: PET imaging and functional MRI (fMRI). For this clinical validation study, we included patients referred to the University Hospital of Liège, Belgium, between January, 2008, and June, 2012, who were diagnosed by our unit with unresponsive wakefulness syndrome, locked-in syndrome, or minimally conscious state with traumatic or non-traumatic causes. We did repeated standardised clinical assessments with the Coma Recovery Scale-Revised (CRS-R), cerebral (18)F-fluorodeoxyglucose (FDG) PET, and fMRI during mental activation tasks. We calculated the diagnostic accuracy of both imaging methods with CRS-R diagnosis as reference. We assessed outcome after 12 months with the Glasgow Outcome Scale-Extended. We included 41 patients with unresponsive wakefulness syndrome, four with locked-in syndrome, and 81 in a minimally conscious state (48=traumatic, 78=non-traumatic; 110=chronic, 16=subacute). (18)F-FDG PET had high sensitivity for identification of patients in a minimally conscious state (93%, 95% CI 85-98) and high congruence (85%, 77-90) with behavioural CRS-R scores. The active fMRI method was less sensitive at diagnosis of a minimally conscious state (45%, 30-61) and had lower overall congruence with behavioural scores (63%, 51-73) than PET imaging. (18)F-FDG PET correctly predicted outcome in 75 of 102 patients (74%, 64-81), and fMRI in 36 of 65 patients (56%, 43-67). 13 of 41 (32%) of the behaviourally unresponsive patients (ie, diagnosed as unresponsive with CRS-R) showed brain activity compatible with (minimal) consciousness (ie, activity associated with consciousness, but diminished compared with fully conscious individuals) on at least one neuroimaging test; 69% of these (9 of 13) patients subsequently recovered consciousness. Cerebral (18)F-FDG PET could be used to complement bedside examinations and predict long-term recovery of patients with unresponsive wakefulness syndrome. Active fMRI might also be useful for differential diagnosis, but seems to be less accurate. The Belgian National Funds for Scientific Research (FNRS), Fonds Léon Fredericq, the European Commission, the James McDonnell Foundation, the Mind Science Foundation, the French Speaking Community Concerted Research Action, the University of Copenhagen, and the University of Liège.

Abstract 19425: Stress Perfusion Cardiac Magnetic Resonance Predicts Risk of Cardiac Events in Patients with Established Coronary Artery Disease

BACKGROUND: Current prognostic risk assessment has limited sensitivity for identification of patients at high risk for cardiac events with established CAD. We evaluated the prognostic value of stress cardiac magnetic resonance (CMR) imaging to reclassify risk in patients with established CAD. METHODS: We performed clinically indicated stress CMR imaging in 815 patients, with follow-up for cardiac death (CD) or acute myocardial infarction (AMI; primary outcome) over a median 1.9 years. Univariate and multivariate Cox regression models were used to determine clinical and imaging characteristics associated with risk. Annual event rates were calculated and stratified by presence and absence of prior CAD. Net reclassification improvement and ROC analysis were used for the addition of inducible ischemia by CMR beyond a best-overall clinical multivariate model of risk for discrimination and reclassification. RESULTS: Of the 815 patients referred for stress CMR, 13 failed to complete CMR (2%), and 97% had interpretable image quality. Inducible ischemia (ISCH) strongly independently predicted primary outcome in CAD patients (HR = 8.17, 95% CI 2.9-23.1, p = 0.0001). No ISCH was associated significantly improved event-free survival in patients with and without CAD (p&lt;0.001) and a &lt;1% annual rate of CD, with lower annual rates of CD/AMI in patients with and without CAD. ISCH improved risk discrimination over a best-overall clinical risk model (p&lt;0.0001). Addition of ISCH to the best-overall clinical model resulted in a net reclassification improvement of 0.229 (95% 0.063-0.391, p&lt;0.05). CONCLUSIONS: Inducible ischemia by stress CMR is a powerful, independent prognostic marker in patients with symptomatic, established CAD. A negative stress CMR is associated with a &lt;1% rate of CD, and reclassifies risk of future cardiac events in patients otherwise considered at moderate or high risk by clinical assessment.

Incremental Benefit of Computer-aided Detection when Used as a Second and Concurrent Reader of CT Colonographic Data: Multiobserver Study

To quantify the changes in reader performance levels, if any, during interpretation of computed tomographic (CT) colonographic data when a computer-aided detection (CAD) system is used as a second or concurrent reader. After institutional review board approval was obtained, 16 experienced radiologists searched for polyps in 112 patients, 56 of whom had 132 polyps. Each case was interpreted on three separate occasions by using an unassisted (without CAD), second-read CAD, or concurrent CAD reading paradigm. The reading paradigm and case order were randomized, with a minimal interval of 1 month between consecutive interpretations. The readers' findings were compared with the reference-truth interpretation. The mean per-patient sensitivity and mean per-patient specificity with CAD were compared with those achieved with unassisted reading. An increase in per-patient sensitivity was considered to be clinically more important than an equivalent decrease in specificity. The mean per-patient sensitivity for identification of patients with polyps of any size increased significantly with use of second-read CAD (mean increase, 7.0%; 95% confidence interval [CI]: 4.0%, 9.8%) and concurrent CAD (mean increase, 4.5%; 95% CI: 0.8%, 8.2%). The mean per-patient specificity did not decrease significantly with use of second-read CAD (mean decrease, -2.5%; 95% CI: -5.2%, 0.1%) or concurrent CAD (mean decrease, -2.2%; 95% CI: -4.6%, 0.2%). With analysis restricted to patients with polyps 6 mm or larger, the benefit in sensitivity with second-read CAD remained (mean increase, 7.1%; 95% CI: 3.0%, 11.1%), whereas the increase with concurrent CAD was not significant (mean increase, 4.2%; 95% CI: -0.5%, 8.9%). Use of second-read CAD significantly increased the per-polyp sensitivity for polyps 6 mm or larger (mean increase, 9.0%; 98.3% CI: 4.9%, 12.8%) and polyps 5 mm or smaller (mean increase, 5.9%; 98.3% CI: 3.2%, 9.1%), but use of concurrent CAD increased the per-polyp sensitivity for only those polyps 5 mm or smaller (mean increase, 4.8%; 98.3% CI: 2.2%, 7.9%). Use of second-read CAD significantly improves readers' per-patient and per-polyp detection. Concurrent CAD is less effective. http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.10100354/-/DC1.

Review article: population screening for colorectal cancer

Colorectal cancer is a common cancer and common cause of death. The mortality rate from colorectal cancer can be reduced by identification and removal of cancer precursors, adenomas, or by detection of cancer at an earlier stage. Pilot screening programmes have demonstrated decreased colorectal cancer mortality; as a result many countries are developing colorectal cancer screening programmes. The most common modalities being evaluated are faecal occult blood testing, flexible sigmoidoscopy and colonoscopy. Implementation of screening tests has been hampered by cost, invasiveness, availability of resources and patient acceptance. New technologies such at computed tomographic colonography and stool screening for molecular markers of neoplasia are in development as potential minimally invasive tools. This review considers who should be screened, which test to use and how often to screen.

Minimal residual disease in hematopoietic malignancy: Technical approaches and clinical significance

New technology continues to provide methods to refine the definition of complete remission in patients with hematopoietic malignancy. Recent evidence indicates that quantitation of residual tumor burden over time may identify gradual increases indicative of potential relapse. It is the general hope that this increased sensitivity for identification of patients with residual tumor burden will allow for a more effective selection of therapeutic alternatives for these patients. In order to accurately assess whether lowering the threshold for definition of remission improves the clinical outcome of patients with MRD, future studies must include several important parameters. Effective clinical studies will require large groups of patients meeting carefully designed diagnostic criteria with strictly controlled, homogenous treatment protocols. In addition, they must utilize a multidisciplinary technical approach for the detection of MRD in order to properly assess the ability of each technology to measure clinically significant parameters. The choice of the most effective technologies and when to test the patient will be identified only through these carefully planned clinical trials. Additional considerations of cost and availability must then enter into utilization decisions as important financial considerations to be weighed against clinical significance.

Myocardial single-photon emission computed tomographic imaging with technetium 99m tetrofosmin: stress-rest imaging with same-day and separate-day rest imaging.

Technetium 99m tetrofosmin is a new ethylene diphosphine ligand for myocardial perfusion imaging and has unique properties. We have compared stress-rest single-photon emission computed tomographic (SPECT) imaging with 99mTc tetrofosmin with same-day and separate-day rest imaging to detect myocardial perfusion defects. Myocardial SPECT imaging was performed in 22 patients with coronary artery disease who had undergone planar thallium 201 imaging and coronary angiography. Single-day (stress-rest) and separate-day rest 99mTc tetrofosmin SPECT protocols were compared in the same patient. Images were assessed by a blinded panel to identify myocardial infarction, ischemia, or normal scans. Overall sensitivity for identification of patients with coronary artery disease was 86% (19/22) by both same-day stress-rest and separate-day rest protocols with 99mTc tetrofosmin (p = NS). Of a total of 396 segments studied, 107 abnormal segments were identified at exercise and 76 and 81 at the same-day and separate-day rest tests, respectively (p = NS). Same-day stress-rest and separate-day rest 99mTc tetrofosmin SPECT protocols were also useful for detecting individual coronary stenosis with a greater than 50% lesion: 80% of the left anterior descending, 93% of the right coronary, and 75% of the left circumflex coronary arteries were detected. Excellent images were obtained with 99mTc tetrofosmin during both stress and rest. 99mTc tetrofosmin imaging with the same-day stress-rest and separate-day rest imaging protocols have similar diagnostic sensitivities for detection of coronary heart disease.