Abnormal modular organization of functional networks in cognitively impaired children with frontal lobe epilepsy.

Many children with frontal lobe epilepsy (FLE) have significant cognitive comorbidity, for which the underlying mechanism has not yet been unraveled, but is likely related to disturbed cerebral network integrity. Using resting-state fMRI, we investigated whether cerebral network characteristics are associated with epilepsy and cognitive comorbidity. We included 37 children with FLE and 41 healthy age-matched controls. Cognitive performance was determined by means of a computerized visual searching task. A connectivity matrix for 82 cortical and subcortical brain regions was generated for each subject by calculating the inter-regional correlation of the fMRI time signals. From the connectivity matrix, graph metrics were calculated and the anatomical configuration of aberrant connections and modular organization was investigated. Both patients and controls displayed efficiently organized networks. However, FLE patients displayed a higher modularity, implying that subnetworks are less interconnected. Impaired cognition was associated with higher modularity scores and abnormal modular organization of the brain, which was mainly expressed as a decrease in long-range and an increase in interhemispheric connectivity in patients. We showed that network modularity analysis provides a sensitive marker for cognitive impairment in FLE and suggest that abnormally interconnected functional subnetworks of the brain might underlie the cognitive problems in children with FLE.

Two point-of-care test-based approaches for the exclusion of deep vein thrombosis in general practice: a cost-effectiveness analysis.

BACKGROUND: In the diagnostic work-up of deep vein thrombosis (DVT), the use of point-of-care-test (POCT) D-dimer assays is emerging as a promising patient-friendly alternative to regular D-dimer assays, but their cost-effectiveness is unknown. We compared the cost-effectiveness of two POCT-based approaches to the most common, laboratory-based, situation. METHODS: A patient-level simulation model was developed to simulate the diagnostic trajectory of patients presenting with symptoms of DVT at the general practitioner (GP). Three strategies were defined for further diagnostic work-up: one based on current guidelines ('regular strategy') and two alternative approaches where a POCT for D-dimer is implemented at the 1) phlebotomy service ('DVT care pathway') and 2) GP practice ('fast-POCT strategy'). Probabilities, costs and health outcomes were obtained from the literature. Costs and effects were determined from a societal perspective over a time horizon of 6 months. Uncertainty in model outcomes was assessed with a one-way sensitivity analysis. RESULTS: The Quality-Adjusted Life Years (QALYs) scores for the three DVT diagnostic work-up strategies were all around 0.43 across a 6 month-time horizon. Cost-savings of the two POCT-based strategies compared to the regular strategy were €103/patient for the DVT care pathway (95% CI: -€117-89), and €87/patient for the fast-POCT strategy (95% CI: -€113-67). CONCLUSIONS: Point-of-care-based approaches result in similar health outcomes compared with regular strategy. Given their expected cost-savings and patient-friendly nature, we recommend implementing a D-dimer POCT device in the diagnostic DVT work-up.

Are the latest point-of-care D-dimer devices ready for use in general practice? A prospective clinical evaluation of five test systems with a capillary blood feature for suspected venous thromboembolism.

INTRODUCTION: We evaluated clinical performance of five novel point-of-care (POC) D-dimer devices with a capillary finger stick feature for predicting venous thromboembolism (VTE) in general practice: Exdia TRF Plus (E), AFIAS-1® (A), Standard F200® (S), LumiraDx™ (L) and Hipro AFS/1® (H). MATERIALS AND METHODS: Primary care patients with a low suspicion of a VTE were asked to consent to (i) draw additional venous blood samples, (ii) perform a capillary POC D-dimer test, (iii) approach their general practitioner afterwards for clinical outcomes. Venous plasma samples were processed on all POC devices and a laboratory-based assay (STA-Liatest®D-Di PLUS assay). Results were compared with clinical outcomes to generate performance characteristics. Capillary and venous blood results were used for a matrix comparison. RESULTS: Venous plasma samples from 511 participants, of whom 57 had VTE, were used for clinical performance analyses. Areas under Receiving Operating Characteristic Curves ranged from 0.90 (95 % CI: 0.86-0.94) (H) to 0.93 (0.90-0.96) (E). All false-negative rates were below 1.4 % (95 % CI: 0.5 %-3.4 %). Matrix comparison demonstrated correlation coefficients ranging from r = 0.11 (95 % CI: -0.15-0.36) (H) to r = 0.94 (0.90-0.97) (A) with concordance percentages ranging from 71.4 % (applying a D-dimer cutoff of 500 ng/mL) (H) to 100 % (applying an age-dependent D-dimer cutoff) (A). CONCLUSIONS: Clinical performance of the POC D-dimer devices for predicting a VTE in low-risk patients was comparable to that of a laboratory-based assay. However, our results indicate that the finger stick feature of certain devices should be further improved. (NL71809.028.19.).