Cost-effectiveness of a telemonitoring programme in patients with cardiovascular diseases compared with standard of care.

OBJECTIVES: The main aim of this work was to analyse the cost-effectiveness of an integrated care concept (NICC) that combines telemonitoring with the support of a care centre in addition to guideline therapy for patients. Secondary aims were to compare health utility and health-related quality of life (QoL) between NICC and standard of care (SoC). METHODS: The randomised controlled CardioCare MV Trial compared NICC and SoC in patients from Mecklenburg-West Pomerania (Germany) with atrial fibrillation, heart failure or treatment-resistant hypertension. QoL was measured using the EQ-5D-5L at baseline, 6 months and 1 year follow-up. Quality-adjusted life years (QALYs), EQ5D utility scores, Visual Analogue Scale (VAS) Scores and VAS adjusted life years (VAS-AL) were calculated. Cost data were obtained from health insurance companies, and the payer perspective was taken in health economic analyses. Quantile regression was used with adjustments for stratification variables. RESULTS: The net benefit of NICC (QALY) was 0.031 (95% CI 0.012 to 0.050; p=0.001) in this trial involving 957 patients. EQ5D Index values, VAS-ALs and VAS were larger for NICC compared with SoC at 1 year follow-up (all p≤0.004). Direct cost per patient and year were €323 (CI €157 to €489) lower in the NICC group. When 2000 patients are served by the care centre, NICC is cost-effective if one is willing to pay €10 652 per QALY per year. CONCLUSION: NICC was associated with higher QoL and health utility. The programme is cost-effective if one is willing to pay approximately €11 000 per QALY per year.

Personalized diagnosis in suspected myocardial infarction.

BACKGROUND: In suspected myocardial infarction (MI), guidelines recommend using high-sensitivity cardiac troponin (hs-cTn)-based approaches. These require fixed assay-specific thresholds and timepoints, without directly integrating clinical information. Using machine-learning techniques including hs-cTn and clinical routine variables, we aimed to build a digital tool to directly estimate the individual probability of MI, allowing for numerous hs-cTn assays. METHODS: In 2,575 patients presenting to the emergency department with suspected MI, two ensembles of machine-learning models using single or serial concentrations of six different hs-cTn assays were derived to estimate the individual MI probability (ARTEMIS model). Discriminative performance of the models was assessed using area under the receiver operating characteristic curve (AUC) and logLoss. Model performance was validated in an external cohort with 1688 patients and tested for global generalizability in 13 international cohorts with 23,411 patients. RESULTS: Eleven routinely available variables including age, sex, cardiovascular risk factors, electrocardiography, and hs-cTn were included in the ARTEMIS models. In the validation and generalization cohorts, excellent discriminative performance was confirmed, superior to hs-cTn only. For the serial hs-cTn measurement model, AUC ranged from 0.92 to 0.98. Good calibration was observed. Using a single hs-cTn measurement, the ARTEMIS model allowed direct rule-out of MI with very high and similar safety but up to tripled efficiency compared to the guideline-recommended strategy. CONCLUSION: We developed and validated diagnostic models to accurately estimate the individual probability of MI, which allow for variable hs-cTn use and flexible timing of resampling. Their digital application may provide rapid, safe and efficient personalized patient care. TRIAL REGISTRATION NUMBERS: Data of following cohorts were used for this project: BACC ( www. CLINICALTRIALS: gov ; NCT02355457), stenoCardia ( www. CLINICALTRIALS: gov ; NCT03227159), ADAPT-BSN ( www.australianclinicaltrials.gov.au ; ACTRN12611001069943), IMPACT ( www.australianclinicaltrials.gov.au , ACTRN12611000206921), ADAPT-RCT ( www.anzctr.org.au ; ANZCTR12610000766011), EDACS-RCT ( www.anzctr.org.au ; ANZCTR12613000745741); DROP-ACS ( https://www.umin.ac.jp , UMIN000030668); High-STEACS ( www. CLINICALTRIALS: gov ; NCT01852123), LUND ( www. CLINICALTRIALS: gov ; NCT05484544), RAPID-CPU ( www. CLINICALTRIALS: gov ; NCT03111862), ROMI ( www. CLINICALTRIALS: gov ; NCT01994577), SAMIE ( https://anzctr.org.au ; ACTRN12621000053820), SEIGE and SAFETY ( www. CLINICALTRIALS: gov ; NCT04772157), STOP-CP ( www. CLINICALTRIALS: gov ; NCT02984436), UTROPIA ( www. CLINICALTRIALS: gov ; NCT02060760).

An Expert-Supervised Registration Method for Multiparameter Description of the Knee Joint Using Serial Imaging.

As knee osteoarthritis is a disease of the entire joint, our pathophysiological understanding could be improved by the characterization of the relationships among the knee components. Diverse quantitative parameters can be characterized using magnetic resonance imaging (MRI) and computed tomography (CT). However, a lack of methods for the coordinated measurement of multiple parameters hinders global analyses. This study aimed to design an expert-supervised registration method to facilitate multiparameter description using complementary image sets obtained by serial imaging. The method is based on three-dimensional tissue models positioned in the image sets of interest using manually placed attraction points. Two datasets, with 10 knees CT-scanned twice and 10 knees imaged by CT and MRI were used to assess the method when registering the distal femur and proximal tibia. The median interoperator registration errors, quantified using the mean absolute distance and Dice index, were ≤0.45 mm and ≥0.96 unit, respectively. These values differed by less than 0.1 mm and 0.005 units compared to the errors obtained with gold standard methods. In conclusion, an expert-supervised registration method was introduced. Its capacity to register the distal femur and proximal tibia supports further developments for multiparameter description of healthy and osteoarthritic knee joints, among other applications.

Analyzing Femorotibial Cartilage Thickness Using Anatomically Standardized Maps: Reproducibility and Reference Data.

Alterations in cartilage thickness (CTh) are a hallmark of knee osteoarthritis, which remain difficult to characterize at high resolution, even with modern magnetic resonance imaging (MRI), due to a paucity of standardization tools. This study aimed to assess a computational anatomy method producing standardized two-dimensional femorotibial CTh maps. The method was assessed with twenty knees, processed following three common experimental scenarios. Cartilage thickness maps were obtained for the femorotibial cartilages by reconstructing bone and cartilage mesh models in tree-dimension, calculating three-dimensional CTh maps, and anatomically standardizing the maps. The intra-operator accuracy (median (interquartile range, IQR) of -0.006 (0.045) mm), precision (0.152 (0.070) mm), entropy (7.02 (0.71) and agreement (0.975 (0.020))) results suggested that the method is adequate to capture the spatial variations in CTh and compare knees at varying osteoarthritis stages. The lower inter-operator precision (0.496 (0.132) mm) and agreement (0.808 (0.108)) indicate a possible loss of sensitivity to detect differences in a setting with multiple operators. The results confirmed the promising potential of anatomically standardized maps, with the lower inter-operator reproducibility stressing the need to coordinate operators. This study also provided essential reference data and indications for future research using CTh maps.

Three-Dimensional Quantification of Bone Mineral Density in the Distal Femur and Proximal Tibia Based on Computed Tomography: In Vitro Evaluation of an Extended Standardization Method.

While alterations in bone mineral density (BMD) are of interest in a number of musculoskeletal conditions affecting the knee, their analysis is limited by a lack of tools able to take full advantage of modern imaging modalities. This study introduced a new method, combining computed tomography (CT) and computational anatomy algorithms, to produce standardized three-dimensional BMD quantification in the distal femur and proximal tibia. The method was evaluated on ten cadaveric knees CT-scanned twice and processed following three different experimental settings to assess the influence of different scans and operators. The median reliability (intraclass correlation coefficient (ICC)) ranged from 0.96 to 0.99 and the median reproducibility (precision error (RMSSD)) ranged from 3.97 to 10.75 mg/cc for the different experimental settings. In conclusion, this paper presented a method to standardize three-dimensional knee BMD with excellent reliability and adequate reproducibility to be used in research and clinical applications. The perspectives offered by this novel method are further reinforced by the fact it relies on conventional CT scan of the knee. The standardization method introduced in this work is not limited to BMD and could be adapted to quantify other bone parameters in three dimension based on CT images or images acquired using different modalities.

A Registration Method for Three-Dimensional Analysis of Bone Mineral Density in the Proximal Tibia.

Although alterations in bone mineral density (BMD) at the proximal tibia have been suggested to play a role in various musculoskeletal conditions, their pathophysiological implications and their value as markers for diagnosis remain unclear. Improving our understanding of proximal tibial BMD requires novel tools for three-dimensional (3D) analysis of BMD distribution. Three-dimensional imaging is possible with computed tomography (CT), but computational anatomy algorithms are missing to standardize the quantification of 3D proximal tibial BMD, preventing distribution analyses. The objectives of this study were to develop and assess a registration method, suitable with routine knee CT scans, to allow the standardized quantification of 3D BMD distribution in the proximal tibia. Second, as an example of application, the study aimed to characterize the distribution of BMD below the tibial cartilages in healthy knees. A method was proposed to register both the surface (vertices) and the content (voxels) of proximal tibias. The method combines rigid transformations to account for differences in bone size and position in the scanner's field of view and to address inconsistencies in the portion of the tibial shaft included in routine CT scan, with a nonrigid transformation locally matching the proximal tibias. The method proved to be highly reproducible and provided a comprehensive description of the relationship between bone depth and BMD. Specifically it reported significantly higher BMD in the first 6 mm of bone than deeper in the proximal tibia. In conclusion, the proposed method offers promising possibilities to analyze BMD and other properties of the tibia in 3D.

New insight on the subchondral bone and cartilage functional unit: Bone mineral density and cartilage thickness are spatially correlated in non-osteoarthritic femoral condyles.

Objective: This study aimed to improve our understanding of the relationship between bone and cartilage by characterizing the morphological coupling between these mechanosensitive tissues exposed to the same mechanical environment within each knee. Specifically, it reanalyzed a prior dataset to test the hypothesis that the locations of thickest cartilage and densest subchondral bone are correlated in non-osteoarthritic femoral condyles. Method: Anatomically standardized maps of cartilage thickness (CTh) and subchondral bone mineral density (sBMD) were calculated for 50 non-osteoarthritic distal femurs based on computed tomography arthrography examinations. The locations of thickest CTh and densest sBMD were identified in the load-bearing region of the medial and lateral compartments, and correlation analyses were performed to quantify the associations between these locations, with inclusion of age, gender, femoral bone size and femorotibial angle as cofounding variables. Paired Student's t-tests were also performed to compare CTh and sBMD locations. Results: Locations of thickest CTh and densest sBMD were positively correlated along the anteroposterior direction in both compartments (r ≥ 0.45, p ≤ 0.001). Furthermore, thickest CTh was more posterior than densest sBMD in the medial (p = 0.014) and lateral (p < 0.001) compartments, and more lateral than densest sBMD in the lateral compartment (p < 0.001). On average, these location differences were of 1.3, 5.3 and 2.1% of the subchondral bone size. Conclusion: The positive spatial relationship between the locations of thickest CTh and densest sBMD supports the idea of a functional cartilage/subchondral bone unit with morphological coupling conditioned by the individual loading pattern.

Comprehensive description of T2 value spatial variations in non-osteoarthritic femoral cartilage using three-dimensional registration of morphological and relaxometry data.

PURPOSE: The aim of this study was to develop and assess a method of quantifying cartilage T2 relaxation times in a series of volumes of interest (VOIs) covering the entire cartilage of the femoral condyles. Subsequently, the method was used to test for T2 spatial variations in non-osteoarthritic (OA) knees. METHODS: Ten non-OA subjects (five female, average 30 years) were enrolled after informed consent. Three-dimensional bone and cartilage models were created by double echo steady state (DESS) morphological magnetic resonance image (MRI) segmentation, and the models were semi-manually registered with multi-slice, multi-echo (MSME) T2 MRI. Mean T2 values were calculated for 12 VOIs derived from cartilage thickness literature and their respective superficial and deep layers. RESULTS: Analyses showed that intra- and inter-rater reliabilities of the presented method were "good" to "excellent" in more than 90% of the VOIs. Additionally, several spatial differences in T2 values were observed, including, for the medial condyle, higher T2 values in the anterior and central VOIs versus in the posterior VOI (p < .05). T2 values were also generally higher in the superficial versus deep layers (p < .05). CONCLUSIONS: The presented MRI T2 analysis method is reliable and provides a comprehensive quantification of spatial heterogeneity of healthy cartilage compositional properties. This method can be further applied to better understand knee OA pathophysiology and potentially define clinically relevant diagnostic features of the disease.

Cartilage can be thicker in advanced osteoarthritic knees: a tridimensional quantitative analysis of cartilage thickness at posterior aspect of femoral condyles.

OBJECTIVE: To test, through tridimensional analysis, whether (1) cartilage thickness at the posterior aspect of femoral condyles differs in knees with medial femorotibial osteoarthritis (OA) compared to non-OA knees; (2) the location of the thickest cartilage at the posterior aspect of femoral condyles differs between OA and non-OA knees. METHODS: CT arthrograms of knees without radiographic OA (n = 30) and with severe medial femorotibial OA (n = 30) were selected retrospectively from patients over 50 years of age. The groups did not differ in gender, age and femoral size. CT arthrograms were segmented to measure the mean cartilage thickness, the maximal cartilage thickness and its location in a region of interest at the posterior aspect of condyles. RESULTS: For the medial condyle, mean and maximum cartilage thicknesses were statistically significantly higher in OA knees compared to non-OA knees [1.66 vs 1.46 mm (p = 0.03) and 2.56 vs 2.14 mm (p = 0.003), respectively]. The thickest cartilage was located in the half most medial aspect of the posterior medial condyle for both groups, without significant difference between groups. For the lateral condyle, no statistically significant difference between non-OA and OA knees was found (p ≥ 0.17). CONCLUSION: Cartilage at the posterior aspect of the medial condyle, but not the lateral condyle, is statistically significantly thicker in advanced medial femorotibial OA knees compared to non-OA knees. The thickest cartilage was located in the half most medial aspect of the posterior medial condyle. These results will serve as the basis for future research to determine the histobiological processes involved in this thicker cartilage. Advances in knowledge: This study, through a quantitative tridimensional approach, shows that cartilage at the posterior aspect of the medial condyles is thicker in severe femorotibial osteoarthritic knees compared to non-OA knees. In the posterior aspect of the medial condyle, the thickest cartilage is located in the vicinity of the center of the half most medial aspect of the posterior medial condyle. These results will serve as the basis for future research to determine the histobiological processes involved in this thicker cartilage.