Budget impact of the Oncotype DX® test compared to other gene expression tests in patients with early breast cancer in Germany.

PURPOSE: Gene expression tests can inform decisions on whether to recommend chemotherapy for patients with HR+, HER2- early breast cancer. The goal of this analysis was to compare treatment costs by an expanded budget impact model of reimbursed gene expression tests in Germany. METHODS: A cost comparison was constructed as an expanded budget impact model to calculate average total costs per patient covered by public health insurance. Based on the strong clinical evidence from the prospective randomized controlled trial TAILORx including more than 10,000 patients with HR+ and node negative breast cancer, the assumption was made that the Oncotype DX® test accurately predicts chemotherapy benefit and clinical outcomes. For the further reimbursed tests (EndoPredict®, MammaPrint®, Prosigna®), results from comparative studies - aligned with prognosis studies - as analyzed in IQWiG Rapid Report D19-01 were applied. RESULTS: The use of the Oncotype DX test led to estimated average savings per patient of 2,500 € vs. EndoPredict, 1,936 € vs. MammaPrint, and 649 € vs. Prosigna. Savings were achieved by reduction of unnecessary chemotherapy use, a consequence of false-positive test results (EndoPredict 73%, MammaPrint 42%, Prosigna 20%). False-negative test results (EndoPredict 5%, MammaPrint 22%, Prosigna 49%) reduced necessary chemotherapies, which initially results in cost savings, but may lead to increased long-term costs associated with management of progressive disease. CONCLUSION: The results from this model suggest that the use of the Oncotype DX test reduces the cost of health care in Germany making it the most cost effective test compared to the further tests.

Cardiac 4D phase-contrast CMR at 9.4 T using self-gated ultra-short echo time (UTE) imaging.

BACKGROUND: Time resolved 4D phase contrast (PC) cardiovascular magnetic resonance (CMR) in mice is challenging due to long scan times, small animal ECG-gating and the rapid blood flow and cardiac motion of small rodents. To overcome several of these technical challenges we implemented a retrospectively self-gated 4D PC radial ultra-short echo-time (UTE) acquisition scheme and assessed its performance in healthy mice by comparing the results with those obtained with an ECG-triggered 4D PC fast low angle shot (FLASH) sequence. METHODS: Cardiac 4D PC CMR images were acquired at 9.4 T in healthy mice using the proposed self-gated radial center-out UTE acquisition scheme (TE/TR of 0.5 ms/3.1 ms) and a standard Cartesian 4D PC imaging sequence (TE/TR of 2.1 ms/5.0 ms) with a four-point Hadamard flow encoding scheme. To validate the proposed UTE flow imaging technique, experiments on a flow phantom with variable pump rates were performed. RESULTS: The anatomical images and flow velocity maps of the proposed 4D PC UTE technique showed reduced artifacts and an improved SNR (left ventricular cavity (LV): 8.9 ± 2.5, myocardium (MC): 15.7 ± 1.9) compared to those obtained using a typical Cartesian FLASH sequence (LV: 5.6 ± 1.2, MC: 10.1 ± 1.4) that was used as a reference. With both sequences comparable flow velocities were obtained in the flow phantom as well as in the ascending aorta (UTE: 132.8 ± 18.3 cm/s, FLASH: 134.7 ± 13.4 cm/s) and pulmonary artery (UTE: 78.5 ± 15.4 cm/s, FLASH: 86.6 ± 6.2 cm/s) of the animals. Self-gated navigator signals derived from information of the oversampled k-space center were successfully extracted for all animals with a higher gating efficiency of time spent on acquiring gated data versus total measurement time (UTE: 61.8 ± 11.5%, FLASH: 48.5 ± 4.9%). CONCLUSIONS: The proposed self-gated 4D PC UTE sequence enables robust and accurate flow velocity mapping of the mouse heart in vivo at high magnetic fields. At the same time SNR, gating efficiency, flow artifacts and image quality all improved compared to the images obtained using the well-established, ECG-triggered, 4D PC FLASH sequence.

The comprehensive ICF core sets for spinal cord injury from the perspective of occupational therapists: a worldwide validation study using the Delphi technique.

OBJECTIVE: To validate the International Classification of Functioning, Disability and Health (ICF) core sets for individuals with spinal cord injury (SCI) in the early post-acute and long-term context from the perspective of occupational therapists (OTs). SETTING: International. METHODS: OTs experienced in the treatment in SCI were asked about problems, resources and aspects of the environment treated by them, in a three-round electronic mail survey using the Delphi technique. Responses were linked to the ICF by two researchers; kappa coefficient was calculated as statistical measure of agreement. RESULTS: In total, 67 experts from 27 countries named 2586 different concepts. For the early post-acute context, 223 concepts were linked to ICF categories. Three ICF categories from the component body function, three ICF categories from the component body structures and five ICF categories from the component activities and participation were not represented in the ICF core set for the early post-acute context with an expert agreement of more than 75%. For the long-term context, 205 concepts were linked to ICF categories. Two ICF categories from the component body function, four ICF categories from the component body structures and two ICF categories from the component activities and participation were not represented in the ICF core set with an expert agreement of more than 75%. CONCLUSION: OTs addressed a vast variety of problems that they take care of in their interventions in persons with SCI. The Comprehensive ICF core sets covered a high percentage of these problems. Further research is necessary on a few aspects that are not included in the ICF core sets for SCI.

The comprehensive ICF core sets for spinal cord injury from the perspective of physical therapists: a worldwide validation study using the Delphi technique.

OBJECTIVE: To validate the International Classification of Functioning, Disability and Health (ICF) Core Set for individuals with spinal cord injury (SCI) in the early post-acute and long-term context from the perspective of physical therapists. SETTING: International. METHODS: Physical therapists experienced in the treatment of SCI were asked about problems, resources and aspects of the environment treated by them, in a three-round electronic mail survey using the Delphi technique. Responses were linked to the ICF by two researches; κ-coefficient was calculated as statistical measure of agreement. RESULTS: In all, 81 experts from 27 countries named 3694 concepts. They were linked to 187 ICF categories for the early post-acute context. Three ICF categories from the component body function, five ICF categories from the component body structures and two ICF categories from the component activities and participation were not represented in the ICF Core Set for the early post-acute context. In all, 207 ICF categories were linked for the long-term context. Four ICF categories from the component body function, five ICF categories from the component body structures and two ICF categories from the component activities and participation were not represented in the ICF Core Set for the long-term context. CONCLUSION: Physical therapists addressed a vast variety of problems that they take care of in their interventions in patients with SCI. The Comprehensive ICF Core Sets covered a high percentage of these problems. Further research is necessary on several responses not covered in the ICF.

Differences in functioning of individuals with tetraplegia and paraplegia according to the International Classification of Functioning, Disability and Health (ICF).

STUDY DESIGN: Cross-sectional, multicenter study. OBJECTIVES: To identify and quantify the differences in functioning of individuals with tetraplegia versus paraplegia using the International Classification of Functioning, Disability and Health (ICF) as a frame of reference. SETTING: International. METHODS: Functional problems of 1048 participants with spinal cord injury in 16 study centers in 14 countries were recorded using ICF categories. The level of significance and odds ratios (OR) for experiencing each of these functional problems were reported for individuals with tetraplegia and paraplegia. Regression models were adjusted for age, age squared, early post-acute or long-term context, gender and for world regions. RESULTS: Persons with tetraplegia are more at risk than persons with paraplegia to have difficulties in 36.4% categories of the component body functions. In the component body structures, 40% of the categories show significant differences. Individuals with tetraplegia indicate problems in three categories, whereas individuals with paraplegia are more likely to indicate problems in one category. Most categories indicating difficulties (56.6%) for persons with tetraplegia were found for the component activities and participation. The component with the highest congruency was the environmental factors. Overall, 3.7% categories (of the persons with tetraplegia as experienced, 2.4% of the categories as barriers, whereas 4.9% were experienced to be facilitators) obtained OR, indicating individuals with tetraplegia having more difficulties. CONCLUSION: The logistic regression analysis identified a variety of differences in functional problems in individuals with tetraplegia compared with individuals with paraplegia. The ICF has the potential to indicate the differences in health conditions.

Diffusion-weighted imaging (DWI) in MR mammography (MRM): clinical comparison of echo planar imaging (EPI) and half-Fourier single-shot turbo spin echo (HASTE) diffusion techniques.

Diffusion-weighted imaging (DWI) techniques have shown potential to differentiate between benign and malignant neoplasms. However, the diagnostic significance of using DWI under routine conditions remains unclear. This study investigated the use of echo planar imaging (EPI) and half-Fourier acquired single-shot turbo spin echo (HASTE)-DWI with respect to the three parameters: lesion visibility, apparent diffusion coefficient (ADC) measurements, and size estimation. Following MRM (1.5 T), EPI- and HASTE-DWI were applied in 65 patients. Lesion visibility on DWI was compared with lesion visibility on subtracted contrast-enhanced T1w images (CE-T1w). Statistical tests were applied to diameter, visibility, and ADC value measurements. Seventy-four lesions were identified. ADC value measurements did not differ significantly between the two DWI sequences. The sensitivity and specificity of routine diagnostics (97.4% and 85.7%) were superior to EPI-DWI (87.2% and 82.9%) and HASTE-DWI (76.9% and 88.6%). Selecting only nonmass lesions, DWI did not prove to be of diagnostic value. Lesion demarcation by DWI was significantly lower compared with that by CE-T1w, with EPI-DWI showing the better performance (p < 0.001). No significant differences were found for size measurements between CE-T1w and DWI. Although clearly inferior compared with CE-T1w imaging, both DWI techniques are applicable for lesion assessment and size measurements.

Application and assessment of a robust elastic motion correction algorithm to dynamic MRI.

The purpose of this study was to assess the performance of a new motion correction algorithm. Twenty-five dynamic MR mammography (MRM) data sets and 25 contrast-enhanced three-dimensional peripheral MR angiographic (MRA) data sets which were affected by patient motion of varying severeness were selected retrospectively from routine examinations. Anonymized data were registered by a new experimental elastic motion correction algorithm. The algorithm works by computing a similarity measure for the two volumes that takes into account expected signal changes due to the presence of a contrast agent while penalizing other signal changes caused by patient motion. A conjugate gradient method is used to find the best possible set of motion parameters that maximizes the similarity measures across the entire volume. Images before and after correction were visually evaluated and scored by experienced radiologists with respect to reduction of motion, improvement of image quality, disappearance of existing lesions or creation of artifactual lesions. It was found that the correction improves image quality (76% for MRM and 96% for MRA) and diagnosability (60% for MRM and 96% for MRA).

Three-dimensional nickel ion transport through porous media using magnetic resonance imaging.

The transport of Ni2+ ions in a column, filled with porous media, was observed in three dimensions and time by magnetic resonance imaging (MRI) in a clinical scanner. For porous media we used glass beads or quartz sand in a saturated continuous flow mode. The magnetic moment of Ni2+ decreased the T1 relaxation time of 1H in aqueous solution. This concentration-dependent effect was used by a fast low angle shot (FLASH) MRI sequence for imaging the concentration of the dissolved ions. Since Ni2+ behaves as a conservative tracer under the chosen conditions, the tracer motion was representative for the water flow in the porous medium. Currently, we can achieve an isotropic spatial resolution of 1.5 mm and a temporal resolution of 170 s. The transport observation gives direct access to hydraulic flow properties of the porous media. The fluid flow velocity field was calculated by a fronttracking method and the statistical properties of the velocities were investigated. We also compared the experimental data with the three-dimensional particle tracking model PARTRACE, which uses the experimental flow field as input.

Investigation of dialysis membranes with atomic force microscopy.

AFM was used to investigate dialysis membranes made of regenerated cellulose by the cuoxam process. The membranes were either Cuprophan or experimental samples, modified with different amounts of diethylaminoethylcellulose (DEAE). Atomic force microscopes with optical-lever detection systems were used to image the dry membranes in air as received from the manufacturer as well as wet membranes in a swollen state under water. Differences could be observed between modified and unmodified as well as between dry and wet membranes.

Reflection electron microscopy and interferometry of atomic steps on gold and platinum single crystal surfaces.

Two beam interferences produced using an electrostatic biprism, which is inserted in the position of the selected area diaphragm of a commercial electron microscope, may be used in reflection electron microscopy to determine the phase shifts induced by structures on single crystal surfaces. A description of our interferometrical and holographical experiments on the phase shift at steps on (111)Au and (111)Pt single crystal surfaces is given and a straight forward interpretation of the results in terms of refraction will be discussed. As a particular result phase shifts of pi and 0.9 pi were measured for monatomic steps on (111)gold and (111)platinum surfaces, respectively.

A TV system for image recording and processing in conventional transmission electron microscopy.

An image processing system for a CTEM is described which is particularly suited for the imaging of radiation-sensitive objects. It consists of an image intensifier device for single electron counting, a digital storage unit and a video recorder for intermediate storage of low-dose image series. During on-line operation the information can be transferred to a computer for further processing. The output can be transferred onto a second digital storage unit and observed on a monitor. The influence on the DQE of the pulse height distribution of the single electron video signals and of a multiple counting are eliminated by means of special electronic components. Various modes of operation and application possibilities of the image processing system are discussed.