A scoping review of metamodeling applications and opportunities for advanced health economic analyses

Introduction: Metamodels, also known as meta-models, surrogate models, or emulators, are used in several fields of research to negate runtime issues with analyzing computational demanding simulation models. This study introduces metamodeling and presents results of a review on metamodeling applications in health economics. Areas covered: A scoping review was performed to identify studies that applied metamodeling methods in a health economic context. After search and selection, 13 publications were found to employ metamodeling methods in health economics. Metamodels were used to perform value of information analysis (n = 5, 38%), deterministic sensitivity analysis (n = 4, 31%), model calibration (n = 1, 8%), probabilistic sensitivity analysis (n = 1), or optimization (n = 1, 8%). One study was found to extrapolate a simulation model to other countries (n = 1, 8%). Applied metamodeling techniques varied considerably between studies, with linear regression being most frequently applied (n = 7, 54%). Expert commentary: Although it has great potential to enable computational demanding analyses of health economic models, metamodeling in health economics is still in its infancy, as illustrated by the limited number of applications and the relatively simple metamodeling methods applied. Comprehensive guidance specific to health economics is needed to provide modelers with the information and tools needed to utilize the full potential of metamodels

Identifying the optimal use of CTCs in the early staging phase of breast cancer

Objectives: Circulating tumour cells (CTCs) in the blood can give important information about the prognosis and treatment options for cancer patients. Methods like cell-search are not sensitive enough because the blood samples are small (7,5 mL). Currently a technique is developed which can separate CTCs from the whole blood and is called the CTC Trap. This study addresses the potential impact of implementing the CTC Trap in addition to currently used imaging techniques in early staging of primary stage I-III breast cancer in women. Methods: The early staging process has been identified using the Dutch breast cancer guideline. This process is displayed in a decision tree. Three points in this process have been identified as possible implementation options for the CTC Trap. A simulation model has been built in Excel to simulate the cost-effectiveness of implementing the CTC Trap at these three different points. Results: Potentially relevant points for the CTC trap are: 1) following negative sentinel lymph node procedure to test for micro metastases, 2) following negative result of initial MRI to test for (micro-) metastases, 3) following negative results of further imaging. Usual care resulted in an average survival of 2,42 years, a 3-year survival of 93,71%, 1,51 QALYs and a cost of € 992,56. When implemented at all 3 implementation points simultaneously CTC Trap resulted in an average survival of 2,84 years, a 3-year survival of 97,46 %, 1,84 QALYS and a total cost of € 6.035,45. Conclusions: CTCs clearly have the potential to improve overall survival. Use of CTCs can potentially improve survival with 0,42 years and improve QALYs with 0,34. Costs do increase at all options but from a health economic perspective it is most valuable to implement CTC Trap in option 1) following negative sentinel lymph node procedure to test for (micro-) metastases

The influence of voluntary upper body exercise on the performance of stimulated paralysed human quadriceps

In this study the influence of voluntary upper body exercise on the performance of stimulated paralysed human quadriceps was investigated in five subjects with spinal cord lesions in the thoracic spine. The experimental setup consisted of computer-controlled stimulation of the quadriceps using electrodes on the surface of the skin, a dynamometer for isometric or isokinetic loading of the lower leg, and a rowing ergometer for upper body exercise. In all subjects, quadriceps fatigue tests were conducted to study the influence of upper body exercise on knee torque during sustained continuous or intermittent stimulation of quadriceps. The relative asymptotic torque appeared to be significantly higher with the presence of upper body exercise than without. This was consistently found both between trials (starting with or without upper body exercise) as well as within trials, when upper body exercise was started or stopped during the trial. No significant influence of upper body exercise on the time constant of initial torque decline was found

A bumpy train ride: A field experiment on insult, culture of honor, and emotional reactions

The present research examined the relationship between adherence to honor norms and emotional reactions after an insult. Participants were 42 Dutch male train travelers, half of whom were insulted by a confederate who bumped into the participant and made a degrading remark. Compared with insulted participants with a weak adherence to honor norms, insulted participants with a strong adherence to honor norms were (a) more angry, (b) less joyful, (c) less fearful, and (d) less resigned. Moreover, insulted participants with a strong adherence to honor norms perceived more anger in subsequent stimuli than not-insulted participants with a strong adherence to these norms. The present findings support a direct relationship among insult, adherence to honor norms, and emotional reactions. © 2007 American Psychological Association

The influence of the reciprocal cable linkage in the advanced reciprocating gait orthosis on paraplegic gait performance

A wide variety of mechanical orthoses is available to provide ambulation to paraplegic patients. Evaluation of energy cost during walking in each of these devices has been acknowledged as an important topic in this field of research. In order to investigate the benefits of a ballistic swing on gait performance in the Advanced Reciprocating Gait Orthosis (ARGO) a study was conducted in which the ARGO was compared with an orthosis with freely swinging legs. This Non Reciprocally linked Orthosis (NRO) was obtained by removing the reciprocal linkage in the subjects' own ARGOs. Subsequently, flexion/extension limits were mounted to permit adjustment of stride length. Six male paraplegic subjects with lesions ranging from T4 to T12 were included in the study. A single case experimental design (B-A-B-A) was conducted in order to improve internal validity. Biomechanical and physiological parameters were assessed and the subjects' preference for either ARGO or NRO was determined.\ud \ud It was found that large inter-individual differences produced insufficient evidence in this study to draw general conclusions about difference in energy expenditure between both orthoses. However, individual analysis of the results showed a reduction of oxygen cost (range: 4%-14%) in the NRO in T9 and T12 lesions, while oxygen cost in subjects with T4 lesions increased markedly (22% and 40%). It is concluded that patients with low level lesions could benefit in terms of oxygen lost from removing the reciprocal cable linkage in the ARGO. However, only one subject preferred the NRO for walking, whereas none of the subject chose the NRO for use in daily living activities. Removal of the reciprocal cable linkage in the ARGO may not be desirable for these patients

The influence of frontal alignment in the advanced reciprocating gait orthosis on energy cost and crutch force requirements during paraplegic gait

Reduction of energy cost and upper body load during paraplegic walking is considered to be an important criterion in future developments of walking systems. A high energy cost limits the maximum walking distance in the current devices, whereas wrist and shoulder pathology can deteriorate because of the high upper body load. A change in alignment of the mechanical brace in the frontal plane, i.e. abduction, can contribute to a more efficient gait pattern with sufficient foot clearance with less pelvic lateral sway. A decrease in pelvic lateral sway after aligning in abduction results in a shift of the centre of mass to the swing leg crutch which may result in a decrease in required crutch force on stance side to maintain foot clearance. Five paraplegic subjects were provided with a standard Advanced Reciprocating Gait Orthosis (ARGO) and an ARGO aligned in 4 different degrees of abduction (0°, 3°, 6° and 9°). After determining an optimal abduction angle for each of the subjects, a cross over design was used to compare the ARGO with the individually optimised abducted orthosis. An abduction angle between 0° and 3° was chosen as optimal abduction angle. Subjects were not able to walk satisfactory with abduction angles 6° and 9°. A significant reduction in crutch peak force on stance side was found (approx. 12% , p < 0.01) in the abducted orthosis. Reduction in crutch force time integral (15%) as well as crutch peak force on swing side (5%) was not significant. No differences in oxygen uptake as well as oxygen cost was found. We concluded that an abduction angle between 0° and 3° is beneficial with respect to upper boHy load, whereas energy requirements did not change