Secondary use of health care data and left-over biosamples within the 'Medical Informatics Initiative' (MII): a quasi-randomized controlled evaluation of patient perceptions and preferences regarding the consent process.

BACKGROUND: Data collected during routine health care and ensuing analytical results bear the potential to provide valuable information to improve the overall health care of patients. However, little is known about how patients prefer to be informed about the possible usage of their routine data and/or biosamples for research purposes before reaching a consent decision. Specifically, we investigated the setting, the timing and the responsible staff for the information and consent process. METHODS: We performed a quasi-randomized controlled trial and compared the method by which patients were informed either in the patient admission area following patient admission by the same staff member (Group A) or in a separate room by another staff member (Group B). The consent decision was hypothetical in nature. Additionally, we evaluated if there was the need for additional time after the information session and before taking the consent decision. Data were collected during a structured interview based on questionnaires where participants reflected on the information and consent process they went through. RESULTS: Questionnaire data were obtained from 157 participants in Group A and 106 participants in Group B. Overall, participants in both groups were satisfied with their experienced process and with the way information was provided. They reported that their (hypothetical) consent decision was freely made. Approximately half of the interested participants in Group B did not show up in the separate room, while all interested participants in Group A could be informed about the secondary use of their routine data and left-over samples. No participants, except for one in Group B, wanted to take extra time for their consent decision. The hypothetical consent rate for both routine data and left-over samples was very high in both groups. CONCLUSIONS: The willingness to support medical research by allowing the use of routine data and left-over samples seems to be widespread among patients. Information concerning this secondary data use may be given by trained administrative staff immediately following patient admission. Patients mainly prefer making a consent decision directly after information is provided and discussed. Furthermore, less patients are informed when the process is organized in a separate room.

Towards a comprehensive and interoperable representation of consent-based data usage permissions in the German medical informatics initiative.

BACKGROUND: The aim of the German Medical Informatics Initiative is to establish a national infrastructure for integrating and sharing health data. To this, Data Integration Centers are set up at university medical centers, which address data harmonization, information security and data protection. To capture patient consent, a common informed consent template has been developed. It consists of different modules addressing permissions for using data and biosamples. On the technical level, a common digital representation of information from signed consent templates is needed. As the partners in the initiative are free to adopt different solutions for managing consent information (e.g. IHE BPPC or HL7 FHIR Consent Resources), we had to develop an interoperability layer. METHODS: First, we compiled an overview of data items required to reflect the information from the MII consent template as well as patient preferences and derived permissions. Next, we created entity-relationship diagrams to formally describe the conceptual data model underlying relevant items. We then compared this data model to conceptual models describing representations of consent information using different interoperability standards. We used the result of this comparison to derive an interoperable representation that can be mapped to common standards. RESULTS: The digital representation needs to capture the following information: (1) version of the consent, (2) consent status for each module, and (3) period of validity of the status. We found that there is no generally accepted solution to represent status information in a manner interoperable with all relevant standards. Hence, we developed a pragmatic solution, comprising codes which describe combinations of modules with a basic set of status labels. We propose to maintain these codes in a public registry called ART-DECOR. We present concrete technical implementations of our approach using HL7 FHIR and IHE BPPC which are also compatible with the open-source consent management software gICS. CONCLUSIONS: The proposed digital representation is (1) generic enough to capture relevant information from a wide range of consent documents and data use regulations and (2) interoperable with common technical standards. We plan to extend our model to include more fine-grained status codes and rules for automated access control.

Predicting Training Gain for a 3 Week Period of Arm Ability Training in the Subacute Stage After Stroke.

Background: Biomarkers for gains of evidence based interventions for upper limb motor training in the subacute stage following stroke have rarely been described. Information about these parameters might help to identify patients who benefit from specific interventions and to determine individually expected behavioral gains for a certain period of therapy. Objective: To evaluate predictors for hand motor outcome after arm ability training in the subacute stage after stroke selected from known potentially relevant parameters (initial motor strength, structural integrity of the pyramidal tract and functional motor cortex integrity). Methods: We applied the arm ability training (AAT) over 3 weeks to a subpopulation of stroke patients with mild arm paresis, i.e., in 14 patients on average 4 weeks after stroke. The following biomarkers were measured before therapy onset: grip strength on the affected hand, transcranial magnetic stimulation recruitment curve steepness over the primary motor hand area [slope ratio between the ipsilesional hemisphere (IH) and contralesional hemisphere (CH)], and diffusion weighted MRI fractional anisotropy (FA) in the posterior limb of the internal capsule (PLIC; determined as a lateralization index between IH and CH). Outcome was assessed as the AATgain (percentage improvement over training). The "Test d'Evaluation des Membres Supérieurs de Personnes Âgées" (TEMPA) was assessed before and after training to test for possible associations of AAT with activity of daily living. Results: A stepwise linear regression identified the lateralization index of PLIC FA as the only significant predictor for AAT-gain (R 2 = 0.519; P = 0.029). AAT-gain was positively associated (r = 0.59; P = 0.028) with improvement in arm function during daily activities (TEMPA). Conclusions: While all mildly affected patients achieved a clinically relevant therapeutic effect, pyramidal tract integrity nevertheless had a modifying role for clinical benefit.

Enhancement of motor learning by focal intermittent theta burst stimulation (iTBS) of either the primary motor (M1) or somatosensory area (S1) in healthy human subjects.

BACKGROUND: Motor rehabilitation after brain damage relies on motor re-learning as induced by specific training. Non-invasive brain stimulation (NIBS) can alter cortical excitability and thereby has a potential to enhance subsequent training-induced learning. Knowledge about any priming effects of NIBS on motor learning in healthy subjects can help to design targeted therapeutic applications in brain-damaged subjects. OBJECTIVE: To examine whether complex motor learning in healthy subjects can be enhanced by intermittent theta burst stimulation (iTBS) to primary motor or sensory cortical areas. METHODS: Eighteen young healthy subjects trained eight different arm motor tasks (arm ability training, AAT) once a day for 5 days using their left non-dominant arm. Except for day 1 (baseline), training was performed after applying an excitatory form of repetitive transcranial magnetic stimulation (iTBS) to either (I) right M1 or (II) S1, or (III) sham stimulation to the right M1. Subjects were randomly assigned to conditions I, II, or III. RESULTS: A principal component analysis of the motor behaviour data suggested eight independent motor abilities corresponding to the 8 trained tasks. AAT induced substantial motor learning across abilities with generalisation to a non-trained test of finger dexterity (Nine-Hole-Peg-Test, NHPT). Participants receiving iTBS (to either M1 or S1) showed better performance with the AAT tasks over the period of training compared to sham stimulation as well as a bigger improvement with the generalisation task (NHPT) for the trained left hand after training completion. CONCLUSION: Priming with an excitatory repetitive transcranial magnetic stimulation as iTBS of either M1 or S1 can enhance motor learning across different sensorimotor abilities.

Changes in motor cortex excitability for the trained and non-trained hand after long-term unilateral motor training.

Repetitive unilateral upper limb motor training does not only affect behavior but also increases excitability of the contralateral primary motor cortex (M1). The behavioral gain is partially transferred to the non-trained side. Changes in M1 intracortical facilitation (ICF) might as well be observed for both hand sides. We measured ICF of both left and right abductor pollicis brevis muscles (APB) before and after a two-week period of arm ability training (AAT) of the left hand in 13 strongly right handed healthy volunteers. Performance with AAT-tasks improved for both the left trained and right untrained hand. ICF for the untrained hand decreased over training while it remained unchanged for the left trained hand. Decrease of ICF for the right hand was moderately associated with an increase of AAT-performance for the untrained right hand. We conclude that ICF-imbalance between dominant and non-dominant hand is sensitive to long-term motor training: training of the non-dominant hand results in a decrease of ICF of the dominant hand. The ICF-decrease is associated with a transfer of training-induced improvement of performance from the non-dominant to the dominant hand.

Priming Hand Motor Training with Repetitive Stimulation of the Fingertips; Performance Gain and Functional Imaging of Training Effects.

BACKGROUND: Application of repetitive electrical stimulation (rES) of the fingers has been shown to improve tactile perception and sensorimotor performance in healthy individuals. OBJECTIVE: To increase motor performance by priming the effects of active motor training (arm ability training; AAT) using rES. METHODS: We compared the performance gain for the training increase of the averaged AAT tasks of both hands in two groups of strongly right-handed healthy volunteers. Functional Magnetic Resonance Imaging (fMRI) before and after AAT was assessed using three tasks for each hand separately: finger sequence tapping, visually guided grip force modulation, and writing. Performance during fMRI was controlled for preciseness and frequency. A total of 30 participants underwent a two-week unilateral left hand AAT, 15 participants with 20 minutes of rES priming of all fingertips of the trained hand, and 15 participants without rES priming. RESULTS: rES-primed AAT improved the trained left-hand performance across all training tasks on average by 32.9%, non-primed AAT improved by 29.5%. This gain in AAT performance with rES priming was predominantly driven by an increased finger tapping velocity. Functional imaging showed comparable changes for both training groups over time. Across all participants, improved AAT performance was associated with a higher contralateral primary somatosensory cortex (S1) fMRI activation magnitude during the grip force modulation task. CONCLUSIONS: This study highlights the importance of S1 for hand motor training gain. In addition, it suggests the usage of rES of the fingertips for priming active hand motor training.

Device-Training for Individuals with Thoracic and Lumbar Spinal Cord Injury Using a Powered Exoskeleton for Technically Assisted Mobility: Achievements and User Satisfaction.

Objective. Results of a device-training for nonambulatory individuals with thoracic and lumbar spinal cord injury (SCI) using a powered exoskeleton for technically assisted mobility with regard to the achieved level of control of the system after training, user satisfaction, and effects on quality of life (QoL). Methods. Observational single centre study with a 4-week to 5-week intensive inpatient device-training using a powered exoskeleton (ReWalk™). Results. All 7 individuals with SCI who commenced the device-training completed the course of training and achieved basic competences to use the system, that is, the ability to stand up, sit down, keep balance while standing, and walk indoors, at least with a close contact guard. User satisfaction with the system and device-training was documented for several aspects. The quality of life evaluation (SF-12v2™) indicated that the use of the powered exoskeleton can have positive effects on the perception of individuals with SCI regarding what they can achieve physically. Few adverse events were observed: minor skin lesions and irritations were observed; no falls occurred. Conclusions. The device-training for individuals with thoracic and lumbar SCI was effective and safe. All trained individuals achieved technically assisted mobility with the exoskeleton while still needing a close contact guard.

Increased ventral premotor cortex recruitment after arm training in an fMRI study with subacute stroke patients.

To investigate therapy associated changes in the cerebral representation of movement after stroke, we used functional magnetic resonance imaging (fMRI) during an active and a passive motor task for the affected and unaffected hand before and after a three week comprehensive hand motor training. Twelve patients in the subacute phase from 2 to 9 weeks after mild to moderate motor stroke were recruited. During fMRI, the active task comprised fist clenching, which was precisely controlled for motor performance by visual feedback of force and frequency. The passive task consisted of wrist flexion-extension of 1Hz frequency by means of a pneumatic driven splint. Arm Ability Training (AAT) was conducted one hour per day over 3 weeks in addition to inward rehabilitative therapy. Performance gain was tested using movements trained with AAT, but also with conventional hand motor tests (Nine-Hole-Peg Test, Box-and-Block Test). Rehabilitation therapy and AAT resulted in considerable improvement of performance in trained tasks and other hand motor functions (e.g., Nine-Hole-Peg Test). FMRI activation in the ventral premotor cortex (vPMC) of the lesioned hemisphere increased over time for the active task only for the affected hand. No such change was present for the passive wrist extension task or the active task with the unaffected hand. In addition, only for the post measurement of the active task performed with the affected hand, bilateral vPMC shows a more pronounced activation than in healthy controls. This finding contradicts the simple "near to normal is good recovery" opinion.

Effects of combining 2 weeks of passive sensory stimulation with active hand motor training in healthy adults.

The gold standard to acquire motor skills is through intensive training and practicing. Recent studies have demonstrated that behavioral gains can also be acquired by mere exposure to repetitive sensory stimulation to drive the plasticity processes. Single application of repetitive electric stimulation (rES) of the fingers has been shown to improve tactile perception in young adults as well as sensorimotor performance in healthy elderly individuals. The combination of repetitive motor training with a preceding rES has not been reported yet. In addition, the impact of such a training on somatosensory tactile and spatial sensitivity as well as on somatosensory cortical activation remains elusive. Therefore, we tested 15 right-handed participants who underwent repetitive electric stimulation of all finger tips of the left hand for 20 minutes prior to one hour of motor training of the left hand over the period of two weeks. Overall, participants substantially improved the motor performance of the left trained hand by 34%, but also showed a relevant transfer to the untrained right hand by 24%. Baseline ipsilateral activation fMRI-magnitude in BA 1 to sensory index finger stimulation predicted training outcome for somatosensory guided movements: those who showed higher ipsilateral activation were those who did profit less from training. Improvement of spatial tactile discrimination was positively associated with gains in pinch grip velocity. Overall, a combination of priming rES and repetitive motor training is capable to induce motor and somatosensory performance increase and representation changes in BA1 in healthy young subjects.

Early stages of motor skill learning and the specific relevance of the cortical motor system--a combined behavioural training and θ burst TMS study.

PURPOSE: To examine whether motor performance and motor learning in healthy subjects can be segregated into a number of distinct motor abilities which are linked to intact processing in different motor-related brain regions (M1, S1, SMA, PMC) early during learning. METHODS: Seven young healthy subjects trained in eight motor arm tasks (Arm Ability Training, AAT) once a day for 5 days using their left non-dominant arm. Except for day 1 (baseline), training was performed before and after applying an inhibitory form of repetitive transcranial magnetic stimulation (cTBS, continuous theta burst) to either M1, S1, SMA, or PMC. RESULTS: A principal component analysis of the motor behaviour data suggested four independent motor abilities: aiming, speed, steadiness, and visuomotor tracking. AAT induced substantial motor learning across abilities. Within session effects of cTBS revealed that activity in primary somatosensory cortex (S1) was relevant for motor performance and learning across all tasks whereas M1 was specifically involved in rapid tapping movements, PMC in ballistic arm navigation in extra-personal space; performance on a non-trained motor tasks was not affected by cTBS. CONCLUSIONS: Cortical sensory and motor areas including S1, M1, and PMC functionally contribute to early motor learning in a differential manner across motor abilities.

Prolonged motor skill learning--a combined behavioural training and θ burst TMS study.

PURPOSE: To assess the behavioural effects of prolonged motor practice in healthy volunteers, and the specific impact of inhibiting different motor-related brain regions in the late phase of motor learning using continuous theta burst transcranial magnetic stimulation (cTBS). METHODS: Twelve subjects trained their non-dominant arm in eight arm motor tasks (Arm Ability Training, AAT) once a day for three weeks (16 sessions). During the last four days, training was performed before and after applying cTBS to either M1, S1, SMA, or PMC. RESULTS: The AAT induced substantial and robust motor learning for the trained arm with variations across tasks. Considerable motor learning was also observed in the non-trained dominant arm with remarkably similar variations across tasks, suggesting that practise improved common underlying sensorimotor capacities (abilities) in addition to effector-specific effects. When applied after prolonged training, inhibitory cTBS showed no detrimental effects on motor performance/learning; M1 cTBS even improved performance in a labyrinth task. CONCLUSIONS: Prolonged training with the non-dominant arm led to profound motor learning across abilities with transfer to the non-trained dominant arm. Unlike during early stages of motor learning, no detrimental effect of cTBS over M1, S1, PMC, or SMA could be substantiated after prolonged motor practice.