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Allied and behavioral health professionals (ABHP) interact with clients who may be at higher risk for substance misuse or substance use disorders (SUD) due to mental health problems, relational problems, and acute/chronic pain due to injury/illness. These problems can lead to more substance misuse and affect daily life activities and overall health and wellbeing. Unfortunately, not enough individuals seek treatment due to stigma associated with substance use, partially because of the lack of properly trained and educated healthcare professionals. The researchers developed an interprofessional training program using the Screening, Brief Intervention, and Referral to Treatment (SBIRT) to develop learning modules focused on understanding the science of addiction, the stigma related to addictions, and the basic interviewing and assessment techniques to support appropriate substance use intervention and referral. The goal was to prepare ABHP students to appropriately address substance use as part of their future professional practice. The SBIRT learning modules used pre/post test quizzes to collect data on the effectiveness. 140 occupational and physical therapy and mental health counselling students completed the training and the results showed a significant increase in participants knowledge supporting the value of the SBIRT training.

Sleep, or the lack thereof, has far-reaching consequences on many aspects of human physiology, cognitive performance, and emotional wellbeing. To ensure undisturbed sleep monitoring, unobtrusive measurements such as ballistocardiogram (BCG) are essential for sustained, real-world data acquisition. Current analysis of BCG data during sleep remains challenging, mainly due to low signal-to-noise ratio, physical movements, as well as high inter- and intra-individual variability. To overcome these challenges, this work proposes a novel approach to improve J-peak extraction from BCG measurements using a supervised deep learning setup. The proposed method consists of the modeling of the discrete reference heartbeat events with a symmetric and continuous kernel-function, referred to as surrogate signal. Deep learning models approximate this surrogate signal from which the target heartbeats are detected. The proposed method with various surrogate signals is compared and evaluated with state-of-the-art methods from both signal processing and machine learning approaches. The BCG dataset was collected over 17 nights using inertial measurement units (IMUs) embedded in a mattress, together with an ECG for reference heartbeats, for a total of 134 h. Moreover, we apply for the first time an evaluation metric specialized for the comparison of event-based time series to assess the quality of heartbeat detection. The results show that the proposed approach demonstrates superior accuracy in heartbeat estimation compared to existing approaches, with an MAE (mean absolute error) of 1.1 s in 64-s windows and 1.38 s in 8-s windows. Furthermore, it is shown that our novel approach outperforms current methods in detecting the location of heartbeats across various evaluation metrics. To the best of our knowledge, this is the first approach to encode temporal events using kernels and the first systematic comparison of various event encodings for event detection using a regression-based sequence-to-sequence model., Competing Interests: Author DH was employed by Das Gesundheitshaus GmbH. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Schranz, Halmich, Mayr and Heib.)

Background: Stroke is a major cause of disability worldwide. Upper limb impairment is prevalent after stroke. One of the post-stroke manifestations is impaired grip force directional control contributing to diminished abilities to grip and manipulate objects necessary for activities of daily living. The objective of this study was to investigate the neural origin of the impaired grip force direction control following stroke. Due to the importance of online adjustment of motor output based on sensory feedback, it was hypothesized that grip force direction control would be associated with cortical sensorimotor integration in stroke survivors., Methods: Ten chronic stroke survivors participated in this study. Cortical sensorimotor integration was quantified by short latency afferent inhibition (SAI), which represents the responsiveness of the primary motor cortex to somatosensory input. Grip force direction control was assessed during paretic grip., Results: Grip force direction control was significantly associated with SAI. This relationship was independent of sensory impairment level., Conclusions: Cortical sensorimotor integration may play a significant role in the grip force direction control important for gripping and manipulating objects with the affected hand following stroke. This knowledge may be used to inform personalized rehabilitation treatment. For example, for patients with impaired grip force direction control, behavioral therapy focusing on feedback motor control, augmented by use of brain stimulation to reinforce cortical sensorimotor integration such as paired associative stimulation, may be applied.

Brain-computer interfaces (BCIs) have emerged as a promising technology for enhancing communication between the human brain and external devices. Electroencephalography (EEG) is particularly promising in this regard because it has high temporal resolution and can be easily worn on the head in everyday life. However, motion artifacts caused by muscle activity, fasciculation, cable swings, or magnetic induction pose significant challenges in real-world BCI applications. In this paper, we present a systematic review of methods for motion artifact reduction in online BCI experiments. Using the PRISMA filter method, we conducted a comprehensive literature search on PubMed, focusing on open access publications from 1966 to 2022. We evaluated 2,333 publications based on predefined filtering rules to identify existing methods and pipelines for motion artifact reduction in EEG data. We present a lookup table of all papers that passed the defined filters, all used methods, and pipelines and compare their overall performance and suitability for online BCI experiments. We summarize suitable methods, algorithms, and concepts for motion artifact reduction in online BCI applications, highlight potential research gaps, and discuss existing community consensus. This review aims to provide a comprehensive overview of the current state of the field and guide researchers in selecting appropriate methods for motion artifact reduction in online BCI experiments., Competing Interests: MS-T and CS were employed by Salzburg Research GmbH. The remaining author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Schmoigl-Tonis, Schranz and Müller-Putz.)

Background: Integrity of the corticospinal tract (CST) is an important biomarker for upper limb motor function following stroke. However, when structurally compromised, other tracts may become relevant for compensation or recovery of function., Methods: We used the ENIGMA Stroke Recovery data set, a multicenter, retrospective, and cross-sectional collection of patients with upper limb impairment during the chronic phase of stroke to test the relevance of tracts in individuals with less and more severe (laterality index of CST fractional anisotropy ≥0.25) CST damage in an observational study design. White matter integrity was quantified using fractional anisotropy for the CST, the superior longitudinal fascicle, and the callosal fibers interconnecting the primary motor cortices between hemispheres. Optic radiations served as a control tract as they have no a priori relevance for the motor system. Pearson correlation was used for testing correlation with upper limb motor function (Fugl-Meyer upper extremity)., Results: From 1235 available data sets, 166 were selected (by imaging, Fugl-Meyer upper extremity, covariates, stroke location, and stage) for analyses. Only individuals with severe CST damage showed a positive association of fractional anisotropy in both callosal fibers interconnecting the primary motor cortices ( r [21]=0.49; P= 0.025) and superior longitudinal fascicle ( r [21]=0.51; P=0 .018) with Fugl-Meyer upper extremity., Conclusions: Our data support the notion that individuals with more severe damage of the CST depend on residual pathways for achieving better upper limb outcome than those with less affected CST., Competing Interests: Disclosures Dr Hordacre has a clinical partnership with Fourier Intelligence. Dr Conforto is a consultant for Boehringer Ingelheim. Dr Kautz reports grants from US Department of Veterans Affairs and grants from National Institute of General Medical Sciences. Dr Thompson has received research grant support from Biogen, Inc, for research unrelated to this article. Dr Warach is a consultant for Genentech and BrainsGate. The other authors report no conflicts.

Background: Patellofemoral instability influences the gait pattern and activity level in adolescents. However, gait biomechanics to cope with recurrent patella instability and its relation to radiological findings has hardly been studied., Methods: We retrospectively analyzed kinematic and kinetic gait analysis data, magnetic resonance images and X-ray of 32 adolescents with unilateral recurrent patellofemoral instability aged 12 to 18 years. Subjects were assigned to 3 groups based on their sagittal knee moment in the loading response and mid stance phase. Kinematic and kinetic differences among the groups were analyzed using a one-way ANOVA. A multinomial logistic regression model provided a further analysis of the relationship between gait biomechanics and MRI as well as X-ray parameters., Findings: All three groups showed different characteristics of the knee kinematics during loading response and single stance: while the patella-norm-loading group showed a slightly reduced knee flexion (p 〈0,01), the patella-unloading group kept the knee nearly extended (p < 0,01) and patella-overloading group showed an increased knee flexion (p = 0,01) compared to the other groups. In single stance the patella-overloading group maintained increased knee flexion (p < 0,01) compared to patella-unloading group and patella-norm-loading group. None of the radiological parameters proved to be related to gait patterns., Interpretation: The paper describes different gait coping strategies and their clinical relevance in subjects with patellofemoral instability. However, we did not find any relation of gait biomechanics to skeletal morphology., Competing Interests: Declaration of Competing Interest The authors declare no competing interests., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Hand sensorimotor deficits often result from stroke, limiting the ability to perform daily living activities. Sensorimotor deficits are heterogeneous among stroke survivors. Previous work suggests a cause of hand deficits is altered neural connectivity. However, the relationships between neural connectivity and specific aspects of sensorimotor control have seldom been explored. Understanding these relationships is important for developing personalized rehabilitation strategies to improve individual patients' specific sensorimotor deficits and, thus, rehabilitation outcomes. Here, we investigated the hypothesis that specific aspects of sensorimotor control will be associated with distinct neural connectivity in chronic stroke survivors. Twelve chronic stroke survivors performed a paretic hand grip-and-relax task while EEG was collected. Four aspects of hand sensorimotor grip control were extracted, including reaction time, relaxation time, force magnitude control, and force direction control. EEG source connectivity in the bilateral sensorimotor regions was calculated in α and β frequency bands during grip preparation and execution. Each of the four hand grip measures was significantly associated with a distinct connectivity measure. These results support further investigations into functional neural connectivity signatures that explain various aspects of sensorimotor control, to assist the development of personalized rehabilitation that targets the specific brain networks responsible for the individuals' distinct sensorimotor deficits.

Knowledge regarding the neural origins of distinct upper extremity impairments may guide the choice of interventions to target neural structures responsible for specific impairments. This cross-sectional pilot study investigated whether different brain networks explain distinct aspects of hand grip performance in stroke survivors. In 22 chronic stroke survivors, hand grip performance was characterized as grip strength, reaction, relaxation times, and control of grip force magnitude and direction. In addition, their brain structural connectomes were constructed from diffusion tensor MRI. Prominent networks were identified based on a two-step factor analysis using the number of streamlines among brain regions relevant to sensorimotor function. We used regression models to estimate the predictive value of sensorimotor network connectivity for hand grip performance measures while controlling for stroke lesion volumes. Each hand grip performance measure correlated with the connectivity of distinct brain sensorimotor networks. These results suggest that different brain networks may be responsible for different aspects of hand grip performance, which leads to varying clinical presentations of upper extremity impairment following stroke. Understanding the brain network correlates for different hand grip performances may facilitate the development of personalized rehabilitation interventions to directly target the responsible brain network for specific impairments in individual patients, thus improving outcomes., (© 2023 The Authors. Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.)

This study investigated the effect of using subthreshold vibration as a peripheral sensory stimulation during therapy on cortical activity. Secondary analysis of a pilot triple-blinded randomized controlled trial. Twelve chronic stroke survivors underwent 2-week upper-extremity task-practice therapy. Half received subthreshold vibratory stimulation on their paretic wrist (treatment group) and the other half did not (control). EEG connectivity and event-related de-/resynchronization for the sensorimotor network during hand grip were examined at pre-intervention, post-intervention and follow-up. Statistically significant group by time interactions were observed for both connectivity and event-related spectral perturbation. For the treatment group, connectivity increased at post-intervention and decreased at follow-up. Event-related desynchronization decreased and event-related resynchronization increased at post-intervention, which was maintained at follow-up. The control group had the opposite trend for connectivity and no change in event-related spectral perturbation. The stimulation altered cortical sensorimotor activity. The findings complement the clinical results of the trial in which the treatment group significantly improved gross manual dexterity while the control group did not. Increased connectivity in the treatment group may indicate neuroplasticity for motor learning, while reduced event-related desynchronization and increased event-related resynchronization may indicate lessened effort for grip and improved inhibitory control. EEG may improve understanding of neural processes underlying motor recovery., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Guarantors of Brain.)

Background: Functional task performance requires proper control of both movement and force generation in three-dimensional space, especially for the hand. Control of force in three dimensions, however, is not explicitly treated in current physical rehabilitation. To address this gap in treatment, we have developed a tool to provide visual feedback on three-dimensional finger force. Our objective is to examine the effectiveness of training with this tool to restore hand function in stroke survivors., Methods: Double-blind randomized controlled trial. All participants undergo 18 1-h training sessions to practice generating volitional finger force of various target directions and magnitudes. The experimental group receives feedback on both force direction and magnitude, while the control group receives feedback on force magnitude only. The primary outcome is hand function as measured by the Action Research Arm Test. Other outcomes include the Box and Block Test, Stroke Impact Scale, ability to direct finger force, muscle activation pattern, and qualitative interviews., Discussion: The protocol for this clinical trial is described in detail. The results of this study will reveal whether explicit training of finger force direction in stroke survivors leads to improved motor control of the hand. This study will also improve the understanding of neuromuscular mechanisms underlying the recovery of hand function., Trial Registration: ClinicalTrials.gov NCT03995069 . Registered on June 21, 2019., (© 2022. The Author(s).)

Background: Post-stroke hand impairment is prevalent and persistent even after a full course of rehabilitation. Hand diminishes stroke survivors' abilities for activities of daily living and independence. One way to improve treatment efficacy is to augment therapy with peripheral sensory stimulation. Recently, a novel sensory stimulation, TheraBracelet, has been developed in which imperceptible vibration is applied during task practice through a wrist-worn device. The objective of this trial is to determine if combining TheraBracelet with hand task practice is superior to hand task practice alone., Methods: A double-blind randomized controlled trial will be used. Chronic stroke survivors will undergo a standardized hand task practice therapy program (3 days/week for 6 weeks) while wearing a device on the paretic wrist. The device will deliver TheraBracelet vibration for the treatment group and no vibration for the control group. The primary outcome is hand function measured by the Wolf Motor Function Test. Other outcomes include the Box and Block Test, Action Research Arm Test, upper extremity use in daily living, biomechanical measure of the sensorimotor grip control, and EEG-based neural communication., Discussion: This research will determine clinical utility of TheraBracelet to guide future translation. The TheraBracelet stimulation is delivered via a wrist-worn device, does not interfere with hand motion, and can be easily integrated into clinical practice. Enhancing hand function should substantially increase stroke survivors' independence and quality of life and reduce caregiver burden., Trial Registration: NCT04569123 . Registered on September 29, 2020., (© 2022. The Author(s).)

Background: Uncertain prognosis presents a challenge for therapists in determining the most efficient course of rehabilitation treatment for individual patients. Cortical Sensorimotor network connectivity may have prognostic utility for upper extremity motor improvement because the integrity of the communication within the sensorimotor network forms the basis for neuroplasticity and recovery., Objective: To investigate if pre-intervention sensorimotor connectivity predicts post-stroke upper extremity motor improvement following therapy., Methods: Secondary analysis of a pilot triple-blind randomized controlled trial. Twelve chronic stroke survivors underwent 2-week task-practice therapy, while receiving vibratory stimulation for the treatment group and no stimulation for the control group. EEG connectivity was obtained pre-intervention. Motor improvement was quantified as change in the Box and Block Test from pre to post-therapy. The association between ipsilesional sensorimotor connectivity and motor improvement was examined using regression, controlling for group. For negative control, contralesional/interhemispheric connectivity and conventional predictors (initial clinical motor score, age, time post-stroke, lesion volume) were examined., Results: Greater ipsilesional sensorimotor alpha connectivity was associated with greater upper extremity motor improvement following therapy for both groups (p < 0.05). Other factors were not significant., Conclusion: EEG connectivity may have a prognostic utility for individual patients' upper extremity motor improvement following therapy in chronic stroke.

Background: Personalizing mechanical ventilation requires the development of reliable bedside monitoring techniques. The multiple-breaths nitrogen washin-washout (MBNW) technique is currently available to measure end-expiratory lung volume (EELV MBNW ), but the precision of the technique may be poor, with percentage errors ranging from 28 to 57%. The primary aim of the study was to evaluate the reliability of a novel MBNW bedside system using fast mainstream sensors to assess EELV in an experimental acute respiratory distress syndrome (ARDS) model, using computed tomography (CT) as the gold standard. The secondary aims of the study were: (1) to evaluate trending ability of the novel system to assess EELV; (2) to evaluate the reliability of estimated alveolar recruitment induced by positive end-expiratory pressure (PEEP) changes computed from EELV MBNW , using CT as the gold standard., Results: Seven pigs were studied in 6 experimental conditions: at baseline, after experimental ARDS and during a decremental PEEP trial at PEEP 16, 12, 6 and 2 cmH 2 O. EELV was computed at each PEEP step by both the MBNW technique (EELV MBNW ) and CT (EELV CT ). Repeatability was assessed by performing replicate measurements. Alveolar recruitment between two consecutive PEEP levels after lung injury was measured with CT (Vrec CT ), and computed from EELV measurements (Vrec MBNW ) as ΔEELV minus the product of ΔPEEP by static compliance. EELV MBNW and EELV CT were significantly correlated (R 2  = 0.97). An acceptable non-constant bias between methods was identified, slightly decreasing toward more negative values as EELV increased. The conversion equation between EELV MBNW and EELV CT was: EELV MBNW  = 0.92 × EELV CT  + 36. The 95% prediction interval of the bias amounted to ± 86 mL and the percentage error between both methods amounted to 13.7%. The median least significant change between repeated measurements amounted to 8% [CI 95% : 4-10%]. EELV MBNW adequately tracked EELV CT changes over time (concordance rate amounting to 100% [CI 95% : 87%-100%] and angular bias amounting to - 2° ± 10°). Vrec MBNW and Vrec CT were significantly correlated (R 2  = 0.92). A non-constant bias between methods was identified, slightly increasing toward more positive values as Vrec increased., Conclusions: We report a new bedside MBNW technique that reliably assesses EELV in an experimental ARDS model with high precision and excellent trending ability., (© 2021. The Author(s).)

Background: Patellar instability is a considerable problem that leads to pain and anxiety during simple functional tasks. Femoral derotational osteotomy has become a common surgical procedure to improve patella mechanics, stability and loading. However, it remains unclear if static (MRI measured) femoral anteversion is sufficient to capture the dynamic femoral rotation during walking and represents a good indication for the surgical procedure. This research investigates the relationship between static femoral anteversion and internally rotated gait in adolescents with patellofemoral instability., Methods: This retrospective study included 30 adolescents with recurrent patella instability (minimum three patella dislocations) aged 12 to 18 years (28 female/2 male; 22 unilateral/8 bilateral). All participants were assessed with 3D gait analysis and the femoral anteversion was examined using a rotational MRI. Multiple kinematic parameter were correlated with the ipsilateral femoral anteversion and tibia torsion using the Pearson coefficient., Findings: The correlation between parameters of dynamic hip rotation (e.g. maximum and mean internal hip rotation in stance and swing) and MRI measured femoral anteversion (mean 26.5° ± 9°) was weak and did not reach statistical significance. We found 47% (14 out of 30) subjects with increased femoral anteversion but normal hip rotation in stance., Interpretation: There was no relationship between increased femoral anteversion and dynamic hip rotation. Consequently, femoral anteversion should not be used as the only indication for femoral derotational osteotomy. Three-dimensional gait analysis might be necessary to assess the appropriate surgical intervention in adolescents with patello femoral instability., (Copyright © 2021. Published by Elsevier Ltd.)

Background: Cerebral palsy (CP) is the most common motor and movement disability in childhood. The mechano-morphological alterations of the spastic muscle itself as well as the functional limitations in CP are well documented. However, the relationship between muscle tendon properties and functional tests in CP remains unknown., Research Question: The aim of this study was to explore the relationship between spastic muscle mechano-morphological properties and functional performance in children with CP., Methods: This study included retrospective data from 22 children with spastic cerebral palsy with a mean age of 12.8 years (19 GMFCS I/3 GMFC II, 15 male/7 female, 8 unilateral involved/14 bilateral). Mechano-morphological properties of gastrocnemius (GM) and Achilles tendon (AT) were correlated with a variety of functional measures, maximal isometric strength, the Muscle Power Sprint test (MPST), 6-minute walk test (6MWT) and 3D-gait analysis using the Pearson Coefficient., Results: Muscle-tendon properties were normalized to remove anthropometric dimensions because of strong associations with anthropometric data. Higher isometric muscle strength was related to longer normalized GM fascicle lengths (r = 0.67, p < 0.01). The distance reached in the 6MWT positively correlated with normalized GM fascicle lengths (r = 0.61, p < 0.01). Higher AT stiffness was associated with faster performance in the MPST (r = 0.77, p < 0.01). Finally, there was an association between ankle power and both longer normalized AT length and shorter muscle belly (r = 0.60 and r = 0.54, p < 0.01)., Significance: The findings of this study give more insight into the function specific adaptations of a spastic muscle-tendon unit. While walking, assessed through the 6MWT, was related to normalized gastrocnemius fascicle length, sprint performance was associated with an increased AT stiffness. These results provide a better understanding of the relationship between functional tasks and spastic muscle-tendon properties, which offers potential for improved and targeted interventions in CP., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Purpose: The purpose of this study was to investigate the effects of functional progressive resistance training (PRT) and high-intensity circuit training (HICT) on the mechano-morphological properties of the plantar flexor muscle-tendon unit in children with spastic cerebral palsy., Methods: Twenty-two children (12.8 [2.6] y old, Gross Motor Function Classification System levels I/II = 19/3) were randomly assigned to either a PRT group or an HICT group. The interventions consisted of functional lower limb exercises, which were performed at home 3 times per week for 8 weeks. Measurements at baseline, preintervention, postintervention, and follow-up were taken to assess ankle joint range of motion and the properties of the gastrocnemius medialis, vastus lateralis, rectus femoris, and Achilles tendon (eg, thickness, strength, stiffness)., Results: Despite a nonsignificant increase in active torque in the HICT group, neither gastrocnemius medialis morphology nor Achilles tendon properties were significantly altered after the interventions. Vastus lateralis thickness increased following PRT only., Conclusions: Functional home-based strength training did not lead to significant changes at the muscular level in children with cerebral palsy. We therefore assume that a more specific stimulus of higher intensity combined with a longer training duration might be necessary to evoke changes in muscles and tendons in individuals with cerebral palsy.

Objective: Does home-based progressive resistance or high-intensity circuit training improve strength, function, activity, or participation in children with cerebral palsy (CP)?, Design: This was the first study on high-intensity circuit training for children with CP. This study was conducted as a randomized prospective controlled pilot study., Setting: Evaluation took place at the gait laboratory of the university hospital, training sessions were performed at home., Participants: Children (N=22) with CP (average age: 12y, 10mo, 19 Gross Motor Function Classification System level I, 3 level II) were randomly assigned either to progressive resistance training (PRT) or high-intensity circuit training (HICT)., Interventions: The PRT group trained with progressive overload, while the HICT group performed as many repetitions as possible within 30-second intervals (8wk, 3 times weekly in both groups)., Main Outcome Measures: Outcome measures stretched over all domains of the International Classification of Functioning, Disability and Health and included muscle strength, muscle power sprint test (MPST), timed stairs test (TST), 6-minute walking test, Gait Profile Score (GPS), timed Up and Go test (TUGT) and participation questionnaires., Results: Only the HICT group was able to improve strength. Furthermore, the HICT group scored better in the MPST, while PRT participants improved in the TST and TUGT. The HICT-group was able to show improvement in the subscores of the parent-reported participation questionnaire. Other measures of mobility or participation did not change., Conclusions: Both programs improved function specific to intervention. However, only the HICT group showed significant strength and participation improvements. Compliance was decent in both groups, but the average training unit was shorter in the HICT group. Both exercise programs showed functional benefits, but HICT might be the preferable option for strengthening in highly functional children with CP., (Copyright © 2018 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.)

Following publication of the original article [1], the author requested for an acknowledgement to retrospectively be added to the 'Acknowledgements' section of the article [1].

Background: Early detection of changes at the muscular level before a contracture develops is important to gain knowledge about the development of deformities in individuals with spasticity. However, little information is available about muscle morphology in children with spastic diplegic cerebral palsy (CP) without contracture or equinus gait. Therefore, the aim of this study was to compare the gastrocnemius medialis (GM) and Achilles tendon architecture of children and adolescents with spastic CP without contracture or equinus gait to that of typically developing (TD) children., Methods: Two-dimensional ultrasonography was used to assess the morphological properties of the GM muscle and Achilles tendon in 10 children with spastic diplegic CP (Gross Motor Function Classification System level I-II) and 12 TD children (mean age 12.0 (2.8) and 11.3 (2.5) years, respectively). The children with CP were not restricted in the performance of daily tasks, and therefore had a high functional capacity. Mean muscle and tendon parameters were statistically compared (independent t-tests or Mann-Whitney U-tests)., Results: When normalized to lower leg length, muscle-tendon unit length and GM muscle belly length were found to be significantly shorter (p < 0.05, effect size (ES) = 1.00 and 0.98, respectively) in the children with spastic CP. Furthermore, there was a tendency for increased Achilles tendon length when expressed as a percentage of muscle-tendon unit length (p = 0.08, ES = - 0.80) in the individuals with CP. This group also showed shorter muscle fascicles (3.4 cm vs. 4.4 cm, p < 0.01, ES = 1.12) and increased fascicle pennation angle (21.9° vs. 18.1°, p < 0.01, ES = - 1.36, respectively). However, muscle thickness and Achilles tendon cross-sectional area did not differ between groups. Resting ankle joint angle was significantly more plantar flexed (- 26.2° vs. - 20.8°, p < 0.05, ES = 1.06) in the children with CP., Conclusions: Morphological alterations of the plantar flexor muscle-tendon unit are also present in children and adolescents with mild forms of spastic CP. These alterations may contribute to functional deficits such as muscle weakness, and therefore have to be considered in the clinical decision-making process, as well as in the selection of therapeutic interventions.

Background: Recent ultrasound studies found increased passive muscle stiffness and no difference in tendon stiffness in highly impaired children and young adults with cerebral palsy. However, it is not known if muscle and tendon mechanical properties are already altered in highly functional children with cerebral palsy. Therefore, the purpose of this study was to compare the mechanical and material properties of the plantar flexors in highly functional children with cerebral palsy and typically developing children., Methods: Besides strength measurements, ultrasonography was used to assess gastrocnemius medialis and Achilles tendon elongation and stiffness, Achilles tendon stress, strain, and Young's modulus in twelve children with cerebral palsy (GMFCS levels I and II) and twelve typically developing peers during passive dorsiflexion rotations as well as maximum voluntary contractions., Findings: Despite no difference in ankle joint stiffness (P>0.05) between groups, passive but not active Achilles tendon stiffness was significantly decreased (-39%) and a tendency of increased passive muscle stiffness was observed even in highly functional children with cerebral palsy. However, material properties of the tendon were not altered. Maximum voluntary contraction showed reduced plantar flexor strength (-48%) in the cerebral palsy group., Interpretation: Even in children with mild spastic cerebral palsy, muscle and tendon mechanical properties are altered. However, it appears that the Achilles tendon stiffness is different only when low forces act on the tendon during passive movements. Although maximum voluntary force is already decreased, forces acting on the Achilles tendon during activity appear to be sufficient to maintain typical material properties., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background: For mechanically ventilated patients with acute respiratory distress syndrome (ARDS), suboptimal PEEP levels can cause ventilator induced lung injury (VILI). In particular, high PEEP and high peak inspiratory pressures (PIP) can cause over distension of alveoli that is associated with VILI. However, PEEP must also be sufficient to maintain recruitment in ARDS lungs. A lung model that accurately and precisely predicts the outcome of an increase in PEEP may allow dangerous high PIP to be avoided, and reduce the incidence of VILI., Methods and Results: Sixteen pressure-flow data sets were collected from nine mechanically ventilated ARDs patients that underwent one or more recruitment manoeuvres. A nonlinear autoregressive (NARX) model was identified on one or more adjacent PEEP steps, and extrapolated to predict PIP at 2, 4, and 6 cmH 2 O PEEP horizons. The analysis considered whether the predicted and measured PIP exceeded a threshold of 40 cmH 2 O. A direct comparison of the method was made using the first order model of pulmonary mechanics (FOM(I)). Additionally, a further, more clinically appropriate method for the FOM was tested, in which the FOM was trained on a single PEEP prior to prediction (FOM(II)). The NARX model exhibited very high sensitivity (> 0.96) in all cases, and a high specificity (> 0.88). While both FOM methods had a high specificity (> 0.96), the sensitivity was much lower, with a mean of 0.68 for FOM(I), and 0.82 for FOM(II)., Conclusions: Clinically, false negatives are more harmful than false positives, as a high PIP may result in distension and VILI. Thus, the NARX model may be more effective than the FOM in allowing clinicians to reduce the risk of applying a PEEP that results in dangerously high airway pressures.

Single event multilevel surgery (SEMLS) has become a standard intervention for children with cerebral palsy (CP). SEMLS proved to improve the gait in bilateral spastic cerebral palsy and those improvements can be maintained in the long term. However there is no evidence on the long-term outcome of unilateral SEMLS in children with unilateral spastic cerebral palsy. The gait analyses and clinical data of 14 children (9 male/5 female, mean age 12.1) with unilateral CP (6 children Gross Motor Function Classification System Scale level I and 8 children level II) were retrospectively reviewed at four time-points: preoperatively, 1year, 3-5 years and approximately 10 years after unilateral SEMLS. The Gait Profile Score (GPS) of the affected leg was used as a main and the number of fine tuning procedures as well as complications rate (Clavien-Dindo classification) as secondary outcome measures. The gait improved postoperatively and the GPS of the affected leg significantly declined by 3.73° which is well above the minimal clinical important difference of 1.6°. No deterioration of GPS occurred throughout the follow-up period. Therefore the postoperative improvement was maintained long-term. However, additional fine-tuning procedures had to be performed during the follow-up in 5 children and three complications occurred (one level II and two level III). The results indicate that children with unilateral cerebral palsy benefit from unilateral SEMLS and maintain gait improvements long-term., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Background: The non-interventional study CONIFER was designed to assess the safety and clinical practicability of deferasirox for the treatment of transfusional iron overload in myelodysplastic syndrome (MDS) patients., Methods: Patients included in the study were diagnosed with MDS and received at least 1 treatment with deferasirox. The observation period covered the time from the initial visit until the last follow-up., Results: The data of 99 patients with MDS scored mainly as International Prognostic Scoring System (IPSS) low and intermediate 1 were evaluated. The mean age of the participants was 75 years and 58% of the patients were male. Iron overload was assessed by serum ferritin level (mean baseline serum ferritin 2,080 ± 1,244 µg/l). Patients were treated for a mean duration of 16 months (mean daily dose at baseline 11.8 ± 7.0 mg/kg). Stratification of serum ferritin levels by deferasirox dose showed a reduction at the higher but no reduction at the lower dose (< 15 mg/kg vs. ≥ 15 mg/kg and < 20 mg/kg vs. ≥ 20 mg/kg). The majority of patients (81%) were affected by at least 1 adverse event, with decreased renal creatinine clearance being the most frequent., Conclusion: Higher doses (≥ 15 mg/kg) of deferasirox effectively and safely reduced serum ferritin levels in MDS patients with transfusional iron overload., (© 2016 S. Karger GmbH, Freiburg.)

Background: Angioedema is an infrequent complication of the use of angiotensin-converting enzyme inhibitors (ACEi) that has an incidence of up to 0.5%. The oropharynx is most commonly affected. Angioedema of the small bowel is a much rarer occurrence; it uniformly presents with abdominal pain of variable duration., Case Report: A 51-year-old man presented to the emergency department (ED) with generalized abdominal pain, emesis, diarrhea, and bloating. Medical history was significant for hypertension and medications included captopril, metoprolol and aspirin. Vital signs and laboratory tests were unremarkable. Due to the presence of significant abdominal tenderness with guarding on examination, a FAST (focused assessment with ultrasound in trauma) examination was performed and revealed free fluid in the abdomen. A computed tomography scan of the abdomen was quickly obtained, which revealed a large amount of simple-appearing free fluid within the abdomen and mucosal edema throughout the small bowel. The patient underwent an emergent diagnostic laparoscopy and was ultimately diagnosed with angioedema of the small bowel, deemed secondary to captopril usage. Captopril was discontinued and symptoms gradually resolved with supportive care. When imaging is obtained in cases such as this one, small bowel submucosal edema and ascites are often present. Supportive care and cessation of ACEi usage are the cornerstones of treatment. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: In patients on ACEi, it is important to keep this diagnosis in mind to potentially avoid an unneeded surgical intervention, as the condition is self-limiting and can be treated primarily with supportive measures., (Published by Elsevier Inc.)

This manuscript presents the concerns around the increasingly common problem of not having readily available or useful "gold standard" measurements. This issue is particularly important in critical care where many measurements used in decision making are surrogates of what we would truly wish to use. However, the question is broad, important and applicable in many other areas.In particular, a gold standard measurement often exists, but is not clinically (or ethically in some cases) feasible. The question is how does one even begin to develop new measurements or surrogates if one has no gold standard to compare with?We raise this issue concisely with a specific example from mechanical ventilation, a core bread and butter therapy in critical care that is also a leading cause of length of stay and cost of care. Our proposed solution centers around a hierarchical validation approach that we believe would ameliorate ethics issues around radiation exposure that make current gold standard measures clinically infeasible, and thus provide a pathway to create a (new) gold standard.

Accurate model parameter identification relies on accurate forward model simulations to guide convergence. However, some forward simulation methodologies lack the precision required to properly define the local objective surface and can cause failed parameter identification. The role of objective surface smoothness in identification of a pulmonary mechanics model was assessed using forward simulation from a novel error-stepping method and a proprietary Runge-Kutta method. The objective surfaces were compared via the identified parameter discrepancy generated in a Monte Carlo simulation and the local smoothness of the objective surfaces they generate. The error-stepping method generated significantly smoother error surfaces in each of the cases tested (p<0.0001) and more accurate model parameter estimates than the Runge-Kutta method in three of the four cases tested (p<0.0001) despite a 75% reduction in computational cost. Of note, parameter discrepancy in most cases was limited to a particular oblique plane, indicating a non-intuitive multi-parameter trade-off was occurring. The error-stepping method consistently improved or equalled the outcomes of the Runge-Kutta time-integration method for forward simulations of the pulmonary mechanics model. This study indicates that accurate parameter identification relies on accurate definition of the local objective function, and that parameter trade-off can occur on oblique planes resulting prematurely halted parameter convergence., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

A 22-year-old morbidly obese, nonpregnant woman presented with left ileofemoral deep vein thrombosis (DVT) presenting as low back pain and bilateral, left greater than right, leg swelling and pain for 2 days. While on heparin, she developed compartment syndrome in her left leg and had evidence of dead muscle tissue at the time of fasciotomy. Three options exist for treatment of ileofemoral DVT: catheter-directed thrombolysis (CDT), CDT plus pharmacomechanical thrombolysis or percutaneous mechanical thrombectomy, and surgical thrombectomy. Catheter-directed thrombolysis alone or in conjunction with pharmacomechanical thrombolysis in patients with low risk of bleeding has shown significant lysis of occlusion in 79% of patients with ileofemoral DVT with relatively low complication rates. Surgical thrombectomy and fasciotomy have not proven to be as effective but are appropriate alternatives if CDT is not available. Standard anticoagulation alone is likely not a sufficient treatment for ileofemoral DVT. Other therapies including CDT, CDT plus pharmacomechanical thrombolysis or percutaneous mechanical thrombectomy, or surgical thrombectomy to address lysis of the clot should be attempted first or in conjunction with anticoagulation for appropriate patients. Catheter-directed thrombolysis with or without pharmacomechanical thrombolysis is the preferred initial treatment.

Patient-specific mathematical models of respiratory mechanics enable substantial insight into patient state and pulmonary dynamics that are not directly measurable. Thus they offer potential e.g. to predict the outcome of ventilator settings for Acute Respiratory Distress Syndrome (ARDS) patients. In this work, an existing static recruitment model is extended by viscoelastic components allowing model simulations in various ventilation scenarios. A hierarchical approach is used to identify the model with measured data of 12 ARDS patients under static and dynamic conditions. Identified parameter values were physiologically plausible and reproduced the measured pressure responses with a median Coefficient of Determination (CD) of 0.972 in the dynamic and 0.992 in the static maneuver. Overall, the model presented incorporates physiological mechanisms, captures ARDS dynamics and viscoelastic tissue properties and is valid under various ventilation patterns.

Patient-specific mathematical models of respiratory mechanics can offer substantial insight into patient state and pulmonary dynamics that are not directly measurable. Thus, they offer significant potential to evaluate and guide patient-specific lung protective ventilator strategies for acute respiratory distress syndrome (ARDS) patients. To assure bedside applicability, the model must be computationally efficient and identifiable from the limited available data, while also capturing dominant dynamics and trends observed in ARDS patients. In this study, an existing static recruitment model is enhanced by considering alveolar distension and implemented in a novel time-continuous dynamic respiratory mechanics model. The model was tested for structural identifiability and a hierarchical gradient descent approach was used to fit the model to low-flow test responses of 12 ARDS patients. Finally, a comprehensive practical identifiability analysis was performed to evaluate the impact of data quality on the model parameters. Identified parameter values were physiologically plausible and very accurately reproduced the measured pressure responses. Structural identifiability of the model was proven, but practical identifiability analysis of the results showed a lack of convexity on the error surface indicating that successful parameter identification is currently not assured in all test sets. Overall, the model presented is physiologically and clinically relevant, captures ARDS dynamics, and uses clinically descriptive parameters. The patient-specific models show the ability to capture pulmonary dynamics directly relevant to patient condition and clinical guidance. These characteristics currently cannot be directly measured or established without such a validated model.

Background: Mechanical ventilation (MV) is the primary form of support for acute respiratory distress syndrome (ARDS) patients. However, intra- and inter- patient-variability reduce the efficacy of general protocols. Model-based approaches to guide MV can be patient-specific. A physiological relevant minimal model and its patient-specific performance are tested to see if it meets this objective above., Methods: Healthy anesthetized piglets weighing 24.0 kg [IQR: 21.0-29.6] underwent a step-wise PEEP increase manoeuvre from 5cmH2O to 20cmH2O. They were ventilated under volume control using Engström Care Station (Datex, General Electric, Finland), with pressure, flow and volume profiles recorded. ARDS was then induced using oleic acid. The data were analyzed with a Minimal Model that identifies patient-specific mean threshold opening and closing pressure (TOP and TCP), and standard deviation (SD) of these TOP and TCP distributions. The trial and use of data were approved by the Ethics Committee of the Medical Faculty of the University of Liege, Belgium., Results and Discussions: 3 of the 9 healthy piglets developed ARDS, and these data sets were included in this study. Model fitting error during inflation and deflation, in healthy or ARDS state is less than 5.0% across all subjects, indicating that the model captures the fundamental lung mechanics during PEEP increase. Mean TOP was 42.4cmH2O [IQR: 38.2-44.6] at PEEP = 5cmH2O and decreased with PEEP to 25.0cmH2O [IQR: 21.5-27.1] at PEEP = 20cmH2O. In contrast, TCP sees a reverse trend, increasing from 10.2cmH2O [IQR: 9.0-10.4] to 19.5cmH2O [IQR: 19.0-19.7]. Mean TOP increased from average 21.2-37.4cmH2O to 30.4-55.2cmH2O between healthy and ARDS subjects, reflecting the higher pressure required to recruit collapsed alveoli. Mean TCP was effectively unchanged., Conclusion: The minimal model is capable of capturing physiologically relevant TOP, TCP and SD of both healthy and ARDS lungs. The model is able to track disease progression and the response to treatment.

Background: Patient-specific respiratory mechanics models can support the evaluation of optimal lung protective ventilator settings during ventilation therapy. Clinical application requires that the individual's model parameter values must be identified with information available at the bedside. Multiple linear regression or gradient-based parameter identification methods are highly sensitive to noise and initial parameter estimates. Thus, they are difficult to apply at the bedside to support therapeutic decisions., Methods: An iterative integral parameter identification method is applied to a second order respiratory mechanics model. The method is compared to the commonly used regression methods and error-mapping approaches using simulated and clinical data. The clinical potential of the method was evaluated on data from 13 Acute Respiratory Distress Syndrome (ARDS) patients., Results: The iterative integral method converged to error minima 350 times faster than the Simplex Search Method using simulation data sets and 50 times faster using clinical data sets. Established regression methods reported erroneous results due to sensitivity to noise. In contrast, the iterative integral method was effective independent of initial parameter estimations, and converged successfully in each case tested., Conclusion: These investigations reveal that the iterative integral method is beneficial with respect to computing time, operator independence and robustness, and thus applicable at the bedside for this clinical application.

The application of respiratory mechanics models combined with standardized ventilation maneuvers enable investigations of patients' lung mechanics at the bedside in order to optimize ventilation therapy. Therefore, the underlying dynamic effects of respiratory mechanics (viscoelasticity, inhomogeneity and recruitment) are uncovered by applying various ventilation maneuvers and subsequently captured by the corresponding model via parameter identification methods. Data sets of patients undergoing quasi-static and dynamic ventilation patterns are available along with a hierarchical model structure for parameter identification and simulation purposes. The applicability of the basic 1(st) order model (FOM) of respiratory mechanics for various flow rates proved to be critical and patient dependent, since distinctive time-depending effects could not be considered. To improve this, a 2(nd) order model (SOM), individualized using data of a SCASS maneuver (Static Compliance Automated Single Step), enables successful simulations of respiratory mechanics in dynamic and quasi-static conditions. Pressure dependent effects such as static recruitment, can be captured by Hickling's nonlinear compliance model. This research illustrates the applicability of various models of respiratory mechanics within the model hierarchy in various circumstances and the ability to distinguish between dynamic and static effects.

Background and Purpose: We sought to investigate the feasibility of the combined use of low-dose recombinant tissue plasminogen activator (rtPA) and tirofiban, a glycoprotein IIb/IIIa (GPIIb/IIIa) receptor antagonist, for systemic thrombolysis in acute stroke., Methods: Consecutive patients who were treated with systemic application of low-dose rtPA and body weight-adjusted tirofiban (rtPA+T group; n=37) were evaluated retrospectively during 1999-2001. Patients in the rtPA+T group were compared with a group of patients treated with a dose of 0.9 mg/kg body weight in a different center (rtPA group; n=119). The 41 patients with infarctions of the middle cerebral artery territory who were not eligible for thrombolytic treatment because of medical contraindications or arrival in the hospital >3 hours after stroke onset served as controls. For matched comparisons, the National Institutes of Health Stroke Scale on admission and the Rankin Scale on discharge 5 days after stroke were used., Results: The patients treated with rtPA+T or rtPA improved (P<0.05) compared with the controls at discharge; patients in the rtPA+T and rtPA groups reached a Rankin Scale score of 0 to 2 in 63% and 55%, respectively, while only 16% of the controls achieved this score. Death rates (8% in rtPA+T group and 5% in rtPA group) were similar among the 2 treatment groups. They included 1 fatal hemorrhage in the rtPA+T group and 4 fatal hemorrhages in the rtPA group. Five percent of the untreated patients developed symptomatic, nonfatal cerebral hemorrhage., Conclusions: Systemic combined thrombolysis with rtPA+T seems to be a feasible treatment in acute stroke.

Eosinophils are potent inflammatory cells involved in allergic reactions. Inhibition of apoptosis of purified eosinophils by certain cytokines has been previously shown to be an important mechanism causing tissue eosinophilia. To elucidate the role of Bcl-2 family members in the inhibition of eosinophil apoptosis, we examined the expression of the known anti-apoptotic genes Bcl-2, Bcl-xL, and A1, as well as Bax and Bcl-xS, which promote apoptosis in other systems. We show herein that freshly isolated human eosinophils express significant amounts of Bcl-xL and Bax, but only little or no Bcl-2, Bcl-xS, or A1. As assessed by reverse transcription-polymerase chain reaction, immunoblotting, flow cytometry, and immunocytochemistry, we show that spontaneous eosinophil apoptosis is associated with a decrease in Bcl-xL mRNA and protein levels. In contrast, stimulation of the cells with granulocyte-macrophage colony-stimulating factor (GM-CSF) or interleukin-5 (IL-5) results in maintenance or upregulation of Bcl-xL mRNA and protein levels. Moreover, Bcl-2 protein is not induced by GM-CSF or IL-5 in purified eosinophils. Bcl-2 protein is also not expressed in tissue eosinophils as assessed by immunohistochemistry using two different eosinophilic tissue models. Furthermore, Bcl-xL antisense but not scrambled phosphorothioate oligodeoxynucleotides can partially block the cytokine-mediated rescue of apoptotic death in these cells. These data suggest that Bcl-xL acts as an anti-apoptotic molecule in eosinophils., (Copyright 1998 by The American Society of Hematology.)

Because glutathione (GSH) in plasma and lymphocytes of HIV-infected patients is low, adjunct therapy with N-acetylcysteine (NAC) to restore GSH homeostasis has been proposed. To investigate the effect of NAC on the GSH status we treated six patients with AIDS with 1.8 g/day of NAC for 2 weeks. During treatment the plasma concentration of cysteine, a precursor for GSH synthesis, increased significantly. Nevertheless, there was no significant increase in GSH in plasma and peripheral blood mononuclear cells. The failure of sulfhydryl supplementation to increase GSH suggests that the low concentrations of the tripeptide are not the result of an increased consumption secondary to an oxidant stress, but rather the consequence of a decreased rate of synthesis of GSH in HIV infection.

Glutathione (GSH) plays an important role in the detoxification of reactive metabolites of oxygen and xenobiotics and as a source of cysteine. Since several clinical situations characterized by low circulating and intracellular GSH have been identified, there is a growing interest in pharmacological interventions to correct a deranged sulfhydril status. Therefore, the systemic bioavailability of orally administered GSH and glutathione monoethyl ester (GSHE) was examined in the rat. Following the intraduodenal administration of 0.5 mmol/kg of GSH and GSHE there was no significant increase in the concentrations of cysteine and GSH in plasma, but hepatic cysteine and GSH increased significantly, albeit transiently. Five mmol/kg of GSH and GSHE significantly increased circulating and hepatic cysteine and GSH. Following the administration of 0.5 and 5 mmol/kg of GSHE low concentrations of the ester were found in plasma and the liver, indicating that GSHE is not readily absorbed from the gastrointestinal tract, although it is not a substrate for gamma-glutamyl-transferase. GSHE resulted in a delayed release of cysteine and GSH compared to GSH, such that the concentrations of GSH and cysteine in liver and plasma were significantly higher 2 h after administration of GSHE than after GSH. The data indicate that the bioavailability of GSH and GSHE is low in the rat. Orally administered GSH and GSHE do not affect the circulating concentrations of GSH and cysteine unless very high doses are administered, but increase hepatic cysteine and GSH at lower doses because of the efficient extraction by the liver of cysteine originating from the breakdown of GSH and GSHE in the gut.

In 1987, the Health Care Financing Administration (HCFA) compiled and released mortality information for 1986 Medicare admissions to 5,971 United States hospitals. Full triennial accreditation surveys were conducted by the Joint Commission on Accreditation of Healthcare Organizations in 1,628 of these institutions in 1986. This report examines the relationship between 1986 Medicare mortality rates and hospital quality, as measured by accreditation survey performance. Hospitals with higher-than-expected and lower-than-expected mortality rates were compared on three measures of accreditation survey performance. These comparisons were made for three mortality groups: overall, stroke, and acute heart disease. No statistically significant (p = 0.05) differences were found in survey performance for any of the mortality groups compared. This lack of association between mortality and hospital quality, as measured by accreditation performance, reinforces concern about the use of mortality rates as measures of quality for public policy or patient decision-making purposes.