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Objective To establish the reference standard of the median nerve conduction study (NCS) in Korea. Methods A total of 648 median motor and 602 median sensory NCSs from 349 Korean healthy volunteers were tested and analyzed prospectively. Equipment calibration, assessment of intra- and inter-rater reliability, and the NCSs per se were conducted according to a predetermined protocol. A reference standard was established from uncertainty components for the following parameters: the onset and peak latencies; the baseline-to-peak and peak-to-peak amplitudes; the area and duration of the negative wave; and the nerve conduction velocity. The effects of sex, age and stimulation intensity were analyzed. Results Each measured value of 648 median motor and 602 median sensory nerves were obtained and presented with both mean and expanded uncertainties, as well as mean and standard deviations. The cut-off values with expanded uncertainty were determined for different age and sex groups. After adjusting for anthropometric covariates, all parameters except duration were affected by age, and sex appeared to influence both duration and area. While stimulation intensity significantly affected some parameters including latencies, the effect sizes were negligible. Conclusion We propose the median NCS reference standard using the largest Korean dataset ever available. The use of the traceable and reliable reference standard is anticipated to promote more accurate and dependable diagnosis and appropriate management of median neuropathies in Korea.

Abstract Muscle strength assessments are vital in rehabilitation, orthopedics, and sports medicine. However, current methods used in clinical settings, such as manual muscle testing and hand-held dynamometers, often lack reliability, and isokinetic dynamometers (IKD), while reliable, are not easily portable. The aim of this study was to design and validate a wearable dynamometry system with high accessibility, accuracy, and reliability, and to validate the device. Therefore, we designed a wearable dynamometry system (WDS) equipped with knee joint torque sensors. To validate this WDS, we measured knee extension and flexion strength in 39 healthy adults using both the IKD and WDS. Comparing maximal isometric torque measurements, WDS and IKD showed strong correlation and good reliability for extension (Pearson’s r: 0.900; intraclass correlation coefficient [ICC]: 0.893; standard error of measurement [SEM]: 9.85%; minimal detectable change [MDC]: 27.31%) and flexion (Pearson’s r: 0.870; ICC: 0.857; SEM: 11.93%; MDC: 33.07%). WDS demonstrated excellent inter-rater (Pearson’s r: 0.990; ICC: 0.993; SEM: 4.05%) and test–retest (Pearson’s r: 0.970; ICC: 0.984; SEM: 6.15%) reliability during extension/flexion. User feedback from 35 participants, including healthcare professionals, underscores WDS's positive user experience and clinical potential. The proposed WDS is a suitable alternative to IKD, providing high accuracy, reliability, and potentially greater accessibility.

Background Although stroke is commonly perceived as occurring in older adults, traumatic brain injury, one of the risk factors for stroke, is a leading cause of death in the younger adults. This study evaluated stroke risk in young‐to‐middle‐aged adults based on traumatic brain injury severity and stroke subtypes. Methods and Results For this retrospective, population‐based, cohort study, data of adults aged 18 to 49 years who were diagnosed with traumatic brain injury were obtained from the Korean National Health Insurance Service between 2010 and 2017. Traumatic brain injury history was measured based on the International Classification of Diseases, Tenth Revision (ICD‐10), codes. Posttraumatic brain injury stroke risk was analyzed using a time‐dependent Cox regression model. At baseline, 518423 patients with traumatic brain injury and 518 423 age‐ and sex‐matched controls were included. The stroke incidence rate per 1000 person‐years was 3.82 in patients with traumatic brain injury and 1.61 in controls. Stroke risk was approximately 1.89 times as high in patients with traumatic brain injury (hazard ratio, 1.89 [95% CI, 1.84–1.95]). After excluding stroke cases that occurred within 12 months following traumatic brain injury, these significant associations remained. In the subgroup analysis, patients with brain injury other than concussion had an approximately 9.34‐fold risk of intracerebral hemorrhage than did the controls. Conclusions Stroke prevention should be a priority even in young‐to‐middle‐aged adult patients with traumatic brain injury. Managing stroke risk factors through regular health checkups and modifying health‐related behaviors is necessary to prevent stroke.

Introduction: Timely diagnosis and prognostication of Alzheimer's disease (AD) and mild cognitive impairment (MCI) are pivotal for effective intervention. Artificial intelligence (AI) in neuroradiology may aid in such appropriate diagnosis and prognostication. This study aimed to evaluate the potential of novel diffusion model-based AI for enhancing AD and MCI diagnosis through superresolution (SR) of brain magnetic resonance (MR) images. Methods: 1.5T brain MR scans of patients with AD or MCI and healthy controls (NC) from Alzheimer's Disease Neuroimaging Initiative 1 (ADNI1) were superresolved to 3T using a novel diffusion model-based generative AI (d3T*) and a convolutional neural network-based model (c3T*). Comparisons of image quality to actual 1.5T and 3T MRI were conducted based on signal-to-noise ratio (SNR), naturalness image quality evaluator (NIQE), and Blind/Referenceless Image Spatial Quality Evaluator (BRISQUE). Voxel-based volumetric analysis was then conducted to study whether 3T* images offered more accurate volumetry than 1.5T images. Binary and multiclass classifications of AD, MCI, and NC were conducted to evaluate whether 3T* images offered superior AD classification performance compared to actual 1.5T MRI. Moreover, CNN-based classifiers were used to predict conversion of MCI to AD, to evaluate the prognostication performance of 3T* images. The classification performances were evaluated using accuracy, sensitivity, specificity, F1 score, Matthews correlation coefficient (MCC), and area under the receiver-operating curves (AUROC). Results: Analysis of variance (ANOVA) detected significant differences in image quality among the 1.5T, c3T*, d3T*, and 3T groups across all metrics. Both c3T* and d3T* showed superior image quality compared to 1.5T MRI in NIQE and BRISQUE with statistical significance. While the hippocampal volumes measured in 3T* and 3T images were not significantly different, the hippocampal volume measured in 1.5T images showed significant difference. 3T*-based AD classifications showed superior performance across all performance metrics compared to 1.5T-based AD classification. Classification performance between d3T* and actual 3T was not significantly different. 3T* images offered superior accuracy in predicting the conversion of MCI to AD than 1.5T images did. Conclusions: The diffusion model-based MRI SR enhances the resolution of brain MR images, significantly improving diagnostic and prognostic accuracy for AD and MCI. Superresolved 3T* images closely matched actual 3T MRIs in quality and volumetric accuracy, and notably improved the prediction performance of conversion from MCI to AD.

Abstract Some individuals with mild traumatic brain injury (mTBI), also known as concussion, have neuropsychiatric and physical problems that last longer than a few months. Symptoms following mTBI are not only impacted by the kind and severity of the injury but also by the post-injury experience and the individual's responses to it, making the persistence of mTBI particularly difficult to predict. We aimed to identify prognostic blood-based protein biomarkers predicting 6-month outcomes, in light of the clinical course after the injury, in a longitudinal mTBI cohort (N = 42). Among 420 target proteins quantified by multiple-reaction monitoring-mass spectrometry assays of blood samples, 31, 43, and 15 proteins were significantly associated with the poor recovery of neuropsychological symptoms at

Abstract Objective The aim of this study is to assess the value of using videofluoroscopic swallowing study (VFSS) for assessing vocal fold paralysis. Methods This was a retrospective study of patients who underwent VFSS with a vocal fold testing maneuver from June 2020 to February 2022, and who had undergone laryngoscopy within 2 weeks before or after VFSS. The vocal fold testing maneuver consisted of making an ‘e’ sound for about 2–3 seconds during VFSS anterior–posterior (AP) view. The diagnostic value of the VFSS was evaluated by a trained reviewer, who assessed the presence and laterality of vocal fold paralysis by examining videos of the patients performing the vocal fold testing maneuver. Intra‐rater reliability was determined by evaluation of the videos by the same reviewer 2 weeks later, and inter‐rater reliability was determined by evaluation by a second reviewer. Results Seventy patients were enrolled in the study. The positive predictive value was 91.43% and the intra‐rater and inter‐rater reliabilities, as determined by Cohen's kappa value, were 0.746 and 0.824 respectively. Conclusions The presence and laterality of vocal fold paralysis were identified accurately and reliably by the reviewers, showing that VFSS can be used to assess vocal fold paralysis. Level of evidence 2.

Abstract The sequential 4-channel neuromuscular electrical stimulation (NMES), based on the normal contractile sequences of swallowing-related muscles, is a new rehabilitative treatment. The objective of this study was to explore the mechanism of the rehabilitative effect of the 4-channel NMES using kinematic analysis of videofluoroscopic swallowing study (VFSS) data. For this post-hoc analysis, we included a subset of participants from the prospective randomized controlled study on the clinical effectiveness of the sequential 4-channel NMES compared with that of the conventional 2-channel NMES. Seventeen subjects (11 and six in the 4- and 2-channel NMES groups, respectively) were eligible for the kinematic analysis of VFSS data. The hyoid bone movement was analyzed by evaluating the distance and time parameters with four peak points (A, B, C, D). The 4-channel NMES group showed significant improvement in vertical distances (A–C), horizontal distance (A–B, A–C), time interval (A–B–C) and total time, compared with their pretreatment data. The 2-channel NMES group showed significant improvements in time interval (A–B); however, the Euclidean distance (A–D) and mean velocity of the Euclidean distance (A-C) were significantly decreased. When the two groups were directly compared, the 4-channel group showed significantly greater improvement in horizontal distance (A–B), Euclidean distance (A–D), time interval (A–B–C), and mean velocity the Euclidean distance (A–D). The results in this study suggest that the sequential 4-channel NMES might lead to the physiologic circular movement of the hyoid bone during swallowing, and therefore be an effective treatment for dysphagia. Trial registration: Clinicaltrials.gov, registration number: NCT03670498.

Abstract Background Dual-task training in Parkinson’s disease (PD) improves spatiotemporal gait parameters, cognition, and quality of life. Virtual reality (VR) has been used as a therapeutic tool for patients to participate in activities in a safe environment, engage in multisensory experiences, and improve motivation and interest in rehabilitation. This study aimed to investigate the feasibility of fully immersive VR exergames with dual-task components in patients with PD. Methods We developed VR exergames (go/no-go punch game, go/no-go stepping game, and number punch game) to improve habitual behavior control using motor–cognitive dual-task performance in patients with PD. The participants underwent 10 sessions 2–3 times a week, consisting of 30 min per session. The Unified Parkinson’s Disease Rating Scale, Timed Up and Go test (TUG) under single- and dual-task (cognitive and physical) conditions, Berg balance scale (BBS), Stroop test, trail-making test, and digit span were evaluated before and after intervention. The Simulator Sickness Questionnaire (SSQ) was used to assess VR cybersickness. Usability was assessed using a self-reported questionnaire. Results Twelve patients were enrolled and completed the entire training session. The mean age of participants was 73.83 ± 6.09 years; mean disease duration was 128.83 ± 76.96 months. The Hoehn and Yahr stages were 2.5 in seven patients and 3 in five patients. A significant improvement was observed in BBS and Stroop color–word test (p = 0.047 and p = 0.003, respectively). TUG time and dual-task interferences showed positive changes, but these changes were not statistically significant. The median SSQ total score was 28.05 (IQR: 29.92), 13.09 (IQR: 11.22), and 35.53 (IQR: 52.36) before, after the first session, and after the final session, respectively; the differences were not significant. Overall satisfaction with the intervention was 6.0 (IQR: 1.25) on a 7-point Likert-type scale. Conclusions Fully immersive VR exergames combined with physical and cognitive tasks may be used for rehabilitation of patients with PD without causing serious adverse effects. Furthermore, the exergames using dual-task components improved executive function and balance. Further development of VR training content may be needed to improve motor and dual-task performances. Trial registration NCT04787549 ( https://clinicaltrials.gov/ct2/show/NCT04787549 )

Abstract Muscle strength assessment is important in predicting clinical and functional outcomes in many disorders. Manual muscle testing, although commonly used, offers suboptimal accuracy and reliability. Isokinetic dynamometers (IKDs) have excellent accuracy and reliability; but are bulky and expensive, offering limited accessibility. This study aimed to design a portable dynamometer that is accessible, accurate and reliable, and to validate the device in a general population. The portable articulated dynamometry system (PADS) is a portable device with an embedded high-precision load cell, designed to measure muscle strength with optimal accuracy. Seventy-two participants underwent maximal isometric and isokinetic knee extensor torque measurement with the PADS and IKD, respectively. The PADS results were cross-validated against IKD results using change in mean (CIM). Interrater and intra-rater reliabilities were assessed using intraclass correlation coefficients, standard error of measurement, and minimal detectable change. The PADS maximal knee extensor strength results were not significantly different from those by IKD (CIM: − 2.13 Nm; 95% CI − 4.74, 0.49 Nm). The PADS showed interrater reliability (Pearson’s r: 0.958; ICC: 0.979; SEM: 5.51%) and excellent intra-rater reliability (Pearson’s r: 0.912; ICC: 0.954; SEM: 8.38%). The proposed PADS may be an effective alternative to IKD, offering good accuracy, reliability, and potentially better accessibility.

Objective To investigate the clinical and swallowing characteristics related to respiratory infection in patients with parkinsonism. Methods One hundred and forty-two patients with parkinsonism who underwent videofluoroscopic swallowing studies (VFSS) were enrolled in this study. The initial clinical and VFSS characteristics were compared between patients with and without a history of respiratory infection in the past year. A multivariate logistic regression model was applied to identify clinical and swallowing characteristics related to respiratory infections. Results Patients with respiratory infections were older (74.75±10.20 years vs. 70.70±8.83 years, p=0.037), had a higher Hoehn and Yahr (H&Y) stage (stage IV–V, 67.9% vs. 49.1%; p=0.047), and were more likely to have a diagnosis of idiopathic Parkinson’s disease (IPD) (67.9% vs. 41.2%, p=0.011) than those without respiratory infections. Among VFSS findings, bolus formation, premature bolus loss, oral transit time, pyriform sinus residues, pharyngeal wall coatings, and penetration/aspiration were significantly worse in patients with respiratory infections (p

Objective To explore the effects of tactile stimulation using air pressure at the auricular branch of the vagus nerve on autonomic activity in healthy individuals. Methods Three types of tactile stimulation were used in this study: continuous low-amplitude, continuous high-amplitude, and pulsed airflow. The tactile stimulations were provided to the cymba concha to investigate autonomic activity in 22 healthy participants. The mean heart rate (HR) and parameters of HR variability, including the standard deviation of R-R intervals (SDNN) and root mean square of successive R-R interval differences (RMSSD) were compared at baseline, stimulation, and recovery periods. Results Two-way repeated measures ANOVA indicated a significant main effect of time on HR (p=0.001), SDNN (p=0.003), and RMSSD (p

Objective To characterize the repetitive transcranial magnetic stimulation (rTMS) induced changes in angiogenic mechanisms across different brain regions. Methods Seventy-nine adult male Sprague-Dawley rats were subjected to a middle cerebral artery occlusion (day 0) and then treated with 1-Hz, 20-Hz, or sham stimulation of their lesioned hemispheres for 2 weeks. The stimulation intensity was set to 100% of the motor threshold. The neurological function was assessed on days 3, 10, and 17. The infarct volume and angiogenesis were measured by histology, immunohistochemistry, Western blot, and real-time polymerase chain reaction (PCR) assays. Brain tissue was harvested from the ischemic core (IC), ischemic border zone (BZ), and contralateral homologous cortex (CH). Results Optical density of angiopoietin1 and synaptophysin in the IC was significantly greater in the low-frequency group than in the sham group (p=0.03 and p=0.03, respectively). The 1-Hz rTMS significantly increased the level of Akt phosphorylation in the BZ (p

Objective Dysphagia is a common clinical condition characterized by difficulty in swallowing. It is sub-classified into oropharyngeal dysphagia, which refers to problems in the mouth and pharynx, and esophageal dysphagia, which refers to problems in the esophageal body and esophagogastric junction. Dysphagia can have a significant negative impact one’s physical health and quality of life as its severity increases. Therefore, proper assessment and management of dysphagia are critical for improving swallowing function and preventing complications. Thus a guideline was developed to provide evidence-based recommendations for assessment and management in patients with dysphagia. Methods Nineteen key questions on dysphagia were developed. These questions dealt with various aspects of problems related to dysphagia, including assessment, management, and complications. A literature search for relevant articles was conducted using Pubmed, Embase, the Cochrane Library, and one domestic database of KoreaMed, until April 2021. The level of evidence and recommendation grade were established according to the Grading of Recommendation Assessment, Development and Evaluation methodology. Results Early screening and assessment of videofluoroscopic swallowing were recommended for assessing the presence of dysphagia. Therapeutic methods, such as tongue and pharyngeal muscle strengthening exercises and neuromuscular electrical stimulation with swallowing therapy, were effective in improving swallowing function and quality of life in patients with dysphagia. Nutritional intervention and an oral care program were also recommended. Conclusion This guideline presents recommendations for the assessment and management of patients with oropharyngeal dysphagia, including rehabilitative strategies.

Objective To develop a set of reference standards for tibial motor, common peroneal motor, sural sensory, and superficial peroneal sensory nerve conduction studies (NCSs) with expanded uncertainty in a healthy Korean population. Methods Standardized procedures were conducted for individual lower extremity NCSs of 199 healthy participants in their 20s (n=100) and 50s (n=99). Mean values and expanded uncertainties for parameters were analyzed with thorough consideration of multiple uncertainty factors under the International Guide to the Expression of Uncertainty in Measurement. In addition, side-to-side differences in onset latency, amplitude, and nerve conduction velocity (NCV) were analyzed. Results Mean (reference range) for distal onset latency, baseline to negative peak amplitude, NCV of tibial motor nerve in males in their 20s were 4.3 ms (3.1–5.4 ms), 7.1 mV (3.4–10.9 mV), and 50.7 m/s (42.2–59.3 m/s), respectively; sural sensory nerve baseline to negative peak amplitude in males in their 20s was 21.7 μV (8.3–35.2 μV). Including the aforementioned data, we present a vast dataset of normative mean values and expanded uncertainties for NCSs of the leg in a healthy Korean population. Furthermore, upper limits for normal side-to-side differences for onset latency, amplitude, and NCV of each nerve are suggested. Conclusion To our knowledge, this is the first study to present the reference standards of leg NCSs with consideration for multifactorial uncertainties in an Asian population. We expect these results to help practitioners make reliable and reproducible clinical decisions.

Abstract Introduction This study aimed to investigate alterations in whole‐brain functional connectivity after a concussion using graph‐theory analysis from global and local perspectives and explore the association between changes in the functional network properties and cognitive performance. Methods Individuals with mild traumatic brain injury (mTBI, n = 29) within a month after injury, and age‐ and sex‐matched healthy controls (n = 29) were included. Graph‐theory measures on functional connectivity assessed using resting state functional magnetic resonance imaging data were acquired from each participant. These included betweenness centrality, strength, clustering coefficient, local efficiency, and global efficiency. Multi‐domain cognitive functions were correlated with the graph‐theory measures. Results In comparison to the controls, the mTBI group showed preserved network characteristics at a global level. However, in the local network, we observed decreased betweenness centrality, clustering coefficient, and local efficiency in several brain areas, including the fronto‐parietal attention network. Network strength at the local level showed mixed‐results in different areas. The betweenness centrality of the right parahippocampus showed a significant positive correlation with the cognitive scores of the verbal learning test only in the mTBI group. Conclusion The intrinsic functional connectivity after mTBI is preserved globally, but is suboptimally organized locally in several areas. This possibly reflects the neurophysiological sequelae of a concussion. The present results may imply that the network property could be used as a potential indicator for clinical outcomes after mTBI.

Purpose. To analyze ocular manifestations, visual field (VF) pattern, and VF test performance in traumatic brain injury (TBI) and stroke patients. Methods. This retrospective, cross-sectional study included 118 patients (236 eyes) with TBI and stroke who had undergone VF testing by standard automated perimetry with the central 24-2 threshold test. Clinical features including best-corrected visual acuity (BCVA), intraocular pressure (IOP), ocular manifestations, and VF test results including VF defect pattern, reliability, and global indices were analyzed and compared between the TBI and stroke patients. Results. In TBI patients, ocular manifestations included strabismus (11.1%), cataract (4.2%), and glaucoma suspect (2.8%), whereas in stroke patients, cataract (15.2%), strabismus (8.5%), diabetic retinopathy (4.9%), extraocular movement (EOM) limitation (3.0%), glaucoma suspect (3.0%), nystagmus (2.4%), drusen (1.2%), and vitreous hemorrhage (1.2%) were found. The VF test results showed that 47 eyes (85.5%) in TBI and 86 (65.2%) in stroke had VF defect; in TBI, the scattered pattern was the most common (56.4%), followed by homonymous hemianopsia (14.5%), homonymous quadrantanopia (10.9%), and total defect (3.6%), whereas in stroke, homonymous hemianopsia was the most common (31.8%), followed by scattered pattern (16.7%), homonymous quadrantanopia (12.1%), and total defect (4.5%). Only 15 eyes (27.3%) in TBI and 32 (24.2%) in stroke showed reliable VF indices. The mean deviation (MD) was −10.5 ± 7.1 dB in TBI and −9.5 ± 6.8 dB in stroke, and the pattern standard deviation (PSD) was 4.9 ± 3.3 dB in TBI and 6.1 ± 3.9 dB in stroke, without statistically significant differences between the two groups. Conclusion. Various ocular manifestations were found, and a considerable proportion of patients were experiencing VF defects and showed unreliable VF test performance. Our findings suggest that accurate evaluation and rehabilitation of visual function should be a matter of greater concern and emphasis in the management of TBI and stroke patients, besides systemic diseases.

Background: The inter- and intrarater variability of conventional computed tomography (CT) classification systems for evaluating the extent of ischemic-edematous insult following traumatic brain injury (TBI) may hinder the robustness of TBI prognostic models.Objective: This study aimed to employ fully automated quantitative densitometric CT parameters and a cutting-edge machine learning algorithm to construct a robust prognostic model for pediatric TBI.Methods: Fifty-eight pediatric patients with TBI who underwent brain CT were retrospectively analyzed. Intracranial densitometric information was derived from the supratentorial region as a distribution representing the proportion of Hounsfield units. Furthermore, a machine learning-based prognostic model based on gradient boosting (i.e., CatBoost) was constructed with leave-one-out cross-validation. At discharge, the outcome was assessed dichotomously with the Glasgow Outcome Scale (favorability: 1–3 vs. 4–5). In-hospital mortality, length of stay (>1 week), and need for surgery were further evaluated as alternative TBI outcome measures.Results: Densitometric parameters indicating reduced brain density due to subtle global ischemic changes were significantly different among the TBI outcome groups, except for need for surgery. The skewed intracranial densitometry of the unfavorable outcome became more distinguishable in the follow-up CT within 48 h. The prognostic model augmented by intracranial densitometric information achieved adequate AUCs for various outcome measures [favorability = 0.83 (95% CI: 0.72–0.94), in-hospital mortality = 0.91 (95% CI: 0.82–1.00), length of stay = 0.83 (95% CI: 0.72–0.94), and need for surgery = 0.71 (95% CI: 0.56–0.86)], and this model showed enhanced performance compared to the conventional CRASH-CT model.Conclusion: Densitometric parameters indicative of global ischemic changes during the acute phase of TBI are predictive of a worse outcome in pediatric patients. The robustness and predictive capacity of conventional TBI prognostic models might be significantly enhanced by incorporating densitometric parameters and machine learning techniques.

Objective: To evaluate the effects of direct swallowing training (DST) alone and combined with oral sensorimotor stimulation (OSMS) on oral feeding ability in very preterm infants.Design: Blinded, parallel group, randomised controlled trial (1:1:1).Setting: Neonatal intensive care unit of a South Korean tertiary hospital.Participants: Preterm infants born at <32 weeks of gestation who achieved full tube feeding.Interventions: Two sessions per day were provided according to the randomly assigned groups (control: two times per day sham intervention; DST: DST and sham interventions, each once a day; DST+OSMS: DST and OSMS interventions, each once a day).Primary Outcome: Time from start to independent oral feeding (IOF).Results: Analyses were conducted in 186 participants based on modified intention-to-treat (63 control; 63 DST; 60 DST+OSMS). The mean time from start to IOF differed significantly between the control, DST and DST+OSMS groups (21.1, 17.2 and 14.8 days, respectively, p=0.02). Compared with non-intervention, DST+OSMS significantly shortened the time from start to IOF (effect size: -0.49; 95% CI: -0.86 to -0.14; p=0.02), whereas DST did not. The proportion of feeding volume taken during the initial 5 min, an index of infants' actual feeding ability when fatigue is minimal, increased earlier in the DST+OSMS than in the DST.Conclusions: In very preterm infants, DST+OSMS led to the accelerated attainment of IOF compared with non-intervention, whereas DST alone did not. The effect of DST+OSMS on oral feeding ability appeared earlier than that of DST alone.Trial Registration Number: ClinicalTrials.gov Registry (NCT02508571). [ABSTRACT FROM AUTHOR]