Efficacy of a Hip Brace for Hip Displacement in Children With Cerebral Palsy: A Randomized Clinical Trial.

Importance: There is no consensus on interventions to slow the progress of hip displacement in patients with cerebral palsy. Objective: To investigate the efficacy of a novel hip brace in preventing progressive hip displacement in patients with cerebral palsy. Design, Setting, and Participants: This 2-group randomized clinical trial was conducted at 4 tertiary hospitals in South Korea from July 2019 to November 2021. Participants included children aged 1 to 10 years with nonambulatory cerebral palsy (Gross Motor Function Classification System level IV or V). Block randomization was used to assign an equal number of patients to the study and control groups via computerized random allocation sequences. Data were analyzed from November to December 2021. Interventions: The intervention group wore the hip brace for at least 12 hours a day for the study duration (ie, 12 months). Follow-up evaluations were performed after 6 and 12 months of wearing the brace. Both groups proceeded with conventional rehabilitation therapy during the trial. Main Outcomes and Measures: The primary outcome was the Reimers migration index (MI) on radiography, as assessed by 3 blinded investigators. Primary outcome variables were analyzed using linear mixed models. Secondary outcomes include change in the Caregiver Priorities & Child Health Index of Life with Disabilities, on which lower scores indicate better quality of life. Results: A total of 66 patients were included, with 33 patients (mean [SD] age, 68.7 [31.6] months; 25 [75.8%] boys) randomized to the intervention group and 33 patients (mean [SD] age, 60.7 [24.9] months; 20 [60.6%] boys) randomized to the control group. The baseline mean (SD) MI was 37.4% (19.3%) in the intervention group and 30.6% (16.3%) in the control group. The mean difference of the MI between the intervention group and control group was -8.7 (95% CI, -10.2 to -7.1) percentage points at 6 months and -12.7 (95% CI, -14.7 to -10.7) percentage points at 12 months. The changes in the Caregiver Priorities & Child Health Index of Life with Disabilities were favorable in the study group and reached statistical significance at the 6-month follow-up compared with the control group (difference, -14.2; 95% CI, -25.2 to -3.3). Conclusions and Relevance: In this randomized clinical trial, the novel hip brace was significantly effective in preventing the progression of hip displacement, compared with the control group. It effectively improved quality of life in patients with nonambulatory cerebral palsy. Therefore, hip brace use could be a promising treatment method to delay hip surgery and improve the quality of life of patients with nonambulatory cerebral palsy. Trial Registration: ClinicalTrials.gov Identifier: NCT04033289.

Use of combined treatment of 3rd-generation cephalosporin, azithromycin and antiviral agents on moderate SARs-CoV-2 patients in South Korea: A retrospective cohort study.

OBJECTIVES: To assess efficacy and safety of the combined treatment of antibiotics (3rd-generation cephalosporin and azithromycin) and antiviral agents (lopinavir/ritonavir or hydroxychloroquine) on moderate COVID-19 patients in South Korea. METHODS: A retrospective cohort study of the 358 laboratory-confirmed SARS-CoV-2 (COVID-19) patients was conducted. 299 patients met inclusion criteria for analysis. Propensity score matching (PSM) and Cox regression method were used to control and adjust for confounding factors. Mild to moderate COVID-19 patients were managed with either CA/LoP (cephalosporin, azithromycin, and lopinavir/ritonavir) (n = 57), CA/HQ (cephalosporin, azithromycin, and hydroxychloroquine) (n = 25) or standard supportive care (n = 217). We analyzed the association between treatment group and standard supportive group in terms of three endpoints: time to symptom resolution, time to viral clearance, and hospital stay duration. Using propensity-score matching analysis, three rounds of propensity-matching analysis were performed to balance baseline characteristics among three cohorts. RESULTS: Kaplan-Meier curves fitted using propensity score-matched data revealed no significant differences on time to symptom resolution, time to viral clearance, hospital stay duration among the three treatment arms (CA/LoP vs Standard, log-rank p-value = 0.2, 0.58, and 0.74 respectively for the three endpoints) (CA/HQ vs Standard, log-rank p-value = 0.46, 0.99, and 0.75 respectively). Similarly, Cox regression analysis on matched cohorts of CA/LoP and standard supportive group showed that hazard ratios of time to symptom resolution (HR: 1.447 [95%-CI: 0.813-2.577]), time to viral clearance(HR: 0.861, [95%-CI: 0.485-1.527]), and hospital stay duration (HR: 0.902, [95%-CI: 0.510-1.595]) were not significant. For CA/HQ and standard supportive group, hazard ratios of the three endpoints all showed no statistical significance (HR: 1.331 [95%-CI:0.631-2.809], 1.005 [95%-CI:0.480-2.105], and 0.887, [95%-CI:0.422-1.862] respectively). No severe adverse event or death was observed in all groups. CONCLUSIONS: Combined treatment of 3rd cephalosporin, azithromycin and either low-dose lopinavir/ritonavir or hydroxychloroquine was not associated with better clinical outcomes in terms of time to symptom resolution, time to viral clearance, and hospital stay duration compared to standard supportive treatment alone. Microbiological evidence should be closely monitored when treating SARS-CoV-2 patients with antibiotics to prevent indiscreet administration of empirical antimicrobial treatments.

Effect of Botulinum Toxin Injection on the Progression of Hip Dislocation in Patients with Spastic Cerebral Palsy: A Pilot Study.

Hip adductor spasticity is a contributing factor to hip dislocation in patients with cerebral palsy (CP). We hypothesized that botulinum toxin injected into the hip adductor muscles would reduce spasticity and help prevent hip dislocation. Twenty patients with bilateral spastic CP aged 2 to 10 years with gross motor function classification system level IV or V were included. Botulinum toxin was injected into the hip adductor muscles at baseline and at 6-month follow-up. Muscle tone was measured with an eight-channel surface electromyography (EMG) recorder. A hip X-ray was performed, and Reimer's hip migration index (MI) was measured. The Wilcoxon signed-rank test was used to compare the surface EMG values of the hip muscles at baseline and follow-up. The mean root mean square surface EMG value of the hip adductor muscles was significantly reduced at 1, 2, 3, and 7 months after the first injection, up to approximately 53% of the baseline. The 1-year progression of the hip MI was -0.04%. Repeated sessions of botulinum toxin injections at the hip adductor muscles significantly reduced muscle tone and hip displacement. A botulinum toxin injection may be used as an adjunctive treatment in the prevention of hip dislocation.

The effect of a flexible thoracolumbar brace on neuromuscular scoliosis: A prospective observational study.

ABSTRACT: Neuromuscular scoliosis is a common deformity seen in patients with neuromuscular diseases. Although rigid thoracolumbosacral orthosis is the most frequently used brace, it has low compliance rates and can lead to complications including skin ulcers. Thus, alternative methods for treating neuromuscular scoliosis are needed. The purpose of this study is to evaluate the clinical effects of a novel flexible brace to prevent the progression of neuromuscular scoliosis.This study is a prospective observational study. Twenty-three patients with neuromuscular scoliosis were enrolled in the study. Among patients diagnosed with neuromuscular disease, spine radiographs were checked for a neuromuscular scoliosis diagnosis. The participants were treated with a novel flexible brace for 6 months. The control group (n = 46) was selected using propensity score matching method from a clinical data warehouse. The Cobb angle was measured and compared between the study and control groups.In the study group, the average Cobb's angle significantly decreased from 47.22 ±â€Š18.9° to 31.8 ±â€Š20.0 when wearing the flexible brace (P < .001). Thus, the correction rate was 36.9%. The annual progression rate was significantly lower in the study group than in the control group (P  < .05).The flexible brace showed a significant correction rate of scoliosis in patients with severe neuromuscular diseases. The flexible brace is an alternative treatment modality for patients with neuromuscular scoliosis. Daily application of the flexible brace during the growing period can reduce the degree of fixed deformity in the long term.

Compensatory Effects of Sequential 4-Channel Neuromuscular Electrical Stimulation for the Treatment of Acute, Subacute, and Chronic Dysphagia in a Prospective, Double-Blinded Randomized Clinical Trial.

Background. The precise mechanism of 2-channel neuromuscular electrical stimulation (NMES) treatment is unknown, and controversy remains over its efficacy. The sequential 4-channel NMES was newly developed based on normal contractile sequences of swallowing-related muscles. Objective. To assess the clinical efficacy of sequential 4-channel NMES during swallowing. Methods. In this prospective RCT, 52 inpatients with dysphagia (acute, subacute, and chronic state) after stroke, brain tumor, or encephalitis were enrolled. Participants who underwent a videofluoroscopic swallowing study (VFSS) and clinical evaluation were enrolled and were randomly assigned to the 4-channel NMES or sham group. The 4-channel NMES and sham groups swallowed thin and honey-like fluids under NMES (sequential stimulation on suprahyoid and infrahyoid) and sham stimulation, respectively. The procedures were evaluated with the VFSS. Pre- and post-treatment evaluations were performed with the videofluoroscopic dysphagia scale (VDS), penetration-aspiration scale (PAS), Likert scale, and kinematic analysis. Results. The 4-channel NMES group showed significantly greater improvements than the sham group with respect to oral VDS, pharyngeal VDS, total VDS, and PAS (P < .05). Furthermore, the Likert scale for satisfaction, easiness, and discomfort for swallowing showed favorable results for the 4-channel NMES group (P < .05). In the kinematic analysis, the peak speed point, distance, and velocity of hyoid movement were significantly greater in the 4-channel NMES group (P < .05). Conclusions. Sequential 4-channel NMES activating the suprahyoid, thyrohyoid, and other infrahyoid muscles during swallowing showed significant clinical improvement with respect to VDS, PAS, and kinematic analysis. Therefore, sequential 4-channel NMES is a potential new functional electrical stimulation system for the treatment of dysphagia.

Clinical effectiveness of the sequential 4-channel NMES compared with that of the conventional 2-channel NMES for the treatment of dysphagia in a prospective double-blind randomized controlled study.

BACKGROUND: To date, conventional swallowing therapies and 2-channel neuromuscular electrical stimulation (NMES) are standard treatments for dysphagia. The precise mechanism of 2-channel NMES treatment has not been determined, and there are controversies regarding the efficacy of this therapy. The sequential 4-channel NMES was recently developed and its action is based on the normal contractile sequence of swallowing-related muscles. OBJECTIVE: To evaluate and compare the rehabilitative effectiveness of the sequential 4-channel NMES with that of conventional 2-channel NMES. METHODS: In this prospective randomized case-control study, 26 subjects with dysphagia were enrolled. All participants received 2- or 4-channel NMES for 2-3 weeks (minimal session: 7 times, treatment duration: 300-800 min). Twelve subjects in the 4-channel NMES group and eleven subjects in the 2-channel NMES group completed the intervention. Initial and follow-up evaluations were performed using the videofluoroscopic dysphagia scale (VDS), the penetration-aspiration scale (PAS), the MD Anderson dysphagia inventory (MDADI), the functional oral intake scale (FOIS), and the Likert scale. RESULTS: The sequential 4-channel NMES group experienced significant improvement in their VDS (oral, pharyngeal, and total), PAS, FOIS, and MDADI (emotional, functional, and physical subsets) scores, based on their pretreatment data. VDS (oral, pharyngeal, and total) and MDADI (emotional and physical subsets) scores, but not PAS and FOIS scores, significantly improved in the 2-channel NMES group posttreatment. When the two groups were directly compared, the 4-channel NMES group showed significant improvement in oral and total VDS scores. CONCLUSIONS: The sequential 4-channel NMES, through its activation of the suprahyoid and thyrohyoid muscles, and other infrahyoid muscles mimicking physiological activation, may be a new effective treatment for dysphagia. TRIAL REGISTRATION: clinicaltrial.gov, registration number: NCT03670498, registered 13 September 2018, https://clinicaltrials.gov/ct2/show/NCT03670498?term=NCT03670498&draw=2&rank=1 .

Electromyographic activation patterns during swallowing in older adults.

Age-related weakness due to atrophy and fatty infiltration in oropharyngeal muscles may be related to dysphagia in older adults. However, little is known about changes in the oropharyngeal muscle activation pattern in older adults. This was a prospective and experimental study. Forty healthy participants (20 older [> 60 years] and 20 young [< 60 years] adults) were enrolled. Six channel surface electrodes were placed over the bilateral suprahyoid (SH), bilateral retrohyoid (RH), thyrohyoid (TH), and sternothyroid (StH) muscles. Electromyography signals were then recorded twice for each patient during swallowing of 2 cc of water, 5 cc of water, and 5 cc of a highly viscous fluid. Latency, duration, and peak amplitude were measured. The activation patterns were the same, in the order of SH, TH, and StH, in both groups. The muscle activation patterns were classified as type I and II; the type I pattern was characterized by a monophasic shape, and the type II comprised a pre-reflex phase and a main phase. The oropharyngeal muscles and SH muscles were found to develop a pre-reflex phase specifically with increasing volume and viscosity of the swallowed fluid. Type I showed a different response to the highly viscous fluid in the older group compared to that in the younger group. However, type II showed concordant changes in the groups. Therefore, healthy older people were found to compensate for swallowing with a pre-reflex phase of muscle activation in response to increased liquid volume and viscosity, to adjust for age-related muscle weakness.

Biomechanical influences of gait patterns on knee joint: Kinematic & EMG analysis.

BACKGROUND: As lumbar spinal stenosis commonly occurs between the L2 and L5 segments, hip abductors are easily affected. However, studies regarding the gait pattern in these patients from the coronal plane have not yet been conducted. PURPOSE: To determine the effects of lumbar spinal stenosis on the gait pattern (stride width and femorotibial angle) and hip abductor surface electromyography in varied stride widths compared with healthy individuals. STUDY DESIGN: Prospective case-control study. METHODS: Seventeen patients and 20 healthy individuals were enrolled. Each participant completed three gait assessments in their normal gait, adducted gait and abducted gait. The femorotibial angle and surface electromyography signals were measured. Pain scores was used to quantify the degree of discomfort in the gluteal area and medial side of the knee. RESULTS: When the hip abductors' surface electromyography signals were normalized by quadriceps femoris, patients group showed significantly higher activation ratios throughout all gait patterns. Generally, surface electromyography signals and ratios were significantly higher during abducted gait compared with a normal gait. Femorotibial angle became significantly closer to the varus in healthy individuals during abducted gait. When femorotibial angle during normal gait was compared between the two groups, patients group exhibited slightly wider stride width and FTA significantly closer to the varus. Pain scores were significantly higher in the patient group and during abducted gait. CONCLUSION: Wider stride widths indicated increased relative activation of the hip abductors, closer proximity between femorotibial angle and varus, and increased pain scores for discomfort. The same tendency was observed in patients group when compared with healthy individuals. Widening of stride width in patients group despite abductor weakness suggests that additional muscle recruitment may be needed to maintain balance. Furthermore, such a distinctive gait pattern exerts increased loading on the medial knee, relating to the escalated risk of degenerative knee osteoarthritis.

Novel design of hollow g-C3N4 nanofibers decorated with MoS2 and S, N-doped graphene for ternary heterostructures.

Herein, we newly design a ternary structure of 1-dimensional hollow g-C3N4 nanofibers (HGCNF) decorated with molybdenum disulfide (MoS2) and sulfur/nitrogen-doped graphene (SNG) via a one-pot hydrothermal treatment at relatively low temperature. The firstly presented HGCNF are fabricated using electrospinning followed by the thermal sintering method. After that, MoS2 is grown onto HGCNF, while SNG covered the structures during the hydrothermal method. We observed the morphological structures, chemical composition and optical absorbance of this ternary HGCNF/SNG/MoS2 structure. Of the as-prepared catalysts, HGCNF/SNG/MoS2 exhibited a good possibility to produce hydrogen as an electrocatalyst. Furthermore, we evaluated its stability performance using chronoamperometry for 48 hours, as well as by 3000 cycles of cyclic voltammetry. From the double-layer capacitance measurement, HGCNF/SNG/MoS2 proved itself as an electrocatalyst due to the higher value of electrocatalytically active sites to be 6.97 × 10-3 F cm-2 than that of only HGCNF (0.18 × 10-5 F cm-2) and the binary structure of HGCNF/MoS2 (2.54 × 10-3 F cm-2). We believe that our novel 1-dimensional ternary HGCNF/SNG/MoS2 structure has expedited the electron pathways by reducing the resistance at interfaces among HGCNF, SNG and MoS2, to be potentially useful for the hydrogen evolution reaction.

Reliability of behavioral tests in the middle cerebral artery occlusion model of rat.

Stroke is one of the leading causes of death and disability worldwide, and its incidence is increasing. To overcome impairment from stroke, translational research for developing new therapeutic technologies has been conducted and middle cerebral artery occlusion (MCAo) in rat is the representative model. Since recovery from neurological impairment in contralateral limbs caused by brain damage is the major goal of treatment, behavioral tests that assess the relevant function are used. To determine therapeutic effect, obtaining reliable results of behavioral assessment is a prerequisite. However, studies on the reliability of behavioral tests in the MCAo rat model and necessity of prior training have not yet been reported. In this study, the authors investigate relative and absolute inter-rater reliabilities of modified neurological severity score (mNSS), cylinder test, and grid-walking test before training and repeated training every week until the reliability of results reached a satisfactory level. The training included repeated learning of the scoring system and decreasing disagreements among the raters. For MCAo modeling, adult male Sprague-Dawley rats were subjected to 90 min of transient MCAo. Six raters conducted behavioral tests via observation of video-recording on sham-operated and MCAo model rats at 3 or 7 days after the intervention. An independent experimenter randomly numbered each video clip to blind the experiment. The results of reliabilities were unacceptable before training and improved to a satisfactory level after 6 weeks of training in all of the tests. In conclusion, mNSS, cylinder test, and grid-walking test on the MCAo rat model are reliable evaluation methods after conducting appropriate training.

Evaluation of dual layered photoanode for enhancement of visible-light-driven applications.

Ternary structures consisting of hollow g-C3N4 nanofibers/MoS2/sulfur, nitrogen-doped graphene and bulk g-C3N4 (TCN) were designed as a dual layered film and fabricated using a spin-coating method. The first ternary structures were spin-coated on fluorine-doped tin oxide (FTO) glass, followed by spin-coating of g-C3N4 film to form dual layers. We characterized the microstructural morphologies, chemical composition/bonding and optical properties of the dual layered film and observed significantly reduced recombination rates of photo-induced electron-hole pairs due to effective separation of the charge carriers. We tested methylene blue (MB) photodegradation and observed remarkable MB degradation by the dual layered film over 5 hours, with a kinetic rate constant of 1.24 × 10-3 min-1, which is about four times faster than that of bare TCN film. Furthermore, we estimated the H2 evolution of the dual layered film to be 44.9 µmol over 5 hours, and carried out stable recycling over 45 hours under visible irradiation. Due to the lower electrochemical impedance spectroscopy (EIS) resistance value of the dual layered film (∼50 ohm cm2) compared to the TCN film, the ternary structures and bulk g-C3N4 film were well-connected as a heterojunction, reducing the resistance at the interface between the film and the electrolyte. These results indicate that the effective separation of the photo-induced electron-hole pairs using the dual layered film dramatically improved its photo-response ability under visible light irradiation.

Direct coating of a g-C3N4 layer onto one-dimensional TiO2 nanocluster/nanorod films for photoactive applications.

We report the coating of metal-free graphitic carbon nitride (g-C3N4) onto titanium dioxide (TiO2) nanorods via a thermal evaporation method. Prior to g-C3N4 coating, TiO2 nanoclusters were grown on TiO2 nanorods to enhance the surface area by dipping in a TiCl3 solution for 12, 24 and 36 h. The prepared films were analyzed to assess the improvement in absorbance and reduction in recombination losses. Nanoclustered TiO2 grown for 24 h and then coated with a g-C3N4 film (i.e., TC_24h_CN) had the highest photocurrent of 235 and 290 µA, respectively, when measured by transient photocurrent and linear sweep voltammetry techniques. The enhanced performance resulted from a reduced recombination of electron-hole pairs. The TC_24h_CN film displayed an excellent photoresponse over 15 h of exposure to visible light and hence could potentially be used in water purification device technology.

Low temperature fabrication of Fe2O3 nanorod film coated with ultra-thin g-C3N4 for a direct z-scheme exerting photocatalytic activities.

We engineered high aspect ratio Fe2O3 nanorods (with an aspect ratio of 17 : 1) coated with g-C3N4 using a sequential solvothermal method at very low temperature followed by a thermal evaporation method. Here, the high aspect ratio Fe2O3 nanorods were directly grown onto the FTO substrate under relatively low pressure conditions. The g-C3N4 was coated onto a uniform Fe2O3 nanorod film as the heterostructure, exhibiting rational band conduction and a valence band that engaged in surface photoredox reactions by a direct z-scheme mechanism. The heterostructures, particularly 0.75g-C3N4@Fe2O3 nanorods, exhibited outstanding photocatalytic activities compared to those of bare Fe2O3 nanorods. In terms of 4-nitrophenol degradation, 0.75g-C3N4@Fe2O3 nanorods degraded all of the organic pollutant within 6 h under visible irradiation at a kinetic constant of 12.71 × 10-3 min-1, about 15-fold more rapidly than bare Fe2O3. Further, the hydrogen evolution rate was 37.06 µmol h-1 g-1, 39-fold higher than that of bare Fe2O3. We suggest that electron and hole pairs are efficiently separated in g-C3N4@Fe2O3 nanorods, thus accelerating surface photoreaction via a direct z-scheme under visible illumination.

Energy Expenditures for Activities of Daily Living in Korean Young Adults: A Preliminary Study.

OBJECTIVE: To investigate the energy expenditure (EE) of Korean young adults based on activities refined to a deskbound lifestyle. METHODS: Sixty-four healthy office workers aged between 25 and 46 years participated in this study. EE was expressed as metabolic equivalent of task (MET). Participants were evaluated in terms of their EE during physical activities of sleeping (n=22), typing (n=37), folding laundry (n=34), dishwashing (n=32), studying (n=18), mopping (n=35), walking (n=33), stair climbing (n=23), and running (n=29). Volume of oxygen consumption was measured by indirect calorimetry K4b(2) (COSMED). The results were compared to the established Compendium MET. RESULTS: The MET of activities were: sleeping, 1.24±0.43; typing, 1.35±0.25; folding laundry, 1.58±0.51; dishwashing, 2.20±0.51; studying, 2.11±0.90; mopping, 2.72±0.69; walking at 4 km/hr, 3.48±0.65; stair climbing of five stories, 6.18±1.08; and running at 8 km/hr, 7.57±0.57. The values of typing and mopping were similar to those in the Compendium, whereas those of sleeping, folding laundry, dishwashing, studying, walking, stair climbing and running were different. CONCLUSION: To our knowledge, this estimation of EE in MET during activities of daily living is the first data of young adults in Korea. These data could be used as a reference to modify the guidelines of physical activities for the age group examined in this study.

Involvement of Immune Responses in the Efficacy of Cord Blood Cell Therapy for Cerebral Palsy.

This study evaluated the efficacy of umbilical cord blood (UCB) cell for patients with cerebral palsy (CP) in a randomized, placebo-controlled, double-blind trial and also assessed factors and mechanisms related to the efficacy. Thirty-six children (ages 6 months to 20 years old) with CP were enrolled and treated with UCB or a placebo. Muscle strength and gross motor function were evaluated at baseline and 1, 3, and 6 months after treatment. Along with function measurements, each subject underwent (18)F-fluorodeoxyglucose positron emission tomography at baseline and 2 weeks after treatment. Cytokine and receptor levels were quantitated in serial blood samples. The UCB group showed greater improvements in muscle strength than the controls at 1 (0.94 vs. -0.35, respectively) and 3 months (2.71 vs. 0.65) after treatment (Ps<0.05). The UCB group also showed greater improvements in gross motor performance than the control group at 6 months (8.54 vs. 2.60) after treatment (P<0.01). Additionally, positron emission tomography scans revealed decreased periventricular inflammation in patients administered UCB, compared with those treated with a placebo. Correlating with enhanced gross motor function, elevations in plasma pentraxin 3 and interleukin-8 levels were observed for up to 12 days after treatment in the UCB group. Meanwhile, increases in blood cells expressing Toll-like receptor 4 were noted at 1 day after treatment in the UCB group, and they were correlated with increased muscle strength at 3 months post-treatment. In this trial, treatment with UCB alone improved motor outcomes and induced systemic immune reactions and anti-inflammatory changes in the brain. Generally, motor outcomes were positively correlated with the number of UCB cells administered: a higher number of cells resulted in better outcomes. Nevertheless, future trials are needed to confirm the long-term efficacy of UCB therapy, as the follow-up duration of the present trial was short.