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.

Clinical Characteristics and Outcomes of COVID-19 Cohort Patients in Daegu Metropolitan City Outbreak in 2020.

BACKGROUND: A coronavirus disease 2019 (COVID-19) outbreak started in February 2020 and was controlled at the end of March 2020 in Daegu, the epicenter of the coronavirus outbreak in Korea. The aim of this study was to describe the clinical course and outcomes of patients with COVID-19 in Daegu. METHODS: In collaboration with Daegu Metropolitan City and Korean Center for Diseases Control, we conducted a retrospective, multicenter cohort study. Demographic, clinical, treatment, and laboratory data, including viral RNA detection, were obtained from the electronic medical records and cohort database and compared between survivors and non-survivors. We used univariate and multi-variable logistic regression methods and Cox regression model and performed Kaplan-Meier analysis to determine the risk factors associated with the 28-day mortality and release from isolation among the patients. RESULTS: In this study, 7,057 laboratory-confirmed patients with COVID-19 (total cohort) who had been diagnosed from February 18 to July 10, 2020 were included. Of the total cohort, 5,467 were asymptomatic to mild patients (77.4%) (asymptomatic 30.6% and mild 46.8%), 985 moderate (14.0%), 380 severe (5.4%), and 225 critical (3.2%). The mortality of the patients was 2.5% (179/7,057). The Cox regression hazard model for the patients with available clinical information (core cohort) (n = 2,254) showed the risk factors for 28-day mortality: age > 70 (hazard ratio [HR], 4.219, P = 0.002), need for O2 supply at admission (HR, 2.995; P = 0.001), fever (> 37.5°C) (HR, 2.808; P = 0.001), diabetes (HR, 2.119; P = 0.008), cancer (HR, 3.043; P = 0.011), dementia (HR, 5.252; P = 0.008), neurological disease (HR, 2.084; P = 0.039), heart failure (HR, 3.234; P = 0.012), and hypertension (HR, 2.160; P = 0.017). The median duration for release from isolation was 33 days (interquartile range, 24.0-46.0) in survivors. The Cox proportional hazard model for the long duration of isolation included severity, age > 70, and dementia. CONCLUSION: Overall, asymptomatic to mild patients were approximately 77% of the total cohort (asymptomatic, 30.6%). The case fatality rate was 2.5%. Risk factors, including older age, need for O2 supply, dementia, and neurological disorder at admission, could help clinicians to identify COVID-19 patients with poor prognosis at an early stage.

Patterns of viral clearance in the natural course of asymptomatic COVID-19: Comparison with symptomatic non-severe COVID-19.

OBJECTIVES: The aim of this study was to elucidate patterns of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) clearance in the natural course of asymptomatic coronavirus disease 2019 (COVID-19). METHODS: Consecutive patients with non-severe COVID-19 were included retrospectively. Asymptomatic patients with a normal body temperature and no evidence of pneumonia throughout the disease course were assigned to the asymptomatic group. The reverse transcription PCR (RT-PCR) assay was repeated every two to five days after the first follow-up RT-PCR assay. Negative conversion was defined as two consecutive negative RT-PCR assay results within a 24-h interval. Rebound of the cycle threshold (Ct) value was defined as negative from the single RT-PCR assay and positive from the following assay. RESULTS: Among a total of 396 patients identified (median age 42.5 years (interquartile range (IQR) 25.0-55.0 years), 35.6% male), 68 (17.2%) were assigned to the asymptomatic group and 328 (82.8%) to the symptomatic group. The time until negative conversion was significantly shorter in the asymptomatic group than in the symptomatic group: median 14.5 days (IQR 11.0-21.0 days) and 18.0 days (IQR 15.0-22.0 days), respectively (p = 0.001). Rebound of Ct values was observed in 78 patients (19.7%). CONCLUSIONS: Time until negative conversion is shorter in asymptomatic COVID-19 than in symptomatic COVID-19. Rebound of Ct values is not uncommon.

Risk factors for disease progression in COVID-19 patients.

BACKGROUND: Coronavirus disease (COVID-19) is rapidly spreading worldwide. Although 10-20% of patients with COVID-19 have severe symptoms, little is known about the risk factors related to the aggravation of COVID-19 symptoms from asymptomatic or mild to severe disease states. METHODS: This retrospective study included 211 patients who were asymptomatic or with mild presentations of COVID-19. We evaluated the differences in demographic and clinical data between the cured (discharged to home) and transferred (aggravated to severe-stage COVID-19) groups. RESULTS: A multivariate logistic analysis showed that body temperature, chills, initial chest X-ray findings, and the presence of diabetes were significantly associated with predicting the progression to severe stage of COVID-19 (p < 0.05). The odds ratio of transfer in patients with COVID-19 increased by 12.7-fold for abnormal findings such as haziness or consolidation in initial chest X-ray, 6.32-fold for initial symptom of chills, and 64.1-fold for diabetes. CONCLUSIONS: Even if patients are asymptomatic or have mild symptoms, clinicians should closely observe patients with COVID-19 presenting with chills, body temperature > 37.5 °C, findings of pneumonia in chest X-ray, or diabetes.

Long-Term Effect of Rigid Foot Orthosis in Children Older Than Six Years With Flexible Flat Foot.

OBJECTIVE: To evaluate the long-term effect of a custom-made rigid foot orthosis (RFO) in children older than 6 years with pes planus (flat foot). METHODS: Medical records of 42 children diagnosed with flexible pes planus who were fitted with RFOs based on the inverted technique and underwent more than four consecutive radiological studies were reviewed. Resting calcaneal stance position (RCSP), anteroposterior talocalcaneal angle, lateral talocalcaneal angle, lateral talometatarsal angle, and calcaneal pitch were initially measured in both feet to evaluate alignment. Followup clinical and radiological evaluations were then performed at 12-18, 24-30, 36-42, and ≥48 months after RFO application. Repeated measures analysis of variance was used to evaluate significant differences. RESULTS: Significant improvements in all radiological indicators and significant progression of RCSP toward the corrective direction were observed after RFO application relative to baseline measurements. CONCLUSION: According to our findings, RFO can induce significant improvements in calcaneus-related radiographic indices and subsequently improve talus-related radiologic indices.

Hand Functions of Myoelectric and 3D-Printed Pressure-Sensored Prosthetics: A Comparative Study.

The loss of an upper limb significantly limits the functional activities of daily living. A huge emphasis is placed on the manipulation, shape, weight, and comfort of a prosthesis, to enable its use as an inherent body part. Even with technological advances, customized upper-extremity myoelectric prosthesis remain heavy and expensive. The high cost of upper-extremity prosthesis is an especially steep economic barrier for patients. Three-dimensional (3D) printing is a promising avenue for reducing the cost of prosthesis. We applied 3D-printed pressure-sensored prosthetics to a traumatic transradial amputee, and compared the hand functions with a customized myoelectric prosthesis. The 3D-printed pressure-sensored prosthetics showed low grip strength and decreased dexterity compared to the conventional myoelectric prosthesis. Although there were a few limitations, the fabrication of prosthesis with 3D printing technology can overcome previous problems such as high production cost, long fabrication period and heavy weight.

The Effects of Talus Control Foot Orthoses in Children with Flexible Flatfoot.

BACKGROUND: A talus control foot orthosis (TCFO) combines an inverted rigid foot orthosis (RFO) with a broad upright portion that rises well above the navicular to cover and protect the talonavicular joint. We sought to identify the therapeutic effect of TCFOs in children with flexible flatfoot. METHODS: Flexible flatfoot was diagnosed in 40 children when either of the feet had greater than 4° valgus of resting calcaneal stance position (RCSP) angle and one of the radiographic indicators was greater than 30° in anteroposterior talocalcaneal angles, 45° in lateral talocalcaneal angles, and 4° in lateral talometatarsal angles and less than 10° of calcaneal pitch in barefoot radiographs. Of 40 children with flexible flatfoot, 20 were fitted with a pair of RFOs and 20 with TCFOs, randomly. Follow-up clinical and radiographic measurements were completed 12 months later. RESULTS: All of the radiographic indicators changed toward the corrective direction in both groups. There were significant improvements in calcaneal pitch and RCSP in both groups (P < .05). In the TCFO group, the anteroposterior talocalcaneal angle and the RCSP showed statistically significant improvement compared with the RFO group. CONCLUSIONS: In this study, the TCFO was more effective than the RFO at treating children with flexible flatfoot.

The Effect of Different Foot Orthosis Inverted Angles on Plantar Pressure in Children with Flexible Flatfeet.

Although orthotic modification using the inverted technique is available for the treatment of flatfoot, empirical evidence for the biomechanical effects of inverted-angle foot orthoses (FOs) is lacking. The aim of this study was to evaluate the effects of different FO inversion angles on plantar pressure during gait in children with flatfoot. Twenty-one children with flexible flatfeet (mean age 9.9 years) were enrolled in this study. The plantar pressures were measured for the rearfoot; medial and lateral midfoot; and medial, central, and lateral forefoot as participants walked on a treadmill while wearing shoes only and shoes with the following 3 orthotic conditions: (i) orthosis with no inverted angle, (ii) orthosis with a 15° inverted angle, and (iii) orthosis with a 30° inverted angle. A one-way repeated measures analysis of variance (ANOVA) with the Bonferroni-adjusted post-hoc test was used to compare the mean values of each orthotic condition. Compared with the shoe only condition, the peak pressure decreased significantly under the medial forefoot and rearfoot with all FOs (p <0.05). However, no significant differences in the peak pressure under the medial forefoot and rearfoot were observed between the FOs. The peak pressure under the medial midfoot increased significantly with all FOs, and a maximal increase in the peak pressure was obtained with a 30° inverted angle orthosis. Furthermore, the contact area under the medial midfoot and rearfoot increased significantly with all FOs, compared with the shoe only condition (p <0.05). Again, no significant differences were observed between the FOs. For plantar pressure redistribution, a FO with a low inverted angle could be effective, accommodative, and convenient for children with flatfoot.

Influence of pelvic asymmetry and idiopathic scoliosis in adolescents on postural balance during sitting.

The effects of pelvic asymmetry and idiopathic scoliosis on postural balance during sitting were studied by measuring inclination angles, pressure distribution, and electromyography. Participants were classified into a control group, pelvic asymmetry group, scoliosis group, and scoliosis with pelvic asymmetry and then performed anterior, posterior, left, and right pelvic tilting while sitting on the unstable board for 5 seconds to assess their postural balance. Inclination and obliquity angles between the groups were measured by an accelerometer located on the unstable board. Pressure distribution (maximum force and peak pressure) was analyzed using a capacitive seat sensor. In addition, surface electrodes were attached to the abdominal and erector spinae muscles of each participant. Inclination and obliquity angles increased more asymmetrically in participants with both pelvic asymmetry and scoliosis than with pelvic asymmetry or scoliosis alone. Maximum forces and peak pressures of each group showed an asymmetrical pressure distribution caused by the difference in height between the left and right pelvis and curve type of the patients' spines when performing anterior, posterior, left, and right pelvic tilting while sitting. Muscle contraction patterns of external oblique, thoracic erector spinae, lumbar erector spinae, and lumbar multifidus muscles may be influenced by spine curve type and region of idiopathic scoliosis. Asymmetrical muscle activities were observed on the convex side of scoliotic patients and these muscle activity patterns were changed by the pelvic asymmetry. From these results, it was confirmed that pelvic asymmetry and idiopathic scoliosis cause postural asymmetry, unequal weight distribution, and muscular imbalance during sitting.

Effects of custom-made rigid foot orthosis on pes planus in children over 6 years old.

OBJECTIVE: To identify the effects of a custom-made rigid foot orthosis (RFO) in children over six years old with pes planus. METHODS: The medical records of 39 children (mean age, 10.3±4.09 years) diagnosed with pes planus, fitted with RFOs, and had who more than two consecutive radiological studies were reviewed. The resting calcaneal stance position (RCSP), anteroposterior talocalcaneal angle (APTCA), lateral talocalcaneal angle (LTTCA), the lateral talometatarsal angle (LTTMA), and calcaneal pitch (CP) of both feet were measured to evaluate foot alignment. After diagnosis, children were fitted with a pair of RFOs and recommended to walk with heel strike and reciprocal arm swing to normalize the gait pattern. A follow-up clinical evaluation with radiological measurements was performed after 12-18 months and after 24 months of RFO application. Post-hoc analysis was used to test for significant differences between the radiological indicators and RCSP. RESULTS: With RFOs, all radiological indicators changed in the corrective direction except LTTCA. RCSP and CP in the third measurement showed significant improvement in comparison with the second and baseline measurements. Additionally, APTCA and LTTMA revealed improvements at the third measurement versus the baseline measurements. CONCLUSION: This study revealed that radiological indicators improved significantly after 24 months of RFO application. A prospective long-term controlled study with radiographical evaluation is necessary to confirm the therapeutic effects of RFOs and to determine the optimal duration of wear in children with pes planus.

The effect of electric cortical stimulation after focal traumatic brain injury in rats.

OBJECTIVE: To evaluate the effects of electric cortical stimulation in the experimentally induced focal traumatic brain injury (TBI) rat model on motor recovery and plasticity of the injured brain. METHOD: Twenty male Sprague-Dawley rats were pre-trained on a single pellet reaching task (SPRT) and on a Rotarod task (RRT) for 14 days. Then, the TBI model was induced by a weight drop device (40 g in weight, 25 cm in height) on the dominant motor cortex, and the electrode was implanted over the perilesional cortical surface. All rats were divided into two groups as follows: Electrical stimulation (ES) group with anodal continuous stimulation (50 Hz and 194 µs duration) or Sham-operated control (SOC) group with no electrical stimulation. The rats were trained SPRT and RRT for 14 days for rehabilitation and measured Garcia's neurologic examination. Histopathological and immunostaining evaluations were performed after the experiment. RESULTS: There were no differences in the slice number in the histological analysis. Garcia's neurologic scores & SPRT were significantly increased in the ES group (p<0.05), yet, there was no difference in RRT in both groups. The ES group showed more expression of c-Fos around the brain injured area than the SOC group. CONCLUSION: Electric cortical stimulation with rehabilitation is considered to be one of the trial methods for motor recovery in TBI. However, more studies should be conducted for the TBI model in order to establish better stimulation methods.

Effect of Stimulation Polarity of Transcranial Direct Current Stimulation on Non-dominant Hand Function.

OBJECTIVE: To evaluate motor excitability and hand function on the non-dominant side according to the polarity of transcranial direct current stimulation (tDCS) on the motor cortex in a healthy person. METHOD: tDCS was applied to the hand motor cortex for 15 minutes at an intensity of 1 mA in 28 healthy right-handed adults. Subjects were divided randomly into four groups: an anodal tDCS of the non-dominant hemisphere group, a cathodal tDCS of the non-dominant hemisphere group, an anodal tDCS of the dominant hemisphere group, and a sham group. We measured the motor evoked potential (MEP) in the abductor pollicis brevis and Jabsen-Taylor hand function test (JTT) in the non-dominant hand prior to and following tDCS. All study procedures were done under double-blind design. RESULTS: There was a significant increase in the MEP amplitude and a significant improvement in the JTT in the non-dominant hand following anodal tDCS of the non-dominant hemisphere (p<0.05). But there was no change in JTT and a significant decrease in the MEP amplitude in the non-dominant hand following cathodal tDCS on the non-dominant hemisphere and anodal tDCS of the dominant hemisphere. CONCLUSION: Non-dominant hand function is improved by increased excitability of the motor cortex. Although motor cortex excitability is decreased in a healthy person, non-dominant hand function is maintained. A homeostatic mechanism in the brain might therefore be involved in preserving this function. Further studies are warranted to examine brain functions to clarify this mechanism.