Efficacy and Safety of GHX02 in the Treatment of Acute Bronchitis and Acute Exacerbation of Chronic Bronchitis: A Phase Ⅱ, Randomized, Double-Blind, Placebo-Controlled, Multicenter Trial

Acute bronchitis and acute exacerbations of chronic bronchitis (AECB) have cough and sputum as the main symptoms with a high prevalence and substantial economic burden. Although the demand for bronchitis treatment increases due to causes, such as air pollution, the appropriateness of antibiotic prescriptions and the effects of current symptomatic treatments for bronchitis are unclear. GHX02, which is a combined formulation containing four herbs, and has been clinically used for bronchitis in South Korea. We conducted a phase II, randomized, double-blind, and placebo-controlled, multicenter trial to evaluate its efficacy and safety. Patients with acute bronchitis or AECB were recruited and randomized to receive high-dose GHX02 (1920 mg/day), standard-dose GHX02 (960 mg/day), or placebo for 7 days. The primary outcome measure was the change in Bronchitis Severity Score (BSS) from baseline to Day 7. The secondary outcomes were the frequency of coughing fits, Questionnaire of Clinical Symptoms of Cough and Sputum (QCSCS), Leicester Cough Questionnaire (LCQ), Integrative Medicine Outcome Scale (IMOS), and Integrative Medicine Patient Satisfaction Scale (IMPSS). A total of 117 patients were randomized to parallel groups (38 in the high-dose GHX02, 41 in the standard-dose GHX02 group, and 38 in the placebo group). The mean differences in BSS from baseline to Day 7 in the treatment groups (4.2 ± 2.0 and 4.5 ± 1.8 in the high-dose GHX02 and standard-dose GHX02 groups, respectively) were higher than the placebo group (3.8 ± 2.1), p = 0.028. The mean differences in the frequency of coughing fits from baseline to Day 7 and IMPSS were better in the GHX02 treatment group than in the placebo group (standard-dose GHX02 group vs placebo group, p = 0.036). The QCSCS, LCQ, IMOS, and GHX02 of the treatment groups also showed more improvement than the placebo group, but there were no statistically significant differences between the groups. There were no severe adverse effects during the trial. This study supports that GHX02 is effective and safe for patients with bronchitis and provides the basis for progression to a phase III study.Clinical Trial Registration: [https://cris.nih.go.kr] WHO International Clinical Trials Registry Platform, Clinical Research Information Service [KCT0003665].

Comparison of visual acuity measured by ETDRS based smart phone applications I sight pro and Peek acuity versus traditional Snellen\\\'s chart visual acuity in children 6-14 years in a tertiary care institute in India

Covid-19 pandemic has led to children missing schools due to which eye care screening activities at schools have taken a backseat. To mitigate this home based visual acuity estimation smartphone applications are increasingly being used for the purpose of tele-ophthalmology purposes, although with no validation of the same. We aim to fulfil this lacunae. Current study was a cross sectional analysis on 286 eyes of 148 children aged between 6years to 14years attending our OPD from April 2021 to June 2021, with non-acute ocular symptomatology. Snellen’s distant visual acuity was compared against the visual acuity recorded by smart phone based Isight pro app and Peek acuity smart phone app. Statistical analysis was performed by Bland Altmann analysis by using SPSS version 21 and p<0.05 was taken as the level of significance. The mean differences between the smartphone-based test Isight pro and the Snellen’s chart and the smartphone-based test Peek acuity and Snellen’s acuity data were 0.06 (95%CI, 0.04–0.08) and 0.07 (95%CI,0.05–0.09) logMAR, respectively. Time taken to test visual acuity by Snellen’s chart was approximately 118.2±21.38 seconds, whereas with Isight pro and Peek acuity smart phone apps the time for testing was approximately 92±15.88 seconds and 94.03±19.73 seconds respectively. P<0.05.The mean visual acuity was comparable with Snellen’s chart and ETDRS based smart phone apps like Isight pro and Peek acuity. The mean time to assess visual acuity was slightly more in Snellen’s acuity than with smart phone based apps. Inability to access eye care services through screening activities in schools has been mitigated effectively by using these smart phone apps. Hence these smart phone apps can be effectively used in tele-ophthalmologic practice and screening activities in these COVID-19 pandemic times.

Down-regulation of MEG3, PANDA and CASC2 as p53-related lncRNAs in breast cancer

TP53 encodes a major tumor suppressor protein which blocks carcinogenesis process in a variety of tissues including breast tissue. Expression and function of this gene is regulated by a number of long non-coding RNAs (lncRNAs) among them are PANDA, MEG3 and CASC2. We measured expression of TP53 and these transcripts in a cohort of Iranian breast cancer patients. Expression levels of TP53, MEG3, CASC2 and PANDA were significantly lower in tumoral samples compared with non-tumoral samples (Posterior mean differences = −4.26, −1.66, −5.98 and −3.13, respectively; P values < 0.0001). Expression of CASC2 was higher in Her2 1+ cases compared with Her2 negative cases (Beta = 1.85, P value = 0.037). Expression levels of MEG3 and TP53 were lower in grade 2 samples compared with grade 1 (Beta = −1.86, P value = 0.006 and Beta = −2.24, P value = 0.003, respectively). There was no other significant association between expression of genes and clinical variables. CASC2 had the best performance among these genes with area under curve value of 0.78 and sensitivity and specificity values of 56.33% and 88.73%, respectively (P value < 0.0001). The current investigation supports the role of TP53-related lncRNAs in the pathogenesis of breast cancer.

Validation of a Human Pose Tracking Algorithm for Measuring Upper Limb Joints: Comparison With Photography-based Goniometry

Background: Range of motion (ROM) measurements are essential for diagnosing and evaluating upper extremity conditions. Clinical goniometry is the most commonly used methods but it is time-consuming and skill-demanding. Recent advances in human tracking algorithm suggest potential for automatic angle measuring from RGB images. It provides an attractive alternative for at-distance measuring. However, the reliability of this method has not been fully established. The purpose of this study is to evaluate if the results of algorithm are as reliable as human raters in upper limb movements.Methods: Thirty healthy young adults (20 males, 10 females) participated in this study. Participants were asked to performed a 6-motion task including movement of shoulder, elbow and wrist. Images of movements were capture by commercial digital camera. Each movement was measured by a pose tracking algorithm and compared with the surgeon-measurement results. The mean differences between the two measurements were compared. Pearson correlation coefficients were used to determine the relationship. Reliability was investigated by the intra-class correlation coefficients.Results: Comparing this algorithm-based method with manual measurement, the mean differences were less than 3 degrees in 5 motions (shoulder abduction: 0.51; shoulder elevation: 2.87; elbow flexion:0.38; elbow extension:0.65; wrist extension: 0.78) except wrist flexion. All the intra-class correlation coefficients were larger than 0.60. The Pearson coefficients also showed high correlations between the two measurements (p<0.001). Conclusions: Our results indicated that pose estimation is a reliable method to measure the shoulder and elbow angles, supporting RGB images for measuring joint ROM. Our results proved the possibility that patients can assess their ROM by photos taken by a digital camera.Trial registration: This study was registered in the Clinical Trials Center of The First Affiliated Hospital, Sun Yat-sen University (2021-387).

Aortic valve repair for the treatment of rheumatic aortic valve disease: a systematic review and meta-analysis

Valvuloplasty for rheumatic aortic valve disease remains controversial. We conducted this study to explore whether aortic valvuloplasty is appropriate for the rheumatic population. A comprehensive search was conducted, and 7 eligible retrospective studies were identified from PubMed, Embase, Medline and Cochrane (up to April 7, 2020) according to the inclusion and exclusion criteria. The data for hospital mortality, 5-year survival, 5-year reoperation, aortic insufficiency grade (AIG) and aortic valve gradient (AVG) were extracted by 2 independent reviewers and were analysed to evaluate the safety and availability of aortic valvuloplasty for rheumatic patients. The heterogeneity of the results was estimated using the Q test and I2 statistics. The fixed pooling model was used when I2 ≤ 50%; otherwise, the random pooling model was selected. 7 articles with 418 patients were included. The pooled hospital mortality, 5-year survival and 5-year reoperation rates were 3.2%, 94.5% and 9.9%, respectively. The heterogeneities of the weighted mean differences (WMD) values of the AIG and AVG between preoperation and postoperation were extremely high (I2 = 81.5%, p < 0.001 in AIG, I2 = 97.6%, p = 0.003 in AVG). Subgroup analysis suggested that the AIG and AVG were improved by 3.03 grades (I2 = 0%, p < 0.001) and 3.16 mmHg (I2 = 0%, p < 0.001) in the European group, respectively. In the Asian group, the AIG and AVG were improved by 2.57 grades (I2 = 0%, p < 0.001) and 34.39 mmHg (I2 = 0%, p < 0.001), respectively. Compared with the values at discharge, the AIG was increased by 0.15 grades (I2 = 0%, p = 0.031) and the AVG was still decreased by 2.07 mmHg (I2 = 0%, p = 0.031) at the time of follow up. Valvuloplasty is safe and effective to treat rheumatic aortic insufficiency and stenosis, and the duration of maintenance required to improve stenosis was longer than that of insufficiency.

The influence of corneal density and thickness on tonometry measurement with goldmann applanation, non-contact and iCare tonometry methods

Purpose To evaluate the effect of corneal density and thickness on the accuracy of tonometry readings obtained via three most used techniques. Method Intraocular pressures of 45 patients’ right eyes were measured using Goldmann Applanation, iCare, and non-contact tonometry methods. Corneal parameters were obtained using the Pentacam Camera System. Data obtained were analyzed using Paired t Test, Pearson’s correlation coefficient, multiple linear regression analysis, and Bland–Altman plots. Results The mean corneal thickness was 545.4 ± 3.93 μm. The mean corneal density of total, stromal, 0–2 mm, and 2–6 mm zones were 27.85 ± 6.23 GSU, 24.61 ± 6.05 GSU, 20.76 ± 2.96 GSU, and 20.81 ± 3.51 GSU respectively. IOP readings had a statistically significant correlation with corneal stromal thickness, as well as with total and stromal density. The stromal density, however, showed higher correlation with the three tonometry methods than did the total density (iCare: − .482 (0.001) stromal density versus− .464 (0.001) total density, NCT: − .376 (0.011) versus − .353 (0.017), GAT: − .306 (0.041) versus − .296 (0.048)). Statistical differences were found in comparing the iCare readings with GAT (P < 0,00) and with NCT (P < 0,00), with mean differences of 1.8 mmHg ± 2.6 and 2.0 mmHg ± 2.6 respectively. GAT and NCT measurements showed no statistical difference (P > 0.05). Conclusion This study shows that both central corneal thickness and stromal density are significant influential factors of reliable IOP readings. It is necessary to consider more corneal biomechanical properties, as well as exercise a high degree of caution in any new attempts towards adjusting an IOP-correction equation.

Relationship of macular ganglion cell complex thickness to choroidal microvasculature drop-out in primary open-angle glaucoma

Background/aimsTo investigate the rate of ganglion cell complex (GCC) thinning in primary open-angle glaucoma (POAG) patients with and without deep-layer microvasculature drop-out (MvD).MethodsPOAG patients who had at least 1.5 years of follow-up and a minimum of three visits were included from the Diagnostic Innovations in Glaucoma Study. MvD was detected at baseline by optical coherence tomography angiography (OCT-A). Area and angular circumference of MvD were evaluated on en face choroidal vessel density images and horizontal B-scans. Rates of global and hemisphere GCC thinning were compared in MvD and non-MvD eyes using linear mixed-effects models.ResultsThirty-six eyes with MvD and 37 eyes without MvD of 63 patients were followed for a mean of 3.3 years. In 30 out of 36 eyes, MvD was localised in the inferotemporal region. While mean baseline visual field mean deviation was similar between the two groups (p=0.128), global GCC thinning was significantly faster in eyes with MvD than in those without MvD (mean differences: −0.50 (95% CI −0.83 to –0.17) µm/year; p=0.003)). Presence of MvD, area and angular circumference of MvD were independently associated with a faster rate of thinning (p=0.002, p=0.031 and p=0.013, respectively).ConclusionIn POAG eyes, GCC thinning is faster in eyes with MvD. Detection of MvD in OCT-A images can assist clinicians to identify patients who are at higher risk for central macula thinning and glaucomatous progression and may require more intensive management.

Quantifying the Opportunity Cost of Resident Involvement in Academic Orthopedic Shoulder Arthroplasty: A Matched – Pair Analysis

Background There is minimal work defining the economic impact of resident participation in shoulder arthroplasty. Thus, this study quantified the opportunity cost of resident participation in total shoulder arthroplasty (TSA) and hemiarthroplasty (HA) by determining differences in operative time, relative value units (RVUs)/hour, and RVUs/case. Methods A retrospective analysis of shoulder arthroplasty procedures were identified from the ACS-NSQIP database from 2006 to 2014 using CPT codes. Demographic, comorbidity, preoperative laboratory data and surgical procedure were used to develop matched cohorts. Mean differences in operative time, RVUs/case and RVUs/hour between attending-only (AO) cases and cases with resident involvement (RI) were examined. Cost analysis was performed to identify differences in RVUs generated per hour in dollars/case. Results A total of 1786 AO and 1102 RI cases were identified. With the exception of PGY-3 and PGY-4 cases, RI cases had lower mean operative times compared to AO cases. The cost of RI was highest for PGY-3 ($199.87 per case) and PGY-4 ($9 .2 9) residents with all other postgraduate years providing a cost reduction. Discussion Involvement of residents was associated with shorter operative times leading to a savings of $29.64 per case. Involvement of intermediate-level (PGY-3) residents were associated with increased costs that ultimately decreased as residents became more senior.