A Practical Approach in Refining Binary Outcome for Treatment Effect of COVID-19 According to Geographical Diversity

The recent COVID-19 pandemic has drawn attention to health and economics worldwide. Initially, diseases only ravage local populations, while a pandemic could aggravate global economic burdens. Lopinavir/Ritonavir is an anti-HIV drug that was used on small scale patients during SARS, but its effectiveness for COVID-19 treatment is still unclear. Previous studies or meta-analysis have retrieved clinical data of subgroup analysis to evaluate the efficacy and safety of Lopinavir/Ritonavir for the treatment of COVID-19 in a few affected regions. However, geographical diversity and small number of studies bias correction were not achieved in such subgroup analysis of published meta-analysis. The present study demonstrates a practical approach in refining the binary outcome for COVID-19 treatment of Lopinavir/Ritonavir according to geographical location diversity and small number of studies (less than or equal to five) for subgroup analysis. After performing practical approach, the risk of adverse event with LPV/RTV for treatment of COVID-19 becomes nonsignificant compared to previous meta-analysis. Furthermore, we also notice heterogeneity of random effect of meta-analysis may be declined after proposed adjustment. In conclusion, proposed practical approach is recommend for performing a subgroup analysis to avoid concentration in a single geographical location and small number of studies bias

Trends and Age-Period-Cohort Effects of Fertility Rate: Analysis of 26,224 Married Women in Taiwan

Taiwan and a few Asian societies have had among the lowest fertility rates in the world for the past decade. Understanding the reasons behind the low fertility and designing policies accordingly to improve fertility has been a priority of governments in the region. It what follows we examine the low fertility rate in Taiwan by studying the trend of actual fertility rate and desired fertility rate in Taiwan using an age-period-cohort (APC) model. Using the Knowledge, Attitude, and Practice (KAP) of contraception survey data between 1973 and 2004, we applied APC analyses on the actual fertility rate and desired fertility rate of married women. We found that youngest cohorts (the mid-cohort year 1983) had 10% higher actual fertility and 15% higher desired fertility compared to those who were born in 1959–1965, respectively. Additionally, we attributed current lowest-low fertility (at or below 1.3) to late marriages. There is a lag between the actual and desired fertility rates in KAP survey due to tempo effect. Furthermore, the trends of the cohort effects of both fertility rates in KAP surveys are reversing in Taiwan. Consequently, increase total fertility rate (TFR) should encourage marriage among the marriageable population and reward married and childbearing households

Comment on Vidart et al. Relationship among Low T3 Levels, Type 3 Deiodinase, Oxidative Stress, and Mortality in Sepsis and Septic Shock: Defining Patient Outcomes. <i>Int. J. Mol. Sci.</i> 2023, <i>24</i>, 3935

In a previously published article, Vidart and colleagues conducted a prospective cohort study to explore the correlation between T3 levels and the risk of sepsis and septic shock in patients, with a follow-up period of 28 days or until deceased. The authors concluded that patients with sepsis and septic shock exhibited a significantly high risk of having low T3 levels. This research provides valuable insights into the clinical perspective in this particular field. However, certain clinical considerations should be addressed to enhance the study’s merit for researchers

Detecting differentially expressed genes in heterogeneous diseases using control-only analysis of variance

Purpose: Microarray technology allows for simultaneously screening many genes and determining which gene(s) are differentially expressed in different disease statuses or different cell types. The analysis of variance (ANOVA) (for a K-sample situation with K &gt; 2) can be used in such occasions to gauge statistical significances. However, the test may be underpowered if the diseases under study are heterogeneous. Methods: The authors propose the &quot;control-only ANOVA&quot; for detecting differentially expressed genes in heterogeneous diseases. Monte-Carlo simulation shows that the test produces quite accurate type 1 error rates for both normal and non-normal data. The statistical power of the control-only ANOVA is higher than that of the conventional ANOVA when the diseases under study are heterogeneous. Results: Analysis of a real data set shows that after Bonferroni correction, the control-only ANOVA detects three differentially expressed genes, whereas the conventional ANOVA can detect only one. Conclusions: The control-only ANOVA is recommended for use when the diseases under study are heterogeneous. (C) 2012 Elsevier Inc. All rights reserved

Increased prevalence of obstructive sleep apnea in patients with pectus excavatum: A pilot study

Objective: Laryngomalacia is the most common congenital laryngeal anomaly and is associated with pectus excavatum (PE). Patients with laryngomalacia and patients with obstructive sleep apnea (OSA) both experience upper airway obstruction, and patients with laryngomalacia had been found to have a higher prevalence of PE. However, no studies have established the prevalence of OSA in patients with PE. We conducted this pilot study to evaluate the prevalence of OSA in patients with PE. Materials and Methods: A total of 42 patients ≥20 years old with PE who were admitted for Nuss surgery to correct PE in Taipei Tzu Chi Hospital between October 2015 and September 2016 were invited to participate in the study; 31 of the 42 patients agreed. All 31 patients completed an Epworth sleepiness scale questionnaire to evaluate excessive daytime sleepiness (EDS) and underwent overnight polysomnography to evaluate OSA before Nuss surgery. Results: The prevalence of snoring in the study participants was 100%. Ten of 31 patients (32.3%) reported EDS. The overall prevalence of OSA with an apnea/hypopnea index ≥5/h was 25.8%, and all patients with OSA were men. Conclusions: The prevalence of OSA in patients with PE seemed to be higher than that previously reported in the general population, implying that OSA might be a potential etiology or, at least, an aggravating factor for the development or progression of PE or might be responsible for the postoperative recurrence of PE in some patients. Further studies are needed to clarify this relationship

PUBLIC INTEREST STATEMENT

Abstract: Background: Microarray technology allows simultaneously detecting thousands of genes within one single experiment. The Student&apos;s t-test (for a twosample situation) can be used to compare the mean expression of a gene, taken from replicate arrays, to detect differential expression under the conditions being studied, such as a disease. However, a general statistical test may have insufficient power to correctly detect differentially expressed genes of heterogeneous and positively skewed data. Methods: Here we define a differentially expressed gene as with significantly different expression in means, variances, or both between the two groups of microarray. Monte Carlo simulation shows that the &quot;half Johnson&apos;s modified t-test&quot; maintains quite accurate type I error rates in normal and non-normal distributions. And the half Johnson&apos;s modified t-test was more powerful than the half Student&apos;s t-test overall when the ratio of standard deviations between case and control groups is greater than 1. Results: Analysis of a colon cancer data shows that when the false discovery rate (FDR) is controlled at 0.05, the half Johnson&apos;s modified t-test can detect 429 differentially expressed genes, which is larger than the number of differentially expressed genes (i.e. 344) detected by the half Student&apos;s t. To ABOUT THE AUTHOR I-Shiang Tzeng is a doctoral researcher in the National Translational Medicine and Clinical trial Resource Center (NTCRC) composed by Academia Sinica, National Taiwan University and National Yang-Ming University, Taiwan. He currently serves as a bioinformatics and biostatistics consultant in NTCRC. He also is an adjunct assistant professor in the department of statistics, National Taipei University, Taiwan. His area of research includes biostatistics and epidemiologic method and further studies proposing the potential powerful method to detect differential expressed genes. His research interests include the field of ageperiod-cohort (APC) modeling from social issues to biological issues as well as the analysis of the APC models that arise in all these applications. PUBLIC INTEREST STATEMENT Gene expression has been a popular research topic in recent years. Student&apos;s t-test is commonly adopted to screen disease-related genes. However, when the researches are focused on heterogeneous and positively skewed expression data, the means of gene expression levels between case and control groups may be similar, and thus, the difference would be insignificant using conventional Student&apos;s t-test. This study proposed half Johnson&apos;s modified t-test to correctly detect differentially expressed genes of heterogeneous and positively skewed data. Test statistics of half Johnson&apos;s modified t-test only considers sample standard deviation of control group, while that of case group is not included. After controlling false discovery rate (cut-off point set at 0.05) of colon cancer gene expression data, half Johnson&apos;s modified t-test could detect 364 more significant genes than conventional Student&apos;s t-test. Half Student t-test is worth recommending as a method for detecting differentially expressed genes in heterogeneous and positively skewed data. . Conclusions: The half Johnson&apos;s modified t-test is recommended for the detection of differentially expressed genes in heterogeneous and ONLY positively skewed data

The healing effect of the collagen-glycosaminoglycan copolymer on corneal thinning

Abstract Background To study the healing processes of partial thickness wounds in the adult rabbit cornea after grafting a porous collagen-glycosaminoglycan copolymer matrix (CG). Methods In this study, the regeneration of surgically-induced rabbit corneal defect implanted with CG was investigated. The corneal partial thickness wound was created by 7.5 mm trephine. The wound was implanted with CG. Effects on wound healing was analyzed using clinical data on epithelial migration and corneal thickness, and histological data on collagen and alpha smooth muscle actin distribution. Results Compared with control group, CG induced a relatively severe inflammatory reaction in grafted cornea until the CG matrix was completely degraded. The new vessel ingrowth and stromal regeneration maintained the corneal thickness. The grafted cornea was significantly thicker (P < 0.001) than the control group. On day 90, the corneal opacity score of the control group was one and the grafted cornea was two. Conclusion CG copolymer matrix can successfully repair the damaged corneal stroma by injury, and regain its thickness. However, CG matrix induced inflammatory healing process thus causing mild corneal haziness and neovascularization

Artificial Intelligence-Assisted Chest X-ray for the Diagnosis of COVID-19: A Systematic Review and Meta-Analysis

Because it is an accessible and routine image test, medical personnel commonly use a chest X-ray for COVID-19 infections. Artificial intelligence (AI) is now widely applied to improve the precision of routine image tests. Hence, we investigated the clinical merit of the chest X-ray to detect COVID-19 when assisted by AI. We used PubMed, Cochrane Library, MedRxiv, ArXiv, and Embase to search for relevant research published between 1 January 2020 and 30 May 2022. We collected essays that dissected AI-based measures used for patients diagnosed with COVID-19 and excluded research lacking measurements using relevant parameters (i.e., sensitivity, specificity, and area under curve). Two independent researchers summarized the information, and discords were eliminated by consensus. A random effects model was used to calculate the pooled sensitivities and specificities. The sensitivity of the included research studies was enhanced by eliminating research with possible heterogeneity. A summary receiver operating characteristic curve (SROC) was generated to investigate the diagnostic value for detecting COVID-19 patients. Nine studies were recruited in this analysis, including 39,603 subjects. The pooled sensitivity and specificity were estimated as 0.9472 (p = 0.0338, 95% CI 0.9009&ndash;0.9959) and 0.9610 (p &lt; 0.0001, 95% CI 0.9428&ndash;0.9795), respectively. The area under the SROC was 0.98 (95% CI 0.94&ndash;1.00). The heterogeneity of diagnostic odds ratio was presented in the recruited studies (I2 = 36.212, p = 0.129). The AI-assisted chest X-ray scan for COVID-19 detection offered excellent diagnostic potential and broader application

Simulating Expansion of the Intracranial Space to Accommodate Brain Swelling after Decompressive Craniectomy: Volumetric Quantification in a 3D CAD Skull Model with Contour Elevation

Background: Decompressive craniectomy (DC) can be used to augment intracranial space and halt brainstem compromise. However, a widely adopted recommendation for optimal surgical extent of the DC procedure is lacking. In the current study, we utilized three-dimensional (3D) computer-assisted design (CAD) skull models with defect contour elevation for quantitative assessment. Methods: DC was performed for 15 consecutive patients, and 3D CAD models of defective skulls with contour elevations (0–50 mm) were reconstructed using commercial software. Quantitative assessments were conducted in these CAD subjects to analyze the effects of volumetric augmentation when elevating the length of the contour and the skull defect size. The final positive results were mathematically verified using a computerized system for numerical integration with the rectangle method. Results: Defect areas of the skull CAD models ranged from 55.7–168.8 cm2, with a mean of 132.3 ± 29.7 cm2. As the contour was elevated outward for 6 mm or above, statistical significance was detected in the volume and the volume-increasing rate, when compared to the results obtained from the regular CAD model. The volume and the volume-increasing rate increased by 3.665 cm3, 0.285% (p &lt; 0.001) per 1 mm of contour elevation), and 0.034% (p &lt; 0.001) per 1 cm2 of increase of defect area, respectively. Moreover, a 1 mm elevation of the contour in Groups 2 (defect area 125–150 cm2) and 3 (defect area &gt;150 cm2, as a proxy for an extremely large skull defect) was shown to augment the volume and the volume-increasing rate by 1.553 cm3, 0.101% (p &lt; 0.001) and 1.126 cm3, 0.072% (p &lt; 0.001), respectively, when compared to those in Group 1 (defect area &lt;125 cm2). The volumetric augmentation achieved by contour elevation for an extremely large skull defect was smaller than that achieved for a large skull defect. Conclusions: The 3D CAD skull model contour elevation method can be effectively used to simulate the extent of a space-occupying swollen brain and to quantitatively assess the extent of brainstem protection in terms of volume augmentation and volume-increasing rate following DC. As the tangential diameter (representing the degree of DC) exceeded the plateau value, volumetric augmentation was attenuated. However, an increasing volumetric augmentation was detected before the plateau value was reached

Correlation of Immune-Inflammatory Markers with Clinical Features and Novel Location-Specific Nomograms for Short-Term Outcomes in Patients with Intracerebral Hemorrhage

(1) Background: We investigated the association of four immune-inflammatory markers with clinical features and established location-specific nomograms to predict mortality risk in patients with intracerebral hemorrhage (ICH). (2) Methods: We retrospectively enrolled 613 inpatients with acute ICH. (3) Results: Overall mortality was 22%, which was highest in pontine hemorrhage and lowest in thalamic hemorrhage. All four immune-inflammatory markers exhibited a positive linear correlation with glucose, ICH volume, ICH score, and discharge Modified Rankin Scale (mRS) score. Significant predictors of death due to lobar/putaminal hemorrhage were age, glucose and creatinine levels, initial Glasgow Coma Scale (GCS) score, ICH volume, and presence of intraventricular hemorrhage. None of the immune-inflammatory markers were significant predictors of unfavorable outcome or death. We selected significant factors to establish nomograms for predicting death due to lobar/putaminal, thalamic, pontine, and cerebellar hemorrhages. The C-statistic for predicting death in model I (comprising factors in the establishment of the nomogram) in each type of ICH was higher than that in model II (comprising ICH score alone), except for cerebellar hemorrhage. These nomograms for predicting death had good discrimination (C-index: 0.889 to 0.975) and prediction probabilities (C-index: 0.890 to 0.965). (4) Conclusions: Higher immune-inflammatory markers were associated with larger ICH volume, worse initial GCS, and unfavorable outcomes, but were not independent prognostic predictors. The location-specific nomograms provided novel and accurate models for predicting mortality risk