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Nevin Manimala Statistics

Prediction of the Occurrence of the Oculocardiac Reflex Based on the Assessment of Heart Rate Variability. An Observational Study

Ophthalmol Ther. 2022 Aug 1. doi: 10.1007/s40123-022-00549-0. Online ahead of print.

ABSTRACT

INTRODUCTION: Ophthalmic surgery is assumed to be safe, but some operations require general anaesthesia which is associated with a number of potential complications. In addition, adverse cardiovascular symptoms, such as severe slowing of the heart rate and, in some cases, cardiac arrest may occur due to the surgical technique. The aim of this study was to determine whether it is possible to predict the occurrence of oculocardiac reflex (OCR) based on heart rate variability (HRV) analysis for autonomic nervous system (ANS) activity assessment measured prior to the induction of anaesthesia and immediately before eyeball traction.

METHODS: Fifty-two adults of both sexes (age range 18-65 years) with American Society of Anesthesiologists (ASA) physical status class 1 and 2 were enrolled in this study. All patients had underwent episcleral buckling under general anaesthesia. High-frequency (HF) changes in HRV are thought to reflect parasympathetic impulse transmission, whereas low-frequency (LF) changes reflect both sympathetic and parasympathetic activity. However, in practice, LF changes can be considered to reflect sympathetic changes. Thus, the LF/HF ratio reflects the actual balance between sympathetic and parasympathetic activity. Based on that, frequency domain HRV parameters from 5-min Holter electrocardiogram recordings before anaesthesia induction and before eyeball traction were used for the analysis. The statistical analysis also included patient age, sex, ASA status and preanaesthesia and premanoeuvre heart rate and blood pressure.

RESULTS: Data from 42 patients were analysed. Oculocardiac reflex was observed in 32 patients (76.2%). No difference was found in the analysed parameters between patients with and without oculocardiac reflex. There was no relationship between the incidence of the OCR and the analysed parameters.

CONCLUSION: The prediction of OCR based on initial ANS tone was not possible, and the initial heart rate, blood pressure, age, sex, and ASA status were not helpful for the identification of patients at risk of this reflex.

TRIAL REGISTRATION: ClinicalTrials.gov identifier no.: NCT01714362.

PMID:35913657 | DOI:10.1007/s40123-022-00549-0

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Nevin Manimala Statistics

Randomized Versus Real-World Evidence on the Efficacy and Toxicity of Checkpoint Inhibitors in Cancer in Patients with Advanced Non-small Cell Lung Cancer or Melanoma: A Meta-analysis

Target Oncol. 2022 Aug 1. doi: 10.1007/s11523-022-00901-1. Online ahead of print.

ABSTRACT

BACKGROUND: Both randomized controlled trials (RCTs) and real-world evidence (RWE) studies provide results regarding the efficacy and toxicity of checkpoint inhibitors in cancer patients. The results from these two sources are considered complementary but whether they are comparable remains unknown.

OBJECTIVE: The aim of this study was to compare the efficacy and toxicity of checkpoint inhibitors between RCTs and RWE studies in patients with advanced non-small cell lung cancer (NSCLC) or melanoma.

PATIENTS AND METHODS: Two electronic databases were searched to identify eligible studies, either RCTs or RWE studies, investigating the efficacy or toxicity of checkpoint inhibitors given for indications that were approved by the European Medicines Agency (EMA) at the date of the last search. A meta-analysis was performed and the pooled estimates of objective response rates (ORR), progression-free survival (PFS), overall survival (OS), and toxicity and treatment discontinuation between RCTs and RWE studies were compared.

RESULTS: In total, 43 RWE studies and 15 RCTs were eligible, with adequate data for pooled estimates for immunotherapy indications regarding NSCLC and melanoma. No statistically significant or clinically meaningful differences in terms of pooled PFS, OS, or rates of treatment discontinuation due to toxicity between RCTs and RWE studies were observed. In some indications, a higher rate of response rates and lower rate of toxicity in favor of RWE was observed.

CONCLUSION: In patients with melanoma or NSCLC, the clinical value of checkpoint inhibitors is evident in both RCTs and real-world settings. Some differences in response or toxicity rates in favor of RWE mainly reflects the inherent difficulties in evaluating these outcomes in RWE studies.

PMID:35913645 | DOI:10.1007/s11523-022-00901-1

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Nevin Manimala Statistics

Top 5 AJSM Papers in Epidemiology and Statistics Over the Past 50 Years

Am J Sports Med. 2022 Aug;50(10):2595-2597. doi: 10.1177/03635465221113347.

NO ABSTRACT

PMID:35913617 | DOI:10.1177/03635465221113347

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Nevin Manimala Statistics

Analysis of a diffusive epidemic system with spatial heterogeneity and lag effect of media impact

J Math Biol. 2022 Aug 1;85(2):17. doi: 10.1007/s00285-022-01780-w.

ABSTRACT

We considered an SIS functional partial differential model cooperated with spatial heterogeneity and lag effect of media impact. The wellposedness including existence and uniqueness of the solution was proved. We defined the basic reproduction number and investigated the threshold dynamics of the model, and discussed the asymptotic behavior and monotonicity of the basic reproduction number associated with the diffusion rate. The local and global Hopf bifurcation at the endemic steady state was investigated theoretically and numerically. There exists numerical cases showing that the larger the number of basic reproduction number, the smaller the final epidemic size. The meaningful conclusion generalizes the previous conclusion of ordinary differential equation.

PMID:35913603 | DOI:10.1007/s00285-022-01780-w

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Nevin Manimala Statistics

A Simple Evolutionary Model of Genetic Robustness After Gene Duplication

J Mol Evol. 2022 Aug 1. doi: 10.1007/s00239-022-10065-1. Online ahead of print.

ABSTRACT

When a dispensable gene is duplicated (referred to the ancestral dispensability denoted by O+), genetic buffering and duplicate compensation together maintain the duplicate redundancy, whereas duplicate compensation is the only mechanism when an essential gene is duplicated (referred to the ancestral essentiality denoted by O). To investigate these evolutionary scenarios of genetic robustness, I formulated a simple mixture model for analyzing duplicate pairs with one of the following states: double dispensable (DD), semi-dispensable (one dispensable one essential, DE), or double essential (EE). This model was applied to the yeast duplicate pairs from a whole-genome duplication (WGD) occurred about 100 million years ago (mya), and the mouse duplicate pairs from a WGD occurred about more than 500 mya. Both case studies revealed that the proportion of essentiality for those duplicates with ancestral essentiality [PE(O)] was much higher than that for those with ancestral dispensability [PE(O+)]. While it was negligible in the yeast duplicate pairs, PE(O+) (about 20%) was shown statistically significant in the mouse duplicate pairs. These findings, together, support the hypothesis that both sub-functionalization and neo-functionalization may play some roles after gene duplication, though the former may be much faster than the later.

PMID:35913597 | DOI:10.1007/s00239-022-10065-1

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Nevin Manimala Statistics

General toxicity and genotoxicity of alternariol: a novel 28-day multi-endpoint assessment in male Sprague-Dawley rats

Mycotoxin Res. 2022 Aug 1. doi: 10.1007/s12550-022-00466-y. Online ahead of print.

ABSTRACT

Alternariol (AOH) is one of the toxins of Alternaria, and it has been widely detected in a variety of foods. It has been reported to be cytotoxic, dermally toxic, genotoxic, and potentially carcinogenic in vitro. However, in vivo toxicity data are lacking. This study used a novel in vivo 28-day multi-endpoint (Pig-a assay + micronucleus test + comet assay) genotoxicity evaluation system to evaluate the general toxicity and genotoxicity of AOH. A total of 42 male Sprague-Dawley rats were randomly distributed into three AOH-treated groups (5.51, 10.03, and 22.05 µg/kg bw), one AOH high-dose recovery group (AOH-HR, 22.05 µg/kg bw), one positive control group (N-ethyl-N-nitrosourea, 40 mg/kg bw), and two vehicle control groups (corn oil and PBS). Treatments were administered by oral gavage for 28 consecutive days. Histopathological lesions were observed in the liver, kidney, and spleen in all AOH-treated groups. No statistical difference was found in each genotoxicity index within 28 days in the AOH-treated groups compared with those in the corn oil group. On day 42, in the AOH-HR group, the rate of Pig-a mutant phenotype reticulocytes (RETCD59-) significantly increased. On day 56, both RETCD59- and the rate of Pig-a mutant phenotype erythrocytes (RBCCD59-) were significantly reduced. These findings indicated that AOH might cumulatively induce genetic mutations.

PMID:35913592 | DOI:10.1007/s12550-022-00466-y

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Nevin Manimala Statistics

Deep-learning prediction of amyloid deposition from early-phase amyloid positron emission tomography imaging

Ann Nucl Med. 2022 Aug 1. doi: 10.1007/s12149-022-01775-z. Online ahead of print.

ABSTRACT

OBJECTIVE: While the use of biomarkers for the detection of early and preclinical Alzheimer’s Disease has become essential, the need to wait for over an hour after injection to obtain sufficient image quality can be challenging for patients with suspected dementia and their caregivers. This study aimed to develop an image-based deep-learning technique to generate delayed uptake patterns of amyloid positron emission tomography (PET) images using only early-phase images obtained from 0-20 min after radiotracer injection.

METHODS: We prepared pairs of early and delayed [11C]PiB dynamic images from 253 patients (cognitively normal n = 32, fronto-temporal dementia n = 39, mild cognitive impairment n = 19, Alzheimer’s disease n = 163) as a training dataset. The neural network was trained with the early images as the input, and the output was the corresponding delayed image. A U-net convolutional neural network (CNN) and a conditional generative adversarial network (C-GAN) were used for the deep-learning architecture and the data augmentation methods, respectively. Then, an independent test data set consisting of early-phase amyloid PET images (n = 19) was used to generate corresponding delayed images using the trained network. Two nuclear medicine physicians interpreted the actual delayed images and predicted delayed images for amyloid positivity. In addition, the concordance of the actual delayed and predicted delayed images was assessed statistically.

RESULTS: The concordance of amyloid positivity between the actual versus AI-predicted delayed images was 79%(κ = 0.60) and 79% (κ = 0.59) for each physician, respectively. In addition, the physicians’ agreement rate was at 89% (κ = 0.79) when the same image was interpreted. And, the actual versus AI-predicted delayed images were not readily distinguishable (correct answer rate, 55% and 47% for each physician, respectively). The statistical comparison of the actual versus the predicted delated images indicated that the peak signal-to-noise ratio (PSNR) was 21.8 dB ± 2.2 dB, and the structural similarity index (SSIM) was 0.45 ± 0.04.

CONCLUSION: This study demonstrates the feasibility of an image-based deep-learning framework to predict delayed patterns of Amyloid PET uptake using only the early phase images. This AI-based image generation method has the potential to reduce scan time for amyloid PET and increase the patient throughput, without sacrificing diagnostic accuracy for amyloid positivity.

PMID:35913591 | DOI:10.1007/s12149-022-01775-z

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Nevin Manimala Statistics

The role of urethral ligation after AUS failure and end stage urethra

Int Urol Nephrol. 2022 Aug 1. doi: 10.1007/s11255-022-03315-0. Online ahead of print.

ABSTRACT

PURPOSE: To provide our single-center experience with an approach to refractory stress urinary incontinence (SUI) with permanent urethral ligation (PUL) and suprapubic tube (SPT) placement, in hopes of contributing to the limited body of research surrounding this surgical treatment option for patients with end-stage urethra (ESU).

METHODS: All patients undergoing PUL with SPT placement from 01/01/2018 to 04/30/2022 were identified from an institutional database. Institutional Review Board exempt status was granted for the conduct of this study. Patients were seen postoperatively at 1 month and 1 year. If there were any concerns of incontinence, an antegrade urethrogram via the SPT was performed. Descriptive statistics were used to evaluate patients.

RESULTS: Seven patients underwent PUL with SPT in our timeframe and were included in the study. All patients previously had an AUS placed, and two patients had a urethral sling previously placed. The median follow-up time was 21 months, ranging between 2 and 48 months. Complications included bladder spasms (43%) and continued leakage per urethra (14%). Of the 7 patients, 6 have reported continence through their urethra at their most recent follow-up.

CONCLUSION: This initial data suggest that PUL with SPT placement may be a viable surgical approach to treating refractory SUI, especially for patients with ESU who wish to avoid the morbidity associated with more formal supravesical diversion. Further study of this technique and longer follow-up is required to determine its long-term efficacy and tolerability for patients.

PMID:35913590 | DOI:10.1007/s11255-022-03315-0

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Nevin Manimala Statistics

Analysis of the Geographic Transmission Differences of COVID-19 in China Caused by Population Movement and Population Density

Bull Math Biol. 2022 Aug 1;84(9):94. doi: 10.1007/s11538-022-01050-2.

ABSTRACT

The coronavirus disease (COVID-19) has led to a global pandemic and caused huge healthy and economic losses. Non-pharmaceutical interventions, especially contact tracing and social distance restrictions, play a vital role in the control of COVID-19. Understanding the spatial impact is essential for designing such a control policy. Based on epidemic data of the confirmed cases after the Wuhan lockdown, we calculate the invasive reproduction numbers of COVID-19 in the different regions of China. Statistical analysis indicates a significant positive correlation between the reproduction numbers and the population input sizes from Wuhan, which indicates that the large-scale population movement contributed a lot to the geographic spread of COVID-19 in China. Moreover, there is a significant positive correlation between reproduction numbers and local population densities, which shows that the higher population density intensifies the spread of disease. Considering that in the early stage, there were sequential imported cases that affected the estimation of reproduction numbers, we classify the imported cases and local cases through the information of epidemiological data and calculate the net invasive reproduction number to quantify the local spread of the epidemic. The results are applied to the design of border control policy on the basis of vaccination coverage.

PMID:35913582 | DOI:10.1007/s11538-022-01050-2

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Nevin Manimala Statistics

Human epididymis protein 4 (HE4) is a novel immunohistochemical marker of neuroendocrine differentiation

Virchows Arch. 2022 Aug 1. doi: 10.1007/s00428-022-03387-4. Online ahead of print.

ABSTRACT

Human epididymis protein 4 (HE4) is originally described as an epididymis specific protein and now clinically used as a serum marker for ovarian carcinoma. However, the expression of HE4 in neuroendocrine neoplasms (NENs) has not been studied. By immunohistochemistry, the expressions of HE4 in 94 normal tissues and 484 NENs which included 242 well-differentiated NENs and 242 poorly differentiated NENs were studied. HE4 was positive in 90/94 (95.7%) of the neuroendocrine cells in normal tissues, 228/242 (94.2%) of well-differentiated NENs, and 206/242 (85.1%) of poorly differentiated NENs, and the expression of HE4 decreased progressively with loss of histological differentiation, with the positive rate of 96.2%, 92.7%, 92.3%, 85.4%, and 84.4% in NET-G1/carcinoid, NET-G2/atypical carcinoid, NET-G3, NEC-LC, and NEC-SC respectively. In NET-G1 and NET-G2, HE4 staining showed a peculiar polarized distribution, with an extraordinarily strong granular staining in subnuclear cytoplasm. A diffuse and uniform cytoplastic HE4 staining was observed in NET-G3 and poorly differentiated NENs. The positive rate of HE4 in primary tumors (91.1%, 387/425) was significantly higher than that of metastases (79.7%, 47/59) (p < 0.05). In a series of 70 pure non-NENs poorly differentiated carcinomas, the specificity rate of HE4 was 92.9% (65/70), which was in line with that of Syn. The negative rate of HE4 was 87.0% (40/46) in the non-neuroendocrine components of the MiNEN cases, which was lower than that of the pure non-neuroendocrine carcinomas (92.9%, 65/70) but without statistical significance (p > 0.05). HE4 may prove to be a useful immunohistochemical marker of neuroendocrine differentiation, although comparative studies and a more extensive analysis of other tissue types are necessary.

PMID:35913578 | DOI:10.1007/s00428-022-03387-4