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Nevin Manimala Statistics

Coronary artery restenosis treatment with plain balloon, drug-coated balloon, or drug-eluting stent: 10-year outcomes of the ISAR-DESIRE 3 trial

Eur Heart J. 2023 Feb 21:ehad026. doi: 10.1093/eurheartj/ehad026. Online ahead of print.

ABSTRACT

AIMS: The best interventional strategy for the treatment of drug-eluting stent (DES) in-stent restenosis (ISR) is still unclear and no data from randomized trials beyond 3-year follow-up are available. We aimed to define 10-year comparative efficacy and safety of plain balloon (PB), paclitaxel-coated balloon (PCB), and paclitaxel-eluting stent (PES) for percutaneous coronary intervention (PCI) of DES-ISR.

METHODS AND RESULTS: Clinical follow-up of patients randomly assigned to PB, PCB, and PES in the ISAR-DESIRE 3 trial was extended to 10 years and events were independently adjudicated. The primary endpoint was a composite of cardiac death, target vessel myocardial infarction, target lesion thrombosis, or target lesion revascularization. The major secondary safety endpoint was a composite of cardiac death, target vessel myocardial infarction, or target lesion thrombosis. The major secondary efficacy endpoint was target lesion revascularization. Incidences by the Kaplan-Meier method were compared by the log-rank test. Risk estimation was primarily performed by Cox proportional hazards regression and supplemented by weighted Cox regression accounting for non-proportional hazards and Royston-Parmar flexible parametric regression with a time-varying coefficient. Primary results were further assessed by landmark, lesion-level, per-protocol, and competing risk analyses. A total of 402 patients (500 lesions) with DES-ISR were randomly assigned to PB angioplasty (134 patients, 160 lesions), PCB angioplasty (137 patients, 172 lesions), and PES implantation (131 patients, 168 lesions). Clinical follow-up did not significantly differ among treatments [PB, 9.62 (4.50-10.02) years; PCB, 10.01 (5.72-10.02) years; PES, 9.08 (3.14-10.02) years; P = 0.300]. At 10 years, the primary composite endpoint occurred in 90 patients (72.0%) assigned to PB, 70 patients (55.9%) assigned to PCB, and 72 patients (62.4%) assigned to PES (P < 0.001). The pairwise comparison between PCB and PES resulted in a non-significant difference [multiplicity-adjusted P = 0.610; Grambsch-Therneau P = 0.004; weighted Cox: hazard ratio (HR) 1.10, 95% confidence interval (CI) 0.80-1.51; Cox: HR 1.10, 95% CI 0.79-1.52; Royston-Parmar: HR 1.08, 95% CI 0.72-1.60]. The major secondary safety endpoint occurred in 39 patients (34.1%) assigned to PB, 39 patients (34.0%) assigned to PCB, and 42 patients (40.0%) assigned to PES (P = 0.564). Target lesion revascularization occurred in 71 patients (58.0%) assigned to PB, 55 patients (43.9%) assigned to PCB, and 42 patients (38.6%) assigned to PES (P < 0.0001). The pairwise comparison between PES and PCB resulted in a non-significant difference (multiplicity-adjusted P = 0.282; Grambsch-Therneau P = 0.002; weighted Cox: HR 0.83, 95% CI 0.56-1.22; Cox: HR 0.81, 95% CI 0.54-1.21; Royston-Parmar: HR 0.75, 95% CI 0.47-1.20). Lesion-level and per-protocol analyses were consistent. At landmark analyses, an excess of death and cardiac death associated with PES compared with PCB was observed within 5 years after PCI, though 10-year differences did not formally reach the threshold of statistical significance after adjustment for multiplicity. Competing risk regression confirmed a non-significant difference in target lesion revascularization between PCB and PES and showed an increased risk of death associated with PES compared with PCB.

CONCLUSION: Ten years after PCI for DES-ISR, the primary and major secondary endpoints between PCB and PES were not significantly different. However, an excess of death and cardiac death within 5 years associated with PES and the results of the competing risk analysis are challenging to interpret and warrant further analysis. PES and PCB significantly reduced target lesion revascularization compared with PB.

PMID:36807512 | DOI:10.1093/eurheartj/ehad026

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Nevin Manimala Statistics

The in vitro biomechanics of anterior arch expansion using fixed lingual appliances with coil springs or archwire stops

Orthod Craniofac Res. 2023 Feb 20. doi: 10.1111/ocr.12640. Online ahead of print.

ABSTRACT

INTRODUCTION: The presented study investigates differences in the biomechanics of straight and mushroom fixed lingual appliances when implementing coil springs and stops for anterior arch expansion.

MATERIALS AND METHODS: An in vitro orthodontic simulator was used to measure three-dimensional forces and moments on each tooth of a simulated maxillary arch. Mushroom and straight archwire forms of 0.016″ NiTi round archwire were considered, using 0.010″x0.030″ NiTi open coils and 0.016″-0.018″ archwire stops (n=44 per group). Teeth in the anterior dental arch were moved from a neutral to crowded position to replicate anterior crowding of central and lateral incisors. Forces and moments of interest for lateral incisors and first premolars were compared using repeated measures mixed multivariate analysis of variance (α=0.05).

RESULTS: Three comparisons between straight vs. mushroom archwires and two comparisons of coil springs vs. stops were not statistically significant. Overall, it was found that use of a straight lingual archwire produced larger differences in forces and moments between using stops and coil springs than when using a mushroom archwire. Using stops produced larger forces and moments for both types of archwires as compared to using coil springs. The largest expansion forces were produced using straight archwires with stops, exceeding 3.0 N of force. Straight archwires with coil springs produced the lowest expansion forces on lateral incisors, just exceeding 1.5 N.

CONCLUSIONS: The findings of this study have elucidated significant differences in the biomechanics of transverse arch expansion using straight or mushroom fixed lingual appliances with coil springs or stops.

PMID:36807468 | DOI:10.1111/ocr.12640

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Nevin Manimala Statistics

Intraobserver and Interobserver Reproducibility of Breast Diffusion-Weighted Imaging Quantitative Parameters: Readout-Segmented vs. Single-Shot Echo-Planar Imaging

J Magn Reson Imaging. 2023 Feb 21. doi: 10.1002/jmri.28655. Online ahead of print.

ABSTRACT

BACKGROUND: The recommended technique for breast diffusion-weighted imaging (DWI) acquisitions is not sufficiently standardized in clinical practice.

PURPOSE: To investigate the intraobserver and interobserver reproducibility of DWI measurements, diffusion-kurtosis imaging (DKI) parameters, and image quality evaluation in breast lesions between single-shot echo-planar imaging (ss-EPI) and readout-segmented echo-planar imaging (rs-EPI).

STUDY TYPE: Prospective.

POPULATION: A total of 295 women with 209 malignant and 86 benign breast lesions.

FIELD STRENGTH/SEQUENCE: A 3-T; fat-saturated T2-weighted MR imaging (T2WI); multi-b-value DWI with both ss-EPI and rs-EPI readouts; T1-weighted dynamic contrast-enhanced MRI (DCE-MRI).

ASSESSMENT: Mean kurtosis (MK), mean diffusion (MD), and apparent diffusion coefficient (ADC) values were measured for each lesion on ss-EPI and rs-EPI, respectively. Image quality was visually evaluated regarding image sharpness, geometric distortion, lesion conspicuity, visualization of anatomic structures, and overall quality. Quantitative and qualitative analyses were performed twice with a time interval of 2 weeks.

STATISTICAL TESTS: Intraobserver and interobserver reproducibility were evaluated using intra-class correlation coefficients (ICC), within-subject coefficient of variation (wCV), and Bland-Altman plots.

RESULTS: MK, MD, and ADC quantitative parameters for breast lesions showed excellent intraobserver and interobserver reproducibility, with ICCs >0.75 and wCV values ranging from 2.51% to 7.08% for both sequences. The wCV values in both intraobserver and interobserver measurements were higher in the ss-EPI sequence (3.63%-7.08%) than that of the rs-EPI sequence (2.51%-3.62%). The wCV values differed in subgroups with different histopathological types of lesions, breast density, lesion morphology, and lesion sizes, respectively. Furthermore, rs-EPI (ICCs, 0.76-0.97; wCV values, 2.41%-6.04%) had better intraobserver and interobserver reproducibility than ss-EPI (ICCs, 0.54-0.90; wCV values, 6.18%-13.69%) with regard to image quality.

DATA CONCLUSION: Compared to the ss-EPI, the rs-EPI sequence showed higher intraobserver and interobserver reproducibility for quantitative diffusion-related parameters and image quality assessments measured in breast DWI and DKI.

EVIDENCE LEVEL: 2.

TECHNICAL EFFICACY: Stage 2.

PMID:36807457 | DOI:10.1002/jmri.28655

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Nevin Manimala Statistics

Associations between actigraphy-derived rest-activity rhythm characteristics and hypertension in United States adults

J Sleep Res. 2023 Feb 20:e13854. doi: 10.1111/jsr.13854. Online ahead of print.

ABSTRACT

People with disrupted circadian rhythms, such as shift workers, have shown a higher risk of hypertension. However, it is unclear whether more subtle differences in diurnal rest-activity rhythms in the population are associated with hypertension. Clarifying the association between the rest-activity rhythm, a modifiable behavioural factor, and hypertension could provide insight into preventing hypertension and possibly cardiovascular diseases. In this study, we investigated the association between rest-activity rhythm characteristics and hypertension in a large representative sample of United States adults. Cross-sectional data were obtained from the National Health and Nutrition Examination Survey 2011-2014 (N = 6726; mean [range] age 49 [20-79] years; 52% women). Five rest-activity rhythm parameters (i.e., pseudo F statistic, amplitude, mesor, amplitude:mesor ratio, and acrophase) were derived from 24-h actigraphy data using the extended cosine model. We performed multiple logistic regression to assess the associations between the rest-activity rhythm parameters and hypertension. Subgroup analysis stratified by age, gender, race/ethnicity, body mass index and diabetes status was also conducted. A weakened overall rest-activity rhythm, characterised by a lower F statistic, was associated with higher odds of hypertension (odds ratio quintile 1 versus quintile 5 [OR Q1vs.Q5 ] 1.61, 95% confidence interval [CI] 1.26-2.05; p trend < 0.001). Similar results were found for lower amplitude (OR Q1vs.Q5 1.51, 95% CI 1.13-2.03; p trend = 0.01) and amplitude:mesor ratio (OR Q1vs.Q5 1.34, 95% CI 1.01-1.78; p trend = 0.03). The results were robust to the adjustment of confounders, individual behaviours including physical activity levels and sleep duration and appeared consistent across subgroups. Possible interaction between the rest-activity rhythm and body mass index was found. Our results support an association between weakened rest-activity rhythms and higher odds of hypertension.

PMID:36807441 | DOI:10.1111/jsr.13854

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Nevin Manimala Statistics

An experimental, computational, and uncertainty analysis study of the rates of iodoalkane trapping by DABCO in solution phase organic media

Phys Chem Chem Phys. 2023 Feb 20. doi: 10.1039/d2cp05286e. Online ahead of print.

ABSTRACT

NMR spectroscopy was used to measure the rates of the first and second substitution reactions between iodoalkane (R = Me, 1-butyl) and DABCO in methanol, acetonitrile and DMSO. Most of the reactions were recorded at three different temperatures, which permitted calculation of the activation parameters from Eyring and Arrhenius plots. Additionally, the reaction rate and heat of reaction for 1-iodobutane + DABCO in acetonitrile and DMSO were also measured using calorimetry. To help interpret experimental results, ab initio calculations were performed on the reactant, product, and transition state entities to understand structures, reaction enthalpies and activation parameters. Markov chain Monte Carlo statistical sampling was used to determine a distribution of kinetic rates with respect to the uncertainties in measured concentrations and correlations between parameters imposed by a kinetics model. The reactions with 1-iodobutane are found to be slower in all cases compared to reactions under similar conditions for iodomethane. This is due to steric crowding around the reaction centre for the larger butyl group compared to methyl which results in a larger activation energy for the reaction.

PMID:36807434 | DOI:10.1039/d2cp05286e

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Nevin Manimala Statistics

Immunogenic Cell Death Inducing Metal Complexes for Cancer Therapy

Angew Chem Int Ed Engl. 2023 Feb 21:e202300662. doi: 10.1002/anie.202300662. Online ahead of print.

ABSTRACT

Cancer is one of the deadliest diseases worldwide. Recent statistics have shown that metastases and tumor relapse are the leading causes of cancer-associated deaths. While traditional treatments are able to efficiently remove the primary tumor, secondary tumors remain poorly accessible. Capitalizing on this there is an urgent need for novel treatment modalities. Among the most promising approaches, increasing research interest has been devoted to immunogenic cell death inducing agents that are able to trigger localized cell death of the cancer cells as well as induce an immune response inside the whole organism. Preliminary studies have shown that immunogenic cell death inducing compounds could be able to overcome metastatic and relapsing tumors. Herein, the application of metal complexes as immunogenic cell death inducing compounds is systematically reviewed.

PMID:36807420 | DOI:10.1002/anie.202300662

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Nevin Manimala Statistics

Gene-environment interaction analysis via deep learning

Genet Epidemiol. 2023 Feb 19. doi: 10.1002/gepi.22518. Online ahead of print.

ABSTRACT

Gene-environment (G-E) interaction analysis plays an important role in studying complex diseases. Extensive methodological research has been conducted on G-E interaction analysis, and the existing methods are mostly based on regression techniques. In many fields including biomedicine and omics, it has been increasingly recognized that deep learning may outperform regression with its unique flexibility (e.g., in accommodating unspecified nonlinear effects) and superior prediction performance. However, there has been a lack of development in deep learning for G-E interaction analysis. In this article, we fill this important knowledge gap and develop a new analysis approach based on deep neural network in conjunction with penalization. The proposed approach can simultaneously conduct model estimation and selection (of important main G effects and G-E interactions), while uniquely respecting the “main effects, interactions” variable selection hierarchy. Simulation shows that it has superior prediction and feature selection performance. The analysis of data on lung adenocarcinoma and skin cutaneous melanoma overall survival further establishes its practical utility. Overall, this study can advance G-E interaction analysis by delivering a powerful new analysis approach based on modern deep learning.

PMID:36807383 | DOI:10.1002/gepi.22518

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Nevin Manimala Statistics

Deep Learning Approach for MRI in the Classification of Anterior Talofibular Ligament Injuries

J Magn Reson Imaging. 2023 Feb 20. doi: 10.1002/jmri.28649. Online ahead of print.

ABSTRACT

BACKGROUND: Diagnosing anterior talofibular ligament (ATFL) injuries differs among radiologists. Further assessment of ATFL tears is valuable for clinical decision-making.

PURPOSE: To establish a deep learning method for classifying ATFL injuries based on magnetic resonance imaging (MRI).

STUDY TYPE: Retrospective.

POPULATION: One thousand seventy-three patients from a single center with ankle MRI within 1 month of reference standard arthroscopy (in-group dataset), were divided into training, validation, and test sets in a ratio of 8:1:1. Additionally, 167 patients from another center were used as an independent out-group dataset.

FIELD STRENGTH/SEQUENCE: Fat-saturation proton density-weighted fast spin-echo sequence at 1.5/3.0 T.

ASSESSMENT: Patients were divided into normal, strain and degeneration, partial tear and complete tear groups (groups 0-3). The complete tear group was divided into five sub-groups by location and the potential avulsion fracture (groups 3.1-3.5). All images were input into AlexNet, VGG11, Small-Sample-Attention Net (SSA-Net), and SSA-Net + Weight Loss for classification. The results were compared with four radiologists with 5-30 years of experience.

STATISTICAL TESTS: Model performance was evaluated by the receiver operating characteristic (ROC) curve, the area under the ROC curve (AUC), and so on. McNemar’s test was used to compare performance among the different models, and between the radiologists and models. The intraclass correlation coefficient (ICC) was used to assess the reliability of the radiologists. P < 0.05 was considered statistically significant.

RESULTS: The average AUC of AlexNet, VGG11, SAA-Net, and SSA-Net + Weight Loss was 0.95, 0.99, 0.99, 0.99 in groups 0-3 and 0.96, 0.99, 0.99, 0.99 in groups 3.1-3.5. The effect of SSA-Net + Weight Loss was similar to SSA-Net but better than AlexNet and VGG11. In the out-group test set, the AUC of SSA-Net + Weight Loss ranged from 0.89 to 0.99. The ICC of radiologists was 0.97-1.00. The effect of SSA-Net + Weight Loss was better than each radiologist in the in-group and out-group test sets.

DATA CONCLUSION: Deep learning has potential to be used for classifying ATFL injuries. SSA-Net + Weight Loss has a better diagnostic effect than radiologists with different experience levels.

LEVEL OF EVIDENCE: 4 TECHNICAL EFFICACY: Stage 2.

PMID:36807381 | DOI:10.1002/jmri.28649

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Nevin Manimala Statistics

Emergent Majorana zero-modes in an intrinsic anti-ferromagnetic topological superconductor Mn2B2 monolayer

Phys Chem Chem Phys. 2023 Feb 20. doi: 10.1039/d2cp05523f. Online ahead of print.

ABSTRACT

Topological superconductors (TSCs) are an exotic field due to the existence of Majorana zero-modes (MZM) in the edge states that obey non-Abelian statistics and can be used to implement topological quantum computations, especially for two-dimensional (2D) materials. Here we predict manganese diboride (Mn2B2) as an intrinsic 2D anti-ferromagnetic (AFM) TSC based on the magnetic and electronic structures of Mn and B atoms. Once Mn2B2 ML enters a superconducting state, MZM will be induced by the spin-polarized helical gapless edge states. The Z2 topological non-trivial properties are confirmed by Wannier charge centers (WCC) and the platform of the spin Hall conductivity near the Fermi level. Phonon-electron coupling (EPC) implies s-wave superconductivity and the critical temperature (Tc) is 6.79 K.

PMID:36807355 | DOI:10.1039/d2cp05523f

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Nevin Manimala Statistics

‘Potentially curative therapies’ for hepatocellular carcinoma: how many patients can actually be cured?

Br J Cancer. 2023 Feb 17. doi: 10.1038/s41416-023-02188-z. Online ahead of print.

ABSTRACT

BACKGROUND: Treatment of hepatocellular carcinoma (HCC) is predicated on early diagnosis such that ‘curative therapies’ can be successfully applied. The term ‘curative’ is, however, poorly quantitated. We aimed to complement our previous work by developing a statistical model to predict cure after ablation and to use this analysis to compare the true curative potential of the various ‘curative’ therapies.

METHODS: We accessed data from 1571 HCC patients treated in 5 centres receiving radiofrequency (RFA) or microwave (MWA) ablation and used flexible parametric modelling to determine the curative fraction. The results of this analysis were then combined with our previous estimations to provide a simple calculator applicable to all patients undergoing potentially curative therapies.

RESULTS: The cure fraction was 18.3% rising to about 40% in patients with good liver function and very small tumours.

CONCLUSION: Cure for HCC treated with ablation occurs in the order of 20% to 30%, similar to that achievable by resection but much inferior to transplantation where the analogous figure is >70%. We provide a ‘calculator’ that permits clinicians to estimate the chance of cure for any individual patient, based on readily available clinical features.

PMID:36807338 | DOI:10.1038/s41416-023-02188-z