Obstetric Anesthesia and Heart Disease: Practical Clinical Considerations.
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ABSTRACT:
SUBMITTER: Meng ML
PROVIDER: S-EPMC8613767 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundCoronary artery disease (CAD) risk traditionally has been assessed using clinical risk factors. We evaluated whether molecular genetic markers for CAD risk could add information to traditional variables.MethodsWe developed a false discovery rate 267-marker genetic risk score (FDR267) from markers that were significantly associated with CAD in the UK Biobank cohort meta-analysis. FDR267 was tested in the Atherosclerosis Risk in Communities cohort using logistic regression and Cox proportional hazards analyses in the European and African American groups.ResultsOur genetic risk score (FDR267) was associated with a 1.45 (95% confidence interval, 1.39-1.51) increase in odds ratio and a 1.32 (95% confidence interval, 1.26-1.38) increase in hazard ratio per standard deviation of the score. The score modestly improved the area under the curve (AUC) statistic when added to a clinical model (ΔAUC = 0.0112, P = 0.0002). FDR267 predicted incident CAD (C-index = 0.60), although it did not improve on clinical risk factors (ΔAUC = 0.0159, P = 0.0965). Individuals in the top quintile of FDR267 genetic risk were at approximately 2-fold increased risk compared with the bottom quintile, which is comparable to risk associated with self-reported family history. The performance of FDR267 was less robust in the African American sample.ConclusionsFDR267 is significantly associated with CAD in the European sample, with an effect size comparable to self-reported family history. FDR267 discriminated between individuals with and without CAD, but did not improve CAD risk prediction over clinical variables. FDR267 was less predictive of CAD risk in African Americans.
| S-EPMC7063618 | biostudies-literature
Project description:Stopping for futility is a useful tool in a clinical trial. It is widely used in single-arm trials in oncology and in many two-arm trials. We review three stopping rules for futility. We give recommendations for the optimal timing of futility looks in two-stage trials in terms of the information fraction and the probability of stopping under the alternative hypothesis. We discuss futility stopping in trials with substantial uncertainty about the variability of the outcome and in crossover trials.
| S-EPMC7954786 | biostudies-literature
Project description:Molecular similarity has been effectively applied to many problems in cheminformatics and computational drug discovery, but modern methods can be prohibitively expensive for large-scale applications. The SCISSORS method rapidly approximates measures of pairwise molecular similarity such as ROCS and LINGO Tanimotos, acting as a filter to quickly reduce the size of a problem. We report an in-depth analysis of SCISSORS performance, including a mapping of the SCISSORS error distribution, benchmarking, and investigation of several algorithmic modifications. We show that SCISSORS can accurately predict multiconformer similarity and suggest a method for estimating optimal SCISSORS parameters in a data set-specific manner. These results are a useful resource for researchers seeking to incorporate SCISSORS into molecular similarity applications.
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Project description:Differential scanning calorimetry (DSC) studies of blood plasma are part of an emerging area of the clinical application of DSC to biofluid analysis. DSC analysis of plasma from healthy individuals and patients with various diseases has revealed changes in the thermal profiles of the major plasma proteins associated with the clinical status of the patient. The sensitivity of DSC to the concentration of proteins, their interactions with other proteins or ligands, or their covalent modification underlies the potential utility of DSC analysis. A growing body of literature has demonstrated the versatility and performance of clinical DSC analysis across a range of biofluids and in a number of disease settings. The principles, practice and challenges of DSC analysis of plasma are described in this article.
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Project description:Local noise power spectra (NPS) have been commonly calculated to represent the noise properties of CT imaging systems, but their properties are significantly affected by the utilized calculation schemes. In this study, the effects of varied calculation parameters on the local NPS were analyzed, and practical suggestions were provided regarding the estimation of local NPS for clinical CT scanners. The uniformity module of a Catphan phantom was scanned with a Philips Brilliance 64 slice CT simulator with varied scanning protocols. Images were reconstructed using FBP and iDose4 iterative reconstruction with noise reduction levels 1, 3, and 6. Local NPS were calculated and compared for varied region of interest (ROI) locations and sizes, image background removal methods, and window functions. Additionally, with a predetermined NPS as a ground truth, local NPS calculation accuracy was compared for computer simulated ROIs, varying the aforementioned parameters in addition to ROI number. An analysis of the effects of these varied calculation parameters on the magnitude and shape of the NPS was conducted. The local NPS varied depending on calculation parameters, particularly at low spatial frequencies below ~ 0.15 mm-1. For the simulation study, NPS calculation error decreased exponentially as ROI number increased. For the Catphan study the NPS magnitude varied as a function of ROI location, which was better observed when using smaller ROI sizes. The image subtraction method for background removal was the most effective at reducing low-frequency background noise, and produced similar results no matter which ROI size or window function was used. The PCA background removal method with a Hann window function produced the closest match to image subtraction, with an average percent difference of 17.5%. Image noise should be analyzed locally by calculating the NPS for small ROI sizes. A minimum ROI size is recommended based on the chosen radial bin size and image pixel dimensions. As the ROI size decreases, the NPS becomes more dependent on the choice of background removal method and window function. The image subtraction method is most accurate, but other methods can achieve similar accuracy if certain window functions are applied. All dependencies should be analyzed and taken into account when considering the interpretation of the NPS for task-based image quality assessment.
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Project description:The current standard of care for patients with high grade gliomas includes surgical resection, chemotherapy, and radiation; but even still the majority of patients experience disease progression and succumb to their illness within a few years of diagnosis. Immunotherapy, which stimulates an anti-tumor immune response, has been revolutionary in the treatment of some hematological and solid malignancies, generating substantial excitement for its potential for patients with glioblastoma. The most commonly used immunotherapies include dendritic cell and peptide vaccines, checkpoint inhibitors, and adoptive T cell therapy. However, to date, the preclinical success of these approaches against high-grade glioma models has not been replicated in human clinical trials. Moreover, the complex response to these biologically active treatments can complicate management decisions, and the neurosurgical oncology community needs to be actively involved in and up to date on the use of these agents in high grade glioma patients. In this review, we discuss the challenges immunotherapy faces for high grade gliomas, the completed and ongoing clinical trials for the major immunotherapies, and the nuances in management for patients being actively treated with one of these agents.
| S-EPMC6642850 | biostudies-literature
Project description:Rationale: Alpha particle emitting radiopharmaceuticals are generating considerable interest for the treatment of disseminated metastatic disease. Molecular imaging of the distribution of these agents is critical to safely and effectively maximize the clinical potential of this emerging drug class. The present studies aim to investigate the feasibility and limitations of quantitative SPECT for 223Ra, 225Ac and 227Th. Methods: Three state-of-the-art SPECT/CT systems were investigated: the GE Discovery NM/CT 670, the GE Optima NM/CT 640, and the Siemens Symbia T6. A series of phantoms, including the NEMA IEC Body phantom, were used to compare and calibrate each camera. Additionally, anthropomorphic physical tumor and vertebrae phantoms were developed and imaged to evaluate the quantitative imaging protocol. Results: This work describes and validates a methodology to calibrate each clinical system. The efficiency of each gamma camera was analyzed and compared. Using the calibration factors obtained with the NEMA phantom, we were able to quantify the activity in 3D-printed tissue phantoms with an error of 2.1%, 3.5% and 11.8% for 223Ra, 225Ac, and 227Th, respectively. Conclusion: The present study validates that quantitative SPECT/CT imaging of 223Ra, 225Ac, and 227Th is achievable but that careful considerations for camera configuration are required. These results will aid in future implementation of SPECT-based patient studies and will help to identify the limiting factors for accurate image-based quantification with alpha particle emitting radionuclides.
| S-EPMC8581409 | biostudies-literature
Project description:In this precision oncology era, where molecular profiling at the individual patient level becomes increasingly accessible and affordable, more and more clinical trials are now driven by biomarkers, with an overarching objective to optimize and personalize disease management. As compared with the conventional clinical development paradigms, where the key is to evaluate treatment effects in histology-defined populations, the choices of biomarker-driven clinical trial designs and analysis plans require additional considerations that are heavily dependent on the nature of biomarkers (eg, prognostic or predictive, integral or integrated) and the credential of biomarkers' performance and clinical utility. Most recently, another major paradigm change in biomarker-driven trials is to conduct multi-agent and/or multihistology master protocols or platform trials. These trials, although they may enjoy substantial infrastructure and logistical advantages, also face unique operational and conduct challenges. Here we provide a concise overview of design options for both the setting of single-biomarker/single-disease and the setting of multiple-biomarker/multiple-disease types. We focus on explaining the trial design and practical considerations and rationale of when to use which designs, as well as how to incorporate various adaptive design components to provide additional flexibility, enhance logistical efficiency, and optimize resource allocation. Lessons learned from real trials are also presented for illustration.
| S-EPMC7446374 | biostudies-literature
Project description:OBJECTIVES:Multiple sclerosis (MS) often occurs in young women and the effect of obstetric anesthesia/analgesia on the disease is poorly understood. No previous study has investigated the course of the disease in women in labor in the Czech Republic. The aim of this study was to evaluate the occurrence or absence of relapses in the 6-month postpartum period in MS parturients with and without obstetric anesthesia/analgesia. MATERIALS AND METHODS:We retrospectively studied all deliveries (n = 58,455) at the University Hospital Brno from 2004 to 2013 and identified those of the women with an ICD-10 code G35 (MS) recorded anytime in their medical history (n = 428). We included only deliveries of women with confirmed diagnosis at the time of labor (n = 70). Statistical analysis was performed using the Fischer Exact Test. RESULTS:There were 70 deliveries of 65 women, including 45 vaginal deliveries and 25 Cesarean deliveries (16 under general anesthesia, 8 with epidural anesthesia and 1 with spinal anesthesia). Epidural obstetric analgesia was performed in 11 deliveries. There was no statistically significant difference in relapses between the vaginal delivery group (n = 15; 33%) and Cesarean section group (n = 10; 40%), p = 0.611. CONCLUSION:Neither delivery mode (vaginal vs Caesarean) nor type of obstetric anesthesia/analgesia was found to have any impact on the course of MS at 6 months postpartum in women with this condition.
| S-EPMC6160638 | biostudies-literature
Project description:Prone positioning has been shown to improve oxygenation for decades. However, proning in awake, non-intubated patients gained acceptance in the last few months since the onset of coronavirus (COVID-19) pandemic. To overcome the shortage of ventilators, to decrease the overwhelming burden on intensive care beds in the pandemic era, and also as invasive ventilation was associated with poor outcomes, proning of awake, spontaneously breathing patients gathered momentum. Being an intervention with minimal risk and requiring minimum assistance, it is now a globally accepted therapy to improve oxygenation in acute hypoxemic respiratory failure in COVID-19 patients. We thus reviewed the literature of awake proning in non-intubated patients and described a safe protocol to practice the same. How to cite this article: Sodhi K, Chanchalani G. Awake Proning: Current Evidence and Practical Considerations. Indian J Crit Care Med 2020;24(12):1236-1241.
| S-EPMC7775938 | biostudies-literature