Category: Nevin Manimala

Endocrine. 2022 Jun 3. doi: 10.1007/s12020-022-03097-6. Online ahead of print.

ABSTRACT

INTRODUCTION: The incidence of small, differentiated thyroid cancer (DTC) cases has been increasing in the United States and the world mainly due to incidental detection because of widespread use of diagnostic modalities. While the option of active surveillance instead of surgical resection is getting more popular, there is still an open discussion about the best approach in these cases.

MATERIALS AND METHODS: The National Cancer Database was queried for patients diagnosed with non-metastatic small T1/N0 DTC between 2004 and 2016, who have known surgical status and Charlson comorbidity index of two or less. We evaluated the overall survival (OS) based on the surgery status using Kaplan-Meier estimates and multivariable cox regression analyses.

RESULTS: A total of 98,501 patients with non-metastatic small DTC were included, within which 96,612 (98.1%) were treated with surgery, and 1889 (1.9%) were not treated with surgery or other ablative modalities. We found that patients who were treated with surgery had better OS compared to patients who were not treated with surgery (mean OS 171 months vs 134.1 months, P < 0.001, median OS was not reached). This difference was still statistically significant even after we used propensity score matching for age, gender, race, Charlson-Deyo score, tumor size, and histology. On multivariate analysis, surgery was associated with better OS (HR 0.218; 95% CI: 0.196-0.244; P < 0.001). Same trend was found in subgroup analysis when we split the cohort according to tumor size (<1 and ≥1 cm), histology (follicular, papillary and Hurthle cell carcinoma), and age (<55 years vs ≥55 years).

CONCLUSION: Patients with non-metastatic small DTC who were treated with surgery had significant improvement in OS compared to patients who were not treated with surgery. Notwithstanding the limitations of the current analysis, these results call for caution prior to recommending routine surveillance for all patients with small DTC.

PMID:35657579 | DOI:10.1007/s12020-022-03097-6

Eur J Drug Metab Pharmacokinet. 2022 Jun 3. doi: 10.1007/s13318-022-00776-7. Online ahead of print.

ABSTRACT

BACKGROUND AND OBJECTIVE: CC-292 is a potent, selective, orally administered small molecule inhibitor of Bruton’s tyrosine kinase (BTK). To support the clinical investigation of CC-292, a randomized, seven-treatment, seven-period, crossover study was conducted to assess the relative bioavailability, pH effect, food effect, and dose-proportionality of two formulated tablets of CC-292.

METHODS: Healthy subjects (n = 24) were enrolled in the study and randomly assigned into different treatment sequences. Blood samples were collected at pre-specified time points to measure the drug concentrations in plasma. Statistical analyses were performed to compare the pharmacokinetics of CC-292 under different conditions.

RESULTS: The relative bioavailability of the newly developed formulation [spray-dried dispersion (SDD)] to the reference formulation (P22) was 1.24. When a single dose of CC-292 SDD tablet was administered under fed conditions, the area under the plasma concentration-time curve from time zero to infinity (AUC_∞) increased by 10.9% and the maximum plasma drug concentration C_max) decreased by 19.4% compared to when CC-292 was administered under fasted conditions. When a single dose of CC-292 SDD tablet was administered after multiple doses of omeprazole, the area under the plasma concentration-time curve from time zero to infinity (AUC_∞) decreased by 36.8% and the maximum plasma drug concentration C_max) decreased by 48.1% compared to when CC-292 was administered alone. Over a dose range of 100-300 mg (SDD formulation), CC-292 exhibited more than dose-proportional increases of drug exposures.

CONCLUSIONS: CC-292 was well tolerated when administered to healthy subjects as single oral doses under all conditions. Food intake had no clinically relevant impact on CC-292 pharmacokinetics compared to fasted conditions. Therefore, CC-292 can be administered with or without food. Co-administration of CC-292 with multiple doses of omeprazole (40 mg) decreased the pharmacokinetic exposure of CC-292. However, the effect was not clinically relevant.

CLINICAL TRIALS REGISTRATION: NCT02433457.

PMID:35657581 | DOI:10.1007/s13318-022-00776-7

J Comput Neurosci. 2022 Jun 3. doi: 10.1007/s10827-022-00820-0. Online ahead of print.

ABSTRACT

The brain is believed to operate in part by making predictions about sensory stimuli and encoding deviations from these predictions in the activity of “prediction error neurons.” This principle defines the widely influential theory of predictive coding. The precise circuitry and plasticity mechanisms through which animals learn to compute and update their predictions are unknown. Homeostatic inhibitory synaptic plasticity is a promising mechanism for training neuronal networks to perform predictive coding. Homeostatic plasticity causes neurons to maintain a steady, baseline firing rate in response to inputs that closely match the inputs on which a network was trained, but firing rates can deviate away from this baseline in response to stimuli that are mismatched from training. We combine computer simulations and mathematical analysis systematically to test the extent to which randomly connected, unstructured networks compute prediction errors after training with homeostatic inhibitory synaptic plasticity. We find that homeostatic plasticity alone is sufficient for computing prediction errors for trivial time-constant stimuli, but not for more realistic time-varying stimuli. We use a mean-field theory of plastic networks to explain our findings and characterize the assumptions under which they apply.

PMID:35657570 | DOI:10.1007/s10827-022-00820-0

Environ Sci Pollut Res Int. 2022 Jun 3. doi: 10.1007/s11356-022-21144-7. Online ahead of print.

ABSTRACT

Childhood overweight and obesity (OWO) has risen dramatically in both developed and developing countries over the past few decades, creating a huge burden of disease. Ambient air pollution and emotional and behavioral problems are important influencing factors of OWO in preschoolers, but few studies have evaluated the impact of air pollution and emotional and behavioral problems on OWO of preschoolers in rural areas and their potential interactions. This study selected 3802 preschool children from 26 kindergartens in 4 rural areas of Anhui Province for a cross-sectional study. A total of 3636 individuals were included in the final analysis. In this study, outdoor air pollutants (PM_2.5 and O₃) were derived from the China Air Pollution Tracking (TAP) data set, matching preschoolers’ external air pollution exposure according to their kindergarten address codes to neighborhoods or administrative villages. OWO were assessed based on WHO Child Growth and Development Standards. Generalized linear model (GLM) and interplot model were used to evaluate the separate effects and potential interactions of air pollutants and emotional and behavioral problems on preschoolers’ OWO. In the separate analysis, we found a significant positive association between air pollution and emotional and behavioral problems and OWO among preschoolers. In the interaction analysis, air pollution could enhance the positive effect of emotional and behavioral problems on OWO in preschoolers. In addition, the effect of air pollution and emotional and behavioral problems on overweight and obesity was stronger in preschoolers aged 5 to 6 years. Finally, we also found a stronger positive association between emotional and behavioral problems among girls, macrosomia, non-left-behind children, and preschoolers without eating problems. This study provided a scientific basis for the control of air pollution and overweight and obesity among preschool children in Anhui Province.

PMID:35657543 | DOI:10.1007/s11356-022-21144-7

Infection. 2022 Jun 3. doi: 10.1007/s15010-022-01852-5. Online ahead of print.

ABSTRACT

PURPOSE: At the beginning of the COVID-19 pandemic, SARS-CoV-2 was often compared to seasonal influenza. We aimed to compare the outcome of hospitalized patients with cancer infected by SARS-CoV-2 or seasonal influenza including intensive care unit admission, mechanical ventilation and in-hospital mortality.

METHODS: We analyzed claims data of patients with a lab-confirmed SARS-CoV-2 or seasonal influenza infection admitted to one of 85 hospitals of a German-wide hospital network between January 2016 and August 2021.

RESULTS: 29,284 patients with COVID-19 and 7442 patients with seasonal influenza were included. Of these, 360 patients with seasonal influenza and 1625 patients with COVID-19 had any kind of cancer. Cancer patients with COVID-19 were more likely to be admitted to the intensive care unit than cancer patients with seasonal influenza (29.4% vs 24.7%; OR 1.31, 95% CI 1.00-1.73 p < .05). No statistical significance was observed in the mechanical ventilation rate for cancer patients with COVID-19 compared to those with seasonal influenza (17.2% vs 13.6% OR 1.34, 95% CI 0.96-1.86 p = .09). 34.9% of cancer patients with COVID-19 and 17.9% with seasonal influenza died (OR 2.45, 95% CI 1.81-3.32 p < .01). Risk factors among cancer patients with COVID-19 or seasonal influenza for in-hospital mortality included the male gender, age, a higher Elixhauser comorbidity index and metastatic cancer.

CONCLUSION: Among cancer patients, SARS-CoV-2 was associated with a higher risk for in-hospital mortality than seasonal influenza. These findings underline the need of protective measurements to prevent an infection with either COVID-19 or seasonal influenza, especially in this high-risk population.

PMID:35657531 | DOI:10.1007/s15010-022-01852-5

Methods Mol Biol. 2022;2526:259-275. doi: 10.1007/978-1-0716-2469-2_19.

ABSTRACT

Cellular redox signaling is triggered by accumulation of various reactive oxygen species (ROS) that integrate with other signaling cascades to enable plants to ultimately respond to (a)biotic stresses. The identification of key regulators underlying redox signaling networks is therefore of high priority. This chapter describes an improved mRNA interactome capture method that allows to systematically detect oxidative stress responsive regulators in the post-transcriptional gene regulation (PTGR) pathway. The protocol includes PSB-D suspension cell culture preparation, setup of oxidative stress conditions, short-term exposure to UV irradiation, cell lysis, pull-down and purification of crosslinked messenger ribonucleoproteins, their mass spectrometric analyses, and identification of proteome by statistical analyses. As result, a comprehensive inventory of the functional oxidative stress responsive RBPome (OxRBPome) is generated, which paves the way toward new insights into PTGR processes in redox signaling.

PMID:35657526 | DOI:10.1007/978-1-0716-2469-2_19

Methods Mol Biol. 2022;2526:241-257. doi: 10.1007/978-1-0716-2469-2_18.

ABSTRACT

Reshaping of the chromatin landscape under oxidative stress is of paramount importance for mounting an effective stress response. Unbiased systemic identification and quantification of histone marks is crucial for understanding the epigenetic component of plant responses to adverse environmental conditions. We describe a detailed method for isolation of plant histones and subsequent bottom-up proteomics approach for characterization of acetylation and methylation status. By performing label-free quantitative mass spectrometry analysis, relative abundances of histone marks can be statistically compared between experimental conditions.

PMID:35657525 | DOI:10.1007/978-1-0716-2469-2_18

J Occup Rehabil. 2022 Jun 3. doi: 10.1007/s10926-022-10048-5. Online ahead of print.

ABSTRACT

Purpose This study sought to determine patterns of opioid use among workers with a compensated lower limb injury, factors associated with opioid use, and how opioid use is associated with time loss duration. Methods Claims and medication data were provided by the workers’ compensation regulator of Victoria, Australia, for claims lodged 2008-2018 from workers aged 15+ years with a lower limb injury. Descriptive statistics showed the number and prevalence of each opioid type (weak/strong) by demographic, claim and injury predictors. Binary and multinomial logistic regression determined the likelihood of any opioid use, and use of strong, weak or a combination of strong and weak opioids by predictors. Cox regression determined the effect of each opioid type on duration of time loss, controlling for predictors. Results There were 51,334 claims and of these 23.6% were dispensed opioids (9.2% for strong opioids only, 6.6% for weak opioids only and 7.8% for a combination). Weak opioids, on average, were dispensed 15 days earlier than strong opioids. Time loss claims and workers with fractures or hip injuries were most likely to be dispensed opioids. All opioids were associated with increased duration of time loss, with those dispensed both weak and strong opioids having the longest duration of time loss. Conclusions Any opioid use was associated with longer time loss duration, with increasing opioid strength having a greater effect. Review of pain management methods should be undertaken to reduce opioid use, which may have a positive impact on duration of time loss and long-term function.

PMID:35657441 | DOI:10.1007/s10926-022-10048-5

J Patient Rep Outcomes. 2022 Jun 3;6(1):59. doi: 10.1186/s41687-022-00464-9.

ABSTRACT

BACKGROUND: The Patient-Reported Outcome Measurement Information System^® (PROMIS^®) was developed to reliably measure health-related quality of life using the patient’s voice. To achieve these aims, PROMIS utilized Item Response Theory methods in its development, validation and implementation. PROMIS measures are typically scored using a specific method to calculate scores, called Expected A Posteriori estimation. BODY: Expected A Posteriori scoring methods are flexible, produce accurate scores and can be efficiently calculated by statistical software. This work seeks to make Expected A Posteriori scoring methods transparent and accessible to a larger audience through description, graphical demonstration and examples. Further applications and practical considerations of Expected A Posteriori scoring are presented and discussed. All materials used in this paper are made available through the R Markdown reproducibility framework and are intended to be reviewed and reused. Commented statistical code for the calculation of Expected A Posteriori scores is included.

CONCLUSION: This work seeks to provide the reader with a summary and visualization of the operation of Expected A Posteriori scoring, as implemented in PROMIS. As PROMIS is increasingly adopted and implemented, this work will provide a basis for making psychometric methods more accessible to the PROMIS user base.

PMID:35657454 | DOI:10.1186/s41687-022-00464-9

Insights Imaging. 2022 Jun 3;13(1):94. doi: 10.1186/s13244-022-01234-3.

ABSTRACT

BACKGROUND: Majority of research and commercial efforts have focussed on use of artificial intelligence (AI) for fracture detection in adults, despite the greater long-term clinical and medicolegal implications of missed fractures in children. The objective of this study was to assess the available literature regarding diagnostic performance of AI tools for paediatric fracture assessment on imaging, and where available, how this compares with the performance of human readers.

MATERIALS AND METHODS: MEDLINE, Embase and Cochrane Library databases were queried for studies published between 1 January 2011 and 2021 using terms related to ‘fracture’, ‘artificial intelligence’, ‘imaging’ and ‘children’. Risk of bias was assessed using a modified QUADAS-2 tool. Descriptive statistics for diagnostic accuracies were collated.

RESULTS: Nine eligible articles from 362 publications were included, with most (8/9) evaluating fracture detection on radiographs, with the elbow being the most common body part. Nearly all articles used data derived from a single institution, and used deep learning methodology with only a few (2/9) performing external validation. Accuracy rates generated by AI ranged from 88.8 to 97.9%. In two of the three articles where AI performance was compared to human readers, sensitivity rates for AI were marginally higher, but this was not statistically significant.

CONCLUSIONS: Wide heterogeneity in the literature with limited information on algorithm performance on external datasets makes it difficult to understand how such tools may generalise to a wider paediatric population. Further research using a multicentric dataset with real-world evaluation would help to better understand the impact of these tools.

PMID:35657439 | DOI:10.1186/s13244-022-01234-3