Tag: pubmed

Psychoneuroendocrinology. 2021 May 17;129:105274. doi: 10.1016/j.psyneuen.2021.105274. Online ahead of print.

ABSTRACT

Left censoring in salivary bioscience data occurs when salivary analyte determinations fall below the lower limit of an assay’s measurement range. Conventional statistical approaches for addressing censored values (i.e., recoding as missing, substituting or extrapolating values) may introduce systematic bias. While specialized censored data statistical approaches (i.e., Maximum Likelihood Estimation, Regression on Ordered Statistics, Kaplan-Meier, and general Tobit regression) are available, these methods are rarely implemented in biobehavioral studies that examine salivary biomeasures, and their application to salivary data analysis may be hindered by their sensitivity to skewed data distributions, outliers, and sample size. This study compares descriptive statistics, correlation coefficients, and regression parameter estimates generated via conventional and specialized censored data approaches using salivary C-reactive protein data. We assess differences in statistical estimates across approach and across two levels of censoring (9% and 15%) and examine the sensitivity of our results to sample size. Overall, findings were similar across conventional and censored data approaches, but the implementation of specialized censored data approaches was more efficient (i.e., required little manipulations to the raw analyte data) and appropriate. Based on our review of the findings, we outline preliminary recommendations to enable investigators to more efficiently and effectively reduce statistical bias when working with left-censored salivary biomeasure data.

PMID:34030086 | DOI:10.1016/j.psyneuen.2021.105274

Transl Oncol. 2021 May 21;14(8):101121. doi: 10.1016/j.tranon.2021.101121. Online ahead of print.

ABSTRACT

BACKGROUND: Lorlatinib is a novel potent ALK inhibitor, with only a few studies reporting the results of its clinical use.

METHODS: This study describes the outcomes of lorlatinib treatment for 35 non-small cell lung cancer patients with ALK rearrangements, who had 2 (n = 5), 1 (n = 26) or none (n = 4) prior tyrosine kinase inhibitors and received lorlatinib mainly within the compassionate use program.

RESULTS: Objective tumor response (OR) and disease control (DC) were registered in 15/35 (43%) and 33/35 (94%) patients, respectively; brain metastases were particularly responsive to the treatment (OR: 22/27 (81%); DC: 27/27 (100%)). Median progression free survival (PFS) was estimated to be 21.8 months, and median overall survival (OS) approached to 70.1 months. Only 4 out of 35 patients experienced no adverse effects; two of them were the only subjects who had no clinical benefit from lorlatinib. PFS and OS in the no-adverse-events lorlatinib users were strikingly lower as compared to the remaining patients (1.1 months vs. 23.7 months and 10.5 months vs. not reached, respectively; p < 0.0001 for both comparisons). ALK translocation variants were known for 28 patients; there was no statistical difference between patients with V.1 and V.3 rearrangements with regard to the OS or PFS.

CONCLUSION: Use of lorlatinib results in excellent disease outcomes, however caution must be taken for patients experiencing no adverse effects from this drug.

PMID:34030112 | DOI:10.1016/j.tranon.2021.101121

Phys Med Biol. 2021 May 24. doi: 10.1088/1361-6560/ac047e. Online ahead of print.

ABSTRACT

Clinical studies in the hypofractionated stereotactic body radiotherapy (SBRT) have shown a reduction in the probability of local tumor control with increasing initial tumor volume. In our earlier work, we obtained and tested an analytical dependence of the TCP (tumor control probability) on the total and hypoxic tumor volumes using conventional radiotherapy model with the linear-quadratic (LQ) cell survival. In this work, this approach is further refined and tested against clinical observations for hypofractionated radiotherapy treatment schedules. Compared to radiotherapy with conventional fractionation schedules, simulations of hypofractionated radiotherapy may require different models for cell survival and the Oxygen Enhancement Ratio (OER). Our TCP simulations in hypofractionated radiotherapy are based on the LQ model and the Universal Survival Curve (USC) developed for the high doses used in SBRT. The predicted trends in local control as a function of the initial tumor volume were evaluated in SBRT for non-small cell lung cancer. Our results show, that both LQ and USC based models cannot describe the TCP reduction for larger tumor volumes observed in the clinical studies if the tumor is considered completely oxygenated. The TCP calculations are in agreement with the clinical data if the subpopulation of radio-resistant hypoxic cells is considered with the volume that increases as initial tumor volume increases. There are two conclusions which follow from our simulations. First, the extent of hypoxia is likely a primary reason of the TCP reduction with increasing the initial tumor volume in SBRT for non-small cell lung cancer. Second, the LQ model can be an acceptable approximation for the TCP calculations in hypofractionated radiotherapy if the tumor response is defined primarily by the hypoxic fraction. The larger value of OER in the hypofractionated radiotherapy compared to the conventional radiotherapy effectively extends the applicability of the LQ model to larger doses.

PMID:34030139 | DOI:10.1088/1361-6560/ac047e

Clin Neurol Neurosurg. 2021 May 19;206:106697. doi: 10.1016/j.clineuro.2021.106697. Online ahead of print.

ABSTRACT

INTRODUCTION: The Charlson Comorbidity Index (CCI) score has been shown to predict 10-year all-cause mortality and post-neurosurgical complications but has never been examined in a far lateral disc herniation (FLDH) population. This study aims to correlate CCI score with adverse outcomes following FLDH repair.

PATIENTS AND METHODS: All patients (n = 144) undergoing discectomy for FLDH at a single, multihospital academic medical system (2013-2020) were retrospectively analyzed. CCI scores were determined for all patients. Univariate logistic regression was used to determine the ability of CCI score to predict adverse outcomes.

RESULTS: Mean age of the population was 61.72 ± 11.55 years, 69 (47.9%) were female, and 126 (87.5%) were non-Hispanic white. Patients underwent either open (n = 92) or endoscopic (n = 52) FLDH repair. Average CCI score among the patient population was 2.87 ± 2.42. Each additional point in CCI score was significantly associated with higher rates of readmission (p = 0.022, p = 0.014) in the 30-day and 30-90-day post-surgery window, respectively, and emergency department visits (p = 0.011) within 30-days. CCI score also predicted risk of reoperation of any kind (p = 0.013) within 30 days of the index operation. In addition, CCI score was predictive of risk of reoperation of any kind (p = 0.008, p < 0.001; respectively) and repeat neurosurgical intervention (p = 0.027, p = 0.027) within 30-days and 90-days of the index admission (either during the same admission or after discharge).

CONCLUSIONS: This study suggests that CCI score is a useful metric to predict of numerous adverse postoperative outcomes following discectomy for FLDH.

PMID:34030078 | DOI:10.1016/j.clineuro.2021.106697

Clin Neurol Neurosurg. 2021 May 20;206:106700. doi: 10.1016/j.clineuro.2021.106700. Online ahead of print.

ABSTRACT

BACKGROUND: Cytokines and chemokines are undoubtedly involved in the pathogenesis of multiple sclerosis (MS). There are many reports that suggest a significant role for Interleukin-33 (IL-33) in the course of MS development, but it is not clear whether negative or positive. We therefore investigated plasma IL-33 levels in patients with relapsing-remitting MS (RRMS).

METHODS: The study consisted of RRMS patients (n = 73) and healthy subjects (n = 54). Blood samples were taken from all and plasma IL-33 levels were then determined using an enzyme-linked immunosorbent assay method. Patients also underwent laboratory and imaging tests and their disability status was assessed.

RESULTS: Plasma IL-33 levels were marginally significantly higher in patients with RRMS (p = 0.07). Higher IL-33 levels are significantly associated with higher age (p = 0.01). There was also a statistically significant negative correlation between plasma IL-33 levels and the number of high signal intensity lesions in T2-weighted MRI (p = 0.03). After dividing the number of lesions into groups < 9 and ≥ 9 T2-weighted lesions, the Student’s t-test for unrelated variables showed a negative correlation, but not statistically significant (p = 0.22), while the Spearman’s correlation showed a marginally significant correlation (p = 0.06) between IL-33 level and number of T2-weighted lesions. IL-33 was also shown to have a significant ability to differentiate RRMS patients from healthy subjects with a sensitivity of 99% and specificity of 70% (p = 0.00).

CONCLUSIONS: Patients with RRMS have elevated plasma IL-33 levels. In RRMS patients with mild disability, high plasma levels of IL-33 may have neuroprotective effects potentially by stimulating remyelination and/or suppressing autoimmune inflammation and damage. Further studies on this matter on a larger number of patients are needed.

PMID:34030079 | DOI:10.1016/j.clineuro.2021.106700

Environ Pollut. 2021 May 12;284:117354. doi: 10.1016/j.envpol.2021.117354. Online ahead of print.

ABSTRACT

Glyphosate herbicide is ubiquitously used in agriculture and weed control. It has now been identified in aquatic ecosystems worldwide, where numerous studies have suggested that it may have both suppressive and stimulatory effects on diverse non-target organisms. We cultured natural biofilms from a hypereutrophic environment to test the effects on periphytic diatoms of exposure to a glyphosate-based herbicide formulation at concentrations from 0 to 10 mg L^-1 of active ingredient. There were clear and significant differences between treatments in diatom community structure after the 15-day experiments. Diversity increased more in low glyphosate treatments relative to higher concentrations, and compositional analyses indicated statistically significant differences between glyphosate treatments. The magnitude of change observed was significantly correlated with glyphosate-based herbicide concentration. Our results show that glyphosate-based herbicides have species-selective effects on benthic diatoms that may significantly alter trajectories of community development and therefore may affect benthic habitats and whole ecosystem function.

PMID:34030084 | DOI:10.1016/j.envpol.2021.117354

Epilepsy Behav. 2021 May 21;121(Pt A):108003. doi: 10.1016/j.yebeh.2021.108003. Online ahead of print.

ABSTRACT

BACKGROUND AND PURPOSE: We performed a systematic review to evaluate available risk models to predict late seizure onset among stroke survivors.

METHODS: We searched major databases (PubMed, SCOPUS, and Cochrane Library) from inception to October 2020 for articles on the development and/or validation of risk models to predict late seizures after a stroke. The impact of models to predict late-onset seizures was also assessed. We included seven articles in the final analysis. For each of these studies, we evaluated the study design and scope of predictors analyzed to derive each model. We assessed the performance of the models during internal and external validation in terms of discrimination and calibration.

RESULTS: Three studies focused on ischemic stroke alone, with c-statistic values ranging from 0.73 to 0.77. The SeLECT model from Switzerland was externally validated in Italian, German, and Austrian cohorts where c-statistics ranged from 0.69 to 0.81. This model along with the PSEiCARe model, were internally validated and calibration performance was provided for both models. The CAVS and CAVE models reported on the risk of late-onset seizures in patients with hemorrhagic stroke. The CAVS model derivation cohort was racially diverse. The CAVS model’s c-statistic was 0.76, while the CAVE model had a c-statistic of 0.81. Calibration and internal validation were not performed for either study. The CAVS model, created from a Finnish population, was externally validated in American and French cohorts, with c-statistics of 0.73 and 0.69, respectively. Finally, the two studies focusing on both types of stroke came from the PoSERS and INPOSE models. Neither model provided c-statistics, calibration metrics, internal or external validation information. We found no evidence of the presence of impact studies to assess the effect of adopting late-onset seizure risk models after stroke on clinical outcomes.

CONCLUSION: The SeLECT model was the only model developed in line with proposed guidelines for appropriate model development. The model, which was externally validated in a very similar and homogeneous population, may need to be tested in a more racially/ethnic diverse and younger population; testing the SeLECT model, accounting for overall brain health is likely to improve the identification of high-risk patients for late post stroke seizures.

PMID:34029995 | DOI:10.1016/j.yebeh.2021.108003

Spectrochim Acta A Mol Biomol Spectrosc. 2021 May 11;260:119943. doi: 10.1016/j.saa.2021.119943. Online ahead of print.

ABSTRACT

A comparative study of successive spectrophotometric resolution technique for the simultaneous determination of a challengeable quaternary mixture of Chlorpheniramine maleate (CPM), Pseudoephedrine hydrochloride (PSE), Ibuprofen (IBU) and Caffeine (CAF) is presented, without preliminary physical separation steps. Several successive steps were applied on built-in spectrophotometer software utilizing zero and/or derivative and/or ratio spectra of the studied components. These methods, namely, Dual amplitude difference (DAD) as a novel method, Constant multiplication coupled with spectrum subtraction method (CM-SS), Factorized first derivative coupled with derivative transformation method (FD¹ -DT) and Derivative ratio method (DD¹). The calibration graphs are linear over the concentration range of 10.0-80.0 μg/mL,150.0-900.0 μg/mL, 200.0-1400.0 μg/mL and 3.0-30.0 μg/mL for CPM, PSE, IBU and CAF, respectively. The specificity of suggested methods was studied via laboratory prepared (diverse ratios) mixtures and were successfully applied for Antiflu® capsules’ analysis. Moreover, sample enrichment via In Silico (via software of spectrophotometer) and In Lab (via spiking with pure sample) techniques was elected for a pharmaceutical dosage form analysis comprising CPM and PSE as minor components. Accuracy, precision and specificity were between the valid limits. Validation steps were done in accordance with the ICH guidelines. Moreover, statistical comparison was carried out between the obtained and reported results for pure powder form and no significant difference appeared.

PMID:34030038 | DOI:10.1016/j.saa.2021.119943

Accid Anal Prev. 2021 May 21;157:106158. doi: 10.1016/j.aap.2021.106158. Online ahead of print.

ABSTRACT

Driving errors and violations are highly relevant to the safe systems approach as human errors tend to be a predominant cause of crash occurrence. In this study, we harness highly detailed pre-crash Naturalistic Driving Study (NDS) data 1) to understand errors and violations in crash, near-crash, and baseline (no event) driving situations, and 2) to explore pathways that lead to crashes in diverse built environments by applying rigorous modeling techniques. The “locality” factor in the NDS data provides information on various types of roadway and environmental surroundings that could influence traffic flow when a precipitating event is observed. Coded by the data reductionists, this variable is used to quantify the associations of diverse environments with crash outcomes both directly and indirectly through mediating driving errors and violations. While the most prevalent errors in crashes were recognition errors such as failing to recognize a situation (39 %) and decision errors such as not braking to avoid a hazard (34 %), performance errors such as poor lateral or longitudinal control or weak judgement (8 %) were most strongly correlated with crash occurrence. Path analysis uncovered direct and indirect relationships between key built-environment factors, errors and violations, and crash propensity. Possibly due to their complexity for drivers, urban environments are associated with higher chances of crashes (by 6.44 %). They can also induce more recognition errors which correlate with an even higher chances of crashes (by 2.16 % with the “total effect” amounting to 8.60 %). Similar statistically significant mediating contributions of recognition errors and decision errors near school zones, business or industrial areas, and moderate residential areas were also observed. From practical applications standpoint, multiple vehicle technologies (e.g., collision warning systems, cruise control, and lane tracking system) and built-environment (roadway) changes have the potential to reduce driving errors and violations which are discussed in the paper.

PMID:34030046 | DOI:10.1016/j.aap.2021.106158

J Pharm Biomed Anal. 2021 May 18;202:114147. doi: 10.1016/j.jpba.2021.114147. Online ahead of print.

ABSTRACT

Epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) acquired resistance remains a major barrier in the clinical treatment of lung adenocarcinoma with epidermal growth factor receptor (EGFR) mutations. Despite extensive efforts, mechanism of acquired resistance has not yet been elucidated clearly. The subject of this study was to characterize the metabolic signatures relevant to acquired EGFR-TKI resistance in pleural effusion (PE), and identify potential biomarkers in PE of patients with acquired EGFR-TKI resistance. PE from EGFR-TKI untreated group (n = 30) and EGFR-TKI resistant group (n = 18) was analyzed using liquid chromatography-mass spectrometry (LCMS) based metabolomic. Multivariate statistical analysis revealed distinctive diff ;erences between the groups. A total of 34 significantly differential metabolites in PE were identified, among which, the acquired EGFR-TKI resistant group had higher levels of l-lysine, taurine, ornithine and citrulline, and lower levels of l-tryptophan, kynurenine, l-phenylalanine, l-leucine, N-formyl-l-methionine, 3-hydroxyphenylacetic acid and N-acetyl-d-phenylalanine in PE than that of the EGFR-TKI untreated group. These metabolites are mainly involved in six amino acid metabolic pathways. In addition, 3-hydroxyphenylacetic acid and N-acetyl-d-phenylalanine showed the highest AUC values of 0.934 and 0.929 in receiver operating characteristic analysis. Through LCMS metabolomics, our study identified potential biomarkers in PE, differentiating EGFR-TKI resistant patients from untreated patients, as well as the mechanisms underlying acquired EGFR-TKI resistance; thus, providing novel insights into acquired EGFR-TKI resistance.

PMID:34029974 | DOI:10.1016/j.jpba.2021.114147