Nevin Manimala

J Clin Pharm Ther. 2022 Jan 15. doi: 10.1111/jcpt.13596. Online ahead of print.

ABSTRACT

WHAT IS KNOWN AND OBJECTIVES: Although the apixaban Food and Drug Administration (FDA) package insert recommends dose reduction in patients administered dual strong inhibitors of p-glycoprotein (P-gp) and cytochrome P-450 (CYP) 3A4, there are limited published data regarding potential drug-drug interactions between apixaban (Eliquis) and common p-glycoprotein (P-gp) and CYP3A4 inhibitors co-administered with statins. The aim of this study was to investigate the degree of elevation relative to apixaban serum peak and trough concentration after the co-administration of amiodarone, diltiazem and statins (atorvastatin, rosuvastatin and simvastatin).

METHODS: Patients prescribed apixaban 5mg twice daily for at least one week were identified from the anticoagulation clinic database and contacted for potential enrolment. A total of 117 volunteers were enrolled with eight excluded due to discontinued use, resulting in 109 volunteers (44 females and 65 males delineated into age groups 40-64 and ≥65 years old) completing the observational study. Fifty-five volunteers were administered apixaban without the P-gp inhibitors amiodarone or diltiazem, with or without statins (atorvastatin, rosuvastatin and simvastatin). Fifty-four volunteers were administered apixaban with either amiodarone or diltiazem, with or without statins (atorvastatin, rosuvastatin or simvastatin). Peak and trough concentrations were assessed for each patient utilizing an apixaban anti-Xa assay.

RESULTS: Of the combinations studied, the mean apixaban trough concentration upon co-administration of amiodarone without a statin was elevated compared to apixaban alone (experimental 156.83 +/- 79.59 ng/ml vs. control 104.09 +/- 44.56 ng/ml; p = 0.04). The co-administration of diltiazem and rosuvastatin, and the administration of amiodarone without a statin led to greater than 1.5-fold increase in apixaban concentrations (peak experimental 315.19 +/- 157.53 ng/ml vs control 207.6 +/- 83.38 ng/ml; p = 0.08 and trough experimental 182.03 +/- 95.93 ng/ml vs control 112.32 +/- 37.78 ng/ml; p = 0.17) suggesting the need to assess dose adjustment for patients per the FDA package insert. In addition, the aggregated mean peak (p = 0.0056) and trough (p = 0.0089) elevation of CYP3A4 experimental groups (atorvastatin and simvastatin) co-administered apixaban and diltiazem were statistically significant compared with the aggregated non-CYP3A4 control groups (no statin and rosuvastatin).

WHAT IS NEW AND CONCLUSION: Herein, we report novel data regarding peak and trough apixaban concentrations after concomitant administration of P-gp and CYP3A4 inhibitors (amiodarone or diltiazem) co-administered with statins (atorvastatin, rosuvastatin or simvastatin). Providers should consider utilizing the apixaban anti-Xa assay or comparative heparin anti-Xa assay to determine if patients require dose reduction to decrease adverse events in high-risk patients prescribed apixaban and concomitant p-glycoprotein and CYP3A4 inhibitors amiodarone or diltiazem with and without a CYP3A4 or non-3A4 statin.

PMID:35032137 | DOI:10.1111/jcpt.13596

NMR Biomed. 2022 Jan 14:e4694. doi: 10.1002/nbm.4694. Online ahead of print.

ABSTRACT

BACKGROUND: The dual up-regulation of TOP2A and EZH2 gene expression has been proposed as a biomarker for recurrence in prostate cancer patients to be treated with radical prostatectomy. Low tissue level of the metabolite citrate has additionally been connected to aggressive disease and recurrence in this patient group. However, for radiotherapy prostate cancer patients, few prognostic biomarkers have been suggested. The main aim of this study was to use an integrated tissue analyses to evaluate metabolites and expression of TOP2A and EZH2 as predictors for recurrence among radiotherapy patients.

METHODS: From 90 prostate cancer patients (56 received neoadjuvant hormonal treatment), 172 transrectal ultrasound-guided (TRUS)-biopsies were collected prior to radiotherapy. Metabolic profiles were acquired from fresh frozen TRUS-biopsies using high resolution-magic angle spinning (HR-MAS) MR spectroscopy. Histopathology and immunohistochemistry staining for TOP2A and EZH2 were performed on TRUS-biopsies containing cancer cells (n=65) from 46 patients, where 24 of these patients (n=31 samples) received hormonal treatment. Eleven radical prostatectomy cohorts of a total of 2059 patients were used for validation in a meta-analysis.

RESULTS: Among radiotherapy patients with up to 11 years of follow-up, low level of citrate was found to predict recurrence, p=0.001 (C-index=0.74). Citrate had a higher predictive ability compared to individual clinical variables, highlighting its strength as a potential biomarker for recurrence. The dual up-regulation of TOP2A and EZH2 was suggested as a biomarker for recurrence, particularly for patients not receiving neoadjuvant hormonal treatment, p=0.001 (C-index=0.84). While citrate was a statistically significant biomarker independent on hormonal treatment status, the current study indicated a potential of glutamine, glutamate and choline as biomarkers for recurrence among patients receiving neoadjuvant hormonal treatment, and glucose among patients not receiving neoadjuvant hormonal treatment.

CONCLUSION: Using an integrated approach, our study shows the potential of citrate and the dual up-regulation of TOP2A and EZH2 as biomarkers for recurrence among radiotherapy patients.

PMID:35032074 | DOI:10.1002/nbm.4694

Endocrine. 2022 Jan 15. doi: 10.1007/s12020-021-02961-1. Online ahead of print.

ABSTRACT

PURPOSE: Little research has investigated the correlation of changes in long-term apolipoprotein B/apolipoprotein A-I (ApoB/ApoA-I) ratio with risk of new-onset type 2 diabetes (T2D) among ordinary people. Therefore, the research took long-term ApoB/ApoA-I ratio trajectories as independent variables for exploring their association with the risk of newly diagnosed T2D.

METHODS: Altogether 5362 non-diabetic participants with a median age of 49 were enrolled in the cohort study. Their ApoB/ApoA-I ratio trajectories from 2016 to 2019 were analyzed and grouped using group-based trajectory modeling. The Kaplan-Meier approach was employed for calculating the newly diagnosed T2D-related incidence with different ApoB/ApoA-I ratio trajectories. A log-rank test was conducted for testing the presence of statistical difference in new-onset T2D incidence among the different ApoB/ApoA-I ratio trajectory groups. A multivariate Cox proportional hazards regression model was adopted for analyzing how ApoB/ApoA-I ratio trajectory changes affected new-onset T2D.

RESULTS: From 2016 to 2019, 199 patients developed T2D (3% in 3 years). The incidence of T2D was 2.0%, 3.28%, 5.86%, and 6.92% for low, middle, upper, and high ApoB/ApoA-I ratio trajectories, respectively. Following adjustment of underlying confounding factors, in contrast to low ApoB/ApoA-I ratio trajectory, new-onset T2D risk ratios and hazard ratio (HR) (95% confidence intervals [CI]) for the middle lower ApoB/ApoA-I ratio trajectory, and upper middle and high ApoB/ApoA-I ratio trajectories were [HR (95% CI)] 1.35(0.88-2.08), 1.98(1.27-3.09) and 2.42(1.35-4.34), respectively, indicating high and statistically significant risks of T2D.

CONCLUSION: Variations of the ApoB/ApoA-I ratio trajectory exerted independent effects on the 3-year incidence of T2D. Long-term monitoring on the ApoB/ApoA-I ratio locus may help improve the identification on patients with T2D.

PMID:35032012 | DOI:10.1007/s12020-021-02961-1

J Racial Ethn Health Disparities. 2022 Jan 15. doi: 10.1007/s40615-021-01210-5. Online ahead of print.

ABSTRACT

The coronavirus (COVID-19) has spread quickly across the nation with a disproportionate impact on Black Americans. Many college-aged students receive their COVID-19-related information through social media and television even though research suggests that social media sources are more likely to be incorrect. Some students report trusting these sources over government sources such as the CDC and WHO. The purpose of this study was to understand Historically Black College and University (HBCU) students’ COVID-19 knowledge, sources of information, and planned precautions. There were 21 in-depth interviews conducted with students attending a large southern HBCU during Spring 2020. Themes regarding knowledge included the following: it is a flu-like condition, it has international roots, there is inaccurate and changing information, and it is a pandemic. Themes regarding sources included: the news, US government and related officials, social media, interactions with family, and other social interactions. Themes regarding severity included the following: statistics, a distrust for hospital reporting, a belief that COVID-19 deaths were conflated with baseline health, peer influence, and familial influence. Themes regarding precautions included the following: proper mask use, hand washing/ sanitizing, avoiding large crowds/small crowds only, physical distancing, COVID-19 testing/symptom monitoring, and COVID-19 vaccination.

PMID:35032009 | DOI:10.1007/s40615-021-01210-5

Environ Sci Pollut Res Int. 2022 Jan 15. doi: 10.1007/s11356-021-17714-w. Online ahead of print.

ABSTRACT

A novel model is presented for reliable estimation of the stability constants of the thiosemicarbazone ligands with different types of toxic heavy metal ions (log β₁₁) in an aqueous solution, which has wide usage in environmental safety and ecotoxicology applications. The biggest reported data of log β₁₁ for 120 metalthiosemicarbazone complexes are used for deriving and testing the novel model. In contrast to available methods where they need the two-dimensional (2D) and three-dimensional (3D) complex molecular descriptors as well as expert users and computer codes, the novel correlation uses four additive and two non-additive structural parameters of thiosemicarbazone ligands. The calculated results of the novel correlation are compared with the outputs of the genetic algorithm with multivariate linear regression method (GA-MLR) as one of the best existing methods, which requires seven complex descriptors. The estimated results for 78 of training as well as 42 of two different test sets were established by external and internal validations. The values of statistical parameters comprising average deviation, average absolute deviation, average absolute relative deviation, absolute maximum deviation, and the coefficient of determination for 73 data of training set of New model/GA-MLR are 0.04/ – 0.25, 1.06/1.31, 14.4/18.7, 3.18/7.92, and 0.830/0.652, respectively. Thus, the predicted results of the new model are worthy as compared to the complex GA-MLR model. Moreover, assessments of various statistical parameters confirm that the new model provides great reliability, goodness-of-fit, accuracy, and precision.

PMID:35031996 | DOI:10.1007/s11356-021-17714-w

Psychometrika. 2022 Jan 15. doi: 10.1007/s11336-021-09833-7. Online ahead of print.

ABSTRACT

Correspondence analysis (CA) is a statistical method for depicting the relationship between two categorical variables, and usually places an emphasis on graphical representations. In this study, we discuss a CA formulation based on canonical correlation analysis (CCA). In CCA-based formulation, the correlations within and between row/column categories in a reduced dimensional space can be expressed by canonical variables. However, in existing CCA-based formulations, only orthogonal rotation is permitted. Herein, we propose an alternative CCA-based formulation that permits oblique rotation. In the proposed formulation, the CA loss function can be defined as maximizing the generalized coefficient of determination, which is a measure of proximity between two variables. Simulation studies and real data examples are presented in order to demonstrate the benefits of the proposed formulation.

PMID:35031941 | DOI:10.1007/s11336-021-09833-7

Ir J Med Sci. 2022 Jan 15. doi: 10.1007/s11845-021-02868-w. Online ahead of print.

ABSTRACT

Nutrition is a basic need and is crucial for the persistence of good health. This awareness has increased since December 2019 during the pandemic that the world is still facing. The importance of nutrition in infectious diseases was emphasized but the relationship between the severity of symptoms and nutrition status of individuals was not examined. This study compared the nutrition status of patients with COVID-19 admitted to the emergency service and the clinical severity of the disease. Based on the nutrition status of the 337 patients included in the study, 87.2% (294) of the patients were in the low-risk group while 12.8% (43) were in the high-risk group in terms of malnutrition. In the analysis conducted to examine the effect of nutrition on the severity of disease, the relationship between NRS 2002 and dyspnea, cough, weakness, fever, and other symptoms was statistically significant. It was concluded that healthy nutrition is crucial during the pandemic, and it is necessary to consider nutrition improvement as a way to cope with emerging viral infections.

PMID:35031937 | DOI:10.1007/s11845-021-02868-w

J Cancer Surviv. 2022 Jan 15. doi: 10.1007/s11764-021-01139-y. Online ahead of print.

ABSTRACT

PURPOSE: AYAs with cancer have unique psychosocial needs, with reproductive health being a primary concern. The ECHO training program provides reproductive health communication training to individuals providing care for AYAs with cancer. The purpose of this project is to describe the growth of ECHO and evaluate changes in learner engagement over a 5-year period.

METHODS: ECHO is an 8-week online training program offered annually, with the program including learning modules, discussion topics and reflections, and synchronous discussions. Reflection quality scores and number of words were compared between the 5 cohorts using ANOVA with a p < .05 level of significance. Descriptive statistics summarized module topics, reflections, and synchronous discussions.

RESULTS: The average number of reflections per unique learner increased each year (1.4 in cohort 1 vs 4.1 in cohort 5), as did average length and quality of reflections (72.1 words in cohort 1 vs 203.4 words in cohort 5, p < .0001; score of 1.21 in cohort 1 vs 4.46 in cohort 5, p < .0001). The percentage of learners in attendance at synchronous discussions increased between cohorts 4 and 5 (4.8% of learners in cohort 4 vs 18.8% of learners cohort 5).

CONCLUSIONS: The ECHO program has seen significant growth and improvement in learner engagement over a 5-year period. This is particularly important given that student learning outcomes in online courses can be predicted by the level of engagement with online content.

IMPLICATIONS FOR CANCER SURVIVORS: As fertility and reproductive health remain a top life goal and discussion priority for AYAs surviving cancer, increasing clinical competencies of AHPs in oncofertility is essential.

PMID:35031917 | DOI:10.1007/s11764-021-01139-y

Antonie Van Leeuwenhoek. 2022 Jan 15. doi: 10.1007/s10482-021-01696-3. Online ahead of print.

ABSTRACT

Current study was undertaken to carry out the genome-wide analysis of a multipotent isolate from desert soil which was previously identified as Bacillus tequilensis based on 16S rDNA analysis. This study also aims to characterize the serine protease and its biocatalytic potentials implying a combination of empirical and in-silico approaches. Next generation sequencing and short read de novo assembly generated the 4,235,084 bp draft genome of Bacillus sp. ZMS-2. Genome sequence analysis by digital DNA:DNA hybridization (dDDH) and average nucleotide identity classified the isolate as Bacillus subtilis ZMS-2 (Bioproject ID: PRJNA691551). Genome annotation revealed 10 antibiotic resistance genes, 8 antibiotic/antifungal gene clusters and 25 genes encoding proteases including subtilisin E, an extracellular alkaline protease. This extracellular protease (ZMS-2 protease) was produced using a statistically optimized medium, purified partially and characterized as alkaline serine protease. The partially purified ZMS-2 protease (780 U/mL) showed a 21 mm zone of casein hydrolysis and dehaired goat skin by pulling out hair with roots. These catalytic potentials of ZMS-2 protease were further confirmed using scanning electron microscopy of casein beads and dehaired skin. The study concludes B. subtilis ZMS-2 as a potent producer of a protease with promising potentials of commercial importance.

PMID:35031913 | DOI:10.1007/s10482-021-01696-3

Community Ment Health J. 2022 Jan 15. doi: 10.1007/s10597-021-00926-2. Online ahead of print.

ABSTRACT

Social capital is a complex concept that is considered an effective factor in the development of societies. Considering the importance of burdens of psychiatric disorders in Iran, we studied the relationship between various dimensions of social capital of parents of children and adolescents and psychiatric disorders among them. In this cross-sectional study, 18,940 parents of children and adolescents aged 6 to 18 years old were randomly selected from all provinces of Iran and were evaluated by the Millon clinical multiaxial inventory-III (MCMI-III) and a modified version of Nahapiet and Ghoshal questionnaire. MCMI-III was designed as a self-report tool for investigating psychiatric clinical disorders and personality traits in the general population. Modified Nahapiet and ghoshal questionnaire has 20 items and measures four components of social capital included trust, values, communication, and collaboration. Validity and reliability of both questionnaires have been approved in Iran. In the regression model, the relationship between social capital components and clinical and sever clinical syndromes, in the form of regression weight and standard weight for trust was – 0.558 and – 0.062 with p value less than 0.0001, and for values was – 0.466 and – 0.057, respectively, with p value less than 0.0001. There was a reverse correlation between social capital components of parents of children and adolescents and psychiatric disorders in Iran. In regression statistical models, the two components of values and trust were negative predictors of psychiatric disorders. Considering the high prevalence of psychiatric disorders in Iran, it seems that the strengthening of cognitive and structural aspects of social capital of parents of children and adolescents is one of the effective factors in reducing the prevalence of these disorders among them.

PMID:35031903 | DOI:10.1007/s10597-021-00926-2