Category: Nevin Manimala

Clin Pharmacol Ther. 2023 Apr 23. doi: 10.1002/cpt.2919. Online ahead of print.

ABSTRACT

Model-Informed Drug Development (MIDD) is a process that integrates drug exposure-based, biological, and statistical models to enhance the benefit-risk balance in drug development. The US Food and Drug Administration (FDA) MIDD Paired Meeting Pilot Program provides a platform to apply MIDD approaches to drug development and to seek regulatory feedback in a collaborative and streamlined process prior to submission for approval. Eli Lilly and Company (Lilly) participated in the Pilot Program to seek agency alignment to enhance the initial approved dosing regimens of cetuximab (Erbitux; Eli Lilly and Company, Indianapolis, Indiana) and ramucirumab (Cyramza; Eli Lilly and Company, Indianapolis, Indiana) without conducting additional clinical trials. Here we describe the overall MIDD strategy at Lilly, the process with the FDA, and the impact of implementing the approach.

PMID:37087634 | DOI:10.1002/cpt.2919

J Vet Emerg Crit Care (San Antonio). 2023 Apr 23. doi: 10.1111/vec.13297. Online ahead of print.

ABSTRACT

OBJECTIVE: To determine the value of microbubble contrast cystosonography in the diagnosis of bladder rupture in animals.

DESIGN: Prospective, method comparison study from November 2019 to October 2020.

SETTING: University teaching hospital.

ANIMALS: Thirty-four ethically sourced cadavers of dogs, rats, and rabbits.

INTERVENTIONS: In a prospective and blinded study, the cadavers were divided into 2 randomized groups: with bladder rupture (CR), and without bladder rupture (SR). Urinary catheterization was performed in all cadavers. Through the urethral catheter, bladders in CR group were ruptured using a rigid stainless steel guide wire. Microbubble contrast was infused into the bladder through the urethral catheter, while a single, blinded observer sonographically assessed the bladder. The time to diagnosis and the number of attempts needed for diagnosis were recorded.

MEASUREMENTS AND MAIN RESULTS: The study included cadavers of 16 female Wistar rats, 6 female dogs, 11 male dogs, and 1 male rabbit. Time to diagnosis in dogs (2.25 ± 0.91 min) was statistically higher when compared to rats (1.15 ± 0.75 min; P = 0.03). Of the 34 cases, incorrect diagnosis of bladder rupture was made in only 2 dogs (6%), indicating a diagnostic sensitivity of 88.88%, specificity of 100%, and an accuracy of 94%. The positive predictive value was 1 and the negative predictive value was 0.9.

CONCLUSIONS: Our study showed that the described method is accurate, sensitive, and specific for the detection of bladder rupture in animal cadavers of different species, size, and sex.

PMID:37087612 | DOI:10.1111/vec.13297

Zhonghua Yi Xue Za Zhi. 2023 Apr 25;103(16):1236-1241. doi: 10.3760/cma.j.cn112137-20221108-02352.

ABSTRACT

Objective: To investigate the effect of different gestational weeks and psychological intervention on pregnancy outcome in patients with monochorionic twin pregnancy. Methods: The clinical data of 68 patients with monochorionic twin pregnancy in the middle and late pregnancy who were treated with radiofrequency ablation in the First Affiliated Hospital of Zhengzhou University from March 2017 to April 2021 were retrospectively analyzed, including 54 patients with single chorionic and single amniotic sac and 14 patients with single chorionic and double amniotic sac. Patients were divided into three groups according to the gestational weeks:<20 weeks (n=36), 20-23 weeks (n=17) and ≥24 weeks (n=15); and were divided into intervention group (n=40) and control group (n=28) according to the preoperative psychological intervention. The pregnancy outcome of patients with different pregnancy reduction and the effect of psychological intervention on pregnancy outcome was analyzed. Results: The age of 68 patients was (30.2±4.6) years old, the gestational age was (22.2±3.2) weeks, and 60 cases (88.2%) were live births after fetal reduction. There were no significant difference in age [(31.8±4.7),(28.3±5.0),(30.3±4.0) years old] (P=0.098), abortion rate, preterm birth rate, live birth rate, delivery mode, gestational week of preterm birth, gestational week of delivery, and neonatal weight between the two groups at different gestational weeks (all P>0.05). The ages of the intervention group and the control group were (30.6±4.7) and (29.4±4.0) years old (P=0.352). After psychological intervention for 40 patients in the intervention group, the anxiety score after pregnancy reduction was reduced from (54.8±6.8) to (37.3±7.3) (P<0.001), while the depression score decreased from (62.7±7.2) to (33.2±2.4) (P<0.001). Compared with patients in the control group (12.5%, n=5), the proportion of postoperative discomfort in the intervention group was higher (53.6%, n=15) (P<0.001). Compared with the control group, there were no statistically significant difference in the postoperative preterm birth rate, abortion rate, live birth rate, delivery mode, gestational week of preterm birth, gestational week of delivery, and neonatal weight in the intervention group (all P>0.05). Conclusions: Radiofrequency ablation is a safe and effective minimally invasive technique. For complex monochorionic twin pregnancies, early fetal reduction (<20 weeks) and preoperative psychological intervention can provide a solid guarantee for a good postoperative pregnancy outcome.

PMID:37087408 | DOI:10.3760/cma.j.cn112137-20221108-02352

Zhonghua Yi Xue Za Zhi. 2023 Apr 25;103(16):1210-1216. doi: 10.3760/cma.j.cn112137-20221101-02275.

ABSTRACT

Objective: To investigate the efficacy and influencing factors of immunotherapy combined with chemotherapy and bevacizumab in patients with non-small cell lung cancer (NSCLC) who failed epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) treatment. Methods: A retrospective analysis was made on the clinical data of 60 NSCLC patients who were treated with immunotherapy combined with chemotherapy and bevacizumab after EGFR-TKIs treatment failure in the Affiliated Cancer Hospital of Shandong First Medical University from January 2019 to March 2022. Patients were followed up by telephone or outpatient review up to October 1, 2022, with a median follow-up of 8.2 months (95%CI: 7.1-9.3). All 60 patients were followed up. The response evaluation criteria in solid tumors were used to evaluate the short-term efficacy. The adverse reactions of patients were evaluated according to the common terminology criteria for adverse events. The survival curve was drawn by Kaplan-Meier method. Cox proportional hazard regression models were utilized to analyze the influencing factors of progression-free survival (PFS). Results: Among the 60 NSCLC patients, 22 were males. The age ranged from 41 to 75 years, with a median age of 61 years. Eleven patients had partial response, 19 patients had stable disease and 30 patients had progressive disease. The median PFS was 8.2 months (95%CI: 7.2-9.2). The median PFS of patients with low expression of programmed death receptor-ligand 1 (PD-L1) [Tumor cell Proportion Score (TPS)<1%], moderate expression of PD-L1 (1%≤TPS≤49%), and high expression of PD-L1 (TPS≥50%) were 6.4 (95%CI: 4.8-8.0), 8.3 (95%CI: 7.3-9.3) and 10.6 months (95%CI: 7.2-14.1), respectively, and there were statistically significant differences (χ²=13.58, P<0.001). Multivariate Cox proportional risk regression model analysis showed that age>65 years old (HR=4.017, 95%CI: 1.468-10.992, P=0.007) was a risk factor for PFS in NSCLC patients who received immunotherapy combined with chemotherapy and bevacizumab after EGFR-TKIs treatment failure. Moderate expression of PD-L1 (HR=0.360, 95%CI: 0.139-0.930, P=0.035) and high expression of PD-L1 (HR=0.155, 95%CI: 0.039-0.625, P=0.009) were protective factors for PFS. Most of the treatment-related adverse reactions in the whole group were grade 1-2, including bone marrow suppression (n=24), nausea (n=25), decreased appetite (n=24), fatigue (n=22), vomiting (n=18), abnormal liver function (n=17), blood creatinine increased (n=10), and so on. These were tolerated by the patients. Conclusions: NSCLC patients who failed EGFR-TKIs treatment can tolerate adverse reactions related to immunotherapy combined with chemotherapy and bevacizumab treatment. PFS is significantly prolonged in those aged≤65 years and those with moderate and high expression of PD-L1.

PMID:37087404 | DOI:10.3760/cma.j.cn112137-20221101-02275

Zhonghua Yi Xue Za Zhi. 2023 Apr 25;103(16):1202-1209. doi: 10.3760/cma.j.cn112137-20221028-02243.

ABSTRACT

Objective: To investigate the prognostic factors of patients with central nervous system (CNS) metastatic non-small cell lung cancer (NSCLC) with positive driver genes. Methods: The clinical data of 103 patients with CNS metastatic NSCLC admitted to Beijing Tongren Hospital from January 2016 to December 2020 were retrospectively analyzed, and the patients were divided into positive driver gene group (patients with driver genes mutation and receiving corresponding targeted therapy) and negative driver gene group. Cox univariate and multivariate regression analyses were performed to identify the factors affecting patients’ prognosis, and the receiver operating characteristic curve (ROC) was used to compare the predictive ability of 4 scoring systems [recursive partitioning analysis (RPA) classes, diagnosis-specific graded prognostic assessment (DS-GPA) index, basic score for brain metastasesn (BS-BM) and (lung-molecular graded prognostic assessment (lung-mol GPA)]on patients’ prognosis. Results: Among the 103 patients, 48 were males and 55 were females, and aged (64.6±9.7) years old. The median survival time of the 103 patients was 24.0 (95%CI: 20.0-28.0) months, the median survival time of the 59 patients in the positive driver gene group was 33.0 (95%CI: 23.4-42.6) months, the median survival time of the 44 patients in the negative driver gene group was 17.0 (95%CI: 14.4-19.6) months, and the difference was statistically significant (χ²=24.69, P<0.001). The results of Cox multivariate analysis showed that the negative driver genes (HR=3.788, 95%CI: 1.951-7.301, P=0.001), Karnofsky performance status (KPS) score<70 (HR=2.613, 95%CI: 1.185-5.761, P=0.017) and neutrophil-to-lymphocyte ratio (NLR)>3.22 (HR=2.714, 95%CI: 1.157-6.365, P=0.022) were independent risk factors affecting the prognosis of patients with CNS metastatic NSCLC. KPS score<70 (HR=3.719, 95%CI: 1.165-11.876, P=0.027) and no radiotherapy (HR=2.032, 95%CI: 1.033-11.364, P=0.041) were independent risk factors affecting the prognosis of patients with CNS metastatic NSCLC with positive driver genes. ROC curve analysis showed that the area under curve (AUC) value of lung-mol GPA was the highest among the 4 scoring systems (AUC=0.843, 95%CI: 0.731-0.956, P<0.001), and the AUC value of the lung-mol GPA combined scoring system (AUC=0.904, 95%CI: 0.816-0.991, P<0.001) was higher than lung-mol GPA. Conclusions: A low KPS score and no cranial radiation therapy are independent risk factors for the prognosis of patients with CNS metastatic NSCLC with positive driver genes; the lung-mol GPA joint scoring system is more conducive to the prognostic assessment of patients with CNS metastatic NSCLC with positive driver genes.

PMID:37087403 | DOI:10.3760/cma.j.cn112137-20221028-02243

BMC Nurs. 2023 Apr 23;22(1):132. doi: 10.1186/s12912-023-01303-y.

ABSTRACT

BACKGROUND: This study aimed to examine the effects of psychological distress, depressive symptoms, and emotional eating behaviors on the health-related quality of life of middle-aged Korean females. This study provides primary data for developing an intervention program to improve the health-related quality of life of middle-aged females.

METHODS: Middle-aged females between 35 and 64 years old, from July 22 to August 10, 2021, were included in this study. The mediating effects of depressive symptoms and emotional eating behaviors on the relationship between psychological distress and health-related quality of life were investigated. A cross-sectional survey was conducted on 325 subjects. Researchers conducted questionnaires measuring psychological distress, depressive symptoms, emotional eating behavior, and health-related quality of life.

RESULTS: The findings of this study demonstrated a correlation between the severity of a female’s depressive symptoms and the degree of their psychological distress, indicating that severe depressive symptoms were associated with negative emotions, which increased emotional eating behaviors. Additionally, more severe depressive symptoms indicated a lower health-related quality of life. Higher psychological distress was associated with increased emotional eating behaviors and lower health-related quality of life. The total and direct effects of psychological distress on the health-related quality of life were statistically significant.

CONCLUSIONS: In this study, psychological distress, depressive symptoms, and emotional eating behaviors affected the health-related quality of life of middle-aged Korean females. This study also confirmed that psychological distress had a direct effect on health-related quality of life. These findings serve as primary data for evidence-based intervention programs that alleviate emotional health problems, such as psychological distress and depressive symptoms in middle-aged females. Moreover, nurses can help develop effective treatment strategies to improve health-related quality of life by identifying and assessing potential symptoms of psychological distress, depressive symptoms, and emotional eating behaviors.

PMID:37087430 | DOI:10.1186/s12912-023-01303-y

Anal Chim Acta. 2023 Jun 1;1258:341185. doi: 10.1016/j.aca.2023.341185. Epub 2023 Apr 6.

ABSTRACT

Identifying the islet heterogeneity (cell types and the proportion of each subpopulation) and their relevance to function and disease will lead to fundamental information for the prevention and therapies of diabetes. Here, we introduce a single-cell phenotypic essay on the heterogeneity within individual pancreatic islets by using the combination of synchrotron infrared microspectroscopy and quantitative calculation. In a mouse model, the cellular heterogeneities at both the whole pancreas and single intact islet level were identified. The variation of biochemical phenotypes successfully subdivided islet cells into five main groups and quantitatively determined their proportion. These findings not only demonstrate single-cell infrared phenomics as a value complementary technique and strategy for the description of cellular heterogeneity within the pancreatic islets but also provide a quick, label-free optical platform for investigating phenotypic heterogeneity at the small-organelle level with single cell resolution.

PMID:37087295 | DOI:10.1016/j.aca.2023.341185

Food Res Int. 2023 May;167:112724. doi: 10.1016/j.foodres.2023.112724. Epub 2023 Mar 21.

ABSTRACT

Increasing concerns about freshwater sources necessitate the management of wastewater, such as the wastewater generated from Clean-in-Place (CIP) operations. In this investigation, a membrane system composed of nanofiltration (NF) and direct contact membrane distillation (DCMD) was proposed to manage model dairy CIP wastewater that contained NaOH as an alkaline cleaning agent. During the NF step, prefiltration by a 4 kDa membrane or a 4 kDa membrane followed by a 200 Da membrane (4 kDa/200 Da) was used to remove the whey protein and lactose. With these two membranes in series of NF, the protein concentration was reduced by 92.4% and the lactose content was reduced to a non-detectable level when compared to the model CIP wastewater. Before concentrating the permeates from NF steps, three DCMD membranes (FR, Solupor, and ST) with different characteristics were evaluated to manage the NF permeates from 4 kDa or 200 Da NF. An increase in the feed temperature from 40 °C to 60 °C resulted in an increase in the water flux during DCMD operation, except for FR. In addition, it was found that ST generated the highest water flux when compared to the other membranes. Using ST and a feed temperature of 60 °C, the permeates from 4 kDa or 4 kDa/200 Da were continuously concentrated for 7 h with DCMD. During this concentration, there was no significant decline in flux. The cleaning effectiveness of the cleaning agent (NaOH) recovered by NF and DCMD was compared with a fresh cleaning solution using quartz crystal microbalance with dissipation (QCM-D). It was found that the cleaning agents recovered by 4 kDa/200 Da NF presented a statistically identical cleaning rate compared to fresh NaOH. This research highlights the potential of NF and DCMD to regenerate alkaline cleaning agents, while reclaiming water from dairy CIP wastewater.

PMID:37087280 | DOI:10.1016/j.foodres.2023.112724

Food Res Int. 2023 May;167:112700. doi: 10.1016/j.foodres.2023.112700. Epub 2023 Mar 17.

ABSTRACT

This study evaluated chemical compositions of green coffee beans from multi-production regions and correlated this information with thermal contaminants in roasted coffee. Using multivariate statistical techniques, formation of 5-hydroxymethylfurfural (5-HMF), furan, 2- and 3-methylfuran were positively correlated with lipid, sucrose, glutamic acid, phenylalanine, margaric acid, linolenic acid and trigonelline in green coffee beans. Moreover, significant positive correlations between acrylamide (AA) levels with aspartic acid, serine, alanine, histidine, asparagine, protein, and caffeine was found in green beans. Despite this, 5-HMF, furan, 2- and 3-methylfuran showed negative correlations with active constitutes (neochlorogenic acid, cryptochlorogenic acid, caffeine, total phenolics (TPC) and total flavonoids contents (TFC)), and several amino acids, and there were slight negative relationships between AA and myristic acid, palmitic acid, chlorogenic acid, sucrose, lipid, TPC and TFC. This study provides valuable enlightenment for the selection of proper coffee beans for production of coffee with high nutrition and low chemical hazardous risks.

PMID:37087268 | DOI:10.1016/j.foodres.2023.112700

Food Res Int. 2023 May;167:112697. doi: 10.1016/j.foodres.2023.112697. Epub 2023 Mar 20.

ABSTRACT

A protocol was optimized to determine the volatile profile from monovarietal virgin olive oil (VOO) by multiple headspace solid-phase microextraction (MHS-SPME) followed by gas chromatography-mass spectrometry (GC-MS) analysis. For this, a Plackett-Burman (PB) and central composite rotational designs (CCRD) were used to define the best condition of extraction. Moreover, fatty acids profile and principal component analysis (PCA) was used to identify markers among the cultivars. The amount of 0.1 g of sample was enough to express the volatile composition of the olive oils by MHS-SPME. Volatile compounds [nonanal, (Z)-3-Hexen-1-ol, (Z)-3-Hexenyl Acetate, Hexyl Acetate, 3-Methylbutyl Acetate, (E)-2-Hexen-1-ol, (E)-2-Hexenyl Acetate] and fatty acids [C17:1, C18, C18:1, C18:2] were those reported such as the markers in the varieties of olive oils. The PCA analysis allowed the classification of the most representative volatiles and fatty acids for each cultivar. Through two principal components was possible to obtain 81.9% of explanation of the variance of the compounds. The compounds were quantified using a validated method. The MHS-SPME combined with multivariate analysis showed a promising tool to identify markers and for the discrimination of olive oil varieties.

PMID:37087263 | DOI:10.1016/j.foodres.2023.112697