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BACKGROUND: An inexpensive, simple, and accurate plasma concentration measurement system is needed to actively conduct pharmacokinetic and pharmacodynamic analyses of vadadustat, hypoxia-inducible factor-prolyl hydroxylase inhibitor, in clinical settings. In this study, the authors aimed to develop a method for measuring vadadustat in human plasma that could be applied for therapeutic drug monitoring using high-performance liquid chromatography with ultraviolet detection (HPLC-UV) in a clinical setting. METHODS: Plasma samples (100 µL) were pretreated with acetonitrile using butyl paraoxybenzoate as an internal standard. Chromatographic separation was performed on a SunShell PFP C18 column (2.6 µm, 4.6 mm × 150 mm). The mobile phase consisted of (A) 20 mM of phosphate buffer (pH 2.4) and (B) acetonitrile (60:40, v/v), delivered isocratically at a flow rate of 1 mL/min. The analytes were detected by UV absorbance at a wavelength of 220 nm, and the column temperature was 40°C. To evaluate the applicability of HPLC-UV in a clinical setting, blood samples were collected at 19 time points from 7 patients who had been taking vadadustat. RESULTS: The calibration curve was linear over the concentration range of 0.2-150 mcg/mL (R2 > 0.99). Intra-assay and interassay accuracy, precision, and stability met the Food and Drug Administration recommendations. The vadadustat plasma concentrations of patients analyzed using the current HPLC-UV method were almost equal to those measured using ultra-performance liquid chromatography-tandem mass spectrometry (mean difference: 0.13 mcg/mL). Large variability in the dose-adjusted plasma concentrations of vadadustat at 12 hours after administration was observed between patients (coefficient of variation = 57.6%). CONCLUSIONS: This HPLC-UV method is a simple, accurate quantification method for evaluating plasma concentrations in patients taking vadadustat in a clinical setting.
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Objective Pembrolizumab plus platinum and pemetrexed (Pemb-Plt-PEM) combination therapy is an effective first-line treatment for advanced non-squamous non-small-cell lung cancer (NSCLC), regardless of programmed death ligand 1 expression. However, the effectiveness and feasibility of first-line Pemb-Plt-PEM therapy in elderly patients (≥75 years old) remain unclear. Therefore, this study investigated the safety and efficacy of first-line Pemb-Plt-PEM in elderly patients with nonsquamous NSCLC. Methods We retrospectively evaluated the data of patients ≥75 years old with non-squamous NSCLC who were treated with first-line Pemb-Plt-PEM from December 2018 to December 2020 at 10 institutes in Japan. Data on patient characteristics, efficacy of pemb-Plt-PEM therapy, and the type and severity of adverse events were reviewed. Results Thirty patients [20 men and 10 women; median age: 76 (range: 75-82) years old] were included in the analysis. The overall response rate, disease control rate, median progression-free survival (PFS), and median overall survival (OS) were 40.0%, 66.7%, and 7.5 and 24.0 months, respectively. The treatment-related deaths were caused by pneumonitis. First-line Pemb-Plt-PEM was associated with the PFS, based on the neutrophil-to-lymphocyte ratio (NLR). The PFS for low and high NLR values was 10.1 and 2.0 months, respectively. Furthermore, the sex and NLR influenced the association between Pemb-Plt-PEM and the OS. The OS for low and high NLR values was 32.8 and 2.6 months, respectively. Conclusion First-line pemb-Plt-PEM therapy is effective and feasible in elderly patients with non-squamous NSCLC.
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BACKGROUND: The antifibrotic agents pirfenidone and nintedanib have been shown to be effective in patients with idiopathic pulmonary fibrosis (IPF). However, discontinuation of antifibrotic drugs is a major clinical concern because of the lack of alternative treatment options. Therefore, we identified factors that may be useful for predicting the termination of antifibrotic agents. METHODS: We retrospectively recruited 280 IPF patients treated with antifibrotic drugs between 2009 and 2018 from seven regional core hospitals in Gunma prefecture, Japan. RESULTS: At four months, the short-term discontinuation group exhibited a significantly worse prognosis in the pirfenidone group and a poorer prognosis in the nintedanib group compared to that in the continuation group. The discontinuation group of pirfenidone at 4 months exhibited lower albumin and higher C-reactive protein (CRP) levels in the sera compared to the group that continued treatment for more than 4 months. In multivariate analysis, the Glasgow prognostic score (GPS), well known as a predictor of cancer prognosis, which comprises serum CRP and albumin levels, predicted early discontinuation and prognosis in the pirfenidone group, whereas the body mass index (BMI) predicted early discontinuation of nintedanib. A high GPS, with both albumin <3.5 g/dL and CRP >1.0 mg/dL, was associated with a poorer prognosis in the pirfenidone group. CONCLUSION: GPS and BMI were significant factors for short-term pirfenidone and nintedanib discontinuation, respectively. Initial evaluation of GPS and BMI prior to antifibrotic therapy may contribute to less interrupted IPF management, thus leading to better prognostic outcomes in patients with IPF.
Subject(s)
Antifibrotic Agents , Idiopathic Pulmonary Fibrosis , Indoles , Humans , Body Mass Index , Prognosis , Retrospective Studies , Treatment Outcome , Idiopathic Pulmonary Fibrosis/chemically induced , Pyridones/therapeutic use , AlbuminsABSTRACT
Purpose This study aimed to compare the image quality between echo planar imaging (EPI) with compressed sensing-sensitivity encoding (EPICS)-based diffusion-weighted imaging (DWI) and conventional parallel imaging (PI)-based DWI of the head and neck. Materials and methods Ten healthy volunteers participated in this study. EPICS-DWI was acquired based on an axial spin-echo EPI sequence with EPICS acceleration factors of 2, 3, and 4, respectively. Conventional PI-DWI was acquired using the same acceleration factors (i.e., 2, 3, and 4). Quantitative assessment was performed by measuring the signal-to-noise ratio (SNR) and apparent diffusion coefficient (ADC) in a circular region of interest (ROI) on the parotid and submandibular glands. For qualitative evaluation, a three-point visual grading system was used to assess the (1) overall image quality and (2) degree of image distortion. Results In the quantitative assessment, the SNR of the parotid gland in EPICS-DWI was significantly higher than that of PI-DWI in acceleration factors of 3 and 4 (p<0.05). In a comparison of ADC values, significant differences were not observed between EPICS-DWI and PI-DWI. In the qualitative assessment, the overall image quality of EPICS-DWI was significantly higher than that of PI-DWI for acceleration factors 3 and 4 (p<0.05). The degree of image distortion was significantly larger in EPICS-DWI with an acceleration factor of 2 than that of 3 or 4 (p<0.01, respectively). Conclusion Under the appropriate parameter setting, EPICS-DWI demonstrated higher SNR and better overall image quality for head and neck imaging than PI-DWI, without increasing image distortion.
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PURPOSE: To assess the utility of deep learning (DL)-based image reconstruction with the combination of compressed sensing (CS) denoising cycle by comparing images reconstructed by conventional CS-based method without DL in fat-suppressed (Fs)-contrast enhanced (CE) three-dimensional (3D) T1-weighted images (T1WIs) of the head and neck. MATERIALS AND METHODS: We retrospectively analyzed the cases of 39 patients who had undergone head and neck Fs-CE 3D T1WI applying reconstructions based on conventional CS and CS augmented by DL, respectively. In the qualitative assessment, we evaluated overall image quality, visualization of anatomical structures, degree of artifacts, lesion conspicuity, and lesion edge sharpness based on a five-point system. In the quantitative assessment, we calculated the signal-to-noise ratios (SNRs) of the lesion and the posterior neck muscle and the contrast-to-noise ratio (CNR) between the lesion and the adjacent muscle. RESULTS: For all items of the qualitative analysis, significantly higher scores were awarded to images with DL-based reconstruction (p < 0.001). In the quantitative analysis, DL-based reconstruction resulted in significantly higher values for both the SNR of lesions (p < 0.001) and posterior neck muscles (p < 0.001). Significantly higher CNRs were also observed in images with DL-based reconstruction (p < 0.001). CONCLUSION: DL-based image reconstruction integrating into the CS-based denoising cycle offered superior image quality compared to the conventional CS method. This technique will be useful for the assessment of patients with head and neck disease.
Subject(s)
Deep Learning , Humans , Retrospective Studies , Signal-To-Noise Ratio , Muscles , Magnetic Resonance Imaging/methods , ArtifactsABSTRACT
PURPOSE: To develop a convolutional neural network (CNN) model to diagnose skull-base invasion by nasopharyngeal malignancies in CT images and evaluate the model's diagnostic performance. MATERIALS AND METHODS: We divided 100 malignant nasopharyngeal tumor lesions into a training (n = 70) and a test (n = 30) dataset. Two head/neck radiologists reviewed CT and MRI images and determined the positive/negative skull-base invasion status of each case (training dataset: 29 invasion-positive and 41 invasion-negative; test dataset: 13 invasion-positive and 17 invasion-negative). Preprocessing involved extracting continuous slices of the nasopharynx and clivus. The preprocessed training dataset was used for transfer learning with Residual Neural Networks 50 to create a diagnostic CNN model, which was then tested on the preprocessed test dataset to determine the invasion status and model performance. Original CT images from the test dataset were reviewed by a radiologist with extensive head/neck imaging experience (senior reader: SR) and another less-experienced radiologist (junior reader: JR). Gradient-weighted class activation maps (Grad-CAMs) were created to visualize the explainability of the invasion status classification. RESULTS: The CNN model's diagnostic accuracy was 0.973, significantly higher than those of the two radiologists (SR: 0.838; JR: 0.595). Receiver operating characteristic curve analysis gave an area under the curve of 0.953 for the CNN model (versus 0.832 and 0.617 for SR and JR; both p < 0.05). The Grad-CAMs suggested that the invasion-negative cases were present predominantly in bone marrow, while the invasion-positive cases exhibited osteosclerosis and nasopharyngeal masses. CONCLUSIONS: This CNN technique would be useful for CT-based diagnosis of skull-base invasion by nasopharyngeal malignancies.
Subject(s)
Deep Learning , Nasopharyngeal Neoplasms , Neoplasm Invasiveness , Tomography, X-Ray Computed , Humans , Nasopharyngeal Neoplasms/diagnostic imaging , Tomography, X-Ray Computed/methods , Neoplasm Invasiveness/diagnostic imaging , Male , Middle Aged , Female , Aged , Adult , Skull Base/diagnostic imaging , Skull Base Neoplasms/diagnostic imaging , Magnetic Resonance Imaging/methods , Sensitivity and Specificity , Retrospective StudiesABSTRACT
OBJECTIVES: We aimed to predict in vitro chemosensitivity assay results from computed tomography (CT) images by applying deep learning (DL) to optimize chemotherapy for pancreatic ductal adenocarcinoma (PDAC). MATERIALS AND METHODS: Preoperative enhanced abdominal CT images and the histoculture drug response assay (HDRA) results were collected from 33 PDAC patients undergoing surgery. Deep learning was performed using CT images of both the HDRA-positive and HDRA-negative groups. We trimmed small patches from the entire tumor area. We established various prediction labels for HDRA results with 5-fluorouracil (FU), gemcitabine (GEM), and paclitaxel (PTX). We built a predictive model using a residual convolutional neural network and used 3-fold cross-validation. RESULTS: Of the 33 patients, effective response to FU, GEM, and PTX by HDRA was observed in 19 (57.6%), 11 (33.3%), and 23 (88.5%) patients, respectively. The average accuracy and the area under the receiver operating characteristic curve (AUC) of the model for predicting the effective response to FU were 93.4% and 0.979, respectively. In the prediction of GEM, the models demonstrated high accuracy (92.8%) and AUC (0.969). Likewise, the model for predicting response to PTX had a high performance (accuracy, 95.9%; AUC, 0.979). CONCLUSIONS: Our CT patch-based DL model exhibited high predictive performance in projecting HDRA results. Our study suggests that the DL approach could possibly provide a noninvasive means for the optimization of chemotherapy.
Subject(s)
Carcinoma, Pancreatic Ductal , Deep Learning , Pancreatic Neoplasms , Humans , Drug Resistance, Neoplasm , Drug Screening Assays, Antitumor , Fluorouracil/therapeutic use , Pancreatic Neoplasms/diagnostic imaging , Pancreatic Neoplasms/drug therapy , Pancreatic Neoplasms/pathology , Gemcitabine , Paclitaxel/pharmacology , Paclitaxel/therapeutic use , Carcinoma, Pancreatic Ductal/diagnostic imaging , Carcinoma, Pancreatic Ductal/drug therapy , TomographyABSTRACT
INTRODUCTION: Pembrolizumab (Pemb) therapy in conjunction with carboplatin and paclitaxel (PTX)/nab-PTX has been efficacious in treating non-small cell lung cancer (NSCLC). However, the response predictors of this combination therapy (Pemb-combination) remain undetermined. We aimed to evaluate whether Glasgow prognostic score (GPS), neutrophil-to-lymphocyte ratio (NLR), body mass index (BMI), platelet-to-lymphocyte ratio (PLR), and prognostic nutritional index (PNI) are potential factors in prognosticating the response to Pemb-combination therapy in advanced NSCLC patients. METHODS: We retrospectively recruited 144 NSCLC patients receiving first-line treatment with Pemb-combination therapy from 13 institutions between December 1, 2018, and December 31, 2020. GPS, NLR, BMI, PLR, and PNI were assessed for their efficacy as prognostic indicators. Cox proportional hazard models and the Kaplan-Meier method were used to compare the progression-free survival (PFS) and overall survival (OS) of the patients. RESULTS: The treatment exhibited a response rate of 63.1% (95% confidence interval [CI]: 55.0-70.6%). Following Pemb-combination administration, the median PFS and OS were 7.3 (95% CI: 5.3-9.4) and 16.5 (95% CI: 13.9-22.1) months, respectively. Contrary to PNI, NLR, GPS, BMI, and PLR did not display substantially different PFS in univariate analysis. However, multivariate analysis did not identify PNI as an independent prognostic factor for PFS. Furthermore, univariate analysis revealed that GPS, BMI, and PLR exhibited similar values for OS but not NLR and PNI. Patients with PNI ≥45 were predicted to have better OS than those with PNI <45 (OS: 23.4 and 13.9 months, respectively, p = 0.0028). Multivariate analysis did not establish NLR as an independent prognostic factor for OS. CONCLUSION: The PNI evidently predicted OS in NSCLC patients treated with Pemb-combination as first-line therapy, thereby validating its efficiency as a prognostic indicator of NSCLC.
Subject(s)
Albumins , Antibodies, Monoclonal, Humanized , Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Humans , Carcinoma, Non-Small-Cell Lung/drug therapy , Prognosis , Nutrition Assessment , Carboplatin , Lung Neoplasms/drug therapy , Retrospective Studies , Lymphocyte Count , Paclitaxel , NeutrophilsABSTRACT
OBJECTIVES: To investigate the utility of deep learning (DL)-based image reconstruction using a model-based approach in head and neck diffusion-weighted imaging (DWI). MATERIALS AND METHODS: We retrospectively analyzed the cases of 41 patients who underwent head/neck DWI. The DWI in 25 patients demonstrated an untreated lesion. We performed qualitative and quantitative assessments in the DWI analyses with both deep learning (DL)- and conventional parallel imaging (PI)-based reconstructions. For the qualitative assessment, we visually evaluated the overall image quality, soft tissue conspicuity, degree of artifact(s), and lesion conspicuity based on a five-point system. In the quantitative assessment, we measured the signal-to-noise ratio (SNR) of the bilateral parotid glands, submandibular gland, the posterior muscle, and the lesion. We then calculated the contrast-to-noise ratio (CNR) between the lesion and the adjacent muscle. RESULTS: Significant differences were observed in the qualitative analysis between the DWI with PI-based and DL-based reconstructions for all of the evaluation items (p < 0.001). In the quantitative analysis, significant differences in the SNR and CNR between the DWI with PI-based and DL-based reconstructions were observed for all of the evaluation items (p = 0.002 ~ p < 0.001). DISCUSSION: DL-based image reconstruction with the model-based technique effectively provided sufficient image quality in head/neck DWI.
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PURPOSE: This study aims to clarify the impact of CYP3A5 and ABCB1 polymorphisms on the pharmacokinetics of vincristine (VCR) in adult patients receiving CHOP therapy. METHODS: Plasma samples were collected immediately after the end of VCR administration and at 1.5, 2.5, 3.5, 5.5, 9.5, 13.5, and 25.5 h after the start of administration. Areas under the plasma concentration-time curves of VCR in the elimination phase (AUC1.5-25.5) were calculated using the linear trapezoidal rule. Half-lives of VCR during the early phase (1.5-5.5 h) and terminal phase (5.5-25.5 h; t1/2γ) were determined according to the log-linear regression of the concentration-time data for at least 3 sampling points. RESULTS: A total of 41 adult patients were enrolled in this study. The median t1/2γ and AUC1.5-25.5 were significantly longer and higher in CYP3A5 non-expressers (CYP3A5*3/*3) than in CYP3A5 expressers (CYP3A5*1/*1 or *1/*3) (21.3 vs 13.8 h, P = 0.005 and 35.5 vs 30.0 ng・h/mL, P = 0.006, respectively). Conversely, there were no significant differences in pharmacokinetic parameters among the ABCB1 c.1236C>T, c.2677G>A/T, c.3435C>T genotype groups. A stepwise selection multiple linear regression analysis showed that the dose of VCR administered and CYP3A5 non-expresser status were independent factors influencing the AUC1.5-25.5 (partial R2 = 0.212, P = 0.002 and partial R2 = 0.143, P = 0.010, respectively). CONCLUSION: The CYP3A5*3 polymorphism was found to be an indicator for predicting exposure to VCR in adult patients receiving CHOP therapy. This information may be useful for the individualization of VCR dosages.
Subject(s)
Cytochrome P-450 CYP3A , Adult , Humans , ATP Binding Cassette Transporter, Subfamily B/genetics , Cytochrome P-450 CYP3A/genetics , Genotype , Half-Life , Ubiquitin-Protein Ligases , VincristineABSTRACT
BACKGROUND: Factors predicting the response to pembrolizumab plus platinum and pemetrexed combination therapy (Pemb-Plt-PEM) in nonsquamous non-small cell lung cancer (non-sq NSCLC) are unclear. We investigated the Glasgow Prognostic (GP) score, neutrophil-to-lymphocyte ratio (NLR), and body mass index (BMI) as predictors of response to initial treatment with combination therapy in individuals with advanced non-sq NSCLC. METHODS: We retrospectively reviewed 236 patients who received initial treatment with combination therapy for non-sq NSCLC at 13 institutions between December 2018 and December 2020. The usefulness of the GP score, NLR, and BMI as prognostic indicators was assessed. Cox proportional hazard models and the Kaplan-Meier method were used to compare progression-free survival (PFS) and overall survival (OS). RESULTS: The response rate was 51.2% (95% CI: 44.9-57.5%). The median PFS and OS after beginning Pemb-Plt-PEM were 8.8 (95% CI: 7.0-11.9) months and 23.6 (95% CI: 18.7-28.6) months, respectively. The NLR independently predicted the efficacy of Pemb-Plt-PEM-the PFS and OS were more prolonged in individuals with NLR <5 than in those with NLR ≥5 (PFS: 12.8 vs. 5.3 months, p = 0.0002; OS: 29.4 vs. 12.0 months, p < 0.0001). BMI predicted the treatment response-individuals with BMI ≥22.0 kg/m2 had longer OS than did those with BMI < 22.0 kg/m2 (OS: 28.4 vs. 18.4 months, p = 0.0086). CONCLUSIONS: The NLR significantly predicted PFS and OS, whereas BMI predicted OS, in individuals who initially received Pemb-Plt-PEM for non-sq NSCLC. These factors might be prognosis predictors in non-sq NSCLC.
Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Humans , Pemetrexed/adverse effects , Platinum , Neutrophils , Retrospective Studies , LymphocytesABSTRACT
We analyzed 4 cases who experienced extravasation of anthracyclines and had dexrazoxane therapy in our hospital. Concerned drugs were 2 adriamycin and 2 amrubicin cases and all cases received steroid ointment therapy, and no cases showed severe condition such as skin ulcer. As dexrazoxane is known to enhance bone marrow suppression of anti-cancer drugs, the nadir of neutropenia and thrombocytopenia was observed from day 10 to 17 in our cases. We made a domestic manual and have used in various professionals. Dexrazoxane would contribute to the reduction of skin damage due to extravasation if we could manage bone marrow suppression successfully.
Subject(s)
Antineoplastic Agents , Dexrazoxane , Razoxane , Humans , Dexrazoxane/therapeutic use , Razoxane/therapeutic use , Antibiotics, Antineoplastic/therapeutic use , Anthracyclines/adverse effects , Antineoplastic Agents/therapeutic useABSTRACT
In this study, we investigated the impact of single nucleotide polymorphisms in solute carrier (SLC) transporters, that is, SLC22A7 c.1586 + 206A > G, SLC22A2 c.808G > T, SLC22A3 c.1233G > A, SLC47A1 c.922-158G > A, and SLC47A2 c.-130G > A, on serum creatinine (SCr) concentrations. This cross-sectional study included residents who participated as volunteers in a health promotion study. Lifestyle data, blood chemical analysis data, and SLC gene polymorphism information were collected from each participant. Univariate analyses were carried out to determine differences between groups and correlations in SCr. Stepwise multiple regression analysis was performed to confirm the independence of factors that were significantly different in the univariate analyses. In multiple regression analyses, muscle mass, serum cystatin C concentrations, body fat percentage, serum albumin concentrations, and SLC47A2 c.-130G/G had the highest contribution to SCr concentrations, in that order (standardized regression coefficients = .505, .332, -.234, .123, and .084, respectively). The final model explained 72.2% of the variability in SCr concentrations. The SLC47A2 c.-130G > A polymorphism may affect creatinine dynamics in the proximal tubules. Further studies are needed to determine the effects of SLC transporter gene polymorphisms on SCr concentrations in patients with various diseases in real-world clinical settings.
Subject(s)
Membrane Transport Proteins , Polymorphism, Single Nucleotide , Humans , Creatinine , Healthy Volunteers , Cross-Sectional StudiesABSTRACT
INTRODUCTION: The authors aimed to examine the impact of single nucleotide polymorphisms in P-glycoprotein, the hepatic uptake transporter organic anion transporter protein 1B1, cytochrome P450 ( CYP ) 3A5, and carboxylesterase-1 ( CES1 ) on the steady-state dose-adjusted trough concentrations of edoxaban (C Edo /D) and M-4 (C M-4 /D). They also investigated whether C M-4 and C Edo affect prothrombin time (PT). METHODS: The analyses included 152 patients with nonvalvular atrial fibrillation (NVAF) undergoing AF catheter ablation. The CYP3A5*3 ; CES1 c.1168-33A>C, c.257+885T>C; SLCO1B1 c.388A>G, c.521T>C; and ABCB1 c.3435C>T, c.2677G>A/T, c.1236C>T genotypes were determined. RESULTS: Stepwise selection multiple linear regression analyses demonstrated that creatinine clearance (Ccr), concomitant use of amiodarone, and SLCO1B1*15 haplotype status were independent factors influencing C M-4 /D (partial R2 = 0.189, 0.098, 0.067, respectively, all P values < 0.005). Ccr and concomitant use of amiodarone were independent factors influencing C Edo /D (partial R2 = 0.260, 0.117, respectively, both P value < 0.001). C Edo and C M-4 showed a weak correlation with PT (ρ = 0.369 and 0.315, both P values < 0.001). CONCLUSIONS: Although information concerning Ccr, concomitant use of amiodarone, and SLCO1B1*15 haplotype may be useful in assessing the pharmacokinetics of edoxaban, further studies are needed to clarify the requirement of PT monitoring at the trough level for dose adjustment of edoxaban in patients with NVAF.
Subject(s)
Amiodarone , Atrial Fibrillation , Humans , Haplotypes , Atrial Fibrillation/drug therapy , Atrial Fibrillation/genetics , Prothrombin Time , Liver-Specific Organic Anion Transporter 1/geneticsABSTRACT
PURPOSE: We examined the impact of polymorphisms in genes encoding cytochrome P450 (CYP) 3A5 (gene code CYP3A5), P-glycoprotein (ABCB1), breast cancer resistance protein (ABCG2), cytochrome P450 oxidoreductase (POR), and pregnane X receptor (PXR; NR1I2) on the daily dose-adjusted steady-state trough concentrations (C0h/D) of apixaban. METHODS: The analyses included 104 patients with non-valvular atrial fibrillation (NVAF) undergoing AF catheter ablation. The CYP3A5*3; ABCG2 421C > A; ABCB1 1236C > T, 2677G > A/T, 3435C > T, and 2482-2236G > A; NR1I2 11156A > C, 11193T > C, and 8055C > T; and POR*28 genotypes were determined. The combination of the noted NR1I2 genotypes determined the PXR*1B haplotype. RESULTS: Multiple linear regression analyses demonstrated that decreased creatinine clearance (Ccr) and the PXR*1B/*1B haplotype correlated with increased C0h/D of apixaban, while the presence of the POR*28 allele correlated with decreased C0h/D of apixaban (partial R2 = 0.168, 0.029, and 0.044, all P < 0.05). The mean (95% CI) of estimated marginal means of apixaban C0h/D calculated using Ccr as a covariate was the highest in POR*28 noncarriers with PXR*1B/*1B (23.5 [21.0-25.9] ng/mL/[mg/day]) and lowest in POR*28 carriers with other haplotypes (16.6 [15.5-17.7] ng/mL/[mg/day]). CONCLUSION: The PXR*1B haplotype and POR*28 genotype statuses, which involve genes that impact the expression of multiple drug-metabolizing enzymes and drug-transporters, may have modest effects on the C0h/D of apixaban, but these effects were found to be small.
Subject(s)
Atrial Fibrillation , Cytochrome P-450 CYP3A , Humans , Cytochrome P-450 CYP3A/genetics , Cytochrome P-450 CYP3A/metabolism , Pregnane X Receptor/genetics , Atrial Fibrillation/drug therapy , Atrial Fibrillation/genetics , ATP Binding Cassette Transporter, Subfamily G, Member 2/genetics , Neoplasm Proteins/genetics , Polymorphism, Genetic , Genotype , Polymorphism, Single NucleotideABSTRACT
BACKGROUND: As members of a medical team, pharmacists are expected to provide optimal patient-centered, evidence-based pharmacotherapy. In Japan, in consideration of the importance of palliative care, a system was initiated for certifying palliative care pharmacists in 2010. However, no studies have evaluated the usefulness of board certification in palliative pharmacy. Therefore, we surveyed the status of medication guidance for the physical and psychological symptoms of patients receiving palliative care and compared the medication guidance provided by certified and uncertified pharmacists. METHODS: The survey was conducted in February and March 2022. Pharmacists registered as members of the Japanese Society of Pharmaceutical Palliative Care and Sciences were surveyed by using a web-based questionnaire and 209 pharmacists responded: the certified pharmacist group comprised 123 (58.9%) pharmacists and the uncertified pharmacist group comprised 86 (41.1%) pharmacists. RESULTS: The certified pharmacist group provided better and more frequent medication guidance, according to responses to four of the six items related to pain relief. Three items were related to non-pain symptom relief, and one of the four items was related to psychiatric symptom relief (P < 0.05). The study showed that the certified pharmacist group received a better rating than the uncertified pharmacist group for involvement in palliative pharmacotherapy leading to improvement of patient quality of life (P < 0.05). CONCLUSION: As compared with uncertified pharmacists, certified pharmacists intervened more proactively and provided a broader range of palliative care.
Subject(s)
Palliative Care , Pharmacists , Humans , Japan , Quality of Life , CertificationABSTRACT
BACKGROUND: In nasal or sinonasal tumors, orbital invasion beyond periorbita by the tumor is one of the important criteria in the selection of the surgical procedure. We investigated the usefulness of the convolutional neural network (CNN)-based deep learning technique for the diagnosis of orbital invasion, using computed tomography (CT) images. METHODS: A total of 168 lesions with malignant nasal or sinonasal tumors were divided into a training dataset (n = 119) and a test dataset (n = 49). The final diagnosis (invasion-positive or -negative) was determined by experienced radiologists who carefully reviewed all of the CT images. In a CNN-based deep learning analysis, a slice of the square target region that included the orbital bone wall was extracted and fed into a deep-learning training session to create a diagnostic model using transfer learning with the Visual Geometry Group 16 (VGG16) model. The test dataset was subsequently tested in CNN-based diagnostic models and by two other radiologists who were not specialized in head and neck radiology. At approx. 2 months after the first reading session, two radiologists again reviewed all of the images in the test dataset, referring to the diagnoses provided by the trained CNN-based diagnostic model. RESULTS: The diagnostic accuracy was 0.92 by the CNN-based diagnostic models, whereas the diagnostic accuracies by the two radiologists at the first reading session were 0.49 and 0.45, respectively. In the second reading session by two radiologists (diagnosing with the assistance by the CNN-based diagnostic model), marked elevations of the diagnostic accuracy were observed (0.94 and 1.00, respectively). CONCLUSION: The CNN-based deep learning technique can be a useful support tool in assessing the presence of orbital invasion on CT images, especially for non-specialized radiologists.
Subject(s)
Deep Learning , Neoplasms , Humans , Neural Networks, Computer , Radiologists , Tomography, X-Ray ComputedABSTRACT
Background: In head and neck cancers, histopathological information is important for the determination of the tumor characteristics and for predicting the prognosis. The aim of this study was to assess the utility of diffusion-weighted T2 (DW-T2) mapping for the evaluation of tumor histological grade in patients with head and neck squamous cell carcinoma (SCC). Methods: The cases of 41 patients with head and neck SCC (21 well/moderately and 17 poorly differentiated SCC) were retrospectively analyzed. All patients received MR scanning using a 3-Tesla MR unit. The conventional T2 value, DW-T2 value, ratio of DW-T2 value to conventional T2 value, and apparent diffusion coefficient (ADC) were calculated using signal information from the DW-T2 mapping sequence with a manually placed region of interest (ROI). Results: ADC values in the poorly differentiated SCC group were significantly lower than those in the moderately/well differentiated SCC group (P<0.05). The ratio of DW-T2 value to conventional T2 value was also significantly different between poorly and moderately/well differentiated SCC groups (P<0.01). Receiver operating characteristic (ROC) curve analysis of ADC values showed a sensitivity of 0.76, specificity of 0.67, positive predictive value (PPV) of 0.62, negative predictive value (NPV) of 0.8, accuracy of 0.71 and area under the curve (AUC) of 0.73, whereas the ROC curve analysis of the ratio of DW-T2 value to conventional T2 value showed a sensitivity of 0.76, specificity of 0.83, PPV of 0.76, NPV of 0.83, accuracy of 0.8 and AUC of 0.82. Conclusions: DW-T2 mapping might be useful as supportive information for the determination of tumor histological grade in patients with head and neck SCC.
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The aim of this study was to investigate the utility of amide proton transfer (APT) imaging for the determination of human papillomavirus (HPV) status in patients with oropharyngeal squamous cell carcinoma (SCC). Thirty-one patients with oropharyngeal SCC were retrospectively evaluated. All patients underwent amide proton transfer imaging using a 3T magnetic resonance (MR) unit. Patients were divided into HPV-positive and -negative groups depending on the pathological findings in their primary tumor. In APT imaging, the primary tumor was delineated with a polygonal region of interest (ROI). Signal information in the ROI was used to calculate the mean, standard deviation (SD) and coefficient of variant (CV) of the APT signals (APT mean, APT SD, and APT CV, respectively). The value of APT CV in the HPV-positive group (0.43â ±â 0.04) was significantly lower than that in the HPV-negative group (0.48â ±â 0.04) (P = .01). There was no significant difference in APT mean (P = .82) or APT SD (P = .13) between the HPV-positive and -negative groups. Receiver operating characteristic (ROC) curve analysis of APT CV had a sensitivity of 0.75, specificity of 0.8, positive predictive value of 0.75, negative predictive value of 0.8, accuracy of 0.77 and area under the curve (AUC) of 0.8. The APT signal in the HPV-negative group was considered heterogeneous compared to the HPV-positive group. This information might be useful for the determination of HPV status in patients with oropharyngeal SCC.