scholarly journals Establishing the characteristics of an effective pharmacogenetic test for clozapine induced agranulocytosis

2014 ◽  
Author(s):  
Moira Verbelen ◽  
David A Collier ◽  
Dan Cohen ◽  
James H MacCabe ◽  
Cathryn M Lewis
Keyword(s):  
High Risk ◽  
Clinical Utility ◽  
Risk Group ◽  
High Sensitivity ◽  
High Risk Group ◽  
Low Risk ◽  
Treatment Resistant ◽  
Pharmacogenetic Test ◽  
Evidence Based Therapy ◽  
The Relationship

Clozapine is the only evidence-based therapy for treatment resistant schizophrenia, but it induces agranulocytosis, a rare but potentially fatal haematological adverse reaction, in less than 1% of users. To improve safety, the drug is subject to mandatory haematological monitoring throughout the course of treatment, which is burdensome for the patient and one of the main reasons clozapine is underused. Therefore, a pharmacogenetic test is clinically useful if it identifies a group of patients for whom the agranulocytosis risk is low enough to alleviate monitoring requirements. Assuming a genotypic marker stratifies patients into a high risk and a low risk group, we explore the relationship between test sensitivity, group size and agranulocytosis risk. High sensitivity minimizes the agranulocytosis risk in the low risk group and is essential for clinical utility, in particular in combination with a small high risk group.

Guanylyl cyclase C (GCC) expression in lymph nodes (LNs) as a determinant of recurrence in stage II colon cancer (CC) patients (pts).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 3639-3639
Author(s):  
Daniel J. Sargent ◽  
Qian Shi ◽  
Sharlene Gill ◽  
Christophe Louvet ◽  
Richard Bernard Everson ◽  
...  
Keyword(s):  
High Risk ◽  
Cox Regression ◽  
Risk Group ◽  
Tumor Grade ◽  
High Risk Group ◽  
Low Risk ◽  
Stage Ii ◽  
Risk Class ◽  
Tissue Procurement ◽  
The Relationship

3639 Background: The first phase of the multi-center prospectively specified retrospective study Validating Indicators To Associate Recurrence (VITAR), assessing the relationship between GCC gene expression in formalin fixed (FFPE) LNs and time to recurrence (TTR) in stage II CC pts not treated with adjuvant chemotherapy (Sargent, Annals Surg Onc 2011), showed promising initial results. Here we report a validation set of 463 new stage II CC pts. Methods: GCC mRNA was quantified by RT-qPCR using FFPE LNs from untreated T3N0 CC pts diagnosed from 1999-2008 with at least 12 LNs examined , blinded to clinical outcomes. Patients were classified by GCC LN ratio (LNR) (high risk: LNR > 0.1; low risk: LNR ≤ 0.1), with LNR defined as ratio of GCC positive to GCC informative LNs. Cox regression models tested the relationship between GCC and the primary endpoint of TTR, adjusted for age, tumor grade, number of LN examined pathologically, and lymphovascular invasion. Mismatch repair (MMR) status was also assessed. All primary analyses and cut-points were pre-specified. Results: 46pts (10%) recurred (rec), median follow-up was 65 months, median LNs examined was 20, and 42% (195/463) were classified high risk. Overall, TTR was not significantly associated with binary GCC LNR risk class (HR=1.47, p=.208) or DFS (HR= 1.39, p=.097). One site’s (n=97) tissue grossing method precluded appropriate LN assessment with existing GCC qualification methods. Excluding this site resulted in a TTR HR=1.91, p=0.051 (multivariate). In a post-hocanalysis excluding this site and using a 3-level GCC risk group of high (LNR > 0.20), intermediate (0.10 < LNR < 0.20) and low (LNR < 0.10), high risk group pts had a 5-yr rec risk of 22% versus 8% in low risk (HR 2.72, p=0.006). MMR status was not significantly associated with TTR (multivariate p=0.30). Conclusions: GCC status is a promising prognostic factor in appropriately staged stage II CC pts not treated with adjuvant therapy independent of traditional histopathology risk factors, but GCC determination must be performed with methodology adapted to the tissue procurement and fixation technique. Outcome associations were strengthened when considering a 3-level GCC categorization.

scholarly journals The Relationship between Locomotive Syndrome Risk, Gait Pattern, and Standing Posture in Young Japanese Women: A Cross-Sectional Study

Healthcare ◽  
2020 ◽  
Vol 8 (4) ◽  
pp. 565
Author(s):  
Yuichi Uesugi ◽  
Saki Kanaya ◽  
Hiroko Nakanishi ◽  
Yoshihiko Naito
Keyword(s):  
High Risk ◽  
Stride Length ◽  
Risk Group ◽  
High Risk Group ◽  
Low Risk ◽  
Locomotive Syndrome ◽  
Standing Posture ◽  
Cross Sectional ◽  
Young Japanese Women ◽  
The Relationship

Young people are also at risk of developing locomotive syndrome for unclear reasons. Therefore, we sought to evaluate the locomotive syndrome risk in young Japanese women and the relationship between standing posture and gait patterns. We used survey materials for physical measurements, locomotive syndrome risk tests, normal and maximum walking test, a standing posture test, and physical activity measures. A questionnaire-based cross-sectional survey was conducted with 100 Japanese female university students. The participants were divided into two groups (high-risk and low-risk groups) based on locomotive syndrome risk tests. The high-risk group accounted for 65.0% of the total participants. The high-risk group had a significantly slower walking speed and lower walking stride length than the low-risk group during maximum walking. Additionally, this high-risk group had a more prone posture than the low-risk group. Furthermore, the low-risk group included more individuals who belonged to middle and high school athletic clubs than the high-risk group. The locomotive syndrome risk was related to the walking pattern, standing posture, and past exercise habits. Therefore, long stride length, correct standing posture, and exercise habits acquired from a young age are important measures for preventing locomotive syndrome in young adults.

The Relationship Between CT Signs of Computed Tomography and Risk Classification of Gastric Stromal Tumors

2021 ◽  
Vol 11 (2) ◽  
pp. 642-647
Author(s):  
Wang Chen ◽  
Rong Guo ◽  
WeiGao Sun ◽  
DingYou Lu
Keyword(s):  
High Risk ◽  
Risk Group ◽  
High Risk Group ◽  
Risk Classification ◽  
Low Risk ◽  
Stromal Tumors ◽  
Medium Risk ◽  
Solid Part ◽  
The Relationship

Objective: The study aims to explore the role of computed tomography (CT) in clinical diagnosis, thus having a preliminary understanding of the relationship between CT signs and the risk of gastric stromal tumors (GSTs). Methods: In this study, 213 patients with GST with complete preoperative CT and postoperative pathological results in Yancheng No. 1 People's Hospital from January 2016 to August 2019 are selected as research objects. The patient's basic information is collected. CT machine (Toshiba 320 row CT and Siemens dualsource CT (Somatom Definition Flash)) is used to examine all patients. The obtained image data are evaluated. Patients are divided into low-risk group, medium risk group and high-risk group according to the risk classification standard of GST. The data collected are analyzed statistically. Results: After risk classification of all patients, 87 patients in low-risk group, 74 in medium-risk group and 52 in high-risk group are found. After further analysis of the risk classification, it is found that there is no significant difference in GST risk classification between the tumor sites (P > 0.05). In the GST risk classification, the smaller the tumor, the more the low-risk group, the larger the tumor, the more the high-risk group, the difference is statistically significant (P < 0.05). In the observation of the relationship between tumor growth pattern and risk classification, it is found that the number of intraluminal growth is the most, while mixed growth is the least (P < 0.05). Further analysis of tumor density, solid part enhancement, distant metastasis and risk grade show that there are significant differences (P < 0.05). Conclusion: As an auxiliary diagnostic method in clinic, CT signs can be used to analyze the relationship with risk grade from tumor location, tumor size, tumor growth mode, tumor density, solid part enhancement degree and tumor distant metastasis, so as to have a more accurate understanding of patients' situation, and provide experimental basis for the later application of CT signs in tumor and auxiliary diagnosis.

scholarly journals A Novel Inflammatory lncRNAs Prognostic Signature for Predicting the Prognosis of Low-Grade Glioma Patients

2021 ◽  
Vol 12 ◽  
Author(s):  
Zijin Xiang ◽  
Xueru Chen ◽  
Qiaoli Lv ◽  
Xiangdong Peng
Keyword(s):  
High Risk ◽  
Risk Model ◽  
Risk Group ◽  
Risk Groups ◽  
High Risk Group ◽  
Low Risk ◽  
Low Grade ◽  
Prognostic Signature ◽  
The Relationship ◽  
Genome Atlas

BackgroundAs immunotherapy has received attention as new treatments for brain cancer, the role of inflammation in the process of glioma is of particular importance. Increasing studies have further shown that long non-coding RNAs (lncRNAs) are important factors that promote the development of glioma. However, the relationship between inflammation-related lncRNAs and the prognosis of glioma patients remains unclear. The purpose of this study is to construct and validate an inflammation-related lncRNA prognostic signature to predict the prognosis of low-grade glioma patients.MethodsBy downloading and analyzing the gene expression data and clinical information of the Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA) patients with low-grade gliomas, we could screen for inflammatory gene-related lncRNAs. Furthermore, through Cox and the Least Absolute Shrinkage and Selection Operator regression analyses, we established a risk model and divided patients into high- and low-risk groups based on the median value of the risk score to analyze the prognosis. In addition, we analyzed the tumor mutation burden (TMB) between the two groups based on somatic mutation data, and explored the difference in copy number variations (CNVs) based on the GISTIC algorithm. Finally, we used the MCPCounter algorithm to study the relationship between the risk model and immune cell infiltration, and used gene set enrichment analysis (GSEA), Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses to explore the enrichment pathways and biological processes of differentially expressed genes between the high- and low-risk groups.ResultsA novel prognostic signature was constructed including 11 inflammatory lncRNAs. This risk model could be an independent prognostic predictor. The patients in the high-risk group had a poor prognosis. There were significant differences in TMB and CNVs for patients in the high- and low-risk groups. In the high-risk group, the immune system was activated more significantly, and the expression of immune checkpoint-related genes was also higher. The GSEA, GO, and KEGG analyses showed that highly expressed genes in the high-risk group were enriched in immune-related processes, while lowly expressed genes were enriched in neuromodulation processes.ConclusionThe risk model of 11 inflammation-related lncRNAs can serve as a promising prognostic biomarker for low-grade gliomas patients.

scholarly journals Ferroptosis regulator genes are a favorable biomarker for hepatocellular carcinoma

2021 ◽  
Author(s):  
Yongfei He ◽  
Shuqi Zhao ◽  
Zhongliu Wei ◽  
Xin Zhou ◽  
Tianyi Liang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
High Risk ◽  
Cox Regression ◽  
Risk Group ◽  
Clinical Information ◽  
High Risk Group ◽  
Low Risk ◽  
The Cancer Genome Atlas ◽  
Regulator Genes ◽  
The Relationship

Abstract BackgroundIn this study, we comprehensively analyzed the relationship between ferroptosis regulator genes (FRGs) and prognosis of hepatocellular carcinoma (HCC), determined the prognostics value of FRGs, established a prediction model, and explored the relationship with immunotherapy for HCC.MethodsThe mRNA transcriptional levels and clinical information of HCC were obtained from The Cancer Genome Atlas (TCGA) database. The 24 FRGs were combined with the differential expression genes (DEGs) of HCC for further analysis. The prognostics values of differential FRGs via the construction of model and validation by the Cox regression analysis.ResultThere were three genes (CARS1, FANCD2, and SLC7A11) were identified as independent risk factors for HCC, and a predictive model was constructed based on CARS1, FANCD2, and SLC7A11. The model showed that the low-risk group HCC patients with a more prolonged overall survival (OS) than the high-risk group (P=0.001). The high-risk group with higher expression of FRGs than the low-risk group. Finally, the relations between FGEs and immune infiltration showed that CARS1, FANCD2, and SLC7A11 had a positive relationship with macrophage infiltration. From these, three genes might be the potential therapeutic targets.ConclusionOur study indicated that CARS1, FANCD2, and SLC7A11 might have potential value for therapeutic strategies as practical and reliable prognostic tools for HCC.

scholarly journals Echocardiography and EuroSCORE II for the stratification of low-gradient severe aortic stenosis and preserved left ventricular ejection fraction

2021 ◽  
Author(s):  
Yan Fan ◽  
Hong Shen ◽  
Brandon Stacey ◽  
David Zhao ◽  
Robert J. Applegate ◽  
...  
Keyword(s):  
High Risk ◽  
Left Ventricular Ejection Fraction ◽  
Risk Group ◽  
Severe Aortic Stenosis ◽  
Left Ventricular ◽  
High Risk Group ◽  
Low Risk ◽  
Left Ventricular Ejection ◽  
Ventricular Ejection Fraction ◽  
Risk Patients

AbstractThe purpose of this study was to explore the utility of echocardiography and the EuroSCORE II in stratifying patients with low-gradient severe aortic stenosis (LG SAS) and preserved left ventricular ejection fraction (LVEF ≥ 50%) with or without aortic valve intervention (AVI). The study included 323 patients with LG SAS (aortic valve area ≤ 1.0 cm2 and mean pressure gradient < 40 mmHg). Patients were divided into two groups: a high-risk group (EuroSCORE II ≥ 4%, n = 115) and a low-risk group (EuroSCORE II < 4%, n = 208). Echocardiographic and clinical characteristics were analyzed. All-cause mortality was used as a clinical outcome during mean follow-up of 2 ± 1.3 years. Two-year cumulative survival was significantly lower in the high-risk group than the low-risk patients (62.3% vs. 81.7%, p = 0.001). AVI tended to reduce mortality in the high-risk patients (70% vs. 59%; p = 0.065). It did not significantly reduce mortality in the low-risk patients (82.8% with AVI vs. 81.2%, p = 0.68). Multivariable analysis identified heart failure, renal dysfunction and stroke volume index (SVi) as independent predictors for mortality. The study suggested that individualization of AVI based on risk stratification could be considered in a patient with LG SAS and preserved LVEF.

scholarly journals SARS-CoV-2 Seroprevalence in Healthcare Workers in Germany: A Follow-Up Study

2021 ◽  
Vol 18 (9) ◽  
pp. 4540
Author(s):  
Johannes Korth ◽  
Benjamin Wilde ◽  
Sebastian Dolff ◽  
Jasmin Frisch ◽  
Michael Jahn ◽  
...  
Keyword(s):  
High Risk ◽  
Healthcare Workers ◽  
Risk Group ◽  
Close Contact ◽  
Virus Transmission ◽  
High Risk Group ◽  
Low Risk ◽  
University Hospital ◽  
Intermediate Risk ◽  
Igg Antibody

SARS-CoV-2 is a worldwide challenge for the medical sector. Healthcare workers (HCW) are a cohort vulnerable to SARS-CoV-2 infection due to frequent and close contact with COVID-19 patients. However, they are also well trained and equipped with protective gear. The SARS-CoV-2 IgG antibody status was assessed at three different time points in 450 HCW of the University Hospital Essen in Germany. HCW were stratified according to contact frequencies with COVID-19 patients in (I) a high-risk group with daily contacts with known COVID-19 patients (n = 338), (II) an intermediate-risk group with daily contacts with non-COVID-19 patients (n = 78), and (III) a low-risk group without patient contacts (n = 34). The overall seroprevalence increased from 2.2% in March–May to 4.0% in June–July to 5.1% in October–December. The SARS-CoV-2 IgG detection rate was not significantly different between the high-risk group (1.8%; 3.8%; 5.5%), the intermediate-risk group (5.1%; 6.3%; 6.1%), and the low-risk group (0%, 0%, 0%). The overall SARS-CoV-2 seroprevalence remained low in HCW in western Germany one year after the outbreak of COVID-19 in Germany, and hygiene standards seemed to be effective in preventing patient-to-staff virus transmission.

scholarly journals Sernbo score predicts survival after intracapsular hip fracture in the elderly

2013 ◽  
Vol 95 (1) ◽  
pp. 29-33 ◽  
Author(s):  
EJC Dawe ◽  
E Lindisfarne ◽  
T Singh ◽  
I McFadyen ◽  
P Stott
Keyword(s):  
Hip Fracture ◽  
High Risk ◽  
Risk Group ◽  
Characteristic Curve ◽  
Social Situation ◽  
High Risk Group ◽  
Low Risk ◽  
Risk Of Death ◽  
Intracapsular Hip Fracture ◽  
The Mean

Introduction The Sernbo score uses four factors (age, social situation, mobility and mental state) to divide patients into a high-risk and a low-risk group. This study sought to assess the use of the Sernbo score in predicting mortality after an intracapsular hip fracture. Methods A total of 259 patients with displaced intracapsular hip fractures were included in the study. Data from prospectively generated databases provided 22 descriptive variables for each patient. These included operative management, blood tests and co-mobidities. Multivariate analysis was used to identify significant predictors of mortality. Results The mean patient age was 85 years and the mean follow-up duration was 1.5 years. The one-year survival rate was 92% (±0.03) in the low-risk group and 65% (±0.046) in the high-risk group. Four variables predicted mortality: Sernbo score >15 (p=0.0023), blood creatinine (p=0.0026), ASA (American Society of Anaesthesiologists) grade >3 (p=0.0038) and non-operative treatment (p=0.0377). Receiver operating characteristic curve analysis showed the Sernbo score as the only predictor of 30-day mortality (area under curve 0.71 [0.65–0.76]). The score had a sensitivity of 92% and a specificity of 51% for prediction of death at 30 days. Conclusions The Sernbo score identifies patients at high risk of death in the 30 days following injury. This very simple score could be used to direct extra early multidisciplinary input to high-risk patients on admission with an intracapsular hip fracture.

Abstract 2126: Twoaces (tia Work-up Asoutpatient: Assessment Of Clincal Efficacy And Safety)

Stroke ◽  
2012 ◽  
Vol 43 (suppl_1) ◽  
Author(s):  
Jenifer Green ◽  
Connie Wolford ◽  
Jean Marc Olivot ◽  
Gregory Albers ◽  
James Castle
Keyword(s):  
High Risk ◽  
Observational Study ◽  
Risk Group ◽  
High Risk Group ◽  
Low Risk ◽  
Stroke Rate ◽  
Significant Stenosis ◽  
Non Invasive ◽  
Low Rate ◽  
Arterial Imaging

Background: Much controversy exists as to which TIA patients need to be admitted to the hospital for evaluation and treatment and which can be sent home. One commonly used trigae tool is the ABCD 2 score (Age, presenting Blood Pressure, Clinical symptoms and Duration, and Diabetes). Although this tool gives good information for determining populations at low risk (score of 0-3) and high risk (score of 6-7) of stroke after TIA, it leaves a large moderate risk population (score of 4-5) for whom no clear triage guidance can be given. As previous studies have found large artery atherosclerosis to be a potent risk factor for stroke after TIA, we attempted to further delineate low and high risk TIA populations with the addition of non-invasive arterial imaging to the ABCD 2 score. Methods: All patients referred to the Stanford Stroke Service for possible TIA within 72 hrs of symptom onset between July 2007 and February 2010, and all patients referred to the Highland Park Stroke Service for possible TIA within 72 hrs of symptom onset after October 2009 were screened for enrollment in this observational study. Exclusion criteria included age <18 years, use of TPA at initial presentation, and symptoms lasting >24 hours. 352 patients were invited to enroll, 3 refused. Of the 349 enrolled, follow-up was obtained in 346 patients at 30 days. Patients were placed into two groups: 1) those with ABCD 2 scores of 0-3 or scores of 4-5 AND no sign of hemodynamically significant stenosis in an artery within the distribution of the TIA (Low Risk Group); and 2) those with ABCD 2 scores of 6-7 or scores of 4-5 AND a hemodynamically significant stenosis in an artery within the distribution of the TIA (High Risk Group). Non-invasive arterial imaging included CT angiogram, MR angiogram, and carotid ultrasound - all used at the discretion of the treating physician. 30 day stroke rates with 95% confidence intervals were recorded. Results: Of the 346 patients enrolled, 295 (85.3%) fell into the "Low Risk Group" based on ABCD 2 scoring and non-invasive arterial imaging. Within that group, the stroke rate at 30 days was 1.0% (3 strokes, 95% CI 0.2-3.1%). Within the "High Risk Group", the stroke rate at 30 days was 5.9% (3 strokes, 95% CI 1.4-16.5%). Within the "Low Risk Group", all 3 of the strokes occurred in patients with ABCD 2 scores of 4-5 (3/133 patients - 2.3% stroke rate with 95% CI 0.5-6.7%). The overall stroke rate was 6/346 (1.7%, 95% CI 0.7-3.8%). Conclusions: In our observational study we found that the overall 30 day stroke rate after TIA was quite low. The percentage of all TIA patients falling into the “Low Risk Group” was quite high, and these patients had a particularly low rate of stroke at 30 days. Given the high number of "Low Risk" patients and the low rate of stroke in that group at 30 days, the vast majority of TIA patients could likely be safely evaluated in an rapid outpatient setting provided that the treating physician is confident of the diagnosis.

Accuracy of the CARG chemotherapy toxicity risk prediction tool in older Indian patients with cancer.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e24023-e24023
Author(s):  
Shreya Gattani ◽  
Vanita Noronha ◽  
Anant Ramaswamy ◽  
Renita Castelino ◽  
Vandhita Nair ◽  
...  
Keyword(s):  
High Risk ◽  
Cancer Patients ◽  
Risk Prediction ◽  
Risk Group ◽  
High Risk Group ◽  
Low Risk ◽  
Chemotherapy Toxicity ◽  
Patients With Cancer ◽  
Indian Patients ◽  
Grade 3

e24023 Background: Clinical judgement alone is inadequate in accurately predicting chemotherapy toxicity in older adult cancer patients. Hurria and colleagues developed and validated, the CARG score (range, 0–17) as a convenient and reliable tool for predicting chemotherapy toxicity in older cancer patients in America, however, its applicability in Indian patients is unknown. Methods: An observational retrospective and prospective study between 2018 and 2020 was conducted in the Department of Medical Oncology at Tata Memorial Hospital, Mumbai, India. The study was approved by the institutional ethics committee (IEC-III; Project No. 900596) and registered in the Clinical Trials Registry of India (CTRI/2020/04/024675). Written informed consent was obtained in the prospective part of the study. Patients aged ≥ 60 years and planned for systemic therapy were evaluated in the geriatric oncology clinic and their CARG score was calculated. Patients were stratified into low (0-4), intermediate (5-9) and high risk (10-17) based on the CARG scores. The CARG score was provided to the treating physicians, along with the results of the geriatric assessment. Chemotherapy-related toxicities were captured from the electronic medical record and graded as per the NCI CTCAE, version 4.0. Results: We assessed 130 patients, with a median age 69 years (IQR, 60 to 84); 72% patients were males. The common malignancies included gastrointestinal (52%) and lung (30%). Approximately 78% patients received polychemotherapy and 53% received full dose chemotherapy. Based on the CARG score, 28 (22%) patients belonged to low risk, 80 (61%) to intermediate risk and 22 (17%) to the high risk category. The AU-ROC of the CARG score in predicting grade 3-5 toxicities was 0.61 (95% CI, 0.51-0.71). The sensitivity and specificity of the CARG score in predicting grade 3-5 toxicities were 60.8% and 78.6%. Grade 3-5 toxicities occurred in 6/28 patients (21%) in the low risk group, compared to 62/102 patients (61%) in the intermediate /high risk group, p = 0.0002. There was also a significant difference in the time to development of grade 3-5 toxicities, which occurred at a median of 2.5 cycles (IQR, 1-3.8) in the intermediate /high risk group and at a median of 6 cycles (IQR, 3.5-8) in the low risk group, p = 0.0011. Conclusions: In older Indian patients with cancer, the CARG score reliably stratifies patients into low risk and intermediate/high risk categories, predicting both the occurrence and the time to occurrence of grade 3-5 toxicities from chemotherapy. The CARG score may aid the oncologist in estimating the risk-benefit ratio of chemotherapy. An important limitation was that we provided the CARG score to the treating oncologists prior to the start of chemotherapy, which may have resulted in alterations in the chemotherapy regimen and dose and may have impacted the CARG risk prediction model. Clinical trial information: CTRI/2020/04/024675.

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