Vanderbilt University

About: Vanderbilt University is a education organization based out in Nashville, Tennessee, United States. It is known for research contribution in the topics: Population & Cancer. The organization has 45066 authors who have published 106528 publications receiving 5435039 citations. The organization is also known as: Vandy.

Computational Methods in Drug Discovery

Abstract: Computer-aided drug discovery/design methods have played a major role in the development of therapeutically important small molecules for over three decades. These methods are broadly classified as either structure-based or ligand-based methods. Structure-based methods are in principle analogous to high-throughput screening in that both target and ligand structure information is imperative. Structure-based approaches include ligand docking, pharmacophore, and ligand design methods. The article discusses theory behind the most important methods and recent successful applications. Ligand-based methods use only ligand information for predicting activity depending on its similarity/dissimilarity to previously known active ligands. We review widely used ligand-based methods such as ligand-based pharmacophores, molecular descriptors, and quantitative structure-activity relationships. In addition, important tools such as target/ligand data bases, homology modeling, ligand fingerprint methods, etc., necessary for successful implementation of various computer-aided drug discovery/design methods in a drug discovery campaign are discussed. Finally, computational methods for toxicity prediction and optimization for favorable physiologic properties are discussed with successful examples from literature.

Alpelisib for PIK3CA-Mutated, Hormone Receptor–Positive Advanced Breast Cancer

Abstract: Background PIK3CA mutations occur in approximately 40% of patients with hormone receptor (HR)–positive, human epidermal growth factor receptor 2 (HER2)–negative breast cancer. The PI3Kα-sp...

Using Multiplexed Assays of Oncogenic Drivers in Lung Cancers to Select Targeted Drugs

Abstract: Importance Targeting oncogenic drivers (genomic alterations critical to cancer development and maintenance) has transformed the care of patients with lung adenocarcinomas. The Lung Cancer Mutation Consortium was formed to perform multiplexed assays testing adenocarcinomas of the lung for drivers in 10 genes to enable clinicians to select targeted treatments and enroll patients into clinical trials. Objectives To determine the frequency of oncogenic drivers in patients with lung adenocarcinomas and to use the data to select treatments targeting the identified driver(s) and measure survival. Design, Setting, and Participants From 2009 through 2012, 14 sites in the United States enrolled patients with metastatic lung adenocarcinomas and a performance status of 0 through 2 and tested their tumors for 10 drivers. Information was collected on patients, therapies, and survival. Interventions Tumors were tested for 10 oncogenic drivers, and results were used to select matched targeted therapies. Main Outcomes and Measures Determination of the frequency of oncogenic drivers, the proportion of patients treated with genotype-directed therapy, and survival. Results From 2009 through 2012, tumors from 1007 patients were tested for at least 1 gene and 733 for 10 genes (patients with full genotyping). An oncogenic driver was found in 466 of 733 patients (64%). Among these 733 tumors, 182 tumors (25%) had the KRAS driver; sensitizing EGFR , 122 (17%); ALK rearrangements, 57 (8%); other EGFR , 29 (4%); 2 or more genes, 24 (3%); ERBB2 (formerly HER2 ), 19 (3%); BRAF , 16 (2%); PIK3CA , 6 ( MET amplification, 5 ( NRAS , 5 ( MEK1 , 1 ( AKT1 , 0. Results were used to select a targeted therapy or trial in 275 of 1007 patients (28%). The median survival was 3.5 years (interquartile range [IQR], 1.96-7.70) for the 260 patients with an oncogenic driver and genotype-directed therapy compared with 2.4 years (IQR, 0.88-6.20) for the 318 patients with any oncogenic driver(s) who did not receive genotype-directed therapy (propensity score–adjusted hazard ratio, 0.69 [95% CI, 0.53-0.9], P = .006). Conclusions and Relevance Actionable drivers were detected in 64% of lung adenocarcinomas. Multiplexed testing aided physicians in selecting therapies. Although individuals with drivers receiving a matched targeted agent lived longer, randomized trials are required to determine if targeting therapy based on oncogenic drivers improves survival. Trial Registration clinicaltrials.gov Identifier:NCT01014286.

Assessment of patient satisfaction in activities of daily living using a modified stanford health assessment questionnaire

Abstract: Patient satisfaction in performing activities of daily living (ADL) was assessed by using a self-administered questionnaire modified from the Stanford Health Assessment Questionnaire (HAQ). The HAQ includes questions to determine a patient's degree of difficulty and need for help and assistive devices in ADL. A modification of the HAQ (MHAQ) was developed to include questions concerning perceived patient satisfaction regarding the same ADL, along with perceived change in degree of difficulty. In order to add additional questions while maintaining the length of the questionnaire in a format suitable in routine care, the number of ADL included in the MHAQ was reduced from 20 to 8. Information regarding degree of difficulty derived from 8 questions in the MHAQ is comparable with that derived from 20 questions in the HAQ. The response of a patient that a specific activity is associated with difficulty in functional capacity was not inevitably associated with the absence of patient satisfaction; 43.7% of patients responding "with some difficulty" and 19.1% of patients responding "with much difficulty" expressed satisfaction with their functional capacity. A major determinant of expression of patient satisfaction was perceived change in difficulty: 81.4% of patients noting that their function was "less difficult now," in contrast to 16.9% of patients responding "more difficult now," expressed satisfaction. These studies suggest that data regarding patient satisfaction and perceived change in difficulty can be assessed to more completely characterize patients' functional status in ADL.

The rising prevalence of chronic low back pain.

Abstract: Background National or state-level estimates on trends in the prevalence of chronic low back pain (LBP) are lacking. The objective of this study was to determine whether the prevalence of chronic LBP and the demographic, health-related, and health care–seeking characteristics of individuals with the condition have changed over the last 14 years. Methods A cross-sectional, telephone survey of a representative sample of North Carolina households was conducted in 1992 and repeated in 2006. A total of 4437 households were contacted in 1992 and 5357 households in 2006 to identify noninstitutionalized adults 21 years or older with chronic (>3 months), impairing LBP or neck pain that limits daily activities. These individuals were interviewed in more detail about their health and health care seeking. Results The prevalence of chronic, impairing LBP rose significantly over the 14-year interval, from 3.9% (95% confidence interval [CI], 3.4%-4.4%) in 1992 to 10.2% (95% CI, 9.3%-11.0%) in 2006. Increases were seen for all adult age strata, in men and women, and in white and black races. Symptom severity and general health were similar for both years. The proportion of individuals who sought care from a health care provider in the past year increased from 73.1% (95% CI, 65.2%-79.8%) to 84.0% (95% CI, 80.8%-86.8%), while the mean number of visits to all health care providers were similar (19.5 [1992] vs 19.4 [2006]). Conclusions The prevalence of chronic, impairing LBP has risen significantly in North Carolina, with continuing high levels of disability and health care use. A substantial portion of the rise in LBP care costs over the past 2 decades may be related to this rising prevalence.