Biennial Analysis of Medication Guide Length and Estimated Readability for New Molecular Entity Drugs, 2011–2017

2021 ◽  
Author(s):  
Paul R. Jones ◽  
Elisabeth J. Walther ◽  
Andrew Nguyen ◽  
Jonas Santiago ◽  
Bryon M. Pearsall
Keyword(s):  
Molecular Entity ◽  
Medication Guide

scholarly journals Hierarchy of evidence in interpretation of clinical significance of drug interactions

2012 ◽  
Vol 65 (1-2) ◽  
pp. 45-49
Author(s):  
Bozana Nikolic ◽  
Miroslav Savic
Keyword(s):  
Drug Metabolism ◽  
Drug Interactions ◽  
Clinical Significance ◽  
Health Professionals ◽  
Molecular Entity ◽  
Population Pharmacokinetic ◽  
Pharmacokinetic Studies ◽  
Potential Interactions

Introduction. Since drug interactions may result in serious adverse effects or failure of therapy, it is of huge importance that health professionals base their decisions about drug prescription, dispensing and administration on reliable research evidence, taking into account the hierarchy of data sources for evaluation. Clinical Significance of Potential Interactions - Information Sources. The sources of data regarding drug interactions are numerous, beginning with various drug reference books. However, they are far from uniformity in the way of choosing and presenting putative clinically relevant interactions. Clinical Significance of Potential Interactions - Interpretation of Information. The difficulties in interpretation of drug interactions are illustrated through the analysis of a published example involving assessment made by two different groups of health professionals. Systematic Evaluation of Drug-Drug Interaction. The potential for interactions is mainly investigated before marketing a drug. Generally, the in vitro, followed by in vivo studies are to be performed. The major metabolic pathways involved in the metabolism of a new molecular entity, as well as the potential of induction of human enzymes involved in drug metabolism are to be examined. In the field of interaction research it is possible to make use of the population pharmacokinetic studies as well as of the pharmacodynamic assessment, and also the postregistration monitoring of the reported adverse reactions and other literature data. Conclusion. In vitro and in vivo drug metabolism and transport studies should be conducted to elucidate the mechanisms and potential for drug-drug interactions. The assessment of their clinical significance should be based on well-defined and validated exposure-response data.

Cardiac Intensive Care Medication Guide

2020 ◽  
pp. 717-723
Author(s):  
Donald Berry ◽  
Jasmine M. Schmitt ◽  
Carol G. Vetterly
Keyword(s):  
Intensive Care ◽  
Medication Guide ◽  
Cardiac Intensive Care

Molecular entity vacancy model

2006 ◽  
Vol 250 (1-2) ◽  
pp. 83-92 ◽  
Author(s):  
Dong Ping Tao
Keyword(s):  
Molecular Entity ◽  
Vacancy Model

Circulating tumor DNA-based genomic profiling of small bowel adenocarcinoma.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 3523-3523
Author(s):  
Pat Gulhati ◽  
Karan Pandya ◽  
Hiba I. Dada ◽  
Christopher R. Cogle ◽  
Jason S. Starr ◽  
...  
Keyword(s):  
Small Bowel ◽  
Large Scale ◽  
Clinical Decision Making ◽  
Circulating Tumor Dna ◽  
Therapeutic Resistance ◽  
Molecular Entity ◽  
Small Bowel Adenocarcinoma ◽  
Genomic Profiling ◽  
Comprehensive Genomic Profiling ◽  
Tumor Dna

3523 Background: Small bowel adenocarcinoma (SBA) is a rare malignancy, with lower incidence, later stage at diagnosis, and worse overall survival compared to other intestinal cancers, such as colorectal cancer (CRC). Since the majority of small bowel tumors are not accessible to endoscopic biopsy, comprehensive genomic profiling using circulating tumor DNA (ctDNA) may enable non-invasive detection of targetable genomic alterations (GA) in SBA patients. In this study, we characterize the ctDNA GA landscape in SBA. Methods: Analysis of 299 ctDNA samples prospectively collected from 265 SBA patients between 2017 to 2020 was performed using a 73 gene next generation sequencing panel (Guardant360). A subset of patients underwent longitudinal analysis of changes in GA associated with systemic therapy. Results: Of the 265 patients, 160 (60.3%) were male; the median age was 66 (range: 21-93 years). The most common GA identified in SBA patients included TP53 [58%], KRAS [44%], and APC [40%]. MSI was detected in 3.4% of SBA patients. When stratified by primary tumor location, APC, KRAS, TP53, PIK3CA, and ARID1A were the most common GA identified in both duodenal and jejunal adenocarcinomas. ERBB2, BRCA2 and CDK6 alterations were enriched in duodenal adenocarcinoma, while NOTCH and BRAF alterations were enriched in jejunal adenocarcinoma. The most common currently-targetable GA identified were ATM [18%], PIK3CA [17%], EGFR [15%], CDK4/6 [11%], BRAF [10%], and ERBB2 [10%]. Unique differences in GA between SBA and CRC were identified: i) the majority of ERBB2 alterations are mutations (89%) in the extracellular domain and kinase domain, not amplifications (11%); ii) the majority of BRAF alterations are non V600E mutations (69%) and amplifications (28%); iii) there is a significantly lower rate of APC mutations (40%). Alterations in DNA damage response pathway proteins, including ATM and BRCA 1/2, were identified in 30% of SBA patients. ATM alterations were more common in patients ³65 years old. The most common mutations predicted to be related to clonal hematopoiesis of indeterminate potential were TP53, KRAS and GNAS. Longitudinal ctDNA analysis in 4 SBA patients revealed loss of mutations associated with therapeutic response (TP53 R342*, MAPK3 R189Q) and acquired mutations associated with therapeutic resistance (NF1 R1968*, MET S170N, RAF1 L613V). Conclusions: This study represents the first large-scale blood-based ctDNA genomic profiling of SBA. SBA represents a unique molecular entity with differences in frequency and types of GA compared to CRC. Variations in GA were noted based on anatomic origin within the small intestine. Longitudinal ctDNA monitoring revealed novel GA associated with therapeutic resistance. Identification of multiple targetable GA may facilitate clinical decision making and improve patient outcomes in SBA, especially when a tissue biopsy is not feasible or sufficient for comprehensive genomic profiling.

scholarly journals A Case of Cholangiolocellular Carcinoma Preoperatively Diagnosed With Typical Imaging Findings

2019 ◽  
Vol 103 (1-2) ◽  
pp. 72-79
Author(s):  
Yoshihiro Mochizuki ◽  
Yuji Iimuro ◽  
Osamu Suzuki ◽  
Yoji Nagashima
Keyword(s):  
Preoperative Diagnosis ◽  
Imaging Finding ◽  
Genomic Analysis ◽  
Liver Neoplasm ◽  
Preoperative Imaging ◽  
Molecular Entity ◽  
Imaging Findings ◽  
Cholangiolocellular Carcinoma ◽  
Case Presentation ◽  
Contrast Enhanced

Introduction: Cholangiolocellular carcinoma (CoCC) is a rare primary liver neoplasm. A recent integrative genomic analysis has revealed that CoCC represents a distinct biliary-derived molecular entity. Several cases of CoCC have been reported so far, but accurate preoperative diagnosis was difficult in most cases. Case presentation: We report a case of 70-year-old woman with CoCC. Preoperative imaging findings revealed several typical signs of CoCC (i.e., thick early ring enhancement in the peripheral area of the tumor and its prolongation, vessel penetration through the tumor, no dilatation of the peripheral bile ducts, and dot-/band-like internal enhancement or a target appearance on contrast-enhanced magnetic resonance imaging). We strongly suspected CoCC from these preoperative imaging findings of the tumor and performed extended left hepatectomy. Pathologic diagnosis was CoCC, and the histologic findings such as peripheral highly cellular areas, central abundant hyalinized/edematous fibrotic stroma, and retained Glisson's sheath structures in the tumor, corresponded closely to each preoperative imaging finding. Immunohistochemical study revealed the tumor cells were positive for cytokeratin 7 and epithelial membrane antigen. The postoperative course was uneventful, and the patient is alive without recurrence for 15 months. The prognosis of CoCC is known to be better than that of cholangiocellular carcinoma, indicating the importance of preoperative differential diagnosis of these tumors. Conclusion: Even though preoperative diagnosis of CoCC is difficult because of its rarity, cautious investigation of preoperative typical imaging findings can possibly lead to accurate diagnosis of CoCC.

Functional and molecular identification of a novel chloride conductance in canine colonic smooth muscle

1998 ◽  
Vol 275 (4) ◽  
pp. C940-C950 ◽  
Author(s):  
Gregory M. Dick ◽  
Karri K. Bradley ◽  
Burton Horowitz ◽  
Joseph R. Hume ◽  
Kenton M. Sanders
Keyword(s):  
Smooth Muscle ◽  
Cell Types ◽  
Molecular Entity ◽  
Hypotonic Solution ◽  
Dependent Manner ◽  
Isolated Cells ◽  
Current Magnitude ◽  
Voltage Dependent ◽  
Numerous Cell

Swelling-activated or volume-sensitive Cl− currents are found in numerous cell types and play a variety of roles in their function; however, molecular characterization of the channels is generally lacking. Recently, the molecular entity responsible for swelling-activated Cl−current in cardiac myocytes has been identified as ClC-3. The goal of our study was to determine whether such a channel exists in smooth muscle cells of the canine colon using both molecular biological and electrophysiological techniques and, if present, to characterize its functional and molecular properties. We hypothesized that ClC-3 is present in colonic smooth muscle and is regulated in a manner similar to the molecular entity cloned from heart. Indeed, the ClC-3 gene was expressed in colonic myocytes, as demonstrated by reverse transcriptase polymerase chain reaction performed on isolated cells. The current activated by decreasing extracellular osmolarity from 300 to 250 mosM was outwardly rectifying and dependent on the Cl− gradient. Current magnitude increased and reversed at more negative potentials when Cl− was replaced by I− or Br−. Tamoxifen ([Z]-1-[p-dimethylaminoethoxy-phenyl]-1,2-diphenyl-1-butene; 10 μM) and DIDS (100 μM) inhibited the current, whereas 25 μM niflumic acid, 10 μM nicardipine, and Ca2+ removal had no effect. Current was inhibited by 1 mM extracellular ATP in a voltage-dependent manner. Cl− current was also regulated by protein kinase C, as phorbol 12,13-dibutyrate (300 nM) decreased Cl− current magnitude, while chelerythrine chloride (30 μM) activated it under isotonic conditions. Our findings indicate that a current activated by hypotonic solution is present in colonic myocytes and is likely mediated by ClC-3. Furthermore, we suggest that the ClC-3 may be an important mechanism controlling depolarization and contraction of colonic smooth muscle under conditions that impose physical stress on the cells.

Sign in / Sign up

Export Citation Format

Share Document