Drug safety: Pregnancy rating classifications and controversies.

PubMed

Wilmer, Erin; Chai, Sandy; Kroumpouzos, George

2016-01-01

This contribution consolidates data on international pregnancy rating classifications, including the former US Food and Drug Administration (FDA), Swedish, and Australian classification systems, as well as the evidence-based medicine system, and discusses discrepancies among them. It reviews the new Pregnancy and Lactation Labeling Rule (PLLR) that replaced the former FDA labeling system with narrative-based labeling requirements. PLLR emphasizes on human data and highlights pregnancy exposure registry information. In this context, the review discusses important data on the safety of most medications used in the management of skin disease in pregnancy. There are also discussions of controversies relevant to the safety of certain dermatologic medications during gestation. Copyright © 2016 Elsevier Inc. All rights reserved.

[Quantitative Prediction of Drug-Drug Interaction Caused by CYP Inhibition and Induction from In Vivo Data and Its Application in Daily Clinical Practices-Proposal for the Pharmacokinetic Interaction Significance Classification System (PISCS)].

PubMed

Ohno, Yoshiyuki

2018-01-01

　Drug-drug interactions (DDIs) can affect the clearance of various drugs from the body; however, these effects are difficult to sufficiently evaluate in clinical studies. This article outlines our approach to improving methods for evaluating and providing drug information relative to the effects of DDIs. In a previous study, total exposure changes to many substrate drugs of CYP caused by the co-administration of inhibitor or inducer drugs were successfully predicted using in vivo data. There are two parameters for the prediction: the contribution ratio of the enzyme to oral clearance for substrates (CR), and either the inhibition ratio for inhibitors (IR) or the increase in clearance of substrates produced by induction (IC). To apply these predictions in daily pharmacotherapy, the clinical significance of any pharmacokinetic changes must be carefully evaluated. We constructed a pharmacokinetic interaction significance classification system (PISCS) in which the clinical significance of DDIs was considered in a systematic manner, according to pharmacokinetic changes. The PISCS suggests that many current 'alert' classifications are potentially inappropriate, especially for drug combinations in which pharmacokinetics have not yet been evaluated. It is expected that PISCS would contribute to constructing a reliable system to alert pharmacists, physicians and consumers of a broad range of pharmacokinetic DDIs in order to more safely manage daily clinical practices.

Rule Based System for Medicine Inventory Control Using Radio Frequency Identification (RFID)

NASA Astrophysics Data System (ADS)

Nugraha, Joanna Ardhyanti Mita; Suryono; Suseno, dan Jatmiko Endro

2018-02-01

Rule based system is very efficient to ensure stock of drug to remain available by utilizing Radio Frequency Identification (RFID) as input means automatically. This method can ensure the stock of drugs to remain available by analyzing the needs of drug users. The research data was the amount of drug usage in hospital for 1 year. The data was processed by using ABC classification to determine the drug with fast, medium and slow movement. In each classification result, rule based algorithm was given for determination of safety stock and Reorder Point (ROP). This research yielded safety stock and ROP values that vary depending on the class of each drug. Validation is done by comparing the calculation of safety stock and reorder point both manually and by system, then, it was found that the mean deviation value at safety stock was 0,03 and and ROP was 0,08.

An attention-based effective neural model for drug-drug interactions extraction.

PubMed

Zheng, Wei; Lin, Hongfei; Luo, Ling; Zhao, Zhehuan; Li, Zhengguang; Zhang, Yijia; Yang, Zhihao; Wang, Jian

2017-10-10

Drug-drug interactions (DDIs) often bring unexpected side effects. The clinical recognition of DDIs is a crucial issue for both patient safety and healthcare cost control. However, although text-mining-based systems explore various methods to classify DDIs, the classification performance with regard to DDIs in long and complex sentences is still unsatisfactory. In this study, we propose an effective model that classifies DDIs from the literature by combining an attention mechanism and a recurrent neural network with long short-term memory (LSTM) units. In our approach, first, a candidate-drug-oriented input attention acting on word-embedding vectors automatically learns which words are more influential for a given drug pair. Next, the inputs merging the position- and POS-embedding vectors are passed to a bidirectional LSTM layer whose outputs at the last time step represent the high-level semantic information of the whole sentence. Finally, a softmax layer performs DDI classification. Experimental results from the DDIExtraction 2013 corpus show that our system performs the best with respect to detection and classification (84.0% and 77.3%, respectively) compared with other state-of-the-art methods. In particular, for the Medline-2013 dataset with long and complex sentences, our F-score far exceeds those of top-ranking systems by 12.6%. Our approach effectively improves the performance of DDI classification tasks. Experimental analysis demonstrates that our model performs better with respect to recognizing not only close-range but also long-range patterns among words, especially for long, complex and compound sentences.

Classification of nervous system withdrawn and approved drugs with ToxPrint features via machine learning strategies.

PubMed

Onay, Aytun; Onay, Melih; Abul, Osman

2017-04-01

Early-phase virtual screening of candidate drug molecules plays a key role in pharmaceutical industry from data mining and machine learning to prevent adverse effects of the drugs. Computational classification methods can distinguish approved drugs from withdrawn ones. We focused on 6 data sets including maximum 110 approved and 110 withdrawn drugs for all and nervous system diseases to distinguish approved drugs from withdrawn ones. In this study, we used support vector machines (SVMs) and ensemble methods (EMs) such as boosted and bagged trees to classify drugs into approved and withdrawn categories. Also, we used CORINA Symphony program to identify Toxprint chemotypes including over 700 predefined chemotypes for determination of risk and safety assesment of candidate drug molecules. In addition, we studied nervous system withdrawn drugs to determine the key fragments with The ParMol package including gSpan algorithm. According to our results, the descriptors named as the number of total chemotypes and bond CN_amine_aliphatic_generic were more significant descriptors. The developed Medium Gaussian SVM model reached 78% prediction accuracy on test set for drug data set including all disease. Here, bagged tree and linear SVM models showed 89% of accuracies for phycholeptics and psychoanaleptics drugs. A set of discriminative fragments in nervous system withdrawn drug (NSWD) data sets was obtained. These fragments responsible for the drugs removed from market were benzene, toluene, N,N-dimethylethylamine, crotylamine, 5-methyl-2,4-heptadiene, octatriene and carbonyl group. This paper covers the development of computational classification methods to distinguish approved drugs from withdrawn ones. In addition, the results of this study indicated the identification of discriminative fragments is of significance to design a new nervous system approved drugs with interpretation of the structures of the NSWDs. Copyright © 2017 Elsevier B.V. All rights reserved.

21 CFR 866.5750 - Radioallergosorbent (RAST) immunological test system.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Radioallergosorbent (RAST) immunological test system. 866.5750 Section 866.5750 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND..., allergies, and other pulmonary disorders. (b) Classification. Class II (performance standards). ...

pH-Dependent solubility and permeability criteria for provisional biopharmaceutics classification (BCS and BDDCS) in early drug discovery.

PubMed

Varma, Manthena V; Gardner, Iain; Steyn, Stefanus J; Nkansah, Paul; Rotter, Charles J; Whitney-Pickett, Carrie; Zhang, Hui; Di, Li; Cram, Michael; Fenner, Katherine S; El-Kattan, Ayman F

2012-05-07

The Biopharmaceutics Classification System (BCS) is a scientific framework that provides a basis for predicting the oral absorption of drugs. These concepts have been extended in the Biopharmaceutics Drug Disposition Classification System (BDDCS) to explain the potential mechanism of drug clearance and understand the effects of uptake and efflux transporters on absorption, distribution, metabolism, and elimination. The objective of present work is to establish criteria for provisional biopharmaceutics classification using pH-dependent passive permeability and aqueous solubility data generated from high throughput screening methodologies in drug discovery settings. The apparent permeability across monolayers of clonal cell line of Madin-Darby canine kidney cells, selected for low endogenous efflux transporter expression, was measured for a set of 105 drugs, with known BCS and BDDCS class. The permeability at apical pH 6.5 for acidic drugs and at pH 7.4 for nonacidic drugs showed a good correlation with the fraction absorbed in human (Fa). Receiver operating characteristic (ROC) curve analysis was utilized to define the permeability class boundary. At permeability ≥ 5 × 10(-6) cm/s, the accuracy of predicting Fa of ≥ 0.90 was 87%. Also, this cutoff showed more than 80% sensitivity and specificity in predicting the literature permeability classes (BCS), and the metabolism classes (BDDCS). The equilibrium solubility of a subset of 49 drugs was measured in pH 1.2 medium, pH 6.5 phosphate buffer, and in FaSSIF medium (pH 6.5). Although dose was not considered, good concordance of the measured solubility with BCS and BDDCS solubility class was achieved, when solubility at pH 1.2 was used for acidic compounds and FaSSIF solubility was used for basic, neutral, and zwitterionic compounds. Using a cutoff of 200 μg/mL, the data set suggested a 93% sensitivity and 86% specificity in predicting both the BCS and BDDCS solubility classes. In conclusion, this study identified pH-dependent permeability and solubility criteria that can be used to assign provisional biopharmaceutics class at early stage of the drug discovery process. Additionally, such a classification system will enable discovery scientists to assess the potential limiting factors to oral absorption, as well as help predict the drug disposition mechanisms and potential drug-drug interactions.

Similarity-based prediction for Anatomical Therapeutic Chemical classification of drugs by integrating multiple data sources.

PubMed

Liu, Zhongyang; Guo, Feifei; Gu, Jiangyong; Wang, Yong; Li, Yang; Wang, Dan; Lu, Liang; Li, Dong; He, Fuchu

2015-06-01

Anatomical Therapeutic Chemical (ATC) classification system, widely applied in almost all drug utilization studies, is currently the most widely recognized classification system for drugs. Currently, new drug entries are added into the system only on users' requests, which leads to seriously incomplete drug coverage of the system, and bioinformatics prediction is helpful during this process. Here we propose a novel prediction model of drug-ATC code associations, using logistic regression to integrate multiple heterogeneous data sources including chemical structures, target proteins, gene expression, side-effects and chemical-chemical associations. The model obtains good performance for the prediction not only on ATC codes of unclassified drugs but also on new ATC codes of classified drugs assessed by cross-validation and independent test sets, and its efficacy exceeds previous methods. Further to facilitate the use, the model is developed into a user-friendly web service SPACE ( S: imilarity-based P: redictor of A: TC C: od E: ), which for each submitted compound, will give candidate ATC codes (ranked according to the decreasing probability_score predicted by the model) together with corresponding supporting evidence. This work not only contributes to knowing drugs' therapeutic, pharmacological and chemical properties, but also provides clues for drug repositioning and side-effect discovery. In addition, the construction of the prediction model also provides a general framework for similarity-based data integration which is suitable for other drug-related studies such as target, side-effect prediction etc. The web service SPACE is available at http://www.bprc.ac.cn/space. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Development of a rational scale to assess the harm of drugs of potential misuse.

PubMed

Nutt, David; King, Leslie A; Saulsbury, William; Blakemore, Colin

2007-03-24

Drug misuse and abuse are major health problems. Harmful drugs are regulated according to classification systems that purport to relate to the harms and risks of each drug. However, the methodology and processes underlying classification systems are generally neither specified nor transparent, which reduces confidence in their accuracy and undermines health education messages. We developed and explored the feasibility of the use of a nine-category matrix of harm, with an expert delphic procedure, to assess the harms of a range of illicit drugs in an evidence-based fashion. We also included five legal drugs of misuse (alcohol, khat, solvents, alkyl nitrites, and tobacco) and one that has since been classified (ketamine) for reference. The process proved practicable, and yielded roughly similar scores and rankings of drug harm when used by two separate groups of experts. The ranking of drugs produced by our assessment of harm differed from those used by current regulatory systems. Our methodology offers a systematic framework and process that could be used by national and international regulatory bodies to assess the harm of current and future drugs of abuse.

G.L. Amidon, H. Lennernas, V.P. Shah, and J.R. Crison. A theoretical basis for a biopharmaceutic drug classification: the correlation of in vitro drug product dissolution and in vivo bioavailability, Pharm Res 12, 413-420, 1995--backstory of BCS.

PubMed

Shah, Vinod P; Amidon, Gordon L

2014-09-01

The Biopharmaceutics Classification System (BCS) has become widely accepted today in the academic, industrial, and regulatory world. While the initial application of the BCS was to regulatory science bioequivalence (BE) issues and related implications, it has come to be utilized widely by the pharmaceutical industry in drug discovery and development as well. This brief manuscript will relate the story of the BCS development. While much of the ground work for the BCS goes back to the pharmacokinetic and drug absorption research by Gordon Amidon (GLA) in the 1970s and 1980s, the realization of the need for a classification or categorization of drug and drug products for setting dissolution standards became apparent to GLA during his 1990-1991 sabbatical year at the FDA. Initiated at the invitation of the then CEDR director, Dr. Carl Peck, to become a visiting scientist at the FDA, the goal was to promote regulatory research at the FDA, in my case, in biopharmaceutics, and to develop a science-based system to simplify regulatory requirements.

The functional therapeutic chemical classification system.

PubMed

Croset, Samuel; Overington, John P; Rebholz-Schuhmann, Dietrich

2014-03-15

Drug repositioning is the discovery of new indications for compounds that have already been approved and used in a clinical setting. Recently, some computational approaches have been suggested to unveil new opportunities in a systematic fashion, by taking into consideration gene expression signatures or chemical features for instance. We present here a novel method based on knowledge integration using semantic technologies, to capture the functional role of approved chemical compounds. In order to computationally generate repositioning hypotheses, we used the Web Ontology Language to formally define the semantics of over 20 000 terms with axioms to correctly denote various modes of action (MoA). Based on an integration of public data, we have automatically assigned over a thousand of approved drugs into these MoA categories. The resulting new resource is called the Functional Therapeutic Chemical Classification System and was further evaluated against the content of the traditional Anatomical Therapeutic Chemical Classification System. We illustrate how the new classification can be used to generate drug repurposing hypotheses, using Alzheimers disease as a use-case. https://www.ebi.ac.uk/chembl/ftc; https://github.com/loopasam/ftc. croset@ebi.ac.uk Supplementary data are available at Bioinformatics online.

Filtering big data from social media--Building an early warning system for adverse drug reactions.

PubMed

Yang, Ming; Kiang, Melody; Shang, Wei

2015-04-01

Adverse drug reactions (ADRs) are believed to be a leading cause of death in the world. Pharmacovigilance systems are aimed at early detection of ADRs. With the popularity of social media, Web forums and discussion boards become important sources of data for consumers to share their drug use experience, as a result may provide useful information on drugs and their adverse reactions. In this study, we propose an automated ADR related posts filtering mechanism using text classification methods. In real-life settings, ADR related messages are highly distributed in social media, while non-ADR related messages are unspecific and topically diverse. It is expensive to manually label a large amount of ADR related messages (positive examples) and non-ADR related messages (negative examples) to train classification systems. To mitigate this challenge, we examine the use of a partially supervised learning classification method to automate the process. We propose a novel pharmacovigilance system leveraging a Latent Dirichlet Allocation modeling module and a partially supervised classification approach. We select drugs with more than 500 threads of discussion, and collect all the original posts and comments of these drugs using an automatic Web spidering program as the text corpus. Various classifiers were trained by varying the number of positive examples and the number of topics. The trained classifiers were applied to 3000 posts published over 60 days. Top-ranked posts from each classifier were pooled and the resulting set of 300 posts was reviewed by a domain expert to evaluate the classifiers. Compare to the alternative approaches using supervised learning methods and three general purpose partially supervised learning methods, our approach performs significantly better in terms of precision, recall, and the F measure (the harmonic mean of precision and recall), based on a computational experiment using online discussion threads from Medhelp. Our design provides satisfactory performance in identifying ADR related posts for post-marketing drug surveillance. The overall design of our system also points out a potentially fruitful direction for building other early warning systems that need to filter big data from social media networks. Copyright © 2015 Elsevier Inc. All rights reserved.

Optimizing solubility and permeability of a biopharmaceutics classification system (BCS) class 4 antibiotic drug using lipophilic fragments disturbing the crystal lattice.

PubMed

Tehler, Ulrika; Fagerberg, Jonas H; Svensson, Richard; Larhed, Mats; Artursson, Per; Bergström, Christel A S

2013-03-28

Esterification was used to simultaneously increase solubility and permeability of ciprofloxacin, a biopharmaceutics classification system (BCS) class 4 drug (low solubility/low permeability) with solid-state limited solubility. Molecular flexibility was increased to disturb the crystal lattice, lower the melting point, and thereby improve the solubility, whereas lipophilicity was increased to enhance the intestinal permeability. These structural changes resulted in BCS class 1 analogues (high solubility/high permeability) emphasizing that simple medicinal chemistry may improve both these properties.

What can we learn in drug allergy management from World Health Organization's international classifications?

PubMed

Tanno, L K; Torres, M J; Castells, M; Demoly, P

2018-05-01

Drug hypersensitivity reactions (DHRs) represent growing health problem worldwide, affecting more than 7% of the general population, and represent an important public health problem. However, knowledge in DHRs morbidity and mortality epidemiological data is still not optimal and international comparable standards remain poorly accessed. Institutional databases worldwide increasingly use the WHO International Classification of Diseases (ICD) system to classify diagnoses, health services utilization, and death data. The misclassification of disorders in the ICD system contributes to a lack of ascertainment and recognition of their importance for healthcare planning and resource allocation. It also hampers clinical practice and prevention actions. To further inform the allergy community and to ensure that the revision process is transparent as advised in the WHO ICD-11 revision agenda, we report the advances and use of the pioneering "Drug hypersensitivity" subsection of ICD-11 and implementation in the WHO International Classification of Health Interventions (ICHI). The new classification addressed to DHRs will enable the collection of more accurate epidemiological data to support quality management of patients with drug allergies and better facilitate healthcare planning and decision-making and public health measures to prevent and reduce the morbidity and mortality attributable to DHRs. © 2017 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.

21 CFR 882.4560 - Stereotaxic instrument.

Code of Federal Regulations, 2012 CFR

2012-04-01

... part of the nervous system. (b) Classification. Class II (performance standards). ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Stereotaxic instrument. 882.4560 Section 882.4560 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED...

21 CFR 882.4560 - Stereotaxic instrument.

Code of Federal Regulations, 2014 CFR

2014-04-01

... part of the nervous system. (b) Classification. Class II (performance standards). ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Stereotaxic instrument. 882.4560 Section 882.4560 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED...

21 CFR 882.4560 - Stereotaxic instrument.

Code of Federal Regulations, 2013 CFR

2013-04-01

... part of the nervous system. (b) Classification. Class II (performance standards). ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Stereotaxic instrument. 882.4560 Section 882.4560 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED...

Applying Biopharmaceutical Classification System (BCS) Criteria to Predict Oral Absorption of Drugs in Dogs: Challenges and Pitfalls.

PubMed

Papich, Mark G; Martinez, Marilyn N

2015-07-01

The Biopharmaceutical Classification System (BCS) has been a prognostic tool for assessing the potential effects of formulation on the human drug oral bioavailability. When used in conjunction with in vitro dissolution tests, the BCS can support the prediction of in vivo product performance and the development of mechanistic models that support formulation assessments through the generation of "what if" scenarios. To date, the applicability of existing human BCS criteria has not been evaluated in dogs, thereby limiting its use in canine drug development. Therefore, we examined 50 drugs for which absolute bioavailability (F) was available both in dogs and humans. The drugs were also evaluated for any potential association between solubility (calculated from the dose number, Do) or lipophilicity (LogP) and F in dogs. In humans, solubility is determined in 250 mL of fluid. However, the appropriate volume for classifying drug solubility in dogs has not been established. In this analysis, the estimated volume of a water flush administered to fasted dogs (6 mL) and a volume of 250 mL scaled to a Beagle dog (35 mL) were examined. In addition, in humans, a Do value greater than 1.0 is used to define a compound as highly soluble and a LogP value greater than 1.72 as high permeability. These same criteria were applied for defining highly soluble and highly permeable in dogs. Whether using 35 or 6 mL to determine Do, the canine solubility classification remained unchanged for all but seven compounds. There were no clear associations between a drug's F in dogs and humans or between the canine value of F and either its human BCS classification, its LogP value, or the canine Do estimate. There was a tendency for those drugs with canine values of F equal to or greater than 80% to have LogP values equal to or greater than 1.0. Exceptions to this observation tended to be those compounds known to be absorbed via mechanisms other than passive diffusion (e.g., via transporters or paracellular transporters). Although there are limitations to the approach used in this study, the results of our assessment strongly suggest that the human BCS classification system requires substantial modification before it can be reliably applied to dogs.

SVM Based Descriptor Selection and Classification of Neurodegenerative Disease Drugs for Pharmacological Modeling.

PubMed

Shahid, Mohammad; Shahzad Cheema, Muhammad; Klenner, Alexander; Younesi, Erfan; Hofmann-Apitius, Martin

2013-03-01

Systems pharmacological modeling of drug mode of action for the next generation of multitarget drugs may open new routes for drug design and discovery. Computational methods are widely used in this context amongst which support vector machines (SVM) have proven successful in addressing the challenge of classifying drugs with similar features. We have applied a variety of such SVM-based approaches, namely SVM-based recursive feature elimination (SVM-RFE). We use the approach to predict the pharmacological properties of drugs widely used against complex neurodegenerative disorders (NDD) and to build an in-silico computational model for the binary classification of NDD drugs from other drugs. Application of an SVM-RFE model to a set of drugs successfully classified NDD drugs from non-NDD drugs and resulted in overall accuracy of ∼80 % with 10 fold cross validation using 40 top ranked molecular descriptors selected out of total 314 descriptors. Moreover, SVM-RFE method outperformed linear discriminant analysis (LDA) based feature selection and classification. The model reduced the multidimensional descriptors space of drugs dramatically and predicted NDD drugs with high accuracy, while avoiding over fitting. Based on these results, NDD-specific focused libraries of drug-like compounds can be designed and existing NDD-specific drugs can be characterized by a well-characterized set of molecular descriptors. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Bath salts and synthetic cathinones: An emerging designer drug phenomenon

PubMed Central

German, Christopher L.; Fleckenstein, Annette E.; Hanson, Glen R.

2014-01-01

The synthetic cathinones are an emerging class of designer drugs abused for psychostimulant and hallucinogenic effects similar to cocaine, methylenedioxymethamphetamine (MDMA), or other amphetamines. Abuse of synthetic cathinones, frequently included in products sold as ‘bath salts’, became prevalent in early 2009, leading to legislative classification throughout Europe in 2010 and schedule I classification within the United States in 2011. Recent pre-clinical and clinical studies indicate dysregulation of central monoamine systems are a principal mechanism of synthetic cathinone action and presumably underlie the behavioral effects and abuse liability associated with these drugs. This review provides insight into the development of synthetic cathinones as substances of abuse, current patterns of their abuse, known mechanisms of their action and toxicology, and the benefits and drawbacks of their classification. PMID:23911668

21 CFR 866.6040 - Gene expression profiling test system for breast cancer prognosis.

Code of Federal Regulations, 2010 CFR

2010-04-01

... cancer prognosis. 866.6040 Section 866.6040 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF... cancer prognosis. (a) Identification. A gene expression profiling test system for breast cancer prognosis... previously diagnosed breast cancer. (b) Classification. Class II (special controls). The special control is...

21 CFR 866.6040 - Gene expression profiling test system for breast cancer prognosis.

Code of Federal Regulations, 2011 CFR

2011-04-01

... cancer prognosis. 866.6040 Section 866.6040 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF... cancer prognosis. (a) Identification. A gene expression profiling test system for breast cancer prognosis... previously diagnosed breast cancer. (b) Classification. Class II (special controls). The special control is...

21 CFR 866.6040 - Gene expression profiling test system for breast cancer prognosis.

Code of Federal Regulations, 2013 CFR

2013-04-01

... cancer prognosis. 866.6040 Section 866.6040 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF... cancer prognosis. (a) Identification. A gene expression profiling test system for breast cancer prognosis... previously diagnosed breast cancer. (b) Classification. Class II (special controls). The special control is...

21 CFR 866.6040 - Gene expression profiling test system for breast cancer prognosis.

Code of Federal Regulations, 2012 CFR

2012-04-01

... cancer prognosis. 866.6040 Section 866.6040 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF... cancer prognosis. (a) Identification. A gene expression profiling test system for breast cancer prognosis... previously diagnosed breast cancer. (b) Classification. Class II (special controls). The special control is...

21 CFR 866.6040 - Gene expression profiling test system for breast cancer prognosis.

Code of Federal Regulations, 2014 CFR

2014-04-01

... cancer prognosis. 866.6040 Section 866.6040 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF... cancer prognosis. (a) Identification. A gene expression profiling test system for breast cancer prognosis... previously diagnosed breast cancer. (b) Classification. Class II (special controls). The special control is...

Categorizing Drugs and Drug-Taking: A More Meaningful Approach.

ERIC Educational Resources Information Center

Gold, Robert S.; Duncan, David F.

This document reviews various definitions of the nature and classification of drugs. Difficulties with existing categorizations which use such bases as clinical utility, molecular structure, effects on the central nervous system, legality, and hazard potential are disucssed. A more meaningful categorization based on the availability and sources of…

21 CFR 868.2610 - Gas pressure gauge.

Code of Federal Regulations, 2013 CFR

2013-04-01

... to measure gas pressure in a medical gas delivery system. (b) Classification. Class I (general... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Gas pressure gauge. 868.2610 Section 868.2610 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL...

21 CFR 868.2610 - Gas pressure gauge.

Code of Federal Regulations, 2010 CFR

2010-04-01

... to measure gas pressure in a medical gas delivery system. (b) Classification. Class I (general... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Gas pressure gauge. 868.2610 Section 868.2610 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL...

21 CFR 868.2610 - Gas pressure gauge.

Code of Federal Regulations, 2012 CFR

2012-04-01

... to measure gas pressure in a medical gas delivery system. (b) Classification. Class I (general... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Gas pressure gauge. 868.2610 Section 868.2610 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL...

21 CFR 868.2610 - Gas pressure gauge.

Code of Federal Regulations, 2014 CFR

2014-04-01

... to measure gas pressure in a medical gas delivery system. (b) Classification. Class I (general... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Gas pressure gauge. 868.2610 Section 868.2610 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL...

21 CFR 868.2610 - Gas pressure gauge.

Code of Federal Regulations, 2011 CFR

2011-04-01

... to measure gas pressure in a medical gas delivery system. (b) Classification. Class I (general... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Gas pressure gauge. 868.2610 Section 868.2610 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL...

A hierarchical anatomical classification schema for prediction of phenotypic side effects

PubMed Central

Kanji, Rakesh

2018-01-01

Prediction of adverse drug reactions is an important problem in drug discovery endeavors which can be addressed with data-driven strategies. SIDER is one of the most reliable and frequently used datasets for identification of key features as well as building machine learning models for side effects prediction. The inherently unbalanced nature of this data presents with a difficult multi-label multi-class problem towards prediction of drug side effects. We highlight the intrinsic issue with SIDER data and methodological flaws in relying on performance measures such as AUC while attempting to predict side effects.We argue for the use of metrics that are robust to class imbalance for evaluation of classifiers. Importantly, we present a ‘hierarchical anatomical classification schema’ which aggregates side effects into organs, sub-systems, and systems. With the help of a weighted performance measure, using 5-fold cross-validation we show that this strategy facilitates biologically meaningful side effects prediction at different levels of anatomical hierarchy. By implementing various machine learning classifiers we show that Random Forest model yields best classification accuracy at each level of coarse-graining. The manually curated, hierarchical schema for side effects can also serve as the basis of future studies towards prediction of adverse reactions and identification of key features linked to specific organ systems. Our study provides a strategy for hierarchical classification of side effects rooted in the anatomy and can pave the way for calibrated expert systems for multi-level prediction of side effects. PMID:29494708

A hierarchical anatomical classification schema for prediction of phenotypic side effects.

PubMed

Wadhwa, Somin; Gupta, Aishwarya; Dokania, Shubham; Kanji, Rakesh; Bagler, Ganesh

2018-01-01

Prediction of adverse drug reactions is an important problem in drug discovery endeavors which can be addressed with data-driven strategies. SIDER is one of the most reliable and frequently used datasets for identification of key features as well as building machine learning models for side effects prediction. The inherently unbalanced nature of this data presents with a difficult multi-label multi-class problem towards prediction of drug side effects. We highlight the intrinsic issue with SIDER data and methodological flaws in relying on performance measures such as AUC while attempting to predict side effects.We argue for the use of metrics that are robust to class imbalance for evaluation of classifiers. Importantly, we present a 'hierarchical anatomical classification schema' which aggregates side effects into organs, sub-systems, and systems. With the help of a weighted performance measure, using 5-fold cross-validation we show that this strategy facilitates biologically meaningful side effects prediction at different levels of anatomical hierarchy. By implementing various machine learning classifiers we show that Random Forest model yields best classification accuracy at each level of coarse-graining. The manually curated, hierarchical schema for side effects can also serve as the basis of future studies towards prediction of adverse reactions and identification of key features linked to specific organ systems. Our study provides a strategy for hierarchical classification of side effects rooted in the anatomy and can pave the way for calibrated expert systems for multi-level prediction of side effects.

Deciphering Suicide and Other Manners of Death Associated with Drug Intoxication: A Centers for Disease Control and Prevention Consultation Meeting Summary.

PubMed

Stone, Deborah M; Holland, Kristin M; Bartholow, Brad; E Logan, Joseph; LiKamWa McIntosh, Wendy; Trudeau, Aimee; Rockett, Ian R H

2017-08-01

Manner of death (MOD) classification (i.e., natural, accident, suicide, homicide, or undetermined cause) affects mortality surveillance and public health research, policy, and practice. Determination of MOD in deaths caused by drug intoxication is challenging, with marked variability across states. The Centers for Disease Control and Prevention hosted a multidisciplinary meeting to discuss drug intoxication deaths as they relate to suicide and other MOD. The meeting objectives were to identify individual-level, system-level, and place-based factors affecting MOD classification and identify potential solutions to classification barriers. Suggested strategies included improved standardization in death scene investigation, toxicology, and autopsy practice; greater accountability; and creation of job aids for investigators. Continued collaboration and coordination of activities are needed among stakeholders to affect prevention efforts.

Adverse drug reactions in Colombian patients, 2007-2013: Analysis of population databases.

PubMed

Machado-Alba, Jorge Enrique; Londoño-Builes, Manuel José; Echeverri-Cataño, Luis Felipe; Ochoa-Orozco, Sergio Andrés

2016-03-03

Recognizing adverse drug reactions (ADRs) is becoming more important in clinical practice.  To determine the frequency of adverse drug reactions and ADR suspicions among the population affiliated to the Colombian health system and to describe the drugs, reactions and associated variables.  We revised ADRs and ADRs suspicion databases from drugs dispensed by Audifarma, S.A., both for inpatient and outpatient care from 2007 to 2013. Variables included ADR report date, city, drug, drug's Anatomical Therapeutic Classification (ATC), ADR severity, ADR type, ADR classification and ADR probability according to the World Health Organization's definitions.  We obtained 5,342 reports for 468 different drugs. The ATC groups with the most reports were anti-infectives for systemic use (25.5%), nervous system agents (17.1%) and cardiovascular system drugs (15.0%). The drugs with the highest number of reports were metamizole (4.2%), enalapril (3.8%), clarithromycin (2.8%), warfarin (2.5%) and ciprofloxacin (2.4%). The most common ADR, classified following the World Health Organization adverse reaction terminology, were: skin and appendages disorders (35.3%), general disorders (14.2%) and gastrointestinal system disorders (11.8%). Overall, 49.4% of the ADRs were classified as "moderate" and 45.1% as "mild".  An increasing number of ADR reports were found coinciding with a worldwide tendency. Differences between inpatient and outpatient ADR reports were found when compared to scientific publications. The information on ADR reports, mainly gathered by the Instituto Nacional de Vigilancia de Medicamentos y Alimentos - Invima, should be made public for academic and institutional use.

Provisional in-silico biopharmaceutics classification (BCS) to guide oral drug product development

PubMed Central

Wolk, Omri; Agbaria, Riad; Dahan, Arik

2014-01-01

The main objective of this work was to investigate in-silico predictions of physicochemical properties, in order to guide oral drug development by provisional biopharmaceutics classification system (BCS). Four in-silico methods were used to estimate LogP: group contribution (CLogP) using two different software programs, atom contribution (ALogP), and element contribution (KLogP). The correlations (r2) of CLogP, ALogP and KLogP versus measured LogP data were 0.97, 0.82, and 0.71, respectively. The classification of drugs with reported intestinal permeability in humans was correct for 64.3%–72.4% of the 29 drugs on the dataset, and for 81.82%–90.91% of the 22 drugs that are passively absorbed using the different in-silico algorithms. Similar permeability classification was obtained with the various in-silico methods. The in-silico calculations, along with experimental melting points, were then incorporated into a thermodynamic equation for solubility estimations that largely matched the reference solubility values. It was revealed that the effect of melting point on the solubility is minor compared to the partition coefficient, and an average melting point (162.7°C) could replace the experimental values, with similar results. The in-silico methods classified 20.76% (±3.07%) as Class 1, 41.51% (±3.32%) as Class 2, 30.49% (±4.47%) as Class 3, and 6.27% (±4.39%) as Class 4. In conclusion, in-silico methods can be used for BCS classification of drugs in early development, from merely their molecular formula and without foreknowledge of their chemical structure, which will allow for the improved selection, engineering, and developability of candidates. These in-silico methods could enhance success rates, reduce costs, and accelerate oral drug products development. PMID:25284986

Geometric classification of scalp hair for valid drug testing, 6 more reliable than 8 hair curl groups.

PubMed

Mkentane, K; Van Wyk, J C; Sishi, N; Gumedze, F; Ngoepe, M; Davids, L M; Khumalo, N P

2017-01-01

Curly hair is reported to contain higher lipid content than straight hair, which may influence incorporation of lipid soluble drugs. The use of race to describe hair curl variation (Asian, Caucasian and African) is unscientific yet common in medical literature (including reports of drug levels in hair). This study investigated the reliability of a geometric classification of hair (based on 3 measurements: the curve diameter, curl index and number of waves). After ethical approval and informed consent, proximal virgin (6cm) hair sampled from the vertex of scalp in 48 healthy volunteers were evaluated. Three raters each scored hairs from 48 volunteers at two occasions each for the 8 and 6-group classifications. One rater applied the 6-group classification to 80 additional volunteers in order to further confirm the reliability of this system. The Kappa statistic was used to assess intra and inter rater agreement. Each rater classified 480 hairs on each occasion. No rater classified any volunteer's 10 hairs into the same group; the most frequently occurring group was used for analysis. The inter-rater agreement was poor for the 8-groups (k = 0.418) but improved for the 6-groups (k = 0.671). The intra-rater agreement also improved (k = 0.444 to 0.648 versus 0.599 to 0.836) for 6-groups; that for the one evaluator for all volunteers was good (k = 0.754). Although small, this is the first study to test the reliability of a geometric classification. The 6-group method is more reliable. However, a digital classification system is likely to reduce operator error. A reliable objective classification of human hair curl is long overdue, particularly with the increasing use of hair as a testing substrate for treatment compliance in Medicine.

A hybrid method for prediction and repositioning of drug Anatomical Therapeutic Chemical classes.

PubMed

Chen, Lei; Lu, Jing; Zhang, Ning; Huang, Tao; Cai, Yu-Dong

2014-04-01

In the Anatomical Therapeutic Chemical (ATC) classification system, therapeutic drugs are divided into 14 main classes according to the organ or system on which they act and their chemical, pharmacological and therapeutic properties. This system, recommended by the World Health Organization (WHO), provides a global standard for classifying medical substances and serves as a tool for international drug utilization research to improve quality of drug use. In view of this, it is necessary to develop effective computational prediction methods to identify the ATC-class of a given drug, which thereby could facilitate further analysis of this system. In this study, we initiated an attempt to develop a prediction method and to gain insights from it by utilizing ontology information of drug compounds. Since only about one-fourth of drugs in the ATC classification system have ontology information, a hybrid prediction method combining the ontology information, chemical interaction information and chemical structure information of drug compounds was proposed for the prediction of drug ATC-classes. As a result, by using the Jackknife test, the 1st prediction accuracies for identifying the 14 main ATC-classes in the training dataset, the internal validation dataset and the external validation dataset were 75.90%, 75.70% and 66.36%, respectively. Analysis of some samples with false-positive predictions in the internal and external validation datasets indicated that some of them may even have a relationship with the false-positive predicted ATC-class, suggesting novel uses of these drugs. It was conceivable that the proposed method could be used as an efficient tool to identify ATC-classes of novel drugs or to discover novel uses of known drugs.

Analysis of chats on French internet forums about drugs and pregnancy.

PubMed

Palosse-Cantaloube, Lucie; Lacroix, Isabelle; Rousseau, Vanessa; Bagheri, Haleh; Montastruc, Jean-Louis; Damase-Michel, Christine

2014-12-01

Some pregnant women use the internet to search for medical information. However, online information is not controlled. The objectives were to describe French online chats about drugs and pregnancy and evaluate the quality and reliability of information shared by internet users. This French descriptive study was performed in November 2012. In order to identify drugs and pregnancy-related forum websites, we used three French key words: forum, pregnancy and drug. We explored the first 10 websites from the search result. Diseases were described using the International Classification of Diseases and drugs classified with the Anatomical Therapeutic Chemical codes and the FDA risk classification. We selected 115 questions that were mainly posted by pregnant internet users in French forums. Drugs raising questions were mostly "nervous system," "anti-infective for systemic use" and "respiratory system" drugs. The risk during pregnancy for nearly half of these drugs had not been evaluated properly. Health professionals were only involved in 7% of the 214 answers. Internet users advised to take a drug in 21% of their answers. Thirty-four percent of those recommended drugs had not been well-evaluated or were potentially at risk during pregnancy. Finally, 12% of the answers could be at risk for pregnant woman. This study shows that information related to drugs and pregnancy in online chats could be at risk for pregnant women. Internet users must be aware that online forums are not reliable sources of information. Copyright © 2014 John Wiley & Sons, Ltd.

Classification and definition of misuse, abuse, and related events in clinical trials: ACTTION systematic review and recommendations.

PubMed

Smith, Shannon M; Dart, Richard C; Katz, Nathaniel P; Paillard, Florence; Adams, Edgar H; Comer, Sandra D; Degroot, Aldemar; Edwards, Robert R; Haddox, J David; Jaffe, Jerome H; Jones, Christopher M; Kleber, Herbert D; Kopecky, Ernest A; Markman, John D; Montoya, Ivan D; O'Brien, Charles; Roland, Carl L; Stanton, Marsha; Strain, Eric C; Vorsanger, Gary; Wasan, Ajay D; Weiss, Roger D; Turk, Dennis C; Dworkin, Robert H

2013-11-01

As the nontherapeutic use of prescription medications escalates, serious associated consequences have also increased. This makes it essential to estimate misuse, abuse, and related events (MAREs) in the development and postmarketing adverse event surveillance and monitoring of prescription drugs accurately. However, classifications and definitions to describe prescription drug MAREs differ depending on the purpose of the classification system, may apply to single events or ongoing patterns of inappropriate use, and are not standardized or systematically employed, thereby complicating the ability to assess MARE occurrence adequately. In a systematic review of existing prescription drug MARE terminology and definitions from consensus efforts, review articles, and major institutions and agencies, MARE terms were often defined inconsistently or idiosyncratically, or had definitions that overlapped with other MARE terms. The Analgesic, Anesthetic, and Addiction Clinical Trials, Translations, Innovations, Opportunities, and Networks (ACTTION) public-private partnership convened an expert panel to develop mutually exclusive and exhaustive consensus classifications and definitions of MAREs occurring in clinical trials of analgesic medications to increase accuracy and consistency in characterizing their occurrence and prevalence in clinical trials. The proposed ACTTION classifications and definitions are designed as a first step in a system to adjudicate MAREs that occur in analgesic clinical trials and postmarketing adverse event surveillance and monitoring, which can be used in conjunction with other methods of assessing a treatment's abuse potential. Copyright © 2013 International Association for the Study of Pain. All rights reserved.

Acute pancreatitis.

PubMed

Talukdar, Rupjyoti; Vege, Santhi S

2015-09-01

To summarize recent data on classification systems, cause, risk factors, severity prediction, nutrition, and drug treatment of acute pancreatitis. Comparison of the Revised Atlanta Classification and Determinant Based Classification has shown heterogeneous results. Simvastatin has a protective effect against acute pancreatitis. Young black male, alcohol, smoldering symptoms, and subsequent diagnosis of chronic pancreatitis are risk factors associated with readmissions after acute pancreatitis. A reliable clinical or laboratory marker or a scoring system to predict severity is lacking. The PYTHON trial has shown that oral feeding with on demand nasoenteric tube feeding after 72 h is as good as nasoenteric tube feeding within 24 h in preventing infections in predicted severe acute pancreatitis. Male sex, multiple organ failure, extent of pancreatic necrosis, and heterogeneous collection are factors associated with failure of percutaneous drainage of pancreatic collections. The newly proposed classification systems of acute pancreatitis need to be evaluated more critically. New biomarkers are needed for severity prediction. Further well designed studies are required to assess the type of enteral nutritional formulations for acute pancreatitis. The optimal minimally invasive method or combination to debride the necrotic collections is evolving. There is a great need for a drug to treat the disease early on to prevent morbidity and mortality.

21 CFR 860.93 - Classification of implants, life-supporting or life-sustaining devices.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Classification of implants, life-supporting or life-sustaining devices. 860.93 Section 860.93 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT... Classification § 860.93 Classification of implants, life-supporting or life-sustaining devices. (a) The...

21 CFR 860.93 - Classification of implants, life-supporting or life-sustaining devices.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Classification of implants, life-supporting or life-sustaining devices. 860.93 Section 860.93 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT... Classification § 860.93 Classification of implants, life-supporting or life-sustaining devices. (a) The...

21 CFR 860.93 - Classification of implants, life-supporting or life-sustaining devices.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Classification of implants, life-supporting or life-sustaining devices. 860.93 Section 860.93 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT... Classification § 860.93 Classification of implants, life-supporting or life-sustaining devices. (a) The...

21 CFR 860.93 - Classification of implants, life-supporting or life-sustaining devices.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Classification of implants, life-supporting or life-sustaining devices. 860.93 Section 860.93 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT... Classification § 860.93 Classification of implants, life-supporting or life-sustaining devices. (a) The...

21 CFR 860.93 - Classification of implants, life-supporting or life-sustaining devices.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Classification of implants, life-supporting or life-sustaining devices. 860.93 Section 860.93 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT... Classification § 860.93 Classification of implants, life-supporting or life-sustaining devices. (a) The...

The comparative pharmacology of some psychotropic drugs*

PubMed Central

Jacobsen, Erik

1959-01-01

Interest in the mode of action of the psychotropic drugs has been growing rapidly during the last few years and at the same time the number of compounds known to be capable of affecting the higher centres of the central nervous system has greatly increased. The diversity of psychic and somatic effects produced by these drugs, the fact that they may have similar effects on some functions but opposite effects on others, and the lack of a precise and universally accepted terminology to describe these properties have led to much confusion and thwarted attempts to arrive at a satisfactory classification. As a contribution to a clearer understanding of the relationships between the psychotropic drugs the author of this review has undertaken a systematic examination of the effects of a number of the better known compounds on the various levels of the central nervous system. The antagonistic and synergistic effects of giving the drugs in combination are also discussed, as well as the possible relationships between the central effects and certain “basic” effects on somatic functions. Although the picture revealed is a very complex one and there are still many gaps, it is possible to recognize a number of characteristic types of psychotropic drug on the basis of which a system of classification may be developed. PMID:14406391

Network Analysis of Drug-target Interactions: A Study on FDA-approved New Molecular Entities Between 2000 to 2015.

PubMed

Lin, Hui-Heng; Zhang, Le-Le; Yan, Ru; Lu, Jin-Jian; Hu, Yuanjia

2017-09-25

The U.S. Food and Drug Administration (FDA) approves new drugs every year. Drug targets are some of the most important interactive molecules for drugs, as they have a significant impact on the therapeutic effects of drugs. In this work, we thoroughly analyzed the data of small molecule drugs approved by the U.S. FDA between 2000 and 2015. Specifically, we focused on seven classes of new molecular entity (NME) classified by the anatomic therapeutic chemical (ATC) classification system. They were NMEs and their corresponding targets for the cardiovascular system, respiratory system, nerve system, general anti-infective systemic, genito-urinary system and sex hormones, alimentary tract and metabolisms, and antineoplastic and immunomodulating agents. To study the drug-target interaction on the systems level, we employed network topological analysis and multipartite network projections. As a result, the drug-target relations of different kinds of drugs were comprehensively characterized and global pictures of drug-target, drug-drug, and target-target interactions were visualized and analyzed from the perspective of network models.

Drug-nutrient interaction in clinical nutrition.

PubMed

Chan, Lingtak-Neander

2002-05-01

Drug-nutrient interactions have been recognized for decades. It is known that improper management of some of these interactions may lead to therapeutic failure or cause serious adverse effects to the patients. While most of the known drug-nutrient interactions involve changes in oral bioavailabilities and absorption of the offending compounds, recent investigations suggest that different mechanisms also exist. A mechanism-derived classification system for drug-nutrient interactions has only recently been developed. This system should facilitate the future research and development of practice guidelines in the identification and management of important interactions.

Harms and benefits associated with psychoactive drugs: findings of an international survey of active drug users

PubMed Central

Morgan, Celia JA; Noronha, Louise A; Muetzelfeldt, Mark; Fielding, Amanda

2013-01-01

There have been several recent efforts in the UK and the Netherlands to describe the harms of psychoactive substances based on ratings of either experts or drug users. This study aimed to assess the perceived benefits as well as harms of widely used recreational drugs, both licit and illicit, in an international sample of drug users. The survey was hosted at https://www.internationaldrugsurvey.org/ and was available in three languages. Residents reported their experience of 15 commonly used drugs or drug classes; regular users then rated their harms and benefits. In all, 5791 individuals from over 40 countries completed the survey, although the majority were from English speaking countries. Rankings of drugs differed across 10 categories of perceived benefits. Skunk and herbal cannabis were ranked consistently beneficial, whilst alcohol and tobacco fell below many classified drugs. There was no correlation at all between users’ harm ranking of drugs and their classification in schedules of the USA or ABC system in the UK. Prescription analgesics, alcohol and tobacco were ranked within the top 10 most harmful drugs. These findings suggest that neither the UK nor US classification systems act to inform users of the harms of psychoactive substances. It is hoped the results might inform health professionals and educators of what are considered to be both the harms and benefits of psychoactive substances to young people. PMID:23438502

Medical Devices; Gastroenterology-Urology Devices; Classification of the Metallic Biliary Stent System for Benign Strictures. Final order.

PubMed

2016-07-13

The Food and Drug Administration (FDA) is classifying the metallic biliary stent system for benign strictures into class II (special controls). The special controls that will apply to the device are identified in this order and will be part of the codified language for the metallic biliary stent system for benign strictures' classification. The Agency is classifying the device into class II (special controls) in order to provide a reasonable assurance of safety and effectiveness of the device.

Deep Learning Applications for Predicting Pharmacological Properties of Drugs and Drug Repurposing Using Transcriptomic Data.

PubMed

Aliper, Alexander; Plis, Sergey; Artemov, Artem; Ulloa, Alvaro; Mamoshina, Polina; Zhavoronkov, Alex

2016-07-05

Deep learning is rapidly advancing many areas of science and technology with multiple success stories in image, text, voice and video recognition, robotics, and autonomous driving. In this paper we demonstrate how deep neural networks (DNN) trained on large transcriptional response data sets can classify various drugs to therapeutic categories solely based on their transcriptional profiles. We used the perturbation samples of 678 drugs across A549, MCF-7, and PC-3 cell lines from the LINCS Project and linked those to 12 therapeutic use categories derived from MeSH. To train the DNN, we utilized both gene level transcriptomic data and transcriptomic data processed using a pathway activation scoring algorithm, for a pooled data set of samples perturbed with different concentrations of the drug for 6 and 24 hours. In both pathway and gene level classification, DNN achieved high classification accuracy and convincingly outperformed the support vector machine (SVM) model on every multiclass classification problem, however, models based on pathway level data performed significantly better. For the first time we demonstrate a deep learning neural net trained on transcriptomic data to recognize pharmacological properties of multiple drugs across different biological systems and conditions. We also propose using deep neural net confusion matrices for drug repositioning. This work is a proof of principle for applying deep learning to drug discovery and development.

Deep learning applications for predicting pharmacological properties of drugs and drug repurposing using transcriptomic data

PubMed Central

Aliper, Alexander; Plis, Sergey; Artemov, Artem; Ulloa, Alvaro; Mamoshina, Polina; Zhavoronkov, Alex

2016-01-01

Deep learning is rapidly advancing many areas of science and technology with multiple success stories in image, text, voice and video recognition, robotics and autonomous driving. In this paper we demonstrate how deep neural networks (DNN) trained on large transcriptional response data sets can classify various drugs to therapeutic categories solely based on their transcriptional profiles. We used the perturbation samples of 678 drugs across A549, MCF‐7 and PC‐3 cell lines from the LINCS project and linked those to 12 therapeutic use categories derived from MeSH. To train the DNN, we utilized both gene level transcriptomic data and transcriptomic data processed using a pathway activation scoring algorithm, for a pooled dataset of samples perturbed with different concentrations of the drug for 6 and 24 hours. In both gene and pathway level classification, DNN convincingly outperformed support vector machine (SVM) model on every multiclass classification problem, however, models based on a pathway level classification perform better. For the first time we demonstrate a deep learning neural net trained on transcriptomic data to recognize pharmacological properties of multiple drugs across different biological systems and conditions. We also propose using deep neural net confusion matrices for drug repositioning. This work is a proof of principle for applying deep learning to drug discovery and development. PMID:27200455

78 FR 56737 - Privacy Act of 1974; System of Records

Federal Register 2010, 2011, 2012, 2013, 2014

2013-09-13

... system as the ``Organized Crime Drug Enforcement Task Forces Management Information System'' (OCDETF MIS... Task Forces Management Information System (OCDETF MIS). SECURITY CLASSIFICATION: Unclassified. SYSTEM... Office of Management and Budget (OMB) Circular No. A-130, notice is hereby given that the Department of...

[Construction of biopharmaceutics classification system of Chinese materia medica].

PubMed

Liu, Yang; Wei, Li; Dong, Ling; Zhu, Mei-Ling; Tang, Ming-Min; Zhang, Lei

2014-12-01

Based on the characteristics of multicomponent of traditional Chinese medicine and drawing lessons from the concepts, methods and techniques of biopharmaceutics classification system (BCS) in chemical field, this study comes up with the science framework of biopharmaceutics classification system of Chinese materia medica (CMMBCS). Using the different comparison method of multicomponent level and the CMMBCS method of overall traditional Chinese medicine, the study constructs the method process while setting forth academic thoughts and analyzing theory. The basic role of this system is clear to reveal the interaction and the related absorption mechanism of multicomponent in traditional Chinese medicine. It also provides new ideas and methods for improving the quality of Chinese materia medica and the development of new drug research.

Ototoxicity (cochleotoxicity) classifications: A review.

PubMed

Crundwell, Gemma; Gomersall, Phil; Baguley, David M

2016-01-01

Drug-mediated ototoxicity, specifically cochleotoxicity, is a concern for patients receiving medications for the treatment of serious illness. A number of classification schemes exist, most of which are based on pure-tone audiometry, in order to assist non-audiological/non-otological specialists in the identification and monitoring of iatrogenic hearing loss. This review identifies the primary classification systems used in cochleototoxicity monitoring. By bringing together classifications published in discipline-specific literature, the paper aims to increase awareness of their relative strengths and limitations in the assessment and monitoring of ototoxic hearing loss and to indicate how future classification systems may improve upon the status-quo. Literature review. PubMed identified 4878 articles containing the search term ototox*. A systematic search identified 13 key classification systems. Cochleotoxicity classification systems can be divided into those which focus on hearing change from a baseline audiogram and those that focus on the functional impact of the hearing loss. Common weaknesses of these grading scales included a lack of sensitivity to small adverse changes in hearing thresholds, a lack of high-frequency audiometry (>8 kHz), and lack of indication of which changes are likely to be clinically significant for communication and quality of life.

A practical classification of untoward drug effects.

PubMed Central

Gysling, E.; Heisler, S.

1975-01-01

All drug effects can be explained as results of complex interactions between the drug, the patient and his condition, and additional extrinsic factors. On the basis of these three "determinants", a practical classification of untoward drug effects (UDE) is suggested. UDE lists using this classification would fulfill the physician's informational needs better than the material with which he is presently provided. PMID:1148971

21 CFR 892.5650 - Manual radionuclide applicator system.

Code of Federal Regulations, 2013 CFR

2013-04-01

... system. (a) Identification. A manual radionuclide applicator system is a manually operated device... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Manual radionuclide applicator system. 892.5650... planning computer programs, and accessories. (b) Classification. Class I (general controls). The device is...

21 CFR 892.5650 - Manual radionuclide applicator system.

Code of Federal Regulations, 2011 CFR

2011-04-01

... system. (a) Identification. A manual radionuclide applicator system is a manually operated device... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Manual radionuclide applicator system. 892.5650... planning computer programs, and accessories. (b) Classification. Class I (general controls). The device is...

21 CFR 892.5650 - Manual radionuclide applicator system.

Code of Federal Regulations, 2010 CFR

2010-04-01

... system. (a) Identification. A manual radionuclide applicator system is a manually operated device... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Manual radionuclide applicator system. 892.5650... planning computer programs, and accessories. (b) Classification. Class I (general controls). The device is...

21 CFR 892.5650 - Manual radionuclide applicator system.

Code of Federal Regulations, 2014 CFR

2014-04-01

... system. (a) Identification. A manual radionuclide applicator system is a manually operated device... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Manual radionuclide applicator system. 892.5650... planning computer programs, and accessories. (b) Classification. Class I (general controls). The device is...

21 CFR 892.5650 - Manual radionuclide applicator system.

Code of Federal Regulations, 2012 CFR

2012-04-01

... system. (a) Identification. A manual radionuclide applicator system is a manually operated device... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Manual radionuclide applicator system. 892.5650... planning computer programs, and accessories. (b) Classification. Class I (general controls). The device is...

21 CFR 866.5270 - C-reactive protein immuno-logical test system.

Code of Federal Regulations, 2013 CFR

2013-04-01

... the C-reactive protein in serum and other body fluids. Measurement of C-reactive protein aids in evaluation of the amount of injury to body tissues. (b) Classification. Class II (performance standards). ....5270 Section 866.5270 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN...

21 CFR 866.5270 - C-reactive protein immuno-logical test system.

Code of Federal Regulations, 2011 CFR

2011-04-01

... the C-reactive protein in serum and other body fluids. Measurement of C-reactive protein aids in evaluation of the amount of injury to body tissues. (b) Classification. Class II (performance standards). ....5270 Section 866.5270 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN...

21 CFR 866.5270 - C-reactive protein immuno-logical test system.

Code of Federal Regulations, 2012 CFR

2012-04-01

... the C-reactive protein in serum and other body fluids. Measurement of C-reactive protein aids in evaluation of the amount of injury to body tissues. (b) Classification. Class II (performance standards). ....5270 Section 866.5270 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN...

21 CFR 866.5270 - C-reactive protein immuno-logical test system.

Code of Federal Regulations, 2014 CFR

2014-04-01

... the C-reactive protein in serum and other body fluids. Measurement of C-reactive protein aids in evaluation of the amount of injury to body tissues. (b) Classification. Class II (performance standards). ....5270 Section 866.5270 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN...

Descriptive and Functional Classifications of Drug Abusers

ERIC Educational Resources Information Center

Carlin, Albert S.; Stauss, Fred F.

1977-01-01

Polydrug (non-opiate-drug) abusers have previously been classified by a variety of typologies that can be characterized as either descriptive, functional, or a combination of both. This investigation proposes two objective scoring systems that classify polydrug users on a streetwise/straight dimension and on a self-medication/recreational-use…

Geometric classification of scalp hair for valid drug testing, 6 more reliable than 8 hair curl groups

PubMed Central

Mkentane, K.; Gumedze, F.; Ngoepe, M.; Davids, L. M.; Khumalo, N. P.

2017-01-01

Introduction Curly hair is reported to contain higher lipid content than straight hair, which may influence incorporation of lipid soluble drugs. The use of race to describe hair curl variation (Asian, Caucasian and African) is unscientific yet common in medical literature (including reports of drug levels in hair). This study investigated the reliability of a geometric classification of hair (based on 3 measurements: the curve diameter, curl index and number of waves). Materials and methods After ethical approval and informed consent, proximal virgin (6cm) hair sampled from the vertex of scalp in 48 healthy volunteers were evaluated. Three raters each scored hairs from 48 volunteers at two occasions each for the 8 and 6-group classifications. One rater applied the 6-group classification to 80 additional volunteers in order to further confirm the reliability of this system. The Kappa statistic was used to assess intra and inter rater agreement. Results Each rater classified 480 hairs on each occasion. No rater classified any volunteer’s 10 hairs into the same group; the most frequently occurring group was used for analysis. The inter-rater agreement was poor for the 8-groups (k = 0.418) but improved for the 6-groups (k = 0.671). The intra-rater agreement also improved (k = 0.444 to 0.648 versus 0.599 to 0.836) for 6-groups; that for the one evaluator for all volunteers was good (k = 0.754). Conclusions Although small, this is the first study to test the reliability of a geometric classification. The 6-group method is more reliable. However, a digital classification system is likely to reduce operator error. A reliable objective classification of human hair curl is long overdue, particularly with the increasing use of hair as a testing substrate for treatment compliance in Medicine. PMID:28570555

21 CFR 7.41 - Health hazard evaluation and recall classification.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 1 2010-04-01 2010-04-01 false Health hazard evaluation and recall classification. 7.41 Section 7.41 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN..., and Industry Responsibilities § 7.41 Health hazard evaluation and recall classification. (a) An...

21 CFR 864.5620 - Automated hemoglobin system.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Automated hemoglobin system. 864.5620 Section 864....5620 Automated hemoglobin system. (a) Identification. An automated hemoglobin system is a fully... hemoglobin content of human blood. (b) Classification. Class II (performance standards). [45 FR 60601, Sept...

21 CFR 864.5620 - Automated hemoglobin system.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Automated hemoglobin system. 864.5620 Section 864....5620 Automated hemoglobin system. (a) Identification. An automated hemoglobin system is a fully... hemoglobin content of human blood. (b) Classification. Class II (performance standards). [45 FR 60601, Sept...

Newer approaches for optimal bioavailability of ocularly delivered drugs: review.

PubMed

Kesavan, K; Balasubramaniam, J; Kant, S; Singh, P N; Pandit, J K

2011-03-01

Eye diseases can cause discomfort and anxiety in patients, with the ultimate fear of loss of vision and facial disfigurement. Many regions of the eye are relatively inaccessible to systemically administered drugs and, as a result, topical drug delivery remains the preferred route in most cases. Drugs may be delivered to treat the precorneal region for conjunctivitis and blepharitis, or to provide intraocular diseases such as glaucoma, uveitis, and cytomegalovirus retinitis. Most of the ophthalmic formulation strategies aim at maximizing ocular drug permeability through prolongation of the drug residence time in the cornea and conjunctival sac, as well as minimizing precorneal drug loss. The conventional topical ocular drug delivery systems show drawbacks such as increased precorneal elimination and high variability in efficacy. Attempts have been made to overcome these problems and enhance ocular bioavailability by the development of newer drug delivery systems. This review is concerned with classification, recent findings and applications and biocompatibility of newer drug delivery systems for the treatment of ocular diseases.

Variability of undetermined manner of death classification in the US.

PubMed

Breiding, M J; Wiersema, B

2006-12-01

To better understand variations in classification of deaths of undetermined intent among states in the National Violent Death Reporting System (NVDRS). Data from the NVDRS and the National Vital Statistics System were used to compare differences among states. Percentages of deaths assigned undetermined intent, rates of deaths of undetermined intent, rates of fatal poisonings broken down by cause of death, composition of poison types within the undetermined-intent classification. Three states within NVDRS (Maryland, Massachusetts, and Rhode Island) evidenced increased numbers of deaths of undetermined intent. These same states exhibited high rates of undetermined death and, more specifically, high rates of undetermined poisoning deaths. Further, these three states evidenced correspondingly lower rates of unintentional poisonings. The types of undetermined poisonings present in these states, but not present in other states, are typically the result of a combination of recreational drugs, alcohol, or prescription drugs. The differing classification among states of many poisoning deaths has implications for the analysis of undetermined deaths within the NVDRS and for the examination of possible/probable suicides contained within the undetermined- or accidental-intent classifications. The NVDRS does not collect information on unintentional poisonings, so in most states data are not collected on these possible/probable suicides. The authors believe this is an opportunity missed to understand the full range of self-harm deaths in the greater detail provided by the NVDRS system. They advocate a broader interpretation of suicide to include the full continuum of deaths resulting from self-harm.

SFINX-a drug-drug interaction database designed for clinical decision support systems.

PubMed

Böttiger, Ylva; Laine, Kari; Andersson, Marine L; Korhonen, Tuomas; Molin, Björn; Ovesjö, Marie-Louise; Tirkkonen, Tuire; Rane, Anders; Gustafsson, Lars L; Eiermann, Birgit

2009-06-01

The aim was to develop a drug-drug interaction database (SFINX) to be integrated into decision support systems or to be used in website solutions for clinical evaluation of interactions. Key elements such as substance properties and names, drug formulations, text structures and references were defined before development of the database. Standard operating procedures for literature searches, text writing rules and a classification system for clinical relevance and documentation level were determined. ATC codes, CAS numbers and country-specific codes for substances were identified and quality assured to ensure safe integration of SFINX into other data systems. Much effort was put into giving short and practical advice regarding clinically relevant drug-drug interactions. SFINX includes over 8,000 interaction pairs and is integrated into Swedish and Finnish computerised decision support systems. Over 31,000 physicians and pharmacists are receiving interaction alerts through SFINX. User feedback is collected for continuous improvement of the content. SFINX is a potentially valuable tool delivering instant information on drug interactions during prescribing and dispensing.

Composite Biomarkers Derived from Micro-Electrode Array Measurements and Computer Simulations Improve the Classification of Drug-Induced Channel Block.

PubMed

Tixier, Eliott; Raphel, Fabien; Lombardi, Damiano; Gerbeau, Jean-Frédéric

2017-01-01

The Micro-Electrode Array (MEA) device enables high-throughput electrophysiology measurements that are less labor-intensive than patch-clamp based techniques. Combined with human-induced pluripotent stem cells cardiomyocytes (hiPSC-CM), it represents a new and promising paradigm for automated and accurate in vitro drug safety evaluation. In this article, the following question is addressed: which features of the MEA signals should be measured to better classify the effects of drugs? A framework for the classification of drugs using MEA measurements is proposed. The classification is based on the ion channels blockades induced by the drugs. It relies on an in silico electrophysiology model of the MEA, a feature selection algorithm and automatic classification tools. An in silico model of the MEA is developed and is used to generate synthetic measurements. An algorithm that extracts MEA measurements features designed to perform well in a classification context is described. These features are called composite biomarkers. A state-of-the-art machine learning program is used to carry out the classification of drugs using experimental MEA measurements. The experiments are carried out using five different drugs: mexiletine, flecainide, diltiazem, moxifloxacin, and dofetilide. We show that the composite biomarkers outperform the classical ones in different classification scenarios. We show that using both synthetic and experimental MEA measurements improves the robustness of the composite biomarkers and that the classification scores are increased.

21 CFR 866.5860 - Total spinal fluid immuno-logical test system.

Code of Federal Regulations, 2014 CFR

2014-04-01

... diagnosis of multiple sclerosis and other diseases of the nervous system. (b) Classification. Class I... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Total spinal fluid immuno-logical test system. 866... SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems § 866...

21 CFR 866.5860 - Total spinal fluid immuno-logical test system.

Code of Federal Regulations, 2013 CFR

2013-04-01

... diagnosis of multiple sclerosis and other diseases of the nervous system. (b) Classification. Class I... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Total spinal fluid immuno-logical test system. 866... SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems § 866...

21 CFR 866.5860 - Total spinal fluid immuno-logical test system.

Code of Federal Regulations, 2011 CFR

2011-04-01

... diagnosis of multiple sclerosis and other diseases of the nervous system. (b) Classification. Class I... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Total spinal fluid immuno-logical test system. 866... SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems § 866...

21 CFR 866.5860 - Total spinal fluid immuno-logical test system.

Code of Federal Regulations, 2012 CFR

2012-04-01

... diagnosis of multiple sclerosis and other diseases of the nervous system. (b) Classification. Class I... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Total spinal fluid immuno-logical test system. 866... SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems § 866...

21 CFR 866.5860 - Total spinal fluid immuno-logical test system.

Code of Federal Regulations, 2010 CFR

2010-04-01

... diagnosis of multiple sclerosis and other diseases of the nervous system. (b) Classification. Class I... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Total spinal fluid immuno-logical test system. 866... SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems § 866...

21 CFR 866.6010 - Tumor-associated antigen immunological test system.

Code of Federal Regulations, 2014 CFR

2014-04-01

..., plasma, urine, or other body fluids. This device is intended as an aid in monitoring patients for disease progress or response to therapy or for the detection of recurrent or residual disease. (b) Classification.... 866.6010 Section 866.6010 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN...

21 CFR 866.6010 - Tumor-associated antigen immunological test system.

Code of Federal Regulations, 2013 CFR

2013-04-01

..., plasma, urine, or other body fluids. This device is intended as an aid in monitoring patients for disease progress or response to therapy or for the detection of recurrent or residual disease. (b) Classification.... 866.6010 Section 866.6010 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN...

21 CFR 866.6010 - Tumor-associated antigen immunological test system.

Code of Federal Regulations, 2012 CFR

2012-04-01

..., plasma, urine, or other body fluids. This device is intended as an aid in monitoring patients for disease progress or response to therapy or for the detection of recurrent or residual disease. (b) Classification.... 866.6010 Section 866.6010 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN...

21 CFR 866.6010 - Tumor-associated antigen immunological test system.

Code of Federal Regulations, 2011 CFR

2011-04-01

..., plasma, urine, or other body fluids. This device is intended as an aid in monitoring patients for disease progress or response to therapy or for the detection of recurrent or residual disease. (b) Classification.... 866.6010 Section 866.6010 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN...

Classification of ligand molecules in PDB with graph match-based structural superposition.

PubMed

Shionyu-Mitsuyama, Clara; Hijikata, Atsushi; Tsuji, Toshiyuki; Shirai, Tsuyoshi

2016-12-01

The fast heuristic graph match algorithm for small molecules, COMPLIG, was improved by adding a structural superposition process to verify the atom-atom matching. The modified method was used to classify the small molecule ligands in the Protein Data Bank (PDB) by their three-dimensional structures, and 16,660 types of ligands in the PDB were classified into 7561 clusters. In contrast, a classification by a previous method (without structure superposition) generated 3371 clusters from the same ligand set. The characteristic feature in the current classification system is the increased number of singleton clusters, which contained only one ligand molecule in a cluster. Inspections of the singletons in the current classification system but not in the previous one implied that the major factors for the isolation were differences in chirality, cyclic conformations, separation of substructures, and bond length. Comparisons between current and previous classification systems revealed that the superposition-based classification was effective in clustering functionally related ligands, such as drugs targeted to specific biological processes, owing to the strictness of the atom-atom matching.

Combating Drug Abuse by Targeting Toll-Like Receptor 4 (TLR4)

DTIC Science & Technology

2013-10-01

dosing with the TLR4 signaling inhibitor (+)- naltrexone ? If so, is Fig  3:  Study  was  conducted  as  previously  described  in...inhibited by systemic dosing with the TLR4 signaling inhibitor (+)- naltrexone ? If so, is morphine reinforcement inhibited by microinjecting LPS-RS into... naltrexone ; drug abuse; glial activation; therapeutic approach to treating drug abuse; opioids; cocaine 16. SECURITY CLASSIFICATION OF: 17

75 FR 68849 - Privacy Act of 1974: System of Records

Federal Register 2010, 2011, 2012, 2013, 2014

2010-11-09

... processing of personal information is conducted within established FAA computer security regulations. A risk... SECURITY CLASSIFICATION: Sensitive, unclassified SYSTEM LOCATION: Federal Aviation Administration (FAA... Enforcement Centers of the Drug Abatement Division; Office of Security and Hazardous Materials; Flight...

21 CFR 864.5700 - Automated platelet aggregation system.

Code of Federal Regulations, 2011 CFR

2011-04-01

... addition of an aggregating reagent to a platelet-rich plasma. (b) Classification. Class II (performance... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Automated platelet aggregation system. 864.5700... § 864.5700 Automated platelet aggregation system. (a) Identification. An automated platelet aggregation...

21 CFR 864.5700 - Automated platelet aggregation system.

Code of Federal Regulations, 2014 CFR

2014-04-01

... addition of an aggregating reagent to a platelet-rich plasma. (b) Classification. Class II (performance... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Automated platelet aggregation system. 864.5700... § 864.5700 Automated platelet aggregation system. (a) Identification. An automated platelet aggregation...

21 CFR 864.5700 - Automated platelet aggregation system.

Code of Federal Regulations, 2013 CFR

2013-04-01

... addition of an aggregating reagent to a platelet-rich plasma. (b) Classification. Class II (performance... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Automated platelet aggregation system. 864.5700... § 864.5700 Automated platelet aggregation system. (a) Identification. An automated platelet aggregation...

21 CFR 864.5700 - Automated platelet aggregation system.

Code of Federal Regulations, 2010 CFR

2010-04-01

... addition of an aggregating reagent to a platelet-rich plasma. (b) Classification. Class II (performance... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Automated platelet aggregation system. 864.5700... § 864.5700 Automated platelet aggregation system. (a) Identification. An automated platelet aggregation...

21 CFR 864.5700 - Automated platelet aggregation system.

Code of Federal Regulations, 2012 CFR

2012-04-01

... addition of an aggregating reagent to a platelet-rich plasma. (b) Classification. Class II (performance... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Automated platelet aggregation system. 864.5700... § 864.5700 Automated platelet aggregation system. (a) Identification. An automated platelet aggregation...

How do researchers categorize drugs, and how do drug users categorize them?

PubMed Central

Lee, Juliet P.; Antin, Tamar M.J.

2011-01-01

This paper considers drug classifications and terms widely used in US survey research, and compares these to classifications and terms used by drug users. We begin with a critical review of drug classification systems, including those oriented to public policy and health services as well as survey research. We then consider the results of a pile sort exercise we conducted with 76 respondents within a mixed method study of Southeast Asian American adolescent and young adult drug users in urban Northern California, USA. We included the pile sort to clarify how respondents handled specific terms which we understood to be related to Ecstasy and methamphetamines. Results of the pile sort were analyzed using graphic layout algorithms as well as content analysis of pile labels. Similar to the national surveys, our respondents consistently differentiated Ecstasy terms from methamphetamine terms. We found high agreement between some specific local terms (thizz, crystal) and popular drug terms, while other terms thought to be mainstream (crank, speed) were reported as unknown by many respondents. In labeling piles, respondents created taxonomies based on consumption method (in particular, pill) as well as the social contexts of use. We conclude by proposing that divergences between drug terms utilized in survey research and those used by drug users may reflect two opposing tendencies: the tendency of survey researchers to utilize standardized language that constructs persons and experiences as relatively homogeneous, varying only within measurable degrees, and the tendency of drug users to utilize specialized language (argot) that reflects their understandings of their experiences as hybrid and diverse. The findings problematize the validity of drug terms and categories used in survey research. PMID:24431475

How do researchers categorize drugs, and how do drug users categorize them?

PubMed

Lee, Juliet P; Antin, Tamar M J

2012-01-01

This paper considers drug classifications and terms widely used in US survey research, and compares these to classifications and terms used by drug users. We begin with a critical review of drug classification systems, including those oriented to public policy and health services as well as survey research. We then consider the results of a pile sort exercise we conducted with 76 respondents within a mixed method study of Southeast Asian American adolescent and young adult drug users in urban Northern California, USA. We included the pile sort to clarify how respondents handled specific terms which we understood to be related to Ecstasy and methamphetamines. Results of the pile sort were analyzed using graphic layout algorithms as well as content analysis of pile labels. Similar to the national surveys, our respondents consistently differentiated Ecstasy terms from methamphetamine terms. We found high agreement between some specific local terms ( thizz , crystal ) and popular drug terms, while other terms thought to be mainstream ( crank , speed ) were reported as unknown by many respondents. In labeling piles, respondents created taxonomies based on consumption method (in particular, pill ) as well as the social contexts of use. We conclude by proposing that divergences between drug terms utilized in survey research and those used by drug users may reflect two opposing tendencies: the tendency of survey researchers to utilize standardized language that constructs persons and experiences as relatively homogeneous, varying only within measurable degrees, and the tendency of drug users to utilize specialized language (argot) that reflects their understandings of their experiences as hybrid and diverse. The findings problematize the validity of drug terms and categories used in survey research.

Analyzing U.S. prescription lists with RxNorm and the ATC/DDD Index.

PubMed

Bodenreider, Olivier; Rodriguez, Laritza M

2014-01-01

To evaluate the suitability of the ATC/DDD Index (Anatomical Therapeutic Chemical (ATC) Classification System/Defined Daily Dose) for analyzing prescription lists in the U.S. We mapped RxNorm clinical drugs to ATC. We used this mapping to classify a large set of prescription drugs with ATC and compared the prescribed daily dose to the defined daily dose (DDD) in ATC. 64% of the 11,422 clinical drugs could be precisely mapped to ATC. 97% of the 87,001 RxNorm codes from the prescription dataset could be classified with ATC, and 97% of the prescribed daily doses could be assessed. Although the mapping of RxNorm ingredients to ATC appears to be largely incomplete, the most frequently prescribed drugs in the prescription dataset we analyzed were covered. This study demonstrates the feasibility of using ATC in conjunction with RxNorm for analyzing U.S. prescription datasets for drug classification and assessment of the prescribed daily doses.

Considerations for a Pediatric Biopharmaceutics Classification System (BCS): application to five drugs.

PubMed

Gandhi, Shivani V; Rodriguez, William; Khan, Mansoor; Polli, James E

2014-06-01

It has been advocated that biopharmaceutic risk assessment should be conducted early in pediatric product development and synchronized with the adult product development program. However, we are unaware of efforts to classify drugs into a Biopharmaceutics Classification System (BCS) framework for pediatric patients. The objective was to classify five drugs into a potential BCS. These five drugs were selected since both oral and intravenous pharmacokinetic data were available for each drug, and covered the four BCS classes in adults. Literature searches for each drug were conducted using Medline and applied to classify drugs with respect to solubility and permeability in pediatric subpopulations. Four pediatric subpopulations were considered: neonates, infants, children, and adolescents. Regarding solubility, dose numbers were calculated using a volume for each subpopulation based on body surface area (BSA) relative to 250 ml for a 1.73 m(2) adult. Dose numbers spanned a range of values, depending upon the pediatric dose formula and subpopulation. Regarding permeability, pharmacokinetic literature data required assumptions and decisions about data collection. Using a devised pediatric BCS framework, there was agreement in adult and pediatric BCS class for two drugs, azithromycin (class 3) and ciprofloxacin (class 4). There was discordance for the three drugs that have high adult permeability since all pediatric permeabilities were low: dolasetron (class 3 in pediatric), ketoprofen (class 4 in pediatric), and voriconazole (class 4 in pediatric). A main contribution of this work is the identification of critical factors required for a pediatric BCS.

Evaluation of the impact of the drug evaluation and classification program on enforcement and adjudication

DOT National Transportation Integrated Search

1992-12-01

This study examined the effect of the Drug Evaluation and Classification (DEC) Program on impaired driving (DWI) enforcement and adjudication. Drug Recognition Experts (DREs) in DEC programs evaluate suspects when drugs other than alcohol are suspect...

A proposed food breakdown classification system to predict food behavior during gastric digestion.

PubMed

Bornhorst, Gail M; Ferrua, Maria J; Singh, R Paul

2015-05-01

The pharmaceutical industry has implemented the Biopharmaceutics Classification System (BCS), which is used to classify drug products based on their solubility and intestinal permeability. The BCS can help predict drug behavior in vivo, the rate-limiting mechanism of absorption, and the likelihood of an in vitro-in vivo correlation. Based on this analysis, we have proposed a Food Breakdown Classification System (FBCS) framework that can be used to classify solid foods according to their initial hardness and their rate of softening during physiological gastric conditions. The proposed FBCS will allow for prediction of food behavior during gastric digestion. The applicability of the FBCS framework in differentiating between dissimilar solid foods was demonstrated using four example foods: raw carrot, boiled potato, white rice, and brown rice. The initial hardness and rate of softening parameter (softening half time) were determined for these foods as well as their hypothesized FBCS class. In addition, we have provided future suggestions as to the methodological and analytical challenges that need to be overcome prior to widespread use and adoption of this classification system. The FBCS gives a framework that may be used to classify food products based on their material properties and their behavior during in vitro gastric digestion, and may also be used to predict in vivo food behavior. As consumer demand increases for functional and "pharma" food products, the food industry will need widespread testing of food products for their structural and functional performance during digestion. © 2015 Institute of Food Technologists®

21 CFR 866.5775 - Rheumatoid factor immuno-logical test system.

Code of Federal Regulations, 2010 CFR

2010-04-01

.... Measurement of rheumatoid factor may aid in the diagnosis of rheumatoid arthritis. (b) Classification. Class... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Rheumatoid factor immuno-logical test system. 866....5775 Rheumatoid factor immuno-logical test system. (a) Identification. A rheumatoid factor...

21 CFR 866.5775 - Rheumatoid factor immuno-logical test system.

Code of Federal Regulations, 2011 CFR

2011-04-01

.... Measurement of rheumatoid factor may aid in the diagnosis of rheumatoid arthritis. (b) Classification. Class... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Rheumatoid factor immuno-logical test system. 866....5775 Rheumatoid factor immuno-logical test system. (a) Identification. A rheumatoid factor...

21 CFR 866.5775 - Rheumatoid factor immuno-logical test system.

Code of Federal Regulations, 2012 CFR

2012-04-01

.... Measurement of rheumatoid factor may aid in the diagnosis of rheumatoid arthritis. (b) Classification. Class... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Rheumatoid factor immuno-logical test system. 866....5775 Rheumatoid factor immuno-logical test system. (a) Identification. A rheumatoid factor...

21 CFR 866.5775 - Rheumatoid factor immuno-logical test system.

Code of Federal Regulations, 2013 CFR

2013-04-01

.... Measurement of rheumatoid factor may aid in the diagnosis of rheumatoid arthritis. (b) Classification. Class... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Rheumatoid factor immuno-logical test system. 866....5775 Rheumatoid factor immuno-logical test system. (a) Identification. A rheumatoid factor...

21 CFR 866.5775 - Rheumatoid factor immuno-logical test system.

Code of Federal Regulations, 2014 CFR

2014-04-01

.... Measurement of rheumatoid factor may aid in the diagnosis of rheumatoid arthritis. (b) Classification. Class... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Rheumatoid factor immuno-logical test system. 866....5775 Rheumatoid factor immuno-logical test system. (a) Identification. A rheumatoid factor...

Multidrug resistance among new tuberculosis cases: detecting local variation through lot quality-assurance sampling.

PubMed

Hedt, Bethany Lynn; van Leth, Frank; Zignol, Matteo; Cobelens, Frank; van Gemert, Wayne; Nhung, Nguyen Viet; Lyepshina, Svitlana; Egwaga, Saidi; Cohen, Ted

2012-03-01

Current methodology for multidrug-resistant tuberculosis (MDR TB) surveys endorsed by the World Health Organization provides estimates of MDR TB prevalence among new cases at the national level. On the aggregate, local variation in the burden of MDR TB may be masked. This paper investigates the utility of applying lot quality-assurance sampling to identify geographic heterogeneity in the proportion of new cases with multidrug resistance. We simulated the performance of lot quality-assurance sampling by applying these classification-based approaches to data collected in the most recent TB drug-resistance surveys in Ukraine, Vietnam, and Tanzania. We explored 3 classification systems- two-way static, three-way static, and three-way truncated sequential sampling-at 2 sets of thresholds: low MDR TB = 2%, high MDR TB = 10%, and low MDR TB = 5%, high MDR TB = 20%. The lot quality-assurance sampling systems identified local variability in the prevalence of multidrug resistance in both high-resistance (Ukraine) and low-resistance settings (Vietnam). In Tanzania, prevalence was uniformly low, and the lot quality-assurance sampling approach did not reveal variability. The three-way classification systems provide additional information, but sample sizes may not be obtainable in some settings. New rapid drug-sensitivity testing methods may allow truncated sequential sampling designs and early stopping within static designs, producing even greater efficiency gains. Lot quality-assurance sampling study designs may offer an efficient approach for collecting critical information on local variability in the burden of multidrug-resistant TB. Before this methodology is adopted, programs must determine appropriate classification thresholds, the most useful classification system, and appropriate weighting if unbiased national estimates are also desired.

21 CFR 201.200 - Disclosure of drug efficacy study evaluations in labeling and advertising.

Code of Federal Regulations, 2010 CFR

2010-04-01

... an exhaustive review of labeling claims made for drugs marketed under new-drug and antibiotic drug... classification in lieu of the Academy's classification. (d) For new drugs and antibiotics, supplements to provide... purchaser or prescriber is not misled by being left unaware through the sponsor's silence that a basic...

Co-Prescription of QT-Interval Prolonging Drugs: An Analysis in a Large Cohort of Geriatric Patients.

PubMed

Schächtele, Simone; Tümena, Thomas; Gaßmann, Karl-Günter; Fromm, Martin F; Maas, Renke

2016-01-01

Drug-induced QT-interval prolongation is associated with occurrence of potentially fatal Torsades de Pointes arrhythmias (TdP). So far, data regarding the overall burden of QT-interval prolonging drugs (QT-drugs) in geriatric patients are limited. This study was performed to assess the individual burden of QT-interval prolonging drugs (QT-drugs) in geriatric polymedicated patients and to identify the most frequent and risky combinations of QT-drugs. In the discharge medication of geriatric patients between July 2009 and June 2013 from the Geriatrics in Bavaria-Database (GiB-DAT) (co)-prescriptions of QT-drugs were investigated. QT-drugs were classified according to a publicly available reference site (CredibleMeds®) as ALL-QT-drugs (associated with any QT-risk) or High-risk-QT-drugs (corresponding to QT-drugs with known risk of Torsades de Pointes according to CredibleMeds®) and in addition as SmPC-high-risk-QT-drugs (according to the German prescribing information (SmPC) contraindicated co-prescription with other QT-drugs). Of a cohort of 130,434 geriatric patients (mean age 81 years, 67% women), prescribed a median of 8 drugs, 76,594 patients (58.7%) received at least one ALL-QT-drug. Co-prescriptions of two or more ALL-QT-drugs were observed in 28,768 (22.1%) patients. Particularly risky co-prescriptions of High-risk-QT-drugs or SmPC-high-risk-QT-drugs with at least on further QT-drug occurred in 55.9% (N = 12,633) and 54.2% (N = 12,429) of these patients, respectively. Consideration of SmPCs (SmPC-high-risk-QT-drugs) allowed the identification of an additional 15% (N = 3,999) patients taking a risky combination that was not covered by the commonly used CredibleMeds® classification. Only 20 drug-drug combinations accounted for more than 90% of these potentially most dangerous co-prescriptions. In a geriatric study population co-prescriptions of two and more QT-drugs were common. A considerable proportion of QT-drugs with higher risk only could be detected by using more than one classification-system. Local adaption of international classifications can improve identification of patients at risk.

From Classification to Epilepsy Ontology and Informatics

PubMed Central

Zhang, Guo-Qiang; Sahoo, Satya S; Lhatoo, Samden D

2012-01-01

Summary The 2010 International League Against Epilepsy (ILAE) classification and terminology commission report proposed a much needed departure from previous classifications to incorporate advances in molecular biology, neuroimaging, and genetics. It proposed an interim classification and defined two key requirements that need to be satisfied. The first is the ability to classify epilepsy in dimensions according to a variety of purposes including clinical research, patient care, and drug discovery. The second is the ability of the classification system to evolve with new discoveries. Multi-dimensionality and flexibility are crucial to the success of any future classification. In addition, a successful classification system must play a central role in the rapidly growing field of epilepsy informatics. An epilepsy ontology, based on classification, will allow information systems to facilitate data-intensive studies and provide a proven route to meeting the two foregoing key requirements. Epilepsy ontology will be a structured terminology system that accommodates proposed and evolving ILAE classifications, the NIH/NINDS Common Data Elements, the ICD systems and explicitly specifies all known relationships between epilepsy concepts in a proper framework. This will aid evidence based epilepsy diagnosis, investigation, treatment and research for a diverse community of clinicians and researchers. Benefits range from systematization of electronic patient records to multi-modal data repositories for research and training manuals for those involved in epilepsy care. Given the complexity, heterogeneity and pace of research advances in the epilepsy domain, such an ontology must be collaboratively developed by key stakeholders in the epilepsy community and experts in knowledge engineering and computer science. PMID:22765502

Integration of Chinese medicine with Western medicine could lead to future medicine: molecular module medicine.

PubMed

Zhang, Chi; Zhang, Ge; Chen, Ke-ji; Lu, Ai-ping

2016-04-01

The development of an effective classification method for human health conditions is essential for precise diagnosis and delivery of tailored therapy to individuals. Contemporary classification of disease systems has properties that limit its information content and usability. Chinese medicine pattern classification has been incorporated with disease classification, and this integrated classification method became more precise because of the increased understanding of the molecular mechanisms. However, we are still facing the complexity of diseases and patterns in the classification of health conditions. With continuing advances in omics methodologies and instrumentation, we are proposing a new classification approach: molecular module classification, which is applying molecular modules to classifying human health status. The initiative would be precisely defining the health status, providing accurate diagnoses, optimizing the therapeutics and improving new drug discovery strategy. Therefore, there would be no current disease diagnosis, no disease pattern classification, and in the future, a new medicine based on this classification, molecular module medicine, could redefine health statuses and reshape the clinical practice.

Classification of current anticancer immunotherapies

PubMed Central

Vacchelli, Erika; Pedro, José-Manuel Bravo-San; Buqué, Aitziber; Senovilla, Laura; Baracco, Elisa Elena; Bloy, Norma; Castoldi, Francesca; Abastado, Jean-Pierre; Agostinis, Patrizia; Apte, Ron N.; Aranda, Fernando; Ayyoub, Maha; Beckhove, Philipp; Blay, Jean-Yves; Bracci, Laura; Caignard, Anne; Castelli, Chiara; Cavallo, Federica; Celis, Estaban; Cerundolo, Vincenzo; Clayton, Aled; Colombo, Mario P.; Coussens, Lisa; Dhodapkar, Madhav V.; Eggermont, Alexander M.; Fearon, Douglas T.; Fridman, Wolf H.; Fučíková, Jitka; Gabrilovich, Dmitry I.; Galon, Jérôme; Garg, Abhishek; Ghiringhelli, François; Giaccone, Giuseppe; Gilboa, Eli; Gnjatic, Sacha; Hoos, Axel; Hosmalin, Anne; Jäger, Dirk; Kalinski, Pawel; Kärre, Klas; Kepp, Oliver; Kiessling, Rolf; Kirkwood, John M.; Klein, Eva; Knuth, Alexander; Lewis, Claire E.; Liblau, Roland; Lotze, Michael T.; Lugli, Enrico; Mach, Jean-Pierre; Mattei, Fabrizio; Mavilio, Domenico; Melero, Ignacio; Melief, Cornelis J.; Mittendorf, Elizabeth A.; Moretta, Lorenzo; Odunsi, Adekunke; Okada, Hideho; Palucka, Anna Karolina; Peter, Marcus E.; Pienta, Kenneth J.; Porgador, Angel; Prendergast, George C.; Rabinovich, Gabriel A.; Restifo, Nicholas P.; Rizvi, Naiyer; Sautès-Fridman, Catherine; Schreiber, Hans; Seliger, Barbara; Shiku, Hiroshi; Silva-Santos, Bruno; Smyth, Mark J.; Speiser, Daniel E.; Spisek, Radek; Srivastava, Pramod K.; Talmadge, James E.; Tartour, Eric; Van Der Burg, Sjoerd H.; Van Den Eynde, Benoît J.; Vile, Richard; Wagner, Hermann; Weber, Jeffrey S.; Whiteside, Theresa L.; Wolchok, Jedd D.; Zitvogel, Laurence; Zou, Weiping

2014-01-01

During the past decades, anticancer immunotherapy has evolved from a promising therapeutic option to a robust clinical reality. Many immunotherapeutic regimens are now approved by the US Food and Drug Administration and the European Medicines Agency for use in cancer patients, and many others are being investigated as standalone therapeutic interventions or combined with conventional treatments in clinical studies. Immunotherapies may be subdivided into “passive” and “active” based on their ability to engage the host immune system against cancer. Since the anticancer activity of most passive immunotherapeutics (including tumor-targeting monoclonal antibodies) also relies on the host immune system, this classification does not properly reflect the complexity of the drug-host-tumor interaction. Alternatively, anticancer immunotherapeutics can be classified according to their antigen specificity. While some immunotherapies specifically target one (or a few) defined tumor-associated antigen(s), others operate in a relatively non-specific manner and boost natural or therapy-elicited anticancer immune responses of unknown and often broad specificity. Here, we propose a critical, integrated classification of anticancer immunotherapies and discuss the clinical relevance of these approaches. PMID:25537519

Development and feasibility of the misuse, abuse, and diversion drug event reporting system (MADDERS®).

PubMed

Treister, Roi; Trudeau, Jeremiah J; Van Inwegen, Richard; Jones, Judith K; Katz, Nathaniel P

2016-12-01

Inappropriate use of analgesic drugs has become increasingly pervasive over the past decade. Currently, drug abuse potential is primarily assessed post-marketing; no validated tools are available to assess this potential in phase II and III clinical trials. This paper describes the development and feasibility testing of a Misuse, Abuse, and Diversion Drug Event Reporting System (MADDERS), which aims to identify potentially abuse-related events and classify them according to a recently developed classification scheme, allowing the quantification of these events in clinical trials. The system was initially conceived and designed with input from experts and patients, followed by field-testing to assess its feasibility and content validity in both completed and ongoing clinical trials. The results suggest that MADDERS is a feasible system with initial validity. It showed higher rates of the triggering events in subjects taking medications with known abuse potential than in patients taking medications without abuse potential. Additionally, experts agreed on the classification of most abuse-related events in MADDERS. MADDERS is a new systematic approach to collect information on potentially abuse-related events in clinical trials and classify them. The system has demonstrated feasibility for implementation. Additional research is ongoing to further evaluate its validity. Currently, there are no validated tools to assess drug abuse potential during clinical trials. Because of its ease of implementation, its systematic approach, and its preliminary validation results, MADDERS could provide such a tool for clinical trials. (Am J Addict 2016;25:641-651). © 2016 American Academy of Addiction Psychiatry.

76 FR 36133 - Draft Guidances for Industry and Food and Drug Administration Staff: Classification of Products...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-21

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-D-0429] Draft Guidances for Industry and Food and Drug Administration Staff: Classification of Products as Drugs... Action'' in the Definition of Device Under Section 201(h) of the Federal Food, Drug, and Cosmetic Act...

Mechanistic Physiologically Based Pharmacokinetic Modeling of the Dissolution and Food Effect of a Biopharmaceutics Classification System IV Compound-The Venetoclax Story.

PubMed

Emami Riedmaier, Arian; Lindley, David J; Hall, Jeffrey A; Castleberry, Steven; Slade, Russell T; Stuart, Patricia; Carr, Robert A; Borchardt, Thomas B; Bow, Daniel A J; Nijsen, Marjoleen

2018-01-01

Venetoclax, a selective B-cell lymphoma-2 inhibitor, is a biopharmaceutics classification system class IV compound. The aim of this study was to develop a physiologically based pharmacokinetic (PBPK) model to mechanistically describe absorption and disposition of an amorphous solid dispersion formulation of venetoclax in humans. A mechanistic PBPK model was developed incorporating measured amorphous solubility, dissolution, metabolism, and plasma protein binding. A middle-out approach was used to define permeability. Model predictions of oral venetoclax pharmacokinetics were verified against clinical studies of fed and fasted healthy volunteers, and clinical drug interaction studies with strong CYP3A inhibitor (ketoconazole) and inducer (rifampicin). Model verification demonstrated accurate prediction of the observed food effect following a low-fat diet. Ratios of predicted versus observed C max and area under the curve of venetoclax were within 0.8- to 1.25-fold of observed ratios for strong CYP3A inhibitor and inducer interactions, indicating that the venetoclax elimination pathway was correctly specified. The verified venetoclax PBPK model is one of the first examples mechanistically capturing absorption, food effect, and exposure of an amorphous solid dispersion formulated compound. This model allows evaluation of untested drug-drug interactions, especially those primarily occurring in the intestine, and paves the way for future modeling of biopharmaceutics classification system IV compounds. Copyright © 2018 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Acute Radiation Sickness Amelioration Analysis

DTIC Science & Technology

1994-05-01

Emetic Drugs 16. PRICE CODE Antagonists 17. SECURITY CLASSIFICATION 18. SECURITY CLASSIFICATION 19, SECURITY CLASSIFICATION 20. LIMITATION OF ABSTRACT OF...102 UNCLASSIFIED mcuIw IA IIIcaIIin or Isis PAW CLASSFIED BY: N/A since Unclassified. DECLASSIFY ON: N/A since Unclassified. SECURITY CLASSIFICATION OF...Approximately 2000 documents relevant to the development of the candidate anti-emetic drugs ondansetron (Zofran, Glaxo Pharmaceuticals) and granisetron

Intestinal permeability study of minoxidil: assessment of minoxidil as a high permeability reference drug for biopharmaceutics classification.

PubMed

Ozawa, Makoto; Tsume, Yasuhiro; Zur, Moran; Dahan, Arik; Amidon, Gordon L

2015-01-05

The purpose of this study was to evaluate minoxidil as a high permeability reference drug for Biopharmaceutics Classification System (BCS). The permeability of minoxidil was determined in in situ intestinal perfusion studies in rodents and permeability studies across Caco-2 cell monolayers. The permeability of minoxidil was compared with that of metoprolol, an FDA reference drug for BCS classification. In rat perfusion studies, the permeability of minoxidil was somewhat higher than that of metoprolol in the jejunum, while minoxidil showed lower permeability than metoprolol in the ileum. The permeability of minoxidil was independent of intestinal segment, while the permeability of metoprolol was region-dependent. Similarly, in mouse perfusion study, the jejunal permeability of minoxidil was 2.5-fold higher than that of metoprolol. Minoxidil and metoprolol showed similar permeability in Caco-2 study at apical pH of 6.5 and basolateral pH of 7.4. The permeability of minoxidil was independent of pH, while metoprolol showed pH-dependent transport in Caco-2 study. Minoxidil exhibited similar permeability in the absorptive direction (AP-BL) in comparison with secretory direction (BL-AP), while metoprolol had higher efflux ratio (ER > 2) at apical pH of 6.5 and basolateral pH of 7.4. No concentration-dependent transport was observed for either minoxidil or metoprolol transport in Caco-2 study. Verapamil did not alter the transport of either compounds across Caco-2 cell monolayers. The permeability of minoxidil was independent of both pH and intestinal segment in intestinal perfusion studies and Caco-2 studies. Caco-2 studies also showed no involvement of carrier mediated transport in the absorption process of minoxidil. These results suggest that minoxidil may be an acceptable reference drug for BCS high permeability classification. However, minoxidil exhibited higher jejunal permeability than metoprolol and thus to use minoxidil as a reference drug would raise the permeability criteria for BCS high permeability classification.

75 FR 78246 - Medicare Program; Re-Chartering of the Advisory Panel on Ambulatory Payment Classification (APC...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-12-15

... Administrator among the fields of hospital payment systems; hospital medical care delivery systems; provider billing and accounting systems; APC groups; Current Procedural Terminology codes; HCPCS codes; the use of, and payment for, drugs, medical devices, and other services in the outpatient setting; and other forms...

Predicting when biliary excretion of parent drug is a major route of elimination in humans.

PubMed

Hosey, Chelsea M; Broccatelli, Fabio; Benet, Leslie Z

2014-09-01

Biliary excretion is an important route of elimination for many drugs, yet measuring the extent of biliary elimination is difficult, invasive, and variable. Biliary elimination has been quantified for few drugs with a limited number of subjects, who are often diseased patients. An accurate prediction of which drugs or new molecular entities are significantly eliminated in the bile may predict potential drug-drug interactions, pharmacokinetics, and toxicities. The Biopharmaceutics Drug Disposition Classification System (BDDCS) characterizes significant routes of drug elimination, identifies potential transporter effects, and is useful in understanding drug-drug interactions. Class 1 and 2 drugs are primarily eliminated in humans via metabolism and will not exhibit significant biliary excretion of parent compound. In contrast, class 3 and 4 drugs are primarily excreted unchanged in the urine or bile. Here, we characterize the significant elimination route of 105 orally administered class 3 and 4 drugs. We introduce and validate a novel model, predicting significant biliary elimination using a simple classification scheme. The model is accurate for 83% of 30 drugs collected after model development. The model corroborates the observation that biliarily eliminated drugs have high molecular weights, while demonstrating the necessity of considering route of administration and extent of metabolism when predicting biliary excretion. Interestingly, a predictor of potential metabolism significantly improves predictions of major elimination routes of poorly metabolized drugs. This model successfully predicts the major elimination route for poorly permeable/poorly metabolized drugs and may be applied prior to human dosing.

[Research progress on current pharmacokinetic evaluation of Chinese herbal medicines].

PubMed

Li, Guofu; Zhao, Haoru; Yang, Jin

2011-03-01

In order to prove safety and efficacy, herbal medicines must undergo the rigorous scientific researches such as pharmacokinetic and bioavailability, before they are put on the market in the foreign countries. Botanical Drug Products promulgated by the US FDA could guide industry sponsors to develop herbal drugs, which was also an important reference for investigating Chinese herbal medicines. This paper reviews and discusses novel approaches for how to assess systemic exposure and pharmacokinetic of Chinese herbal medicines, which were in line with FDA guidance. This mainly focus on identifying pharmacokinetic markers of botanical products, integral pharmacokinetic study of multiple components, Biopharmaceutics drug disposition classification system, and population pharmacokinetic-pharmacodynamic study in herb-drug interaction.

Uso del Registro de Solicitudes de Medicamentos no Incluidos en el Listado de Medicamentos Esenciales como Nueva Fuente de Información en los Sistemas Nacionales de Farmacovigilancia.

PubMed

Buendía, Jefferson Antonio; Zuluaga Salazar, Andrés Felipe; Vacca González, Claudia Patricia

2013-12-01

To describe the frequency of adverse drugs events (ADEs) as possible causes of request of drugs not included in national essential Medicines list in Colombia. This was a descriptive study developed in a private medical insurance company in Bogota, Colombia. Data were obtained from drug request form of drugs not included in a national essential Medicines list. We analyzed the content of the notes to identify the records related to the occurrence of ADEs in the period 2008 to 2009. Information concerning the adverse event and the drug involved was recorded in a data collection instrument developed by the researchers. The pharmacological classification of drugs was performed according to the Anatomical Therapeutic Chemical Classification System (ATC). We study 3,336 request forms of drugs not included in a national essential Medicines list. The level 1 groups of the ATC of drugs with greater frequency of ADEs were the cardiovascular agents (47%), nervous system agents (24%) and antineoplastic and immunomodulating agents (15%). The great majority was cases of light severity (62.7%) and classified as possible (48.4%). The results of this study support the innovative approach of using request form of drug not included in national essential Medicines list to obtain information regarding ADEs in developing countries; recognizing the importance of looking for new sources of report of adverse reactions to diminish the under-notification of ADEs. © 2013 International Society for Pharmacoeconomics and Outcomes Research (ISPOR) Published by International Society for Pharmacoeconomics and Outcomes Research (ISPOR) All rights reserved.

Panacea, a semantic-enabled drug recommendations discovery framework.

PubMed

Doulaverakis, Charalampos; Nikolaidis, George; Kleontas, Athanasios; Kompatsiaris, Ioannis

2014-03-06

Personalized drug prescription can be benefited from the use of intelligent information management and sharing. International standard classifications and terminologies have been developed in order to provide unique and unambiguous information representation. Such standards can be used as the basis of automated decision support systems for providing drug-drug and drug-disease interaction discovery. Additionally, Semantic Web technologies have been proposed in earlier works, in order to support such systems. The paper presents Panacea, a semantic framework capable of offering drug-drug and drug-diseases interaction discovery. For enabling this kind of service, medical information and terminology had to be translated to ontological terms and be appropriately coupled with medical knowledge of the field. International standard classifications and terminologies, provide the backbone of the common representation of medical data while the medical knowledge of drug interactions is represented by a rule base which makes use of the aforementioned standards. Representation is based on a lightweight ontology. A layered reasoning approach is implemented where at the first layer ontological inference is used in order to discover underlying knowledge, while at the second layer a two-step rule selection strategy is followed resulting in a computationally efficient reasoning approach. Details of the system architecture are presented while also giving an outline of the difficulties that had to be overcome. Panacea is evaluated both in terms of quality of recommendations against real clinical data and performance. The quality recommendation gave useful insights regarding requirements for real world deployment and revealed several parameters that affected the recommendation results. Performance-wise, Panacea is compared to a previous published work by the authors, a service for drug recommendations named GalenOWL, and presents their differences in modeling and approach to the problem, while also pinpointing the advantages of Panacea. Overall, the paper presents a framework for providing an efficient drug recommendations service where Semantic Web technologies are coupled with traditional business rule engines.

Drug-related acute renal failure in hospitalised patients.

PubMed

Iavecchia, Lujan; Cereza García, Gloria; Sabaté Gallego, Mònica; Vidal Guitart, Xavier; Ramos Terrades, Natalia; de la Torre, Judith; Segarra Medrano, Alfons; Agustí Escasany, Antònia

2015-01-01

The information available on the incidence and the characteristics of patients with acute renal failure (ARF) related to drugs is scarce. To estimate the incidence of drug-related ARF in hospitalised patients and to compare their characteristics with those of patients with ARF due to other causes. We selected a prospective cohort of patients with ARF during hospital admission (July 2010-July 2011). Information on patients' demographics, medical antecedents, ARF risk factors, ARF severity according to the RIFLE classification and hospital drug administration was collected. We analysed the relationship of drugs with the ARF episodes using Spanish Pharmacovigilance System methods and algorithm. A total of 194 cases had an episode of hospital-acquired ARF. The median age of patients was 72 years [IQR 20]; 60% were men. The ARF incidence during hospitalization was 9.6 per 1,000 admissions. According to the RIFLE classification, a risk of kidney damage or kidney injury was present in 77.8% of cases. In 105 (54.1%) cases, ARF was drug-related; the drugs most frequently involved were diuretics, agents acting on the renin-angiotensin system, immunosuppressants, β-blocking agents, calcium channel blockers, contrast media and non-steroid anti-inflammatory drugs. Patients with drug-related ARF had more multi-morbidity, fewer ARF risk factors and lower mortality. Half of ARF episodes during hospitalisation were drug related. Patients with drug-related ARF had higher cardiovascular morbidity than those with ARF related to other causes, but they had a lower frequency of ARF risk factors and mortality. Copyright © 2015 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.

Health Instruction Packages: Drug Dosage, Classification, and Mixing.

ERIC Educational Resources Information Center

Bracchi, Dorothy P.; And Others

Text, illustrations, and exercises are utilized in a set of seven learning modules to instruct nursing students in the fundamentals of drug classification, dosage, and mixing. The first module, by Dorothy Bracchi, teaches the student to identify six classifications of medication often administered to orthopedic patients: anti-neurospasmolytic…

Discerning suicide in drug intoxication deaths: Paucity and primacy of suicide notes and psychiatric history.

PubMed

Rockett, Ian R H; Caine, Eric D; Connery, Hilary S; D'Onofrio, Gail; Gunnell, David J; Miller, Ted R; Nolte, Kurt B; Kaplan, Mark S; Kapusta, Nestor D; Lilly, Christa L; Nelson, Lewis S; Putnam, Sandra L; Stack, Steven; Värnik, Peeter; Webster, Lynn R; Jia, Haomiao

2018-01-01

A paucity of corroborative psychological and psychiatric evidence may be inhibiting detection of drug intoxication suicides in the United States. We evaluated the relative importance of suicide notes and psychiatric history in the classification of suicide by drug intoxication versus firearm (gunshot wound) plus hanging/suffocation-the other two major, but overtly violent methods. This observational multilevel (individual/county), multivariable study employed a generalized linear mixed model (GLMM) to analyze pooled suicides and undetermined intent deaths, as possible suicides, among the population aged 15 years and older in the 17 states participating in the National Violent Death Reporting System throughout 2011-2013. The outcome measure was relative odds of suicide versus undetermined classification, adjusted for demographics, precipitating circumstances, and investigation characteristics. A suicide note, prior suicide attempt, or affective disorder was documented in less than one-third of suicides and one-quarter of undetermined deaths. The prevalence gaps were larger among drug intoxication cases than gunshot/hanging cases. The latter were more likely than intoxication cases to be classified as suicide versus undetermined manner of death (adjusted odds ratio [OR], 41.14; 95% CI, 34.43-49.15), as were cases documenting a suicide note (OR, 33.90; 95% CI, 26.11-44.05), prior suicide attempt (OR, 2.42; 95% CI, 2.11-2.77), or depression (OR, 1.61; 95% CI, 1.38 to 1.88), or bipolar disorder (OR, 1.41; 95% CI, 1.10-1.81). Stratification by mechanism/cause intensified the association between a note and suicide classification for intoxication cases (OR, 45.43; 95% CI, 31.06-66.58). Prior suicide attempt (OR, 2.64; 95% CI, 2.19-3.18) and depression (OR, 1.48; 95% CI, 1.17-1.87) were associated with suicide classification in intoxication but not gunshot/hanging cases. Without psychological/psychiatric evidence contributing to manner of death classification, suicide by drug intoxication in the US is likely profoundly under-reported. Findings harbor adverse implications for surveillance, etiologic understanding, and prevention of suicides and drug deaths.

Discerning suicide in drug intoxication deaths: Paucity and primacy of suicide notes and psychiatric history

PubMed Central

Caine, Eric D.; Connery, Hilary S.; D’Onofrio, Gail; Gunnell, David J.; Miller, Ted R.; Nolte, Kurt B.; Kaplan, Mark S.; Kapusta, Nestor D.; Lilly, Christa L.; Nelson, Lewis S.; Putnam, Sandra L.; Stack, Steven; Värnik, Peeter; Webster, Lynn R.; Jia, Haomiao

2018-01-01

Objective A paucity of corroborative psychological and psychiatric evidence may be inhibiting detection of drug intoxication suicides in the United States. We evaluated the relative importance of suicide notes and psychiatric history in the classification of suicide by drug intoxication versus firearm (gunshot wound) plus hanging/suffocation—the other two major, but overtly violent methods. Methods This observational multilevel (individual/county), multivariable study employed a generalized linear mixed model (GLMM) to analyze pooled suicides and undetermined intent deaths, as possible suicides, among the population aged 15 years and older in the 17 states participating in the National Violent Death Reporting System throughout 2011–2013. The outcome measure was relative odds of suicide versus undetermined classification, adjusted for demographics, precipitating circumstances, and investigation characteristics. Results A suicide note, prior suicide attempt, or affective disorder was documented in less than one-third of suicides and one-quarter of undetermined deaths. The prevalence gaps were larger among drug intoxication cases than gunshot/hanging cases. The latter were more likely than intoxication cases to be classified as suicide versus undetermined manner of death (adjusted odds ratio [OR], 41.14; 95% CI, 34.43–49.15), as were cases documenting a suicide note (OR, 33.90; 95% CI, 26.11–44.05), prior suicide attempt (OR, 2.42; 95% CI, 2.11–2.77), or depression (OR, 1.61; 95% CI, 1.38 to 1.88), or bipolar disorder (OR, 1.41; 95% CI, 1.10–1.81). Stratification by mechanism/cause intensified the association between a note and suicide classification for intoxication cases (OR, 45.43; 95% CI, 31.06–66.58). Prior suicide attempt (OR, 2.64; 95% CI, 2.19–3.18) and depression (OR, 1.48; 95% CI, 1.17–1.87) were associated with suicide classification in intoxication but not gunshot/hanging cases. Conclusions Without psychological/psychiatric evidence contributing to manner of death classification, suicide by drug intoxication in the US is likely profoundly under-reported. Findings harbor adverse implications for surveillance, etiologic understanding, and prevention of suicides and drug deaths. PMID:29320540

[Prescription of drugs with ASMR V in patients over 65 years in a primary care ambulatory setting. Drug prescription analysis in the Midi-Pyrénées region (France)].

PubMed

Bismuth, Serge; Chalvignac, Caroline; Bagheri, Haleh; Oustric, Stéphane

2010-12-20

In French patients over 65 years, drug intake is characterized by polytherapy, causing iatrogenic events. The general practitioner is the main actor in the follow-up and reassessment of drug prescriptions. To assess the proportion of ASMR V (Amélioration du service medical rendu - additional therapeutic benefit versus current standards) drugs [drugs producing no medical improvement] prescribed to patients over 65 years in the management of a chronic disease. In May 2009, 849 drug prescriptions were collected from 34 general practitioners in the Midi-Pyrénées region. Specialties with ASMR V were classified according to the anatomical therapeutic chemical (ATC) classification system. 58.8% of the prescriptions concerned female patients; 67.4% of the prescriptions contained at least one ASMR-V drug. Approximately 20% of the prescriptions in subjects over 65 years contained ASMR-V drugs. This study shows that older subjects are being prescribed a significant number of ASMR-V drugs. However, this classification combines several situations, including a product line extension, a fixed combination of preexisting drugs, an insufficient therapeutic benefit, the absence of additional therapeutic benefit versus a comparative drug, the absence of comparative study in some indications, or a less favorable benefit-risk ratio comparing to that of the reference drug.This classification includes as well the generic drugs prescribed using the international non proprietary names. This study did not analyze the influence of certain factors, such as treatment history, history of drug allergy or dose titration, which could influence the physician's decision. Following this study, it appears useful to extend this type of survey to other general practitioners in other French regions, and to analyze the reasons for prescribing ASMR-V drugs. These data would help increasing general practitioners' awareness of "proper drug use" to reduce the proportion of "inadequate" drugs prescribed to older subjects. One could also consider conducting a survey amongst older patients under polytherapy, to question them on the treatments taken.

Floating drug delivery systems: a review.

PubMed

Arora, Shweta; Ali, Javed; Ahuja, Alka; Khar, Roop K; Baboota, Sanjula

2005-10-19

The purpose of writing this review on floating drug delivery systems (FDDS) was to compile the recent literature with special focus on the principal mechanism of floatation to achieve gastric retention. The recent developments of FDDS including the physiological and formulation variables affecting gastric retention, approaches to design single-unit and multiple-unit floating systems, and their classification and formulation aspects are covered in detail. This review also summarizes the in vitro techniques, in vivo studies to evaluate the performance and application of floating systems, and applications of these systems. These systems are useful to several problems encountered during the development of a pharmaceutical dosage form.

Medical Devices; Hematology and Pathology Devices; Classification of the Whole Slide Imaging System. Final order.

PubMed

2018-01-02

The Food and Drug Administration (FDA or we) is classifying the whole slide imaging system into class II (special controls). The special controls that apply to the device type are identified in this order and will be part of the codified language for the whole slide imaging system's classification. We are taking this action because we have determined that classifying the device into class II (special controls) will provide a reasonable assurance of safety and effectiveness of the device. We believe this action will also enhance patients' access to beneficial innovative devices, in part by reducing regulatory burdens.

Medical Devices; Clinical Chemistry and Clinical Toxicology Devices; Classification of the Organophosphate Test System. Final order.

PubMed

2017-10-18

The Food and Drug Administration (FDA or we) is classifying the organophosphate test system into class II (special controls). The special controls that apply to the device type are identified in this order and will be part of the codified language for the organophosphate test system's classification. We are taking this action because we have determined that classifying the device into class II (special controls) will provide a reasonable assurance of safety and effectiveness of the device. We believe this action will also enhance patients' access to beneficial innovative devices, in part by reducing regulatory burdens.

Medical Devices; Hematology and Pathology Devices; Classification of a Cervical Intraepithelial Neoplasia Test System. Final order.

PubMed

2018-01-03

The Food and Drug Administration (FDA or we) is classifying the cervical intraepithelial neoplasia (CIN) test system into class II (special controls). The special controls that apply to the device type are identified in this order and will be part of the codified language for the CIN test system's classification. We are taking this action because we have determined that classifying the device into class II (special controls) will provide a reasonable assurance of safety and effectiveness of the device. We believe this action will also enhance patients' access to beneficial innovative devices, in part by reducing regulatory burdens.

Multidrug Resistance among New Tuberculosis Cases: Detecting Local Variation through Lot Quality-Assurance Sampling

PubMed Central

Lynn Hedt, Bethany; van Leth, Frank; Zignol, Matteo; Cobelens, Frank; van Gemert, Wayne; Viet Nhung, Nguyen; Lyepshina, Svitlana; Egwaga, Saidi; Cohen, Ted

2012-01-01

Background Current methodology for multidrug-resistant TB (MDR TB) surveys endorsed by the World Health Organization provides estimates of MDR TB prevalence among new cases at the national level. On the aggregate, local variation in the burden of MDR TB may be masked. This paper investigates the utility of applying lot quality-assurance sampling to identify geographic heterogeneity in the proportion of new cases with multidrug resistance. Methods We simulated the performance of lot quality-assurance sampling by applying these classification-based approaches to data collected in the most recent TB drug-resistance surveys in Ukraine, Vietnam, and Tanzania. We explored three classification systems—two-way static, three-way static, and three-way truncated sequential sampling—at two sets of thresholds: low MDR TB = 2%, high MDR TB = 10%, and low MDR TB = 5%, high MDR TB = 20%. Results The lot quality-assurance sampling systems identified local variability in the prevalence of multidrug resistance in both high-resistance (Ukraine) and low-resistance settings (Vietnam). In Tanzania, prevalence was uniformly low, and the lot quality-assurance sampling approach did not reveal variability. The three-way classification systems provide additional information, but sample sizes may not be obtainable in some settings. New rapid drug-sensitivity testing methods may allow truncated sequential sampling designs and early stopping within static designs, producing even greater efficiency gains. Conclusions Lot quality-assurance sampling study designs may offer an efficient approach for collecting critical information on local variability in the burden of multidrug-resistant TB. Before this methodology is adopted, programs must determine appropriate classification thresholds, the most useful classification system, and appropriate weighting if unbiased national estimates are also desired. PMID:22249242

Trends in oral drug bioavailability following bariatric surgery: examining the variable extent of impact on exposure of different drug classes.

PubMed

Darwich, Adam S; Henderson, Kathryn; Burgin, Angela; Ward, Nicola; Whittam, Janet; Ammori, Basil J; Ashcroft, Darren M; Rostami-Hodjegan, Amin

2012-11-01

Changes to oral drug bioavailability have been observed post bariatric surgery. However, the magnitude and the direction of changes have not been assessed systematically to provide insights into the parameters governing the observed trends. Understanding these can help with dose adjustments. Analysis of drug characteristics based on a biopharmaceutical classification system is not adequate to explain observed trends in altered oral drug bioavailability following bariatric surgery, although the findings suggest solubility to play an important role. To identify the most commonly prescribed drugs in a bariatric surgery population and to assess existing evidence regarding trends in oral drug bioavailability post bariatric surgery. A retrospective audit was undertaken to document commonly prescribed drugs amongst patients undergoing bariatric surgery in an NHS hospital in the UK and to assess practice for drug administration following bariatric surgery. The available literature was examined for trends relating to drug permeability and solubility with regards to the Biopharmaceutics Classification System (BCS) and main route of elimination. No significant difference in the 'post/pre surgery oral drug exposure ratio' (ppR) was apparent between BCS class I to IV drugs, with regards to dose number (Do) or main route of elimination. Drugs classified as 'solubility limited' displayed an overall reduction as compared with 'freely soluble' compounds, as well as an unaltered and increased ppR. Clinical studies establishing guidelines for commonly prescribed drugs, and the monitoring of drugs exhibiting a narrow therapeutic window or without a readily assessed clinical endpoint, are warranted. Using mechanistically based pharmacokinetic modelling for simulating the multivariate nature of changes in drug exposure may serve as a useful tool in the further understanding of postoperative trends in oral drug exposure and in developing practical clinical guidance. © 2012 The Authors. British Journal of Clinical Pharmacology © 2012 The British Pharmacological Society.

Polymeric micelles as a new drug carrier system and their required considerations for clinical trials.

PubMed

Yokoyama, Masayuki

2010-02-01

A polymeric micelle is a macromolecular assembly composed of an inner core and an outer shell, and most typically is formed from block copolymers. In the last two decades, polymeric micelles have been actively studied as a new type of drug carrier system, in particular for drug targeting of anticancer drugs to solid tumors. In this review, polymeric micelle drug carrier systems are discussed with a focus on toxicities of the polymeric micelle carrier systems and on pharmacological activities of the block copolymers. In the first section, the importance of the above-mentioned evaluation of these properties is explained, as this importance does not seem to be well recognized compared with the importance of targeting and enhanced pharmacological activity of drugs, particularly in the basic studies. Then, designs, types and classifications of the polymeric micelle system are briefly summarized and explained, followed by a detailed discussion regarding several examples of polymeric micelle carrier systems. Readers will gain a strategy of drug delivery with polymeric carriers as well as recent progress of the polymeric micelle carrier systems in their basic studies and clinical trials. The purpose of this review is to achieve tight connections between the basic studies and clinical trials.

Antibiotic Resistance and Single-Nucleotide Polymorphism Cluster Grouping Type in a Multinational Sample of Resistant Mycobacterium tuberculosis Isolates▿

PubMed Central

Brimacombe, M.; Hazbon, M.; Motiwala, A. S.; Alland, D.

2007-01-01

A single-nucleotide polymorphism-based cluster grouping (SCG) classification system for Mycobacterium tuberculosis was used to examine antibiotic resistance type and resistance mutations in relationship to specific evolutionary lineages. Drug resistance and resistance mutations were seen across all SCGs. SCG-2 had higher proportions of katG codon 315 mutations and resistance to four drugs. PMID:17846140

Crystal-liquid Fugacity Ratio as a Surrogate Parameter for Intestinal Permeability.

PubMed

Zakeri-Milani, Parvin; Fasihi, Zohreh; Akbari, Jafar; Jannatabadi, Ensieh; Barzegar-Jalali, Mohammad; Loebenberg, Raimar; Valizadeh, Hadi

We assessed the feasibility of using crystal-liquid fugacity ratio (CLFR) as an alternative parameter for intestinal permeability in the biopharmaceutical classification (BCS) of passively absorbed drugs. Dose number, fraction of dose absorbed, intestinal permeability, and intrinsic dissolution rate were used as the input parameters. CLFR was determined using thermodynamic parameters i.e., melting point, molar fusion enthalpy, and entropy of drug molecules obtained using differential scanning calorimetry. The CLFR values were in the range of 0.06-41.76 mole percent. There was a close relationship between CLFR and in vivo intestinal permeability (r > 0.8). CLFR values of greater than 2 mole percent corresponded to complete intestinal absorption. Applying CLFR versus dose number or intrinsic dissolution rate, more than 92% of tested drugs were correctly classified with respect to the reported classification system on the basis of human intestinal permeability and solubility. This investigation revealed that the CLFR might be an appropriate parameter for quantitative biopharmaceutical classification. This could be attributed to the fact that CLFR could be a measure of solubility of compounds in lipid bilayer which was found in this study to be directly proportional to the intestinal permeability of compounds. This classification enables researchers to define characteristics for intestinal absorption of all four BCS drug classes using suitable cutoff points for both intrinsic dissolution rate and crystal-liquid fugacity ratio. Therefore, it may be used as a surrogate for permeability studies. This article is open to POST-PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by clicking on ABSTRACT on the issue's contents page.

Drug-induced glucose-6-phosphate dehydrogenase deficiency-related hemolysis risk assessment.

PubMed

Yang, Yang; Li, Zuofeng; Nan, Peng; Zhang, Xiaoyan

2011-06-01

Glucose-6-phosphate dehydrogenase (G6PD) is an essential enzyme that protects human red blood cells from premature destruction caused by oxidative damage. People suffering from G6PD deficiency would be vulnerable to various oxidative substances, such as fava beans and oxidant drugs. Until now, many institutes, organizations or domain experts have compiled low-risk or high-risk drugs collection for patients with G6PD deficiency, mainly from the case report or clinical trails. Recently, we have explored a classification system to predict drug-induced hemolytic potential. In this paper, we screen the normally used over-the-counter (OTC) drugs for "high-risk" and "low-risk" ones to G6PD deficient patients by this system. Copyright © 2011 Elsevier Ltd. All rights reserved.

Co-Prescription of QT-Interval Prolonging Drugs: An Analysis in a Large Cohort of Geriatric Patients

PubMed Central

Schächtele, Simone; Tümena, Thomas; Gaßmann, Karl-Günter; Fromm, Martin F.; Maas, Renke

2016-01-01

Background Drug-induced QT-interval prolongation is associated with occurrence of potentially fatal Torsades de Pointes arrhythmias (TdP). So far, data regarding the overall burden of QT-interval prolonging drugs (QT-drugs) in geriatric patients are limited. Objective This study was performed to assess the individual burden of QT-interval prolonging drugs (QT-drugs) in geriatric polymedicated patients and to identify the most frequent and risky combinations of QT-drugs. Methods In the discharge medication of geriatric patients between July 2009 and June 2013 from the Geriatrics in Bavaria–Database (GiB-DAT) (co)-prescriptions of QT-drugs were investigated. QT-drugs were classified according to a publicly available reference site (CredibleMeds®) as ALL-QT-drugs (associated with any QT-risk) or High-risk-QT-drugs (corresponding to QT-drugs with known risk of Torsades de Pointes according to CredibleMeds®) and in addition as SmPC-high-risk-QT-drugs (according to the German prescribing information (SmPC) contraindicated co-prescription with other QT-drugs). Results Of a cohort of 130,434 geriatric patients (mean age 81 years, 67% women), prescribed a median of 8 drugs, 76,594 patients (58.7%) received at least one ALL-QT-drug. Co-prescriptions of two or more ALL-QT-drugs were observed in 28,768 (22.1%) patients. Particularly risky co-prescriptions of High-risk-QT-drugs or SmPC-high-risk-QT-drugs with at least on further QT-drug occurred in 55.9% (N = 12,633) and 54.2% (N = 12,429) of these patients, respectively. Consideration of SmPCs (SmPC-high-risk-QT-drugs) allowed the identification of an additional 15% (N = 3,999) patients taking a risky combination that was not covered by the commonly used CredibleMeds® classification. Only 20 drug-drug combinations accounted for more than 90% of these potentially most dangerous co-prescriptions. Conclusion In a geriatric study population co-prescriptions of two and more QT-drugs were common. A considerable proportion of QT-drugs with higher risk only could be detected by using more than one classification-system. Local adaption of international classifications can improve identification of patients at risk. PMID:27192430

Polymeric Amorphous Solid Dispersions: A Review of Amorphization, Crystallization, Stabilization, Solid-State Characterization, and Aqueous Solubilization of Biopharmaceutical Classification System Class II Drugs.

PubMed

Baghel, Shrawan; Cathcart, Helen; O'Reilly, Niall J

2016-09-01

Poor water solubility of many drugs has emerged as one of the major challenges in the pharmaceutical world. Polymer-based amorphous solid dispersions have been considered as the major advancement in overcoming limited aqueous solubility and oral absorption issues. The principle drawback of this approach is that they can lack necessary stability and revert to the crystalline form on storage. Significant upfront development is, therefore, required to generate stable amorphous formulations. A thorough understanding of the processes occurring at a molecular level is imperative for the rational design of amorphous solid dispersion products. This review attempts to address the critical molecular and thermodynamic aspects governing the physicochemical properties of such systems. A brief introduction to Biopharmaceutical Classification System, solid dispersions, glass transition, and solubility advantage of amorphous drugs is provided. The objective of this review is to weigh the current understanding of solid dispersion chemistry and to critically review the theoretical, technical, and molecular aspects of solid dispersions (amorphization and crystallization) and potential advantage of polymers (stabilization and solubilization) as inert, hydrophilic, pharmaceutical carrier matrices. In addition, different preformulation tools for the rational selection of polymers, state-of-the-art techniques for preparation and characterization of polymeric amorphous solid dispersions, and drug supersaturation in gastric media are also discussed. Copyright © 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Bioequivalence of Oral Products and the Biopharmaceutics Classification System: Science, Regulation, and Public Policy

PubMed Central

Amidon, KS; Langguth, P; Lennernäs, H; Yu, L; Amidon, GL

2011-01-01

The demonstration of bioequivalence (BE) is an essential requirement for ensuring that patients receive a product that performs as indicated by the label. The BE standard for a particular product is set by its innovator, and this standard must subsequently be matched by generic drug products. The Biopharmaceutics Classification System (BCS) sets a scientific basis for an improved BE standard for immediate-release solid oral dosage forms. In this paper, we discuss BE and the BCS, as well as the issues that are currently relevant to BE as a pharmaceutical product standard. PMID:21775984

The "high solubility" definition of the current FDA Guidance on Biopharmaceutical Classification System may be too strict for acidic drugs.

PubMed

Yazdanian, Mehran; Briggs, Katherine; Jankovsky, Corinne; Hawi, Amale

2004-02-01

The purpose of this study was to assess if the definition of high solubility as proposed in the FDA Guidance on Biopharmaceutical Classification System (BCS) is too strict for highly permeable acidic drugs. The solubility and permeability values of 20 (18 acidic and 2 non-acidic) nonsteroidal anti-inflammatory drugs (NSAID) were determined. The NSAIDs were grouped into three different sets having acetic acid, propionic acid, or other acidic moieties such as fenamate, oxicam, and salicylate. Two nonacidic NSAIDs (celecoxib and rofecoxib) were also included for comparison purposes. Equilibrium solubility values were determined at pH 1.2, 5.0, 7.4, and in biorelevant media simulating fed intestinal fluid at pH 5.0. For a select number of acids, we also measured solubility values in media simulating gastric and fasted intestinal fluids. Permeability classification was established relative to that of reference drugs in the Caco-2 cell permeability model. Permeability coefficients for all drugs were measured at concentrations corresponding to the lowest and highest marketed dose strengths dissolved in 250 ml volume, and their potential interaction with cellular efflux pumps was investigated. All NSAIDs with different acidic functional groups were classified as highly permeable based on their Caco-2 cell permeability. Only ketorolac appeared to have a potential for interaction with cellular efflux pumps. Solubility classification was based on comparison of equilibrium solubility at pH 1.2, 5.0. and 7.4 relative to marketed dose strengths in 250 ml. The pKa values for the acidic NSAIDs studied were between 3.5 and 5.1. and, as expected, their solubility increased dramatically at pH 7.4 compared to pH 1.2. Only three NSAIDs, ketorolac, ketoprofen. and acetyl salicylic acid, meet the current criteria for high solubility over the entire pH range. However, with the exception of ibuprofen, oxaprozin, and mefenamic acid, the remaining compounds can be classified as Class I drugs (high solubility-high permeability) relative to solubility at pH 7.4. The use of bio-relevant media simulating gastric and intestinal milieu for solubility measurements or increasing the dose volume to 500 ml did not provide for a better boundary for solubility classification. Based on the current definition of solubility, 15 of the 18 acidic NSAIDs in this study will be classified as Class II compounds as the solubility criteria applies to the entire pH range of 1.2 to 7.4, although the low solubility criteria does not hold true over the entire pH range. Whence, of the 18 acidic drugs, 15 can be classified as Class I based on the pH 7.4 solubility alone. This finding is intriguing because these drugs exhibit Class I behavior as their absorption does not seem to be dissolution or solubility limited. It could then be argued that for acidic drugs, the boundaries for solubility are too restrictive. Solubility at pH > 5 (pH in duodenum) may be more appropriate because most compounds are mainly absorbed in the intestinal region. Consideration for an intermediate solubility classification for highly permeable ionizable compounds that reflects physiological conditions seems warranted.

Hematology and pathology devices; reclassification; restricted devices; OTC test sample collection systems for drugs of abuse testing. Food and Drug Administration, HHS. Final rule.

PubMed

2000-04-07

The Food and Drug Administration (FDA) is reclassifying over-the-counter (OTC) test sample collection systems for drugs of abuse testing from class III (premarket approval) into class I (general controls) and exempting them from premarket notification (510(k)) and current good manufacturing practice (CGMP) requirements. FDA is also designating OTC test sample collection systems for drugs of abuse testing as restricted devices under the Federal Food, Drug, and Cosmetic Act (the act) and establishing restrictions intended to assure consumers that: The underlying laboratory test(s) are accurate and reliable; the laboratory performing the test(s) has adequate expertise and competency; and the product has adequate labeling and methods of communicating test results to consumers. Finally, FDA is adding a conforming amendment to the existing classification regulation for specimen transport and storage containers to clarify that it does not apply to specimen transport and storage containers that are part of an OTC test sample collection system for the purpose of testing for the presence of drugs of abuse or their metabolites in a laboratory.

Classification of stimuli-responsive polymers as anticancer drug delivery systems.

PubMed

Taghizadeh, Bita; Taranejoo, Shahrouz; Monemian, Seyed Ali; Salehi Moghaddam, Zoha; Daliri, Karim; Derakhshankhah, Hossein; Derakhshani, Zaynab

2015-02-01

Although several anticancer drugs have been introduced as chemotherapeutic agents, the effective treatment of cancer remains a challenge. Major limitations in the application of anticancer drugs include their nonspecificity, wide biodistribution, short half-life, low concentration in tumor tissue and systemic toxicity. Drug delivery to the tumor site has become feasible in recent years, and recent advances in the development of new drug delivery systems for controlled drug release in tumor tissues with reduced side effects show great promise. In this field, the use of biodegradable polymers as drug carriers has attracted the most attention. However, drug release is still difficult to control even when a polymeric drug carrier is used. The design of pharmaceutical polymers that respond to external stimuli (known as stimuli-responsive polymers) such as temperature, pH, electric or magnetic field, enzymes, ultrasound waves, etc. appears to be a successful approach. In these systems, drug release is triggered by different stimuli. The purpose of this review is to summarize different types of polymeric drug carriers and stimuli, in addition to the combination use of stimuli in order to achieve a better controlled drug release, and it discusses their potential strengths and applications. A survey of the recent literature on various stimuli-responsive drug delivery systems is also provided and perspectives on possible future developments in controlled drug release at tumor site have been discussed.

Classification of toxicity effects of biotransformed hepatic drugs using whale optimized support vector machines.

PubMed

Tharwat, Alaa; Moemen, Yasmine S; Hassanien, Aboul Ella

2017-04-01

Measuring toxicity is an important step in drug development. Nevertheless, the current experimental methods used to estimate the drug toxicity are expensive and time-consuming, indicating that they are not suitable for large-scale evaluation of drug toxicity in the early stage of drug development. Hence, there is a high demand to develop computational models that can predict the drug toxicity risks. In this study, we used a dataset that consists of 553 drugs that biotransformed in liver. The toxic effects were calculated for the current data, namely, mutagenic, tumorigenic, irritant and reproductive effect. Each drug is represented by 31 chemical descriptors (features). The proposed model consists of three phases. In the first phase, the most discriminative subset of features is selected using rough set-based methods to reduce the classification time while improving the classification performance. In the second phase, different sampling methods such as Random Under-Sampling, Random Over-Sampling and Synthetic Minority Oversampling Technique (SMOTE), BorderLine SMOTE and Safe Level SMOTE are used to solve the problem of imbalanced dataset. In the third phase, the Support Vector Machines (SVM) classifier is used to classify an unknown drug into toxic or non-toxic. SVM parameters such as the penalty parameter and kernel parameter have a great impact on the classification accuracy of the model. In this paper, Whale Optimization Algorithm (WOA) has been proposed to optimize the parameters of SVM, so that the classification error can be reduced. The experimental results proved that the proposed model achieved high sensitivity to all toxic effects. Overall, the high sensitivity of the WOA+SVM model indicates that it could be used for the prediction of drug toxicity in the early stage of drug development. Copyright © 2017 Elsevier Inc. All rights reserved.

Classification of drug molecules considering their IC50 values using mixed-integer linear programming based hyper-boxes method.

PubMed

Armutlu, Pelin; Ozdemir, Muhittin E; Uney-Yuksektepe, Fadime; Kavakli, I Halil; Turkay, Metin

2008-10-03

A priori analysis of the activity of drugs on the target protein by computational approaches can be useful in narrowing down drug candidates for further experimental tests. Currently, there are a large number of computational methods that predict the activity of drugs on proteins. In this study, we approach the activity prediction problem as a classification problem and, we aim to improve the classification accuracy by introducing an algorithm that combines partial least squares regression with mixed-integer programming based hyper-boxes classification method, where drug molecules are classified as low active or high active regarding their binding activity (IC50 values) on target proteins. We also aim to determine the most significant molecular descriptors for the drug molecules. We first apply our approach by analyzing the activities of widely known inhibitor datasets including Acetylcholinesterase (ACHE), Benzodiazepine Receptor (BZR), Dihydrofolate Reductase (DHFR), Cyclooxygenase-2 (COX-2) with known IC50 values. The results at this stage proved that our approach consistently gives better classification accuracies compared to 63 other reported classification methods such as SVM, Naïve Bayes, where we were able to predict the experimentally determined IC50 values with a worst case accuracy of 96%. To further test applicability of this approach we first created dataset for Cytochrome P450 C17 inhibitors and then predicted their activities with 100% accuracy. Our results indicate that this approach can be utilized to predict the inhibitory effects of inhibitors based on their molecular descriptors. This approach will not only enhance drug discovery process, but also save time and resources committed.

Prescription drug use during pregnancy in Southern Tigray region, North Ethiopia.

PubMed

Molla, Fantahun; Assen, Admassu; Abrha, Solomon; Masresha, Birhanetensay; Gashaw, Arega; Wondimu, Abrham; Belete, Yared; Melkam, Wondim

2017-06-05

Judicious utilization of drugs rescues the fetus from the harmful effects while treating the health problems of the pregnant women. This study aimed at evaluating drug utilization pattern and its associated factors among pregnant women in Southern Tigray, Ethiopia. Institution based cross-sectional study was conducted among 647 pregnant women who had been attending obstetrics-gynecology and antenatal care units in different health facilities of Southern Tigray region. The study participants were selected using multistage sampling technique. Data collection was done using pre-tested semi-structured questionnaires and by reviewing antenatal follow-up cards. Descriptive and inferential statistics were analyzed, to assess drug utilization pattern and its associated factors among pregnant women, using SPSS version 20 software. Of 647 pregnant women, 87.5% were prescribed with at least one medication. As per the United States Food and Drug Administration (US-FDA) risk classification system, 87.7, 7.9, 3.9, and 0.5% of the prescribed drug were from category A, B, C and D, respectively. Prescription drug use was more likely among gynecology ward visitors [AOR = 8.97, 95% Cl (2.69-29.88)] and among those who visited health facilities for the first time during their first [AOR =2.65, 95% Cl (1.44-4.84)] and second [AOR = 2.50, 95% Cl (1.36-4.61)] trimesters. Majority of the study population used safe and appropriate medications according to US-FDA risk classification system, with the exception of low proportion (0.5%) of medication with potential risk for the fetus. The average number of drug prescribed per pregnant women was in the recommended range of WHO drug use indicators guideline.

[A comparative study of coding and information systems for the evaluation of medical and social conditions: the case of addictive disorders].

PubMed

Bourdais-Mannone, Claire; Cherikh, Faredj; Gicquel, Nathalie; Gelsi, Eve; Jove, Frédérique; Staccini, Pascal

2011-01-01

The purpose of this study was to conduct a descriptive and comparative analysis of the tools used by healthcare professionals specializing in addictive disorders to promote a rapprochement of information systems. The evaluation guide used to assess the compensation needs of disabled persons treated in "Maisons Départementales des Personnes Handicapées" (centres for disabled people) organizes information in different areas, including a psychological component. The guide includes social and environmental information in the "Recueil Commun sur les Addictions et les Prises en charges" (Joint Report on Drug Addiction and Drug Treatment). While the program for the medicalization of information systems includes care data, the current information about social situations remains inadequate. The international classification of diseases provides synthetic diagnostic codes to describe substance use, etiologic factors and the somatic and psychological complications inherent to addictive disorders. The current system could be radically simplified and harmonized and would benefit from adopting a more individualized approach to non-substance behavioral addictions. The international classification of disabilities provides tools for evaluating the psychological component included in the recent definition of addictive disorders. Legal information should play an integral role in the structure of the information system and in international classifications. The prevalence of episodes of care and treatment of addictive and psychological disorders was assessed at Nice University Hospital in all disciplines. Except in addiction treatment units, very few patients were found to have a RECAP file.

Biowaiver extension potential and IVIVC for BCS Class II drugs by formulation design: Case study for cyclosporine self-microemulsifying formulation.

PubMed

Yang, Su-Geun

2010-11-01

The objective of this work was to suggest the biowaiver potential of biopharmaceutical classification system (BCS) Class II drugs in self-microemulsifying drug delivery systems (SMEDDS) which are known to increase the solubility, dissolution and oral absorption of water-insoluble drugs. Cyclosporine was selected as a representative BCS Class II drug. New generic candidate of cyclosporine SMEDDS (test) was applied for the study with brand SMEDDS (reference I) and cyclosporine self-emulsifying drug delivery systems (SEDDS, reference II). Solubility and dissolution of cyclosporine from SMEDDS were critically enhanced, which were the similar behaviors with BCS class I drug. The test showed the identical dissolution rate and the equivalent bioavailability (0.34, 0.42 and 0.68 of p values for AUC₀(→)₂₄(h), C(max) and T(max), respectively) with the reference I. Based on the results, level A in vitro-in vivo correlation (IVIVC) was established from these two SMEDDS formulations. This study serves as a good example for speculating the biowaiver extension potential of BCS Class II drugs specifically in solubilizing formulation such as SMEDDS.

Medical Devices; Hematology and Pathology Devices; Classification of the Flow Cytometric Test System for Hematopoietic Neoplasms. Final order.

PubMed

2017-12-27

The Food and Drug Administration (FDA or we) is classifying the flow cytometric test system for hematopoietic neoplasms into class II (special controls). The special controls that apply to the device type are identified in this order and will be part of the codified language for the flow cytometric test system for hematopoietic neoplasms' classification. We are taking this action because we have determined that classifying the device into class II (special controls) will provide a reasonable assurance of safety and effectiveness of the device. We believe this action will also enhance patients' access to beneficial innovative devices, in part by reducing regulatory burdens.

Medical devices; hematology and pathology devices; classification of early growth response 1 gene fluorescence in-situ hybridization test system for specimen characterization. Final order.

PubMed

2014-09-03

The Food and Drug Administration (FDA) is classifying early growth response 1 (EGR1) gene fluorescence in-situ hybridization (FISH) test system for specimen characterization into class II (special controls). The special controls that will apply to this device are identified in this order and will be part of the codified language for the early growth response 1 (EGR1) gene fluorescence in-site hybridization (FISH) test system for specimen characterization classification. The Agency is classifying the device into class II (special controls) in order to provide a reasonable assurance of safety and effectiveness of the device.

A reaction limited in vivo dissolution model for the study of drug absorption: Towards a new paradigm for the biopharmaceutic classification of drugs.

PubMed

Macheras, Panos; Iliadis, Athanassios; Melagraki, Georgia

2018-05-30

The aim of this work is to develop a gastrointestinal (GI) drug absorption model based on a reaction limited model of dissolution and consider its impact on the biopharmaceutic classification of drugs. Estimates for the fraction of dose absorbed as a function of dose, solubility, reaction/dissolution rate constant and the stoichiometry of drug-GI fluids reaction/dissolution were derived by numerical solution of the model equations. The undissolved drug dose and the reaction/dissolution rate constant drive the dissolution rate and determine the extent of absorption when high-constant drug permeability throughout the gastrointestinal tract is assumed. Dose is an important element of drug-GI fluids reaction/dissolution while solubility exclusively acts as an upper limit for drug concentrations in the lumen. The 3D plots of fraction of dose absorbed as a function of dose and reaction/dissolution rate constant for highly soluble and low soluble drugs for different "stoichiometries" (0.7, 1.0, 2.0) of the drug-reaction/dissolution with the GI fluids revealed that high extent of absorption was found assuming high drug- reaction/dissolution rate constant and high drug solubility. The model equations were used to simulate in vivo supersaturation and precipitation phenomena. The model developed provides the theoretical basis for the interpretation of the extent of drug's absorption on the basis of the parameters associated with the drug-GI fluids reaction/dissolution. A new paradigm emerges for the biopharmaceutic classification of drugs, namely, a model independent biopharmaceutic classification scheme of four drug categories based on either the fulfillment or not of the current dissolution criteria and the high or low % drug metabolism. Copyright © 2018. Published by Elsevier B.V.

Pediatric Biopharmaceutical Classification System: Using Age-Appropriate Initial Gastric Volume.

PubMed

Shawahna, Ramzi

2016-05-01

Development of optimized pediatric formulations for oral administration can be challenging, time consuming, and financially intensive process. Since its inception, the biopharmaceutical classification system (BCS) has facilitated the development of oral drug formulations destined for adults. At least theoretically, the BCS principles are applied also to pediatrics. A comprehensive age-appropriate BCS has not been fully developed. The objective of this work was to provisionally classify oral drugs listed on the latest World Health Organization's Essential Medicines List for Children into an age-appropriate BCS. A total of 38 orally administered drugs were included in this classification. Dose numbers were calculated using age-appropriate initial gastric volume for neonates, 6-month-old infants, and children aging 1 year through adulthood. Using age-appropriate initial gastric volume and British National Formulary age-specific dosing recommendations in the calculation of dose numbers, the solubility classes shifted from low to high in pediatric subpopulations of 12 years and older for amoxicillin, 5 years, 12 years and older for cephalexin, 9 years and older for chloramphenicol, 3-4 years, 9-11 and 15 years and older for diazepam, 18 years and older (adult) for doxycycline and erythromycin, 8 years and older for phenobarbital, 10 years and older for prednisolone, and 15 years and older for trimethoprim. Pediatric biopharmaceutics are not fully understood where several knowledge gaps have been recently emphasized. The current biowaiver criteria are not suitable for safe application in all pediatric populations.

[Designer drugs in Finland].

PubMed

Tacke, Ulrich; den Hollander, Bjørnar; Simojoki, Kaarlo; Korpi, Esa R; Pihlainen, Katja; Alho, Hannu

2011-01-01

Designer drugs are synthetic psychotropic drugs which are marketed as "legal drugs". Their emergence, rapid spreading and unpredictable effects have challenged the health and substance abuse care. The slow process of classification of an abusable drug has provided too many possibilities for spreading the designer drugs. Once a certain substance receives an illegal drugs classification, dealers and users usually move to another, slightly different molecule that is still legal. In Finland, the Narcotics Act has been amended to the effect that the addition of a new substance to the illegal drug list does not require an amendment to the law.

Inferring anatomical therapeutic chemical (ATC) class of drugs using shortest path and random walk with restart algorithms.

PubMed

Chen, Lei; Liu, Tao; Zhao, Xian

2018-06-01

The anatomical therapeutic chemical (ATC) classification system is a widely accepted drug classification scheme. This system comprises five levels and includes several classes in each level. Drugs are classified into classes according to their therapeutic effects and characteristics. The first level includes 14 main classes. In this study, we proposed two network-based models to infer novel potential chemicals deemed to belong in the first level of ATC classification. To build these models, two large chemical networks were constructed using the chemical-chemical interaction information retrieved from the Search Tool for Interactions of Chemicals (STITCH). Two classic network algorithms, shortest path (SP) and random walk with restart (RWR) algorithms, were executed on the corresponding network to mine novel chemicals for each ATC class using the validated drugs in a class as seed nodes. Then, the obtained chemicals yielded by these two algorithms were further evaluated by a permutation test and an association test. The former can exclude chemicals produced by the structure of the network, i.e., false positive discoveries. By contrast, the latter identifies the most important chemicals that have strong associations with the ATC class. Comparisons indicated that the two models can provide quite dissimilar results, suggesting that the results yielded by one model can be essential supplements for those obtained by the other model. In addition, several representative inferred chemicals were analyzed to confirm the reliability of the results generated by the two models. This article is part of a Special Issue entitled: Accelerating Precision Medicine through Genetic and Genomic Big Data Analysis edited by Yudong Cai & Tao Huang. Copyright © 2017 Elsevier B.V. All rights reserved.

Transporter taxonomy - a comparison of different transport protein classification schemes.

PubMed

Viereck, Michael; Gaulton, Anna; Digles, Daniela; Ecker, Gerhard F

2014-06-01

Currently, there are more than 800 well characterized human membrane transport proteins (including channels and transporters) and there are estimates that about 10% (approx. 2000) of all human genes are related to transport. Membrane transport proteins are of interest as potential drug targets, for drug delivery, and as a cause of side effects and drug–drug interactions. In light of the development of Open PHACTS, which provides an open pharmacological space, we analyzed selected membrane transport protein classification schemes (Transporter Classification Database, ChEMBL, IUPHAR/BPS Guide to Pharmacology, and Gene Ontology) for their ability to serve as a basis for pharmacology driven protein classification. A comparison of these membrane transport protein classification schemes by using a set of clinically relevant transporters as use-case reveals the strengths and weaknesses of the different taxonomy approaches.

The classification and application of toxic Chinese materia medica.

PubMed

Liu, Xinmin; Wang, Qiong; Song, Guangqing; Zhang, Guangping; Ye, Zuguang; Williamson, Elizabeth M

2014-03-01

Many important drugs in the Chinese materia medica (CMM) are known to be toxic, and it has long been recognized in classical Chinese medical theory that toxicity can arise directly from the components of a single CMM or may be induced by an interaction between combined CMM. Traditional Chinese Medicine presents a unique set of pharmaceutical theories that include particular methods for processing, combining and decocting, and these techniques contribute to reducing toxicity as well as enhancing efficacy. The current classification of toxic CMM drugs, traditional methods for processing toxic CMM and the prohibited use of certain combinations, is based on traditional experience and ancient texts and monographs, but accumulating evidence increasingly supports their use to eliminate or reduce toxicity. Modern methods are now being used to evaluate the safety of CMM; however, a new system for describing the toxicity of Chinese herbal medicines may need to be established to take into account those herbs whose toxicity is delayed or otherwise hidden, and which have not been incorporated into the traditional classification. This review explains the existing classification and justifies it where appropriate, using experimental results often originally published in Chinese and previously not available outside China. Copyright © 2013 John Wiley & Sons, Ltd.

SOCIAL MEDIA MINING SHARED TASK WORKSHOP.

PubMed

Sarker, Abeed; Nikfarjam, Azadeh; Gonzalez, Graciela

2016-01-01

Social media has evolved into a crucial resource for obtaining large volumes of real-time information. The promise of social media has been realized by the public health domain, and recent research has addressed some important challenges in that domain by utilizing social media data. Tasks such as monitoring flu trends, viral disease outbreaks, medication abuse, and adverse drug reactions are some examples of studies where data from social media have been exploited. The focus of this workshop is to explore solutions to three important natural language processing challenges for domain-specific social media text: (i) text classification, (ii) information extraction, and (iii) concept normalization. To explore different approaches to solving these problems on social media data, we designed a shared task which was open to participants globally. We designed three tasks using our in-house annotated Twitter data on adverse drug reactions. Task 1 involved automatic classification of adverse drug reaction assertive user posts; Task 2 focused on extracting specific adverse drug reaction mentions from user posts; and Task 3, which was slightly ill-defined due to the complex nature of the problem, involved normalizing user mentions of adverse drug reactions to standardized concept IDs. A total of 11 teams participated, and a total of 24 (18 for Task 1, and 6 for Task 2) system runs were submitted. Following the evaluation of the systems, and an assessment of their innovation/novelty, we accepted 7 descriptive manuscripts for publication--5 for Task 1 and 2 for Task 2. We provide descriptions of the tasks, data, and participating systems in this paper.

A consensus approach to the classification of pediatric pulmonary hypertensive vascular disease: Report from the PVRI Pediatric Taskforce, Panama 2011

PubMed Central

del Cerro, Maria Jesus; Abman, Steven; Diaz, Gabriel; Freudenthal, Alexandra Heath; Freudenthal, Franz; Harikrishnan, S.; Haworth, Sheila G.; Ivy, Dunbar; Lopes, Antonio A.; Raj, J. Usha; Sandoval, Julio; Stenmark, Kurt; Adatia, Ian

2011-01-01

Current classifications of pulmonary hypertension have contributed a great deal to our understanding of pulmonary vascular disease, facilitated drug trials, and improved our understanding of congenital heart disease in adult survivors. However, these classifications are not applicable readily to pediatric disease. The classification system that we propose is based firmly in clinical practice. The specific aims of this new system are to improve diagnostic strategies, to promote appropriate clinical investigation, to improve our understanding of disease pathogenesis, physiology and epidemiology, and to guide the development of human disease models in laboratory and animal studies. It should be also an educational resource. We emphasize the concepts of perinatal maladaptation, maldevelopment and pulmonary hypoplasia as causative factors in pediatric pulmonary hypertension. We highlight the importance of genetic, chromosomal and multiple congenital malformation syndromes in the presentation of pediatric pulmonary hypertension. We divide pediatric pulmonary hypertensive vascular disease into 10 broad categories. PMID:21874158

Systems Biology of Glucocorticoids in Muscle Disease

DTIC Science & Technology

2010-10-01

Introduction Duchenne muscular dystrophy (DMD) is the most common and incurable muscular dystrophy of childhood. Muscle regeneration fails with...SUBJECT TERMS Duchenne Muscular dystrophy , Glucocorticoids, Systems biology, Drug mechanism 16. SECURITY CLASSIFICATION OF: U 17. LIMITATION...better targeted and more effective therapies for Duchenne muscular dystrophy dynamically. This MDA grant proposal is led by Dr. Eric Hoffman, and it

Classifications for carcinogenesis of antitumoral drugs.

PubMed

Binetti, R; Costamagna, F M; Marcello, I

2003-12-01

The aim of this review is to support the medical staff engaged in tumor therapy with the carcinogenicity, mutagenicity, developmental toxicity classification of a large number of chemiotherapic drugs by national and international Agencies; it also gives their rationale and the few cases for which the classification varies among, for example, the European Union and the United States of America. A large list of such drugs, producers, commercial names, CAS numbers and chemical names is reported. This list is subject to changes for the quick development in this field: many drugs are retired and many more are introduced in clinical practice. The list is updated to the summer 2003 and retains many drugs which have more than one use or have limited use. The protection of the medical personnel using antitumor chemiotherapics can need retrospective epidemiological investigations and obsolete drugs are of importance for some of the past exposures.

Implementing the Biopharmaceutics Classification System in Drug Development: Reconciling Similarities, Differences, and Shared Challenges in the EMA and US-FDA-Recommended Approaches.

PubMed

Cardot, J-M; Garcia Arieta, A; Paixao, P; Tasevska, I; Davit, B

2016-07-01

The US-FDA recently posted a draft guideline for industry recommending procedures necessary to obtain a biowaiver for immediate-release oral dosage forms based on the Biopharmaceutics Classification System (BCS). This review compares the present FDA BCS biowaiver approach, with the existing European Medicines Agency (EMA) approach, with an emphasis on similarities, difficulties, and shared challenges. Some specifics of the current EMA BCS guideline are compared with those in the recently published draft US-FDA BCS guideline. In particular, similarities and differences in the EMA versus US-FDA approaches to establishing drug solubility, permeability, dissolution, and formulation suitability for BCS biowaiver are critically reviewed. Several case studies are presented to illustrate the (i) challenges of applying for BCS biowaivers for global registration in the face of differences in the EMA and US-FDA BCS biowaiver criteria, as well as (ii) challenges inherent in applying for BCS class I or III designation and common to both jurisdictions.

Use of the Biopharmaceutics Drug Disposition Classification System (BDDCS) to Help Predict the Occurrence of Idiosyncratic Cutaneous Adverse Drug Reactions Associated with Antiepileptic Drug Usage.

PubMed

Chan, Rosa; Wei, Chun-Yu; Chen, Yuan-Tsong; Benet, Leslie Z

2016-05-01

Cutaneous adverse reactions (CARs) from antiepileptic drugs (AEDs) are common, ranging from mild to life-threatening, including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). The identification of subjects carrying the HLA-B*15:02, an inherited allelic variant of the HLA-B gene, and the avoidance of carbamazepine (CBZ) therapy in these subjects are strongly associated with a decrease in the incidence of carbamazepine-induced SJS/TEN. In spite of the strong genetic associations, the initiation of hypersensitivity for AEDs is still not very well characterized. Predicting the potential for other AEDs to cause adverse reactions will be undoubtedly beneficial to avoid CARs, which is the focus of this report. Here, we explore the use of the Biopharmaceutics Drug Disposition Classification System (BDDCS) to distinguish AEDs associated with and without CARs by examining the binding relationship of AEDs to HLA-B*15:02 and data from extensive reviews of medical records. We also evaluate the lack of benefit from a Hong Kong population policy on the effects of screening for HLA-B*15:02 and previous incorrect structure-activity hypotheses. Our analysis concludes that BDDCS class 2 AEDs are more prone to cause adverse cutaneous reactions than certain BDDCS class 1 AEDs and that BDDCS Class 3 drugs have the lowest levels of cutaneous adverse reactions. We propose that BDDCS Class 3 AEDs should be preferentially used for patients with Asian backgrounds (i.e., Han Chinese, Thai, and Malaysian populations) if possible and in patients predisposed to skin rashes.

Classification of highly unbalanced CYP450 data of drugs using cost sensitive machine learning techniques.

PubMed

Eitrich, T; Kless, A; Druska, C; Meyer, W; Grotendorst, J

2007-01-01

In this paper, we study the classifications of unbalanced data sets of drugs. As an example we chose a data set of 2D6 inhibitors of cytochrome P450. The human cytochrome P450 2D6 isoform plays a key role in the metabolism of many drugs in the preclinical drug discovery process. We have collected a data set from annotated public data and calculated physicochemical properties with chemoinformatics methods. On top of this data, we have built classifiers based on machine learning methods. Data sets with different class distributions lead to the effect that conventional machine learning methods are biased toward the larger class. To overcome this problem and to obtain sensitive but also accurate classifiers we combine machine learning and feature selection methods with techniques addressing the problem of unbalanced classification, such as oversampling and threshold moving. We have used our own implementation of a support vector machine algorithm as well as the maximum entropy method. Our feature selection is based on the unsupervised McCabe method. The classification results from our test set are compared structurally with compounds from the training set. We show that the applied algorithms enable the effective high throughput in silico classification of potential drug candidates.

Drug-related problems: evaluation of a classification system in the daily practice of a Swiss University Hospital.

PubMed

Lampert, Markus L; Kraehenbuehl, Stephan; Hug, Balthasar L

2008-12-01

To evaluate the Pharmaceutical Care Network Europe (PCNE) classification system as a tool for documenting the impact of a hospital clinical pharmacology service. Two medical wards comprising totally 85 beds in a university hospital. Number of events classified with the PCNE-system, their acceptance by the medical staff and cost implications. Clinical pharmacy review of pharmacotherapy on ward rounds and from case notes were documented, and identified drug-related problems (DRPs) were classified using the PCNE system version 5.00. During 70 observation days 216 interventions were registered of which 213 (98.6%) could be classified: 128 (60.1%) were detected by reviewing the case notes, 33 (15.5%) on ward rounds, 32 (15.0%) by direct reporting to the clinical pharmacist (CP), and 20 (9.4%) on non-formulary prescriptions. Of 148 suggested interventions by the CP 123 (83.0%) were approved by the responsible physician, 12 ADR reports (8.1%) were submitted to the local pharmacovigilance centre and 31 (20.9%) specific information given without further need for action. An evaluation of the DRPs showed that direct drug costs of 2,058 within the study period or 10,731 per year could be avoided. We consider the PCNE system to be a practical tool in the hospital setting, which demonstrates the values of a clinical pharmacy service in terms of identifying and reducing DRPs and also has the potential to reduce prescribing costs.

Multicomponent systems with cyclodextrins and hydrophilic polymers for the delivery of Efavirenz.

PubMed

Vieira, Alexandre Couto Carneiro; Ferreira Fontes, Danilo Augusto; Chaves, Luise Lopes; Alves, Lariza Darlene Santos; de Freitas Neto, José Lourenço; de La Roca Soares, Monica Felts; Soares-Sobrinho, Jose L; Rolim, Larissa Araújo; Rolim-Neto, Pedro José

2015-10-05

Efavirenz (EFZ) is one of the most used drugs in the treatment of AIDS and is the first antiretroviral choice. However, since it has low solubility, it does not exhibit suitable bioavailability, which interferes with its therapeutic action and is classified as a class II drug according Biopharmaceutical Classification System (low solubility and high permeability). Among several drug delivery systems, the multicomponent systems with cyclodextrins and hydrophilic polymers are a promising alternative for increasing the aqueous solubility of the drug. The present study aimed to develop and characterize in a ternary system of EFZ, MβCD and PVP K30. The results showed that the solid ternary system provided a large increase in the dissolution rate which was greater than 80% and was characterized by DSC, TG, XRD, FT-IR and SEM. The use of the ternary system (EFZ, MβCD and PVP K30 1%) proved to be a viable, effective and safe delivery of the drug. The addition of the hydrophilic polymer appeared to be suitable for the development of a solid oral pharmaceutical product, with possible industrial scale-up and with low concentration of CDs (cyclodextrins). Copyright © 2015 Elsevier Ltd. All rights reserved.

Food and drug interactions: a general review.

PubMed

Ötles, Semih; Senturk, Ahmet

2014-01-01

Although it is well known and identified that drug-drug interactions exist, the recognition of importance of food and drug interactions to practice has been growing much slower. On the other hand, drug-food/nutrient interactions continue to grow with the common use of medications. Beside the awareness of this type of interactions, food-drug interaction studies are critical to evaluate appropriate dosing, timing, and formulation of new drug candidates. Drug-food interactions take place mechanistically due to altered intestinal transport and metabolism, or systemic distribution, metabolism and excretion. In addition, some people have greater risk of food and drug interactions who have a poor diet, have serious health problems, childrens and pregnant women. In this article, basic informations about importance, classifications, transporters and enzymes of drug and nutrient interaction are given and some specific examples of both drug and nutrients and influences on each other are included.

Comparison of rates of potentially inappropriate medication use according to the Zhan criteria for VA versus private sector medicare HMOs.

PubMed

Barnett, Mitchell J; Perry, Paul J; Langstaff, Jodi D; Kaboli, Peter J

2006-06-01

Inappropriate prescribing in the elderly is common, but rates across different health care systems and the impact of formulary restrictions are not well described. To determine if rates of inappropriate medication use in the elderly differ between the Veterans Affairs (VA) health care system and the private sector Medicare health maintenance organization (HMO) patients. A cross-sectional study design compared administrative pharmacy claims from 10 distinct geographic regions in the United States in the VA health care system and 10 analogous regions for patients enrolled in Medicare HMOs. The cohorts included 123,633 VA and 157,517 Medicare HMO patients aged 65 years and older. Inappropriate medication use was identified using the Zhan modification of the Beers criteria, which categorizes 33 potentially inappropriate drugs into 3 major classifications: "always avoid," "rarely appropriate," and "some indications." Comparisons between the VA health care system and the private sector Medicare HMO were performed for overall differences and stratified by gender and age. The drug formulary status of the Zhan-criteria drugs was known for the VA health system but not for the Medicare HMO patients. Compared with private sector patients, VA patients were less likely to receive any inappropriate medication (21% vs. 29%, P <0.001), and in each classification: always avoid (2% vs. 5%, P <0.001), rarely appropriate (8% vs. 13%, P<0.001), and some indications (15% vs. 17%, P <0.001). The rate of inappropriate drug use was lower in the VA compared with the private sector for males (21% vs. 24%, P <0.001) and females (28% vs. 32%, P <0.001). Differences were consistent when stratified by age. Compared with private sector Medicare HMOs, elderly VA patients were less likely to receive medications defined by the Zhan criteria as potentially inappropriate. A restrictive formulary that excludes 12 of the 33 Zhan criteria drugs may be a factor in the reduction of undesired prescribing patterns in elderly populations.

Wavelet images and Chou's pseudo amino acid composition for protein classification.

PubMed

Nanni, Loris; Brahnam, Sheryl; Lumini, Alessandra

2012-08-01

The last decade has seen an explosion in the collection of protein data. To actualize the potential offered by this wealth of data, it is important to develop machine systems capable of classifying and extracting features from proteins. Reliable machine systems for protein classification offer many benefits, including the promise of finding novel drugs and vaccines. In developing our system, we analyze and compare several feature extraction methods used in protein classification that are based on the calculation of texture descriptors starting from a wavelet representation of the protein. We then feed these texture-based representations of the protein into an Adaboost ensemble of neural network or a support vector machine classifier. In addition, we perform experiments that combine our feature extraction methods with a standard method that is based on the Chou's pseudo amino acid composition. Using several datasets, we show that our best approach outperforms standard methods. The Matlab code of the proposed protein descriptors is available at http://bias.csr.unibo.it/nanni/wave.rar .

The Consensus Molecular Subtypes of Colorectal Cancer

PubMed Central

Guinney, Justin; Dienstmann, Rodrigo; Wang, Xin; de Reyniès, Aurélien; Schlicker, Andreas; Soneson, Charlotte; Marisa, Laetitia; Roepman, Paul; Nyamundanda, Gift; Angelino, Paolo; Bot, Brian M.; Morris, Jeffrey S.; Simon, Iris M.; Gerster, Sarah; Fessler, Evelyn; de Sousa e Melo, Felipe; Missiaglia, Edoardo; Ramay, Hena; Barras, David; Homicsko, Krisztian; Maru, Dipen; Manyam, Ganiraju C.; Broom, Bradley; Boige, Valerie; Perez-Villamil, Beatriz; Laderas, Ted; Salazar, Ramon; Gray, Joe W.; Hanahan, Douglas; Tabernero, Josep; Bernards, Rene; Friend, Stephen H.; Laurent-Puig, Pierre; Medema, Jan Paul; Sadanandam, Anguraj; Wessels, Lodewyk; Delorenzi, Mauro; Kopetz, Scott; Vermeulen, Louis; Tejpar, Sabine

2015-01-01

Colorectal cancer (CRC) is a frequently lethal disease with heterogeneous outcomes and drug responses. To resolve inconsistencies among the reported gene expression–based CRC classifications and facilitate clinical translation, we formed an international consortium dedicated to large-scale data sharing and analytics across expert groups. We show marked interconnectivity between six independent classification systems coalescing into four consensus molecular subtypes (CMS) with distinguishing features: CMS1 (MSI Immune, 14%), hypermutated, microsatellite unstable, strong immune activation; CMS2 (Canonical, 37%), epithelial, chromosomally unstable, marked WNT and MYC signaling activation; CMS3 (Metabolic, 13%), epithelial, evident metabolic dysregulation; and CMS4 (Mesenchymal, 23%), prominent transforming growth factor β activation, stromal invasion, and angiogenesis. Samples with mixed features (13%) possibly represent a transition phenotype or intra-tumoral heterogeneity. We consider the CMS groups the most robust classification system currently available for CRC – with clear biological interpretability – and the basis for future clinical stratification and subtype–based targeted interventions. PMID:26457759

Formulation Strategies to Improve the Bioavailability of Poorly Absorbed Drugs with Special Emphasis on Self-Emulsifying Systems

PubMed Central

Gupta, Shweta; Kesarla, Rajesh

2013-01-01

Poorly water-soluble drug candidates are becoming more prevalent. It has been estimated that approximately 60–70% of the drug molecules are insufficiently soluble in aqueous media and/or have very low permeability to allow for their adequate and reproducible absorption from the gastrointestinal tract (GIT) following oral administration. Formulation scientists have to adopt various strategies to enhance their absorption. Lipidic formulations are found to be a promising approach to combat the challenges. In this review article, potential advantages and drawbacks of various conventional techniques and the newer approaches specifically the self-emulsifying systems are discussed. Various components of the self-emulsifying systems and their selection criteria are critically reviewed. The attempts of various scientists to transform the liquid self-emulsifying drug delivery systems (SEDDS) to solid-SEDDS by adsorption, spray drying, lyophilization, melt granulation, extrusion, and so forth to formulate various dosage forms like self emulsifying capsules, tablets, controlled release pellets, beads, microspheres, nanoparticles, suppositories, implants, and so forth have also been included. Formulation of SEDDS is a potential strategy to deliver new drug molecules with enhanced bioavailability mostly exhibiting poor aqueous solubility. The self-emulsifying system offers various advantages over other drug delivery systems having potential to solve various problems associated with drugs of all the classes of biopharmaceutical classification system (BCS). PMID:24459591

Drug-related webpages classification based on multi-modal local decision fusion

NASA Astrophysics Data System (ADS)

Hu, Ruiguang; Su, Xiaojing; Liu, Yanxin

2018-03-01

In this paper, multi-modal local decision fusion is used for drug-related webpages classification. First, meaningful text are extracted through HTML parsing, and effective images are chosen by the FOCARSS algorithm. Second, six SVM classifiers are trained for six kinds of drug-taking instruments, which are represented by PHOG. One SVM classifier is trained for the cannabis, which is represented by the mid-feature of BOW model. For each instance in a webpage, seven SVMs give seven labels for its image, and other seven labels are given by searching the names of drug-taking instruments and cannabis in its related text. Concatenating seven labels of image and seven labels of text, the representation of those instances in webpages are generated. Last, Multi-Instance Learning is used to classify those drugrelated webpages. Experimental results demonstrate that the classification accuracy of multi-instance learning with multi-modal local decision fusion is much higher than those of single-modal classification.

Correlation-based pattern recognition for implantable defibrillators.

PubMed Central

Wilkins, J.

1996-01-01

An estimated 300,000 Americans die each year from cardiac arrhythmias. Historically, drug therapy or surgery were the only treatment options available for patients suffering from arrhythmias. Recently, implantable arrhythmia management devices have been developed. These devices allow abnormal cardiac rhythms to be sensed and corrected in vivo. Proper arrhythmia classification is critical to selecting the appropriate therapeutic intervention. The classification problem is made more challenging by the power/computation constraints imposed by the short battery life of implantable devices. Current devices utilize heart rate-based classification algorithms. Although easy to implement, rate-based approaches have unacceptably high error rates in distinguishing supraventricular tachycardia (SVT) from ventricular tachycardia (VT). Conventional morphology assessment techniques used in ECG analysis often require too much computation to be practical for implantable devices. In this paper, a computationally-efficient, arrhythmia classification architecture using correlation-based morphology assessment is presented. The architecture classifies individuals heart beats by assessing similarity between an incoming cardiac signal vector and a series of prestored class templates. A series of these beat classifications are used to make an overall rhythm assessment. The system makes use of several new results in the field of pattern recognition. The resulting system achieved excellent accuracy in discriminating SVT and VT. PMID:8947674

[Recent advances in metabonomics].

PubMed

Xu, Guo-Wang; Lu, Xin; Yang, Sheng-Li

2007-12-01

Metabonomics (or metabolomics) aims at the comprehensive and quantitative analysis of the wide arrays of metabolites in biological samples. Metabonomics has been labeled as one of the new" -omics" joining genomics, transcriptomics, and proteomics as a science employed toward the understanding of global systems biology. It has been widely applied in many research areas including drug toxicology, biomarker discovery, functional genomics, and molecular pathology etc. The comprehensive analysis of the metabonome is particularly challenging due to the diverse chemical natures of metabolites. Metabonomics investigations require special approaches for sample preparation, data-rich analytical chemical measurements, and information mining. The outputs from a metabonomics study allow sample classification, biomarker discovery, and interpretation of the reasons for classification information. This review focuses on the currently new advances in various technical platforms of metabonomics and its applications in drug discovery and development, disease biomarker identification, plant and microbe related fields.

Healthcare professionals' agreement on clinical relevance of drug-related problems among elderly patients.

PubMed

Bech, Christine Flagstad; Frederiksen, Tine; Villesen, Christine Tilsted; Højsted, Jette; Nielsen, Per Rotbøll; Kjeldsen, Lene Juel; Nørgaard, Lotte Stig; Christrup, Lona Louring

2018-02-01

Background Disagreement among healthcare professionals on the clinical relevance of drug-related problems can lead to suboptimal treatment and increased healthcare costs. Elderly patients with chronic non-cancer pain and comorbidity are at increased risk of drug related problems compared to other patient groups due to complex medication regimes and transition of care. Objective To investigate the agreement among healthcare professionals on their classification of clinical relevance of drug-related problems in elderly patients with chronic non-cancer pain and comorbidity. Setting Multidisciplinary Pain Centre, Rigshospitalet, Copenhagen, Denmark. Method A pharmacist performed medication review on elderly patients with chronic non-cancer pain and comorbidity, identified their drug-related problems and classified these problems in accordance with an existing categorization system. A five-member clinical panel rated the drug-related problems' clinical relevance in accordance with a five-level rating scale, and their agreement was compared using Fleiss' κ. Main outcome measure Healthcare professionals' agreement on clinical relevance of drug related problems, using Fleiss' κ. Results Thirty patients were included in the study. A total of 162 drug related problems were identified, out of which 54% were of lower clinical relevance (level 0-2) and 46% of higher clinical relevance (level 3-4). Only slight agreement (κ = 0.12) was found between the panellists' classifications of clinical relevance using a five-level rating scale. Conclusion The clinical pharmacist identified drug related problems of lower and higher clinical relevance. Poor overall agreement on the severity of the drug related problems was found among the panelists.

Deep Learning in Label-free Cell Classification

PubMed Central

Chen, Claire Lifan; Mahjoubfar, Ata; Tai, Li-Chia; Blaby, Ian K.; Huang, Allen; Niazi, Kayvan Reza; Jalali, Bahram

2016-01-01

Label-free cell analysis is essential to personalized genomics, cancer diagnostics, and drug development as it avoids adverse effects of staining reagents on cellular viability and cell signaling. However, currently available label-free cell assays mostly rely only on a single feature and lack sufficient differentiation. Also, the sample size analyzed by these assays is limited due to their low throughput. Here, we integrate feature extraction and deep learning with high-throughput quantitative imaging enabled by photonic time stretch, achieving record high accuracy in label-free cell classification. Our system captures quantitative optical phase and intensity images and extracts multiple biophysical features of individual cells. These biophysical measurements form a hyperdimensional feature space in which supervised learning is performed for cell classification. We compare various learning algorithms including artificial neural network, support vector machine, logistic regression, and a novel deep learning pipeline, which adopts global optimization of receiver operating characteristics. As a validation of the enhanced sensitivity and specificity of our system, we show classification of white blood T-cells against colon cancer cells, as well as lipid accumulating algal strains for biofuel production. This system opens up a new path to data-driven phenotypic diagnosis and better understanding of the heterogeneous gene expressions in cells. PMID:26975219

Deep Learning in Label-free Cell Classification

NASA Astrophysics Data System (ADS)

Chen, Claire Lifan; Mahjoubfar, Ata; Tai, Li-Chia; Blaby, Ian K.; Huang, Allen; Niazi, Kayvan Reza; Jalali, Bahram

2016-03-01

Label-free cell analysis is essential to personalized genomics, cancer diagnostics, and drug development as it avoids adverse effects of staining reagents on cellular viability and cell signaling. However, currently available label-free cell assays mostly rely only on a single feature and lack sufficient differentiation. Also, the sample size analyzed by these assays is limited due to their low throughput. Here, we integrate feature extraction and deep learning with high-throughput quantitative imaging enabled by photonic time stretch, achieving record high accuracy in label-free cell classification. Our system captures quantitative optical phase and intensity images and extracts multiple biophysical features of individual cells. These biophysical measurements form a hyperdimensional feature space in which supervised learning is performed for cell classification. We compare various learning algorithms including artificial neural network, support vector machine, logistic regression, and a novel deep learning pipeline, which adopts global optimization of receiver operating characteristics. As a validation of the enhanced sensitivity and specificity of our system, we show classification of white blood T-cells against colon cancer cells, as well as lipid accumulating algal strains for biofuel production. This system opens up a new path to data-driven phenotypic diagnosis and better understanding of the heterogeneous gene expressions in cells.

The Geogenomic Mutational Atlas of Pathogens (GoMAP) Web System

PubMed Central

Sargeant, David P.; Hedden, Michael W.; Deverasetty, Sandeep; Strong, Christy L.; Alaniz, Izua J.; Bartlett, Alexandria N.; Brandon, Nicholas R.; Brooks, Steven B.; Brown, Frederick A.; Bufi, Flaviona; Chakarova, Monika; David, Roxanne P.; Dobritch, Karlyn M.; Guerra, Horacio P.; Levit, Kelvy S.; Mathew, Kiran R.; Matti, Ray; Maza, Dorothea Q.; Mistry, Sabyasachy; Novakovic, Nemanja; Pomerantz, Austin; Rafalski, Timothy F.; Rathnayake, Viraj; Rezapour, Noura; Ross, Christian A.; Schooler, Steve G.; Songao, Sarah; Tuggle, Sean L.; Wing, Helen J.; Yousif, Sandy; Schiller, Martin R.

2014-01-01

We present a new approach for pathogen surveillance we call Geogenomics. Geogenomics examines the geographic distribution of the genomes of pathogens, with a particular emphasis on those mutations that give rise to drug resistance. We engineered a new web system called Geogenomic Mutational Atlas of Pathogens (GoMAP) that enables investigation of the global distribution of individual drug resistance mutations. As a test case we examined mutations associated with HIV resistance to FDA-approved antiretroviral drugs. GoMAP-HIV makes use of existing public drug resistance and HIV protein sequence data to examine the distribution of 872 drug resistance mutations in ∼502,000 sequences for many countries in the world. We also implemented a broadened classification scheme for HIV drug resistance mutations. Several patterns for geographic distributions of resistance mutations were identified by visual mining using this web tool. GoMAP-HIV is an open access web application available at http://www.bio-toolkit.com/GoMap/project/ PMID:24675726

The Geogenomic Mutational Atlas of Pathogens (GoMAP) web system.

PubMed

Sargeant, David P; Hedden, Michael W; Deverasetty, Sandeep; Strong, Christy L; Alaniz, Izua J; Bartlett, Alexandria N; Brandon, Nicholas R; Brooks, Steven B; Brown, Frederick A; Bufi, Flaviona; Chakarova, Monika; David, Roxanne P; Dobritch, Karlyn M; Guerra, Horacio P; Levit, Kelvy S; Mathew, Kiran R; Matti, Ray; Maza, Dorothea Q; Mistry, Sabyasachy; Novakovic, Nemanja; Pomerantz, Austin; Rafalski, Timothy F; Rathnayake, Viraj; Rezapour, Noura; Ross, Christian A; Schooler, Steve G; Songao, Sarah; Tuggle, Sean L; Wing, Helen J; Yousif, Sandy; Schiller, Martin R

2014-01-01

We present a new approach for pathogen surveillance we call Geogenomics. Geogenomics examines the geographic distribution of the genomes of pathogens, with a particular emphasis on those mutations that give rise to drug resistance. We engineered a new web system called Geogenomic Mutational Atlas of Pathogens (GoMAP) that enables investigation of the global distribution of individual drug resistance mutations. As a test case we examined mutations associated with HIV resistance to FDA-approved antiretroviral drugs. GoMAP-HIV makes use of existing public drug resistance and HIV protein sequence data to examine the distribution of 872 drug resistance mutations in ∼ 502,000 sequences for many countries in the world. We also implemented a broadened classification scheme for HIV drug resistance mutations. Several patterns for geographic distributions of resistance mutations were identified by visual mining using this web tool. GoMAP-HIV is an open access web application available at http://www.bio-toolkit.com/GoMap/project/

Study on Biopharmaceutics Classification and Oral Bioavailability of a Novel Multikinase Inhibitor NCE for Cancer Therapy

PubMed Central

Yang, Yang; Fan, Chun-Mei; He, Xuan; Ren, Ke; Zhang, Jin-Kun; He, Ying-Ju; Yu, Luo-Ting; Zhao, Ying-Lan; Gong, Chang-Yang; Zheng, Yu; Song, Xiang-Rong; Zeng, Jun

2014-01-01

Specific biopharmaceutics classification investigation and study on phamacokinetic profile of a novel drug candidate (2-methylcarbamoyl-4-{4-[3- (trifluoromethyl) benzamido] phenoxy} pyridinium 4-methylbenzenesulfonate monohydrate, NCE) were carried out. Equilibrium solubility and intrinsic dissolution rate (IDR) of NCE were estimated in different phosphate buffers. Effective intestinal permeability (Peff) of NCE was determined using single-pass intestinal perfusion technique in rat duodenum, jejunum and ileum at three concentrations. Theophylline (high permeability) and ranitidine (low permeability) were also applied to access the permeability of NCE as reference compounds. The bioavailability after intragastrical and intravenous administration was measured in beagle dogs. The solubility of NCE in tested phosphate buffers was quite low with the maximum solubility of 81.73 μg/mL at pH 1.0. The intrinsic dissolution ratio of NCE was 1 × 10−4 mg·min−1·cm−2. The Peff value of NCE in all intestinal segments was more proximate to the high-permeability reference theophylline. Therefore, NCE was classified as class II drug according to Biopharmaceutics Classification System due to its low solubility and high intestinal permeability. In addition, concentration-dependent permeability was not observed in all the segments, indicating that there might be passive transportation for NCE. The absolute oral bioavailability of NCE in beagle dogs was 26.75%. Therefore, dissolution promotion will be crucial for oral formulation development and intravenous administration route will also be suggested for further NCE formulation development. All the data would provide a reference for biopharmaceutics classification research of other novel drug candidates. PMID:24776763

Study on biopharmaceutics classification and oral bioavailability of a novel multikinase inhibitor NCE for cancer therapy.

PubMed

Yang, Yang; Fan, Chun-Mei; He, Xuan; Ren, Ke; Zhang, Jin-Kun; He, Ying-Ju; Yu, Luo-Ting; Zhao, Ying-Lan; Gong, Chang-Yang; Zheng, Yu; Song, Xiang-Rong; Zeng, Jun

2014-04-25

Specific biopharmaceutics classification investigation and study on phamacokinetic profile of a novel drug candidate (2-methylcarbamoyl-4-{4-[3- (trifluoromethyl) benzamido] phenoxy} pyridinium 4-methylbenzenesulfonate monohydrate, NCE) were carried out. Equilibrium solubility and intrinsic dissolution rate (IDR) of NCE were estimated in different phosphate buffers. Effective intestinal permeability (P(eff)) of NCE was determined using single-pass intestinal perfusion technique in rat duodenum, jejunum and ileum at three concentrations. Theophylline (high permeability) and ranitidine (low permeability) were also applied to access the permeability of NCE as reference compounds. The bioavailability after intragastrical and intravenous administration was measured in beagle dogs. The solubility of NCE in tested phosphate buffers was quite low with the maximum solubility of 81.73 μg/mL at pH 1.0. The intrinsic dissolution ratio of NCE was 1 × 10⁻⁴ mg·min⁻¹·cm⁻². The P(eff) value of NCE in all intestinal segments was more proximate to the high-permeability reference theophylline. Therefore, NCE was classified as class II drug according to Biopharmaceutics Classification System due to its low solubility and high intestinal permeability. In addition, concentration-dependent permeability was not observed in all the segments, indicating that there might be passive transportation for NCE. The absolute oral bioavailability of NCE in beagle dogs was 26.75%. Therefore, dissolution promotion will be crucial for oral formulation development and intravenous administration route will also be suggested for further NCE formulation development. All the data would provide a reference for biopharmaceutics classification research of other novel drug candidates.

Confronting Death From Drug Self-Intoxication (DDSI): Prevention Through a Better Definition

PubMed Central

Smith, Gordon S.; Caine, Eric D.; Kapusta, Nestor D.; Hanzlick, Randy L.; Larkin, G. Luke; Naylor, Charles P. E.; Nolte, Kurt B.; Miller, Ted R.; Putnam, Sandra L.; De Leo, Diego; Kleinig, John; Stack, Steven; Todd, Knox H.; Fraser, David W.

2014-01-01

Suicide and other self-directed violence deaths are likely grossly underestimated, reflecting inappropriate classification of many drug intoxication deaths as accidents or unintentional and heterogeneous ascertainment and coding practices across states. As the tide of prescription and illicit drug-poisoning deaths is rising, public health and research needs would be better satisfied by considering most of these deaths a result of self-intoxication. Epidemiologists and prevention scientists could design better intervention strategies by focusing on premorbid behavior. We propose incorporating deaths from drug self-intoxication and investigations of all poisoning deaths into the National Violent Death Reporting System, which contains misclassified homicides and undetermined intent deaths, to facilitate efforts to comprehend and reverse the surging rate of drug intoxication fatalities. PMID:25320874

Classification of a large microarray data set: Algorithm comparison and analysis of drug signatures

PubMed Central

Natsoulis, Georges; El Ghaoui, Laurent; Lanckriet, Gert R.G.; Tolley, Alexander M.; Leroy, Fabrice; Dunlea, Shane; Eynon, Barrett P.; Pearson, Cecelia I.; Tugendreich, Stuart; Jarnagin, Kurt

2005-01-01

A large gene expression database has been produced that characterizes the gene expression and physiological effects of hundreds of approved and withdrawn drugs, toxicants, and biochemical standards in various organs of live rats. In order to derive useful biological knowledge from this large database, a variety of supervised classification algorithms were compared using a 597-microarray subset of the data. Our studies show that several types of linear classifiers based on Support Vector Machines (SVMs) and Logistic Regression can be used to derive readily interpretable drug signatures with high classification performance. Both methods can be tuned to produce classifiers of drug treatments in the form of short, weighted gene lists which upon analysis reveal that some of the signature genes have a positive contribution (act as “rewards” for the class-of-interest) while others have a negative contribution (act as “penalties”) to the classification decision. The combination of reward and penalty genes enhances performance by keeping the number of false positive treatments low. The results of these algorithms are combined with feature selection techniques that further reduce the length of the drug signatures, an important step towards the development of useful diagnostic biomarkers and low-cost assays. Multiple signatures with no genes in common can be generated for the same classification end-point. Comparison of these gene lists identifies biological processes characteristic of a given class. PMID:15867433

Quality assurance of chemical ingredient classification for the National Drug File - Reference Terminology.

PubMed

Zheng, Ling; Yumak, Hasan; Chen, Ling; Ochs, Christopher; Geller, James; Kapusnik-Uner, Joan; Perl, Yehoshua

2017-09-01

The National Drug File - Reference Terminology (NDF-RT) is a large and complex drug terminology consisting of several classification hierarchies on top of an extensive collection of drug concepts. These hierarchies provide important information about clinical drugs, e.g., their chemical ingredients, mechanisms of action, dosage form and physiological effects. Within NDF-RT such information is represented using tens of thousands of roles connecting drugs to classifications. In previous studies, we have introduced various kinds of Abstraction Networks to summarize the content and structure of terminologies in order to facilitate their visual comprehension, and support quality assurance of terminologies. However, these previous kinds of Abstraction Networks are not appropriate for summarizing the NDF-RT classification hierarchies, due to its unique structure. In this paper, we present the novel Ingredient Abstraction Network (IAbN) to summarize, visualize and support the audit of NDF-RT's Chemical Ingredients hierarchy and its associated drugs. A common theme in our quality assurance framework is to use characterizations of sets of concepts, revealed by the Abstraction Network structure, to capture concepts, the modeling of which is more complex than for other concepts. For the IAbN, we characterize drug ingredient concepts as more complex if they belong to IAbN groups with multiple parent groups. We show that such concepts have a statistically significantly higher rate of errors than a control sample and identify two especially common patterns of errors. Copyright © 2017 Elsevier Inc. All rights reserved.

[Diagnosis-related groups as an instrument to develop suitable case-based lump sums in hematology and oncology].

PubMed

Thalheimer, Markus

2011-01-01

In 2003 a new reimbursement system was established for German hospitals. The approximately 17 million inpatient cases per year are now reimbursed based on a per-case payment regarding diagnoses and procedures, which was developed from an internationally approved system. The aim was a better conformity of costs and efforts in in-patient cases. In the first 2 years after implementation, the German diagnosis-related group (DRG) system was not able to adequately represent the complex structures of treatment in hematological and oncological in-patients. By creating new diagnoses and procedures (International Classification of Diseases 10 (ICD-10) and Surgical Operations and Procedures Classification System (OPS) catalogues), generating new DRGs and better splitting of existing ones, the hematology and oncology field could be much better described in the following years. The implementation of about 70 'co-payment structures' for new and expensive drugs and procedures in oncology was also crucial. To reimburse innovations, an additional system of co-payments for innovations was established to bridge the time until innovations are represented within the DRG system itself. In summary, hematological and oncological in-patients, including cases with extraordinary costs, are meanwhile well mapped in the German reimbursement system. Any tendencies to rationing could thereby be avoided, as most of the established procedures and costly drugs are adequately represented in the DRG system. Copyright © 2011 S. Karger AG, Basel.

Multidrug-resistant bacteria infection and nursing quality management application in the department of physical examination.

PubMed

Xu, Li; Luo, Qiang; Chen, Liangzhen; Jiao, Lingmei

2017-09-01

The main problem of clinical prevention and control of multi drug resistant bacteria infection is to strengthen the monitoring of pathogenic bacteria spectrum, this study research on the multi drug-resistant bacteria infection and nursing quality management application in the department of physical examination. The results of this study showed that the number of patients with multiple drug resistant infections showed an increasing trend. Therefore, once the patients with multiple drug-resistant bacteria infection are found, the prevention and control of the patients with multiple drug-resistant bacteria should be strictly followed, and the patient's medication care should be highly valued. Also, the nurses need to be classified based on the knowledge and skill characteristics of the nurses in the department of physical examination, and compare the nursing effect before and after classification and grouping. The physicians and individuals receiving physical examinations in the department of physical examination had a higher degree of satisfaction for nursing effect after classification compared with those before classification. Classification and grouping management helps improve the nursing quality and overall quality of the nurses in the department of physical examination.

Evaluation of γ-cyclodextrin effect on permeation of lipophilic drugs: application of cellophane/fused octanol membrane.

PubMed

Muankaew, Chutimon; Jansook, Phatsawee; Loftsson, Thorsteinn

2017-06-01

According to the Biopharmaceutics Classification System, oral bioavailability of drugs is determined by their aqueous solubility and the ability of the dissolved drug molecules to permeate lipophilic biological membranes. Similarly topical bioavailability of ophthalmic drugs is determined by their solubility in the aqueous tear fluid and their ability to permeate the lipophilic cornea. Enabling pharmaceutical excipients such as cyclodextrins can have profound effect on the drug bioavailability. However, to fully appreciate such enabling excipients, the relationship between their effects and the physicochemical properties of the permeating drug needs to be known. In this study, the permeation enhancing effect of γ-cyclodextrin (γCD) on saturated drug solutions containing hydrocortisone (HC), irbesartan (IBS), or telmisartan (TEL) was evaluated using cellophane and fused cellulose-octanol membranes in a conventional Franz diffusion cell system. The flux (J), the flux ratio (J R ) and the apparent permeability coefficients (P app ) demonstrate that γCD increases drug permeability. However, its efficacy depends on the drug properties. Addition of γCD increased P app of HC (unionized) and IBS (partially ionized) through the dual membrane but decreased the P app of TEL (fully ionized) that displays low complexation efficacy. The dual cellophane-octanol membrane system was simple to use and gave reproducible results.

Modeling Liver-Related Adverse Effects of Drugs Using kNN QSAR Method

PubMed Central

Rodgers, Amie D.; Zhu, Hao; Fourches, Dennis; Rusyn, Ivan; Tropsha, Alexander

2010-01-01

Adverse effects of drugs (AEDs) continue to be a major cause of drug withdrawals both in development and post-marketing. While liver-related AEDs are a major concern for drug safety, there are few in silico models for predicting human liver toxicity for drug candidates. We have applied the Quantitative Structure Activity Relationship (QSAR) approach to model liver AEDs. In this study, we aimed to construct a QSAR model capable of binary classification (active vs. inactive) of drugs for liver AEDs based on chemical structure. To build QSAR models, we have employed an FDA spontaneous reporting database of human liver AEDs (elevations in activity of serum liver enzymes), which contains data on approximately 500 approved drugs. Approximately 200 compounds with wide clinical data coverage, structural similarity and balanced (40/60) active/inactive ratio were selected for modeling and divided into multiple training/test and external validation sets. QSAR models were developed using the k nearest neighbor method and validated using external datasets. Models with high sensitivity (>73%) and specificity (>94%) for prediction of liver AEDs in external validation sets were developed. To test applicability of the models, three chemical databases (World Drug Index, Prestwick Chemical Library, and Biowisdom Liver Intelligence Module) were screened in silico and the validity of predictions was determined, where possible, by comparing model-based classification with assertions in publicly available literature. Validated QSAR models of liver AEDs based on the data from the FDA spontaneous reporting system can be employed as sensitive and specific predictors of AEDs in pre-clinical screening of drug candidates for potential hepatotoxicity in humans. PMID:20192250

Cell classification using big data analytics plus time stretch imaging (Conference Presentation)

NASA Astrophysics Data System (ADS)

Jalali, Bahram; Chen, Claire L.; Mahjoubfar, Ata

2016-09-01

We show that blood cells can be classified with high accuracy and high throughput by combining machine learning with time stretch quantitative phase imaging. Our diagnostic system captures quantitative phase images in a flow microscope at millions of frames per second and extracts multiple biophysical features from individual cells including morphological characteristics, light absorption and scattering parameters, and protein concentration. These parameters form a hyperdimensional feature space in which supervised learning and cell classification is performed. We show binary classification of T-cells against colon cancer cells, as well classification of algae cell strains with high and low lipid content. The label-free screening averts the negative impact of staining reagents on cellular viability or cell signaling. The combination of time stretch machine vision and learning offers unprecedented cell analysis capabilities for cancer diagnostics, drug development and liquid biopsy for personalized genomics.

A systematic approach to prioritize drug targets using machine learning, a molecular descriptor-based classification model, and high-throughput screening of plant derived molecules: a case study in oral cancer.

PubMed

Randhawa, Vinay; Kumar Singh, Anil; Acharya, Vishal

2015-12-01

Systems-biology inspired identification of drug targets and machine learning-based screening of small molecules which modulate their activity have the potential to revolutionize modern drug discovery by complementing conventional methods. To utilize the effectiveness of such pipelines, we first analyzed the dysregulated gene pairs between control and tumor samples and then implemented an ensemble-based feature selection approach to prioritize targets in oral squamous cell carcinoma (OSCC) for therapeutic exploration. Based on the structural information of known inhibitors of CXCR4-one of the best targets identified in this study-a feature selection was implemented for the identification of optimal structural features (molecular descriptor) based on which a classification model was generated. Furthermore, the CXCR4-centered descriptor-based classification model was finally utilized to screen a repository of plant derived small-molecules to obtain potential inhibitors. The application of our methodology may assist effective selection of the best targets which may have previously been overlooked, that in turn will lead to the development of new oral cancer medications. The small molecules identified in this study can be ideal candidates for trials as potential novel anti-oral cancer agents. Importantly, distinct steps of this whole study may provide reference for the analysis of other complex human diseases.

Pharmacoepidemiological Data from Drug Dispensing Charities as a Measure of Health Patterns in a Population not Assisted by the Italian National Health Service.

PubMed

Bini, Silvia; Cerri, Cesare; Rigamonti, Antonello E; Bertazzi, Pietro A; Fiorini, Gianfrancesco; Cella, Silvano G

2016-08-19

We analysed drug dispensation by charitable organisations in a year time. Drugs were grouped according to the Anatomic Therapeutic Chemical classification and the amount dispensed was calculated with the system of the Daily Defined Dose (DDD) and expressed as DDD/1000 subjects/day. A number of 87,550 subjects were studied (13,308 Italians; 74,242 Immigrants). Though we noticed a great sesonal variability, the drugs most frequently dispensed were those for the respiratory, cardiovascular and gastrointestinal system and antibiotics, which is different from the rest of the Italian population and the immigrant population assisted by our National Health Service (NHS). We also found that chronic diseases are increasing in these subjects. We conclude that the subjects not receiving NHS assitance have, at least in part, different health patterns and requirements. This should be considered when planning tailored interventions.

Drug related webpages classification using images and text information based on multi-kernel learning

NASA Astrophysics Data System (ADS)

Hu, Ruiguang; Xiao, Liping; Zheng, Wenjuan

2015-12-01

In this paper, multi-kernel learning(MKL) is used for drug-related webpages classification. First, body text and image-label text are extracted through HTML parsing, and valid images are chosen by the FOCARSS algorithm. Second, text based BOW model is used to generate text representation, and image-based BOW model is used to generate images representation. Last, text and images representation are fused with a few methods. Experimental results demonstrate that the classification accuracy of MKL is higher than those of all other fusion methods in decision level and feature level, and much higher than the accuracy of single-modal classification.

Variable Classification of Drug-Intoxication Suicides across US States: A Partial Artifact of Forensics?

PubMed

Rockett, Ian R H; Hobbs, Gerald R; Wu, Dan; Jia, Haomiao; Nolte, Kurt B; Smith, Gordon S; Putnam, Sandra L; Caine, Eric D

2015-01-01

The 21st-century epidemic of pharmaceutical and other drug-intoxication deaths in the United States (US) has likely precipitated an increase in misclassified, undercounted suicides. Drug-intoxication suicides are highly prone to be misclassified as accident or undetermined. Misclassification adversely impacts suicide and other injury mortality surveillance, etiologic understanding, prevention, and hence clinical and public health policy formation and practice. To evaluate whether observed variation in the relative magnitude of drug-intoxication suicides across US states is a partial artifact of the scope and quality of toxicological testing and type of medicolegal death investigation system. This was a national, state-based, ecological study of 111,583 drug-intoxication fatalities, whose manner of death was suicide, accident, or undetermined. The proportion of (nonhomicide) drug-intoxication deaths classified by medical examiners and coroners as suicide was analyzed relative to the proportion of death certificates citing one or more specific drugs and two types of state death investigation systems. Our model incorporated five sociodemographic covariates. Data covered the period 2008-2010, and derived from NCHS's Multiple Cause-of-Death public use files. Across states, the proportion of drug-intoxication suicides ranged from 0.058 in Louisiana to 0.286 in South Dakota and the rate from 1 per 100,000 population in North Dakota to 4 in New Mexico. There was a low correlation between combined accident and undetermined drug-intoxication death rates and corresponding suicide rates (Spearman's rho = 0.38; p<0.01). Citation of 1 or more specific drugs on the death certificate was positively associated with the relative odds of a state classifying a nonhomicide drug-intoxication death as suicide rather than accident or undetermined, adjusting for region and type of state death investigation system (odds ratio, 1.062; 95% CI,1.016-1.110). Region, too, was a significant predictor. Relative to the South, a 10% increase in drug citation was associated with 43% (95% CI,11%-83%), 41% (95% CI,7%-85%), and 33% (95% CI,1%-76%) higher odds of a suicide classification in the West, Midwest, and Northeast, respectively. Large interstate variation in the relative magnitude of nonhomicide drug-intoxication deaths classified as suicide by medical examiners and coroners in the US appears partially an artifact of geographic region and degree of toxicological assessment in the case ascertainment process. Etiologic understanding and prevention of drug-induced suicides and other drug-intoxication deaths first require rigorous standardization involving accurate concepts, definitions, and case ascertainment.

Variable Classification of Drug-Intoxication Suicides across US States: A Partial Artifact of Forensics?

PubMed Central

Rockett, Ian R. H.; Hobbs, Gerald R.; Wu, Dan; Jia, Haomiao; Nolte, Kurt B.; Smith, Gordon S.; Putnam, Sandra L.; Caine, Eric D.

2015-01-01

Background The 21st-century epidemic of pharmaceutical and other drug-intoxication deaths in the United States (US) has likely precipitated an increase in misclassified, undercounted suicides. Drug-intoxication suicides are highly prone to be misclassified as accident or undetermined. Misclassification adversely impacts suicide and other injury mortality surveillance, etiologic understanding, prevention, and hence clinical and public health policy formation and practice. Objective To evaluate whether observed variation in the relative magnitude of drug-intoxication suicides across US states is a partial artifact of the scope and quality of toxicological testing and type of medicolegal death investigation system. Methods This was a national, state-based, ecological study of 111,583 drug-intoxication fatalities, whose manner of death was suicide, accident, or undetermined. The proportion of (nonhomicide) drug-intoxication deaths classified by medical examiners and coroners as suicide was analyzed relative to the proportion of death certificates citing one or more specific drugs and two types of state death investigation systems. Our model incorporated five sociodemographic covariates. Data covered the period 2008–2010, and derived from NCHS’s Multiple Cause-of-Death public use files. Results Across states, the proportion of drug-intoxication suicides ranged from 0.058 in Louisiana to 0.286 in South Dakota and the rate from 1 per 100,000 population in North Dakota to 4 in New Mexico. There was a low correlation between combined accident and undetermined drug-intoxication death rates and corresponding suicide rates (Spearman’s rho = 0.38; p<0.01). Citation of 1 or more specific drugs on the death certificate was positively associated with the relative odds of a state classifying a nonhomicide drug-intoxication death as suicide rather than accident or undetermined, adjusting for region and type of state death investigation system (odds ratio, 1.062; 95% CI,1.016–1.110). Region, too, was a significant predictor. Relative to the South, a 10% increase in drug citation was associated with 43% (95% CI,11%-83%), 41% (95% CI,7%-85%), and 33% (95% CI,1%-76%) higher odds of a suicide classification in the West, Midwest, and Northeast, respectively. Conclusion Large interstate variation in the relative magnitude of nonhomicide drug-intoxication deaths classified as suicide by medical examiners and coroners in the US appears partially an artifact of geographic region and degree of toxicological assessment in the case ascertainment process. Etiologic understanding and prevention of drug-induced suicides and other drug-intoxication deaths first require rigorous standardization involving accurate concepts, definitions, and case ascertainment. PMID:26295155

International guidelines for bioequivalence of systemically available orally administered generic drug products: a survey of similarities and differences.

PubMed

Davit, Barbara; Braddy, April C; Conner, Dale P; Yu, Lawrence X

2013-10-01

The objective of this article is to discuss the similarities and differences among bioequivalence approaches used by international regulatory authorities when reviewing applications for marketing new generic drug products which are systemically active and intended for oral administration. We focused on the 13 jurisdictions and organizations participating in the International Generic Drug Regulators Pilot. These are Australia, Brazil, Canada, China, Chinese Taipei, the European Medicines Association, Japan, Mexico, Singapore, South Korea, Switzerland, the USA, and the World Health Organization. We began with a comparison of how the various jurisdictions and organizations define a generic product and its corresponding reference product. We then compared the following bioequivalence approaches: recommended bioequivalence study designs, method of pharmacokinetic calculations and bioequivalence acceptance limits, recommendations for modifying bioequivalence study designs and limits for highly variable drugs and narrow therapeutic index drugs, provisions for waiving bioequivalence study requirements (granting biowaivers), and implementation of the Biopharmaceutics Classification System. We observed that, overall, there are more similarities than differences in bioequivalence approaches among the regulatory authorities surveyed.

Beyond liposomes: Recent advances on lipid based nanostructures for poorly soluble/poorly permeable drug delivery.

PubMed

Teixeira, M C; Carbone, C; Souto, E B

2017-10-01

Solid lipid nanoparticle (SLN), nanostructured lipid carriers (NLC) and hybrid nanoparticles, have gained increasing interest as drug delivery systems because of their potential to load and release drugs from the Biopharmaceutical classification system (BCS) of class II (low solubility and high permeability) and of class IV (low solubility and low permeability). Lipid properties (e.g. high solubilizing potential, biocompatibility, biotolerability, biodegradability and distinct route of absorption) contribute for the improvement of the bioavailability of these drugs for a set of administration routes. Their interest continues to grow, as translated by the number of patents being field worldwide. This paper discusses the recent advances on the use of SLN, NLC and lipid-polymer hybrid nanoparticles for the loading of lipophilic, poorly water-soluble and poorly permeable drugs, being developed for oral, topical, parenteral and ocular administration, also discussing the industrial applications of these systems. A review of the patents filled between 2014 and 2017, concerning the original inventions of lipid nanocarriers, is also provided. Copyright © 2017 Elsevier Ltd. All rights reserved.

Drug interaction databases in medical literature: transparency of ownership, funding, classification algorithms, level of documentation, and staff qualifications. A systematic review.

PubMed

Kongsholm, Gertrud Gansmo; Nielsen, Anna Katrine Toft; Damkier, Per

2015-11-01

It is well documented that drug-drug interaction databases (DIDs) differ substantially with respect to classification of drug-drug interactions (DDIs). The aim of this study was to study online available transparency of ownership, funding, information, classifications, staff training, and underlying documentation of the five most commonly used open access English language-based online DIDs and the three most commonly used subscription English language-based online DIDs in the literature. We conducted a systematic literature search to identify the five most commonly used open access and the three most commonly used subscription DIDs in the medical literature. The following parameters were assessed for each of the databases: Ownership, classification of interactions, primary information sources, and staff qualification. We compared the overall proportion of yes/no answers from open access databases and subscription databases by Fisher's exact test-both prior to and after requesting missing information. Among open access DIDs, 20/60 items could be verified from the webpage directly compared to 24/36 for the subscription DIDs (p = 0.0028). Following personal request, these numbers rose to 22/60 and 30/36, respectively (p < 0.0001). For items within the "classification of interaction" domain, proportions were 3/25 versus 11/15 available from the webpage (P = 0.0001) and 3/25 versus 15/15 (p < 0.0001) available upon personal request. Available information on online available transparency of ownership, funding, information, classifications, staff training, and underlying documentation varies substantially among various DIDs. Open access DIDs had a statistically lower score on parameters assessed.

A Computer Oriented Scheme for Coding Chemicals in the Field of Biomedicine.

ERIC Educational Resources Information Center

Bobka, Marilyn E.; Subramaniam, J.B.

The chemical coding scheme of the Medical Coding Scheme (MCS), developed for use in the Comparative Systems Laboratory (CSL), is outlined and evaluated in this report. The chemical coding scheme provides a classification scheme and encoding method for drugs and chemical terms. Using the scheme complicated chemical structures may be expressed…

Adenosine monophosphate-activated protein kinase-based classification of diabetes pharmacotherapy

PubMed Central

Dutta, D; Kalra, S; Sharma, M

2017-01-01

The current classification of both diabetes and antidiabetes medication is complex, preventing a treating physician from choosing the most appropriate treatment for an individual patient, sometimes resulting in patient-drug mismatch. We propose a novel, simple systematic classification of drugs, based on their effect on adenosine monophosphate-activated protein kinase (AMPK). AMPK is the master regular of energy metabolism, an energy sensor, activated when cellular energy levels are low, resulting in activation of catabolic process, and inactivation of anabolic process, having a beneficial effect on glycemia in diabetes. This listing of drugs makes it easier for students and practitioners to analyze drug profiles and match them with patient requirements. It also facilitates choice of rational combinations, with complementary modes of action. Drugs are classified as stimulators, inhibitors, mixed action, possible action, and no action on AMPK activity. Metformin and glitazones are pure stimulators of AMPK. Incretin-based therapies have a mixed action on AMPK. Sulfonylureas either inhibit AMPK or have no effect on AMPK. Glycemic efficacy of alpha-glucosidase inhibitors, sodium glucose co-transporter-2 inhibitor, colesevelam, and bromocriptine may also involve AMPK activation, which warrants further evaluation. Berberine, salicylates, and resveratrol are newer promising agents in the management of diabetes, having well-documented evidence of AMPK stimulation medicated glycemic efficacy. Hence, AMPK-based classification of antidiabetes medications provides a holistic unifying understanding of pharmacotherapy in diabetes. This classification is flexible with a scope for inclusion of promising agents of future. PMID:27652986

Hydrogels for Hydrophobic Drug Delivery. Classification, Synthesis and Applications

PubMed Central

Stewart, Sarah; Ervine, Michael; Al-Kasasbeh, Rehan; Donnelly, Ryan F.

2018-01-01

Hydrogels have been shown to be very useful in the field of drug delivery due to their high biocompatibility and ability to sustain delivery. Therefore, the tuning of their properties should be the focus of study to optimise their potential. Hydrogels have been generally limited to the delivery of hydrophilic drugs. However, as many of the new drugs coming to market are hydrophobic in nature, new approaches for integrating hydrophobic drugs into hydrogels should be developed. This article discusses the possible new ways to incorporate hydrophobic drugs within hydrogel structures that have been developed through research. This review describes hydrogel-based systems for hydrophobic compound delivery included in the literature. The section covers all the main types of hydrogels, including physical hydrogels and chemical hydrogels. Additionally, reported applications of these hydrogels are described in the subsequent sections. PMID:29364833

The New Drug Conditional Approval Process in China: Challenges and Opportunities.

PubMed

Yao, Xuefang; Ding, Jinxi; Liu, Yingfang; Li, Penghui

2017-05-01

Our aim was to characterize the newly established new drug conditional approval process in China and discuss the challenges and opportunities with respect to new drug research and development and registration. We examined the new approval program through literature review, law analysis, and data analysis. Data were derived from published materials, such as journal articles, government publications, press releases, and news articles, along with statistical data from INSIGHT-China Pharma Databases, the China Food and Drug Administration website, the Center for Drug Evaluation website, the US Food and Drug Administration website, and search results published by Google. Currently, there is a large backlog of New Drug Applications in China, mainly because of the prolonged review time at the China Food and Drug Administration, resulting in a lag in drug approvals. In 2015, the Chinese government implemented the drug review and registration system reform and tackled this issue through various approaches, such as setting up a drug review fee system, adjusting the drug registration classification, and establishing innovative review pathways, including the conditional approval process. In Europe and the United States, programs comparable to the conditional approval program in China have been well developed. The conditional approval program recently established in China is an expedited new drug approval process that is expected to affect new drug development at home and abroad and profoundly influence the public health and the pharmaceutical industry in China. Like any program in its initial stage, the conditional approval program is facing several challenges, including setting up a robust system, formatting new drug clinical research requirements, and improving the regulatory agency's function for drug review and approval. The program is expected to evolve and improve as part of the government mandate of the drug registration system reform. Copyright © 2017 Elsevier HS Journals, Inc. All rights reserved.

Drug use in patients with dementia: a register-based study in the health region of Girona (Catalonia/Spain).

PubMed

Avila-Castells, Pilar; Garre-Olmo, Josep; Calvó-Perxas, Laia; Turró-Garriga, Oriol; Alsina, Elisabet; Carmona, Olga; Perkal, Héctor; Roig, Anna Maria; Cuy, Josep Ma; Lozano, Manuela; Molins, Albert; Vallmajó, Natàlia; López-Pousa, Secundino

2013-05-01

To describe the pattern of drug consumption among patients with dementia in a geographically defined general population in Catalonia (Spain), and to determine its association with age, gender, type of dementia and severity indicators. Cross-sectional study that included 1,894 cases of dementia registered by the Registry of Dementias of Girona from 2007 to 2009. Prescribed drugs were categorized according to the Anatomical Therapeutic Chemical (ATC) classification. A descriptive analysis of drug consumption was stratified according to age, gender, dementia subtypes and dementia severity. Binary logistic regression models were adjusted to detect the association of these variables with drug consumption according to the ATC groups. The most commonly prescribed drugs were for the central nervous system (CNS) (96.4 %), cardiovascular system (79.4 %) and digestive and metabolic system categories (77.7 %). No significant differences were found between the use of nervous system drugs and age, gender, dementia subtypes or dementia severity. The use of alimentary tract and metabolism related drugs, as well as cardiovascular and blood system drugs, were positively correlated with age and secondary dementia. The prevalence of use of cardiovascular and musculoskeletal drugs was higher in women than in men (OR: 1.34; OR: 1.26 respectively). A negative association was found between the severity of dementia and the use of musculoskeletal drugs (OR: 0.71), while its use was significantly higher in the youngest patients (OR: 1.71). Almost all patients with dementia received a CNS drug, being at risk of inappropriate treatment. Treatment for comorbidities in patients with dementia should not be withheld on the basis of age or dementia severity, but rather on the benefit/risk ratio of its prescription. Further studies are needed to evaluate potentially inappropriate drug use and possible untreated conditions in this population.

Characteristics of FDA drug recalls: A 30-month analysis.

PubMed

Hall, Kelsey; Stewart, Tyler; Chang, Jongwha; Freeman, Maisha Kelly

2016-02-15

The characteristics of drug recalls issued over 30 months by the Food and Drug Administration (FDA) were analyzed. All FDA-issued recalls for drugs (prescription and nonprescription, including dietary supplements) and biological products issued from June 20, 2012, to December 31, 2014, were included in this retrospective analysis. Data for all drug recalls were downloaded and sorted by the inclusion criteria from weekly FDA enforcement reports. The following data were analyzed: product type, recall firm, type of recall firm (compounding or noncompounding), country, voluntary or involuntary recall, method of communication of recall, recall number, FDA recall classification (class I, II, or III), product availability (prescription or nonprescription), reason for recall, recall initiation date, and recall report date. A total of 21,120 products were recalled during the 30-month study period. Of these, 3,045 drug products (14.4%) met the inclusion criteria and were analyzed. A total of 348 total manufacturers were associated with recalled drug products. The 5 firms most frequently involved in recalls accounted for 299, 273, 212, 118, and 112 recalls. The most common reasons for recalls were contamination, mislabeling, adverse reaction, defective product, and incorrect potency. There was a significant association between FDA recall classification and the following outcomes: reasons for recall, product availability, type of recall firm, and form of communication. An investigation of FDA drug recalls revealed that the five most common recall reasons were contamination, mislabeling, adverse reaction, defective product, and incorrect potency. Compounding firms were associated more frequently with contamination than were noncompounding firms. Copyright © 2016 by the American Society of Health-System Pharmacists, Inc. All rights reserved.

Pre-systemic metabolism of orally administered drugs and strategies to overcome it.

PubMed

Pereira de Sousa, Irene; Bernkop-Schnürch, Andreas

2014-10-28

The oral bioavailability of numerous drugs is not only limited by poor solubility and/or poor membrane permeability as addressed by the biopharmaceutical classification system (BCS) but also by a pre-systemic metabolism taking place to a high extent in the intestine. Enzymes responsible for metabolic reactions in the intestine include cytochromes P450 (CYP450), transferases, peptidases and proteases. Furthermore, in the gut nucleases, lipases as well as glycosidases influence the metabolic pathway of drugs and nutrients. A crucial role is also played by the intestinal microflora able to metabolize a wide broad of pharmaceutical compounds. Strategies to provide a protective effect towards an intestinal pre-systemic metabolism are based on the co-administration of enzyme inhibitor being optimally immobilized on unabsorbable and undegradable polymeric excipients in order to keep them concentrated there where an inhibitory effect is needed. Furthermore, certain polymeric excipients such as polyacrylates exhibit per se enzyme inhibitory properties. In addition, by incorporating drugs in cyclodextrines, in self-emulsifying drug delivery systems (SEDDS) or liposomes a protective effect towards an intestinal enzymatic attack can be achieved. Being aware of the important role of this pre-systemic metabolism by integrating it in the BCS as third dimension and keeping strategies to overcome this enzymatic barrier in mind, the therapeutic efficacy of many orally given drugs can certainly be substantially improved. Copyright © 2014 Elsevier B.V. All rights reserved.

SWOT analysis of Banff: strengths, weaknesses, opportunities and threats of the international Banff consensus process and classification system for renal allograft pathology.

PubMed

Mengel, M; Sis, B; Halloran, P F

2007-10-01

The Banff process defined the diagnostic histologic lesions for renal allograft rejection and created a standardized classification system where none had existed. By correcting this deficit the process had universal impact on clinical practice and clinical and basic research. All trials of new drugs since the early 1990s benefited, because the Banff classification of lesions permitted the end point of biopsy-proven rejection. The Banff process has strengths, weaknesses, opportunities and threats (SWOT). The strength is its self-organizing group structure to create consensus. Consensus does not mean correctness: defining consensus is essential if a widely held view is to be proved wrong. The weaknesses of the Banff process are the absence of an independent external standard to test the classification; and its almost exclusive reliance on histopathology, which has inherent limitations in intra- and interobserver reproducibility, particularly at the interface between borderline and rejection, is exactly where clinicians demand precision. The opportunity lies in the new technology such as transcriptomics, which can form an external standard and can be incorporated into a new classification combining the elegance of histopathology and the objectivity of transcriptomics. The threat is the degree to which the renal transplant community will participate in and support this process.

Deep Learning in Label-free Cell Classification

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chen, Claire Lifan; Mahjoubfar, Ata; Tai, Li-Chia

Label-free cell analysis is essential to personalized genomics, cancer diagnostics, and drug development as it avoids adverse effects of staining reagents on cellular viability and cell signaling. However, currently available label-free cell assays mostly rely only on a single feature and lack sufficient differentiation. Also, the sample size analyzed by these assays is limited due to their low throughput. Here, we integrate feature extraction and deep learning with high-throughput quantitative imaging enabled by photonic time stretch, achieving record high accuracy in label-free cell classification. Our system captures quantitative optical phase and intensity images and extracts multiple biophysical features of individualmore » cells. These biophysical measurements form a hyperdimensional feature space in which supervised learning is performed for cell classification. We compare various learning algorithms including artificial neural network, support vector machine, logistic regression, and a novel deep learning pipeline, which adopts global optimization of receiver operating characteristics. As a validation of the enhanced sensitivity and specificity of our system, we show classification of white blood T-cells against colon cancer cells, as well as lipid accumulating algal strains for biofuel production. In conclusion, this system opens up a new path to data-driven phenotypic diagnosis and better understanding of the heterogeneous gene expressions in cells.« less

Deep Learning in Label-free Cell Classification

DOE PAGES

Chen, Claire Lifan; Mahjoubfar, Ata; Tai, Li-Chia; ...

2016-03-15

Label-free cell analysis is essential to personalized genomics, cancer diagnostics, and drug development as it avoids adverse effects of staining reagents on cellular viability and cell signaling. However, currently available label-free cell assays mostly rely only on a single feature and lack sufficient differentiation. Also, the sample size analyzed by these assays is limited due to their low throughput. Here, we integrate feature extraction and deep learning with high-throughput quantitative imaging enabled by photonic time stretch, achieving record high accuracy in label-free cell classification. Our system captures quantitative optical phase and intensity images and extracts multiple biophysical features of individualmore » cells. These biophysical measurements form a hyperdimensional feature space in which supervised learning is performed for cell classification. We compare various learning algorithms including artificial neural network, support vector machine, logistic regression, and a novel deep learning pipeline, which adopts global optimization of receiver operating characteristics. As a validation of the enhanced sensitivity and specificity of our system, we show classification of white blood T-cells against colon cancer cells, as well as lipid accumulating algal strains for biofuel production. In conclusion, this system opens up a new path to data-driven phenotypic diagnosis and better understanding of the heterogeneous gene expressions in cells.« less

21 CFR 860.5 - Confidentiality and use of data and information submitted in connection with classification and...

Code of Federal Regulations, 2013 CFR

2013-04-01

... submitted in connection with classification and reclassification. 860.5 Section 860.5 Food and Drugs FOOD... DEVICE CLASSIFICATION PROCEDURES General § 860.5 Confidentiality and use of data and information submitted in connection with classification and reclassification. (a) This section governs the availability...

21 CFR 860.5 - Confidentiality and use of data and information submitted in connection with classification and...

Code of Federal Regulations, 2012 CFR

2012-04-01

... submitted in connection with classification and reclassification. 860.5 Section 860.5 Food and Drugs FOOD... DEVICE CLASSIFICATION PROCEDURES General § 860.5 Confidentiality and use of data and information submitted in connection with classification and reclassification. (a) This section governs the availability...

21 CFR 860.5 - Confidentiality and use of data and information submitted in connection with classification and...

Code of Federal Regulations, 2014 CFR

2014-04-01

... submitted in connection with classification and reclassification. 860.5 Section 860.5 Food and Drugs FOOD... DEVICE CLASSIFICATION PROCEDURES General § 860.5 Confidentiality and use of data and information submitted in connection with classification and reclassification. (a) This section governs the availability...

21 CFR 860.5 - Confidentiality and use of data and information submitted in connection with classification and...

Code of Federal Regulations, 2011 CFR

2011-04-01

... submitted in connection with classification and reclassification. 860.5 Section 860.5 Food and Drugs FOOD... DEVICE CLASSIFICATION PROCEDURES General § 860.5 Confidentiality and use of data and information submitted in connection with classification and reclassification. (a) This section governs the availability...

21 CFR 860.5 - Confidentiality and use of data and information submitted in connection with classification and...

Code of Federal Regulations, 2010 CFR

2010-04-01

... submitted in connection with classification and reclassification. 860.5 Section 860.5 Food and Drugs FOOD... DEVICE CLASSIFICATION PROCEDURES General § 860.5 Confidentiality and use of data and information submitted in connection with classification and reclassification. (a) This section governs the availability...

Towards linking patients and clinical information: detecting UMLS concepts in e-mail.

PubMed

Brennan, Patricia Flatley; Aronson, Alan R

2003-01-01

The purpose of this project is to explore the feasibility of detecting terms within the electronic messages of patients that could be used to effectively search electronic knowledge resources and bring health information resources into the hands of patients. Our team is exploring the application of the natural language processing (NLP) tools built within the Lister Hill Center at the National Library of Medicine (NLM) to the challenge of detecting relevant concepts from the Unified Medical Language System (UMLS) within the free text of lay people's electronic messages (e-mail). We obtained a sample of electronic messages sent by patients participating in a randomized field evaluation of an internet-based home care support service to the project nurse, and we subjected elements of these messages to a series of analyses using several vocabularies from the UMLS Metathesaurus and the selected NLP tools. The nursing vocabularies provide an excellent starting point for this exercise because their domain encompasses patient's responses to health challenges. In successive runs we augmented six nursing vocabularies (NANDA Nursing Diagnosis, Nursing Interventions Classification, Nursing Outcomes Classification, Home Health Classification, Omaha System, and the Patient Care Data Set) with selected sets of clinical terminologies (International Classification of Primary Care; International Classification of Primary Care- American English; Micromedex DRUGDEX; National Drug Data File; Thesaurus of Psychological Terms; WHO Adverse Drug Reaction Terminology) and then additionally with either Medical Subject Heading (MeSH) or SNOMED International terms. The best performance was obtained when the nursing vocabularies were complemented with selected clinical terminologies. These findings have implications not only for facilitating lay people's access to electronic knowledge resources but may also be of assistance in developing new tools to aid in linking free text (e.g., clinical notes) to lexically complex knowledge resources such as those emerging from the Human Genome Project.

[Machine Learning-based Prediction of Seizure-inducing Action as an Adverse Drug Effect].

PubMed

Gao, Mengxuan; Sato, Motoshige; Ikegaya, Yuji

2018-01-01

　During the preclinical research period of drug development, animal testing is widely used to help screen out a drug's dangerous side effects. However, it remains difficult to predict side effects within the central nervous system. Here, we introduce a machine learning-based in vitro system designed to detect seizure-inducing side effects before clinical trial. We recorded local field potentials from the CA1 alveus in acute mouse neocortico-hippocampal slices that were bath-perfused with each of 14 different drugs, and at 5 different concentrations of each drug. For each of these experimental conditions, we collected seizure-like neuronal activity and merged their waveforms as one graphic image, which was further converted into a feature vector using Caffe, an open framework for deep learning. In the space of the first two principal components, the support vector machine completely separated the vectors (i.e., doses of individual drugs) that induced seizure-like events, and identified diphenhydramine, enoxacin, strychnine and theophylline as "seizure-inducing" drugs, which have indeed been reported to induce seizures in clinical situations. Thus, this artificial intelligence-based classification may provide a new platform to pre-clinically detect seizure-inducing side effects of drugs.

21 CFR 860.1 - Scope.

Code of Federal Regulations, 2010 CFR

2010-04-01

... DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES MEDICAL DEVICE...) of the act with respect to the classification and reclassification of devices intended for human use... information submitted to classification panels or to the Commissioner in connection with classification and...

21 CFR 860.1 - Scope.

Code of Federal Regulations, 2011 CFR

2011-04-01

... DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES MEDICAL DEVICE...) of the act with respect to the classification and reclassification of devices intended for human use... information submitted to classification panels or to the Commissioner in connection with classification and...

Physiologically Based Pharmacokinetic and Absorption Modeling for Osmotic Pump Products.

PubMed

Ni, Zhanglin; Talattof, Arjang; Fan, Jianghong; Tsakalozou, Eleftheria; Sharan, Satish; Sun, Dajun; Wen, Hong; Zhao, Liang; Zhang, Xinyuan

2017-07-01

Physiologically based pharmacokinetic (PBPK) and absorption modeling approaches were employed for oral extended-release (ER) drug products based on an osmotic drug delivery system (osmotic pumps). The purpose was to systemically evaluate the in vivo relevance of in vitro dissolution for this type of formulation. As expected, in vitro dissolution appeared to be generally predictive of in vivo PK profiles, because of the unique feature of this delivery system that the in vitro and in vivo release of osmotic pump drug products is less susceptible to surrounding environment in the gastrointestinal (GI) tract such as pH, hydrodynamic, and food effects. The present study considered BCS (Biopharmaceutics Classification System) class 1, 2, and 3 drug products with half-lives ranging from 2 to greater than 24 h. In some cases, the colonic absorption models needed to be adjusted to account for absorption in the colon. C max (maximum plasma concentration) and AUCt (area under the concentration curve) of the studied drug products were sensitive to changes in colon permeability and segmental GI transit times in a drug product-dependent manner. While improvement of the methodology is still warranted for more precise prediction (e.g., colonic absorption and dynamic movement in the GI tract), the results from the present study further emphasized the advantage of using PBPK modeling in addressing product-specific questions arising from regulatory review and drug development.

Analysis on the infections change and measures for the multiple drug-resistant bacteria of neurology.

PubMed

Zang, Wenju

2016-05-01

To analyze the bacterial infection situations and the separation situations of multiple drug-resistant bacteria of the neurology of Zhengzhou People's hospital from Feb. 2012 to Dec. 2014. The patients data of neurology were retrieved by means of the doctor workstation system. The infection sites, the classification and drug-resistant feature of bacteria were classified and summarized in Excel. Finally, Compared with the infection sites, the classification and drug-resistant feature of bacteria at different year. The data obtained use SPSS 19.0 software to do statistical analysis. The infection rate of bacteria in neurology from Year 2012 to 2014 declined from 4.99% to 3.41%. But the constitution of the infection sites of bacteria had no significant changes. Staphylococcus aureus still was the majority in the infections of gram-positive bacteria, and Escherichia coli was the majority in the infections of gram-negative bacteria, and there were no significant changes in the ranking of the past three years. The separation rate of Acihetobacter baumanii and Pseudomonas aeruginosa in gram-negative bacteria gradually escalated. There were definite efficiencies in the prevention and control of the bacterial infections in neurology in the past three years. But the situation of prevention and control was still severe at the same time.

Drug-Associated Acute Kidney Injury Identified in the United States Food and Drug Administration Adverse Event Reporting System Database.

PubMed

Welch, Hanna K; Kellum, John A; Kane-Gill, Sandra L

2018-06-08

Acute kidney injury (AKI) is a common condition associated with both short-term and long-term consequences including dialysis, chronic kidney disease, and mortality. Although the United States Food and Drug Administration Adverse Event Reporting System (FAERS) database is a powerful tool to examine drug-associated events, to our knowledge, no study has analyzed this database to identify the most common drugs reported with AKI. The objective of this study was to analyze AKI reports and associated medications in the FAERS database. Retrospective pharmacovigilance disproportionality analysis. FAERS database. We queried the FAERS database for reports of AKI from 2004 quarter 1 through 2015 quarter 3. Extracted drugs were assessed using published references and categorized as known, possible, or new potential nephrotoxins. The reporting odds ratio (ROR), a measure of reporting disproportionality, was calculated for the 20 most frequently reported drugs in each category. We retrieved 7,241,385 adverse event reports, of which 193,996 (2.7%) included a report of AKI. Of the AKI reports, 16.5% were known nephrotoxins, 18.6% were possible nephrotoxins, and 64.8% were new potential nephrotoxins. Among the most commonly reported drugs, those with the highest AKI ROR were aprotinin (7,614 reports; ROR 115.70, 95% confidence interval [CI] 110.63-121.01), sodium phosphate (1,687 reports; ROR 55.81, 95% CI 51.78-60.17), furosemide (1,743 reports; ROR 12.61, 95% CI 11.94-13.32), vancomycin (1,270 reports, ROR 12.19, 95% CI 11.45-12.99), and metformin (4,701 reports; ROR 10.65, 95% CI 10.31-11.00). The combined RORs for the 20 most frequently reported drugs with each nephrotoxin classification were 3.71 (95% CI 3.66-3.76) for known nephrotoxins, 2.09 (95% CI 2.06-2.12) for possible nephrotoxins, and 1.55 (95% CI 1.53-1.57) for new potential nephrotoxins. AKI was a common reason for adverse event reporting in the FAERS. Most AKI reports were generated for medications not recognized as nephrotoxic according to our classification system. This report provides data on medications needing further research to determine the risk of AKI with these new potential nephrotoxins. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Revealing Significant Relations between Chemical/Biological Features and Activity: Associative Classification Mining for Drug Discovery

ERIC Educational Resources Information Center

Yu, Pulan

2012-01-01

Classification, clustering and association mining are major tasks of data mining and have been widely used for knowledge discovery. Associative classification mining, the combination of both association rule mining and classification, has emerged as an indispensable way to support decision making and scientific research. In particular, it offers a…

Associations of gender and age groups on the knowledge and use of drug information resources by American pharmacists.

PubMed

Carvajal, Manuel J; Clauson, Kevin A; Gershman, Jennifer; Polen, Hyla H

2013-04-01

To explore knowledge and use of drug information resources by pharmacists and identify patterns influenced by gender and age-group classification. A survey questionnaire was mailed nationwide to 1,000 practitioners working in community (n = 500) and hospital (n = 500) settings who answer drug information questions as part of their expected job responsibilities. Responses pertaining to drug information resource use and knowledge of different types of drug-related queries, resource media preferences, and perceived adequacy of resources maintained in the pharmacy were analyzed by gender and age group. The t statistic was used to test for significant differences of means and percentages between genders and between age groups. Descriptive statistics were used to characterize other findings. Gender and age group classification influenced patterns of knowledge and use of drug information resources by pharmacists. They also affected pharmacists' perceptions of the most common types of questions prompting them to consult a drug information reference, as well as the resources consulted. Micromedex, exclusively available in electronic format, was the most commonly consulted resource overall by pharmacists. Lexi-Comp Online was the leading choice by women, preferred over Micromedex, but was not one of the top two resources selected by men. This study successfully identified the influence of gender and age-group classification in assessing drug information resource knowledge and use of general and specific types of drug-related queries.

Cannabis - from cultivar to chemovar.

PubMed

Hazekamp, A; Fischedick, J T

2012-01-01

The medicinal use of Cannabis is increasing as countries worldwide are setting up official programs to provide patients with access to safe sources of medicinal-grade Cannabis. An important question that remains to be answered is which of the many varieties of Cannabis should be made available for medicinal use. Drug varieties of Cannabis are commonly distinguished through the use of popular names, with a major distinction being made between Indica and Sativa types. Although more than 700 different cultivars have already been described, it is unclear whether such classification reflects any relevant differences in chemical composition. Some attempts have been made to classify Cannabis varieties based on chemical composition, but they have mainly been useful for forensic applications, distinguishing drug varieties, with high THC content, from the non-drug hemp varieties. The biologically active terpenoids have not been included in these approaches. For a clearer understanding of the medicinal properties of the Cannabis plant, a better classification system, based on a range of potentially active constituents, is needed. The cannabinoids and terpenoids, present in high concentrations in Cannabis flowers, are the main candidates. In this study, we compared cultivars obtained from multiple sources. Based on the analysis of 28 major compounds present in these samples, followed by principal component analysis (PCA) of the quantitative data, we were able to identify the Cannabis constituents that defined the samples into distinct chemovar groups. The study indicates the usefulness of a PCA approach for chemotaxonomic classification of Cannabis varieties. Copyright © 2012 John Wiley & Sons, Ltd.

Biopharmaceutics permeability classification of lorcaserin, a selective 5-hydroxytryptamine 2C agonist: method suitability and permeability class membership.

PubMed

Chen, Chuan; Ma, Michael G; Fullenwider, Cody L; Chen, Weichao G; Sadeque, Abu J M

2013-12-02

The objectives of the study were (1) to demonstrate that a Caco-2 cell-based permeability assay, developed in our laboratory, is suitable to identify the permeability classification according to the US Food and Drug Administration Biopharmaceutics Classification System guidance, and (2) to use the validated Caco-2 method to determine permeability class membership of lorcaserin. Lorcaserin, marketed in United States as Belviq, is a selective human 5-hydroxytryptamine 2C agonist used for weight management. First, the permeability of twenty commercially available drugs was determined in the apical-to-basolateral direction at a final concentration of 10 μM, with the pH of transporter buffer in the apical and basolateral compartments being 6.8 and 7.4, respectively. A rank-order relationship between in vitro permeability results and the extent of human intestinal absorption for the drugs tested was observed. Second, the apparent permeability coefficient values of lorcaserin at 2, 20, and 200 μM and apical pH values of 6.8 and 7.4 in the apical-to-basolateral direction were determined using the validated method and found to be comparable to those of the high-permeability internal standard metoprolol. Lorcaserin permeability across Caco-2 cell monolayers was not dependent on the variation of apical pH. Furthermore, lorcaserin was not a substrate for efflux transporters such as P-glycoprotein. In conclusion, using the validated Caco-2 permeability assay, it was shown that lorcaserin is a highly permeable compound.

Feedback control methods for drug dosage optimisation. Concepts, classification and clinical application.

PubMed

Vozeh, S; Steimer, J L

1985-01-01

The concept of feedback control methods for drug dosage optimisation is described from the viewpoint of control theory. The control system consists of 5 parts: (a) patient (the controlled process); (b) response (the measured feedback); (c) model (the mathematical description of the process); (d) adaptor (to update the parameters); and (e) controller (to determine optimum dosing strategy). In addition to the conventional distinction between open-loop and closed-loop control systems, a classification is proposed for dosage optimisation techniques which distinguishes between tight-loop and loose-loop methods depending on whether physician's interaction is absent or included as part of the control step. Unlike engineering problems where the process can usually be controlled by fully automated devices, therapeutic situations often require that the physician be included in the decision-making process to determine the 'optimal' dosing strategy. Tight-loop and loose-loop methods can be further divided into adaptive and non-adaptive, depending on the presence of the adaptor. The main application areas of tight-loop feedback control methods are general anaesthesia, control of blood pressure, and insulin delivery devices. Loose-loop feedback methods have been used for oral anticoagulation and in therapeutic drug monitoring. The methodology, advantages and limitations of the different approaches are reviewed. A general feature common to all application areas could be observed: to perform well under routine clinical conditions, which are characterised by large interpatient variability and sometimes also intrapatient changes, control systems should be adaptive. Apart from application in routine drug treatment, feedback control methods represent an important research tool. They can be applied for the investigation of pathophysiological and pharmacodynamic processes. A most promising application is the evaluation of the relationship between an intermediate response (e.g. drug level), which is often used as feedback for dosage adjustment, and the final therapeutic goal.

Acute kidney injury: not just acute renal failure anymore?

PubMed

Dirkes, Susan

2011-02-01

Until recently, no uniform standard existed for diagnosing and classifying acute renal failure. To clarify diagnosis, the Acute Dialysis Quality Initiative group stated its consensus on the need for a clear definition and classification system of renal dysfunction with measurable criteria. Today the term acute kidney injury has replaced the term acute renal failure, with an understanding that such injury is a common clinical problem in critically ill patients and typically is predictive of an increase in morbidity and mortality. A classification system, known as RIFLE (risk of injury, injury, failure, loss of function, and end-stage renal failure), includes specific goals for preventing acute kidney injury: adequate hydration, maintenance of renal perfusion, limiting exposure to nephrotoxins, drug protective strategies, and the use of renal replacement therapies that reduce renal injury.

Discriminating Drug-Like Compounds by Partition Trees with Quantum Similarity Indices and Graph Invariants.

PubMed

Julián-Ortiz, Jesus V de; Gozalbes, Rafael; Besalú, Emili

2016-01-01

The search for new drug candidates in databases is of paramount importance in pharmaceutical chemistry. The selection of molecular subsets is greatly optimized and much more promising when potential drug-like molecules are detected a priori. In this work, about one hundred thousand molecules are ranked following a new methodology: a drug/non-drug classifier constructed by a consensual set of classification trees. The classification trees arise from the stochastic generation of training sets, which in turn are used to estimate probability factors of test molecules to be drug-like compounds. Molecules were represented by Topological Quantum Similarity Indices and their Graph Theoretical counterparts. The contribution of the present paper consists of presenting an effective ranking method able to improve the probability of finding drug-like substances by using these types of molecular descriptors.

Addiction and disability: moral and policy issues.

PubMed

Wasserman, David

2004-02-01

This article discusses the conceptual, ethical, and policy issues raised by the legal classification of drug addiction as an impairment, and of some nonusing drug addicts as people with disabilities. It focuses on the questions of (1) what moral judgments, if any, underlie the classification of addiction as an impairment; (2) whether it makes sense to apportion the burdens of drug addiction between chemical, biological, social, political, and other causes; (3) how considerations of distributive justice may compel or constrain measures to ease the burdens of drug addiction; and (4) whether it is justifiable to deny the current users of illegal substances legal protections available to the current users of legal substances.

Application of Snyder-Dolan classification scheme to the selection of "orthogonal" columns for fast screening of illicit drugs and impurity profiling of pharmaceuticals--I. Isocratic elution.

PubMed

Fan, Wenzhe; Zhang, Yu; Carr, Peter W; Rutan, Sarah C; Dumarey, Melanie; Schellinger, Adam P; Pritts, Wayne

2009-09-18

Fourteen judiciously selected reversed phase columns were tested with 18 cationic drug solutes under the isocratic elution conditions advised in the Snyder-Dolan (S-D) hydrophobic subtraction method of column classification. The standard errors (S.E.) of the least squares regressions of logk' vs. logk'(REF) were obtained for a given column against a reference column and used to compare and classify columns based on their selectivity. The results are consistent with those obtained with a study of the 16 test solutes recommended by Snyder and Dolan. To the extent these drugs are representative, these results show that the S-D classification scheme is also generally applicable to pharmaceuticals under isocratic conditions. That is, those columns judged to be similar based on the 16 S-D solutes were similar based on the 18 drugs; furthermore those columns judged to have significantly different selectivities based on the 16 S-D probes appeared to be quite different for the drugs as well. Given that the S-D method has been used to classify more than 400 different types of reversed phases the extension to cationic drugs is a significant finding.

Chemical action: what is it, and why does it really matter?

NASA Astrophysics Data System (ADS)

Koolage, W. John; Hall, Ralph

2011-04-01

Nanotechnology, as with many technologies before it, places a strain on existing legislation and poses a challenge to all administrative agencies tasked with regulating technology-based products. It is easy to see how statutory schemes become outdated, as our ability to understand and affect the world progresses. In this article, we address the regulatory problems that nanotechnology posses for the Food and Drug Administration's (FDA) classification structure for "drugs" and "devices." The last major modification to these terms was in 1976, with the enactment of the Medical Device Amendments. There are serious practical differences for a classification as a drug or device in terms of time to market and research. Drugs are classified, primarily, as acting by "chemical action." We lay out some legal, philosophic, and scientific tools that serve to provide a useful, as well as legally and scientifically faithful, distinction between drugs and devices for the purpose of regulatory classification. These issues we raise are worth the consideration of anyone who is interested in the regulation of nano-products or other novel technologies.

Synthesis and size classification of metal oxide nanoparticles for biomedical applications

NASA Astrophysics Data System (ADS)

Atsumi, Takashi; Jeyadevan, Balachandran; Sato, Yoshinori; Tamura, Kazuchika; Aiba, Setsuya; Tohji, Kazuyuki

2004-12-01

Magnetic nanoparticles are considered for biomedical applications, such as the medium in magnetic resonance imaging, hyperthermia, drug delivery, and for the purification or classification of DNA or virus. The performance of magnetic nanoparticles in biomedical application such as hyperthermia depends very much on the magnetic properties, size and size distribution. We briefly described the basic idea behind their use in drug delivery, magnetic separation and hyperthermia and discussed the prerequisite properties magnetic particles for biomedical applications. Finally reported the synthesis and classification scheme to prepare magnetite (Fe3O4) nanoparticles with narrow size distribution for magnetic fluid hyperthermia.

GalenOWL: Ontology-based drug recommendations discovery

PubMed Central

2012-01-01

Background Identification of drug-drug and drug-diseases interactions can pose a difficult problem to cope with, as the increasingly large number of available drugs coupled with the ongoing research activities in the pharmaceutical domain, make the task of discovering relevant information difficult. Although international standards, such as the ICD-10 classification and the UNII registration, have been developed in order to enable efficient knowledge sharing, medical staff needs to be constantly updated in order to effectively discover drug interactions before prescription. The use of Semantic Web technologies has been proposed in earlier works, in order to tackle this problem. Results This work presents a semantic-enabled online service, named GalenOWL, capable of offering real time drug-drug and drug-diseases interaction discovery. For enabling this kind of service, medical information and terminology had to be translated to ontological terms and be appropriately coupled with medical knowledge of the field. International standards such as the aforementioned ICD-10 and UNII, provide the backbone of the common representation of medical data, while the medical knowledge of drug interactions is represented by a rule base which makes use of the aforementioned standards. Details of the system architecture are presented while also giving an outline of the difficulties that had to be overcome. A comparison of the developed ontology-based system with a similar system developed using a traditional business logic rule engine is performed, giving insights on the advantages and drawbacks of both implementations. Conclusions The use of Semantic Web technologies has been found to be a good match for developing drug recommendation systems. Ontologies can effectively encapsulate medical knowledge and rule-based reasoning can capture and encode the drug interactions knowledge. PMID:23256945

In silico and in vitro methods to optimize the performance of experimental gastroretentive floating mini-tablets.

PubMed

Eberle, Veronika A; Häring, Armella; Schoelkopf, Joachim; Gane, Patrick A C; Huwyler, Jörg; Puchkov, Maxim

2016-01-01

Development of floating drug delivery systems (FDDS) is challenging. To facilitate this task, an evaluation method was proposed, which allows for a combined investigation of drug release and flotation. It was the aim of the study to use functionalized calcium carbonate (FCC)-based lipophilic mini-tablet formulations as a model system to design FDDS with a floating behavior characterized by no floating lag time, prolonged flotation and loss of floating capability after complete drug release. Release of the model drug caffeine from the mini-tablets was assessed in vitro by a custom-built stomach model. A cellular automata-based model was used to simulate tablet dissolution. Based on the in silico data, floating forces were calculated and analyzed as a function of caffeine release. Two floating behaviors were identified for mini-tablets: linear decrease of the floating force and maintaining of the floating capability until complete caffeine release. An optimal mini-tablet formulation with desired drug release time and floating behavior was developed and tested. A classification system for a range of varied floating behavior of FDDS was proposed. The FCC-based mini-tablets had an ideal floating behavior: duration of flotation is defined and floating capability decreases after completion of drug release.

The use of biopharmaceutic classification of drugs in drug discovery and development: current status and future extension.

PubMed

Lennernäs, Hans; Abrahamsson, Bertil

2005-03-01

Bioavailability (BA) and bioequivalence (BE) play a central role in pharmaceutical product development and BE studies are presently being conducted for New Drug Applications (NDAs) of new compounds, in supplementary NDAs for new medical indications and product line extensions, in Abbreviated New Drug Applications (ANDAs) of generic products and in applications for scale-up and post-approval changes. The Biopharmaceutics Classification System (BCS) has been developed to provide a scientific approach for classifying drug compounds based on solubility as related to dose and intestinal permeability in combination with the dissolution properties of the oral immediaterelease (IR) dosage form. The aim of the BCS is to provide a regulatory tool for replacing certain BE studies by accurate in-vitro dissolution tests. The aim of this review is to present the status of the BCS and discuss its future application in pharmaceutical product development. The future application of the BCS is most likely increasingly important when the present framework gains increased recognition, which will probably be the case if the BCS borders for certain class II and III drugs are extended. The future revision of the BCS guidelines by the regulatory agencies in communication with academic and industrial scientists is exciting and will hopefully result in an increased applicability in drug development. Finally, we emphasize the great use of the BCS as a simple tool in early drug development to determine the rate-limiting step in the oral absorption process, which has facilitated the information between different experts involved in the overall drug development process. This increased awareness of a proper biopharmaceutical characterization of new drugs may in the future result in drug molecules with a sufficiently high permeability, solubility and dissolution rate, and that will automatically increase the importance of the BCS as a regulatory tool over time.

Oral and transdermal drug delivery systems: role of lipid-based lyotropic liquid crystals.

PubMed

Rajabalaya, Rajan; Musa, Muhammad Nuh; Kifli, Nurolaini; David, Sheba R

2017-01-01

Liquid crystal (LC) dosage forms, particularly those using lipid-based lyotropic LCs (LLCs), have generated considerable interest as potential drug delivery systems. LCs have the physical properties of liquids but retain some of the structural characteristics of crystalline solids. They are compatible with hydrophobic and hydrophilic compounds of many different classes and can protect even biologicals and nucleic acids from degradation. This review, focused on research conducted over the past 5 years, discusses the structural evaluation of LCs and their effects in drug formulations. The structural classification of LLCs into lamellar, hexagonal and micellar cubic phases is described. The structures of these phases are influenced by the addition of surfactants, which include a variety of nontoxic, biodegradable lipids; these also enhance drug solubility. LLC structure influences drug localization, particle size and viscosity, which, in turn, determine drug delivery properties. Through several specific examples, we describe the applications of LLCs in oral and topical drug formulations, the latter including transdermal and ocular delivery. In oral LLC formulations, micelle compositions and the resulting LLC structures can determine drug solubilization and stability as well as intestinal transport and absorption. Similarly, in topical LLC formulations, composition can influence whether the drug is retained in the skin or delivered transdermally. Owing to their enhancement of drug stability and promotion of controlled drug delivery, LLCs are becoming increasingly popular in pharmaceutical formulations.

Oral and transdermal drug delivery systems: role of lipid-based lyotropic liquid crystals

PubMed Central

Rajabalaya, Rajan; Musa, Muhammad Nuh; Kifli, Nurolaini; David, Sheba R

2017-01-01

Liquid crystal (LC) dosage forms, particularly those using lipid-based lyotropic LCs (LLCs), have generated considerable interest as potential drug delivery systems. LCs have the physical properties of liquids but retain some of the structural characteristics of crystalline solids. They are compatible with hydrophobic and hydrophilic compounds of many different classes and can protect even biologicals and nucleic acids from degradation. This review, focused on research conducted over the past 5 years, discusses the structural evaluation of LCs and their effects in drug formulations. The structural classification of LLCs into lamellar, hexagonal and micellar cubic phases is described. The structures of these phases are influenced by the addition of surfactants, which include a variety of nontoxic, biodegradable lipids; these also enhance drug solubility. LLC structure influences drug localization, particle size and viscosity, which, in turn, determine drug delivery properties. Through several specific examples, we describe the applications of LLCs in oral and topical drug formulations, the latter including transdermal and ocular delivery. In oral LLC formulations, micelle compositions and the resulting LLC structures can determine drug solubilization and stability as well as intestinal transport and absorption. Similarly, in topical LLC formulations, composition can influence whether the drug is retained in the skin or delivered transdermally. Owing to their enhancement of drug stability and promotion of controlled drug delivery, LLCs are becoming increasingly popular in pharmaceutical formulations. PMID:28243062

Adverse Drug Events in Children: How Big is the Problem?

PubMed

Zed, Peter J

2015-01-01

Adverse drug events in children is an under appreciated but significant cause of health care contact resulting in ED visits and hospital admissions with associated resource utilization. In recent years we have started to better understand the impact of ADEs in children but there remains significant questions that must be addressed to further improve our understanding of the etiology of these ADEs and strategies for prevention and management. This paper will describe what is known regarding the frequency, severity, preventability and classification of ADEs in children. It will also describe some of the challenges and unanswered questions regarding patient, drug and system factors, which contribute to ADEs in children. Finally, areas of future research will be identified to further improve our understanding of ADEs in children to inform prevention strategies as well as early recognition and management approaches to minimize the significant ADEs can have on children, families and our health care system.

Toward the establishment of standardized in vitro tests for lipid-based formulations, part 4: proposing a new lipid formulation performance classification system.

PubMed

Williams, Hywel D; Sassene, Philip; Kleberg, Karen; Calderone, Marilyn; Igonin, Annabel; Jule, Eduardo; Vertommen, Jan; Blundell, Ross; Benameur, Hassan; Müllertz, Anette; Porter, Christopher J H; Pouton, Colin W

2014-08-01

The Lipid Formulation Classification System Consortium looks to develop standardized in vitro tests and to generate much-needed performance criteria for lipid-based formulations (LBFs). This article highlights the value of performing a second, more stressful digestion test to identify LBFs near a performance threshold and to facilitate lead formulation selection in instances where several LBF prototypes perform adequately under standard digestion conditions (but where further discrimination is necessary). Stressed digestion tests can be designed based on an understanding of the factors that affect LBF performance, including the degree of supersaturation generated on dispersion/digestion. Stresses evaluated included decreasing LBF concentration (↓LBF), increasing bile salt, and decreasing pH. Their capacity to stress LBFs was dependent on LBF composition and drug type: ↓LBF was a stressor to medium-chain glyceride-rich LBFs, but not more hydrophilic surfactant-rich LBFs, whereas decreasing pH stressed tolfenamic acid LBFs, but not fenofibrate LBFs. Lastly, a new Performance Classification System, that is, LBF composition independent, is proposed to promote standardized LBF comparisons, encourage robust LBF development, and facilitate dialogue with the regulatory authorities. This classification system is based on the concept that performance evaluations across three in vitro tests, designed to subject a LBF to progressively more challenging conditions, will enable effective LBF discrimination and performance grading. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

Associations of gender and age groups on the knowledge and use of drug information resources by American pharmacists

PubMed Central

Carvajal, Manuel J.; Clauson, Kevin A.; Gershman, Jennifer; Polen, Hyla H.

Objective To explore knowledge and use of drug information resources by pharmacists and identify patterns influenced by gender and age-group classification. Methods A survey questionnaire was mailed nationwide to 1,000 practitioners working in community (n = 500) and hospital (n = 500) settings who answer drug information questions as part of their expected job responsibilities. Responses pertaining to drug information resource use and knowledge of different types of drug-related queries, resource media preferences, and perceived adequacy of resources maintained in the pharmacy were analyzed by gender and age group. The t statistic was used to test for significant differences of means and percentages between genders and between age groups. Descriptive statistics were used to characterize other findings. Results Gender and age group classification influenced patterns of knowledge and use of drug information resources by pharmacists. They also affected pharmacists’ perceptions of the most common types of questions prompting them to consult a drug information reference, as well as the resources consulted. Micromedex, exclusively available in electronic format, was the most commonly consulted resource overall by pharmacists. Lexi-Comp Online was the leading choice by women, preferred over Micromedex, but was not one of the top two resources selected by men. Conclusions This study successfully identified the influence of gender and age-group classification in assessing drug information resource knowledge and use of general and specific types of drug-related queries. PMID:24155853

Insight into the Development of Dissolution Media for BCS Class II Drugs: A Review from Quality Control and Prediction of In Vivo Performance Perspectives.

PubMed

Wu, Chunnuan; Liu, Yan; He, Zhonggui; Sun, Jin

2016-01-01

To assess in vivo behavior through in vitro method, the dissolution test is mostly used, both for quality control (QC) and for development purpose. In view of the fact that a dissolution test can hardly achieve two goals at the same time, the design of dissolution testing generally varies along with the development stage of drug products and therefore the selection of dissolution media may change with the goals of the dissolution test. To serve the QC purpose, a dissolution medium is designed to provide a sink condition; for development purpose, the dissolution medium is required to simulate the physiological conditions in the gastrointestinal tract as far as possible. In this review, we intended to provide an initial introduction to the various dissolution media applied for QC and formulation development purposes for poorly water soluble drugs. We focused on these methods like addition of cosolvents, surfactants and utilization of biphasic media, applied to provide sink conditions which are difficult to be achieved by simple aqueous buffers for lipophilic drugs, and introduced the development of physiologically relevant media for human and animals like dog and rat with respect to the choice of buffers, bile salts, lipids and so on. In addition, we further discussed the influence of biorelevant dissolution media on the modification of drug Biopharmaceutical Classification System (BCS) classification, especially for BCS class II drugs with low solubility and high permeability, the solubility of which is relatively sensitive to the presence of bile salts and lipids.

A cross-national examination of differences in classification of lifetime alcohol use disorder between DSM-IV and DSM-5: Findings from the World Mental Health Survey

PubMed Central

Slade, Tim; Chiu, Wai-Tat; Glantz, Meyer; Kessler, Ronald C.; Lago, Luise; Sampson, Nancy; Al-Hamzawi, Ali; Florescu, Silvia; Moskalewicz, Jacek; Murphy, Sam; Navarro-Mateu, Fernando; de Galvis, Yolanda Torres; Viana, Maria Carmen; Xavier, Miguel; Degenhardt, Louisa

2016-01-01

Aims To examine the diagnostic overlap in DSM-IV and DSM-5 alcohol use disorder (AUD) and determine the clinical correlates of changing diagnostic status across the two classification systems. Design DSM-IV and DSM-5 definitions of AUD were compared using cross-national community survey data. Setting Nine low-, middle- and high-income countries. Participants/Cases 31,367 respondents to surveys in the World Health Organization World Mental Health Survey Initiative. Measures Composite International Diagnostic Interview, version 3.0 was used to derive DSM-IV and DSM-5 lifetime diagnoses of AUD. Clinical characteristics, also assessed in the surveys, included lifetime DSM-IV anxiety, mood and drug use disorders, lifetime suicidal ideation, plan and attempt, general functional impairment and psychological distress. Findings Compared to DSM-IV AUD (12.3%, SE=0.3%), the DSM-5 definition yielded slightly lower prevalence estimates (10.8%, SE=0.2%). Almost one third (n=802) of all DSM-IV Abuse cases switched to sub-threshold according to DSM-5 and one quarter (n=467) of all DSM-IV diagnostic orphans switched to mild AUD according to DSM-5. New cases of DSM-5 AUD were largely similar to those who maintained their AUD across both classifications. Similarly, new DSM-5 non-cases were similar to those who were sub-threshold across both classifications. The exception to this was with regards to the prevalence of any lifetime drug use disorder. Conclusions In this large cross-national community sample, the prevalence of DSM-5 lifetime AUD was only slightly lower than the prevalence of DSM-IV lifetime AUD. Nonetheless there was considerable diagnostic switching, with a large number of people inconsistently identified across the two DSM classifications. PMID:27426631

Statistical investigation of simulated intestinal fluid composition on the equilibrium solubility of biopharmaceutics classification system class II drugs.

PubMed

Khadra, Ibrahim; Zhou, Zhou; Dunn, Claire; Wilson, Clive G; Halbert, Gavin

2015-01-25

A drug's solubility and dissolution behaviour within the gastrointestinal tract is a key property for successful administration by the oral route and one of the key factors in the biopharmaceutics classification system. This property can be determined by investigating drug solubility in human intestinal fluid (HIF) but this is difficult to obtain and highly variable, which has led to the development of multiple simulated intestinal fluid (SIF) recipes. Using a statistical design of experiment (DoE) technique this paper has investigated the effects and interactions on equilibrium drug solubility of seven typical SIF components (sodium taurocholate, lecithin, sodium phosphate, sodium chloride, pH, pancreatin and sodium oleate) within concentration ranges relevant to human intestinal fluid values. A range of poorly soluble drugs with acidic (naproxen, indomethacin, phenytoin, and piroxicam), basic (aprepitant, carvedilol, zafirlukast, tadalafil) or neutral (fenofibrate, griseofulvin, felodipine and probucol) properties have been investigated. The equilibrium solubility results determined are comparable with literature studies of the drugs in either HIF or SIF indicating that the DoE is operating in the correct space. With the exception of pancreatin, all of the factors individually had a statistically significant influence on equilibrium solubility with variations in magnitude of effect between the acidic and basic or neutral compounds and drug specific interactions were evident. Interestingly for the neutral compounds pH was the factor with the second largest solubility effect. Around one third of all the possible factor combinations showed a significant influence on equilibrium solubility with variations in interaction significance and magnitude of effect between the acidic and basic or neutral compounds. The least number of significant media component interactions were noted for the acidic compounds with three and the greatest for the neutral compounds at seven, with again drug specific effects evident. This indicates that a drug's equilibrium solubility in SIF is influenced depending upon drug type by between eight to fourteen individual or combinations of media components with some of these drug specific. This illustrates the complex nature of these fluids and provides for individual drugs a visualisation of the possible solubility envelope within the gastrointestinal tract, which may be of importance for modelling in vivo behaviour. In addition the results indicate that the design of experiment approach can be employed to provide greater detail of drug solubility behaviour, possible drug specific interactions and influence of variations in gastrointestinal media components due to disease. The approach is also feasible and amenable to adaptation for high throughput screening of drug candidates. Copyright © 2014 Elsevier B.V. All rights reserved.

Drug-related problems in institutionalized, polymedicated elderly patients: opportunities for pharmacist intervention.

PubMed

Silva, Cristina; Ramalho, Célia; Luz, Isabel; Monteiro, Joaquim; Fresco, Paula

2015-04-01

An aging population and the increasing prevalence of chronic diseases have led to the increased use of medicines. Portugal is one of the European countries where more medicines are consumed and the associated expense is higher. Medicines are associated with enormous health benefits but also with the potential to cause illness and death. A drug related problem (DRP) is an "an event or circumstance involving drug therapy that actually or potentially interferes with desired health outcomes". In the U.S., they represent the 4th-6th leading cause of death and have an estimated cost of 130 billion dollars. Moreover, many of these DRP can be avoided. Elderly are at increased risk of DRP due to multiple factors: pluripathology and consequent polypharmacy, complex dosing regimens, pharmacokinetic/pharmacodynamic and functional/cognitive changes. Therefore, this population would be the one who would benefit most from the prevention, detection and control of DRP. The role of the pharmacist as an integral element of health care has been recognized by various international and European organizations. Providing pharmaceutical care as a patient-centered activity, focusing on their needs related to pharmacotherapy, contributes to guarantee that drug expenditure is a good investment, with benefits that outweigh potential risks. To evaluate the need for pharmaceutical care implementation in institutionalized, polymedicated elderly. Descriptive observational cross-sectional study carried out in six Portuguese nursing homes, selected by convenience, in November-December 2013. Each institution selected up to six patients, according to the following inclusion criteria: age ≥65 years, number of medications ≥5 and ability to respond to an interview. All participants signed an informed consent form. Pharmacists carried out a structured interview with each patient and consulted patient medical records to gather demographic data and information on health problems and medications used. To identify DRP, official drug information sources were consulted, and the STOPP and START tool was used. The ATC, the ICD-10 and the PCNE Classification V 6.2 classification systems were used for medicines, health problems and DRP classifications, respectively. For each medicine used, the cheapest equivalent available was also identified. The sample included 31 elderly (64.52 % female, mean age 81.65 ± 6.86). On average, subjects presented a mean of 7.94 ± 2.76 health problems with diseases of the circulatory system being the most common. The sample used a median of ten medicines per patient. Those medicines working in the cardiovascular, nervous and digestive systems were the most frequently used (29.75, 29.43 and 19.30 %, respectively). A total of 484 DRP (median: 15 DRP/patient) was found. The most common DRP were Adverse Drug Event, non-allergic (49.51 %), Drug treatment more costly than necessary (19.11 %), Effect of drug treatment not optimal (14.82 %) and Unnecessary drug treatment (6.16 %). The most cost-effective proposal, would lead to a saving of 3,950/year in the studied sample. These results reinforce the need for the implementation of pharmaceutical care services to institutionalized elderly, necessary to improve medicines efficacy and safety, better clinical outcomes and cost reduction.

Abuse-deterrent formulations: part 1 - development of a formulation-based classification system.

PubMed

Mastropietro, David J; Omidian, Hossein

2015-02-01

Strategies have been implemented to decrease the large proportion of individuals misusing abusable prescription medications. Abuse-deterrent formulations (ADFs) have been grown to incorporate many different technologies that still lack a systematic naming and organizational nomenclature. Without a proper classification system, it has been challenging to properly identify ADFs, study and determine common traits or characteristics and simplify communication within the field. This article introduces a classification system for all ADF approaches and examines the physical, chemical and pharmacological characteristics of a formulation by placing them into primary, secondary and tertiary categories. Primary approaches block tampering done directly to the product. Secondary approaches work in vivo after the product is administered. Tertiary approaches use materials that discourage abuse but do not stop tampering. Part 2 of this article discusses proprietary technologies, patents and products utilizing primary approaches. Drug products using opioid antagonists and aversive agents have been seen over the past few decades to discourage primarily overuse and injection. However, innovation in formulation development has introduced products capable of deterring multiple forms of tampering and abuse. Often, this is accomplished using known excipients and manufacturing methods that are repurposed to prevent crushing, extraction and syringeability.

Drugs in Mental Retardation: Treatment or Tragedy?

ERIC Educational Resources Information Center

Aman, Michael G.

1985-01-01

Treatment of mentally retarded persons with psychotropic and anticonvulsant drugs is discussed in terms of drug classification, rationale for use, attitudes toward use, and clinical research findings. The literature on neuroleptic, anticonvulsant, anxiolytic, and cerebral stimulant drugs is summarized. Controversial reports that some medications…

Boosting drug named entity recognition using an aggregate classifier.

PubMed

Korkontzelos, Ioannis; Piliouras, Dimitrios; Dowsey, Andrew W; Ananiadou, Sophia

2015-10-01

Drug named entity recognition (NER) is a critical step for complex biomedical NLP tasks such as the extraction of pharmacogenomic, pharmacodynamic and pharmacokinetic parameters. Large quantities of high quality training data are almost always a prerequisite for employing supervised machine-learning techniques to achieve high classification performance. However, the human labour needed to produce and maintain such resources is a significant limitation. In this study, we improve the performance of drug NER without relying exclusively on manual annotations. We perform drug NER using either a small gold-standard corpus (120 abstracts) or no corpus at all. In our approach, we develop a voting system to combine a number of heterogeneous models, based on dictionary knowledge, gold-standard corpora and silver annotations, to enhance performance. To improve recall, we employed genetic programming to evolve 11 regular-expression patterns that capture common drug suffixes and used them as an extra means for recognition. Our approach uses a dictionary of drug names, i.e. DrugBank, a small manually annotated corpus, i.e. the pharmacokinetic corpus, and a part of the UKPMC database, as raw biomedical text. Gold-standard and silver annotated data are used to train maximum entropy and multinomial logistic regression classifiers. Aggregating drug NER methods, based on gold-standard annotations, dictionary knowledge and patterns, improved the performance on models trained on gold-standard annotations, only, achieving a maximum F-score of 95%. In addition, combining models trained on silver annotations, dictionary knowledge and patterns are shown to achieve comparable performance to models trained exclusively on gold-standard data. The main reason appears to be the morphological similarities shared among drug names. We conclude that gold-standard data are not a hard requirement for drug NER. Combining heterogeneous models build on dictionary knowledge can achieve similar or comparable classification performance with that of the best performing model trained on gold-standard annotations. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

The impact of cardiovascular drugs on the efficacy of local anesthesia in dentistry.

PubMed

Milosavljevic, Мarko J; Jankovic, Slobodan M

2016-12-01

Drugs used chronically by patients with diseases of the cardiovascular system (group C of the ATC classification) may act on adrenergic receptors and/or certain ion channels, which gives them the potential to interact with the action of local dental anesthetics. The aim of the study was to investigate the effect of systemically administered chronic cardiovascular medication (oral route) on the efficacy of intraoral local anesthesia in patients with diseases of the cardiovascular system. This was a prospective cohort study which analyzed the efficacy of local terminal anesthesia (onset of anesthesia, duration anesthetized area) in the upper jaw of 70 patients: 40 patients on medication for cardiovascular system disorders and 30 patients who were not using these drugs (the control group). The following cardiovascular drugs were used: beta blockers, angiotensin converting enzyme inhibitors, calcium channel blockers, vasodilatators, diuretics, angiotensin receptor blockers, antiarrhythmics, statins and alfa blockers. The onset of anesthesia on the vestibular side was faster in those taking cardiovascular drugs (40.50±19.87 s) than the control patients (58.93±31.07 s; P = 0.004) and duration of anesthesia on this side was shorter. Although the difference was not significant, it was evident that on vestibular and palatal side the anesthetized area was more rapidly reduced in the patients taking cardiovascular drugs. The duration of cardiovascular therapy also had a significant impact on the anesthetized area. Drugs acting on cardiovascular system may influence the effect of local anesthetics used in dentistry, possibly through interaction with autonomic receptors and ion channels.

Application of Snyder-Dolan Classification Scheme to the Selection of “Orthogonal” Columns for Fast Screening for Illicit Drugs and Impurity Profiling of Pharmaceuticals - I. Isocratic Elution

PubMed Central

Fan, Wenzhe; Zhang, Yu; Carr, Peter W.; Rutan, Sarah C.; Dumarey, Melanie; Schellinger, Adam P.; Pritts, Wayne

2011-01-01

Fourteen judiciously selected reversed-phase columns were tested with 18 cationic drug solutes under the isocratic elution conditions advised in the Snyder-Dolan (S-D) hydrophobic subtraction method of column classification. The standard errors (S.E.) of the least squares regressions of log k′ vs. log k′REF were obtained for a given column against a reference column and used to compare and classify columns based on their selectivity. The results are consistent with those obtained with a study of the 16 test solutes recommended by Snyder and Dolan. To the extent that these drugs are representative these results show that the S-D classification scheme is also generally applicable to pharmaceuticals under isocratic conditions. That is, those columns judged to be similar based on the S-D 16 solutes were similar based on the 18 drugs; furthermore those columns judged to have significantly different selectivities based on the 16 S-D probes appeared to be quite different for the drugs as well. Given that the S-D method has been used to classify more than 400 different types of reversed phases the extension to cationic drugs is a significant finding. PMID:19698948

Balance System

NASA Technical Reports Server (NTRS)

1988-01-01

TherEx Inc.'s AT-1 Computerized Ataxiameter precisely evaluates posture and balance disturbances that commonly accompany neurological and musculoskeletal disorders. Complete system includes two-strain gauged footplates, signal conditioning circuitry, a computer monitor, printer and a stand-alone tiltable balance platform. AT-1 serves as assessment tool, treatment monitor, and rehabilitation training device. It allows clinician to document quantitatively the outcome of treatment and analyze data over time to develop outcome standards for several classifications of patients. It can evaluate specifically the effects of surgery, drug treatment, physical therapy or prosthetic devices.

Network medicine in disease analysis and therapeutics.

PubMed

Chen, B; Butte, A J

2013-12-01

Two parallel trends are occurring in drug discovery. The first is that we are moving away from a symptom-based disease classification system to a system based on molecules and molecular states. The second is that we are shifting from targeting a single molecule toward targeting multiple molecules, pathways, or networks. Network medicine is an approach to understanding disease and discovering therapeutics looking at many molecules and how they interrelate, and it may play a critical role in the adoption of both trends.

Enhanced Patient Expectant and Antiemetic Drug Efficacy

DTIC Science & Technology

1999-07-01

Breast Cancer Nausea and Vomiting Expectancy Patient Information Antiemetic Side Effect 15. NUMBER OF PAGES 15 16. PRICE CODE 17. SECURITY ...CLASSIFICATION OF REPORT Unclassified 18. SECURITY CLASSIFICATION OF THIS PAGE Unclassified 19. SECURITY CLASSIFICATION OF ABSTRACT...5-HT3 receptor antagonist class of antiemetics (ondansetron, granisetron , tropisitron) have greatly reduced chemotherapy-related vomiting, this has

76 FR 69034 - Microbiology Devices; Classification of In Vitro Diagnostic Device for Yersinia Species Detection

Federal Register 2010, 2011, 2012, 2013, 2014

2011-11-07

... Drug Administration 21 CFR Part 866 Microbiology Devices; Classification of In Vitro Diagnostic Device... CFR Part 866 [Docket No. FDA-2011-N-0729] Microbiology Devices; Classification of In Vitro Diagnostic... of the Microbiology Devices Advisory Panel (the panel). FDA is publishing in this document the...

Cold atmospheric pressure plasma for treatment of chronic wounds: drug or medical device?

PubMed

Kramer, A; Conway, B R; Meissner, K; Scholz, F; Rauch, B H; Moroder, A; Ehlers, A; Meixner, A J; Heidecke, C-D; Partecke, L I; Kietzmann, M; Assadian, O

2017-08-02

The use of cold atmospheric pressure plasma (CAPP) as a new therapeutic option to aid the healing of chronic wounds appears promising. Currently, uncertainty exists regarding their classification as medical device or medical drug. Because the classification of CAPP has medical, legal, and economic consequences as well as implications for the level of preclinical and clinical testing, the correct classification is not an academic exercise, but an ethical need. A multidisciplinary team of physicians, surgeons, pharmacists, physicists and lawyers has analysed the physical and technical characteristics as well as legal conditions of the biological action of CAPP. It was concluded that the mode of action of the locally generated CAPP, with its main active components being different radicals, is pharmacological and not physical in nature. Depending on the intended use, CAPP should be classified as a drug, which is generated by use of a medical device directly at the point of therapeutic application.

78 FR 24754 - Guidance for Industry on Regulatory Classification of Pharmaceutical Co-Crystals; Availability

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-26

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-D-0800... and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug Administration (FDA) is... this guidance to the Division of Drug Information, Center for Drug Evaluation and Research, Food and...

Comparative evaluation of the drug interaction screening programs MediQ and ID PHARMA CHECK in neurological inpatients.

PubMed

Zorina, Olesya I; Haueis, Patrick; Semmler, Alexander; Marti, Isabelle; Gonzenbach, Roman R; Guzek, Markus; Kullak-Ublick, Gerd A; Weller, Michael; Russmann, Stefan

2012-08-01

The comparative evaluation of clinical decision support software (CDSS) programs regarding their sensitivity and positive predictive value for the identification of clinically relevant drug interactions. In this research, we used a cross-sectional study that identified potential drug interactions using the CDSS MediQ and the ID PHARMA CHECK in 484 neurological inpatients. Interactions were reclassified according to the Zurich Interaction System, a multidimensional classification that incorporates the Operational Classification of Drug Interactions. In 484 patients with 2812 prescriptions, MediQ and ID PHARMA CHECK generated a total of 1759 and 1082 alerts, respectively. MediQ identified 658 unique potentially interacting combinations, 8 classified as "high danger," 164 as "average danger," and 486 as "low danger." ID PHARMA CHECK detected 336 combinations assigned to one or several of 12 risk and management categories. Altogether, both CDSS issued alerts relating to 808 unique potentially interacting combinations. According to the Zurich Interaction System, 6 of these were contraindicated, 25 were provisionally contraindicated, 190 carried a conditional risk, and 587 had a minimal risk of adverse events. The positive predictive value for alerts having at least a conditional risk was 0.24 for MediQ and 0.48 for ID PHARMA CHECK. CDSS showed major differences in the identification and grading of interactions, and many interactions were only identified by one of the two CDSS. For both programs, only a small proportion of all identified interactions appeared clinically relevant, and the selected display of alerts that imply management changes is a key issue in the further development and local setup of such programs. Copyright © 2012 John Wiley & Sons, Ltd.

Chemical Proteomics and Structural Biology Define EPHA2 Inhibition by Clinical Kinase Drugs.

PubMed

Heinzlmeir, Stephanie; Kudlinzki, Denis; Sreeramulu, Sridhar; Klaeger, Susan; Gande, Santosh Lakshmi; Linhard, Verena; Wilhelm, Mathias; Qiao, Huichao; Helm, Dominic; Ruprecht, Benjamin; Saxena, Krishna; Médard, Guillaume; Schwalbe, Harald; Kuster, Bernhard

2016-12-16

The receptor tyrosine kinase EPHA2 (Ephrin type-A receptor 2) plays important roles in oncogenesis, metastasis, and treatment resistance, yet therapeutic targeting, drug discovery, or investigation of EPHA2 biology is hampered by the lack of appropriate inhibitors and structural information. Here, we used chemical proteomics to survey 235 clinical kinase inhibitors for their kinase selectivity and identified 24 drugs with submicromolar affinities for EPHA2. NMR-based conformational dynamics together with nine new cocrystal structures delineated drug-EPHA2 interactions in full detail. The combination of selectivity profiling, structure determination, and kinome wide sequence alignment allowed the development of a classification system in which amino acids in the drug binding site of EPHA2 are categorized into key, scaffold, potency, and selectivity residues. This scheme should be generally applicable in kinase drug discovery, and we anticipate that the provided information will greatly facilitate the development of selective EPHA2 inhibitors in particular and the repurposing of clinical kinase inhibitors in general.

21 CFR 884.5435 - Unscented menstrual pad.

Code of Federal Regulations, 2010 CFR

2010-04-01

... those with added antimicrobial agents or other drugs. (b) Classification. Class I (general controls... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Unscented menstrual pad. 884.5435 Section 884.5435 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED...

Scientific perspectives on extending the provision for waivers of in vivo bioavailability and bioequivalence studies for drug products containing high solubility-low permeability drugs (BCS-Class 3).

PubMed

Stavchansky, Salomon

2008-06-01

Recently, there has been increased interest in extending the provision for waivers of in vivo bioavailability and bioequivalence (BA-BE) studies that appeared in the guidance published by the Food and Drug Administration (FDA) (1) to pharmaceutical products containing Class 3 drugs (High solubility-Low Permeability). The extension of the Biopharmaceutics Classification System (BCS) to Class 3 drugs is meritorious because of its impact on public health policy considerations. The rate limiting step in the absorption of Class 3 drugs is the permeability through the intestinal membrane. This commentary will focus its attention on the scientific considerations which need to be examined to assess the risk and the benefit prior to granting a waiver of in vivo bioavailability and/or bioequivalence studies for Class 3 drugs. It will examine the forces affecting the interconnectivity of the neuronal, immunological and hormonal systems in the gastrointestinal tract that may affect its permeability and functionality. It will also challenge the assumption that in vitro dissolution and in vitro permeability studies in tissue cultures in the presence and absence of excipients are good predictors for in vivo dissolution and in vivo permeability which are at the heart of the BCS.

Purely in silico BCS classification: science based quality standards for the world's drugs.

PubMed

Dahan, Arik; Wolk, Omri; Kim, Young Hoon; Ramachandran, Chandrasekharan; Crippen, Gordon M; Takagi, Toshihide; Bermejo, Marival; Amidon, Gordon L

2013-11-04

BCS classification is a vital tool in the development of both generic and innovative drug products. The purpose of this work was to provisionally classify the world's top selling oral drugs according to the BCS, using in silico methods. Three different in silico methods were examined: the well-established group contribution (CLogP) and atom contribution (ALogP) methods, and a new method based solely on the molecular formula and element contribution (KLogP). Metoprolol was used as the benchmark for the low/high permeability class boundary. Solubility was estimated in silico using a thermodynamic equation that relies on the partition coefficient and melting point. The validity of each method was affirmed by comparison to reference data and literature. We then used each method to provisionally classify the orally administered, IR drug products found in the WHO Model list of Essential Medicines, and the top-selling oral drug products in the United States (US), Great Britain (GB), Spain (ES), Israel (IL), Japan (JP), and South Korea (KR). A combined list of 363 drugs was compiled from the various lists, and 257 drugs were classified using the different in silico permeability methods and literature solubility data, as well as BDDCS classification. Lastly, we calculated the solubility values for 185 drugs from the combined set using in silico approach. Permeability classification with the different in silico methods was correct for 69-72.4% of the 29 reference drugs with known human jejunal permeability, and for 84.6-92.9% of the 14 FDA reference drugs in the set. The correlations (r(2)) between experimental log P values of 154 drugs and their CLogP, ALogP and KLogP were 0.97, 0.82 and 0.71, respectively. The different in silico permeability methods produced comparable results: 30-34% of the US, GB, ES and IL top selling drugs were class 1, 27-36.4% were class 2, 22-25.5% were class 3, and 5.46-14% were class 4 drugs, while ∼8% could not be classified. The WHO list included significantly less class 1 and more class 3 drugs in comparison to the countries' lists, probably due to differences in commonly used drugs in developing vs industrial countries. BDDCS classified more drugs as class 1 compared to in silico BCS, likely due to the more lax benchmark for metabolism (70%), in comparison to the strict permeability benchmark (metoprolol). For 185 out of the 363 drugs, in silico solubility values were calculated, and successfully matched the literature solubility data. In conclusion, relatively simple in silico methods can be used to estimate both permeability and solubility. While CLogP produced the best correlation to experimental values, even KLogP, the most simplified in silico method that is based on molecular formula with no knowledge of molecular structure, produced comparable BCS classification to the sophisticated methods. This KLogP, when combined with a mean melting point and estimated dose, can be used to provisionally classify potential drugs from just molecular formula, even before synthesis. 49-59% of the world's top-selling drugs are highly soluble (class 1 and class 3), and are therefore candidates for waivers of in vivo bioequivalence studies. For these drugs, the replacement of expensive human studies with affordable in vitro dissolution tests would ensure their bioequivalence, and encourage the development and availability of generic drug products in both industrial and developing countries.

Metabolic profiling using HPLC allows classification of drugs according to their mechanisms of action in HL-1 cardiomyocytes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Strigun, Alexander; Wahrheit, Judith; Beckers, Simone

Along with hepatotoxicity, cardiotoxic side effects remain one of the major reasons for drug withdrawals and boxed warnings. Prediction methods for cardiotoxicity are insufficient. High content screening comprising of not only electrophysiological characterization but also cellular molecular alterations are expected to improve the cardiotoxicity prediction potential. Metabolomic approaches recently have become an important focus of research in pharmacological testing and prediction. In this study, the culture medium supernatants from HL-1 cardiomyocytes after exposure to drugs from different classes (analgesics, antimetabolites, anthracyclines, antihistamines, channel blockers) were analyzed to determine specific metabolic footprints in response to the tested drugs. Since most drugsmore » influence energy metabolism in cardiac cells, the metabolite 'sub-profile' consisting of glucose, lactate, pyruvate and amino acids was considered. These metabolites were quantified using HPLC in samples after exposure of cells to test compounds of the respective drug groups. The studied drug concentrations were selected from concentration response curves for each drug. The metabolite profiles were randomly split into training/validation and test set; and then analysed using multivariate statistics (principal component analysis and discriminant analysis). Discriminant analysis resulted in clustering of drugs according to their modes of action. After cross validation and cross model validation, the underlying training data were able to predict 50%-80% of conditions to the correct classification group. We show that HPLC based characterisation of known cell culture medium components is sufficient to predict a drug's potential classification according to its mode of action.« less

Do the recommended standards for in vitro biopharmaceutic classification of drug permeability meet the "passive transport" criterion for biowaivers?

PubMed

Žakelj, Simon; Berginc, Katja; Roškar, Robert; Kraljič, Bor; Kristl, Albin

2013-01-01

BCS based biowaivers are recognized by major regulatory agencies. An application for a biowaiver can be supported by or even based on "in vitro" measurements of drug permeability. However, guidelines limit the application of biowaivers to drug substances that are transported only by passive mechanisms. Regarding published permeability data as well as measurements obtained in our institution, one can rarely observe drug substances that conform to this very strict criterion. Therefore, we measured the apparent permeability coefficients of 13 drugs recommended by FDA's Guidance to be used as standards for "in vitro" permeability classification. The asymmetry of permeability data determined for both directions (mucosal-to-serosal and serosalto- mucosal) through the rat small intestine revealed significant active transport for four out of the nine high-permeability standards and for all four low-permeability standard drugs. As could be expected, this asymmetry was abolished at 4°C on rat intestine. The permeability of all nine high-permeability, but none of the low permeability standards, was also much lower when measured with intestinal tissue, Caco-2 cell monolayers or artificial membranes at 4°C compared to standard conditions (37°C). Additionally, concurrent testing of several standard drugs revealed that membrane transport can be affected by the use of internal permeability standards. The implications of the results are discussed regarding the regulatory aspects of biopharmaceutical classification, good practice in drug permeability evaluation and regarding the general relevance of transport proteins with broad specificity in drug absorption.

A comparative study of disease genes and drug targets in the human protein interactome

PubMed Central

2015-01-01

Background Disease genes cause or contribute genetically to the development of the most complex diseases. Drugs are the major approaches to treat the complex disease through interacting with their targets. Thus, drug targets are critical for treatment efficacy. However, the interrelationship between the disease genes and drug targets is not clear. Results In this study, we comprehensively compared the network properties of disease genes and drug targets for five major disease categories (cancer, cardiovascular disease, immune system disease, metabolic disease, and nervous system disease). We first collected disease genes from genome-wide association studies (GWAS) for five disease categories and collected their corresponding drugs based on drugs' Anatomical Therapeutic Chemical (ATC) classification. Then, we obtained the drug targets for these five different disease categories. We found that, though the intersections between disease genes and drug targets were small, disease genes were significantly enriched in targets compared to their enrichment in human protein-coding genes. We further compared network properties of the proteins encoded by disease genes and drug targets in human protein-protein interaction networks (interactome). The results showed that the drug targets tended to have higher degree, higher betweenness, and lower clustering coefficient in cancer Furthermore, we observed a clear fraction increase of disease proteins or drug targets in the near neighborhood compared with the randomized genes. Conclusions The study presents the first comprehensive comparison of the disease genes and drug targets in the context of interactome. The results provide some foundational network characteristics for further designing computational strategies to predict novel drug targets and drug repurposing. PMID:25861037

A comparative study of disease genes and drug targets in the human protein interactome.

PubMed

Sun, Jingchun; Zhu, Kevin; Zheng, W; Xu, Hua

2015-01-01

Disease genes cause or contribute genetically to the development of the most complex diseases. Drugs are the major approaches to treat the complex disease through interacting with their targets. Thus, drug targets are critical for treatment efficacy. However, the interrelationship between the disease genes and drug targets is not clear. In this study, we comprehensively compared the network properties of disease genes and drug targets for five major disease categories (cancer, cardiovascular disease, immune system disease, metabolic disease, and nervous system disease). We first collected disease genes from genome-wide association studies (GWAS) for five disease categories and collected their corresponding drugs based on drugs' Anatomical Therapeutic Chemical (ATC) classification. Then, we obtained the drug targets for these five different disease categories. We found that, though the intersections between disease genes and drug targets were small, disease genes were significantly enriched in targets compared to their enrichment in human protein-coding genes. We further compared network properties of the proteins encoded by disease genes and drug targets in human protein-protein interaction networks (interactome). The results showed that the drug targets tended to have higher degree, higher betweenness, and lower clustering coefficient in cancer Furthermore, we observed a clear fraction increase of disease proteins or drug targets in the near neighborhood compared with the randomized genes. The study presents the first comprehensive comparison of the disease genes and drug targets in the context of interactome. The results provide some foundational network characteristics for further designing computational strategies to predict novel drug targets and drug repurposing.

Fluorescently labeled bevacizumab in human breast cancer: defining the classification threshold

NASA Astrophysics Data System (ADS)

Koch, Maximilian; de Jong, Johannes S.; Glatz, Jürgen; Symvoulidis, Panagiotis; Lamberts, Laetitia E.; Adams, Arthur L. L.; Kranendonk, Mariëtte E. G.; Terwisscha van Scheltinga, Anton G. T.; Aichler, Michaela; Jansen, Liesbeth; de Vries, Jakob; Lub-de Hooge, Marjolijn N.; Schröder, Carolien P.; Jorritsma-Smit, Annelies; Linssen, Matthijs D.; de Boer, Esther; van der Vegt, Bert; Nagengast, Wouter B.; Elias, Sjoerd G.; Oliveira, Sabrina; Witkamp, Arjen J.; Mali, Willem P. Th. M.; Van der Wall, Elsken; Garcia-Allende, P. Beatriz; van Diest, Paul J.; de Vries, Elisabeth G. E.; Walch, Axel; van Dam, Gooitzen M.; Ntziachristos, Vasilis

2017-07-01

In-vivo fluorescently labelled drug (bevacizumab) breast cancer specimen where obtained from patients. We propose a new structured method to determine the optimal classification threshold in targeted fluorescence intra-operative imaging.

21 CFR 864.9050 - Blood bank supplies.

Code of Federal Regulations, 2010 CFR

2010-04-01

... Biologics Evaluation and Research of the Food and Drug Administration. (b) Classification. Class I (general... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Blood bank supplies. 864.9050 Section 864.9050 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED...

21 CFR 864.9050 - Blood bank supplies.

Code of Federal Regulations, 2011 CFR

2011-04-01

... Biologics Evaluation and Research of the Food and Drug Administration. (b) Classification. Class I (general... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Blood bank supplies. 864.9050 Section 864.9050 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED...

21 CFR 884.5460 - Scented or scented deodorized menstrual tampon.

Code of Federal Regulations, 2010 CFR

2010-04-01

... menstrual tampons treated with added antimicrobial agents or other drugs. (b) Classification. Class II... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Scented or scented deodorized menstrual tampon. 884.5460 Section 884.5460 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN...

Enhanced Patient Expectation and Antiemetic Drug Efficacy

DTIC Science & Technology

1999-07-01

NUMBER OF PAGES 15 Breast Cancer Expectancy Antiemetic Nausea and Vomiting Patient Information Side Effect 16. PRICE CODE 17. SECURITY CLASSIFICATION 18... SECURITY CLASSIFICATION OF THIS 19. SECURITY CLASSIFICATION 20. LIMITATION OF ABSTRACT OF REPORT PAGE OF ABSTRACT Unclassified Unclassified...by the introduction of the 5-HT 3 receptor antagonist class of antiemetics (ondansetron, granisetron , tropisitron) have greatly reduced chemotherapy

76 FR 36993 - Medical Devices; Neurological Devices; Clarification of Classification for Human Dura Mater...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-24

...; Clarification of Classification for Human Dura Mater; Technical Amendment AGENCY: Food and Drug Administration... amending the device regulations to clarify the applicability of the device classification for human dura..., human dura mater is now defined under 21 CFR 1271.3(d) as a HCT/P. As such, it is regulated under...

Drug induced hepatotoxicity: data from the Serbian pharmacovigilance database.

PubMed

Petronijevic, Marija; Ilic, Katarina; Suzuki, Ayako

2011-04-01

The main aim of this study was to determine the most frequently reported drugs to the Serbian Pharmacovigilance Database (SPD) with suspected induced hepatotoxicity. Additionally, reasons for the low reporting rate of adverse drug reactions (ADRs) in Serbia were identified. Retrospective observational study of spontaneously reported ADRs recorded in the SPD from January 1995 to December 2008 was performed. The Medical Dictionary for Regulatory Activities (MedDRA) was used to identify cases of hepatobiliary disorders (HD). Drugs were classified using the Anatomical Therapeutic Chemical (ATC) classification. Medline and WHO-UMC databases were used to address specific queries suggested by our results. The questionnaire was used to investigate the health care professionals' knowledge and practice related to spontaneous reporting. Among the 1804 reports of ADRs recorded in the SPD between 1995 and 2008, 70 (3.9%) cases of HD were identified. Drugs most frequently associated with hepatotoxicity were anti-infectives for systemic use, drugs affecting the nervous system, herbal products, hypolipemics, and anticoagulant drugs (26.83, 24.39, 12.20, 9.76, and 8.54% cases, respectively). Four cases (5.71%) of liver injury resulted in death, which accounted for 10.26% of all ADR fatalities reported to the SPD. The main reasons for not reporting ADRs were lack of reporting knowledge (30.26%), well-known ADRs (29.89%), and insecurity about causality relationship (15.50%). Anti-infectives, nervous system drugs, and herbal products were the most common drug classes reported for hepatotoxicity in Serbia. There is a need for additional education about ADRs, and enhanced reporting by health care professionals. Copyright © 2011 John Wiley & Sons, Ltd.

Drug Scene Syllabus, A Manual on Drugs and Volatile Chemical of Potential Abuse.

ERIC Educational Resources Information Center

Johnson, Robert B.; And Others

A brief historical review of attempts to control the abuse of drugs introduces a series of tables listing pertinent information about drugs of potential abuse. Each table provides the common commercial and slang names for the drugs, their medical and legal classification, their potential for emotional and physical dependence, whether the user…

Adverse events caused by potential drug-drug interactions in an intensive care unit of a teaching hospital

PubMed Central

Alvim, Mariana Macedo; da Silva, Lidiane Ayres; Leite, Isabel Cristina Gonçalves; Silvério, Marcelo Silva

2015-01-01

Objective To evaluate the incidence of potential drug-drug interactions in an intensive care unit of a hospital, focusing on antimicrobial drugs. Methods This cross-sectional study analyzed electronic prescriptions of patients admitted to the intensive care unit of a teaching hospital between January 1 and March 31, 2014 and assessed potential drug-drug interactions associated with antimicrobial drugs. Antimicrobial drug consumption levels were expressed in daily doses per 100 patient-days. The search and classification of the interactions were based on the Micromedex® system. Results The daily prescriptions of 82 patients were analyzed, totaling 656 prescriptions. Antimicrobial drugs represented 25% of all prescription drugs, with meropenem, vancomycin and ceftriaxone being the most prescribed medications. According to the approach of daily dose per 100 patient-days, the most commonly used antimicrobial drugs were cefepime, meropenem, sulfamethoxazole + trimethoprim and ciprofloxacin. The mean number of interactions per patient was 2.6. Among the interactions, 51% were classified as contraindicated or significantly severe. Highly significant interactions (clinical value 1 and 2) were observed with a prevalence of 98%. Conclusion The current study demonstrated that antimicrobial drugs are frequently prescribed in intensive care units and present a very high number of potential drug-drug interactions, with most of them being considered highly significant. PMID:26761473

Pharmaceutical consumption and cost in patients with dementia: A longitudinal study by the Registry of Dementias of Girona (ReDeGi) in Catalonia (Spain).

PubMed

Turró-Garriga, O; Calvó-Perxas, L; Albaladejo, R; Alsina, E; Cuy, J M; Llinàs-Reglà, J; Roig, A M; Serena, J; Vallmajó, N; Viñas, M; López-Pousa, S; Vilalta-Franch, J; Garre-Olmo, J

2015-01-01

Drug spending increases exponentially from the age of 65-70 years, and dementia is one of the diseases significantly contributing to this increase. Our aim was to describe pharmaceutical consumption and cost in patients with dementia, using the Anatomical Therapeutic Chemical (ATC) classification system. We also assessed the evolution of costs and consumption, and the variables associated to this evolution during three years. Three years prospective cohort study using data from the ReDeGi and the Health Region of Girona (HRG) Pharmacy Unit database from the Public Catalan Healthcare Service (PCHS). Frequency of consumption and costs of ATC categories of drugs were calculated. Sample of 869 patients with dementia, most of them with a diagnosis of degenerative dementia (72.6%), and in a mild stage of the disease (68.2%). Central nervous system (CNS) drugs had the highest consumption rate (97.2%), followed by metabolic system drugs (80.1%), and cardiovascular system drugs (75.4%). Total pharmaceutical cost was of 2124.8 € per patient/year (standard deviation (SD)=1018.5 €), and spending on CNS drugs was 55.5% of the total cost. After 36 months, pharmaceutical cost increased in 694.9 € (SD=1741.9), which was associated with dementia severity and institutionalization at baseline. Pharmaceutical consumption and costs are high in patients with dementia, and they increase with time, showing an association with baseline dementia severity and institutionalization. CNS drugs are the pharmaceuticals with highest prescription rates and associated costs. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Integrating in Silico and in Vitro Approaches To Predict Drug Accessibility to the Central Nervous System.

PubMed

Zhang, Yan-Yan; Liu, Houfu; Summerfield, Scott G; Luscombe, Christopher N; Sahi, Jasminder

2016-05-02

Estimation of uptake across the blood-brain barrier (BBB) is key to designing central nervous system (CNS) therapeutics. In silico approaches ranging from physicochemical rules to quantitative structure-activity relationship (QSAR) models are utilized to predict potential for CNS penetration of new chemical entities. However, there are still gaps in our knowledge of (1) the relationship between marketed human drug derived CNS-accessible chemical space and preclinical neuropharmacokinetic (neuroPK) data, (2) interpretability of the selected physicochemical descriptors, and (3) correlation of the in vitro human P-glycoprotein (P-gp) efflux ratio (ER) and in vivo rodent unbound brain-to-blood ratio (Kp,uu), as these are assays routinely used to predict clinical CNS exposure, during drug discovery. To close these gaps, we explored the CNS druglike property boundaries of 920 market oral drugs (315 CNS and 605 non-CNS) and 846 compounds (54 CNS drugs and 792 proprietary GlaxoSmithKline compounds) with available rat Kp,uu data. The exact permeability coefficient (Pexact) and P-gp ER were determined for 176 compounds from the rat Kp,uu data set. Receiver operating characteristic curves were performed to evaluate the predictive power of human P-gp ER for rat Kp,uu. Our data demonstrates that simple physicochemical rules (most acidic pKa ≥ 9.5 and TPSA < 100) in combination with P-gp ER < 1.5 provide mechanistic insights for filtering BBB permeable compounds. For comparison, six classification modeling methods were investigated using multiple sets of in silico molecular descriptors. We present a random forest model with excellent predictive power (∼0.75 overall accuracy) using the rat neuroPK data set. We also observed good concordance between the structural interpretation results and physicochemical descriptor importance from the Kp,uu classification QSAR model. In summary, we propose a novel, hybrid in silico/in vitro approach and an in silico screening model for the effective development of chemical series with the potential to achieve optimal CNS exposure.

Blood alcohol analysis alone versus comprehensive toxicological analysis - Systematic investigation of missed co-ingested other drugs in suspected alcohol-impaired drivers.

PubMed

Steuer, Andrea E; Eisenbeiss, Lisa; Kraemer, Thomas

2016-10-01

Driving under the influence of alcohol and/or drugs (DUID) is a safety issue of increasing public concern. When a police officer has reasonable grounds to classify a driver as impaired, he may arrange for a blood sample to be taken. In many countries, alcohol analysis only is ordered if impairment is suspected to be exclusively due to alcohol while comprehensive toxicological screening will be performed if additional suspicion for other illegal drugs of abuse (DoA) or medicinal drugs is on hand. The aim of the present study was firstly to evaluate whether signs of impairment can be differentiated to be caused by alcohol alone or a combination of alcohol and other driving-impairing drugs and secondly to which extent additional drugs are missed in suspected alcohol-impaired drivers. A total of 293 DUID cases (negative n=41; alcohol positive only, n=131; alcohol+active drug positive, n=121) analyzed in 2015 in the Canton of Zurich were evaluated for their documented impairment symptoms by translating these into a severity score and comparing them applying principle component analysis (PCA). Additional 500 cases suspected for alcohol-impaired driving only were reanalyzed using comprehensive LC-MS/MS screening methods covering about 1500 compounds. Drugs detected were classified for severity of driving impairment using the classification system established in the DRUID study of the European Commission. As partly expected from the pharmacological and toxicological point of view, PCA analysis revealed no differences between signs of impairment caused by alcohol alone and those caused by alcohol plus at least one active drug. Breaking it down to different blood alcohol concentration ranges, only between 0.3 and 0.5g/kg trends could be observed in terms of more severe impairment for combined alcohol and drug intake. In the 500 blood samples retrospectively analyzed in this study, a total of 330 additional drugs could be detected; in some cases up to 9 co-ingested ones. In total, 37% of all cases were positive for additional drugs, thereby 15% of classic DoAs and further 9% of prescription drugs with a severe risk to cause driving impairment based on the DRUID classification system. A decision whether signs of impairment are related to alcohol alone or to the combination of alcohol and other drugs is impossible. Taking into consideration the high rate of missed drugs in DUI cases, police should think about increasing the number of DUID cases in countries were sanctioning differs between alcohol and alcohol plus drug impaired driving. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Global Health: Epilepsy.

PubMed

Ali, Amza

2018-04-01

Epilepsy is a frequently misunderstood and highly stigmatized condition. Major treatment gaps exist across the world, most so in areas of financial constraint. Classification permits the best approaches to treatment and to ascertaining prognosis. The International League Against Epilepsy's new classification system emphasizes clinical aspects and utilizes all available resources to determine whether it is a focal or generalized epilepsy. The most important tools are a careful history, clinical examination, electroencephalography, and appropriate neuroimaging. Inadequate, delayed, and incomplete evaluation may lead to misdiagnosis and costly mismanagement. Treatment is generally pharmacological, with approximately 20 to 30% of patients eventually proving refractory to medications and thus becoming potential surgical candidates. The type of epilepsy, age, gender, comorbidities, drug interactions, and drug cost are important factors in choosing an antiepileptic drug (AED). The teratogenic potential of some AEDs, weight gain, and menstrual hormone-related issues are important considerations in women. The impact of AEDs on bone health is critical in all age groups, particularly in the elderly. Psychiatric problems, mostly depression and anxiety, can have a great impact on seizure control and overall quality of life. Finally, effective partnerships and collaborations can bring resources, both human and financial, to regions that would otherwise find it impossible to effect change on their own. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

A health record integrated clinical decision support system to support prescriptions of pharmaceutical drugs in patients with reduced renal function: design, development and proof of concept.

PubMed

Shemeikka, Tero; Bastholm-Rahmner, Pia; Elinder, Carl-Gustaf; Vég, Anikó; Törnqvist, Elisabeth; Cornelius, Birgitta; Korkmaz, Seher

2015-06-01

To develop and verify proof of concept for a clinical decision support system (CDSS) to support prescriptions of pharmaceutical drugs in patients with reduced renal function, integrated in an electronic health record system (EHR) used in both hospitals and primary care. A pilot study in one geriatric clinic, one internal medicine admission ward and two outpatient healthcare centers was evaluated with a questionnaire focusing on the usefulness of the CDSS. The usage of the system was followed in a log. The CDSS is considered to increase the attention on patients with impaired renal function, provides a better understanding of dosing and is time saving. The calculated glomerular filtration rate (eGFR) and the dosing recommendation classification were perceived useful while the recommendation texts and background had been used to a lesser extent. Few previous systems are used in primary care and cover this number of drugs. The global assessment of the CDSS scored high but some elements were used to a limited extent possibly due to accessibility or that texts were considered difficult to absorb. Choosing a formula for the calculation of eGFR in a CDSS may be problematic. A real-time CDSS to support kidney-related drug prescribing in both hospital and outpatient settings is valuable to the physicians. It has the potential to improve quality of drug prescribing by increasing the attention on patients with renal insufficiency and the knowledge of their drug dosing. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Evaluation of new antiemetic agents and definition of antineoplastic agent emetogenicity--an update.

PubMed

Grunberg, Steven M; Osoba, David; Hesketh, Paul J; Gralla, Richard J; Borjeson, Sussanne; Rapoport, Bernardo L; du Bois, Andreas; Tonato, Maurizio

2005-02-01

Development of effective antiemetic therapy depends upon an understanding of both the antiemetic agents and the emetogenic challenges these agents are designed to address. New potential antiemetic agents should be studied in an orderly manner, proceeding from phase I to phase II open-label trials and then to randomized double-blind phase III trials comparing new agents and regimens to best standard therapy. Use of placebos in place of antiemetic therapy against highly or moderately emetogenic chemotherapy is unacceptable. Nausea and vomiting should be evaluated separately and for both the acute and delayed periods. Defining the emetogenicity of new antineoplastic agents is a challenge, since such data are often not reliably recorded during early drug development. A four-level classification system is proposed for emetogenicity of intravenous antineoplastic agents. A separate four-level classification system for emetogenicity of oral antineoplastic agents, which are often given over an extended period of time, is also proposed.

76 FR 43582 - Cardiovascular Devices; Classification of Electrocardiograph Electrodes

Federal Register 2010, 2011, 2012, 2013, 2014

2011-07-21

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration 21 CFR Part 870 [Docket No. FDA-2007-N-0092] (Formerly Docket No. 2007N-0308) Cardiovascular Devices; Classification of... amended as follows: [[Page 43585

76 FR 68767 - Draft Guidance for Industry and Food and Drug Administration Staff; De Novo Classification...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-11-07

... and Radiological Health (CDRH) guidance documents is available at http://www.fda.gov/MedicalDevices... ``De Novo Classification Process (Evaluation of Automatic Class III Designation)'' from CDRH you may...

Dissolution properties of co-amorphous drug-amino acid formulations in buffer and biorelevant media.

PubMed

Heikkinen, A T; DeClerck, L; Löbmann, K; Grohganz, H; Rades, T; Laitinen, R

2015-07-01

Co-amorphous formulations, particularly binary drug-amino acid mixtures, have been shown to provide enhanced dissolution for poorly-soluble drugs and improved physical stability of the amorphous state. However, to date the dissolution properties (mainly intrinsic dissolution rate) of the co-amorphous formulations have been tested only in buffers and their supersaturation ability remain unexplored. Consequently, dissolution studies in simulated intestinal fluids need to be conducted in order to better evaluate the potential of these systems in increasing the oral bioavailability of biopharmaceutics classification system class II drugs. In this study, solubility and dissolution properties of the co-amorphous simvastatin-lysine, gibenclamide-serine, glibenclamide-threonine and glibenclamide-serine-threonine were studied in phosphate buffer pH 7.2 and biorelevant media (fasted and fed state simulated intestinal fluids (FaSSIF and FeSSIF, respectively)). The co-amorphous formulations were found to provide a long-lasting supersaturation and improve the dissolution of the drugs compared to the crystalline and amorphous drugs alone in buffer. Similar improvement, but in lesser extent, was observed in biorelevant media suggesting that a dissolution advantage observed in aqueous buffers may overestimate the advantage in vivo. However, the results show that, in addition to stability advantage shown earlier, co-amorphous drug-amino acid formulations provide dissolution advantage over crystalline drugs in both aqueous and biorelevant conditions.

Detection of dechallenge in spontaneous reporting systems: a comparison of Bayes methods.

PubMed

Banu, A Bazila; Alias Balamurugan, S Appavu; Thirumalaikolundusubramanian, Ponniah

2014-01-01

Dechallenge is a response observed for the reduction or disappearance of adverse drug reactions (ADR) on withdrawal of a drug from a patient. Currently available algorithms to detect dechallenge have limitations. Hence, there is a need to compare available new methods. To detect dechallenge in Spontaneous Reporting Systems, data-mining algorithms like Naive Bayes and Improved Naive Bayes were applied for comparing the performance of the algorithms in terms of accuracy and error. Analyzing the factors of dechallenge like outcome and disease category will help medical practitioners and pharmaceutical industries to determine the reasons for dechallenge in order to take essential steps toward drug safety. Adverse drug reactions of the year 2011 and 2012 were downloaded from the United States Food and Drug Administration's database. The outcome of classification algorithms showed that Improved Naive Bayes algorithm outperformed Naive Bayes with accuracy of 90.11% and error of 9.8% in detecting the dechallenge. Detecting dechallenge for unknown samples are essential for proper prescription. To overcome the issues exposed by Naive Bayes algorithm, Improved Naive Bayes algorithm can be used to detect dechallenge in terms of higher accuracy and minimal error.

[Counterfeit pharmaceuticals in Peru].

PubMed

Exebio, Luis E Moreno; Rodríguez, Javier; Sayritupac, Freddy

2010-02-01

To determine the quantity of counterfeit pharmaceutical drugs found by the National Quality Control Center (Centro Nacional de Control de Calidad (CNCC), Instituto Nacional de Salud, Peru) during the period from 2005&2008, and the types and properties of these drugs. A form was created to amass the relevant data collected directly from CNCC reports. The reports underwent a review and analysis process, and where counterfeiting was confirmed, it was categorized by type into one of four groups. The percentage of counterfeit drugs relative to the total drugs evaluated was: 3.0% in 2005, 5.0% in 2006, 7.3% in 2007, and 9.2% in 2008. The main groups of counterfeit drugs, classified according to the World Health Organization Anatomical Therapeutic Chemical Classification System, were: alimentary tract and metabolism, 34.5% (29.1%-39.8%); antiinfectives for systemic use, 21.1% (16.5%-25.7%); nervous system, 17.1% (12.8%-21.3%); and musculo-skeletal system, 15.4% (11.3%-19.5%). The most common type of forgery occurred in cases where the drug contained the correct amount of active ingredients, but the manufacturer was one other than the one indicated (62.4% of the total counterfeit drugs); and medications that did not contain any active ingredient (22.4%). Of the counterfeit drugs, 61.0% (56.0%-67.0%) were national brands and 39.0%, (33.0%-44.0%) were imported. The pharmaceutical formulations with the highest rate of forgery were tablets, 66.0% (60.0%-71.0%); injectables, 19.0% (14.0%-23.0%); and capsules 7.0% (4.0%-10.0%). From 2005-2008, drug counterfeiting had an average annual variation of 45%. Drug counterfeiting was shown to be most prevalent among national brands - as opposed to imported medications - although the types and formulations of the fake drugs attest to a certain level of sophistication employed in the forgery process. The counterfeiting of life-saving drugs, such as antimicrobials, signifies a serious public health threat.

Illicit Trafficking in the Western Hemisphere: Developing an Operational Approach to Defeat Smuggling within the Region

DTIC Science & Technology

2017-03-31

and political stability. The threat is currently so pervasive that solving it is impossible without significant strategic reframing. A design ...approach will offer a better understanding of the functions and systems used for illicit trafficking. An operational design will be useful for developing a...illicit drugs, human trafficking, USSOUTHCOM, trafficking, operational design 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT

Study of the Effects of Drugs upon the Cardiovascular and Respiratory Systems

DTIC Science & Technology

1986-06-01

ed. The C.V. Mosby Company, St . Louis, 1971. Spence, 3.T., Underwood, B.3., Duncan, C.P., and Cotton, J.W. Elementary Statistics. Appleton- Century ...I.I)" ,,,- 20. DISTRIBUTION/AVAILABILITY OF ABSTRACT 21 . ABSTRACT SECURITY CLASSIFICATION C3 UNCLASSIFIED/UNLIMITED 0 SAME AS RPT. - OTIC USERS...50, resistance units - -. ° ! U { {{{{{{ {{{{{{{{{{{{{{{ { {{{{ I {{{ {{{{ { {{{{{{ {{{{{{{ {{{{{ 21 3. Calibration of the Buxco Data Logger Model DL

A proposal for a drug product Manufacturing Classification System (MCS) for oral solid dosage forms.

PubMed

Leane, Michael; Pitt, Kendal; Reynolds, Gavin

2015-01-01

This paper proposes the development of a drug product Manufacturing Classification System (MCS) based on processing route. It summarizes conclusions from a dedicated APS conference and subsequent discussion within APS focus groups and the MCS working party. The MCS is intended as a tool for pharmaceutical scientists to rank the feasibility of different processing routes for the manufacture of oral solid dosage forms, based on selected properties of the API and the needs of the formulation. It has many applications in pharmaceutical development, in particular, it will provide a common understanding of risk by defining what the "right particles" are, enable the selection of the best process, and aid subsequent transfer to manufacturing. The ultimate aim is one of prediction of product developability and processability based upon previous experience. This paper is intended to stimulate contribution from a broad range of stakeholders to develop the MCS concept further and apply it to practice. In particular, opinions are sought on what API properties are important when selecting or modifying materials to enable an efficient and robust pharmaceutical manufacturing process. Feedback can be given by replying to our dedicated e-mail address (mcs@apsgb.org); completing the survey on our LinkedIn site; or by attending one of our planned conference roundtable sessions.

Prediction of Effective Drug Combinations by an Improved Naïve Bayesian Algorithm.

PubMed

Bai, Li-Yue; Dai, Hao; Xu, Qin; Junaid, Muhammad; Peng, Shao-Liang; Zhu, Xiaolei; Xiong, Yi; Wei, Dong-Qing

2018-02-05

Drug combinatorial therapy is a promising strategy for combating complex diseases due to its fewer side effects, lower toxicity and better efficacy. However, it is not feasible to determine all the effective drug combinations in the vast space of possible combinations given the increasing number of approved drugs in the market, since the experimental methods for identification of effective drug combinations are both labor- and time-consuming. In this study, we conducted systematic analysis of various types of features to characterize pairs of drugs. These features included information about the targets of the drugs, the pathway in which the target protein of a drug was involved in, side effects of drugs, metabolic enzymes of the drugs, and drug transporters. The latter two features (metabolic enzymes and drug transporters) were related to the metabolism and transportation properties of drugs, which were not analyzed or used in previous studies. Then, we devised a novel improved naïve Bayesian algorithm to construct classification models to predict effective drug combinations by using the individual types of features mentioned above. Our results indicated that the performance of our proposed method was indeed better than the naïve Bayesian algorithm and other conventional classification algorithms such as support vector machine and K-nearest neighbor.

Data Mining and Machine Learning Models for Predicting Drug Likeness and their Disease or Organ Category

NASA Astrophysics Data System (ADS)

Yosipof, Abraham; Guedes, Rita C.; García-Sosa, Alfonso T.

2018-05-01

Data mining approaches can uncover underlying patterns in chemical and pharmacological property space decisive for drug discovery and development. Two of the most common approaches are visualization and machine learning methods. Visualization methods use dimensionality reduction techniques in order to reduce multi-dimension data into 2D or 3D representations with a minimal loss of information. Machine learning attempts to find correlations between specific activities or classifications for a set of compounds and their features by means of recurring mathematical models. Both models take advantage of the different and deep relationships that can exist between features of compounds, and helpfully provide classification of compounds based on such features. Drug-likeness has been studied from several viewpoints, but here we provide the first implementation in chemoinformatics of the t-Distributed Stochastic Neighbor Embedding (t-SNE) method for the visualization and the representation of chemical space, and the use of different machine learning methods separately and together to form a new ensemble learning method called AL Boost. The models obtained from AL Boost synergistically combine decision tree, random forests (RF), support vector machine (SVM), artificial neuronal network (ANN), k nearest neighbors (kNN), and logistic regression models. In this work, we show that together they form a predictive model that not only improves the predictive force but also decreases bias. This resulted in a corrected classification rate of over 0.81, as well as higher sensitivity and specificity rates for the models. In addition, separation and good models were also achieved for disease categories such as antineoplastic compounds and nervous system diseases, among others. Such models can be used to guide decision on the feature landscape of compounds and their likeness to either drugs or other characteristics, such as specific or multiple disease-category(ies) or organ(s) of action of a molecule.

Data Mining and Machine Learning Models for Predicting Drug Likeness and Their Disease or Organ Category.

PubMed

Yosipof, Abraham; Guedes, Rita C; García-Sosa, Alfonso T

2018-01-01

Data mining approaches can uncover underlying patterns in chemical and pharmacological property space decisive for drug discovery and development. Two of the most common approaches are visualization and machine learning methods. Visualization methods use dimensionality reduction techniques in order to reduce multi-dimension data into 2D or 3D representations with a minimal loss of information. Machine learning attempts to find correlations between specific activities or classifications for a set of compounds and their features by means of recurring mathematical models. Both models take advantage of the different and deep relationships that can exist between features of compounds, and helpfully provide classification of compounds based on such features or in case of visualization methods uncover underlying patterns in the feature space. Drug-likeness has been studied from several viewpoints, but here we provide the first implementation in chemoinformatics of the t-Distributed Stochastic Neighbor Embedding (t-SNE) method for the visualization and the representation of chemical space, and the use of different machine learning methods separately and together to form a new ensemble learning method called AL Boost. The models obtained from AL Boost synergistically combine decision tree, random forests (RF), support vector machine (SVM), artificial neural network (ANN), k nearest neighbors (kNN), and logistic regression models. In this work, we show that together they form a predictive model that not only improves the predictive force but also decreases bias. This resulted in a corrected classification rate of over 0.81, as well as higher sensitivity and specificity rates for the models. In addition, separation and good models were also achieved for disease categories such as antineoplastic compounds and nervous system diseases, among others. Such models can be used to guide decision on the feature landscape of compounds and their likeness to either drugs or other characteristics, such as specific or multiple disease-category(ies) or organ(s) of action of a molecule.

Clinical aspects of autoimmune rheumatic diseases.

PubMed

Goldblatt, Fiona; O'Neill, Sean G

2013-08-31

Multisystem autoimmune rheumatic diseases are heterogeneous rare disorders associated with substantial morbidity and mortality. Efforts to create international consensus within the past decade have resulted in the publication of new classification or nomenclature criteria for several autoimmune rheumatic diseases, specifically for systemic lupus erythematosus, Sjögren's syndrome, and the systemic vasculitides. Substantial progress has been made in the formulation of new criteria in systemic sclerosis and idiopathic inflammatory myositis. Although the autoimmune rheumatic diseases share many common features and clinical presentations, differentiation between the diseases is crucial because of important distinctions in clinical course, appropriate drugs, and prognoses. We review some of the dilemmas in the diagnosis of these autoimmune rheumatic diseases, and focus on the importance of new classification criteria, clinical assessment, and interpretation of autoimmune serology. In this era of improvement of mortality rates for patients with autoimmune rheumatic diseases, we pay particular attention to the effect of leading complications, specifically cardiovascular manifestations and cancer, and we update epidemiology and prognosis. Copyright © 2013 Elsevier Ltd. All rights reserved.

Automatic indexing in a drug information portal.

PubMed

Sakji, Saoussen; Letord, Catherine; Dahamna, Badisse; Kergourlay, Ivan; Pereira, Suzanne; Joubert, Michel; Darmoni, Stéfan

2009-01-01

The objective of this work is to create a bilingual (French/English) Drug Information Portal (DIP), in a multi-terminological context and to emphasize its exploitation by an ATC automatic indexing allowing having more pertinent information about substances, organs or systems on which drugs act and their therapeutic and chemical characteristics. The development of the DIP was based on the CISMeF portal, which catalogues and indexes the most important and quality-controlled sources of institutional health information in French. DIP has created specific functionalities and uses specific drugs terminologies such as the ATC classification which used to automatic index the DIP resources. DIP is the result of collaboration between the CISMeF team and the VIDAL Company, specialized in drug information. DIP is conceived to facilitate the user information retrieval. The ATC automatic indexing provided relevant results in 76% of cases. Using multi-terminological context and in the framework of the drug field, indexing drugs with the appropriate codes or/and terms revealed to be very important to have the appropriate information storage and retrieval. The main challenge in the coming year is to increase the accuracy of the approach.

21 CFR 884.1425 - Perineometer.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Perineometer. 884.1425 Section 884.1425 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES... correct, through exercise, uninary incontinence or sexual dysfunction. (b) Classification. Class II...

21 CFR 884.1425 - Perineometer.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Perineometer. 884.1425 Section 884.1425 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES... correct, through exercise, uninary incontinence or sexual dysfunction. (b) Classification. Class II...

21 CFR 884.1425 - Perineometer.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Perineometer. 884.1425 Section 884.1425 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES... correct, through exercise, uninary incontinence or sexual dysfunction. (b) Classification. Class II...

21 CFR 884.1425 - Perineometer.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Perineometer. 884.1425 Section 884.1425 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES... correct, through exercise, uninary incontinence or sexual dysfunction. (b) Classification. Class II...

21 CFR 884.1425 - Perineometer.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Perineometer. 884.1425 Section 884.1425 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES... correct, through exercise, uninary incontinence or sexual dysfunction. (b) Classification. Class II...

21 CFR 868.1900 - Diagnostic pulmonary-function interpretation calculator.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Diagnostic pulmonary-function interpretation calculator. 868.1900 Section 868.1900 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND... pulmonary-function values. (b) Classification. Class II (performance standards). ...

21 CFR 868.1900 - Diagnostic pulmonary-function interpretation calculator.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Diagnostic pulmonary-function interpretation calculator. 868.1900 Section 868.1900 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND... pulmonary-function values. (b) Classification. Class II (performance standards). ...

21 CFR 868.1620 - Halothane gas analyzer.

Code of Federal Regulations, 2010 CFR

2010-04-01

... infrared or ultraviolet radiation. (b) Classification. Class II (performance standards). ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Halothane gas analyzer. 868.1620 Section 868.1620 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED...

76 FR 75551 - Draft Guidance for Industry on Regulatory Classification of Pharmaceutical Co-Crystals; Availability

Federal Register 2010, 2011, 2012, 2013, 2014

2011-12-02

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-D-0800... AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug Administration (FDA... Research, Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 51, rm. 2201, Silver Spring, MD...

GA(M)E-QSAR: a novel, fully automatic genetic-algorithm-(meta)-ensembles approach for binary classification in ligand-based drug design.

PubMed

Pérez-Castillo, Yunierkis; Lazar, Cosmin; Taminau, Jonatan; Froeyen, Mathy; Cabrera-Pérez, Miguel Ángel; Nowé, Ann

2012-09-24

Computer-aided drug design has become an important component of the drug discovery process. Despite the advances in this field, there is not a unique modeling approach that can be successfully applied to solve the whole range of problems faced during QSAR modeling. Feature selection and ensemble modeling are active areas of research in ligand-based drug design. Here we introduce the GA(M)E-QSAR algorithm that combines the search and optimization capabilities of Genetic Algorithms with the simplicity of the Adaboost ensemble-based classification algorithm to solve binary classification problems. We also explore the usefulness of Meta-Ensembles trained with Adaboost and Voting schemes to further improve the accuracy, generalization, and robustness of the optimal Adaboost Single Ensemble derived from the Genetic Algorithm optimization. We evaluated the performance of our algorithm using five data sets from the literature and found that it is capable of yielding similar or better classification results to what has been reported for these data sets with a higher enrichment of active compounds relative to the whole actives subset when only the most active chemicals are considered. More important, we compared our methodology with state of the art feature selection and classification approaches and found that it can provide highly accurate, robust, and generalizable models. In the case of the Adaboost Ensembles derived from the Genetic Algorithm search, the final models are quite simple since they consist of a weighted sum of the output of single feature classifiers. Furthermore, the Adaboost scores can be used as ranking criterion to prioritize chemicals for synthesis and biological evaluation after virtual screening experiments.

"When 'Bad' is 'Good'": Identifying Personal Communication and Sentiment in Drug-Related Tweets.

PubMed

Daniulaityte, Raminta; Chen, Lu; Lamy, Francois R; Carlson, Robert G; Thirunarayan, Krishnaprasad; Sheth, Amit

2016-10-24

To harness the full potential of social media for epidemiological surveillance of drug abuse trends, the field needs a greater level of automation in processing and analyzing social media content. The objective of the study is to describe the development of supervised machine-learning techniques for the eDrugTrends platform to automatically classify tweets by type/source of communication (personal, official/media, retail) and sentiment (positive, negative, neutral) expressed in cannabis- and synthetic cannabinoid-related tweets. Tweets were collected using Twitter streaming Application Programming Interface and filtered through the eDrugTrends platform using keywords related to cannabis, marijuana edibles, marijuana concentrates, and synthetic cannabinoids. After creating coding rules and assessing intercoder reliability, a manually labeled data set (N=4000) was developed by coding several batches of randomly selected subsets of tweets extracted from the pool of 15,623,869 collected by eDrugTrends (May-November 2015). Out of 4000 tweets, 25% (1000/4000) were used to build source classifiers and 75% (3000/4000) were used for sentiment classifiers. Logistic Regression (LR), Naive Bayes (NB), and Support Vector Machines (SVM) were used to train the classifiers. Source classification (n=1000) tested Approach 1 that used short URLs, and Approach 2 where URLs were expanded and included into the bag-of-words analysis. For sentiment classification, Approach 1 used all tweets, regardless of their source/type (n=3000), while Approach 2 applied sentiment classification to personal communication tweets only (2633/3000, 88%). Multiclass and binary classification tasks were examined, and machine-learning sentiment classifier performance was compared with Valence Aware Dictionary for sEntiment Reasoning (VADER), a lexicon and rule-based method. The performance of each classifier was assessed using 5-fold cross validation that calculated average F-scores. One-tailed t test was used to determine if differences in F-scores were statistically significant. In multiclass source classification, the use of expanded URLs did not contribute to significant improvement in classifier performance (0.7972 vs 0.8102 for SVM, P=.19). In binary classification, the identification of all source categories improved significantly when unshortened URLs were used, with personal communication tweets benefiting the most (0.8736 vs 0.8200, P<.001). In multiclass sentiment classification Approach 1, SVM (0.6723) performed similarly to NB (0.6683) and LR (0.6703). In Approach 2, SVM (0.7062) did not differ from NB (0.6980, P=.13) or LR (F=0.6931, P=.05), but it was over 40% more accurate than VADER (F=0.5030, P<.001). In multiclass task, improvements in sentiment classification (Approach 2 vs Approach 1) did not reach statistical significance (eg, SVM: 0.7062 vs 0.6723, P=.052). In binary sentiment classification (positive vs negative), Approach 2 (focus on personal communication tweets only) improved classification results, compared with Approach 1, for LR (0.8752 vs 0.8516, P=.04) and SVM (0.8800 vs 0.8557, P=.045). The study provides an example of the use of supervised machine learning methods to categorize cannabis- and synthetic cannabinoid-related tweets with fairly high accuracy. Use of these content analysis tools along with geographic identification capabilities developed by the eDrugTrends platform will provide powerful methods for tracking regional changes in user opinions related to cannabis and synthetic cannabinoids use over time and across different regions.

Buoyancy-generating agents for stomach-specific drug delivery: an overview with special emphasis on floating behavior.

PubMed

Ishak, Rania A H

2015-01-01

Gastric retentive drug delivery provides a promising technology exhibiting an extended gastric residence and a drug release independent of patient related variables. It is usually useful in improving local gastric treatment as well as overcoming drug-related problems .i.e. drugs having narrow absorption window, short half-life or low intestinal solubility. Buoyancy is considered one of the most promising approaches for gastro-retention of dosage forms. Floating drug delivery systems have a bulk density lower than gastric fluids and thus remain buoyant in the stomach causing an increase in gastric residence time. The buoyancy of these systems is attained by the aid of substances responsible to generate the low density. Various agents with different mechanisms were adopted either gas-generating agents, air entrapping swellable polymers, inherent low density substances, porous excipients, hollow/porous particles inducing preparation techniques or sublimating agents. Therefore, this review gives an exclusive descriptive classification of the different categories of these buoyancy-generating agents while representing the related research works. An overview is also conducted to describe relevant techniques assessing the floating behavior of such dosage forms either in vitro or in vivo. Finally, a collection representing FDA-approved floating pharmaceutical products is adopted with emphasis on the buoyancy-generating agent type used in each product.

Medical devices; hematology and pathology devices; classification of the Factor V Leiden DNA mutation detection systems devices. Final rule.

PubMed

2004-03-16

The Food and Drug Administration (FDA) is classifying the Factor V Leiden deoxyribonucleic acid (DNA) mutation detections systems device into class II (special controls). The special control that will apply to the device is the guidance document entitled "Class II Special Controls Guidance Document: Factor V Leiden DNA Mutation Detection Systems." The agency is taking this action in response to a petition submitted under the Federal Food, Drug, and Cosmetic Act (the act) as amended by the Medical Device Amendments of 1976 (the 1976 amendments), the Safe Medical Devices Act of 1990 (SMDA), the Food and Drug Administration Modernization Act of 1997 (FDAMA), and the Medical Device User Fee and Modernization Act of 2002. The agency is classifying this device into class II (special controls) in order to provide a reasonable assurance of safety and effectiveness of the device. Elsewhere in this issue of the Federal Register, FDA is publishing a notice of availability of a guidance document that is the special control for this device.

Biopharmaceutics classification of puerarin and comparison of perfusion approaches in rats.

PubMed

Li, Hewei; Dong, Ling; Liu, Yang; Wang, Guopeng; Wang, Gang; Qiao, Yanjiang

2014-05-15

The present study was conducted to characterize the biopharmaceutics classification system (BCS) category of puerarin in terms of intrinsic dissolution rate (IDR) and rat intestinal permeability and to investigate the poor intestinal absorption probably related to the drug metabolism in the gut wall of rats. Equilibrium solubility of puerarin was determined in various phosphate buffers and water, and IDR was estimated by measuring the dissolution of a non-disintegrating compact. Intestinal permeability (Peff and Pblood) of puerarin was determined using the technology of in situ single-pass intestinal perfusion (SPIP) and intestinal perfusion with venous sampling (IPVS) in fasted rats. Metabolism of puerarin in intestinal tissue was tested by S9 incubation in vitro. The aqueous solubility of puerarin in phosphate buffers and water was good with a maximum solubility of 7.56 mg/mL at pH 7.4. Obtained IDR values of puerarin were in the range of 0.360-1.088 mg/min/cm(2), with maximum and minimum IDR value of pH 7.4 and pH 4.0, respectively. The Peff was 1.252 × 10(-5)cm/s determined by SPIP and the Pblood was 0.068×10(-5)cm/s by IPVS in jejunum at puerarin 80 μg/mL. The metabolism rate of puerarin determined by the intestinal S9 fraction indicated that the gut wall metabolism of puerarin is one cause of poor absorption. According to the proposed classification of drugs and the results obtained from equilibrium solubility, IDR, Peff and Pblood, it is concluded that puerarin could be categorized IV drug of the BCS based on its low solubility and low intestinal permeability values. Copyright © 2014 Elsevier B.V. All rights reserved.

Statistical classification of drug incidents due to look-alike sound-alike mix-ups.

PubMed

Wong, Zoie Shui Yee

2016-06-01

It has been recognised that medication names that look or sound similar are a cause of medication errors. This study builds statistical classifiers for identifying medication incidents due to look-alike sound-alike mix-ups. A total of 227 patient safety incident advisories related to medication were obtained from the Canadian Patient Safety Institute's Global Patient Safety Alerts system. Eight feature selection strategies based on frequent terms, frequent drug terms and constituent terms were performed. Statistical text classifiers based on logistic regression, support vector machines with linear, polynomial, radial-basis and sigmoid kernels and decision tree were trained and tested. The models developed achieved an average accuracy of above 0.8 across all the model settings. The receiver operating characteristic curves indicated the classifiers performed reasonably well. The results obtained in this study suggest that statistical text classification can be a feasible method for identifying medication incidents due to look-alike sound-alike mix-ups based on a database of advisories from Global Patient Safety Alerts. © The Author(s) 2014.

Using RxNorm and NDF-RT to classify medication data extracted from electronic health records: experiences from the Rochester Epidemiology Project.

PubMed

Pathak, Jyotishman; Murphy, Sean P; Willaert, Brian N; Kremers, Hilal M; Yawn, Barbara P; Rocca, Walter A; Chute, Christopher G

2011-01-01

RxNorm and NDF-RT published by the National Library of Medicine (NLM) and Veterans Affairs (VA), respectively, are two publicly available federal medication terminologies. In this study, we evaluate the applicability of RxNorm and National Drug File-Reference Terminology (NDF-RT) for extraction and classification of medication data retrieved using structured querying and natural language processing techniques from electronic health records at two different medical centers within the Rochester Epidemiology Project (REP). Specifically, we explore how mappings between RxNorm concept codes and NDF-RT drug classes can be leveraged for hierarchical organization and grouping of REP medication data, identify gaps and coverage issues, and analyze the recently released NLM's NDF-RT Web service API. Our study concludes that RxNorm and NDF-RT can be applied together for classification of medication extracted from multiple EHR systems, although several issues and challenges remain to be addressed. We further conclude that the Web service APIs developed by the NLM provide useful functionalities for such activities.

Adverse Drug Reactions in Children: The Double-Edged Sword of Therapeutics.

PubMed

Elzagallaai, A A; Greff, Mje; Rieder, M J

2017-06-01

Adverse drug reactions (ADRs) represent a major health problem worldwide, with high morbidity and mortality rates. ADRs are classified into Type A (augmented) and Type B (bizarre) ADRs, with the former group being more common and the latter less common but often severe and clinically more problematic due to their unpredictable nature and occurrence at any dose. Pediatric populations are especially vulnerable to ADRs due to the lack of data for this age group from the drug development process and because of the wide use of off-label and unlicensed use of drugs. Children are more prone to specific types of ADRs because of the level of maturity of body systems involved in absorption, metabolism, transportation, and elimination of drugs. This state-of-the-art review provides an overview of definitions, classifications, epidemiology, and pathophysiology of ADRs and discusses the available evidence for related risk factors and causes of ADRs in the pediatric population. © 2017 American Society for Clinical Pharmacology and Therapeutics.

Skin manifestations of drug allergy

PubMed Central

Ardern-Jones, Michael R; Friedmann, Peter S

2011-01-01

Cutaneous adverse drug reactions range from mild to severe and from those localized only to skin to those associated with systemic disease. It is important to distinguish features of cutaneous drug reactions which help classify the underlying mechanism and likely prognosis as both of these influence management decisions, some of which necessarily have to be taken rapidly. Severe cutaneous reactions are generally T cell-mediated, yet this immunological process is frequently poorly understood and principles for identification of the culprit drug are different to those of IgE mediated allergic reactions. Furthermore, intervention in severe skin manifestations of drug allergy is frequently necessary. However, a substantial literature reports on success or otherwise of glucocorticoids, cyclophsphamide, ciclosporin, intravenous immunoglobulin and anti-tumour necrosis factor therapy for the treatment of toxic epidermal necrolysis without clear consensus. As well as reviewing the recommended supportive measures and evidence base for interventions, this review aims to provide a mechanistic overview relating to a proposed clinical classification to assist the assessment and management of these complex patients. PMID:21480947

What do primary care practitioners want to know? A content analysis of questions asked at the point of care.

PubMed

Bjerre, Lise M; Paterson, Nicholas R; McGowan, Jessie; Hogg, William; Campbell, Craig M; Viner, Gary; Archibald, Douglas

2013-01-01

Assessing physician needs to develop continuing medical education (CME) activities is an integral part of CME curriculum development. The purpose of the present study was to demonstrate the feasibility of identifying areas of perceived greatest needs for continuing medical education (CME) by using questions collected electronically at the point of care. This study is a secondary analysis of the "Just-in-Time" (JIT) information librarian consultation service database of questions using quantitative content analysis methods. The original JIT project demonstrated the feasibility of a real-time librarian service for answering questions asked by primary care clinicians at the point of care using a Web-based platform or handheld device. Data were collected from 88 primary care practitioners in Ontario, Canada, from October 2005 to April 2006. Questions were answered in less than 15 minutes, enabling clinicians to use the answer during patient encounters. Description of type and frequency of questions asked, including the organ system on which the questions focused, was produced using 2 classification systems, the "taxonomy of generic clinical questions" (TGCQ), and the International Classification for Primary Care version 2 (ICPC-2). Of the original 1889 questions, 1871 (99.0%) were suitable for analysis. A total of 970 (52%) of questions related to therapy; of these, 671 (69.2%) addressed questions about drug therapy, representing 36% of all questions. Questions related to diagnosis (24.8%) and epidemiology (13.5%) were also common. Organ systems questions concerning musculoskeletal, endocrine, skin, cardiac, and digestive systems were asked more than other categories. Questions collected at the point of care provide a valuable and unique source of information on the true learning needs of practicing clinicians. The TGCQ classification allowed us to show that a majority of questions had to do with treatment, particularly drug treatment, whereas the use of the ICPC-2 classification illustrated the great variety of questions asked about the diverse conditions encountered in primary care. It is feasible to use electronically collected questions asked by primary care clinicians in clinical practice to categorize self-identified knowledge and practice needs. This could be used to inform the development of future learning activities. Copyright © 2013 The Alliance for Continuing Education in the Health Professions, the Society for Academic Continuing Medical Education, and the Council on CME, Association for Hospital Medical Education.

The role of networks and artificial intelligence in nanotechnology design and analysis.

PubMed

Hudson, D L; Cohen, M E

2004-05-01

Techniques with their origins in artificial intelligence have had a great impact on many areas of biomedicine. Expert-based systems have been used to develop computer-assisted decision aids. Neural networks have been used extensively in disease classification and more recently in many bioinformatics applications including genomics and drug design. Network theory in general has proved useful in modeling all aspects of biomedicine from healthcare organizational structure to biochemical pathways. These methods show promise in applications involving nanotechnology both in the design phase and in interpretation of system functioning.

21 CFR 870.4340 - Cardiopulmonary bypass level sensing monitor and/or control.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Cardiopulmonary bypass level sensing monitor and/or control. 870.4340 Section 870.4340 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF... value. (b) Classification. Class II (performance standards). ...

21 CFR 870.4340 - Cardiopulmonary bypass level sensing monitor and/or control.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Cardiopulmonary bypass level sensing monitor and/or control. 870.4340 Section 870.4340 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF... value. (b) Classification. Class II (performance standards). ...

21 CFR 876.4770 - Urethrotome.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Urethrotome. 876.4770 Section 876.4770 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES.... Some urethrotomes incorporate an optical channel for visual control. (b) Classification. Class II...

21 CFR 886.4440 - AC-powered magnet.

Code of Federal Regulations, 2014 CFR

2014-04-01

... metallic foreign bodies from eye tissue. (b) Classification. Class II. ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false AC-powered magnet. 886.4440 Section 886.4440 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL...

21 CFR 886.4440 - AC-powered magnet.

Code of Federal Regulations, 2012 CFR

2012-04-01

... metallic foreign bodies from eye tissue. (b) Classification. Class II. ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false AC-powered magnet. 886.4440 Section 886.4440 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL...

21 CFR 886.4440 - AC-powered magnet.

Code of Federal Regulations, 2011 CFR

2011-04-01

... metallic foreign bodies from eye tissue. (b) Classification. Class II. ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false AC-powered magnet. 886.4440 Section 886.4440 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL...

21 CFR 886.4440 - AC-powered magnet.

Code of Federal Regulations, 2013 CFR

2013-04-01

... metallic foreign bodies from eye tissue. (b) Classification. Class II. ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false AC-powered magnet. 886.4440 Section 886.4440 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL...

21 CFR 880.6920 - Syringe needle introducer.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Syringe needle introducer. 880.6920 Section 880.6920 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... depth below the skin surface. (b) Classification. Class II (performance standards). ...

21 CFR 880.6920 - Syringe needle introducer.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Syringe needle introducer. 880.6920 Section 880.6920 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... depth below the skin surface. (b) Classification. Class II (performance standards). ...

Interrater reliability of the international consensus definition of drug-resistant epilepsy: a pilot study.

PubMed

Hao, Xiao-ting; Wong, Irina S M; Kwan, Patrick

2011-10-01

We evaluated the interrater reliability of the consensus definition of drug-resistant epilepsy proposed by the International League Against Epilepsy. According to the definition framework, outcome of each antiepileptic drug (AED) trial was categorized as "seizure freedom" or "treatment failure." This level 1 assessment was used to determine the level 2 classification, which defined drug-resistant epilepsy as the failure of adequate trials of two or more AED schedules to achieve sustained seizure freedom. Two raters classified treatment outcomes of 150 patients independently. The patients had received a total of 428 trials of AEDs. Categorization of level 1 outcome to individual AED trials by the raters was consistent in 413 (96.5%). For the level 2 classification of drug-resistant or drug-responsive epilepsy, there was absolute agreement between the raters in 141 patients (94%), with a κ index of 0.91 (P<0.001). The definition appeared to have a high degree of interrater reliability in this setting. Copyright © 2011 Elsevier Inc. All rights reserved.

Acute Pancreatitis and Use of Pancreatitis-Associated Drugs: A 10-Year Population-Based Cohort Study.

PubMed

Bertilsson, Sara; Kalaitzakis, Evangelos

2015-10-01

To assess the use of acute pancreatitis (AP)-associated drugs in patients with AP, the relation between sales of these drugs and the incidence of AP, and the potential impact on AP severity and recurrence. All patients with incident AP between 2003 and 2012, in a well-defined area, were retrospectively identified. Data regarding AP etiology, severity, and recurrence and use of AP-associated drugs were extracted from medical records. Drugs were classified according to an evidence-based classification system. Annual drug sales data were obtained from the Swedish drug administration service. Overall, 1457 cases of incident AP were identified. Acute pancreatitis-associated drug users increased from 32% in 2003 to 51% in 2012, reflecting increasing user rates in the general population. The incidence of AP increased during the study period but was not related to AP-associated drug user rates (P > 0.05). Recurrent AP occurred in 23% but was unrelated to AP-associated drug use (P > 0.05). In logistic regression analysis, after adjustment for comorbidity, AP-associated drug use was not related to AP severity (P > 0.05). Use of AP-associated drugs is increasingly frequent in patients with AP. However, it does not have any major impact on the observed epidemiological changes in occurrence, severity, or recurrence of AP.

Legal and health variations in drug litigation injunctions granted in Minas Gerais

PubMed Central

Coelho, Tiago Lopes; Ferré, Felipe; Campos, Orozimbo Henriques; Acurcio, Francisco de Assis; Cherchiglia, Mariângela Leal; Andrade, Eli Iola Gurgel

2014-01-01

OBJECTIVE To investigate the factors related to the granting of preliminary court orders [injunctions] in drug litigations. METHODS A retrospective descriptive study of drug lawsuits in the State of Minas Gerais, Southeastern Brazil, was conducted from October 1999 to 2009. The database consists of 6,112 lawsuits, out of which 6,044 had motions for injunctions and 5,167 included the requisition of drugs. Those with more than one beneficiary were excluded, which totaled 5,072 examined suits. The variables for complete, partial, and suppressed motions were treated as dependent and assessed in relation to those that were independent – lawsuits (year, type, legal representation, defendant, court in which it was filed, adjudication time), drugs (level five of the anatomical therapeutic chemical classification), and diseases (chapter of the International Classification of Diseases). Statistical analyses were performed using the Chi-square test. RESULTS Out of the 5,072 lawsuits with injunctions, 4,184 (82.5%) had the injunctions granted. Granting varied from 95.8% of the total lawsuits in 2004 to 76.9% in 2008. Where there was legal representation, granting exceeded 80.0% and in lawsuits without representation, it did not exceed 66.9%. In public civil actions (89.1%), granting was higher relative to ordinary lawsuits (82.8%) and injunctions (80.1%). Federal courts granted only 68.6% of the injunctions, while the state courts granted 84.8%. Diseases of the digestive system and neoplasms received up to 87.0% in granting, while diseases of the nervous system, mental and behavioral disorders, and diseases of the skin and subcutaneous tissue received granting below 78.6% and showed a high proportion of suspended injunctions (10.9%). Injunctions involving paroxetine, somatropin, and ferrous sulfate drugs were all granted, while less than 54.0% of those involving escitalopram, sodium diclofenac, and nortriptyline were granted. CONCLUSIONS There are significant differences in the granting of injunctions, depending on the procedural and clinical variances. Important trends in the pattern of judicial action were observed, particularly, in the reduced granting [of injunctions] over the period. PMID:25372172

A physarum-inspired prize-collecting steiner tree approach to identify subnetworks for drug repositioning.

PubMed

Sun, Yahui; Hameed, Pathima Nusrath; Verspoor, Karin; Halgamuge, Saman

2016-12-05

Drug repositioning can reduce the time, costs and risks of drug development by identifying new therapeutic effects for known drugs. It is challenging to reposition drugs as pharmacological data is large and complex. Subnetwork identification has already been used to simplify the visualization and interpretation of biological data, but it has not been applied to drug repositioning so far. In this paper, we fill this gap by proposing a new Physarum-inspired Prize-Collecting Steiner Tree algorithm to identify subnetworks for drug repositioning. Drug Similarity Networks (DSN) are generated using the chemical, therapeutic, protein, and phenotype features of drugs. In DSNs, vertex prizes and edge costs represent the similarities and dissimilarities between drugs respectively, and terminals represent drugs in the cardiovascular class, as defined in the Anatomical Therapeutic Chemical classification system. A new Physarum-inspired Prize-Collecting Steiner Tree algorithm is proposed in this paper to identify subnetworks. We apply both the proposed algorithm and the widely-used GW algorithm to identify subnetworks in our 18 generated DSNs. In these DSNs, our proposed algorithm identifies subnetworks with an average Rand Index of 81.1%, while the GW algorithm can only identify subnetworks with an average Rand Index of 64.1%. We select 9 subnetworks with high Rand Index to find drug repositioning opportunities. 10 frequently occurring drugs in these subnetworks are identified as candidates to be repositioned for cardiovascular diseases. We find evidence to support previous discoveries that nitroglycerin, theophylline and acarbose may be able to be repositioned for cardiovascular diseases. Moreover, we identify seven previously unknown drug candidates that also may interact with the biological cardiovascular system. These discoveries show our proposed Prize-Collecting Steiner Tree approach as a promising strategy for drug repositioning.

The complexity of intestinal permeability: Assigning the correct BCS classification through careful data interpretation.

PubMed

Zur, Moran; Hanson, Allison S; Dahan, Arik

2014-09-30

While the solubility parameter is fairly straightforward when assigning BCS classification, the intestinal permeability (Peff) is more complex than generally recognized. In this paper we emphasize this complexity through the analysis of codeine, a commonly used antitussive/analgesic drug. Codeine was previously classified as a low-permeability compound, based on its lower LogP compared to metoprolol, a marker for the low-high permeability class boundary. In contrast, high fraction of dose absorbed (Fabs) was reported for codeine, which challenges the generally recognized Peff-Fabs correlation. The purpose of this study was to clarify this ambiguity through elucidation of codeine's BCS solubility/permeability class membership. Codeine's BCS solubility class was determined, and its intestinal permeability throughout the small intestine was investigated, both in vitro and in vivo in rats. Codeine was found to be unequivocally a high-solubility compound. All in vitro studies indicated that codeine's permeability is higher than metoprolol's. In vivo studies in rats showed similar permeability for both drugs throughout the entire small-intestine. In conclusion, codeine was found to be a BCS Class I compound. No Peff-Fabs discrepancy is involved in its absorption; rather, it reflects the risk of assigning BCS classification based on merely limited physicochemical characteristics. A thorough investigation using multiple experimental methods is prudent before assigning a BCS classification, to avoid misjudgment in various settings, e.g., drug discovery, formulation design, drug development and regulation. Copyright © 2013 Elsevier B.V. All rights reserved.

Report on Gang Violence in Maryland

DTIC Science & Technology

1994-07-01

possession of a firearm, and drug kingpin statutes. 14 . Consider juvenile witness protection programs for youths under eighteen years of age. Scho... 14 . SUBJECT TERMS 15. NUMBER OF PAGES 16. PRICE CODE 17. SECURITY CLASSIFICATION 18. SECURITY CLASSIFICATION 19. SECURITY CLASSIFICATION 20 IIAINOF...limitations. Cite any Block 2. Report Date. Full publication date availability to the public. Enter additional including day, month, and year , if available

Drugs Most Frequently Involved in Drug Overdose Deaths: United States, 2010-2014.

PubMed

Warner, Margaret; Trinidad, James P; Bastian, Brigham A; Minino, Arialdi M; Hedegaard, Holly

2016-12-01

Objectives-This report identifies the specific drugs most frequently involved in drug overdose deaths in the United States from 2010 through 2014. Methods-The 2010-2014 National Vital Statistics System mortality files were linked to electronic files containing literal text information from death certificates. Drug overdose was defined using the International Classification of Diseases, Tenth Revision underlying cause-of-death codes X40-X44 (unintentional), X60-X64 (suicide), X85 (homicide), and Y10-Y14 (undetermined intent). Among deaths with an underlying cause of death of drug overdose, the literal text in three fields of the death certificate (i.e., the cause of death from Part I, significant conditions contributing to death from Part II, and a description of how the injury occurred from Box 43) were searched to identify drug mentions. Search term lists were developed using existing drug classification systems as well as from manual review of the literal text. The search term list was then used to identify the specific drugs involved in overdose deaths. Descriptive statistics were reported for drug overdose deaths involving the 10 most frequently mentioned drugs on death certificates. Tables and figures presenting information on the specific drugs involved in deaths are based on deaths with mention of at least one specific drug on the death certificate. Results-From 2010 through 2014, the number of drug overdose deaths per year increased 23%, from 38,329 in 2010 to 47,055 in 2014. During this time period, the percentage of drug overdose deaths involving at least one specific drug increased, from 67% in 2010 to 78% in 2014. Among drug overdose deaths with at least one drug specified on the death certificate, the 10 drugs most frequently involved in overdose deaths included the following opioids: heroin, oxycodone, methadone, morphine, hydrocodone, and fentanyl; the following benzodiazepines: alprazolam and diazepam; and the following stimulants: cocaine and methamphetamine. During this 5-year period, the age-adjusted rate of drug overdose deaths involving heroin more than tripled, and the rate of drug overdose deaths involving methamphetamine more than doubled. The rate of drug overdose deaths involving fentanyl more than doubled in a single year (from 2013 to 2014). In 2014, of the 36,667 drug overdose deaths involving at least one specific drug, 52% of these deaths specified one drug, 38% specified two or three drugs, and 11% specified four or more drugs. Conclusions-Analysis of the literal text from death certificates can be used to identify patterns in the specific drugs most frequently involved in drug overdose deaths. From 2010 through 2014, the top 10 drugs involved were the same, but the relative ranking and age-adjusted rates for deaths involving these drugs changed. Literal text analysis also revealed that many drug overdose deaths involved multiple drugs. Findings should be interpreted in light of the improvement in the quality of the data that resulted from better reporting of specific drugs on death certificates from 2010 through 2014. Relative increases in the death rates involving specific drugs and the rankings of these drugs may be affected by improvements in reporting, real increases in the numbers of death, or both. All material appearing in this report is in the public domain and may be reproduced or copied without permission; citation as to source, however, is appreciated.

21 CFR 886.1050 - Adaptometer (biophotometer).

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Adaptometer (biophotometer). 886.1050 Section 886.1050 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... (regeneration of the visual purple) and the minimum light threshold. (b) Classification. Class I (general...

21 CFR 892.1950 - Radiographic anthropomorphic phantom.

Code of Federal Regulations, 2012 CFR

2012-04-01

... purposes to simulate a human body for positioning radiographic equipment. (b) Classification. Class I... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Radiographic anthropomorphic phantom. 892.1950 Section 892.1950 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES...

21 CFR 892.1950 - Radiographic anthropomorphic phantom.

Code of Federal Regulations, 2014 CFR

2014-04-01

... purposes to simulate a human body for positioning radiographic equipment. (b) Classification. Class I... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Radiographic anthropomorphic phantom. 892.1950 Section 892.1950 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES...

21 CFR 892.1950 - Radiographic anthropomorphic phantom.

Code of Federal Regulations, 2013 CFR

2013-04-01

... purposes to simulate a human body for positioning radiographic equipment. (b) Classification. Class I... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Radiographic anthropomorphic phantom. 892.1950 Section 892.1950 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES...

21 CFR 880.6890 - General purpose disinfectants.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false General purpose disinfectants. 880.6890 Section 880.6890 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... topical contact with intact skin. (b) Classification. Class I (general controls). The device is exempt...

21 CFR 892.1950 - Radiographic anthropomorphic phantom.

Code of Federal Regulations, 2010 CFR

2010-04-01

... purposes to simulate a human body for positioning radiographic equipment. (b) Classification. Class I... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Radiographic anthropomorphic phantom. 892.1950 Section 892.1950 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES...

21 CFR 892.1950 - Radiographic anthropomorphic phantom.

Code of Federal Regulations, 2011 CFR

2011-04-01

... purposes to simulate a human body for positioning radiographic equipment. (b) Classification. Class I... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Radiographic anthropomorphic phantom. 892.1950 Section 892.1950 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES...

21 CFR 882.5330 - Preformed nonalterable cranioplasty plate.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Preformed nonalterable cranioplasty plate. 882.5330 Section 882.5330 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... without changing the chemical behavior of the material. (b) Classification. Class II (performance...

21 CFR 882.5330 - Preformed nonalterable cranioplasty plate.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Preformed nonalterable cranioplasty plate. 882.5330 Section 882.5330 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... without changing the chemical behavior of the material. (b) Classification. Class II (performance...

21 CFR 882.5330 - Preformed nonalterable cranioplasty plate.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Preformed nonalterable cranioplasty plate. 882.5330 Section 882.5330 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... without changing the chemical behavior of the material. (b) Classification. Class II (performance...

21 CFR 884.5225 - Abdominal decompression chamber.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Abdominal decompression chamber. 884.5225 Section 884.5225 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... abdominal pain during pregnancy or labor. (b) Classification. Class III (premarket approval). (c) Date PMA...

Establishing the pharmaceutical quality of Chinese herbal medicine: a provisional BCS classification.

PubMed

Fong, Sophia Y K; Liu, Mary; Wei, Hai; Löbenberg, Raimar; Kanfer, Isadore; Lee, Vincent H L; Amidon, Gordon L; Zuo, Zhong

2013-05-06

The Biopharmaceutical Classification System (BCS), which is a scientific approach to categorize active drug ingredient based on its solubility and intestinal permeability into one of the four classes, has been used to set the pharmaceutical quality standards for drug products in western society. However, it has received little attention in the area of Chinese herbal medicine (CHM). This is likely, in part, due to the presence of multiple active components as well as lack of standardization of CHM. In this report, we apply BCS classification to CHMs provisionally as a basis for establishing improved in vitro quality standards. Based on a top-200 drugs selling list in China, a total of 31 CHM products comprising 50 official active marker compounds (AMCs) were provisionally classified according to BCS. Information on AMC content and doses of these CHM products were retrieved from the Chinese Pharmacopoeia. BCS parameters including solubility and permeability of the AMCs were predicted in silico (ACD/Laboratories). A BCS classification of CHMs according to biopharmaceutical properties of their AMCs is demonstrated to be feasible in the current study and can be used to provide a minimum set of quality standards. Our provisional results showed that 44% of the included AMCs were classified as Class III (high solubility, low permeability), followed by Class II (26%), Class I (18%), and Class IV (12%). A similar trend was observed when CHMs were classified in accordance with the BCS class of AMCs. Most (45%) of the included CHMs were classified as Class III, followed by Class II (16%), Class I (10%), and Class IV (6%); whereas 23% of the CHMs were of mixed class due to the presence of multiple individual AMCs with different BCS classifications. Moreover, about 60% of the AMCs were classified as high-solubility compounds (Class I and Class III), suggesting an important role for an in vitro dissolution test in setting quality control standards ensuring consistent biopharmaceutical quality for the commercially available CHM products. That is, provisionally, more than half of the AMCs of the top-selling CHMs included in this study would be candidates for a bioequivalence (BE) biowaiver, based on WHO recommendations and EMEA guidelines. Thus a dissolution requirement on these AMCs would represent a significant advance in the pharmaceutical quality of CHM today.

[Doses of anti-infectives for systemic use are scarcely notified in clinical cases reported to the Revista Española de Anestesiología y Reanimación].

PubMed

Gerónimo-Pardo, M

2014-01-01

To describe the frequency of dose notification of antiinfectives for systemic use in clinical cases published in Revista Española de Anestesiología y Reanimación. Review of individualized clinical cases published in the sections «Clinical case» or «Letter to the Editor» of the above mentioned journal from year 2010 to 2012, and identification of the drugs and their therapeutic regimens cited in such publications, being dose notification the main variable. Drugs have been classified according to the Anatomical Therapeutic Chemical Classification System. One thousand one hundred and thirty-five drugs cited 1,317 times were identified in 167 articles describing the clinical pictures of 182 patients, 73 of the citations (5.6%) regarding to drugs belonging to group J (Antiinfectives for systemic use) which were divided into perioperative prophylaxis (n=15) and active treatment (n=58). Doses were scarcely notified for group J drugs as a whole (27.4%), but especially for active treatment (17.2%) compared to perioperative prophylaxis (66.7%), percentage which was similar to those more classical anesthetic drugs (fentanyl: 86.6%; remifentanil: 70.5%; sevoflurane: 78%; propofol: 79%; rocuronium:79.6%; cisatracurium: 68.4%) or even for antiemetics (ondansetron: 92.3%; dexamethasone: 84.6%). Quality of case reports could be improved by including dose notification for antiinfective agents. Copyright © 2013 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Published by Elsevier España. All rights reserved.

A Cross-National Examination of Differences in Classification of Lifetime Alcohol Use Disorder Between DSM-IV and DSM-5: Findings from the World Mental Health Survey.

PubMed

Slade, Tim; Chiu, Wai-Tat; Glantz, Meyer; Kessler, Ronald C; Lago, Luise; Sampson, Nancy; Al-Hamzawi, Ali; Florescu, Silvia; Moskalewicz, Jacek; Murphy, Sam; Navarro-Mateu, Fernando; Torres de Galvis, Yolanda; Viana, Maria Carmen; Xavier, Miguel; Degenhardt, Louisa

2016-08-01

The current study sought to examine the diagnostic overlap in DSM-IV and DSM-5 alcohol use disorder (AUD) and determine the clinical correlates of changing diagnostic status across the 2 classification systems. DSM-IV and DSM-5 definitions of AUD were compared using cross-national community survey data in 9 low-, middle-, and high-income countries. Participants were 31,367 respondents to surveys in the World Health Organization's World Mental Health Survey Initiative. The Composite International Diagnostic Interview, version 3.0, was used to derive DSM-IV and DSM-5 lifetime diagnoses of AUD. Clinical characteristics, also assessed in the surveys, included lifetime DSM-IV anxiety; mood and drug use disorders; lifetime suicidal ideation, plan, and attempt; general functional impairment; and psychological distress. Compared with DSM-IV AUD (12.3%, SE = 0.3%), the DSM-5 definition yielded slightly lower prevalence estimates (10.8%, SE = 0.2%). Almost one-third (n = 802) of all DSM-IV abuse cases switched to subthreshold according to DSM-5 and one-quarter (n = 467) of all DSM-IV diagnostic orphans switched to mild AUD according to DSM-5. New cases of DSM-5 AUD were largely similar to those who maintained their AUD across both classifications. Similarly, new DSM-5 noncases were similar to those who were subthreshold across both classifications. The exception to this was with regard to the prevalence of any lifetime drug use disorder. In this large cross-national community sample, the prevalence of DSM-5 lifetime AUD was only slightly lower than the prevalence of DSM-IV lifetime AUD. Nonetheless, there was considerable diagnostic switching, with a large number of people inconsistently identified across the 2 DSM classifications. Copyright © 2016 by the Research Society on Alcoholism.

Columbia Classification Algorithm of Suicide Assessment (C-CASA): classification of suicidal events in the FDA's pediatric suicidal risk analysis of antidepressants.

PubMed

Posner, Kelly; Oquendo, Maria A; Gould, Madelyn; Stanley, Barbara; Davies, Mark

2007-07-01

To evaluate the link between antidepressants and suicidal behavior and ideation (suicidality) in youth, adverse events from pediatric clinical trials were classified in order to identify suicidal events. The authors describe the Columbia Classification Algorithm for Suicide Assessment (C-CASA), a standardized suicidal rating system that provided data for the pediatric suicidal risk analysis of antidepressants conducted by the Food and Drug Administration (FDA). Adverse events (N=427) from 25 pediatric antidepressant clinical trials were systematically identified by pharmaceutical companies. Randomly assigned adverse events were evaluated by three of nine independent expert suicidologists using the Columbia classification algorithm. Reliability of the C-CASA ratings and agreement with pharmaceutical company classification were estimated. Twenty-six new, possibly suicidal events (behavior and ideation) that were not originally identified by pharmaceutical companies were identified in the C-CASA, and 12 events originally labeled as suicidal by pharmaceutical companies were eliminated, which resulted in a total of 38 discrepant ratings. For the specific label of "suicide attempt," a relatively low level of agreement was observed between the C-CASA and pharmaceutical company ratings, with the C-CASA reporting a 50% reduction in ratings. Thus, although the C-CASA resulted in the identification of more suicidal events overall, fewer events were classified as suicide attempts. Additionally, the C-CASA ratings were highly reliable (intraclass correlation coefficient [ICC]=0.89). Utilizing a methodical, anchored approach to categorizing suicidality provides an accurate and comprehensive identification of suicidal events. The FDA's audit of the C-CASA demonstrated excellent transportability of this approach. The Columbia algorithm was used to classify suicidal adverse events in the recent FDA adult antidepressant safety analyses and has also been mandated to be applied to all anticonvulsant trials and other centrally acting agents and nonpsychotropic drugs.

Columbia Classification Algorithm of Suicide Assessment (C-CASA): Classification of Suicidal Events in the FDA’s Pediatric Suicidal Risk Analysis of Antidepressants

PubMed Central

Posner, Kelly; Oquendo, Maria A.; Gould, Madelyn; Stanley, Barbara; Davies, Mark

2013-01-01

Objective To evaluate the link between antidepressants and suicidal behavior and ideation (suicidality) in youth, adverse events from pediatric clinical trials were classified in order to identify suicidal events. The authors describe the Columbia Classification Algorithm for Suicide Assessment (C-CASA), a standardized suicidal rating system that provided data for the pediatric suicidal risk analysis of antide-pressants conducted by the Food and Drug Administration (FDA). Method Adverse events (N=427) from 25 pediatric antidepressant clinical trials were systematically identified by pharmaceutical companies. Randomly assigned adverse events were evaluated by three of nine independent expert suicidologists using the Columbia classification algorithm. Reliability of the C-CASA ratings and agreement with pharmaceutical company classification were estimated. Results Twenty-six new, possibly suicidal events (behavior and ideation) that were not originally identified by pharmaceutical companies were identified in the C-CASA, and 12 events originally labeled as suicidal by pharmaceutical companies were eliminated, which resulted in a total of 38 discrepant ratings. For the specific label of “suicide attempt,” a relatively low level of agreement was observed between the C-CASA and pharmaceutical company ratings, with the C-CASA reporting a 50% reduction in ratings. Thus, although the C-CASA resulted in the identification of more suicidal events overall, fewer events were classified as suicide attempts. Additionally, the C-CASA ratings were highly reliable (intraclass correlation coefficient [ICC]=0.89). Conclusions Utilizing a methodical, anchored approach to categorizing suicidality provides an accurate and comprehensive identification of suicidal events. The FDA’s audit of the C-CASA demonstrated excellent transportability of this approach. The Columbia algorithm was used to classify suicidal adverse events in the recent FDA adult antidepressant safety analyses and has also been mandated to be applied to all anticonvulsant trials and other centrally acting agents and nonpsychotropic drugs. PMID:17606655

What criteria for pharmaceuticals reimbursement? An empirical analysis of the evaluation of "medical service rendered" by reimbursable drugs in France.

PubMed

Le Pen, C; Priol, G; Lilliu, H

2003-01-01

The criteria for the registration of new drugs may differ from the criteria for drug reimbursement. In 2000 the French government entrusted the French Medicines Agency with determining the "medical service rendered" (MSR) for each reimbursable drug. The goal was to determine which drugs could be classified with an "insufficient" MSR and therefore should be taken out of the scope of health insurance. We analyze the concepts and methods used for this evaluation and the kind of results that are obtained. We collected data on the result of MSR classification and the criteria used to perform this classification (efficacy-security, severity of the disease,place in the therapeutic strategy, existence of therapeutic alternative, public health value) for a sample of 1453 drugs belonging to five therapeutic areas. We used statistical analysis to determine what were the most influential criteria. Only two criteria - efficacy and disease severity - suffice to very largely explain the MSR classification. The other criteria contribute little added value. Some of these criteria clearly suffer from a lack of clarification, leading to different interpretations according to therapeutic class or even according to drug or drug family. The evaluation procedure differs between therapeutic classes, at least at intermediate MSR levels. Analysis of the French experience with MSR shows that the evaluation procedure has not succeeded in completely breaking away from the traditional logic of the marketing authorization and registration, as witnessed by the importance of the "efficacy/safety" criterion, the absence of an economic criterion, and the vagueness of the "public health value" criterion, which one would have thought would instead be decisive.

Ontology-based literature mining and class effect analysis of adverse drug reactions associated with neuropathy-inducing drugs.

PubMed

Hur, Junguk; Özgür, Arzucan; He, Yongqun

2018-06-07

Adverse drug reactions (ADRs), also called as drug adverse events (AEs), are reported in the FDA drug labels; however, it is a big challenge to properly retrieve and analyze the ADRs and their potential relationships from textual data. Previously, we identified and ontologically modeled over 240 drugs that can induce peripheral neuropathy through mining public drug-related databases and drug labels. However, the ADR mechanisms of these drugs are still unclear. In this study, we aimed to develop an ontology-based literature mining system to identify ADRs from drug labels and to elucidate potential mechanisms of the neuropathy-inducing drugs (NIDs). We developed and applied an ontology-based SciMiner literature mining strategy to mine ADRs from the drug labels provided in the Text Analysis Conference (TAC) 2017, which included drug labels for 53 neuropathy-inducing drugs (NIDs). We identified an average of 243 ADRs per NID and constructed an ADR-ADR network, which consists of 29 ADR nodes and 149 edges, including only those ADR-ADR pairs found in at least 50% of NIDs. Comparison to the ADR-ADR network of non-NIDs revealed that the ADRs such as pruritus, pyrexia, thrombocytopenia, nervousness, asthenia, acute lymphocytic leukaemia were highly enriched in the NID network. Our ChEBI-based ontology analysis identified three benzimidazole NIDs (i.e., lansoprazole, omeprazole, and pantoprazole), which were associated with 43 ADRs. Based on ontology-based drug class effect definition, the benzimidazole drug group has a drug class effect on all of these 43 ADRs. Many of these 43 ADRs also exist in the enriched NID ADR network. Our Ontology of Adverse Events (OAE) classification further found that these 43 benzimidazole-related ADRs were distributed in many systems, primarily in behavioral and neurological, digestive, skin, and immune systems. Our study demonstrates that ontology-based literature mining and network analysis can efficiently identify and study specific group of drugs and their associated ADRs. Furthermore, our analysis of drug class effects identified 3 benzimidazole drugs sharing 43 ADRs, leading to new hypothesis generation and possible mechanism understanding of drug-induced peripheral neuropathy.

Using FDA reports to inform a classification for health information technology safety problems

PubMed Central

Ong, Mei-Sing; Runciman, William; Coiera, Enrico

2011-01-01

Objective To expand an emerging classification for problems with health information technology (HIT) using reports submitted to the US Food and Drug Administration Manufacturer and User Facility Device Experience (MAUDE) database. Design HIT events submitted to MAUDE were retrieved using a standardized search strategy. Using an emerging classification with 32 categories of HIT problems, a subset of relevant events were iteratively analyzed to identify new categories. Two coders then independently classified the remaining events into one or more categories. Free-text descriptions were analyzed to identify the consequences of events. Measurements Descriptive statistics by number of reported problems per category and by consequence; inter-rater reliability analysis using the κ statistic for the major categories and consequences. Results A search of 899 768 reports from January 2008 to July 2010 yielded 1100 reports about HIT. After removing duplicate and unrelated reports, 678 reports describing 436 events remained. The authors identified four new categories to describe problems with software functionality, system configuration, interface with devices, and network configuration; the authors' classification with 32 categories of HIT problems was expanded by the addition of these four categories. Examination of the 436 events revealed 712 problems, 96% were machine-related, and 4% were problems at the human–computer interface. Almost half (46%) of the events related to hazardous circumstances. Of the 46 events (11%) associated with patient harm, four deaths were linked to HIT problems (0.9% of 436 events). Conclusions Only 0.1% of the MAUDE reports searched were related to HIT. Nevertheless, Food and Drug Administration reports did prove to be a useful new source of information about the nature of software problems and their safety implications with potential to inform strategies for safe design and implementation. PMID:21903979

Summary of the NICHD-BPCA Pediatric Formulation Initiatives Workshop-Pediatric Biopharmaceutics Classification System (PBCS) Working Group

PubMed Central

Abdel-Rahman, Susan; Amidon, Gordon L.; Kaul, Ajay; Lukacova, Viera; Vinks, Alexander A.; Knipp, Gregory

2012-01-01

The Biopharmaceutics Classification System (BCS) allows compounds to be classified based on their in vitro solubility and intestinal permeability. The BCS has found widespread use in the pharmaceutical community as an enabling guide for the rational selection of compounds, formulation for clinical advancement and generic biowaivers. The Pediatric Biopharmaceutics Classification System (PBCS) working group was convened to consider the possibility of developing an analogous pediatric based classification system. Since there are distinct developmental differences that can alter intestinal contents, volumes, permeability and potentially biorelevant solubilities at the different ages, the PBCS working group focused on identifying age specific issues that would need to be considered in establishing a flexible, yet rigorous PBCS. Objective To summarize the findings of the PBCS working group and provide insights into considerations required for the development of a pediatric based biopharmaceutics classification system. Methods Through several meetings conducted both at The Eunice Kennedy Shriver National Institute of Child Health, Human Development (NICHD)-US Pediatric Formulation Initiative (PFI) workshop (November 2011) and via teleconferences, the PBCS working group considered several high level questions that were raised to frame the classification system. In addition, the PBCS working group identified a number of knowledge gaps that would need to be addressed in order to develop a rigorous PBCS. Results It was determined that for a PBCS to be truly meaningful, it would need to be broken down into several different age groups that would account for developmental changes in intestinal permeability, luminal contents, and gastrointestinal transit. Several critical knowledge gaps where identified including: 1) a lack of fully understanding the ontogeny of drug metabolizing enzymes and transporters along the gastrointestinal (GI) tract, in the liver and in the kidney; 2) an incomplete understanding of age-based changes in the GI, liver and kidney physiology; 3) a clear need to better understand age-based intestinal permeability and fraction absorbed required to develop the PBCS; 4) a clear need for the development and organization of pediatric tissue biobanks to serve as a source for ontogenic research; and 5) a lack of literature published in age-based pediatric pharmacokinetics in order to build Physiologically- and Population-Based Pharmacokinetic (PBPK) databases. Conclusions To begin the process of establishing a PBPK model, ten pediatric therapeutic agents were selected (based on their adult BCS classifications). Those agents should be targeted for additional research in the future. The PBCS working group also identified several areas where a greater emphasis on research is needed to enable the development of a PBCS. PMID:23149009

Automatic Identification of Messages Related to Adverse Drug Reactions from Online User Reviews using Feature-based Classification.

PubMed

Liu, Jingfang; Zhang, Pengzhu; Lu, Yingjie

2014-11-01

User-generated medical messages on Internet contain extensive information related to adverse drug reactions (ADRs) and are known as valuable resources for post-marketing drug surveillance. The aim of this study was to find an effective method to identify messages related to ADRs automatically from online user reviews. We conducted experiments on online user reviews using different feature set and different classification technique. Firstly, the messages from three communities, allergy community, schizophrenia community and pain management community, were collected, the 3000 messages were annotated. Secondly, the N-gram-based features set and medical domain-specific features set were generated. Thirdly, three classification techniques, SVM, C4.5 and Naïve Bayes, were used to perform classification tasks separately. Finally, we evaluated the performance of different method using different feature set and different classification technique by comparing the metrics including accuracy and F-measure. In terms of accuracy, the accuracy of SVM classifier was higher than 0.8, the accuracy of C4.5 classifier or Naïve Bayes classifier was lower than 0.8; meanwhile, the combination feature sets including n-gram-based feature set and domain-specific feature set consistently outperformed single feature set. In terms of F-measure, the highest F-measure is 0.895 which was achieved by using combination feature sets and a SVM classifier. In all, we can get the best classification performance by using combination feature sets and SVM classifier. By using combination feature sets and SVM classifier, we can get an effective method to identify messages related to ADRs automatically from online user reviews.

Solid self-nanoemulsifying delivery systems as a platform technology for formulation of poorly soluble drugs.

PubMed

Bansal, Tripta; Mustafa, Gulam; Khan, Zeenat I; Ahmad, Farhaan J; Khar, Roop K; Talegaonkar, Sushama

2008-01-01

New drug discovery programs produce molecules with poor physico-chemical properties, making delivery of these molecules at the right proportion into the body a big challenge to the formulation scientist. The various options available to overcome the hurdle include solvent precipitation, micronisation/nanonization using high-pressure homogenization or jet milling, salt formation, use of microspheres, solid dispersions, cogrinding, complexation, and many others. Self-nanoemulsifying systems (SNES) form one of the most popular and commercially viable approaches for delivery of poorly soluble drugs exhibiting dissolution rate limited absorption, especially those belonging to the Biopharmaceutics Classification System II/IV. SNES are essentially an isotropic blend of oils, surfactants, and/or cosolvents that emulsify spontaneously to produce oil in water nanoemulsion when introduced into aqueous phase under gentle agitation. Conventional SNES consist of liquid forms filled in hard or soft gelatin capsules, which are least preferred due to leaching and leakage phenomenon, interaction with capsule shell components, handling difficulties, machinability, and stability problems. Solidification of these liquid systems to yield solid self-nanoemulsifying systems (SSNES) offer a possible solution to the mentioned complications, and that is why these systems have attracted wide attention. Other than the advantages and wide application of SSNEDS, the present paper focuses on formulation considerations, selection, and function of solidifying excipients; techniques of preparation; and case studies of drugs selected from different therapeutic categories. Developments in the techniques for in vitro evaluation of SSNEDS have also been discussed.

21 CFR 874.1100 - Earphone cushion for audiometric testing.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Earphone cushion for audiometric testing. 874.1100 Section 874.1100 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... connection path) between the audiometer earphone and the patient's ear. (b) Classification. Class I (general...

21 CFR 874.1100 - Earphone cushion for audiometric testing.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Earphone cushion for audiometric testing. 874.1100 Section 874.1100 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... connection path) between the audiometer earphone and the patient's ear. (b) Classification. Class I (general...

21 CFR 886.3600 - Intraocular lens.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Intraocular lens. 886.3600 Section 886.3600 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL... the natural lens of an eye. (b) Classification. Class III. (c) Date PMA or notice of completion of a...

21 CFR 886.1300 - Afterimage flasher.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Afterimage flasher. 886.1300 Section 886.1300 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL... corresponding points on the retina have the same directional value). (b) Classification. Class II. [55 FR 48441...

21 CFR 886.1300 - Afterimage flasher.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Afterimage flasher. 886.1300 Section 886.1300 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL... corresponding points on the retina have the same directional value). (b) Classification. Class II. [55 FR 48441...

21 CFR 886.1790 - Nearpoint ruler.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Nearpoint ruler. 886.1790 Section 886.1790 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL... to which the visual lines are directed when convergence is at its maximum). (b) Classification. Class...

21 CFR 886.1190 - Distometer.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Distometer. 886.1190 Section 886.1190 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES... the change of the visual image when a lens is in place. (b) Classification. Class I (general controls...

21 CFR 886.4445 - Permanent magnet.

Code of Federal Regulations, 2014 CFR

2014-04-01

... foreign bodies from eye tissue. (b) Classification. Class I (general controls). The device is exempt from... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Permanent magnet. 886.4445 Section 886.4445 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL...

21 CFR 886.4445 - Permanent magnet.

Code of Federal Regulations, 2013 CFR

2013-04-01

... foreign bodies from eye tissue. (b) Classification. Class I (general controls). The device is exempt from... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Permanent magnet. 886.4445 Section 886.4445 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL...

21 CFR 886.4445 - Permanent magnet.

Code of Federal Regulations, 2012 CFR

2012-04-01

... foreign bodies from eye tissue. (b) Classification. Class I (general controls). The device is exempt from... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Permanent magnet. 886.4445 Section 886.4445 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL...

21 CFR 886.4445 - Permanent magnet.

Code of Federal Regulations, 2011 CFR

2011-04-01

... foreign bodies from eye tissue. (b) Classification. Class I (general controls). The device is exempt from... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Permanent magnet. 886.4445 Section 886.4445 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL...

21 CFR 880.6250 - Patient examination glove.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Patient examination glove. 880.6250 Section 880.6250 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... contamination between patient and examiner. (b) Classification. Class I (general controls). [45 FR 69682-69737...

21 CFR 892.5780 - Light beam patient position indicator.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Light beam patient position indicator. 892.5780 Section 892.5780 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... patient and to monitor alignment of the radiation beam with the patient's anatomy. (b) Classification...

21 CFR 892.5780 - Light beam patient position indicator.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Light beam patient position indicator. 892.5780 Section 892.5780 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... patient and to monitor alignment of the radiation beam with the patient's anatomy. (b) Classification...

21 CFR 892.5780 - Light beam patient position indicator.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Light beam patient position indicator. 892.5780 Section 892.5780 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... patient and to monitor alignment of the radiation beam with the patient's anatomy. (b) Classification...

21 CFR 892.5780 - Light beam patient position indicator.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Light beam patient position indicator. 892.5780 Section 892.5780 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... patient and to monitor alignment of the radiation beam with the patient's anatomy. (b) Classification...

21 CFR 870.3610 - Implantable pacemaker pulse generator.

Code of Federal Regulations, 2010 CFR

2010-04-01

... asynchronous devices implanted in the human body. (b) Classification. Class III (premarket approval). (c) Date... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Implantable pacemaker pulse generator. 870.3610 Section 870.3610 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES...

21 CFR 870.3610 - Implantable pacemaker pulse generator.

Code of Federal Regulations, 2011 CFR

2011-04-01

... asynchronous devices implanted in the human body. (b) Classification. Class III (premarket approval). (c) Date... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Implantable pacemaker pulse generator. 870.3610 Section 870.3610 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES...

21 CFR 868.1575 - Gas collection vessel.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Gas collection vessel. 868.1575 Section 868.1575 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... for subsequent analysis. It does not include a sampling pump. (b) Classification. Class I (general...

21 CFR 868.1575 - Gas collection vessel.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Gas collection vessel. 868.1575 Section 868.1575 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... for subsequent analysis. It does not include a sampling pump. (b) Classification. Class I (general...

21 CFR 868.1575 - Gas collection vessel.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Gas collection vessel. 868.1575 Section 868.1575 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... for subsequent analysis. It does not include a sampling pump. (b) Classification. Class I (general...

21 CFR 888.5940 - Cast component.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Cast component. 888.5940 Section 888.5940 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES... the cast heel, toe cap, cast support, and walking iron. (b) Classification. Class I (general controls...

21 CFR 888.5940 - Cast component.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Cast component. 888.5940 Section 888.5940 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES... the cast heel, toe cap, cast support, and walking iron. (b) Classification. Class I (general controls...

MO-DE-207B-03: Improved Cancer Classification Using Patient-Specific Biological Pathway Information Via Gene Expression Data

DOE Office of Scientific and Technical Information (OSTI.GOV)

Young, M; Craft, D

Purpose: To develop an efficient, pathway-based classification system using network biology statistics to assist in patient-specific response predictions to radiation and drug therapies across multiple cancer types. Methods: We developed PICS (Pathway Informed Classification System), a novel two-step cancer classification algorithm. In PICS, a matrix m of mRNA expression values for a patient cohort is collapsed into a matrix p of biological pathways. The entries of p, which we term pathway scores, are obtained from either principal component analysis (PCA), normal tissue centroid (NTC), or gene expression deviation (GED). The pathway score matrix is clustered using both k-means and hierarchicalmore » clustering, and a clustering is judged by how well it groups patients into distinct survival classes. The most effective pathway scoring/clustering combination, per clustering p-value, thus generates various ‘signatures’ for conventional and functional cancer classification. Results: PICS successfully regularized large dimension gene data, separated normal and cancerous tissues, and clustered a large patient cohort spanning six cancer types. Furthermore, PICS clustered patient cohorts into distinct, statistically-significant survival groups. For a suboptimally-debulked ovarian cancer set, the pathway-classified Kaplan-Meier survival curve (p = .00127) showed significant improvement over that of a prior gene expression-classified study (p = .0179). For a pancreatic cancer set, the pathway-classified Kaplan-Meier survival curve (p = .00141) showed significant improvement over that of a prior gene expression-classified study (p = .04). Pathway-based classification confirmed biomarkers for the pyrimidine, WNT-signaling, glycerophosphoglycerol, beta-alanine, and panthothenic acid pathways for ovarian cancer. Despite its robust nature, PICS requires significantly less run time than current pathway scoring methods. Conclusion: This work validates the PICS method to improve cancer classification using biological pathways. Patients are classified with greater specificity and physiological relevance as compared to current gene-specific approaches. Focus now moves to utilizing PICS for pan-cancer patient-specific treatment response prediction.« less

Combined effects of the drug distribution and mucus diffusion properties of self-microemulsifying drug delivery systems on the oral absorption of fenofibrate.

PubMed

Sunazuka, Yushi; Ueda, Keisuke; Higashi, Kenjirou; Tanaka, Yusuke; Moribe, Kunikazu

2018-05-24

We present the absorption improvement mechanism of fenofibrate (FFB), a Biopharmaceutics Classification System (BCS) class II drug, from self-microemulsifying drug delivery systems (SMEDDS), centered on improving the diffusion of FFB through the unstirred water layer (UWL). Four SMEDDS formulations containing Labrafac™ lipophile WL 1349 (WL1349) or Labrafil ® M 1944CS (M1944) oils and NIKKOL HCO-40 (HCO40) or NIKKOL HCO-60 (HCO60) surfactants were prepared. Every SMEDDS formulation formed microemulsion droplets of approximately 30 nm. In vitro tests showed that the microemulsion droplets containing M1944 had relatively small FFB solubilization capacities, causing larger amounts of FFB to be dissolved in the bulk water phase, compared to the droplets containing WL1349. The diffusivity of the microemulsion droplets through the mucin solution layer was enhanced when using HCO40 compared to HCO60. The oral absorption in rats was the highest when using the SMEDDS formulation containing M1944 and HCO40. High FFB distribution in the bulk water phase and fast diffusion of microemulsion droplets through the mucus layer contributed to the efficient delivery of FFB molecules through the UWL to the epithelial cells, leading to enhanced FFB absorption. Copyright © 2018 Elsevier B.V. All rights reserved.

FDA marketing claims, and the practitioner.

PubMed

Runner, Susan

2006-03-01

The Food and Drug Administration (FDA) is the federal agency that is tasked with regulating market entry for medical devices. The laws that govern this process are codified in the Federal Food Drug and Cosmetic Act (the Act) and the regulations are based on this law. The medical device amendments to the Act were instituted in 1976, instituting the methods for classification of medical devices and the format for the premarket review of devices. Information for practitioners on how medical devices come to market, what data are required, how specific claims are cleared, and how the practitioner can give input to the system are critical for the further development of safe and effective medical devices.

Standardisation of the FAERS database: a systematic approach to manually recoding drug name variants.

PubMed

Wong, Carmen K; Ho, Samuel S; Saini, Bandana; Hibbs, David E; Fois, Romano A

2015-07-01

The US Food and Drug Administration Adverse Event Reporting System (FAERS), one of the world's largest spontaneous reporting systems, is difficult to use because of report duplication and a lack of standardisation in the recording of drug names. Unresolved data quality issues may distort statistical analyses, rendering the results difficult to interpret when detecting and monitoring adverse effects of pharmaceutical products. The aim of this study was to develop and implement a data cleaning protocol to identify and resolve drug nomenclature issues. The key 'data treatment' plan involved standardising drug names held in the FAERS database. Four million five hundred and six thousand five hundred and seventy-seven. Individual Safety Reports submitted to the FAERS between 1 January 2003 and 31 August 2012 were included for this study. OpenRefine was used to standardise drug name variants in the database such that they were consistent with international non-proprietary nomenclature defined by the World Health Organisation Anatomical Therapeutic Chemical classification. Drug variants where generic constituents could not be confidently determined, undecipherable drug names and non-medicinal products were retained verbatim. After the standardisation process, more than 16 611 916 drug entries were cleaned to their relevant international non-proprietary name. The cleaned drug table comprised 71 858 drug name variants and includes both standardised and original terms. Ninety-nine per cent of drug names was standardised using this method. The millions of reports enclosed in the FAERS contain valuable information that is of interest to pharmacovigilance, toxicology and post-marketing surveillance researchers. With the standardisation of the drug nomenclature, the database can be better utilised by research groups around the world. Copyright © 2015 John Wiley & Sons, Ltd.

Surveillance of contrast-media-induced hypersensitivity reactions using signals from an electronic medical recording system.

PubMed

Kim, Min-Hye; Park, Chang-Han; Kim, Duk-In; Kim, Kyung-Mook; Kim, Hui-Kyu; Lim, Kyu-Hyoung; Song, Woo-Jung; Lee, Sang-Min; Kim, Sae-Hoon; Kwon, Hyouk-Soo; Park, Heung-Woo; Yoon, Chang-Jin; Cho, Sang-Heon; Min, Kyung-Up; Kim, You-Young; Chang, Yoon-Seok

2012-03-01

Contrast-media (CM) hypersensitivity is a well-known adverse drug reaction. Surveillance of adverse drug reactions usually depends on spontaneous reports. However, the rate of spontaneous reports is low. Recent progress in information technology enables the electronic search on signals of adverse drug reactions from electronic medical recording (EMR) systems. To analyze the incidence and clinical characteristics of CM hypersensitivity using an EMR-based surveillance system. The surveillance system used signals from standardized terms within the international classification of nursing practice terms that can indicate symptoms of CM hypersensitivity and from the order codes for procedures that used contrast media, antihistamine, and epinephrine. The search strategy was validated by allergists comparing the electronic search strategy versus manually reviewing medical charts over one month. The main study covered for one year period. Detection rate of the electronic search method was 0.9% (7/759), while that of the manual search method was 0.8% (6/759). EMR-based electronic search method was highly efficient: reduced the charts that needed to be reviewed by 96% (28/759). The sensitivity of electronic screening was 66.7%, specificity was 99.6%, and the negative predictive value was 99.7%. CM hypersensitivity reactions were noted in 266 among 12,483 cases (2.1%). Urticaria was the most frequent symptom (74.4%). CT was the most frequent procedure (3.6%) that induced CM hypersensitivity. A surveillance system using EMR may be a useful tool in the study of drug hypersensitivity epidemiology and may be used in an adverse drug reaction alarm system and as a clinical, decision making support system. Copyright © 2012 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Use of ATC to describe duplicate medications in primary care prescriptions.

PubMed

Lim, Chiao Mei; Aryani Md Yusof, Faridah; Selvarajah, Sharmini; Lim, Teck Onn

2011-10-01

We aimed to demonstrate the suitability of the Anatomical Therapeutic Chemical Classification (ATC) to describe duplicate drugs and duplicate drug classes in prescription data and describe the pattern of duplicates from public and private primary care clinics of Kuala Lumpur, Malaysia. We analyzed prescription data year 2005 from all 14 public clinics in Kuala Lumpur with 12,157 prescriptions, and a sample of 188 private clinics with 25,612 prescriptions. As ATC Level 5 code represents the molecule and Level 4 represents the pharmacological subgroup, we used repetitions of codes in the same prescription to describe duplicate drugs or duplicate drug classes and compared them between the public and private clinics. At Level 4 ATC, prescriptions with duplicates drug classes were 1.46% of all prescriptions in private and 0.04% in public clinics. At Level 5 ATC, prescriptions with duplicate drugs were 1.81% for private and 0.95% for public clinics. In private clinics at Level 5, 73.3% of prescriptions with duplicates involved systemic combination drugs; at Level 4, 40.3% involved systemic combination drugs. In the public sector at Level 5, 95.7% of prescriptions with duplicates involved topical products. Repetitions of the same ATC codes were mostly useful to describe duplicate medications; however, we recommend avoid using ATC codes for tropical products for this purpose due to ambiguity. Combination products were often involved in duplicate prescribing; redesign of these products might improve prescribing quality. Duplicates occurred more often in private clinics than public clinics in Malaysia.

Trends in oral drug bioavailability following bariatric surgery: examining the variable extent of impact on exposure of different drug classes

PubMed Central

Darwich, Adam S; Henderson, Kathryn; Burgin, Angela; Ward, Nicola; Whittam, Janet; Ammori, Basil J; Ashcroft, Darren M; Rostami-Hodjegan, Amin

2012-01-01

AIMS To identify the most commonly prescribed drugs in a bariatric surgery population and to assess existing evidence regarding trends in oral drug bioavailability post bariatric surgery. METHODS A retrospective audit was undertaken to document commonly prescribed drugs amongst patients undergoing bariatric surgery in an NHS hospital in the UK and to assess practice for drug administration following bariatric surgery. The available literature was examined for trends relating to drug permeability and solubility with regards to the Biopharmaceutics Classification System (BCS) and main route of elimination. RESULTS No significant difference in the ‘post/pre surgery oral drug exposure ratio’ (ppR) was apparent between BCS class I to IV drugs, with regards to dose number (Do) or main route of elimination. Drugs classified as ‘solubility limited’ displayed an overall reduction as compared with ‘freely soluble’ compounds, as well as an unaltered and increased ppR. CONCLUSION Clinical studies establishing guidelines for commonly prescribed drugs, and the monitoring of drugs exhibiting a narrow therapeutic window or without a readily assessed clinical endpoint, are warranted. Using mechanistically based pharmacokinetic modelling for simulating the multivariate nature of changes in drug exposure may serve as a useful tool in the further understanding of postoperative trends in oral drug exposure and in developing practical clinical guidance. PMID:22463107

Toward a Reasoned Classification of Diseases Using Physico-Chemical Based Phenotypes

PubMed Central

Schwartz, Laurent; Lafitte, Olivier; da Veiga Moreira, Jorgelindo

2018-01-01

Background: Diseases and health conditions have been classified according to anatomical site, etiological, and clinical criteria. Physico-chemical mechanisms underlying the biology of diseases, such as the flow of energy through cells and tissues, have been often overlooked in classification systems. Objective: We propose a conceptual framework toward the development of an energy-oriented classification of diseases, based on the principles of physical chemistry. Methods: A review of literature on the physical chemistry of biological interactions in a number of diseases is traced from the point of view of the fluid and solid mechanics, electricity, and chemistry. Results: We found consistent evidence in literature of decreased and/or increased physical and chemical forces intertwined with biological processes of numerous diseases, which allowed the identification of mechanical, electric and chemical phenotypes of diseases. Discussion: Biological mechanisms of diseases need to be evaluated and integrated into more comprehensive theories that should account with principles of physics and chemistry. A hypothetical model is proposed relating the natural history of diseases to mechanical stress, electric field, and chemical equilibria (ATP) changes. The present perspective toward an innovative disease classification may improve drug-repurposing strategies in the future. PMID:29541031

[Detection and classification of medication errors at Joan XXIII University Hospital].

PubMed

Jornet Montaña, S; Canadell Vilarrasa, L; Calabuig Mũoz, M; Riera Sendra, G; Vuelta Arce, M; Bardají Ruiz, A; Gallart Mora, M J

2004-01-01

Medication errors are multifactorial and multidisciplinary, and may originate in processes such as drug prescription, transcription, dispensation, preparation and administration. The goal of this work was to measure the incidence of detectable medication errors that arise within a unit dose drug distribution and control system, from drug prescription to drug administration, by means of an observational method confined to the Pharmacy Department, as well as a voluntary, anonymous report system. The acceptance of this voluntary report system's implementation was also assessed. A prospective descriptive study was conducted. Data collection was performed at the Pharmacy Department from a review of prescribed medical orders, a review of pharmaceutical transcriptions, a review of dispensed medication and a review of medication returned in unit dose medication carts. A voluntary, anonymous report system centralized in the Pharmacy Department was also set up to detect medication errors. Prescription errors were the most frequent (1.12%), closely followed by dispensation errors (1.04%). Transcription errors (0.42%) and administration errors (0.69%) had the lowest overall incidence. Voluntary report involved only 4.25% of all detected errors, whereas unit dose medication cart review contributed the most to error detection. Recognizing the incidence and types of medication errors that occur in a health-care setting allows us to analyze their causes and effect changes in different stages of the process in order to ensure maximal patient safety.

'Designer drugs'. Recognizing and managing their toxic effects.

PubMed

Sternbach, G L; Varon, J

1992-06-01

"Adam," "Eve," "ecstasy," "China white." Illicit street drugs such as these are called designer drugs because they are designed to elicit certain effects and to bypass legal classification. Unfortunately, use and abuse of such substances can lead to serious medical problems and even death. Drs Sternbach and Varon describe the best-known compounds and discuss clinical characteristics and management of designer drug intoxication.

Validity of the prenatal risk overview for detecting drug use disorders in pregnancy.

PubMed

Harrison, Patricia A; Godecker, Amy; Sidebottom, Abbey

2012-11-01

To validate the Prenatal Risk Overview (PRO) drug use questions against a structured diagnostic interview among pregnant women. Prenatal care patients were administered the PRO at intake and then asked to consent to a research diagnostic interview. Of 1,367 women asked to participate, 1,274 consented and 745 completed the study. Three drug use items comprised one of 13 PRO psychosocial risk domains. The Structured Clinical Interview for DSM-IV (SCID) was used as the validation instrument. To assess criterion validity, the Moderate/High and High Risk classifications were cross-tabulated with SCID Drug Use Disorder diagnoses. In response to the PRO, almost one third of participants (29.4%) reported drug use during the 12 months pre-pregnancy awareness and 11.0% reported use post-pregnancy awareness; 7.0% met SCID diagnostic criteria for Drug Abuse, Drug Dependence, or both, primarily for marijuana use. Drug Use Disorder sensitivity and specificity rates for the PRO Moderate/High Risk classifications were 88.5% and 74.3%, respectively, and for High Risk only, 78.8% and 87.3%. The PRO yielded substantial self-reporting of drug use before and after pregnancy awareness with high sensitivity and specificity for detecting Drug Use Disorders. PRO results can inform decisions about appropriate clinical responses. © 2012 Wiley Periodicals, Inc.

Evaluation of the use of partition coefficients and molecular surface properties as predictors of drug absorption: a provisional biopharmaceutical classification of the list of national essential medicines of Pakistan

PubMed Central

Shawahna, R.; Rahman, NU.

2011-01-01

Background and the purpose of the study Partition coefficients (log D and log P) and molecular surface area (PSA) are potential predictors of the intestinal permeability of drugs. The aim of this investigation was to evaluate and compare these intestinal permeability indicators. Methods Aqueous solubility data were obtained from literature or calculated using ACD/Labs and ALOGPS. Permeability data were predicted based on log P, log D at pH 6.0 (log D6.0), and PSA. Results Metoprolol's log P, log D6.0, and a PSA of <65 Å correctly predicted 55.9%, 50.8% and 54.2% of permeability classes, respectively. Labetalol's log P, log D6.0 and PSA correctly predicted 54.2%, 64.4% and 61% of permeability classes, respectively. Log D6.0 correlated well (81%) with Caco-2 permeability (Papp). Of the list of national essential medicines, 135 orally administered drugs were classified into biopharmaceutical classification system (BCS). Of these, 57 (42.2%), 28 (20.7%), 44 (32.6%), and 6 (4.4%) were class I, II, III and IV respectively. Conclusion Log D6.0 showed better prediction capability than log P. Metoprolol as permeability internal standard was more conservative than labetalol. PMID:22615645

Artificial Lipid Membrane Permeability Method for Predicting Intestinal Drug Transport: Probing the Determining Step in the Oral Absorption of Sulfadiazine; Influence of the Formation of Binary and Ternary Complexes with Cyclodextrins.

PubMed

Delrivo, Alicia; Aloisio, Carolina; Longhi, Marcela R; Granero, Gladys

2018-04-01

We propose an in vitro permeability assay by using a modified lipid membrane to predict the in vivo intestinal passive permeability of drugs. Two conditions were tested, one with a gradient pH (pH 5.5 donor/pH 7.4 receptor) and the other with an iso-pH 7.4. The predictability of the method was established by correlating the obtained apparent intestinal permeability coefficients (P app ) and the oral dose fraction absorbed in humans (f a ) of 16 drugs with different absorption properties. The P app values correlated well with the absorption rates under the two conditions, and the method showed high predictability and good reproducibility. On the other hand, with this method, we successfully predicted the transport characteristics of oral sulfadiazine (SDZ). Also, the tradeoff between the increase in the solubility of SDZ by its complex formation with cyclodextrins and/or aminoacids and its oral permeability was assessed. Results suggest that SDZ is transported through the gastrointestinal epithelium by passive diffusion in a pH-dependent manner. These results support the classification of SDZ as a high/low borderline permeability compound and are in agreement with the Biopharmaceutics Classification Systems (BCS). This conclusion is consistent with the in vivo pharmacokinetic properties of SDZ.

Advice on drug safety in pregnancy: are there differences between commonly used sources of information?

PubMed

Frost Widnes, Sofia K; Schjøtt, Jan

2008-01-01

Safety regarding use in pregnancy is not established for many drugs. Inconsistencies between sources providing drug information can give rise to confusion with possible therapeutic consequences. Therefore, it is important to measure clinically important differences between drug information sources. The objective of this study was to compare two easily accessible Norwegian sources providing advice on drug safety in pregnancy - the product monographs in the Felleskatalog (FK), published by the pharmaceutical companies, and the five regional Drug Information Centres (DICs) in Norway - in addition to assessing the frequency of questions regarding drug safety in pregnancy made to the DICs according to the Anatomical Therapeutic Chemical (ATC) classification system. Advice on drug use in pregnancy provided by the DICs in 2003 and 2005 were compared with advice in the product monographs for the respective drugs in the FK. Comparison of advice was based on categorization to one of four categories: can be used, benefit-risk assessment, should not be used, or no available information. A total of 443 drug advice were categorized. Seven out of ten of drugs frequently enquired about, according to the ATC system, were drugs acting on the nervous system (group N). For 208 (47%) of the drugs, advice differed between the DICs and FK. Advice from the FK was significantly (p < 0.01) more restrictive than advice from the DICs. There were no differences in the level of consistency of advice between drugs that were newly introduced and those that had been on the market for a longer time, advice regarding use of drugs in the first trimester and advice regarding use of drugs in the second or third trimester, or between advice provided during 2003 and during 2005. The results of this study show considerable differences between two Norwegian sources providing advice on the use of drugs in pregnancy. Based on the knowledge that healthcare providers choose sources of information in a random manner, our results may be of clinical importance. We believe that the problem with heterogeneous drug information on this subject is not confined to Norway and that our results should be of international interest.

Medical devices; hematology and pathology devices; classification of cord blood processing system and storage container. Final rule.

PubMed

2007-02-01

The Food and Drug Administration (FDA) is classifying a cord blood processing system and storage container into class II (special controls). The special control that will apply to this device is the guidance document entitled "Class II Special Controls Guidance Document: Cord Blood Processing System and Storage Container." FDA is classifying this device into class II (special controls) in order to provide a reasonable assurance of safety and effectiveness of this device. Elsewhere in this issue of the Federal Register, FDA is announcing the availability of the guidance document that will serve as the special control for this device.

Applications of artificial neural network in AIDS research and therapy.

PubMed

Sardari, S; Sardari, D

2002-01-01

In recent years considerable effort has been devoted to applying pattern recognition techniques to the complex task of data analysis in drug research. Artificial neural networks (ANN) methodology is a modeling method with great ability to adapt to a new situation, or control an unknown system, using data acquired in previous experiments. In this paper, a brief history of ANN and the basic concepts behind the computing, the mathematical and algorithmic formulation of each of the techniques, and their developmental background is presented. Based on the abilities of ANNs in pattern recognition and estimation of system outputs from the known inputs, the neural network can be considered as a tool for molecular data analysis and interpretation. Analysis by neural networks improves the classification accuracy, data quantification and reduces the number of analogues necessary for correct classification of biologically active compounds. Conformational analysis and quantifying the components in mixtures using NMR spectra, aqueous solubility prediction and structure-activity correlation are among the reported applications of ANN as a new modeling method. Ranging from drug design and discovery to structure and dosage form design, the potential pharmaceutical applications of the ANN methodology are significant. In the areas of clinical monitoring, utilization of molecular simulation and design of bioactive structures, ANN would make the study of the status of the health and disease possible and brings their predicted chemotherapeutic response closer to reality.

Machine learning-based prediction of adverse drug effects: An example of seizure-inducing compounds.

PubMed

Gao, Mengxuan; Igata, Hideyoshi; Takeuchi, Aoi; Sato, Kaoru; Ikegaya, Yuji

2017-02-01

Various biological factors have been implicated in convulsive seizures, involving side effects of drugs. For the preclinical safety assessment of drug development, it is difficult to predict seizure-inducing side effects. Here, we introduced a machine learning-based in vitro system designed to detect seizure-inducing side effects. We recorded local field potentials from the CA1 alveus in acute mouse neocortico-hippocampal slices, while 14 drugs were bath-perfused at 5 different concentrations each. For each experimental condition, we collected seizure-like neuronal activity and merged their waveforms as one graphic image, which was further converted into a feature vector using Caffe, an open framework for deep learning. In the space of the first two principal components, the support vector machine completely separated the vectors (i.e., doses of individual drugs) that induced seizure-like events and identified diphenhydramine, enoxacin, strychnine and theophylline as "seizure-inducing" drugs, which indeed were reported to induce seizures in clinical situations. Thus, this artificial intelligence-based classification may provide a new platform to detect the seizure-inducing side effects of preclinical drugs. Copyright © 2017 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

Contemporary review of drug-induced pancreatitis: A different perspective

PubMed Central

Hung, Whitney Y; Abreu Lanfranco, Odaliz

2014-01-01

Although gallstone and alcohol use have been considered the most common causes of acute pancreatitis, hundreds of frequently prescribed medications are associated with this disease state. The true incidence is unknown since there are few population based studies available. The knowledge of drug induced acute pancreatitis is limited by the availability and the quality of the evidence as the majority of data is extrapolated from case reports. Establishing a definitive causal relationship between a drug and acute pancreatitis poses a challenge to clinicians. Several causative agent classification systems are often used to identify the suspected agents. They require regular updates since new drug induced acute pancreatitis cases are reported continuously. In addition, infrequently prescribed medications and herbal medications are often omitted. Furthermore, identification of drug induced acute pancreatitis with new medications often requires accumulation of post market case reports. The unrealistic expectation for a comprehensive list of medications and the multifactorial nature of acute pancreatitis call for a different approach. In this article, we review the potential mechanisms of drug induced acute pancreatitis and provide the perspective of deductive reasoning in order to allow clinicians to identify potential drug induced acute pancreatitis with limited data. PMID:25400984

21 CFR 880.5430 - Nonelectrically powered fluid injector.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Nonelectrically powered fluid injector. 880.5430 Section 880.5430 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... skin and deliver the fluid to the body. It may be used for mass inoculations. (b) Classification. Class...

77 FR 19534 - Medical Devices; Immunology and Microbiology Devices; Classification of Norovirus Serological...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-04-02

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration 21 CFR Part 866 [Docket No... Serological Reagents; Correction AGENCY: Food and Drug Administration, HHS. ACTION: Final rule; correction. SUMMARY: In the Federal Register of March 9, 2012 (76 FR 14272), the Food and Drug Administration (FDA...

21 CFR 886.5928 - Soft (hydrophilic) contact lens care products.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Soft (hydrophilic) contact lens care products. 886.5928 Section 886.5928 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... means of heat. (b) Classification. Class II (Special Controls) Guidance Document: “Guidance for Industry...

Evaluating the safety and dosing of drugs in patients with liver cirrhosis by literature review and expert opinion

PubMed Central

Weersink, Rianne A; Bouma, Margriet; Burger, David M; Drenth, Joost P H; Hunfeld, Nicole G M; Kranenborg, Minke; Monster-Simons, Margje H; van Putten, Sandra A W; Metselaar, Herold J; Taxis, Katja; Borgsteede, Sander D

2016-01-01

Introduction Liver cirrhosis can have a major impact on drug pharmacokinetics and pharmacodynamics. Patients with cirrhosis often suffer from potentially preventable adverse drug reactions. Guidelines on safe prescribing for these patients are lacking. The aim of this study is to develop a systematic method for evaluating the safety and optimal dosage of drugs in patients with liver cirrhosis. Methods and analysis For each drug, a six-step evaluation process will be followed. (1) Available evidence on the pharmacokinetics and safety of a drug in patients with liver cirrhosis will be collected from the Summary of Product Characteristics (SmPC) and a systematic literature review will be performed. (2) Data regarding two outcomes, namely pharmacokinetics and safety, will be extracted and presented in a standardised assessment report. (3) A safety classification and dosage suggestion will be proposed for each drug. (4) An expert panel will discuss the validity and clinical relevance of this suggested advice. (5) Advices will be implemented in all relevant Clinical Decision Support Systems in the Netherlands and published on a website for patients and healthcare professionals. (6) The continuity of the advices will be guaranteed by a yearly check of new literature and comments on the advices. This protocol will be applied in the evaluation of a selection of drugs: (A) drugs used to treat (complications of) liver cirrhosis, and (B) drugs frequently prescribed to the general population. Ethics and dissemination Since this study does not directly involve human participants, it does not require ethical clearance. Besides implementation on a website and in clinical decision support systems, we aim to publish the generated advices of one or two drug classes in a peer-reviewed journal and at conference meetings. PMID:27733414

New workflow for classification of genetic variants' pathogenicity applied to hereditary recurrent fevers by the International Study Group for Systemic Autoinflammatory Diseases (INSAID).

PubMed

Van Gijn, Marielle E; Ceccherini, Isabella; Shinar, Yael; Carbo, Ellen C; Slofstra, Mariska; Arostegui, Juan I; Sarrabay, Guillaume; Rowczenio, Dorota; Omoyımnı, Ebun; Balci-Peynircioglu, Banu; Hoffman, Hal M; Milhavet, Florian; Swertz, Morris A; Touitou, Isabelle

2018-03-29

Hereditary recurrent fevers (HRFs) are rare inflammatory diseases sharing similar clinical symptoms and effectively treated with anti-inflammatory biological drugs. Accurate diagnosis of HRF relies heavily on genetic testing. This study aimed to obtain an experts' consensus on the clinical significance of gene variants in four well-known HRF genes: MEFV , TNFRSF1A , NLRP3 and MVK . We configured a MOLGENIS web platform to share and analyse pathogenicity classifications of the variants and to manage a consensus-based classification process. Four experts in HRF genetics submitted independent classifications of 858 variants. Classifications were driven to consensus by recruiting four more expert opinions and by targeting discordant classifications in five iterative rounds. Consensus classification was reached for 804/858 variants (94%). None of the unsolved variants (6%) remained with opposite classifications (eg, pathogenic vs benign). New mutational hotspots were found in all genes. We noted a lower pathogenic variant load and a higher fraction of variants with unknown or unsolved clinical significance in the MEFV gene. Applying a consensus-driven process on the pathogenicity assessment of experts yielded rapid classification of almost all variants of four HRF genes. The high-throughput database will profoundly assist clinicians and geneticists in the diagnosis of HRFs. The configured MOLGENIS platform and consensus evolution protocol are usable for assembly of other variant pathogenicity databases. The MOLGENIS software is available for reuse at http://github.com/molgenis/molgenis; the specific HRF configuration is available at http://molgenis.org/said/. The HRF pathogenicity classifications will be published on the INFEVERS database at https://fmf.igh.cnrs.fr/ISSAID/infevers/. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Computer simulations for bioequivalence trials: Selection of analyte in BCS class II and IV drugs with first-pass metabolism, two metabolic pathways and intestinal efflux transporter.

PubMed

Mangas-Sanjuan, Victor; Navarro-Fontestad, Carmen; García-Arieta, Alfredo; Trocóniz, Iñaki F; Bermejo, Marival

2018-05-30

A semi-physiological two compartment pharmacokinetic model with two active metabolites (primary (PM) and secondary metabolites (SM)) with saturable and non-saturable pre-systemic efflux transporter, intestinal and hepatic metabolism has been developed. The aim of this work is to explore in several scenarios which analyte (parent drug or any of the metabolites) is the most sensitive to changes in drug product performance (i.e. differences in in vivo dissolution) and to make recommendations based on the simulations outcome. A total of 128 scenarios (2 Biopharmaceutics Classification System (BCS) drug types, 2 levels of K M Pgp , in 4 metabolic scenarios at 2 dose levels in 4 quality levels of the drug product) were simulated for BCS class II and IV drugs. Monte Carlo simulations of all bioequivalence studies were performed in NONMEM 7.3. Results showed the parent drug (PD) was the most sensitive analyte for bioequivalence trials in all the studied scenarios. PM and SM revealed less or the same sensitivity to detect differences in pharmaceutical quality as the PD. Another relevant result is that mean point estimate of C max and AUC methodology from Monte Carlo simulations allows to select more accurately the most sensitive analyte compared to the criterion on the percentage of failed or successful BE studies, even for metabolites which frequently show greater variability than PD. Copyright © 2018 Elsevier B.V. All rights reserved.

Development of a biphasic dissolution test for Deferasirox dispersible tablets and its application in establishing an in vitro-in vivo correlation.

PubMed

Al Durdunji, Amal; AlKhatib, Hatim S; Al-Ghazawi, Mutasim

2016-05-01

In a biphasic dissolution medium, the integration of the in vitro dissolution of a drug in an aqueous phase and its subsequent partitioning into an organic phase is hypothesized to simulate the in vivo drug absorption. Such a methodology is expected to improve the probability of achieving a successful in vitro-in vivo correlation. Dissolution of Dispersible tablets of Deferasirox, a biopharmaceutics classification system type II compound, was studied in a biphasic dissolution medium using a flow-through dissolution apparatus coupled to a paddle apparatus. The experimental parameters associated with dissolution were optimized to discriminate between Deferasirox dispersible tablets of different formulations. The dissolution profiles obtained from this system were subsequently used to construct a level A in vitro-in vivo correlation. Copyright © 2016 Elsevier B.V. All rights reserved.

Wearable sensor platform and mobile application for use in cognitive behavioral therapy for drug addiction and PTSD.

PubMed

Fletcher, Richard Ribón; Tam, Sharon; Omojola, Olufemi; Redemske, Richard; Kwan, Joyce

2011-01-01

We present a wearable sensor platform designed for monitoring and studying autonomic nervous system (ANS) activity for the purpose of mental health treatment and interventions. The mobile sensor system consists of a sensor band worn on the ankle that continuously monitors electrodermal activity (EDA), 3-axis acceleration, and temperature. A custom-designed ECG heart monitor worn on the chest is also used as an optional part of the system. The EDA signal from the ankle bands provides a measure sympathetic nervous system activity and used to detect arousal events. The optional ECG data can be used to improve the sensor classification algorithm and provide a measure of emotional "valence." Both types of sensor bands contain a Bluetooth radio that enables communication with the patient's mobile phone. When a specific arousal event is detected, the phone automatically presents therapeutic and empathetic messages to the patient in the tradition of Cognitive Behavioral Therapy (CBT). As an example of clinical use, we describe how the system is currently being used in an ongoing study for patients with drug-addiction and post-traumatic stress disorder (PTSD).

Pharmaceutical management through environmental product labeling in Sweden.

PubMed

Wennmalm, Ake; Gunnarsson, Bo

2009-07-01

There is an increased awareness that medicinal products for human use may cause negative effects in the environment. In Sweden a voluntary environmental classification system for drugs has been established in collaboration between producers, authorities and the public health care, and used for five years. The idea is to enhance the market demand for medicines with less environmental impact, which in turn will stimulate the producers to design future medicines to be more environmentally friendly. The system is open to the public and based on assessment of the active ingredient in the medicinal product into several classes of risk and hazard, respectively. It is closely related to the EMEA guidelines. Risk is expressed as the ratio between the predicted environmental concentration (PEC) of the active ingredient (AI) and its predicted no effect concentration (PNEC). The hazard is expressed in terms of the AI's persistence, potential to bioaccumulation, and eco-toxicity. Drug data for the classification are delivered by the respective producers. Hitherto more than 300 AI, representing more than 50% of the Swedish volume of drug use, have been classified. Data for risk assessment were missing in 47% of AI. Among drugs with data 7% had a PEC/PNEC ratio >1, and another 7% had a ratio between 0.1 and 1. The AIs with highest ratio (>10) were two estrogens. Data for hazard assessment were lacking in 16% of the AI. Among drugs with environmental data 92% were not ready biodegradable, 23% had potential to bioaccumulation, and 61% were toxic to aquatic organisms at a concentration below 1 mg/l. These data are utilized by regional pharmaceutical expert groups when selecting substances to be recommended in public health care in Sweden. They may also be used by prescribing doctors who want to identify the environmentally most favourable substance among several with equivalent medical effect. We conclude that environmental data on human medicinal products are often missing, or reveal unfavourable environmental properties. A proper judgement of the environmental impact of an AI requires a joint evaluation of its risk and hazard. We suggest that the pharmaceutical producers should highlight environmental precaution when designing new AIs, and that the environmental data should be transparent to the general public.

Developmental defects in zebrafish for classification of EGF pathway inhibitors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pruvot, Benoist; Curé, Yoann; Djiotsa, Joachim

2014-01-15

One of the major challenges when testing drug candidates targeted at a specific pathway in whole animals is the discrimination between specific effects and unwanted, off-target effects. Here we used the zebrafish to define several developmental defects caused by impairment of Egf signaling, a major pathway of interest in tumor biology. We inactivated Egf signaling by genetically blocking Egf expression or using specific inhibitors of the Egf receptor function. We show that the combined occurrence of defects in cartilage formation, disturbance of blood flow in the trunk and a decrease of myelin basic protein expression represent good indicators for impairmentmore » of Egf signaling. Finally, we present a classification of known tyrosine kinase inhibitors according to their specificity for the Egf pathway. In conclusion, we show that developmental indicators can help to discriminate between specific effects on the target pathway from off-target effects in molecularly targeted drug screening experiments in whole animal systems. - Highlights: • We analyze the functions of Egf signaling on zebrafish development. • Genetic blocking of Egf expression causes cartilage, myelin and circulatory defects. • Chemical inhibition of Egf receptor function causes similar defects. • Developmental defects can reveal the specificity of Egf pathway inhibitors.« less

Metabolomic profiling to identify potential serum biomarkers for schizophrenia and risperidone action.

PubMed

Xuan, Jiekun; Pan, Guihua; Qiu, Yunping; Yang, Lun; Su, Mingming; Liu, Yumin; Chen, Jian; Feng, Guoyin; Fang, Yiru; Jia, Wei; Xing, Qinghe; He, Lin

2011-12-02

Despite recent advances in understanding the pathophysiology of schizophrenia and the mechanisms of antipsychotic drug action, the development of biomarkers for diagnosis and therapeutic monitoring in schizophrenia remains challenging. Metabolomics provides a powerful approach to discover diagnostic and therapeutic biomarkers by analyzing global changes in an individual's metabolic profile in response to pathophysiological stimuli or drug intervention. In this study, we performed gas chromatography-mass spectrometry based metabolomic profiling in serum of unmedicated schizophrenic patients before and after an 8-week risperidone monotherapy, to detect potential biomarkers associated with schizophrenia and risperidone treatment. Twenty-two marker metabolites contributing to the complete separation of schizophrenic patients from matched healthy controls were identified, with citrate, palmitic acid, myo-inositol, and allantoin exhibiting the best combined classification performance. Twenty marker metabolites contributing to the complete separation between posttreatment and pretreatment patients were identified, with myo-inositol, uric acid, and tryptophan showing the maximum combined classification performance. Metabolic pathways including energy metabolism, antioxidant defense systems, neurotransmitter metabolism, fatty acid biosynthesis, and phospholipid metabolism were found to be disturbed in schizophrenic patients and partially normalized following risperidone therapy. Further study of these metabolites may facilitate the development of noninvasive biomarkers and more efficient therapeutic strategies for schizophrenia.

Drug Use and Sexually Transmitted Diseases among Female and Male Arrested Youths

PubMed Central

Dembo, Richard; Belenko, Steven; Childs, Kristina; Wareham, Jennifer

2009-01-01

Knowledge of the rates and correlates of juvenile offenders’ sexually transmitted diseases (STD) has been limited to samples of incarcerated youths comprised mostly of males. Data collected on 442 female and 506 male youths processed at a centralized intake facility enabled us to study this important public health problem among a sample of juvenile offenders at the front end of the justice system. Female-male, multi-group latent class analyses identified two subgroups, High Risk and Lower Risk, of youths described by a latent construct of risk based on drug test results, STD test results, and a classification for the seriousness of arrest charge. The results found: (1) a similar classification distinguished High Risk and Lower Risk male and female youths, and (2) important gender group differences in sexual risk related factors (e.g., substance use during sexual encounters). Among the youths in this sample who tested positive for an STD, 66% of the girls and 57% of the boys were released back into the community after arrest. Overall, our findings raise serious public health and social welfare concerns, for both the youths and the community. Prevention and intervention implications of these findings are also discussed. PMID:18979194

Novel Hypoxia-Directed Cancer Therapeutics

DTIC Science & Technology

2017-07-01

as anti-cancer therapies. 15. SUBJECT TERMS Hypoxia-inducible factors, mass-spectrometry, drug discovery, kidney cancer 16. SECURITY CLASSIFICATION...programs required for driving solid tumor growth in cancers of kidney , pancreas, stomach, colon and skin. We seek the discovery of drug-like...drug discovery, kidney cancer. 5 What opportunities for training and professional development has the project provided? How were the

Exploring drug-target interaction networks of illicit drugs.

PubMed

Atreya, Ravi V; Sun, Jingchun; Zhao, Zhongming

2013-01-01

Drug addiction is a complex and chronic mental disease, which places a large burden on the American healthcare system due to its negative effects on patients and their families. Recently, network pharmacology is emerging as a promising approach to drug discovery by integrating network biology and polypharmacology, allowing for a deeper understanding of molecular mechanisms of drug actions at the systems level. This study seeks to apply this approach for investigation of illicit drugs and their targets in order to elucidate their interaction patterns and potential secondary drugs that can aid future research and clinical care. In this study, we extracted 188 illicit substances and their related information from the DrugBank database. The data process revealed 86 illicit drugs targeting a total of 73 unique human genes, which forms an illicit drug-target network. Compared to the full drug-target network from DrugBank, illicit drugs and their target genes tend to cluster together and form four subnetworks, corresponding to four major medication categories: depressants, stimulants, analgesics, and steroids. External analysis of Anatomical Therapeutic Chemical (ATC) second sublevel classifications confirmed that the illicit drugs have neurological functions or act via mechanisms of stimulants, opioids, and steroids. To further explore other drugs potentially having associations with illicit drugs, we constructed an illicit-extended drug-target network by adding the drugs that have the same target(s) as illicit drugs to the illicit drug-target network. After analyzing the degree and betweenness of the network, we identified hubs and bridge nodes, which might play important roles in the development and treatment of drug addiction. Among them, 49 non-illicit drugs might have potential to be used to treat addiction or have addictive effects, including some results that are supported by previous studies. This study presents the first systematic review of the network characteristics of illicit drugs, their targets, and other drugs that share the targets of these illicit drugs. The results, though preliminary, provide some novel insights into the molecular mechanisms of drug addiction. The observation of illicit-related drugs, with partial verification from previous studies, demonstrated that the network-assisted approach is promising for the identification of drug repositioning.

Exploring drug-target interaction networks of illicit drugs

PubMed Central

2013-01-01

Background Drug addiction is a complex and chronic mental disease, which places a large burden on the American healthcare system due to its negative effects on patients and their families. Recently, network pharmacology is emerging as a promising approach to drug discovery by integrating network biology and polypharmacology, allowing for a deeper understanding of molecular mechanisms of drug actions at the systems level. This study seeks to apply this approach for investigation of illicit drugs and their targets in order to elucidate their interaction patterns and potential secondary drugs that can aid future research and clinical care. Results In this study, we extracted 188 illicit substances and their related information from the DrugBank database. The data process revealed 86 illicit drugs targeting a total of 73 unique human genes, which forms an illicit drug-target network. Compared to the full drug-target network from DrugBank, illicit drugs and their target genes tend to cluster together and form four subnetworks, corresponding to four major medication categories: depressants, stimulants, analgesics, and steroids. External analysis of Anatomical Therapeutic Chemical (ATC) second sublevel classifications confirmed that the illicit drugs have neurological functions or act via mechanisms of stimulants, opioids, and steroids. To further explore other drugs potentially having associations with illicit drugs, we constructed an illicit-extended drug-target network by adding the drugs that have the same target(s) as illicit drugs to the illicit drug-target network. After analyzing the degree and betweenness of the network, we identified hubs and bridge nodes, which might play important roles in the development and treatment of drug addiction. Among them, 49 non-illicit drugs might have potential to be used to treat addiction or have addictive effects, including some results that are supported by previous studies. Conclusions This study presents the first systematic review of the network characteristics of illicit drugs, their targets, and other drugs that share the targets of these illicit drugs. The results, though preliminary, provide some novel insights into the molecular mechanisms of drug addiction. The observation of illicit-related drugs, with partial verification from previous studies, demonstrated that the network-assisted approach is promising for the identification of drug repositioning. PMID:24268016

Combining automatic table classification and relationship extraction in extracting anticancer drug-side effect pairs from full-text articles.

PubMed

Xu, Rong; Wang, QuanQiu

2015-02-01

Anticancer drug-associated side effect knowledge often exists in multiple heterogeneous and complementary data sources. A comprehensive anticancer drug-side effect (drug-SE) relationship knowledge base is important for computation-based drug target discovery, drug toxicity predication and drug repositioning. In this study, we present a two-step approach by combining table classification and relationship extraction to extract drug-SE pairs from a large number of high-profile oncological full-text articles. The data consists of 31,255 tables downloaded from the Journal of Oncology (JCO). We first trained a statistical classifier to classify tables into SE-related and -unrelated categories. We then extracted drug-SE pairs from SE-related tables. We compared drug side effect knowledge extracted from JCO tables to that derived from FDA drug labels. Finally, we systematically analyzed relationships between anti-cancer drug-associated side effects and drug-associated gene targets, metabolism genes, and disease indications. The statistical table classifier is effective in classifying tables into SE-related and -unrelated (precision: 0.711; recall: 0.941; F1: 0.810). We extracted a total of 26,918 drug-SE pairs from SE-related tables with a precision of 0.605, a recall of 0.460, and a F1 of 0.520. Drug-SE pairs extracted from JCO tables is largely complementary to those derived from FDA drug labels; as many as 84.7% of the pairs extracted from JCO tables have not been included a side effect database constructed from FDA drug labels. Side effects associated with anticancer drugs positively correlate with drug target genes, drug metabolism genes, and disease indications. Copyright © 2014 Elsevier Inc. All rights reserved.

21 CFR 882.5910 - Dura substitute.

Code of Federal Regulations, 2010 CFR

2010-04-01

...) Identification. A dura substitute is a sheet or material that is used to repair the dura mater (the membrane surrounding the brain). (b) Classification. Class II (performance standards). ... and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL...

The impact of supersaturation level for oral absorption of BCS class IIb drugs, dipyridamole and ketoconazole, using in vivo predictive dissolution system: Gastrointestinal Simulator (GIS).

PubMed

Tsume, Yasuhiro; Matsui, Kazuki; Searls, Amanda L; Takeuchi, Susumu; Amidon, Gregory E; Sun, Duxin; Amidon, Gordon L

2017-05-01

The development of formulations and the assessment of oral drug absorption for Biopharmaceutical Classification System (BCS) class IIb drugs is often a difficult issue due to the potential for supersaturation and precipitation in the gastrointestinal (GI) tract. The physiological environment in the GI tract largely influences in vivo drug dissolution rates of those drugs. Thus, those physiological factors should be incorporated into the in vitro system to better assess in vivo performance of BCS class IIb drugs. In order to predict oral bioperformance, an in vitro dissolution system with multiple compartments incorporating physiologically relevant factors would be expected to more accurately predict in vivo phenomena than a one-compartment dissolution system like USP Apparatus 2 because, for example, the pH change occurring in the human GI tract can be better replicated in a multi-compartmental platform. The Gastrointestinal Simulator (GIS) consists of three compartments, the gastric, duodenal and jejunal chambers, and is a practical in vitro dissolution apparatus to predict in vivo dissolution for oral dosage forms. This system can demonstrate supersaturation and precipitation and, therefore, has the potential to predict in vivo bioperformance of oral dosage forms where this phenomenon may occur. In this report, in vitro studies were performed with dipyridamole and ketoconazole to evaluate the precipitation rates and the relationship between the supersaturation levels and oral absorption of BCS class II weak base drugs. To evaluate the impact of observed supersaturation levels on oral absorption, a study utilizing the GIS in combination with mouse intestinal infusion was conducted. Supersaturation levels observed in the GIS enhanced dipyridamole and ketoconazole absorption in mouse, and a good correlation between their supersaturation levels and their concentration in plasma was observed. The GIS, therefore, appears to represent in vivo dissolution phenomena and demonstrate supersaturation and precipitation of dipyridamole and ketoconazole. We therefore conclude that the GIS has been shown to be a good biopredictive tool to predict in vivo bioperformance of BCS class IIb drugs that can be used to optimize oral formulations. Copyright © 2017. Published by Elsevier B.V.

In silico prediction of drug-induced myelotoxicity by using Naïve Bayes method.

PubMed

Zhang, Hui; Yu, Peng; Zhang, Teng-Guo; Kang, Yan-Li; Zhao, Xiao; Li, Yuan-Yuan; He, Jia-Hui; Zhang, Ji

2015-11-01

Drug-induced myelotoxicity usually leads to decrease the production of platelets, red cells, and white cells. Thus, early identification and characterization of myelotoxicity hazard in drug development is very necessary. The purpose of this investigation was to develop a prediction model of drug-induced myelotoxicity by using a Naïve Bayes classifier. For comparison, other prediction models based on support vector machine and single-hidden-layer feed-forward neural network  methods were also established. Among all the prediction models, the Naïve Bayes classification model showed the best prediction performance, which offered an average overall prediction accuracy of [Formula: see text] for the training set and [Formula: see text] for the external test set. The significant contributions of this study are that we first developed a Naïve Bayes classification model of drug-induced myelotoxicity adverse effect using a larger scale dataset, which could be employed for the prediction of drug-induced myelotoxicity. In addition, several important molecular descriptors and substructures of myelotoxic compounds have been identified, which should be taken into consideration in the design of new candidate compounds to produce safer and more effective drugs, ultimately reducing the attrition rate in later stages of drug development.

Incorporation of support vector machines in the LIBS toolbox for sensitive and robust classification amidst unexpected sample and system variability

PubMed Central

ChariDingari, Narahara; Barman, Ishan; Myakalwar, Ashwin Kumar; Tewari, Surya P.; Kumar, G. Manoj

2012-01-01

Despite the intrinsic elemental analysis capability and lack of sample preparation requirements, laser-induced breakdown spectroscopy (LIBS) has not been extensively used for real world applications, e.g. quality assurance and process monitoring. Specifically, variability in sample, system and experimental parameters in LIBS studies present a substantive hurdle for robust classification, even when standard multivariate chemometric techniques are used for analysis. Considering pharmaceutical sample investigation as an example, we propose the use of support vector machines (SVM) as a non-linear classification method over conventional linear techniques such as soft independent modeling of class analogy (SIMCA) and partial least-squares discriminant analysis (PLS-DA) for discrimination based on LIBS measurements. Using over-the-counter pharmaceutical samples, we demonstrate that application of SVM enables statistically significant improvements in prospective classification accuracy (sensitivity), due to its ability to address variability in LIBS sample ablation and plasma self-absorption behavior. Furthermore, our results reveal that SVM provides nearly 10% improvement in correct allocation rate and a concomitant reduction in misclassification rates of 75% (cf. PLS-DA) and 80% (cf. SIMCA)-when measurements from samples not included in the training set are incorporated in the test data – highlighting its robustness. While further studies on a wider matrix of sample types performed using different LIBS systems is needed to fully characterize the capability of SVM to provide superior predictions, we anticipate that the improved sensitivity and robustness observed here will facilitate application of the proposed LIBS-SVM toolbox for screening drugs and detecting counterfeit samples as well as in related areas of forensic and biological sample analysis. PMID:22292496

Incorporation of support vector machines in the LIBS toolbox for sensitive and robust classification amidst unexpected sample and system variability.

PubMed

Dingari, Narahara Chari; Barman, Ishan; Myakalwar, Ashwin Kumar; Tewari, Surya P; Kumar Gundawar, Manoj

2012-03-20

Despite the intrinsic elemental analysis capability and lack of sample preparation requirements, laser-induced breakdown spectroscopy (LIBS) has not been extensively used for real-world applications, e.g., quality assurance and process monitoring. Specifically, variability in sample, system, and experimental parameters in LIBS studies present a substantive hurdle for robust classification, even when standard multivariate chemometric techniques are used for analysis. Considering pharmaceutical sample investigation as an example, we propose the use of support vector machines (SVM) as a nonlinear classification method over conventional linear techniques such as soft independent modeling of class analogy (SIMCA) and partial least-squares discriminant analysis (PLS-DA) for discrimination based on LIBS measurements. Using over-the-counter pharmaceutical samples, we demonstrate that the application of SVM enables statistically significant improvements in prospective classification accuracy (sensitivity), because of its ability to address variability in LIBS sample ablation and plasma self-absorption behavior. Furthermore, our results reveal that SVM provides nearly 10% improvement in correct allocation rate and a concomitant reduction in misclassification rates of 75% (cf. PLS-DA) and 80% (cf. SIMCA)-when measurements from samples not included in the training set are incorporated in the test data-highlighting its robustness. While further studies on a wider matrix of sample types performed using different LIBS systems is needed to fully characterize the capability of SVM to provide superior predictions, we anticipate that the improved sensitivity and robustness observed here will facilitate application of the proposed LIBS-SVM toolbox for screening drugs and detecting counterfeit samples, as well as in related areas of forensic and biological sample analysis.

Predicting Drug-induced Hepatotoxicity Using QSAR and Toxicogenomics Approaches

PubMed Central

Low, Yen; Uehara, Takeki; Minowa, Yohsuke; Yamada, Hiroshi; Ohno, Yasuo; Urushidani, Tetsuro; Sedykh, Alexander; Muratov, Eugene; Fourches, Denis; Zhu, Hao; Rusyn, Ivan; Tropsha, Alexander

2014-01-01

Quantitative Structure-Activity Relationship (QSAR) modeling and toxicogenomics are used independently as predictive tools in toxicology. In this study, we evaluated the power of several statistical models for predicting drug hepatotoxicity in rats using different descriptors of drug molecules, namely their chemical descriptors and toxicogenomic profiles. The records were taken from the Toxicogenomics Project rat liver microarray database containing information on 127 drugs (http://toxico.nibio.go.jp/datalist.html). The model endpoint was hepatotoxicity in the rat following 28 days of exposure, established by liver histopathology and serum chemistry. First, we developed multiple conventional QSAR classification models using a comprehensive set of chemical descriptors and several classification methods (k nearest neighbor, support vector machines, random forests, and distance weighted discrimination). With chemical descriptors alone, external predictivity (Correct Classification Rate, CCR) from 5-fold external cross-validation was 61%. Next, the same classification methods were employed to build models using only toxicogenomic data (24h after a single exposure) treated as biological descriptors. The optimized models used only 85 selected toxicogenomic descriptors and had CCR as high as 76%. Finally, hybrid models combining both chemical descriptors and transcripts were developed; their CCRs were between 68 and 77%. Although the accuracy of hybrid models did not exceed that of the models based on toxicogenomic data alone, the use of both chemical and biological descriptors enriched the interpretation of the models. In addition to finding 85 transcripts that were predictive and highly relevant to the mechanisms of drug-induced liver injury, chemical structural alerts for hepatotoxicity were also identified. These results suggest that concurrent exploration of the chemical features and acute treatment-induced changes in transcript levels will both enrich the mechanistic understanding of sub-chronic liver injury and afford models capable of accurate prediction of hepatotoxicity from chemical structure and short-term assay results. PMID:21699217

Popular intoxicants: what lessons can be learned from the last 40 years of alcohol and cannabis regulation?

PubMed

Weissenborn, Ruth; Nutt, David J

2012-02-01

In this paper we discuss the relative physical, psychological and social harms of the two most frequently used intoxicant drugs in the UK, namely cannabis and alcohol. Over the past 40 years, the use of both drugs has risen significantly with differential consequences. It is argued that increased policing of cannabis use under the current drug classification system will lead to increased criminalization of young people, but is unlikely to significantly reduce the rates of schizophrenia and psychosis. In comparison, increases in alcohol drinking are related to significant increases in liver cirrhosis hospital admissions and mortality, at a time when mortality rates from other major causes are on the decline. A recent expert-led comparison of the health and social harms to the user and to others caused by the most commonly used drugs in the UK showed alcohol to be more than twice as harmful as cannabis to users, and five times as harmful as cannabis to others. The findings underline the need for a coherent, evidence-based drugs policy that enables individuals to make informed decisions about the consequences of their drug use.

Oromucosal multilayer films for tailor-made, controlled drug delivery.

PubMed

Lindert, Sandra; Breitkreutz, Jörg

2017-11-01

The oral mucosa has recently become increasingly important as an alternative administration route for tailor-made, controlled drug delivery. Oromucosal multilayer films, assigned to the monograph oromucosal preparations in the Ph.Eur. may be a promising dosage form to overcome the requirements related to this drug delivery site. Areas covered: We provide an overview of multilayer films as drug delivery tools, and discuss manufacturing processes and characterization methods. We focus on the suitability of characterization methods for particular requirements of multilayer films. A classification was performed covering indication areas and APIs incorporated in multilayer film systems for oromucosal use in order to provide a summary of data published in this field. Expert opinion: The shift in drug development to high molecular weight drugs will influence the field of pharmaceutical development and delivery technologies. For a high number of indication areas, such as hormonal disorders, cardiovascular diseases or local treatment of infections, the flexible layer design of oromucosal multilayer films provides a promising option for tailor-made, controlled delivery of APIs to or through defined surfaces in the oral cavity. However, there is a lack of discriminating or standardized testing methods to assess the quality of multilayer films in a reliable way.

Hierarchical classification strategy for Phenotype extraction from epidermal growth factor receptor endocytosis screening.

PubMed

Cao, Lu; Graauw, Marjo de; Yan, Kuan; Winkel, Leah; Verbeek, Fons J

2016-05-03

Endocytosis is regarded as a mechanism of attenuating the epidermal growth factor receptor (EGFR) signaling and of receptor degradation. There is increasing evidence becoming available showing that breast cancer progression is associated with a defect in EGFR endocytosis. In order to find related Ribonucleic acid (RNA) regulators in this process, high-throughput imaging with fluorescent markers is used to visualize the complex EGFR endocytosis process. Subsequently a dedicated automatic image and data analysis system is developed and applied to extract the phenotype measurement and distinguish different developmental episodes from a huge amount of images acquired through high-throughput imaging. For the image analysis, a phenotype measurement quantifies the important image information into distinct features or measurements. Therefore, the manner in which prominent measurements are chosen to represent the dynamics of the EGFR process becomes a crucial step for the identification of the phenotype. In the subsequent data analysis, classification is used to categorize each observation by making use of all prominent measurements obtained from image analysis. Therefore, a better construction for a classification strategy will support to raise the performance level in our image and data analysis system. In this paper, we illustrate an integrated analysis method for EGFR signalling through image analysis of microscopy images. Sophisticated wavelet-based texture measurements are used to obtain a good description of the characteristic stages in the EGFR signalling. A hierarchical classification strategy is designed to improve the recognition of phenotypic episodes of EGFR during endocytosis. Different strategies for normalization, feature selection and classification are evaluated. The results of performance assessment clearly demonstrate that our hierarchical classification scheme combined with a selected set of features provides a notable improvement in the temporal analysis of EGFR endocytosis. Moreover, it is shown that the addition of the wavelet-based texture features contributes to this improvement. Our workflow can be applied to drug discovery to analyze defected EGFR endocytosis processes.

IDM-PhyChm-Ens: intelligent decision-making ensemble methodology for classification of human breast cancer using physicochemical properties of amino acids.

PubMed

Ali, Safdar; Majid, Abdul; Khan, Asifullah

2014-04-01

Development of an accurate and reliable intelligent decision-making method for the construction of cancer diagnosis system is one of the fast growing research areas of health sciences. Such decision-making system can provide adequate information for cancer diagnosis and drug discovery. Descriptors derived from physicochemical properties of protein sequences are very useful for classifying cancerous proteins. Recently, several interesting research studies have been reported on breast cancer classification. To this end, we propose the exploitation of the physicochemical properties of amino acids in protein primary sequences such as hydrophobicity (Hd) and hydrophilicity (Hb) for breast cancer classification. Hd and Hb properties of amino acids, in recent literature, are reported to be quite effective in characterizing the constituent amino acids and are used to study protein foldings, interactions, structures, and sequence-order effects. Especially, using these physicochemical properties, we observed that proline, serine, tyrosine, cysteine, arginine, and asparagine amino acids offer high discrimination between cancerous and healthy proteins. In addition, unlike traditional ensemble classification approaches, the proposed 'IDM-PhyChm-Ens' method was developed by combining the decision spaces of a specific classifier trained on different feature spaces. The different feature spaces used were amino acid composition, split amino acid composition, and pseudo amino acid composition. Consequently, we have exploited different feature spaces using Hd and Hb properties of amino acids to develop an accurate method for classification of cancerous protein sequences. We developed ensemble classifiers using diverse learning algorithms such as random forest (RF), support vector machines (SVM), and K-nearest neighbor (KNN) trained on different feature spaces. We observed that ensemble-RF, in case of cancer classification, performed better than ensemble-SVM and ensemble-KNN. Our analysis demonstrates that ensemble-RF, ensemble-SVM and ensemble-KNN are more effective than their individual counterparts. The proposed 'IDM-PhyChm-Ens' method has shown improved performance compared to existing techniques.

77 FR 14272 - Medical Devices; Immunology and Microbiology Devices; Classification of Norovirus Serological...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-03-09

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration 21 CFR Part 866 [Docket No. FDA-2012-N-0165] Medical Devices; Immunology and Microbiology Devices; Classification of Norovirus... AND MICROBIOLOGY DEVICES 0 1. The authority citation for 21 CFR part 866 continues to read as follows...

78 FR 21612 - Medical Device Classification Product Codes; Guidance for Industry and Food and Drug...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-11

... (CDRH) and the Center for Biologics Evaluation and Research (CBER). DATES: Submit either electronic or...-addressed adhesive label to assist that office in processing your request, or fax your request to CDRH at... CDRH's Classification Product Code structure and organization. These 16 Panels have largely been the...

Creating a Canonical Scientific and Technical Information Classification System for NCSTRL+

NASA Technical Reports Server (NTRS)

Tiffany, Melissa E.; Nelson, Michael L.

1998-01-01

The purpose of this paper is to describe the new subject classification system for the NCSTRL+ project. NCSTRL+ is a canonical digital library (DL) based on the Networked Computer Science Technical Report Library (NCSTRL). The current NCSTRL+ classification system uses the NASA Scientific and Technical (STI) subject classifications, which has a bias towards the aerospace, aeronautics, and engineering disciplines. Examination of other scientific and technical information classification systems showed similar discipline-centric weaknesses. Traditional, library-oriented classification systems represented all disciplines, but were too generalized to serve the needs of a scientific and technically oriented digital library. Lack of a suitable existing classification system led to the creation of a lightweight, balanced, general classification system that allows the mapping of more specialized classification schemes into the new framework. We have developed the following classification system to give equal weight to all STI disciplines, while being compact and lightweight.

A multi-sensor scenario for coastal surveillance

NASA Astrophysics Data System (ADS)

van den Broek, A. C.; van den Broek, S. P.; van den Heuvel, J. C.; Schwering, P. B. W.; van Heijningen, A. W. P.

2007-10-01

Maritime borders and coastal zones are susceptible to threats such as drug trafficking, piracy, undermining economical activities. At TNO Defence, Security and Safety various studies aim at improving situational awareness in a coastal zone. In this study we focus on multi-sensor surveillance of the coastal environment. We present a study on improving classification results for small sea surface targets using an advanced sensor suite and a scenario in which a small boat is approaching the coast. A next generation sensor suite mounted on a tower has been defined consisting of a maritime surveillance and tracking radar system, capable of producing range profiles and ISAR imagery of ships, an advanced infrared camera and a laser range profiler. For this suite we have developed a multi-sensor classification procedure, which is used to evaluate the capabilities for recognizing and identifying non-cooperative ships in coastal waters. We have found that the different sensors give complementary information. Each sensor has its own specific distance range in which it contributes most. A multi-sensor approach reduces the number of misclassifications and reliable classification results are obtained earlier compared to a single sensor approach.

21 CFR 886.1700 - Pupillometer.

Code of Federal Regulations, 2010 CFR

2010-04-01

... eye. (b) Classification. Class I (general controls). The AC-powered device and the manual device are... Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES OPHTHALMIC DEVICES Diagnostic Devices § 886.1700 Pupillometer. (a) Identification. A pupillometer is an AC...

Drug use before and during pregnancy in Serbia.

PubMed

Odalovic, Marina; Vezmar Kovacevic, Sandra; Ilic, Katarina; Sabo, Ana; Tasic, Ljiljana

2012-10-01

Observation of drug use patterns during pregnancy is necessary for the recognition of potential bad practices and improvement of safe drug use in pregnancy. To investigate prescription and over the counter drug use among Serbian women in the 6 months before pregnancy and in the first 6 months of pregnancy, and to evaluate the drugs used according to the risk to a fetus. Setting Six maternity care units and five community pharmacies. A multi-center study was performed in Serbia during the period from March 2009-March 2010. A self-reporting questionnaire was used as a data source. Food and Drug Administration (FDA) risk classification system was used to determine the risk of used drugs for the fetus. Differences between subgroups were assessed using McNemar's test on paired proportions. Main outcome measure Proportion of women exposed to drugs or class of drugs. The overall drug exposure was higher in pregnancy (34.7 %) than before pregnancy (29.9 %), p > 0.05, in the cohort of 311 pregnant women. A significantly greater prescription drug use, 19.0 versus 27.3 % of women, p < 0.05, and less selfmedication with over the counter drugs in pregnancy, 15.1 versus 8.7 %, p < 0.05, were observed. Commonly used drugs were musculoskeletal drugs, analgesics/antipyretics and respiratory system drugs before pregnancy (13.8, 12.5, and 6.4 % of women, respectively), and progestogens, analgesics/antipyretics, and antibiotics for the systemic use in pregnancy (9.0, 7.7, and 7.4 %, respectively). A greater exposure to drugs belonging to the FDA risk category A (3.9 vs. 60.8 %, p < 0.05), B (18.0 vs. 19.6 %, p > 0.05), C (10.0 vs. 10.3 %, p > 0.05) and D (2.9 vs. 10.9 %, p < 0.05), as well as less exposure to drugs belonging to category X (0.3 vs. 0 %, p > 0.05) were observed in pregnancy. Folic acid was used by 60.8 % of women in pregnancy, and by only 3.9 % before pregnancy. Besides higher overall drug use in pregnancy than before pregnancy, particularly the use of progestogens, and, subsequently, D category drugs, less selfmedication with over the counter drugs was observed in pregnancy. Insufficient use of folic acid before pregnancy requires public health service activities.

Measuring CAMD technique performance. 2. How "druglike" are drugs? Implications of Random test set selection exemplified using druglikeness classification models.

PubMed

Good, Andrew C; Hermsmeier, Mark A

2007-01-01

Research into the advancement of computer-aided molecular design (CAMD) has a tendency to focus on the discipline of algorithm development. Such efforts are often wrought to the detriment of the data set selection and analysis used in said algorithm validation. Here we highlight the potential problems this can cause in the context of druglikeness classification. More rigorous efforts are applied to the selection of decoy (nondruglike) molecules from the ACD. Comparisons are made between model performance using the standard technique of random test set creation with test sets derived from explicit ontological separation by drug class. The dangers of viewing druglike space as sufficiently coherent to permit simple classification are highlighted. In addition the issues inherent in applying unfiltered data and random test set selection to (Q)SAR models utilizing large and supposedly heterogeneous databases are discussed.

The effects and consequences of selected club drugs.

PubMed

Freese, Thomas E; Miotto, Karen; Reback, Cathy J

2002-09-01

Ecstasy (MDMA), gamma-hydroxybutyrate (GHB), ketamine, and methamphetamine are 4 examples of club drugs that are increasing in popularity. Although the pharmacological classifications of these drugs vary, MDMA has structural similarities to both amphetamine and the hallucinogen mescaline. Ketamine and GHB are anesthetic agents and methamphetamine is a long-acting psychostimulant. Medical visits for club drug-related toxicity have sharply increased across the country. This article provides a brief review of the literature on club drugs. Copyright 2002 Elsevier Science Inc.

Antiprotozoan lead discovery by aligning dry and wet screening: prediction, synthesis, and biological assay of novel quinoxalinones.

PubMed

Martins Alho, Miriam A; Marrero-Ponce, Yovani; Barigye, Stephen J; Meneses-Marcel, Alfredo; Machado Tugores, Yanetsy; Montero-Torres, Alina; Gómez-Barrio, Alicia; Nogal, Juan J; García-Sánchez, Rory N; Vega, María Celeste; Rolón, Miriam; Martínez-Fernández, Antonio R; Escario, José A; Pérez-Giménez, Facundo; Garcia-Domenech, Ramón; Rivera, Norma; Mondragón, Ricardo; Mondragón, Mónica; Ibarra-Velarde, Froylán; Lopez-Arencibia, Atteneri; Martín-Navarro, Carmen; Lorenzo-Morales, Jacob; Cabrera-Serra, Maria Gabriela; Piñero, Jose; Tytgat, Jan; Chicharro, Roberto; Arán, Vicente J

2014-03-01

Protozoan parasites have been one of the most significant public health problems for centuries and several human infections caused by them have massive global impact. Most of the current drugs used to treat these illnesses have been used for decades and have many limitations such as the emergence of drug resistance, severe side-effects, low-to-medium drug efficacy, administration routes, cost, etc. These drugs have been largely neglected as models for drug development because they are majorly used in countries with limited resources and as a consequence with scarce marketing possibilities. Nowadays, there is a pressing need to identify and develop new drug-based antiprotozoan therapies. In an effort to overcome this problem, the main purpose of this study is to develop a QSARs-based ensemble classifier for antiprotozoan drug-like entities from a heterogeneous compounds collection. Here, we use some of the TOMOCOMD-CARDD molecular descriptors and linear discriminant analysis (LDA) to derive individual linear classification functions in order to discriminate between antiprotozoan and non-antiprotozoan compounds as a way to enable the computational screening of virtual combinatorial datasets and/or drugs already approved. Firstly, we construct a wide-spectrum benchmark database comprising of 680 organic chemicals with great structural variability (254 of them antiprotozoan agents and 426 to drugs having other clinical uses). This series of compounds was processed by a k-means cluster analysis in order to design training and predicting sets. In total, seven discriminant functions were obtained, by using the whole set of atom-based linear indices. All the LDA-based QSAR models show accuracies above 85% in the training set and values of Matthews correlation coefficients (C) vary from 0.70 to 0.86. The external validation set shows rather-good global classifications of around 80% (92.05% for best equation). Later, we developed a multi-agent QSAR classification system, in which the individual QSAR outputs are the inputs of the aforementioned fusion approach. Finally, the fusion model was used for the identification of a novel generation of lead-like antiprotozoan compounds by using ligand-based virtual screening of 'available' small molecules (with synthetic feasibility) in our 'in-house' library. A new molecular subsystem (quinoxalinones) was then theoretically selected as a promising lead series, and its derivatives subsequently synthesized, structurally characterized, and experimentally assayed by using in vitro screening that took into consideration a battery of five parasite-based assays. The chemicals 11(12) and 16 are the most active (hits) against apicomplexa (sporozoa) and mastigophora (flagellata) subphylum parasites, respectively. Both compounds depicted good activity in every protozoan in vitro panel and they did not show unspecific cytotoxicity on the host cells. The described technical framework seems to be a promising QSAR-classifier tool for the molecular discovery and development of novel classes of broad-antiprotozoan-spectrum drugs, which may meet the dual challenges posed by drug-resistant parasites and the rapid progression of protozoan illnesses. Copyright © 2014 Elsevier Ltd. All rights reserved.

Methodological Issues in Predicting Pediatric Epilepsy Surgery Candidates Through Natural Language Processing and Machine Learning

PubMed Central

Cohen, Kevin Bretonnel; Glass, Benjamin; Greiner, Hansel M.; Holland-Bouley, Katherine; Standridge, Shannon; Arya, Ravindra; Faist, Robert; Morita, Diego; Mangano, Francesco; Connolly, Brian; Glauser, Tracy; Pestian, John

2016-01-01

Objective: We describe the development and evaluation of a system that uses machine learning and natural language processing techniques to identify potential candidates for surgical intervention for drug-resistant pediatric epilepsy. The data are comprised of free-text clinical notes extracted from the electronic health record (EHR). Both known clinical outcomes from the EHR and manual chart annotations provide gold standards for the patient’s status. The following hypotheses are then tested: 1) machine learning methods can identify epilepsy surgery candidates as well as physicians do and 2) machine learning methods can identify candidates earlier than physicians do. These hypotheses are tested by systematically evaluating the effects of the data source, amount of training data, class balance, classification algorithm, and feature set on classifier performance. The results support both hypotheses, with F-measures ranging from 0.71 to 0.82. The feature set, classification algorithm, amount of training data, class balance, and gold standard all significantly affected classification performance. It was further observed that classification performance was better than the highest agreement between two annotators, even at one year before documented surgery referral. The results demonstrate that such machine learning methods can contribute to predicting pediatric epilepsy surgery candidates and reducing lag time to surgery referral. PMID:27257386

Machine Learning of Human Pluripotent Stem Cell-Derived Engineered Cardiac Tissue Contractility for Automated Drug Classification.

PubMed

Lee, Eugene K; Tran, David D; Keung, Wendy; Chan, Patrick; Wong, Gabriel; Chan, Camie W; Costa, Kevin D; Li, Ronald A; Khine, Michelle

2017-11-14

Accurately predicting cardioactive effects of new molecular entities for therapeutics remains a daunting challenge. Immense research effort has been focused toward creating new screening platforms that utilize human pluripotent stem cell (hPSC)-derived cardiomyocytes and three-dimensional engineered cardiac tissue constructs to better recapitulate human heart function and drug responses. As these new platforms become increasingly sophisticated and high throughput, the drug screens result in larger multidimensional datasets. Improved automated analysis methods must therefore be developed in parallel to fully comprehend the cellular response across a multidimensional parameter space. Here, we describe the use of machine learning to comprehensively analyze 17 functional parameters derived from force readouts of hPSC-derived ventricular cardiac tissue strips (hvCTS) electrically paced at a range of frequencies and exposed to a library of compounds. A generated metric is effective for then determining the cardioactivity of a given drug. Furthermore, we demonstrate a classification model that can automatically predict the mechanistic action of an unknown cardioactive drug. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

MLViS: A Web Tool for Machine Learning-Based Virtual Screening in Early-Phase of Drug Discovery and Development

PubMed Central

Korkmaz, Selcuk; Zararsiz, Gokmen; Goksuluk, Dincer

2015-01-01

Virtual screening is an important step in early-phase of drug discovery process. Since there are thousands of compounds, this step should be both fast and effective in order to distinguish drug-like and nondrug-like molecules. Statistical machine learning methods are widely used in drug discovery studies for classification purpose. Here, we aim to develop a new tool, which can classify molecules as drug-like and nondrug-like based on various machine learning methods, including discriminant, tree-based, kernel-based, ensemble and other algorithms. To construct this tool, first, performances of twenty-three different machine learning algorithms are compared by ten different measures, then, ten best performing algorithms have been selected based on principal component and hierarchical cluster analysis results. Besides classification, this application has also ability to create heat map and dendrogram for visual inspection of the molecules through hierarchical cluster analysis. Moreover, users can connect the PubChem database to download molecular information and to create two-dimensional structures of compounds. This application is freely available through www.biosoft.hacettepe.edu.tr/MLViS/. PMID:25928885

Management of focal-onset seizures: an update on drug treatment.

PubMed

Johannessen, Svein I; Ben-Menachem, Elinor

2006-01-01

Focal-onset seizures are manifestations of abnormal epileptic firing of brain cells in a localised area or areas of the brain. The diagnosis of focal-onset seizures initially entails an EEG, a detailed history from the patient and eyewitnesses, as well as computer tomographic or, preferably, magnetic resonance imaging scans. Video EEG to record ictal events may be necessary to establish the correct diagnosis. Focal seizures are classified according to the International Classification of Epileptic Seizures and International Classification of Epilepsies and Epilepsy Syndromes. It is important to try to decide how the seizure event fits into this system in order to successfully evaluate and optimise treatment, as well as to give detailed information to the patient about their seizures and prognosis. Once the decision to treat the seizures has been made, the physician must choose which medication is the most appropriate to begin with. Carbamazepine, phenytoin or valproic acid (sodium valproate) are often rated as first-line drugs, but factors such as adverse-effect profiles, age, possibility of pregnancy, and concomitant diseases and medication also need to be considered. Most of the newer antiepileptic drugs (AEDs) appear to have good efficacy and better tolerability than the older agents, but evidence to support their superiority is scarce and has led to conflicting advice in several guidelines. Among the newer AEDs, lamotrigine, gabapentin, topiramate and oxcarbazepine have obtained monotherapy indication in many countries. The higher costs of the newer AEDs may inhibit their wider use, especially in poorer countries.

Transporter-Enzyme Interplay: Deconvoluting Effects of Hepatic Transporters and Enzymes on Drug Disposition Using Static and Dynamic Mechanistic Models.

PubMed

Varma, Manthena V; El-Kattan, Ayman F

2016-07-01

A large body of evidence suggests hepatic uptake transporters, organic anion-transporting polypeptides (OATPs), are of high clinical relevance in determining the pharmacokinetics of substrate drugs, based on which recent regulatory guidances to industry recommend appropriate assessment of investigational drugs for the potential drug interactions. We recently proposed an extended clearance classification system (ECCS) framework in which the systemic clearance of class 1B and 3B drugs is likely determined by hepatic uptake. The ECCS framework therefore predicts the possibility of drug-drug interactions (DDIs) involving OATPs and the effects of genetic variants of SLCO1B1 early in the discovery and facilitates decision making in the candidate selection and progression. Although OATP-mediated uptake is often the rate-determining process in the hepatic clearance of substrate drugs, metabolic and/or biliary components also contribute to the overall hepatic disposition and, more importantly, to liver exposure. Clinical evidence suggests that alteration in biliary efflux transport or metabolic enzymes associated with genetic polymorphism leads to change in the pharmacodynamic response of statins, for which the pharmacological target resides in the liver. Perpetrator drugs may show inhibitory and/or induction effects on transporters and enzymes simultaneously. It is therefore important to adopt models that frame these multiple processes in a mechanistic sense for quantitative DDI predictions and to deconvolute the effects of individual processes on the plasma and hepatic exposure. In vitro data-informed mechanistic static and physiologically based pharmacokinetic models are proven useful in rationalizing and predicting transporter-mediated DDIs and the complex DDIs involving transporter-enzyme interplay. © 2016, The American College of Clinical Pharmacology.

A web-based land cover classification system based on ontology model of different classification systems

NASA Astrophysics Data System (ADS)

Lin, Y.; Chen, X.

2016-12-01

Land cover classification systems used in remote sensing image data have been developed to meet the needs for depicting land covers in scientific investigations and policy decisions. However, accuracy assessments of a spate of data sets demonstrate that compared with the real physiognomy, each of the thematic map of specific land cover classification system contains some unavoidable flaws and unintended deviation. This work proposes a web-based land cover classification system, an integrated prototype, based on an ontology model of various classification systems, each of which is assigned the same weight in the final determination of land cover type. Ontology, a formal explication of specific concepts and relations, is employed in this prototype to build up the connections among different systems to resolve the naming conflicts. The process is initialized by measuring semantic similarity between terminologies in the systems and the search key to produce certain set of satisfied classifications, and carries on through searching the predefined relations in concepts of all classification systems to generate classification maps with user-specified land cover type highlighted, based on probability calculated by votes from data sets with different classification system adopted. The present system is verified and validated by comparing the classification results with those most common systems. Due to full consideration and meaningful expression of each classification system using ontology and the convenience that the web brings with itself, this system, as a preliminary model, proposes a flexible and extensible architecture for classification system integration and data fusion, thereby providing a strong foundation for the future work.

Psychiatric comorbidity among terminally ill patients in general practice in the Netherlands: a comparison between patients with cancer and heart failure.

PubMed

Ng, Chong Guan; Dijkstra, Ellen; Smeets, Hugo; Boks, Marco P M; de Wit, Niek J

2013-01-01

It is unclear whether psychiatric disorders are specifically related to the terminal phase of cancer, or independent of the underlying disease. To investigate the rate of psychiatric comorbidity and psychotropic drugs prescription in terminally ill patients in the GP setting, comparing both patients with terminal cancer and heart failure. Retrospective cohort study using the Utrecht General Practitioner Research Network. Equally-sized groups of patients with terminal cancer and heart failure were randomly selected from the database of four general practices over the years 2005-2009. Psychiatric comorbidities were determined using the International Classification for Primary Care (ICPC) codes and psychotropic drugs prescriptions using the Anatomical Therapeutic Chemical (ATC) Classification System codes. A total of 191 terminally ill patients were included in the study (111 with cancer and 80 with heart failure). The mean age for patients with terminal cancer (70.8 years, standard deviation [SD] = 12.8) was 15 years younger than that of patients with heart failure (85.6 years, SD = 9.2). Half of the terminally ill patients (50.3 %) were prescribed psychotropics, but only 13.6% of them had obtained a psychiatric diagnosis. There were no significant differences in prevalence of psychiatric disease and psychotropic drug prescription between patients with terminal cancer and heart failure. The results demonstrate a high use of psychotropic drugs in terminally ill patients, often in the absence of a formal diagnosis of a psychiatric disorder. The absence of differences between patients with cancer and heart failure suggests that psychiatric diagnoses and increased psychotropic prescriptions are primarily related to the terminal stage of the disease and not to the background of cancer or heart failure.

The Drug Abuse Prevention and Control Act of 1970: Retrospective Assessments of Disparate Treatment and Consequential Impact.

PubMed

Yamatani, Hide; Feit, Marvin; Mann, Aaron

2017-01-01

Although the basic paradigm of the U.S. federal drug policy targeting the supply and demand reduction has not changed since its enactment in 1970, there have been seriously undesirable disparate treatments and impacts among various population groups. Although U.S. Congress could not define what is discrimination, it did provide two major criteria for the assessment of discriminatory practices as follows: (a) disparate treatment-basing a key decision on association with any of the five prohibited individual's demographic classifications (race, color, religion, sex, or national origin); and (b) disparate impact-correlation between any of the five prohibited demographic classifications and the key outcomes. In reference to those criteria, this article describes evidence-based indicators of national failure of the Comprehensive Drug Abuse Prevention and Control Act.

[The clinical and X-ray classification of osteonecrosis of the low jaw].

PubMed

Medvedev, Iu A; Basin, E M; Sokolina, I A

2013-01-01

To elaborate a clinical and X-ray classification of osteonecrosis of the low jaw in people with desomorphine or pervitin addiction. Ninety-two patients with drug addiction who had undergone orthopantomography, direct frontal X-ray of the skull, and multislice computed tomography, followed by multiplanar and three-dimensional imaging reconstruction were examined. One hundred thirty four X-ray films and 74 computed tomographic images were analyzed. The authors proposed a clinical and X-ray classification of osteonecrosis of the low jaw in people with desomorphine or pervitin addiction and elaborated recommendations for surgical interventions on the basis of the developed classification. The developed clinical and X-ray classification and recommendations for surgical interventions may be used to treat osteonecroses of various etiology.

Comparative study of classification algorithms for immunosignaturing data

PubMed Central

2012-01-01

Background High-throughput technologies such as DNA, RNA, protein, antibody and peptide microarrays are often used to examine differences across drug treatments, diseases, transgenic animals, and others. Typically one trains a classification system by gathering large amounts of probe-level data, selecting informative features, and classifies test samples using a small number of features. As new microarrays are invented, classification systems that worked well for other array types may not be ideal. Expression microarrays, arguably one of the most prevalent array types, have been used for years to help develop classification algorithms. Many biological assumptions are built into classifiers that were designed for these types of data. One of the more problematic is the assumption of independence, both at the probe level and again at the biological level. Probes for RNA transcripts are designed to bind single transcripts. At the biological level, many genes have dependencies across transcriptional pathways where co-regulation of transcriptional units may make many genes appear as being completely dependent. Thus, algorithms that perform well for gene expression data may not be suitable when other technologies with different binding characteristics exist. The immunosignaturing microarray is based on complex mixtures of antibodies binding to arrays of random sequence peptides. It relies on many-to-many binding of antibodies to the random sequence peptides. Each peptide can bind multiple antibodies and each antibody can bind multiple peptides. This technology has been shown to be highly reproducible and appears promising for diagnosing a variety of disease states. However, it is not clear what is the optimal classification algorithm for analyzing this new type of data. Results We characterized several classification algorithms to analyze immunosignaturing data. We selected several datasets that range from easy to difficult to classify, from simple monoclonal binding to complex binding patterns in asthma patients. We then classified the biological samples using 17 different classification algorithms. Using a wide variety of assessment criteria, we found ‘Naïve Bayes’ far more useful than other widely used methods due to its simplicity, robustness, speed and accuracy. Conclusions ‘Naïve Bayes’ algorithm appears to accommodate the complex patterns hidden within multilayered immunosignaturing microarray data due to its fundamental mathematical properties. PMID:22720696

Application of the BCS biowaiver approach to assessing bioequivalence of orally disintegrating tablets with immediate release formulations.

PubMed

Ono, Asami; Sugano, Kiyohiko

2014-11-20

The aim of this study was to compare the dissolution profiles of oral disintegrating tablets (ODTs) and immediate release (IR) formulations in order to experimentally validate the regulatory biowaiver scheme (BWS) for biopharmaceutical classification system (BCS) class III drugs. We examined six drugs that show clinical bioequivalence between the ODTs and IR formulations: taltirelin, olopatadine, droxidopa, famotidine, fexofenadine, and hydrochlorothiazide. The dissolution profiles of these drugs were evaluated using the compendium paddle apparatus at pH 1.2 and 6.8. Taltirelin and olopatadine showed very rapid dissolution and met the dissolution criteria in the BWS, whereas droxidopa, famotidine, fexofenadine, and hydrochlorothiazide did not. Furthermore, in the case of famotidine, fexofenadine, and hydrochlorothiazide, the ODTs and IR formulations showed dissimilar dissolution profiles. The dose-to-solubility ratio (D:S) of these drugs was larger than that of the other drugs. The results of this study suggest that extension of the BCS-BWS to ODTs and IR formulations of BCS class III drugs is appropriate. Furthermore, for BCS class III drugs with relatively high D:S, clinical bioequivalence would be achievable even when two formulations showed different dissolution profiles in vitro. Copyright © 2014 Elsevier B.V. All rights reserved.

Microemulsion utility in pharmaceuticals: Implications for multi-drug delivery.

PubMed

Callender, Shannon P; Mathews, Jessica A; Kobernyk, Katherine; Wettig, Shawn D

2017-06-30

Emulsion technology has been utilized extensively in the pharmaceutical industry. This article presents a comprehensive review of the literature on an important subcategory of emulsions, microemulsions. Microemulsions are optically transparent, thermodynamically stable colloidal systems, 10-100nm diameter, that form spontaneously upon mixing of oil, water and emulsifier. This review is the first to address advantages and disadvantages, as well as considerations and challenges in multi-drug delivery. For the period 1 January 2011-30 April 2016, 431 publications related to microemulsion drug delivery were identified and screened according to microemulsion, drug classification, and surfactant types. Results indicate the use of microemulsions predominantly in lipophilic drug delivery (79.4%) via oil-in-water microemulsions and non-ionic surfactants (90%) for oral or topical administration. Cancer is the disease state most targeted followed by inflammatory diseases, microbial infections and cardiovascular disease. Key generalizations from this analysis include: 1) microemulsion formulation is largely based on trial-and-error despite over 1200 publications related to microemulsion drug delivery since their discovery in 1943; 2) characterization using methods including interfacial tension, droplet size, electrical conductivity, turbidity and viscosity may provide additional information for greater predictability; 3) microemulsion drug delivery publications arise primarily from China (27%) and India (21%) suggesting additional research opportunities elsewhere. Copyright © 2017 Elsevier B.V. All rights reserved.

Physiologically Based Absorption Modeling to Impact Biopharmaceutics and Formulation Strategies in Drug Development-Industry Case Studies.

PubMed

Kesisoglou, Filippos; Chung, John; van Asperen, Judith; Heimbach, Tycho

2016-09-01

In recent years, there has been a significant increase in use of physiologically based pharmacokinetic models in drug development and regulatory applications. Although most of the published examples have focused on aspects such as first-in-human (FIH) dose predictions or drug-drug interactions, several publications have highlighted the application of these models in the biopharmaceutics field and their use to inform formulation development. In this report, we present 5 case studies of use of such models in this biopharmaceutics/formulation space across different pharmaceutical companies. The case studies cover different aspects of biopharmaceutics or formulation questions including (1) prediction of absorption prior to FIH studies; (2) optimization of formulation and dissolution method post-FIH data; (3) early exploration of a modified-release formulation; (4) addressing bridging questions for late-stage formulation changes; and (5) prediction of pharmacokinetics in the fed state for a Biopharmaceutics Classification System class I drug with fasted state data. The discussion of the case studies focuses on how such models can facilitate decisions and biopharmaceutic understanding of drug candidates and the opportunities for increased use and acceptance of such models in drug development and regulatory interactions. Copyright © 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Analysis of the drug formulary and the purchasing process at a Moroccan university medical center.

PubMed

Lachhab, Z; Serragui, S; Hassar, M; Cherrah, Y; Errougani, A; Ahid, S

2018-05-31

To give an overview of the pharmaceutical policy in the largest medical center in Morocco, a developing country in socio-economic transition. This is an analytical descriptive study of the drug formulary and the purchasing process carried out at the Ibn Sina University Medical Center. Our formulary included 830 drugs belonging to 14 classes according to the Anatomical, Therapeutic and Chemical (ATC) Classification System. There was a respective predominance of class N (21.8%), class B (13.5%), and class J (12.6%). Injectable route was dominant (46%). Drugs had a significant actual benefit in 70% (according to the French Data), reimbursable in 42.8%, essential in 29.2% according to World Health Organization (WHO) list, and in 36.9% according to the Moroccan list. The calls for tenders included 542 drugs representing 65% of the formulary, and the attribution rate was 71%. The main reason for non-attribution was the lack of offers. Generics accounted for 45% by volume and 26.5% by value. With this first study, we were able to identify key indicators on drugs used in the largest medical center in Morocco. The current challenge is to introduce pharmacoeconomics in decision making concerning the updates of the drug formulary.

Trends in prescription drug expenditures by Medicaid enrollees.

PubMed

Banthin, Jessica S; Miller, G Edward

2006-05-01

As prescription drug expenditures consume an increasingly larger portion of Medicaid budgets, states are anxious to control drug costs without endangering enrollees' health. In this report, we analyzed recent trends in Medicaid prescription drug expenditures by therapeutic classes and subclasses. Identifying the fastest growing categories of drugs, where drugs are grouped into clinically relevant classes and subclasses, can help policymakers decide where to focus their cost containment efforts. We used data from the Medical Expenditure Panel Survey linked to a prescription drug therapeutic classification system, to examine trends between 1996/1997 and 2001/2002 in utilization and expenditures for the noninstitutionalized Medicaid population. We separated aggregate trends into changes in population with use and changes in expenditures per user, and percent generic. We also highlighted differences within the Medicaid population, including children, adults, disabled, and elderly. We found rapid growth in expenditures for antidepressants, antipsychotics, antihyperlipidemics, antidiabetic agents, antihistamines, COX-2 inhibitors, and proton pump inhibitors and found evidence supporting the rapid take-up of new drugs. In some cases these increases are the result of increased expenditures per user and in other cases the overall growth also comes from an increase in the population with use. Medicaid programs may want to reassess their cost-containment policies in light of the rapid take-up of new drugs. Our analysis also identifies areas in which more information is needed on the comparative effectiveness of new versus existing treatments.

42 CFR 412.620 - Patient classification system.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 42 Public Health 2 2010-10-01 2010-10-01 false Patient classification system. 412.620 Section 412... Inpatient Rehabilitation Hospitals and Rehabilitation Units § 412.620 Patient classification system. (a) Classification methodology. (1) A patient classification system is used to classify patients in inpatient...

42 CFR 412.620 - Patient classification system.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 42 Public Health 2 2011-10-01 2011-10-01 false Patient classification system. 412.620 Section 412... Inpatient Rehabilitation Hospitals and Rehabilitation Units § 412.620 Patient classification system. (a) Classification methodology. (1) A patient classification system is used to classify patients in inpatient...

Physicochemical characterisation and investigation of the bonding mechanisms of API-titanate nanotube composites as new drug carrier systems.

PubMed

Sipos, Barbara; Pintye-Hódi, Klára; Kónya, Zoltán; Kelemen, András; Regdon, Géza; Sovány, Tamás

2017-02-25

Titanate nanotube (TNT) has recently been explored as a new carrier material for active pharmaceutical ingredients (API). The aim of the present work was to reveal the physicochemical properties of API-TNT composites, focusing on the interactions between the TNTs and the incorporated APIs. Drugs belonging to different Biopharmaceutical Classification System (BCS) classes were loaded into TNTs: diltiazem hydrochloride (BCS I.), diclofenac sodium (BCS II.), atenolol (BCS III.) and hydrochlorothiazide (BCS IV.). Experimental results demonstrated that it is feasible for spiral cross-sectioned titanate nanotubes to carry drugs and maintain their bioactivity. The structural properties of the composites were characterized by a range of analytical techniques, including FT-IR, DSC, TG-MS, etc. The interactions between APIs and TNTs were identified as electrostatic attractions, mainly dominated by hydrogen bonds. Based on the results, it can be stated that the strength of the association depends on the hydrogen donor strength of the API. The drug release of incorporated APIs was evaluated from compressed tablets and compared to that of pure APIs. Differences noticed in the dissolution profiles due to incorporation showed a correlation with the strength of interactions between the APIs and the TNTs observed in the above analytical studies. Copyright © 2016 Elsevier B.V. All rights reserved.

AI-augmented time stretch microscopy

NASA Astrophysics Data System (ADS)

Mahjoubfar, Ata; Chen, Claire L.; Lin, Jiahao; Jalali, Bahram

2017-02-01

Cell reagents used in biomedical analysis often change behavior of the cells that they are attached to, inhibiting their native signaling. On the other hand, label-free cell analysis techniques have long been viewed as challenging either due to insufficient accuracy by limited features, or because of low throughput as a sacrifice of improved precision. We present a recently developed artificial-intelligence augmented microscope, which builds upon high-throughput time stretch quantitative phase imaging (TS-QPI) and deep learning to perform label-free cell classification with record high-accuracy. Our system captures quantitative optical phase and intensity images simultaneously by frequency multiplexing, extracts multiple biophysical features of the individual cells from these images fused, and feeds these features into a supervised machine learning model for classification. The enhanced performance of our system compared to other label-free assays is demonstrated by classification of white blood T-cells versus colon cancer cells and lipid accumulating algal strains for biofuel production, which is as much as five-fold reduction in inaccuracy. This system obtains the accuracy required in practical applications such as personalized drug development, while the cells remain intact and the throughput is not sacrificed. Here, we introduce a data acquisition scheme based on quadrature phase demodulation that enables interruptionless storage of TS-QPI cell images. Our proof of principle demonstration is capable of saving 40 TB of cell images in about four hours, i.e. pictures of every single cell in 10 mL of a sample.

Transintestinal transport mechanisms of 5-aminosalicylic acid (in situ rat intestine perfusion, Caco-2 cells) and Biopharmaceutics Classification System.

PubMed

Smetanová, Libuše; Stětinová, Věra; Kholová, Dagmar; Kuneš, Martin; Nobilis, Milan; Svoboda, Zbyněk; Květina, Jaroslav

2013-09-01

The aim of the study was 1) to estimate permeability of 5-aminosalicylic acid (5-ASA), 2) to categorize 5-ASA according to BCS (Biopharmaceutics Classification System), and 3) to contribute to determination of 5-ASA transintestinal transport and biotransformation mechanisms. The in situ rat intestine perfusion was used as an initial method to study 5-ASA transport. The amount of 5-ASA (released from tablet) transferred into portal circulation reached 5.79 ± 0.24%. During this transport, the intestinal formation of 5-ASA main metabolite (N-ac-5-ASA) occurred. N-ac-5-ASA was found in perfusate both from intestinal lumen and from v. portae. In in vitro Caco-2 monolayers, transport of 5-ASA (10-1000 µmol/l) was studied in apical-basolateral and basolateral-apical direction (iso-pH 7.4 conditions). The transport of total 5-ASA (parent drug plus intracellularly formed N-ac-5-ASA) was linear with time, concentration- and direction-dependent. Higher basolateral-apical (secretory) transport was mainly caused by higher transport of the metabolite (suggesting metabolite efflux transport). Transport of 5-ASA (only parent drug) was saturable (transepithelial carrier-mediated) at low doses, dominated by passive, paracellular process in higher doses which was confirmed by increased 5-ASA transport using Ca2+-free transport medium. The estimated low 5-ASA permeability and its low solubility enable to classify 5-ASA as BCS class IV.

Vaccine adverse event text mining system for extracting features from vaccine safety reports.

PubMed

Botsis, Taxiarchis; Buttolph, Thomas; Nguyen, Michael D; Winiecki, Scott; Woo, Emily Jane; Ball, Robert

2012-01-01

To develop and evaluate a text mining system for extracting key clinical features from vaccine adverse event reporting system (VAERS) narratives to aid in the automated review of adverse event reports. Based upon clinical significance to VAERS reviewing physicians, we defined the primary (diagnosis and cause of death) and secondary features (eg, symptoms) for extraction. We built a novel vaccine adverse event text mining (VaeTM) system based on a semantic text mining strategy. The performance of VaeTM was evaluated using a total of 300 VAERS reports in three sequential evaluations of 100 reports each. Moreover, we evaluated the VaeTM contribution to case classification; an information retrieval-based approach was used for the identification of anaphylaxis cases in a set of reports and was compared with two other methods: a dedicated text classifier and an online tool. The performance metrics of VaeTM were text mining metrics: recall, precision and F-measure. We also conducted a qualitative difference analysis and calculated sensitivity and specificity for classification of anaphylaxis cases based on the above three approaches. VaeTM performed best in extracting diagnosis, second level diagnosis, drug, vaccine, and lot number features (lenient F-measure in the third evaluation: 0.897, 0.817, 0.858, 0.874, and 0.914, respectively). In terms of case classification, high sensitivity was achieved (83.1%); this was equal and better compared to the text classifier (83.1%) and the online tool (40.7%), respectively. Our VaeTM implementation of a semantic text mining strategy shows promise in providing accurate and efficient extraction of key features from VAERS narratives.

77 FR 125 - Draft Guidance for Industry and Food and Drug Administration Staff; Medical Device Classification...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-01-03

... medical devices regulated by the Center for Devices and Radiological Health (CDRH) and the Center for... assist that office in processing your request, or fax your request to CDRH at (301) 847-8149. The draft... parts 862 through 892)) have been the basis for the CDRH's Classification Product Code structure and...

From micro- to nanostructured implantable device for local anesthetic delivery

PubMed Central

Zorzetto, Laura; Brambilla, Paola; Marcello, Elena; Bloise, Nora; De Gregori, Manuela; Cobianchi, Lorenzo; Peloso, Andrea; Allegri, Massimo; Visai, Livia; Petrini, Paola

2016-01-01

Local anesthetics block the transmission of painful stimuli to the brain by acting on ion channels of nociceptor fibers, and find application in the management of acute and chronic pain. Despite the key role they play in modern medicine, their cardio and neurotoxicity (together with their short half-life) stress the need for developing implantable devices for tailored local drug release, with the aim of counterbalancing their side effects and prolonging their pharmacological activity. This review discusses the evolution of the physical forms of local anesthetic delivery systems during the past decades. Depending on the use of different biocompatible materials (degradable polyesters, thermosensitive hydrogels, and liposomes and hydrogels from natural polymers) and manufacturing processes, these systems can be classified as films or micro- or nanostructured devices. We analyze and summarize the production techniques according to this classification, focusing on their relative advantages and disadvantages. The most relevant trend reported in this work highlights the effort of moving from microstructured to nanostructured systems, with the aim of reaching a scale comparable to the biological environment. Improved intracellular penetration compared to microstructured systems, indeed, provides specific drug absorption into the targeted tissue and can lead to an enhancement of its bioavailability and retention time. Nanostructured systems are realized by the modification of existing manufacturing processes (interfacial deposition and nanoprecipitation for degradable polyester particles and high- or low-temperature homogenization for liposomes) or development of novel strategies (electrospun matrices and nanogels). The high surface-to-volume ratio that characterizes nanostructured devices often leads to a burst drug release. This drawback needs to be addressed to fully exploit the advantage of the interaction between the target tissues and the drug: possible strategies could involve specific binding between the drug and the material chosen for the device, and a multiscale approach to reach a tailored, prolonged drug release. PMID:27354799

Comparison of several chemometric methods of libraries and classifiers for the analysis of expired drugs based on Raman spectra.

PubMed

Gao, Qun; Liu, Yan; Li, Hao; Chen, Hui; Chai, Yifeng; Lu, Feng

2014-06-01

Some expired drugs are difficult to detect by conventional means. If they are repackaged and sold back into market, they will constitute a new public health challenge. For the detection of repackaged expired drugs within specification, paracetamol tablet from a manufacturer was used as a model drug in this study for comparison of Raman spectra-based library verification and classification methods. Raman spectra of different batches of paracetamol tablets were collected and a library including standard spectra of unexpired batches of tablets was established. The Raman spectrum of each sample was identified by cosine and correlation with the standard spectrum. The average HQI of the suspicious samples and the standard spectrum were calculated. The optimum threshold values were 0.997 and 0.998 respectively as a result of ROC and four evaluations, for which the accuracy was up to 97%. Three supervised classifiers, PLS-DA, SVM and k-NN, were chosen to establish two-class classification models and compared subsequently. They were used to establish a classification of expired batches and an unexpired batch, and predict the suspect samples. The average accuracy was 90.12%, 96.80% and 89.37% respectively. Different pre-processing techniques were tried to find that first derivative was optimal for methods of libraries and max-min normalization was optimal for that of classifiers. The results obtained from these studies indicated both libraries and classifier methods could detect the expired drugs effectively, and they should be used complementarily in the fast-screening. Copyright © 2014 Elsevier B.V. All rights reserved.

Intra- and Interobserver Reliability of Three Classification Systems for Hallux Rigidus.

PubMed

Dillard, Sarita; Schilero, Christina; Chiang, Sharon; Pham, Peter

2018-04-18

There are over ten classification systems currently used in the staging of hallux rigidus. This results in confusion and inconsistency with radiographic interpretation and treatment. The reliability of hallux rigidus classification systems has not yet been tested. The purpose of this study was to evaluate intra- and interobserver reliability using three commonly used classifications for hallux rigidus. Twenty-one plain radiograph sets were presented to ten ACFAS board-certified foot and ankle surgeons. Each physician classified each radiograph based on clinical experience and knowledge according to the Regnauld, Roukis, and Hattrup and Johnson classification systems. The two-way mixed single-measure consistency intraclass correlation was used to calculate intra- and interrater reliability. The intrarater reliability of individual sets for the Roukis and Hattrup and Johnson classification systems was "fair to good" (Roukis, 0.62±0.19; Hattrup and Johnson, 0.62±0.28), whereas the intrarater reliability of individual sets for the Regnauld system bordered between "fair to good" and "poor" (0.43±0.24). The interrater reliability of the mean classification was "excellent" for all three classification systems. Conclusions Reliable and reproducible classification systems are essential for treatment and prognostic implications in hallux rigidus. In our study, Roukis classification system had the best intrarater reliability. Although there are various classification systems for hallux rigidus, our results indicate that all three of these classification systems show reliability and reproducibility.

Effects of gross motor function and manual function levels on performance-based ADL motor skills of children with spastic cerebral palsy.

PubMed

Park, Myoung-Ok

2017-02-01

[Purpose] The purpose of this study was to determine effects of Gross Motor Function Classification System and Manual Ability Classification System levels on performance-based motor skills of children with spastic cerebral palsy. [Subjects and Methods] Twenty-three children with cerebral palsy were included. The Assessment of Motor and Process Skills was used to evaluate performance-based motor skills in daily life. Gross motor function was assessed using Gross Motor Function Classification Systems, and manual function was measured using the Manual Ability Classification System. [Results] Motor skills in daily activities were significantly different on Gross Motor Function Classification System level and Manual Ability Classification System level. According to the results of multiple regression analysis, children categorized as Gross Motor Function Classification System level III scored lower in terms of performance based motor skills than Gross Motor Function Classification System level I children. Also, when analyzed with respect to Manual Ability Classification System level, level II was lower than level I, and level III was lower than level II in terms of performance based motor skills. [Conclusion] The results of this study indicate that performance-based motor skills differ among children categorized based on Gross Motor Function Classification System and Manual Ability Classification System levels of cerebral palsy.

78 FR 18252 - Prevailing Rate Systems; North American Industry Classification System Based Federal Wage System...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-03-26

...-AM78 Prevailing Rate Systems; North American Industry Classification System Based Federal Wage System... 2007 North American Industry Classification System (NAICS) codes currently used in Federal Wage System... (OPM) issued a final rule (73 FR 45853) to update the 2002 North American Industry Classification...

PREDICTING ABUSE POTENTIAL OF STIMULANTS AND OTHER DOPAMINERGIC DRUGS: OVERVIEW AND RECOMMENDATIONS

PubMed Central

Huskinson, Sally L.; Naylor, Jennifer E.; Rowlett, James K.; Freeman, Kevin B.

2014-01-01

Examination of a drug’s abuse potential at multiple levels of analysis (molecular/cellular action, whole-organism behavior, epidemiological data) is an essential component to regulating controlled substances under the Controlled Substances Act (CSA). We reviewed studies that examined several central nervous system (CNS) stimulants, focusing on those with primarily dopaminergic actions, in drug self-administration, drug discrimination, and physical dependence. For drug self-administration and drug discrimination, we distinguished between experiments conducted with rats and nonhuman primates (NHP) to highlight the common and unique attributes of each model in the assessment of abuse potential. Our review of drug self-administration studies suggests that this procedure is important in predicting abuse potential of dopaminergic compounds, but there were many false positives. We recommended that tests to determine how reinforcing a drug is relative to a known drug of abuse may be more predictive of abuse potential than tests that yield a binary, yes-or-no classification. Several false positives also occurred with drug discrimination. With this procedure, we recommended that future research follow a standard decision-tree approach that may require examining the drug being tested for abuse potential as the training stimulus. This approach would also allow several known drugs of abuse to be tested for substitution, and this may reduce false positives. Finally, we reviewed evidence of physical dependence with stimulants and discussed the feasibility of modeling these phenomena in nonhuman animals in a rational and practical fashion. PMID:24662599

Working memory subsystems are impaired in chronic drug dependents.

PubMed

Soliman, Abdrabo Moghazy; Gadelrab, Hesham Fathy; Elfar, Rania Mohamed

2013-06-01

A large body of research that has investigated substance dependence and working memory (WM) resources, yet no prior study has used a comprehensive test battery to examine the impact of chronic drug dependence on WM as a multi-component system. This study examined the efficiency of several WM components in participants who were chronic drug dependents. In addition, the functioning of the four WM components was compared among dependents of various types of drugs. In total, 128 chronic drug dependents participated in this study. Their average age was 38.48 years, and they were classified into four drug-dependence groups. Chronic drug dependents were compared with a 36-participant control group that had a mean age of 37.6 years. A WM test battery that comprised eight tests and that assessed each of four WM components was administered to each participant. Compared with the control group, all four groups of drug dependents had significantly poorer test performance on all of the WM tasks. Among the four groups of drug users, the polydrug group had the poorest performance scores on each of the eight tasks, and the performance scores of the marijuana group were the least affected. Finally, the forward digit span task and the logical memory tasks were less sensitive than other tasks when differentiating between marijuana users and the normal participants. The four components of WM are impaired among chronic drug dependents. These results have implications for the development of tools, classification methods and therapeutic strategies for drug dependents.

[Drugs in pregnancy].

PubMed

Danchev, N; Astrug, A; Tsankova, V; Nikolova, I

2006-01-01

The use of drugs in pregnancy is being discussed. The influence of different factors, both physiological and drug related (physicochemical characteristics, dose, duration of pharmacotherapy) on the processes of absorption, distribution, protein binding, metabolism and excretion are reviewed. The up-to-date classification of the drugs in relation to their effects on the fetus is presented. Special emphasize is given to drugs (antibiotics, cardio-vascular, psychotropic etc.) used for the treatment of acute and chronic conditions in the course of pregnancy. Drugs used for symptoms like pain, high temperature and constipation are also reviewed. Recommendations for the use of safer drugs in pregnancy are given. Drugs with proven teratogenic effects are presented.

Documentation of pharmaceutical care: Validation of an intervention oriented classification system.

PubMed

Maes, Karen A; Studer, Helene; Berger, Jérôme; Hersberger, Kurt E; Lampert, Markus L

2017-12-01

During the dispensing process, pharmacists may come across technical and clinical issues requiring a pharmaceutical intervention (PI). An intervention-oriented classification system is a helpful tool to document these PIs in a structured manner. Therefore, we developed the PharmDISC classification system (Pharmacists' Documentation of Interventions in Seamless Care). The aim of this study was to evaluate the PharmDISC system in the daily practice environment (in terms of interrater reliability, appropriateness, interpretability, acceptability, feasibility, and validity); to assess its user satisfaction, the descriptive manual, and the online training; and to explore first implementation aspects. Twenty-one pharmacists from different community pharmacies each classified 30 prescriptions requiring a PI with the PharmDISC system on 5 selected days within 5 weeks. Interrater reliability was determined using model PIs and Fleiss's kappa coefficients (κ) were calculated. User satisfaction was assessed by questionnaire with a 4-point Likert scale. The main outcome measures were interrater reliability (κ); appropriateness, interpretability, validity (ratio of completely classified PIs/all PIs); feasibility, and acceptability (user satisfaction and suggestions). The PharmDISC system reached an average substantial agreement (κ = 0.66). Of documented 519 PIs, 430 (82.9%) were completely classified. Most users found the system comprehensive (median user agreement 3 [2/3.25 quartiles]) and practical (3[2.75/3]). The PharmDISC system raised the awareness regarding drug-related problems for most users (n = 16). To facilitate its implementation, an electronic version that automatically connects to the prescription together with a task manager for PIs needing follow-up was suggested. Barriers could be time expenditure and lack of understanding the benefits. Substantial interrater reliability and acceptable user satisfaction indicate that the PharmDISC system is a valid system to document PIs in daily community pharmacy practice. © 2017 John Wiley & Sons, Ltd.

Deep learning of mutation-gene-drug relations from the literature.

PubMed

Lee, Kyubum; Kim, Byounggun; Choi, Yonghwa; Kim, Sunkyu; Shin, Wonho; Lee, Sunwon; Park, Sungjoon; Kim, Seongsoon; Tan, Aik Choon; Kang, Jaewoo

2018-01-25

Molecular biomarkers that can predict drug efficacy in cancer patients are crucial components for the advancement of precision medicine. However, identifying these molecular biomarkers remains a laborious and challenging task. Next-generation sequencing of patients and preclinical models have increasingly led to the identification of novel gene-mutation-drug relations, and these results have been reported and published in the scientific literature. Here, we present two new computational methods that utilize all the PubMed articles as domain specific background knowledge to assist in the extraction and curation of gene-mutation-drug relations from the literature. The first method uses the Biomedical Entity Search Tool (BEST) scoring results as some of the features to train the machine learning classifiers. The second method uses not only the BEST scoring results, but also word vectors in a deep convolutional neural network model that are constructed from and trained on numerous documents such as PubMed abstracts and Google News articles. Using the features obtained from both the BEST search engine scores and word vectors, we extract mutation-gene and mutation-drug relations from the literature using machine learning classifiers such as random forest and deep convolutional neural networks. Our methods achieved better results compared with the state-of-the-art methods. We used our proposed features in a simple machine learning model, and obtained F1-scores of 0.96 and 0.82 for mutation-gene and mutation-drug relation classification, respectively. We also developed a deep learning classification model using convolutional neural networks, BEST scores, and the word embeddings that are pre-trained on PubMed or Google News data. Using deep learning, the classification accuracy improved, and F1-scores of 0.96 and 0.86 were obtained for the mutation-gene and mutation-drug relations, respectively. We believe that our computational methods described in this research could be used as an important tool in identifying molecular biomarkers that predict drug responses in cancer patients. We also built a database of these mutation-gene-drug relations that were extracted from all the PubMed abstracts. We believe that our database can prove to be a valuable resource for precision medicine researchers.

Summary of the National Institute of Child Health and Human Development-best pharmaceuticals for Children Act Pediatric Formulation Initiatives Workshop-Pediatric Biopharmaceutics Classification System Working Group.

PubMed

Abdel-Rahman, Susan M; Amidon, Gordon L; Kaul, Ajay; Lukacova, Viera; Vinks, Alexander A; Knipp, Gregory T

2012-11-01

The Biopharmaceutics Classification System (BCS) allows compounds to be classified based on their in vitro solubility and intestinal permeability. The BCS has found widespread use in the pharmaceutical community to be an enabling guide for the rational selection of compounds, formulation for clinical advancement, and generic biowaivers. The Pediatric Biopharmaceutics Classification System (PBCS) Working Group was convened to consider the possibility of developing an analogous pediatric-based classification system. Because there are distinct developmental differences that can alter intestinal contents, volumes, permeability, and potentially biorelevant solubilities at different ages, the PBCS Working Group focused on identifying age-specific issues that need to be considered in establishing a flexible, yet rigorous PBCS. We summarized the findings of the PBCS Working Group and provided insights into considerations required for the development of a PBCS. Through several meetings conducted both at The Eunice Kennedy Shriver National Institute of Child Health, Human Development-US Pediatric Formulation Initiative Workshop (November 2011) and via teleconferences, the PBCS Working Group considered several high-level questions that were raised to frame the classification system. In addition, the PBCS Working Group identified a number of knowledge gaps that need to be addressed to develop a rigorous PBCS. It was determined that for a PBCS to be truly meaningful, it needs to be broken down into several different age groups that account for developmental changes in intestinal permeability, luminal contents, and gastrointestinal (GI) transit. Several critical knowledge gaps were identified, including (1) a lack of fully understanding the ontogeny of drug metabolizing enzymes and transporters along the GI tract, in the liver, and in the kidney; (2) an incomplete understanding of age-based changes in the GI, liver, and kidney physiology; (3) a clear need to better understand age-based intestinal permeability and fraction absorbed required to develop the PBCS; (4) a clear need for the development and organization of pediatric tissue biobanks to serve as a source for ontogenic research; and (5) a lack of literature published in age-based pediatric pharmacokinetics to build physiologically- and population-based pharmacokinetic (PBPK) databases. To begin the process of establishing a PBPK model, 10 pediatric therapeutic agents were selected (based on their adult BCS classifications). These agents should be targeted for additional research in the future. The PBCS Working Group also identified several areas where greater emphasis on research was needed to enable the development of a PBCS. Copyright © 2012 Elsevier HS Journals, Inc. All rights reserved.

Utilization of self-medication and prescription drugs among 15-year-old children from the German GINIplus birth cohort.

PubMed

Italia, Salvatore; Brand, Helmut; Heinrich, Joachim; Berdel, Dietrich; von Berg, Andrea; Wolfenstetter, Silke Britta

2015-11-01

The objective was to analyse paediatric drug utilization in relation to self-medication, prescription drugs, and the most reported therapeutic drug categories. Data were collected for 3013 children on their utilization of drugs (4-week prevalence) from a German birth cohort study (GINIplus, 15-year follow-up) using a self-administered questionnaire. The drugs were grouped into over-the-counter drugs and prescription drugs, and were classified according to the anatomical therapeutic chemical classification system. Predictors were analysed using a logistic regression model with four independent variables (gender, study area, maternal education, and parental income). Some 69% of the reported 2489 drugs were over-the-counter drugs, and 31% were prescription drugs. The 4-week prevalence for using any type of drug was 41.0%. Drug categories with high prevalence rates of use were antiinflammatory drugs (10.3%), analgesics (7.1%), and antiallergics (5.0%). Factors associated with higher use of over-the-counter drugs were female gender (OR = 1.56, p < 0.0001) and higher maternal education (OR = 1.60, p = 0.0021; university degree vs. secondary high school). Maternal education was correlated with the use of prescribed or self-medicated antiallergics (positive association) and contraceptives (negative association). The use of antibiotics, methylphenidate, and drugs for thyroid therapy was associated with lower parental income. The use of over-the-counter drugs in 15-year-old children from the GINIplus birth cohort is very common and is predicted by socioeconomic factors such as maternal education. This has to be considered by health care managers when deciding about the exclusion of over-the-counter drugs (normally used for self-medication) from reimbursement or the deregulation of drug sales. Copyright © 2015 John Wiley & Sons, Ltd.

[Determining factors for the use of anxiolytic and hypnotic drugs in the elderly].

PubMed

Téllez-Lapeira, Juan M; López-Torres Hidalgo, Jesús; Gálvez-Alcaraz, Luis; Párraga-Martínez, Ignacio; Boix-Gras, Clotilde; García-Ruiz, Antonio

To estimate the prevalence of self-reported anxiety/hypnotics use in adults 65 years and older and identify potential factors that determine the use of these drugs. Cross-sectional study conducted on a study population of 1,161 non-institutionalised adults 65 years old and older with enough ability to conduct a personal interview. Participants were randomly selected from health care registers. The main outcomes of interest included consumption of anxiolytics, hypnotics and other drugs (filed by ATC classification system), mood (based on the Yesavage geriatric depression scale), cognitive status (Pfeiffer questionnaire), physical-functional assessment of basic activities of daily living (Katz index), health problems (ICPC-2 classification WONCA), and sociodemographic variables. The prevalence of self-reported anxiety/hypnotics consumption was 16.6% (95% CI: 14.5 - 18.7), of which 90.5% were benzodiazepines (BZD), mainly lorazepam (39.4% of BZD). Long half-life BZD accounted for 24.7% of BZD. Hypnotics accounted for 27.5% of anxiolytics/hypnotics. The use of sedatives/hypnotics was independently associated with other drugs (non-psychotropics) consumption (OR 6.8, 95% CI: 2.1-22.0), presence of established depression (OR: 2.5; 95% CI: 1.0 -5.9), presence of 4 or more comorbidities (OR: 2.0; 95% CI: 1.4-2.9), being female (OR 2.1, 95% CI: 1.5-3.1) and being dependent for basic activities of daily living (OR: 1.8, 95% CI: 1.1-2.9). The prevalence of sedatives/hypnotics use in the elderly from Albacete is high. Several factors were identified as potential determinants of sedatives/hypnotics use in our study population. It will be important to evaluate the misuse of these drugs in order to develop effective, efficient and safe prescription strategies. Copyright © 2016 SEGG. Publicado por Elsevier España, S.L.U. All rights reserved.

Drug overdose surveillance using hospital discharge data.

PubMed

Slavova, Svetla; Bunn, Terry L; Talbert, Jeffery

2014-01-01

We compared three methods for identifying drug overdose cases in inpatient hospital discharge data on their ability to classify drug overdoses by intent and drug type(s) involved. We compared three International Classification of Diseases, Ninth Revision, Clinical Modification code-based case definitions using Kentucky hospital discharge data for 2000-2011. The first definition (Definition 1) was based on the external-cause-of-injury (E-code) matrix. The other two definitions were based on the Injury Surveillance Workgroup on Poisoning (ISW7) consensus recommendations for national and state poisoning surveillance using the principal diagnosis or first E-code (Definition 2) or any diagnosis/E-code (Definition 3). Definition 3 identified almost 50% more drug overdose cases than did Definition 1. The increase was largely due to cases with a first-listed E-code describing a drug overdose but a principal diagnosis that was different from drug overdose (e.g., mental disorders, or respiratory or circulatory system failure). Regardless of the definition, more than 53% of the hospitalizations were self-inflicted drug overdoses; benzodiazepines were involved in about 30% of the hospitalizations. The 2011 age-adjusted drug overdose hospitalization rate in Kentucky was 146/100,000 population using Definition 3 and 107/100,000 population using Definition 1. The ISW7 drug overdose definition using any drug poisoning diagnosis/E-code (Definition 3) is potentially the highest sensitivity definition for counting drug overdose hospitalizations, including by intent and drug type(s) involved. As the states enact policies and plan for adequate treatment resources, standardized drug overdose definitions are critical for accurate reporting, trend analysis, policy evaluation, and state-to-state comparison.

Rodent motor and neuropsychological behaviour measured in home cages using the integrated modular platform SmartCage™

PubMed Central

Khroyan, Taline V; Zhang, Jingxi; Yang, Liya; Zou, Bende; Xie, James; Pascual, Conrado; Malik, Adam; Xie, Julian; Zaveri, Nurulain T; Vazquez, Jacqueline; Polgar, Willma; Toll, Lawrence; Fang, Jidong; Xie, Xinmin

2017-01-01

SUMMARY To facilitate investigation of diverse rodent behaviours in rodents’ home cages, we have developed an integrated modular platform, the SmartCage™ system (AfaSci, Inc. Burlingame, CA, USA), which enables automated neurobehavioural phenotypic analysis and in vivo drug screening in a relatively higher-throughput and more objective manner.The individual platform consists of an infrared array, a vibration floor sensor and a variety of modular devices. One computer can simultaneously operate up to 16 platforms via USB cables.The SmartCage™ detects drug-induced increases and decreases in activity levels, as well as changes in movement patterns. Wake and sleep states of mice can be detected using the vibration floor sensor. The arousal state classification achieved up to 98% accuracy compared with results obtained by electroencephalography and electromyography. More complex behaviours, including motor coordination, anxiety-related behaviours and social approach behaviour, can be assessed using appropriate modular devices and the results obtained are comparable with results obtained using conventional methods.In conclusion, the SmartCage™ system provides an automated and accurate tool to quantify various rodent behaviours in a ‘stress-free’ environment. This system, combined with the validated testing protocols, offers powerful a tool kit for transgenic phenotyping and in vivo drug screening. PMID:22540540

Medicine reclassification processes and regulations for proper use of over-the-counter self-care medicines in Japan.

PubMed

Nomura, Kaori; Kitagawa, Yuki; Yuda, Yasukatsu; Takano-Ohmuro, Hiromi

2016-01-01

Japan has actively reclassified substances ranging from prescription drugs to over-the-counter (OTC) drugs in recent years. The sale of most OTC drugs was deregulated several times and pharmacists' supervision was deemed no longer mandatory. Japan established a new OTC evaluation system in 2015 to hear opinions from various stakeholders regarding medicine types to be reclassified. This study aimed to examine the new framework to identify candidate substances for reclassification. Moreover, we examined how to manage the safe, self-care use of OTC drugs in Japan. The necessary regulatory information on OTC approvals as of January 2015 was collected using an Internet search and relevant databases. To highlight the characteristics of OTC drugs in Japan, the UK was selected as a comparison country because it too was actively promoting the reclassification of medicines from prescription to nonprescription status, and because of economic similarity. Japan and the UK have a risk-based classification for nonprescription medicines. Japan has made OTC drugs available with mandatory pharmacists' supervision, face-to-face with pharmacists, or online instruction, which is similar to the "pharmacy medicine" practiced in the UK. Japan recently reformed the reclassification process to involve physicians and the public in the process; some interactions were back to "prescription-only medicine" in the UK. It is expected that the opinion of marketers, medical professionals, and the public will improve the discussion that will greatly contribute to the safe use of drugs. Monitoring the new system will be noteworthy to ensure that OTC drug users are managing their self-care properly and visiting a doctor only when necessary. The supply methods are similar in Japan and the UK; however, the expected growth in the Japanese OTC market by the Cabinet and the industry is still uncertain.

[High prevalence of off-label and unlicensed drug prescribing in a Brazilian intensive care unit].

PubMed

Ferreira, Lilian de Abreu; Ibiapina, Cássio da Cunha; Machado, Márcia Gomes Penido; Fagundes, Eleonora Druve Tavares

2012-01-01

To describe the use and determine the prevalence of off-label and unlicensed drug use prescribing in a pediatric intensive care unit in a Southeastern Brazilian hospital Cross-sectional study of inpatients in a pediatric intensive care unit from May 2008 through January 2009. The classification according to the Brazilian regulatory agency (Agência de Vigilância Sanitária - Anvisa) approval criteria was based on the Anvisa electronic package insert list, Pharmaceuticals Dictionary, and the analysis was conducted through R software. We analysed 1,054 prescription items for 73 patients. Females predominated (52%), and the patients' age ranged from 0 to 16 years. Among the prescribed items, 23.4% were off-label, 12.6% were unlicensed, 1.4% were both off-label and unlicensed, 86% had at least one item off-label, and 67% had at least one unlicensed drug. The most frequently prescribed therapeutic groups were systemic anti-bacterial, analgesic, psycholeptic, and antiasmathic agents. The current study results confirm the high prevalence of unlicensed and off-label drug use in a pediatric intensive care unit.

Transepithelial transport of biperiden hydrochloride in Caco-2 cell monolayers.

PubMed

Abalos, Ivana S; Rodríguez, Yanina I; Lozano, Verónica; Cereseto, Marina; Mussini, Maria V; Spinetto, Marta E; Chiale, Carlos; Pesce, Guido

2012-09-01

The aim of this research has been to determine the biperiden hydrochloride permeability in Caco-2 model, in order to classify it based on the Biopharmaceutics Classification System (BCS). The World Health Organization (WHO) as well as many other authors have provisionally assigned the drug as BCS class I (high solubility-high permeability) or III (high solubility-low permeability), based on different methods. We determined biperiden BCS class by comparing its permeability to 5 pre-defined compounds: atenolol and ranitidine hydrochloride (low permeability group) and metoprolol tartrate, sodium naproxen and theophylline (high permeability group). Since biperiden permeability was higher than those obtained for high permeability drugs, we classified it as a BCS class I compound. On the other hand, as no differences were obtained for permeability values when apical to basolateral and basolateral to apical fluxes were studied, this drug cannot act as a substrate of efflux transporters. As a consequence of our results, we suggest that the widely used antiparkinsonian drug, biperiden, should be candidate for a waiver of in vivo bioequivalence studies. Copyright © 2012 Elsevier B.V. All rights reserved.

Anticancer patent landscape and technology assessment of Indian public-funded research institutes and organizations.

PubMed

Dara, Ajay; Sangamwar, Abhay T

2014-08-01

This review discusses the various drug therapeutic targets and latest technologies of anticancer patents from 10 Indian public-funded research organizations covering more than 150 esteemed institutes. We have identified and reported the leading assignee and inventors along with their collaboration network and, thereby, have analyzed the various patent trends, geographical distributions, citation maps, Derwent World Patents Index, international patent classification analysis and the like. This article provides the insights of 1905 patent documents from 191 families and discusses in-depth anticancer technology through categorization studies at the level of drug discovery, drug development and treatment and diagnosis. In addition, various cancer targets were correlated with recent technologies so as to identify the white spaces for upcoming technologies. Over a period of 13 years (1990 - 2013) the main focus of Indian cancer research was in the field of synthetic chemistry and natural extracts followed by the pharmaceutical compositions and combinations, whereas, the white spaces for future cancer remedy were identified from research in the areas of cancer stem cell lines, vaccines, gene therapy, nano formulations with targeted drug delivery systems as core and latest technologies.

Clinical toxicology of newer recreational drugs.

PubMed

Hill, Simon L; Thomas, Simon H L

2011-10-01

Novel synthetic 'designer' drugs with stimulant, ecstasy-like (entactogenic) and/or hallucinogenic properties have become increasingly popular among recreational drug users in recent years. The substances used change frequently in response to market trends and legislative controls and it is an important challenge for poisons centres and clinical toxicologists to remain updated on the pharmacological and toxicological effects of these emerging agents. To review the available information on newer synthetic stimulant, entactogenic and hallucinogenic drugs, provide a framework for classification of these drugs based on chemical structure and describe their pharmacology and clinical toxicology. A comprehensive review of the published literature was performed using PUBMED and Medline databases, together with additional non-peer reviewed information sources, including books, media reports, government publications and internet resources, including drug user web forums. Novel synthetic stimulant, entactogenic or hallucinogenic designer drugs are increasingly available to users as demonstrated by user surveys, poisons centre calls, activity on internet drug forums, hospital attendance data and mortality data. Some population sub groups such as younger adults who attend dance music clubs are more likely to use these substances. The internet plays an important role in determining the awareness of and availability of these newer drugs of abuse. Most novel synthetic stimulant, entactogenic or hallucinogenic drugs of abuse can be classified according to chemical structure as piperazines (e.g. benzylpiperazine (BZP), trifluoromethylphenylpiperazine), phenethylamines (e.g. 2C or D-series of ring-substituted amfetamines, benzodifurans, cathinones, aminoindans), tryptamines (e.g. dimethyltryptamine, alpha-methyltryptamine, ethyltryptamine, 5-methoxy-alphamethyltryptamine) or piperidines and related substances (e.g. desoxypipradrol, diphenylprolinol). Alternatively classification may be based on clinical effects as either primarily stimulant, entactogenic or hallucinogenic, although most drugs have a combination of such effects. CLINICAL TOXICOLOGY: Piperazines, phenethylamines, tryptamines and piperidines have actions at multiple central nervous system (CNS) receptor sites, with patterns of effects varying between agents. Predominantly stimulant drugs (e.g. benzylpiperazine, mephedrone, naphyrone, diphenylprolinol) inhibit monoamine (especially dopamine) reuptake and are characteristically associated with a sympathomimetic toxidrome. Entactogenic drugs (e.g. phenylpiperazines, methylone) provoke central serotonin release, while newer hallucinogens (e.g. 5-methoxy-N,N-diisopropyltryptamine (5-MeO-DiPT), 2,5-dimethoxy-4-bromoamfetamine (DOB)) are serotonin receptor agonists. As a result, serotoninergic effects predominate in toxicity. There are limited reliable data to guide clinicians managing patients with toxicity due to these substances. The harms associated with emerging recreational drugs are not fully documented, although it is clear that they are not without risk. Management of users with acute toxic effects is pragmatic and primarily extrapolated from experience with longer established stimulant or hallucinogenic drugs such as amfetamines, 3,4-methylenedioxymethamfetamine (MDMA) and lysergic acid diethylamide (LSD).

Personality Disorders Classification and Symptoms in Cocaine and Opioid Addicts.

ERIC Educational Resources Information Center

Malow, Robert M.; And Others

1989-01-01

Examined extent to which personality disorders and associated symptom criteria were found among 117 cocaine- and opioid-dependent men in drug dependence treatment unit. Drug groups were distinguished by higher rates of antisocial and borderline symptomatology rather than by features associated with other personality disorders. Different…

21 CFR 888.4150 - Calipers for clinical use.

Code of Federal Regulations, 2012 CFR

2012-04-01

....4150 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... or diameter of a part of the body or the distance between two body surfaces, such as for measuring an excised skeletal specimen to determine the proper replacement size of a prosthesis. (b) Classification...

21 CFR 888.4150 - Calipers for clinical use.

Code of Federal Regulations, 2013 CFR

2013-04-01

....4150 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... or diameter of a part of the body or the distance between two body surfaces, such as for measuring an excised skeletal specimen to determine the proper replacement size of a prosthesis. (b) Classification...

21 CFR 888.4150 - Calipers for clinical use.

Code of Federal Regulations, 2014 CFR

2014-04-01

....4150 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... or diameter of a part of the body or the distance between two body surfaces, such as for measuring an excised skeletal specimen to determine the proper replacement size of a prosthesis. (b) Classification...

21 CFR 888.4150 - Calipers for clinical use.

Code of Federal Regulations, 2011 CFR

2011-04-01

....4150 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... or diameter of a part of the body or the distance between two body surfaces, such as for measuring an excised skeletal specimen to determine the proper replacement size of a prosthesis. (b) Classification...

Understanding the use of standardized nursing terminology and classification systems in published research: A case study using the International Classification for Nursing Practice(®).

PubMed

Strudwick, Gillian; Hardiker, Nicholas R

2016-10-01

In the era of evidenced based healthcare, nursing is required to demonstrate that care provided by nurses is associated with optimal patient outcomes, and a high degree of quality and safety. The use of standardized nursing terminologies and classification systems are a way that nursing documentation can be leveraged to generate evidence related to nursing practice. Several widely-reported nursing specific terminologies and classifications systems currently exist including the Clinical Care Classification System, International Classification for Nursing Practice(®), Nursing Intervention Classification, Nursing Outcome Classification, Omaha System, Perioperative Nursing Data Set and NANDA International. However, the influence of these systems on demonstrating the value of nursing and the professions' impact on quality, safety and patient outcomes in published research is relatively unknown. This paper seeks to understand the use of standardized nursing terminology and classification systems in published research, using the International Classification for Nursing Practice(®) as a case study. A systematic review of international published empirical studies on, or using, the International Classification for Nursing Practice(®) were completed using Medline and the Cumulative Index for Nursing and Allied Health Literature. Since 2006, 38 studies have been published on the International Classification for Nursing Practice(®). The main objectives of the published studies have been to validate the appropriateness of the classification system for particular care areas or populations, further develop the classification system, or utilize it to support the generation of new nursing knowledge. To date, most studies have focused on the classification system itself, and a lesser number of studies have used the system to generate information about the outcomes of nursing practice. Based on the published literature that features the International Classification for Nursing Practice, standardized nursing terminology and classification systems appear to be well developed for various populations, settings and to harmonize with other health-related terminology systems. However, the use of the systems to generate new nursing knowledge, and to validate nursing practice is still in its infancy. There is an opportunity now to utilize the well-developed systems in their current state to further what is know about nursing practice, and how best to demonstrate improvements in patient outcomes through nursing care. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Biowaiver Monographs for Immediate Release Solid Oral Dosage Forms: Proguanil Hydrochloride.

PubMed

Plöger, Gerlinde F; Abrahamsson, Bertil; Cristofoletti, Rodrigo; Groot, Dirk W; Langguth, Peter; Mehta, Mehul U; Parr, Alan; Polli, James E; Shah, Vinod P; Tajiri, Tomokazu; Dressman, Jennifer B

2018-07-01

Literature data relevant to the decision to waive in vivo bioequivalence testing for the approval of generic immediate release solid oral dosage forms of proguanil hydrochloride are reviewed. To elucidate the Biopharmaceutics Classification System (BCS) classification, experimental solubility and dissolution studies were also carried out. The antimalarial proguanil hydrochloride, effective via the parent compound proguanil and the metabolite cycloguanil, is not considered to be a narrow therapeutic index drug. Proguanil hydrochloride salt was shown to be highly soluble according to the U.S. Food and Drug Administration, World Health Organization, and European Medicines Agency guidelines, but data for permeability are inconclusive. Therefore, proguanil hydrochloride is conservatively classified as a BCS class 3 substance. In view of this information and the assessment of risks associated with a false positive decision, a BCS-based biowaiver approval procedure can be recommended for orally administered solid immediate release products containing proguanil hydrochloride, provided well-known excipients are used in usual amounts and provided the in vitro dissolution of the test and reference products is very rapid (85% or more are dissolved in 15 min at pH 1.2, 4.5, and 6.8) and is performed according to the current requirements for BCS-based biowaivers. Copyright © 2018 American Pharmacists Association®. All rights reserved.

Orthopedic devices; classification for the resorbable calcium salt bone void filler device. Final rule.

PubMed

2003-06-02

The Food and Drug Administration (FDA) is classifying the resorbable calcium salt bone void filler device intended to fill bony voids or gaps of the extremities, spine, and pelvis that are caused by trauma or surgery and are not intrinsic to the stability of the bony structure into class II (special controls). Elsewhere in this issue of the Federal Register, FDA is announcing the availability of a class II special controls guidance entitled "Class II Special Controls Guidance Document: Resorbable Calcium Salt Bone Void Filler Device; Guidance for Industry and FDA." This action is being undertaken based on new information submitted in a classification proposal from Wright Medical Technology under the Federal Food, Drug, and Cosmetic Act as amended by the Medical Device Amendments of 1976, the Safe Medical Devices Act of 1990, and the Food and Drug Administration Modernization Act of 1997.

Autoradiographic Distribution and Applied Pharmacological Characteristics of Dextromethorphan and Related Antitissue/Anticonvulsant Drugs and Novel Analogs

DTIC Science & Technology

1993-10-01

AD-A273 247 AD____ CONTRACT NO: DAMD17-90-C-0124 TITLE: AUTORADIOGRAPHIC DISTRIBUTION AND APPLIED PHARMACOLOGICAL CHARACTERISTICS OF DEXTROMETHORPHAN ...Anticonvulsants, Antitissue, Dextromethorphan , Autoradiography, Pharmacokinetics 16. PRICE CODE 17. SECURITY CLASSIFICATION 18. SECURITY CLASSIFICATION...middle cerebral artery occlusion model with dextromethorphan , carbetapentane and three of the carbetapentane analogues, 11, B and D, which were

Diagnostic criteria, severity classification and guidelines of systemic sclerosis.

PubMed

Asano, Yoshihide; Jinnin, Masatoshi; Kawaguchi, Yasushi; Kuwana, Masataka; Goto, Daisuke; Sato, Shinichi; Takehara, Kazuhiko; Hatano, Masaru; Fujimoto, Manabu; Mugii, Naoki; Ihn, Hironobu

2018-06-01

Several effective drugs have been identified for the treatment of systemic sclerosis (SSc). However, in advanced cases, not only their effectiveness is reduced but they may be also harmful due to their side-effects. Therefore, early diagnosis and early treatment is most important for the treatment of SSc. We established diagnostic criteria for SSc in 2003 and early diagnostic criteria for SSc in 2011, for the purpose of developing evaluation of each organ in SSc. Moreover, in November 2013, the American College of Rheumatology and the European Rheumatology Association jointly developed new diagnostic criteria for increasing their sensitivity and specificity, so we revised our diagnostic criteria and severity classification of SSc. Furthermore, we have revised the clinical guideline based on the newest evidence. In particular, the clinical guideline was established by clinical questions based on evidence-based medicine according to the New Minds Clinical Practice Guideline Creation Manual (version 1.0). We aimed to make the guideline easy to use and reliable based on the newest evidence, and to present guidance as specific as possible for various clinical problems in treatment of SSc. © 2018 Japanese Dermatological Association.

Ecological Land Classification: Applications to Identify the Productive Potential of Southern Forests

Treesearch

Dennis L. Mengel; D. Thompson Tew; [Editors

1991-01-01

Eighteen papers representing four categories-Regional Overviews; Classification System Development; Classification System Interpretation; Mapping/GIS Applications in Classification Systems-present the state of the art in forest-land classification and evaluation in the South. In addition, nine poster papers are presented.

Medication errors: problems and recommendations from a consensus meeting

PubMed Central

Agrawal, Abha; Aronson, Jeffrey K; Britten, Nicky; Ferner, Robin E; de Smet, Peter A; Fialová, Daniela; Fitzgerald, Richard J; Likić, Robert; Maxwell, Simon R; Meyboom, Ronald H; Minuz, Pietro; Onder, Graziano; Schachter, Michael; Velo, Giampaolo

2009-01-01

Here we discuss 15 recommendations for reducing the risks of medication errors: Provision of sufficient undergraduate learning opportunities to make medical students safe prescribers. Provision of opportunities for students to practise skills that help to reduce errors. Education of students about common types of medication errors and how to avoid them. Education of prescribers in taking accurate drug histories. Assessment in medical schools of prescribing knowledge and skills and demonstration that newly qualified doctors are safe prescribers. European harmonization of prescribing and safety recommendations and regulatory measures, with regular feedback about rational drug use. Comprehensive assessment of elderly patients for declining function. Exploration of low-dose regimens for elderly patients and preparation of special formulations as required. Training for all health-care professionals in drug use, adverse effects, and medication errors in elderly people. More involvement of pharmacists in clinical practice. Introduction of integrated prescription forms and national implementation in individual countries. Development of better monitoring systems for detecting medication errors, based on classification and analysis of spontaneous reports of previous reactions, and for investigating the possible role of medication errors when patients die. Use of IT systems, when available, to provide methods of avoiding medication errors; standardization, proper evaluation, and certification of clinical information systems. Nonjudgmental communication with patients about their concerns and elicitation of symptoms that they perceive to be adverse drug reactions. Avoidance of defensive reactions if patients mention symptoms resulting from medication errors. PMID:19594525

Flight evaluation of advanced third-generation midwave infrared sensor

NASA Astrophysics Data System (ADS)

Shen, Chyau N.; Donn, Matthew

1998-08-01

In FY-97 the Counter Drug Optical Upgrade (CDOU) demonstration program was initiated by the Program Executive Office for Counter Drug to increase the detection and classification ranges of P-3 counter drug aircraft by using advanced staring infrared sensors. The demonstration hardware is a `pin-for-pin' replacement of the AAS-36 Infrared Detection Set (IRDS) located under the nose radome of a P-3 aircraft. The hardware consists of a 3rd generation mid-wave infrared (MWIR) sensor integrated into a three axis-stabilized turret. The sensor, when installed on the P- 3, has a hemispheric field of regard and analysis has shown it will be capable of detecting and classifying Suspected Drug Trafficking Aircraft and Vessels at ranges several factors over the current IRDS. This paper will discuss the CDOU system and it's lab, ground, and flight evaluation results. Test targets included target templates, range targets, dedicated target boats, and targets of opportunity at the Naval Air Warfare Center Aircraft Division and at operational test sites. The objectives of these tests were to: (1) Validate the integration concept of the CDOU package into the P-3 aircraft. (2) Validate the end-to-end functionality of the system, including sensor/turret controls and recording of imagery during flight. (3) Evaluate the system sensitivity and resolution on a set of verified resolution targets templates. (4) Validate the ability of the 3rd generation MWIR sensor to detect and classify targets at a significantly increased range.

Conjugation of Hot-Melt Extrusion with High-Pressure Homogenization: a Novel Method of Continuously Preparing Nanocrystal Solid Dispersions.

PubMed

Ye, Xingyou; Patil, Hemlata; Feng, Xin; Tiwari, Roshan V; Lu, Jiannan; Gryczke, Andreas; Kolter, Karl; Langley, Nigel; Majumdar, Soumyajit; Neupane, Dipesh; Mishra, Sanjay R; Repka, Michael A

2016-02-01

Over the past few decades, nanocrystal formulations have evolved as promising drug delivery systems owing to their ability to enhance the bioavailability and maintain the stability of poorly water-soluble drugs. However, conventional methods of preparing nanocrystal formulations, such as spray drying and freeze drying, have some drawbacks including high cost, time and energy inefficiency, traces of residual solvent, and difficulties in continuous operation. Therefore, new techniques for the production of nanocrystal formulations are necessary. The main objective of this study was to introduce a new technique for the production of nanocrystal solid dispersions (NCSDs) by combining high-pressure homogenization (HPH) and hot-melt extrusion (HME). Efavirenz (EFZ), a Biopharmaceutics Classification System class II drug, which is used for the treatment of human immunodeficiency virus (HIV) type I, was selected as the model drug for this study. A nanosuspension (NS) was first prepared by HPH using sodium lauryl sulfate (SLS) and Kollidon® 30 as a stabilizer system. The NS was then mixed with Soluplus® in the extruder barrel, and the water was removed by evaporation. The decreased particle size and crystalline state of EFZ were confirmed by scanning electron microscopy, zeta particle size analysis, and differential scanning calorimetry. The increased dissolution rate was also determined. EFZ NCSD was found to be highly stable after storage for 6 months. In summary, the conjugation of HPH with HME technology was demonstrated to be a promising novel method for the production of NCSDs.

Hot-Melt Extrusion: from Theory to Application in Pharmaceutical Formulation.

PubMed

Patil, Hemlata; Tiwari, Roshan V; Repka, Michael A

2016-02-01

Hot-melt extrusion (HME) is a promising technology for the production of new chemical entities in the developmental pipeline and for improving products already on the market. In drug discovery and development, industry estimates that more than 50% of active pharmaceutical ingredients currently used belong to the biopharmaceutical classification system II (BCS class II), which are characterized as poorly water-soluble compounds and result in formulations with low bioavailability. Therefore, there is a critical need for the pharmaceutical industry to develop formulations that will enhance the solubility and ultimately the bioavailability of these compounds. HME technology also offers an opportunity to earn intellectual property, which is evident from an increasing number of patents and publications that have included it as a novel pharmaceutical formulation technology over the past decades. This review had a threefold objective. First, it sought to provide an overview of HME principles and present detailed engineered extrusion equipment designs. Second, it included a number of published reports on the application of HME techniques that covered the fields of solid dispersions, microencapsulation, taste masking, targeted drug delivery systems, sustained release, films, nanotechnology, floating drug delivery systems, implants, and continuous manufacturing using the wet granulation process. Lastly, this review discussed the importance of using the quality by design approach in drug development, evaluated the process analytical technology used in pharmaceutical HME monitoring and control, discussed techniques used in HME, and emphasized the potential for monitoring and controlling hot-melt technology.

Evaluating the safety and dosing of drugs in patients with liver cirrhosis by literature review and expert opinion.

PubMed

Weersink, Rianne A; Bouma, Margriet; Burger, David M; Drenth, Joost P H; Hunfeld, Nicole G M; Kranenborg, Minke; Monster-Simons, Margje H; van Putten, Sandra A W; Metselaar, Herold J; Taxis, Katja; Borgsteede, Sander D

2016-10-12

Liver cirrhosis can have a major impact on drug pharmacokinetics and pharmacodynamics. Patients with cirrhosis often suffer from potentially preventable adverse drug reactions. Guidelines on safe prescribing for these patients are lacking. The aim of this study is to develop a systematic method for evaluating the safety and optimal dosage of drugs in patients with liver cirrhosis. For each drug, a six-step evaluation process will be followed. (1) Available evidence on the pharmacokinetics and safety of a drug in patients with liver cirrhosis will be collected from the Summary of Product Characteristics (SmPC) and a systematic literature review will be performed. (2) Data regarding two outcomes, namely pharmacokinetics and safety, will be extracted and presented in a standardised assessment report. (3) A safety classification and dosage suggestion will be proposed for each drug. (4) An expert panel will discuss the validity and clinical relevance of this suggested advice. (5) Advices will be implemented in all relevant Clinical Decision Support Systems in the Netherlands and published on a website for patients and healthcare professionals. (6) The continuity of the advices will be guaranteed by a yearly check of new literature and comments on the advices. This protocol will be applied in the evaluation of a selection of drugs: (A) drugs used to treat (complications of) liver cirrhosis, and (B) drugs frequently prescribed to the general population. Since this study does not directly involve human participants, it does not require ethical clearance. Besides implementation on a website and in clinical decision support systems, we aim to publish the generated advices of one or two drug classes in a peer-reviewed journal and at conference meetings. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

In silico prediction of multiple-category classification model for cytochrome P450 inhibitors and non-inhibitors using machine-learning method.

PubMed

Lee, J H; Basith, S; Cui, M; Kim, B; Choi, S

2017-10-01

The cytochrome P450 (CYP) enzyme superfamily is involved in phase I metabolism which chemically modifies a variety of substrates via oxidative reactions to make them more water-soluble and easier to eliminate. Inhibition of these enzymes leads to undesirable effects, including toxic drug accumulations and adverse drug-drug interactions. Hence, it is necessary to develop in silico models that can predict the inhibition potential of compounds for different CYP isoforms. This study focused on five major CYP isoforms, including CYP1A2, 2C9, 2C19, 2D6 and 3A4, that are responsible for more than 90% of the metabolism of clinical drugs. The main aim of this study is to develop a multiple-category classification model (MCM) for the major CYP isoforms using a Laplacian-modified naïve Bayesian method. The dataset composed of more than 4500 compounds was collected from the PubChem Bioassay database. VolSurf+ descriptors and FCFP_8 fingerprint were used as input features to build classification models. The results demonstrated that the developed MCM using Laplacian-modified naïve Bayesian method was successful in classifying inhibitors and non-inhibitors for each CYP isoform. Moreover, the accuracy, sensitivity and specificity values for both training and test sets were above 80% and also yielded satisfactory area under the receiver operating characteristic curve and Matthews correlation coefficient values.

42 CFR 412.513 - Patient classification system.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 42 Public Health 2 2010-10-01 2010-10-01 false Patient classification system. 412.513 Section 412... Long-Term Care Hospitals § 412.513 Patient classification system. (a) Classification methodology. CMS...-DRGs. (1) The classification of a particular discharge is based, as appropriate, on the patient's age...