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Sample records for individual drug class

  1. Predictors of trend in CD4-positive T-cell count and mortality among HIV-1-infected individuals with virological failure to all three antiretroviral-drug classes

    DEFF Research Database (Denmark)

    Ledergerber, Bruno; Lundgren, Jens D; Walker, A Sarah

    2014-01-01

    Treatment strategies for patients in whom HIV replication is not suppressed after exposure to several drug classes remain unclear. We aimed to assess the inter-relations between viral load, CD4-cell count, and clinical outcome in patients who had experienced three-class virological failure....

  2. Pre-Class Planning for Individualized Accounting

    Science.gov (United States)

    Clayton, Dean; Brooke, Joyce Ann

    1974-01-01

    Pre-class planning of individualized accounting is involved with goals, objectives, and activities developed and selected by the teacher in providing compatibility between accounting content and teaching strategy. A systematic arrangement of activities should be developed so that students can understand and apply accounting principles at their own…

  3. Risk of myocardial infarction in patients with HIV infection exposed to specific individual antiretroviral drugs from the 3 major drug classes: the data collection on adverse events of anti-HIV drugs (D:A:D) study

    DEFF Research Database (Denmark)

    Worm, Signe Westring; Sabin, Caroline; Weber, Rainer

    2010-01-01

    BACKGROUND. The risk of myocardial infarction (MI) in patients with human immunodeficiency virus (HIV) infection has been assessed in 13 anti-HIV drugs in the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study. METHODS. Poisson regression models were adjusted for cardiovascular risk...... factors, cohort, calendar year, and use of other antiretroviral drugs and assessed the association between MI risk and cumulative (per year) or recent (current or in the past 6 months) use of antiretroviral drugs, with >30,000 person-years of exposure. RESULTS. Over 178,835 person-years, 580 patients......% CI, 1.01-1.17], respectively) after adjustment for lipids but were not altered further after adjustment for other metabolic parameters. CONCLUSIONS. Of the drugs considered, only indinavir, lopinavir-ritonavir, didanosine, and abacavir were associated with a significantly increased risk of MI...

  4. Anticancer properties of distinct antimalarial drug classes.

    Directory of Open Access Journals (Sweden)

    Rob Hooft van Huijsduijnen

    Full Text Available We have tested five distinct classes of established and experimental antimalarial drugs for their anticancer potential, using a panel of 91 human cancer lines. Three classes of drugs: artemisinins, synthetic peroxides and DHFR (dihydrofolate reductase inhibitors effected potent inhibition of proliferation with IC50s in the nM- low µM range, whereas a DHODH (dihydroorotate dehydrogenase and a putative kinase inhibitor displayed no activity. Furthermore, significant synergies were identified with erlotinib, imatinib, cisplatin, dasatinib and vincristine. Cluster analysis of the antimalarials based on their differential inhibition of the various cancer lines clearly segregated the synthetic peroxides OZ277 and OZ439 from the artemisinin cluster that included artesunate, dihydroartemisinin and artemisone, and from the DHFR inhibitors pyrimethamine and P218 (a parasite DHFR inhibitor, emphasizing their shared mode of action. In order to further understand the basis of the selectivity of these compounds against different cancers, microarray-based gene expression data for 85 of the used cell lines were generated. For each compound, distinct sets of genes were identified whose expression significantly correlated with compound sensitivity. Several of the antimalarials tested in this study have well-established and excellent safety profiles with a plasma exposure, when conservatively used in malaria, that is well above the IC50s that we identified in this study. Given their unique mode of action and potential for unique synergies with established anticancer drugs, our results provide a strong basis to further explore the potential application of these compounds in cancer in pre-clinical or and clinical settings.

  5. Anticancer Properties of Distinct Antimalarial Drug Classes

    Science.gov (United States)

    Hooft van Huijsduijnen, Rob; Guy, R. Kiplin; Chibale, Kelly; Haynes, Richard K.; Peitz, Ingmar; Kelter, Gerhard; Phillips, Margaret A.; Vennerstrom, Jonathan L.; Yuthavong, Yongyuth; Wells, Timothy N. C.

    2013-01-01

    We have tested five distinct classes of established and experimental antimalarial drugs for their anticancer potential, using a panel of 91 human cancer lines. Three classes of drugs: artemisinins, synthetic peroxides and DHFR (dihydrofolate reductase) inhibitors effected potent inhibition of proliferation with IC50s in the nM- low µM range, whereas a DHODH (dihydroorotate dehydrogenase) and a putative kinase inhibitor displayed no activity. Furthermore, significant synergies were identified with erlotinib, imatinib, cisplatin, dasatinib and vincristine. Cluster analysis of the antimalarials based on their differential inhibition of the various cancer lines clearly segregated the synthetic peroxides OZ277 and OZ439 from the artemisinin cluster that included artesunate, dihydroartemisinin and artemisone, and from the DHFR inhibitors pyrimethamine and P218 (a parasite DHFR inhibitor), emphasizing their shared mode of action. In order to further understand the basis of the selectivity of these compounds against different cancers, microarray-based gene expression data for 85 of the used cell lines were generated. For each compound, distinct sets of genes were identified whose expression significantly correlated with compound sensitivity. Several of the antimalarials tested in this study have well-established and excellent safety profiles with a plasma exposure, when conservatively used in malaria, that is well above the IC50s that we identified in this study. Given their unique mode of action and potential for unique synergies with established anticancer drugs, our results provide a strong basis to further explore the potential application of these compounds in cancer in pre-clinical or and clinical settings. PMID:24391728

  6. From class society to the individualized society?

    DEFF Research Database (Denmark)

    Rasborg, Klaus

    2017-01-01

    change and social reproduction in the form of an attempt to think the differentiated (stratified) forms of individualization in reflexive modernity. The assumption is that there is adifferentiation in reflexive modern people’s ability to deal with the requirements of individualization, depending...

  7. Social class, power, and selfishness: when and why upper and lower class individuals behave unethically.

    Science.gov (United States)

    Dubois, David; Rucker, Derek D; Galinsky, Adam D

    2015-03-01

    Are the rich more unethical than the poor? To answer this question, the current research introduces a key conceptual distinction between selfish and unethical behavior. Based on this distinction, the current article offers 2 novel findings that illuminate the relationship between social class and unethical behavior. First, the effects of social class on unethical behavior are not invariant; rather, the effects of social class are moderated by whether unethical behavior benefits the self or others. Replicating past work, social class positively predicted unethical behavior; however, this relationship was only observed when that behavior was self-beneficial. When unethical behavior was performed to benefit others, social class negatively predicted unethical behavior; lower class individuals were more likely than upper class individuals to engage in unethical behavior. Overall, social class predicts people's tendency to behave selfishly, rather than predicting unethical behavior per se. Second, individuals' sense of power drove the effects of social class on unethical behavior. Evidence for this relationship was provided in three forms. First, income, but not education level, predicted unethical behavior. Second, feelings of power mediated the effect of social class on unethical behavior, but feelings of status did not. Third, two distinct manipulations of power produced the same moderation by self-versus-other beneficiary as was found with social class. The current theoretical framework and data both synthesize and help to explain a range of findings in the social class and power literatures. PsycINFO Database Record (c) 2015 APA, all rights reserved.

  8. Individual class evaluation and effective teaching characteristics in integrated curricula.

    Science.gov (United States)

    Hwang, Jung Eun; Kim, Na Jin; Song, Meiying; Cui, Yinji; Kim, Eun Ju; Park, In Ae; Lee, Hye In; Gong, Hye Jin; Kim, Su Young

    2017-12-12

    In an integrated curriculum, multiple instructors take part in a course in the form of team teaching. Accordingly, medical schools strive to manage each course run by numerous instructors. As part of the curriculum management, course evaluation is conducted, but a single, retrospective course evaluation does not comprehensively capture student perception of classes by different instructors. This study aimed to demonstrate the need for individual class evaluation, and further to identify teaching characteristics that instructors need to keep in mind when preparing classes. From 2014 to 2015, students at one medical school left comments on evaluation forms after each class. Courses were also assessed after each course. Their comments were categorized by connotation (positive or negative) and by subject. Within each subject category, test scores were compared between positively and negatively mentioned classes. The Mann-Whitney U test was performed to test group differences in scores. The same method was applied to the course evaluation data. Test results for course evaluation showed group difference only in the practice/participation category. However, test results for individual class evaluation showed group differences in six categories: difficulty, main points, attitude, media/contents, interest, and materials. That is, the test scores of classes positively mentioned in six domains were significantly higher than those of negatively mentioned classes. It was proved that individual class evaluation is needed to manage multi-instructor courses in integrated curricula of medical schools. Based on the students' extensive feedback, we identified teaching characteristics statistically related to academic achievement. School authorities can utilize these findings to encourage instructors to develop effective teaching characteristics in class preparation.

  9. Properties of Protein Drug Target Classes

    Science.gov (United States)

    Bull, Simon C.; Doig, Andrew J.

    2015-01-01

    Accurate identification of drug targets is a crucial part of any drug development program. We mined the human proteome to discover properties of proteins that may be important in determining their suitability for pharmaceutical modulation. Data was gathered concerning each protein’s sequence, post-translational modifications, secondary structure, germline variants, expression profile and drug target status. The data was then analysed to determine features for which the target and non-target proteins had significantly different values. This analysis was repeated for subsets of the proteome consisting of all G-protein coupled receptors, ion channels, kinases and proteases, as well as proteins that are implicated in cancer. Machine learning was used to quantify the proteins in each dataset in terms of their potential to serve as a drug target. This was accomplished by first inducing a random forest that could distinguish between its targets and non-targets, and then using the random forest to quantify the drug target likeness of the non-targets. The properties that can best differentiate targets from non-targets were primarily those that are directly related to a protein’s sequence (e.g. secondary structure). Germline variants, expression levels and interactions between proteins had minimal discriminative power. Overall, the best indicators of drug target likeness were found to be the proteins’ hydrophobicities, in vivo half-lives, propensity for being membrane bound and the fraction of non-polar amino acids in their sequences. In terms of predicting potential targets, datasets of proteases, ion channels and cancer proteins were able to induce random forests that were highly capable of distinguishing between targets and non-targets. The non-target proteins predicted to be targets by these random forests comprise the set of the most suitable potential future drug targets, and should therefore be prioritised when building a drug development programme. PMID

  10. Safety learning from drugs of the same class

    DEFF Research Database (Denmark)

    Stefansdottir, G; Knol, M J; Arnardottir, A H

    2012-01-01

    This study was aimed at assessing the extent of safety learning from data pertaining to other drugs of the same class. We studied drug classes for which the first and second drugs were centrally registered in the European Union from 1995 to 2008. We assessed whether adverse drug reactions (ADRs......) associated with one of the drugs also appeared in the Summary of Product Characteristics (SPC) of the other drug, either initially or during the postmarketing phase. We identified 977 ADRs from 19 drug pairs, of which 393 ADRs (40.2%) were listed in the SPCs of both drugs of a pair. Of these 393 that were...... present in both SPCs of a drug pair, 241 (61.3%) were present when the drug entered the market and 152 (30.7%) appeared in the postmarketing phase. The mention of ADRs in the SPCs of both same-class drugs in the postmarketing phase was associated with type A ADRs, marketing in the same regulator country...

  11. The glatiramoid class of immunomodulator drugs.

    Science.gov (United States)

    Varkony, Haim; Weinstein, Vera; Klinger, Ety; Sterling, Jeffrey; Cooperman, Helena; Komlosh, Turi; Ladkani, David; Schwartz, Rivka

    2009-03-01

    Glatiramer acetate (GA) is a complex heterogenous mixture of polypeptides with immunomodulatory activity approved for treatment of relapsing-remitting multiple sclerosis. GA is the first, and was until recently, the only member of the glatiramoids, a family of synthetic copolymer mixtures comprising the four amino acids, L-glutamic acid, L-alanine, L-lysine and L-tyrosine, in a defined molar ratio. Another glatiramoid, protiramer, was recently evaluated in preclinical studies and in two small Phase II clinical trials with relapsing-remitting multiple sclerosis patients. Due to the complexity and heterogeneity of GA and other glatiramoids, the clinically active epitopes within the mixture cannot be identified and the consistency of polypeptide sequences within the mixture is dependent on a tightly controlled manufacturing process. Although no two glatiramoids can be proved identical, it is possible to differentiate among members of the glatiramoid class using analytical methods and immunological and biological markers. Even slight differences in the distribution of molecular masses or in the composition of antigenic polypeptide sequences among glatiramoids can significantly influence their efficacy, toxicity and immunogenicity profiles. Experience with GA may be instructive regarding important safety and efficacy considerations for new glatiramoid mixtures now in development.

  12. Class of Antiretroviral Drugs and the Risk of Myocardial Infarction

    DEFF Research Database (Denmark)

    Friis-Møller, Nina; Reiss, P; Sabin, CA

    2007-01-01

    BACKGROUND: We have previously demonstrated an association between combination antiretroviral therapy and the risk of myocardial infarction. It is not clear whether this association differs according to the class of antiretroviral drugs. We conducted a study to investigate the association of cumu...

  13. Class of Antiretroviral Drugs and the Risk of Myocardial Infarction

    DEFF Research Database (Denmark)

    Friis-Møller, Nina; Reiss, P.; Sabin, C.A.

    2007-01-01

    of myocardial infarction, which is partly explained by dyslipidemia. We found no evidence of such an association for nonnucleoside reverse-transcriptase inhibitors; however, the number of person-years of observation for exposure to this class of drug was less than that for exposure to protease inhibitors...

  14. Drumming: An Innovative Alternative for Drug Addicted Individuals

    Science.gov (United States)

    Hill, John C.; Hains, Bryan; Ricketts, Kristina

    2017-01-01

    Drug abuse has been a persistent problem within the United States. Among the nation, Kentucky ranks third in drug overdose and drug mortality rates, with numbers quadrupling from 1999 to 2010. Recent statistics indicate drug offenders account or a significant portion of individuals within the criminal justice system, directly affecting the…

  15. Antimicrobial peptides: a new class of antimalarial drugs?

    Directory of Open Access Journals (Sweden)

    Nuno eVale

    2014-12-01

    Full Text Available A range of antimicrobial peptides (AMP exhibit activity on malaria parasites, Plasmodium spp, in their blood or mosquito stages, or both. These peptides include a diverse array of both natural and synthetic molecules varying greatly in size, charge, hydrophobicity and secondary structure features. Along with an overview of relevant literature reports regarding AMP that display antiplasmodial activity, this review makes a few considerations about those molecules as a potential new class of antimalarial drugs.

  16. Lay theories about social class buffer lower-class individuals against poor self-rated health and negative affect.

    Science.gov (United States)

    Tan, Jacinth J X; Kraus, Michael W

    2015-03-01

    The economic conditions of one's life can profoundly and systematically influence health outcomes over the life course. Our present research demonstrates that rejecting the notion that social class categories are biologically determined-a nonessentialist belief-buffers lower-class individuals from poor self-rated health and negative affect, whereas conceiving of social class categories as rooted in biology-an essentialist belief-does not. In Study 1, lower-class individuals self-reported poorer health than upper-class individuals when they endorsed essentialist beliefs but showed no such difference when they rejected such beliefs. Exposure to essentialist theories of social class also led lower-class individuals to report greater feelings of negative self-conscious emotions (Studies 2 and 3), and perceive poorer health (Study 3) than upper-class individuals, whereas exposure to nonessentialist theories did not lead to such differences. Discussion considers how lay theories of social class potentially shape long-term trajectories of health and affect of lower-class individuals. © 2015 by the Society for Personality and Social Psychology, Inc.

  17. Drug monitoring and individual dose optimization of antimicrobial drugs : oxazolidinones

    NARCIS (Netherlands)

    Cattaneo, Dario; Alffenaar, Jan-Willem; Neely, Michael

    INTRODUCTION: Oxazolidinones are synthetic antibiotics with bacteriostatic activity against Gram-positive pathogens. Linezolid, the first marketed oxazolidinone, has shown also activity against Mycobaterium tuberculosis, including multidrug-resistant and extensively drug-resistant strains. Recently,

  18. Use of non-antiretroviral drugs among individuals with and without HIV-infection

    DEFF Research Database (Denmark)

    Rasmussen, Line D; Kronborg, Gitte; Larsen, Carsten S

    2017-01-01

    AIM: We investigated the use of non-antiretroviral drugs in the HIV-infected compared to the general population. METHODS: From the Danish HIV Cohort Study, we identified all HIV-infected individuals older than 18 years at HIV diagnosis who received care in Denmark through 1995-2013 and reported...... no injection drug abuse or hepatitis C infection. Population controls were identified from The Danish Civil Registration System and matched on age and gender (5:1). We analyzed the proportion of individuals who redeemed 0-1, 2-4, 5-9, or 10 or more non-antiretroviral drugs. Data were analyzed according...... to calendar time, age, time from initiation of combination antiretroviral therapy (cART) and stratified by gender, geographical origin and route of HIV transmission. We further analyzed the use of the 25 most used non-antiretroviral drug classes. RESULTS: We identified 4,928 HIV-infected individuals (median...

  19. The biowaiver extension for BCS class III drugs: the effect of dissolution rate on the bioequivalence of BCS class III immediate-release drugs predicted by computer simulation.

    Science.gov (United States)

    Tsume, Yasuhiro; Amidon, Gordon L

    2010-08-02

    The Biopharmaceutical Classification System (BCS) guidance issued by the FDA allows waivers for in vivo bioavailability and bioequivalence studies for immediate-release (IR) solid oral dosage forms only for BCS class I drugs. However, a number of drugs within BCS class III have been proposed to be eligible for biowaivers. The World Health Organization (WHO) has shortened the requisite dissolution time of BCS class III drugs on their Essential Medicine List (EML) from 30 to 15 min for extended biowaivers; however, the impact of the shorter dissolution time on AUC(0-inf) and C(max) is unknown. The objectives of this investigation were to assess the ability of gastrointestinal simulation software to predict the oral absorption of the BCS class I drugs propranolol and metoprolol and the BCS class III drugs cimetidine, atenolol, and amoxicillin, and to perform in silico bioequivalence studies to assess the feasibility of extending biowaivers to BCS class III drugs. The drug absorption from the gastrointestinal tract was predicted using physicochemical and pharmacokinetic properties of test drugs provided by GastroPlus (version 6.0). Virtual trials with a 200 mL dose volume at different drug release rates (T(85%) = 15 to 180 min) were performed to predict the oral absorption (C(max) and AUC(0-inf)) of the above drugs. Both BCS class I drugs satisfied bioequivalence with regard to the release rates up to 120 min. The results with BCS class III drugs demonstrated bioequivalence using the prolonged release rate, T(85%) = 45 or 60 min, indicating that the dissolution standard for bioequivalence is dependent on the intestinal membrane permeability and permeability profile throughout the gastrointestinal tract. The results of GastroPlus simulations indicate that the dissolution rate of BCS class III drugs could be prolonged to the point where dissolution, rather than permeability, would control the overall absorption. For BCS class III drugs with intestinal absorption patterns

  20. [Cephalometric analysis in individuals with Class II/2 malocclusions].

    Science.gov (United States)

    Rak, D

    1990-06-01

    Various orthodontic anomalies class II/2, classified into several experimental groups, and eugnathic occlusion serving as controls, were studied by roentgencephalometry. The objective of the study was to detect possible distinctions in the quantitative values of the chosen variables and to select those which discriminate the group of class II/2 orthodontic anomalies most significantly. Attempts were made to ascertain whether or not there were sex-related differences. The teleroentgenograma of 241 examines, aged 10 to 18 years, of both sexes, were analyzed. The experimental group consisted of 61 examinees class II/2 orthodontic anomalies. The control group consisted of 180 examinees with eugnathic occlusion. Latero-lateral skull roentgenograms were taken according to the rules of roentgencephalometry. Using acetate paper, the drawings of profile teleroentgenograms were elaborated and the reference points and lineas were entered. A total of 38 variables were analyzed, of which 10 were linear, 19 angular, 8 variables were obtained by mathematical calculations, and the age variable was also analyzed. For statistical analyses and electronic computer was used. The results are presented in tables and graphs. The results obtained have shown: that, when compared to the findings in the control group, the subjects in the experimental groups manifested significant changes in the following craniofacial characteristics: retroposition and retroinclination of the upper incisors; increased difference of the position of the apical basis of the jaw; marked convexity of the osseous profile; mandibular retrognathism and increased proportion of the maxillary compared to mandibular base; that, with regard to the sex of the examines, only linear variables of significantly discriminating character were selected. Thus it could be concluded that there were no significant sex differences among the morphological characteristics of the viscerocranium.

  1. Analysis of smoke trailers at individual classes of atmosphere stability

    International Nuclear Information System (INIS)

    Carach, V.; Macala, J.

    2007-01-01

    At the present most endangered element of the environment is currently atmosphere and its pollution that rapidly accrue. Pollutants are emitted from air pollution sources. The output of pollutant from air pollution source is creating so-called smoke screen. Smoke screens can be observed from point sources of air pollution - smokestacks, up-cast. The purpose of this article was to build theoretical models of smoke screens rise from point source at different meteorological conditions characterized with fifth classes of atmosphere stability. (authors)

  2. Respirable antisense oligonucleotides: a new drug class for respiratory disease

    Directory of Open Access Journals (Sweden)

    Tanaka Makoto

    2000-12-01

    Full Text Available Abstract Respirable antisense oligonucleotides (RASONs, which attenuate specific disease-associated mRNAs, represent a new class of respiratory therapeutics with considerable potential. RASONs overcome previous obstacles that have impeded the development of antisense therapeutics targeting diseases in other organ systems. RASONs are delivered directly to the target tissue via inhalation; their uptake seems to be enhanced by cationic properties inherent in pulmonary surfactant, and, because of the markedly different target properties of mRNA and proteins, they can have very long durations of effect compared with traditional drugs targeting the protein of the same gene. RASONs contain chemical modifications that decrease their degradation by cellular nucleases. However, total insensitivity to nucleases is probably not an optimal design criterion for RASONs, because moderate nuclease sensitivity can prevent their systemic delivery, decreasing the potential for systemic toxicity. EPI-2010 is a 21-mer phosphorothioate RASON that attenuates bronchoconstriction, inflammation and surfactant depletion in preclinical models of human asthma, has a duration of effect of seven days, and seems to undergo minimal systemic delivery.

  3. Social class differences in self, attribution, and attention: socially expansive individualism of middle-class Americans.

    Science.gov (United States)

    Bowman, Nicholas A; Kitayama, Shinobu; Nisbett, Richard E

    2009-07-01

    Although U.S. culture strongly sanctions the ideal of independence, the specific ways in which independence is realized may be variable depending, among other factors, on social class. Characterized by relative scarcity of social and material resources, working-class (WC) Americans were expected to strongly value self-reliance. In contrast, with choices among abundant resources, middle-class (MC) Americans were expected to value personal control and social expansiveness. In support of this analysis, relative to their WC counterparts, MC Americans reported more support from friends and greater likelihood of giving and receiving advice but less self-reliance (Study 1). Furthermore, we found evidence that this social difference has cognitive consequences: College students with MC backgrounds were more likely than their WC counterparts were to endorse situational attributions for others' behavior (Studies 2a and 2b) as well as to show holistic visual attention (Study 3).

  4. Social-Class Differences in Consumer Choices: Working-Class Individuals Are More Sensitive to Choices of Others Than Middle-Class Individuals.

    Science.gov (United States)

    Na, Jinkyung; McDonough, Ian M; Chan, Micaela Y; Park, Denise C

    2016-04-01

    The present research shows that, when making choices, working-class Americans are more affected by others' opinions than middle-class Americans due to differences in independent versus interdependent self-construal. Experiment 1 revealed that when working-class Americans made decisions to buy products, they were more influenced by the choices of others than middle-class Americans. In contrast, middle-class Americans were more likely to misremember others' choices to be consistent with their own choices. In other words, working-class Americans adjusted their choices to the preference of others, whereas middle-class Americans distorted others' preferences to fit their choices. Supporting our prediction that this social-class effect is closely linked to the independent versus interdependent self-construal, we showed that the differences in self-construal across cultures qualified the social-class effects on choices (Experiment 2). Moreover, when we experimentally manipulated self-construal in Experiment 3, we found that it mediated the corresponding changes in choices regardless of social class. © 2016 by the Society for Personality and Social Psychology, Inc.

  5. Technology and Teaching: Promoting Active Learning Using Individual Response Technology in Large Introductory Psychology Classes

    Science.gov (United States)

    Poirier, Christopher R.; Feldman, Robert S.

    2007-01-01

    Individual response technology (IRT), in which students use wireless handsets to communicate real-time responses, permits the recording and display of aggregated student responses during class. In comparison to a traditional class that did not employ IRT, students using IRT performed better on exams and held positive attitudes toward the…

  6. Drug induced xerostomia in elderly individuals: An institutional study

    Directory of Open Access Journals (Sweden)

    Shishir Ram Shetty

    2012-01-01

    Full Text Available Introduction : With better health care facilities and nutritional levels the average life expectancy of Indian population has been on the rise over the years. Most of the geriatric population is under long-term medication. Aim : The aim of this study was to evaluate the synergistic effect of multiple xerostomia drugs. Materials and Methods : Unstimulated saliva was measured in 60 geriatric patients, and xerostomia questionnaire and quality-of-life scale were also administered. Results : There was a very highly significant reduction in the salivary flow rates of patients under multiple xerostomia-inducing drugs. Conclusion : The synergistic effect of the xerostomia inducing medication could be the possible factor responsible for reduced salivary flow in elderly individuals using such drugs

  7. Which Classes of Prescription Drugs Are Commonly Misused?

    Science.gov (United States)

    ... Alcohol Club Drugs Cocaine Fentanyl Hallucinogens Inhalants Heroin Marijuana MDMA (Ecstasy/Molly) Methamphetamine Opioids Over-the-Counter Medicines Prescription Medicines Steroids (Anabolic) Synthetic Cannabinoids (K2/Spice) Synthetic Cathinones (Bath Salts) Tobacco/ ...

  8. Micro-macro multilevel latent class models with multiple discrete individual-level variables

    NARCIS (Netherlands)

    Bennink, M.; Croon, M.A.; Kroon, B.; Vermunt, J.K.

    2016-01-01

    An existing micro-macro method for a single individual-level variable is extended to the multivariate situation by presenting two multilevel latent class models in which multiple discrete individual-level variables are used to explain a group-level outcome. As in the univariate case, the

  9. Individual and class room predictors of same-cultural friendship preferences in multicultural schools

    NARCIS (Netherlands)

    Stefanek, E.; Strohmeier, D.; Van De Schoot, R.

    2015-01-01

    This study was an investigation of individual and contextual predictors for same-cultural friendship preferences among non-immigrant (N = 125), Turkish (N ¼ 196) and former Yugoslavian (N = 256) immigrant youths (M age = 14.39 years) in 36 multicultural classes. At the individual level age, gender,

  10. Individual differences in the production of word classes in eight specific language-impaired preschoolers.

    Science.gov (United States)

    Le Normand, M T; Chevrie-Muller, C

    1991-01-01

    The production of word classes in eight 53-62-month-old specific language-impaired (SLI) children was described and compared with that of 30 normal 24-33-month-old children in the same play situation. SLI subjects and nonimpaired children were selected within specified mean length of utterance ranges (low MLU versus high MLU). Production of word classes by subjects was evaluated in order to determine (1) whether SLI children showed a similar or a different word-class profile among themselves and when compared with non-impaired children and (2) whether MLU related to word classes would be useful as a single clinical index in assessment of language acquisition. Results showed that scores of SLI children in production of word classes reflect important individual differences among subjects. In the high-MLU sample, all SLI children produced each word class relatively within the same range as the nonimpaired group. In the low-MLU sample two SLI children were very different in their word-class profile and individual differences were further confirmed by a discriminant function analysis. Correlations between MLU and word classes were significant in nonimpaired children for all variables except Questions and Onomatopoeia and were only significant in SLI children for Verbs, Prepositions, and Personal Pronouns. Such findings contribute support to the view that there is "deviant" pattern of language in SLI children and once again questions whether MLU is one of the best discriminating indicators to use in the clinical assessment of language organization.

  11. Children’s and Adolescents’ Snacking: Interplay between the Individual and the School Class

    Directory of Open Access Journals (Sweden)

    Helge eGiese

    2015-09-01

    Full Text Available Objective: In schools, perceived norms of classmates facilitate but can also inhibit unhealthy food intake in children and adolescents. However, the role of actual class behaviors and attitudes is less established. Thus, the present study examined classmates’ actual eating behavior and food preferences in relation to actual food intake. In addition, it tested whether these normative effects are facilitated by corresponding individual and class food preferences or a positive social self-concept.Methods: The food preferences, social self-concept, and unhealthy snacking frequency of 734 Finnish, 829 German, and 555 Romanian children and adolescents (aged 8-19 from 127 school-classes were assessed.Results: Multilevel analysis at individual and class level showed that classmates shared similar snacking habits (14.7% variance. Moreover, the unhealthy food preference of a school-class was associated with its collective snacking (χ²(1 = 54.67, p < .001, PRV = .32. This effect was facilitated by individual, unhealthy food preferences (χ²(1 = 16.72, p < .001, PRV = .57 and a positive social self-concept (χ²(1 = 5.91, p = .015, PRV = .12.Conclusions: Actual class norms are related to children’s and adolescents’ eating, but their impact depends on individual differences in preferences and social self-concept.

  12. Influence of Bariatric Surgery on the Use and Pharmacokinetics of Some Major Drug Classes

    NARCIS (Netherlands)

    Yska, Jan Peter; van der Linde, Susanne; Tapper, Veronique V.; Apers, Jan A.; Emous, Marloes; Totte, Erik R.; Wilffert, Bob; van Roon, Eric N.

    The purpose of this review is to evaluate the influence of bariatric surgery on the use and pharmacokinetics of some frequently used drugs. A PubMed literature search was conducted. Literature was included on influence of bariatric surgery on pharmacoepidemiology and pharmacokinetics. Drug classes

  13. Drug-target interaction prediction via class imbalance-aware ensemble learning.

    Science.gov (United States)

    Ezzat, Ali; Wu, Min; Li, Xiao-Li; Kwoh, Chee-Keong

    2016-12-22

    Multiple computational methods for predicting drug-target interactions have been developed to facilitate the drug discovery process. These methods use available data on known drug-target interactions to train classifiers with the purpose of predicting new undiscovered interactions. However, a key challenge regarding this data that has not yet been addressed by these methods, namely class imbalance, is potentially degrading the prediction performance. Class imbalance can be divided into two sub-problems. Firstly, the number of known interacting drug-target pairs is much smaller than that of non-interacting drug-target pairs. This imbalance ratio between interacting and non-interacting drug-target pairs is referred to as the between-class imbalance. Between-class imbalance degrades prediction performance due to the bias in prediction results towards the majority class (i.e. the non-interacting pairs), leading to more prediction errors in the minority class (i.e. the interacting pairs). Secondly, there are multiple types of drug-target interactions in the data with some types having relatively fewer members (or are less represented) than others. This variation in representation of the different interaction types leads to another kind of imbalance referred to as the within-class imbalance. In within-class imbalance, prediction results are biased towards the better represented interaction types, leading to more prediction errors in the less represented interaction types. We propose an ensemble learning method that incorporates techniques to address the issues of between-class imbalance and within-class imbalance. Experiments show that the proposed method improves results over 4 state-of-the-art methods. In addition, we simulated cases for new drugs and targets to see how our method would perform in predicting their interactions. New drugs and targets are those for which no prior interactions are known. Our method displayed satisfactory prediction performance and was

  14. Longitudinal relationships between individual and class norms supporting dating violence and perpetration of dating violence.

    Science.gov (United States)

    Taylor, Katherine A; Sullivan, Terri N; Farrell, Albert D

    2015-03-01

    Dating violence is commonly perpetrated in adolescence, making it imperative to understand risk factors in order to inform prevention efforts. Although individual norms supporting dating violence are strongly related to its perpetration, few studies have examined their longitudinal impact. Moreover, the influence of class norms (i.e., norms for students in the same grade, cohort, and school) supporting dating violence on perpetration has rarely been studied. The current study examined longitudinal relationships between individual and class norms supporting dating violence and perpetration of physical and psychological dating violence. Participants were two cohorts of sixth graders from 37 schools who were in dating relationships at Wave 1 and 6 months later at Wave 2 (N = 2,022; 43% female; 52% African American, 21% Latino/a, 20% White, and 7% other). The analyses used a multilevel approach, with students represented at Level 1 and classes (n = 74) at Level 2. The models tested direct effects of Wave 1 individual and class norms supporting dating violence on subsequent changes in perpetration of dating violence at Wave 2 and the extent to which gender moderated these relationships. The findings indicated that greater individual norms supporting male dating violence predicted greater change in perpetration of physical and psychological dating violence and greater individual norms supporting female dating violence predicted greater change in perpetration of psychological dating violence. Greater class norms supporting male dating violence predicted greater change in perpetration of physical dating violence; whereas greater class norms supporting female dating violence predicted less change in perpetration of physical dating violence. These findings highlight the need to address norms in early adolescence.

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

    Science.gov (United States)

    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

  16. Forecasting craniofacial growth in individuals with class III malocclusion by computational modelling.

    Science.gov (United States)

    Auconi, Pietro; Scazzocchio, Marco; Defraia, Efisio; McNamara, James A; Franchi, Lorenzo

    2014-04-01

    To develop a mathematical model that adequately represented the pattern of craniofacial growth in class III subject consistently, with the goal of using this information to make growth predictions that could be amenable to longitudinal verification and clinical use. A combination of computational techniques (i.e. Fuzzy clustering and Network analysis) was applied to cephalometric data derived from 429 untreated growing female patients with class III malocclusion to visualize craniofacial growth dynamics and correlations. Four age groups of subjects were examined individually: from 7 to 9 years of age, from 10 to 12 years, from 13 to 14 years, and from 15 to 17 years. The connections between pathway components of class III craniofacial growth can be visualized from Network profiles. Fuzzy clustering analysis was able to define further growth patterns and coherences of the traditionally reported dentoskeletal characteristics of this structural imbalance. Craniofacial growth can be visualized as a biological, space-constraint-based optimization process; the prediction of individual growth trajectories depends on the rate of membership to a specific 'winner' cluster, i.e. on a specific individual growth strategy. The reliability of the information thus gained was tested to forecast craniofacial growth of 28 untreated female class III subjects followed longitudinally. The combination of Fuzzy clustering and Network algorithms allowed the development of principles for combining multiple auxological cephalometric features into a joint global model and to predict the individual risk of the facial pattern imbalance during growth.

  17. Training Class Inclusion Responding in Typically Developing Children and Individuals with Autism

    Science.gov (United States)

    Ming, Siri; Mulhern, Teresa; Stewart, Ian; Moran, Laura; Bynum, Kellie

    2018-01-01

    In a "class inclusion" task, a child must respond to stimuli as being involved in two different though hierarchically related categories. This study used a Relational Frame Theory (RFT) paradigm to assess and train this ability in three typically developing preschoolers and three individuals with autism spectrum disorder, all of whom had…

  18. Comparing Different Classes of Reinforcement to Increase Expressive Language for Individuals with Autism

    Science.gov (United States)

    Leaf, Justin B.; Dale, Stephanie; Kassardjian, Alyne; Tsuji, Kathleen H.; Taubman, Mitchell; McEachin, John J.; Leaf, Ronald B.; Oppenheim-Leaf, Misty L.

    2014-01-01

    One of the basic principles of applied behavior analysis is that behavior change is largely due to that behavior being reinforced. Therefore the use of positive reinforcement is a key component of most behavioral programs for individuals diagnosed with autism. In this study we compared four different classes of reinforcers (i.e., food, praise,…

  19. Fitness levels and physical activity among class A drug users entering prison.

    Science.gov (United States)

    Fischer, Jan; Butt, Christine; Dawes, Helen; Foster, Charlie; Neale, Joanne; Plugge, Emma; Wheeler, Carly; Wright, Nat

    2012-12-01

    Physical activity could benefit drug users' physiological and mental health. Previous research has suggested that physical activity levels change when drug users enter prison. Twenty-five class A drug users who were new to prison answered physical activity and drug use cross-sectional questionnaires, took a submaximal fitness test and wore a pedometer for 1 week. Participants' mean aerobic capacity was estimated as 49 mls O2/kg/min (±12 SD). Their mean self-reported walking distance outside of prison was 4.67 miles on an average day (±4.14 SD). Pedometer data suggest they walked a mean of 1.8 miles/day in prison. Many class A drug users entering prison had high levels of fitness and physical activity before admission, often gained from walking. Walking activity reduced when they entered prison, posing a challenge to maintaining healthy activity levels.

  20. Kinase inhibitors: a new class of antirheumatic drugs

    Directory of Open Access Journals (Sweden)

    Kyttaris VC

    2012-09-01

    Full Text Available Vasileios C KyttarisDivision of Rheumatology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USAAbstract: The outlook for patients with rheumatoid arthritis has improved significantly over the last three decades with the use of disease-modifying antirheumatic drugs. However, despite the use of methotrexate, cytokine inhibitors, and molecules targeting T and B cells, a percentage of patients do not respond or lose their response over time. The autoimmune process in rheumatoid arthritis depends on activation of immune cells, which utilize intracellular kinases to respond to external stimuli such as cytokines, immune complexes, and antigens. In the past decade, small molecules targeting several kinases, such as p38 MAPK, Syk, and JAK have been developed. Several p38 MAPK inhibitors proved ineffective in treating rheumatoid arthritis. The Syk inhibitor, fostamatinib, proved superior to placebo in Phase II trials and is currently under Phase III investigation. Tofacitinib, a JAK1/3 inhibitor, was shown to be efficacious in two Phase III trials, while VX-509, a JAK3 inhibitor, showed promising results in a Phase II trial. Fostamatinib and tofacitinib were associated with increased rates of infection, elevation of liver enzymes, and neutropenia. Moreover, fostamatinib caused elevations of blood pressure and diarrhea, while tofacitinib was associated with an increase in creatinine and elevation of lipid levels.Keywords: rheumatoid arthritis, kinase inhibitors, mitogen-activated phosphokinase p38, spleen tyrosine kinase, Janus kinases

  1. Genotypic drug resistance and long-term mortality in patients with triple-class antiretroviral drug failure

    DEFF Research Database (Denmark)

    Lohse, Nicolai; Jørgensen, LB; Kronborg, G

    2007-01-01

    OBJECTIVE: To examine the prevalence of drug-resistance-associated mutations in HIV patients with triple-drug class virological failure (TCF) and their association with long-term mortality. DESIGN: Population-based study from the Danish HIV Cohort Study (DHCS). METHODS: We included all patients...... range 2-10), and 81 (61%) patients had mutations conferring resistance towards all three major drug classes. In a regression model adjusted for CD4+ T-cell count, HIV RNA, year of TCF, age, gender and previous inferior antiretroviral therapy, harbouring > or =9 versus ... in the DHCS who experienced TCF between January 1995 and November 2004, and we performed genotypic resistance tests for International AIDS Society (IAS)-USA primary mutations on virus from plasma samples taken around the date of TCF. We computed time to all-cause death from date of TCF. The relative risk...

  2. 46 CFR 4.05-12 - Alcohol or drug use by individuals directly involved in casualties.

    Science.gov (United States)

    2010-10-01

    ... 46 Shipping 1 2010-10-01 2010-10-01 false Alcohol or drug use by individuals directly involved in... § 4.05-12 Alcohol or drug use by individuals directly involved in casualties. (a) For each marine... evidence of alcohol or drug use by individuals directly involved in the casualty. (b) The marine employer...

  3. 46 CFR 122.210 - Alcohol or drug use by individuals directly involved in casualties.

    Science.gov (United States)

    2010-10-01

    ... 46 Shipping 4 2010-10-01 2010-10-01 false Alcohol or drug use by individuals directly involved in... PASSENGERS OPERATIONS Marine Casualties and Voyage Records § 122.210 Alcohol or drug use by individuals... alcohol or drug use by individuals directly involved in the casualty. (b) The owner, agent, master, or...

  4. 77 FR 16123 - Draft Guidance for Industry and Food and Drug Administration Staff; Class II Special Controls...

    Science.gov (United States)

    2012-03-19

    ... Guidance for Industry and Food and Drug Administration Staff; Class II Special Controls Guidance Document... Drug Administration 21 CFR Part 866 Draft Guidance for Industry and Food and Drug Administration Staff; Class II Special Controls Guidance Document: Nucleic Acid-Based In Vitro Diagnostic Devices for the...

  5. 76 FR 29251 - Guidance for Industry and Food and Drug Administration Staff; Class II Special Controls; Guidance...

    Science.gov (United States)

    2011-05-20

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2006-D-0094] Guidance for Industry and Food and Drug Administration Staff; Class II Special Controls; Guidance Document... of the guidance entitled ``Guidance for Industry and Food and Drug Administration Staff; Class II...

  6. Health behaviour among adolescents in Denmark: influence of school class and individual risk factors

    DEFF Research Database (Denmark)

    Johansen, Anette; Rasmussen, Søren; Madsen, Mette

    2006-01-01

    the mother's socioeconomic status and the included health behaviour measurements; however, adolescents from the lower socioeconomic groups had a higher risk of unhealthy dietary habits and adolescents whose mothers were unemployed had a significantly lower risk of drinking alcohol weekly versus all other...... adolescents. Not living with both biological parents, focusing on friends, and not being very academically proficient were associated with an increased risk of harmful health behaviour. Health behaviour varied substantially between school classes, especially for daily smoking, weekly alcohol consumption......AIMS: The aim of this study was to assess the relative influence of school class on health behaviour among adolescents versus that of the family's socioeconomic status and individual factors among adolescents. METHODS: The material comprised 3,458 students in grades 8 and 9 in 244 school classes...

  7. Beyond 'Doing Gender': Incorporating Race, Class, Place, and Life Transitions into Feminist Drug Research.

    Science.gov (United States)

    Miller, Jody; Carbone-Lopez, Kristin

    2015-05-01

    This essay draws from our research with US rural women methamphetamine users in 2009 to offer strategies for "revisioning" the drug use(r) field to better understand the impact of gender on drug use and drug market participation. We highlight the insights and limitations of a popular strategy in feminist research that conceptualizes gender as performance- commonly referred to as "doing gender"-using illustrations from our research. We encourage scholars to move beyond a primarily normative orientation in studying gender, and investigate gendered organizational features of social life including their intersections with other aspects of social inequality such as those of race, class, and place. In addition, we suggest that feminist scholars can integrate gender in a rigorous way into theoretical perspectives that are typically inattentive to its import, as a means of challenging, enriching, and refining research on drug use, drug users, and drug market participation.

  8. The Nucleus Accumbens: Mechanisms of Addiction across Drug Classes Reflect the Importance of Glutamate Homeostasis

    Science.gov (United States)

    Heinsbroek, J. A.; Gipson, C. D.; Kupchik, Y. M.; Spencer, S.; Smith, A. C. W.; Roberts-Wolfe, D.; Kalivas, P. W.

    2016-01-01

    The nucleus accumbens is a major input structure of the basal ganglia and integrates information from cortical and limbic structures to mediate goal-directed behaviors. Chronic exposure to several classes of drugs of abuse disrupts plasticity in this region, allowing drug-associated cues to engender a pathologic motivation for drug seeking. A number of alterations in glutamatergic transmission occur within the nucleus accumbens after withdrawal from chronic drug exposure. These drug-induced neuroadaptations serve as the molecular basis for relapse vulnerability. In this review, we focus on the role that glutamate signal transduction in the nucleus accumbens plays in addiction-related behaviors. First, we explore the nucleus accumbens, including the cell types and neuronal populations present as well as afferent and efferent connections. Next we discuss rodent models of addiction and assess the viability of these models for testing candidate pharmacotherapies for the prevention of relapse. Then we provide a review of the literature describing how synaptic plasticity in the accumbens is altered after exposure to drugs of abuse and withdrawal and also how pharmacological manipulation of glutamate systems in the accumbens can inhibit drug seeking in the laboratory setting. Finally, we examine results from clinical trials in which pharmacotherapies designed to manipulate glutamate systems have been effective in treating relapse in human patients. Further elucidation of how drugs of abuse alter glutamatergic plasticity within the accumbens will be necessary for the development of new therapeutics for the treatment of addiction across all classes of addictive substances. PMID:27363441

  9. Effect of circuit class versus individual task specific training on balance in post-stroke patients

    International Nuclear Information System (INIS)

    Basri, R.; Ali, A.; Ullah, S.; Naseem, M.; Haq, Z.U.

    2017-01-01

    Objective: To compare the efficacy of circuit class versus individual, task specific training on balance, in post stroke patients. Methods: From a total of 64 participants, 32 participants were treated in circuit based workstations, while 32 participants were treated individually for 4 weeks. Importantly, both groups were treated with standard balance physiotherapy protocols. The treatment was delivered for 5 days per week with 1.5 hours daily. The patients were evaluated for three outcome measures i.e. berg balance scale, time up and go test and for motor assessment scale at baseline and after treatment. Results: Patients in both groups reported significant improvement after 4 weeks of training program compared to baseline on all outcome measures, except time up and go test that did not significantly improve in individual group. Compared to individual group, circuit group reported more improvement on berg balance scale scores (31.33 versus 37.80), time up and go test (23.13sec versus 16.67sec) and on motor assessment scale scores (18.77 versus 20.63) respectively. Conclusion: Circuit class training is more efficacious in improving balance in stroke patients as compared to individual task specific training. (author)

  10. 21 CFR 310.517 - Labeling for oral hypoglycemic drugs of the sulfonylurea class.

    Science.gov (United States)

    2010-04-01

    ... vascular complications in patients with non-insulin-dependent diabetes. The study involved 823 patients who... Diabetes Program clinical trial has reported an association between the administration of tolbutamide and... drugs of the sulfonylurea class shall include in boldface type at the beginning of the “Warnings...

  11. HLA-class II alleles in patients with drug-resistant pulmonary tuberculosis in Kazakhstan.

    Science.gov (United States)

    Kuranov, A B; Kozhamkulov, U A; Vavilov, M N; Belova, E S; Bismilda, V L; Alenova, A H; Ismailov, S S; Momynaliev, K T

    2014-02-01

    The human leukocyte antigen (HLA) system has a major role in the regulation of the immune response as it is involved in the defense against pathogens. Some studies have reported that HLA class II genes play a strong role in severe cases of pulmonary tuberculosis (PTB) in several populations. Thus the aim of the study was to compare the HLA-class II alleles of patients with drug resistant tuberculosis with those of healthy controls from the same ethnic group in Kazakhstan. The aim of the present study was to evaluate the correlation of HLA-class II alleles by patients with drug resistant tuberculosis and the healthy controls of the same ethnic group in Kazakhstan. The HLA-class II alleles of 76 patients with tuberculosis (TB) and 157 healthy volunteers were investigated using sequence-based typing (SBT)-method. HLA-DQA1*03:02 HLA-DRB1*08:01 and DRB1*08:03 occurred more frequently (P = 0.05) in patients with drug resistant tuberculosis than in controls. We observed a possible association between certain HLA alleles and TB that are specific for the Kazakh population. Further studies are needed to confirm our findings using a larger number of patients with drug resistant tuberculosis. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  12. Effectiveness of recommended drug classes in secondary prevention of acute coronary syndrome in France

    NARCIS (Netherlands)

    Bezin, Julien; Groenwold, Rolf; Ali, Sanni; Lassalle, Régis; De Boer, Anthonius; Moore, Nicholas; Klungel, Olaf; Pariente, Antoine

    Background: Guidelines for cardiovascular secondary prevention are based on evidence from relatively old clinical trials and need to be evaluated in daily clinical practice. Objectives: To evaluate effectiveness of the recommended drug classes after an acute coronary syndrome (ACS) for secondary

  13. Happy classes make happy students: Classmates' well-being predicts individual student well-being.

    Science.gov (United States)

    King, Ronnel B; Datu, Jesus Alfonso

    2017-12-01

    Student well-being has mostly been studied as an individual phenomenon with little research investigating how the well-being of one's classmates could influence a student's well-being. The aim of the current study was to examine how the aggregate well-being of students who comprise a class could predict students' subsequent well-being (Time 2 well-being) after controlling for the effects of prior well-being (Time 1 well-being) as well as key demographic variables such as gender and age. Two studies among Filipino secondary school students were conducted. In Study 1, 788 students from 21 classes participated; in Study 2, 404 students from 10 classes participated. For Study 1, questionnaires assessing students' life satisfaction, positive affect and negative affect were administered twice seven months apart. For Study 2, the well-being questionnaires were administered twice, three months apart. Hierarchical linear modeling was used with level 1 (Time 1 individual well-being, gender, and age) and level 2 (class well-being) predictors. Results across the two studies provided converging lines of evidence: students who were in classes with higher levels of life satisfaction and positive affect were also more likely to have higher life satisfaction and positive affect at Time 2. The study indicated that the well-being of a student partly depends on the well-being of their classmates providing evidence for the social contagion of well-being in the classroom context. Copyright © 2017 Society for the Study of School Psychology. Published by Elsevier Ltd. All rights reserved.

  14. 46 CFR 185.210 - Alcohol or drug use by individuals directly involved in casualties.

    Science.gov (United States)

    2010-10-01

    ... 46 Shipping 7 2010-10-01 2010-10-01 false Alcohol or drug use by individuals directly involved in... whether there is any evidence of alcohol or drug use by individuals directly involved in the casualty. (b... evidence of drug or alcohol use, or evidence of intoxication, has been obtained; and (2) Specifies the...

  15. 75 FR 70271 - Guidance for Industry and Food and Drug Administration Staff; Class II Special Controls Guidance...

    Science.gov (United States)

    2010-11-17

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-D-0515] Guidance for Industry and Food and Drug Administration Staff; Class II Special Controls Guidance Document...: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug Administration (FDA) is...

  16. Individualization of anticancer therapy; molecular targets of novel drugs in oncology

    Directory of Open Access Journals (Sweden)

    Katarzyna Regulska

    2012-11-01

    Full Text Available Deregulation of cellular signal transduction, caused by gene mutations, has been recognized as a basic factor of cancer initiation, promotion and progression. Thus, the ability to control the activity of overstimulated signal molecules by the use of appropriate inhibitors became the idea of targeted cancer therapy, which has provided an effective tool to normalize the molecular disorders in malignant cells and to treat certain types of cancer. The molecularly targeted drugs are divided into two major pharmaceutical classes: monoclonal antibodies and small-molecule kinase inhibitors. This review presents a summary of their characteristics, analyzing their chemical structures, specified molecular targets, mechanisms of action and indications for use. Also the molecules subjected to preclinical trials or phase I, II and III clinical trials evaluating their efficiency and safety are presented. Moreover, the article discusses further perspectives for development of targeted therapies focusing on three major directions: systematic searching and discovery of new targets that are oncogenic drivers, improving the pharmacological properties of currently known drugs, and developing strategies to overcome drug resistance. Finally, the role of proper pharmacodiagnostics as a key to rational anticancer therapy has been emphasized since the verification of reliable predictive biomarkers is a basis of individualized medicine in oncology. 

  17. "Waiting on the words": procedures and outcomes of a drama class for individuals with aphasia.

    Science.gov (United States)

    Cherney, Leora R; Oehring, Ann K; Whipple, Keith; Rubenstein, Ted

    2011-08-01

    Drama therapy offers an authentic medium through which people with aphasia can interact and share their experiences. We describe the rationale and procedures of a drama class, informed by the principles and practices of drama therapy, in which individuals with chronic aphasia conceptualized, wrote, and produced a play addressing their experiences of having, living with, and coping with the effects of aphasia. Sessions were cofacilitated by a speech-language pathologist and a drama therapist. We describe the drama activities and techniques in each of four distinct stages of a drama therapy process through which the group transitioned. We also summarize patient-reported outcomes of a representational group of seven participants. Subscales of the Burden of Stroke Scale and the Communication Confidence Rating Scale for Aphasia were administered before and after participation in the 18-week class. Means, standard deviations, and effect sizes were computed. Results indicated perceived improvements in both communication and mood. © Thieme Medical Publishers.

  18. Prediction of solubility and permeability class membership: provisional BCS classification of the world's top oral drugs.

    Science.gov (United States)

    Dahan, Arik; Miller, Jonathan M; Amidon, Gordon L

    2009-12-01

    The Biopharmaceutics Classification System (BCS) categorizes drugs into one of four biopharmaceutical classes according to their water solubility and membrane permeability characteristics and broadly allows the prediction of the rate-limiting step in the intestinal absorption process following oral administration. Since its introduction in 1995, the BCS has generated remarkable impact on the global pharmaceutical sciences arena, in drug discovery, development, and regulation, and extensive validation/discussion/extension of the BCS is continuously published in the literature. The BCS has been effectively implanted by drug regulatory agencies around the world in setting bioavailability/bioequivalence standards for immediate-release (IR) oral drug product approval. In this review, we describe the BCS scientific framework and impact on regulatory practice of oral drug products and review the provisional BCS classification of the top drugs on the global market. The Biopharmaceutical Drug Disposition Classification System and its association with the BCS are discussed as well. One notable finding of the provisional BCS classification is that the clinical performance of the majority of approved IR oral drug products essential for human health can be assured with an in vitro dissolution test, rather than empirical in vivo human studies.

  19. 75 FR 69089 - Guidance for Industry and Food and Drug Administration Staff; Class II Special Controls Guidance...

    Science.gov (United States)

    2010-11-10

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-D-0514] Guidance for Industry and Food and Drug Administration Staff; Class II Special Controls Guidance Document... Administration (FDA) is announcing the availability of the guidance entitled ``Class II Special Controls Guidance...

  20. The Nucleus Accumbens: Mechanisms of Addiction across Drug Classes Reflect the Importance of Glutamate Homeostasis.

    Science.gov (United States)

    Scofield, M D; Heinsbroek, J A; Gipson, C D; Kupchik, Y M; Spencer, S; Smith, A C W; Roberts-Wolfe, D; Kalivas, P W

    2016-07-01

    The nucleus accumbens is a major input structure of the basal ganglia and integrates information from cortical and limbic structures to mediate goal-directed behaviors. Chronic exposure to several classes of drugs of abuse disrupts plasticity in this region, allowing drug-associated cues to engender a pathologic motivation for drug seeking. A number of alterations in glutamatergic transmission occur within the nucleus accumbens after withdrawal from chronic drug exposure. These drug-induced neuroadaptations serve as the molecular basis for relapse vulnerability. In this review, we focus on the role that glutamate signal transduction in the nucleus accumbens plays in addiction-related behaviors. First, we explore the nucleus accumbens, including the cell types and neuronal populations present as well as afferent and efferent connections. Next we discuss rodent models of addiction and assess the viability of these models for testing candidate pharmacotherapies for the prevention of relapse. Then we provide a review of the literature describing how synaptic plasticity in the accumbens is altered after exposure to drugs of abuse and withdrawal and also how pharmacological manipulation of glutamate systems in the accumbens can inhibit drug seeking in the laboratory setting. Finally, we examine results from clinical trials in which pharmacotherapies designed to manipulate glutamate systems have been effective in treating relapse in human patients. Further elucidation of how drugs of abuse alter glutamatergic plasticity within the accumbens will be necessary for the development of new therapeutics for the treatment of addiction across all classes of addictive substances. Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.

  1. A survey of the FDA's AERS database regarding muscle and tendon adverse events linked to the statin drug class.

    Directory of Open Access Journals (Sweden)

    Keith B Hoffman

    Full Text Available BACKGROUND: Cholesterol management drugs known as statins are widely used and often well tolerated; however, a variety of muscle-related side effects can arise. These adverse events (AEs can have serious impact, and form a significant barrier to therapy adherence. Surveillance of post-marketing AEs is of vital importance to understand real-world AEs and reporting differences between individual statin drugs. We conducted a review of post-approval muscle and tendon AE reports in association with statin use, to assess differences within the drug class. METHODS: We analyzed all case reports from the FDA AE Reporting System (AERS database linking muscle-related AEs to statin use (07/01/2005-03/31/2011. Drugs examined were: atorvastatin, simvastatin, lovastatin, pravastatin, rosuvastatin, and fluvastatin. RESULTS: Relative risk rates for rosuvastatin were consistently higher than other statins. Atorvastatin and simvastatin showed intermediate risks, while pravastatin and lovastatin appeared to have the lowest risk rates. Relative risk of muscle-related AEs, therefore, approximately tracked with per milligram LDL-lowering potency, with fluvastatin an apparent exception. Incorporating all muscle categories, rates for atorvastatin, simvastatin, pravastatin, and lovastatin were, respectively, 55%, 26%, 17%, and 7.5% as high, as rosuvastatin, approximately tracking per milligram potency (Rosuvastatin>Atorvastatin>Simvastatin>Pravastatin ≈ Lovastatin and comporting with findings of other studies. Relative potency, therefore, appears to be a fundamental predictor of muscle-related AE risk, with fluvastatin, the least potent statin, an apparent exception (risk 74% vs rosuvastatin. INTERPRETATION: AE reporting rates differed strikingly for drugs within the statin class, with relative reporting aligning substantially with potency. The data presented in this report offer important reference points for the selection of statins for cholesterol management in

  2. Correlations between dentoskeletal variables and deep bite in Class II Division 1 individuals

    Directory of Open Access Journals (Sweden)

    Leandro Silva Marques

    2011-02-01

    Full Text Available This study aimed to evaluate the cephalometric pattern of Class II Division 1 individuals with deep bite, and to determine possible correlations between dentoskeletal variables and deep bite. Comparisons were also made between genders and cases that were to be treated both with and without premolar extraction. A total of 70 lateral cephalograms were used, from both male (n = 35 and female (n = 35 individuals with an average age of 11.6 years, who simultaneously presented with ANB > 5º and overbite > 4 mm. Statistical analysis involved parametric (t-test and non-parametric (Mann-Whitney tests for independent samples, as well as the Spearman correlation test (p < 0.05. The values of Go-Me, Ar-Pog, PM-1 and PM-CMI were higher in males (p < 0.05. However, no significant differences were found among the averages of the cephalometric measurements when the sample was divided by treatment with and without extraction. Deep bite was positively correlated to the PM-1 and SNA measurements, and negatively correlated to the Go-Me, Ar-Pog, SNB and SNGoMe measurements. The main factors associated with the determination of deep bite in Angle's Class II Division 1 cases were: greater lower anterior dentoalveolar growth and/or lower incisor extrusion, horizontal growth pattern, maxillary protrusion and mandibular retrusion.

  3. Friendship networks of inner-city adults: a latent class analysis and multi-level regression of supporter types and the association of supporter latent class membership with supporter and recipient drug use.

    Science.gov (United States)

    Bohnert, Amy S B; German, Danielle; Knowlton, Amy R; Latkin, Carl A

    2010-03-01

    Social support is a multi-dimensional construct that is important to drug use cessation. The present study identified types of supportive friends among the social network members in a community-based sample and examined the relationship of supporter-type classes with supporter, recipient, and supporter-recipient relationship characteristics. We hypothesized that the most supportive network members and their support recipients would be less likely to be current heroin/cocaine users. Participants (n=1453) were recruited from low-income neighborhoods with a high prevalence of drug use. Participants identified their friends via a network inventory, and all nominated friends were included in a latent class analysis and grouped based on their probability of providing seven types of support. These latent classes were included as the dependent variable in a multi-level regression of supporter drug use, recipient drug use, and other characteristics. The best-fitting latent class model identified five support patterns: friends who provided Little/No Support, Low/Moderate Support, High Support, Socialization Support, and Financial Support. In bivariate models, friends in the High, Low/Moderate, and Financial Support were less likely to use heroin or cocaine and had less conflict with and were more trusted by the support recipient than friends in the Low/No Support class. Individuals with supporters in those same support classes compared to the Low/No Support class were less likely to use heroin or cocaine, or to be homeless or female. Multivariable models suggested similar trends. Those with current heroin/cocaine use were less likely to provide or receive comprehensive support from friends. Published by Elsevier Ireland Ltd.

  4. Patent extension policy for paediatric indications: an evaluation of the impact within three drug classes in a state Medicaid programme.

    Science.gov (United States)

    Nelson, Richard E; McAdam-Marx, Carrie; Evans, Megan L; Ward, Robert; Campbell, Benjamin; Brixner, Diana; Lafleur, Joanne

    2011-05-01

    expiration date if the patent extension had not been granted. Medicaid rebates were assumed to be 15.1% for branded products and 11% for generics. The 6-month extension policy was estimated to cost Utah's Medicaid $US2.2 (95% CI 1.9, 2.4) million for these three drug classes over the 18 months following the original patent expiration date (year 2007 values). Projected to the US Medicaid population, this cost was $US430 (95% CI 371, 475) million. For the individual drugs that we examined, the percentage cost decrease in reimbursement amount resulting from exclusivity expiration and generic entry ranged from 24.4% (p branded drugs evaluated were given market exclusivity extensions for conducting studies of their medications in children. The costs found in this study are just a small portion of the total paid, which include those born by other payers. Whether the benefits of this policy outweigh these costs is an open question, but these results suggest that the costs to Medicaid and thus taxpayers are substantial.

  5. 77 FR 37058 - Draft Guidance for Industry and Food and Drug Administration Staff; Class II Special Controls...

    Science.gov (United States)

    2012-06-20

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA 2012-D-0304] Draft Guidance for Industry and Food and Drug Administration Staff; Class II Special Controls Guidance... Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug Administration (FDA) is announcing the...

  6. 76 FR 20992 - Guidance for Industry and Food and Drug Administration Staff; Class II Special Controls Guidance...

    Science.gov (United States)

    2011-04-14

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-D-0189] Guidance for Industry and Food and Drug Administration Staff; Class II Special Controls Guidance Document: Low Level Laser System for Aesthetic Use; Availability AGENCY: Food and Drug Administration, HHS...

  7. 75 FR 68364 - Guidance for Industry and Food and Drug Administration Staff; Class II Special Controls Guidance...

    Science.gov (United States)

    2010-11-05

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2008-D-0275] Guidance for Industry and Food and Drug Administration Staff; Class II Special Controls Guidance Document: Full-Field Digital Mammography System; Availability AGENCY: Food and Drug Administration, HHS. [[Page...

  8. 76 FR 16425 - Guidance for Industry and Food and Drug Administration Staff; Class II Special Controls Guidance...

    Science.gov (United States)

    2011-03-23

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-D-0028] Guidance for Industry and Food and Drug Administration Staff; Class II Special Controls Guidance Document: Ovarian Adnexal Mass Assessment Score Test System; Availability AGENCY: Food and Drug Administration, HHS...

  9. 76 FR 6622 - Guidance for Industry and Food and Drug Administration Staff; Class II Special Controls Guidance...

    Science.gov (United States)

    2011-02-07

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-D-0645] Guidance for Industry and Food and Drug Administration Staff; Class II Special Controls Guidance Document: Contact Cooling System for Aesthetic Use; Availability AGENCY: Food and Drug Administration, HHS. ACTION...

  10. 76 FR 22906 - Guidance for Industry and Food and Drug Administration Staff; Class II Special Controls Guidance...

    Science.gov (United States)

    2011-04-25

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2006-D-0094] Guidance for Industry and Food and Drug Administration Staff; Class II Special Controls Guidance Document: Topical Oxygen Chamber for Extremities; Availability AGENCY: Food and Drug Administration, HHS. ACTION...

  11. 76 FR 43332 - Guidance for Industry and Food and Drug Administration Staff; Class II Special Controls Guidance...

    Science.gov (United States)

    2011-07-20

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-D-0500] Guidance for Industry and Food and Drug Administration Staff; Class II Special Controls Guidance Document: Focused Ultrasound Stimulator System for Aesthetic Use; Availability AGENCY: Food and Drug Administration...

  12. 76 FR 43690 - Guidance for Industry and Food and Drug Administration Staff; Class II Special Controls Guidance...

    Science.gov (United States)

    2011-07-21

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2007-D-0149] (Formerly 2007D-0309) Guidance for Industry and Food and Drug Administration Staff; Class II Special Controls Guidance Document: Electrocardiograph Electrodes; Availability AGENCY: Food and Drug...

  13. 77 FR 14403 - Guidance for Industry and Food and Drug Administration Staff; Class II Special Controls Guidance...

    Science.gov (United States)

    2012-03-09

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2012-D-0167] Guidance for Industry and Food and Drug Administration Staff; Class II Special Controls Guidance Document: Norovirus Serological Reagents; Availability AGENCY: Food and Drug Administration, HHS. ACTION: Notice...

  14. Cause-specific cardiovascular risk associated with nonsteroidal antiinflammatory drugs among healthy individuals

    DEFF Research Database (Denmark)

    Fosbøl, Emil Loldrup; Folke, Fredrik; Jacobsen, Søren

    2010-01-01

    Studies have raised concern on the cardiovascular safety of nonsteroidal antiinflammatory drugs (NSAIDs). We studied safety of NSAID therapy in a nationwide cohort of healthy individuals.......Studies have raised concern on the cardiovascular safety of nonsteroidal antiinflammatory drugs (NSAIDs). We studied safety of NSAID therapy in a nationwide cohort of healthy individuals....

  15. Income and the use of prescription drugs for near retirement individuals

    DEFF Research Database (Denmark)

    Leth-Petersen, Søren; Skipper, Niels

    2014-01-01

    In this paper, we estimate how demand for prescription drugs varies with income for a sample of near retirement individuals. The analysis is based on a novel panel data set with information about the purchase of prescription drugs for a large number of Danish individuals over the period 1995...

  16. Competitive pricing within pharmaceutical classes: evidence on "follow-on" drugs in Germany 1993-2008.

    Science.gov (United States)

    Mueller, Michael T; Frenzel, Alexander

    2015-01-01

    Competition from "follow-on" drugs has been a highly controversial issue. Manufacturers launching new molecules in existing drug classes have often been criticized for inflating health systems' expenses, but it has been argued that such drugs increase therapeutic options. Economic theory suggests that follow-on drugs induce price competition. We contribute to this discussion by addressing the topic of pricing at market entry and price development in the German market. We measure determinants of price strategies of follow-on drugs using regression analyses, considering all new molecules launched in the German market from 1993 to 2008. Prices of products are standardized on defined daily dosages controlling for sales volumes based on data from the IMS Health DPM database and for the therapeutic quality of a new product using ratings by Fricke/Klaus as a proxy for innovation. We identify prices correlating with therapeutic value at market entry. While the first two molecules engage in quality competition, price discounts below the market price can be observed from the third entrant on. Price discounts are even more distinct in development races with several drugs entering the market within 2 years and in classes with a low degree of therapeutic differentiation. Prices remain relatively constant over time. This study contributes to assessments of competition in pharmaceutical markets focusing on price strategies of new market entrants. After an initial phase of market building, further follow-on products induce price competition. Largely unchanged prices after 4 years may be interpreted as quality competition and can be attributed to prices in Germany being anchor points for international price referencing.

  17. Mentor Social Capital, Individual Agency and Working-Class Student Learning Outcomes: Revisiting the Structure/Agency Dialectic

    Science.gov (United States)

    Lovett, Trevor William

    2014-01-01

    This investigation explores factors that contributed to the disparate learning identities of two white baby-boomer brothers from the same working-class family. The research, part of a broader phenomenological study into the influences of working-class masculinities and schooling offers an insight into the individual family members' differential…

  18. Lipid Based Formulations of Biopharmaceutics Classification System (BCS Class II Drugs: Strategy, Formulations, Methods and Saturation

    Directory of Open Access Journals (Sweden)

    Šoltýsová I.

    2016-12-01

    Full Text Available Active ingredients in pharmaceuticals differ by their physico-chemical properties and their bioavailability therefore varies. The most frequently used and most convenient way of administration of medicines is oral, however many drugs are little soluble in water. Thus they are not sufficiently effective and suitable for such administration. For this reason a system of lipid based formulations (LBF was developed. Series of formulations were prepared and tested in water and biorelevant media. On the basis of selection criteria, there were selected formulations with the best emulsification potential, good dispersion in the environment and physical stability. Samples of structurally different drugs included in the Class II of the Biopharmaceutics classification system (BCS were obtained, namely Griseofulvin, Glibenclamide, Carbamazepine, Haloperidol, Itraconazol, Triclosan, Praziquantel and Rifaximin, for testing of maximal saturation in formulations prepared from commercially available excipients. Methods were developed for preparation of formulations, observation of emulsification and its description, determination of maximum solubility of drug samples in the respective formulation and subsequent analysis. Saturation of formulations with drugs showed that formulations 80 % XA and 20 % Xh, 35 % XF and 65 % Xh were best able to dissolve the drugs which supports the hypothesis that it is desirable to identify limited series of formulations which could be generally applied for this purpose.

  19. Spectral determination of individual rare earths in different classes of inorganic compounds

    International Nuclear Information System (INIS)

    Karpenko, L.I.; Fadeeva, L.A.; Shevchenko, L.D.

    1979-01-01

    The conditions are found allowing to analyze various inorganic compounds for rare-earth elements without separation from non-rare-earth components. The influence of the plasma composition on the intensity of spectral lines of rare-earth elements is studied. The relative intensity of homologous spectral lines of various rare-earth elements remains constant regardless of the plasma composition. The conditions are found for the determination of individual rare-earth elements acting as both alloying additives (Csub(n) -- n x 10 -1 -n x 10 -3 %), and basic components (up to tens of per cent) in different classes of inorganic compounds of 1-7 elements. The general method is developed for the determination of individual rare-earth elements in mixtures of oxides of rare-earth elements, complex fluorides of rare-earth elements and elements of group 2, gallates, borates, germanates, vanadates of rare-earth elements and aluminium; zirconates-titanates of lead and barium, containing modifying additives of rare-earth elements, complex chalcogenides of rare-earth elements and elements of group 5

  20. Latent Class Analysis of Polysubstance Use, Sexual Risk Behaviors, and Infectious Disease Among South African Drug Users

    Science.gov (United States)

    Trenz, Rebecca C.; Scherer, Michael; Duncan, Alexandra; Harrell, Paul; Moleko, Anne Gloria; Latimer, William

    2013-01-01

    Background HIV transmission risk among non-injection drug users is high due to the co-occurrence of drug use and sexual risk behaviors. The purpose of the current study was to identify patterns of drug use among polysubstance users within a high HIV prevalence population. Methods The study sample included 409 substance users from the Pretoria region of South Africa. Substances used by 20% or more the sample included: cigarettes, alcohol, marijuana and heroin in combination, marijuana and cigarettes in combination, and crack cocaine. Latent class analysis was used to identify patterns of polysubstance use based on types of drugs used. Multivariate logistic regression analyses compared classes on demographics, sexual risk behavior, and disease status. Results Four classes of substance use were found: MJ+Cig (40.8%), MJ+Her (30.8%), Crack (24.7%), and Low Use (3.7%). The MJ+Cig class was 6.7 times more likely to use alcohol and 3 times more likely to use drugs before/during sex with steady partners than the Crack class. The MJ+Cig class was16 times more likely to use alcohol before/during sex with steady partners than the MJ+Her class. The Crack class was 6.1 times more likely to engage in transactional sex and less likely to use drugs before/during steady sex than the MJ+Her class. Conclusions Findings illustrate patterns of drug use among a polysubstance using population that differ in sexual risk behavior. Intervention strategies should address substance use, particularly smoking as a route of administration (ROA), and sexual risk behaviors that best fit this high-risk population. PMID:23562370

  1. An improved approach to measuring drug innovation finds steady rates of first-in-class pharmaceuticals, 1987-2011.

    Science.gov (United States)

    Lanthier, Michael; Miller, Kathleen L; Nardinelli, Clark; Woodcock, Janet

    2013-08-01

    For more than a decade, industry analysts and policy makers have raised concerns about declining pharmaceutical innovation, citing declining numbers of new molecular entities (NMEs) approved in the United States each year. Yet there is little consensus on whether this is the best measure of "innovation." We examined NME approvals during 1987-2011 and propose the three distinct subcategories of NMEs--first-in-class, advance-in-class, and addition-to-class--to provide more nuanced and informative insights into underlying trends. We found that trends in NME approvals were largely driven by addition-to-class, or "me too," drug approvals, while first-in-class approvals remained fairly steady over the study period. Moreover, the higher proportion of first-in-class drug approvals over the most recent decade is an encouraging sign of the health of the industry as a whole.

  2. Increasing complexity: which drug class to choose for treatment of hypertension in the elderly?

    Directory of Open Access Journals (Sweden)

    Kaiser EA

    2014-03-01

    Full Text Available Edelgard Anna Kaiser,1 Ulrich Lotze,2 Hans Hendrik Schäfer1,31Roche Diagnostics International AG, Rotkreuz, Switzerland; 2Department of Internal Medicine, DRK-Manniske-Krankenhaus Bad Frankenhausen, Bad Frankenhausen, Germany; 3Institute of Anatomy II, University Hospital Jena, Friedrich-Schiller University, Jena, GermanyAbstract: Treatment of hypertension in the elderly is expected to become more complex in the coming decades. Based on the current landscape of clinical trials, guideline recommendations remain inconclusive. The present review discusses the latest evidence derived from studies available in 2013 and investigates optimal blood pressure (BP and preferred treatment substances. Three common archetypes are discussed that hamper the treatment of hypertension in the very elderly. In addition, this paper presents the current recommendations of the NICE 2011, JNC7 2013-update, ESH/ESC 2013, CHEP 2013, JNC8 and ASH/ISH guidelines for elderly patients. Advantages of the six main substance classes, namely diuretics, beta-blockers (BBs, calcium channel blockers (CCBs, angiotensin-converting enzyme inhibitors (ACEIs, angiotensin receptor blockers (ARBs, and direct renin inhibitors (DRIs are discussed. Medical and economic implications of drug administration in the very elderly are presented. Avoidance of treatment-related adverse effects has become increasingly relevant. Current substance classes are equally effective, with similar effects on cardiovascular outcomes. Selection of substances should therefore also be based on collateral advantages of drugs that extend beyond BP reduction. The combination of ACEIs and diuretics appears to be favorable in managing systolic/diastolic hypertension. Diuretics are a preferred and cheap combination drug, and the combination with CCBs is recommended for patients with isolated systolic hypertension. ACEIs and CCBs are favorable for patients with dementia, while CCBs and ARBs imply substantial cost

  3. 76 FR 28688 - Draft Guidance for Industry and Food and Drug Administration Staff; Class II Special Controls...

    Science.gov (United States)

    2011-05-18

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration 21 CFR Part 866 [Docket No. FDA-2011-D-0102] Draft Guidance for Industry and Food and Drug Administration Staff; Class II Special Controls Guidance Document: In Vitro Diagnostic Devices for Bacillus Species Detection AGENCY: Food and...

  4. 76 FR 48870 - Guidance for Industry and Food and Drug Administration Staff; Class II Special Controls Guidance...

    Science.gov (United States)

    2011-08-09

    ... selection inclusion and exclusion criteria section. The revisions define and differentiate the required... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-D-0428] Guidance for Industry and Food and Drug Administration Staff; Class II Special Controls Guidance Document...

  5. 75 FR 59726 - Draft Guidance for Industry and Food and Drug Administration Staff; Class II Special Controls...

    Science.gov (United States)

    2010-09-28

    ... method comparison section and the sample selection inclusion and exclusion criteria section. The... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-D-0428] Draft Guidance for Industry and Food and Drug Administration Staff; Class II Special Controls Guidance...

  6. Individualization of treatments with drugs metabolized by CES1: combining genetics and metabolomics

    DEFF Research Database (Denmark)

    Rasmussen, Henrik B.; Bjerre, Ditte; Linnet, Kristian

    2015-01-01

    CES1 is involved in the hydrolysis of ester group-containing xenobiotic and endobiotic compounds including several essential and commonly used drugs. The individual variation in the efficacy and tolerability of many drugs metabolized by CES1 is considerable. Hence, there is a large interest in in...

  7. Robust Framework to Combine Diverse Classifiers Assigning Distributed Confidence to Individual Classifiers at Class Level

    Directory of Open Access Journals (Sweden)

    Shehzad Khalid

    2014-01-01

    Full Text Available We have presented a classification framework that combines multiple heterogeneous classifiers in the presence of class label noise. An extension of m-Mediods based modeling is presented that generates model of various classes whilst identifying and filtering noisy training data. This noise free data is further used to learn model for other classifiers such as GMM and SVM. A weight learning method is then introduced to learn weights on each class for different classifiers to construct an ensemble. For this purpose, we applied genetic algorithm to search for an optimal weight vector on which classifier ensemble is expected to give the best accuracy. The proposed approach is evaluated on variety of real life datasets. It is also compared with existing standard ensemble techniques such as Adaboost, Bagging, and Random Subspace Methods. Experimental results show the superiority of proposed ensemble method as compared to its competitors, especially in the presence of class label noise and imbalance classes.

  8. 10 CFR 26.67 - Random drug and alcohol testing of individuals who have applied for authorization.

    Science.gov (United States)

    2010-01-01

    ... 10 Energy 1 2010-01-01 2010-01-01 false Random drug and alcohol testing of individuals who have... PROGRAMS Granting and Maintaining Authorization § 26.67 Random drug and alcohol testing of individuals who... other entity relies on drug and alcohol tests that were conducted before the individual applied for...

  9. Prediction of individual mandibular changes induced by functional jaw orthopedics followed by fixed appliances in Class II patients.

    Science.gov (United States)

    Franchi, Lorenzo; Baccetti, Tiziano

    2006-11-01

    To identify pretreatment cephalometric variables for the prediction of individual mandibular outcomes of functional jaw orthopedics (FJO) followed by fixed appliances in Class II patients treated at the peak in mandibular growth. The study was performed on 51 subjects (24 females, 27 males) with Class II malocclusion. First-phase therapy was accomplished with a twin block in 16 subjects, a stainless steel crown Herbst in 15 subjects, and an acrylic splint Herbst in 20 subjects. Lateral cephalograms were available at the start of treatment with FJO and at the completion of fixed appliance therapy. All subjects received FJO at the peak in mandibular growth (CS 3 at T1). Individual responsiveness to Class II treatment including FJO was defined on the basis of the T2-T1 increment in total mandibular length (Co-Gn) when compared with untreated Class II subjects. Discriminant analysis identified a single predictive parameter (Co-Go-Me degrees) with a classification power of 80%. Pretreatment vertical and sagittal parameters were not able to improve the prediction based upon the mandibular angle. A Class II patient at the peak in skeletal maturation (CS 3) with a pretreatment Co-Go-Me degrees smaller than 125.5 degrees is expected to respond favorably to treatment including FJO. A Class II patient at CS 3 with a pretreatment value for Co-Go-Me degrees greater than 125.5 degrees is expected to respond poorly to treatment including FJO.

  10. Inhibitors of type II NADH:menaquinone oxidoreductase represent a class of antitubercular drugs

    Science.gov (United States)

    Weinstein, Edward A.; Yano, Takahiro; Li, Lin-Sheng; Avarbock, David; Avarbock, Andrew; Helm, Douglas; McColm, Andrew A.; Duncan, Ken; Lonsdale, John T.; Rubin, Harvey

    2005-01-01

    Mycobacterium tuberculosis (Mtb) is an obligate aerobe that is capable of long-term persistence under conditions of low oxygen tension. Analysis of the Mtb genome predicts the existence of a branched aerobic respiratory chain terminating in a cytochrome bd system and a cytochrome aa3 system. Both chains can be initiated with type II NADH:menaquinone oxidoreductase. We present a detailed biochemical characterization of the aerobic respiratory chains from Mtb and show that phenothiazine analogs specifically inhibit NADH:menaquinone oxidoreductase activity. The emergence of drug-resistant strains of Mtb has prompted a search for antimycobacterial agents. Several phenothiazines analogs are highly tuberculocidal in vitro, suppress Mtb growth in a mouse model of acute infection, and represent lead compounds that may give rise to a class of selective antibiotics. PMID:15767566

  11. Universal, class-specific and drug-specific reversal agents for the new oral anticoagulants.

    Science.gov (United States)

    Ansell, Jack E

    2016-02-01

    Although there is controversy about the absolute need for a reversal agent for the new direct oral anticoagulants (DOACs), the absence of such an agent is a barrier to more widespread use of these agents. For the management of major life-threatening bleeding with the DOACs, most authorities recommend the use of four factor prothrombin complex concentrates, although the evidence to support their use in terms of improving outcomes is meager. At the present time, there are three antidotes in development and poised to enter the market. Idarucizumab is a drug-specific antidote targeted to reverse the direct thrombin inhibitor, dabigatran. Andexanet alfa is a class-specific antidote targeted to reverse the oral direct factor Xa inhibitors as well as the indirect inhibitor, enoxaparin. Ciraparantag is a universal antidote targeted to reverse the direct thrombin and factor Xa inhibitors as well as the indirect inhibitor, enoxaparin.

  12. Serum concentrations of apelin-17 isoform vary in accordance to blood pressure categories in individuals with obesity class 3.

    Science.gov (United States)

    Cano Martínez, Luis Javier; Coral Vázquez, Ramón Mauricio; Méndez, Juan Pablo; Trejo, Silvia; Pérez Razo, Juan Carlos; Canto, Patricia

    2018-04-13

    The aim of this study was to investigate if serum concentrations of apelin-36, apelin-17, apelin-13 or apelin-12 were different in obesity class 3 individuals with hypertension, when compared to those without hypertension (normal or high-normal). Twenty six individuals with obesity class 3-related hypertension and thirty three individuals without hypertension, who were divided in individuals with normal (n = 23) or with high-normal (n = 10) blood pressure (BP) were analyzed. All individuals presented obesity class 3, without diabetes mellitus. Measurements of all apelin isoforms were performed using enzyme-linked immunosorbent assay kits. Analysis of differences between groups of Apelin isoform concentrations was performed by a One-way ANOVA, with a Tukey test post hoc. The individuals of the hypertensive group presented a slightly lower serum concentration of all apelin isoforms, but these differences were not statistically significant. These results were more evident when the group of patients without hypertension were divided based in normal and high-normal BP, observing that apelin-17 isoform were higher in individuals with high-normal BP in comparison to subjects with normal BP (P = 0.018); concentrations were also higher when compared to subjects with hypertension (P = 0.004). To our knowledge, this is the first study regarding the differences of apelin-17 isoform concentrations in individuals pertaining to different categories of BP, who presented obesity class 3. The group of patients that presented hypertension showed a lower concentration of all isoforms. This observation could be due to the fact that these patients were taking antihypertensive medication.

  13. Aligning Coordination Class Theory with a New Context: Applying a Theory of Individual Learning to Group Learning

    Science.gov (United States)

    Barth-Cohen, Lauren A.; Wittmann, Michael C.

    2017-01-01

    This article presents an empirical analysis of conceptual difficulties encountered and ways students made progress in learning at both individual and group levels in a classroom environment in which the students used an embodied modeling activity to make sense of a specific scientific scenario. The theoretical framework, coordination class theory,…

  14. The Role of Self-Monitoring in Assessing Individual Students' Quantity and Quality of Comments in Large-Class Discussion

    Science.gov (United States)

    Carstens, B. A.; Wright, J. M.; Coles, J. T.; McCleary, L. N.; Williams, R. L.

    2013-01-01

    This study developed a reliable and valid self-monitoring procedure for student use in recording and rating the quality of their individual comments in large college classes. Students used daily record cards immediately to record and rate each comment they made each day. However, a limit was set on the amount of credit students could claim for…

  15. Income and the use of prescription drugs for near retirement individuals

    DEFF Research Database (Denmark)

    Leth-Petersen, Søren; Skipper, Niels

    Understanding how demand for prescription drugs responds to changes in income is important for assessing the welfare consequences of reforms affecting income. This becomes more imminent as age progresses, because the use of prescription drugs and the associated budgetary burden increases dramatic......Understanding how demand for prescription drugs responds to changes in income is important for assessing the welfare consequences of reforms affecting income. This becomes more imminent as age progresses, because the use of prescription drugs and the associated budgetary burden increases...... dramatically from about age 55. In this paper we estimate how demand for prescription drugs varies with income for a sample of near retirement individuals. Estimating the prescription drug demand response to income changes is complicated because an important explanatory variable, the health capital......, is unobserved, and because demand is potentially dynamic, for example because some drugs are habitual. The analysis is based on a novel panel data set with information about purchase of prescription drug demand for a very large number of Danish individuals over the period 1995-2003. Our preferred model...

  16. Management of skeletal Class III malocclusion with reverse pull headgear in a growing individual

    OpenAIRE

    Ambreen Afzal; Hasnain Sakrani; Norisha Ehsan Mahmood; Kamellia Mehershahi; Fatima Burney

    2016-01-01

    Skeletal Class III malocclusion is considered to be one of the most difficult orthodontic problems to treat. This malocclusion is associated with the retrognathic maxilla or prognathic mandible or sometimes a combination of both. The treatment of such cases requires an integrated approach and a comprehensive treatment plan including growth modification, dental camouflage, or orthognathic surgery. In a growing patient, orthopedic correction of skeletal Class III malocclusion with the help of a...

  17. Individual differences and vulnerability to drug addiction: a focus on the endocannabinoid system.

    Science.gov (United States)

    Sagheddu, Claudia; Melis, Miriam

    2015-01-01

    Vulnerability to drug addiction depends upon the interactions between the biological makeup of the individual, the environment, and age. These interactions are complex and difficult to tease apart. Since dopamine is involved in the rewarding effects of drugs of abuse, it is postulated that innate differences in mesocorticolimbic pathway can influence the response to drug exposure. In particular, higher and lower expression of dopamine D2 receptors in the ventral striatum (i.e. a marker of dopamine function) has been considered a putative protective and a risk factor, respectively, that can influence one's susceptibility to continued drug abuse as well as the transition to addiction. This phenomenon, which is phylogenetically preserved, appears to be a compensatory change to increased impulse activity of midbrain dopamine neurons. Hence, dopamine neuronal excitability plays a fundamental role in the diverse stages of the drug addiction cycle. In this review, a framework for the evidence that modulation of dopamine neuronal activity plays in the context of vulnerability to drug addiction will be presented. Furthermore, since endogenous cannabinoids serve as retrograde messengers to shape afferent neuronal activity in a short- and long-lasting fashion, their role in individual differences and vulnerability to drug addiction will be discussed.

  18. Injection Drug Use and Hepatitis C as Risk Factors for Mortality in HIV-Infected Individuals

    DEFF Research Database (Denmark)

    May, Margaret T; Justice, Amy C; Birnie, Kate

    2015-01-01

    BACKGROUND: HIV-infected individuals with a history of transmission through injection drug use (IDU) have poorer survival than other risk groups. The extent to which higher rates of hepatitis C (HCV) infection in IDU explain survival differences is unclear. METHODS: Adults who started...

  19. Individuals with severe mental illnesses have improved eating behaviors and cooking skills after attending a 6-week nutrition cooking class.

    Science.gov (United States)

    Clark, Alena; Bezyak, Jill; Testerman, Nora

    2015-09-01

    This study assessed current meal planning/cooking behaviors and dietary intake of individuals with severe mental illnesses and determined differences after a 6-week nutrition education cooking class. Eighteen individuals with severe mental illnesses participated in a 6-week nutrition education cooking class and completed pre- and posttest 24-hr recalls and a postretrospective survey. Paired samples t tests were used. Participants met their calories needs, but they consumed high amounts of sodium and fat and low amounts of fiber. Significant increases in calcium, vitamin D, grains, and fruit occurred from pre- to posttest (p cooking and grocery shopping skills improved. Participants desire nutrition education programming that includes simple messages, hands-on cooking demonstrations, and health-related incentives. More research is needed to determine how nutrition education programs lead to sustained knowledge and behavior change within this specialized population. (c) 2015 APA, all rights reserved).

  20. Stepwise latent class models for explaining group-level putcomes using discrete individual-level predictors

    NARCIS (Netherlands)

    Bennink, Margot; Croon, M.A.; Vermunt, J.K.

    2015-01-01

    Explaining group-level outcomes from individual-level predictors requires aggregating the individual-level scores to the group level and correcting the group-level estimates for measurement errors in the aggregated scores. However, for discrete variables it is not clear how to perform the

  1. In silico prediction of drug dissolution and absorption with variation in intestinal pH for BCS class II weak acid drugs: ibuprofen and ketoprofen.

    Science.gov (United States)

    Tsume, Yasuhiro; Langguth, Peter; Garcia-Arieta, Alfredo; Amidon, Gordon L

    2012-10-01

    The FDA Biopharmaceutical Classification System guidance allows waivers for in vivo bioavailability and bioequivalence studies for immediate-release solid oral dosage forms only for BCS class I. Extensions of the in vivo biowaiver for a number of drugs in BCS class III and BCS class II have been proposed, in particular, BCS class II weak acids. However, a discrepancy between the in vivo BE results and in vitro dissolution results for BCS class II acids was recently observed. The objectives of this study were to determine the oral absorption of BCS class II weak acids via simulation software and to determine if the in vitro dissolution test with various dissolution media could be sufficient for in vitro bioequivalence studies of ibuprofen and ketoprofen as models of carboxylic acid drugs. The oral absorption of these BCS class II acids from the gastrointestinal tract was predicted by GastroPlus™. Ibuprofen did not satisfy the bioequivalence criteria at lower settings of intestinal pH of 6.0. Further the experimental dissolution of ibuprofen tablets in a low concentration phosphate buffer at pH 6.0 (the average buffer capacity 2.2 mmol l (-1) /pH) was dramatically reduced compared with the dissolution in SIF (the average buffer capacity 12.6 mmol l (-1) /pH). Thus these predictions for the oral absorption of BCS class II acids indicate that the absorption patterns depend largely on the intestinal pH and buffer strength and must be considered carefully for a bioequivalence test. Simulation software may be a very useful tool to aid the selection of dissolution media that may be useful in setting an in vitro bioequivalence dissolution standard. Copyright © 2012 John Wiley & Sons, Ltd.

  2. In Silico Prediction of Drug Dissolution and Absorption with variation in Intestinal pH for BCS Class II Weak Acid Drugs: Ibuprofen and Ketoprofen§

    Science.gov (United States)

    Tsume, Yasuhiro; Langguth, Peter; Garcia-Arieta, Alfredo; Amidon, Gordon L.

    2012-01-01

    The FDA Biopharmaceutical Classification System guidance allows waivers for in vivo bioavailability and bioequivalence studies for immediate-release solid oral dosage forms only for BCS class I. Extensions of the in vivo biowaiver for a number of drugs in BCS Class III and BCS class II have been proposed, particularly, BCS class II weak acids. However, a discrepancy between the in vivo- BE results and in vitro- dissolution results for a BCS class II acids was recently observed. The objectives of this study were to determine the oral absorption of BCS class II weak acids via simulation software and to determine if the in vitro dissolution test with various dissolution media could be sufficient for in vitro bioequivalence studies of ibuprofen and ketoprofen as models of carboxylic acid drugs. The oral absorption of these BCS class II acids from the gastrointestinal tract was predicted by GastroPlus™. Ibuprofen did not satisfy the bioequivalence criteria at lower settings of intestinal pH=6.0. Further the experimental dissolution of ibuprofen tablets in the low concentration phosphate buffer at pH 6.0 (the average buffer capacity 2.2 mmol L-1/pH) was dramatically reduced compared to the dissolution in SIF (the average buffer capacity 12.6 mmol L -1/pH). Thus these predictions for oral absorption of BCS class II acids indicate that the absorption patterns largely depend on the intestinal pH and buffer strength and must be carefully considered for a bioequivalence test. Simulation software may be very useful tool to aid the selection of dissolution media that may be useful in setting an in vitro bioequivalence dissolution standard. PMID:22815122

  3. Management of skeletal Class III malocclusion with reverse pull headgear in a growing individual

    Directory of Open Access Journals (Sweden)

    Ambreen Afzal

    2016-01-01

    Full Text Available Skeletal Class III malocclusion is considered to be one of the most difficult orthodontic problems to treat. This malocclusion is associated with the retrognathic maxilla or prognathic mandible or sometimes a combination of both. The treatment of such cases requires an integrated approach and a comprehensive treatment plan including growth modification, dental camouflage, or orthognathic surgery. In a growing patient, orthopedic correction of skeletal Class III malocclusion with the help of a reverse pull headgear is crucial as it can reduce the chances of further surgical treatment to correct the skeletal discrepancy. This case report describes the management of skeletal Class III malocclusion in a 12-year-old female child with a retrognathic maxilla. The patient did not have any other genetic abnormality or significant known comorbidity. The treatment plan involved fixed orthodontic appliance therapy in combination with a reverse pull headgear for an orthopedic effect. This treatment was continued for 3 years, and well-aligned dental arches with a positive over jet were achieved at the conclusion of treatment. Using facemask therapy in conjunction with fixed orthodontic appliances has been a successful treatment option in growing children. Treatment should be carried out as early as possible to correct the skeletal discrepancy nonsurgically and achieve better results.

  4. Nephrogenic systemic fibrosis and class labeling of gadolinium-based contrast agents by the Food and Drug Administration.

    Science.gov (United States)

    Yang, Lucie; Krefting, Ira; Gorovets, Alex; Marzella, Louis; Kaiser, James; Boucher, Robert; Rieves, Dwaine

    2012-10-01

    In 2007, the Food and Drug Administration requested that manufacturers of all approved gadolinium-based contrast agents (GBCAs), drugs widely used in magnetic resonance imaging, use nearly identical text in their product labeling to describe the risk of nephrogenic systemic fibrosis (NSF). Accumulating information about NSF risks led to revision of the labeling text for all of these drugs in 2010. The present report summarizes the basis and purpose of this class-labeling approach and describes some of the related challenges, given the evolutionary nature of the NSF risk evidence. The class-labeling approach for presentation of product risk is designed to decrease the occurrence of NSF and to enhance the safe use of GBCAs in radiologic practice. © RSNA, 2012.

  5. Students who developed logical reasoning skills reported improved confidence in drug dose calculation: Feedback from remedial maths classes.

    Science.gov (United States)

    Shelton, Chris

    2016-06-01

    The safe administration of drugs is a focus of attention in healthcare. It is regarded as acceptable that a formula card or mnemonic can be used to find the correct dose and fill a prescription even though this removes any requirement for performing the underlying computation. Feedback and discussion in class reveal that confidence in arithmetic skills can be low even when students are able to pass the end of semester drug calculation exam. To see if confidence in the understanding and performance of arithmetic for drug calculations can be increased by emphasising student's innate powers of logical reasoning after reflection. Remedial classes offered for students who have declared a dislike or lack of confidence in arithmetic have been developed from student feedback adopting a reasoning by logical step methodology. Students who gave up two hours of their free learning time were observed to engage seriously with the learning methods, focussing on the innate ability to perform logical reasoning necessary for drug calculation problems. Working in small groups allowed some discussion of the route to the answer and this was followed by class discussion and reflection. The results were recorded as weekly self-assessment scores for confidence in calculation. A self-selecting group who successfully completed the end of semester drug calculation exam reported low to moderate confidence in arithmetic. After four weeks focussing on logical skills a significant increase in self-belief was measured. This continued to rise in students who remained in the classes. Many students hold a negative belief regarding their own mathematical abilities. This restricts the learning of arithmetic skills making alternate routes using mnemonics and memorised steps an attractive alternative. Practising stepwise logical reasoning skills consolidated by personal reflection has been effective in developing student's confidence and awareness of their innate powers of deduction supporting an

  6. Individual Differences and Social Influences on the Neurobehavioral Pharmacology of Abused Drugs

    Science.gov (United States)

    Neisewander, J. L.; Kelly, T. H.

    2013-01-01

    The interaction of drugs with biologic targets is a critical area of research, particularly for the development of medications to treat substance use disorders. In addition to understanding these drug-target interactions, however, there is a need to understand more fully the psychosocial influences that moderate these interactions. The first section of this review introduces some examples from human behavioral pharmacology that illustrate the clinical importance of this research. The second section covers preclinical evidence to characterize some of the key individual differences that alter drug sensitivity and abuse vulnerability, related primarily to differences in response to novelty and impulsivity. Evidence is presented to indicate that critical neuropharmacological mechanisms associated with these individual differences involve integrated neurocircuits underlying stress, reward, and behavioral inhibitory processes. The third section covers social influences on drug abuse vulnerability, including effects experienced during infancy, adolescence, and young adulthood, such as maternal separation, housing conditions, and social interactions (defeat, play, and social rank). Some of the same neurocircuits involved in individual differences also are altered by social influences, although the precise neurochemical and cellular mechanisms involved remain to be elucidated fully. Finally, some speculation is offered about the implications of this research for the prevention and treatment of substance abuse. PMID:23343975

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

    Science.gov (United States)

    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.

  8. Relationship between Individual Characteristics and High Risk Behavior in Intravenous Drug Addicts in Ardabil, 2012

    Directory of Open Access Journals (Sweden)

    Nasrin Fouladi

    2014-12-01

    Full Text Available Background & objectives: Addiction is one of the problems in world threating the social, economic and culture factors. It is essential to have an accurate knowledge about the characteristics of drug users in order to diminish the high-risk behaviors of intravenous drug addicts. This research has been done to assess relationship between individual characteristics and high risk behavior in intravenous drug addicts.   Method: In this descriptive-analytic research, 360 drug users were selected from different places in Ardabil city and interviewed by a prepared questionnaire. The data were analyzed using descriptive and analytical tests including t-test, Pearson correlation and ANOVA with SPSS statistical software.   Results: The results showed that the age, gender, material status, job position, age of addiction start, age of injection start, injection frequency, injection frequency per day, syringe supply place and the partner’s gender during recent few months had no significant difference compared to drug users with needle sharing and without needle sharing. The educational level of drug users with needle sharing was lower (P=0.037 and the number of new syringe usage per month was also lesser (P=0.001. They predicted to be more likely infected with AIDS (P=0.001 and had a less argument with their partner about using condom, also mostly have not used condom at their last sexual relationship (P=0.001. The average number of their partners during last three months was high (P=0.003 and there was a meaningful relationship between true sense of peril and using condom in drug users with needle sharing group (p=0.001.   Conclusion: There is a significant relationship between the true sense of danger and the using condom. It is necessary to have an appropriate advertising to increase using condoms among injecting drug users.

  9. Limited Representation of Individuals with Disabilities in Early Childhood Classes: Alarming or Status Quo?

    Science.gov (United States)

    Favazza, Paddy C.; Ostrosky, Michaelene M.; Meyer, Lori E.; Yu, SeonYeong; Mouzourou, Chryso

    2017-01-01

    UNICEF's new Millennium Development Goals and Beyond (2015. http://www.un.org/millenniumgoals/) focus on the needs of the largest marginalised minority, individuals with disabilities, challenging us to examine issues related to exclusion and develop strategies for making an authentic sense of belonging and high-quality early childhood education a…

  10. Unique molecular landscapes in cancer: implications for individualized, curated drug combinations.

    Science.gov (United States)

    Wheler, Jennifer; Lee, J Jack; Kurzrock, Razelle

    2014-12-15

    With increasingly sophisticated technologies in molecular biology and "omic" platforms to analyze patients' tumors, more molecular diversity and complexity in cancer are being observed. Recently, we noted unique genomic profiles in a group of patients with metastatic breast cancer based on an analysis with next-generation sequencing. Among 57 consecutive patients, no two had the same molecular portfolio. Applied genomics therefore appears to represent a disruptive innovation in that it unveils a heterogeneity to metastatic cancer that may be ill-suited to canonical clinical trials and practice paradigms. Upon recognizing that patients have unique tumor landscapes, it is possible that there may be a "mismatch" between our traditional clinical trials system that selects patients based on common characteristics to evaluate a drug (drug-centric approach) and optimal treatment based on curated, individualized drug combinations for each patient (patient-centric approach). ©2014 American Association for Cancer Research.

  11. Individualized drug dosing using RBF-Galerkin method: Case of anemia management in chronic kidney disease.

    Science.gov (United States)

    Mirinejad, Hossein; Gaweda, Adam E; Brier, Michael E; Zurada, Jacek M; Inanc, Tamer

    2017-09-01

    Anemia is a common comorbidity in patients with chronic kidney disease (CKD) and is frequently associated with decreased physical component of quality of life, as well as adverse cardiovascular events. Current treatment methods for renal anemia are mostly population-based approaches treating individual patients with a one-size-fits-all model. However, FDA recommendations stipulate individualized anemia treatment with precise control of the hemoglobin concentration and minimal drug utilization. In accordance with these recommendations, this work presents an individualized drug dosing approach to anemia management by leveraging the theory of optimal control. A Multiple Receding Horizon Control (MRHC) approach based on the RBF-Galerkin optimization method is proposed for individualized anemia management in CKD patients. Recently developed by the authors, the RBF-Galerkin method uses the radial basis function approximation along with the Galerkin error projection to solve constrained optimal control problems numerically. The proposed approach is applied to generate optimal dosing recommendations for individual patients. Performance of the proposed approach (MRHC) is compared in silico to that of a population-based anemia management protocol and an individualized multiple model predictive control method for two case scenarios: hemoglobin measurement with and without observational errors. In silico comparison indicates that hemoglobin concentration with MRHC method has less variation among the methods, especially in presence of measurement errors. In addition, the average achieved hemoglobin level from the MRHC is significantly closer to the target hemoglobin than that of the other two methods, according to the analysis of variance (ANOVA) statistical test. Furthermore, drug dosages recommended by the MRHC are more stable and accurate and reach the steady-state value notably faster than those generated by the other two methods. The proposed method is highly efficient for

  12. Examining substance use among rural Appalachian and urban non-Appalachian individuals participating in drug court.

    Science.gov (United States)

    Shannon, Lisa M; Perkins, Elizabeth B; Neal, Connie

    2014-02-01

    The study purpose was to examine differences in substance use among individuals in drug court (N = 583) in rural Appalachian (n = 301) and urban non-Appalachian areas (n = 282). A series of logistic regression analyses suggested individuals in the rural Appalachian area were significantly more likely to report lifetime use of cocaine, illicit opiates, and illicit benzodiazepines, but they were less likely to report methamphetamine use when compared with individuals in the urban non-Appalachian area. Regarding past 30-day use, a series of logistic regression analyses suggested individuals in the rural Appalachian area were significantly more likely to use marijuana, illicit opiates, and illicit benzodiazepines, but they were less likely to report crack cocaine use when compared with individuals in the urban non-Appalachian area. Identifying differences which exist in substance use is the first step in generating evidence-based structural changes in treatment drug court programs. Future research should focus on better understanding context in terms of demographic, geographic, and economic conditions, which may be of critical influence on substance use and treatment planning.

  13. A cocaine context renews drug seeking preferentially in a subset of individuals.

    Science.gov (United States)

    Saunders, Benjamin T; O'Donnell, Elizabeth G; Aurbach, Elyse L; Robinson, Terry E

    2014-11-01

    Addiction is characterized by a high propensity for relapse, in part because cues associated with drugs can acquire Pavlovian incentive motivational properties, and acting as incentive stimuli, such cues can instigate and invigorate drug-seeking behavior. There is, however, considerable individual variation in the propensity to attribute incentive salience to reward cues. Discrete and localizable reward cues act as much more effective incentive stimuli in some rats ('sign-trackers', STs), than others ('goal-trackers', GTs). We asked whether similar individual variation exists for contextual cues associated with cocaine. Cocaine context conditioned motivation was quantified in two ways: (1) the ability of a cocaine context to evoke conditioned hyperactivity and (2) the ability of a context in which cocaine was previously self-administered to renew cocaine-seeking behavior. Finally, we assessed the effects of intra-accumbens core flupenthixol, a nonselective dopamine receptor antagonist, on context renewal. In contrast to studies using discrete cues, a cocaine context spurred greater conditioned hyperactivity, and more robustly renewed extinguished cocaine seeking in GTs than STs. In addition, cocaine context renewal was blocked by antagonism of dopamine receptors in the accumbens core. Thus, contextual cues associated with cocaine preferentially acquire motivational control over behavior in different individuals than do discrete cues, and in these individuals the ability of a cocaine context to create conditioned motivation for cocaine requires dopamine in the core of the nucleus accumbens. We speculate that different individuals may be preferentially sensitive to different 'triggers' of relapse.

  14. Outlier populations: individual and social network correlates of solvent-using injection drug users.

    Directory of Open Access Journals (Sweden)

    Souradet Y Shaw

    Full Text Available We previously identified a high prevalence of Hepatitis C (HCV amongst solvent-using injection drug users (S-IDU relative to other injection drug users within the same locality. Here we incorporated social network variables to better characterize some of the behavioural characteristics that may be putting this specific subgroup of IDU at elevated disease risk.A cross-sectional survey of at-risk populations was carried out in Winnipeg, Canada in 2009. Individuals reporting any history of injection drug and/or solvent use were included in the study. Associations between subgroup membership, infection with HCV and HIV and individual and social network variables were examined.In relation to other IDU, S-IDU were more likely to be infected with HCV, to report ever having shared a syringe, and to associate with other IDU. They were further differentiated in terms of their self-reported sexual orientation, ethnicity and in the injection drugs typically used.Solvent use stands as a proxy measure of numerous other characteristics that put this group of IDU at higher risk of infection. Provision of adequate services to ostracized subpopulations may result in wider population-level benefits.

  15. Gastrointestinal Behavior of Weakly Acidic BCS Class II Drugs in Man--Case Study of Diclofenac Potassium.

    Science.gov (United States)

    Van Den Abeele, Jens; Brouwers, Joachim; Mattheus, Ruben; Tack, Jan; Augustijns, Patrick

    2016-02-01

    This study aimed to investigate the gastrointestinal supersaturation and precipitation behavior of a weakly acidic Biopharmaceutics Classification System (BCS) Class II drug in healthy volunteers. For this purpose, a tablet containing 50 mg diclofenac potassium (Cataflam(®)) was predissolved in 240 mL of water and this solution was subsequently orally administered to five healthy volunteers under fasted and fed state conditions with or without concomitant use of a proton-pump inhibitor (PPI) (40 mg esomeprazole, Nexiam(®)). Subsequently, total diclofenac content and dissolved intraluminal drug concentrations as well as drug thermodynamic solubility were determined in gastrointestinal aspirates. In all volunteers, gastric supersaturation resulted in precipitation of diclofenac in the stomach. The extent of precipitation correlated well with gastric pH (r = - 0.78). pH dependency of precipitation was corroborated by the absence of precipitate in the stomach after coadministration of a meal and/or a PPI. Diclofenac was found to be fully dissolved in the duodenum in all test conditions. It can be concluded that substantial pH-dependent gastric precipitation of a weakly acidic BCS Class II drug administered as a solution occurs in humans. With regard to its implications for intestinal absorption, results suggest the instantaneous redissolution of gastric drug precipitate upon transfer to the duodenum. Copyright © 2016. Published by Elsevier Inc.

  16. A Comparative Analysis of Pair-work and Individual Assignments In two ELT Grammar Classes

    Directory of Open Access Journals (Sweden)

    Olcay Sert

    2005-10-01

    Full Text Available Assignments prepared in pair-work have long been evaluated to be more successful whencompared to individually prepared assignments in many respects in foreign language learningcontexts. However, there is not much research conducted to reveal the advantages of pair-work in preparing assignments and the linguistic characteristics of the finished texts. In this paper, depending upon an experimental study with the first year students in Department of EnglishLanguage Teaching at Hacettepe University, quality of pair-work assignments and the factors affecting the preparation process are discussed and compared to individual assignments. Results indicate a variety of advantages of student collaboration in preparing written work since outputsare far more grammatical, include less spelling mistakes, and indicate a higher level ofgrammatical awareness. Additionally, pair-work helps students build positive interpersonalrelationships and create a high level of academic solidarity and confidence.

  17. Prescription Monitoring Program Trends Among Individuals Arrested in Maine for Trafficking Prescription Drugs in 2014.

    Science.gov (United States)

    McCall, Kenneth; Nichols, Stephanie D; Holt, Christina; Ochs, Leslie; Cattabriga, Gary; Tu, Chunhao

    2016-06-01

    To evaluate controlled substance prescribing trends available in the Maine Prescription Monitoring Program (PMP) among individuals arrested for prescription drug "trafficking." The demographic characteristics of the individuals who had matching prescription records in the PMP within 90 days of the arrest were identified. A population-based, retrospective cohort study using data from the Maine Diversion Alert Program (DAP) and the Maine PMP. The study population consisted of persons arrested for trafficking prescription drugs in Maine during the 2014 calendar year from January 1 to December 31. There were 594 trafficking arrests reported by the Maine DAP in 2014. The study population consisted of the 235 persons (40%) with arrests involving controlled prescription medications. The mean age of these persons was 33 years (range 18-77 yrs), and 156 (66%) were male. Arrests involved 154 prescription opioids (65%), seven stimulants (3%), seven benzodiazepines (3%), and 77 unspecified controlled prescription drugs (33%). A minority of individuals (n=57, 24%) had a prescription record in the PMP that matched the substance involved in the arrest. Only one person with matching PMP and arrest records utilized ≥ 5 prescribers, while none used ≥ 5 pharmacies within 90 days before the arrest. Payment methods for matching prescriptions were commercial insurance (n=28, 49%), Medicaid (n=19, 33%), Medicare (n=5, 9%), and cash (n=5, 9%). The majority (76%) of persons arrested for prescription drug trafficking did not have PMP records and did not directly obtain the diverted medication from a licensed pharmacy. Traditional red flags, like cash payment and using multiple prescribers or pharmacies, were uncommon. Therefore, arrest records for diversion and PMPs are distinct and complementary tools for identifying individuals at risk for substance misuse. © 2016 Pharmacotherapy Publications, Inc.

  18. Analysis of individual drug use as a time-varying determinant of exposure in prospective population-based cohort studies

    NARCIS (Netherlands)

    B.H.Ch. Stricker (Bruno); Th. Stijnen (Theo)

    2010-01-01

    textabstractIn pharmaco-epidemiology, the use of drugs is the determinant of interest when studying exposure-outcome associations. The increased availability of computerized information about drug use on an individual basis has greatly facilitated analyses of drug effects on a population-based

  19. Gradient of association between parenting styles and patterns of drug use in adolescence: A latent class analysis.

    Science.gov (United States)

    Valente, Juliana Y; Cogo-Moreira, Hugo; Sanchez, Zila M

    2017-11-01

    To identify different patterns of drug use in adolescence and determine if these are associated with parenting styles and other sociodemographic factors. A latent class analysis was conducted using baseline data collected in a sample (n=6381) from a randomized controlled trial conducted to evaluate the effectiveness of the #Tamojunto drug-use prevention program, carried out with 7th- and 8th-grade public school students in six Brazilian cities. Three latent classes were identified among the students: 1) abstainers/low users (81.54%), 2) alcohol users/binge drinkers (16.65%), and 3) polydrug users (1.80%). A gradient of inverse association was found between parenting styles (authoritative, authoritarian, and indulgent, with the neglectful style as a reference point) and the classes "alcohol users/binge drinkers" (aOR=0.36, 95%CI=0.27-0.47; aOR=0.56, 95%CI=0.43-0.72; and aOR=0.64, 95%CI=0.51-0.80, respectively) and "polydrug users" (aOR=0.09, 95%CI=0.03-0.24; aOR=0.23, 95%CI=0.11-0.52; and aOR=0.24, 95%CI=0.08-0.74, respectively). Associations were also revealed between the latent classes and the adolescent's age and socioeconomic status. The results suggest that activities to develop parenting skills should be included in school programs aimed at the prevention of drug use among adolescents in order to reduce neglectful practices and thereby possibly reduce drug use among the children. Copyright © 2017. Published by Elsevier B.V.

  20. The Combination of GIS and Biphasic to Better Predict In Vivo Dissolution of BCS Class IIb Drugs, Ketoconazole and Raloxifene.

    Science.gov (United States)

    Tsume, Yasuhiro; Igawa, Naoto; Drelich, Adam J; Amidon, Gregory E; Amidon, Gordon L

    2018-01-01

    The formulation developments and the in vivo assessment of Biopharmaceutical Classification System (BCS) class II drugs are challenging due to their low solubility and high permeability in the human gastrointestinal (GI) tract. Since the GI environment influences the drug dissolution of BCS class II drugs, the human GI characteristics should be incorporated into the in vitro dissolution system to predict bioperformance of BCS class II drugs. An absorptive compartment may be important in dissolution apparatus for BCS class II drugs, especially for bases (BCS IIb) because of high permeability, precipitation, and supersaturation. Thus, the in vitro dissolution system with an absorptive compartment may help predicting the in vivo phenomena of BCS class II drugs better than compendial dissolution apparatuses. In this study, an absorptive compartment (a biphasic device) was introduced to a gastrointestinal simulator. This addition was evaluated if this in vitro system could improve the prediction of in vivo dissolution for BCS class IIb drugs, ketoconazole and raloxifene, and subsequent absorption. The gastrointestinal simulator is a practical in vivo predictive tool and exhibited an improved in vivo prediction utilizing the biphasic format and thus a better tool for evaluating the bioperformance of BCS class IIb drugs than compendial apparatuses. Copyright © 2018. Published by Elsevier Inc.

  1. Development of sustained and dual drug release co-extrusion formulations for individual dosing.

    Science.gov (United States)

    Laukamp, Eva Julia; Vynckier, An-Katrien; Voorspoels, Jody; Thommes, Markus; Breitkreutz, Joerg

    2015-01-01

    In personalized medicine and patient-centered medical treatment individual dosing of medicines is crucial. The Solid Dosage Pen (SDP) allows for an individual dosing of solid drug carriers by cutting them into tablet-like slices. The aim of the present study was the development of sustained release and dual release formulations with carbamazepine (CBZ) via hot-melt co-extrusion for the use in the SDP. The selection of appropriate coat- and core-formulations was performed by adapting the mechanical properties (like tensile strength and E-modulus) for example. By using different excipients (polyethyleneglycols, poloxamers, white wax, stearic acid, and carnauba wax) and drug loadings (30-50%) tailored dissolution kinetics was achieved showing cube root or zero order release mechanisms. Besides a biphasic drug release, the dose-dependent dissolution characteristics of sustained release formulations were minimized by a co-extruded wax-coated formulation. The dissolution profiles of the co-extrudates were confirmed during short term stability study (six months at 21.0 ± 0.2 °C, 45%r.h.). Due to a good layer adhesion of core and coat and adequate mechanical properties (maximum cutting force of 35.8 ± 2.0 N and 26.4 ± 2.8 N and E-modulus of 118.1 ± 8.4 and 33.9 ± 4.5 MPa for the dual drug release and the wax-coated co-extrudates, respectively) cutting off doses via the SDP was precise. While differences of the process parameters (like the barrel temperature) between the core- and the coat-layer resulted in unsatisfying content uniformities for the wax-coated co-extrudates, the content uniformity of the dual drug release co-extrudates was found to be in compliance with pharmacopoeial specification. Copyright © 2015 Elsevier B.V. All rights reserved.

  2. Simultaneous screening and confirmation of multiple classes of drug residues in fish by liquid chromatography-ion trap mass spectrometry.

    Science.gov (United States)

    Smith, Shani; Gieseker, Charles; Reimschuessel, Renate; Decker, Christie-Sue; Carson, Mary C

    2009-11-13

    LC-ion trap mass spectrometry was used to screen and confirm 38 compounds from a variety of drug classes in four species of fish: trout, salmon, catfish, and tilapia. Samples were extracted with acetonitrile and hexane. The acetonitrile phase was evaporated, redissolved in water and acetonitrile, and analyzed by gradient chromatography on a phenyl column. MS(2) or MS(3) spectra were monitored for each compound. Qualitative method performance was evaluated by the analysis over several days of replicate samples of control fish, fish fortified with a drug mixture at 1 ppm, 0.1 ppm and 0.01 ppm, and fish dosed with a representative from each drug class. Half of the 38 drugs were confirmed at 0.01 ppm, the lowest fortification level. This included all of the quinolones and fluoroquinolones, the macrolides, malachite green, and most of the imidazoles. Florfenicol amine, metronidazole, sulfonamides, tetracyclines, and most of the betalactams were confirmed at 0.1 ppm. Ivermectin and penicillin G were only detectable in the 1 ppm fortified samples. With the exception of amoxicillin, emamectin, metronidazole, and tylosin, residue presence was confirmed in all the dosed fish.

  3. Evaluation of Students' Perceptions Towards An Innovative Teaching-Learning Method During Pharmacology Revision Classes: Autobiography of Drugs.

    Science.gov (United States)

    Joshi, Anuradha; Ganjiwale, Jaishree

    2015-07-01

    Various studies in medical education have shown that active learning strategies should be incorporated into the teaching-learning process to make learning more effective, efficient and meaningful. The aim of this study was to evaluate student's perceptions on an innovative revision method conducted in Pharmacology i.e. in form of Autobiography of Drugs. The main objective of study was to help students revise the core topics in Pharmacology in an interesting way. Questionnaire based survey on a newer method of pharmacology revision in two batches of second year MBBS students of a tertiary care teaching medical college. Various sessions on Autobiography of Drugs were conducted amongst two batches of second year MBBS students, during their Pharmacology revision classes. Student's perceptions were documented with the help of a five point likert scale through a questionnaire regarding quality, content and usefulness of this method. Descriptive analysis. Students of both the batches appreciated the innovative method taken up for revision. The median scores in most of the domains in both batches were four out of five, indicative of good response. Feedback from open-ended questions also revealed that the innovative module on "Autobiography of Drugs" was taken as a positive learning experience by students. Autobiography of drugs has been used to help students recall topics that they have learnt through other teachings methods. Autobiography sessions in Pharmacology during revision slots, can be one of the interesting ways in helping students revise and recall topics which have already been taught in theory classes.

  4. An inert 3D emulsification device for individual precipitation and concentration of amorphous drug nanoparticles.

    Science.gov (United States)

    Lorenz, T; Bojko, S; Bunjes, H; Dietzel, A

    2018-02-13

    Nanosizing increases the specific surface of drug particles, leading to faster dissolution inside the organism and improving the bioavailability of poorly water-soluble drugs. A novel approach for the preparation of drug nanoparticles in water using chemically inert microfluidic emulsification devices is presented in this paper. A lithographic fabrication sequence was established, allowing fabrication of intersecting and coaxial channels of different depths in glass as is required for 3D flow-focusing. Fenofibrate was used as a model for active pharmaceutical ingredients with very low water solubility in the experiments. It was dissolved in ethyl acetate and emulsified in water, as allowed by the 3D flow-focusing geometry. In the thread formation regime, the drug solution turned into monodisperse droplets of sizes down to below 1 μm. Fast supersaturation occurs individually in each droplet, as the disperse phase solvent progressively diffuses into the surrounding water. Liquid antisolvent precipitation results in highly monodisperse and amorphous nanoparticles of sizes down to 128 nm which can be precisely controlled by the continuous and disperse phase pressure. By comparing optically measured droplet sizes with particle sizes by dynamic light scattering, we could confirm that exactly one particle forms in every droplet. Furthermore, a downstream on-chip concentration allowed withdrawal of major volumes of only the continuous phase fluid which enabled an increase of particle concentration by up to 250 times.

  5. 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)

    OpenAIRE

    Stavchansky, Salomon

    2008-01-01

    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 ...

  6. A multi-scale modeling framework for individualized, spatiotemporal prediction of drug effects and toxicological risk

    Directory of Open Access Journals (Sweden)

    Juan Guillermo eDiaz Ochoa

    2013-01-01

    Full Text Available In this study, we focus on a novel multi-scale modeling approach for spatiotemporal prediction of the distribution of substances and resulting hepatotoxicity by combining cellular models, a 2D liver model, and whole-body model. As a case study, we focused on predicting human hepatotoxicity upon treatment with acetaminophen based on in vitro toxicity data and potential inter-individual variability in gene expression and enzyme activities. By aggregating mechanistic, genome-based in silico cells to a novel 2D liver model and eventually to a whole body model, we predicted pharmacokinetic properties, metabolism, and the onset of hepatotoxicity in an in silico patient. Depending on the concentration of acetaminophen in the liver and the accumulation of toxic metabolites, cell integrity in the liver as a function of space and time as well as changes in the elimination rate of substances were estimated. We show that the variations in elimination rates also influence the distribution of acetaminophen and its metabolites in the whole body. Our results are in agreement with experimental results. What is more, the integrated model also predicted variations in drug toxicity depending on alterations of metabolic enzyme activities. Variations in enzyme activity, in turn, reflect genetic characteristics or diseases of individuals. In conclusion, this framework presents an important basis for efficiently integrating inter-individual variability data into models, paving the way for personalized or stratified predictions of drug toxicity and efficacy.

  7. Quantifying the Effectiveness of Dose Individualization by Simulation for a Drug With Moderate Pharmacokinetic Variability.

    Science.gov (United States)

    Liefaard, Lia; Chen, Chao

    2015-10-01

    Dose individualization can reduce variability in exposure. The objective of this work was to quantify, through pharmacokinetic (PK) simulation, the potential for reducing the variability in exposure by dose individualization for a drug with moderate PK variability between subjects and between occasions within a subject, and a narrow therapeutic window. Using a population PK model that includes between-subject and between-occasion variability for apparent clearance, individual PK profiles in a trial of 300 subjects after a test dose were simulated. From the simulated data, datasets were created mimicking various sampling regimens (from single predose sample to full profile samples over 12 hours) on 1 or more occasions (1, 2, 3, 5, or 10 visits). Using these datasets, individual apparent clearance values were estimated, which were then used to calculate an individualized dose for a predefined target area under the concentration-time curve (AUC), based on the available formulation strengths. The proportion of people whose mean AUC was within a predefined therapeutic AUC range was calculated for the test (before) and the individualized dose (after), and compared between the different sampling scenarios. The maximum increase in proportion of subjects with an AUC within the range was 20%. To achieve this benefit, PK samples over 4 hours from 100 dosing occasions were required. As a result of the dose adjustment, the AUC of 7.3% of the subjects moved from inside the therapeutic range to outside of the range. This work shows how modeling and simulation can help assess the benefit and risk of dose individualization for a compound with variability between subjects and between occasions. The framework can be applied to similar situations with a defined set of conditions (eg, therapeutic window, tablet strengths, and PK and/or pharmacodynamic sampling scheme) to inform dose change and to assess the utility of dose individualization against certain success criteria.

  8. Atomoxetine effects on attentional bias to drug-related cues in cocaine dependent individuals.

    Science.gov (United States)

    Passamonti, Luca; Luijten, M; Ziauddeen, H; Coyle-Gilchrist, I T S; Rittman, T; Brain, S A E; Regenthal, R; Franken, I H A; Sahakian, B J; Bullmore, E T; Robbins, T W; Ersche, K D

    2017-08-01

    Biased attention towards drug-related cues and reduced inhibitory control over the regulation of drug-intake characterize drug addiction. The noradrenaline system has been critically implicated in both attentional and response inhibitory processes and is directly affected by drugs such as cocaine. We examined the potentially beneficial effects of the noradrenaline reuptake inhibitor atomoxetine in improving cognitive control during two tasks that used cocaine- and non-cocaine-related stimuli. A double-blind, placebo-controlled, and cross-over psycho-pharmacological design was employed. A single oral dose of atomoxetine (40 mg) was administered to 28 cocaine-dependent individuals (CDIs) and 28 healthy controls. All participants performed a pictorial attentional bias task involving both cocaine- and non-cocaine-related pictures as well as a verbal go/no-go task composed of cocaine- and food-related words. As expected, CDIs showed attentional bias to cocaine-related cues whilst controls did not. More importantly, however, atomoxetine, relative to placebo, significantly attenuated attentional bias in CDIs (F 26  = 6.73, P = 0.01). During the go/no-go task, there was a treatment × trial × group interaction, although this finding only showed a trend towards statistical significance (F 26  = 3.38, P = 0.07). Our findings suggest that atomoxetine reduces attentional bias to drug-related cues in CDIs. This may result from atomoxetine's modulation of the balance between tonic/phasic activity in the locus coeruleus and the possibly parallel enhancement of noradrenergic neurotransmission within the prefrontal cortex. Studying how cognitive enhancers such as atomoxetine influence key neurocognitive indices in cocaine addiction may help to develop reliable biomarkers for patient stratification in future clinical trials.

  9. Poor School Satisfaction and Number of Cannabis Using Peers within School Classes as Individual Risk Factors for Cannabis Use among Adolescents

    Science.gov (United States)

    Hoff, Dominic A.; Andersen, Anette; Holstein, Bjorn E.

    2010-01-01

    There is little information available on the topic of poor school satisfaction as a risk factor for cannabis use among adolescents. We examined if there was an association between poor school satisfaction, school class cannabis use and individual cannabis use. Further, we investigated if many cannabis users within the school class statistically…

  10. Design and study of piracetam-like nootropics, controversial members of the problematic class of cognition-enhancing drugs.

    Science.gov (United States)

    Gualtieri, Fulvio; Manetti, Dina; Romanelli, Maria Novella; Ghelardini, Carla

    2002-01-01

    Cognition enhancers are drugs able to facilitate attentional abilities and acquisition, storage and retrieval of information, and to attenuate the impairment of cognitive functions associated with head traumas, stroke, age and age-related pathologies. Development of cognition enhancers is still a difficult task because of complexity of the brain functions, poor predictivity of animal tests and lengthy and expensive clinical trials. After the early serendipitous discovery of first generation cognition enhancers, current research is based on a variety of working hypotheses, derived from the progress of knowledge in the neurobiopathology of cognitive processes. Among other classes of drugs, piracetam-like cognition enhancers (nootropics) have never reached general acceptance, in spite of their excellent tolerability and safety. In the present review, after a general discussion of the problems connected with the design and development of cognition enhancers, the class is examined in more detail. Reasons for the problems encountered by nootropics, compounds therapeutically available and those in development, their structure activity relationships and mechanisms of action are discussed. Recent developments which hopefully will lead to a revival of the class are reviewed.

  11. Interpretation of Ocular Melanin Drug Binding Assays. Alternatives to the Model of Multiple Classes of Independent Sites.

    Science.gov (United States)

    Manzanares, José A; Rimpelä, Anna-Kaisa; Urtti, Arto

    2016-04-04

    Melanin has a high binding affinity for a wide range of drugs. The determination of the melanin binding capacity and its binding affinity are important, e.g., in the determination of the ocular drug distribution, the prediction of drug effects in the eye, and the trans-scleral drug delivery. The binding parameters estimated from a given data set vary significantly when using different isotherms or different nonlinear fitting methods. In this work, the commonly used bi-Langmuir isotherm, which assumes two classes of independent sites, is confronted with the Sips isotherm. Direct, log-log, and Scatchard plots are used, and the interpretation of the binding curves in the latter is critically analyzed. In addition to the goodness of fit, the emphasis is placed on the physical meaning of the binding parameters. The bi-Langmuir model imposes a bimodal distribution of binding energies for the sites on the melanin granules, but the actual distribution is most likely continuous and unimodal, as assumed by the Sips isotherm. Hence, the latter describes more accurately the distribution of binding energies and also the experimental results of melanin binding to drugs and metal ions. Simulations are used to show that the existence of two classes of sites cannot be confirmed on the sole basis of the shape of the binding curve in the Scatchard plot, and that serious doubts may appear on the meaning of the binding parameters of the bi-Langmuir model. Experimental results of melanin binding to chloroquine and metoprolol are used to illustrate the importance of the choice of the binding isotherm and of the method used to evaluate the binding parameters.

  12. Resistance to different classes of drugs is associated with impaired apoptosis in childhood acute lymphoblastic leukemia

    NARCIS (Netherlands)

    A. Holleman (Amy); M.L. den Boer (Monique); K.M. Kazemier (Karin); G.E. Janka-Schaub (Gritta); R. Pieters (Rob)

    2003-01-01

    textabstractResistance of leukemic cells to chemotherapeutic agents is associated with an unfavorable outcome in pediatric acute lymphoblastic leukemia (ALL). To investigate the underlying mechanisms of cellular drug resistance, the activation of various apoptotic parameters in

  13. Assessing the drug-likeness of lamellarins, a marine-derived natural product class with diverse oncological activities.

    Science.gov (United States)

    Chittchang, Montakarn; Gleeson, M Paul; Ploypradith, Poonsakdi; Ruchirawat, Somsak

    2010-06-01

    Natural products currently represent an underutilized source of leads for the pharmaceutical industry, especially when one considers that almost 50% of all drugs were either derived from such sources or are very closely related. Lamellarins are a class of natural products with diverse biological activities and have entered into preclinical development for the treatment of multidrug-resistant tumors. Although these compounds demonstrated good cell penetration, as observed by their low microM activity in whole cell models, they have not been extensively profiled from a physicochemical point of view, and this is the goal of this study. For this study, we have determined the experimental logP values of a set of 25 lamellarins, given it is the single most important parameter in determining multiple ADMET parameters. We also discuss the relationship between this natural product class, natural product derivatives in development and on the market, oral marketed drugs, as well as drug molecules in development, using a range of physicochemical parameters in conjunction with principal components analysis (PCA). The impact of this systematic analysis on our ongoing medicinal chemistry strategy is also discussed. Copyright (c) 2010 Elsevier Masson SAS. All rights reserved.

  14. Use of individual protection equipment and collective in case of accident during the transport of radioactive product - class 7

    International Nuclear Information System (INIS)

    Pastura, Valeria da F. e S.; Carvalho, Natanael Bruno de

    2013-01-01

    The personal protective equipment (PPE) are devices used by professionals against potential radiological hazards that may threaten the health or safety in the event of an accident or incident during the transport of radioactive material. The collective protection equipment (CPE) devices are used in place of the accident in order to protect people and the environment from risks such as safety signs, among others. This work will be part of the new edition of the NBR 9735 - Set of equipment for emergencies in land transport of dangerous goods - edited by the Brazilian Association of Technical Standards ABNT - National Standardization Forum which CNEN participates in the Study Committee - CB16 namely, dangerous, accounting for Class 7 radioactive materials. The Standard 9735 establishes the minimum set of equipment for emergencies in Inland transport of dangerous goods, consisting of protective equipment to be used by the driver and staff involved (if any) in the transport operations of transport units, equipment for signaling, isolation of the area of occurrence (fault, accident and/or emergency). Thus, we will present a set of individual and collective equipment that must accompany the carriage of Class 7 products to meet the radiological accident situations and also establish a training base for the driver as the use of them. (author)

  15. Ranking the Harm of Alcohol, Tobacco and Illicit Drugs for the Individual and the Population

    NARCIS (Netherlands)

    van Amsterdam, Jan; Opperhuizen, Antoon; Koeter, Maarten; van den Brink, Wim

    2010-01-01

    Drug policy makers continuously face a changing pattern of drug use, i.e. new drugs appear on the market, the popularity of certain drugs changes or drugs are used in another way or another combination. For legislative purposes, drugs have mostly been classified according to their addictive potency.

  16. Motivation deficits and use of alcohol and illicit drugs among individuals with schizophrenia.

    Science.gov (United States)

    Bahorik, Amber L; Greeno, Catherine G; Cochran, Gerald; Cornelius, Jack R; Eack, Shaun M

    2017-07-01

    This study examined the impact of substance use on intrinsic motivation and evaluated the association between intrinsic motivation and substance use recovery among individuals with schizophrenia. Alcohol and illicit drug use and intrinsic motivation were evaluated at baseline and 6-months for 1434 individuals with schizophrenia from the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) using self-rated substance use assessments and a derived motivation measure from the Heinrichs-Carpenter Quality of Life Scale. Results revealed patients had moderate motivation deficits overall and a considerable number were using alcohol or illicit drugs at baseline (n=576; 40.2%). Regression models at baseline showed patients with low levels of motivation had higher odds of substance use and those who were using substances had greater motivation deficits. At 6-months, substance using patients continued to demonstrate greater motivation deficits; however, those with high levels of motivation exhibited a greater reduction in their use of substances. Findings remained significant after adjusting for clinical confounds and were consistent across any substance, alcohol, and cannabis use. Our results emphasize concerns about substance use compounding motivation deficits in schizophrenia, and suggest that disentangling the motivation-substance use relationship in schizophrenia may facilitate efforts aimed at ameliorating these challenges and improving outcomes. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

  17. Individualized prediction of seizure relapse and outcomes following antiepileptic drug withdrawal after pediatric epilepsy surgery.

    Science.gov (United States)

    Lamberink, Herm J; Boshuisen, Kim; Otte, Willem M; Geleijns, Karin; Braun, Kees P J

    2018-03-01

    The objective of this study was to create a clinically useful tool for individualized prediction of seizure outcomes following antiepileptic drug withdrawal after pediatric epilepsy surgery. We used data from the European retrospective TimeToStop study, which included 766 children from 15 centers, to perform a proportional hazard regression analysis. The 2 outcome measures were seizure recurrence and seizure freedom in the last year of follow-up. Prognostic factors were identified through systematic review of the literature. The strongest predictors for each outcome were selected through backward selection, after which nomograms were created. The final models included 3 to 5 factors per model. Discrimination in terms of adjusted concordance statistic was 0.68 (95% confidence interval [CI] 0.67-0.69) for predicting seizure recurrence and 0.73 (95% CI 0.72-0.75) for predicting eventual seizure freedom. An online prediction tool is provided on www.epilepsypredictiontools.info/ttswithdrawal. The presented models can improve counseling of patients and parents regarding postoperative antiepileptic drug policies, by estimating individualized risks of seizure recurrence and eventual outcome. Wiley Periodicals, Inc. © 2018 International League Against Epilepsy.

  18. Latent classes of polydrug and polyroute use and associations with human immunodeficiency virus risk behaviours and overdose among people who inject drugs in Tijuana, Baja California, Mexico.

    Science.gov (United States)

    Meacham, Meredith C; Roesch, Scott C; Strathdee, Steffanie A; Lindsay, Suzanne; Gonzalez-Zuniga, Patricia; Gaines, Tommi L

    2018-01-01

    Patterns of polydrug use among people who inject drugs (PWID) may be differentially associated with overdose and unique human immunodeficiency virus (HIV) risk factors. Subgroups of PWID in Tijuana, Mexico, were identified based on substances used, route of administration, frequency of use and co-injection indicators. Participants were PWID residing in Tijuana age ≥18 years sampled from 2011 to 2012 who reported injecting an illicit substance in the past month (n = 735). Latent class analysis identified discrete classes of polydrug use characterised by 11 indicators of past 6 months substance use. Multinomial logistic regression examined class membership association with HIV risk behaviours, overdose and other covariates using an automated three-step procedure in mplus to account for classification error. Participants were classified into five subgroups. Two polydrug and polyroute classes were defined by use of multiple substances through several routes of administration and were primarily distinguished from each other by cocaine use (class 1: 5%) or no cocaine use (class 2: 29%). The other classes consisted primarily of injectors: cocaine, methamphetamine and heroin injection (class 3: 4%); methamphetamine and heroin injection (class 4: 10%); and heroin injection (class 5: 52%). Compared with the heroin-only injection class, memberships in the two polydrug and polyroute use classes were independently associated with both HIV injection and sexual risk behaviours. Substance use patterns among PWID in Tijuana are highly heterogeneous, and polydrug and polyroute users are a high-risk subgroup who may require more tailored prevention and treatment interventions. [Meacham MC, Roesch SC, Strathdee SA, Lindsay S, Gonzalez-Zuniga P, Gaines TL. Latent classes of polydrug and polyroute use and associations with human immunodeficiency virus risk behaviours and overdose among people who inject drugs in Tijuana, Baja California, Mexico. Drug Alcohol Rev 2018;37:128-136].

  19. TMC125 exerts similar initial antiviral potency as a five-drug, triple class antiretroviral regimen

    NARCIS (Netherlands)

    Sankatsing, Sanjay U. C.; Weverling, Gerrit J.; Peeters, Monika; van't Klooster, Gerben; Gruzdev, Boris; Rakhmanova, Aza; Danner, Sven A.; Jurriaans, Suzanne; Prins, Jan M.; Lange, Joep M. A.

    2003-01-01

    Objective: TMC125, a next generation, non-nucleoside reverse transcriptase inhibitor (NNRTI), demonstrated a remarkable decline of plasma HIV-1 RNA during a phase IIa study. We compared the initial rate of decline of plasma HIV-1 RNA achieved by TMC125 monotherapy with that of a triple class,

  20. Transmitted drug resistance and type of infection in newly diagnosed HIV-1 individuals in Honduras.

    Science.gov (United States)

    Murillo, Wendy; Paz-Bailey, Gabriela; Morales, Sonia; Monterroso, Edgar; Paredes, Mayte; Dobbs, Trudy; Parekh, Bharat S; Albert, Jan; Rivera, Ivette Lorenzana de

    2010-12-01

    Transmitted drug resistance (TDR) reduces the efficacy of antiretroviral treatment and is a public health concern. To gain insight in the epidemiology of TDR in Honduras by evaluating the amount of TDR in a representative sample of newly diagnosed individuals and by determining whether these are recent or established infections. Two hundred treatment-naïve, newly diagnosed HIV-positive individuals representing different population groups (general population, Garifunas ethnic group, female sex workers and men who have sex with men) and different geographic regions were enrolled during April 2004-April 2007. The HIV-1 pol gene was sequenced to identify drug-resistant mutations and TDR was scored as recommended by the WHO. Specimens were classified as recent or established infections using the BED assay. Among 200 samples analyzed from Honduran patients the prevalence of TDR was 7% (95% CI: 3.9-11.5%), 5% for non-nucleoside reverse transcriptase inhibitors (NNRTIs), 3% for nucleoside reverse transcriptase inhibitors (NRTIs) and 0.5% for protease inhibitors (PIs). Testing of these samples with the BED assay revealed that 12% of the specimens were associated with recent infections. TDR was significantly more common in specimens with recent infection (21%) than established infection (5%) (p=0.016). The prevalence of TDR in Honduras was moderate (7%). The percentage of specimens who were recently infected was low (12%), suggesting that late HIV diagnosis is common. The TDR prevalence was higher in recent than in established infections, which may indicate that TDR is increasing over time. The higher prevalence of NNRTI and NRTI mutations as compared to PI mutations is probably due to a broader and longer use of these drugs in Honduras. Copyright © 2010 Elsevier B.V. All rights reserved.

  1. Peer-led, transformative learning approaches increase classroom engagement in care self-management classes during inpatient rehabilitation of individuals with spinal cord injury.

    Science.gov (United States)

    Gassaway, Julie; Jones, Michael L; Sweatman, W Mark; Young, Tamara

    2017-10-16

    Evaluate effects of revised education classes on classroom engagement during inpatient rehabilitation for individuals with spinal cord injury/disease (SCI/D). Multiple-baseline, quasi-experimental design with video recorded engagement observations during conventional and revised education classes; visual and statistical analysis of difference in positive engagement responses observed in classes using each approach. 81 patients (72% male, 73% white, mean age 36 SD 15.6) admitted for SCI/D inpatient rehabilitation in a non-profit rehabilitation hospital, who attended one or more of 33 care self-management education classes that were video recorded. All study activities were approved by the host facility institutional review board. Conventional nurse-led self-management classes were replaced with revised peer-led classes incorporating approaches to promote transformative learning. Revised classes were introduced across three subject areas in a step-wise fashion over 15 weeks. Positive engagement responses (asking questions, participating in discussion, gesturing, raising hand, or otherwise noting approval) were documented from video recordings of 14 conventional and 19 revised education classes. Significantly higher average (per patient per class) positive engagement responses were observed in the revised compared to conventional classes (p=0.008). Redesigning SCI inpatient rehabilitation care self-management classes to promote transformative learning increased patient engagement. Additional research is needed to examine longer term outcomes and replicability in other settings.

  2. Individual and contextual determinants of regional variation in prescription drug use: an analysis of administrative data from British Columbia.

    Directory of Open Access Journals (Sweden)

    Steven G Morgan

    2010-12-01

    Full Text Available Increasing attention is being paid to variations in the use of prescription drugs because their role in health care has grown to the point where their use can be considered a proxy for health system performance. Studies have shown that prescription drug use varies across regions in the US, UK, and Canada by more than would be predicted based on age and health status alone. In this paper, we explore the determinants of variations in the use of prescription drugs, drawing on health services theories of access to care.We conducted a cross-sectional analysis using population-based administrative health care data for British Columbia (BC, Canada. We used logistic and hierarchical regressions to analyze the effects of individual- and area-level determinants of use of prescriptions overall and rates of purchase of prescriptions from five therapeutic categories representing a range of indications: antihypertensives, statins, acid reducing drugs, opioid drugs, and antidepressants. To indicate the relative scale of regional variations and the importance of individual- and area-level variables in explaining them, we computed standardized rates of utilization for 49 local health areas in BC.We found that characteristics of individuals and the areas in which they live affect likelihood of prescription drug purchase. Individual-level factors influenced prescription drug purchases in ways generally consistent with behavioral models of health services use. Contextual variables exerted influences that differed by type of drug studied. Population health, education levels, and ethnic composition of local areas were associated with significant differences in the likelihood of purchasing medications. Relatively modest regional variations remained after both individual-level and area-level determinants were taken into account.The results of this study suggest that individual- and area-level factors should be considered when studying variations in the use of

  3. Individual and contextual determinants of regional variation in prescription drug use: an analysis of administrative data from British Columbia.

    Science.gov (United States)

    Morgan, Steven G; Cunningham, Colleen M; Hanley, Gillian E

    2010-12-29

    Increasing attention is being paid to variations in the use of prescription drugs because their role in health care has grown to the point where their use can be considered a proxy for health system performance. Studies have shown that prescription drug use varies across regions in the US, UK, and Canada by more than would be predicted based on age and health status alone. In this paper, we explore the determinants of variations in the use of prescription drugs, drawing on health services theories of access to care. We conducted a cross-sectional analysis using population-based administrative health care data for British Columbia (BC), Canada. We used logistic and hierarchical regressions to analyze the effects of individual- and area-level determinants of use of prescriptions overall and rates of purchase of prescriptions from five therapeutic categories representing a range of indications: antihypertensives, statins, acid reducing drugs, opioid drugs, and antidepressants. To indicate the relative scale of regional variations and the importance of individual- and area-level variables in explaining them, we computed standardized rates of utilization for 49 local health areas in BC. We found that characteristics of individuals and the areas in which they live affect likelihood of prescription drug purchase. Individual-level factors influenced prescription drug purchases in ways generally consistent with behavioral models of health services use. Contextual variables exerted influences that differed by type of drug studied. Population health, education levels, and ethnic composition of local areas were associated with significant differences in the likelihood of purchasing medications. Relatively modest regional variations remained after both individual-level and area-level determinants were taken into account. The results of this study suggest that individual- and area-level factors should be considered when studying variations in the use of prescription drugs. Some

  4. A chemically inert drug can stimulate T cells in vitro by their T cell receptor in non-sensitised individuals

    International Nuclear Information System (INIS)

    Engler, Olivier B.; Strasser, Ingrid; Naisbitt, Dean J.; Cerny, Andreas; Pichler, Werner J.

    2004-01-01

    Drugs can interact with T cell receptors (TCR) after binding to peptide-MHC structures. This binding may involve the formation of a stable, covalent bond between a chemically reactive drug and MHC or the peptide embedded within. Alternatively, if the drug is chemically inert, the binding may be non-covalent and readily reversible. Both types of drug presentation account for a substantial number of adverse side effects to drugs. Presently no tests are available to predict the ability of chemically inert drugs to stimulate an immune response. Here we present data on the successful induction of a primary T cell immune response in vitro against a chemically inert drug using blood from healthy individuals, previously not exposed to the drug. Blood lymphocytes were stimulated by the chemically inert drug sulfamethoxazole and the protein-reactive drug-metabolite sulfamethoxazole-nitroso in the presence of IL-2. 9/10 individuals reacted in response to sulfamethoxazole-nitroso, but only three reacted to the chemically inert compound sulfamethoxazole. Drug reactive T cells could be detected after 14-35 days of cell culture by drug-specific proliferation or cytotoxicity, which was MHC-restricted. These cells were CD4, CD8 positive or CD4/CD8 double positive and T cell clones generated secreted Th0 type cytokines. Drug interaction lead to down-regulation of specific TCR. These data confirm the ability of chemically inert drugs to stimulate certain T cells by their TCR and may provide the opportunity to screen new drugs for their ability to interact with TCRs

  5. Antiepileptic Drug Behavioral Side Effects in Individuals with Mental Retardation and the Use of Behavioral Measurement Techniques.

    Science.gov (United States)

    Kalachnik, John E.; And Others

    1995-01-01

    Behavioral psychology measurement methods helped assess antiepileptic drug behavioral side effects in five individuals with mental retardation who could not verbally communicate presence of side effects. When the suspected antiepileptic drug was altered, an 81% reduction of maladaptive behaviors occurred. The measurement methods enabled systematic…

  6. The application of individual approach in how to conduct aerobics classes with students of different levels of preparedness.

    Directory of Open Access Journals (Sweden)

    Barybina L.N.

    2012-09-01

    Full Text Available The aim of this work was to develop a system of classes in aerobics in high school with an individual approach. On this subject has been analyzed about 15 references. 105 students took part in an experiment. The technique, which combines fitness aerobics and step aerobics. The technique allows to take into account the physical capacity, functional differences, the level of preparedness and dealing with their needs, as well as to use an individual approach in the selection of means and methods of physical education. We propose the organization of activities in which the hall can simultaneously engage up to 5-6 subgroups: students with low fitness and low levels of coordination abilities, students with an average level of physical fitness and low levels of coordination abilities, students with high levels of physical fitness and low levels of coordination abilities, students with an average level of physical fitness and a high level of coordination abilities, students with high levels of physical fitness and coordination abilities.

  7. Asymmetric responsiveness of physician prescription behavior to drug promotion of competitive brands within an established therapeutic drug class.

    Science.gov (United States)

    Pedan, Alex; Wu, Hongsheng

    2011-04-01

    This article examines the impact of direct-to-physician, direct-to-consumer, and other marketing activities by pharmaceutical companies on a mature drug category which is in the later stage of its life cycle and in which generics have accrued a significant market share. The main objective of this article is to quantitatively estimate the impact of pharmaceutical promotions on physician prescribing behavior for three different statin brands, after controlling for factors such as patient, physician and physician practice characteristics, generic pressure, et cetera. Using unique panel data of physicians, combined with patient pharmacy prescription records, the authors developed a physician level generalized linear regression model. The generalized estimating equations method was used to account for within physician serial correlations and estimate physician population averaged effects. The findings reveal that even though on average the marketing efforts affect the brand share positively, the magnitude of the effects is very brand specific. Generally, each statin brand has its own trend and because of this, the best choice of predictors for one brand could be suboptimal for another.

  8. RNA disruption is associated with response to multiple classes of chemotherapy drugs in tumor cell lines

    International Nuclear Information System (INIS)

    Narendrula, Rashmi; Mispel-Beyer, Kyle; Guo, Baoqing; Parissenti, Amadeo M.; Pritzker, Laura B.; Pritzker, Ken; Masilamani, Twinkle; Wang, Xiaohui; Lannér, Carita

    2016-01-01

    Cellular stressors and apoptosis-inducing agents have been shown to induce ribosomal RNA (rRNA) degradation in eukaryotic cells. Recently, RNA degradation in vivo was observed in patients with locally advanced breast cancer, where mid-treatment tumor RNA degradation was associated with complete tumor destruction and enhanced patient survival. However, it is not clear how widespread chemotherapy induced “RNA disruption” is, the extent to which it is associated with drug response or what the underlying mechanisms are. Ovarian (A2780, CaOV3) and breast (MDA-MB-231, MCF-7, BT474, SKBR3) cancer cell lines were treated with several cytotoxic chemotherapy drugs and total RNA was isolated. RNA was also prepared from docetaxel resistant A2780DXL and carboplatin resistant A2780CBN cells following drug exposure. Disruption of RNA was analyzed by capillary electrophoresis. Northern blotting was performed using probes complementary to the 28S and 18S rRNA to determine the origins of degradation bands. Apoptosis activation was assessed by flow cytometric monitoring of annexin-V and propidium iodide (PI) binding to cells and by measuring caspase-3 activation. The link between apoptosis and RNA degradation (disruption) was investigated using a caspase-3 inhibitor. All chemotherapy drugs tested were capable of inducing similar RNA disruption patterns. Docetaxel treatment of the resistant A2780DXL cells and carboplatin treatment of the A2780CBN cells did not result in RNA disruption. Northern blotting indicated that two RNA disruption bands were derived from the 3’-end of the 28S rRNA. Annexin-V and PI staining of docetaxel treated cells, along with assessment of caspase-3 activation, showed concurrent initiation of apoptosis and RNA disruption, while inhibition of caspase-3 activity significantly reduced RNA disruption. Supporting the in vivo evidence, our results demonstrate that RNA disruption is induced by multiple chemotherapy agents in cell lines from different tissues

  9. RNA disruption is associated with response to multiple classes of chemotherapy drugs in tumor cell lines.

    Science.gov (United States)

    Narendrula, Rashmi; Mispel-Beyer, Kyle; Guo, Baoqing; Parissenti, Amadeo M; Pritzker, Laura B; Pritzker, Ken; Masilamani, Twinkle; Wang, Xiaohui; Lannér, Carita

    2016-02-24

    Cellular stressors and apoptosis-inducing agents have been shown to induce ribosomal RNA (rRNA) degradation in eukaryotic cells. Recently, RNA degradation in vivo was observed in patients with locally advanced breast cancer, where mid-treatment tumor RNA degradation was associated with complete tumor destruction and enhanced patient survival. However, it is not clear how widespread chemotherapy induced "RNA disruption" is, the extent to which it is associated with drug response or what the underlying mechanisms are. Ovarian (A2780, CaOV3) and breast (MDA-MB-231, MCF-7, BT474, SKBR3) cancer cell lines were treated with several cytotoxic chemotherapy drugs and total RNA was isolated. RNA was also prepared from docetaxel resistant A2780DXL and carboplatin resistant A2780CBN cells following drug exposure. Disruption of RNA was analyzed by capillary electrophoresis. Northern blotting was performed using probes complementary to the 28S and 18S rRNA to determine the origins of degradation bands. Apoptosis activation was assessed by flow cytometric monitoring of annexin-V and propidium iodide (PI) binding to cells and by measuring caspase-3 activation. The link between apoptosis and RNA degradation (disruption) was investigated using a caspase-3 inhibitor. All chemotherapy drugs tested were capable of inducing similar RNA disruption patterns. Docetaxel treatment of the resistant A2780DXL cells and carboplatin treatment of the A2780CBN cells did not result in RNA disruption. Northern blotting indicated that two RNA disruption bands were derived from the 3'-end of the 28S rRNA. Annexin-V and PI staining of docetaxel treated cells, along with assessment of caspase-3 activation, showed concurrent initiation of apoptosis and RNA disruption, while inhibition of caspase-3 activity significantly reduced RNA disruption. Supporting the in vivo evidence, our results demonstrate that RNA disruption is induced by multiple chemotherapy agents in cell lines from different tissues and is

  10. Substituted 2-Phenyl-Imidazopyridines: A New Class of Drug Leads for Human African Trypanosomiasis

    Science.gov (United States)

    Tatipaka, Hari Babu; Gillespie, J. Robert; Chatterjee, Arnab K.; Norcross, Neil R.; Hulverson, Matthew A.; Ranade, Ranae M.; Nagendar, Pendem; Creason, Sharon A.; McQueen, Joshua; Duster, Nicole A.; Nagle, Advait; Supek, Frantisek; Molteni, Valentina; Wenzler, Tanja; Brun, Reto; Glynne, Richard; Buckner, Frederick S.; Gelb, Michael H.

    2014-01-01

    A phenotypic screen of a compound library for antiparasitic activity on Trypanosoma brucei, the causative agent of human African trypanosomiasis, led to the identification of substituted 2-(3-aminophenyl) oxazolopyridines as a starting point for hit-to-lead medicinal chemistry. A total of 110 analogues were prepared, which led to the identification of 64, a substituted 2-(3-aminophenyl) imidazopyridine. This compound showed antiparasitic activity in vitro with an EC50 of 2 nM and displayed reasonable drug-like properties when tested in a number of in vitro assays. The compound was orally bioavailable and displayed good plasma and brain exposure in mice. Compound 64 cured mice infected with Trypanosoma brucei when dosed orally down to 2.5 mg/kg. Given its potent anti-parasitic properties and its ease of synthesis, compound 64 represents a new lead for the development of drugs to treat human African trypanosomiasis. PMID:24354316

  11. Biowaiver study of oral tabletted ethylcellulose microcapsules of a BCS class I drug

    Directory of Open Access Journals (Sweden)

    Ghulam Murtaza

    2009-08-01

    Full Text Available This article describes the preparation and characterization (in vitro and in vivo of three different sustained-release salbutamol sulfate−ethylcellulose tabletted microparticles (T1, T2 and T3 and reference sustained release tablet (Ventolin 8 mg SR, GSK. In vitro characterization included dissolution study, scanning electron microscopy, UV and FTIR spectroscopy, X−ray diffractometry and thermal analysis. A validated HPLC−fluorescent detection method was adopted to conduct bioavailability studies in young healthy human volunteers. The microparticles exhibited an irregular and slightly aggregated morphology with fine rheological properties. No strong chemical interaction was found between drug and polymer. A good linear correlation (R2 = 0.9224, 0.945, 0.9363 and 0.9694 for T1, T2, T3 and reference formulations, respectively was obtained between the percent cumulative drug released (in vitro and the percent cumulative drug absorbed (in vivo data of these formulations at specific time points to develop level A in vitro−in vivo correlation. However, T2 was found closer to the reference formulation that shows a reliable prediction of the plasma concentrations obtained following a single dose of salbutamol sulfate modified release formulations.

  12. Antiepileptic drug monotherapy for epilepsy: a network meta-analysis of individual participant data.

    Science.gov (United States)

    Nevitt, Sarah J; Sudell, Maria; Weston, Jennifer; Tudur Smith, Catrin; Marson, Anthony G

    2017-12-15

    Epilepsy is a common neurological condition with a worldwide prevalence of around 1%. Approximately 60% to 70% of people with epilepsy will achieve a longer-term remission from seizures, and most achieve that remission shortly after starting antiepileptic drug treatment. Most people with epilepsy are treated with a single antiepileptic drug (monotherapy) and current guidelines from the National Institute for Health and Care Excellence (NICE) in the United Kingdom for adults and children recommend carbamazepine or lamotrigine as first-line treatment for partial onset seizures and sodium valproate for generalised onset seizures; however a range of other antiepileptic drug (AED) treatments are available, and evidence is needed regarding their comparative effectiveness in order to inform treatment choices. To compare the time to withdrawal of allocated treatment, remission and first seizure of 10 AEDs (carbamazepine, phenytoin, sodium valproate, phenobarbitone, oxcarbazepine, lamotrigine, gabapentin, topiramate, levetiracetam, zonisamide) currently used as monotherapy in children and adults with partial onset seizures (simple partial, complex partial or secondary generalised) or generalised tonic-clonic seizures with or without other generalised seizure types (absence, myoclonus). We searched the following databases: Cochrane Epilepsy's Specialised Register, CENTRAL, MEDLINE and SCOPUS, and two clinical trials registers. We handsearched relevant journals and contacted pharmaceutical companies, original trial investigators, and experts in the field. The date of the most recent search was 27 July 2016. We included randomised controlled trials of a monotherapy design in adults or children with partial onset seizures or generalised onset tonic-clonic seizures (with or without other generalised seizure types). This was an individual participant data (IPD) review and network meta-analysis. Our primary outcome was 'time to withdrawal of allocated treatment', and our secondary

  13. Evaluation of Students’ Perceptions Towards An Innovative Teaching-Learning Method During Pharmacology Revision Classes: Autobiography of Drugs

    Science.gov (United States)

    Ganjiwale, Jaishree

    2015-01-01

    Introduction Various studies in medical education have shown that active learning strategies should be incorporated into the teaching–learning process to make learning more effective, efficient and meaningful. Objectives The aim of this study was to evaluate student’s perceptions on an innovative revision method conducted in Pharmacology i.e. in form of Autobiography of Drugs. The main objective of study was to help students revise the core topics in Pharmacology in an interesting way. Settings and Design Questionnaire based survey on a newer method of pharmacology revision in two batches of second year MBBS students of a tertiary care teaching medical college. Materials and Methods Various sessions on Autobiography of Drugs were conducted amongst two batches of second year MBBS students, during their Pharmacology revision classes. Student’s perceptions were documented with the help of a five point likert scale through a questionnaire regarding quality, content and usefulness of this method. Statistical analysis used Descriptive analysis. Results Students of both the batches appreciated the innovative method taken up for revision. The median scores in most of the domains in both batches were four out of five, indicative of good response. Feedback from open-ended questions also revealed that the innovative module on “Autobiography of Drugs” was taken as a positive learning experience by students. Conclusions Autobiography of drugs has been used to help students recall topics that they have learnt through other teachings methods. Autobiography sessions in Pharmacology during revision slots, can be one of the interesting ways in helping students revise and recall topics which have already been taught in theory classes. PMID:26393138

  14. Solubility enhancement of BCS Class II drug by solid phospholipid dispersions: Spray drying versus freeze-drying.

    Science.gov (United States)

    Fong, Sophia Yui Kau; Ibisogly, Asiye; Bauer-Brandl, Annette

    2015-12-30

    The poor aqueous solubility of BCS Class II drugs represents a major challenge for oral dosage form development. Using celecoxib (CXB) as model drug, the current study adopted a novel solid phospholipid nanoparticle (SPLN) approach and compared the effect of two commonly used industrial manufacturing methods, spray- and freeze-drying, on the solubility and dissolution enhancement of CXB. CXB was formulated with Phospholipoid E80 (PL) and trehalose at different CXB:PL:trehalose ratios, of which 1:10:16 was the optimal formulation. Spherical amorphous SPLNs with average diameters <1μm were produced by spray-drying; while amorphous 'matrix'-like structures of solid PL dispersion with larger particle sizes were prepared by freeze-drying. Formulations from both methods significantly enhanced the dissolution rates, apparent solubility, and molecularly dissolved concentration of CXB in phosphate buffer (PBS, pH 6.5) and in biorelevant fasted state simulated intestinal fluid (FaSSIF, pH 6.5) (p<0.05). While similar dissolution rates were found, the spray-dried SPLNs had a larger enhancement in apparent solubility (29- to 132-fold) as well as molecular solubility (18-fold) of CXB at equilibrium (p<0.05). The strong capability of the spray-dried SPLNs to attain 'true' supersaturation state makes them a promising approach for bioavailability enhancement of poorly soluble drugs. Copyright © 2015 Elsevier B.V. All rights reserved.

  15. Drug-class-specific changes in the volume and cost of antidiabetic medications in Poland between 2012 and 2015.

    Science.gov (United States)

    Śliwczyński, Andrzej; Brzozowska, Melania; Jacyna, Andrzej; Iltchev, Petre; Iwańczuk, Tymoteusz; Wierzba, Waldemar; Marczak, Michał; Orlewska, Katarzyna; Szymański, Piotr; Orlewska, Ewa

    2017-01-01

    to investigate the drug-class-specific changes in the volume and cost of antidiabetic medications in Poland in 2012-2015. This retrospective analysis was conducted based on the National Health Fund database covering an entire Polish population. The volume of antidiabetic medications is reported according to ATC/DDD methodology, costs-in current international dollars, based on purchasing power parity. During a 4-year observational period the number of patients, consumption of antidiabetic drugs and costs increased by 17%, 21% and 20%, respectively. Biguanides are the basic diabetes medication with a 39% market share. The insulin market is still dominated by human insulins, new antidiabetics (incretins, thiazolidinediones) are practically absent. Insulins had the largest share in diabetes medications expenditures (67% in 2015). The increase in antidiabetic medications costs over the analysed period of time was mainly caused by the increased use of insulin analogues. The observed tendencies correspond to the evidence-based HTA recommendations. The reimbursement status, the ratio of cost to clinical outcomes and data on the long-term safety have a deciding impact on how a drug is used.

  16. Drug and cell type-specific regulation of genes with different classes of estrogen receptor beta-selective agonists.

    Directory of Open Access Journals (Sweden)

    Sreenivasan Paruthiyil

    2009-07-01

    Full Text Available Estrogens produce biological effects by interacting with two estrogen receptors, ERalpha and ERbeta. Drugs that selectively target ERalpha or ERbeta might be safer for conditions that have been traditionally treated with non-selective estrogens. Several synthetic and natural ERbeta-selective compounds have been identified. One class of ERbeta-selective agonists is represented by ERB-041 (WAY-202041 which binds to ERbeta much greater than ERalpha. A second class of ERbeta-selective agonists derived from plants include MF101, nyasol and liquiritigenin that bind similarly to both ERs, but only activate transcription with ERbeta. Diarylpropionitrile represents a third class of ERbeta-selective compounds because its selectivity is due to a combination of greater binding to ERbeta and transcriptional activity. However, it is unclear if these three classes of ERbeta-selective compounds produce similar biological activities. The goals of these studies were to determine the relative ERbeta selectivity and pattern of gene expression of these three classes of ERbeta-selective compounds compared to estradiol (E(2, which is a non-selective ER agonist. U2OS cells stably transfected with ERalpha or ERbeta were treated with E(2 or the ERbeta-selective compounds for 6 h. Microarray data demonstrated that ERB-041, MF101 and liquiritigenin were the most ERbeta-selective agonists compared to estradiol, followed by nyasol and then diarylpropionitrile. FRET analysis showed that all compounds induced a similar conformation of ERbeta, which is consistent with the finding that most genes regulated by the ERbeta-selective compounds were similar to each other and E(2. However, there were some classes of genes differentially regulated by the ERbeta agonists and E(2. Two ERbeta-selective compounds, MF101 and liquiritigenin had cell type-specific effects as they regulated different genes in HeLa, Caco-2 and Ishikawa cell lines expressing ERbeta. Our gene profiling studies

  17. 'At-risk' individuals' responses to direct to consumer advertising of prescription drugs: a nationally representative cross-sectional study.

    Science.gov (United States)

    Khalil Zadeh, Neda; Robertson, Kirsten; Green, James A

    2017-12-06

    The factors determining individuals' self-reported behavioural responses to direct to consumer advertising of prescription drugs were explored with an emphasis on 'at-risk' individuals' responses. Nationally representative cross-sectional survey. Community living adults in New Zealand. 2057 adults (51% women). Self-reported behavioural responses to drug advertising (asking a physician for a prescription, asking a physician for more information about an illness, searching the internet for more information regarding an illness and asking a pharmacist for more information about a drug). Multivariate logistic regressions determined whether participants' self-reported behavioural responses to drug advertising were predicted by attitudes towards advertising and drug advertising, judgements about safety and effectiveness of advertised drugs, self-reported health status, materialism, online search behaviour as well as demographic variables. Identifying as Indian and to a less extent Chinese, Māori and 'other' ethnicities were the strongest predictors of one or more self-reported responses (ORs 1.76-5.00, Ps advertising (ORs 1.34-1.61, all Psadvertising and may make uninformed decisions accordingly. The outcomes raise significant concerns relating to the ethicality of drug advertising and suggest a need for stricter guidelines to ensure that drug advertisements provided by pharmaceutical companies are ethical. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  18. A "novel" association to treat pain: tramadol/dexketoprofen. The first drug of a "new pharmacological class".

    Science.gov (United States)

    Fornasari, D; Allegri, M; Gerboni, S; Fanelli, Guido

    2017-04-28

     Acute and chronic pain have an important socio-economical impact. In order to help physicians to choose the appropriate drug, especially for cancer pain, in 1986 WHO has developed a three-step analgesic "ladder" for cancer pain relief in adults. Later it has also been used for acute pain and chronic non-cancer pain. In step I nonsteroidal anti-inflammatory drugs (NSAIDs) are considered with or without adjuvants, in step II the use of weak opioids for mild-moderate pain, with or without NSAIDs and adjuvant, is suggested, while the step III is reserved to strong opioids for moderate-severe pain with or without non-opioids or adjuvants. In the last two decades, a better pathophysiology knowledge has improved pain management shifting our view from the pain ladder to a modern pain pyramid, in which drugs are selected not only on the basis of pain intensity, but mainly according to mechanisms underlying pain, including peripheral and spinal sensitization which is the main trigger of chronic pain. The best pharmacological approach has become multimodal, in which drugs belonging to different steps should be combined, matching the mechanisms of action with the type of pain. An important corollary of combining analgesic drugs with different mechanism of action is that proper matching achieves the same effect with lower doses, better outcome and fewer adverse effects. In this new perspective, fixed-dose pharmaceutical combinations of different drugs are very useful to fulfil pharmacodynamics, pharmacokinetics and adherence criteria, enriching the pain pyramid of half-steps between the first and second step and between the second and third step. Hence, a new fixed combination of a NSAID with peripheral and central anti-infilammatory activities, such as dexketoprofen, and a weak opioid, such as tramadol, with double analgesic activity in the spinal cord as an opioid and, at the same time, on the descending modulatory pathways, is expected to cover a wide range of acute and

  19. PROFILE SOCIAL CLASS OF INDIVIDUALS ASSISTED IN A SOCIAL ORGANIZATION IN THE CAMAÇARI-BA CITY

    Directory of Open Access Journals (Sweden)

    Milene de Andrade Carvalho

    2012-04-01

    Full Text Available The city of Camaçari-Ba in the Bahia is considered the biggest territory of the region metropolitan area of Salvador-B. This population has presented considerable growth in the Human Development Index (HDI, with magnifying of the life expectancy and industrial cycle. The biggest social organization situated in the city and considered satate reference of social inclusion are develops entailed diverse actions to the participation of the city departments, except on actions to the healt secretariat. This study one is about a research of transverse whose objective was to identify the profile of 227 individuals assisted by social organization Prof. Raimundo Pinheiro, located in the mentioned city. The results had indicated the presence of a predominant age range next to 60 years, the relation between income and scholarity, the high frequency of chronic pain and relation enters the chronic use of drugs, activities of daily life and occupational activities. It is necessary that the activities of the social organization contemplate the logic of the intersectoral and include secretariat of health in its organizational politics.

  20. Improving introspection to inform free will regarding the choice by healthy individuals to use or not use cognitive enhancing drugs.

    Science.gov (United States)

    Thaler, David S

    2009-06-16

    A commentary in Nature entitled "Towards responsible use of cognitive-enhancing drugs by the healthy" (Greely et al 2008 Nature 456: 702-705) offers an opportunity to move toward a humane societal appreciation of mind-altering drugs. Using cognitive enhancing drugs as an exemplar, this article presents a series of hypotheses concerning how an individual might learn optimal use. The essence of the proposal is that individuals can cultivate sensitivity to the effects of ever-smaller amounts of psychoactive drugs thereby making harm less likely and benign effects more probable. Four interrelated hypotheses are presented and briefly discussed. 1. Humans can learn to discriminate ever-smaller doses of at least some mind-altering drugs; a learning program can be designed or discovered that will have this outcome. 2. The skill to discriminate drugs and dose can be generalized, i.e. if learned with one drug a second one is easier and so on. 3. Cultivating this skill/knack would be beneficial in leading to choices informed by a more accurate sense of mind-body interactions. 4. From a philosophical point of view learning the effects of ever-smaller doses of psychoactive agents offers a novel path into and to transcend the objective/subjective barrier and the mind/body problem.Whatever the fate of these specific hypotheses, discussion of cognitive enhancing drugs for healthy individuals has the potential to inspire innovative educational and public policy initiatives toward all types of mind-altering drugs and the people who use them.

  1. Improving introspection to inform free will regarding the choice by healthy individuals to use or not use cognitive enhancing drugs

    Directory of Open Access Journals (Sweden)

    Thaler David S

    2009-06-01

    Full Text Available Abstract A commentary in Nature entitled "Towards responsible use of cognitive-enhancing drugs by the healthy" (Greely et al 2008 Nature 456: 702–705 offers an opportunity to move toward a humane societal appreciation of mind-altering drugs. Using cognitive enhancing drugs as an exemplar, this article presents a series of hypotheses concerning how an individual might learn optimal use. The essence of the proposal is that individuals can cultivate sensitivity to the effects of ever-smaller amounts of psychoactive drugs thereby making harm less likely and benign effects more probable. Four interrelated hypotheses are presented and briefly discussed. 1. Humans can learn to discriminate ever-smaller doses of at least some mind-altering drugs; a learning program can be designed or discovered that will have this outcome. 2. The skill to discriminate drugs and dose can be generalized, i.e. if learned with one drug a second one is easier and so on. 3. Cultivating this skill/knack would be beneficial in leading to choices informed by a more accurate sense of mind-body interactions. 4. From a philosophical point of view learning the effects of ever-smaller doses of psychoactive agents offers a novel path into and to transcend the objective/subjective barrier and the mind/body problem. Whatever the fate of these specific hypotheses, discussion of cognitive enhancing drugs for healthy individuals has the potential to inspire innovative educational and public policy initiatives toward all types of mind-altering drugs and the people who use them.

  2. Atomoxetine effects on attentional bias to drug-related cues in cocaine dependent individuals

    NARCIS (Netherlands)

    Passamonti, L. (Luca); M. Luijten (Maartje); Ziauddeen, H.; I. Coyle-Gilchrist (Ian); Rittman, T.; Brain, S.A.E.; Regenthal, R.; I.H.A. Franken (Ingmar); Sahakian, B.J.; Bullmore, E.T.; Robbins, T.W.; Ersche, K.D.

    2017-01-01

    textabstractRationale: Biased attention towards drug-related cues and reduced inhibitory control over the regulation of drug-intake characterize drug addiction. The noradrenaline system has been critically implicated in both attentional and response inhibitory processes and is directly affected by

  3. FDM 3D printing of modified drug-delivery systems using hot melt extrusion: a new approach for individualized therapy.

    Science.gov (United States)

    Cunha-Filho, Marcilio; Araújo, Maísa Rp; Gelfuso, Guilherme M; Gratieri, Tais

    2017-11-01

    The production process of 3D-printed drugs offers unique advantages such as the possibility of individualizing the drug therapy and easily associating different drugs and release technologies in the same pharmaceutical unit. Fused deposition modeling, a 3D printing technique, seems especially interesting for pharmaceutical applications, due to its low cost, precise and reproducible control of the printed structures, and versatility for industrial and laboratory scale. This technique combined with another technology already adapted for the pharmaceutical industry, the hot melt extrusion, is able to incorporate various mechanisms of modified drug release. This special report aims to bring together data of the experimental progress achieved using the fused deposition modeling 3D printing combined with hot melt extrusion technique and its potential in drug delivery. [Formula: see text].

  4. Promising cardiovascular and blood pressure effects of the SGLT2 inhibitors: a new class of antidiabetic drugs.

    Science.gov (United States)

    Chrysant, S G

    2017-03-01

    Patients with type 2 diabetes mellitus (T2DM) exhibit an increased risk of cardiovascular (CV) events. Treatment of these patients with traditional as well as newer glucose-lowering drugs has not demonstrated superiority in CV outcomes compared to placebo, despite effective control of diabetes. However, the recently FDA-approved sodium-glucose cotransporter 2 (SGLT2) inhibitors for the treatment of T2DM have demonstrated promising CV-protecting and blood pressure-lowering effects in addition to their effectiveness in glucose lowering, making them a novel class of drugs for the treatment of T2DM. So far, there are three SGLT2 inhibitors approved by the FDA and EMA for the treatment of T2DM: canagliflozin, dapagliflozin and empagliflozin. They exert their antihyperglycemic effect through inhibition of SGLT2 in the kidney and significantly reduce glucose reabsorption from the proximal renal tubule. By blocking glucose reabsorption, they lead to loss of calories, weight, abdominal and total body fat, blood pressure and CV complications. One CV outcomes randomized trial and several short-term studies have shown reductions in CV events and blood pressure in patients with T2DM. It is the hope that large ongoing long-term outcome studies will provide further much-needed information, when they are completed. Copyright 2017 Clarivate Analytics.

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

    Science.gov (United States)

    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.

  6. Illicit and nonmedical drug use among Asian Americans, Native Hawaiians/Pacific Islanders, and mixed-race individuals

    Science.gov (United States)

    Wu, Li-Tzy; Blazer, Dan G.; Swartz, Marvin S.; Burchett, Bruce; Brady, Kathleen T.

    2013-01-01

    Background The racial/ethnic composition of the United States is shifting rapidly, with non-Hispanic Asian-Americans, Native Hawaiians/Pacific Islanders (NHs/PIs), and mixed-race individuals the fastest growing segments of the population. We determined new drug use estimates for these rising groups. Prevalences among Whites were included as a comparison. Methods Data were from the 2005–2011 National Surveys on Drug Use and Health. Substance use among respondents aged ≥12 years was assessed by computer-assisted self-interviewing methods. Respondents’ self-reported race/ethnicity, age, gender, household income, government assistance, county type, residential stability, major depressive episode, history of being arrested, tobacco use, and alcohol use were examined as correlates. We stratified the analysis by race/ethnicity and used logistic regression to estimate odds of drug use. Results Prevalence of past-year marijuana use among Whites increased from 10.7% in 2005 to 11.6–11.8% in 2009–2011 (PAsian-Americans, NHs/PIs, and mixed-race people; but use of any drug, especially marijuana, was prevalent among NHs/PIs and mixed-race people (21.2% and 23.3%, respectively, in 2011). Compared with Asian-Americans, NHs/PIs had higher odds of marijuana use, and mixed-race individuals had higher odds of using marijuana, cocaine, hallucinogens, stimulants, sedatives, and tranquilizers. Compared with Whites, mixed-race individuals had greater odds of any drug use, mainly marijuana, and NHs/PIs resembled Whites in odds of any drug use. Conclusions Findings reveal alarmingly prevalent drug use among NHs/PIs and mixed-race people. Research on drug use is needed in these rising populations to inform prevention and treatment efforts. PMID:23890491

  7. Craving Responses to Methamphetamine and Sexual Visual Cues in Individuals With Methamphetamine Use Disorder After Long-Term Drug Rehabilitation

    Directory of Open Access Journals (Sweden)

    Shucai Huang

    2018-04-01

    Full Text Available Studies utilizing functional magnetic resonance imaging (fMRI cue-reactivity paradigms have demonstrated that short-term abstinent or current methamphetamine (MA users have increased brain activity in the ventral striatum, caudate nucleus and medial frontal cortex, when exposed to MA-related visual cues. However, patterns of brain activity following cue-reactivity in subjects with long-term MA abstinence, especially long-term compulsory drug rehabilitation, have not been well studied. To enrich knowledge in this field, functional brain imaging was conducted during a cue-reactivity paradigm task in 28 individuals with MA use disorder following long-term compulsory drug rehabilitation, and 27 healthy control subjects. The results showed that, when compared with controls, individuals with MA use disorder displayed elevated activity in the bilateral medial prefrontal cortex (mPFC and right lateral posterior cingulate cortex in response to MA-related images. Additionally, the anterior cingulate region of mPFC activation during the MA-related cue-reactivity paradigm was positively correlated with craving alterations and previous frequency of drug use. No significant differences in brain activity in response to pornographic images were found between the two groups. Compared to MA cues, individuals with MA use disorder had increased activation in the occipital lobe when exposed to pornographic cues. In conclusion, the present study indicates that, even after long-term drug rehabilitation, individuals with MA use disorder have unique brain activity when exposed to MA-related cues. Additionally, our results illustrate that the libido brain response might be restored, and that sexual demand might be more robust than drug demand, in individuals with MA use disorder following long-term drug rehabilitation.

  8. Craving Responses to Methamphetamine and Sexual Visual Cues in Individuals With Methamphetamine Use Disorder After Long-Term Drug Rehabilitation.

    Science.gov (United States)

    Huang, Shucai; Zhang, Zhixue; Dai, Yuanyuan; Zhang, Changcun; Yang, Cheng; Fan, Lidan; Liu, Jun; Hao, Wei; Chen, Hongxian

    2018-01-01

    Studies utilizing functional magnetic resonance imaging (fMRI) cue-reactivity paradigms have demonstrated that short-term abstinent or current methamphetamine (MA) users have increased brain activity in the ventral striatum, caudate nucleus and medial frontal cortex, when exposed to MA-related visual cues. However, patterns of brain activity following cue-reactivity in subjects with long-term MA abstinence, especially long-term compulsory drug rehabilitation, have not been well studied. To enrich knowledge in this field, functional brain imaging was conducted during a cue-reactivity paradigm task in 28 individuals with MA use disorder following long-term compulsory drug rehabilitation, and 27 healthy control subjects. The results showed that, when compared with controls, individuals with MA use disorder displayed elevated activity in the bilateral medial prefrontal cortex (mPFC) and right lateral posterior cingulate cortex in response to MA-related images. Additionally, the anterior cingulate region of mPFC activation during the MA-related cue-reactivity paradigm was positively correlated with craving alterations and previous frequency of drug use. No significant differences in brain activity in response to pornographic images were found between the two groups. Compared to MA cues, individuals with MA use disorder had increased activation in the occipital lobe when exposed to pornographic cues. In conclusion, the present study indicates that, even after long-term drug rehabilitation, individuals with MA use disorder have unique brain activity when exposed to MA-related cues. Additionally, our results illustrate that the libido brain response might be restored, and that sexual demand might be more robust than drug demand, in individuals with MA use disorder following long-term drug rehabilitation.

  9. Muscle individual phospholipid classes throughout the processing of dry-cured ham: influence of pre-cure freezing.

    Science.gov (United States)

    Pérez-Palacios, Trinidad; Ruiz, Jorge; Dewettinck, Koen; Le, Thien Trung; Antequera, Teresa

    2010-03-01

    This paper aims to study the profile of phospholipid (PL) classes of Iberian ham throughout its processing and the changes it underwent due to the influence of the pre-cure freezing treatment. The general profile of each PL class did not vary during the ripening stage. Phosphatidylcholine (PC) showed the highest proportion, followed by phosphatidyletanolamine (PE) and phosphatidylserine (PS) and phosphatidylinositol (PI) being the minor PL. The four PL classes were highly hydrolysed during the salting stage and their degradation continued during the rest of the processing. Pre-cure freezing of Iberian ham influenced the levels of the four PL classes at the initial stage, all of them being higher in refrigerated (R) than in pre-cure frozen (F) hams. Moreover, the pattern of hydrolysis was not the same in these two groups. Copyright 2009 Elsevier Ltd. All rights reserved.

  10. Denial of pain medication by health care providers predicts in-hospital illicit drug use among individuals who use illicit drugs.

    Science.gov (United States)

    Ti, Lianping; Voon, Pauline; Dobrer, Sabina; Montaner, Julio; Wood, Evan; Kerr, Thomas

    2015-01-01

    Undertreated pain is common among people who use illicit drugs (PWUD), and can often reflect the reluctance of health care providers to provide pain medication to individuals with substance use disorders. To investigate the relationship between having ever been denied pain medication by a health care provider and having ever reported using illicit drugs in hospital. Data were derived from participants enrolled in two Canadian prospective cohort studies between December 2012 and May 2013. Using bivariable and multivariable logistic regression analyses, the relationship between having ever been denied pain medication by a health care provider and having ever reported using illicit drugs in hospital was examined. Among 1053 PWUD who had experienced ≥ 1 hospitalization, 452 (44%) reported having ever used illicit drugs while in hospital and 491(48%) reported having ever been denied pain medication. In a multivariable model adjusted for confounders, having been denied pain medication was positively associated with having used illicit drugs in hospital (adjusted OR 1.46 [95% CI 1.14 to 1.88]). The results of the present study suggest that the denial of pain medication is associated with the use of illicit drugs while hospitalized. These findings raise questions about how to appropriately manage addiction and pain among PWUD and indicate the potential role that harm reduction programs may play in hospital settings.

  11. 20 CFR 416.936 - Treatment required for individuals whose drug addiction or alcoholism is a contributing factor...

    Science.gov (United States)

    2010-04-01

    ... 20 Employees' Benefits 2 2010-04-01 2010-04-01 false Treatment required for individuals whose drug addiction or alcoholism is a contributing factor material to the determination of disability. 416.936 Section 416.936 Employees' Benefits SOCIAL SECURITY ADMINISTRATION SUPPLEMENTAL SECURITY INCOME FOR THE AGED, BLIND, AND DISABLED Determining...

  12. 20 CFR 404.1536 - Treatment required for individuals whose drug addiction or alcoholism is a contributing factor...

    Science.gov (United States)

    2010-04-01

    ... 20 Employees' Benefits 2 2010-04-01 2010-04-01 false Treatment required for individuals whose drug addiction or alcoholism is a contributing factor material to the determination of disability. 404.1536 Section 404.1536 Employees' Benefits SOCIAL SECURITY ADMINISTRATION FEDERAL OLD-AGE, SURVIVORS AND DISABILITY INSURANCE (1950- ) Determining...

  13. Impact of cancer diagnosis and treatment on glycaemic control among individuals with colorectal cancer using glucose lowering drugs

    NARCIS (Netherlands)

    Zanders, M.M.J.; van Herk-Sukel, M.P.P.; Herings, R.M.C.; van de Poll-Franse, L.V.; Haak, H.

    2016-01-01

    Aims This study aims to evaluate the impact of cancer and its treatment on HbA1c values among individuals with colorectal cancer (CRC) using glucose-lowering drugs (GLDs). Methods Patients with primary CRC (1998–2011) were selected from the Eindhoven Cancer Registry and linked to the PHARMO Database

  14. RxClass

    Data.gov (United States)

    U.S. Department of Health & Human Services — The RxClass Browser is a web application for exploring and navigating through the class hierarchies to find the RxNorm drug members associated with each class....

  15. Effectiveness and sustainability of the ViSC Social Competence Program to prevent cyberbullying and cyber-victimization: Class and individual level moderators.

    Science.gov (United States)

    Gradinger, Petra; Yanagida, Takuya; Strohmeier, Dagmar; Spiel, Christiane

    2016-01-01

    We investigated whether the general anti-bullying program ViSC sustainably prevents cyberbullying and cyber-victimization. A longitudinal randomized control group design was used to examine (i) program effectiveness immediately after a 1 year implementation phase and (ii) sustainable program effects 6 months later taking several moderators on the class level (class climate and ethnic diversity) and on the individual level (gender, age, internet usage, traditional bullying/victimization) into account. Effectiveness (e.g., the change between waves 2 and 1) was examined in 2,042 students (47.6% girls), aged 11.7 years (SD = 0.88) enrolled in 18 schools and 103 classes. Sustainability (e.g., the change between waves 3 and 2) was examined in a sub-sample of 6 schools and 35 classes comprising 659 students. The self-assessment multiple-item scales showed longitudinal and multiple group invariance. Factor scores were extracted to compute difference scores for effectiveness (Posttest minus Pretest) and sustainability (Follow-up test minus Posttest) for cyberbullying and cyber-victimization. Multilevel Modeling was applied to examine (i) the effectiveness and (ii) the sustainability of the ViSC intervention controlling for several individual and class level variables. Controlling for covariates, it was demonstrated that the ViSC program is effective in preventing cyberbullying and cyber-victimization and that the effects are sustainable after 6 months. The consequences for cyberbullying prevention are discussed. © 2016 Wiley Periodicals, Inc.

  16. Drug administration errors in an institution for individuals with intellectual disability : an observational study

    NARCIS (Netherlands)

    van den Bemt, P M L A; Robertz, R; de Jong, A L; van Roon, E N; Leufkens, H G M

    BACKGROUND: Medication errors can result in harm, unless barriers to prevent them are present. Drug administration errors are less likely to be prevented, because they occur in the last stage of the drug distribution process. This is especially the case in non-alert patients, as patients often form

  17. CYP2C9 Genotype vs. Metabolic Phenotype for Individual Drug Dosing—A Correlation Analysis Using Flurbiprofen as Probe Drug

    Science.gov (United States)

    Vogl, Silvia; Lutz, Roman W.; Schönfelder, Gilbert; Lutz, Werner K.

    2015-01-01

    Currently, genotyping of patients for polymorphic enzymes responsible for metabolic elimination is considered a possibility to adjust drug dose levels. For a patient to profit from this procedure, the interindividual differences in drug metabolism within one genotype should be smaller than those between different genotypes. We studied a large cohort of healthy young adults (283 subjects), correlating their CYP2C9 genotype to a simple phenotyping metric, using flurbiprofen as probe drug. Genotyping was conducted for CYP2C9*1, *2, *3. The urinary metabolic ratio MR (concentration of CYP2C9-dependent metabolite divided by concentration of flurbiprofen) determined two hours after flurbiprofen (8.75 mg) administration served as phenotyping metric. Linear statistical models correlating genotype and phenotype provided highly significant allele-specific MR estimates of 0.596 for the wild type allele CYP2C9*1, 0.405 for CYP2C9*2 (68 % of wild type), and 0.113 for CYP2C9*3 (19 % of wild type). If these estimates were used for flurbiprofen dose adjustment, taking 100 % for genotype *1/*1, an average reduction to 84 %, 60 %, 68 %, 43 %, and 19 % would result for genotype *1/*2, *1/*3, *2/*2, *2/*3, and *3/*3, respectively. Due to the large individual variation within genotypes with coefficients of variation ≥ 20 % and supposing the normal distribution, one in three individuals would be out of the average optimum dose by more than 20 %, one in 20 would be 40 % off. Whether this problem also applies to other CYPs and other drugs has to be investigated case by case. Our data for the given example, however, puts the benefit of individual drug dosing to question, if it is exclusively based on genotype. PMID:25775139

  18. CYP2C9 genotype vs. metabolic phenotype for individual drug dosing--a correlation analysis using flurbiprofen as probe drug.

    Science.gov (United States)

    Vogl, Silvia; Lutz, Roman W; Schönfelder, Gilbert; Lutz, Werner K

    2015-01-01

    Currently, genotyping of patients for polymorphic enzymes responsible for metabolic elimination is considered a possibility to adjust drug dose levels. For a patient to profit from this procedure, the interindividual differences in drug metabolism within one genotype should be smaller than those between different genotypes. We studied a large cohort of healthy young adults (283 subjects), correlating their CYP2C9 genotype to a simple phenotyping metric, using flurbiprofen as probe drug. Genotyping was conducted for CYP2C9*1, *2, *3. The urinary metabolic ratio MR (concentration of CYP2C9-dependent metabolite divided by concentration of flurbiprofen) determined two hours after flurbiprofen (8.75 mg) administration served as phenotyping metric. Linear statistical models correlating genotype and phenotype provided highly significant allele-specific MR estimates of 0.596 for the wild type allele CYP2C9*1, 0.405 for CYP2C9*2 (68 % of wild type), and 0.113 for CYP2C9*3 (19 % of wild type). If these estimates were used for flurbiprofen dose adjustment, taking 100 % for genotype *1/*1, an average reduction to 84 %, 60 %, 68 %, 43 %, and 19 % would result for genotype *1/*2, *1/*3, *2/*2, *2/*3, and *3/*3, respectively. Due to the large individual variation within genotypes with coefficients of variation ≥ 20 % and supposing the normal distribution, one in three individuals would be out of the average optimum dose by more than 20 %, one in 20 would be 40 % off. Whether this problem also applies to other CYPs and other drugs has to be investigated case by case. Our data for the given example, however, puts the benefit of individual drug dosing to question, if it is exclusively based on genotype.

  19. CYP2C9 genotype vs. metabolic phenotype for individual drug dosing--a correlation analysis using flurbiprofen as probe drug.

    Directory of Open Access Journals (Sweden)

    Silvia Vogl

    Full Text Available Currently, genotyping of patients for polymorphic enzymes responsible for metabolic elimination is considered a possibility to adjust drug dose levels. For a patient to profit from this procedure, the interindividual differences in drug metabolism within one genotype should be smaller than those between different genotypes. We studied a large cohort of healthy young adults (283 subjects, correlating their CYP2C9 genotype to a simple phenotyping metric, using flurbiprofen as probe drug. Genotyping was conducted for CYP2C9*1, *2, *3. The urinary metabolic ratio MR (concentration of CYP2C9-dependent metabolite divided by concentration of flurbiprofen determined two hours after flurbiprofen (8.75 mg administration served as phenotyping metric. Linear statistical models correlating genotype and phenotype provided highly significant allele-specific MR estimates of 0.596 for the wild type allele CYP2C9*1, 0.405 for CYP2C9*2 (68 % of wild type, and 0.113 for CYP2C9*3 (19 % of wild type. If these estimates were used for flurbiprofen dose adjustment, taking 100 % for genotype *1/*1, an average reduction to 84 %, 60 %, 68 %, 43 %, and 19 % would result for genotype *1/*2, *1/*3, *2/*2, *2/*3, and *3/*3, respectively. Due to the large individual variation within genotypes with coefficients of variation ≥ 20 % and supposing the normal distribution, one in three individuals would be out of the average optimum dose by more than 20 %, one in 20 would be 40 % off. Whether this problem also applies to other CYPs and other drugs has to be investigated case by case. Our data for the given example, however, puts the benefit of individual drug dosing to question, if it is exclusively based on genotype.

  20. Predicting Intra-Individual Academic Achievement Trajectories of Adolescents Nested in Class Environment: Influence of motivation, implicit theory of intelligence, self-esteem and parenting

    Directory of Open Access Journals (Sweden)

    Isabelle Roskam

    2007-05-01

    Full Text Available In a longitudinal study conducted on 1130 adolescents (557 male and 573 female in the 1st-6th grades from Belgian secondary schools, we tested the influence of individual factors (motivational constructs, implicit theory of intelligence and self-esteem and environmental determinants (parenting and class environment of academic achievement (grades in mathematics, language arts and GPA at three points in time. Using hierarchical linear models, we observed a decrease of grade over the course of the study, reciprocal relations between motivational constructs, self-esteem and academic achievement, a strong positive impact of supportive parenting and a moderate influence of class environment.

  1. Molecular Phylogenetics of Transmitted Drug Resistance in Newly Diagnosed HIV Type 1 Individuals in Denmark, a Nation-Wide Study

    DEFF Research Database (Denmark)

    Audelin, Anne Margrethe; Gerstoft, Jan; Obel, Niels

    2011-01-01

    Abstract Highly active antiretroviral treatment is compromised by viral resistance mutations. Transmitted drug resistance (TDR) is therefore monitored closely, but follow-up studies of these patients are limited. Virus from 1405 individuals diagnosed with HIV-1 in Denmark between 2001 and 2009...... without resistance mutations. We observed no difference in progression of the infection between individuals infected with TDR and individuals infected with wild-type HIV-1. The prevalence of TDR is low in Denmark and transmission of dual-drug-resistant HIV-1 is infrequent. The TDR isolates were shown...... resulting in a prevalence of 6.1%, with no changes over time. The main resistance mutations were nucleoside reverse transcriptase inhibitor (NRTI) mutation 215 revertants, as well as nonnucleoside reverse transcriptase inhibitor (NNRTI) mutation 103N/S and protease inhibitor (PI) mutations 90M and 85V...

  2. Molecular phylogenetics of transmitted drug resistance in newly diagnosed HIV Type 1 individuals in Denmark: a nation-wide study

    DEFF Research Database (Denmark)

    Audelin, Anne Margrethe; Gerstoft, Jan; Obel, Niels

    2011-01-01

    Abstract Highly active antiretroviral treatment is compromised by viral resistance mutations. Transmitted drug resistance (TDR) is therefore monitored closely, but follow-up studies of these patients are limited. Virus from 1405 individuals diagnosed with HIV-1 in Denmark between 2001 and 2009...... without resistance mutations. We observed no difference in progression of the infection between individuals infected with TDR and individuals infected with wild-type HIV-1. The prevalence of TDR is low in Denmark and transmission of dual-drug-resistant HIV-1 is infrequent. The TDR isolates were shown...... resulting in a prevalence of 6.1%, with no changes over time. The main resistance mutations were nucleoside reverse transcriptase inhibitor (NRTI) mutation 215 revertants, as well as nonnucleoside reverse transcriptase inhibitor (NNRTI) mutation 103N/S and protease inhibitor (PI) mutations 90M and 85V...

  3. 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).

    Science.gov (United States)

    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.

  4. Cebranopadol, a novel first-in-class analgesic drug candidate: first experience in patients with chronic low back pain in a randomized clinical trial.

    Science.gov (United States)

    Christoph, Annette; Eerdekens, Marie-Henriette; Kok, Maurits; Volkers, Gisela; Freynhagen, Rainer

    2017-09-01

    Chronic low back pain (LBP) is a common condition, usually with the involvement of nociceptive and neuropathic pain components, high economic burden and impact on quality of life. Cebranopadol is a potent, first-in-class drug candidate with a novel mechanistic approach, combining nociceptin/orphanin FQ peptide and opioid peptide receptor agonism. We conducted the first phase II, randomized, double-blind, placebo- and active-controlled trial, evaluating the analgesic efficacy, safety, and tolerability of cebranopadol in patients with moderate-to-severe chronic LBP with and without neuropathic pain component. Patients were treated for 14 weeks with cebranopadol 200, 400, or 600 μg once daily, tapentadol 200 mg twice daily, or placebo. The primary efficacy endpoints were the change from baseline pain to the weekly average 24-hour pain during the entire 12 weeks and during week 12 of the maintenance phase. Cebranopadol demonstrated analgesic efficacy, with statistically significant and clinically relevant improvements over placebo for all doses as did tapentadol. The responder analysis (≥30% or ≥50% pain reduction) confirmed these results. Cebranopadol and tapentadol displayed beneficial effects on sleep and functionality. Cebranopadol treatment was safe, with higher doses leading to higher treatment discontinuations because of treatment-emergent adverse events occurring mostly during titration. Those patients reaching the target doses had an acceptable tolerability profile. The incidence rate of most frequently reported treatment-emergent adverse events during maintenance phase was ≤10%. Although further optimizing the titration scheme to the optimal dose for individual patients is essential, cebranopadol is a new drug candidate with a novel mechanistic approach for potential chronic LBP treatment.

  5. Association of individual non-steroidal anti-inflammatory drugs and chronic kidney disease: a population-based case control study.

    Directory of Open Access Journals (Sweden)

    Ylenia Ingrasciotta

    Full Text Available Non-steroidal anti-inflammatory agents (NSAIDs are known to be associated with renal damage. No clear evidence exists regarding differential risk of chronic kidney disease (CKD, specifically, across various NSAIDs.The aim of this population-based case-control study was to evaluate the association between use of individual NSAIDs and risk of CKD in a general population of Southern Italy.A nested case-control study was carried out using the general practice Arianna database, identifying incident CKD patients as cases and matched controls from 2006 to 2011. The date of first CKD diagnosis was defined as the index date (ID. Conditional logistic regressions were performed to estimate the risk of CKD associated with NSAIDs by class and individual drugs as compared to non-use during different time windows (within one year, six or three months prior to ID, with the latter being defined as current users. Among current users, the effect of cumulative exposure to these drugs was evaluated.Overall, 1,989 CKD cases and 7,906 matched controls were identified. A statistically significant increase in the risk of CKD was found for current users of oxicams (adjusted OR: 1.68; 95% CI: 1.15-2.44 and concerning individual compounds, for ketorolac (adj. OR: 2.54; 95% CI: 1.45-4.44, meloxicam (adj. OR: 1.98; 95% CI: 1.01-3.87 and piroxicam (adj. OR: 1.95; 95% CI: 1.19-3.21.The risk of CKD varies across individual NSAIDs. Increased risk has been found for ketorolac, which may precipitate subclinical CKD through acute renal damage, and long-term exposure to oxicams, especially meloxicam and piroxicam.

  6. Anxiety, bulimia, drug and alcohol addiction, depression, and schizophrenia: what do you think about their aetiology, dangerousness, social distance, and treatment? A latent class analysis approach.

    Science.gov (United States)

    Mannarini, Stefania; Boffo, Marilisa

    2015-01-01

    Mental illness stigma is a serious societal problem and a critical impediment to treatment seeking for mentally ill people. To improve the understanding of mental illness stigma, this study focuses on the simultaneous analysis of people's aetiological beliefs, attitudes (i.e. perceived dangerousness and social distance), and recommended treatments related to several mental disorders by devising an over-arching latent structure that could explain the relations among these variables. Three hundred and sixty university students randomly received an unlabelled vignette depicting one of six mental disorders to be evaluated on the four variables on a Likert-type scale. A one-factor Latent Class Analysis (LCA) model was hypothesized, which comprised the four manifest variables as indicators and the mental disorder as external variable. The main findings were the following: (a) a one-factor LCA model was retrieved; (b) alcohol and drug addictions are the most strongly stigmatized; (c) a realistic opinion about the causes and treatment of schizophrenia, anxiety, bulimia, and depression was associated to lower prejudicial attitudes and social rejection. Beyond the general appraisal of mental illness an individual might have, the results generally point to the acknowledgement of the specific features of different diagnostic categories. The implications of the present results are discussed in the framework of a better understanding of mental illness stigma.

  7. Generating genius: how an Alzheimer's drug became considered a 'cognitive enhancer' for healthy individuals.

    Science.gov (United States)

    Wade, Lucie; Forlini, Cynthia; Racine, Eric

    2014-05-12

    Donepezil, an acetylcholinesterase inhibitor used in the treatment of Alzheimer's disease, has been widely cited in media and bioethics literature on cognitive enhancement (CE) as having the potential to improve the cognitive ability of healthy individuals. In both literatures, this claim has been repeatedly supported by the results of a small study published by Yesavage et al. in 2002 on non-demented pilots (30-70 years old). The factors contributing to this specific interpretation of this study's results are unclear. We examined print media and interdisciplinary bioethics coverage of this small study, aiming to provide insight into how evidence from research may be shaped within different discourses, potentially influencing important policy, ethics, and clinical decisions. Systematic qualitative content analysis was used to examine how this study was reported in 27 media and 22 bioethics articles. Articles were analyzed for content related to: (1) headlines and titles; (2) colloquialisms; and, (3) accuracy of reporting of the characteristics and results of the study. In media and bioethics articles referencing this small study, strong claims were made about donepezil as a CE drug. The majority of headlines, titles, and colloquialisms used enhancement language and the majority of these suggest that donepezil could be used to enhance intellectual ability. Further, both literatures moved between reporting the results of the primary study and magnifying the perceived connection between these results and the CE debate that was alluded to in the primary study. Specific descriptions of the results overwhelmingly reported an improvement in performance on a flight simulator, while more general statements claimed donepezil enhanced cognitive performance. Further, a high level of reporting accuracy was found regarding study characteristics of the original study, but variable levels of accuracy surrounded the presentation of complex characteristics (i.e., methods) or

  8. Individual and couple-level risk factors for hepatitis C infection among heterosexual drug users: a multilevel dyadic analysis.

    Science.gov (United States)

    McMahon, James M; Pouget, Enrique R; Tortu, Stephanie

    2007-06-01

    Hepatitis C virus (HCV) is the most common bloodborne pathogen in the United States and is a leading cause of liver-related morbidity and mortality. Although it is known that HCV is most commonly transmitted among injection drug users, the role of sexual transmission in the spread of HCV remains controversial because of inconsistent findings across studies involving heterosexual couples. A novel multilevel modeling technique designed to overcome the limitations of previous research was performed to assess multiple risk factors for HCV while partitioning the source of risk at the individual and couple level. The analysis was performed on risk exposure and HCV screening data obtained from 265 drug-using couples in East Harlem, New York City. In multivariable analysis, significant individual risk factors for HCV included a history of injection drug use, tattooing, and older age. At the couple level, HCV infection tended to cluster within couples, and this interdependence was accounted for by couples' drug-injection behavior. Individual and couple-level sexual behavior was not associated with HCV infection. Our results are consistent with prior research indicating that sexual contact plays little role in HCV transmission. Rather, couples' injection behavior appears to account for the clustering of HCV within heterosexual dyads.

  9. Biowaiver extension potential to BCS Class III high solubility-low permeability drugs: bridging evidence for metformin immediate-release tablet.

    Science.gov (United States)

    Cheng, Ching-Ling; Yu, Lawrence X; Lee, Hwei-Ling; Yang, Chyun-Yu; Lue, Chang-Sha; Chou, Chen-Hsi

    2004-07-01

    The biopharmaceutics classification system (BCS) allows biowaiver for rapid dissolving immediate-release (IR) products of Class I drugs (high solubility and high permeability). The possibility of extending biowaivers to Class III high solubility and low permeability drugs is currently under scrutiny. In vivo bioequivalence data of different formulations of Class III drugs would support such an extension. The objective of this work was to demonstrate the bioequivalence of two marketed IR tablet products of a Class III drug, metformin hydrochloride, that are rapidly dissolving and have similar in vitro dissolution profiles. The effect of race on the systemic exposure of metformin was also explored. A randomized, open-label, two-period crossover study was conducted in 12 healthy Chinese male volunteers. Each subject received a single-dose of 500 mg of each product after an overnight fasting. The plasma concentrations of metformin were followed for 24 h. No significant formulation effect was found for the bioequivalence metrics: areas under concentration-time curve (AUC0-t, AUC0-infinity) and maximal concentration (Cmax). The 90% confidence intervals for the ratio of means were found within the acceptance range of 80-125% for the log-transformed data. Based on these results, it was concluded that the two IR products are bioequivalent. The pharmacokinetic parameters of metformin in Chinese for both products were similar and were in good agreement with those reported for metformin IR tablets in other ethnic populations. This study serves as an example for supporting biowaiver for BCS Class III drugs.

  10. Psychiatric disorders among individuals who drive after the recent use of alcohol and drugs.

    Science.gov (United States)

    Faller, Sibele; Webster, J Matthew; Leukefeld, Carl G; Bumaguin, Daniela Benzano; Duarte, Paulina do Carmo Arruda Vieira; De Boni, Raquel; Pechansky, Flavio

    2012-10-01

    This cross-sectional study assessed the prevalence of psychiatric disorders among drivers , as well as the association between recent alcohol and drug use and psychiatric diagnoses using telephone interviews. Drivers (n = 1,134) included in a roadside survey from 25 Brazilian state capitals were given a breathalyzer test, and their saliva was tested for psychoactive drugs. A telephone interview was conducted to perform psychiatric disorder evaluations using the MINI. This association was analyzed with a Poisson regression model. The prevalence of any psychiatric disorder was 40.5% among drivers with recent alcohol or drug use, compared with 12.9% among the other drivers. Alcohol/drug-positive drivers reported a higher prevalence of depression (19.4%), mania (6.5%), hypomania (5.4%), post-traumatic stress disorder (8.6%), antisocial personality (7.8%), and substance/alcohol abuse or dependence (48.1%) compared with other drivers (3.5, 2.5, 2.1, 0.5, 1.3 and 18.3% [p < 0.001], respectively). Drivers with recent alcohol or drug use were 2.5 times more likely to have a psychiatric diagnosis (CI: 1.8-3.6, p < 0.001). This is the first study in a low-/middle-income country to evaluate psychiatric disorders in drivers with recent alcohol or drug using telephone interviews. Psychiatric disorders were found to be associated with drug and alcohol use. This type of epidemiological information for curtailing related driving problems, as these psychiatric conditions are diagnosable. The results of this study can aid in the design of interventions, treatment programs and focused psychiatric evaluations, both in Brazil and abroad.

  11. Investigation of the effect of solubility increase at the main absorption site on bioavailability of BCS class II drug (risperidone) using liquisolid technique.

    Science.gov (United States)

    Khames, Ahmed

    2017-11-01

    BCS class II drugs usually suffer inadequate bioavailability as dissolution step is the absorption rate limiting step. In this work, the effect of solubility increase at the main absorption site for these drugs was investigated using risperidone as a drug model. Liquisolid technique was applied to prepare risperidone per-oral tablets of high dissolution rate at intestinal pH (6.8) using versatile nonionic surfactants of high solubilizing ability [Transcutol HP, Labrasol and Labrasol/Labrafil (1:1) mixture] as liquid vehicles at different drug concentrations (10-30%) and fixed (R). The prepared liquisolid tablets were fully evaluated and the dissolution rate at pH 6.8 was investigated. The formulae that showed significantly different release rate were selected and subjected to mathematical modeling using DE 25 , MDT and similarity factor (f2). Depending on mathematical modeling results, formula of higher dissolution rate was subjected to solid state characterization using differential scanning calorimetric (DSC), infrared spectroscopy (IR) and X-ray diffraction (XRD). Finally, the drug bioavailability was studied in comparison to conventional tablets in rabbits. Results showed that liquisolid tablet prepared using Labrasol/Labrafil (1:1) mixture as liquid vehicle containing 10% risperidone is a compatible formula with law drug crystallinity and higher dissolution rate (100% in 25 min). The drug bioavailability was significantly increased in comparison to the conventional tablets (1441.711 μg h/mL and 137.518 μg/mL in comparison to 321.011 μg h/mL and 38.673 μg/mL for AUC and Cp max , respectively). This led to the conclusion that liquisolid technique was efficiently improved drug solubility and solubility increase of BCS class II drugs at their main absorption site significantly increases their bioavailability.

  12. Cardiovascular safety of non-steroidal anti-inflammatory drugs among healthy individuals

    DEFF Research Database (Denmark)

    Fosbøl, Emil Loldrup; Køber, Lars; Torp-Pedersen, Christian

    2010-01-01

    Studies have raised concern on the cardiovascular safety of NSAIDs. We studied safety of NSAID therapy in a nationwide cohort of healthy individuals.......Studies have raised concern on the cardiovascular safety of NSAIDs. We studied safety of NSAID therapy in a nationwide cohort of healthy individuals....

  13. Recapitulation of Clinical Individual Susceptibility to Drug-Induced QT Prolongation in Healthy Subjects Using iPSC-Derived Cardiomyocytes

    Directory of Open Access Journals (Sweden)

    Tadahiro Shinozawa

    2017-02-01

    Full Text Available To predict drug-induced serious adverse events (SAE in clinical trials, a model using a panel of cells derived from human induced pluripotent stem cells (hiPSCs of individuals with different susceptibilities could facilitate major advancements in translational research in terms of safety and pharmaco-economics. However, it is unclear whether hiPSC-derived cells can recapitulate interindividual differences in drug-induced SAE susceptibility in populations not having genetic disorders such as healthy subjects. Here, we evaluated individual differences in SAE susceptibility based on an in vitro model using hiPSC-derived cardiomyocytes (hiPSC-CMs as a pilot study. hiPSCs were generated from blood samples of ten healthy volunteers with different susceptibilities to moxifloxacin (Mox-induced QT prolongation. Different Mox-induced field potential duration (FPD prolongation values were observed in the hiPSC-CMs from each individual. Interestingly, the QT interval was significantly positively correlated with FPD at clinically relevant concentrations (r > 0.66 in multiple analyses including concentration-QT analysis. Genomic analysis showed no interindividual significant differences in known target-binding sites for Mox and other drugs such as the hERG channel subunit, and baseline QT ranges were normal. The results suggest that hiPSC-CMs from healthy subjects recapitulate susceptibility to Mox-induced QT prolongation and provide proof of concept for in vitro preclinical trials.

  14. Therapeutic drug monitoring to individualize the dosing of pazopanib: a pharmacokinetic feasibility study

    NARCIS (Netherlands)

    Wit, D. de; Erp, N. van; Hartigh, J. den; Wolterbeek, R..; Hollander-van Deursen, M. den; Labots, M.; Guchelaar (LUMC), H.J.; Verheul, H.M.; Gelderblom, H.

    2015-01-01

    BACKGROUND: Patients treated with the standard dose of pazopanib show a large interpatient variability in drug exposure defined as the area under the plasma concentration-time curve (AUC0-24h). The primary objective of this study was to evaluate the feasibility of pharmacokinetics (PK)-guided

  15. Creating Democratic Class Rooms in Asian Contexts: The Influences of Individual and School Level Factors on Open Classroom Climate

    Science.gov (United States)

    Kuang, Xiaoxue; Kennedy, Kerry J.; Mok, Magdalena Mo Ching

    2018-01-01

    Purpose: Literature indicates that open classroom climate (OCC) is a positive influence on civic outcomes. Few studies have explored factors that appear to facilitate OCC. Most research on OCC has focused on Western countries. The emphasis has been on individual student characteristics related to OCC with little attention made to school level…

  16. Development and psychometric testing the Health of Body, Mind and Spirit Scale for assessing individuals who have drug abuse histories.

    Science.gov (United States)

    Sun, Fan-Ko; Chiang, Chun-Ying; Lu, Chu-Yun; Yu, Pei-Jane; Liao, Tzu-Chiao; Lan, Chu-Mei

    2018-03-01

    To develop the Health of Body, Mind and Spirit Scale (HBMSS), which was designed to assess drug abusers' health condition. Helping drug abusers to become healthy is important to healthcare professionals. However, no instrument exists to assess drug abusers' state of health. A cross-sectional questionnaire survey was implemented to examine the validity of the HBMSS. Data were collected from 2015-2016 at one drug abuse prevention centre in Taiwan. Participants (N = 320) who had abused drugs were invited to complete a preliminary 64-item version of the HBMSS. An item analysis, criterion-related validity analysis (using the Relapse Prediction Scale [RPS] score), split-half reliability testing and confirmatory factor analysis (CFA) were conducted to examine the psychometric properties of the HBMSS. The final version of the HBMSS contained 15 items that were divided into three subscales: the health of the body, mind and spirit. Cronbach's α and split-half reliability coefficients were all above .85. The factor loading of each item was between .74-.95. The HBMSS had satisfactory criterion-related validity with the RPS score (r = -.50, p < .001). A second-order CFA was conducted on the HBMSS. The fit indexes were good, χ 2  = 184.060, df = 94, χ 2 /df = 1.958 (p = .000). The entire HBMSS and the subscales had satisfactory reliability and validity. Healthcare professionals could use the HBMSS to evaluate the condition of the health of individuals with a drug abuse history. © 2017 John Wiley & Sons Ltd.

  17. Comparing Perceived Adequacy of Help Received Among Different Classes of Individuals with Severe Mental Disorders at Five-Year Follow-Up: A Longitudinal Cluster Analysis.

    Science.gov (United States)

    Fleury, Marie-Josée; Grenier, Guy; Bamvita, Jean-Marie

    2017-11-13

    This study developed a typology describing change in the perceived adequacy of help received among 204 individuals with severe mental disorders, 5 years after transfer to the community following a major mental health reform in Quebec (Canada). Participant typologies were constructed using a two-step cluster analysis. There were significant differences between T0 and T2 for perceived adequacy of help received and other independent variables, including seriousness of needs, help from services or relatives, and care continuity. Five classes emerged from the analysis. Perceived adequacy of help received at T2 increased for Class 1, mainly comprised of older women with mood disorders. Overall, greater care continuity and levels of help from services and relatives related to higher perceived AHR. Changes in perceived adequacy of help received resulting from several combinations of associated variables indicate that MH service delivery should respond to specific profiles and determinants.

  18. Single Nucleotide Polymorphisms in Cellular Drug Transporters Are Associated with Intolerance to Antiretroviral Therapy in Brazilian HIV-1 Positive Individuals.

    Directory of Open Access Journals (Sweden)

    Mônica Barcellos Arruda

    Full Text Available Adverse reactions are the main cause of treatment discontinuation among HIV+ individuals. Genes related to drug absorption, distribution, metabolism and excretion (ADME influence drug bioavailability and treatment response. We have investigated the association between single nucleotide polymorphisms (SNPs in 29 ADME genes and intolerance to therapy in a case-control study including 764 individuals. Results showed that 15 SNPs were associated with intolerance to nucleoside and 11 to non-nucleoside reverse transcriptase inhibitors (NRTIs and NNRTIs, and 8 to protease inhibitors (PIs containing regimens under alpha = 0.05. After Bonferroni adjustment, two associations remained statistically significant. SNP rs2712816, at SLCO2B1 was associated to intolerance to NRTIs (ORGA/AA = 2.37; p = 0.0001, while rs4148396, at ABCC2, conferred risk of intolerance to PIs containing regimens (ORCT/TT = 2.64; p = 0.00009. Accordingly, haplotypes carrying rs2712816A and rs4148396T alleles were also associated to risk of intolerance to NRTIs and PIs, respectively. Our data reinforce the role of drug transporters in response to HIV therapy and may contribute to a future development of personalized therapies.

  19. Tear Film Break-Up Time: Comparison between Patients using Psychiatric Drugs and Healthy Individuals

    Directory of Open Access Journals (Sweden)

    Parvin Dibajnia

    2014-09-01

    Full Text Available Background: Ocular dryness is a well-recognized adverse side effect of many medications. The purpose of this study was to compare tear film stability between psychiatric patients that use lithium carbonate or carbamazepine and normal cases. Materials and Methods: Tear film break up time test was performed in three groups, 30 patients using lithium carbonate, 30 patients using carbamazepine and 30 normal cases. Values of the TBUTs were compared among groups by the independent t-test. Results: Differences between both of patients and control groups were significant (p<0.0001. Conclusion: The results show that these drugs contribute to decrease of tear film break up time.

  20. 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).

    Science.gov (United States)

    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

  1. Therapeutic drug monitoring for the individualization of docetaxel dosing: a randomized pharmacokinetic study

    NARCIS (Netherlands)

    Engels, Frederike K.; Loos, Walter J.; van der Bol, Jessica M.; de Bruijn, Peter; Mathijssen, Ron H. J.; Verweij, Jaap; Mathot, Ron A. A.

    2011-01-01

    Docetaxel pharmacokinetic (PK) parameters, notably clearance and exposure (AUC), are characterized by large interindividual variability. The purpose of this study was to evaluate the effect of PK-guided [area under the plasma concentration versus time curve (AUC) targeted], individualized docetaxel

  2. Individualized treatment of multidrug-resistant tuberculosis using therapeutic drug monitoring

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    Mathieu S Bolhuis

    2016-01-01

    Conclusion: TDM is highly valuable to individualize and optimize treatment of complex MDR-TB patients. TDM is routinely applied in Tuberculosis Center Beatrixoord, and high success rates for treatment of MDR-TB patients have been achieved. DBS and LSS make implementation of TDM feasible, even in low- and middle-income countries.

  3. HIV-1 diversity and drug-resistant mutations in infected individuals in Changchun, China.

    Directory of Open Access Journals (Sweden)

    Ming Yan

    Full Text Available OBJECTIVES: Human immunodeficiency virus type 1 (HIV-1 infection has been detected in all provinces of China. Although epidemiological and phylogenetic studies have been conducted in many regions, such analyses are lacking from Jilin province in northeastern China. METHOD: Epidemiological and phylogenetic analyses, as well as detection of drug-resistant mutations, were conducted on 57 HIV-1 infected patients from Changchun city identified and confirmed through annual surveillance by local Centers for Disease Control in Jilin province of northeastern China in 2012. RESULTS: Sexual contact was determined to be the major pathway for HIV-1 transmission in Jilin, where hetero- and homosexual activities contributed almost equally. Phylogenetic analyses detected multiple subtypes of HIV-1 including subtype G circulating in Jilin, with multiple origins for each of them. Both subtype B and CRF01_AE were dominant, and evidence of subtype B transmitting between different high-risk groups was observed. Mutations in the viral protease at position 71 indicated the presence of a selective pressure. Several drug-resistant mutations were detected, although they were predicted with low-level resistance to antiviral treatments. CONCLUSIONS: Information from this study fills the gap in knowledge of HIV-1 transmission in Changchun city, Jilin province, China. By revealing the origin and evolutionary status of local HIV-1 strains, this work contributes to ongoing efforts in the control and prevention of AIDS.

  4. The effect of individual antiretroviral drugs on body composition in HIV-infected persons initiating highly active antiretroviral therapy.

    Science.gov (United States)

    Shlay, Judith C; Sharma, Shweta; Peng, Grace; Gibert, Cynthia L; Grunfeld, Carl

    2009-07-01

    To examine the long-term effects of individual antiretroviral drugs on body composition among 416 persons initiating antiretroviral therapy (ART). In a substudy of a clinical trial of persons initiating ART, changes in body composition attributable to individual ART were examined. ARTs assessed were as follows: indinavir, ritonavir, nelfinavir, efavirenz, nevirapine, stavudine (d4T), zidovudine (ZDV), lamivudine (3TC), didanosine, and abacavir. Skinfolds and circumferences were measured at baseline and every 4 months. Mid arm, mid thigh, and waist subcutaneous tissue areas and nonsubcutaneous tissue areas were calculated. Rates of change per year of exposure to each individual ART drug were determined using multivariate longitudinal regression. d4T and ZDV use was associated with losses in subcutaneous tissue area and skinfold thickness. 3TC use was associated with gains in all subcutaneous tissue areas and skinfold thickness, whereas abacavir use was associated with an increase in waist subcutaneous tissue area. Indinavir was associated with gains in waist subcutaneous tissue area, whereas indinavir, efavirenz, and nevirapine were associated with increases in upper back skinfolds. d4T use was also associated with increases in all nonsubcutaneous tissue areas; 3TC use was associated with the greatest increase in waist nonsubcutaneous tissue area. In this prospective nonrandomized evaluation, the nucleoside reverse transcriptase inhibitors d4T and ZDV were associated with decreases in subcutaneous tissue areas, whereas 3TC use was associated with increased subcutaneous tissue areas and waist nonsubcutaneous tissue area.

  5. Assessment of divine proportion in the cranial structure of individuals with Angle Class II malocclusion on lateral cephalograms

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    Marcos André dos Santos da Silva

    2012-06-01

    Full Text Available INTRODUCTION: The study of the Divine Proportion (Φ = 1.618 began with the Greeks, having as main researchers the mathematician Pythagoras and the sculptor Phidias. In Dentistry, Ricketts (1981-82 was an early to study this issue. OBJECTIVE: This study proposed to evaluate how some cephalometric measures are presented in relation to the Divine Proportion, with the total of 52 proportions, formed by 28 cephalometric landmarks. METHODS: Lateral cephalograms of 40 Class II adults patients aging from 17 to 45 years (13 male and 27 female were evaluated. The linear distances between the landmarks were measured using Radiocef Studio software. RESULTS: After statistical analysis, the data shown an average of 65,48% in the Divine Proportion, 17,5% in the relation Ans-Op/V1S-DM16 and 97,5% in the relations Na-Me/Na-PoNa e Na-PoNa/Na-Gn. CONCLUSION: Among all cephalometric measurements investigated, the lower facial third and the dental arches showed the smallest percentages of Divine Proportion.

  6. Diabetes education through group classes leads to better care and outcomes than individual counselling in adults: a population-based cohort study.

    Science.gov (United States)

    Hwee, Jeremiah; Cauch-Dudek, Karen; Victor, J Charles; Ng, Ryan; Shah, Baiju R

    2014-05-09

    Self-management education, supported by multidisciplinary health care teams, is essential for optimal diabetes management. We sought to determine whether acute diabetes complications or quality of care differed for patients in routine clinical care when their self-management education was delivered through group diabetes education classes versus individual counselling. With the use of population-level administrative and primary data, all diabetic patients in Ontario who attended a self-management education program in 2006 were identified and grouped according to whether they attended group classes (n=12,234), individual counselling (n=55,761) or a mixture of both (n=9,829). Acute complications and quality of care in the following year were compared among groups. Compared with those attending individual counselling, patients who attended group classes were less likely to have emergency department visits for hypo/hyperglycemia (odds ratio 0.54, 95% confidence interval [CI]: 0.42-0.68), hypo/hyperglycemia hospitalizations (OR 0.49, CI: 0.32-0.75) or foot ulcers/cellulitis (OR 0.64, CI: 0.50-0.81). They were more likely to have adequate HbA1c testing (OR 1.10, CI: 1.05-1.15) and lipid testing (OR 1.25, CI: 1.19-1.32), and were more likely to receive statins (OR 1.22, CI: 1.07-1.39). Group self-management education was associated with fewer acute complications and some improvements in processes of care. Group sessions can offer care to more patients with reduced human resource requirements. With increased pressure to find efficiencies in health care delivery, group diabetes education may provide an opportunity to deliver less resource-intensive care that simultaneously improves patient care.

  7. Big-data-based edge biomarkers: study on dynamical drug sensitivity and resistance in individuals.

    Science.gov (United States)

    Zeng, Tao; Zhang, Wanwei; Yu, Xiangtian; Liu, Xiaoping; Li, Meiyi; Chen, Luonan

    2016-07-01

    Big-data-based edge biomarker is a new concept to characterize disease features based on biomedical big data in a dynamical and network manner, which also provides alternative strategies to indicate disease status in single samples. This article gives a comprehensive review on big-data-based edge biomarkers for complex diseases in an individual patient, which are defined as biomarkers based on network information and high-dimensional data. Specifically, we firstly introduce the sources and structures of biomedical big data accessible in public for edge biomarker and disease study. We show that biomedical big data are typically 'small-sample size in high-dimension space', i.e. small samples but with high dimensions on features (e.g. omics data) for each individual, in contrast to traditional big data in many other fields characterized as 'large-sample size in low-dimension space', i.e. big samples but with low dimensions on features. Then, we demonstrate the concept, model and algorithm for edge biomarkers and further big-data-based edge biomarkers. Dissimilar to conventional biomarkers, edge biomarkers, e.g. module biomarkers in module network rewiring-analysis, are able to predict the disease state by learning differential associations between molecules rather than differential expressions of molecules during disease progression or treatment in individual patients. In particular, in contrast to using the information of the common molecules or edges (i.e.molecule-pairs) across a population in traditional biomarkers including network and edge biomarkers, big-data-based edge biomarkers are specific for each individual and thus can accurately evaluate the disease state by considering the individual heterogeneity. Therefore, the measurement of big data in a high-dimensional space is required not only in the learning process but also in the diagnosing or predicting process of the tested individual. Finally, we provide a case study on analyzing the temporal expression

  8. Crosslinked hydrogels?a promising class of insoluble solid molecular dispersion carriers for enhancing the delivery of poorly soluble drugs

    OpenAIRE

    Sun, Dajun D.; Lee, Ping I.

    2014-01-01

    Water-insoluble materials containing amorphous solid dispersions (ASD) are an emerging category of drug carriers which can effectively improve dissolution kinetics and kinetic solubility of poorly soluble drugs. ASDs based on water-insoluble crosslinked hydrogels have unique features in contrast to those based on conventional water-soluble and water-insoluble carriers. For example, solid molecular dispersions of poorly soluble drugs in poly(2-hydroxyethyl methacrylate) (PHEMA) can maintain a ...

  9. [Changing the focus: an exploratory study of drug use and workplace violence among women of popular classes in Rio de Janeiro, Brazil].

    Science.gov (United States)

    David, Helena Maria Scherlowski Leal; Caufield, Catherine

    2005-01-01

    This exploratory study aimed to investigate factors related to the use of illicit and licit drugs and workplace violence in a group of women from popular classes in the city of Rio de Janeiro. We used a descriptive and analytic quantitative approach was used, as well as a qualitative approach through in-depth interviews with women who suffered or were suffering workplace violence, using the collective subject discourse analysis methodology. The results showed sociodemographic and work situations that can be considered as possible risk factors for drug consumption and workplace violence. The qualitative analysis shows how this group perceives the phenomena of drug use and workplace violence, expanding the comprehension about these issues and providing conceptual and methodological elements for additional studies on this subject.

  10. Hair cortisol in drug-naïve first-episode individuals with psychosis

    Directory of Open Access Journals (Sweden)

    Elvis H. Andrade

    2016-03-01

    Full Text Available Objectives: To compare hair cortisol concentrations (HCC in drug-naïve first-episode psychosis (FEP patients and healthy controls and to investigate the correlations between HCC and psychopathology. Methods: Twenty-four drug-naïve FEP patients and 27 gender- and age-matched healthy control subjects were recruited. The Structured Clinical Interview for DSM-IV (SCID-1 was used to confirm/rule out diagnoses, and the Positive and Negative Symptoms Scale (PANSS was used to assess symptom severity. Hair samples (2-3 cm long obtained from the posterior vertex region of the scalp were processed in 1-cm segments considering a hair growth rate of 1 cm per month. The 1-cm segments were classified according to their proximity to the scalp: segment A was the closest to the scalp and referred to the month prior to inclusion in the study. Segments B and C referred to the 2nd and 3rd months prior to the time of evaluation respectively. Hair steroid extraction was performed using a known protocol. Results: Two-way analysis of covariance (ANCOVA with gender and age as covariates revealed a group effect (F1.106 = 4.899, p = 0.029 on HCC. Between-segment differences correlated with total PANSS score and with PANSS General Psychopathology subscale and total score. Conclusions: Our findings suggest that hypothalamic-pituitary-adrenal (HPA axis, as assessed by long-term (3-month cortisol concentration, is abnormal in the early stages of psychosis. The magnitude of changes in HCC over time prior to the FEP correlates to psychopathology. HPA axis abnormalities might begin prior to full-blown clinical presentation requiring hospital admission.

  11. Using the IGCRA (individual, group, classroom reflective action technique to enhance teaching and learning in large accountancy classes

    Directory of Open Access Journals (Sweden)

    Cristina Poyatos

    2011-02-01

    Full Text Available First year accounting has generally been perceived as one of the more challenging first year business courses for university students. Various Classroom Assessment Techniques (CATs have been proposed to attempt to enrich and enhance student learning, with these studies generally positioning students as learners alone. This paper uses an educational case study approach and examines the implementation of the IGCRA (individual, group, classroom reflective action technique, a Classroom Assessment Technique, on first year accounting students’ learning performance. Building on theoretical frameworks in the areas of cognitive learning, social development, and dialogical learning, the technique uses reports to promote reflection on both learning and teaching. IGCRA was found to promote feedback on the effectiveness of student, as well as teacher satisfaction. Moreover, the results indicated formative feedback can assist to improve the learning and learning environment for a large group of first year accounting students. Clear guidelines for its implementation are provided in the paper.

  12. Differential physiological and behavioral cues observed in individuals smoking botanical marijuana versus synthetic cannabinoid drugs.

    Science.gov (United States)

    Chase, Peter B; Hawkins, Jeff; Mosier, Jarrod; Jimenez, Ernest; Boesen, Keith; Logan, Barry K; Walter, Frank G

    2016-01-01

    Synthetic cannabinoid use has increased in many states, and medicinal and/or recreational marijuana use has been legalized in some states. These changes present challenges to law enforcement drug recognition experts (DREs) who determine whether drivers are impaired by synthetic cannabinoids or marijuana, as well as to clinical toxicologists who care for patients with complications from synthetic cannabinoids and marijuana. Our goal was to compare what effects synthetic cannabinoids and marijuana had on performance and behavior, including driving impairment, by reviewing records generated by law enforcement DREs who evaluated motorists arrested for impaired driving. Data were from a retrospective, convenience sample of de-identified arrest reports from impaired drivers suspected of using synthetic cannabinoids (n = 100) or marijuana (n = 33). Inclusion criteria were arrested drivers who admitted to using either synthetic cannabinoids or marijuana, or who possessed either synthetic cannabinoids or marijuana; who also had a DRE evaluation at the scene; and whose blood screens were negative for alcohol and other drugs. Exclusion criteria were impaired drivers arrested with other intoxicants found in their drug or alcohol blood screens. Blood samples were analyzed for 20 popular synthetic cannabinoids by using liquid chromatography-tandem mass spectrometry. Delta-9-tetrahydrocannabinol (THC) and THC-COOH were quantified by gas chromatography-mass spectrometry. Statistical significance was determined by using Fisher's exact test or Student's t-test, where appropriate, to compare the frequency of characteristics of those in the synthetic cannabinoid group versus those in the marijuana group. 16 synthetic cannabinoid and 25 marijuana records met selection criteria; the drivers of these records were arrested for moving violations. Median age for the synthetic cannabinoid group (n = 16, 15 males) was 20 years (IQR 19-23 years). Median age for the marijuana group (n = 25, 21

  13. Analysing malaria drug trials on a per-individual or per-clone basis: a comparison of methods.

    Science.gov (United States)

    Jaki, Thomas; Parry, Alice; Winter, Katherine; Hastings, Ian

    2013-07-30

    There are a variety of methods used to estimate the effectiveness of antimalarial drugs in clinical trials, invariably on a per-person basis. A person, however, may have more than one malaria infection present at the time of treatment. We evaluate currently used methods for analysing malaria trials on a per-individual basis and introduce a novel method to estimate the cure rate on a per-infection (clone) basis. We used simulated and real data to highlight the differences of the various methods. We give special attention to classifying outcomes as cured, recrudescent (infections that never fully cleared) or ambiguous on the basis of genetic markers at three loci. To estimate cure rates on a per-clone basis, we used the genetic information within an individual before treatment to determine the number of clones present. We used the genetic information obtained at the time of treatment failure to classify clones as recrudescence or new infections. On the per-individual level, we find that the most accurate methods of classification label an individual as newly infected if all alleles are different at the beginning and at the time of failure and as a recrudescence if all or some alleles were the same. The most appropriate analysis method is survival analysis or alternatively for complete data/per-protocol analysis a proportion estimate that treats new infections as successes. We show that the analysis of drug effectiveness on a per-clone basis estimates the cure rate accurately and allows more detailed evaluation of the performance of the treatment. Copyright © 2012 John Wiley & Sons, Ltd.

  14. Impact of a weekly dance class on the functional mobility and on the quality of life of individuals with Parkinson´s disease

    Directory of Open Access Journals (Sweden)

    Lisa eHeiberger

    2011-10-01

    Full Text Available Individuals with Parkinson´s disease (PD mainly suffer from motor impairments which increase the risk of falls and lead to a decline of quality of life. Several studies investigated the long-term effect of dance for people with PD. The aims of the present study were to investigate (i the short-term effects of dance (i.e. the effect immediately after the dance class on motor control in individuals with PD and (ii the long-term effects of 8 months of participation in the weekly dance class on the quality of life of the PD patients and their caregivers. The dance lessons took place in a ballet studio and were led by a professional dancer. Eleven people with moderate to severe PD (58-85 years old were subjected to a motor and quality of life assessments. With respect to the motor assessments the Unified Parkinson Disease Rating Scale III (UPDRS III, the Timed up and go – Test (TUG and the Semitandem – Test (SeTa before and after the dance class were used. With respect to the quality of life and well-being we applied Quality of Life Scale (QOLS as well as the Westheimer questionnaire. Additionally, we asked the caregivers to fill out the Questionnaire for caregivers. We found a significant beneficial short-term effect for the total score of the UPDRS motor score. The strongest improvements were in rigidity scores followed by significant improvements in hand movements, finger taps and facial expression. No significant changes were found for TUG and for SeTA. The results of the questionnaires showed positive effects of the dance class on social life, health, body-feeling and mobility, and on every day life competences of the PD patients. Beneficial effect was also found for the caregivers. The findings demonstrate that dance has beneficial effect on the functional mobility of individuals with PD. Further, dance improves the quality of life of the patients and their caregivers. Dance may lead to better therapeutic strategies as it is engaging and

  15. HIV-1 drug resistance surveillance in antiretroviral treatment-naive individuals from a reference hospital in Guatemala, 2010-2013.

    Science.gov (United States)

    Avila-Ríos, Santiago; García-Morales, Claudia; Garrido-Rodríguez, Daniela; Tapia-Trejo, Daniela; Girón-Callejas, Amalia Carolina; Mendizábal-Burastero, Ricardo; Escobar-Urias, Ingrid Yessenia; García-González, Blanca Leticia; Navas-Castillo, Sabrina; Pinzón-Meza, Rodolfo; Mejía-Villatoro, Carlos Rodolfo; Reyes-Terán, Gustavo

    2015-04-01

    The recent expansion of antiretroviral treatment (ART) coverage in middle/low-income countries has been associated with increasing prevalence of HIV pre-ART drug resistance (PDR). We assessed PDR prevalence, patterns, and trends in Guatemala. Blood samples from 1,084 ART-naive individuals, enrolled from October 2010 to December 2013 at the Roosevelt Hospital in Guatemala City, were obtained. PDR was evaluated using the WHO mutation list for transmitted drug resistance (TDR) surveillance. An overall PDR prevalence of 7.3% (95% CI 5.8-9.0%) was observed for the whole study period. TDR to nonnucleoside reverse transcriptase inhibitors (NNRTI) was the highest (4.9%, p500 and 350-500 CD4(+) T cells/μl (7.4% and 8.7%, respectively) compared to individuals with Guatemala remains at an intermediate level. Nevertheless, we have shown evidence suggesting increasing trends in NNRTI PDR, which need to be taken into account in national HIV management policies.

  16. Individual and combined effects of cannabis and tobacco on drug reward processing in non-dependent users.

    Science.gov (United States)

    Hindocha, Chandni; Lawn, Will; Freeman, Tom P; Curran, H Valerie

    2017-11-01

    Cannabis and tobacco are often smoked simultaneously in joints, and this practice may increase the risks of developing tobacco and/or cannabis use disorders. Currently, there is no human experimental research on how these drugs interact on addiction-related measures. This study aimed to investigate how cannabis and tobacco, each alone and combined together in joints, affected individuals' demand for cannabis puffs and cigarettes, explicit liking of drug and non-drug-related stimuli and craving. A double-blind, 2 (active cannabis, placebo cannabis) × 2 (active tobacco, placebo tobacco) crossover design was used with 24 non-dependent cannabis and tobacco smokers. They completed a pleasantness rating task (PRT), a marijuana purchase task (MPT) and a cigarette purchase task (CPT) alongside measures of craving pre- and post-drug administration. Relative to placebo cannabis, active cannabis reduced liking of cannabis-associated stimuli and increased response time to all stimuli except cigarette-related stimuli. Relative to placebo cannabis, active cannabis decreased demand for cannabis puffs (trends for breakpoint and elasticity) and cigarettes (breakpoint, P max , O max ) on several characteristics of the purchase tasks. We found no evidence that active tobacco, both alone or combined with cannabis, had an effect on liking, demand or craving. Acutely, cannabis reduced liking of cannabis-related stimuli and demand for cannabis itself. Acute cannabis also reduced demand for cigarettes on the CPT. Acute tobacco administration did not affect demand or pleasantness ratings for cigarettes themselves or cannabis. In non-dependent cannabis and tobacco co-users, tobacco did not influence the rewarding effects of cannabis.

  17. Preparation, in-vitro and in-vivo evaluation of spray-dried ternary solid dispersion of biopharmaceutics classification system class II model drug.

    Science.gov (United States)

    Paidi, Sharan K; Jena, Sunil K; Ahuja, Bhupesh K; Devasari, Naresh; Suresh, Sarasija

    2015-05-01

    The objective of this study was to investigate the impact of a novel spray-dried ternary solid dispersion (TSD) on the dissolution rate and bioavailability of a biopharmaceutics classification system (BCS) class II model drug, atorvastatin calcium trihydrate (ATC), and evaluate its in-vitro and in-vivo performance. TSD of ATC was prepared by spray-drying method employing ethanol/water solvent systems. The TSD formulations, composed of hydroxypropyl methylcellulose (HPMC E5) and nicotinamide, were optimized by rotatable central composite design. Physicochemical characterization along with dissolution, stability and pharmacokinetic study of optimized TSD was evaluated. The optimized TSD was found to be amorphous with spherical shape morphology. It exhibited a fourfold increase in dissolution rate in comparison to ATC, with a considerable enhancement in oral bioavailability (relative bioavailability of 134.11%). Physicochemical characterization and dissolution study of optimized TSD at the end of stability studies clearly indicated that the stability of optimized TSD was due to hydrogen bonding between drug and HPMC E5 and nicotinamide. This bonding remained unaffected even under stressful conditions of high temperature and humidity. The TSD exhibits a significant increase in dissolution rate, and for this reason should be useful as an efficacious tool to enhance the bioavailability of BCS class II drug molecule, ATC. © 2015 Royal Pharmaceutical Society.

  18. Bayesian inference for multivariate meta-analysis Box-Cox transformation models for individual patient data with applications to evaluation of cholesterol-lowering drugs.

    Science.gov (United States)

    Kim, Sungduk; Chen, Ming-Hui; Ibrahim, Joseph G; Shah, Arvind K; Lin, Jianxin

    2013-10-15

    In this paper, we propose a class of Box-Cox transformation regression models with multidimensional random effects for analyzing multivariate responses for individual patient data in meta-analysis. Our modeling formulation uses a multivariate normal response meta-analysis model with multivariate random effects, in which each response is allowed to have its own Box-Cox transformation. Prior distributions are specified for the Box-Cox transformation parameters as well as the regression coefficients in this complex model, and the deviance information criterion is used to select the best transformation model. Because the model is quite complex, we develop a novel Monte Carlo Markov chain sampling scheme to sample from the joint posterior of the parameters. This model is motivated by a very rich dataset comprising 26 clinical trials involving cholesterol-lowering drugs where the goal is to jointly model the three-dimensional response consisting of low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), and triglycerides (TG) (LDL-C, HDL-C, TG). Because the joint distribution of (LDL-C, HDL-C, TG) is not multivariate normal and in fact quite skewed, a Box-Cox transformation is needed to achieve normality. In the clinical literature, these three variables are usually analyzed univariately; however, a multivariate approach would be more appropriate because these variables are correlated with each other. We carry out a detailed analysis of these data by using the proposed methodology. Copyright © 2013 John Wiley & Sons, Ltd.

  19. Bayesian inference for multivariate meta-analysis Box-Cox transformation models for individual patient data with applications to evaluation of cholesterol lowering drugs

    Science.gov (United States)

    Kim, Sungduk; Chen, Ming-Hui; Ibrahim, Joseph G.; Shah, Arvind K.; Lin, Jianxin

    2013-01-01

    In this paper, we propose a class of Box-Cox transformation regression models with multidimensional random effects for analyzing multivariate responses for individual patient data (IPD) in meta-analysis. Our modeling formulation uses a multivariate normal response meta-analysis model with multivariate random effects, in which each response is allowed to have its own Box-Cox transformation. Prior distributions are specified for the Box-Cox transformation parameters as well as the regression coefficients in this complex model, and the Deviance Information Criterion (DIC) is used to select the best transformation model. Since the model is quite complex, a novel Monte Carlo Markov chain (MCMC) sampling scheme is developed to sample from the joint posterior of the parameters. This model is motivated by a very rich dataset comprising 26 clinical trials involving cholesterol lowering drugs where the goal is to jointly model the three dimensional response consisting of Low Density Lipoprotein Cholesterol (LDL-C), High Density Lipoprotein Cholesterol (HDL-C), and Triglycerides (TG) (LDL-C, HDL-C, TG). Since the joint distribution of (LDL-C, HDL-C, TG) is not multivariate normal and in fact quite skewed, a Box-Cox transformation is needed to achieve normality. In the clinical literature, these three variables are usually analyzed univariately: however, a multivariate approach would be more appropriate since these variables are correlated with each other. A detailed analysis of these data is carried out using the proposed methodology. PMID:23580436

  20. 75 FR 54637 - Guidance for Industry and Food and Drug Administration Staff; Class II Special Controls Guidance...

    Science.gov (United States)

    2010-09-08

    ... conferencing and electronic submissions, Mammography Matters, and other device-oriented information. The CDRH... approval) into class II (special controls). DATES: Submit written or electronic comments on this guidance... electronic access to the guidance. Submit electronic comments on the guidance to http://www.regulations.gov...

  1. Effects of lifestyle interventions that include a physical activity component in class II and III obese individuals: a systematic review and meta-analysis.

    Directory of Open Access Journals (Sweden)

    Aurélie Baillot

    Full Text Available In class II and III obese individuals, lifestyle intervention is the first step to achieve weight loss and treat obesity-related comorbidities before considering bariatric surgery. A systematic review, meta-analysis, and meta-regression were performed to assess the impact of lifestyle interventions incorporating a physical activity (PA component on health outcomes of class II and III obese individuals.An electronic search was conducted in 4 databases (Medline, Scopus, CINAHL and Sportdiscus. Two independent investigators selected original studies assessing the impact of lifestyle interventions with PA components on anthropometric parameters, cardiometabolic risk factors (fat mass, blood pressure, lipid and glucose metabolism, behaviour modification (PA and nutritional changes, and quality of life in adults with body mass index (BMI ≥ 35 kg/m2. Estimates were pooled using a random-effect model (DerSimonian and Laird method. Heterogeneity between studies was assessed by the Cochran's chi-square test and quantified through an estimation of the I².Of the 3,170 identified articles, 56 met our eligibility criteria, with a large majority of uncontrolled studies (80%. The meta-analysis based on uncontrolled studies showed significant heterogeneity among all included studies. The pooled mean difference in weight loss was 8.9 kg (95% CI, 10.2-7.7; p < 0.01 and 2.8 kg/m² in BMI loss (95% CI, 3.4-2.2; p < 0.01. Long-term interventions produced superior weight loss (11.3 kg compared to short-term (7.2 kg and intermediate-term (8.0 kg interventions. A significant global effect of lifestyle intervention on fat mass, waist circumference, blood pressure, total cholesterol, LDL-C, triglycerides and fasting insulin was found (p<0.01, without significant effect on HDL-C and fasting blood glucose.Lifestyle interventions incorporating a PA component can improve weight and various cardiometabolic risk factors in class II and III obese individuals. However, further

  2. Combination of anti-retroviral drugs and radioimmunotherapy specifically kills infected cells from HIV infected individuals

    Directory of Open Access Journals (Sweden)

    Dina Tsukrov

    2016-09-01

    Full Text Available Eliminating virally infected cells is an essential component of any HIV eradication strategy. Radioimmunotherapy (RIT, a clinically established method for killing cells using radiolabeled antibodies, was recently applied to target HIV-1 gp41 antigen expressed on the surface of infect-ed cells. Since gp41 expression by infected cells is likely down-regulated in patients on an-tiretroviral therapy (ART, we evaluated the ability of RIT to kill ART-treated infected cells us-ing both in vitro models and lymphocytes isolated from HIV-infected subjects. Human peripheral blood mononuclear cells (PBMCs were infected with HIV and cultured in the presence of two clinically relevant ART combinations. Scatchard analysis of the 2556 human monoclonal anti-body to HIV gp41 binding to the infected and ART-treated cells demonstrated sufficient residual expression of gp41 on the cell surface to warrant subsequent RIT. This is the first time the quantification of gp41 post-ART is being reported. Cells were then treated with Bismuth-213-labeled 2556 antibody. conjugated to the human monoclonal antibody 2556, which binds to HIV gp41. Cell survival was quantified by Trypan blue and residual viremia by p24 ELISA. Cell surface gp41 expression was assessed by Scatchard analysis. The experiments were repeated using PBMCs isolated from blood specimens obtained from 15 HIV-infected individuals: ten on ART and five ART-naive. We found that 213Bi-2556 killed ART-treated infected PBMCs and reduced viral production to undetectable levels. ART and RIT co-treatment was more effective at reducing viral load in vitro than either therapy alone, indicating that gp41 expression under ART was sufficient to allow 213Bi-2556 to deliver cytocidal doses of radiation to infected cells. This study provides proof of concept that 213Bi-2556 may represent an innovative and effective targeting method for killing HIV-infected cells treated with ART, and supports continued development of 213Bi

  3. Crosslinked hydrogels—a promising class of insoluble solid molecular dispersion carriers for enhancing the delivery of poorly soluble drugs

    Directory of Open Access Journals (Sweden)

    Dajun D. Sun

    2014-02-01

    Full Text Available Water-insoluble materials containing amorphous solid dispersions (ASD are an emerging category of drug carriers which can effectively improve dissolution kinetics and kinetic solubility of poorly soluble drugs. ASDs based on water-insoluble crosslinked hydrogels have unique features in contrast to those based on conventional water-soluble and water-insoluble carriers. For example, solid molecular dispersions of poorly soluble drugs in poly(2-hydroxyethyl methacrylate (PHEMA can maintain a high level of supersaturation over a prolonged period of time via a feedback-controlled diffusion mechanism thus avoiding the initial surge of supersaturation followed by a sharp decline in drug concentration typically encountered with ASDs based on water-soluble polymers. The creation of both immediate- and controlled-release ASD dosage forms is also achievable with the PHEMA based hydrogels. So far, ASD systems based on glassy PHEMA have been shown to be very effective in retarding precipitation of amorphous drugs in the solid state to achieve a robust physical stability. This review summarizes recent research efforts in investigating the potential of developing crosslinked PHEMA hydrogels as a promising alternative to conventional water-soluble ASD carriers, and a related finding that the rate of supersaturation generation does affect the kinetic solubility profiles implications to hydrogel based ASDs.

  4. Crosslinked hydrogels-a promising class of insoluble solid molecular dispersion carriers for enhancing the delivery of poorly soluble drugs.

    Science.gov (United States)

    Sun, Dajun D; Lee, Ping I

    2014-02-01

    Water-insoluble materials containing amorphous solid dispersions (ASD) are an emerging category of drug carriers which can effectively improve dissolution kinetics and kinetic solubility of poorly soluble drugs. ASDs based on water-insoluble crosslinked hydrogels have unique features in contrast to those based on conventional water-soluble and water-insoluble carriers. For example, solid molecular dispersions of poorly soluble drugs in poly(2-hydroxyethyl methacrylate) (PHEMA) can maintain a high level of supersaturation over a prolonged period of time via a feedback-controlled diffusion mechanism thus avoiding the initial surge of supersaturation followed by a sharp decline in drug concentration typically encountered with ASDs based on water-soluble polymers. The creation of both immediate- and controlled-release ASD dosage forms is also achievable with the PHEMA based hydrogels. So far, ASD systems based on glassy PHEMA have been shown to be very effective in retarding precipitation of amorphous drugs in the solid state to achieve a robust physical stability. This review summarizes recent research efforts in investigating the potential of developing crosslinked PHEMA hydrogels as a promising alternative to conventional water-soluble ASD carriers, and a related finding that the rate of supersaturation generation does affect the kinetic solubility profiles implications to hydrogel based ASDs.

  5. Multi-class multi-residue analysis of veterinary drugs in meat using enhanced matrix removal lipid cleanup and liquid chromatography-tandem mass spectrometry.

    Science.gov (United States)

    Zhao, Limian; Lucas, Derick; Long, David; Richter, Bruce; Stevens, Joan

    2018-05-11

    This study presents the development and validation of a quantitation method for the analysis of multi-class, multi-residue veterinary drugs using lipid removal cleanup cartridges, enhanced matrix removal lipid (EMR-Lipid), for different meat matrices by liquid chromatography tandem mass spectrometry detection. Meat samples were extracted using a two-step solid-liquid extraction followed by pass-through sample cleanup. The method was optimized based on the buffer and solvent composition, solvent additive additions, and EMR-Lipid cartridge cleanup. The developed method was then validated in five meat matrices, porcine muscle, bovine muscle, bovine liver, bovine kidney and chicken liver to evaluate the method performance characteristics, such as absolute recoveries and precision at three spiking levels, calibration curve linearity, limit of quantitation (LOQ) and matrix effect. The results showed that >90% of veterinary drug analytes achieved satisfactory recovery results of 60-120%. Over 97% analytes achieved excellent reproducibility results (relative standard deviation (RSD) meat matrices. The matrix co-extractive removal efficiency by weight provided by EMR-lipid cartridge cleanup was 42-58% in samples. The post column infusion study showed that the matrix ion suppression was reduced for samples with the EMR-Lipid cartridge cleanup. The reduced matrix ion suppression effect was also confirmed with 30%) for all tested veterinary drugs in all of meat matrices. The results showed that the two-step solid-liquid extraction provides efficient extraction for the entire spectrum of veterinary drugs, including the difficult classes such as tetracyclines, beta-lactams etc. EMR-Lipid cartridges after extraction provided efficient sample cleanup with easy streamlined protocol and minimal impacts on analytes recovery, improving method reliability and consistency. Copyright © 2018 Elsevier B.V. All rights reserved.

  6. Variation in the suppression or enhancement of responses related to drug habits as a function of stimulus classes and competing response categories.

    Science.gov (United States)

    Haertzen, C A; Ross, F E

    1980-08-01

    Male prisoners who were opiate addicts (N = 47) were given three Process Association Tests of Addiction containing stimuli which evoked responses characteristic of three levels of drug habits: beginning and ending stage of addiction, intermediate stage of addiction, and an advanced level of addiction. Each test required subjects to associate 278 word stimuli with one of five options which were randomly selected from among 20 options covering the stages of addiction, steps in drug taking, and drug effects. The purpose of the study was to determine whether responses to particular options suppressed or enhanced responses to other options. A strong interaction was found between the classes of stimuli and the response options which produced suppression or enhancement. This interaction made it possible to develop a suppression scale to measure the effect of each class of stimulus. Popular responses most frequently suppressed responses of other options. Thus, when the stimuli were clean, responses of "to be clean" and "to live a normal life," which are sensitive indicators of the beginning or ending stages of addiction , suppressed responses of other stages. The response of "to be high," a prime indicator of an intermediate habit, suppressed responses of other options when the stimuli were drug names. Responses of "to be hooked" and "to fix," which are specific indicators of a strong habit, and "to be high," which is a nonspecific indicator of a strong habit, suppressed responses of many other options. In the development of new association tests the analysis of suppression could provide a basis for selectively varying option groupings in order to increase or decrease the frequently of certain responses.

  7. Anti-human immunodeficiency virus-1 antibody titers in injection drug users compared to sexually infected individuals

    Directory of Open Access Journals (Sweden)

    Bongertz Vera

    2003-01-01

    Full Text Available Sera from infected injection drug users (IDU have shown to have antibodies against synthetic human immunodeficiency virus-1 (HIV-1 envelope peptides more frequently. In this study, reactivity of 48 IDU plasma were compared to 60 plasmas obtained from sexually infected individuals (S. The overall reactivity of plasma from IDU compared to S was higher, and the reactivity titers were much higher for IDU plasma than S. IDU plasma also showed a broader antibody response. The higher reactivity titers were observed mainly for the gp41 immunodominant epitope and V3 peptides corresponding to the consensus sequences of HIV-1 subtypes/variants prevalent in Brazil (B, F, C indicating the specificity in the higher immune response of IDU.

  8. Anti-human immunodeficiency virus-1 antibody titers in injection drug users compared to sexually infected individuals.

    Science.gov (United States)

    Bongertz, Vera; Ouverney, Elaine Priscilla; Teixeira, Sylvia L M; Silva-de-Jesus, Carlos; Hacker, Mariana A; Morgado, Mariza G; Bastos, Francisco I

    2003-03-01

    Sera from infected injection drug users (IDU) have shown to have antibodies against synthetic human immunodeficiency virus-1 (HIV-1) envelope peptides more frequently. In this study, reactivity of 48 IDU plasma were compared to 60 plasmas obtained from sexually infected individuals (S). The overall reactivity of plasma from IDU compared to S was higher, and the reactivity titers were much higher for IDU plasma than S. IDU plasma also showed a broader antibody response. The higher reactivity titers were observed mainly for the gp41 immunodominant epitope and V3 peptides corresponding to the consensus sequences of HIV-1 subtypes/variants prevalent in Brazil (B, F, C) indicating the specificity in the higher immune response of IDU.

  9. Word classes

    DEFF Research Database (Denmark)

    Rijkhoff, Jan

    2007-01-01

    in grammatical descriptions of some 50 languages, which together constitute a representative sample of the world’s languages (Hengeveld et al. 2004: 529). It appears that there are both quantitative and qualitative differences between word class systems of individual languages. Whereas some languages employ...... a parts-of-speech system that includes the categories Verb, Noun, Adjective and Adverb, other languages may use only a subset of these four lexical categories. Furthermore, quite a few languages have a major word class whose members cannot be classified in terms of the categories Verb – Noun – Adjective...... – Adverb, because they have properties that are strongly associated with at least two of these four traditional word classes (e.g. Adjective and Adverb). Finally, this article discusses some of the ways in which word class distinctions interact with other grammatical domains, such as syntax and morphology....

  10. Development of a New Class of Drugs to Inhibit All Forms of Androgen Receptor in Castration Resistant Prostate Cancers

    Science.gov (United States)

    2016-10-01

    titration methods (protein in the syringe, ligand in the cell), we were able to obtain a reproducible thermogram for the ligand binding reaction...to VPC-14449 as a model drug to assist on other related projects. 1. Tam, K., Dalal, K., Hsing, M., Cheng, C.W., Chiang, Y.T., Sharma, A., Peacock

  11. Large-Scale Off-Target Identification Using Fast and Accurate Dual Regularized One-Class Collaborative Filtering and Its Application to Drug Repurposing.

    Directory of Open Access Journals (Sweden)

    Hansaim Lim

    2016-10-01

    Full Text Available Target-based screening is one of the major approaches in drug discovery. Besides the intended target, unexpected drug off-target interactions often occur, and many of them have not been recognized and characterized. The off-target interactions can be responsible for either therapeutic or side effects. Thus, identifying the genome-wide off-targets of lead compounds or existing drugs will be critical for designing effective and safe drugs, and providing new opportunities for drug repurposing. Although many computational methods have been developed to predict drug-target interactions, they are either less accurate than the one that we are proposing here or computationally too intensive, thereby limiting their capability for large-scale off-target identification. In addition, the performances of most machine learning based algorithms have been mainly evaluated to predict off-target interactions in the same gene family for hundreds of chemicals. It is not clear how these algorithms perform in terms of detecting off-targets across gene families on a proteome scale. Here, we are presenting a fast and accurate off-target prediction method, REMAP, which is based on a dual regularized one-class collaborative filtering algorithm, to explore continuous chemical space, protein space, and their interactome on a large scale. When tested in a reliable, extensive, and cross-gene family benchmark, REMAP outperforms the state-of-the-art methods. Furthermore, REMAP is highly scalable. It can screen a dataset of 200 thousands chemicals against 20 thousands proteins within 2 hours. Using the reconstructed genome-wide target profile as the fingerprint of a chemical compound, we predicted that seven FDA-approved drugs can be repurposed as novel anti-cancer therapies. The anti-cancer activity of six of them is supported by experimental evidences. Thus, REMAP is a valuable addition to the existing in silico toolbox for drug target identification, drug repurposing

  12. Large-Scale Off-Target Identification Using Fast and Accurate Dual Regularized One-Class Collaborative Filtering and Its Application to Drug Repurposing.

    Science.gov (United States)

    Lim, Hansaim; Poleksic, Aleksandar; Yao, Yuan; Tong, Hanghang; He, Di; Zhuang, Luke; Meng, Patrick; Xie, Lei

    2016-10-01

    Target-based screening is one of the major approaches in drug discovery. Besides the intended target, unexpected drug off-target interactions often occur, and many of them have not been recognized and characterized. The off-target interactions can be responsible for either therapeutic or side effects. Thus, identifying the genome-wide off-targets of lead compounds or existing drugs will be critical for designing effective and safe drugs, and providing new opportunities for drug repurposing. Although many computational methods have been developed to predict drug-target interactions, they are either less accurate than the one that we are proposing here or computationally too intensive, thereby limiting their capability for large-scale off-target identification. In addition, the performances of most machine learning based algorithms have been mainly evaluated to predict off-target interactions in the same gene family for hundreds of chemicals. It is not clear how these algorithms perform in terms of detecting off-targets across gene families on a proteome scale. Here, we are presenting a fast and accurate off-target prediction method, REMAP, which is based on a dual regularized one-class collaborative filtering algorithm, to explore continuous chemical space, protein space, and their interactome on a large scale. When tested in a reliable, extensive, and cross-gene family benchmark, REMAP outperforms the state-of-the-art methods. Furthermore, REMAP is highly scalable. It can screen a dataset of 200 thousands chemicals against 20 thousands proteins within 2 hours. Using the reconstructed genome-wide target profile as the fingerprint of a chemical compound, we predicted that seven FDA-approved drugs can be repurposed as novel anti-cancer therapies. The anti-cancer activity of six of them is supported by experimental evidences. Thus, REMAP is a valuable addition to the existing in silico toolbox for drug target identification, drug repurposing, phenotypic screening, and

  13. Ecological momentary assessment of daily discrimination experiences and nicotine, alcohol, and drug use among sexual and gender minority individuals.

    Science.gov (United States)

    Livingston, Nicholas A; Flentje, Annesa; Heck, Nicholas C; Szalda-Petree, Allen; Cochran, Bryan N

    2017-12-01

    Sexual and gender minority (SGM) individuals experience elevated rates of minority stress, which has been linked to higher rates of nicotine and substance use. Research on this disparity to date is largely predicated on methodology that is insensitive to within day SGM-based discrimination experiences, or their relation to momentary nicotine and substance use risk. We address this knowledge gap in the current study using ecological momentary assessment (EMA). Fifty SGM individuals, between 18 and 45 years of age, were recruited from an inland northwestern university, regardless of their nicotine or substance use history, and invited to participate in an EMA study. Each were prompted to provide data, six times daily (between 10:00 a.m. and 10:00 p.m.) for 14 days, regarding SGM-based discrimination, other forms of mistreatment, and nicotine, drug, and alcohol use since their last prompt. Discrimination experiences that occurred since individuals' last measurement prompt were associated with greater odds of nicotine and substance use during the same measurement window. Substance use was also more likely to occur in relation to discrimination reported two measurements prior in lagged models. Relative to other forms of mistreatment, discrimination effects were consistently larger in magnitude and became stronger throughout the day/evening. This study adds to existing minority stress research by highlighting the both immediate and delayed correlates of daily SGM-based discrimination experiences. These results also contribute to our understanding of daily stress processes and provide insight into ways we might mitigate these effects using real-time monitoring and intervention technology. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  14. The Effects of the CW-FIT Group Contingency on Class-Wide and Individual Behavior in an Urban First Grade Classroom

    Science.gov (United States)

    Naylor, Anna Schmidt; Kamps, Debra; Wills, Howard

    2018-01-01

    The current study examined the effects of the Class-wide Function-related Intervention Teams (CW-FIT), a class-wide group contingency, on the on-task behavior of all students in a first grade class and the on-task and disruptive behavior of three target students within that class who were nominated by their teacher through a behavioral screening.…

  15. Use of antipsychotic drugs in individuals with intellectual disability (ID) in the Netherlands : prevalence and reasons for prescription

    NARCIS (Netherlands)

    de Kuijper, G.; Hoekstra, P.; Visser, F.; Scholte, F. A.; Penning, C.; Evenhuis, H.

    Background We investigated antipsychotic drug prescription practice of Dutch ID physicians, studying prevalence of antipsychotic drug use, reasons for prescription and the relationship between these reasons and patient characteristics. Methods A cross-sectional study of medical and pharmaceutical

  16. [Framework on drug interactions between herbal medicine and western medicine: building Ⅰ/Ⅱ/Ⅲ class pathways of interactions].

    Science.gov (United States)

    Jin, Rui; Huang, Jian-Mei; Wang, Yu-Guang; Zhang, Bing

    2016-02-01

    Combined use of Chinese medicine and western medicine is one of the hot spots in the domestic medical and academic fields for many years. There are lots of involved reports and studies on interaction problems due to combined used of Chinese medicine and western medicine, however, framework understanding is still rarely seen, affecting the clinical rationality of drug combinations. Actually, the inference ideas of drug interactions in clinical practice are more extensive and practical, and the overall viewpoint and pragmatic idea are the important factors in evaluating the rationality of clinical drug combinations. Based on above points, this paper systemically analyzed the existing information and examples, deeply discuss the embryology background (environment and action mechanism of interactions), and principally divided the interactions into three important and independent categories. Among the three categories, the first category (Ⅰapproach) was defined as the physical/chemical reactions after direct contact in vivo or in vitro, such as the combination of Chinese medicine injections and western medicine injections (in vitro), combination of bromide and Chinese medicines containing cinnabar (in vivo). The evaluation method for such interactions may be generalized theory of Acid-Base reaction. The second category (Ⅱ approach) was defined as the interactions through the pharmacokinetic process including absorption (such as the combination of aspirin and Huowei capsule), distribution (such as the combination of artosin and medicinal herbs containing coumarin), metabolism (such as the combination of phenobarbital and glycyrrhiza) and excretion (such as the combination of furadantin and Crataegi Fructus). The existing pharmacokinetic theory can act as the evaluation method for this type of interaction. The third category (Ⅲ approach) was defined as the synergy/antagonism interactions by pharmacological effects or biological pathways. The combination of warfarin

  17. Toxicity assessments of nonsteroidal anti-inflammatory drugs in isolated mitochondria, rat hepatocytes, and zebrafish show good concordance across chemical classes

    International Nuclear Information System (INIS)

    Nadanaciva, Sashi; Aleo, Michael D.; Strock, Christopher J.; Stedman, Donald B.; Wang, Huijun; Will, Yvonne

    2013-01-01

    To reduce costly late-stage compound attrition, there has been an increased focus on assessing compounds in in vitro assays that predict attributes of human safety liabilities, before preclinical in vivo studies are done. Relevant questions when choosing a panel of assays for predicting toxicity are (a) whether there is general concordance in the data among the assays, and (b) whether, in a retrospective analysis, the rank order of toxicity of compounds in the assays correlates with the known safety profile of the drugs in humans. The aim of our study was to answer these questions using nonsteroidal anti-inflammatory drugs (NSAIDs) as a test set since NSAIDs are generally associated with gastrointestinal injury, hepatotoxicity, and/or cardiovascular risk, with mitochondrial impairment and endoplasmic reticulum stress being possible contributing factors. Eleven NSAIDs, flufenamic acid, tolfenamic acid, mefenamic acid, diclofenac, meloxicam, sudoxicam, piroxicam, diflunisal, acetylsalicylic acid, nimesulide, and sulindac (and its two metabolites, sulindac sulfide and sulindac sulfone), were tested for their effects on (a) the respiration of rat liver mitochondria, (b) a panel of mechanistic endpoints in rat hepatocytes, and (c) the viability and organ morphology of zebrafish. We show good concordance for distinguishing among/between NSAID chemical classes in the observations among the three approaches. Furthermore, the assays were complementary and able to correctly identify “toxic” and “non-toxic” drugs in accordance with their human safety profile, with emphasis on hepatic and gastrointestinal safety. We recommend implementing our multi-assay approach in the drug discovery process to reduce compound attrition. - Highlights: • NSAIDS cause liver and GI toxicity. • Mitochondrial uncoupling contributes to NSAID liver toxicity. • ER stress is a mechanism that contributes to liver toxicity. • Zebrafish and cell based assays are complimentary

  18. Toxicity assessments of nonsteroidal anti-inflammatory drugs in isolated mitochondria, rat hepatocytes, and zebrafish show good concordance across chemical classes

    Energy Technology Data Exchange (ETDEWEB)

    Nadanaciva, Sashi [Compound Safety Prediction, Worldwide Medicinal Chemistry, Pfizer, Inc., Groton, CT 06340 (United States); Aleo, Michael D. [Drug Safety Research and Development, Pfizer Inc., Groton, CT 06340 (United States); Strock, Christopher J. [Cyprotex US, Watertown, MA 02472 (United States); Stedman, Donald B. [Drug Safety Research and Development, Pfizer Inc., Groton, CT 06340 (United States); Wang, Huijun [Computational Sciences, Pfizer Inc., Groton, CT 06340 (United States); Will, Yvonne, E-mail: yvonne.will@pfizer.com [Compound Safety Prediction, Worldwide Medicinal Chemistry, Pfizer, Inc., Groton, CT 06340 (United States)

    2013-10-15

    To reduce costly late-stage compound attrition, there has been an increased focus on assessing compounds in in vitro assays that predict attributes of human safety liabilities, before preclinical in vivo studies are done. Relevant questions when choosing a panel of assays for predicting toxicity are (a) whether there is general concordance in the data among the assays, and (b) whether, in a retrospective analysis, the rank order of toxicity of compounds in the assays correlates with the known safety profile of the drugs in humans. The aim of our study was to answer these questions using nonsteroidal anti-inflammatory drugs (NSAIDs) as a test set since NSAIDs are generally associated with gastrointestinal injury, hepatotoxicity, and/or cardiovascular risk, with mitochondrial impairment and endoplasmic reticulum stress being possible contributing factors. Eleven NSAIDs, flufenamic acid, tolfenamic acid, mefenamic acid, diclofenac, meloxicam, sudoxicam, piroxicam, diflunisal, acetylsalicylic acid, nimesulide, and sulindac (and its two metabolites, sulindac sulfide and sulindac sulfone), were tested for their effects on (a) the respiration of rat liver mitochondria, (b) a panel of mechanistic endpoints in rat hepatocytes, and (c) the viability and organ morphology of zebrafish. We show good concordance for distinguishing among/between NSAID chemical classes in the observations among the three approaches. Furthermore, the assays were complementary and able to correctly identify “toxic” and “non-toxic” drugs in accordance with their human safety profile, with emphasis on hepatic and gastrointestinal safety. We recommend implementing our multi-assay approach in the drug discovery process to reduce compound attrition. - Highlights: • NSAIDS cause liver and GI toxicity. • Mitochondrial uncoupling contributes to NSAID liver toxicity. • ER stress is a mechanism that contributes to liver toxicity. • Zebrafish and cell based assays are complimentary.

  19. Antivertiginous drug therapy does not hinder the efficacy of individualized vibrotactile neurofeedback training for vestibular rehabilitation - a randomized trial.

    Science.gov (United States)

    Basta, Dietmar; Borsellino, Liliana; Ernst, Arne

    2017-12-01

    Vestibular rehabilitation using individualized vibrotactile neurofeedback training (IVNT) can lead to significant improvement in the postural stability of patients with vestibular symptoms of different origins. However, some of these patients have complex, severe dizziness, meaning that a pharmacological pretreatment or parallel (to vestibular rehabilitation) treatment can help them perform the rehabilitation exercises. Hence, the present study investigated the influence of a pharmacological treatment on the efficacy of vibrotactile neurofeedback training in patients with chronic, noncompensated vestibulopathies. All participants performed IVNT for ∼10 min each day for 2 weeks. In addition, every second participant was selected randomly to receive oral medication (20 mg cinnarizine and 40 mg dimenhydrinate per tablet), taking three tables per day. Trunk and ankle sway and postural stability were measured. In addition, the dizziness handicap inventory was evaluated immediately before training on the last day of training and 6 months after training. After the 10-day period of IVNT, both groups showed a statistically significant improvement in all parameters tested. A follow-up analysis after 6 months showed a long-term efficacy for the IVNT, that is, the patients remained significantly improved in their postural stability. The antivertiginous therapy did not hinder the efficacy of the IVNT. The present results indicate that IVNT even in combination with an antivertiginous drug therapy is an effective treatment regime for patients with disabling vertigo of different origins.

  20. The Protective Effect of Pregnancy on Risk for Drug Abuse: A Population, Co-Relative, Co-Spouse, and Within-Individual Analysis.

    Science.gov (United States)

    Kendler, Kenneth S; Ohlsson, Henrik; Svikis, Dace S; Sundquist, Kristina; Sundquist, Jan

    2017-10-01

    The authors sought to determine whether pregnancy is an intrinsic motivator for cessation of drug abuse. The authors conducted prospective cohort, co-relative, co-spouse, and within-person analyses of registration for drug abuse during pregnancy among Swedish women born between 1980 and 1990 who gave birth between ages 20 and 35 (N=149,512). Drug abuse was assessed from medical, criminal, and pharmacy registries. In the population, rates of drug abuse were lower during pregnancy (unadjusted odds ratio=0.67, 95% CI=0.60, 0.74). Compared with population results, the negative association between pregnancy and drug abuse was moderately stronger in cousins (odds ratio=0.49, 95% CI=0.39, 0.62) and substantially stronger in siblings (odds ratio=0.35, 95% CI=0.24, 0.51) discordant for pregnancy. The estimated odds ratio for drug abuse in pregnancy-discordant monozygotic twins was even stronger, at 0.17 (95% CI=0.10, 0.31). Within individuals, the odds ratio for drug abuse while pregnant compared with an equivalent prepregnancy interval was similar to that seen in pregnancy-discordant monozygotic twins, at 0.22 (95% CI=0.19, 0.26). Compared with cohabiting fathers, mothers had a greater reduction in risk for drug abuse during pregnancy (odds ratio=0.40, 95% CI=0.34, 0.47). Pregnancy was more protective in women with low parental education and without a cohabiting, actively drug-abusing father. Compared with prepregnancy baseline, within-individual analyses indicate that risk for drug abuse is also substantially reduced in the postpartum period, for example, the odds ratio for postpartum days 0-242 was 0.13 (95% CI=0.11, 0.16). Risk for drug abuse in women is substantially reduced during pregnancy. Multiple analyses suggest that this association is largely causal, suggesting that pregnancy is indeed a strong intrinsic motivator for drug abuse cessation. Similar strong protective effects may be present in the immediate postpartum period. Our results have implications for our

  1. The business cycle and drug use in Australia: evidence from repeated cross-sections of individual level data.

    Science.gov (United States)

    Chalmers, Jenny; Ritter, Alison

    2011-09-01

    This paper examined the implications of the business cycle for cannabis and alcohol use. What little we know about cannabis use suggests that young Americans (teenagers and adults in their early 20s) seem more inclined to use illicit drugs and to use them more frequently with rises in the unemployment rate. In contrast, a more fulsome alcohol literature suggests that participation in drinking is unaffected by the business cycle. Heavy drinkers drink less during economic downturns and their reduced use counteracts the fact that light drinkers might drink a little more. Using individual level data from repeated cross-sections of Australia's National Drug Strategy Household Survey (NDSHS), spanning 1991-2007, this study examined the relationship between cannabis and alcohol use of Australians aged 14-49 years and the unemployment rate and real income per capita, two indicators of the business cycle. Australians in their late 20s, 30s and 40s drink less frequently during economic downturns. If unemployment rate rises are accompanied by falls in income per capita, younger Australians will also drink less frequently. Recent participation in cannabis use (within the last year) increases with falls in income per capita regardless of age, although the increase is less marked for young people (14-24 years). Whereas the participation rate of people aged 25-49 years also falls with rising unemployment rates, the participation of younger people increases. Cannabis users younger than 35 will use more frequently as the unemployment rate rises. In contrast, older Australians will use less frequently. Australia's recent economic slowdown has been characterised by rising unemployment rates without accompanying falls in income per capita. Based on our findings this slowdown should have encouraged young Australians aged 14-24 years to both drink and use cannabis more frequently. The slowdown would have had little impact on the frequency of drinking of older Australians. However it

  2. Urea Derivatives of 2-Aryl-benzothiazol-5-amines: A New Class of Potential Drugs for Human African Trypanosomiasis.

    Science.gov (United States)

    Patrick, Donald A; Gillespie, J Robert; McQueen, Joshua; Hulverson, Matthew A; Ranade, Ranae M; Creason, Sharon A; Herbst, Zackary M; Gelb, Michael H; Buckner, Frederick S; Tidwell, Richard R

    2017-02-09

    A previous publication from this lab (Patrick, et al. Bioorg. Med. Chem. 2016, 24 , 2451 - 2465 ) explored the antitrypanosomal activities of novel derivatives of 2-(2-benzamido)ethyl-4-phenylthiazole (1), which had been identified as a hit against Trypanosoma brucei, the causative agent of human African trypanosomiasis. While a number of these compounds, particularly the urea analogues, were quite potent, these molecules as a whole exhibited poor metabolic stability. The present work describes the synthesis of 65 new analogues arising from medicinal chemistry optimization at different sites on the molecule. The most promising compounds were the urea derivatives of 2-aryl-benzothiazol-5-amines. One such analogue, (S)-2-(3,4-difluorophenyl)-5-(3-fluoro-N-pyrrolidylamido)benzothiazole (57) was chosen for in vivo efficacy studies based upon in vitro activity, metabolic stability, and brain penetration. This compound attained 5/5 cures in murine models of both early and late stage human African trypanosomiasis, representing a new lead for the development of drugs to combat this neglected disease.

  3. The Predictive Role of Difficulties in Emotion Regulation and Self-Control with Susceptibility to Addiction in Drug-Dependent Individuals

    OpenAIRE

    Mahmoud Shirazi; Monavar Janfaza

    2015-01-01

    Objective: The present study aimed to examine the predictive role of difficulties in emotion regulation and self-control in potential for addiction among drug-dependent individuals. Method: This was a correlational study which falls within the category of descriptive studies. The statistical population of the current study included all patients under treatment in outpatient health centers in Bam, among whom 315 individuals were selected through cluster sampling method as the participants of t...

  4. Molecular evolution of Theta-class glutathione transferase for enhanced activity with the anticancer drug 1,3-bis-(2-chloroethyl)-1-nitrosourea and other alkylating agents.

    Science.gov (United States)

    Larsson, Anna-Karin; Shokeer, Abeer; Mannervik, Bengt

    2010-05-01

    Glutathione transferase (GST) displaying enhanced activity with the cytostatic drug 1,3-bis-(2-chloroethyl)-1-nitrosourea (BCNU) and structurally related alkylating agents was obtained by molecular evolution. Mutant libraries created by recursive recombination of cDNA coding for human and rodent Theta-class GSTs were heterologously expressed in Escherichia coli and screened with the surrogate substrate 4-nitrophenethyl bromide (NPB) for enhanced alkyltransferase activity. A mutant with a 70-fold increased catalytic efficiency with NPB, compared to human GST T1-1, was isolated. The efficiency in degrading BCNU had improved 170-fold, significantly more than with the model substrate NPB. The enhanced catalytic activity of the mutant GST was also 2-fold higher with BCNU than wild-type mouse GST T1-1, which is 80-fold more efficient than wild-type human GST T1-1. We propose that GSTs catalyzing inactivation of anticancer drugs may find clinical use in protecting sensitive normal tissues to toxic side-effects in treated patients, and as selectable markers in gene therapy. Copyright 2010 Elsevier Inc. All rights reserved.

  5. Crystal structures of three classes of non-steroidal anti-inflammatory drugs in complex with aldo-keto reductase 1C3.

    Directory of Open Access Journals (Sweden)

    Jack U Flanagan

    Full Text Available Aldo-keto reductase 1C3 (AKR1C3 catalyses the NADPH dependent reduction of carbonyl groups in a number of important steroid and prostanoid molecules. The enzyme is also over-expressed in prostate and breast cancer and its expression is correlated with the aggressiveness of the disease. The steroid products of AKR1C3 catalysis are important in proliferative signalling of hormone-responsive cells, while the prostanoid products promote prostaglandin-dependent proliferative pathways. In these ways, AKR1C3 contributes to tumour development and maintenance, and suggest that inhibition of AKR1C3 activity is an attractive target for the development of new anti-cancer therapies. Non-steroidal anti-inflammatory drugs (NSAIDs are one well-known class of compounds that inhibits AKR1C3, yet crystal structures have only been determined for this enzyme with flufenamic acid, indomethacin, and closely related analogues bound. While the flufenamic acid and indomethacin structures have been used to design novel inhibitors, they provide only limited coverage of the NSAIDs that inhibit AKR1C3 and that may be used for the development of new AKR1C3 targeted drugs. To understand how other NSAIDs bind to AKR1C3, we have determined ten crystal structures of AKR1C3 complexes that cover three different classes of NSAID, N-phenylanthranilic acids (meclofenamic acid, mefenamic acid, arylpropionic acids (flurbiprofen, ibuprofen, naproxen, and indomethacin analogues (indomethacin, sulindac, zomepirac. The N-phenylanthranilic and arylpropionic acids bind to common sites including the enzyme catalytic centre and a constitutive active site pocket, with the arylpropionic acids probing the constitutive pocket more effectively. By contrast, indomethacin and the indomethacin analogues sulindac and zomepirac, display three distinctly different binding modes that explain their relative inhibition of the AKR1C family members. This new data from ten crystal structures greatly broadens

  6. Injection Drug Use, Unemployment, and Severe Food Insecurity Among HIV-HCV Co-Infected Individuals: A Mediation Analysis.

    Science.gov (United States)

    McLinden, Taylor; Moodie, Erica E M; Hamelin, Anne-Marie; Harper, Sam; Walmsley, Sharon L; Paradis, Gilles; Aibibula, Wusiman; Klein, Marina B; Cox, Joseph

    2017-12-01

    Severe food insecurity (FI), which indicates reduced food intake, is common among HIV-hepatitis C virus (HCV) co-infected individuals. Given the importance of unemployment as a proximal risk factor for FI, this mediation analysis examines a potential mechanism through which injection drug use (IDU) is associated with severe FI. We used biannual data from the Canadian Co-infection Cohort (N = 429 with 3 study visits, 2012-2015). IDU in the past 6 months (exposure) and current unemployment (mediator) were self-reported. Severe FI in the following 6 months (outcome) was measured using the Household Food Security Survey Module. An overall association and a controlled direct effect were estimated using marginal structural models. Among participants, 32% engaged in IDU, 78% were unemployed, and 29% experienced severe FI. After adjustment for confounding and addressing censoring through weighting, the overall association (through all potential pathways) between IDU and severe FI was: risk ratio (RR) = 1.69 (95% confidence interval [CI] = 1.15-2.48). The controlled direct effect (the association through all potential pathways except that of unemployment) was: RR = 1.65 (95% CI = 1.08-2.53). We found evidence of an overall association between IDU and severe FI and estimated a controlled direct effect that is suggestive of pathways from IDU to severe FI that are not mediated by unemployment. Specifically, an overall association and a controlled direct effect that are similar in magnitude suggests that the potential impact of IDU on unemployment is not the primary mechanism through which IDU is associated with severe FI. Therefore, while further research is required to understand the mechanisms linking IDU and severe FI, the strong overall association suggests that reductions in IDU may mitigate severe FI in this vulnerable subset of the HIV-positive population.

  7. An in vitro study of antifungal drug susceptibility of Candida species isolated from human immunodeficiency virus seropositive and human immunodeficiency virus seronegative individuals in Lucknow population Uttar Pradesh.

    Science.gov (United States)

    Dar, Mohammad Shafi; Sreedar, Gadiputi; Shukla, Abhilasha; Gupta, Prashant; Rehan, Ahmad Danish; George, Jiji

    2015-01-01

    Candidiasis is the most common opportunistic infection in human immunodeficiency virus (HIV) seropositive patients, starting from asymptomatic colonization to pathogenic forms and gradual colonization of non-albicans in patients with advanced immunosuppression leads to resistance for azole group of antifungal drugs with high rate of morbidity and mortality. To isolate the Candida species and determine of antifungal drug susceptibility against fluconazole, itraconazole, nystatin, amphotericin B, and clotrimazolein HIV seropositive and control individuals, with or without clinical oropharyngeal candidiasis (OPC). Includes samples from faucial region of 70 subjects with and without clinical candidiasis in HIV seropositive and controls were aseptically inoculated onto Sabaraud's Dextrose Agar media and yeasts were identified for the specific species by Corn Meal Agar, sugar fermentation and heat tolerance tests. Antifungal drug susceptibility of the isolated species was done against above-mentioned drugs by E-test and disc diffusion method. The commonly isolated species in HIV seropositive and controls were Candida albicans, Candida glabrata and Candida tropicalis Candida guilliermondii and Candida dubliniensis isolated only in HIV seropositive patients. Susceptibility against selected antifungal drugs was observed more in HIV-negative individuals whereas susceptible dose-dependent and resistance were predominant in HIV-positive patients. Resistance is the major problem in the therapy of OPC, especially in HIV seropositive patients due to aggressive and prolonged use of antifungal agents, therefore, our study emphasizes the need for antifungal drug susceptibility testing whenever antifungal treatment is desired, especially in HIV-infected subjects.

  8. Effectiveness of Gross Model-Based Emotion Regulation Strategies Training on Anger Reduction in Drug-Dependent Individuals and its Sustainability in Follow-up.

    Science.gov (United States)

    Massah, Omid; Sohrabi, Faramarz; A'azami, Yousef; Doostian, Younes; Farhoudian, Ali; Daneshmand, Reza

    2016-03-01

    Emotion plays an important role in adapting to life changes and stressful events. Difficulty regulating emotions is one of the problems drug abusers often face, and teaching these individuals to express and manage their emotions can be effective on improving their difficult circumstances. The present study aimed to determine the effectiveness of the Gross model-based emotion regulation strategies training on anger reduction in drug-dependent individuals. The present study had a quasi-experimental design wherein pretest-posttest evaluations were applied using a control group. The population under study included addicts attending Marivan's methadone maintenance therapy centers in 2012 - 2013. Convenience sampling was used to select 30 substance-dependent individuals undergoing maintenance treatment who were then randomly assigned to the experiment and control groups. The experiment group received its training in eight two-hour sessions. Data were analyzed using analysis of co-variance and paired t-test. There was significant reduction in anger symptoms of drug-dependent individuals after gross model based emotion regulation training (ERT) (P emotion regulation strategies training. Based on the results of this study, we may conclude that the gross model based emotion regulation strategies training can be applied alongside other therapies to treat drug abusers undergoing rehabilitation.

  9. The association between detected drug resistance mutations and CD4(+) T-cell decline in HIV-positive individuals maintained on a failing treatment regimen

    DEFF Research Database (Denmark)

    Schultze, Anna; Paredes, Roger; Sabin, Caroline

    2018-01-01

    BACKGROUND: To analyse the effect of drug resistance mutations (DRM) on CD4 cell trends in HIV-positive people maintained on virologically failing antiretroviral therapy (ART). METHODS: Individuals from two large cohorts experiencing virological failure (VF) while maintained on ART with >1 CD4...

  10. Use of Antipsychotic Drugs in Individuals with Intellectual Disability (ID) in the Netherlands: Prevalence and Reasons for Prescription

    Science.gov (United States)

    de Kuijper, G.; Hoekstra, P.; Visser, F.; Scholte, F. A.; Penning, C.; Evenhuis, H.

    2010-01-01

    Background: We investigated antipsychotic drug prescription practice of Dutch ID physicians, studying prevalence of antipsychotic drug use, reasons for prescription and the relationship between these reasons and patient characteristics. Methods: A cross-sectional study of medical and pharmaceutical records in a population living in residential…

  11. Providing patients with information about disease-modifying anti-rheumatic drugs: Individually or in groups? A pilot randomized controlled trial comparing adherence and satisfaction.

    Science.gov (United States)

    Homer, Dawn; Nightingale, Peter; Jobanputra, Paresh

    2009-06-01

    Communicating information about disease-modifying anti-rheumatic drugs (DMARDs) before patients start treatment is a key role for some rheumatology clinical nurse specialists. This is done in our unit to promote understanding of the risks and benefits of drug therapy and encourage timely and reliable use of DMARDs. Information is routinely provided individually but this can lead to delays in starting treatment because of limited nursing resources. In this randomized trial we tested the feasibility of giving patients, who were about to start on a DMARD, information about the drug in groups and compared this with information given individually. Adults with a clinical diagnosis of rheumatoid arthritis or psoriatic arthritis who were referred to the nursing team for counselling about starting on methotrexate, sulfasalazine or leflunomide were included. Patients who had previously taken a DMARD were not excluded and those consenting were randomized to receive drug information individually or in groups (of three to six patients). We provided all patients with written materials about the relevant drug and discussed the risks and benefits of drug use verbally. Patients allocated to group counselling received this intervention in a teaching room, with a slide presentation. The primary outcome was adherence with medication use, ascertained by pill counts, self-report diaries and prescription dispensation. Secondary outcomes included satisfaction with information about medicines (SIMS) by questionnaire; time taken to provide information; adherence to scheduled hospital appointments and blood monitoring schedules; and DMARD continuation rates at four and twelve months. Of 127 eligible patients referred for counselling about DMARDs, 62 consented to take part: 32 were randomized to receive drug information individually and 30 to receiving it in groups. Patients allocated to the two different interventions were comparable for age and diagnoses at baseline but more patients

  12. A Bayesian approach for incorporating economic factors in sample size design for clinical trials of individual drugs and portfolios of drugs.

    Science.gov (United States)

    Patel, Nitin R; Ankolekar, Suresh

    2007-11-30

    Classical approaches to clinical trial design ignore economic factors that determine economic viability of a new drug. We address the choice of sample size in Phase III trials as a decision theory problem using a hybrid approach that takes a Bayesian view from the perspective of a drug company and a classical Neyman-Pearson view from the perspective of regulatory authorities. We incorporate relevant economic factors in the analysis to determine the optimal sample size to maximize the expected profit for the company. We extend the analysis to account for risk by using a 'satisficing' objective function that maximizes the chance of meeting a management-specified target level of profit. We extend the models for single drugs to a portfolio of clinical trials and optimize the sample sizes to maximize the expected profit subject to budget constraints. Further, we address the portfolio risk and optimize the sample sizes to maximize the probability of achieving a given target of expected profit.

  13. Prevention of prescription errors by computerized, on-line, individual patient related surveillance of drug order entry.

    Science.gov (United States)

    Oliven, A; Zalman, D; Shilankov, Y; Yeshurun, D; Odeh, M

    2002-01-01

    Computerized prescription of drugs is expected to reduce the number of many preventable drug ordering errors. In the present study we evaluated the usefullness of a computerized drug order entry (CDOE) system in reducing prescription errors. A department of internal medicine using a comprehensive CDOE, which included also patient-related drug-laboratory, drug-disease and drug-allergy on-line surveillance was compared to a similar department in which drug orders were handwritten. CDOE reduced prescription errors to 25-35%. The causes of errors remained similar, and most errors, on both departments, were associated with abnormal renal function and electrolyte balance. Residual errors remaining on the CDOE-using department were due to handwriting on the typed order, failure to feed patients' diseases, and system failures. The use of CDOE was associated with a significant reduction in mean hospital stay and in the number of changes performed in the prescription. The findings of this study both quantity the impact of comprehensive CDOE on prescription errors and delineate the causes for remaining errors.

  14. Generating genius: how an Alzheimer’s drug became considered a ‘cognitive enhancer’ for healthy individuals

    Science.gov (United States)

    2014-01-01

    Background Donepezil, an acetylcholinesterase inhibitor used in the treatment of Alzheimer’s disease, has been widely cited in media and bioethics literature on cognitive enhancement (CE) as having the potential to improve the cognitive ability of healthy individuals. In both literatures, this claim has been repeatedly supported by the results of a small study published by Yesavage et al. in 2002 on non-demented pilots (30–70 years old). The factors contributing to this specific interpretation of this study’s results are unclear. Methods We examined print media and interdisciplinary bioethics coverage of this small study, aiming to provide insight into how evidence from research may be shaped within different discourses, potentially influencing important policy, ethics, and clinical decisions. Systematic qualitative content analysis was used to examine how this study was reported in 27 media and 22 bioethics articles. Articles were analyzed for content related to: (1) headlines and titles; (2) colloquialisms; and, (3) accuracy of reporting of the characteristics and results of the study. Results In media and bioethics articles referencing this small study, strong claims were made about donepezil as a CE drug. The majority of headlines, titles, and colloquialisms used enhancement language and the majority of these suggest that donepezil could be used to enhance intellectual ability. Further, both literatures moved between reporting the results of the primary study and magnifying the perceived connection between these results and the CE debate that was alluded to in the primary study. Specific descriptions of the results overwhelmingly reported an improvement in performance on a flight simulator, while more general statements claimed donepezil enhanced cognitive performance. Further, a high level of reporting accuracy was found regarding study characteristics of the original study, but variable levels of accuracy surrounded the presentation of complex

  15. Systematic review of studies generating individual participant data on the efficacy of drugs for treating soil-transmitted helminthiases and the case for data-sharing.

    Science.gov (United States)

    Halder, Julia B; Benton, Joanne; Julé, Amélie M; Guérin, Phillipe J; Olliaro, Piero L; Basáñez, María-Gloria; Walker, Martin

    2017-10-01

    Preventive chemotherapy and transmission control (PCT) by mass drug administration is the cornerstone of the World Health Organization (WHO)'s policy to control soil-transmitted helminthiases (STHs) caused by Ascaris lumbricoides (roundworm), Trichuris trichiura (whipworm) and hookworm species (Necator americanus and Ancylostama duodenale) which affect over 1 billion people globally. Despite consensus that drug efficacies should be monitored for signs of decline that could jeopardise the effectiveness of PCT, systematic monitoring and evaluation is seldom implemented. Drug trials mostly report aggregate efficacies in groups of participants, but heterogeneities in design complicate classical meta-analyses of these data. Individual participant data (IPD) permit more detailed analysis of drug efficacies, offering increased sensitivity to identify atypical responses potentially caused by emerging drug resistance. We performed a systematic literature review to identify studies concluding after 2000 that collected IPD suitable for estimating drug efficacy against STH. We included studies that administered a variety of anthelmintics with follow ups less than 60 days after treatment. We estimated the number of IPD and extracted cohort- and study-level meta-data. We estimate that there exist individual data on approximately 35,000 participants from 129 studies conducted in 39 countries, including 34 out of 103 countries where PCT is recommended. We find significant heterogeneity in diagnostic methods, times of outcome assessment, and the reported measure of efficacy. We also quantify cohorts comprising pre-school age children, pregnant women, and co-infected participants, including with HIV. We argue that establishing a global IPD repository would improve the capacity to monitor and evaluate the efficacy of anthelmintic drugs, respond to changes and safeguard the ongoing effectiveness of PCT. Establishing a fair, transparent data governance policy will be key for the

  16. Systematic review of studies generating individual participant data on the efficacy of drugs for treating soil-transmitted helminthiases and the case for data-sharing.

    Directory of Open Access Journals (Sweden)

    Julia B Halder

    2017-10-01

    Full Text Available Preventive chemotherapy and transmission control (PCT by mass drug administration is the cornerstone of the World Health Organization (WHO's policy to control soil-transmitted helminthiases (STHs caused by Ascaris lumbricoides (roundworm, Trichuris trichiura (whipworm and hookworm species (Necator americanus and Ancylostama duodenale which affect over 1 billion people globally. Despite consensus that drug efficacies should be monitored for signs of decline that could jeopardise the effectiveness of PCT, systematic monitoring and evaluation is seldom implemented. Drug trials mostly report aggregate efficacies in groups of participants, but heterogeneities in design complicate classical meta-analyses of these data. Individual participant data (IPD permit more detailed analysis of drug efficacies, offering increased sensitivity to identify atypical responses potentially caused by emerging drug resistance.We performed a systematic literature review to identify studies concluding after 2000 that collected IPD suitable for estimating drug efficacy against STH. We included studies that administered a variety of anthelmintics with follow ups less than 60 days after treatment. We estimated the number of IPD and extracted cohort- and study-level meta-data.We estimate that there exist individual data on approximately 35,000 participants from 129 studies conducted in 39 countries, including 34 out of 103 countries where PCT is recommended. We find significant heterogeneity in diagnostic methods, times of outcome assessment, and the reported measure of efficacy. We also quantify cohorts comprising pre-school age children, pregnant women, and co-infected participants, including with HIV.We argue that establishing a global IPD repository would improve the capacity to monitor and evaluate the efficacy of anthelmintic drugs, respond to changes and safeguard the ongoing effectiveness of PCT. Establishing a fair, transparent data governance policy will be key for

  17. Acurácia de informações sobre classes de medicamentos obtidas com questionário postal aplicado a idosos - Rio de Janeiro, RJ Accuracy of drug class information obtained from a postal questionnaire to elderly respondents

    Directory of Open Access Journals (Sweden)

    Maria Estrella L. Vasconcelos

    2009-12-01

    Brasileiros, using two approaches (postal and home visit to collect information from retirees who were 60 years old or older and beneficiaries of Brazil's national social security system (INSS. Statistics used were: simple kappa (k, adjusted kappa (PABAK, weighted kappa, intraclass correlation coefficients, indicators of sensitivity and specificity, and Luiz et al's graph method. RESULTS: 234 elderly (male = 42%; female = 58%; mean = 71.7 years answered both approaches. Concordance between the postal and face-to-face interview approaches was excellent (k=0.94 for hypoglycemics; very good (k = 0.83-0.82 for angiotensin-converting enzyme inhibitors and anti-hypertensives; good (k = 0.71 for diuretics; and reasonable (k = 0.47 for non-steroidal anti-inflammatories. Concordance was good (k = 0.61 for information on the total number of medications used. The validity of the postal approach was high, at times total, for the drugs used in treating diabetes (sensitivity and specificity = 100%, followed by anti-hypertensives. The lowest values obtained were for non-steroidal anti-inflammatories (sensitivity = 64%; specificity = 88%. CONCLUSION: the postal approach can be used to obtain accurate information on classes of medications used by a population aged 60 years or more with a social profile similar to that of social security beneficiaries.

  18. pH-Dependent Solubility and Dissolution Behavior of Carvedilol--Case Example of a Weakly Basic BCS Class II Drug.

    Science.gov (United States)

    Hamed, Rania; Awadallah, Areeg; Sunoqrot, Suhair; Tarawneh, Ola; Nazzal, Sami; AlBaraghthi, Tamadur; Al Sayyad, Jihan; Abbas, Aiman

    2016-04-01

    The objective of this study was to investigate the pH-dependent solubility and dissolution of weakly basic Biopharmaceutical Classification Systems (BCS) class II drugs, characterized by low solubility and high permeability, using carvedilol, a weak base with a pK a value of 7.8, as a model drug. A series of solubility and in vitro dissolution studies was carried out using media that simulate the gastric and intestinal fluids and cover the physiological pH range of the GI from 1.2 to 7.8. The effect of ionic strength, buffer capacity, and buffer species of the dissolution media on the solubility and dissolution behavior of carvedilol was also investigated. The study revealed that carvedilol exhibited a typical weak base pH-dependent solubility profile with a high solubility at low pH (545.1-2591.4 μg/mL within the pH range 1.2-5.0) and low solubility at high pH (5.8-51.9 μg/mL within the pH range 6.5-7.8). The dissolution behavior of carvedilol was consistent with the solubility results, where carvedilol release was complete (95.8-98.2% released within 60 min) in media simulating the gastric fluid (pH 1.2-5.0) and relatively low (15.9-86.2% released within 240 min) in media simulating the intestinal fluid (pH 6.5-7.8). It was found that the buffer species of the dissolution media may influence the solubility and consequently the percentage of carvedilol released by forming carvedilol salts of varying solubilities. Carvedilol solubility and dissolution decreased with increasing ionic strength, while lowering the buffer capacity resulted in a decrease in carvedilol solubility and dissolution rate.

  19. In Vitro Investigation of the Individual Contributions of Ultrasound-Induced Stable and Inertial Cavitation in Targeted Drug Delivery.

    Science.gov (United States)

    Gourevich, Dana; Volovick, Alexander; Dogadkin, Osnat; Wang, Lijun; Mulvana, Helen; Medan, Yoav; Melzer, Andreas; Cochran, Sandy

    2015-07-01

    Ultrasound-mediated targeted drug delivery is a therapeutic modality under development with the potential to treat cancer. Its ability to produce local hyperthermia and cell poration through cavitation non-invasively makes it a candidate to trigger drug delivery. Hyperthermia offers greater potential for control, particularly with magnetic resonance imaging temperature measurement. However, cavitation may offer reduced treatment times, with real-time measurement of ultrasonic spectra indicating drug dose and treatment success. Here, a clinical magnetic resonance imaging-guided focused ultrasound surgery system was used to study ultrasound-mediated targeted drug delivery in vitro. Drug uptake into breast cancer cells in the vicinity of ultrasound contrast agent was correlated with occurrence and quantity of stable and inertial cavitation, classified according to subharmonic spectra. During stable cavitation, intracellular drug uptake increased by a factor up to 3.2 compared with the control. Reported here are the value of cavitation monitoring with a clinical system and its subsequent employment for dose optimization. Copyright © 2015 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

  20. Individual-level socioeconomic status and community-level inequality as determinants of stigma towards persons living with HIV who inject drugs in Thai Nguyen, Vietnam

    Science.gov (United States)

    Lim, Travis; Zelaya, Carla; Latkin, Carl; Quan, Vu Minh; Frangakis, Constantine; Ha, Tran Viet; Minh, Nguyen Le; Go, Vivian

    2013-01-01

    Introduction HIV infection may be affected by multiple complex socioeconomic status (SES) factors, especially individual socioeconomic disadvantage and community-level inequality. At the same time, stigma towards HIV and marginalized groups has exacerbated persistent concentrated epidemics among key populations, such as persons who inject drugs (PWID) in Vietnam. Stigma researchers argue that stigma fundamentally depends on the existence of economic power differences in a community. In rapidly growing economies like Vietnam, the increasing gap in income and education levels, as well as an individual's absolute income and education, may create social conditions that facilitate stigma related to injecting drug use and HIV. Methods A cross-sectional baseline survey assessing different types of stigma and key socioeconomic characteristics was administered to 1674 PWID and 1349 community members living in physical proximity throughout the 32 communes in Thai Nguyen province, Vietnam. We created four stigma scales, including HIV-related and drug-related stigma reported by both PWID and community members. We then used ecologic Spearman's correlation, ordinary least-squares regression and multi-level generalized estimating equations to examine community-level inequality associations, individual-level SES associations and multi-level SES associations with different types of stigma, respectively. Results There was little urban–rural difference in stigma among communes. Higher income inequality was marginally associated with drug-related stigma reported by community members (p=0.087), and higher education inequality was significantly associated with higher HIV-related stigma reported by both PWID and community members (pstigma (HIV and drug related) reported by both PWID and community members. Part-time employed PWID reported more experiences and perceptions of drug-related stigma, while conversely unemployed community members reported enacting lower drug-related stigma

  1. Individual-level socioeconomic status and community-level inequality as determinants of stigma towards persons living with HIV who inject drugs in Thai Nguyen, Vietnam.

    Science.gov (United States)

    Lim, Travis; Zelaya, Carla; Latkin, Carl; Quan, Vu Minh; Frangakis, Constantine; Ha, Tran Viet; Minh, Nguyen Le; Go, Vivian

    2013-11-13

    HIV infection may be affected by multiple complex socioeconomic status (SES) factors, especially individual socioeconomic disadvantage and community-level inequality. At the same time, stigma towards HIV and marginalized groups has exacerbated persistent concentrated epidemics among key populations, such as persons who inject drugs (PWID) in Vietnam. Stigma researchers argue that stigma fundamentally depends on the existence of economic power differences in a community. In rapidly growing economies like Vietnam, the increasing gap in income and education levels, as well as an individual's absolute income and education, may create social conditions that facilitate stigma related to injecting drug use and HIV. A cross-sectional baseline survey assessing different types of stigma and key socioeconomic characteristics was administered to 1674 PWID and 1349 community members living in physical proximity throughout the 32 communes in Thai Nguyen province, Vietnam. We created four stigma scales, including HIV-related and drug-related stigma reported by both PWID and community members. We then used ecologic Spearman's correlation, ordinary least-squares regression and multi-level generalized estimating equations to examine community-level inequality associations, individual-level SES associations and multi-level SES associations with different types of stigma, respectively. There was little urban-rural difference in stigma among communes. Higher income inequality was marginally associated with drug-related stigma reported by community members (p=0.087), and higher education inequality was significantly associated with higher HIV-related stigma reported by both PWID and community members (pinequality and HIV-related stigma is superseded by the effect of individual-level education. The results of the study confirm that socioeconomic factors at both the individual level and community level affect different types of stigma in different ways. Attention should be paid to these

  2. Gender differences in the association of individual social class and neighbourhood unemployment rate with prevalent type 2 diabetes mellitus: a cross-sectional study from the DIAB-CORE consortium.

    Science.gov (United States)

    Müller, Grit; Hartwig, Saskia; Greiser, Karin Halina; Moebus, Susanne; Pundt, Noreen; Schipf, Sabine; Völzke, Henry; Maier, Werner; Meisinger, Christa; Tamayo, Teresa; Rathmann, Wolfgang; Berger, Klaus

    2013-06-21

    To analyse gender differences in the relationship of individual social class, employment status and neighbourhood unemployment rate with present type 2 diabetes mellitus (T2DM). Five cross-sectional studies. Studies were conducted in five regions of Germany from 1997 to 2006. The sample consisted of 8871 individuals residing in 226 neighbourhoods from five urban regions. Prevalent T2DM. We found significant multiplicative interactions between gender and the individual variables--social class and employment status. Social class was statistically significantly associated with T2DM in men and women, whereby this association was stronger in women (lower vs higher social class: OR 2.68 (95% CIs 1.66 to 4.34)) than men (lower vs higher social class: OR 1.78 (95% CI 1.22 to 2.58)). Significant associations of employment status and T2DM were only found in women (unemployed vs employed: OR 1.73 (95% CI 1.02 to 2.92); retired vs employed: OR 1.77 (95% CI 1.10 to 2.84); others vs employed: OR 1.64 (95% CI 1.01 to 2.67)). Neighbourhood unemployment rate was associated with T2DM in men (high vs low tertile: OR 1.52 (95% CI 1.18 to 1.96)). Between-study and between-neighbourhood variations in T2DM prevalence were more pronounced in women. The considered covariates helped to explain statistically the variation in T2DM prevalence among men, but not among women. Social class was inversely associated with T2DM in both men and women, whereby the association was more pronounced in women. Employment status only affected T2DM in women. Neighbourhood unemployment rate is an important predictor of T2DM in men, but not in women.

  3. The Impact of Agentic and Communal Exercise Messages on Individuals' Exercise Class Attitudes, Self-Efficacy Beliefs, and Intention to Attend.

    Science.gov (United States)

    Howle, Timothy C; Dimmock, James A; Ntoumanis, Nikos; Chatzisarantis, Nikos L D; Sparks, Cassandra; Jackson, Ben

    2017-12-01

    We tested the effects of advertisements about a fictitious exercise class-derived using the theoretical constructs of agency and communion-on recipients' perceptions about, and interest in, the class. The final sample consisted of 150 adults (M age  = 44.69, SD = 15.83). Results revealed that participants who received a communal-oriented message reported significantly greater exercise task self-efficacy and more positive affective attitudes relative to those who received an agentic-oriented message. Communal (relative to agentic) messages were also indirectly responsible for greater intentions to attend the class, via more positive self-efficacy beliefs and affective attitudes. These findings were obtained despite the use of another manipulation to orient participants to either agency or communion goals. The results indicate that the primacy of communion over agency for message recipients may extend to exercise settings and may occur irrespective of whether participants are situationally oriented toward agency or communion.

  4. Risk of myocardial infarction and death associated with the use of nonsteroidal anti-inflammatory drugs (NSAIDs) among healthy individuals: a nationwide cohort study

    DEFF Research Database (Denmark)

    Fosbøl, E L; Gislason, G H; Jacobsen, S

    2008-01-01

    Use of some nonsteroidal anti-inflammatory drugs (NSAIDs) is associated with increased cardiovascular risk in several patient groups, but whether this excess risk exists in apparently healthy individuals has not been clarified. Using a historical cohort design, we estimated the risk of death...... and myocardial infarction associated with the use of NSAIDs. Participants in the study were selected from the Danish population and were defined as healthy according to a history of no hospital admissions and no concomitant selected pharmacotherapy. The source population consisted of 4,614,807 individuals...

  5. Relative efficacy of topical non-steroidal anti-inflammatory drugs and topical capsaicin in osteoarthritis: Protocol for an individual patient data meta-analysis

    OpenAIRE

    Persson, M.S.M. (Monica); Fu, Y. (Yu); Bhattacharya, A. (Archan); Goh, S.-L. (Siew-Li); Middelkoop, Marienke; Bierma-Zeinstra, Sita; Walsh, D. (David); Doherty, Michael; Zhang, Weiya

    2016-01-01

    Background Pain is the most troubling issue to patients with osteoarthritis (OA), yet current pharmacological treatments offer only small-to-moderate pain reduction. Current guidelines therefore emphasise the need to identify predictors of treatment response. In line with these recommendations, an individual patient data (IPD) meta-analysis will be conducted. The study aims to investigate the relative treatment effects of topical non-steroidal anti-inflammatory drugs (NSAIDs) and topical caps...

  6. 21 CFR 1303.21 - Individual manufacturing quotas.

    Science.gov (United States)

    2010-04-01

    ... controlled substance listed in Schedule I or II, and who applies for a manufacturing quota, an individual... basic class. Any manufacturing quota fixed and issued by the Administrator shall be subject to his... 21 Food and Drugs 9 2010-04-01 2010-04-01 false Individual manufacturing quotas. 1303.21 Section...

  7. The Predictive Role of Difficulties in Emotion Regulation and Self-Control with Susceptibility to Addiction in Drug-Dependent Individuals

    Directory of Open Access Journals (Sweden)

    Mahmoud Shirazi

    2015-06-01

    Full Text Available Objective: The present study aimed to examine the predictive role of difficulties in emotion regulation and self-control in potential for addiction among drug-dependent individuals. Method: This was a correlational study which falls within the category of descriptive studies. The statistical population of the current study included all patients under treatment in outpatient health centers in Bam, among whom 315 individuals were selected through cluster sampling method as the participants of the study. Difficulties in Emotion Regulation Scale, Self-Control Scale, and Addiction Susceptibility Questionnaire were used for data collection purposes. Results: The results indicated that difficulties engaging in goal directed behavior, impulse control difficulties, lack of emotional awareness, and lack of emotional clarity (dimensions of difficulties in emotion regulation had a significant positive correlation with potential for addiction. In addition, there was a negative significant relationship between self-control and potential for addiction among drug-dependent individuals. Conclusion: In addition to common methods of abstinence from drug dependence, teaching self-control and emotional control techniques to addicted patients can help them reduce their dependence.

  8. Prediction of interindividual variation in drug plasma levels in vivo from individual enzyme kinetic data and physiologically based pharmacokinetic modeling

    NARCIS (Netherlands)

    Bogaards, J.J.P.; Hissink, E.M.; Briggs, M.; Weaver, R.; Jochemsen, R.; Jackson, P.; Bertrand, M.; Bladeren, P. van

    2000-01-01

    A strategy is presented to predict interindividual variation in drug plasma levels in vivo by the use of physiologically based pharmacokinetic modeling and human in vitro metabolic parameters, obtained through the combined use of microsomes containing single cytochrome P450 enzymes and a human liver

  9. Recreational Drug Use among Chinese MSM and Transgender Individuals: Results from a National Online Cross-Sectional Study.

    Directory of Open Access Journals (Sweden)

    Peizhen Zhao

    Full Text Available Recreational drug use has increased considerably among Chinese men who have sex with men (MSM. The phenomenon has the potentially to increase HIV transmission among Chinese MSM. The aims of this study were: 1 to investigate the prevalence of recreational drug use among Chinese MSM, and 2 to explore the correlation between gay smartphone based sex-seeking applications (gay apps, HIV/STIs testing, group sex, commercial sex, sexual roles and poppers use among Chinese MSM.MSM who were born biologically male, were at least 16 years of age and had engaged in anal sex with a man at least once were recruited through a nation-wide online survey in 2014. Information regarding socio-demographics, risk behaviors, recreational drug use, HIV and other STIs testing history and gay app use were collected. Univariate and multivariate analysis were used to determine factors associated with recreational drug use among Chinese MSM.Among 1424 participating MSM, 1100 (77.3% reported ever using recreational drugs in their lifetime. In the last 12 months, 303 (21.3% used poppers, 34 (2.4% used crystal meth and 15 (1.0% used ecstasy. The mean age of respondents was 25.6±6.8 years, 72.9% identified as gay, 41.3% were students, and 83.8% had never been married. Multiple logistic regression models revealed that compared with non-popper users, popper users were more likely to have been tested for HIV (adjusted OR (aOR = 1.50, 95% CI: 1.15-1.96 and other STIs (aOR = 1.65, 95% CI: 1.26-2.17. In addition, popper users were more likely to engage in group sex (aOR = 2.63, 95% CI:1.80-3.86, commercial sex (aOR = 1.86, 95% CI:1.13-3.06 and used gay mobile apps to seek sexual partners (aOR = 2.10, 95% CI:1.58-2.80.Chinese MSM has a high rate of recreational drug use, including poppers. Public health programs serving MSM may consider integrating intervention programs to decrease recreational drug use related harms.

  10. Recreational Drug Use among Chinese MSM and Transgender Individuals: Results from a National Online Cross-Sectional Study.

    Science.gov (United States)

    Zhao, Peizhen; Tang, Songyuan; Wang, Cheng; Zhang, Ye; Best, John; Tangthanasup, Thitikarn May; Huang, Shujie; Yang, Bin; Wei, Chongyi; Tucker, Joseph D; Tang, Weiming

    2017-01-01

    Recreational drug use has increased considerably among Chinese men who have sex with men (MSM). The phenomenon has the potentially to increase HIV transmission among Chinese MSM. The aims of this study were: 1) to investigate the prevalence of recreational drug use among Chinese MSM, and 2) to explore the correlation between gay smartphone based sex-seeking applications (gay apps), HIV/STIs testing, group sex, commercial sex, sexual roles and poppers use among Chinese MSM. MSM who were born biologically male, were at least 16 years of age and had engaged in anal sex with a man at least once were recruited through a nation-wide online survey in 2014. Information regarding socio-demographics, risk behaviors, recreational drug use, HIV and other STIs testing history and gay app use were collected. Univariate and multivariate analysis were used to determine factors associated with recreational drug use among Chinese MSM. Among 1424 participating MSM, 1100 (77.3%) reported ever using recreational drugs in their lifetime. In the last 12 months, 303 (21.3%) used poppers, 34 (2.4%) used crystal meth and 15 (1.0%) used ecstasy. The mean age of respondents was 25.6±6.8 years, 72.9% identified as gay, 41.3% were students, and 83.8% had never been married. Multiple logistic regression models revealed that compared with non-popper users, popper users were more likely to have been tested for HIV (adjusted OR (aOR) = 1.50, 95% CI: 1.15-1.96) and other STIs (aOR = 1.65, 95% CI: 1.26-2.17). In addition, popper users were more likely to engage in group sex (aOR = 2.63, 95% CI:1.80-3.86), commercial sex (aOR = 1.86, 95% CI:1.13-3.06) and used gay mobile apps to seek sexual partners (aOR = 2.10, 95% CI:1.58-2.80). Chinese MSM has a high rate of recreational drug use, including poppers. Public health programs serving MSM may consider integrating intervention programs to decrease recreational drug use related harms.

  11. A New Class III Antiarrhythmic Drug Niferidil Prolongs Action Potentials in Guinea Pig Atrial Myocardium via Inhibition of Rapid Delayed Rectifier.

    Science.gov (United States)

    Abramochkin, Denis V; Kuzmin, Vladislav S; Rosenshtraukh, Leonid V

    2017-12-01

    A new class III antiarrhythmic drug niferidil (RG-2) has been introduced as a highly effective therapy for cases of persistent atrial fibrillation, but ionic mechanisms of its action are poorly understood. In the present study, the effects of niferidil on action potential (AP) waveform and potassium currents responsible for AP repolarization were investigated in guinea pig atrial myocardium. APs were recorded with sharp glass microelectrodes in multicellular atrial preparations. Whole-cell patch-clamp technique was used to measure K + currents in isolated myocytes. In multicellular atrial preparations, 10 -8  M niferidil effectively prolonged APs by 15.2 ± 2.8% at 90% repolarization level. However, even the highest tested concentrations, 10 -6  M and 10 -5  M failed to prolong APs more than 32.5% of control duration. The estimated concentration of niferedil for half-maximal AP prolongation was 1.13 × 10 -8  M. Among the potassium currents responsible for AP repolarization phase, I K1 was found to be almost insensitive to niferidil. However, another inward rectifier, I KACh , was effectively suppressed by micromolar concentrations of niferidil with IC 50  = 9.2 × 10 -6  M. I KATP was much less sensitive to the drug with IC 50  = 2.26 × 10 -4  M. The slow component of delayed rectifier, I Ks , also demonstrated low sensitivity to niferidil-the highest used concentration, 10 -4  M, decreased peak I Ks density to 46.2 ± 5.5% of control. Unlike I Ks , the rapid component of delayed rectifier, I Kr , appeared to be extremely sensitive to niferidil. The IC 50 was 1.26 × 10 -9  M. I Kr measured in ventricular myocytes was found to be less sensitive to niferidil with IC 50  = 3.82 × 10 -8  M. Niferidil prolongs APs in guinea pig atrial myocardium via inhibition of I Kr .

  12. Individualized monitoring of drug bioavailability and immunogenicity in rheumatoid arthritis patients treated with the tumor necrosis factor alpha inhibitor infliximab

    DEFF Research Database (Denmark)

    Bendtzen, Klaus; Geborek, Pierre; Svenson, Morten

    2006-01-01

    Infliximab, an anti-tumor necrosis factor alpha (anti-TNFalpha) antibody, is effective in the treatment of several immunoinflammatory diseases. However, many patients experience primary or secondary response failure, suggesting that individualization of treatment regimens may be beneficial...

  13. Active methamphetamine use is associated with transmitted drug resistance to non-nucleoside reverse transcriptase inhibitors in individuals with HIV infection of unknown duration.

    Science.gov (United States)

    Cachay, Edward R; Moini, Niousha; Kosakovsky Pond, Sergei L; Pesano, Rick; Lie, Yolanda S; Aiem, Heidi; Butler, David M; Letendre, Scott; Mathews, Wm Christopher; Smith, Davey M

    2007-01-01

    Frequent methamphetamine use among recently HIV infected individuals is associated with transmitted drug resistance (TDR) to non-nucleoside reverse transcriptase inhibitors (NNRTI); however, the reversion time of TDR to drug susceptible HIV may exceed 3 years. We assessed whether recreational substance use is associated with detectable TDR among individuals newly diagnosed with HIV infection of unknown duration. Cross-sectional analysis. Subjects were enrolled at the University California, San Diego Early Intervention Program. Demographic, clinical and substance use data were collected using structured interviews. Genotypic resistance testing was performed using GeneSeq, Monogram Biosciences. We analyzed the association between substance use and TDR using bivariate analyses and the corresponding transmission networks using phylogenetic models. Between April 2004 and July 2006, 115 individuals with genotype data were enrolled. The prevalence of alcohol, marijuana and methamphetamine use were 98%, 71% and 64% respectively. Only active methamphetamine use in the 30 days prior to HIV diagnosis was independently associated with TDR to NNRTI (OR: 6.6; p=0.002). Despite not knowing the duration of their HIV infection, individuals reporting active methamphetamine use in the 30 days prior to HIV diagnosis are at an increased risk of having HIV strains that are resistant to NNRTI.

  14. Active Methamphetamine Use is Associated with Transmitted Drug Resis-tance to Non-Nucleoside Reverse Transcriptase Inhibitors in Individuals with HIV Infection of Unknown Duration

    Science.gov (United States)

    Cachay, Edward R; Moini, Niousha; Kosakovsky Pond, Sergei L; Pesano, Rick; Lie, Yolanda S; Aiem, Heidi; Butler, David M; Letendre, Scott; Mathews, Wm. Christopher; Smith, Davey M

    2007-01-01

    Background: Frequent methamphetamine use among recently HIV infected individuals is associated with transmitted drug resistance (TDR) to non-nucleoside reverse transcriptase inhibitors (NNRTI); however, the reversion time of TDR to drug susceptible HIV may exceed 3 years. We assessed whether recreational substance use is associated with detectable TDR among individuals newly diagnosed with HIV infection of unknown duration. Design: Cross-sectional analysis. Methods: Subjects were enrolled at the University California, San Diego Early Intervention Program. Demographic, clinical and substance use data were collected using structured interviews. Genotypic resistance testing was performed using GeneSeq™, Monogram Biosciences. We analyzed the association between substance use and TDR using bivariate analyses and the corresponding transmission networks using phylogenetic models. Results: Between April 2004 and July 2006, 115 individuals with genotype data were enrolled. The prevalence of alcohol, marijuana and methamphetamine use were 98%, 71% and 64% respectively. Only active methamphetamine use in the 30 days prior to HIV diagnosis was independently associated with TDR to NNRTI (OR: 6.6; p=0.002). Conclusion: Despite not knowing the duration of their HIV infection, individuals reporting active methamphetamine use in the 30 days prior to HIV diagnosis are at an increased risk of having HIV strains that are resistant to NNRTI. PMID:18923691

  15. Transfer Behavior of the Weakly Acidic BCS Class II Drug Valsartan from the Stomach to the Small Intestine During Fasted and Fed States.

    Science.gov (United States)

    Hamed, Rania; Alnadi, Sabreen Hasan

    2018-05-07

    The objective of this study was to investigate the transfer behavior of the weakly acidic BCS class II drug valsartan from the stomach to the small intestine during fasted and fed states. An in vitro transfer model previously introduced by Kostewicz et al. (J Pharm Pharmacol 56(1):43-51, 2004) based on a syringe pump and a USP paddle apparatus was used to determine the concentration profiles of valsartan in the small intestine. Donor phases of simulated gastric fluid during fasted (FaSSGF) and fed (FeSSGF) states were used to predisperse Diovan® tablets (160 mg valsartan). The initial concentrations of valsartan in FaSSGF and FeSSGF were 6.2 and 91.8%, respectively. Valsartan dispersions were then transferred to acceptor phases that simulate intestinal fluid and cover the physiological properties (pH, buffer capacity, and ionic strength) of the gastrointestinal fluid at a flow rate of 2 mL/min. The pH measurements were reported at time intervals corresponded to those of the transfer experiments to investigate the effect of percent dissolved of valsartan in the donor phase on lowering the pH of the acceptor phases. The f2 similarity test was used to compare the concentration profiles in the acceptor phases. In fasted state, the concentration of valsartan in the acceptor phases ranged between 33.1 and 89.4% after 240 min. Whereas in fed state, valsartan was fully dissolved in all acceptor phases within a range of 94.5-104.9% after 240 min. Therefore, the transfer model provides a useful screen for the concentrations of valsartan in the small intestine during fasted and fed states.

  16. Molecular epidemiology of HIV type 1 infection in Iran: genomic evidence of CRF35_AD predominance and CRF01_AE infection among individuals associated with injection drug use.

    Science.gov (United States)

    Jahanbakhsh, Fatemeh; Ibe, Shiro; Hattori, Junko; Monavari, Seyed Hamid Reza; Matsuda, Masakazu; Maejima, Masami; Iwatani, Yasumasa; Memarnejadian, Arash; Keyvani, Hossein; Azadmanesh, Kayhan; Sugiura, Wataru

    2013-01-01

    To understand the molecular epidemiology of HIV-1 infection in Iran, we conducted the first study to analyze the genome sequence of Iranian HIV-1 isolates. For this cross-sectional study, we enrolled 10 HIV-1-infected individuals associated with injection drug use from Tehran, Shiraz, and Kermanshah. Near full-length genome sequences obtained from their plasma samples were used for phylogenetic tree and similarity plotting analyses. Among 10 isolates, nine were clearly identified as CRF35_AD and the remaining one as CRF01_AE. Interestingly, five of our Iranian CRF35_AD isolates made two clusters with 10 Afghan CRF35_AD isolates in a phylogenetic tree, indicating epidemiological connections among injection drug users in Iran and Afghanistan. In contrast, our CRF01_AE isolate had no genetic relationship with any other CRF01_AE isolates worldwide, even from Afghanistan. This study provides the first genomic evidence of HIV-1 CRF35_AD predominance and CRF01_AE infection among individuals associated with injection drug use in Iran.

  17. An investigation on drug resistance of viridance group streptococci isolated from 3-12 years healthy individuals

    Directory of Open Access Journals (Sweden)

    Abasalt Borji

    2010-11-01

    Full Text Available Background: Nowadays, dental and oral infections are regarded as major threats to human health whose treatments are always prime concern of dental surgeons. Staphylococci, streptococci, actinomycetes and mycoplasma are the most common causative agents of such infections.The objective of this study was to investigate drug resistance of viridance group streptococci (VGS isolated from healthy children between 3-12 years old versus common antibiotics utilized in dentistry. The findings of this study can help dentists using the antibiotic of choice in remedial practices as well as assessment of sensitivity or resistance of VGS.Materials and Method: In this cross sectional study saliva samples from of 213 healthy children aged between 3-12 years from their buccal surface of posterior teeth were collected and after culture. species were isolated. Next, drug sensitivity test was carried out by disc diffusion technique to find out sensitivity or resistance of VGS to penicillin, erythromycin, vancomycin, clindamycin, cephotaxim and cephteriaxon.Result: Our findings revealed that resistance of VGS to antibiotics including: clindamycin, penicillin, cephteriaxon, erythromycin, vancomycin and cephotaxim was 59.6%, 52.6%, 30.5%, 12.2%, 10.8% and 1.5% and sensitivity of VGS to such antibiotics was 19.7%, 29.6%, 23%, 13.4%, 4.5% and 29.6% respectively.Conclusion: The results showed widespread resistance of VGS against chosen antibiotics, this indicates considerable use of antibiotics in this region.Controlled use and prescription of different antibiotics as well as increasing people knowledge about misuse of antibiotics in order to decrease the drug resistance is important

  18. Prediction of individual patient response to chemotherapy by the fluorometric microculture cytotoxicity assay (FMCA) using drug specific cut-off limits and a Bayesian model.

    Science.gov (United States)

    Larsson, R; Nygren, P

    1993-01-01

    The semiautomated fluorometric microculture cytotoxicity assay (FMCA) based on the measurement of fluorescence generated from cellular hydrolysis of fluorescein diacetate (FDA) to fluorescein in microtiter plates, has been used for determination of cytotoxic drug resistance of tumor cells from patients with hematological and solid tumors. In the present study we describe a calibration procedure based on statistically derived cut-off limits and assay-predicted response probabilities using Bayes' theorem. Test results at a specified drug concentration were divided into three categories: low, intermediate or extreme drug resistance (LDR, IDR and EDR, respectively) using the median and median +1 standard deviation as the cut-off limits. When correlated with clinical outcome, LDR samples showed a higher response rate than expected, IDR a lower and EDR samples no response at all. The sensitivity and specificity of the test, using the median as cut-off limit, were 0.92 and 0.69 respectively. By fitting these test characteristics to a statistical model based on Bayes' theorem it is possible to calculate response probabilities for each individual patient taking into consideration not only the test characteristics and the particular assay result, but also the clinical and patient specific characteristics influencing the pre-test probability of response. EDR predicts clinical drug resistance with high specificity and is also observed in tumor types with high response rate.

  19. Therapeutic drug monitoring of atypical antipsychotic drugs

    Directory of Open Access Journals (Sweden)

    Grundmann Milan

    2014-12-01

    Full Text Available Schizophrenia is a severe psychiatric disorder often associated with cognitive impairment and affective, mainly depressive, symptoms. Antipsychotic medication is the primary intervention for stabilization of acute psychotic episodes and prevention of recurrences and relapses in patients with schizophrenia. Typical antipsychotics, the older class of antipsychotic agents, are currently used much less frequently than newer atypical antipsychotics. Therapeutic drug monitoring (TDM of antipsychotic drugs is the specific method of clinical pharmacology, which involves measurement of drug serum concentrations followed by interpretation and good cooperation with the clinician. TDM is a powerful tool that allows tailor-made treatment for the specific needs of individual patients. It can help in monitoring adherence, dose adjustment, minimizing the risk of toxicity and in cost-effectiveness in the treatment of psychiatric disorders. The review provides complex knowledge indispensable to clinical pharmacologists, pharmacists and clinicians for interpretation of TDM results.

  20. Dependent Classes

    DEFF Research Database (Denmark)

    Gasiunas, Vaidas; Mezini, Mira; Ostermann, Klaus

    2007-01-01

    of dependent classes and a machine-checked type soundness proof in Isabelle/HOL [29], the first of this kind for a language with virtual classes and path-dependent types. [29] T.Nipkow, L.C. Poulson, and M. Wenzel. Isabelle/HOL -- A Proof Assistant for Higher-Order Logic, volume 2283 of LNCS, Springer, 2002......Virtual classes allow nested classes to be refined in subclasses. In this way nested classes can be seen as dependent abstractions of the objects of the enclosing classes. Expressing dependency via nesting, however, has two limitations: Abstractions that depend on more than one object cannot...... be modeled and a class must know all classes that depend on its objects. This paper presents dependent classes, a generalization of virtual classes that expresses similar semantics by parameterization rather than by nesting. This increases expressivity of class variations as well as the flexibility...

  1. Models of Alcohol and Other Drug Treatment for Consideration When Working with Deaf and Hard of Hearing Individuals.

    Science.gov (United States)

    Guthmann, Debra

    This paper discusses several models for treating chemical dependency in individuals who are deaf or hard of hearing. It begins by describing the 12-step model, a comprehensive, multi-disciplinary approach to the treatment of addiction which is abstinence oriented and based on the principles of Alcoholics Anonymous. This model includes group…

  2. Changes over time in risk factors for cardiovascular disease and use of lipid-lowering drugs in HIV-infected individuals and impact on myocardial infarction

    DEFF Research Database (Denmark)

    Sabin, C A; d'Arminio Monforte, A; Friis-Moller, N

    2008-01-01

    for CVD and the use of lipid-lowering therapy in HIV-infected individuals and assessed the impact of any changes on the incidence of myocardial infarction. METHODS: The Data Collection on Adverse Events of Anti-HIV Drugs Study is a collaboration of 11 cohorts of HIV-infected patients that included follow...... was more common for those with abnormal lipid values and those with traditional risk factors for CVD (male sex, older age, higher body mass index [calculated as the weight in kilograms divided by the square of the height in meters], family and personal history of CVD, and diabetes mellitus). After...... controlling for these, use of lipid-lowering drugs became relatively less common over time. The incidence of myocardial infarction (0.32 cases per 100 person-years [PY]; 95% confidence interval [CI], 0.29-0.35 cases per 100 PY) appeared to remain stable. However, after controlling for changes in risk factors...

  3. EFFECT OF ANTIHYPERTENSIVE THERAPY BASED ON NEW METHOD OF INDIVIDUAL CHOICE OF DRUGS ON LEFT VENTRICULAR HYPERTROPHY IN ELDERLY PATIENTS

    Directory of Open Access Journals (Sweden)

    K. I. Pshenichkin

    2015-12-01

    Full Text Available Aim. To study the effects of antihypertensive therapy based on consideration of individual heart rhythm variability (HRV on left ventricular hypertrophy (LVH in hypertensive elderly patients.Material and methods. 60 hypertensive elderly patients with LVH were included in the study. They were split in two groups (30 people in each one. Patients of the group-I had common antihypertensive therapy. Patients of group-II received medications prescribed with consideration of individual heart rate variability. Holter monitoring with analysis of HRV, 24-hour blood pressure monitoring and ultrasonography were conducted initially and 18 months after treatment beginning.Results. BP control was reached in the majority of patients of both groups. The patients of group-II in comparison with patients of group-I had reduction of low- high frequency power ratio (LF/HF and higher rate of LVH reduction. Relationship between LVH dynamics and ratio LF/HF was found.Conclusion. Arterial hypertension therapy considering individual HRV contributes in LVH reduction in elderly patients.

  4. Calendar time trends in the incidence and prevalence of triple-class virologic failure in antiretroviral drug-experienced people with HIV in Europe

    DEFF Research Database (Denmark)

    Nakagawa, Fumiyo; Lodwick, Rebecca; Costagliola, Dominique

    2012-01-01

    Despite the increasing success of antiretroviral therapy (ART), virologic failure of the 3 original classes [triple-class virologic failure, (TCVF)] still develops in a small minority of patients who started therapy in the triple combination ART era. Trends in the incidence and prevalence of TCVF...

  5. Individual variation of human S1P₁ coding sequence leads to heterogeneity in receptor function and drug interactions.

    Science.gov (United States)

    Obinata, Hideru; Gutkind, Sarah; Stitham, Jeremiah; Okuno, Toshiaki; Yokomizo, Takehiko; Hwa, John; Hla, Timothy

    2014-12-01

    Sphingosine 1-phosphate receptor 1 (S1P₁), an abundantly-expressed G protein-coupled receptor which regulates key vascular and immune responses, is a therapeutic target in autoimmune diseases. Fingolimod/Gilenya (FTY720), an oral medication for relapsing-remitting multiple sclerosis, targets S1P₁ receptors on immune and neural cells to suppress neuroinflammation. However, suppression of endothelial S1P₁ receptors is associated with cardiac and vascular adverse effects. Here we report the genetic variations of the S1P₁ coding region from exon sequencing of >12,000 individuals and their functional consequences. We conducted functional analyses of 14 nonsynonymous single nucleotide polymorphisms (SNPs) of the S1PR1 gene. One SNP mutant (Arg¹²⁰ to Pro) failed to transmit sphingosine 1-phosphate (S1P)-induced intracellular signals such as calcium increase and activation of p44/42 MAPK and Akt. Two other mutants (Ile⁴⁵ to Thr and Gly³⁰⁵ to Cys) showed normal intracellular signals but impaired S1P-induced endocytosis, which made the receptor resistant to FTY720-induced degradation. Another SNP mutant (Arg¹³ to Gly) demonstrated protection from coronary artery disease in a high cardiovascular risk population. Individuals with this mutation showed a significantly lower percentage of multi-vessel coronary obstruction in a risk factor-matched case-control study. This study suggests that individual genetic variations of S1P₁ can influence receptor function and, therefore, infer differential disease risks and interaction with S1P₁-targeted therapeutics. Copyright © 2014 by the American Society for Biochemistry and Molecular Biology, Inc.

  6. Novel approach to characterising individuals with low back-related leg pain: cluster identification with latent class analysis and 12-month follow-up.

    Science.gov (United States)

    Stynes, Siobhán; Konstantinou, Kika; Ogollah, Reuben; Hay, Elaine M; Dunn, Kate M

    2018-04-01

    Traditionally, low back-related leg pain (LBLP) is diagnosed clinically as referred leg pain or sciatica (nerve root involvement). However, within the spectrum of LBLP, we hypothesised that there may be other unrecognised patient subgroups. This study aimed to identify clusters of patients with LBLP using latent class analysis and describe their clinical course. The study population was 609 LBLP primary care consulters. Variables from clinical assessment were included in the latent class analysis. Characteristics of the statistically identified clusters were compared, and their clinical course over 1 year was described. A 5 cluster solution was optimal. Cluster 1 (n = 104) had mild leg pain severity and was considered to represent a referred leg pain group with no clinical signs, suggesting nerve root involvement (sciatica). Cluster 2 (n = 122), cluster 3 (n = 188), and cluster 4 (n = 69) had mild, moderate, and severe pain and disability, respectively, and response to clinical assessment items suggested categories of mild, moderate, and severe sciatica. Cluster 5 (n = 126) had high pain and disability, longer pain duration, and more comorbidities and was difficult to map to a clinical diagnosis. Most improvement for pain and disability was seen in the first 4 months for all clusters. At 12 months, the proportion of patients reporting recovery ranged from 27% for cluster 5 to 45% for cluster 2 (mild sciatica). This is the first study that empirically shows the variability in profile and clinical course of patients with LBLP including sciatica. More homogenous groups were identified, which could be considered in future clinical and research settings.

  7. Genotypic Characterization of Human Immunodeficiency Virus Type 1 Derived from Antiretroviral Drug-Treated Individuals Residing in Earthquake-Affected Areas in Nepal.

    Science.gov (United States)

    Negi, Bharat Singh; Kotaki, Tomohiro; Joshi, Sunil Kumar; Bastola, Anup; Nakazawa, Minato; Kameoka, Masanori

    2017-09-01

    Molecular epidemiological data on human immunodeficiency virus type 1 (HIV-1) are limited in Nepal and have not been available in areas affected by the April 2015 earthquake. Therefore, we conducted a genotypic study on HIV-1 genes derived from individuals on antiretroviral therapy residing in 14 districts in Nepal highly affected by the earthquake. HIV-1 genomic fragments were amplified from 40 blood samples of HIV treatment-failure individuals, and a sequencing analysis was performed on these genes. In the 40 samples, 29 protease, 32 reverse transcriptase, 25 gag, and 21 env genes were sequenced. HIV-1 subtyping revealed that subtype C (84.2%, 32/38) was the major subtype prevalent in the region, while CRF01_AE (7.9%, 3/38) and other recombinant forms (7.9%, 3/38) were also detected. In addition, major drug resistance mutations were identified in 21.9% (7/32) of samples, indicating the possible emergence of HIV-1 drug resistance in earthquake-affected areas in Nepal.

  8. Examination of the inventory of drug use consequences with individuals with serious and persistent mental illness and co-occurring substance use disorders.

    Science.gov (United States)

    Bennett, Melanie E; Nidecker, Melissa; Strong Kinnaman, Joanna E; Li, Lan; Bellack, Alan S

    2009-01-01

    The Inventory of Drug Use Consequences (InDUC) ( [1] ) is a 50-item measure that evaluates lifetime and recent consequences of substance use. This study examined the psychometric properties of a modified version of the Inventory of Drug Use Consequences (InDUC-M) in individuals with serious and persistent mental illness (SPMI) and co-occurring substance use disorders (SUDs). We examined self-reported consequences in the sample, evaluated internal consistency, identified items for a brief form of the InDUC-M, and explored relationships with indicators of substance use severity. InDUC-M Lifetime and Recent subscales showed good internal consistency and were related to other measures of substance use and problems. A brief version of the InDUC-M Recent (SIP-M) showed excellent internal consistency and was highly correlated with both Lifetime and Recent subscales. The InDUC-M and the SIP-M performed well in individuals with SPMI and SUDs. Overall, these findings are a useful first step in determining the utility of the InDUC-M in people with SPMI and SUDs.

  9. Cutting Classes

    Science.gov (United States)

    Hacker, Andrew

    1976-01-01

    Provides critical reviews of three books, "The Political Economy of Social Class", "Ethnicity: Theory and Experience," and "Ethnicity in the United States," focusing on the political economy of social class and ethnicity. (Author/AM)

  10. Culture and social class.

    Science.gov (United States)

    Miyamoto, Yuri

    2017-12-01

    A large body of research in Western cultures has demonstrated the psychological and health effects of social class. This review outlines a cultural psychological approach to social stratification by comparing psychological and health manifestations of social class across Western and East Asian cultures. These comparisons suggest that cultural meaning systems shape how people make meaning and respond to material/structural conditions associated with social class, thereby leading to culturally divergent manifestations of social class. Specifically, unlike their counterparts in Western cultures, individuals of high social class in East Asian cultures tend to show high conformity and other-orientated psychological attributes. In addition, cultures differ in how social class impacts health (i.e. on which bases, through which pathways, and to what extent). Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. Histoculture and the immunodeficient mouse come to the cancer clinic - rational approaches to individualizing cancer-therapy and new drug-evaluation (review).

    Science.gov (United States)

    Hoffman, R

    1992-09-01

    Originating from the experiments of Alexis Carrel, tissues in culture were originally grown in three dimensions and maintained important in vivo-like structural and functional properties. However, in modem times, monolayer cell culture methods have become predominant despite losses of structural and functional properties of the cells. Strangeways, Fell, Leighton, Sutherland and others have designed various methods of three-dimensional culture using cellulose supports, mesh supports, collagen gel or sponge supports and floatation that allow tissues to maintain many in vivo-like properties such as native architecture, differentiated functions, gene regulation, invasive properties and drug sensitivities which are very different than cells in monolayer cultures. Collagen-sponge-gel-supported histoculture has been shown to support the growth and native three-dimensional architecture of both tumor and normal tissue, often for long periods of time. This method of histoculture was utilized to develop a chemosensitivity assay for individual cancer patients by assessing the effects of drug on the patients' histocultured tumor. Various end points to measure drug response have been utilized in histoculture, including [H-3]thymidine incorporation measured by histological autoradiography and the use of vital dyes to indicate cell viability. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H tetrazolium bromide (MTT) end point was applied to the histoculture assay in an attempt to increase in vitro-in vivo correlation. The chemosensitivities of 16 human tumor lines were determined in vitro by the histoculture assay, and retrospectively correlated to their in vivo chemosensitivity as xenografts in nude mice. The overall correlation rate of the efficacy results of the drug-response assay to in vivo chemosensitivities was 89.8%, with 90.0% true-positive and 89.7% true-negative rates, 81.7% sensitivity and 94.6% specificity, thereby indicating potential clinical use for tumor

  12. Characterization of respiratory drug delivery with enhanced condensational growth using an individual path model of the entire tracheobronchial airways.

    Science.gov (United States)

    Tian, Geng; Longest, Philip Worth; Su, Guoguang; Hindle, Michael

    2011-03-01

    The objective of this study was to evaluate the delivery of inhaled pharmaceutical aerosols using an enhanced condensational growth (ECG) approach in an airway model extending from the oral cavity to the end of the tracheobronchial (TB) region. The geometry consisted of an elliptical mouth-throat (MT) model, the upper TB airways extending to bifurcation B3, and a subsequent individual path model entering the right lower lobe of the lung. Submicrometer monodisperse aerosols with diameters of 560 and 900 nm were delivered to the mouth inlet under control (25 °C with subsaturated air) or ECG (39 or 42 °C with saturated air) conditions. Flow fields and droplet characteristics were simulated using a computational fluid dynamics model that was previously demonstrated to accurately predict aerosol size growth and deposition. Results indicated that both the control and ECG delivery cases produced very little deposition in the MT and upper TB model (approximately 1%). Under ECG delivery conditions, large size increases of the aerosol droplets were observed resulting in mass median aerodynamic diameters of 2.4-3.3 μm exiting B5. This increase in aerosol size produced an order of magnitude increase in aerosol deposition within the TB airways compared with the controls, with TB deposition efficiencies of approximately 32-46% for ECG conditions. Estimates of downstream pulmonary deposition indicted near full lung retention of the aerosol during ECG delivery. Furthermore, targeting the region of TB deposition by controlling the inlet temperature conditions and initial aerosol size also appeared possible.

  13. Identification of Immunogenic Cytotoxic T Lymphocyte Epitopes Containing Drug Resistance Mutations in Antiretroviral Treatment-Naïve HIV-Infected Individuals.

    Directory of Open Access Journals (Sweden)

    Juan Blanco-Heredia

    Full Text Available Therapeutic HIV vaccines may prove helpful to intensify antiretroviral treatment (ART efficacy and may be an integral part of future cure strategies.We examined IFN-gamma ELISpot responses to a panel of 218 HIV clade B consensus-based HIV protease-reverse transcriptase peptides, designed to mimic previously described and predicted cytotoxic T lymphocyte epitopes overlapping drug resistance (DR positions, that either included the consensus sequence or the DR variant sequence, in 49 ART-naïve HIV-infected individuals. Next generation sequencing was used to assess the presence of minority DR variants in circulating viral populations.Although a wide spectrum of differential magnitudes of response to DR vs. WT peptide pairs was observed, responses to DR peptides were frequent and strong in the study cohort. No difference between the median magnitudes of response to DR vs. WT peptides was observed. Interestingly, of the 22 peptides that were recognized by >15% of the participants, two-thirds (64% corresponded to DR peptides. When analysing responses per peptide pair per individual, responses to only WT (median 4 pairs/individual or DR (median 6 pairs/individual were more common than responses to both WT and DR (median 2 pairs/individual; p<0.001. While the presence of ELISpot responses to WT peptides was frequently associated with the presence of the corresponding peptide sequence in the patient's virus (mean 68% of cases, responses to DR peptides were generally not associated with the presence of DR mutations in the viral population, even at low frequencies (mean 1.4% of cases; p = 0.0002.Our data suggests that DR peptides are frequently immunogenic and raises the potential benefit of broadening the antigens included in a therapeutic vaccine approach to immunogenic epitopes containing common DR sequences. Further studies are needed to assess the quality of responses elicited by DR peptides.

  14. Influence of individual and social contextual factors on changes in leisure-time physical activity in working-class populations: results of the Healthy Directions–Small Businesses Study

    Science.gov (United States)

    Stoddard, Anne; Bennett, Gary G.; Wolin, Kathleen Y.; Sorensen, Glorian G.

    2012-01-01

    Background As part of the Harvard Cancer Prevention Program Project, we sought to address disparities reflected in social class and race/ethnicity by developing and testing a behavioral intervention model that targeted fruit and vegetable consumption, red meat consumption, multivitamin intake, and physical activity in working-class, multiethnic populations. Methods This paper examined the associations between change in leisure-time physical activity and individual and social contextual factors in participants employed in small businesses (n = 850) at both baseline and at 18-month final. Results In bivariate analyses, age, language acculturation, social ties, and workplace social capital were significantly associated with physical activity at final. In multivariable analyses, being younger and having high language acculturation were significantly associated with greater leisuretime physical activity at final; high workplace social capital was significantly associated with a decline in physical activity at final. Conclusion These findings have implications for understanding factors that are integral to promoting change in physical activity among working-class, multiethnic populations. PMID:22806257

  15. Medical and nonmedical users of prescription drugs among college students.

    Science.gov (United States)

    Rozenbroek, Katelyn; Rothstein, William G

    2011-01-01

    To examine medical and nonmedical users of prescription opioids, central nervous system depressants, and stimulants taken individually and in combination. Undergraduates at an urban mid-Atlantic university with 12,000 students. A questionnaire administered in classes provided 413 responses, with a usable response rate of 94%. Nonmedical users obtained prescription drugs from friends and took them with friends. More nonmedical users than medical users took combinations of drugs. Nonmedical users did not show strong preferences for particular drugs. Nonmedical users compared to medical users who took only 1 drug were more likely to take stimulants and less likely to take opioids. The nonmedical use of prescription drugs by college students is a social activity that involves sharing drugs and taking combinations of drugs with friends. Discouraging nonmedical use must focus on the dangers of combining drugs, sharing drugs, and using social gatherings to consume drugs.

  16. Class impressions : Higher social class elicits lower prosociality

    NARCIS (Netherlands)

    Van Doesum, Niels J.; Tybur, Joshua M.; Van Lange, Paul A.M.

    2017-01-01

    Social class predicts numerous important life outcomes and social orientations. To date, literature has mainly examined how an individual's own class shapes interactions with others. But how prosocially do people treat others they perceive as coming from lower, middle, or higher social classes?

  17. Class Action and Class Settlement in a European Perspective

    DEFF Research Database (Denmark)

    Werlauff, Erik

    2013-01-01

    The article analyses the options for introducing common European rules on class action lawsuits with an opt-out-model in individual cases. An analysis is made of how the risks of misuse of class actions can be prevented. The article considers the Dutch rules on class settlements (the WCAM procedure...

  18. Utilização de medicamentos por indivíduos HIV positivos: abordagem qualitativa Utilization of prescribed drugs by HIV infected individuals: qualitative approach

    Directory of Open Access Journals (Sweden)

    Francisco A. Acurcio

    1999-02-01

    Full Text Available OBJETIVO: Analisar, em sua dimensão qualitativa, a utilização de medicamentos por indivíduos infectados pelo HIV, durante o processo de procura e atendimento em serviços de saúde. MÉTODOS: Foram realizadas 52 entrevistas semi-estruturadas com pacientes, trabalhadores da saúde e voluntários de organizações não-governamentais, e revistos 1.079 prontuários médicos para obtenção de informações sobre a utilização de medicamentos por portadores do HIV, cuja primeira visita a um dos serviços públicos de referência estudados ocorreu entre janeiro de 1989 e dezembro de 1992. RESULTADOS: Os problemas relacionados à utilização de anti-retrovirais foram: recusa ao uso, dificuldade de obtenção e de cumprimento da prescrição. Outros problemas foram a auto-medicação, dificuldade de obter medicamentos para patologias associadas e de cumprimento da prescrição de sulfas. CONCLUSÕES: Os resultados permitiram compreender melhor os principais obstáculos e dificuldades vivenciados pelo usuário dos serviços, desde o ato da prescrição até a continuidade do tratamento.OBJECTIVE: The assessment, in its qualitative dimension, of the utilization - by HIV infected individuals - of selected prescribed drugs during the process of the search for and the obtaining of care in public health services in Belo Horizonte, Brazil. METHOD: Fifty two semi-structured interviews with patients, health care workers and non- governamental organizations volunteers were carried out and 1,079 medical records were reviewed. Data were obtained on the utilization of prescribed drugs by HIV infected individuals, whose first visit to one of the public services studied occurred between January 1989 and December 1992. Problems related to the use of anti-retroviral and/or opportunistic infection medication were identified and a qualitative description of their possible causes and consequences was commented on. RESULTS: Refusal to use, difficulty in obtaining and

  19. Simultaneous analysis of aminoglycosides with many other classes of drug residues in bovine tissues by ultrahigh-performance liquid chromatography-tandem mass spectrometry using an ion-pairing reagent added to final extracts.

    Science.gov (United States)

    Lehotay, Steven J; Lightfield, Alan R

    2018-01-01

    The way to maximize scope of analysis, sample throughput, and laboratory efficiency in the monitoring of veterinary drug residues in food animals is to determine as many analytes as possible as fast as possible in as few methods as possible. Capital and overhead expenses are also reduced by using fewer instruments in the overall monitoring scheme. Traditionally, the highly polar aminoglycoside antibiotics require different chromatographic conditions from other classes of drugs, but in this work, we demonstrate that an ion-pairing reagent (sodium 1-heptanesulfonate) added to the combined final extracts from two sample preparation methods attains good separation of 174 targeted drugs, including 9 aminoglycosides, in the same 10.5-min ultrahigh-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) analysis. The full method was validated in bovine kidney, liver, and muscle tissues according to US regulatory protocols, and 137-146 (79-84%) of the drugs gave between 70 and 120% average recoveries with ≤ 25% RSDs in the different types of tissues spiked at 0.5, 1, and 2 times the regulatory levels of interest (10-1000 ng/g depending on the drug). This method increases sample throughput and the possible number of drugs monitored in the US National Residue Program, and requires only one UHPLC-MS/MS method and instrument for analysis rather than two by the previous scheme. Graphical abstract Outline of the streamlined approach to monitor 174 veterinary drugs, including aminoglycosides, in bovine tissues by combining two extracts of the same sample with an ion-pairing reagent for analysis by UHPLC-MS/MS.

  20. Temporal trends in genital warts among individuals covered by the public prescription drug insurance plan in the province of Quebec, Canada, from 1998 to 2007.

    Science.gov (United States)

    Steben, Marc; Ouhoummane, Najwa; Rodier, Caroline; Brassard, Paul

    2013-04-01

    We assessed temporal trend in the incidence and prevalence of genital warts (GWs) in the province of Quebec, Canada, between 1998 and 2007 as a baseline for future assessment of the impact of Quebec human papillomavirus vaccination program. Data on GWs were obtained from the linkage of the physician service claims and the public insurance drug plan databases. Genital warts were identified through a prescription of podofilox, a medical procedure code specific to GWs or a diagnosis code for viral warts followed by a prescription of imiquimod or fluorouracil within 2 weeks. An episode was considered incident if it was preceded by a 12-month interval period free of GWs care. During the study period, a total of 27,138 episodes of GWs occurred among 24,267 individuals. The age-standardized incidence rate increased over time in men and women. The highest incidence was observed in women aged 20 to 24 years (391.9/100,000) and in men aged 25 to 29 years (383.3/100,000). Similar trends in prevalence were observed. The incidence and prevalence of GWs has increased among the population covered by the public insurance drug plan in Quebec.

  1. Artemether-Lumefantrine Combination Therapy for Treatment of Uncomplicated Malaria: The Potential for Complex Interactions with Antiretroviral Drugs in HIV-Infected Individuals

    Directory of Open Access Journals (Sweden)

    Pauline Byakika-Kibwika

    2011-01-01

    Full Text Available Treatment of malaria in HIV-infected individuals receiving antiretroviral therapy (ART poses significant challenges. Artemether-lumefantrine (AL is one of the artemisisnin-based combination therapies recommended for treatment of malaria. The drug combination is highly efficacious against sensitive and multidrug resistant falciparum malaria. Both artemether and lumefantrine are metabolized by hepatic cytochrome P450 (CYP450 enzymes which metabolize the protease inhibitors (PIs and nonnucleoside reverse transcriptase inhibitors (NNRTIs used for HIV treatment. Coadministration of NNRTIs and PIs with AL could potentially cause complex pharmacokinetic drug interactions. NNRTI by inducing CYP450 3A4 enzyme and PIs by inhibiting CYP450 3A4 enzymes could influence both artemether and lumefantrine concentrations and their active metabolites dihydroartemisinin and desbutyl-lumefantrine, predisposing patients to poor treatment response, toxicity, and risk for development of resistance. There are scanty data on these interactions and their consequences. Pharmacokinetic studies to evaluate these interactions in the target populations are urgently needed.

  2. Depression longitudinally mediates the association of appearance concerns to ART non-adherence in HIV-infected individuals with a history of injection drug use.

    Science.gov (United States)

    Blashill, Aaron J; Gordon, Janna R; Safren, Steven A

    2014-02-01

    Appearance concerns are common among HIV-infected individuals, and previous cross-sectional and longitudinal data indicate that these concerns are associated with antiretroviral therapy (ART) non-adherence. However, to date, no known prospective data have explored the mechanism behind this relationship. Thus, the aim of the current study was to test depression severity as a prospective mediator of the relationship between appearance concerns and ART non-adherence in HIV-infected individuals with a history of injection drug use (IDU). Participants were 89 HIV-infected individuals with a history of IDU who participated in a prospective, randomized controlled trial of cognitive behavioral therapy for depression and medication adherence. Clinician-administered measures of depression severity and appearance concerns, along with electronic monitoring of ART non-adherence were included. Data were analyzed using longitudinal linear mixed-level modeling, and mediation was tested via the Monte Carlo Method of Assessing Mediation. Appearance concerns were predictive of depression severity, γ = .31, SE = .076, 95 % CI [.16, .46], t = 4.1, p = .0001, and depression severity was predictive of ART non-adherence, γ = 3.3, SE = 1.3, 95 % CI [.8, 5.8], t = 2.6, p = .01. The effect of appearance concerns on ART non-adherence, however, was significantly mediated by depression severity, γ = 1.02, 95 % CI [.21, 2.1]. Appearance concerns are associated with depression severity, which in turn is associated with ART non-adherence. Integrative interventions addressing appearance concerns, depression and ART adherence are needed, as this is one potential pathway towards worse health outcomes in HIV-infected individuals.

  3. Neuronal representation of individual heroin choices in the orbitofrontal cortex.

    Science.gov (United States)

    Guillem, Karine; Brenot, Viridiana; Durand, Audrey; Ahmed, Serge H

    2018-05-01

    Drug addiction is a harmful preference for drug use over and at the expense of other non-drug-related activities. We previously identified in the rat orbitofrontal cortex (OFC) a mechanism that influences individual preferences between cocaine use and an alternative action rewarded by a non-drug reward (i.e. sweet water). Here, we sought to test the generality of this mechanism to a different addictive drug, heroin. OFC neuronal activity was recorded while rats responded for heroin or the alternative non-drug reward separately or while they chose between the two. First, we found that heroin-rewarded and sweet water-rewarded actions were encoded by two non-overlapping OFC neuronal populations and that the relative size of the heroin population represented individual drug choices. Second, OFC neurons encoding the preferred action-which was the non-drug action in the large majority of individuals-progressively fired more than non-preferred action-coding neurons 1 second after the onset of choice trials and around 1 second before the preferred action was actually chosen, suggesting a pre-choice neuronal competition for action selection. Together with a previous study on cocaine choice, the present study on heroin choice reveals important commonalities in how OFC neurons encode individual drug choices and preferences across different classes of drugs. It also reveals some drug-specific differences in OFC encoding activity. Notably, the proportion of neurons that non-selectively encode both the drug and the non-drug reward was higher when the drug was heroin (present study) than when it was cocaine (previous study). We will discuss the potential functional significance of these commonalities and differences in OFC neuronal activity across different drugs for understanding drug choice. © 2017 Society for the Study of Addiction.

  4. Predictors of CD4(+) T-Cell Counts of HIV Type 1–Infected Persons After Virologic Failure of All 3 Original Antiretroviral Drug Classes

    DEFF Research Database (Denmark)

    Costagliola, Dominique; Ledergerber, Bruno; Torti, Carlo

    2013-01-01

    Low CD4(+) T-cell counts are the main factor leading to clinical progression in human immunodeficiency virus type 1 (HIV-1) infection. We aimed to investigate factors affecting CD4(+) T-cell counts after triple-class virological failure....

  5. The influence of psychological variables on health-related quality of life among HIV-positive individuals with a history of intravenous drug use.

    Science.gov (United States)

    Psaros, Christina; O'Cleirigh, Conall; Bullis, Jacqueline R; Markowitz, Sarah M; Safren, Steven A

    2013-01-01

    Intravenous drug use (IDU) remains a prominent pathway of HIV transmission in the United States, though little is known about modifiable factors influencing quality of life among IDUs. The goal of this study was to evaluate the influence of psychological variables (e.g., depression and anxiety) on health-related quality of life among HIV-positive individuals with a history of IDU who were enrolled in outpatient treatment for opioid dependence. 108 HIV-positive individuals with a history of IDU and participating in current outpatient treatment for opiate dependence who were screened for participation in a depression and adherence study reported sociodemographic data, depressive and anxiety symptoms, and health-related quality of life (HRQoL; Multidimensional Health Assessment using the ACTG-SF 21). Multiple regression models controlling for disease stage and background characteristics identified significant negative relationships between General Health Perception and Functioning without Pain for anxiety and depression, and between Role Functioning and Physical Functioning for anxiety. CD4 cell count was significantly related to Physical Functioning only. Results indicate that distress (both depression and anxiety) contribute significantly to variation in HRQoL over and above the effects of disease variables. Effective depression and anxiety treatment may result in improved overall functioning.

  6. Drug Trafficking in Haiti

    National Research Council Canada - National Science Library

    Burns, DeEtta

    2002-01-01

    .... The thesis argues that Haiti's geographic location, political culture, illegal immigrants, entrepreneurial class and weak institutions have made it a major transshipment point for drugs to the United...

  7. Drug-induced liver injury associated with HIV medications.

    Science.gov (United States)

    Jain, Mamta K

    2007-08-01

    Antiretroviral therapy (ART) for HIV infection frequently has been associated with elevated liver enzyme levels. Determining the cause of elevated liver enzyme levels in patients who have HIV is difficult because ART usually consists of three different drugs, patients may be taking additional hepatotoxic medications and patients who have HIV often suffer from other liver diseases. Several agents, however, are recognized as having noteworthy and specific patterns of toxicity. This article reviews the different HIV drug classes, incidence of elevated liver enzyme values by class and by individual drug, risk factors, specific toxicities, and possible mechanisms of injury.

  8. An in vitro larval migration assay for assessing anthelmintic activity of different drug classes against Ascaris suum

    DEFF Research Database (Denmark)

    Zhao, Jianguo; Williams, Andrew R; Hansen, Tina Vicky Alstrup

    2017-01-01

    and agar gel larval migration assay to test the effect of benzimidazole and tetrahydropyrimidin/imidazothiazole anthelmintics against nine isolates of A. suum collected from locations in China and Denmark. Drugs tested were thiabendazole, fenbendazole, mebendazole, levamisole, and pyrantel. The percentages...

  9. Preemptive Genotyping for Personalized Medicine: Design of the Right Drug, Right Dose, Right Time – Using Genomic Data to Individualize Treatment Protocol

    Science.gov (United States)

    Bielinski, Suzette J.; Olson, Janet E.; Pathak, Jyotishman; Weinshilboum, Richard M.; Wang, Liewei; Lyke, Kelly J.; Ryu, Euijung; Targonski, Paul V.; Van Norstrand, Michael D.; Hathcock, Matthew A.; Takahashi, Paul Y.; McCormick, Jennifer B.; Johnson, Kiley J.; Maschke, Karen J.; Rohrer Vitek, Carolyn R.; Ellingson, Marissa S.; Wieben, Eric D.; Farrugia, Gianrico; Morrisette, Jody A.; Kruckeberg, Keri J.; Bruflat, Jamie K.; Peterson, Lisa M.; Blommel, Joseph H.; Skierka, Jennifer M.; Ferber, Matthew J.; Black, John L.; Baudhuin, Linnea M.; Klee, Eric W.; Ross, Jason L.; Veldhuizen, Tamra L.; Schultz, Cloann G.; Caraballo, Pedro J.; Freimuth, Robert R.; Chute, Christopher G.; Kullo, Iftikhar J.

    2014-01-01

    Objective To report the design and implementation of the Right Drug, Right Dose, Right Time: Using Genomic Data to Individualize Treatment Protocol that was developed to test the concept that prescribers can deliver genome guided therapy at the point-of-care by using preemptive pharmacogenomics (PGx) data and clinical decision support (CDS) integrated in the electronic medical record (EMR). Patients and Methods We used a multivariable prediction model to identify patients with a high risk of initiating statin therapy within 3 years. The model was used to target a study cohort most likely to benefit from preemptive PGx testing among Mayo Clinic Biobank participants with a recruitment goal of 1000 patients. Cox proportional hazards model was utilized using the variables selected through the Lasso shrinkage method. An operational CDS model was adapted to implement PGx rules within the EMR. Results The prediction model included age, sex, race, and 6 chronic diseases categorized by the Clinical Classifications Software for ICD-9 codes (dyslipidemia, diabetes, peripheral atherosclerosis, disease of the blood-forming organs, coronary atherosclerosis and other heart diseases, and hypertension). Of the 2000 Biobank participants invited, 50% provided blood samples, 13% refused, 28% did not respond, and 9% consented but did not provide a blood sample within the recruitment window (October 4, 2012 – March 20, 2013). Preemptive PGx testing included CYP2D6 genotyping and targeted sequencing of 84 PGx genes. Synchronous real-time CDS is integrated in the EMR and flags potential patient-specific drug-gene interactions and provides therapeutic guidance. Conclusion These interventions will improve understanding and implementation of genomic data in clinical practice. PMID:24388019

  10. Potential of prescription registries to capture individual-level use of aspirin and other nonsteroidal anti-inflammatory drugs in Denmark: trends in utilization 1999–2012

    Directory of Open Access Journals (Sweden)

    Schmidt M

    2014-05-01

    Full Text Available Morten Schmidt,1 Jesper Hallas,2 Søren Friis1,31Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark; 2Department of Clinical Pharmacology, University of Southern Denmark, Odense, Denmark; 3Danish Cancer Society Research Center, Danish Cancer Society, Copenhagen, DenmarkBackground: Due to over-the-counter availability, no consensus exists on whether adequate information on nonsteroidal anti-inflammatory drug (NSAID use can be obtained from prescription registries.Objectives: To examine utilization of aspirin and nonaspirin NSAIDs in Denmark between 1999 and 2012 and to quantify the proportion of total sales that was sold on prescription.Method: Based on nationwide data from the Danish Serum Institute and the Danish National Prescription Registry, we retrieved sales statistics for the Danish primary health care sector to calculate 1-year prevalences of prescription users of aspirin or nonaspirin NSAIDs, and to estimate the corresponding proportions of total sales dispensed on prescription.Results: Both low-dose aspirin and nonaspirin NSAIDs were commonly used in the Danish population between 1999 and 2012, particularly among elderly individuals. The 1-year prevalence of prescribed low-dose aspirin increased throughout the study period, notably among men. Nonaspirin NSAID use was frequent in all age groups above 15 years and showed a female preponderance. Overall, the prevalence of prescribed nonaspirin NSAIDs decreased moderately after 2004, but substantial variation according to NSAID subtype was observed; ibuprofen use increased, use of all newer selective cyclooxygenase-2 inhibitors nearly ceased after 2004, diclofenac use decreased by nearly 50% after 2008, and naproxen use remained stable. As of 2012, the prescribed proportion of individual-level NSAID sales was 92% for low-dose aspirin, 66% for ibuprofen, and 100% for all other NSAIDs.Conclusion: The potential for identifying NSAID use from prescription

  11. “We fear the police, and the police fear us”: Structural and individual barriers and facilitators to HIV medication adherence among injection drug users in Kiev, Ukraine

    Science.gov (United States)

    Mimiaga, Matthew J.; Safren, Steven A.; Dvoryak, Sergiy; Reisner, Sari L.; Needle, Richard; Woody, George

    2010-01-01

    Ukraine has one of the most severe HIV/AIDS epidemics in Europe, with an estimated 1.63% of the population living with HIV/AIDS in 2007. Injection drug use (IDU) remains the predominant mode of transmission in Kiev—the capital and largest city. Prior reports suggest that the HIV infection rate among IDUs in Kiev reaches 33%, and many have poor and inequitable access to highly active antiretroviral therapy (HAART). Among those with access to HAART, little is understood about barriers and facilitators to HAART medication adherence. In 5/2009, two semi-structured focus groups were conducted with HIV-infected IDUs seeking treatment at the City AIDS Center, Kiev. The goal was to use this information to adapt and tailor, to Ukrainian culture, an evidence-based intervention for improving adherence to HAART. All 16 participants attributed HIV infection to IDU. Their average age was 31.6 (SD=7.0), average time with HIV 5.7 years (SD=4.0), average time on HAART 2.5 years (SD=1.7), average time as IDU 14.6 years (SD=6.8), and 88% were on opioid substitution therapy. The most salient themes related to adherence barriers included: (1) harassment and discrimination by police; (2) opioid dependence; (3) complexity of drug regimen; (4) side effects; (5) forgetting; (6) co-occurring mental health problems; and (7) HIV stigma. Facilitators of adherence included: (1) cues for pill taking; (2) support and reminders from family, significant other, and friends; (3) opioid substitution therapy; and (4) wanting improved health. Additional factors explored included: 1) knowledge about HAART; (2) storage of medications; and (3) IDU and sexual risk behaviors. Findings highlighted structural and individual barriers to adherence. At the structural level, police discrimination and harassment was reported to be a major barrier to adherence to opioid substitution therapy and HAART. Privacy and stigma were barriers at the individual level. Recommendations for adherence interventions included

  12. Initial clinical experience with the first drug (sacubitril/valsartan) in a new class - angiotensin receptor neprilysin inhibitors in patients with heart failure with reduced left ventricular ejection fraction in Poland.

    Science.gov (United States)

    Kałużna-Oleksy, Marta; Kolasa, Jolanta; Migaj, Jacek; Pawlak, Agnieszka; Lelonek, Małgorzata; Nessler, Jadwiga; Straburzyńska-Migaj, Ewa

    2018-01-01

    Sacubitril/valsartan is the first drug from a new class of angiotensin receptor neprilysin inhibitors (ARNIs) recommended in the new European Society of Cardiology guidelines instead of angiotensin converting enzyme inhibitors (ACEI), or angiotensin receptor blockers (ARB) that are used if ACEI are not tolerated. Sacubitril/valsartan is recommended for further reduction in the risk of hospitalisation or death in outpatients with heart failure with reduced ejection fraction (HFrEF) if symptoms continue despite optimal treatment with ACEI/ARB, beta-blockers, and mineralocorticoid antagonists. The aim of this study is to present the initial experience with regard to the effectiveness, tolerance, and safety of sacubitril/valsartan in the outpatient cardiology practice in Poland. The study is a retrospective analysis of data obtained through a questionnaire filled in by the physicians who initiated the sacubitril/valsartan treatment in patients with HFrEF between 1 June 2016 and 30 September 2016. Patients were followed-up for three months. The analysis included data on 28 patients aged 61 ± 16 years, of whom 85.7% were males. The drug was used in patients in New York Heart Association (NYHA) class I-III. In 25 (89.2%) patients sacubitril/valsartan was started at the lowest dose (24/26 mg BID). During follow-up the sacubitril/valsartan-treated patients had a reduction in HF symptoms assessed using the NYHA functional class (p = 0.001), a significant drop in N-terminal-pro B-type natriuretic peptide levels (mean, from 2900 to 2270 pg/mL; p = 0.008), and improved exercise tolerance, which occurred shortly after treatment initiation - after a mean of 28 days. It was demonstrated that the use of sacubitril/valsartan in outpatients with HFrEF is safe and is associated with a significant clinical improvement.

  13. 1-[(2-arylthiazol-4-yl)methyl]azoles as a new class of anticonvulsants: design, synthesis, in vivo screening, and in silico drug-like properties.

    Science.gov (United States)

    Ahangar, Nematollah; Ayati, Adile; Alipour, Eskandar; Pashapour, Arsalan; Foroumadi, Alireza; Emami, Saeed

    2011-11-01

    A series of novel thiazole incorporated (arylalkyl)azoles were synthesized and screened for their anticonvulsant properties using maximal electroshock and pentylenetetrazole models in mice. Among target compounds, 1-[(2-(4-chlorophenyl)thiazol-4-yl)methyl]-1H-imidazole (compound 4b), 1-[(2-phenylthiazol-4-yl)methyl]-1H-1,2,4-tria-zole (8a), and its 4-chlorophenyl analog (compound 8b) were able to display noticeable anticonvulsant activity in both pentylenetetrazole and maximal electroshock tests with percentage protection range of 33-100%. A computational study was carried out for prediction of pharmacokinetics properties and drug-likeness. The structure-activity relationship and in silico drug relevant properties (molecular weight, topological polar surface area, clog P, hydrogen bond donors, hydrogen bond acceptors, and log BB) confirmed that the compounds were within the range set by Lipinski's rule-of-five, and possessing favorable physicochemical properties for acting as CNS-drugs, making them potentially promising agents for epilepsy therapy. © 2011 John Wiley & Sons A/S.

  14. Social class, social mobility and risk of psychiatric disorder--a population-based longitudinal study.

    Directory of Open Access Journals (Sweden)

    Sanna Tiikkaja

    Full Text Available OBJECTIVES: This study explored how adult social class and social mobility between parental and own adult social class is related to psychiatric disorder. MATERIAL AND METHODS: In this prospective cohort study, over 1 million employed Swedes born in 1949-1959 were included. Information on parental class (1960 and own mid-life social class (1980 and 1990 was retrieved from the censuses and categorised as High Non-manual, Low Non-manual, High Manual, Low Manual and Self-employed. After identifying adult class, individuals were followed for psychiatric disorder by first admission of schizophrenia, alcoholism and drug dependency, affective psychosis and neurosis or personality disorder (N=24,659 from the Swedish Patient Register. We used Poisson regression analysis to estimate first admission rates of psychiatric disorder per 100,000 person-years and relative risks (RR by adult social class (treated as a time-varying covariate. The RRs of psychiatric disorder among the Non-manual and Manual classes were also estimated by magnitude of social mobility. RESULTS: The rate of psychiatric disorder was significantly higher among individuals belonging to the Low manual class as compared with the High Non-manual class. Compared to High Non-manual class, the risk for psychiatric disorder ranged from 2.07 (Low Manual class to 1.38 (Low Non-manual class. Parental class had a minor impact on these estimates. Among the Non-manual and Manual classes, downward mobility was associated with increased risk and upward mobility with decreased risk of psychiatric disorder. In addition, downward mobility was inversely associated with the magnitude of social mobility, independent of parental class. CONCLUSIONS: Independently of parental social class, the risk of psychiatric disorder increases with increased downward social mobility and decreases with increased upward mobility.

  15. Social class, social mobility and risk of psychiatric disorder--a population-based longitudinal study.

    Science.gov (United States)

    Tiikkaja, Sanna; Sandin, Sven; Malki, Ninoa; Modin, Bitte; Sparén, Pär; Hultman, Christina M

    2013-01-01

    This study explored how adult social class and social mobility between parental and own adult social class is related to psychiatric disorder. In this prospective cohort study, over 1 million employed Swedes born in 1949-1959 were included. Information on parental class (1960) and own mid-life social class (1980 and 1990) was retrieved from the censuses and categorised as High Non-manual, Low Non-manual, High Manual, Low Manual and Self-employed. After identifying adult class, individuals were followed for psychiatric disorder by first admission of schizophrenia, alcoholism and drug dependency, affective psychosis and neurosis or personality disorder (N=24,659) from the Swedish Patient Register. We used Poisson regression analysis to estimate first admission rates of psychiatric disorder per 100,000 person-years and relative risks (RR) by adult social class (treated as a time-varying covariate). The RRs of psychiatric disorder among the Non-manual and Manual classes were also estimated by magnitude of social mobility. The rate of psychiatric disorder was significantly higher among individuals belonging to the Low manual class as compared with the High Non-manual class. Compared to High Non-manual class, the risk for psychiatric disorder ranged from 2.07 (Low Manual class) to 1.38 (Low Non-manual class). Parental class had a minor impact on these estimates. Among the Non-manual and Manual classes, downward mobility was associated with increased risk and upward mobility with decreased risk of psychiatric disorder. In addition, downward mobility was inversely associated with the magnitude of social mobility, independent of parental class. Independently of parental social class, the risk of psychiatric disorder increases with increased downward social mobility and decreases with increased upward mobility.

  16. Social Class, Social Mobility and Risk of Psychiatric Disorder - A Population-Based Longitudinal Study

    Science.gov (United States)

    Tiikkaja, Sanna; Sandin, Sven; Malki, Ninoa; Modin, Bitte; Sparén, Pär; Hultman, Christina M.

    2013-01-01

    Objectives This study explored how adult social class and social mobility between parental and own adult social class is related to psychiatric disorder. Material and Methods In this prospective cohort study, over 1 million employed Swedes born in 1949-1959 were included. Information on parental class (1960) and own mid-life social class (1980 and 1990) was retrieved from the censuses and categorised as High Non-manual, Low Non-manual, High Manual, Low Manual and Self-employed. After identifying adult class, individuals were followed for psychiatric disorder by first admission of schizophrenia, alcoholism and drug dependency, affective psychosis and neurosis or personality disorder (N=24 659) from the Swedish Patient Register. We used Poisson regression analysis to estimate first admission rates of psychiatric disorder per 100 000 person-years and relative risks (RR) by adult social class (treated as a time-varying covariate). The RRs of psychiatric disorder among the Non-manual and Manual classes were also estimated by magnitude of social mobility. Results The rate of psychiatric disorder was significantly higher among individuals belonging to the Low manual class as compared with the High Non-manual class. Compared to High Non-manual class, the risk for psychiatric disorder ranged from 2.07 (Low Manual class) to 1.38 (Low Non-manual class). Parental class had a minor impact on these estimates. Among the Non-manual and Manual classes, downward mobility was associated with increased risk and upward mobility with decreased risk of psychiatric disorder. In addition, downward mobility was inversely associated with the magnitude of social mobility, independent of parental class. Conclusions Independently of parental social class, the risk of psychiatric disorder increases with increased downward social mobility and decreases with increased upward mobility. PMID:24260104

  17. Geographic and temporal trends in the molecular epidemiology and genetic mechanisms of transmitted HIV-1 drug resistance: an individual-patient- and sequence-level meta-analysis.

    Science.gov (United States)

    Rhee, Soo-Yon; Blanco, Jose Luis; Jordan, Michael R; Taylor, Jonathan; Lemey, Philippe; Varghese, Vici; Hamers, Raph L; Bertagnolio, Silvia; Rinke de Wit, Tobias F; Aghokeng, Avelin F; Albert, Jan; Avi, Radko; Avila-Rios, Santiago; Bessong, Pascal O; Brooks, James I; Boucher, Charles A B; Brumme, Zabrina L; Busch, Michael P; Bussmann, Hermann; Chaix, Marie-Laure; Chin, Bum Sik; D'Aquin, Toni T; De Gascun, Cillian F; Derache, Anne; Descamps, Diane; Deshpande, Alaka K; Djoko, Cyrille F; Eshleman, Susan H; Fleury, Herve; Frange, Pierre; Fujisaki, Seiichiro; Harrigan, P Richard; Hattori, Junko; Holguin, Africa; Hunt, Gillian M; Ichimura, Hiroshi; Kaleebu, Pontiano; Katzenstein, David; Kiertiburanakul, Sasisopin; Kim, Jerome H; Kim, Sung Soon; Li, Yanpeng; Lutsar, Irja; Morris, Lynn; Ndembi, Nicaise; Ng, Kee Peng; Paranjape, Ramesh S; Peeters, Martine; Poljak, Mario; Price, Matt A; Ragonnet-Cronin, Manon L; Reyes-Terán, Gustavo; Rolland, Morgane; Sirivichayakul, Sunee; Smith, Davey M; Soares, Marcelo A; Soriano, Vincent V; Ssemwanga, Deogratius; Stanojevic, Maja; Stefani, Mariane A; Sugiura, Wataru; Sungkanuparph, Somnuek; Tanuri, Amilcar; Tee, Kok Keng; Truong, Hong-Ha M; van de Vijver, David A M C; Vidal, Nicole; Yang, Chunfu; Yang, Rongge; Yebra, Gonzalo; Ioannidis, John P A; Vandamme, Anne-Mieke; Shafer, Robert W

    2015-04-01

    Regional and subtype-specific mutational patterns of HIV-1 transmitted drug resistance (TDR) are essential for informing first-line antiretroviral (ARV) therapy guidelines and designing diagnostic assays for use in regions where standard genotypic resistance testing is not affordable. We sought to understand the molecular epidemiology of TDR and to identify the HIV-1 drug-resistance mutations responsible for TDR in different regions and virus subtypes. We reviewed all GenBank submissions of HIV-1 reverse transcriptase sequences with or without protease and identified 287 studies published between March 1, 2000, and December 31, 2013, with more than 25 recently or chronically infected ARV-naïve individuals. These studies comprised 50,870 individuals from 111 countries. Each set of study sequences was analyzed for phylogenetic clustering and the presence of 93 surveillance drug-resistance mutations (SDRMs). The median overall TDR prevalence in sub-Saharan Africa (SSA), south/southeast Asia (SSEA), upper-income Asian countries, Latin America/Caribbean, Europe, and North America was 2.8%, 2.9%, 5.6%, 7.6%, 9.4%, and 11.5%, respectively. In SSA, there was a yearly 1.09-fold (95% CI: 1.05-1.14) increase in odds of TDR since national ARV scale-up attributable to an increase in non-nucleoside reverse transcriptase inhibitor (NNRTI) resistance. The odds of NNRTI-associated TDR also increased in Latin America/Caribbean (odds ratio [OR] = 1.16; 95% CI: 1.06-1.25), North America (OR = 1.19; 95% CI: 1.12-1.26), Europe (OR = 1.07; 95% CI: 1.01-1.13), and upper-income Asian countries (OR = 1.33; 95% CI: 1.12-1.55). In SSEA, there was no significant change in the odds of TDR since national ARV scale-up (OR = 0.97; 95% CI: 0.92-1.02). An analysis limited to sequences with mixtures at less than 0.5% of their nucleotide positions—a proxy for recent infection—yielded trends comparable to those obtained using the complete dataset. Four NNRTI SDRMs—K101E, K103N, Y181C, and G190A

  18. Effect of Safety Issues with HIV Drugs on the Approval Process of Other Drugs in the Same Class An Analysis of European Public Assessment Reports : an analysis of European public assessment reports

    NARCIS (Netherlands)

    Arnardottir, Arna H.; Haaijer-Ruskamp, Flora M.; Straus, Sabine M. J.; de Graeff, Pieter A.; Mol, Peter G. M.

    2011-01-01

    Background: Knowledge on the safety of new medicines is limited at the time of market entry. Nearly half of all drugs used to treat HIV registered in the EU required >= 1 Direct Healthcare Professional Communication (DHPC) in the past 10 years for safety issues identified post-approval. Objective:

  19. Class size versus class composition

    DEFF Research Database (Denmark)

    Jones, Sam

    Raising schooling quality in low-income countries is a pressing challenge. Substantial research has considered the impact of cutting class sizes on skills acquisition. Considerably less attention has been given to the extent to which peer effects, which refer to class composition, also may affect...... bias from omitted variables, the preferred IV results indicate considerable negative effects due to larger class sizes and larger numbers of overage-for-grade peers. The latter, driven by the highly prevalent practices of grade repetition and academic redshirting, should be considered an important...

  20. Efficiency analysis of using tailored individual doses of radioiodine and fine tuning using a low-dose antithyroid drug in the treatment of Graves' disease.

    Science.gov (United States)

    Liu, Chang-Jiang; Dong, Yan-Yu; Wang, Yi-Wei; Wang, Kai-Hua; Zeng, Qun-Yan

    2011-03-01

    To evaluate the effect of using tailored individual doses of radioiodine (¹³¹I) and fine tuning using low-dose antithyroid drug (ATD) in the treatment of Graves' disease, and an attempt to establish a therapeutic strategy that can keep both high rate of euthyroidism and low incidence of hypothyroidism. The dose of radioiodine was calculated using the calculated dose formula, and low-dose ATD was used as a way of fine tuning during follow-up. The intended dose of radioiodine was modified according to the patient's age at radioiodine therapy, thyroid size, and duration of hyperthyroidism before radioiodine therapy in the study group; it was set as 2.96 MBq/g of thyroid in the control group. Twenty patients with Graves' disease were nonrandomly assigned to the control group and 98 patients with Graves' disease to the study group. The outcomes, which included euthyroidism, hypothyroidism, and persistent hyperthyroidism, were determined according to the patients' states at the end of follow-up. In the study group, 74 patients (75.5%) achieved the euthyroid state, six patients (6.1%) became hypothyroid, and 18 patients (18.4%) remained hyperthyroid. The rate of euthyroidism was statistically different between the study group and the control group (75.5 vs. 50%, P=0.03). Of 98 patients with Graves' disease in the study group, 19 patients were additionally treated with ATD during follow-up, and 12 patients achieved euthyroidism. In different age groups or duration of hyperthyroidism groups, the rate of euthyroidism was not statistically different among subgroups of goiter grade 1, grade 2, and grade 3 (P>0.05). Similarly, in different age groups or duration of hyperthyroidism groups, the incidence of hypothyroidism was not statistically different among subgroups of goiter grade 1, grade 2, and grade 3 (P>0.05). However, binary logistic regression analysis showed that thyroid size was associated with overtreatment and undertreatment in our study. Individual doses of

  1. Prevalencia de enteroparásitos en individuos de centros de rehabilitacion a drogas del estado Zulia, Venezuela | Prevalence of enteroparasites in individuals of drug rehabilitation centers in Zulia state–Venezuela

    Directory of Open Access Journals (Sweden)

    Ángela Bracho Mora

    2017-11-01

    Full Text Available To determine the prevalence of intestinal parasites in drug-addicted individuals that have been detained in two rehabilitation centers in Zulia state, a cross-sectional descriptive study was accomplished in which 98 fecal samples from persons of both sexes, aged between 15 and 65 years, were collected. The samples were analyzed by direct and concentrated examination with the coproparasitological Formalin-ether (Ritchie method; likewise, the staining technique Kinyoun was used to search for intestinal coccidia. The overall prevalence of intestinal parasites was 70.41%; among them, 56.52% of individuals were monoparasitized and 43.48% polyparasitized. Up to three parasitic associations were found in each individual. With respect to the parasite species found, Blastocystis spp. (62.24% was the most frequent in terms of chromist/protozoas and within helminths, Hookworms were found in 6.12% of individuals and occupied the first place in prevalence. The highest percentage of parasitized individuals was observed in young adults (20-39 years with 63.77%, but no significant difference was observed with other age groups. Significant differences (p < 0.001 were observed amongst individuals that were parasitized with respect to the drug consumed, with a higher prevalence among individuals that had consumed cocaine. It has been concluded that the drug situation does not seem to be an important variable that promotes or limits the acquisition of common intestinal parasites, as sanitary conditions remain to be critical in acquiring them.

  2. NEW DATA ON THE SAFETY OF NONSTEROIDAL ANTI-INFLAMMATORY DRUGS: THE CONCEPT OF THE HIGH CLASS-SPECIFIC CARDIOVASCULAR RISK OF SELECTIVE CYCLOOXYGENASE-2 INHIBITORS IS OUTDATED

    Directory of Open Access Journals (Sweden)

    A. E. Karateev

    2017-01-01

    Full Text Available The results of the PRECISION trial were published in late 2016. During this trial, a total of 24,081 patients at high cardiovascular risk took celecoxib 200-400 mg/day, naproxen 750–1000 mg/day or ibuprofen 1800–2400 mg/day for more than 1.5 years (20.3±16.0 months. The findings show that the frequency of vascular catastrophes (death, nonfatal myocardial infarction, and stroke in patients receiving celecoxib was not higher than that of the similar complications in those taking the control drugs. At the same time, celecoxib demonstrated a statistically significant advantage in reducing the risk of serious gastrointestinal complications. New evidence refutes the concept of high cardiovascular risk that is common to all coxibs and confirms the provisions of national guidelines for the rational use of nonsteroidal anti-inflammatory drugs (NSAIDs, which were published in 2015. This review presents recent data on the risk of NSAID-related complications, including a brief description of the design and results of the PRECISION trial. 

  3. Effect of intrathecal non-NMDA EAA receptor antagonist LY293558 in rats: a new class of drugs for spinal anesthesia.

    Science.gov (United States)

    Von Bergen, Nicholas H; Subieta, Alberto; Brennan, Timothy J

    2002-07-01

    Excitatory amino acid receptors are important for both sensory and motor function in the spinal cord. We studied the effects of intrathecal LY293558, a competitive non-N-methyl-D-aspartate excitatory amino acid receptor antagonist, on motor and sensory function in rats to determine whether drugs blocking these receptors could potentially be used as alternative agents to local anesthetics for spinal anesthesia. Rats were tested before and 15-240 min after intrathecal injection of 5 nmol (in 10 microl) LY293558. Sensory function was tested at the hind paw using withdrawal response to pin prick and withdrawal to pinch with sharp forceps. Motor performance (ambulation, placing reflex, and Rotorod time), blood pressure, and heart rate were also evaluated. Some tests were repeated the next day. Responses after LY293558 were compared to injection of 40 microl bupivacaine, 0.75%. Pin-prick responses at the forepaw, chest, abdomen, hind leg, and hind paw were also examined after intrathecal LY293558. Intrathecal LY293558 blocked both sensory and motor responses through 180 min; complete recovery was present the following day. No change in blood pressure or heart rate occurred. The effects of LY293558 were more pronounced and sustained than those of bupivacaine. Segmental blockade of the response to pin prick was present after LY293558. Drugs like LY293558 that block alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA)/kainate receptors may be an alternative to local anesthetics for spinal anesthesia in humans.

  4. Individualization of antiretroviral therapy

    Directory of Open Access Journals (Sweden)

    Pavlos R

    2011-12-01

    Full Text Available Rebecca Pavlos, Elizabeth J PhillipsInstitute for Immunology and Infectious Diseases, Murdoch University, Murdoch, Western Australia, AustraliaAbstract: Antiretroviral therapy (ART has evolved considerably over the last three decades. From the early days of monotherapy with high toxicities and pill burdens, through to larger pill burdens and more potent combination therapies, and finally, from 2005 and beyond where we now have the choice of low pill burdens and once-daily therapies. More convenient and less toxic regimens are also becoming available, even in resource-poor settings. An understanding of the individual variation in response to ART, both efficacy and toxicity, has evolved over this time. The strong association of the major histocompatibility class I allele HLA-B*5701 and abacavir hypersensitivity, and its translation and use in routine HIV clinical practice as a predictive marker with 100% negative predictive value, has been a success story and a notable example of the challenges and triumphs in bringing pharmacogenetics to the clinic. In real clinical practice, however, it is going to be the exception rather than the rule that individual biomarkers will definitively guide patient therapy. The need for individualized approaches to ART has been further increased by the importance of non-AIDS comorbidities in HIV clinical practice. In the future, the ideal utilization of the individualized approach to ART will likely consist of a combined approach using a combination of knowledge of drug, virus, and host (pharmacogenetic and pharmacoecologic [factors in the individual's environment that may be dynamic over time] information to guide the truly personalized prescription. This review will focus on our knowledge of the pharmacogenetics of the efficacy and toxicity of currently available antiretroviral agents and the current and potential utility of such information and approaches in present and future HIV clinical care.Keywords: HIV

  5. Social Classes

    DEFF Research Database (Denmark)

    Aktor, Mikael

    2018-01-01

    . Although this social structure was ideal in nature and not equally confirmed in other genres of ancient and medieval literature, it has nevertheless had an immense impact on Indian society. The chapter presents an overview of the system with its three privileged classes, the Brahmins, the Kṣatriyas......The notions of class (varṇa) and caste (jāti) run through the dharmaśāstra literature (i.e. Hindu Law Books) on all levels. They regulate marriage, economic transactions, work, punishment, penance, entitlement to rituals, identity markers like the sacred thread, and social interaction in general...

  6. Birthing Classes

    Science.gov (United States)

    ... management options. Breastfeeding basics. Caring for baby at home. Birthing classes are not just for new parents, though. ... midwife. Postpartum care. Caring for your baby at home, including baby first aid. Lamaze One of the most popular birthing techniques in the U.S., Lamaze has been around ...

  7. The successful binomium of multivariate strategies and electrophoresis for the Quality by Design separation of a class of drugs: the case of triptans.

    Science.gov (United States)

    Pasquini, Benedetta; Orlandini, Serena; Del Bubba, Massimo; Bertol, Elisabetta; Furlanetto, Sandra

    2015-11-01

    Quality by Design (QbD) approach was followed having as analytical target profile the determination of different antimigraine drugs (seven triptans, TRP) available on the market. Multivariate strategies were used for defining the design space and solvent-modified MEKC was the selected analytical method. The versatility of electrophoretic technique, allowing a fine modulation of experimental parameters, made it possible to define the design space (DS). The DS limited a suitable range of experimental parameters in which all possible combinations of variables led to an electrokinetic method able to determine all the considered analytes with a predefined quality. Design of experiments and risk analysis fully assisted the method development from the initial investigation of MEKC knowledge space to the DS definition and finally to the control strategy. Applying the working operative conditions, the baseline separation of TRP was obtained in less than 9 min. The method was finally used for the quantification of three TRP in different pharmaceutical products. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  8. Role of individual, peer and family factors in the use of cannabis and other illicit drugs: A longitudinal analysis among Finnish adolescent twins

    NARCIS (Netherlands)

    T. Korhonen (Tellervo); A.C. Huizink (Anja); D.M. Dick (Danielle); L. Pulkkinen (Lea); R.J. Rose (Richard); J. Kaprio (Jaakko)

    2008-01-01

    textabstractBackground: Although use of illicit drugs shows varying degree of heritability, the influence of shared and unique environmental factors predominate among adolescents. We explored factors predicting use of cannabis and other illicit drugs among Finnish adolescent twins. Methods: We used

  9. Investigating the Discriminatory Power of BCS-Biowaiver in Vitro Methodology to Detect Bioavailability Differences between Immediate Release Products Containing a Class I Drug.

    Science.gov (United States)

    Colón-Useche, Sarin; González-Álvarez, Isabel; Mangas-Sanjuan, Victor; González-Álvarez, Marta; Pastoriza, Pilar; Molina-Martínez, Irene; Bermejo, Marival; García-Arieta, Alfredo

    2015-09-08

    The purpose of this work is to investigate the discriminatory power of the Biopharmaceutics Classification System (BCS)-biowaiver in vitro methodology, i.e., to investigate if a BCS-biowaiver approach would have detected the Cmax differences observed between two zolpidem tablets and to identify the cause of the in vivo difference. Several dissolution conditions were tested with three zolpidem formulations: the reference (Stilnox), a bioequivalent formulation (BE), and a nonbioequivalent formulation (N-BE). Zolpidem is highly soluble at pH 1.2, 4.5, and 6.8. Its permeability in Caco-2 cells is higher than that of metoprolol and its transport mechanism is passive diffusion. None of the excipients (alone or in combination) showed any effect on permeability. All formulations dissolved more than 85% in 15 min in the paddle apparatus at 50 rpm in all dissolution media. However, at 30 rpm the nonbioequivalent formulation exhibited a slower dissolution rate. A slower gastric emptying rate was also observed in rats for the nonbioequivalent formulation. A slower disintegration and dissolution or a delay in gastric emptying might explain the Cmax infra-bioavailability for a highly permeable drug with short half-life. The BCS-biowaiver approach would have declared bioequivalence, although the in vivo study was not conclusive but detected a 14% mean difference in Cmax that precluded the bioequivalence demonstration. Nonetheless, these findings suggest that a slower dissolution rate is more discriminatory and that rotation speeds higher than 50 rpm should not be used in BCS-biowaivers, even if a coning effect occurs.

  10. Individualizing Services, Individualizing Responsibility

    DEFF Research Database (Denmark)

    Garsten, Christina; Hollertz, Katarina; Jacobsson, Kerstin

    possibilities for individual voice, autonomy and self-determination in the local delivery of activation policy? What barriers do specific organisational models and practices imply for clients to choose, determine and access tailor-made programmes and services? What policy technologies are at work in governing......-oriented, and the normative demands placed on individuals appear increasingly totalizing, concerning the whole individual rather than the job-related aspects only. The paper is based on 23 in-depth interviews with individual clients as well as individual caseworkers and other professionals engaged in client-related work...

  11. Coding Class

    DEFF Research Database (Denmark)

    Ejsing-Duun, Stine; Hansbøl, Mikala

    Denne rapport rummer evaluering og dokumentation af Coding Class projektet1. Coding Class projektet blev igangsat i skoleåret 2016/2017 af IT-Branchen i samarbejde med en række medlemsvirksomheder, Københavns kommune, Vejle Kommune, Styrelsen for IT- og Læring (STIL) og den frivillige forening...... Coding Pirates2. Rapporten er forfattet af Docent i digitale læringsressourcer og forskningskoordinator for forsknings- og udviklingsmiljøet Digitalisering i Skolen (DiS), Mikala Hansbøl, fra Institut for Skole og Læring ved Professionshøjskolen Metropol; og Lektor i læringsteknologi, interaktionsdesign......, design tænkning og design-pædagogik, Stine Ejsing-Duun fra Forskningslab: It og Læringsdesign (ILD-LAB) ved Institut for kommunikation og psykologi, Aalborg Universitet i København. Vi har fulgt og gennemført evaluering og dokumentation af Coding Class projektet i perioden november 2016 til maj 2017...

  12. Social class, contextualism, and empathic accuracy.

    Science.gov (United States)

    Kraus, Michael W; Côté, Stéphane; Keltner, Dacher

    2010-11-01

    Recent research suggests that lower-class individuals favor explanations of personal and political outcomes that are oriented to features of the external environment. We extended this work by testing the hypothesis that, as a result, individuals of a lower social class are more empathically accurate in judging the emotions of other people. In three studies, lower-class individuals (compared with upper-class individuals) received higher scores on a test of empathic accuracy (Study 1), judged the emotions of an interaction partner more accurately (Study 2), and made more accurate inferences about emotion from static images of muscle movements in the eyes (Study 3). Moreover, the association between social class and empathic accuracy was explained by the tendency for lower-class individuals to explain social events in terms of features of the external environment. The implications of class-based patterns in empathic accuracy for well-being and relationship outcomes are discussed.

  13. Co-morbidity and clinically significant interactions between antiepileptic drugs and other drugs in elderly patients with newly diagnosed epilepsy.

    Science.gov (United States)

    Bruun, Emmi; Virta, Lauri J; Kälviäinen, Reetta; Keränen, Tapani

    2017-08-01

    A study was conducted to investigate the frequency of potential pharmacokinetic drug-to-drug interactions in elderly patients with newly diagnosed epilepsy. We also investigated co-morbid conditions associated with epilepsy. From the register of Kuopio University Hospital (KUH) we identified community-dwelling patients aged 65 or above with newly diagnosed epilepsy and in whom use of the first individual antiepileptic drug (AED) began in 2000-2013 (n=529). Furthermore, register data of the Social Insurance Institution of Finland were used for assessing potential interactions in a nationwide cohort of elderly subjects with newly diagnosed epilepsy. We extracted all patients aged 65 or above who had received special reimbursement for the cost of AEDs prescribed on account of epilepsy in 2012 where their first AED was recorded in 2011-2012 as monotherapy (n=1081). Clinically relevant drug interactions (of class C or D) at the time of starting of the first AED, as assessed via the SFINX-PHARAO database, were analysed. Hypertension (67%), dyslipidemia (45%), and ischaemic stroke (32%) were the most common co-morbid conditions in the hospital cohort of patients. In these patients, excessive polypharmacy (more than 10 concomitant drugs) was identified in 27% of cases. Of the patients started on carbamazepine, 52 subjects (32%) had one class-C or class-D drug interaction and 51 (31%) had two or more C- or D-class interactions. Only 2% of the subjects started on valproate exhibited a class-C interaction. None of the subjects using oxcarbazepine displayed class-C or class-D interactions. Patients with 3-5 (OR 4.22; p=0.05) or over six (OR 8.86; p=0.003) other drugs were more likely to have C- or D-class interaction. The most common drugs with potential interactions with carbamazepine were dihydropyridine calcium-blockers, statins, warfarin, and psychotropic drugs. Elderly patients with newly diagnosed epilepsy are at high risk of clinically relevant pharmacokinetic

  14. 24 CFR 5.854 - When must I prohibit admission of individuals who have engaged in drug-related criminal activity?

    Science.gov (United States)

    2010-04-01

    ... for Criminal Activity or Alcohol Abuse Denying Admissions § 5.854 When must I prohibit admission of... a pattern of illegal use of a drug may interfere with the health, safety, or right to peaceful...

  15. Segmental dependent transport of low permeability compounds along the small intestine due to P-glycoprotein: the role of efflux transport in the oral absorption of BCS class III drugs.

    Science.gov (United States)

    Dahan, Arik; Amidon, Gordon L

    2009-01-01

    The purpose of this study was to investigate the role of P-gp efflux in the in vivo intestinal absorption process of BCS class III P-gp substrates, i.e. high-solubility low-permeability drugs. The in vivo permeability of two H (2)-antagonists, cimetidine and famotidine, was determined by the single-pass intestinal perfusion model in different regions of the rat small intestine, in the presence or absence of the P-gp inhibitor verapamil. The apical to basolateral (AP-BL) and the BL-AP transport of the compounds in the presence or absence of various efflux transporters inhibitors (verapamil, erythromycin, quinidine, MK-571 and fumitremorgin C) was investigated across Caco-2 cell monolayers. P-gp expression levels in the different intestinal segments were confirmed by immunoblotting. Cimetidine and famotidine exhibited segmental dependent permeability through the gut wall, with decreased P(eff) in the distal ileum in comparison to the proximal regions of the intestine. Coperfusion of verapamil with the drugs significantly increased the permeability in the ileum, while no significant change in the jejunal permeability was observed. Both drugs exhibited significantly greater BL-AP than AP-BL Caco-2 permeability, indicative of net mucosal secretion. Concentration dependent decrease of this secretion was obtained by the P-gp inhibitors verapamil, erythromycin and quinidine, while no effect was evident by the MRP2 inhibitor MK-571 and the BCRP inhibitor FTC, indicating that P-gp is the transporter mediates the intestinal efflux of cimetidine and famotidine. P-gp levels throughout the intestine were inversely related to the in vivo permeability of the drugs from the different segments. The data demonstrate that for these high-solubility low-permeability P-gp substrates, P-gp limits in vivo intestinal absorption in the distal segments of the small intestine; however P-gp plays a minimal role in the proximal intestinal segments due to significant lower P-gp expression levels

  16. Individual and population level impacts of illicit drug use, sexual risk behaviours on sexually transmitted infections among young Aboriginal and Torres Strait Islander people: results from the GOANNA survey

    Directory of Open Access Journals (Sweden)

    Handan Wand

    2016-07-01

    Full Text Available Abstract Background Sexually transmitted infections (STIs have been increasing among Australian Indigenous young people for over two decades. Little is known about the association between alcohol and other drug use and sexual risk behaviours and diagnosis of STIs among this population. Methods A cross-sectional, community based self-administered survey was conducted among young Aboriginal people aged 16–29 years of age. Questionnaires included socio-demographic characteristics, knowledge, sexual risk behaviours alcohol and other drug use and health service access including self-reported history of diagnosis with a STI. Logistic regression models and population attributable risks were used to assess individual and population level impacts of illicit drug use on high risk sexual behaviours and ever reported diagnosis of an STI. Results Of the 2877 participants, 2320 (81 % identified as sexually active and were included in this study. More than 50 % of the study population reported that they had used at least one illicit drug in past year. Cannabis, ecstasy and methamphetamines were the three most commonly used illicit drugs in the past year. The prevalence of self-reported STI diagnosis was 25 %. Compared with people who did not report using illicit drugs, risky alcohol use and sexual behaviours including inconsistent condom use, multiple sexual partners in the past year and sex with casual partners were all significantly higher among illicit drug users. In adjusted analysis, participants who reported using illicit drugs were significantly more likely to engage in sexual risk behaviours and to ever have been diagnosed with an STI. Adjusted Odds Ratios ranged from 1.86 to 3.00 (males and from 1.43 to 2.46 (females. At the population level, more than 70 % of the STI diagnoses were attributed to illicit drug-use and sexual risk behaviours for males and females. Conclusion Illicit drug use in this population is relatively high compared to other

  17. Short history of regulations and approved indications of antimicrobial drugs for food animals in the USA.

    Science.gov (United States)

    Volkova, V V; DeMars, Z

    2017-06-01

    We review historical availability and regulation, and recent indications of antimicrobial drugs for food animals in the USA. We summarize the timeline of introduction of individual antimicrobial drug classes from the 1930s to present, history of regulation of antimicrobial drugs from the 1930s to present and indications of antimicrobial drugs in 1996-2014 for food animals in the USA. The history of antimicrobial drug regulation demonstrates a historical precedent for harmonized regulations of antimicrobials 'for human and other animals' in the USA. © 2016 John Wiley & Sons Ltd.

  18. Relapse to opioid use in opioid-dependent individuals released from compulsory drug detention centres compared with those from voluntary methadone treatment centres in Malaysia: a two-arm, prospective observational study.

    Science.gov (United States)

    Wegman, Martin P; Altice, Frederick L; Kaur, Sangeeth; Rajandaran, Vanesa; Osornprasop, Sutayut; Wilson, David; Wilson, David P; Kamarulzaman, Adeeba

    2017-02-01

    Detention of people who use drugs into compulsory drug detention centres (CDDCs) is common throughout East and Southeast Asia. Evidence-based pharmacological therapies for treating substance use disorders, such as opioid agonist treatments with methadone, are generally unavailable in these settings. We used a unique opportunity where CDDCs coexisted with voluntary drug treatment centres (VTCs) providing methadone in Malaysia to compare the timing and occurrence of opioid relapse (measured using urine drug testing) in individuals transitioning from CDDCs versus methadone maintenance in VTCs. We did a parallel, two-arm, prospective observational study of opioid-dependent individuals aged 18 years and older who were treated in Malaysia in the Klang Valley in two settings: CDDCs and VTCs. We used sequential sampling to recruit individuals. Assessed individuals in CDDCs were required to participate in services such as counselling sessions and manual labour. Assessed individuals in VTCs could voluntarily access many of the components available in CDDCs, in addition to methadone therapy. We undertook urinary drug tests and behavioural interviews to assess individuals at baseline and at 1, 3, 6, 9, and 12 months post-release. The primary outcome was time to opioid relapse post-release in the community confirmed by urinary drug testing in individuals who had undergone baseline interviewing and at least one urine drug test (our analytic sample). Relapse rates between the groups were compared using time-to-event methods. This study is registered at ClinicalTrials.gov (NCT02698098). Between July 17, 2012, and August 21, 2014, we screened 168 CDDC attendees and 113 VTC inpatients; of these, 89 from CDDCs and 95 from VTCs were included in our analytic sample. The baseline characteristics of the two groups were similar. In unadjusted analyses, CDDC participants had significantly more rapid relapse to opioid use post-release compared with VTC participants (median time to relapse

  19. On the motivational properties of reward cues: Individual differences.

    Science.gov (United States)

    Robinson, Terry E; Yager, Lindsay M; Cogan, Elizabeth S; Saunders, Benjamin T

    2014-01-01

    Cues associated with rewards, such as food or drugs of abuse, can themselves acquire motivational properties. Acting as incentive stimuli, such cues can exert powerful control over motivated behavior, and in the case of cues associated with drugs, they can goad continued drug-seeking behavior and relapse. However, recent studies reviewed here suggest that there are large individual differences in the extent to which food and drug cues are attributed with incentive salience. Rats prone to approach reward cues (sign-trackers) attribute greater motivational value to discrete localizable cues and interoceptive cues than do rats less prone to approach reward cues (goal-trackers). In contrast, contextual cues appear to exert greater control over motivated behavior in goal-trackers than sign-trackers. It is possible to predict, therefore, before any experience with drugs, in which animals specific classes of drug cues will most likely reinstate drug-seeking behavior. The finding that different individuals may be sensitive to different triggers capable of motivating behavior and producing relapse suggests there may be different pathways to addiction, and has implications for thinking about individualized treatment. This article is part of a Special Issue entitled 'NIDA 40th Anniversary Issue'. Copyright © 2013 Elsevier Ltd. All rights reserved.

  20. Personality, Drug Preference, Drug Use, and Drug Availability

    Science.gov (United States)

    Feldman, Marc; Boyer, Bret; Kumar, V. K.; Prout, Maurice

    2011-01-01

    This study examined the relationship between drug preference, drug use, drug availability, and personality among individuals (n = 100) in treatment for substance abuse in an effort to replicate the results of an earlier study (Feldman, Kumar, Angelini, Pekala, & Porter, 2007) designed to test prediction derived from Eysenck's (1957, 1967)…

  1. 21 CFR 1405.655 - Individual.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 9 2010-04-01 2010-04-01 false Individual. 1405.655 Section 1405.655 Food and Drugs OFFICE OF NATIONAL DRUG CONTROL POLICY GOVERNMENTWIDE REQUIREMENTS FOR DRUG-FREE WORKPLACE (FINANCIAL ASSISTANCE) Definitions § 1405.655 Individual. Individual means a natural person. ...

  2. Adverse Drug Reactions Reported With Cholinesterase Inhibitors : An Analysis of 16 Years of Individual Case Safety Reports From VigiBase

    NARCIS (Netherlands)

    Kroeger, Edeltraut; Mouls, Marie; Wilchesky, Machelle; Berkers, Mieke; Carmichael, Pierre-Hugues; van Marum, Rob; Souverein, Patrick; Egberts, Toine; Laroche, Marie-Laure

    2015-01-01

    Background: No worldwide pharmacovigilance study evaluating the spectrum of adverse drug reactions (ADRs) induced by cholinesterase inhibitors (ChEI) in Alzheimer's disease has been conducted since their emergence on the market. Objective: To describe ChEI related ADRs in Alzheimer's disease

  3. Adverse Drug Reactions Reported With Cholinesterase Inhibitors: An Analysis of 16 Years of Individual Case Safety Reports From VigiBase

    NARCIS (Netherlands)

    Kroger, E.; Mouls, M.; Wilchesky, M.; Berkers, M.; Carmichael, P.H.; van Marum, R.J.; Souverein, P.; Egberts, T.; Laroche, M.L.

    2015-01-01

    Background: No worldwide pharmacovigilance study evaluating the spectrum of adverse drug reactions (ADRs) induced by cholinesterase inhibitors (ChEI) in Alzheimer’s disease has been conducted since their emergence on the market. Objective: To describe ChEI related ADRs in Alzheimer’s disease

  4. Geographic and temporal trends in the molecular epidemiology and genetic mechanisms of transmitted HIV-1 drug resistance: an individual-patient- and sequence-level meta-analysis

    NARCIS (Netherlands)

    Rhee, Soo-Yon; Blanco, Jose Luis; Jordan, Michael R.; Taylor, Jonathan; Lemey, Philippe; Varghese, Vici; Hamers, Raph L.; Bertagnolio, Silvia; Rinke de Wit, Tobias F.; Aghokeng, Avelin F.; Albert, Jan; Avi, Radko; Avila-Rios, Santiago; Bessong, Pascal O.; Brooks, James I.; Boucher, Charles A. B.; Brumme, Zabrina L.; Busch, Michael P.; Bussmann, Hermann; Chaix, Marie-Laure; Chin, Bum Sik; D'Aquin, Toni T.; de Gascun, Cillian F.; Derache, Anne; Descamps, Diane; Deshpande, Alaka K.; Djoko, Cyrille F.; Eshleman, Susan H.; Fleury, Herve; Frange, Pierre; Fujisaki, Seiichiro; Harrigan, P. Richard; Hattori, Junko; Holguin, Africa; Hunt, Gillian M.; Ichimura, Hiroshi; Kaleebu, Pontiano; Katzenstein, David; Kiertiburanakul, Sasisopin; Kim, Jerome H.; Kim, Sung Soon; Li, Yanpeng; Lutsar, Irja; Morris, Lynn; Ndembi, Nicaise; Ng, Kee Peng; Paranjape, Ramesh S.; Peeters, Martine; Poljak, Mario; Price, Matt A.; Ragonnet-Cronin, Manon L.; Reyes-Terán, Gustavo; Rolland, Morgane; Sirivichayakul, Sunee; Smith, Davey M.; Soares, Marcelo A.; Soriano, Vincent V.; Ssemwanga, Deogratius; Stanojevic, Maja; Stefani, Mariane A.; Sugiura, Wataru; Sungkanuparph, Somnuek; Tanuri, Amilcar; tee, Kok Keng; Truong, Hong-Ha M.; van de Vijver, David A. M. C.; Vidal, Nicole; Yang, Chunfu; Yang, Rongge; Yebra, Gonzalo; Ioannidis, John P. A.; Vandamme, Anne-Mieke; Shafer, Robert W.

    2015-01-01

    Regional and subtype-specific mutational patterns of HIV-1 transmitted drug resistance (TDR) are essential for informing first-line antiretroviral (ARV) therapy guidelines and designing diagnostic assays for use in regions where standard genotypic resistance testing is not affordable. We sought to

  5. Coronary Artery Bypass Surgery Versus Drug-Eluting Stent Implantation for Left Main or Multivessel Coronary Artery Disease A Meta-Analysis of Individual Patient Data

    NARCIS (Netherlands)

    Lee, Cheol Whan; Ahn, Jung-Min; Cavalcante, Rafael; Sotomi, Yohei; Onuma, Yoshinobu; Suwannasom, Pannipa; Tenekecioglu, Erhan; Yun, Sung-Cheol; Park, Duk-Woo; Kang, Soo-Jin; Lee, Seung-Whan; Kim, Young-Hak; Park, Seong-Wook; Serruys, Patrick W.; Park, Seung-Jung

    2016-01-01

    OBJECTIVES The authors undertook a patient-level meta-analysis to compare long-term outcomes after coronary artery bypass grafting (CABG) versus percutaneous coronary intervention (PCI) with drug-eluting stents (DES) in 3,280 patients with left main or multivessel coronary artery disease (CAD).

  6. Geographic and Temporal Trends in the Molecular Epidemiology and Genetic Mechanisms of Transmitted HIV-1 Drug Resistance: An Individual-Patient- and Sequence-Level Meta-Analysis

    NARCIS (Netherlands)

    S.Y. Rhee (Soo Yoon); J.L. Blanco (Jose Luis); M.R. Jordan (Michael); J. Taylor (Jonathan); P. Lemey (Philippe); V. Varghese (Vici); R.L. Hamers (Raph); S. Bertagnolio (Silvia); M. De Wit (Meike); A.F. Aghokeng (Avelin); J. Albert (Jan); R. Avi (Radko); S. Avila-Rios (Santiago); P.O. Bessong (Pascal O.); J.I. Brooks (James I.); C.A.B. Boucher (Charles); Z.L. Brumme (Zabrina L.); M.P. Busch (Michael P.); H. Bussmann (Hermann); M.L. Chaix (Marie Laure); B.S. Chin (Bum Sik); T.T. D’Aquin (Toni T.); C. de Gascun (Cillian); A. Derache (Anne); D. Descamps (Diane); A.K. Deshpande (Alaka K.); C.F. Djoko (Cyrille F.); S.H. Eshleman (Susan H.); H. Fleury (Hervé); P. Frange (Pierre); S. Fujisaki (Seiichiro); P. Harrigan (Pr); J. Hattori (Junko); A. Holguin (Africa); G.M. Hunt (Gillian M.); H. Ichimura (Hiroshi); P. Kaleebu (Pontiano); D. Katzenstein (David); S. Kiertiburanakul (Sasisopin); J.H. Kim (Jerome H.); S.S. Kim (Sung Soon); Y. Li (Yanpeng); I. Lutsar (Irja); L. Morris (L.); N. Ndembi (Nicaise); K.P. NG (Kee Peng); R.S. Paranjape (Ramesh S.); M.C. Peeters (Marian); M. Poljak (Mario); M.A. Price (Matt A.); M.L. Ragonnet-Cronin (Manon L.); G. Reyes-Terán (Gustavo); M. Rolland (Morgane); S. Sirivichayakul (Sunee); D.M. Smith (Davey M.); M.A. Soares (Marcelo A.); V. Soriano (Virtudes); D. Ssemwanga (Deogratius); M. Stanojevic (Maja); M.A. Stefani (Mariane A.); W. Sugiura (Wataru); S. Sungkanuparph (Somnuek); A. Tanuri (Amilcar); K.K. Tee (Kok Keng); H.-H.M. Truong (Hong-Ha M.); D.A.M.C. van de Vijver (David); N. Vidal (Nicole); C. Yang (Chunfu); R. Yang (Rongge); G. Yebra (Gonzalo); J.P.A. Ioannidis (John); A.M. Vandamme (Anne Mieke); R.W. Shafer (Robert)

    2015-01-01

    textabstractRegional and subtype-specific mutational patterns of HIV-1 transmitted drug resistance (TDR) are essential for informing first-line antiretroviral (ARV) therapy guidelines and designing diagnostic assays for use in regions where standard genotypic resistance testing is not affordable. We

  7. Evaluation and optimized selection of supersaturating drug delivery systems of posaconazole (BCS class 2b) in the gastrointestinal simulator (GIS): An in vitro-in silico-in vivo approach.

    Science.gov (United States)

    Hens, Bart; Bermejo, Marival; Tsume, Yasuhiro; Gonzalez-Alvarez, Isabel; Ruan, Hao; Matsui, Kazuki; Amidon, Gregory E; Cavanagh, Katie L; Kuminek, Gislaine; Benninghoff, Gail; Fan, Jianghong; Rodríguez-Hornedo, Naír; Amidon, Gordon L

    2018-03-30

    Supersaturating drug delivery systems (SDDS) have been put forward in the recent decades in order to circumvent the issue of low aqueous solubility. Prior to the start of clinical trials, these enabling formulations should be adequately explored in in vitro/in silico studies in order to understand their in vivo performance and to select the most appropriate and effective formulation in terms of oral bioavailability and therapeutic outcome. The purpose of this work was to evaluate the in vivo performance of four different oral formulations of posaconazole (categorized as a biopharmaceutics classification system (BCS) class 2b compound) based on the in vitro concentrations in the gastrointestinal simulator (GIS), coupled with an in silico pharmacokinetic model to predict their systemic profiles. Recently published intraluminal and systemic concentrations of posaconazole for these formulations served as a reference to validate the in vitro and in silico results. Additionally, the morphology of the formed precipitate of posaconazole was visualized and characterized by optical microscopy studies and thermal analysis. This multidisciplinary work demonstrates an in vitro-in silico-in vivo approach that provides a scientific basis for screening SDDS by a user-friendly formulation predictive dissolution (fPD) device in order to rank these formulations towards their in vivo performance. Copyright © 2018. Published by Elsevier B.V.

  8. A survey of antiepileptic drug responses identifies drugs with potential efficacy for seizure control in Wolf-Hirschhorn syndrome.

    Science.gov (United States)

    Ho, Karen S; Markham, Leah M; Twede, Hope; Lortz, Amanda; Olson, Lenora M; Sheng, Xiaoming; Weng, Cindy; Wassman, E Robert; Newcomb, Tara; Wassman, E Robert; Carey, John C; Battaglia, Agatino

    2018-04-01

    Seizures are present in over 90% of infants and children with Wolf-Hirschhorn syndrome (WHS). When present, they significantly affect quality of life. The goal of this study was to use caregiver reports to describe the comparative efficacies of commonly used antiepileptic medications in a large population of individuals with WHS. A web-based, confidential caregiver survey was developed to capture seizure semiology and a chronologic record of seizure treatments as well as responses to each treatment. Adverse events for each drug were also cataloged. We received 141 complete survey responses (47% response rate) describing the seizures of individuals ranging in age from 4months to 61years (90 females: 51 males). Using the Early Childhood Epilepsy Severity Scale (E-Chess), WHS-associated seizures are demonstrably severe regardless of deletion size. The best-performing antiepileptic drugs (AEDs) for controlling seizures in this cohort were broad spectrum drugs clobazam, levetiracetam, and lamotrigine; whereas, the three commonly used carboxamide class drugs: carbamazepine, phenytoin, and oxcarbazepine, were reported to have little effect on, or even exacerbate, seizures. The carboxamide class drugs, along with phenobarbital and topiramate, were also associated with the highest rate of intolerance due to cooccurrence of adverse events. Levetiracetam, clobazam, and clonazepam demonstrated higher tolerability and comparatively less severe adverse events (Wilcoxon rank sum comparison between performance of levetiracetam and carboxamide class drugs gives a psyndromes which may have complex seizure etiologies. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

  9. Drug-induced immune hemolytic anemia

    Science.gov (United States)

    Immune hemolytic anemia secondary to drugs; Anemia - immune hemolytic - secondary to drugs ... Drugs that can cause this type of hemolytic anemia include: Cephalosporins (a class of antibiotics), most common ...

  10. Class composition influences on pupils' cognitive development

    NARCIS (Netherlands)

    Peetsma, T.; van der Veen, I.; Koopman, P.; van Schooten, E.

    2006-01-01

    The proportion of low-achieving children in a class can affect the progress of individual pupils in that class. Having a large proportion of low achievers in a class could slow down growth in cognitive achievement but, might also boost such growth, due to the effects of specialist teaching geared to

  11. HIV drug resistance early warning indicators in cohorts of individuals starting antiretroviral therapy between 2004 and 2009: World Health Organization global report from 50 countries.

    Science.gov (United States)

    Bennett, Diane E; Jordan, Michael R; Bertagnolio, Silvia; Hong, Steven Y; Ravasi, Giovanni; McMahon, James H; Saadani, Ahmed; Kelley, Karen F

    2012-05-01

    The World Health Organization developed a set of human immunodeficiency virus drug resistance (HIVDR) early warning indicators (EWIs) to assess antiretroviral therapy clinic and program factors associated with HIVDR. EWIs are monitored by abstracting data routinely recorded in clinical records, and the results enable clinics and program managers to identify problems that should be addressed to minimize preventable emergence of HIVDR in clinic populations. As of June 2011, 50 countries monitored EWIs, covering 131 686 patients initiating antiretroviral treatment between 2004 and 2009 at 2107 clinics. HIVDR prevention is associated with patient care (appropriate prescribing and patient monitoring), patient behavior (adherence), and clinic/program management efforts to reduce treatment interruptions (follow up, retention on first-line ART, procurement and supply management of antiretroviral drugs). EWIs measure these factors and the results have been used to optimize patient and population treatment outcomes.

  12. Drug-Induced Dental Caries: A Disproportionality Analysis Using Data from VigiBase.

    Science.gov (United States)

    de Campaigno, Emilie Patras; Kebir, Inès; Montastruc, Jean-Louis; Rueter, Manuela; Maret, Delphine; Lapeyre-Mestre, Maryse; Sallerin, Brigitte; Despas, Fabien

    2017-12-01

    Dental caries is defined as a pathological breakdown of the tooth. It is an infectious phenomenon involving a multifactorial aetiology. The impact of drugs on cariogenic risk has been poorly investigated. In this study, we identified drugs suspected to induce dental caries as adverse drug reactions (ADRs) and then studied a possible pathogenic mechanism for each drug that had a statistically significant disproportionality. We extracted individual case safety reports of dental caries associated with drugs from VigiBase ® (the World Health Organization global individual case safety report database). We calculated disproportionality for each drug with a reporting odds ratio (ROR) and 99% confidence interval. We analysed the pharmacodynamics of each drug that had a statistically significant disproportionality. In VigiBase ® , 5229 safety reports for dental caries concerning 733 drugs were identified. Among these drugs, 88 had a significant ROR, and for 65 of them (73.9%), no information about dental caries was found in the summaries of the product characteristics, the Micromedex ® DRUGDEX, or the Martindale databases. Regarding the pharmacological classes of drugs involved in dental caries, we identified bisphosphonates, atropinic drugs, antidepressants, corticoids, immunomodulating drugs, antipsychotics, antiepileptics, opioids and β 2 -adrenoreceptor agonist drugs. Regarding possible pathogenic mechanisms for these drugs, we identified changes in salivary flow/composition for 54 drugs (61.4%), bone metabolism changes for 31 drugs (35.2%), hyperglycaemia for 32 drugs (36.4%) and/or immunosuppression for 23 drugs (26.1%). For nine drugs (10.2%), the mechanism was unclear. We identified 88 drugs with a significant positive disproportionality for dental caries. Special attention has to be paid to bisphosphonates, atropinic drugs, immunosuppressants and drugs causing hyperglycaemia.

  13. Mudando o foco: um estudo exploratório sobre uso de drogas e violência no trabalho entre mulheres das classes populares da cidade do Rio de Janeiro, Brasil Cambiando el foco: un estudio exploratorio acerca del uso de drogas y violência en el trabalho de mujeres de las classes populares de Rio de Janeiro, Brasil Changing the focus: an exploratory study of drug use and worplace violence among women of popular classes in Rio de Janeiro, Brazil

    Directory of Open Access Journals (Sweden)

    Helena Maria Scherlowski Leal David

    2005-12-01

    .This exploratory study aimed to investigate factors related to the use of illicit and licit drugs and workplace violence in a group of women from popular classes in the city of Rio de Janeiro. We used a descriptive and analytic quantitative approach was used, as well as a qualitative approach through in-depth interviews with women who suffered or were suffering workplace violence, using the collective subject discourse analysis methodology. The results showed sociodemographic and work situations that can be considered as possible risk factors for drug consumption and workplace violence. The qualitative analysis shows how this group perceives the phenomena of drug use and workplace violence, expanding the comprehension about these issues and providing conceptual and methodological elements for additional studies on this subject.

  14. Prevalence and characteristics of addictive behaviors in a community sample: A latent class analysis.

    Science.gov (United States)

    Deleuze, Jory; Rochat, Lucien; Romo, Lucia; Van der Linden, Martial; Achab, Sophia; Thorens, Gabriel; Khazaal, Yasser; Zullino, Daniele; Maurage, Pierre; Rothen, Stéphane; Billieux, Joël

    2015-06-01

    While addictions to substances such as alcohol, tobacco, and other drugs have been extensively investigated, interest has been growing in potential non-substance-related addictive behaviors (e.g., excessive gambling, buying or playing video games). In the current study, we sought to determine the prevalence and characteristics of a wide range of addictive behaviors in a general population sample and to identify reliable subgroups of individuals displaying addictive behaviors. Seven hundred seventy participants completed an online survey. The survey screened for the presence and characteristics of the main recognized substance and behavioral addictions (alcohol, tobacco, cannabis, other drugs, gambling, compulsive shopping, intensive exercise, Internet and mobile phone overuse, intensive work involvement, and overeating) in a three-month period. Key aspects of addiction were measured for each reported behavior, including negative outcomes, emotional triggers (positive and negative emotional contexts), search for stimulation or pleasure, loss of control, and cognitive salience. Latent class analysis allowed us to identify three theoretically and clinically relevant subgroups of individuals. The first class groups problematic users, i.e., addiction-prone individuals. The second class groups at-risk users who frequently engage in potentially addictive behaviors to regulate emotional states (especially overinvolvement in common behaviors such as eating, working, or buying). The third class groups individuals who are not prone to addictive behaviors. The existence of different groups in the population sheds new light on the distinction between problematic and non-problematic addiction-like behaviors.

  15. Glomerular filtration rate equations overestimate creatinine clearance in older individuals enrolled in the Baltimore Longitudinal Study on Aging: impact on renal drug dosing.

    Science.gov (United States)

    Dowling, Thomas C; Wang, En-Shih; Ferrucci, Luigi; Sorkin, John D

    2013-09-01

    To evaluate the performance of kidney function estimation equations and to determine the frequency of drug dose discordance in an older population. Cross-sectional analysis of data from community-dwelling volunteers randomly selected from the Baltimore Longitudinal Study of Aging from January 1, 2005, to December 31, 2010. A total of 269 men and women with a mean ± SD age of 81 ± 6 years, mean serum creatinine concentration (Scr ) of 1.1 ± 0.4 mg/dl, and mean 24-hour measured creatinine clearance (mClcr ) of 53 ± 13 ml/minute. Kidney function was estimated by using the following equations: Cockcroft-Gault (CG), Modification of Diet in Renal Disease (MDRD), and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI). The performance of each equation was assessed by measuring bias and precision relative to mClcr . Dose calculation errors (discordance) were determined for 10 drugs requiring renal dosage adjustments to avoid toxicity when compared with the dosages approved by the Food and Drug Administration. The CG equation was the least biased estimate of mClcr . The MDRD and CKD-EPI equations were significantly positively biased compared with CG (mean ± SD 34 ± 20% and 22 ± 15%, respectively, prenal impairment. Thus equations estimating glomerular filtration rate should not be substituted in place of the CG equation in older adults for the purpose of renal dosage adjustments. In addition, the common practice of rounding or replacing low Scr values with an arbitrary value of 1.0 mg/dl for use in the CG equation should be avoided. Additional studies that evaluate alternative eGFR equations in the older populations that incorporate pharmacokinetic and pharmacodynamic outcomes measures are needed. © 2013 Pharmacotherapy Publications, Inc.

  16. Initial Virologic Response and HIV Drug Resistance Among HIV-Infected Individuals Initiating First-line Antiretroviral Therapy at 2 Clinics in Chennai and Mumbai, India

    Science.gov (United States)

    Hingankar, Nitin K.; Thorat, Smita R.; Deshpande, Alaka; Rajasekaran, S.; Chandrasekar, C.; Kumar, Suria; Srikantiah, Padmini; Chaturbhuj, Devidas N.; Datkar, Sharda R.; Deshmukh, Pravin S.; Kulkarni, Smita S.; Sane, Suvarna; Reddy, D. C. S.; Garg, Renu; Jordan, Michael R.; Kabra, Sandhya; Paranjape, Ramesh S.

    2012-01-01

    Human immunodeficiency virus drug resistance (HIVDR) in cohorts of patients initiating antiretroviral therapy (ART) at clinics in Chennai and Mumbai, India, was assessed following World Health Organization (WHO) guidelines. Twelve months after ART initiation, 75% and 64.6% of participants at the Chennai and Mumbai clinics, respectively, achieved viral load suppression of Mumbai due to high rates of loss to follow-up. Findings highlight the need for defaulter tracing and scale-up of routine viral load testing to identify patients failing first-line ART. PMID:22544202

  17. Efavirenz or nevirapine in three-drug combination therapy with two nucleoside or nucleotide-reverse transcriptase inhibitors for initial treatment of HIV infection in antiretroviral-naïve individuals.

    Science.gov (United States)

    Mbuagbaw, Lawrence; Mursleen, Sara; Irlam, James H; Spaulding, Alicen B; Rutherford, George W; Siegfried, Nandi

    2016-12-10

    The advent of highly active antiretroviral therapy (ART) has reduced the morbidity and mortality due to HIV infection. The World Health Organization (WHO) ART guidelines focus on three classes of antiretroviral drugs, namely nucleoside or nucleotide reverse transcriptase inhibitors (NRTI), non-nucleoside reverse transcriptase inhibitors (NNRTI) and protease inhibitors. Two of the most common medications given as first-line treatment are the NNRTIs, efavirenz (EFV) and nevirapine (NVP). It is unclear which NNRTI is more efficacious for initial therapy. This systematic review was first published in 2010. To determine which non-nucleoside reverse transcriptase inhibitor, either EFV or NVP, is more effective in suppressing viral load when given in combination with two nucleoside reverse transcriptase inhibitors as part of initial antiretroviral therapy for HIV infection in adults and children. We attempted to identify all relevant studies, regardless of language or publication status, in electronic databases and conference proceedings up to 12 August 2016. We searched MEDLINE, Embase, the Cochrane Central Register of Controlled Trials (CENTRAL), the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) and ClinicalTrials.gov to 12 August 2016. We searched LILACS (Latin American and Caribbean Health Sciences Literature) and the Web of Science from 1996 to 12 August 2016. We checked the National Library of Medicine (NLM) Gateway from 1996 to 2009, as it was no longer available after 2009. We included all randomized controlled trials (RCTs) that compared EFV to NVP in people with HIV without prior exposure to ART, irrespective of the dosage or NRTI's given in combination.The primary outcome of interest was virological success. Other primary outcomes included mortality, clinical progression to AIDS, severe adverse events, and discontinuation of therapy for any reason. Secondary outcomes were change in CD4 count, treatment failure

  18. Influence of orthopedic treatment on hard and soft facial structures of individuals presenting with Class II, Division 1 malocclusion: a comparative study A influência do tratamento ortopédico nas estruturas faciais de indivíduos com má oclusão de Classe II, 1ª Divisão: um estudo comparativo

    Directory of Open Access Journals (Sweden)

    Liliana Ávila Maltagliati

    2004-06-01

    Full Text Available The purpose of this investigation was to comparatively evaluate the cephalometric changes in soft and hard tissues related to treatment of Class II, division 1 malocclusion with activator-headgear and Bionator appliances. Twenty-four individuals formed the activator-headgear group and twenty-five comprised the Bionator group, while other twenty-four presenting the same malocclusion did not receive any intervention and served as controls. Lateral headfilms were taken at the beginning and at the end of the observation period and were digitized with computerized cephalometrics; cephalometric analysis was performed and the results were submitted to statistical test. According to the methodology employed, our findings suggested that both appliances do not significantly alter the growth path, and also they were not able to modify the posterior inferior height and the sagittal and vertical position of the upper lip. The lower lip and the soft menton were only slightly modified by the orthopedic appliances, but the mentolabial sulcus showed a significant decrease in deepness compared to the control group. Of statistical significance, only the anterior inferior hard and soft facial heights and the lower lip height increased more in the treated groups.Esta pesquisa teve por objetivo avaliar, comparativamente, as alterações cefalométricas tegumentares e esqueléticas, decorrentes do tratamento das más oclusões de classe II, 1a divisão, com o ativador combinado com a ancoragem extrabucal e com o bionator. O grupo tratado com o ativador combinado com a ancoragem extrabucal foi composto por 24 indivíduos e o grupo tratado com o bionator compreendeu 25 pacientes, enquanto que outros 24 indivíduos compuseram o grupo controle, apresentando a mesma má oclusão, porém sem terem sido submetidos a nenhuma terapia ortodôntica. Obteve-se telerradiografias laterais de todos os indivíduos no início e final do período de observação que foram digitalizadas

  19. [Club drugs].

    Science.gov (United States)

    Guerreiro, Diogo Frasquilho; Carmo, Ana Lisa; da Silva, Joaquim Alves; Navarro, Rita; Góis, Carlos

    2011-01-01

    Club drugs are the following substances: Methylenedioxymethamphetamine (MDMA); Methamphetamine; Lysergic Acid Diethylamide (LSD); Ketamine; Gamma-hydroxybutyrate (GHB) and Flunitrazepam. These substances are mainly used by adolescents and young adults, mostly in recreational settings like dance clubs and rave parties. These drugs have diverse psychotropic effects, are associated with several degrees of toxicity, dependence and long term adverse effects. Some have been used for several decades, while others are relatively recent substances of abuse. They have distinct pharmacodynamic and pharmacokinetic properties, are not easy to detect and, many times, the use of club drugs is under diagnosed. Although the use of these drugs is increasingly common, few health professionals feel comfortable with the diagnosis and treatment. The authors performed a systematic literature review, with the goal of synthesising the existing knowledge about club drugs, namely epidemiology, mechanism of action, detection, adverse reactions and treatment. The purpose of this article is creating in Portuguese language a knowledge data base on club drugs, that health professionals of various specialties can use as a reference when dealing with individual with this kind of drug abuse.

  20. The Prevalence of Transmitted Drug Resistance in Newly Diagnosed HIV-Infected Individuals in Croatia: The Role of Transmission Clusters of Men Who Have Sex with Men Carrying the T215S Surveillance Drug Resistance Mutation

    Science.gov (United States)

    Grgic, Ivana; Lunar, Maja M.; Poljak, Mario; Vince, Adriana; Vrakela, Ivana Baca; Planinic, Ana; Seme, Katja; Begovac, Josip

    2013-01-01

    Abstract The aim of this study was to determine the prevalence of transmitted drug resistance (TDR) in newly diagnosed and treatment-naive HIV-infected patients from Croatia and evaluate a possible contribution of transmission clusters to the spread of resistant virus. The study enrolled treatment-naive HIV-infected patients that entered clinical care at the Croatian Reference Center for HIV/AIDS between 2006 and 2008. The protease gene and a part of the reverse transcriptase gene of the HIV-1 genome were sequenced by using the Trugene HIV-1 Genotyping System. The prevalence of transmitted drug resistance was analyzed by using the surveillance drug resistance mutations (SDRM) list recommended by the WHO in 2009. We report findings for 118 of 180 eligible patients (65.6% coverage). SDRM were detected in 26 of 118 patients (22.0%) who were infected with subtype B and belonged mostly to the men having sex with men (MSM). The majority of patients with primary resistance carried SDRM associated with resistance to nucleoside analogues reverse transcriptase inhibitors (NRTIs, 23 of 118 patients, 19.5%). The most frequently found NRTI SDRM was T215S (17 of 118 patients, 14.4%). SDRM associated with resistance to nonnucleoside reverse transcriptase inhibitors were detected in three (2.5%) patients and primary resistance to protease inhibitors was not detected. Non-B subtypes were detected in 13/118 patients (11%). A total of 12 transmission pairs and eight distinct transmission clusters were identified with the largest cluster harboring sequences from 19 patients; among them all but two were carrying the T215S mutation. This study showed a high prevalence of TDR in newly diagnosed MSM from Croatia and is an important contribution concerning the relationship between local transmission clusters and the spread of resistant virus. PMID:22906365

  1. Drug Facts

    Medline Plus

    Full Text Available ... Why Is It So Hard to Quit Drugs? Effects of Drugs Drug Use and Other People Drug ... Unborn Children Drug Use and Your Health Other Effects on the Body Drug Use Hurts Brains Drug ...

  2. Potential of prescription registries to capture individual-level use of aspirin and other nonsteroidal anti-inflammatory drugs in Denmark: trends in utilization 1999-2012

    DEFF Research Database (Denmark)

    Schmidt, M.; Hallas, J.; Friis, S.

    2014-01-01

    according to NSAID subtype was observed; ibuprofen use increased, use of all newer selective cyclooxygenase-2 inhibitors nearly ceased after 2004, diclofenac use decreased by nearly 50% after 2008, and naproxen use remained stable. As of 2012, the prescribed proportion of individual-level NSAID sales was 92...... and to quantify the proportion of total sales that was sold on prescription. METHOD: Based on nationwide data from the Danish Serum Institute and the Danish National Prescription Registry, we retrieved sales statistics for the Danish primary health care sector to calculate 1-year prevalences of prescription users...... of aspirin or nonaspirin NSAIDs, and to estimate the corresponding proportions of total sales dispensed on prescription. RESULTS: Both low-dose aspirin and nonaspirin NSAIDs were commonly used in the Danish population between 1999 and 2012, particularly among elderly individuals. The 1-year prevalence...

  3. A Virtual Class Calculus

    DEFF Research Database (Denmark)

    Ernst, Erik; Ostermann, Klaus; Cook, William Randall

    2006-01-01

    Virtual classes are class-valued attributes of objects. Like virtual methods, virtual classes are defined in an object's class and may be redefined within subclasses. They resemble inner classes, which are also defined within a class, but virtual classes are accessed through object instances...... model for virtual classes has been a long-standing open question. This paper presents a virtual class calculus, vc, that captures the essence of virtual classes in these full-fledged programming languages. The key contributions of the paper are a formalization of the dynamic and static semantics of vc...

  4. Social Desirability Bias and Prevalence of Sexual HIV Risk Behaviors Among People Who Use Drugs in Baltimore, Maryland: Implications for Identifying Individuals Prone to Underreporting Sexual Risk Behaviors.

    Science.gov (United States)

    Rao, Amrita; Tobin, Karin; Davey-Rothwell, Melissa; Latkin, Carl A

    2017-07-01

    The role of social desirability bias (SDB) in self-reported HIV risk behaviors continues to be problematic. This study examined whether SDB was associated with self-reported, via audio computer assisted self-interviewing, sexual risk behaviors among people who use drugs. The present study was conducted among 559 participants who reported having a recent sexual partner at their 6-month visit of a longitudinal study. Robust Poisson regression was used to model the association between SDB and five risk behaviors. Analyses were stratified by gender and partner type. Higher scores of SDB were associated with decreased reporting of selling sex and having more than one sexual partner. Higher SDB scores were associated with increased reporting of always using condoms during oral, vaginal, and anal sex. Gender-specific differences were observed. The inclusion of a measure of SDB in data collection, along with other strategies, can be used to both identify and reduce self-report biases.

  5. Drug specificity in drug versus food choice in male rats.

    Science.gov (United States)

    Tunstall, Brendan J; Riley, Anthony L; Kearns, David N

    2014-08-01

    Although different classes of drug differ in their mechanisms of reinforcement and effects on behavior, little research has focused on differences in self-administration behaviors maintained by users of these drugs. Persistent drug choice despite available reinforcement alternatives has been proposed to model behavior relevant to addiction. The present study used a within-subjects procedure, where male rats (Long-Evans, N = 16) were given a choice between cocaine (1.0 mg/kg/infusion) and food (a single 45-mg grain pellet) or between heroin (0.02 mg/kg/infusion) and food in separate phases (drug order counterbalanced). All rats were initially trained to self-administer each drug, and the doses used were based on previous studies showing that small subsets of rats tend to prefer drug over food reinforcement. The goal of the present study was to determine whether rats that prefer cocaine would also prefer heroin. Choice sessions consisted of 2 forced-choice trials with each reinforcer, followed by 14 free-choice trials (all trials separated by 10-min intertrial interval). Replicating previous results, small subsets of rats preferred either cocaine (5 of the 16 rats) or heroin (2 of the 16 rats) to the food alternative. Although 1 of the 16 rats demonstrated a preference for both cocaine and heroin to the food alternative, there was no relationship between degree of cocaine and heroin preference in individual rats. The substance-specific pattern of drug preference observed suggests that at least in this animal model, the tendencies to prefer cocaine or heroin in preference to a nondrug alternative are distinct behavioral phenomena.

  6. Drugs for insomnia.

    Science.gov (United States)

    Zisapel, Nava

    2012-09-01

    Sleep is a vital neurochemical process involving sleep-promoting and arousal centers in the brain. Insomnia is a pervasive disorder characterized by difficulties in initiating or maintaining or non-refreshing (poor quality) sleep and clinically significant daytime distress. Insomnia is more prevalent in women and old age and puts sufferers at significant physical and mental health risks. This review summarizes published data on the current and emerging insomnia drug classes, rationale for development and associated risks/benefits. (Summary of Product Characteristics and Medline search on "hypnotic" or specific drug names and "Insomnia"). GABA(A) receptor modulators facilitate sleep onset and some improve maintenance but increase risk of dependence, memory, cognitive and psychomotor impairments, falls, accidents and mortality. Melatonin receptor agonists improve quality of sleep and/or sleep onset but response may develop over several days. They have more benign safety profiles and are indicated for milder insomnia, longer usage and (prolonged release melatonin) older patients. Histamine H-1 receptor antagonists improve sleep maintenance but their effects on cognition, memory and falls remain to be demonstrated. Late-stage pipeline orexin OX1/OX2 and serotonin 5HT2A receptor antagonists may hold the potential to address several unmet needs in insomnia pharmacotherapy but safety issues cast some doubts over their future. Current and new insomnia drugs in the pipeline target different sleep regulating mechanisms and symptoms and have different tolerability profiles. Drug selection would ideally be based on improvement in the quality of patients' sleep, overall quality of life and functional status weighed against risk to the individual and public health.

  7. Imagining class: A study into material social class position, subjective identification, and voting behavior across Europe.

    Science.gov (United States)

    D'Hooge, Lorenzo; Achterberg, Peter; Reeskens, Tim

    2018-02-01

    The traditional approach to class voting has largely ignored the question whether material class positions coincide with subjective class identification. Following Sosnaud et al. (2013), this study evaluates party preferences when Europeans' material and subjective social class do not coincide. Seminal studies on voting behavior have suggested that members of lower classes are more likely to vote for the economic left and cultural right and that higher classes demonstrate the opposite pattern. Yet, these studies have on the one hand overlooked the possibility that there is a mismatch between the material class people can be classified in and the class they think they are part of, and on the other hand the consequences of this discordant class identification on voting behavior. Analyzing the 2009 wave of the European Elections Study, we find that the majority of the Europeans discordantly identify with the middle class, whereas only a minority of the lower and higher classes concordantly identify with their material social class. Further, material class only seems to predict economic voting behavior when it coincides with subjective class; for instance, individuals who have an inflated class identification are more likely to vote for the economic left, even when they materially can be classified as middle or high class. We conclude this paper with a discussion on scholarly debates concerning class and politics. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. 21 CFR 25.33 - Animal drugs.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 1 2010-04-01 2010-04-01 false Animal drugs. 25.33 Section 25.33 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ENVIRONMENTAL IMPACT CONSIDERATIONS Categorical Exclusions § 25.33 Animal drugs. The classes of actions listed in this section are...

  9. 器官移植受者免疫抑制药物的个体化治疗与药物基因组学研究%Pharmacogenomics and individual therapy of immunosuppressive drugs in transplant recipients

    Institute of Scientific and Technical Information of China (English)

    王兰兰

    2012-01-01

    Long-term using of immunosuppressants is necessary to prolong the lifetime of transplanted organ and transplant recipients after transplantation.Due to the great variation in metabolism of immunosuppressive drug,there is the close correlation between drug concentration and rejection or organ injury induced by immunosuppressants.The gene polymorphism of multidrug resistance protein (MDR) and cytochrome P450 isoenzyme (CYP450) could lead to the difference of expression or activation of corresponding coded proteins.Individual gene polymorphism causes not only some special drug metabolism difference,but the huge diversity of the distribution of drug metabolism and drug target function.Except for the clinical therapeutic drug monitoring,detecting hereditary variation and gene polymorphism,analyzing the significance of individual gene polymorphism in drug effect and toxicity,applying individual treatment in clinical treatment research,will be the new mission and challenge for the clinical laboratory technologists.%器官移植为保证移植器官在受者体内生存,需长期使用免疫抑制剂.免疫抑制药物在体内代谢的个体差异大,其血药浓度高低与肝、肾毒性损害和排斥反应密切相关.药物代谢转运蛋白(MDR)和药物代谢细胞色素P450同工酶(CYP450)的基因多态性可导致其编码的蛋白表达或活性呈现多态性,不同个体间对某种特定药物代谢的差异是不同个体编码基因的遗传多态性相互作用的结果,这种相互作用导致药物代谢分布以及药物靶标作用的较大差异.在常规临床血药浓度监测基础上,通过研究药物疗效中的遗传变异,分析个体遗传基因组成在决定药物疗效和代谢毒性的特征,检测个体药物反应遗传基因型和表型或基因多态性,预测个体对药物的治疗剂量已开始逐步应用于药物治疗的临床研究,这是临床检验工作者将面临的新任务与挑战.

  10. A Retrospective Chart Review of Treatment Seeking Middle Aged Individuals at a Tertiary Care Substance Use Disorder Treatment Centre in North Part of India over Five Successive Years: Findings from Drug Abuse Monitoring System

    Directory of Open Access Journals (Sweden)

    Yatan Pal Singh Balhara

    2013-01-01

    Full Text Available Adolescents and young adults continue to remain the main focus of attention with regards to substance use related problems. There has been a limited focus on illicit substance use among middle aged and elderly population. The current study explored the changing trends of substance use among treatment seeking middle aged individuals (aged 40–60 years at a tertiary level drug dependence treatment centre. The questionnaire used to gather information for the study is a 19-item structured questionnaire. It includes information on various sociodemographic variables, “current,” and “ever” use of substance. Information is also collected on variables related to high risk injecting drug use and HIV status of the individuals. There has been consistent increase in the population of treatment seekers over five years. Over the five-year period, the absolute percentage increase in treatment seeking population is approximately 21%. Polysubstance use was found to increase significantly over five-study years (PTrend = 0.007.

  11. Ethnicity, class, and civil war

    DEFF Research Database (Denmark)

    Hechter, Michael Norman; Siroky, David

    2016-01-01

    of political instability. These two types of conflict result from distinct principles of group solidarity – ethnicity and class – and since each individual is simultaneously a member of an ethnic group (or many such groups) and a particular class, these two principles vary in the degree to which......Why are some countries prone to ethno-nationalist conflict, whereas others are plagued by class conflict? This is a question that has seldom been raised and rarely been examined empirically. This paper presents a social-structural theory to account for the variable incidence of these two forms......-group inequalities are high, and within-group inequalities low, ethnicity should be the dominant principle of group solidarity and serve as the primary basis of group conflict. By contrast, in countries where between-group inequalities are low, and within-group inequalities high, class is more likely to serve...

  12. Class categories and the subjective dimension of class: the case of Denmark.

    Science.gov (United States)

    Harrits, Gitte Sommer; Pedersen, Helene Helboe

    2018-03-01

    Class relations have been proven to affect various aspects of social life, even in modern individualized societies. However, following claims on individualization and the so-called 'death of class' thesis, studying the subjective dimension of class - that is, the way individuals perceive of class relations and their own position within them - has gone out of style. We argue that even in equalized societies, subjective class perceptions may still influence attitudes and behaviour as they evolve to fit modern class relations. To explore the existence as well as structure and content of perceived social classes, this article investigates how people describe society and social groups in focus group discussions. We find that groups in different positions in terms of education and economy all tend to apply hierarchical class categories to describe Danish society, which is normally seen as one of the most equal societies and political systems in the world. In addition, we find that economic resources serve as a baseline for the hierarchical ordering, often supplemented with notions of education, lifestyle and/or occupational profile. Even though people are somewhat uncomfortable with the notion of class, their descriptions of Danish society and classes are surprisingly similar within and across groups. We conclude that not only do class relations matter; people are also highly aware of the existing classes and able to position themselves and others according to their notion of classes. © London School of Economics and Political Science 2017.

  13. Metformin alters the gut microbiome of individuals with treatment-naive type 2 diabetes, contributing to the therapeutic effects of the drug

    DEFF Research Database (Denmark)

    Wu, Hao; Esteve, Eduardo; Tremaroli, Valentina

    2017-01-01

    months and showed that metformin had strong effects on the gut microbiome. These results were verified in a subset of the placebo group that switched to metformin 6 months after the start of the trial. Transfer of fecal samples (obtained before and 4 months after treatment) from metformin-treated donors......Metformin is widely used in the treatment of type 2 diabetes (T2D), but its mechanism of action is poorly defined. Recent evidence implicates the gut microbiota as a site of metformin action. In a double-blind study, we randomized individuals with treatment-naive T2D to placebo or metformin for 4...... to germ-free mice showed that glucose tolerance was improved in mice that received metformin-altered microbiota. By directly investigating metformin-microbiota interactions in a gut simulator, we showed that metformin affected pathways with common biological functions in species from two different phyla...

  14. Current evidence of anti-tumor necrosis factor α treatment efficacy in childhood chronic uveitis: a systematic review and meta-analysis approach of individual drugs.

    Science.gov (United States)

    Simonini, Gabriele; Druce, Katie; Cimaz, Rolando; Macfarlane, Gary J; Jones, Gareth T

    2014-07-01

    To summarize evidence regarding the effectiveness of anti-tumor necrosis factor α (anti-TNFα) treatments in childhood autoimmune chronic uveitis (ACU), refractory to previous disease-modifying antirheumatic drugs (DMARDs). A systematic search between January 2000 and October 2012 was conducted using EMBase, Ovid Medline, Evidence-Based Medicine (EBM) Reviews: American College of Physicians Journal Club, Cochrane libraries, and EBM Reviews. Studies investigating the efficacy of anti-TNFα therapy, in children ages ≤16 years, as the first treatment with a biologic agent for ACU, refractory to topical and/or systemic steroid therapy and at least 1 DMARD, were eligible for inclusion. The primary outcome measure was the improvement of intraocular inflammation, as defined by the Standardization of Uveitis Nomenclature Working Group criteria. We determined a combined estimate of the proportion of children responding to anti-TNFα treatment, including etanercept (ETA), infliximab (INF), or adalimumab (ADA). We initially identified 989 articles, of which 148 were potentially eligible. In total, 22 retrospective chart reviews and 1 randomized clinical trial were deemed eligible, thus including 229 children (ADA: n = 31, ETA: n = 54, and INF: n = 144). On pooled analysis of observational studies, the proportion of responding children was 87% (95% confidence interval [95% CI] 75-98%) for ADA, 72% (95% CI 64-79%) for INF, and 33% (95% CI 19-47%) for ETA. There was no difference in the proportion of responders between ADA and INF (χ(2) = 3.06, P = 0.08), although both showed superior efficacy compared with ETA (ADA versus ETA: χ(2) = 20.9, P < 0.001 and INF versus ETA: χ(2) = 20.9, P < 0.001). Although randomized controlled trials are needed, the available evidence suggests that INF and ADA provide proven similar benefits in the treatment of childhood ACU, and they are both superior to ETA. Copyright © 2014 by the American College of Rheumatology.

  15. Chemokine (C-C motif) receptor 5-using envelopes predominate in dual/mixed-tropic HIV from the plasma of drug-naive individuals.

    Science.gov (United States)

    Irlbeck, David M; Amrine-Madsen, Heather; Kitrinos, Kathryn M; Labranche, Celia C; Demarest, James F

    2008-07-31

    HIV-1 utilizes CD4 and either chemokine (C-C motif) receptor 5 (CCR5) or chemokine (C-X-C motif) receptor 4 (CXCR4) to gain entry into host cells. Small molecule CCR5 antagonists are currently being developed for the treatment of HIV-1 infection. Because HIV-1 may also use CXCR4 for entry, the use of CCR5 entry inhibitors is controversial for patients harboring CCR5-using and CXCR4-using (dual/mixed-tropic) viruses. The goal of the present study was to determine the proportion of CCR5-tropic and CXCR4-tropic viruses in dual/mixed-tropic virus isolates from drug-naïve patients and the phenotypic and genotypic relationships of viruses that use CCR5 or CXCR4 or both. Fourteen antiretroviral-naive HIV-1-infected patients were identified as having population coreceptor tropism readout of dual/mixed-tropic viruses. Intrapatient comparisons of coreceptor tropism and genotype of env clones were conducted on plasma virus from each patient. Population HIV-1 envelope tropism and susceptibility to the CCR5 entry inhibitor, aplaviroc, were performed using the Monogram Biosciences Trofile Assay. Twelve env clones from each patient were analyzed for coreceptor tropism, aplaviroc sensitivity, genotype, and intrapatient phylogenetic relationships. Viral populations from antiretroviral-naive patients with dual/mixed-tropic virus are composed primarily of CCR5-tropic env clones mixed with those that use both coreceptors (R5X4-tropic) and, occasionally, CXCR4-tropic env clones. Interestingly, the efficiency of CXCR4 use by R5X4-tropic env clones varied with their genetic relationships to CCR5-tropic env clones from the same patient. These data show that the majority of viruses in these dual/mixed-tropic populations use CCR5 and suggest that antiretroviral-naive patients may benefit from combination therapy that includes CCR5 entry inhibitors.

  16. Exploring Class-Based Intersectionality

    Science.gov (United States)

    Block, David; Corona, Victor

    2014-01-01

    This paper argues that language, culture and identity researchers need to take the intersectionality of identity inscriptions seriously and, further to this, that an intersectional approach which emanates from an interest in social class provides a productive way to examine the lives and experience of individuals living in multicultural societies.…

  17. Drug Facts

    Medline Plus

    Full Text Available ... Get Addicted to Drugs? Does Addiction Run in Families? Why Is It So Hard to Quit Drugs? ... Drug Use and Other People Drug Use and Families Drug Use and Kids Drug Use and Unborn ...

  18. Drug Facts

    Medline Plus

    Full Text Available ... Facts Search form Search Menu Home Drugs That People Abuse Alcohol Facts Bath Salts Facts Cocaine (Coke, ... Drugs? Effects of Drugs Drug Use and Other People Drug Use and Families Drug Use and Kids ...

  19. Drug Facts

    Medline Plus

    Full Text Available ... People Drug Use and Families Drug Use and Kids Drug Use and Unborn Children Drug Use and ... Children and Teens Stay Drug-Free Talking to Kids About Drugs: What to Say if You Used ...

  20. [Non steroidal anti-inflammatory drugs and rheumatic diseases].

    Science.gov (United States)

    Cossermelli, W; Pastor, E H

    1995-01-01

    Nonsteroidal anti-inflammatory drugs (NSAID) comprise an important class of medicaments that reduced the symptoms of inflamation in rheumatic disease. This article emphasizes similarities and class characteristics of the NSAID, mechanisms of action, and drug-interactions.

  1. Fragmentation of toxicologically relevant drugs in positive-ion liquid chromatography-tandem mass spectrometry.

    Science.gov (United States)

    Niessen, W M A

    2011-01-01

    The identification of drugs and related compounds by LC-MS-MS is an important analytical challenge in several application areas, including clinical and forensic toxicology, doping control analysis, and environmental analysis. Although target-compound based analytical strategies are most frequently applied, at some point the information content of the MS-MS spectra becomes relevant. In this article, the positive-ion MS-MS spectra of a wide variety of drugs and related substances are discussed. Starting point was an MS-MS mass spectral library of toxicologically relevant compounds, available on the internet. The positive-ion MS-MS spectra of ∼570 compounds were interpreted by chemical and therapeutic class, thus involving a wide variety of drug compound classes, such benzodiazepines, beta-blockers, angiotensin-converting enzyme inhibitors, phenothiazines, dihydropyridine calcium channel blockers, diuretics, local anesthetics, vasodilators, as well as various subclasses of anti-diabetic, antidepressant, analgesic, and antihistaminic drugs. In addition, the scientific literature was searched for available MS-MS data of these compound classes and the interpretation thereof. The results of this elaborate study are presented in this article. For each individual compound class, the emphasis is on class-specific fragmentation, as discussing fragmentation of all individual compounds would take far too much space. The recognition of class-specific fragmentation may be quite informative in determining the compound class of a specific unknown, which may further help in the identification. In addition, knowledge on (class-specific) fragmentation may further help in the optimization of the selectivity in targeted analytical approaches of compounds of one particular class. Copyright © 2011 Wiley Periodicals, Inc.

  2. Social defeat protocol and relevant biomarkers, implications for stress response physiology, drug abuse, mood disorders and individual stress vulnerability: a systematic review of the last decade.

    Science.gov (United States)

    Vasconcelos, Mailton; Stein, Dirson João; de Almeida, Rosa Maria M

    2015-01-01

    Social defeat (SD) in rats, which results from male intraspecific confrontations, is ethologically relevant and useful to understand stress effects on physiology and behavior. A systematic review of studies about biomarkers induced by the SD protocol and published from 2002 to 2013 was carried out in the electronic databases PubMed, Web of Knowledge and ScienceDirect. The search terms were: social defeat, rat, neurotrophins, neuroinflammatory markers, and transcriptional factors. Classical and recently discovered biomarkers were found to be relevant in stress-induced states. Findings were summarized in accordance to the length of exposure to stress: single, repeated, intermittent and continuous SD. This review found that the brain-derived neurotrophic factor (BDNF) is a distinct marker of stress adaptation. Along with glucocorticoids and catecholamines, BDNF seems to be important in understanding stress physiology. The SD model provides a relevant tool to study stress response features, development of addictive behaviors, clinic depression and anxiety, as well as individual differences in vulnerability and resilience to stress.

  3. Social defeat protocol and relevant biomarkers, implications for stress response physiology, drug abuse, mood disorders and individual stress vulnerability: a systematic review of the last decade

    Directory of Open Access Journals (Sweden)

    Mailton Vasconcelos

    2015-06-01

    Full Text Available Introduction: Social defeat (SD in rats, which results from male intraspecific confrontations, is ethologically relevant and useful to understand stress effects on physiology and behavior.Methods: A systematic review of studies about biomarkers induced by the SD protocol and published from 2002 to 2013 was carried out in the electronic databases PubMed, Web of Knowledge and ScienceDirect. The search terms were: social defeat, rat, neurotrophins, neuroinflammatory markers, and transcriptional factors.Results: Classical and recently discovered biomarkers were found to be relevant in stress-induced states. Findings were summarized in accordance to the length of exposure to stress: single, repeated, intermittent and continuous SD. This review found that the brain-derived neurotrophic factor (BDNF is a distinct marker of stress adaptation. Along with glucocorticoids and catecholamines, BDNF seems to be important in understanding stress physiology.Conclusion: The SD model provides a relevant tool to study stress response features, development of addictive behaviors, clinic depression and anxiety, as well as individual differences in vulnerability and resilience to stress.

  4. An analysis of legal warnings after drug approval in Thailand.

    Science.gov (United States)

    Sriphiromya, Pakawadee; Theeraroungchaisri, Anuchai

    2015-02-01

    Drug risk management has many tools for minimizing risk and black-boxed warnings (BBWs) are one of those tools. Some serious adverse drug reactions (ADRs) emerge only after a drug is marketed and used in a larger population. In Thailand, additional legal warnings after drug approval, in the form of black-boxed warnings, may be applied. Review of their characteristics can assist in the development of effective risk mitigation. This study was a cross sectional review of all legal warnings imposed in Thailand after drug approval (2003-2012). Any boxed warnings for biological products and revised warnings which were not related to safety were excluded. Nine legal warnings were evaluated. Seven related to drugs classes and two to individual drugs. The warnings involved four main types of predictable ADRs: drug-disease interactions, side effects, overdose and drug-drug interactions. The average time from first ADRs reported to legal warnings implementation was 12 years. The triggers were from both safety signals in Thailand and regulatory measures in other countries outside Thailand. Copyright © 2014 Elsevier Inc. All rights reserved.

  5. Motives for using: a comparison of prescription opioid, marijuana and cocaine dependent individuals.

    Science.gov (United States)

    Hartwell, Karen J; Back, Sudie E; McRae-Clark, Aimee L; Shaftman, Stephanie R; Brady, Kathleen T

    2012-04-01

    Identification of the motives for drug use is critical to the development of effective interventions. Furthermore, consideration of the differences in motives for drug use across substance dependent populations may assist in tailoring interventions. To date, few studies have systematically compared motives for substance use across drug classes. The current study examined motives for drug use between non-treatment seeking individuals with current prescription opioid, marijuana, or cocaine dependence. Participants (N=227) completed the Inventory of Drug-Taking Situations (IDTS; Annis, Turner & Sklar,1997), which contains eight subscales assessing motives for drug use. The findings revealed that prescription opioid dependent individuals scored significantly higher than all other groups on the Physical Discomfort, Testing Personal Control and Conflict with Others subscales. Both the prescription opioid and cocaine dependent groups scored significantly higher than the marijuana group on the Urges or a Temptation to Use subscale. In contrast, marijuana dependent individuals scored highest on the Pleasant Emotions and Pleasant Times with Others subscales. The marked differences revealed in motives for drug use could be used in the development and implementation of specific treatment interventions for prescription opioid, marijuana and cocaine dependent individuals. Published by Elsevier Ltd.

  6. Polypharmacy: correlations with sex, age and drug regimen

    DEFF Research Database (Denmark)

    Bjerrum, L; Søgaard, J; Hallas, J

    1998-01-01

    by inhabitants in the county of Funen (n = 466567). The number of individuals concurrently using two to four drugs (minor PP) and five or more drugs (major PP) was calculated on a random day in 1994. Drugs were classified according to the Anatomical Therapeutical Chemical (ATC) classification index. The main...... therapeutic class (second level of the ATC code) was used as an indicator for the type of health problem. A stepwise backwards logistic regression was used to identify predictors of major PP. Odds ratios were calculated for different drug classes, and the age and sex of all drug users. RESULTS: On a random...... day, 8.3% of the population were exposed to minor PP and 1.2% to major PP. The prevalence of PP increased with age, and from the age of 70 years, two thirds of all drug users were PP users. Drug use was 50% more prevalent among women than men, but over the age of 70, the sexes did not differ...

  7. Sociology of Drug Consumption

    OpenAIRE

    2004-01-01

    In this article which is a review of sociological ideas and studies of drug abusers in social situation, drug addiction steps (particularly alcohol, heroin and cocaine consumption) are revised and some explanations are made. Also, the role of some sociological ideas in drug addiction is considered in which Anomie Theory reads: "because of such duality, the individuals who are not satisfied with their role are in hurt." According to this theory, drug users choose seclusion and neglecting usual...

  8. Rings in drugs.

    Science.gov (United States)

    Taylor, Richard D; MacCoss, Malcolm; Lawson, Alastair D G

    2014-07-24

    We have analyzed the rings, ring systems, and frameworks in drugs listed in the FDA Orange Book to understand the frequency, timelines, molecular property space, and the application of these rings in different therapeutic areas and target classes. This analysis shows that there are only 351 ring systems and 1197 frameworks in drugs that came onto the market before 2013. Furthermore, on average six new ring systems enter drug space each year and approximately 28% of new drugs contain a new ring system. Moreover, it is very unusual for a drug to contain more than one new ring system and the majority of the most frequently used ring systems (83%) were first used in drugs developed prior to 1983. These observations give insight into the chemical novelty of drugs and potentially efficient ways to assess compound libraries and develop compounds from hit identification to lead optimization and beyond.

  9. The structural dynamics of social class.

    Science.gov (United States)

    Kraus, Michael W; Park, Jun Won

    2017-12-01

    Individual agency accounts of social class persist in society and even in psychological science despite clear evidence for the role of social structures. This article argues that social class is defined by the structural dynamics of society. Specifically, access to powerful networks, groups, and institutions, and inequalities in wealth and other economic resources shape proximal social environments that influence how individuals express their internal states and motivations. An account of social class that highlights the means by which structures shape and are shaped by individuals guides our understanding of how people move up or down in the social class hierarchy, and provides a framework for interpreting neuroscience studies, experimental paradigms, and approaches that attempt to intervene on social class disparities. Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. Exploring social class differences at work

    OpenAIRE

    Evans, Samantha

    2016-01-01

    This paper is part of a wider project that investigates how organisational and individual factors within the workplace contribute to social class differences and inequality by examining the relative impact of objective and subjective indicators of social class on explicit (e.g. salary, promotions) and implicit (e.g. career satisfaction, quality of working life, stress and well-being) career and work outcomes. \\ud There is increasing recognition that social class differences play a crucial rol...

  11. Polydrug Use and HIV Risk Among People Who Inject Heroin in Tijuana, Mexico: A Latent Class Analysis.

    Science.gov (United States)

    Meacham, Meredith C; Rudolph, Abby E; Strathdee, Steffanie A; Rusch, Melanie L; Brouwer, Kimberly C; Patterson, Thomas L; Vera, Alicia; Rangel, Gudelia; Roesch, Scott C

    2015-01-01

    Although most people who inject drugs (PWID) in Tijuana, Mexico, primarily inject heroin, injection and non-injection use of methamphetamine and cocaine is common. We examined patterns of polydrug use among heroin injectors to inform prevention and treatment of drug use and its health and social consequences. Participants were PWID residing in Tijuana, aged ≥18 years who reported heroin injection in the past six months and were recruited through respondent-driven sampling (n = 1,025). Latent class analysis was conducted to assign individuals to classes on a probabilistic basis, using four indicators of past six-month polydrug and polyroute use: cocaine injecting, cocaine smoking or snorting, methamphetamine injecting, and methamphetamine smoking or snorting. Latent class membership was regressed onto covariates in a multinomial logistic regression. Latent class analyses testing 1, 2, 3, and 4 classes were fit, with the 3-class solution fitting best. Class 1 was defined by predominantly heroin use (50.2%, n = 515); class 2 by methamphetamine and heroin use (43.7%, n = 448), and class 3 by methamphetamine, cocaine, and heroin use (6.0%, n = 62). Bivariate and multivariate analyses indicated a group of methamphetamine and cocaine users that exhibited higher-risk sexual practices and lower heroin injecting frequency, and a group of methamphetamine users who were younger and more likely to be female. Discrete subtypes of heroin PWID were identified based on methamphetamine and cocaine use patterns. These findings have identified subtypes of heroin injectors who require more tailored interventions to reduce the health and social harms of injecting drug use.

  12. Reimbursement-Based Economics--What Is It and How Can We Use It to Inform Drug Policy Reform?

    Science.gov (United States)

    Coyle, Doug; Lee, Karen M; Mamdani, Muhammad; Sabarre, Kelley-Anne; Tingley, Kylie

    2015-01-01

    In Ontario, approximately $3.8 billion is spent annually on publicly funded drug programs. The annual growth in Ontario Public Drug Program (OPDP) expenditure has been limited to 1.2% over the course of 3 years. Concurrently, the Ontario Drug Policy Research Network (ODPRN) was appointed to conduct drug class review research relating to formulary modernization within the OPDP. Drug class reviews by ODPRN incorporate a novel methodological technique called reimbursement-based economics, which focuses on reimbursement strategies and may be particularly relevant for policy-makers. To describe the reimbursement-based economics approach. Reimbursement-based economics aims to identify the optimal reimbursement strategy for drug classes by incorporating a review of economic literature, comprehensive budget impact analyses, and consideration of cost-effectiveness. This 3-step approach is novel in its focus on the economic impact of alternate reimbursement strategies rather than individual therapies. The methods involved within the reimbursement-based approach are detailed. To facilitate the description, summary methods and findings from a recent application to formulary modernization with respect to the drug class tryptamine-based selective serotonin receptor agonists (triptans) used to treat migraine headaches are presented. The application of reimbursement-based economics in drug policy reforms allows policy-makers to consider the cost-effectiveness and budget impact of different reimbursement strategies allowing consideration of the trade-off between potential cost savings vs increased access to cost-effective treatments. © 2015 American Headache Society.

  13. Atomoxetine could improve intra-individual variability in drug-naïve adults with attention-deficit/hyperactivity disorder comparably with methylphenidate: A head-to-head randomized clinical trial.

    Science.gov (United States)

    Ni, Hsing-Chang; Hwang Gu, Shoou-Lian; Lin, Hsiang-Yuan; Lin, Yu-Ju; Yang, Li-Kuang; Huang, Hui-Chun; Gau, Susan Shur-Fen

    2016-05-01

    Intra-individual variability in reaction time (IIV-RT) is common in individuals with attention-deficit/hyperactivity disorder (ADHD). It can be improved by stimulants. However, the effects of atomoxetine on IIV-RT are inconclusive. We aimed to investigate the effects of atomoxetine on IIV-RT, and directly compared its efficacy with methylphenidate in adults with ADHD. An 8-10 week, open-label, head-to-head, randomized clinical trial was conducted in 52 drug-naïve adults with ADHD, who were randomly assigned to two treatment groups: immediate-release methylphenidate (n=26) thrice daily (10-20 mg per dose) and atomoxetine once daily (n=26) (0.5-1.2 mg/kg/day). IIV-RT, derived from the Conners' continuous performance test (CCPT), was represented by the Gaussian (reaction time standard error, RTSE) and ex-Gaussian models (sigma and tau). Other neuropsychological functions, including response errors and mean of reaction time, were also measured. Participants received CCPT assessments at baseline and week 8-10 (60.4±6.3 days). We found comparable improvements in performances of CCPT between the immediate-release methylphenidate- and atomoxetine-treated groups. Both medications significantly improved IIV-RT in terms of reducing tau values with comparable efficacy. In addition, both medications significantly improved inhibitory control by reducing commission errors. Our results provide evidence to support that atomoxetine could improve IIV-RT and inhibitory control, of comparable efficacy with immediate-release methylphenidate, in drug-naïve adults with ADHD. Shared and unique mechanisms underpinning these medication effects on IIV-RT awaits further investigation. © The Author(s) 2016.

  14. Hepatic transporter drug-drug interactions: an evaluation of approaches and methodologies.

    Science.gov (United States)

    Williamson, Beth; Riley, Robert J

    2017-12-01

    Drug-drug interactions (DDIs) continue to account for 5% of hospital admissions and therefore remain a major regulatory concern. Effective, quantitative prediction of DDIs will reduce unexpected clinical findings and encourage projects to frontload DDI investigations rather than concentrating on risk management ('manage the baggage') later in drug development. A key challenge in DDI prediction is the discrepancies between reported models. Areas covered: The current synopsis focuses on four recent influential publications on hepatic drug transporter DDIs using static models that tackle interactions with individual transporters and in combination with other drug transporters and metabolising enzymes. These models vary in their assumptions (including input parameters), transparency, reproducibility and complexity. In this review, these facets are compared and contrasted with recommendations made as to their application. Expert opinion: Over the past decade, static models have evolved from simple [I]/k i models to incorporate victim and perpetrator disposition mechanisms including the absorption rate constant, the fraction of the drug metabolised/eliminated and/or clearance concepts. Nonetheless, models that comprise additional parameters and complexity do not necessarily out-perform simpler models with fewer inputs. Further, consideration of the property space to exploit some drug target classes has also highlighted the fine balance required between frontloading and back-loading studies to design out or 'manage the baggage'.

  15. Impact of nanotechnology on drug delivery.

    Science.gov (United States)

    Farokhzad, Omid C; Langer, Robert

    2009-01-27

    Nanotechnology is the engineering and manufacturing of materials at the atomic and molecular scale. In its strictest definition from the National Nanotechnology Initiative, nanotechnology refers to structures roughly in the 1-100 nm size regime in at least one dimension. Despite this size restriction, nanotechnology commonly refers to structures that are up to several hundred nanometers in size and that are developed by top-down or bottom-up engineering of individual components. Herein, we focus on the application of nanotechnology to drug delivery and highlight several areas of opportunity where current and emerging nanotechnologies could enable entirely novel classes of therapeutics.

  16. Combination Classes and "Hora de comunicacion."

    Science.gov (United States)

    Eldredge, Dee L.

    1989-01-01

    Ways to combine small classes of higher education students studying Spanish at various levels are described, including judicious use of language laboratories, staggering of the different level groups, and rotation of activities geared toward students' individual proficiency levels. (CB)

  17. Social class rank, essentialism, and punitive judgment.

    Science.gov (United States)

    Kraus, Michael W; Keltner, Dacher

    2013-08-01

    Recent evidence suggests that perceptions of social class rank influence a variety of social cognitive tendencies, from patterns of causal attribution to moral judgment. In the present studies we tested the hypotheses that upper-class rank individuals would be more likely to endorse essentialist lay theories of social class categories (i.e., that social class is founded in genetically based, biological differences) than would lower-class rank individuals and that these beliefs would decrease support for restorative justice--which seeks to rehabilitate offenders, rather than punish unlawful action. Across studies, higher social class rank was associated with increased essentialism of social class categories (Studies 1, 2, and 4) and decreased support for restorative justice (Study 4). Moreover, manipulated essentialist beliefs decreased preferences for restorative justice (Study 3), and the association between social class rank and class-based essentialist theories was explained by the tendency to endorse beliefs in a just world (Study 2). Implications for how class-based essentialist beliefs potentially constrain social opportunity and mobility are discussed.

  18. Social class and prosocial behavior: current evidence, caveats, and questions.

    Science.gov (United States)

    Piff, Paul K; Robinson, Angela R

    2017-12-01

    This review synthesizes research on social class and prosocial behavior. Individuals of lower social class display increased attention to others and greater sensitivity to others' welfare compared to individuals of higher social class, who exhibit more self-oriented patterns of social cognition. As a result, lower-class individuals are more likely to engage in other-beneficial prosocial behavior, whereas higher-class individuals are more prone to engage in self-beneficial behavior. Although the extant evidence indicates that higher social class standing may tend to undermine prosocial impulses, we propose that the effects of social class on prosocial behavior may also depend on three crucial factors: motivation, identity, and inequality. We discuss how and why these factors may moderate class differences in prosociality and offer promising lines of inquiry for future research. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. Drug Facts

    Medline Plus

    Full Text Available ... Treatment and Recovery Resources? Prevention Help Children and Teens Stay Drug-Free Talking to Kids About Drugs: What to Say if You Used Drugs in the Past Drug Use ... Videos Information About Drugs Alcohol ...

  20. Drug Allergy

    Science.gov (United States)

    ... Loss of consciousness Other conditions resulting from drug allergy Less common drug allergy reactions occur days or ... you take the drug. Drugs commonly linked to allergies Although any drug can cause an allergic reaction, ...

  1. 38 CFR 48.655 - Individual.

    Science.gov (United States)

    2010-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 2 2010-07-01 2010-07-01 false Individual. 48.655...) GOVERNMENTWIDE REQUIREMENTS FOR DRUG-FREE WORKPLACE (FINANCIAL ASSISTANCE) Definitions § 48.655 Individual. Individual means a natural person. ...

  2. Associação entre doença hepática gordurosa não alcoólica e marcadores de lesão/função hepática com componentes da síndrome metabólica em indivíduos obesos classe III Association between non-alcoholic fatty liver disease and liver function/injury markers with metabolic syndrome components in class III obese individuals

    Directory of Open Access Journals (Sweden)

    Gabriela Villaça Chaves

    2012-06-01

    Full Text Available OBJETIVO: Investigar a associação entre doença hepática gordurosa não alcoólica (DHGNA e os marcadores de lesão e função hepática com os componentes da síndrome metabólica (SM em indivíduos obesos classe III. MÉTODOS: A população estudada foi constituída por 144 pacientes com obesidade classe III (IMC > a 40 kg/m². A SM foi identificada segundo o critério do NCEP ATP III, por meio da determinação do perfil lipídico, glicemia e insulina basal. Foram quantificados ainda os marcadores de função e lesão hepática. A resistência à insulina (RI foi verificada pelo índice HOMA-IR e o diagnóstico da DHGNA por ressonância magnética. Os cálculos estatísticos foram realizados pelo programa estatístico SPSS na versão 13.0. A associação foi verificada pelo teste Mann-Whitney e qui-quadrado, com nível de significância de 5%. RESULTADOS: Foi encontrada associação significativa entre o diagnóstico de SM e DHGNA (χ² = 6,84; p = 0,01. Quanto aos componentes diagnósticos para SM, constatou-se associação positiva e significativa entre HDL-c (p = 0,05, circunferência da cintura (p OBJECTIVE: To investigate the association between non-alcoholic fatty liver disease (NAFLD and liver function/injury markers with components of metabolic syndrome (MS in class III obese individuals. METHODS: The study population consisted of 144 patients with class III obesity (body mass index [BMI] > 40 kg/m². MS was diagnosed according to the National Cholesterol Education Program - Adult Treatment Panel III (NCEP ATP III criteria, by determining the lipid profile, blood glucose and basal insulin. Liver function/injury markers were also quantified. Insulin resistance (IR was measured by HOMA-IR and NAFLD diagnosis was established by magnetic resonance imaging (MRI. Statistical calculations were performed by SPSS version 13.0. The association was assessed by the Mann-Whitney and Chi-square tests, with a level of significance set at 5

  3. Sex Differences in Drug Abuse

    OpenAIRE

    Becker, Jill B.; Hu, Ming

    2007-01-01

    Sex differences are present for all of the phases of drug abuse (initiation, escalation of use, addiction, and relapse following abstinence). While there are some differences among specific classes of abused drugs, the general pattern of sex differences is the same for all drugs of abuse. Females begin regularly self-administering licit and illicit drugs of abuse at lower doses than do males, use escalates more rapidly to addiction, and females are at greater risk for relapse following abstin...

  4. Bioadhesive polymeric platforms for transmucosal drug delivery ...

    African Journals Online (AJOL)

    Bioadhesive polymeric platforms for transmucosal drug delivery systems – a review. ... administration of certain classes of drugs, especially peptides and proteins. ... characteristics of desired bioadhesive polymers, this article then proceeds to ...

  5. Chemical reaction vector embeddings: towards predicting drug metabolism in the human gut microbiome.

    Science.gov (United States)

    Mallory, Emily K; Acharya, Ambika; Rensi, Stefano E; Turnbaugh, Peter J; Bright, Roselie A; Altman, Russ B

    2018-01-01

    Bacteria in the human gut have the ability to activate, inactivate, and reactivate drugs with both intended and unintended effects. For example, the drug digoxin is reduced to the inactive metabolite dihydrodigoxin by the gut Actinobacterium E. lenta, and patients colonized with high levels of drug metabolizing strains may have limited response to the drug. Understanding the complete space of drugs that are metabolized by the human gut microbiome is critical for predicting bacteria-drug relationships and their effects on individual patient response. Discovery and validation of drug metabolism via bacterial enzymes has yielded >50 drugs after nearly a century of experimental research. However, there are limited computational tools for screening drugs for potential metabolism by the gut microbiome. We developed a pipeline for comparing and characterizing chemical transformations using continuous vector representations of molecular structure learned using unsupervised representation learning. We applied this pipeline to chemical reaction data from MetaCyc to characterize the utility of vector representations for chemical reaction transformations. After clustering molecular and reaction vectors, we performed enrichment analyses and queries to characterize the space. We detected enriched enzyme names, Gene Ontology terms, and Enzyme Consortium (EC) classes within reaction clusters. In addition, we queried reactions against drug-metabolite transformations known to be metabolized by the human gut microbiome. The top results for these known drug transformations contained similar substructure modifications to the original drug pair. This work enables high throughput screening of drugs and their resulting metabolites against chemical reactions common to gut bacteria.

  6. Recreational drugs of abuse.

    Science.gov (United States)

    Albertson, Timothy E

    2014-02-01

    The use of recreational drugs of abuse continues to expand without limitations to national boundaries, social status, race, or education. Beyond the prevalence of illicit drug use and dependence, their contribution to the global burden of disease and death are large and troubling. All medical providers should be aware of the evolving drugs of abuse and their medical and social consequences. In addition to heroin and stimulants such as cocaine and methamphetamine, new designer stimulants called "bath salts" and cannabinoids called "spice," along with the abuse of prescription drugs and volatile substances, are now widely recognized problems in many societies. The wide variety and continuingly expanding clinical manifestations of toxicity of recreational drugs of abuse is not widely appreciated by clinicians. This edition attempts to summarize six major classes of drugs of abuse and their clinical effects with special emphasis on their immunological and respiratory effects.

  7. Immunosuppressive drugs and fertility

    OpenAIRE

    Leroy, Clara; Rigot, Jean-Marc; Leroy, Maryse; Decanter, Christine; Le Mapihan, Kristell; Parent, Anne-Sophie; Le Guillou, Anne-Claire; Yakoub-Agha, Ibrahim; Dharancy, Sébastien; Noel, Christian; Vantyghem, Marie-Christine

    2015-01-01

    Immunosuppressive drugs are used in the treatment of inflammatory and autoimmune diseases, as well as in transplantation. Frequently prescribed in young people, these treatments may have deleterious effects on fertility, pregnancy outcomes and the unborn child. This review aims to summarize the main gonadal side effects of immunosuppressants, to detail the effects on fertility and pregnancy of each class of drug, and to provide recommendations on the management of patients who are seen prior ...

  8. The White Adolescent's Drug Odyssey.

    Science.gov (United States)

    Lipton, Douglas S.; Marel, Rozanne

    1980-01-01

    Presents a "typical" case history of a White middle-class teenager who becomes involved with marihuana and subsequently begins to abuse other drugs. Sociological findings from other research are interspersed in the anecdotal account. (GC)

  9. Individualized Medicine

    Energy Technology Data Exchange (ETDEWEB)

    Mariella, R.

    2000-08-29

    The recent focus of microelectromechanical-systems (MEMS) based instrumentation has largely dealt with increasing the throughput of established processes, including drug screening/drug discovery/combinatorial chemistry, or the miniaturization of accepted bench-top instruments. The miniaturization and automation of procedures that were previously performed manually are included in these activities. We suggest that BioMEMS instrumentation will adopt an additional direction, that of providing information and capabilities to the physician that are not available, today.

  10. [Hepatox: database on hepatotoxic drugs].

    Science.gov (United States)

    Quinton, A; Latry, P; Biour, M

    1993-01-01

    Hepatox is a data base on the hepatotoxic drugs file published every year in Gastroentérologie Clinique et Biologique. The program was developed under Omnis 7 for Apple computers, and under Visual Basic Professional Toolkit and Code Base for IBM PC and compatibles computers. The data base includes forms of 866 drugs identified by their approved name and those of their 1,300 corresponding proprietary names in France; drugs are distributed among 104 pharmacological classes. It is possible to have instantaneously access to the card of a drug identified by its approved name. Acceding to a drug identified by its proprietary name gives a list of the approved name of its components; going from a name of this list to the correspondent card of hepatoxicity is immediate. It is easy to extract lists of drugs responsible of a type of hepatic injury, and a table of types of hepatic injuries induced by the drugs of a pharmacological class.

  11. Class 1 Areas

    Data.gov (United States)

    U.S. Environmental Protection Agency — A "Class 1" area is a geographic area recognized by the EPA as being of the highest environmental quality and requiring maximum protection. Class I areas are areas...

  12. PRCR Classes and Activities

    Data.gov (United States)

    Town of Cary, North Carolina — This data is specific to Parks and Recreation classes, workshops, and activities within the course catalog. It contains an entry for upcoming classes.*This data set...

  13. Class Notes for "Class-Y-News."

    Science.gov (United States)

    Stuart, Judy L.

    1991-01-01

    A self-contained class of students with mild to moderate disabilities published a monthly newsletter which was distributed to students' families. Students became involved in writing, typing, drawing, folding, basic editing, and disseminating. (JDD)

  14. Classed identities in adolescence

    OpenAIRE

    Jay, Sarah

    2015-01-01

    peer-reviewed The central argument of this thesis is that social class remains a persistent system of inequality in education, health, life chances and opportunities. Therefore class matters. But why is it that so little attention has been paid to class in the psychological literature? Three papers are presented here which draw together theoretical advances in psychological understandings of group processes and sociological understandings of the complexity of class. As western labour marke...

  15. The emergence of the work class "family farmer" as individuals with rights in the path of the Brazilian rural syndicalism A emergência dos "agricultores familiares" como sujeitos de direitos na trajetória do sindicalismo rural brasileiro

    Directory of Open Access Journals (Sweden)

    Everton Lazzaretti Picolotto

    2009-01-01

    Full Text Available The process of the family farmers' recognition as individuals with rights demonstrates having their first roots, in spite of being recent, if compared to the history of the Brazilian rural syndicalism, still in the constitution of the labor-syndical legislation in 1930. Therefore, seeking to explore that process the present paper has as objective to analyze the family farmers' emergence as individuals of rights in the contemporary Brazilian society, analyzing the processes of formation of the rural syndicalism and the expansion of the labor law for the rural workers as a form of accomplishment of a "regulated citizenship" until the decade of 1970; the urge to the official syndicalism, the structuring of a "new syndicalism" and the new social actors' appearance in the field, which made possible the enlargement of the citizenship spaces in the period of re-democratization in Brazil; the "crisis" of the new syndicalism, the creation of new syndical structures "apart" of the official structure (syndicalism of the family agriculture and the emergency of the "family farmers" as subject of rights in the recent periodO processo de reconhecimento dos agricultores familiares como sujeitos de direitos apesar de ser recente quando pensado a partir da trajetória do sindicalismo rural brasileiro demonstra ter suas primeiras raízes ainda na constituição da legislação trabalhista-sindical dos anos de 1930. Visando explorar esse processo o artigo tem por objetivo analisar a emergência dos agricultores familiares como sujeitos de direitos na sociedade brasileira contemporânea. Analisa-se os processos de formação do sindicalismo rural e de expansão da legislação trabalhista para os trabalhadores rurais como forma de realização de uma "cidadania regulada" até a década de 1970; o questionamento do sindicalismo oficial, a estruturação de um "novo sindicalismo" e a emergência de novos atores sociais no campo, que possibilitaram a ampliação dos

  16. Identifying classes of persons with mild intellectual disability or borderline intellectual functioning: a latent class analysis.

    Science.gov (United States)

    Nouwens, Peter J G; Lucas, Rosanne; Smulders, Nienke B M; Embregts, Petri J C M; van Nieuwenhuizen, Chijs

    2017-07-17

    Persons with mild intellectual disability or borderline intellectual functioning are often studied as a single group with similar characteristics. However, there are indications that differences exist within this population. Therefore, the aim of this study was to identify classes of persons with mild intellectual disability or borderline intellectual functioning and to examine whether these classes are related to individual and/or environmental characteristics. Latent class analysis was performed using file data of 250 eligible participants with a mean age of 26.1 (SD 13.8, range 3-70) years. Five distinct classes of persons with mild intellectual disability or borderline intellectual functioning were found. These classes significantly differed in individual and environmental characteristics. For example, persons with a mild intellectual disability experienced fewer problems than those with borderline intellectual disability. The identification of five classes implies that a differentiated approach is required towards persons with mild intellectual disability or borderline intellectual functioning.

  17. Nonimaging detectors in drug development and approval.

    Science.gov (United States)

    Wagner, H N

    2001-07-01

    Regulatory applications for imaging biomarkers will expand in proportion to the validation of specific parameters as they apply to individual questions in the management of disease. This validation is likely to be applicable only to a particular class of drug or a single mechanism of action. Awareness among the world's regulatory authorities of the potential for these emerging technologies is high, but so is the cost to the sponsor (including the logistics of including images in a dossier), and therefore the pharmaceutical industry must evaluate carefully the potential benefit of each technology for its drug development programs, just as the authorities must consider carefully the extent to which the method is valid for the use to which the applicant has put it. For well-characterized tracer systems, it may be possible to design inexpensive cameras that make rapid assessments.

  18. Drug Safety

    Science.gov (United States)

    ... over-the-counter drug. The FDA evaluates the safety of a drug by looking at Side effects ... clinical trials The FDA also monitors a drug's safety after approval. For you, drug safety means buying ...

  19. Drug Abuse

    Science.gov (United States)

    ... Cocaine Heroin Inhalants Marijuana Prescription drugs, including opioids Drug abuse also plays a role in many major social problems, such as drugged driving, violence, stress, and child abuse. Drug abuse can lead to ...

  20. Drug Facts

    Medline Plus

    Full Text Available ... Use and Unborn Children Drug Use and Your Health Other Effects on the Body Drug Use Hurts Brains Drug Use and Mental Health Problems Often Happen Together The Link Between Drug ...

  1. Drug Facts

    Medline Plus

    Full Text Available ... Drug Use and Kids Drug Use and Unborn Children Drug Use and Your Health Other Effects on ... Someone Find Treatment and Recovery Resources? Prevention Help Children and Teens Stay Drug-Free Talking to Kids ...

  2. Club Drugs

    Science.gov (United States)

    ... uses. Other uses of these drugs are abuse. Club drugs are also sometimes used as "date rape" drugs, to make someone unable to say no to or fight back against sexual assault. Abusing these drugs can ...

  3. Glutamatergic transmission in drug reward: implications for drug addiction

    OpenAIRE

    D'Souza, Manoranjan S.

    2015-01-01

    Individuals addicted to drugs of abuse such as alcohol, nicotine, cocaine, and heroin are a significant burden on healthcare systems all over the world. The positive reinforcing (rewarding) effects of the above mentioned drugs play a major role in the initiation and maintenance of the drug-taking habit. Thus, understanding the neurochemical mechanisms underlying the reinforcing effects of drugs of abuse is critical to reducing the burden of drug addiction in society. Over the last two decades...

  4. Radioimmunoassay of drugs in body fluids in a forensic context

    International Nuclear Information System (INIS)

    Smith, R.N.

    1988-01-01

    The first article of the volume describes the theory and practice of RIA with particular reference to the analysis of drugs in body fluids in a forensic context. RIA theory is outlined from basic principles but the inherent assumptions are often inapplicable in practice and so the empirical design of an assay is considered in detail. Particular emphasis is given to the development of assays for drugs screening that detect classes of structurally related compounds rather than individual drugs. The preparation of radiolabelled drugs, the synthesis of immunogens for raising anitisera, the production of polyclonal and monoclonal antisera, and methods for separating free and antibody-bound antigens are reviewed. Quality assurance, trouble-shooting and the possible hazards of forensic RIA are discussed, and published RIA methods for drug analysis are tabulated. Many non-isotopic immunoassays have been developed in recent years but are omitted from this account because to date they are less applicable than RIA to samples such as haemolysed blood that are frequently encountered in forensic toxicology. Future progress in forensic drug RIA is likely to be concerned with applying the technique to more compounds, improving the methods for preparing immunogens and radiolabelled drugs, and investigating the use of monoclonal anti-drug antibodies. (orig./MG)

  5. Loosely coupled class families

    DEFF Research Database (Denmark)

    Ernst, Erik

    2001-01-01

    are expressed using virtual classes seem to be very tightly coupled internally. While clients have achieved the freedom to dynamically use one or the other family, it seems that any given family contains a xed set of classes and we will need to create an entire family of its own just in order to replace one...... of the members with another class. This paper shows how to express class families in such a manner that the classes in these families can be used in many dierent combinations, still enabling family polymorphism and ensuring type safety....

  6. [New oral antidiabetic drugs].

    Science.gov (United States)

    Féry, F

    2014-09-01

    The therapeutic options for type 2 diabetes have grown considerably in recent years with the successive emergence on the market of glitazones, incretin mimetics, gliptins and very soon gliflozins. Meanwhile, physicians have been advised to take into account individual patient characteristics and preferences when setting glycemic targets and choosing the most appropriate molecule. Faced with an abundance of options, clinicians, even those specialized in diabetology, are left confused and are divided in their choices. To guide them in their practice, the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD) jointly published a position statement in 2012. The guidelines posit that the main criteria to be considered are glucose-lowering efficacy, risk of hypoglycemia, effect on body weight, side effects and costs. Not surprisingly, they propose metformin as first line treatment but do not formulate a precise indication regarding the molecule to be introduced in case of metformin contra-indication, intolerance or monotherapy failure. In addition, there is no mention of gliflozins, which were still under evaluation at the time but are now approved and already marketed in some countries. Here we review the mechanisms of action, efficacy and side effects of the two most recent drug classes, namely incretin-based therapies and gliflozins, and try to position them in the therapeutic algorithm of type 2 diabetes.

  7. Microfluidic device for drug delivery

    Science.gov (United States)

    Beebe, David J. (Inventor); MacDonald, Michael J. (Inventor); Eddington, David T. (Inventor); Mensing, Glennys A. (Inventor)

    2010-01-01

    A microfluidic device is provided for delivering a drug to an individual. The microfluidic device includes a body that defines a reservoir for receiving the drug therein. A valve interconnects the reservoir to an output needle that is insertable into the skin of an individual. A pressure source urges the drug from the reservoir toward the needle. The valve is movable between a closed position preventing the flow of the drug from the reservoir to the output needle and an open position allowing for the flow of the drug from the reservoir to the output needle in response to a predetermined condition in the physiological fluids of the individual.

  8. Vitiligo, drug induced (image)

    Science.gov (United States)

    ... this person's face have resulted from drug-induced vitiligo. Loss of melanin, the primary skin pigment, occasionally ... is the case with this individual. The typical vitiligo lesion is flat and depigmented, but maintains the ...

  9. Risk of triple-class virological failure in children with HIV: a retrospective cohort study

    DEFF Research Database (Denmark)

    Castro, Hannah; Judd, Ali; Gibb, Diana M

    2011-01-01

    In adults with HIV treated with antiretroviral drug regimens from within the three original drug classes (nucleoside or nucleotide reverse transcriptase inhibitors [NRTIs], non-NRTIs [NNRTIs], and protease inhibitors), virological failure occurs slowly, suggesting that long-term virological...... failure to the three original drugs classes in children....

  10. Individual Education.

    Science.gov (United States)

    Corsini, Raymond

    1981-01-01

    Paper presented at the 66th Convention of the International Association of Pupil Personnel Workers, October 20, 1980, Baltimore, Maryland, describes individual education based on the principles of Alfred Adler. Defines six advantages of individual education, emphasizing student responsibility, mutual respect, and allowing students to progress at…

  11. The False Promise of Class-Size Reduction

    Science.gov (United States)

    Chingos, Matthew M.

    2011-01-01

    Class-size reduction, or CSR, is enormously popular with parents, teachers, and the public in general. Many parents believe that their children will benefit from more individualized attention in a smaller class and many teachers find smaller classes easier to manage. The pupil-teacher ratio is an easy statistic for the public to monitor as a…

  12. Drug-induced hair loss.

    Science.gov (United States)

    2016-05-01

    Hair loss can have major psychological consequences. It can be due to a wide variety of causes, including hormonal disorders, dietary factors, infections, inflammation, trauma, emotional factors, and cancer. Drugs can also induce hair loss, by interacting with the hair growth cycle. Drug-induced hair loss may be immediate or delayed, sudden or gradual, and diffuse or localised. It is usually reversible after drug discontinuation. The drugs most often implicated in hair loss are anticancer agents, interferon, azole antifungals, lithium, immunosuppressants, and many other drugs belonging to a variety of pharmacological classes.

  13. Sex differences in drug abuse.

    Science.gov (United States)

    Becker, Jill B; Hu, Ming

    2008-01-01

    Sex differences are present for all of the phases of drug abuse (initiation, escalation of use, addiction, and relapse following abstinence). While there are some differences among specific classes of abused drugs, the general pattern of sex differences is the same for all drugs of abuse. Females begin regularly self-administering licit and illicit drugs of abuse at lower doses than do males, use escalates more rapidly to addiction, and females are at greater risk for relapse following abstinence. In this review, sex differences in drug abuse are discussed for humans and in animal models. The possible neuroendocrine mechanisms mediating these sex differences are discussed.

  14. BDDCS Class Prediction for New Molecular Entities

    DEFF Research Database (Denmark)

    Broccatelli, Fabio; Cruciani, Gabriele; Benet, Leslie Z.

    2012-01-01

    M) predicts high versus low intestinal permeability rate, and vice versa, at least when uptake transporters or paracellular transport is not involved. We recently published a collection of over 900 marketed drugs classified for BDDCS. We suggest that a reliable model for predicting BDDCS class, integrated...... chemistry compounds (over 30,000 chemicals). Based on this application, we suggest that solubility, and not permeability, is the major difference between NMEs and drugs. We anticipate that the forecast of BDDCS categories in early drug discovery may lead to a significant R&D cost reduction....... descriptors calculated or derived from the VolSurf+ software. For each molecule, a probability of BDDCS class membership was given, based on predicted EoM, FDA solubility (FDAS) and their confidence scores. The accuracy in predicting FDAS was 78% in training and 77% in validation, while for EoM prediction...

  15. STUDY OF A TREND IN THE FREQUENCY OF USING MAIN DRUG CLASSES INDICATED FOR THE TREATMENT OF PATIENTS WITH CHRONIC CORONARY HEART DISEASE IN 2004 TO 2014: DATA FROM THE CHD PROGNOSIS REGISTRY

    Directory of Open Access Journals (Sweden)

    S. N. Tolpygina

    2016-01-01

    Full Text Available Objective: to estimate a trend in the frequency of using drugs with their proven effect on disease outcome in patients with chronic coronary heart disease (CHD in 2004–2014 within the CHD PROGNOSIS registry. Materials and methods. The investigation included data from the CHD PROGNOSIS registry on 303 patients with verified CHD during the 2004–2007 reference hospitalization at the National Research Center for Preventive Medicine, who made a control visit 4 years later, and those on 125 patients who had come following 7 years. Results. There was a low frequency of prescribing the drugs that were able to improve prognosis in patients with stable CHD prior to the 2004–2007 reference hospitalization with an increase at discharge and with a further reduction during outpatient treatment. 7.6 and 86.5% of the patients took statins; 68 and 96 % received disaggregants; 24.8 and 94 % used β-adrenoblockers (β-AB, and 19 and 83 % had angiotensin-converting enzyme (ACE inhibitors before hospitalization and at discharge, respectively (p < 0.001. Four and seven years after discharge, there were reductions in the frequency of using statins to 67 and 70 %, disaggregants to 80 and 90 %, β-AB to 80 and 75 %, and ACE inhibitors to 66 and 65 %, respectively (p < 0.01. At the same time, the above-mentioned drugs were taken by 15 and 69 % of patients on admission and at discharge, respectively (p < 0.001, by 41 and 35 % after 4 and 7 years (p < 0.01. In 2004 to 2014, most drugs were used at low and moderate doses with a gradual increase in the share of generics. Conclusion. The therapy in patients with stable CHD was characterized by a low frequency of using the drugs with their proven effect on prognosis prior to the 2004–2007 reference hospitalization with an increase and a decrease in the frequency of their use on discharge and after 4 and 7 years. During 10 years, β-AB, ACE inhibitors/angiotensin II receptor antagonists, and statins were used mainly at

  16. Class, Culture and Politics

    DEFF Research Database (Denmark)

    Harrits, Gitte Sommer

    2013-01-01

    Even though contemporary discussions of class have moved forward towards recognizing a multidimensional concept of class, empirical analyses tend to focus on cultural practices in a rather narrow sense, that is, as practices of cultural consumption or practices of education. As a result......, discussions within political sociology have not yet utilized the merits of a multidimensional conception of class. In light of this, the article suggests a comprehensive Bourdieusian framework for class analysis, integrating culture as both a structural phenomenon co-constitutive of class and as symbolic...... practice. Further, the article explores this theoretical framework in a multiple correspondence analysis of a Danish survey, demonstrating how class and political practices are indeed homologous. However, the analysis also points at several elements of field autonomy, and the concluding discussion...

  17. Class network routing

    Science.gov (United States)

    Bhanot, Gyan [Princeton, NJ; Blumrich, Matthias A [Ridgefield, CT; Chen, Dong [Croton On Hudson, NY; Coteus, Paul W [Yorktown Heights, NY; Gara, Alan G [Mount Kisco, NY; Giampapa, Mark E [Irvington, NY; Heidelberger, Philip [Cortlandt Manor, NY; Steinmacher-Burow, Burkhard D [Mount Kisco, NY; Takken, Todd E [Mount Kisco, NY; Vranas, Pavlos M [Bedford Hills, NY

    2009-09-08

    Class network routing is implemented in a network such as a computer network comprising a plurality of parallel compute processors at nodes thereof. Class network routing allows a compute processor to broadcast a message to a range (one or more) of other compute processors in the computer network, such as processors in a column or a row. Normally this type of operation requires a separate message to be sent to each processor. With class network routing pursuant to the invention, a single message is sufficient, which generally reduces the total number of messages in the network as well as the latency to do a broadcast. Class network routing is also applied to dense matrix inversion algorithms on distributed memory parallel supercomputers with hardware class function (multicast) capability. This is achieved by exploiting the fact that the communication patterns of dense matrix inversion can be served by hardware class functions, which results in faster execution times.

  18. Semantic Analysis of Virtual Classes and Nested Classes

    DEFF Research Database (Denmark)

    Madsen, Ole Lehrmann

    1999-01-01

    Virtual classes and nested classes are distinguishing features of BETA. Nested classes originated from Simula, but until recently they have not been part of main stream object- oriented languages. C++ has a restricted form of nested classes and they were included in Java 1.1. Virtual classes...... classes and parameterized classes have been made. Although virtual classes and nested classes have been used in BETA for more than a decade, their implementation has not been published. The purpose of this paper is to contribute to the understanding of virtual classes and nested classes by presenting...

  19. Class in disguise

    DEFF Research Database (Denmark)

    Faber, Stine Thidemann; Prieur, Annick

    This paper asks how class can have importance in one of the worlds’ most equal societies: Denmark. The answer is that class here appears in disguised forms. The field under study is a city, Aalborg, in the midst of transition from a stronghold of industrialism to a post industrial economy. The pa....... The paper also raises questions about how sociological discourses may contribute to the veiling of class....

  20. Drug-drug interactions among recently hospitalised patients--frequent but mostly clinically insignificant

    DEFF Research Database (Denmark)

    Glintborg, Bente; Andersen, Stig Ejdrup; Dalhoff, Kim

    2005-01-01

    OBJECTIVE: Patients use and store considerable amounts of drugs. The aim of the present study was to identify potential drug-drug interactions between drugs used by patients recently discharged from the hospital and, subsequently, to estimate the clinical implications of these interactions. METHODS......: Patients were visited within 1 week following their discharge from hospital and interviewed about their drug use. Stored products were inspected. We used a bibliography (Hansten and Horn; Wolters Kluwer Health, St. Louis, Mo., 2004) to identify and classify potential drug-drug interactions. RESULTS......: eight per patient; range: 1-24). With respect to those drugs used daily or on demand, 476 potential interactions were identified (126 patients); none were class 1 (always avoid drug combination) and 25 were class 2 (usually avoid combination; 24 patients). Eleven of the potential class 2 interactions...

  1. Characteristics and drug utilization patterns for heavy users of prescription drugs among the elderly

    DEFF Research Database (Denmark)

    Øymoen, Anita; Pottegård, Anton; Almarsdóttir, Anna Birna

    2015-01-01

    drug users accounted for 75.4% of their use in 2012, and five of these were cardiovascular drugs. The development over time for the ten most used drug classes followed the same pattern among heavy drug users and in the general population. CONCLUSION: There is a skewed utilization of prescription drugs...... frequently used drugs among heavy drug users and development in use over time. METHOD: This is a descriptive study. Heavy drug users were defined as the accumulated top 1 percentile who accounted for the largest share of prescription drug use measured in number of dispensed defined daily doses (DDDs...

  2. Hazards and Benefits of Drug Interaction

    Science.gov (United States)

    Labianca, Dominick A.

    1978-01-01

    Most cases of drug toxicity are direct consequences of drug misuse--either intentional or inadvertent. Discusses two types of drug interaction--synergistic and antagonistic. The former produces a combined effect greater than the sum of the effects of the individual drugs concerned; the latter is produced when the desired action of one drug is…

  3. Gait and Function in Class III Obesity

    Directory of Open Access Journals (Sweden)

    Catherine Ling

    2012-01-01

    Full Text Available Walking, more specifically gait, is an essential component of daily living. Walking is a very different activity for individuals with a Body Mass Index (BMI of 40 or more (Class III obesity compared with those who are overweight or obese with a BMI between 26–35. Yet all obesity weight classes receive the same physical activity guidelines and recommendations. This observational study examined the components of function and disability in a group with Class III obesity and a group that is overweight or has Class I obesity. Significant differences were found between the groups in the areas of gait, body size, health condition, and activity capacity and participation. The Timed Up and Go test, gait velocity, hip circumference, and stance width appear to be most predictive of activity capacity as observed during gait assessment. The findings indicate that Class III-related gait is pathologic and not a normal adaptation.

  4. Social power and social class: conceptualization, consequences, and current challenges.

    Science.gov (United States)

    Rucker, Derek D; Galinsky, Adam D

    2017-12-01

    This article offers a primer on social power and social class with respect to their theoretical importance, conceptual distinction, and empirical relationship. We introduce and define the constructs of social power, social class, and one's psychological sense of power. We next explore the complex relationship between social power and social class. Because social class can produce a sense of power within an individual, studies on social power can inform theory and research on social class. We conclude with a discussion of the current challenges and future opportunities for the study of social power and social class. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. 21 CFR 25.31 - Human drugs and biologics.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 1 2010-04-01 2010-04-01 false Human drugs and biologics. 25.31 Section 25.31 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ENVIRONMENTAL IMPACT CONSIDERATIONS Categorical Exclusions § 25.31 Human drugs and biologics. The classes of...

  6. A benefit-risk assessment of class III antiarrhythmic agents

    DEFF Research Database (Denmark)

    Brendorp, Bente; Pedersen, Oledyg; Torp-Pedersen, Christian

    2002-01-01

    , which differentiates them from the others. However, all have potential serious adverse events. Proarrhythmia, especially torsade de pointes, is a common problem making the benefit-risk ratio of these drugs a key question. Class III drugs have been evaluated in different settings: primary and secondary...... prevention of ventricular arrhythmias and in treatment of atrial fibrillation or flutter. Based on existing evidence there is no routine indication for antiarrhythmic drug therapy other than beta-blockers in patients at high risk of sudden death. Subgroup analyses of trials with amiodarone and dofetilide......-intervals or - in the future - from genetic testing. Class III drugs are effective in converting atrial fibrillation to sinus rhythm and for the maintenance of sinus rhythm after conversion. This is currently by far the most important indication for this class of drugs. As defined by recent guidelines, amiodarone...

  7. Drug metabolism and ageing.

    Science.gov (United States)

    Wynne, Hilary

    2005-06-01

    Older people are major consumers of drugs and because of this, as well as co-morbidity and age-related changes in pharmacokinetics and pharmacodynamics, are at risk of associated adverse drug reactions. While age does not alter drug absorption in a clinically significant way, and age-related changes in volume of drug distribution and protein binding are not of concern in chronic therapy, reduction in hepatic drug clearance is clinically important. Liver blood flow falls by about 35% between young adulthood and old age, and liver size by about 24-35% over the same period. First-pass metabolism of oral drugs avidly cleared by the liver and clearance of capacity-limited hepatically metabolized drugs fall in parallel with the fall in liver size, and clearance of drugs with a high hepatic extraction ratio falls in parallel with the fall in hepatic blood flow. In normal ageing, in general, activity of the cytochrome P450 enzymes is preserved, although a decline in frail older people has been noted, as well as in association with liver disease, cancer, trauma, sepsis, critical illness and renal failure. As the contribution of age, co-morbidity and concurrent drug therapy to altered drug clearance is impossible to predict in an individual older patient, it is wise to start any drug at a low dose and increase this slowly, monitoring carefully for beneficial and adverse effects.

  8. Teaching Social Class

    Science.gov (United States)

    Tablante, Courtney B.; Fiske, Susan T.

    2015-01-01

    Discussing socioeconomic status in college classes can be challenging. Both teachers and students feel uncomfortable, yet social class matters more than ever. This is especially true, given increased income inequality in the United States and indications that higher education does not reduce this inequality as much as many people hope. Resources…

  9. Generalized Fourier transforms classes

    DEFF Research Database (Denmark)

    Berntsen, Svend; Møller, Steen

    2002-01-01

    The Fourier class of integral transforms with kernels $B(\\omega r)$ has by definition inverse transforms with kernel $B(-\\omega r)$. The space of such transforms is explicitly constructed. A slightly more general class of generalized Fourier transforms are introduced. From the general theory...

  10. Cutting Class Harms Grades

    Science.gov (United States)

    Taylor, Lewis A., III

    2012-01-01

    An accessible business school population of undergraduate students was investigated in three independent, but related studies to determine effects on grades due to cutting class and failing to take advantage of optional reviews and study quizzes. It was hypothesized that cutting classes harms exam scores, attending preexam reviews helps exam…

  11. Social class at birth and risk of psychosis.

    Science.gov (United States)

    O'Donoghue, Brian; Fanning, Felicity; Lyne, John; Renwick, Laoise; Madigan, Kevin; Kinsella, Anthony; Lane, Abbie; Turner, Niall; O'Callaghan, Eadbhard; Clarke, Mary

    2015-12-01

    Individuals with psychotic disorders are represented more in the lower social classes, yet there is conflicting evidence to whether these individuals drift into the lower social classes or whether lower social class is a risk factor for developing psychosis. The aim of this study was to examine whether the social class at birth is a risk factor for developing psychosis. We included individuals with a first episode of psychosis (FEP) whose social class at birth was determined from birth records. We employed a case-control study design and also compared the distribution of the social classes at birth of the cases to that of the general population. A total of 380 individuals with an FEP and 760 controls were included in the case-control study. The odds ratio for developing an FEP associated with social class (low vs high) was .62 (95% confidence interval (CI): .46-.85, p social class at birth have a reduced risk of psychosis. Individuals born between 1961 and 1980 with an FEP were more likely to be from a higher social class at birth compared to the general population (60.8% vs 36.7%, χ(2) = 60.85, df = 1, p social class at birth is associated with a greater risk for developing a psychotic disorder; however, this effect may show temporal variation. © The Author(s) 2015.

  12. Class and compassion: socioeconomic factors predict responses to suffering.

    Science.gov (United States)

    Stellar, Jennifer E; Manzo, Vida M; Kraus, Michael W; Keltner, Dacher

    2012-06-01

    Previous research indicates that lower-class individuals experience elevated negative emotions as compared with their upper-class counterparts. We examine how the environments of lower-class individuals can also promote greater compassionate responding-that is, concern for the suffering or well-being of others. In the present research, we investigate class-based differences in dispositional compassion and its activation in situations wherein others are suffering. Across studies, relative to their upper-class counterparts, lower-class individuals reported elevated dispositional compassion (Study 1), as well as greater self-reported compassion during a compassion-inducing video (Study 2) and for another person during a social interaction (Study 3). Lower-class individuals also exhibited heart rate deceleration-a physiological response associated with orienting to the social environment and engaging with others-during the compassion-inducing video (Study 2). We discuss a potential mechanism of class-based influences on compassion, whereby lower-class individuals' are more attuned to others' distress, relative to their upper-class counterparts.

  13. Individualizing Medicare.

    Science.gov (United States)

    Chollet, D J

    1999-05-01

    Despite the enactment of significant changes to the Medicare program in 1997, Medicare's Hospital Insurance trust fund is projected to be exhausted just as the baby boom enters retirement. To address Medicare's financial difficulties, a number of reform proposals have been offered, including several to individualize Medicare financing and benefits. These proposals would attempt to increase Medicare revenues and reduce Medicare expenditures by having individuals bear risk--investment market risk before retirement and insurance market risk after retirement. Many fundamental aspects of these proposals have yet to be worked out, including how to guarantee a baseline level of saving for health insurance after retirement, how retirees might finance unanticipated health insurance price increases after retirement, the potential implications for Medicaid of inadequate individual saving, and whether the administrative cost of making the system fair and adequate ultimately would eliminate any rate-of-return advantages from allowing workers to invest their Medicare contributions in corporate stocks and bonds.

  14. Drug allergies

    Science.gov (United States)

    Allergic reaction - drug (medication); Drug hypersensitivity; Medication hypersensitivity ... A drug allergy involves an immune response in the body that produces an allergic reaction to a medicine. The first time ...

  15. Study Drugs

    Science.gov (United States)

    ... to quit, they may have withdrawal symptoms like depression, thoughts of suicide, intense drug cravings, sleep problems, and fatigue. The health risks aren't the only downside to study drugs. Students caught with illegal prescription drugs may get suspended ...

  16. Drug Facts

    Medline Plus

    Full Text Available ... symptoms of someone with a drug use problem? How Does Drug Use Become an Addiction? What Makes Someone More Likely to Get Addicted to Drugs? Does Addiction Run in Families? Why Is It So Hard to ...

  17. Drug Facts

    Medline Plus

    Full Text Available ... Other Effects on the Body Drug Use Hurts Brains Drug Use and Mental Health Problems Often Happen ... to prescription drugs. The addiction slowly took over his life. I need different people around me. To ...

  18. Drug Reactions

    Science.gov (United States)

    ... problem is interactions, which may occur between Two drugs, such as aspirin and blood thinners Drugs and food, such as statins and grapefruit Drugs and supplements, such as ginkgo and blood thinners ...

  19. Drug Facts

    Science.gov (United States)

    ... Makes Someone More Likely to Get Addicted to Drugs? Does Addiction Run in Families? Why Is It So Hard ... the text to you. This website talks about drug abuse, addiction, and treatment. Watch Videos Information About Drugs Alcohol ...

  20. Social class rank, threat vigilance, and hostile reactivity.

    Science.gov (United States)

    Kraus, Michael W; Horberg, E J; Goetz, Jennifer L; Keltner, Dacher

    2011-10-01

    Lower-class individuals, because of their lower rank in society, are theorized to be more vigilant to social threats relative to their high-ranking upper-class counterparts. This class-related vigilance to threat, the authors predicted, would shape the emotional content of social interactions in systematic ways. In Study 1, participants engaged in a teasing interaction with a close friend. Lower-class participants--measured in terms of social class rank in society and within the friendship--more accurately tracked the hostile emotions of their friend. As a result, lower-class individuals experienced more hostile emotion contagion relative to upper-class participants. In Study 2, lower-class participants manipulated to experience lower subjective socioeconomic rank showed more hostile reactivity to ambiguous social scenarios relative to upper-class participants and to lower-class participants experiencing elevated socioeconomic rank. The results suggest that class affects expectations, perception, and experience of hostile emotion, particularly in situations in which lower-class individuals perceive their subordinate rank.

  1. Multi-class Mode of Action Classification of Toxic Compounds Using Logic Based Kernel Methods.

    Science.gov (United States)

    Lodhi, Huma; Muggleton, Stephen; Sternberg, Mike J E

    2010-09-17

    Toxicity prediction is essential for drug design and development of effective therapeutics. In this paper we present an in silico strategy, to identify the mode of action of toxic compounds, that is based on the use of a novel logic based kernel method. The technique uses support vector machines in conjunction with the kernels constructed from first order rules induced by an Inductive Logic Programming system. It constructs multi-class models by using a divide and conquer reduction strategy that splits multi-classes into binary groups and solves each individual problem recursively hence generating an underlying decision list structure. In order to evaluate the effectiveness of the approach for chemoinformatics problems like predictive toxicology, we apply it to toxicity classification in aquatic systems. The method is used to identify and classify 442 compounds with respect to the mode of action. The experimental results show that the technique successfully classifies toxic compounds and can be useful in assessing environmental risks. Experimental comparison of the performance of the proposed multi-class scheme with the standard multi-class Inductive Logic Programming algorithm and multi-class Support Vector Machine yields statistically significant results and demonstrates the potential power and benefits of the approach in identifying compounds of various toxic mechanisms. Copyright © 2010 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  2. Classes of modules

    CERN Document Server

    Dauns, John

    2006-01-01

    Because traditional ring theory places restrictive hypotheses on all submodules of a module, its results apply only to small classes of already well understood examples. Often, modules with infinite Goldie dimension have finite-type dimension, making them amenable to use with type dimension, but not Goldie dimension. By working with natural classes and type submodules (TS), Classes of Modules develops the foundations and tools for the next generation of ring and module theory. It shows how to achieve positive results by placing restrictive hypotheses on a small subset of the complement submodules, Furthermore, it explains the existence of various direct sum decompositions merely as special cases of type direct sum decompositions. Carefully developing the foundations of the subject, the authors begin by providing background on the terminology and introducing the different module classes. The modules classes consist of torsion, torsion-free, s[M], natural, and prenatural. They expand the discussion by exploring...

  3. Dendrimers for Drug Delivery

    Directory of Open Access Journals (Sweden)

    Abhay Singh Chauhan

    2018-04-01

    Full Text Available Dendrimers have come a long way in the last 25 years since their inception. Originally created as a wonder molecule of chemistry, dendrimer is now in the fourth class of polymers. Dr. Donald Tomalia first published his seminal work on Poly(amidoamine (PAMAM dendrimers in 1985. Application of dendrimers as a drug delivery system started in late 1990s. Dendrimers for drug delivery are employed using two approaches: (i formulation and (ii nanoconstruct. In the formulation approach, drugs are physically entrapped in a dendrimer using non-covalent interactions, whereas drugs are covalently coupled on dendrimers in the nanoconstruct approach. We have demonstrated the utility of PAMAM dendrimers for enhancing solubility, stability and oral bioavailability of various drugs. Drug entrapment and drug release from dendrimers can be controlled by modifying dendrimer surfaces and generations. PAMAM dendrimers are also shown to increase transdermal permeation and specific drug targeting. Dendrimer platforms can be engineered to attach targeting ligands and imaging molecules to create a nanodevice. Dendrimer nanotechnology, due to its multifunctional ability, has the potential to create next generation nanodevices.

  4. Hidden costs of HIV treatment in Spain: inefficiency of the antiretroviral drug packaging.

    Science.gov (United States)

    Llibre-Codina, Josep M; Andreu-Crespo, Angels; Cardona-Peitx, Gloria; Sala-Piñol, Ferran; Clotet-Sala, Bonaventura; Bonafont-Pujol, Xavier

    2014-01-01

    Antiretroviral drugs in Spain are delivered by law only in hospital pharmacies. Commercial packages meet variable quality standards when dispensed drugs are returned due to treatment changes or adherence problems Nearly 20-25% of the initial regimens will be changed at 48 weeks for different reasons. We evaluated the economic impact on public health system of the inability of using returned drugs due to inefficient packaging. We defined socially efficient packaging as the best adapted one to being delivered in unit dose to outpatients and classified: Class A - Drug packed in unit doses with complete info (name of drug, dosage in mg, lot, and expiring date) in each unit, maintaining complete information of the drug if returned when the external package is opened. Class B - packed in blisters with complete info in the blister, but not in unit doses, without special conservation conditions (should be re-packed in unit doses in the pharmacy before its dispensation to assure a class A excellence). Class C - packed in plastic containers with complete info written only on a label over the container, would allow repackaging only before its initial delivery, but not when returned. Class D - drug packed in plastic containers with manufacturer's warning that the product cannot be placed outside of the original package due to special conditions of conservation (fridge, humidity) that doesn't allow a unit dose repackaging or reusing an opened container. We analysed a 12-month period (July 2011-June 2012) in a hospital-based HIV outpatient pharmacy that serves 2413 treated individuals. Patients generated 23,574 visits to pharmacy, and received 48,325 drug packages, with 2.529.137 pills delivered. The patients suffered 1051 treatment changes for any reason. A total amount of 122.945€ in treatment were returned to pharmacy in opened packages during the study period. 47.139.91€ would be totally lost, mainly due to being packaged in class C and D boxes, the equivalent of

  5. Social class, dementia and the fourth age.

    Science.gov (United States)

    Jones, Ian Rees

    2017-02-01

    Research addressing social class and dementia has largely focused on measures of socioeconomic status as causal risk factors for dementia and in observed differences in diagnosis, treatment and care. This large body of work has produced important insights but also contains numerous problems and weaknesses. Research needs to take account of the ways in which ageing and social class have been transformed in tandem with the economic, social and cultural coordinates of late modernity. These changes have particular consequences for individual identities and social relations. With this in mind this article adopts a critical gaze on research that considers interactions between dementia and social class in three key areas: (i) epidemiological approaches to inequalities in risk (ii) the role of social class in diagnosis and treatment and (iii) class in the framing of care and access to care. Following this, the article considers studies of dementia and social class that focus on lay understandings and biographical accounts. Sociological insights in this field come from the view that dementia and social class are embedded in social relations. Thus, forms of distinction based on class relations may still play an important role in the lived experience of dementia. © 2017 Foundation for the Sociology of Health & Illness.

  6. Collective individualism

    DEFF Research Database (Denmark)

    Baarts, Charlotte

    2009-01-01

    at a construction site. An ethnographic fieldwork, in which the researcher worked as an apprentice, will provide detailed and experiencenear insights into the complexity of these processes. Findings show that individualist and collectivist preferences influence the amount of risk the individual worker will assume...

  7. In vitro dissolution of generic immediate-release solid oral dosage forms containing BCS class I drugs: comparative assessment of metronidazole, zidovudine, and amoxicillin versus relevant comparator pharmaceutical products in South Africa and India.

    Science.gov (United States)

    Reddy, Nallagundla H S; Patnala, Srinivas; Löbenberg, Raimar; Kanfer, Isadore

    2014-10-01

    Biowaivers are recommended for immediate-release solid oral dosage forms using dissolution testing as a surrogate for in vivo bioequivalence studies. Several guidance are currently available (the World Health Organization (WHO), the US FDA, and the EMEA) where the conditions are described. In this study, definitions, criteria, and methodologies according to the WHO have been applied. The dissolution performances of immediate-release metronidazole, zidovudine, and amoxicillin products purchased in South African and Indian markets were compared to the relevant comparator pharmaceutical product (CPP)/reference product. The dissolution performances were studied using US Pharmacopeia (USP) apparatus 2 (paddle) set at 75 rpm in each of three dissolution media (pH1.2, 4.5, and 6.8). Concentrations of metronidazole, zidovudine, and amoxicillin in each dissolution media were determined by HPLC. Of the 11 metronidazole products tested, only 8 could be considered as very rapidly dissolving products as defined by the WHO, whereas 2 of those products could be considered as rapidly dissolving products but did not comply with the f 2 acceptance criteria in pH 6.8. All 11 zidovudine products were very rapidly dissolving, whereas in the case of the 14 amoxicillin products tested, none of those products met any of the WHO criteria. This study indicates that not all generic products containing the same biopharmaceutics classification system (BCS) I drug and in similar strength and dosage form are necessarily in vitro equivalent. Hence, there is a need for ongoing market surveillance to determine whether marketed generic products containing BCS I drugs meet the release requirements to confirm their in vitro bioequivalence to the respective reference product.

  8. Individualization of poverty?

    DEFF Research Database (Denmark)

    Bak, Carsten Kronborg

    2015-01-01

    The German Sociologist Ulrich Beck is best known for his book “Risk Society” which has been discussed extensively; however Beck’s claims about modern poverty have not received the same attention among poverty researchers. The individualization perspective views poverty as a relatively transient...... phenomenon and the democratization perspective views the risk of poverty as spread equally in the population. Both perspectives challenge the mainstream tradition of class analysis, and therefore both view poverty as largely independent of traditional stratification factors. In this article, I argue...

  9. Pharmacogenetics of Anti-Diabetes Drugs

    Directory of Open Access Journals (Sweden)

    Johanna K. DiStefano

    2010-08-01

    Full Text Available A variety of treatment modalities exist for individuals with type 2 diabetes mellitus (T2D. In addition to dietary and physical activity interventions, T2D is also treated pharmacologically with nine major classes of approved drugs. These medications include insulin and its analogues, sulfonylureas, biguanides, thiazolidinediones (TZDs, meglitinides, α-glucosidase inhibitors, amylin analogues, incretin hormone mimetics, and dipeptidyl peptidase 4 (DPP4 inhibitors. Pharmacological treatment strategies for T2D are typically based on efficacy, yet favorable responses to such therapeutics are oftentimes variable and difficult to predict. Characterization of drug response is expected to substantially enhance our ability to provide patients with the most effective treatment strategy given their individual backgrounds, yet pharmacogenetic study of diabetes medications is still in its infancy. To date, major pharmacogenetic studies have focused on response to sulfonylureas, biguanides, and TZDs. Here, we provide a comprehensive review of pharmacogenetics investigations of these specific anti-diabetes medications. We focus not only on the results of these studies, but also on how experimental design, study sample issues, and definition of ‘response’ can significantly impact our interpretation of findings. Understanding the pharmacogenetics of anti-diabetes medications will provide critical baseline information for the development and implementation of genetic screening into therapeutic decision making, and lay the foundation for “individualized medicine” for patients with T2D.

  10. Social-class differences in self-concept clarity and their implications for well-being.

    Science.gov (United States)

    Na, Jinkyung; Chan, Micaela Y; Lodi-Smith, Jennifer; Park, Denise C

    2018-06-01

    A consistent/stable sense of the self is more valued in middle-class contexts than working-class contexts; hence, we predicted that middle-class individuals would have higher self-concept clarity than working-class individuals. It is further expected that self-concept clarity would be more important to one's well-being among middle-class individuals than among working-class individuals. Supporting these predictions, self-concept clarity was positively associated with higher social class. Moreover, although self-concept clarity was associated with higher life satisfaction and better mental health, the association significantly attenuated among working-class individuals. In addition, self-concept clarity was not associated with physical health and its association with physical health did not interact with social class.

  11. Factors associated with patterns of mobile technology use among persons who inject drugs.

    Science.gov (United States)

    Collins, Kelly M; Armenta, Richard F; Cuevas-Mota, Jazmine; Liu, Lin; Strathdee, Steffanie A; Garfein, Richard S

    2016-01-01

    New and innovative methods of delivering interventions are needed to further reduce risky behaviors and increase overall health among persons who inject drugs (PWID). Mobile health (mHealth) interventions have potential for reaching PWID; however, little is known about mobile technology use (MTU) in this population. In this study, the authors identify patterns of MTU and identified factors associated with MTU among a cohort of PWID. Data were collected through a longitudinal cohort study examining drug use, risk behaviors, and health status among PWID in San Diego, California. Latent class analysis (LCA) was used to define patterns of MTU (i.e., making voice calls, text messaging, and mobile Internet access). Multinomial logistic regression was then used to identify demographic characteristics, risk behaviors, and health indicators associated with mobile technology use class. In LCA, a 4-class solution fit the data best. Class 1 was defined by low MTU (22%, n = 100); class 2, by PWID who accessed the Internet using a mobile device but did not use voice or text messaging (20%, n = 95); class 3, by primarily voice, text, and connected Internet use (17%, n = 91); and class 4, by high MTU (41%, n = 175). Compared with low MTU, high MTU class members were more likely to be younger, have higher socioeconomic status, sell drugs, and inject methamphetamine daily. The majority of PWID in San Diego use mobile technology for voice, text, and/or Internet access, indicating that rapid uptake of mHealth interventions may be possible in this population. However, low ownership and use of mobile technology among older and/or homeless individuals will need to be considered when implementing mHealth interventions among PWID.

  12. Individual monitoring

    International Nuclear Information System (INIS)

    2004-01-01

    This Practical Radiation Technical Manual is one of a series which has been designed to provide guidance on radiological protection for employers, Radiation Protection Officers, managers and other technically competent persons who have a responsibility to ensure the safety of employees working with ionizing radiation. The Manual may be used together with the appropriate IAEA Practical Radiation Safety Manual to provide adequate training, instruction or information on individual monitoring for all employees engaged in work with ionizing radiations. Sources of ionizing radiation have a large number of applications in the workplace. The exposures of the individual workers involved may need to be routinely monitored and records kept of their cumulative radiation doses. There are also occasions when it is necessary to retrospectively determine a dose which may have been received by a worker. This Manual explains the basic terminology associated with individual monitoring and describes the principal types of dosimeters and other related techniques and their application in the workplace. The Manual will be of most benefit if it forms part of more comprehensive training or is supplemented by the advice of a qualified expert in radiation protection. Most of the dosimeters and techniques described in this Manual can only be provided by qualified experts

  13. Social Class Dialogues and the Fostering of Class Consciousness

    Science.gov (United States)

    Madden, Meredith

    2015-01-01

    How do critical pedagogies promote undergraduate students' awareness of social class, social class identity, and social class inequalities in education? How do undergraduate students experience class consciousness-raising in the intergroup dialogue classroom? This qualitative study explores undergraduate students' class consciousness-raising in an…

  14. Drug Facts

    Medline Plus

    Full Text Available ... Drug Use Hurts Brains Drug Use and Mental Health Problems Often Happen Together The Link Between Drug Use and HIV/AIDS Treatment & Recovery Why Does a Person Need Treatment? Does Drug Treatment Work? What Are the Treatment Options? What Is Recovery? ...

  15. Drug Facts

    Medline Plus

    Full Text Available ... 4357) at any time to find drug treatment centers near you. I want my daughter to avoid drugs. "Debbie" has been drug-free for years. She wants her daughter to stay away from drugs. But she's afraid ...

  16. Optimizing UML Class Diagrams

    Directory of Open Access Journals (Sweden)

    Sergievskiy Maxim

    2018-01-01

    Full Text Available Most of object-oriented development technologies rely on the use of the universal modeling language UML; class diagrams play a very important role in the design process play, used to build a software system model. Modern CASE tools, which are the basic tools for object-oriented development, can’t be used to optimize UML diagrams. In this manuscript we will explain how, based on the use of design patterns and anti-patterns, class diagrams could be verified and optimized. Certain transformations can be carried out automatically; in other cases, potential inefficiencies will be indicated and recommendations given. This study also discusses additional CASE tools for validating and optimizing of UML class diagrams. For this purpose, a plugin has been developed that analyzes an XMI file containing a description of class diagrams.

  17. Classes of Heart Failure

    Science.gov (United States)

    ... Introduction Types of Heart Failure Classes of Heart Failure Heart Failure in Children Advanced Heart Failure • Causes and ... and Advanced HF • Tools and Resources • Personal Stories Heart Failure Questions to Ask Your Doctor Use these questions ...

  18. Drug abuse in athletes

    Directory of Open Access Journals (Sweden)

    Reardon CL

    2014-08-01

    Full Text Available Claudia L Reardon, Shane Creado Department of Psychiatry, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA Abstract: Drug abuse occurs in all sports and at most levels of competition. Athletic life may lead to drug abuse for a number of reasons, including for performance enhancement, to self-treat otherwise untreated mental illness, and to deal with stressors, such as pressure to perform, injuries, physical pain, and retirement from sport. This review examines the history of doping in athletes, the effects of different classes of substances used for doping, side effects of doping, the role of anti-doping organizations, and treatment of affected athletes. Doping goes back to ancient times, prior to the development of organized sports. Performance-enhancing drugs have continued to evolve, with “advances” in doping strategies driven by improved drug testing detection methods and advances in scientific research that can lead to the discovery and use of substances that may later be banned. Many sports organizations have come to ban the use of performance-enhancing drugs and have very strict consequences for people caught using them. There is variable evidence for the performance-enhancing effects and side effects of the various substances that are used for doping. Drug abuse in athletes should be addressed with preventive measures, education, motivational interviewing, and, when indicated, pharmacologic interventions. Keywords: doping, athletes, steroids, drug abuse, mental illness

  19. Generalized Fourier transforms classes

    DEFF Research Database (Denmark)

    Berntsen, Svend; Møller, Steen

    2002-01-01

    The Fourier class of integral transforms with kernels $B(\\omega r)$ has by definition inverse transforms with kernel $B(-\\omega r)$. The space of such transforms is explicitly constructed. A slightly more general class of generalized Fourier transforms are introduced. From the general theory foll...... follows that integral transform with kernels which are products of a Bessel and a Hankel function or which is of a certain general hypergeometric type have inverse transforms of the same structure....

  20. Nordic Walking Classes

    CERN Multimedia

    Fitness Club

    2015-01-01

    Four classes of one hour each are held on Tuesdays. RDV barracks parking at Entrance A, 10 minutes before class time. Spring Course 2015: 05.05/12.05/19.05/26.05 Prices 40 CHF per session + 10 CHF club membership 5 CHF/hour pole rental Check out our schedule and enroll at: https://espace.cern.ch/club-fitness/Lists/Nordic%20Walking/NewForm.aspx? Hope to see you among us! fitness.club@cern.ch

  1. Relapse to opioid use in opioid-dependent individuals released from compulsory drug detention centres compared with those from voluntary methadone treatment centres in Malaysia: a two-arm, prospective observational study

    Directory of Open Access Journals (Sweden)

    Martin P Wegman, BSc

    2017-02-01

    Funding: The World Bank Group, Doris Duke Charitable Foundation, National Institute on Drug Abuse, Australian National Health & Medical Research Council, National Institute of Mental Health, and the University of Malaya-Malaysian Ministry of Higher Education High Impact Research Grant.

  2. Do Convolutional Neural Networks Learn Class Hierarchy?

    Science.gov (United States)

    Bilal, Alsallakh; Jourabloo, Amin; Ye, Mao; Liu, Xiaoming; Ren, Liu

    2018-01-01

    Convolutional Neural Networks (CNNs) currently achieve state-of-the-art accuracy in image classification. With a growing number of classes, the accuracy usually drops as the possibilities of confusion increase. Interestingly, the class confusion patterns follow a hierarchical structure over the classes. We present visual-analytics methods to reveal and analyze this hierarchy of similar classes in relation with CNN-internal data. We found that this hierarchy not only dictates the confusion patterns between the classes, it furthermore dictates the learning behavior of CNNs. In particular, the early layers in these networks develop feature detectors that can separate high-level groups of classes quite well, even after a few training epochs. In contrast, the latter layers require substantially more epochs to develop specialized feature detectors that can separate individual classes. We demonstrate how these insights are key to significant improvement in accuracy by designing hierarchy-aware CNNs that accelerate model convergence and alleviate overfitting. We further demonstrate how our methods help in identifying various quality issues in the training data.

  3. Student Communities and Individualism in American Cinema

    Science.gov (United States)

    Warnick, Bryan R.; Dawson, Heather S.; Smith, D. Spencer; Vosburg-Bluem, Bethany

    2010-01-01

    Hollywood films partially construct how Americans think about education. Recent work on the representation of schools in American cinema has highlighted the role of class difference in shaping school film genres. It has also advanced the idea that a nuanced understanding of American individualism helps to explain why the different class genres are…

  4. Safety class methodology

    International Nuclear Information System (INIS)

    Donner, E.B.; Low, J.M.; Lux, C.R.

    1992-01-01

    DOE Order 6430.1A, General Design Criteria (GDC), requires that DOE facilities be evaluated with respect to ''safety class items.'' Although the GDC defines safety class items, it does not provide a methodology for selecting safety class items. The methodology described in this paper was developed to assure that Safety Class Items at the Savannah River Site (SRS) are selected in a consistent and technically defensible manner. Safety class items are those in the highest of four categories determined to be of special importance to nuclear safety and, merit appropriately higher-quality design, fabrication, and industrial test standards and codes. The identification of safety class items is approached using a cascading strategy that begins at the 'safety function' level (i.e., a cooling function, ventilation function, etc.) and proceeds down to the system, component, or structure level. Thus, the items that are required to support a safety function are SCls. The basic steps in this procedure apply to the determination of SCls for both new project activities, and for operating facilities. The GDC lists six characteristics of SCls to be considered as a starting point for safety item classification. They are as follows: 1. Those items whose failure would produce exposure consequences that would exceed the guidelines in Section 1300-1.4, ''Guidance on Limiting Exposure of the Public,'' at the site boundary or nearest point of public access 2. Those items required to maintain operating parameters within the safety limits specified in the Operational Safety Requirements during normal operations and anticipated operational occurrences. 3. Those items required for nuclear criticality safety. 4. Those items required to monitor the release of radioactive material to the environment during and after a Design Basis Accident. Those items required to achieve, and maintain the facility in a safe shutdown condition 6. Those items that control Safety Class Item listed above

  5. Sociology of Drug Consumption

    Directory of Open Access Journals (Sweden)

    2004-02-01

    Full Text Available In this article which is a review of sociological ideas and studies of drug abusers in social situation, drug addiction steps (particularly alcohol, heroin and cocaine consumption are revised and some explanations are made. Also, the role of some sociological ideas in drug addiction is considered in which Anomie Theory reads: "because of such duality, the individuals who are not satisfied with their role are in hurt." According to this theory, drug users choose seclusion and neglecting usual social aims as well as competitive situations. Association of Differentiation Theory claims that drug use behavior is a learned behavior and the first learning occurs in a friendly small group (i.e. youngsters. Social Control theory believes that one can predict normal and abnormal behaviors through the rate of individuals' social commitments. Internal and external controls also determine commitment rate. Micro-cultural theory considers drug use as a compatibility with abnormal micro-culture rules. Symbolic Mutual Action Believes that the etiquettes which society attribute to individuals/behaviors determine their acquired social reactions rather than any inherited acquisition.

  6. Analytical toxicology of emerging drugs of abuse--an update.

    Science.gov (United States)

    Meyer, Markus R; Peters, Frank T

    2012-12-01

    The steady increase of new drugs of abuse on the illicit drug market is a great challenge for analytical toxicologists. Because most of these new drugs or drug classes are not included in established analytical methods targeting classic drugs of abuse, analytical procedures must be adapted or new procedures must be developed to cover such new compounds. This review summarizes procedures for analysis of these drugs of abuse published from January 2009 to January 2012 covering the following classes of emerging drugs of abuse as follows: β-keto-amphetamines, pyrrolidinophenones, tryptamines, and synthetic cannabinoids.

  7. Substance use - prescription drugs

    Science.gov (United States)

    Substance use disorder - prescription drugs; Substance abuse - prescription drugs; Drug abuse - prescription drugs; Drug use - prescription drugs; Narcotics - substance use; Opioid - substance use; Sedative - substance ...

  8. Pharmacogenomics of GPCR Drug Targets

    DEFF Research Database (Denmark)

    Hauser, Alexander Sebastian; Chavali, Sreenivas; Masuho, Ikuo

    2018-01-01

    Natural genetic variation in the human genome is a cause of individual differences in responses to medications and is an underappreciated burden on public health. Although 108 G-protein-coupled receptors (GPCRs) are the targets of 475 (∼34%) Food and Drug Administration (FDA)-approved drugs...... and account for a global sales volume of over 180 billion US dollars annually, the prevalence of genetic variation among GPCRs targeted by drugs is unknown. By analyzing data from 68,496 individuals, we find that GPCRs targeted by drugs show genetic variation within functional regions such as drug......- and effector-binding sites in the human population. We experimentally show that certain variants of μ-opioid and Cholecystokinin-A receptors could lead to altered or adverse drug response. By analyzing UK National Health Service drug prescription and sales data, we suggest that characterizing GPCR variants...

  9. Grapefruit and drug interactions.

    Science.gov (United States)

    2012-12-01

    Since the late 1980s, grapefruit juice has been known to affect the metabolism of certain drugs. Several serious adverse effects involving drug interactions with grapefruit juice have been published in detail. The components of grapefruit juice vary considerably depending on the variety, maturity and origin of the fruit, local climatic conditions, and the manufacturing process. No single component accounts for all observed interactions. Other grapefruit products are also occasionally implicated, including preserves, lyophylised grapefruit juice, powdered whole grapefruit, grapefruit seed extract, and zest. Clinical reports of drug interactions with grapefruit juice are supported by pharmacokinetic studies, each usually involving about 10 healthy volunteers, in which the probable clinical consequences were extrapolated from the observed plasma concentrations. Grapefruit juice inhibits CYP3A4, the cytochrome P450 isoenzyme most often involved in drug metabolism. This increases plasma concentrations of the drugs concerned, creating a risk of overdose and dose-dependent adverse effects. Grapefruit juice also inhibits several other cytochrome P450 isoenzymes, but they are less frequently implicated in interactions with clinical consequences. Drugs interacting with grapefruit and inducing serious clinical consequences (confirmed or very probable) include: immunosuppressants, some statins, benzodiazepines, most calcium channel blockers, indinavir and carbamazepine. There are large inter-individual differences in enzyme efficiency. Along with the variable composition of grapefruit juice, this makes it difficult to predict the magnitude and clinical consequences of drug interactions with grapefruit juice in a given patient. There is increasing evidence that transporter proteins such as organic anion transporters and P-glycoprotein are involved in interactions between drugs and grapefruit juice. In practice, numerous drugs interact with grapefruit juice. Although only a few

  10. Polymer architecture and drug delivery.

    Science.gov (United States)

    Qiu, Li Yan; Bae, You Han

    2006-01-01

    Polymers occupy a major portion of materials used for controlled release formulations and drug-targeting systems because this class of materials presents seemingly endless diversity in topology and chemistry. This is a crucial advantage over other classes of materials to meet the ever-increasing requirements of new designs of drug delivery formulations. The polymer architecture (topology) describes the shape of a single polymer molecule. Every natural, seminatural, and synthetic polymer falls into one of categorized architectures: linear, graft, branched, cross-linked, block, star-shaped, and dendron/dendrimer topology. Although this topic spans a truly broad area in polymer science, this review introduces polymer architectures along with brief synthetic approaches for pharmaceutical scientists who are not familiar with polymer science, summarizes the characteristic properties of each architecture useful for drug delivery applications, and covers recent advances in drug delivery relevant to polymer architecture.

  11. Translation in ESL Classes

    Directory of Open Access Journals (Sweden)

    Nagy Imola Katalin

    2015-12-01

    Full Text Available The problem of translation in foreign language classes cannot be dealt with unless we attempt to make an overview of what translation meant for language teaching in different periods of language pedagogy. From the translation-oriented grammar-translation method through the complete ban on translation and mother tongue during the times of the audio-lingual approaches, we have come today to reconsider the role and status of translation in ESL classes. This article attempts to advocate for translation as a useful ESL class activity, which can completely fulfil the requirements of communicativeness. We also attempt to identify some activities and games, which rely on translation in some books published in the 1990s and the 2000s.

  12. Class and eating: Family meals in Britain.

    Science.gov (United States)

    Jarosz, Ewa

    2017-09-01

    This paper examines social differentiation in eating patterns in Britain. It focuses on family meals among individuals with under-age children. Eating with family members has been associated with improvement in wellbeing, nutritional status, and school performance of the children. Modern lifestyles may pose a challenge to commensal eating for all groups, but the scale of the impact varies between social classes, with some groups at higher risk of shortening or skipping family meal time. Eating patterns are differentiated by individual's social class; they have also been associated with educational attainment, work schedules, and household composition. The objective of this study is to disaggregate the effect of these variables. Using data from the 2014/2015 UK Time Use Survey I analyse the net effect of social class, education, income, work and family characteristics on the frequency and duration of family meals. Individuals in the highest occupational class dedicate more time overall to family meals. However, class effect becomes insignificant when other variables, such as education or income, are controlled for. This study finds that higher educated individuals have more frequent family meals, and more affluent individuals spend more time at the table with their household members. Work characteristics are associated with frequency of meals, but not with their duration. Finally, household composition matters for how people eat. Parents of younger children eat with their family members more frequently than parents of teenagers. Single parents, a notoriously time-poor category, spend the least amount of time eating with their families and have fewer commensal meals. Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. Drug plan design incentives among Medicare prescription drug plans.

    Science.gov (United States)

    Huskamp, Haiden A; Keating, Nancy L; Dalton, Jesse B; Chernew, Michael E; Newhouse, Joseph P

    2014-07-01

    Medicare Advantage prescription drug plans (MA-PDs) and standalone prescription drug plans (PDPs) face different incentives for plan design resulting from the scope of covered benefits (only outpatient drugs for PDPs versus all drug and nondrug services for Medicare Advantage [MA]/MA-PDs). The objective is to begin to explore how MA-PDs and PDPs may be responding to their different incentives related to benefit design. We compared 2012 PDP and MA-PD average formulary coverage, prior authorization (PA) or step therapy use, and copayment requirements for drugs in 6 classes used commonly among Medicare beneficiaries. We primarily used 2012 Prescription Drug Plan Formulary and Pharmacy Network Files and MA enrollment data. 2011 Truven Health MarketScan claims were used to estimate drug prices and to compute drug market share. Average coverage and PA/step rates, and average copayment requirements, were weighted by plan enrollment and drug market share. MA-PDs are generally more likely to cover and less likely to require PA/step for brand name drugs with generic alternatives than PDPs, and MA-PDs often have lower copayment requirements for these drugs. For brands without generics, we generally found no differences in average rates of coverage or PA/step, but MA-PDs were more likely to cover all brands without generics in a class. We found modest, confirmatory evidence suggesting that PDPs and MA-PDs respond to different incentives for plan design. Future research is needed to understand the factors that influence Medicare drug plan design decisions.

  14. Emerging drugs of abuse.

    Science.gov (United States)

    Nelson, Michael E; Bryant, Sean M; Aks, Steven E

    2014-02-01

    Many new emerging drugs of abuse are marketed as legal highs despite being labeled "not for human consumption" to avoid regulation. The availability of these substances over the Internet and in "head shops" has lead to a multitude of emergency department visits with severe complications including deaths worldwide. Despite recent media attention, many of the newer drugs of abuse are still largely unknown by health care providers. Slight alterations of the basic chemical structure of substances create an entirely new drug no longer regulated by current laws and an ever-changing landscape of clinical effects. The purity of each substance with exact pharmacokinetic and toxicity profiles is largely unknown. Many of these substances can be grouped by the class of drug and includes synthetic cannabinoids, synthetic cathinones, phenethylamines, as well as piperazine derivatives. Resultant effects generally include psychoactive and sympathomimetic-like symptoms. Additionally, prescription medications, performance enhancing medications, and herbal supplements are also becoming more commonly abused. Most new drugs of abuse have no specific antidote and management largely involves symptom based goal directed supportive care with benzodiazepines as a useful adjunct. This paper will focus on the history, epidemiology, clinical effects, laboratory analysis, and management strategy for many of these emerging drugs of abuse. Copyright © 2014 Elsevier Inc. All rights reserved.

  15. New drugs of abuse.

    Science.gov (United States)

    Rech, Megan A; Donahey, Elisabeth; Cappiello Dziedzic, Jacqueline M; Oh, Laura; Greenhalgh, Elizabeth

    2015-02-01

    Drug abuse is a common problem and growing concern in the United States, and over the past decade, novel or atypical drugs have emerged and have become increasingly popular. Recognition and treatment of new drugs of abuse pose many challenges for health care providers due to lack of quantitative reporting and routine surveillance, and the difficulty of detection in routine blood and urine analyses. Furthermore, street manufacturers are able to rapidly adapt and develop new synthetic isolates of older drugs as soon as law enforcement agencies render them illegal. In this article, we describe the clinical and adverse effects and purported pharmacology of several new classes of drugs of abuse including synthetic cannabinoids, synthetic cathinones, salvia, desomorphine, and kratom. Because many of these substances can have severe or life-threatening adverse effects, knowledge of general toxicology is key in recognizing acute intoxication and overdose; however, typical toxidromes (e.g., cholinergic, sympathomimetic, opioid, etc.) are not precipitated by many of these agents. Medical management of patients who abuse or overdose on these drugs largely consists of supportive care, although naloxone may be used as an antidote for desomorphine overdose. Symptoms of aggression and psychosis may be treated with sedation (benzodiazepines, propofol) and antipsychotics (haloperidol or atypical agents such as quetiapine or ziprasidone). Other facets of management to consider include treatment for withdrawal or addiction, nutrition support, and potential for transmission of infectious diseases. © 2014 Pharmacotherapy Publications, Inc.

  16. A cephalometric analysis of Class II dentate subjects to establish a formula to determine the occlusal plane in Class II edentate subjects: A neo adjunct

    OpenAIRE

    Nikita Sinha; K Mahendranadh Reddy; Nidhi Gupta; Y M Shastry

    2017-01-01

    Purpose: Occlusal plane (OP) differs considerably in participants with skeletal Class I and Class II participants. In this study, cephalometrics has been used to help in the determination of orientation of the OP utilizing the nonresorbable bony anatomic landmarks in skeletal Class II participants and an attempt has been made to predict and examine the OP in individuals with skeletal class II jaw relationship. Materials and Methods: One hundred dentulous participants with skeletal Class II...

  17. MIDDLE CLASS MOVEMENTS

    OpenAIRE

    Dr. K. Sravana Kumar

    2016-01-01

    The middle class is placed between labour and capital. It neither directly awns the means of production that pumps out the surplus generated by wage labour power, nor does it, by its own labour, produce the surplus which has use and exchange value. Broadly speaking, this class consists of the petty bourgeoisie and the white-collar workers. The former are either self-employed or involved in the distribution of commodities and the latter are non-manual office workers, supervisors and profession...

  18. Talking Class in Tehroon

    DEFF Research Database (Denmark)

    Elling, Rasmus Christian; Rezakhani, Khodadad

    2016-01-01

    Persian, like any other language, is laced with references to class, both blatant and subtle. With idioms and metaphors, Iranians can identify and situate others, and thus themselves, within hierarchies of social status and privilege, both real and imagined. Some class-related terms can be traced...... back to medieval times, whereas others are of modern vintage, the linguistic legacy of television shows, pop songs, social media memes or street vernacular. Every day, it seems, an infectious set of phrases appears that make yesterday’s seem embarrassingly antiquated....

  19. Diabetes Drugs and Cardiovascular Safety

    Directory of Open Access Journals (Sweden)

    Ji Cheol Bae

    2016-06-01

    Full Text Available Diabetes is a well-known risk factor of cardiovascular morbidity and mortality, and the beneficial effect of improved glycemic control on cardiovascular complications has been well established. However, the rosiglitazone experience aroused awareness of potential cardiovascular risk associated with diabetes drugs and prompted the U.S. Food and Drug Administration to issue new guidelines about cardiovascular risk. Through postmarketing cardiovascular safety trials, some drugs demonstrated cardiovascular benefits, while some antidiabetic drugs raised concern about a possible increased cardiovascular risk associated with drug use. With the development of new classes of drugs, treatment options became wider and the complexity of glycemic management in type 2 diabetes has increased. When choosing the appropriate treatment strategy for patients with type 2 diabetes at high cardiovascular risk, not only the glucose-lowering effects, but also overall benefits and risks for cardiovascular disease should be taken into consideration.

  20. Drug Facts

    Medline Plus

    Full Text Available ... abuse, addiction, and treatment. Watch Videos Information About Drugs Alcohol Bath Salts Cocaine Heroin Marijuana MDMA Meth Pain Medicines Spice (K2) Tobacco/Nicotine Other Drugs You can ...