Student drug testing and positive school climates: testing the relation between two school characteristics and drug use behavior in a longitudinal study.

PubMed

Sznitman, Sharon R; Romer, Daniel

2014-01-01

Fostering positive school climates and student drug testing have been separately proposed as strategies to reduce student drug use in high schools. To assess the promise of these strategies, the present research examined whether positive school climates and/or student drug testing successfully predicted changes in youth substance use over a 1-year follow-up. Two waves of panel data from a sample of 361 high school students, assessed 1 year apart, were analyzed. Changes in reported initiation and escalation in frequency of alcohol, cigarette, and marijuana use as a function of perceived student drug testing and positive school climates were analyzed, while we held constant prior substance use. Perceived student drug testing was not associated with changes in substance use, whereas perceived positive school climates were associated with a reduction in cigarette and marijuana initiation and a reduction in escalation of frequency of cigarette use at 1-year follow-up. However, perceived positive school climates were not associated with a reduction in alcohol use. Student drug testing appears to be less associated with substance use than positive school climates. Nevertheless, even favorable school climates may not be able to influence the use of alcohol, which appears to be quite normative in this age group.

FEATURE 3, LARGE GUN POSITION, SHOWING MULTIPLE COMPARTMENTS, VIEW FACING ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

FEATURE 3, LARGE GUN POSITION, SHOWING MULTIPLE COMPARTMENTS, VIEW FACING SOUTH. - Naval Air Station Barbers Point, Anti-Aircraft Battery Complex-Large Gun Position, East of Coral Sea Road, northwest of Hamilton Road, Ewa, Honolulu County, HI

FEATURE A. CONCRETE ANTIAIRCRAFT GUN POSITION, SHOWING CORAL RUBBLE BERM, ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

FEATURE A. CONCRETE ANTI-AIRCRAFT GUN POSITION, SHOWING CORAL RUBBLE BERM, VIEW FACING SOUTHEAST. - Naval Air Station Barbers Point, Battery-Anti-Aircraft Gun Position, South of Point Cruz Road & west of Coral Sea Road, Ewa, Honolulu County, HI

FEATURE 3, LARGE GUN POSITION, SHOWING MULTIPLE COMPARTMENTS, VIEW FACING ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

FEATURE 3, LARGE GUN POSITION, SHOWING MULTIPLE COMPARTMENTS, VIEW FACING SOUTH (with scale stick). - Naval Air Station Barbers Point, Anti-Aircraft Battery Complex-Large Gun Position, East of Coral Sea Road, northwest of Hamilton Road, Ewa, Honolulu County, HI

Experimental Lung Cancer Drug Shows Early Promise | Frederick National Laboratory for Cancer Research

Cancer.gov

A first-of-its-kind drug is showing early promise in attacking certain lung cancers that are hard to treat because they build up resistance to conventional chemotherapy. The drug, CO-1686, performed well in a preclinical study involving xenograft and

Rapid detection of in vitro antituberculous drug resistance among smear-positive respiratory samples using microcolony detection-based direct drug susceptibility testing method.

PubMed

Iftikhar, Irim; Irfan, Seema; Farooqi, Joveria; Azizullah, Zahida; Hasan, Rumina

2017-01-01

With the rise in multidrug-resistant tuberculosis, there is a search for newer techniques that will rapidly detect drug-resistant Mycobacterium tuberculosis. Although molecular techniques can detect resistance, culture is still considered gold standard, especially in resource-limited settings where quick, cheap, and easy techniques are needed. The aim of the study was to evaluate microcolony method thin layer agar (TLA) for quick detection of resistance against the first- and second-line antituberculous drugs in clinical isolates. This was a cross-sectional study performed at Aga Khan University Hospital. A total of 87 Z-N stain smear-positive pulmonary samples were received and indirect drug susceptibility test (ID-DST) was performed using Lowenstein-Jensen and mycobacteria growth indicator tube. Direct DST was performed using TLA on 7H10 agar. TLA was observed twice weekly under microscope for 4 weeks. Sensitivity, specificity, and accuracy were calculated for TLA using indirect susceptibility method as the gold standard. Level of agreement was calculated using Kappa score. TLA showed sensitivity of 89% and 95.2% for isoniazid and rifampicin, while for ethionamide, ofloxacin, and injectable aminoglycosides, it was 96.6%, 92.1%, and 100%, respectively. Specificity for the first-line drugs was >95% while second-line drugs ranged from 70% to 100%. Mean time to positivity was 10.2 days by TLA as compared to 43.1 days by ID-DST. TLA is a quick and reliable method in identifying resistance, especially in resource-limited settings. However, additional liquid culture can be set up as backup, especially in patients on therapy to avoid false negative results.

A Retrospective Analysis of Urine Drugs of Abuse Immunoassay True Positive Rates at a National Reference Laboratory.

PubMed

Johnson-Davis, Kamisha L; Sadler, Aaron J; Genzen, Jonathan R

2016-03-01

Urine drug screens are commonly performed to identify drug use or monitor adherence to drug therapy. The purpose of this retrospective study was to evaluate the true positive and false positive rates of one of our in-house urine drug screen panels. The urine drugs of abuse panel studied consists of screening by immunoassay then positive immunoassay results were confirmed by mass spectrometry. Reagents from Syva and Microgenics were used for the immunoassay screen. The screen was performed on a Beckman AU5810 random access automated clinical analyzer. The percent of true positives for each immunoassay was determined. Agreement with previously validated GC-MS or LC-MS-MS confirmatory methods was also evaluated. There were 8,825 de-identified screening results for each of the drugs in the panel, except for alcohol (N = 2,296). The percent of samples that screened positive were: 10.0% for amphetamine/methamphetamine/3,4-methylenedioxy-methamphetamine (MDMA), 12.8% for benzodiazepines, 43.7% for opiates (including oxycodone) and 20.3% for tetrahydrocannabinol (THC). The false positive rate for amphetamine/methamphetamine was ∼14%, ∼34% for opiates (excluding oxycodone), 25% for propoxyphene and 100% for phencyclidine and MDMA immunoassays. Based on the results from this retrospective study, the true positive rate for THC drug use among adults were similar to the rate of illicit drug use in young adults from the 2013 National Survey; however, our positivity rate for cocaine was higher than the National Survey. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

[How children show positive and negative relationships on their drawings].

PubMed

Gramel, Sabine

2005-01-01

This study analyses, whether pictures of children showing a positive relationship are significantly different from those showing a negative one with respect to several criteria. The study involved a random selection of 45 children aged 4;6 to 11;6 years. The children painted a picture with themselves and a person they liked and a picture of themselves with someone they disliked. For the most part, the children drew pictures of themselves with peers both with respect to positive as well as negative images. In an interview afterwards, the children specified the criteria in their drawings by which the quality of the particular relationship can be identified. Positive and negative relationship paintings differ in the character of activity described. The sun as an element in children's paintings is painted not more frequent on positive compared to negative pictures. The colour black is used more often in the drawings signifying negative relationships. While girls used more colour in negative relationship drawings, boys used more colour in the positive ones. There was no significant difference in the use of favourite colours and decorative elements between the two groups. Only in negative relationship drawings people were looking away from each other. Smiling individuals were more common in the positive relationship pictures and in pictures painted by the 6 to 8 year olds. A greater distance between the individuals emerged on negative relationship drawings of the girls.

Predicting Drug-Target Interactions Based on Small Positive Samples.

PubMed

Hu, Pengwei; Chan, Keith C C; Hu, Yanxing

2018-01-01

A basic task in drug discovery is to find new medication in the form of candidate compounds that act on a target protein. In other words, a drug has to interact with a target and such drug-target interaction (DTI) is not expected to be random. Significant and interesting patterns are expected to be hidden in them. If these patterns can be discovered, new drugs are expected to be more easily discoverable. Currently, a number of computational methods have been proposed to predict DTIs based on their similarity. However, such as approach does not allow biochemical features to be directly considered. As a result, some methods have been proposed to try to discover patterns in physicochemical interactions. Since the number of potential negative DTIs are very high both in absolute terms and in comparison to that of the known ones, these methods are rather computationally expensive and they can only rely on subsets, rather than the full set, of negative DTIs for training and validation. As there is always a relatively high chance for negative DTIs to be falsely identified and as only partial subset of such DTIs is considered, existing approaches can be further improved to better predict DTIs. In this paper, we present a novel approach, called ODT (one class drug target interaction prediction), for such purpose. One main task of ODT is to discover association patterns between interacting drugs and proteins from the chemical structure of the former and the protein sequence network of the latter. ODT does so in two phases. First, the DTI-network is transformed to a representation by structural properties. Second, it applies a oneclass classification algorithm to build a prediction model based only on known positive interactions. We compared the best AUROC scores of the ODT with several state-of-art approaches on Gold standard data. The prediction accuracy of the ODT is superior in comparison with all the other methods at GPCRs dataset and Ion channels dataset. Performance

Recreational drug use and related social factors among HIV-positive men in Japan.

PubMed

Togari, Taisuke; Inoue, Yoji; Takaku, Yosuke; Abe, Sakurako; Hosokawa, Rikuya; Itagaki, Takashi; Yoshizawa, Shigeyuki; Oki, Sachiko; Katakura, Naoko; Yamauchi, Asae; Wakabayashi, Chihiro; Yajima, Takashi

2016-07-01

This study aims to determine the relationship between recreational drug use in HIV-positive males in the past year and socio-economic factors and/or social support networks in Japan. A national online survey in a cross-sectional study was conducted by HIV Futures Japan project from July 2013 to February 2014. Of the 1095 HIV-positive individuals who responded, 913 responses were determined to be valid; responses from the 875 males were analysed. A total of 282 participants used addictive drugs (32.2%) in past year. New psychoactive substances were used by 121 participants (13.8%), methamphetamine or amphetamine by 47 (5.4%), air dusters/sprays/gas by 31 (3.5%), 5-methoxy-N,N-diisopropyltryptamine (5MeO-DIPT) by 16 (1.8%) and cannabis (1.0%) by 9. Multiple logistic regression analysis was performed with the use of alkyl nitrites, addictive drugs, air dusters and thinners, which are low illegality, as dependent variables. We found that the odds ratio (95% confidence interval) for use among participants with full-time and temp/contracted/part-time employees compared to management/administration professions were 2.59 (0.99-6.77) and 2.61 (0.91-7.51). Also, a correlation was observed between alkyl nitrites and new psychoactive substances and usage rates in people engaged in few HIV-positive networks. It is necessary to develop targeted policies for drug use prevention and user support among HIV-positive men and to support and provide care for drug users who are isolated or have a narrow HIV/AIDS support network.

Multi-drug-resistant tuberculosis in HIV positive patients in Eastern Europe.

PubMed

Post, Frank A; Grint, Daniel; Werlinrud, Anne Marie; Panteleev, Alexander; Riekstina, Vieja; Malashenkov, Evgeniy A; Skrahina, Alena; Duiculescu, Dan; Podlekareva, Daria; Karpov, Igor; Bondarenko, Vasiliy; Chentsova, Nelly; Lundgren, Jens; Mocroft, Amanda; Kirk, Ole; Miro, Jose M

2014-03-01

Observational data from Eastern Europe on the management and outcome of multi-drug-resistant tuberculosis (MDR TB) in HIV positive populations remain sparse in the English-language literature. We compared clinical characteristics and outcomes of 55 patients who were diagnosed with HIV and MDR TB in Eastern Europe between 2004 and 2006 to 89 patients whose Mycobacterium tuberculosis isolates were susceptible to isoniazid and rifampicin. Patients with HIV and MDR TB were young and predominantly male with high rates of intravenous drug use, imprisonment and hepatitis C co-infection. Eighty-four per cent of patients with MDR TB had no history of previous TB drug exposure suggesting that the majority of MDR TB resulted from transmission of drug-resistant M. tuberculosis. The use of non-standardized tuberculosis treatment was common, and the use of antiretroviral therapy infrequent. Compared to those with susceptible tuberculosis, patients with MDR TB were less likely to achieve cure or complete tuberculosis treatment (21.8% vs. 62.9%, p < 0.0001), and they were more likely to die (65.5% vs. 27.0%, p < 0.0001). Our study documents suboptimal management and poor outcomes in HIV positive patients with MDR TB. Implementation of WHO guidelines, rapid TB diagnostics and TB drug susceptibility testing for all patients remain a priority in this region. Copyright © 2013 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

10 CFR 707.7 - Random drug testing requirements and identification of testing designated positions.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 10 Energy 4 2012-01-01 2012-01-01 false Random drug testing requirements and identification of... PROGRAMS AT DOE SITES Procedures § 707.7 Random drug testing requirements and identification of testing... evidence of the use of illegal drugs of employees in testing designated positions identified in this...

10 CFR 707.7 - Random drug testing requirements and identification of testing designated positions.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 10 Energy 4 2014-01-01 2014-01-01 false Random drug testing requirements and identification of... PROGRAMS AT DOE SITES Procedures § 707.7 Random drug testing requirements and identification of testing... evidence of the use of illegal drugs of employees in testing designated positions identified in this...

10 CFR 707.7 - Random drug testing requirements and identification of testing designated positions.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 10 Energy 4 2011-01-01 2011-01-01 false Random drug testing requirements and identification of... PROGRAMS AT DOE SITES Procedures § 707.7 Random drug testing requirements and identification of testing... evidence of the use of illegal drugs of employees in testing designated positions identified in this...

10 CFR 707.7 - Random drug testing requirements and identification of testing designated positions.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 10 Energy 4 2013-01-01 2013-01-01 false Random drug testing requirements and identification of... PROGRAMS AT DOE SITES Procedures § 707.7 Random drug testing requirements and identification of testing... evidence of the use of illegal drugs of employees in testing designated positions identified in this...

10 CFR 707.7 - Random drug testing requirements and identification of testing designated positions.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 10 Energy 4 2010-01-01 2010-01-01 false Random drug testing requirements and identification of... PROGRAMS AT DOE SITES Procedures § 707.7 Random drug testing requirements and identification of testing... evidence of the use of illegal drugs of employees in testing designated positions identified in this...

Sexual Risk Taking among HIV-Positive Injection Drug Users: Contexts, Characteristics, and Implications for Prevention

ERIC Educational Resources Information Center

Knight, Kelly R.; Purcell, David; Dawson-Rose, Carol; Halkitis, Perry N.; Gomez, Cynthia A.

2005-01-01

HIV-positive injection drug users (IDUs) (N = 161) were recruited to complete a qualitative interview and a quantitative survey about sexual behavior and transmission risk. We identified two contexts in which exposure encounters occurred most commonly for HIV-positive IDUs: in intimate serodiscordant relationships and in the drug/sex economy.…

Risks, prices, and positions: A social network analysis of illegal drug trafficking in the world-economy.

PubMed

Boivin, Rémi

2014-03-01

Illegal drug prices are extremely high, compared to similar goods. There is, however, considerable variation in value depending on place, market level and type of drugs. A prominent framework for the study of illegal drugs is the "risks and prices" model (Reuter & Kleiman, 1986). Enforcement is seen as a "tax" added to the regular price. In this paper, it is argued that such economic models are not sufficient to explain price variations at country-level. Drug markets are analysed as global trade networks in which a country's position has an impact on various features, including illegal drug prices. This paper uses social network analysis (SNA) to explain price markups between pairs of countries involved in the trafficking of illegal drugs between 1998 and 2007. It aims to explore a simple question: why do prices increase between two countries? Using relational data from various international organizations, separate trade networks were built for cocaine, heroin and cannabis. Wholesale price markups are predicted with measures of supply, demand, risks of seizures, geographic distance and global positioning within the networks. Reported prices (in $US) and purchasing power parity-adjusted values are analysed. Drug prices increase more sharply when drugs are headed to countries where law enforcement imposes higher costs on traffickers. The position and role of a country in global drug markets are also closely associated with the value of drugs. Price markups are lower if the destination country is a transit to large potential markets. Furthermore, price markups for cocaine and heroin are more pronounced when drugs are exported to countries that are better positioned in the legitimate world-economy, suggesting that relations in legal and illegal markets are directed in opposite directions. Consistent with the world-system perspective, evidence is found of coherent world drug markets driven by both local realities and international relations. Copyright © 2013 Elsevier B

Case Reports of Aripiprazole Causing False-Positive Urine Amphetamine Drug Screens in Children.

PubMed

Kaplan, Justin; Shah, Pooja; Faley, Brian; Siegel, Mark E

2015-12-01

Urine drug screens (UDSs) are used to identify the presence of certain medications. One limitation of UDSs is the potential for false-positive results caused by cross-reactivity with other substances. Amphetamines have an extensive list of cross-reacting medications. The literature contains reports of false-positive amphetamine UDSs with multiple antidepressants and antipsychotics. We present 2 cases of presumed false-positive UDSs for amphetamines after ingestion of aripiprazole. Case 1 was a 16-month-old girl who accidently ingested 15 to 45 mg of aripiprazole. She was lethargic and ataxic at home with 1 episode of vomiting containing no identifiable tablets. She remained sluggish with periods of irritability and was admitted for observation. UDS on 2 consecutive days came back positive for amphetamines. Case 2 was of a 20-month-old girl who was brought into the hospital after accidental ingestion of an unknown quantity of her father's medications which included aripiprazole. UDS on the first day of admission came back positive only for amphetamines. Confirmatory testing with gas chromatography-mass spectrometry (GC-MS) on the blood and urine samples were also performed for both patients on presentation to detect amphetamines and were subsequently negative. Both patients returned to baseline and were discharged from the hospital. To our knowledge, these cases represent the first reports of false-positive amphetamine urine drug tests with aripiprazole. In both cases, aripiprazole was the drug with the highest likelihood of causing the positive amphetamine screen. The implications of these false-positives include the possibility of unnecessary treatment and monitoring of patients. Copyright © 2015 by the American Academy of Pediatrics.

Differences in treatment outcome between male alcohol dependent offenders of domestic violence with and without positive drug screens.

PubMed

Easton, Caroline J; Mandel, Dolores; Babuscio, Theresa; Rounsaville, Bruce J; Carroll, Kathleen M

2007-10-01

Men who are violent toward their partners tend to have a dual problem with alcohol and drug use, yet little is known about differences between men with single rather than dual problems. This study was one of the first to evaluate differences between alcohol dependent men who were arrested for Intimate Partner Violence (IPV) with and without concurrent illicit drug use. Seventy-eight participants were randomly assigned to manual-guided group behavioral therapies (Cognitive Behavioral Therapy or Twelve Step Facilitation) and assessed across 12 weeks of treatment. Despite denying drug use at baseline, thirty-two clients (43%) tested positive for illicit drug use (cocaine and marijuana) during the 12 weeks of treatment. The study specifically addressed whether there were differences between clients using alcohol only versus individuals using both alcohol + drugs in terms of 1) baseline characteristics; 2) treatment compliance (e.g., attendance and substance use during treatment; and 3) treatment outcomes (alcohol, drug use, anger management, and aggression at the completion of treatment). The results showed that there were comparatively few differences between the alcohol versus the alcohol + drug using groups at baseline. Regarding treatment compliance and retention, alcohol + drug using participants attended significantly fewer sessions, had significantly fewer percent days abstinence from alcohol use, significantly more total days of positive breathalyzer results. Regarding treatment outcomes across anger management and aggression scores, the alcohol + drug using participants had significantly more impairments in anger management styles from pre- to post-treatment. However, there were no differences between the groups across verbal or physical aggression. Both groups improved in their verbal aggression from pre- to post-treatment. The findings suggest that alcohol dependent men who continue to use illicit drugs may require additional interventions to effectively

[SICI-GISE position paper on drug-coated balloon use in the coronary district].

PubMed

Cortese, Bernardo; Sgueglia, Gregory A; Berti, Sergio; Biondi-Zoccai, Giuseppe; Colombo, Antonio; Limbruno, Ugo; Bedogni, Francesco; Cremonesi, Alberto

2013-10-01

Drug-coated balloons are a new tool for the treatment of patients with coronary artery disease. The main feature of this technology is a rapid and homogeneous transfer of an antiproliferative drug (paclitaxel) to the vessel wall just at the time of balloon inflation, when neointimal proliferation, in response to angioplasty, is the highest. Moreover, drug-coated balloons share adjunctive advantages over stents: the absence of permanent scaffold and polymer, the respect of the original coronary anatomy, and limited inflammatory stimuli, thereby allowing for short-term dual antiplatelet therapy. At present, a variety of devices are available in the market, with limited scientific data for the vast majority of them. Thus, the Italian Society of Interventional Cardiology (SICI-GISE) decided to coordinate the efforts of a group of renowned experts in this field, in order to produce a position paper on the correct use of drug-coated balloons in all settings of coronary artery disease, giving a class of indication to each one, based on clinical evidence. This position paper represents a quick reference for operators, investigators and manufacturers to promote the understanding and the correct use of the drug-coated balloon technology in everyday clinical practice.

1. OBLIQUE VIEW, NORTH AND EAST SIDES. VIEW SHOWS POSITION ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

1. OBLIQUE VIEW, NORTH AND EAST SIDES. VIEW SHOWS POSITION OF BUILDING UNDER LEG OF TOWER 33. - Chollas Heights Naval Radio Transmitting Facility, PERS Support Storage Building, 6410 Zero Road, San Diego, San Diego County, CA

4. VENTILATION FAN SHOWING RELATIVE POSITION IN THE AIR TUNNEL. ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

4. VENTILATION FAN SHOWING RELATIVE POSITION IN THE AIR TUNNEL. - Hot Springs National Park, Bathhouse Row, Ozark Bathhouse: Mechanical & Piping Systems, State Highway 7, 1 mile north of U.S. Highway 70, Hot Springs, Garland County, AR

Positive and negative ion mode ESI-MS and MS/MS for studying drug-DNA complexes

NASA Astrophysics Data System (ADS)

Rosu, Frédéric; Pirotte, Sophie; Pauw, Edwin De; Gabelica, Valérie

2006-07-01

We report systematic investigation of duplex DNA complexes with minor groove binders (Hoechsts 33258 and 33342, netropsin and DAPI) and intercalators (daunomycin, doxorubicin, actinomycin D, ethidium, cryptolepine, neocryptolepine, m-Amsacrine, proflavine, ellipticine and mitoxantrone) by ESI-MS and ESI-MS/MS in the negative ion mode and in the positive ion mode. The apparent solution phase equilibrium binding constants can be determined by measuring relative intensities in the ESI-MS spectrum. While negative ion mode gives reliable results, positive ion mode gives a systematic underestimation of the binding constants and even a complete suppression of the complexes for intercalators lacking functional groups capable of interacting in the grooves. In the second part of the paper we systematically compare MS/MS fragmentation channels and breakdown curves in the positive and the negative modes, and discuss the possible uses and caveats of MS/MS in drug-DNA complexes. In the negative mode, the drugs can be separated in three groups: (1) those that leave the complex with no net charge; (2) those that leave the complex with a negative charge; and (3) those that remain attached on the strands upon dissociation of the duplex due to their positive charge. In the positive ion mode, all complexes fragment via the loss of protonated drug. Information on the stabilization of the complex by drug-DNA noncovalent interactions can be obtained straightforwardly only in the case of neutral drug loss. In all other cases, proton affinity (in the positive ion mode), gas-phase basicity (in the negative ion mode) and coulombic repulsion are the major factors influencing the fragmentation channel and the dissociation kinetics.

Racial discrimination, socioeconomic position, and illicit drug use among US Blacks.

PubMed

Carliner, Hannah; Delker, Erin; Fink, David S; Keyes, Katherine M; Hasin, Deborah S

2016-04-01

We assessed the relationship of self-reported racial discrimination with illicit drug use among US Blacks, and whether this differed by socioeconomic position (SEP). Among 6587 Black participants in Wave 2 of the National Epidemiologic Survey on Alcohol and Related Conditions (2004-2005), we used multiple logistic regression models to test the association between racial discrimination (measured on the 6-item Experiences of Discrimination scale) and past-year illicit drug use, and whether this differed by SEP. Racial discrimination was associated with past-year drug use [adjusted odds ratio (aOR) 2.32; 95 % confidence interval (CI) 1.70, 3.16] and with frequent drug use (aOR 1.91; 95 % CI 1.22, 2.99). For frequent illicit drug use, this relationship was stronger among higher SEP participants (aOR 3.55; 95 % CI 2.09, 6.02; p interaction < 0.01). The stronger association between racial discrimination and frequent illicit drug use among higher SEP Blacks suggests a complex interplay between disadvantaged and privileged statuses that merits further investigation. The finding of a significant difference by SEP highlights the importance of considering differences within heterogeneous race/ethnic groups when investigating health disparities.

5. UNIT VENTILATOR, MEN'S BATH HALL, SHOWING POSITION AGAINST WALL ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

5. UNIT VENTILATOR, MEN'S BATH HALL, SHOWING POSITION AGAINST WALL ABOVE THE BATHS. - Hot Springs National Park, Bathhouse Row, Ozark Bathhouse: Mechanical & Piping Systems, State Highway 7, 1 mile north of U.S. Highway 70, Hot Springs, Garland County, AR

Lixisenatide, a drug developed to treat type 2 diabetes, shows neuroprotective effects in a mouse model of Alzheimer's disease.

PubMed

McClean, Paula L; Hölscher, Christian

2014-11-01

Type 2 diabetes is a risk factor for developing Alzheimer's disease (AD). In the brains of AD patients, insulin signalling is desensitised. The incretin hormone Glucagon-like peptide-1 (GLP-1) facilitates insulin signalling, and analogues such as liraglutide are on the market as treatments for type 2 diabetes. We have previously shown that liraglutide showed neuroprotective effects in the APPswe/PS1ΔE9 mouse model of AD. Here, we test the GLP-1 receptor agonist lixisenatide in the same mouse model and compare the effects to liraglutide. After ten weeks of daily i.p. injections with liraglutide (2.5 or 25 nmol/kg) or lixisenatide (1 or 10 nmol/kg) or saline of APP/PS1 mice at an age when amyloid plaques had already formed, performance in an object recognition task was improved in APP/PS1 mice by both drugs at all doses tested. When analysing synaptic plasticity in the hippocampus, LTP was strongly increased in APP/PS1 mice by either drug. Lixisenatide (1 nmol/kg) was most effective. The reduction of synapse numbers seen in APP/PS1 mice was prevented by the drugs. The amyloid plaque load and dense-core Congo red positive plaque load in the cortex was reduced by both drugs at all doses. The chronic inflammation response (microglial activation) was also reduced by all treatments. The results demonstrate that the GLP-1 receptor agonists liraglutide and lixisenatide which are on the market as treatments for type 2 diabetes show promise as potential drug treatments of AD. Lixisenatide was equally effective at a lower dose compared to liraglutide in some of the parameters measured. Copyright © 2014 Elsevier Ltd. All rights reserved.

Position paper from the Spanish Society of Rheumatology on biosimilar drugs.

PubMed

Abad Hernández, Miguel Ángel; Andreu, José Luis; Caracuel Ruiz, Miguel Ángel; Belmonte Serrano, Miguel Ángel; Díaz-González, Federico; Moreno Muelas, José Vicente

2015-01-01

A biosimilar (BS) is a biological drug that contains a version of the active substance of an already authorized original biological product. The BSs are marketed after patent period of the original drug has ended and once it has been demonstrated that the differences regarding the innovative medicine have no relevant effect on its safety or clinical efficacy. The Spanish Society of Rheumatology, in line with the European Medicines Agency, considers that because of its nature and complexity of production, a BS cannot be considered to be the same as a generic drug. The Spanish Society of Rheumatology expresses an unequivocal commitment to the sustainability of the health system in our country and our steadfast alignment with all measures designed to ensure continuity, without reducing the quality of care. Therefore, we believe that the advent of BSs will likely facilitate access of patients with rheumatic diseases to the biological drugs. This article reviews the European Medicines Agency requirements for authorization, the Spanish legal framework and controversies on BS and presents the position paper of the Spanish Society of Rheumatology on these drugs. Copyright © 2015 Elsevier España, S.L.U. All rights reserved.

Responses to Positive Results from Suspicionless Random Drug Tests in US Public School Districts

ERIC Educational Resources Information Center

Ringwalt, Chris; Vincus, Amy A.; Ennett, Susan T.; Hanley, Sean; Bowling, J. Michael; Yacoubian, George S., Jr.; Rohrbach, Louise A.

2009-01-01

Background: Little is known about the context in which school-based suspicionless random drug testing (SRDT) occurs. The primary purpose of the current study was to describe school districts' responses to students' first positive result in districts with SRDT programs. Methods: Data were collected in spring 2005 from 1612 drug prevention…

Different policy outcomes of the new drugs and currently listed drugs under the positive list system in South Korea.

PubMed

Lee, Eui-Kyung; Kim, Bo-Yeon; Lim, Jae-Young; Park, Mi-Hai

2012-01-01

Four years have passed since the positive list system was implemented in South Korea. The system was received well because it has fulfilled its intended objective of enhancing the cost-effectiveness of new drugs. With regard to currently listed drugs, however, debate has lingered since the reevaluation of the cost-effectiveness by therapeutic group. This study intended to review the lessons learned and compromises reached in implementing an evidence-based national formulary. Currently listed drugs are very different from new drugs. In terms of effectiveness, the level of existing evidence tends to be lower for currently listed drugs. Also, the evaluation plan was quite delayed because of the vast amount of literature. In the political decision-making process, a coalition was formed by the pharmaceutical companies with physicians, and the government had difficulty responding because of the strong resistance against the reevaluation of currently listed drugs. Although idealistic, it was an attempt to apply the same standard of cost-effectiveness for currently listed drugs as that for new drugs. To successfully implement the system, however, some factors that need to be considered were limitation of available evidence on currently listed drugs and specific strategies employed against political resistance. Copyright © 2012 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

Lonely Individuals Do Not Show Interpersonal Self-Positivity Bias: Evidence From N400

PubMed Central

Zhu, Min; Zhu, Changzheng; Gao, Xiangping; Luo, Junlong

2018-01-01

Self-positivity bias is one of the well-studied psychological phenomena, however, little is known about the bias in the specific dimension on social interaction, which we called herein interpersonal self-positivity bias—people tend to evaluate themselves more positively on social interactions, prefer to be included rather than to be excluded by others. In the present study, we used a modified self-reference task associated with N400 to verify such bias and explore whether impoverished social interaction (loneliness) could modulate it. Findings showed that exclusion verbs elicited larger N400 amplitudes than inclusion verbs, suggesting that most people have interpersonal self-positivity bias. However, loneliness was significantly correlated with N400 effect, showing those with high scores of loneliness had smaller differences in the N400 than those with lower scores. These findings indicated impoverished social interaction weakens interpersonal self-positivity bias; however, the underlying mechanisms need to be explored in future research. PMID:29681875

Stress processes in HIV-positive African American mothers: moderating effects of drug abuse history.

PubMed

Burns, Myron J; Feaster, Daniel J; Mitrani, Victoria B; Ow, Christina; Szapocznik, José

2008-01-01

This study examined the mechanism by which stressors, dissatisfaction with family, perceived control, social support, and coping were related to psychological distress in a sample of HIV-positive African American mothers. Additional analyses explored whether women who had a history of a drug abuse or dependence diagnosis differed either on levels of the study variables or the model pathways. The results indicated that HIV-positive African American mothers who had higher levels of stressors perceived their stressors as a whole to be less controllable. Coping resources, available social support and perceived control, were positively associated with active coping and negatively associated with psychological distress. Avoidant coping was the most important predictor of psychological distress. Furthermore, the effect of avoidant coping on psychological distress was stronger for mothers with a history of drug diagnosis. The implications of these findings for targeting interventions are discussed.

A trend analysis of laboratory positive propoxyphene workplace urine drug screens before and after the product recall.

PubMed

Price, James

2015-01-01

Propoxyphene was withdrawn from the US market in November 2010. This drug is still tested for in the workplace as part of expanded panel nonregulated testing. A convenience sample of urine specimens (n = 7838) were provided by workers from various industries. The percentage of positive specimens with 95% confidence intervals was calculated for each year of the study. Logistic regression was used to assess the impact of the year upon the propoxyphene result. The prevalence of positive propoxyphene tests was much higher before the product's withdrawal from the market. Logistic regression provided evidence of a decreasing linear trend (P < 0.000; β = -0.71). The odds ratio signifies that for every additional year the urine specimens were 0.49 times less likely to be positive for propoxyphene. This favors the determination that the change in propoxyphene positive drug test over the years is not by chance. The conclusion supports no longer performing nonregulated workplace propoxyphene urine drug testing for this population.

Stress processes in HIV-positive African American mothers: Moderating effects of drug abuse history

PubMed Central

BURNS, MYRON J.; FEASTER, DANIEL J.; MITRANI, VICTORIA B.; OW, CHRISTINA; SZAPOCZNIK, JOSÉ

2008-01-01

This study examined the mechanism by which stressors, dissatisfaction with family, perceived control, social support, and coping were related to psychological distress in a sample of HIV-positive African American mothers. Additional analyses explored whether women who had a history of a drug abuse or dependence diagnosis differed either on levels of the study variables or the model pathways. The results indicated that HIV-positive African American mothers who had higher levels of stressors perceived their stressors as a whole to be less controllable. Coping resources, available social support and perceived control, were positively associated with active coping and negatively associated with psychological distress. Avoidant coping was the most important predictor of psychological distress. Furthermore, the effect of avoidant coping on psychological distress was stronger for mothers with a history of drug diagnosis. The implications of these findings for targeting interventions are discussed. PMID:18027126

Student Drug Testing in the Context of Positive and Negative School Climates: Results from a National Survey

ERIC Educational Resources Information Center

Sznitman, Sharon R.; Dunlop, Sally M.; Nalkur, Priya; Khurana, Atika; Romer, Daniel

2012-01-01

Positive school climates and student drug testing have been separately proposed as strategies to reduce student substance use in high schools. However, the effects of drug testing programs may depend on the favorability of school climates. This study examined the association between school drug testing programs and student substance use in schools…

The drug target genes show higher evolutionary conservation than non-target genes.

PubMed

Lv, Wenhua; Xu, Yongdeng; Guo, Yiying; Yu, Ziqi; Feng, Guanglong; Liu, Panpan; Luan, Meiwei; Zhu, Hongjie; Liu, Guiyou; Zhang, Mingming; Lv, Hongchao; Duan, Lian; Shang, Zhenwei; Li, Jin; Jiang, Yongshuai; Zhang, Ruijie

2016-01-26

Although evidence indicates that drug target genes share some common evolutionary features, there have been few studies analyzing evolutionary features of drug targets from an overall level. Therefore, we conducted an analysis which aimed to investigate the evolutionary characteristics of drug target genes. We compared the evolutionary conservation between human drug target genes and non-target genes by combining both the evolutionary features and network topological properties in human protein-protein interaction network. The evolution rate, conservation score and the percentage of orthologous genes of 21 species were included in our study. Meanwhile, four topological features including the average shortest path length, betweenness centrality, clustering coefficient and degree were considered for comparison analysis. Then we got four results as following: compared with non-drug target genes, 1) drug target genes had lower evolutionary rates; 2) drug target genes had higher conservation scores; 3) drug target genes had higher percentages of orthologous genes and 4) drug target genes had a tighter network structure including higher degrees, betweenness centrality, clustering coefficients and lower average shortest path lengths. These results demonstrate that drug target genes are more evolutionarily conserved than non-drug target genes. We hope that our study will provide valuable information for other researchers who are interested in evolutionary conservation of drug targets.

IET. Tank building (TAN627). Plans, elevation, details. shows position of ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

IET. Tank building (TAN-627). Plans, elevation, details. shows position of tanks within building and concrete supports. Ralph M. Parsons 902-4-ANP-627-A&S 420. Date: Fabruary 1954. Approved by INEEL Classification Office for public release. INEEL index code no. 035-0627-00-693-106975 - Idaho National Engineering Laboratory, Test Area North, Scoville, Butte County, ID

Title: Studies on drug switchability showed heterogeneity in methodological approaches: a scoping review.

PubMed

Belleudi, Valeria; Trotta, Francesco; Vecchi, Simona; Amato, Laura; Addis, Antonio; Davoli, Marina

2018-05-16

Several drugs share the same therapeutic indication, including those undergoing patent expiration. Concerns on the interchangeability are frequent in clinical practice, challenging the evaluation of switchability through observational research. To conduct a scoping review of observational studies on drug switchability to identify methodological strategies adopted to deal with bias and confounding. We searched PubMed, EMBASE, and Web of Science (updated 1/31/2017) to identify studies evaluating switchability in terms of effectiveness/safety outcomes or compliance. Three reviewers independently screened studies extracting all characteristics. Strategies to address confounding, particularly, previous drug use and switching reasons were considered. All findings were summarized in descriptive analyses. Thirty-two studies, published in the last 10 years, met the inclusion criteria. Epilepsy, cardiovascular and rheumatology were the most frequently represented clinical areas. 75% of the studies reported data on effectiveness/safety outcomes. The most frequent study design was cohort (65.6%) followed by case-control (21.9%) and self-controlled (12.5%). Case-control and case-crossover studies showed homogeneous methodological strategies to deal with bias and confounding. Among cohort studies, the confounding associated with previous drug use was addressed introducing variables in multivariate model (47.3%) or selecting only adherent patients (14.3%). Around 30% of cohort studies did not report reasons for switching. In the remaining 70%, clinical parameters or previous occurrence of outcomes were measured to identify switching connected with lack of effectiveness or adverse events. This study represents a starting point for researchers and administrators who are approaching the investigation and assessment of issues related to interchangeability of drugs. Copyright © 2018. Published by Elsevier Inc.

Anti-Jo-1 antibody-positive patients show a characteristic necrotizing perifascicular myositis.

PubMed

Mescam-Mancini, Lénaig; Allenbach, Yves; Hervier, Baptiste; Devilliers, Hervé; Mariampillay, Kuberaka; Dubourg, Odile; Maisonobe, Thierry; Gherardi, Romain; Mezin, Paulette; Preusse, Corinna; Stenzel, Werner; Benveniste, Olivier

2015-09-01

Idiopathic inflammatory myopathies can be classified as polymyositis, dermatomyositis, immune-mediated necrotizing myopathy, sporadic inclusion body myositis or non-specific myositis. Anti-Jo-1 antibody-positive patients are assigned to either polymyositis or dermatomyositis suggesting overlapping pathological features. We aimed to determine if anti-Jo-1 antibody-positive myopathy has a specific morphological phenotype. In a series of 53 muscle biopsies of anti-Jo-1 antibody-positive patients, relevant descriptive criteria defining a characteristic morphological pattern were identified. They were tested in a second series of anti-Jo-1 antibody-positive patients and compared to 63 biopsies from patients suffering from other idiopathic inflammatory myopathies. In anti-Jo-1 antibody-positive patients, necrotic fibres, which strongly clustered in perifascicular regions, were frequently observed. Sarcolemmal complement deposition was detected specifically in perifascicular areas. Inflammation was mainly located in the perimysium and around vessels in 90.6%. Perimysial fragmentation was observed in 90% of cases. Major histocompatibility complex class I staining was diffusely positive, with a perifascicular reinforcement. Multivariate analysis showed that criteria defining perifascicular pathology: perifascicular necrosis, atrophy, and perimysial fragmentation allow the distinction of anti-Jo-1 antibody-positive patients, among patients suffering from other idiopathic inflammatory myopathies. Anti-Jo-1 antibody-positive patients displayed perifascicular necrosis, whereas dermatomyositis patients exhibited perifascicular atrophy. © The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Weighing the Consequences: Self-Disclosure of HIV-Positive Status among African American Injection Drug Users

ERIC Educational Resources Information Center

Valle, Maribel; Levy, Judith

2009-01-01

Theorists posit that personal decisions to disclose being HIV positive are made based on the perceived consequences of that disclosure. This study examines the perceived costs and benefits of self-disclosure among African American injection drug users (IDUs). A total of 80 African American IDUs were interviewed in-depth subsequent to testing HIV…

Medicare Prescription Drug Plan Enrollees Report Less Positive Experiences Than Their Medicare Advantage Counterparts.

PubMed

Elliott, Marc N; Landon, Bruce E; Zaslavsky, Alan M; Edwards, Carol; Orr, Nathan; Beckett, Megan K; Mallett, Joshua; Cleary, Paul D

2016-03-01

Since 2006, Medicare beneficiaries have been able to obtain prescription drug coverage through standalone prescription drug plans or their Medicare Advantage (MA) health plan, options exercised in 2015 by 72 percent of beneficiaries. Using data from community-dwelling Medicare beneficiaries older than age sixty-four in 700 plans surveyed from 2007 to 2014, we compared beneficiaries' assessments of Medicare prescription drug coverage when provided by standalone plans or integrated into an MA plan. Beneficiaries in standalone plans consistently reported less positive experiences with prescription drug plans (ease of getting medications, getting coverage information, and getting cost information) than their MA counterparts. Because MA plans are responsible for overall health care costs, they might have more integrated systems and greater incentives than standalone prescription drug plans to provide enrollees medications and information effectively, including, since 2010, quality bonus payments to these MA plans under provisions of the Affordable Care Act. Project HOPE—The People-to-People Health Foundation, Inc.

Multi-drug resistant oral Candida species isolated from HIV-positive patients in South Africa and Cameroon.

PubMed

Dos Santos Abrantes, Pedro Miguel; McArthur, Carole P; Africa, Charlene Wilma Joyce

2014-06-01

Candida species are a common cause of infection in immune-compromised HIV-positive individuals, who are usually treated with the antifungal drug, fluconazole, in public hospitals in Africa. However, information about the prevalence of drug resistance to fluconazole and other antifungal agents on Candida species is very limited. This study examined 128 Candida isolates from South Africa and 126 Cameroonian Candida isolates for determination of species prevalence and antifungal drug susceptibility. The isolates were characterized by growth on chromogenic and selective media and by their susceptibility to 9 antifungal drugs tested using the TREK™ YeastOne9 drug panel (Thermo Scientific, USA). Eighty-three percent (82.8%) of South African isolates were Candida albicans (106 isolates), 9.4% were Candida glabrata (12 isolates), and 7.8% were Candida dubliniensis (10 isolates). Of the Cameroonian isolates, 73.02% were C. albicans (92 isolates); 19.05% C. glabrata (24 isolates); 3.2% Candida tropicalis (4 isolates); 2.4% Candida krusei (3 isolates); 1.59% either Candida kefyr, Candida parapsilopsis, or Candida lusitaneae (2 isolates); and 0.79% C. dubliniensis (1 isolate). Widespread C. albicans resistance to azoles was detected phenotypically in both populations. Differences in drug resistance were seen within C. glabrata found in both populations. Echinocandin drugs were more effective on isolates obtained from the Cameroon than in South Africa. A multiple-drug resistant C. dubliniensis strain isolated from the South African samples was inhibited only by 5-flucytosine in vitro on the YO9 panel. Drug resistance among oral Candida species is common among African HIV patients in these 2 countries. Regional surveillance of Candida species drug susceptibility should be undertaken to ensure effective treatment for HIV-positive patients. Copyright © 2014 Elsevier Inc. All rights reserved.

New York Report Shows Two of Every Three Students Have Used Drugs.

ERIC Educational Resources Information Center

Change, 1981

1981-01-01

A survey of drug use and use of drugs and alcohol among undergraduates in New York State revealed that two out of three full-time students have recently (six months prior to the survey) taken an illegal drug or used a legal drug nonmedically. (MLW)

Developing and implementing a positive behavioral reinforcement intervention in prison-based drug treatment: Project BRITE.

PubMed

Burdon, William M; St De Lore, Jef; Prendergast, Michael L

2011-09-01

Within prison settings, the reliance on punishment for controlling inappropriate or noncompliant behavior is self-evident. What is not so evident is the similarity between this reliance on punishment and the use of positive reinforcements to increase desired behaviors. However, seldom do inmates receive positive reinforcement for engaging in prosocial behaviors or, for inmates receiving drug treatment, behaviors that are consistent with or support their recovery. This study provides an overview of the development and implementation of a positive behavioral reinforcement intervention in male and female prison-based drug treatment programs. The active involvement of institutional staff, treatment staff, and inmates enrolled in the treatment programs in the development of the intervention along with the successful branding of the intervention were effective at promoting support and participation. However, these factors may also have ultimately impacted the ability of the randomized design to reliably demonstrate the effectiveness of the intervention.

Crack-cocaine use accelerates HIV disease progression in a cohort of HIV-positive drug users.

PubMed

Baum, Marianna K; Rafie, Carlin; Lai, Shenghan; Sales, Sabrina; Page, Bryan; Campa, Adriana

2009-01-01

HIV infection is prevalent among substance abusers. The effects of specific illicit drugs on HIV disease progression have not been established. We evaluated the relationship between substances of abuse and HIV disease progression in a cohort of HIV-1-positive active drug users. A prospective, 30-month, longitudinal study was conducted on 222 HIV-1 seropositive drug users in Miami, FL. History of illicit drug, alcohol, and medication use, CD4+ cell count, and viral load were performed every 6 months. Crack-cocaine users were 2.14 times [95% confidence interval (CI): 1.08 to 4.25, P = 0.029] more likely to present a decline of CD4 to showed a greater risk for HIV disease progression than nonusers (hazard ratio = 3.946; 95% CI: 1.049 to 14.85, P = 0.042). Crack-cocaine use facilitates HIV disease progression by reducing adherence in those on HAART and by accelerating disease progression independently of HAART.

Developing and Implementing a Positive Behavioral Reinforcement Intervention in Prison-Based Drug Treatment: Project BRITE

PubMed Central

Burdon, William M.; De Lore, Jef St.; Prendergast, Michael L.

2012-01-01

Within prison settings, the reliance on punishment for controlling inappropriate or non-compliant behavior is self-evident. What is not so evident is the similarity between this reliance on punishment and the use of positive reinforcements to increase desired behaviors. However, seldom do inmates receive positive reinforcement for engaging in prosocial behaviors or, for inmates receiving drug treatment, behaviors that are consistent with or support their recovery. This study provides an overview of the development and implementation of a positive behavioral reinforcement intervention in male and female prison-based drug treatment programs. The active involvement of institutional staff, treatment staff, and inmates enrolled in the treatment programs in the development of the intervention along with the successful branding of the intervention were effective at promoting support and participation. However, these factors may also have ultimately impacted the ability of the randomized design to reliably demonstrate the effectiveness of the intervention. PMID:22185038

Prescription drugs associated with false-positive results when using faecal immunochemical tests for colorectal cancer screening.

PubMed

Ibáñez-Sanz, Gemma; Garcia, Montse; Rodríguez-Moranta, Francisco; Binefa, Gemma; Gómez-Matas, Javier; Domènech, Xènia; Vidal, Carmen; Soriano, Antonio; Moreno, Víctor

2016-10-01

The most common side effect in population screening programmes is a false-positive result which leads to unnecessary risks and costs. To identify factors associated with false-positive results in a colorectal cancer screening programme with the faecal immunochemical test (FIT). Cross-sectional study of 472 participants with a positive FIT who underwent colonoscopy for confirmation of diagnosis between 2013 and 2014. A false-positive result was defined as having a positive FIT (≥20μg haemoglobin per gram of faeces) and follow-up colonoscopy without intermediate/high-risk lesions or cancer. Women showed a two-fold increased likelihood of a false-positive result compared with men (adjusted OR, 2.3; 95%CI, 1.5-3.4), but no female-specific factor was identified. The other variables associated with a false-positive result were successive screening (adjusted OR, 1.5; 95%CI, 1.0-2.2), anal disorders (adjusted OR, 3.1; 95%CI, 2.1-4.5) and the use of proton pump inhibitors (adjusted OR, 1.8; 95%CI, 1.1-2.9). Successive screening and proton pump inhibitor use were associated with FP in men. None of the other drugs were related to a false-positive FIT. Concurrent use of proton pump inhibitors at the time of FIT might increase the likelihood of a false-positive result. Further investigation is needed to determine whether discontinuing them could decrease the false-positive rate. Copyright © 2016 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

Target-Independent Prediction of Drug Synergies Using Only Drug Lipophilicity

PubMed Central

2015-01-01

Physicochemical properties of compounds have been instrumental in selecting lead compounds with increased drug-likeness. However, the relationship between physicochemical properties of constituent drugs and the tendency to exhibit drug interaction has not been systematically studied. We assembled physicochemical descriptors for a set of antifungal compounds (“drugs”) previously examined for interaction. Analyzing the relationship between molecular weight, lipophilicity, H-bond donor, and H-bond acceptor values for drugs and their propensity to show pairwise antifungal drug synergy, we found that combinations of two lipophilic drugs had a greater tendency to show drug synergy. We developed a more refined decision tree model that successfully predicted drug synergy in stringent cross-validation tests based on only lipophilicity of drugs. Our predictions achieved a precision of 63% and allowed successful prediction for 58% of synergistic drug pairs, suggesting that this phenomenon can extend our understanding for a substantial fraction of synergistic drug interactions. We also generated and analyzed a large-scale synergistic human toxicity network, in which we observed that combinations of lipophilic compounds show a tendency for increased toxicity. Thus, lipophilicity, a simple and easily determined molecular descriptor, is a powerful predictor of drug synergy. It is well established that lipophilic compounds (i) are promiscuous, having many targets in the cell, and (ii) often penetrate into the cell via the cellular membrane by passive diffusion. We discuss the positive relationship between drug lipophilicity and drug synergy in the context of potential drug synergy mechanisms. PMID:25026390

Multifunctionalized iron oxide nanoparticles for selective drug delivery to CD44-positive cancer cells

NASA Astrophysics Data System (ADS)

Aires, Antonio; Ocampo, Sandra M.; Simões, Bruno M.; Josefa Rodríguez, María; Cadenas, Jael F.; Couleaud, Pierre; Spence, Katherine; Latorre, Alfonso; Miranda, Rodolfo; Somoza, Álvaro; Clarke, Robert B.; Carrascosa, José L.; Cortajarena, Aitziber L.

2016-02-01

Nanomedicine nowadays offers novel solutions in cancer therapy and diagnosis by introducing multimodal treatments and imaging tools in one single formulation. Nanoparticles acting as nanocarriers change the solubility, biodistribution and efficiency of therapeutic molecules, reducing their side effects. In order to successfully apply these novel therapeutic approaches, efforts are focused on the biological functionalization of the nanoparticles to improve the selectivity towards cancer cells. In this work, we present the synthesis and characterization of novel multifunctionalized iron oxide magnetic nanoparticles (MNPs) with antiCD44 antibody and gemcitabine derivatives, and their application for the selective treatment of CD44-positive cancer cells. The lymphocyte homing receptor CD44 is overexpressed in a large variety of cancer cells, but also in cancer stem cells (CSCs) and circulating tumor cells (CTCs). Therefore, targeting CD44-overexpressing cells is a challenging and promising anticancer strategy. Firstly, we demonstrate the targeting of antiCD44 functionalized MNPs to different CD44-positive cancer cell lines using a CD44-negative non-tumorigenic cell line as a control, and verify the specificity by ultrastructural characterization and downregulation of CD44 expression. Finally, we show the selective drug delivery potential of the MNPs by the killing of CD44-positive cancer cells using a CD44-negative non-tumorigenic cell line as a control. In conclusion, the proposed multifunctionalized MNPs represent an excellent biocompatible nanoplatform for selective CD44-positive cancer therapy in vitro.

Environmental and biological monitoring of platinum-containing drugs in two hospital pharmacies using positive air pressure isolators.

PubMed

Kopp, Bettina; Crauste-Manciet, Sylvie; Guibert, Agnès; Mourier, Wilhelmine; Guerrault-Moro, Marie-Noelle; Ferrari, Sylvie; Jomier, Jean-Yves; Brossard, Denis; Schierl, Rudolf

2013-04-01

Environmental and biological monitoring of platinum containing drugs was implemented in two French hospital pharmacies using positive air pressure isolators and having similar working procedures when preparing antineoplastic drugs. Wipe sampling of surfaces, gloves, and vials was performed in the preparation room and in storage areas. All employees involved in the preparation of antineoplastic drugs were tested for urinary platinum on Monday before work and Friday after shift. Only traces of platinum were detected on surfaces in the preparation room outside the isolators (less than 1.61 pg cm(-2)). However, in one center, significant contamination was found in the storage area of the drug vials, which can most likely be linked to the rupture of a platinum vial and due to inefficient cleaning procedures. Surfaces inside the isolators were found to be contaminated (maximum: 198.4 pg cm(-2)). A higher level of contamination was detected in one pharmacy and could be explained by the lack of overgloving with regular changes during the preparation process. Nitrile gloves used during drug handling outside the isolator showed the highest platinum concentration (maximum: 5.86 ng per pair). With regards to platinum urine concentration, no significant difference was found between exposed and unexposed pharmacy personnel. Isolator technology combined with individual protective measures seems to be efficient to protect workers from occupational exposure to antineoplastic drugs, whereas specific individual protective procedures implemented were focussing on the risk of handling vials outside the isolator (e.g. high frequency of glove changing). Moreover, overgloving inside the isolator would contribute to substantially decrease inner surface contamination and should be recommended in order to limit the transfer of chemical contamination to the end products.

Trauma exposure and heavy drinking and drug use among college students: Identifying the roles of negative and positive affect lability in a daily diary study.

PubMed

Weiss, Nicole H; Bold, Krysten W; Contractor, Ateka A; Sullivan, Tami P; Armeli, Stephen; Tennen, Howard

2018-04-01

Trauma exposure is linked to heavy drinking and drug use among college students. Extant research reveals positive associations between negative affect lability and both trauma exposure and alcohol use. This study aimed to extend past research by using daily diary methods to test whether (a) individuals with (versus without) trauma exposure experience greater negative and positive affect lability, (b) negative and positive affect lability are associated with heavy drinking and drug use, and (c) negative and positive affect lability mediate the relations between trauma exposure and heavy drinking and drug use. Participants were 1640 college students (M age=19.2, 54% female, 80% European American) who provided daily diary data for 30days via online surveys. Daily diaries assessed negative and positive affect and substance use (i.e., percent days of heavy drinking, percent days of drug use, total number of drugs used). Individuals with (versus without) a history of trauma exposure demonstrated higher levels of negative and positive affect lability. Negative, but not positive, affect lability was associated with percent days of heavy drinking, percent days of drug use, and total number of drugs used, and mediated the associations between trauma exposure and heavy drinking and drug use outcomes. Findings provide support for the underlying role of negative affect lability in the relations between trauma exposure and heavy drinking and drug use among college students, suggesting that treatments targeting negative affect lability may potentially serve to reduce heavy drinking and drug use among trauma-exposed college students. Copyright © 2017 Elsevier Ltd. All rights reserved.

Increased Prevalence of Controlled Viremia and Decreased Rates of HIV Drug Resistance Among HIV-Positive People Who Use Illicit Drugs During a Community-wide Treatment-as-Prevention Initiative.

PubMed

Milloy, M-J; Wood, Evan; Kerr, Thomas; Hogg, Bob; Guillemi, Silvia; Harrigan, P Richard; Montaner, Julio

2016-03-01

Although treatment-as prevention (TasP) is a new cornerstone of global human immunodeficiency virus (HIV)-AIDS strategies, its effect among HIV-positive people who use illicit drugs (PWUD) has yet to be evaluated. We sought to describe longitudinal trends in exposure to antiretroviral therapy (ART), plasma HIV-1 RNA viral load (VL) and HIV drug resistance during a community-wide TasP intervention. We used data from the AIDS Care Cohort to Evaluate Exposure to Survival Services study, a prospective cohort of HIV-positive PWUD linked to HIV clinical monitoring records. We estimated longitudinal changes in the proportion of individuals with VL <50 copies/mL and rates of HIV drug resistance using generalized estimating equations (GEE) and extended Cox models. Between 1 January 2006 and 30 June 2014, 819 individuals were recruited and contributed 1 or more VL observation. During that time, the proportion of individuals with nondetectable VL increased from 28% to 63% (P < .001). In a multivariable GEE model, later year of observation was independently and positively associated with greater likelihood of nondetectable VL (adjusted odds ratio = 1.20 per year; P < .001). Although the proportion of individuals on ART increased, the incidence of HIV drug resistance declined (adjusted hazard ratio = 0.78 per year; P = .011). We observed significant improvements in several measures of exposure to ART and virologic status, including declines in HIV drug resistance, in this large long-running community-recruited cohort of HIV-seropositive illicit drug users during a community-wide ART expansion intervention. Our findings support continued efforts to scale up ART coverage among HIV-positive PWUD. © The Author 2015. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

Construction of an Integrated Positive Youth Development Conceptual Framework for the Prevention of the Use of Psychotropic Drugs among Adolescents

PubMed Central

Lee, Tak Yan

2011-01-01

This is a theoretical paper with an aim to construct an integrated conceptual framework for the prevention of adolescents' use and abuse of psychotropic drugs. This paper first reports the subjective reasons for adolescents' drug use and abuse in Hong Kong and reviews the theoretical underpinnings. Theories of drug use and abuse, including neurological, pharmacological, genetic predisposition, psychological, and sociological theories, were reviewed. It provides a critical re-examination of crucial factors that support the construction of a conceptual framework for primary prevention of adolescents' drug use and abuse building on, with minor revision, the model of victimization and substance abuse among women presented by Logan et al. This revised model provides a comprehensive and coherent framework synthesized from theories of drug abuse. This paper then provides empirical support for integrating a positive youth development perspective in the revised model. It further explains how the 15 empirically sound constructs identified by Catalano et al. and used in a positive youth development program, the Project P.A.T.H.S., relate generally to the components of the revised model to formulate an integrated positive youth development conceptual framework for primary prevention of adolescent drug use. Theoretical and practical implications as well as limitations and recommendations are discussed. PMID:22194671

Positive and negative consequences of HIV disclosure among seropositive injection drug users.

PubMed

Parsons, Jeffrey T; VanOra, Jason; Missildine, Whitney; Purcell, David W; Gómez, Cynthia A

2004-10-01

This study examines HIV status disclosure in an ethnically diverse sample of HIV-seropositive injection drug users (IDUs) from New York City and San Francisco. Qualitative interviews were conducted with 158 participants. Analyses revealed a number of negative and positive consequences of disclosing serostatus to sexual partners. Negative consequences included stigma, rejection by sexual partners and others, loss of intimacy, and threats to personal well-being. Positive rewards resulting from disclosure included increased social support and intimacy with partners, reaffirmation of one's sense of self, and the opportunity to share personal experiences and feelings with sexual partners. The role of responsibility in impacting disclosure and nondisclosure revealed varied patterns in terms of how this construct impacts disclosure and resulting behaviors with sexual partners. Some participants used particular strategies, such as getting involved in seroconcordant relationships or minimizing intimacy in relationships, in order to combat potential negative outcomes of disclosure. For others, positive rewards were viewed as important enough to risk negative consequences. Interventions for HIV-positive IDUs are discussed.

The Role of Internalized Stigma in the Disclosure of Injecting Drug Use Among People Who Inject Drugs and Self-Report as HIV-Positive in Kohtla-Järve, Estonia.

PubMed

Johannson, Annika; Vorobjov, Sigrid; Heimer, Robert; Dovidio, John F; Uusküla, Anneli

2017-04-01

Disclosure of injecting drug use and its associations with stigma have received very little research attention. This cross-sectional study examined the role of internalized HIV and drug stigma (i.e., self-stigmatization) in the disclosure of injecting drug use among people who inject drugs (PWID) self-reporting as HIV-positive (n = 312) in Kohtla-Järve, Estonia. The internalization of both stigmas was relatively high. On average, PWID disclosed to three disclosure targets out of seven. Disclosure was highest to close friends and health care workers and lowest to employers and casual sex partners. Internalized drug stigma was negatively associated with disclosure to other family members (AOR = 0.48; 95% CI 0.30-0.77) and health care workers (AOR = 0.46; 95% CI 0.25-0.87). Internalized HIV stigma was positively associated with disclosure to health care workers (AOR = 2.26; 95% CI 1.27-4.00). No interaction effect of internalized stigmas on disclosures emerged. We concluded that effects of internalized stigmas on disclosures are few and not uniform.

Antiparkinson drug--Mucuna pruriens shows antioxidant and metal chelating activity.

PubMed

Dhanasekaran, Muralikrishnan; Tharakan, Binu; Manyam, Bala V

2008-01-01

Parkinson's disease is a neurodegenerative disorder for which no neurorestorative therapeutic treatment is currently available. Oxidative stress plays an important role in the pathophysiology of Parkinson's disease. The ancient Indian medical system, Ayurveda, traditionally uses Mucuna pruriens to treat Parkinson's disease. In our earlier studies, Mucuna pruriens has been shown to possess antiparkinson and neuroprotective effects in animal models of Parkinson's disease. The antioxidant activity of Mucuna pruriens was demonstrated by its ability to scavenge DPPH radicals, ABTS radicals and reactive oxygen species. Mucuna pruriens significantly inhibited the oxidation of lipids and deoxyribose sugar. Mucuna pruriens exhibited divalent iron chelating activity and did not show any genotoxic/mutagenic effect on the plasmid DNA. These results suggest that the neuroprotective and neurorestorative effect of Mucuna pruriens may be related to its antioxidant activity independent of the symptomatic effect. In addition, the drug appears to be therapeutically safe in the treatment of patients with Parkinson's disease. Copyright (c) 2007 John Wiley & Sons, Ltd.

Prevalence and predictors of depressive symptoms among HIV-positive men who inject drugs in Vietnam.

PubMed

Levintow, Sara N; Pence, Brian W; Ha, Tran Viet; Minh, Nguyen Le; Sripaipan, Teerada; Latkin, Carl A; Vu, Pham The; Quan, Vu Minh; Frangakis, Constantine; Go, Vivian F

2018-01-01

HIV infection is common among people who inject drugs (PWID), and HIV-positive PWID may be particularly vulnerable to depression. This study measured the prevalence of depressive symptoms and the factors associated with severe symptoms among 455 HIV-positive PWID in Thai Nguyen, Vietnam. We used cross-sectional data from PWID in a randomized controlled trial of an intervention to reduce high-risk injecting and sexual behaviors in Thai Nguyen from 2009-2013. Depressive symptoms were measured with the Center for Epidemiologic Studies Depression Scale (CES-D). We used logistic regression to assess demographic, clinical, and psychosocial predictors of severe depressive symptoms (CES-D≥23) with prevalence odds ratios (POR) and 95% confidence intervals (CI). The prevalence of severe depressive symptoms (CES-D≥23) was 44%. 25% of participants had mild to moderate depressive symptoms (16≤CES-D<23), and 31% experienced no depressive symptoms (CES-D<16). Not being married, self-rated poor health, greater frequency of injection drug use, history of overdose, no alcohol use, and daily cigarette smoking were positively associated with severe depressive symptoms in unadjusted models and remained predictive in a multivariable model. The strongest predictors of depressive symptoms were self-reported poor health (POR = 2.94, 95% CI: 1.82, 4.76), no current alcohol use (POR = 2.35, 95% CI: 1.47, 3.77), and not currently married or cohabitating (POR = 2.21, 95% CI = 1.40, 3.47). Severe depressive symptoms were common among HIV-positive PWID in Thai Nguyen and were strongly associated with demographic, clinical, and psychosocial factors. Interventions that promote social support from family and reduce drug dependence may particularly benefit PWID experiencing severe depressive symptoms. Greater recognition and treatment of depressive symptoms has the potential to enhance quality of life and improve HIV clinical outcomes for PWID.

A sensitive assay for urinary cocaine metabolite benzoylecgonine shows more positive results and longer half-lives than those using traditional cut-offs.

PubMed

Nickley, Joyce; Pesce, Amadeo J; Krock, Kevin

2017-08-01

Cocaine is a common drug of abuse. To detect its use, a screening detection concentration for the cocaine metabolite benzoylecgonine is commonly set at 150 ng/mL and its confirmatory cut-off is set at 100 ng/mL. Studies have suggested that these cut-offs may be set too high, allowing some patients with this substance abuse problem to be missed or improperly monitored. With the advent of liquid chromatography-tandem mass spectrometry (LC-MS/MS) technology it is possible to reliably detect and quantify lower concentrations of its metabolite benzoylecgonine as part of a larger drug panel. One purpose of the study was to establish if there was a significant increase in detection of cocaine use with a ten-fold more sensitive cut-off. A very sensitive dilute and shoot assay for benzoylecgonine was developed with a lower limit of quantitation of 5 ng/mL. Validation of the 5 ng/mL cut-off was achieved by plotting all the positive cocaine observations as a frequency distribution on a logarithmic scale. The number of positive results with measurable concentrations below the typical industry 100 ng/mL cut-off level but above the high sensitivity 5 ng/mL cut-off level was observed to be 51.9% of the observed positives. The lower cut-off also allowed a re-evaluation of the window of detection after cessation of use. It was observed to be between 17 and 22 days. © 2016 Precision Diagnostics, LLC. Drug Testing and Analysis published by John Wiley & Sons, Ltd. © 2016 Precision Diagnostics, LLC. Drug Testing and Analysis published by John Wiley & Sons, Ltd.

Bioluminescent Imaging of Trypanosoma brucei Shows Preferential Testis Dissemination Which May Hamper Drug Efficacy in Sleeping Sickness

PubMed Central

Claes, Filip; Vodnala, Suman K.; van Reet, Nick; Boucher, Nathalie; Lunden-Miguel, Hilda; Baltz, Theo; Goddeeris, Bruno Maria; Büscher, Philippe; Rottenberg, Martin E.

2009-01-01

Monitoring Trypanosoma spread using real-time imaging in vivo provides a fast method to evaluate parasite distribution especially in immunoprivileged locations. Here, we generated monomorphic and pleomorphic recombinant Trypanosoma brucei expressing the Renilla luciferase. In vitro luciferase activity measurements confirmed the uptake of the coelenterazine substrate by live parasites and light emission. We further validated the use of Renilla luciferase-tagged trypanosomes for real-time bioluminescent in vivo analysis. Interestingly, a preferential testis tropism was observed with both the monomorphic and pleomorphic recombinants. This is of importance when considering trypanocidal drug development, since parasites might be protected from many drugs by the blood-testis barrier. This hypothesis was supported by our final study of the efficacy of treatment with trypanocidal drugs in T. brucei-infected mice. We showed that parasites located in the testis, as compared to those located in the abdominal cavity, were not readily cleared by the drugs. PMID:19621071

In vitro susceptibility of 137 Candida sp. isolates from HIV positive patients to several antifungal drugs.

PubMed

Magaldi, S; Mata, S; Hartung, C; Verde, G; Deibis, L; Roldán, Y; Marcano, C

2001-01-01

Oropharyngeal candidiasis caused by various species of Candida is one of the most common infections in HIV seropositive or AIDS patients. Drug resistance among these yeasts is an increasing problem. We studied the frequency of resistance profile to fluconazole, itraconazole, ketoconazole, amphotericin B and terbinafine of 137 isolates of Candida sp. From HIV positive or AIDS patients with oropharyngeal candidiasis at Instituto de Inmunología, U.C.V. and the Hospital "Jose Ignacio Baldó", Caracas Venezuela, using the well diffusion susceptibility test (Magaldi et al.). We found that nearly 10% of C. albicans isolates were primarily fluconazole resistant, 45% of C. albicans isolates from patients with previous treatment were resistant to fluconazole, of which 93% showed cross-resistance to itraconazole, and even about 30% of C. tropicalis (n = 13) were resistant to fluconazole and/or itraconazole. To this respect, several recent reports have been described antifungal cross-resistance among azoles. Therefore, we consider that C. tropicalis should be added to the growing list of yeast in which antifungal drug resistance is common. This report could be useful for therapeutic aspect in AIDS patients with oral candidiasis.

Drug-coated balloon treatment of coronary artery disease: a position paper of the Italian Society of Interventional Cardiology.

PubMed

Cortese, Bernardo; Berti, Sergio; Biondi-Zoccai, Giuseppe; Colombo, Antonio; Limbruno, Ugo; Bedogni, Francesco; Cremonesi, Alberto; Silva, Pedro Leon; Sgueglia, Gregory A

2014-02-15

Drug-coated balloons are a new tool for the treatment of patients with coronary artery disease. The main feature of this technology is a rapid and homogenous transfer of an antiproliferative drug (paclitaxel) to the vessel wall just at the time of balloon inflation, when neointimal proliferation, in response to angioplasty, is the highest. Moreover, drug-coated balloons share adjuntive advantages over stents: the absence of permanent scaffold and polymer, the respect of the original coronary anatomy, and limited inflammatory stimuli, thereby allowing for short-term dual antiplatelet therapy. To this day, a lot of devices are available in the market, with limited scientific data for the vast majority of them. Thus, the Italian scientific society of interventional cardiologists GISE decided to coordinate the efforts of a group of reknown experts on the field, in order to obtain a Position Paper on the correct use of drug-coated balloons in all the settings of coronary artery disease, giving a class of indication to each one, based on the clinical evidence. This Position Paper represents a quick reference for operators, investigators, and manufactures to promote the understanding and the correct use of the drug-coated balloon technology in everyday clinical practice. Copyright © 2013 Wiley Periodicals, Inc.

A cost-utility analysis of drug treatments in patients with HBeAg-positive chronic hepatitis B in Thailand

PubMed Central

2014-01-01

Background Only lamivudine has been included for patients with chronic hepatitis B (CHB) in the National List of Essential Drugs (NLED), a pharmaceutical reimbursement list in Thailand. There have also been no economic evaluation studies of CHB drug treatments conducted in Thailand yet. In order to fill this gap in policy research, the objective of this study was to compare the cost-utility of each drug therapy (Figure 1) with palliative care in patients with HBeAg-positive CHB. Methods A cost-utility analysis using an economic evaluation model was performed to compare each drug treatment for HBeAg-positive CHB patients. A Markov model was used to estimate the relevant costs and health outcomes during a lifetime horizon based on a societal perspective. Direct medical costs, direct non-medical costs, and indirect costs were included, and health outcomes were denoted in life years (LYs) and quality-adjusted life years (QALYs). The results were presented as an incremental cost effectiveness ratio (ICER) in Thai baht (THB) per LY or QALY gained. One-way sensitivity and probabilistic sensitivity analyses were applied to investigate the effects of model parameter uncertainties. Results The ICER values of providing generic lamivudine with the addition of tenofovir when drug resistance occurred, generic lamivudine with the addition of tenofovir based on the road map guideline, and tenofovir monotherapy were -14,000 (USD -467), -8,000 (USD -267) , and -5,000 (USD -167) THB per QALY gained, respectively. However, when taking into account all parameter uncertainties in the model, providing generic lamivudine with the addition of tenofovir when drug resistance occurred (78% and 75%) and tenofovir monotherapy (18% and 24%) would yield higher probabilities of being cost-effective at the societal willingness to pay thresholds of 100,000 (USD 3,333) and 300,000 (USD 10,000) THB per QALY gained in Thailand, respectively. Conclusions Based on the policy recommendations from this

Methamphetamine functions as a positive and negative drug feature in a Pavlovian appetitive discrimination task.

PubMed

Reichel, Carmela M; Wilkinson, Jamie L; Bevins, Rick A

2007-12-01

This research determined the ability of methamphetamine to serve as a positive or negative feature, and assessed the ability of bupropion, cocaine, and naloxone to substitute for the methamphetamine features. Rats received methamphetamine (0.5 mg/kg, intraperitoneally) or saline 15 min before a conditioning session. For the feature positive (FP) group, offset of 15-s cue lights was followed by access to sucrose on methamphetamine sessions; sucrose was withheld during saline sessions. For the feature negative (FN) group, the light offset was followed by sucrose on saline sessions; sucrose was withheld during methamphetamine sessions. During acquisition, the FP group had higher responding on methamphetamine sessions than on saline sessions. For the FN group, responding was higher on saline sessions than on methamphetamine sessions. Conditioned responding was sensitive to methamphetamine dose. For the FP group, bupropion and cocaine fully and partially substituted for methamphetamine, respectively. In contrast, both drugs fully substituted for methamphetamine in the FN group. Naloxone did not substitute in either set of rats. FP-trained rats were more sensitive to the locomotor stimulating effects of the test drugs than FN-trained rats. This research demonstrates that the pharmacological effects of methamphetamine function as a FP or FN in this Pavlovian discrimination task and that training history can affect conditioned responding and locomotor effects evoked by a drug.

FUNCTIONAL ANALYSIS OF A NOVEL POSITIVE ALLOSTERIC MODULATOR OF AMPA RECEPTORS DERIVED FROM A STRUCTURE-BASED DRUG DESIGN STRATEGY

PubMed Central

Harms, Jonathan E.; Benveniste, Morris; Maclean, John K. F.; Partin, Kathryn M.; Jamieson, Craig

2012-01-01

Positive allosteric modulators of α-amino-3-hydroxy-5-methyl-isoxazole-propionic acid (AMPA) receptors facilitate synaptic plasticity and can improve various forms of learning and memory. These modulators show promise as therapeutic agents for the treatment of neurological disorders such as schizophrenia, ADHD, and mental depression. Three classes of positive modulator, the benzamides, the thiadiazides, and the biarylsulfonamides differentially occupy a solvent accessible binding pocket at the interface between the two subunits that form the AMPA receptor ligand-binding pocket. Here, we describe the electrophysiological properties of a new chemotype derived from a structure-based drug design strategy (SBDD), which makes similar receptor interactions compared to previously reported classes of modulator. This pyrazole amide derivative, JAMI1001A, with a promising developability profile, efficaciously modulates AMPA receptor deactivation and desensitization of both flip and flop receptor isoforms. PMID:22735771

Prevalence of Adverse Drug Reactions to Highly Active Antiretroviral Therapy (HAART) among HIV Positive Patients in Imam Khomeini Hospital of Tehran, Iran.

PubMed

Koochak, Hamid E; Babaii, Azita; Pourdast, Alia; Golrokhy, Raheleh; Rasoolinejad, Mehrnaz; Khodaei, Sepideh; Moghadam, Saeed R J; Taheri, Reza R; Seyed Alinaghi, Seyed Ahmad

2017-01-01

The present study assessed the prevalence of adverse drug reactions (ADRs) among HIV positive patients taking antiretroviral therapy referred to Imam Khomeini Hospital in Tehran, Iran. This is a cross sectional study regarding side effects of Highly Active Antiretroviral Therapy (HAART) in HIV positive patients referred to Voluntary Counseling and Testing (VCT) center in Imam Khomeini Hospital of Tehran, Iran during a period of the year 2009 to 2010. Two hundred patients under antiretroviral treatment evaluated for the side effects of drug based on available records, face to face interviews and written lab data. Data was collected from a sample of 200 HIV positive patients (72% male). Injection drug use was the most common route of HIV transmission. Co-Infections with Hepatitis C virus (HCV) found in the majority of patients (60.5%). Tuberculosis was the most prevalent opportunistic infection. One hundred eighty eight (94%) patients experienced at least one adverse drug reaction. The most frequent clinical and paraclinical findings were skin rash (28%) and abnormal liver function tests (36%). Given the high prevalence of adverse drug reactions among HIV positive patients taking antiretroviral therapy (ART) in this study, clinicians should be aware of ADRs at the initiation of ART as complications can affect patients' adherence to the therapy. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

A sensitive assay for urinary cocaine metabolite benzoylecgonine shows more positive results and longer half‐lives than those using traditional cut‐offs

PubMed Central

Nickley, Joyce; Krock, Kevin

2017-01-01

Cocaine is a common drug of abuse. To detect its use, a screening detection concentration for the cocaine metabolite benzoylecgonine is commonly set at 150 ng/mL and its confirmatory cut‐off is set at 100 ng/mL. Studies have suggested that these cut‐offs may be set too high, allowing some patients with this substance abuse problem to be missed or improperly monitored. With the advent of liquid chromatography–tandem mass spectrometry (LC–MS/MS) technology it is possible to reliably detect and quantify lower concentrations of its metabolite benzoylecgonine as part of a larger drug panel. One purpose of the study was to establish if there was a significant increase in detection of cocaine use with a ten‐fold more sensitive cut‐off. A very sensitive dilute and shoot assay for benzoylecgonine was developed with a lower limit of quantitation of 5 ng/mL. Validation of the 5 ng/mL cut‐off was achieved by plotting all the positive cocaine observations as a frequency distribution on a logarithmic scale. The number of positive results with measurable concentrations below the typical industry 100 ng/mL cut‐off level but above the high sensitivity 5 ng/mL cut‐off level was observed to be 51.9% of the observed positives. The lower cut‐off also allowed a re‐evaluation of the window of detection after cessation of use. It was observed to be between 17 and 22 days. © 2016 Precision Diagnostics, LLC. Drug Testing and Analysis published by John Wiley & Sons, Ltd. PMID:28024167

Screening pharmaceuticals for possible carcinogenic effects: initial positive results for drugs not previously screened

PubMed Central

Friedman, Gary D.; Udaltsova, Natalia; Chan, James; Quesenberry, Charles P; Habel, Laurel A.

2010-01-01

Objective We screened commonly used prescription drugs for possible carcinogenic effects. Methods In a large health care program we identified 105 commonly used drugs, not previously screened. Recipients were followed for up to 12½ years for incident cancer. Nested case-control analyses of 55 cancer sites and all combined included up to ten matched controls per case, with lag of at least two years between drug dispensing and cancer. Positive associations entailed a relative risk (RR) of 1.50, with p≤ 0.01 and higher risk for three or more, than for one prescription. Evaluation included further analyses, searches of the literature, and clinical judgment. Results There were 101 associations of interest for 61 drugs. Sixty-six associations were judged to have involved substantial confounding. We found evidence that of the remaining 35, the following associations may not be due to chance: sulindac with gallbladder cancer and leukemia, hyoscyamine with non-Hodgkin lymphoma, nortriptyline with esophageal and hepatic cancer, oxazepam with lung cancer, both fluoxetine and paroxetine with testicular cancer, hydrochlorothiazide with renal and lip cancer, and nifedipine with lip cancer. Conclusions These preliminary findings suggest that further studies are indicated regarding sulindac, hyoscyamine, nortriptyline, oxazepam, fluoxetine, paroxetine, hydrochlorothiazide and nifedipine. PMID:19582585

Drug allergy passport and other documentation for patients with drug hypersensitivity - An ENDA/EAACI Drug Allergy Interest Group Position Paper.

PubMed

Brockow, K; Aberer, W; Atanaskovic-Markovic, M; Bavbek, S; Bircher, A; Bilo, B; Blanca, M; Bonadonna, P; Burbach, G; Calogiuri, G; Caruso, C; Celik, G; Cernadas, J; Chiriac, A; Demoly, P; Oude Elberink, J N G; Fernandez, J; Gomes, E; Garvey, L H; Gooi, J; Gotua, M; Grosber, M; Kauppi, P; Kvedariene, V; Laguna, J J; Makowska, J S; Mosbech, H; Nakonechna, A; Papadopolous, N G; Ring, J; Romano, A; Rockmann, H; Sargur, R; Sedlackova, L; Sigurdardottir, S; Schnyder, B; Storaas, T; Torres, M; Zidarn, M; Terreehorst, I

2016-11-01

The strongest and best-documented risk factor for drug hypersensitivity (DH) is the history of a previous reaction. Accidental exposures to drugs may lead to severe or even fatal reactions in sensitized patients. Preventable prescription errors are common. They are often due to inadequate medical history or poor risk assessment of recurrence of drug reaction. Proper documentation is essential information for the doctor to make sound therapeutic decision. The European Network on Drug Allergy and Drug Allergy Interest Group of the European Academy of Allergy and Clinical Immunology have formed a task force and developed a drug allergy passport as well as general guidelines of drug allergy documentation. A drug allergy passport, a drug allergy alert card, a certificate, and a discharge letter after medical evaluation are adequate means to document DH in a patient. They are to be handed to the patient who is advised to carry the documentation at all times especially when away from home. A drug allergy passport should at least contain information on the culprit drug(s) including international nonproprietary name, clinical manifestations including severity, diagnostic measures, potential cross-reactivity, alternative drugs to prescribe, and where more detailed information can be obtained from the issuer. It should be given to patients only after full allergy workup. In the future, electronic prescription systems with alert functions will become more common and should include the same information as in paper-based documentation. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Hepatitis B, C, and D virus infection showing distinct patterns between injection drug users and the general population.

PubMed

Chen, Fei; Zhang, Jian; Guo, Fengfan; Wen, Bo; Luo, Shan; Yuan, Dongping; Lin, Yingbiao; Ou, Wensheng; Tang, Ping; Dai, Guozhi; Li, Fangfang; Liu, Wenpei; Qu, Xiaowang

2017-02-01

Hepatitis B, C, and D virus (HBV, HCV, and HDV) infections are known to be prevalent in injection drug users (IDUs); however, the relationship between the molecular epidemiologic features of hepatitis virus infection in high-risk individuals and the general population has not yet been established. In total, 1049 IDUs and 672 individuals who underwent physical examinations at Chenzhou hospital, Hunan Province, China, were enrolled. HBV, HCV, and HDV infections were screened with serologic tests in both populations. HBsAg-positive, anti-HCV IgG-positive, and anti-HDV IgG-positive samples were further confirmed by polymerase chain reaction, quantitative polymerase chain reaction, and DNA sequencing. Significantly higher HBV (21.54 vs 16.52%, P = 0.01), HCV (45.95% vs 1.34%, P < 0.001), and HDV (5.62% vs 0.30%, P < 0.001) infections were detected in IDUs compared with the general population. The dual infection of HBV/HCV or HBV/HDV was also significantly higher in IDUs than in the general population. HBV genotype B and HDV genotype II were dominants in both populations. HCV infection showed genotype 6a (49.52%) dominant in IDUs, but genotype 1b accounted for 50% infection, which was followed by genotype 6a (33.33%) in the general population. Higher viral loads were associated with HBV genotype B and HCV genotype 6a compared with non-dominant genotypic infections. HBV and HDV infections shared similar patterns by IDUs and the general populations, and HCV infection exhibited distinct features between two populations. Our results suggest different molecular epidemiologic characteristics of HBV, HCV, and HDV infection in two populations. © 2016 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

Amorphous stabilization and dissolution enhancement of amorphous ternary solid dispersions: combination of polymers showing drug-polymer interaction for synergistic effects.

PubMed

Prasad, Dev; Chauhan, Harsh; Atef, Eman

2014-11-01

The purpose of this study was to understand the combined effect of two polymers showing drug-polymer interactions on amorphous stabilization and dissolution enhancement of indomethacin (IND) in amorphous ternary solid dispersions. The mechanism responsible for the enhanced stability and dissolution of IND in amorphous ternary systems was studied by exploring the miscibility and intermolecular interactions between IND and polymers through thermal and spectroscopic analysis. Eudragit E100 and PVP K90 at low concentrations (2.5%-40%, w/w) were used to prepare amorphous binary and ternary solid dispersions by solvent evaporation. Stability results showed that amorphous ternary solid dispersions have better stability compared with amorphous binary solid dispersions. The dissolution of IND from the ternary dispersion was substantially higher than the binary dispersions as well as amorphous drug. Melting point depression of physical mixtures reveals that the drug was miscible in both the polymers; however, greater miscibility was observed in ternary physical mixtures. The IR analysis confirmed intermolecular interactions between IND and individual polymers. These interactions were found to be intact in ternary systems. These results suggest that the combination of two polymers showing drug-polymer interaction offers synergistic enhancement in amorphous stability and dissolution in ternary solid dispersions. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

Sex, drugs and moral goals: reproductive strategies and views about recreational drugs

PubMed Central

Kurzban, Robert; Dukes, Amber; Weeden, Jason

2010-01-01

Humans, unlike most other species, show intense interest in the activities of conspecifics, even when the activities in question pose no obvious fitness threat or opportunity. Here, we investigate one content domain in which people show substantial interest, the use of drugs for non-medical purposes. Drawing from two subject populations—one undergraduate and one Internet-based—we look at the relationships among (i) abstract political commitments; (ii) attitudes about sexuality; and (iii) views surrounding recreational drugs. Whereas some theories suggest that drug views are best understood as the result of abstract political ideology, we suggest that these views can be better understood in the context of reproductive strategy. We show that, as predicted by a strategic construal, drug attitudes are best predicted by sexual items rather than abstract political commitments and, further, that the relationship between factors such as political ideology and drugs, while positive, are reduced to zero or nearly zero when items assessing sexuality are controlled for. We conclude that considering morality from the standpoint of strategic interests is a potentially useful way to understand why humans care about third party behaviour. PMID:20554547

A comparative analysis of the impact of a positive list system on new chemical entity drugs and incrementally modified drugs in South Korea.

PubMed

Ha, DongMun; Choi, Yong; Kim, Dae Up; Chung, Kyu Hyuck; Lee, Eui-Kyung

2011-07-01

Medical costs in South Korea have risen, in part due to increased demand and consumption of pharmaceutical products by an aging population and also because of the introduction of newer, more expensive drugs. In an effort to stabilize the financing of health insurance and alleviate the financial burden on individuals, the government implemented a policy changing the national health insurance drug-listing system from a negative list system to a positive list system (PLS). The goal of this study was to compare differences in drug-listing rates for new chemical entities (NCEs) and incrementally modified drugs (IMDs) after South Korea introduced the PLS in December 2006. Parameters significantly affecting NCE and IMD listings were also identified. New drug-listing data for 2007 and 2008 were obtained from the databases of the Health Insurance Review Agency and the Ministry of Health and Welfare. Descriptive analyses on the reimbursement rate and logistic regression analysis were conducted. Statistical significance was tested for all results, and P < 0.05 was considered statistically significant. A total of 150 reimbursement applications (79 for NCEs, 71 for IMDs) were examined for this study. The overall drug-listing rate was lower than before the introduction of the PLS. Drug reimbursement rates for NCEs (50.6%) were lower than those for IMDs (74.6%) (P = 0.0025). However, the price negotiation rate was 85.0% for NCEs compared with 73.6% for IMDs (P = 0.1847). The time required for both reimbursement and drug pricing was significantly longer for NCE than for IMD listings (P < 0.05). Cost-effectiveness and budget impact were 2 significant variables affecting the listing of NCEs. However, no significant variable was identified for IMDs. The PLS challenges the drug-listing system by decreasing the drug-listing rate and lengthening the period for reimbursement determinations. These effects were more pronounced for NCE listings than for IMD listings. Crown Copyright © 2011

Repurposing Salicylanilide Anthelmintic Drugs to Combat Drug Resistant Staphylococcus aureus

PubMed Central

Rajamuthiah, Rajmohan; Fuchs, Beth Burgwyn; Conery, Annie L.; Kim, Wooseong; Jayamani, Elamparithi; Kwon, Bumsup; Ausubel, Frederick M.; Mylonakis, Eleftherios

2015-01-01

Staphylococcus aureus is a Gram-positive bacterium that has become the leading cause of hospital acquired infections in the US. Repurposing Food and Drug Administration (FDA) approved drugs for antimicrobial therapy involves lower risks and costs compared to de novo development of novel antimicrobial agents. In this study, we examined the antimicrobial properties of two commercially available anthelmintic drugs. The FDA approved drug niclosamide and the veterinary drug oxyclozanide displayed strong in vivo and in vitro activity against methicillin resistant S. aureus (minimum inhibitory concentration (MIC): 0.125 and 0.5 μg/ml respectively; minimum effective concentration: ≤ 0.78 μg/ml for both drugs). The two drugs were also effective against another Gram-positive bacteria Enterococcus faecium (MIC 0.25 and 2 μg/ml respectively), but not against the Gram-negative species Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacter aerogenes. The in vitro antimicrobial activity of niclosamide and oxyclozanide were determined against methicillin, vancomycin, linezolid or daptomycin resistant S. aureus clinical isolates, with MICs at 0.0625-0.5 and 0.125-2 μg/ml for niclosamide and oxyclozanide respectively. A time-kill study demonstrated that niclosamide is bacteriostatic, whereas oxyclozanide is bactericidal. Interestingly, oxyclozanide permeabilized the bacterial membrane but neither of the anthelmintic drugs exhibited demonstrable toxicity to sheep erythrocytes. Oxyclozanide was non-toxic to HepG2 human liver carcinoma cells within the range of its in vitro MICs but niclosamide displayed toxicity even at low concentrations. These data show that the salicylanilide anthelmintic drugs niclosamide and oxyclozanide are suitable candidates for mechanism of action studies and further clinical evaluation for treatment of staphylococcal infections. PMID:25897961

The effects of setarud on the immunological status of HIV-positive patients: Efficacy of a novel multi-herbal drug.

PubMed

Gholamzadeh Baeis, Mehdi; Amiri, Ghasem; Miladinia, Mojtaba

2017-01-01

This study examines the effect of the addition of IMOD, a novel multi-herbal drug to the highly active anti-retroviral therapy (HAART) regimen, on the immunological status of HIV-positive patients. A randomized two-parallel-group (HAART group versus HAART+IMOD group), pretest-posttest design was used.Sixty patients with indications for treatment with the HAART regimen participated. One week before and 2 days after the treatments, immunological parameters including total lymphocyte count (TLC) and CD4 cell count were assessed.The intervention group received the HAART regimen plus IMOD every day for 3 months. The control group received only the HAART regimen every day for 3 months. In the intervention group, a significant difference was observed in CD4between before and after drug therapy (CD4 was increased). However, in the control group, the difference in CD4 was not significant before and after drug therapy. The difference in TLC was not significantly different between the two groups before and after therapy. Nevertheless, TLC was higher in the intervention group. IMOD (as a herbal drug) has been successfully added to the HAART regimen to improve the immunological status of HIV-positive patients.

Prevalence of drug abuse among workers: strengths and pitfalls of the recent Italian Workplace Drug Testing (WDT) legislation.

PubMed

Kazanga, Isabel; Tameni, Silvia; Piccinotti, Alberto; Floris, Ivan; Zanchetti, Gabriele; Polettini, Aldo

2012-02-10

In 2008 a Workplace Drug Testing (WDT) law became effective in Italy for workers involved in public/private transportation, oil/gas companies, and explosives/fireworks industry with the aim to ensure public safety for the community. To examine and elaborate WDT data collected on a large group of workers (over 43,500) during March 2009-February 2010 in order to highlight pros and cons and to draw suggestions for policies in the field. Northern Italy. After ≤ 24 h notification, workers provided a urine sample screened for opiates, methadone, buprenorphine, cocaine, amphetamines, ecstasy, and cannabinoids (THC) by immunoassay. Positives were confirmed by GC-MS. The positive rate was 2.0%, THC being most frequent drug (1.3%; cocaine, 0.4%; opioids, 0.3%). 6.9% of the positive workers tested positive for ≥ 2 classes (most often THC+cocaine). Gender ratio and mean age were significantly lower in positives (F/M=0.007; 35.5 ± 8.3 years) than negatives (0.016 and 40.7 ± 9.5, respectively). No decline in rates of positives and an increase of diluted samples over time were observed. The highest rates of positives were detected when sampling was performed just before/after week-end and during morning hours. Possible correlation between job type and drugs used were observed (e.g. more cocaine positives among road vehicle-drivers than among lift truck-drivers). Declared use of medicine/illicit drugs during the preceding week showed that illicit drug use was likely not always detected in urine and that almost 4% workers declared use of medicine drugs possibly affecting performance. This survey enabled to evidence relevant pitfalls of the law and to define strategies to improve the outcomes of WDT policies. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Genomics and drug profiling of fatal TCF3-HLF-positive acute lymphoblastic leukemia identifies recurrent mutation patterns and therapeutic options

PubMed Central

Bornhauser, Beat; Gombert, Michael; Kratsch, Christina; Stütz, Adrian M.; Sultan, Marc; Tchinda, Joelle; Worth, Catherine L.; Amstislavskiy, Vyacheslav; Badarinarayan, Nandini; Baruchel, André; Bartram, Thies; Basso, Giuseppe; Canpolat, Cengiz; Cario, Gunnar; Cavé, Hélène; Dakaj, Dardane; Delorenzi, Mauro; Dobay, Maria Pamela; Eckert, Cornelia; Ellinghaus, Eva; Eugster, Sabrina; Frismantas, Viktoras; Ginzel, Sebastian; Haas, Oskar A.; Heidenreich, Olaf; Hemmrich-Stanisak, Georg; Hezaveh, Kebria; Höll, Jessica I.; Hornhardt, Sabine; Husemann, Peter; Kachroo, Priyadarshini; Kratz, Christian P.; te Kronnie, Geertruy; Marovca, Blerim; Niggli, Felix; McHardy, Alice C.; Moorman, Anthony V.; Panzer-Grümayer, Renate; Petersen, Britt S.; Raeder, Benjamin; Ralser, Meryem; Rosenstiel, Philip; Schäfer, Daniel; Schrappe, Martin; Schreiber, Stefan; Schütte, Moritz; Stade, Björn; Thiele, Ralf; von der Weid, Nicolas; Vora, Ajay; Zaliova, Marketa; Zhang, Langhui; Zichner, Thomas; Zimmermann, Martin; Lehrach, Hans; Borkhardt, Arndt; Bourquin, Jean-Pierre; Franke, Andre; Korbel, Jan O.; Stanulla, Martin; Yaspo, Marie-Laure

2015-01-01

TCF3-HLF-fusion positive acute lymphoblastic leukemia (ALL) is currently incurable. Employing an integrated approach, we uncovered distinct mutation, gene expression, and drug response profiles in TCF3-HLF-positive and treatment-responsive TCF3-PBX1-positive ALL. Recurrent intragenic deletions of PAX5 or VPREB1 were identified in constellation with TCF3-HLF. Moreover somatic mutations in the non-translocated allele of TCF3 and a reduction of PAX5 gene dosage in TCF3-HLF ALL suggest cooperation within a restricted genetic context. The enrichment for stem cell and myeloid features in the TCF3-HLF signature may reflect reprogramming by TCF3-HLF of a lymphoid-committed cell of origin towards a hybrid, drug-resistant hematopoietic state. Drug response profiling of matched patient-derived xenografts revealed a distinct profile for TCF3-HLF ALL with resistance to conventional chemotherapeutics, but sensitivity towards glucocorticoids, anthracyclines and agents in clinical development. Striking on-target sensitivity was achieved with the BCL2-specific inhibitor venetoclax (ABT-199). This integrated approach thus provides alternative treatment options for this deadly disease. PMID:26214592

Predicting and understanding comprehensive drug-drug interactions via semi-nonnegative matrix factorization.

PubMed

Yu, Hui; Mao, Kui-Tao; Shi, Jian-Yu; Huang, Hua; Chen, Zhi; Dong, Kai; Yiu, Siu-Ming

2018-04-11

Drug-drug interactions (DDIs) always cause unexpected and even adverse drug reactions. It is important to identify DDIs before drugs are used in the market. However, preclinical identification of DDIs requires much money and time. Computational approaches have exhibited their abilities to predict potential DDIs on a large scale by utilizing pre-market drug properties (e.g. chemical structure). Nevertheless, none of them can predict two comprehensive types of DDIs, including enhancive and degressive DDIs, which increases and decreases the behaviors of the interacting drugs respectively. There is a lack of systematic analysis on the structural relationship among known DDIs. Revealing such a relationship is very important, because it is able to help understand how DDIs occur. Both the prediction of comprehensive DDIs and the discovery of structural relationship among them play an important guidance when making a co-prescription. In this work, treating a set of comprehensive DDIs as a signed network, we design a novel model (DDINMF) for the prediction of enhancive and degressive DDIs based on semi-nonnegative matrix factorization. Inspiringly, DDINMF achieves the conventional DDI prediction (AUROC = 0.872 and AUPR = 0.605) and the comprehensive DDI prediction (AUROC = 0.796 and AUPR = 0.579). Compared with two state-of-the-art approaches, DDINMF shows it superiority. Finally, representing DDIs as a binary network and a signed network respectively, an analysis based on NMF reveals crucial knowledge hidden among DDIs. Our approach is able to predict not only conventional binary DDIs but also comprehensive DDIs. More importantly, it reveals several key points about the DDI network: (1) both binary and signed networks show fairly clear clusters, in which both drug degree and the difference between positive degree and negative degree show significant distribution; (2) the drugs having large degrees tend to have a larger difference between positive degree

Family Checkup: Positive Parenting Prevents Drug Abuse

MedlinePlus

... 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/ ...

Rational Design of Novel Allosteric Dihydrofolate Reductase Inhibitors Showing Antibacterial Effects on Drug-Resistant Escherichia coli Escape Variants.

PubMed

Srinivasan, Bharath; Rodrigues, João V; Tonddast-Navaei, Sam; Shakhnovich, Eugene; Skolnick, Jeffrey

2017-07-21

In drug discovery, systematic variations of substituents on a common scaffold and bioisosteric replacements are often used to generate diversity and obtain molecules with better biological effects. However, this could saturate the small-molecule diversity pool resulting in drug resistance. On the other hand, conventional drug discovery relies on targeting known pockets on protein surfaces leading to drug resistance by mutations of critical pocket residues. Here, we present a two-pronged strategy of designing novel drugs that target unique pockets on a protein's surface to overcome the above problems. Dihydrofolate reductase, DHFR, is a critical enzyme involved in thymidine and purine nucleotide biosynthesis. Several classes of compounds that are structural analogues of the substrate dihydrofolate have been explored for their antifolate activity. Here, we describe 10 novel small-molecule inhibitors of Escherichia coli DHFR, EcDHFR, belonging to the stilbenoid, deoxybenzoin, and chalcone family of compounds discovered by a combination of pocket-based virtual ligand screening and systematic scaffold hopping. These inhibitors show a unique uncompetitive or noncompetitive inhibition mechanism, distinct from those reported for all known inhibitors of DHFR, indicative of binding to a unique pocket distinct from either substrate or cofactor-binding pockets. Furthermore, we demonstrate that rescue mutants of EcDHFR, with reduced affinity to all known classes of DHFR inhibitors, are inhibited at the same concentration as the wild-type. These compounds also exhibit antibacterial activity against E. coli harboring the drug-resistant variant of DHFR. This discovery is the first report on a novel class of inhibitors targeting a unique pocket on EcDHFR.

[Impacts of antiretroviral treatment on drug use and high risk sexual behaviors among HIV-positive MMT clients].

PubMed

Qian, Xiaoai; Cao, Xiaobin; Zhao, Yan; Wang, Changhe; Luo, Wei; Rou, Keming; Zhang, Bo; Min, Xiangdong; Duan, Song; Tang, Renhai; Wu, Zunyou

2015-06-01

To explore the impacts of antiretroviral treatment on drug use and high risk sexual behaviors among HIV-positive MMT clients. A cross-sectional study was conducted in patients undergoing ART (ART-experienced) and patients not undergoing ART (ART-naive) attending MMT in 5 clinics in Yunnan Honghe and Dehong prefectures in 2014. A questionnaire was designed to collect socio-demographic characteristics, ART and MMT information and sexual and drug use behaviors within 3 months before the investigation was conducted. Logistic regression analysis was conducted to identify the predictors for drug use and risky sexual behaviors. A total of 328 cases were included in the analysis, among which 202 were ART-experienced and 126 were ART-naÏve. Among 152 respondents who were sexually active, 61 (40.1%) reported having unprotected sex (UPS) with their regular partners in the prior 3 months. A total of 57.6% (189/328) of the respondents used drugs in the prior 3 months. Multiple logistic regression analysis revealed that younger than 35 years old (OR = 3.57, 95% CI: 1.23-10.37), fertility desire (OR = 4.47, 95% CI: 1.49-13.41), partner being HIV-positive (OR = 4.62, 95% CI: 1.80-11.86), length of MMT attendance less than 5 years (OR = 2.92, 95% CI: 1.14-7.53), agreed that it was necessary to use condom no matter the viral load is high or low (OR = 0.14, 95% CI: 0.04-0.51) were protective factors of UPS in the prior 3 months. Multiple logistic regression analysis revealed that being Han (OR = 0.46, 95% CI: 0.24-0.89), feeling having good health status (OR = 0.39, 95% CI: 0.18-0.85), being enrolled in ART (OR = 0.32, 95% CI: 0.17-0.60) were protective factors for drug use in the prior three months, having contact with drug using friends (OR = 4.41, 95% CI: 2.31-8.29), having experience of missing an MMT dose (OR = 3.47, 95% CI: 1.92-6.29), and not satisfied with current MMT dose (OR = 13.92, 95% CI: 3.24-59.93) were risk factors for drug use during the prior three months. ART was

FOXP2 Targets Show Evidence of Positive Selection in European Populations

PubMed Central

Ayub, Qasim; Yngvadottir, Bryndis; Chen, Yuan; Xue, Yali; Hu, Min; Vernes, Sonja C.; Fisher, Simon E.; Tyler-Smith, Chris

2013-01-01

Forkhead box P2 (FOXP2) is a highly conserved transcription factor that has been implicated in human speech and language disorders and plays important roles in the plasticity of the developing brain. The pattern of nucleotide polymorphisms in FOXP2 in modern populations suggests that it has been the target of positive (Darwinian) selection during recent human evolution. In our study, we searched for evidence of selection that might have followed FOXP2 adaptations in modern humans. We examined whether or not putative FOXP2 targets identified by chromatin-immunoprecipitation genomic screening show evidence of positive selection. We developed an algorithm that, for any given gene list, systematically generates matched lists of control genes from the Ensembl database, collates summary statistics for three frequency-spectrum-based neutrality tests from the low-coverage resequencing data of the 1000 Genomes Project, and determines whether these statistics are significantly different between the given gene targets and the set of controls. Overall, there was strong evidence of selection of FOXP2 targets in Europeans, but not in the Han Chinese, Japanese, or Yoruba populations. Significant outliers included several genes linked to cellular movement, reproduction, development, and immune cell trafficking, and 13 of these constituted a significant network associated with cardiac arteriopathy. Strong signals of selection were observed for CNTNAP2 and RBFOX1, key neurally expressed genes that have been consistently identified as direct FOXP2 targets in multiple studies and that have themselves been associated with neurodevelopmental disorders involving language dysfunction. PMID:23602712

Prevalence and trends of drugged driving in Canada.

PubMed

Robertson, Robyn D; Mainegra Hing, Marisela; Pashley, Charlotte R; Brown, Steve W; Vanlaar, Ward G M

2017-02-01

This study evaluates prevalence and trends in drugged driving in Canada based on multiple indicators collected from the Road Safety Monitor (RSM) and Canada's National Fatality Database maintained by the Traffic Injury Research Foundation (TIRF). The objective of this paper is to identify the state of drug-positive driving in Canada, as well as to make comparisons with data from previous years to determine whether changes have occurred. Available data from the RSM on self-reported drugged driving behaviours were collected and analyzed using multivariate techniques in various years spanning from 2002 to 2015. Data from TIRF's National Fatality Database from 2000 to 2012 were also analyzed to evaluate trends and prevalence of drugs in fatally injured drivers across Canada. Additionally, differences among drugged drivers with respect to gender and age were studied. Analyses of the RSM data and of the National Fatality Database showed that, as a whole, the prevalence of drugged driving has remained relatively stable over the past decade, with some changes noticed in specific years for some drug types. Specifically from the RSM, there was a 62.5% increase from the 1.6% of drivers reporting driving within two hours of using marijuana in 2013 to 2.6% in 2015. The analyses of the fatality data revealed a 16.9% increase in the percentage of fatally injured drivers testing positive for drugs between 2000 and 2012 (from 33.56% to 39.24%). Cocaine-positive fatally injured drivers increased from 3.6% in 2000 to 6.2% in 2012. Similarly, marijuana-positive fatally injured drivers increased from 12.8% in 2000 to 19.7% in 2012. Results showed varying characteristics with respect to gender and age among self-reported and fatally injured drugged drivers. Drugged driving behaviours remain prevalent among Canadian drivers and drugs continue to be found in over one-third of tested fatally injured drivers. Although self-reported behaviours have neither decreased nor increased overall in

Evaluation of the Triage TOX Drug Screen Assay for Detection of 11 Drugs of Abuse and Therapeutic Drugs.

PubMed

Bang, Hae In; Jang, Mi Ae; Lee, Yong Wha

2017-11-01

The demand for rapid and broad clinical toxicology screens is on the rise. Recently, a new rapid toxicology screening test, the Triage TOX Drug Screen (Alere Inc., USA), which can simultaneously detect 11 drugs of abuse and therapeutic drugs with an instrument-read cartridge, was developed. In the present study, we evaluated the efficacy of this new on-site immunoassay using 105 urine specimens; the results were compared with those obtained by using ultra-performance liquid chromatography with tandem mass spectrometry (UPLC-TMS). Precision was evaluated according to the CLSI EP12-A2 for analyte concentrations near the cutoff, including C₅₀ and±30% of C₅₀, for each drug using standard materials. The C₅₀ specimens yielded 35-65% positive results and the±30% concentration range of all evaluated drugs encompassed the C₅-C₉₅ interval. The overall percent agreement of the Triage TOX Drug Screen was 92.4-100% compared with UPLC-TMS; however, the Triage TOX Drug Screen results showed some discordant cases including acetaminophen, amphetamine, benzodiazepine, opiates, and tricyclic antidepressants. The overall performance of the Triage TOX Drug Screen assay was comparable to that of UPLC-TMS for screening of drug intoxication in hospitals. This assay could constitute a useful screening method for drugs of abuse and therapeutic drugs in urine. © The Korean Society for Laboratory Medicine.

HPLC-high-resolution mass spectrometry with polarity switching for increasing throughput of human in vitro cocktail drug-drug interaction assay.

PubMed

Ramanathan, Ragu; Ghosal, Anima; Ramanathan, Lakshmi; Comstock, Kate; Shen, Helen; Ramanathan, Dil

2018-05-01

Evaluation of HPLC-high-resolution mass spectrometry (HPLC-HRMS) full scan with polarity switching for increasing throughput of human in vitro cocktail drug-drug interaction assay. Microsomal incubates were analyzed using a high resolution and high mass accuracy Q-Exactive mass spectrometer to collect integrated qualitative and quantitative (qual/quant) data. Within assay, positive-to-negative polarity switching HPLC-HRMS method allowed quantification of eight and two probe compounds in the positive and negative ionization modes, respectively, while monitoring for LOR and its metabolites. LOR-inhibited CYP2C19 and showed higher activity for CYP2D6, CYP2E1 and CYP3A4. Overall, LC-HRMS-based nontargeted full scan quantitation allowed to improve the throughput of the in vitro cocktail drug-drug interaction assay.

Hibiscus vitifolius (Linn.) root extracts shows potent protective action against anti-tubercular drug induced hepatotoxicity.

PubMed

Samuel, Anbu Jeba Sunilson John; Mohan, Syam; Chellappan, Dinesh Kumar; Kalusalingam, Anandarajagopal; Ariamuthu, Saraswathi

2012-05-07

The roots of Hibiscus vitifolius Linn. (Malvaceae) is used for the treatment of jaundice in the folklore system of medicine in India. This study is an attempt to evaluate the hepatoprotective activity of the roots of Hibiscus vitifolius against anti-tubercular drug induced hepatotoxicity. Hepatotoxicity was induced in albino rats of either sex by oral administration of a combination of three anti-tubercular drugs. Petroleum ether, chloroform, methanol and aqueous extracts of roots of Hibiscus vitifolius (400mg/kg/day) were evaluated for their possible hepatoprotective potential. All the extracts were found to be safe up to a dose of 2000mg/kg. Among the four extracts studied, oral administration of methanol extract of Hibiscus vitifolius at 400mg/kg showed significant difference in all the parameters when compared to control. There was a significant (P<0.001) reduction in the levels of serum aspartate amino transaminase, alanine amino transferase, alkaline phosphatase, lactate dehydrogenase, total and direct bilirubin, where as an increase was found in the levels of total cholesterol, total protein and albumin. Liver homogenate studies showed a significant increase in the levels of total protein, phospholipids and glycogen, and a reduction in the levels of total lipids, triglycerides, and cholesterol against control animals. In the tissue anti-oxidant studies, we found a significant increase in the levels of catalase and superoxide dismutase, whereas there was marked reduction in the levels of thiobarbituric acid reactive substances, as compared to control. Histology of liver sections of the animals treated with the extracts showed significant reduction of necrosis and fatty formation when compared with control specimens. These findings suggest that the root extracts of Hibiscus vitifolius have potent hepatoprotective activity, thereby justifying its ethnopharmacological claim. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Albumin nanoparticle encapsulation of potent cytotoxic therapeutics shows sustained drug release and alleviates cancer drug toxicity.

PubMed

Wang, Hangxiang; Wu, Jiaping; Xu, Li; Xie, Ke; Chen, Chao; Dong, Yuehan

2017-02-23

We here provide the first report on the construction of nanoparticles formulating highly potent cytotoxic therapeutics using albumin. Maytansinoid DM1 can be efficiently integrated into albumin nanoparticles, resulting in remarkable alleviation of in vivo drug toxicity and expanding the repertoire of albumin technology available for cancer therapy.

FOXP2 targets show evidence of positive selection in European populations.

PubMed

Ayub, Qasim; Yngvadottir, Bryndis; Chen, Yuan; Xue, Yali; Hu, Min; Vernes, Sonja C; Fisher, Simon E; Tyler-Smith, Chris

2013-05-02

Forkhead box P2 (FOXP2) is a highly conserved transcription factor that has been implicated in human speech and language disorders and plays important roles in the plasticity of the developing brain. The pattern of nucleotide polymorphisms in FOXP2 in modern populations suggests that it has been the target of positive (Darwinian) selection during recent human evolution. In our study, we searched for evidence of selection that might have followed FOXP2 adaptations in modern humans. We examined whether or not putative FOXP2 targets identified by chromatin-immunoprecipitation genomic screening show evidence of positive selection. We developed an algorithm that, for any given gene list, systematically generates matched lists of control genes from the Ensembl database, collates summary statistics for three frequency-spectrum-based neutrality tests from the low-coverage resequencing data of the 1000 Genomes Project, and determines whether these statistics are significantly different between the given gene targets and the set of controls. Overall, there was strong evidence of selection of FOXP2 targets in Europeans, but not in the Han Chinese, Japanese, or Yoruba populations. Significant outliers included several genes linked to cellular movement, reproduction, development, and immune cell trafficking, and 13 of these constituted a significant network associated with cardiac arteriopathy. Strong signals of selection were observed for CNTNAP2 and RBFOX1, key neurally expressed genes that have been consistently identified as direct FOXP2 targets in multiple studies and that have themselves been associated with neurodevelopmental disorders involving language dysfunction. Copyright © 2013 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

Influenza vaccination of HIV-1-positive and HIV-1-negative former intravenous drug users.

PubMed

Amendola, A; Boschini, A; Colzani, D; Anselmi, G; Oltolina, A; Zucconi, R; Begnini, M; Besana, S; Tanzi, E; Zanetti, A R

2001-12-01

The immunogenicity of an anti-influenza vaccine was assessed in 409 former intravenous drug user volunteers and its effect on the levels of HIV-1 RNA, proviral DNA and on CD4+ lymphocyte counts in a subset HIV-1-positive subjects was measured. HIV-1-positive individuals (n = 72) were divided into three groups on the basis of their CD4+ lymphocyte counts, while the 337 HIV-1-negative participants were allocated into group four. Haemagglutination inhibiting (HI) responses varied from 45.8 to 70% in the HIV-1-positive subjects and were significantly higher in group four (80.7% responses to the H1N1 strain, 81.6% to the H3N2 strain, and 83% to the B strain). The percentage of subjects with HI protective antibody titres (> or = 1:40) increased significantly after vaccination, especially in HIV-1 uninfected subjects. Immunization caused no significant changes in CD4+ counts and in neither plasma HIV-1 RNA nor proviral DNA levels. Therefore, vaccination against influenza may benefit persons infected by HIV-1. Copyright 2001 Wiley-Liss, Inc.

Drug assertiveness and sexual risk-taking behavior in a sample of HIV-positive, methamphetamine-using men who have sex with men

PubMed Central

Semple, Shirley J.; Strathdee, Steffanie A.; Zians, Jim; McQuaid, John R.; Patterson, Thomas L.

2011-01-01

Drug assertiveness skills have been demonstrated effective in reducing substance use behaviors among patients with alcohol- or heroin-use disorders. This study examined the association between drug assertiveness and methamphetamine use, psychological factors, and sexual risk behaviors in a sample of 250 HIV-positive men who have sex with men (MSM) enrolled in a safer sex intervention in San Diego, CA. Less assertiveness in turning down drugs was associated with greater frequency and larger amounts of methamphetamine use, lower self-esteem, higher scores on a measure of sexual sensation-seeking, and greater attendance at risky sexual venues. These data suggest that drug assertiveness training should be incorporated into drug abuse treatment programs and other risk reduction interventions for methamphetamine users. PMID:21550758

Tau Positive Neurons Show Marked Mitochondrial Loss and Nuclear Degradation in Alzheimer's Disease.

PubMed

Wee, Melissa; Chegini, Fariba; Power, John H T; Majd, Shohreh

2018-06-12

Alzheimer's disease (AD) pathology consists of intraneuronal neurofibrillary tangles, made of hyperphosphorylated tau and extracellular accumulation of beta amyloid (Aβ) in Aβ plaques. There is an extensive debate as to which pathology initiates and responsible for cellular loss in AD. Using confocal and light microscopy, post mortem brains from control and AD cases, an antibody to SOD2 as a marker for mitochondria and an antibody to all forms of tau, we analyzed mitochondrial density in tau positive neurons along with nuclear degradation by calculating the raw integrative density. Our findings showed an extensive staining of aggregated tau in cell bodies, dystrophic neurites and neurofilaments in AD with minimal staining in control tissue, along with a marked decrease in mitochondria in tau positive (tau+) neurons. The control or tau negative (tau-) neurons in AD contained an even distribution of mitochondria, which was greatly diminished in tau+ neurons by 40%. There were no significant differences between control and tau- neurons in AD. Tau+ neurons showed marked nuclear degradation which appeared to progress with the extent of tau aggregation. The aggregated tau infiltrated and appeared to break the nuclear envelope with progressively more DNA exiting the nucleus and associating with accumulating of intracellular tau. We report mitochondrial decrease is likely due to a decrease in protein synthesis rather than a redistribution of mitochondria because of decreased axonal transport. We suggest that the decrease in mitochondria and nuclear degradation are key mechanisms for the neuronal loss seen in AD. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Drug assertiveness and sexual risk-taking behavior in a sample of HIV-positive, methamphetamine-using men who have sex with men.

PubMed

Semple, Shirley J; Strathdee, Steffanie A; Zians, Jim; McQuaid, John R; Patterson, Thomas L

2011-10-01

Drug assertiveness skills have been demonstrated to be effective in reducing substance use behaviors among patients with alcohol or heroin use disorders. This study examined the association between drug assertiveness and methamphetamine use, psychological factors, and sexual risk behaviors in a sample of 250 HIV-positive men who have sex with men enrolled in a safer sex intervention in San Diego, CA. Less assertiveness in turning down drugs was associated with greater frequency and larger amounts of methamphetamine use, lower self-esteem, higher scores on a measure of sexual sensation seeking, and greater attendance at risky sexual venues. These data suggest that drug assertiveness training should be incorporated into drug abuse treatment programs and other risk reduction interventions for methamphetamine users. Copyright © 2011 Elsevier Inc. All rights reserved.

Antineutrophil Cytoplasmic Antibody-Positive Small-Vessel Vasculitis Associated with Antithyroid Drug Therapy: How Significant Is the Clinical Problem?

PubMed

Balavoine, Anne-Sophie; Glinoer, Daniel; Dubucquoi, Sylvain; Wémeau, Jean-Louis

2015-12-01

The aim of this review was to delineate the characteristics of antineutrophil cytoplasmic antibody (ANCA)-associated small-vessel vasculitis associated with antithyroid drugs (ATD). A PubMed search was made for English language articles using the search terms antithyroid drugs AND ANCA OR ANCA-associated vasculitis. The literature includes approximately 260 case reports of ANCA-associated small-vessel vasculitis related to ATD, with 75% of these associated with thiouracil derivatives (propylthiouracil [PTU]) and 25% with methyl-mercapto-imidazole derivatives (MMI/TMZ). The prevalence of ANCA-positive cases caused by ATD varied between 4% and 64% with PTU (median 30%), and 0% and 16% with MMI/TMZ (median 6%). Young age and the duration of ATD therapy were the main factors contributing to the emergence of ANCA positivity. Before ATD therapy initiation, the prevalence of ANCA-positive patients was 0-13%. During ATD administration, 20% of patients were found to be positive for ANCA. Only 15% of ANCA-positive patients treated with ATD exhibited clinical evidence of vasculitis, corresponding to 3% of all patients who received ATD. Clinical manifestations of ANCA-associated vasculitis related to ATD were extremely heterogeneous. When vasculitis occurred, ATD withdrawal was usually followed by rapid clinical improvement and a favorable prognosis. ANCA screening is not systematically recommended for individuals on ATD therapy, particularly given the decreasing use of PTU in favor of TMZ/MMI. Particular attention should be given to the pediatric population with Graves' disease who receive ATD, as well as patients treated with thiouracil derivatives and those on long-term ATD therapy.

[Estimation of activity of pharmakopeal disinfectants and antiseptics against Gram-negative and Gram-positive bacteria isolated from clinical specimens, drugs and environment].

PubMed

Grzybowska, Wanda; Młynarczyk, Grazyna; Młynarczyk, Andrzej; Bocian, Ewa; Luczak, Mirosław; Tyski, Stefan

2007-01-01

The MIC of nine different disinfectants and antiseptics were determined for the Gram-negative and Gram-positive bacteria. Strains originated from clinical specimens, drugs and environment. A sensitivity was determined against chlorhexidinum digluconate (Gram-negative: 0,625-80 mg/L, Gram-positive: 0,3-10 mg/L), benzalconium chloride (Gram-negative: 2,5-1280 mg/L, Gram-positive: 1,25-20 mg/L), salicilic acid (Gram-negative and Gram-positive: 400-1600 mg/L), benzoic acid (Gram-negative: 800-1600 mg/L, Gram-positive: 400-1 600 mg/L), boric acid (Gram-negative: 800-12 800 mg/L, Gram-positive: 1 600-6400 mg/L), chloramine B (Gram-negative: 1600-6400 mg/L, Gram-positive:800- 6400 mg/L), jodine (Gram-negative: 200-1600 mg/L, Gram-positive: 200-1600 mg/L), etacridine lactate (Gram-negative: 40 do > 20480 mg/L, Gram-positive: 40-1280 mg/L) and resorcine (Gram-negative: 1600-6400 mg/L, Gram-positive: 800-6400 mg/L). Diversified values of MIC for different strains were obtained, especially in the case of benzalconium chloride, etacridine lactate, chlorhexidinum digluconate, boric acid and iodine. Strains isolated from environment were usually more susceptible to examined compounds than clinical strains. The biggest diversification of sensitivity was observed among strains originated from drugs where besides sensitive appeared strains characterizing by very high MIC values of some substances, eg. boric acid.

21 CFR 1314.150 - Order To show cause.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 9 2010-04-01 2010-04-01 false Order To show cause. 1314.150 Section 1314.150 Food and Drugs DRUG ENFORCEMENT ADMINISTRATION, DEPARTMENT OF JUSTICE RETAIL SALE OF SCHEDULED LISTED CHEMICAL PRODUCTS Order to Show Cause § 1314.150 Order To show cause. (a) If, upon information gathered by...

Draft Genome Sequence of Brevibacillus laterosporus OSY-I1, a Strain That Produces Brevibacillin, Which Combats Drug-Resistant Gram-Positive Bacteria

PubMed Central

Yang, Xu; Yesil, Mustafa; Xiaoli, Lingzi; Dudley, Edward G.

2017-01-01

ABSTRACT Brevibacillus laterosporus OSY-I1 is a Gram-positive spore-forming bacterium isolated from soil. The bacterium produces brevibacillin, an antimicrobial lipopeptide effective against several drug-resistant Gram-positive bacteria. Here, we present the draft genome sequence of the strain OSY-I1 and the gene cluster responsible for the biosynthesis of brevibacillin. PMID:29025947

4H-Chromene-based anticancer agents towards multi-drug resistant HL60/MX2 human leukemia: SAR at the 4th and 6th positions.

PubMed

Puppala, Manohar; Zhao, Xinghua; Casemore, Denise; Zhou, Bo; Aridoss, Gopalakrishnan; Narayanapillai, Sreekanth; Xing, Chengguo

2016-03-15

4H-Chromene-based compounds, for example, CXL017, CXL035, and CXL055, have a unique anticancer potential that they selectively kill multi-drug resistant cancer cells. Reported herein is the extended structure-activity relationship (SAR) study, focusing on the ester functional group at the 4th position and the conformation at the 6th position. Sharp SARs were observed at both positions with respect to cellular cytotoxic potency and selectivity between the parental HL60 and the multi-drug resistant HL60/MX2 cells. These results provide critical guidance for future medicinal optimization. Copyright © 2016. Published by Elsevier Ltd.

Relationships Between Illicit Drug Use and Body Mass Index Among Adolescents.

PubMed

Blackstone, Sarah R; Herrmann, Lynn K

2016-02-01

Prior research has established associations between body mass index (BMI) and use of alcohol, tobacco, and marijuana. However, little research has been done investigating the relationship between other common illicit drugs and BMI trends. The present study investigated whether adolescents who reported using illicit drugs showed differences in BMI compared to peers who reported no drug use. There was a positive relationship between drug use and BMI as well as the number of drugs used and BMI. The results suggested that the positive relationship between the use of illicit drugs and BMI is largely due to smoking. Further research needs to ascertain whether smoking, illicit drug use, or both are among the first of many unhealthy behaviors that can subsequently lead to greater gains in BMI. Implications for health educators are discussed. © 2015 Society for Public Health Education.

Expanded Circulating Tumor Cells from a Patient with ALK-Positive Lung Cancer Present with EML4-ALK Rearrangement Along with Resistance Mutation and Enable Drug Sensitivity Testing: A Case Study.

PubMed

Zhang, Zhuo; Shiratsuchi, Hiroe; Palanisamy, Nallasivam; Nagrath, Sunitha; Ramnath, Nithya

2017-02-01

The emergence of liquid biopsy using circulating tumor cells (CTCs) as a resource to identify genomic alterations in cancer presents new opportunities for diagnosis, therapy, and surveillance. We identified EML4-ALK gene rearrangement in expanded CTCs from a patient with ALK-positive lung adenocarcinoma. At the time of radiographic progression, CTCs obtained from the patient revealed a drug resistance mutation (i.e., L1196M on the ALK gene). CTCs were expanded ex vivo and drug sensitivity testing was performed using two ALK inhibitors, crizotinib and ceritinib. The half maximal inhibitory concentration of ceritinib was 1664 nM compared with crizotinib (2268 nM), showing that ceritinib was a more potent ALK inhibitor. We show that it is feasible to detect serial genetic alterations in expanded CTCs and perform in vitro drug screening. These findings support the clinical utility of CTCs not only for diagnosis, but also a potential tool for drug sensitivity testing in distinct subsets of lung cancer and for personalized precision medicine. Copyright © 2016 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

Fluency of pharmaceutical drug names predicts perceived hazardousness, assumed side effects and willingness to buy.

PubMed

Dohle, Simone; Siegrist, Michael

2014-10-01

The impact of pharmaceutical drug names on people's evaluations and behavioural intentions is still uncertain. According to the representativeness heuristic, evaluations should be more positive for complex drug names; in contrast, fluency theory suggests that evaluations should be more positive for simple drug names. Results of three experimental studies showed that complex drug names were perceived as more hazardous than simple drug names and negatively influenced willingness to buy. The results are of particular importance given the fact that there is a worldwide trend to make more drugs available for self-medication. © The Author(s) 2013.

Targets of drugs are generally, and targets of drugs having side effects are specifically good spreaders of human interactome perturbations.

PubMed

Perez-Lopez, Áron R; Szalay, Kristóf Z; Türei, Dénes; Módos, Dezső; Lenti, Katalin; Korcsmáros, Tamás; Csermely, Peter

2015-05-11

Network-based methods are playing an increasingly important role in drug design. Our main question in this paper was whether the efficiency of drug target proteins to spread perturbations in the human interactome is larger if the binding drugs have side effects, as compared to those which have no reported side effects. Our results showed that in general, drug targets were better spreaders of perturbations than non-target proteins, and in particular, targets of drugs with side effects were also better spreaders of perturbations than targets of drugs having no reported side effects in human protein-protein interaction networks. Colorectal cancer-related proteins were good spreaders and had a high centrality, while type 2 diabetes-related proteins showed an average spreading efficiency and had an average centrality in the human interactome. Moreover, the interactome-distance between drug targets and disease-related proteins was higher in diabetes than in colorectal cancer. Our results may help a better understanding of the network position and dynamics of drug targets and disease-related proteins, and may contribute to develop additional, network-based tests to increase the potential safety of drug candidates.

Targets of drugs are generally, and targets of drugs having side effects are specifically good spreaders of human interactome perturbations

NASA Astrophysics Data System (ADS)

Perez-Lopez, Áron R.; Szalay, Kristóf Z.; Türei, Dénes; Módos, Dezső; Lenti, Katalin; Korcsmáros, Tamás; Csermely, Peter

2015-05-01

Network-based methods are playing an increasingly important role in drug design. Our main question in this paper was whether the efficiency of drug target proteins to spread perturbations in the human interactome is larger if the binding drugs have side effects, as compared to those which have no reported side effects. Our results showed that in general, drug targets were better spreaders of perturbations than non-target proteins, and in particular, targets of drugs with side effects were also better spreaders of perturbations than targets of drugs having no reported side effects in human protein-protein interaction networks. Colorectal cancer-related proteins were good spreaders and had a high centrality, while type 2 diabetes-related proteins showed an average spreading efficiency and had an average centrality in the human interactome. Moreover, the interactome-distance between drug targets and disease-related proteins was higher in diabetes than in colorectal cancer. Our results may help a better understanding of the network position and dynamics of drug targets and disease-related proteins, and may contribute to develop additional, network-based tests to increase the potential safety of drug candidates.

Targets of drugs are generally, and targets of drugs having side effects are specifically good spreaders of human interactome perturbations

PubMed Central

Perez-Lopez, Áron R.; Szalay, Kristóf Z.; Türei, Dénes; Módos, Dezső; Lenti, Katalin; Korcsmáros, Tamás; Csermely, Peter

2015-01-01

Network-based methods are playing an increasingly important role in drug design. Our main question in this paper was whether the efficiency of drug target proteins to spread perturbations in the human interactome is larger if the binding drugs have side effects, as compared to those which have no reported side effects. Our results showed that in general, drug targets were better spreaders of perturbations than non-target proteins, and in particular, targets of drugs with side effects were also better spreaders of perturbations than targets of drugs having no reported side effects in human protein-protein interaction networks. Colorectal cancer-related proteins were good spreaders and had a high centrality, while type 2 diabetes-related proteins showed an average spreading efficiency and had an average centrality in the human interactome. Moreover, the interactome-distance between drug targets and disease-related proteins was higher in diabetes than in colorectal cancer. Our results may help a better understanding of the network position and dynamics of drug targets and disease-related proteins, and may contribute to develop additional, network-based tests to increase the potential safety of drug candidates. PMID:25960144

Health Information Technology Continues to Show Positive Effect on Medical Outcomes: Systematic Review.

PubMed

Kruse, Clemens Scott; Beane, Amanda

2018-02-05

Health information technology (HIT) has been introduced into the health care industry since the 1960s when mainframes assisted with financial transactions, but questions remained about HIT's contribution to medical outcomes. Several systematic reviews since the 1990s have focused on this relationship. This review updates the literature. The purpose of this review was to analyze the current literature for the impact of HIT on medical outcomes. We hypothesized that there is a positive association between the adoption of HIT and medical outcomes. We queried the Cumulative Index of Nursing and Allied Health Literature (CINAHL) and Medical Literature Analysis and Retrieval System Online (MEDLINE) by PubMed databases for peer-reviewed publications in the last 5 years that defined an HIT intervention and an effect on medical outcomes in terms of efficiency or effectiveness. We structured the review from the Primary Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA), and we conducted the review in accordance with the Assessment for Multiple Systematic Reviews (AMSTAR). We narrowed our search from 3636 papers to 37 for final analysis. At least one improved medical outcome as a result of HIT adoption was identified in 81% (25/37) of research studies that met inclusion criteria, thus strongly supporting our hypothesis. No statistical difference in outcomes was identified as a result of HIT in 19% of included studies. Twelve categories of HIT and three categories of outcomes occurred 38 and 65 times, respectively. A strong majority of the literature shows positive effects of HIT on the effectiveness of medical outcomes, which positively supports efforts that prepare for stage 3 of meaningful use. This aligns with previous reviews in other time frames. ©Clemens Scott Kruse, Amanda Beane. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 05.02.2018.

Nonnatural deaths among users of illicit drugs: pathological findings and illicit drug abuse stigmata.

PubMed

Delaveris, Gerd Jorunn Møller; Hoff-Olsen, Per; Rogde, Sidsel

2015-03-01

The aim of the study was to provide information on illicit drug abuse stigmata and general pathological findings among an adult narcotic drug-using population aged 20 to 59 years whose death was nonnatural. A total of 1603 medicolegal autopsy reports from 2000 to 2009 concerning cases positive for morphine, heroin, amphetamines, ecstasy, cannabis, LSD (lysergic acid diethylamide), PCP (phencyclidine), and high levels of GHB (γ-hydroxybutyric acid) in addition to methadone and buprenorphine were investigated. Reported findings of hepatitis, portal lymphadenopathy, recent injection marks, drug user's equipment, and numbers of significant pathological conditions were registered and analyzed according to cases positive for opiates, opioids (OPs), and central nervous system (CNS)-stimulating illicit drugs, respectively. Of the selected cases, 1305 were positive for one or more opiate or OP. Cases positive for OPs had significantly more findings of noninfectious pathological conditions. Hepatitis, portal lymphadenopathy, recent injections marks findings of drug user's equipment were all findings found more frequently among the opiate OP-positive individuals. Portal lymphadenopathy was significantly more often found in cases with hepatitis than in cases with other or no infection. In the population positive for CNS stimulants, hepatitis recent injection marks were more frequent findings than in the CNS stimulant-negative group, irrespective of whether they were opiate OP positive or negative.

NIH-supported trial drug shows benefit in children with previously treated cancers

Cancer.gov

Young patients with some types of advanced cancer, for whom standard treatment had failed, had their tumors disappear during treatment with a drug that both targets and blocks a protein associated with their disease. These findings are from a Phase I, mul

Using Positive Youth Development Constructs to Design a Drug Education Curriculum for Junior Secondary Students in Hong Kong

PubMed Central

Lam, Ching Man; Lau, Patrick S. Y.; Law, Ben M. F.; Poon, Y. H.

2011-01-01

This paper outlines the design of a new curriculum for positive youth development (P.A.T.H.S. II) in Hong Kong. The paper discusses the conceptual base for designing a drug-education curriculum for junior-secondary students using four positive youth development constructs—cognitive competence, emotional competence, beliefs in the future, and self-efficacy. The program design is premised on the belief that adolescents do have developmental assets; therefore, the curriculum is designed to develop their psychosocial competencies. The goal of the curriculum is to develop the selfhood of these youths and ultimately achieve the goal of successful adolescent development. PMID:22194667

Spatial Analysis of HIV Positive Injection Drug Users in San Francisco, 1987 to 2005

PubMed Central

Martinez, Alexis N.; Mobley, Lee R.; Lorvick, Jennifer; Novak, Scott P.; Lopez, Andrea M.; Kral, Alex H.

2014-01-01

Spatial analyses of HIV/AIDS related outcomes are growing in popularity as a tool to understand geographic changes in the epidemic and inform the effectiveness of community-based prevention and treatment programs. The Urban Health Study was a serial, cross-sectional epidemiological study of injection drug users (IDUs) in San Francisco between 1987 and 2005 (N = 29,914). HIV testing was conducted for every participant. Participant residence was geocoded to the level of the United States Census tract for every observation in dataset. Local indicator of spatial autocorrelation (LISA) tests were used to identify univariate and bivariate Census tract clusters of HIV positive IDUs in two time periods. We further compared three tract level characteristics (% poverty, % African Americans, and % unemployment) across areas of clustered and non-clustered tracts. We identified significant spatial clustering of high numbers of HIV positive IDUs in the early period (1987–1995) and late period (1996–2005). We found significant bivariate clusters of Census tracts where HIV positive IDUs and tract level poverty were above average compared to the surrounding areas. Our data suggest that poverty, rather than race, was an important neighborhood characteristic associated with the spatial distribution of HIV in SF and its spatial diffusion over time. PMID:24722543

Different requirements for cAMP response element binding protein in positive and negative reinforcing properties of drugs of abuse.

PubMed

Walters, C L; Blendy, J A

2001-12-01

Addiction is a complex process that relies on the ability of an organism to integrate positive and negative properties of drugs of abuse. Therefore, studying the reinforcing as well as aversive components of drugs of abuse in a single model system will enable us to understand the role of final common mediators, such as cAMP response element-binding protein (CREB), in the addiction process. To this end, we analyzed mice with a mutation in the alpha and Delta isoforms of the CREB gene. Previously we have shown that CREB(alphaDelta) mutant mice in a mixed genetic background show attenuated signs of physical dependence, as measured by the classic signs of withdrawal. We have generated a uniform genetically stable F1 hybrid (129SvEv/C57BL/6) mouse line harboring the CREB mutation. We have found the functional activity of CREB in these F1 hybrid mice to be dramatically reduced compared with their wild-type littermates. These mice maintain a reduced withdrawal phenotype after chronic morphine. We are now poised to examine a number of complex behavioral phenotypes related to addiction in a well defined CREB-deficient mouse model. We demonstrate that the aversive properties of morphine are still present in CREB mutant mice despite a reduction of physical withdrawal. On the other hand, these mice do not respond to the reinforcing properties of morphine in a conditioned place preference paradigm. In contrast, CREB mutant mice demonstrate an enhanced response to the reinforcing properties of cocaine compared with their wild-type controls in both conditioned place preference and sensitization behaviors. These data may provide the first paradigm for differential vulnerability to various drugs of abuse.

One patient with schizophrenia showed reduced drug-induced extrapyramidal symptoms as a result of an alternative regimen of treatment with paliperidone 3 and 6 mg every other day.

PubMed

Suzuki, Hidenobu; Hibino, Hiroyuki; Inoue, Yuichi; Matsumoto, Hideo; Mikami, Katsunaka

2017-01-01

Schizophrenia is a chronic disease that requires long-term management with antipsychotics. Antipsychotic drugs are given by tapering their dose, extending the dosing interval, and so on, as part of a treatment strategy to minimize the adverse effects while at the same time maintaining efficacy. We report the case of one patient with schizophrenia in whom the clinical symptoms were alleviated after treatment with 6 mg paliperidone. However, the patient developed extrapyramidal syndrome, for which 3 and 6 mg paliperidone were administered alternately every other day. Extrapyramidal syndrome was assessed using the Drug-Induced Extrapyramidal Symptoms Scale, Abnormal Involuntary Movement Scale, or Barnes Akathisia Scale. There was improvement in Drug-Induced Extrapyramidal Symptoms Scale score and Abnormal Involuntary Movement Scale score. However, there was almost no change in the Positive and Negative Syndrome Scale total score, positive score, negative score, or general score. The results indicate the possibility of lessened adverse effects as a result of an alternative regimen of treatment with paliperidone 3 and 6 mg every other day in the maintenance phase.

Dysphoric students show higher use of the observer perspective in their retrieval of positive versus negative autobiographical memories

PubMed Central

Nelis, Sabine; Debeer, Elise; Holmes, Emily A.; Raes, Filip

2013-01-01

Autobiographical memories are retrieved as images from either a field perspective or an observer perspective. The observer perspective is thought to dull emotion. Positive affect is blunted in depressed mood. Consequently, are positive events recalled from an observer perspective in depressed mood? We investigated the relationship between memory vantage perspective and depressive symptoms in a student sample. Participants completed the Autobiographical Memory Test (AMT; Williams & Broadbent, 1986) and assessed the perspective accompanying each memory. The Beck Depression Inventory-II (BDI-II; Beck, Steer, & Brown, 1996) and the Responses to Positive Affect questionnaire (RPA; Feldman, Joormann, & Johnson, 2008) were administered. The results showed a small positive association between depressive symptoms and the use of an observer perspective for positive autobiographical memories, but not for negative memories. Furthermore, comparing a subgroup with clinically significant symptom levels (dysphoric students) with non-dysphoric individuals revealed that dysphoric students used an observer perspective more for positive memories compared with negative memories. This was not the case for non-dysphoric students. The observer perspective in dysphorics was associated with a dampening cognitive style in response to positive experiences. PMID:23083015

Attitudes towards drug legalization among drug users.

PubMed

Trevino, Roberto A; Richard, Alan J

2002-01-01

Research shows that support for legalization of drugs varies significantly among different sociodemographic and political groups. Yet there is little research examining the degree of support for legalization of drugs among drug users. This paper examines how frequency and type of drug use affect the support for legalization of drugs after adjusting for the effects of political affiliation and sociodemographic characteristics. A sample of 188 drug users and non-drug users were asked whether they would support the legalization of marijuana, cocaine, and heroin. Respondents reported their use of marijuana, crack, cocaine, heroin, speedball, and/or methamphetamines during the previous 30 days. Support for legalization of drugs was analyzed by estimating three separate logistic regressions. The results showed that the support for the legalization of drugs depended on the definition of "drug user" and the type of drug. In general, however, the results showed that marijuana users were more likely to support legalizing marijuana, but they were less likely to support the legalization of cocaine and heroin. On the other hand, users of crack, cocaine, heroin, speedball, and/or methamphetamines were more likely to support legalizing all drugs including cocaine and heroin.

Drug Usage and Attitude Toward Drugs Among College Students

ERIC Educational Resources Information Center

Cross, Herbert J.; Keir, Richard G.

1971-01-01

Results of the data presented suggest that there is considerable experimentation among college students with illegal drugs, especially marijuana. Their attitudes toward other drugs still seems cautious. Marijuana, however, seems-to be accepted and generally positively evaluated. (Author)

Drug use in pregnant women-a pilot study of the coherence between reported use of drugs and presence of drugs in plasma.

PubMed

Wolgast, Emelie; Josefsson, Ann; Josefsson, Martin; Lilliecreutz, Caroline; Reis, Margareta

2018-04-01

In Sweden, information on drug use during pregnancy is obtained through an interview and recorded in a standardized medical record at every visit to the antenatal care clinic throughout the pregnancy. Antenatal, delivery, and neonatal records constitute the basis for the Swedish Medical Birth Register (MBR). The purpose of this exploratory study was to investigate the reliability of reported drug use by simultaneous screening for drug substances in the blood stream of the pregnant woman and thereby validate self-reported data in the MBR. Plasma samples from 200 women were obtained at gestational weeks 10-12 and 25 and screened for drugs by using ultra-high performance liquid chromatography with time of flight mass spectrometry (UHPLC-TOF-MS). The results from the analysis were then compared to medical records. At the first sampling occasion, the drugs found by screening had been reported by 86% of the women and on the second sampling, 85.5%. Missed reported information was clearly associated with drugs for occasional use. The most common drugs in plasma taken in early and mid-pregnancy were meclizine and paracetamol. Two types of continuously used drugs, selective serotonin reuptake inhibitors and propranolol, were used. All women using them reported it and the drug screening revealed a 100% coherence. This study shows good coherence between reported drug intake and the drugs found in plasma samples, which in turn positively validates the MBR.

Legalization of drugs of abuse and the pediatrician.

PubMed

Schwartz, R H

1991-10-01

Growing numbers of individuals are proposing that drugs be legalized in the United States, with claims that federal, state, and local efforts to prohibit the use of illicit drugs are irrational and unenforceable. "Drug reform" advocates include persons of all political persuasions. Ironically, the call for drug reform comes at a time when trends in drug abuse, as reflected in national and state surveys, show a promising decline. It also is contradictory to at least one recent public opinion poll, in which respondents opposed the legalization of marijuana by a five-to-one margin. While their position is by no means unanimous, proponents of drug reform generally base their arguments on several key premises, such as elimination of or reductions in drug trafficking, enforcement, and interdiction expenditures; increased tax revenues from the legal sale of drugs; and reductions in health-care expenses associated with drug treatment. Reform advocates further claim that legalization would not be followed by an increase in drug use. The validity of each of these arguments is highly questionable. Legalization is a simplistic, short-sighted solution to a complex issue with public health, economic, criminal justice, and societal ramifications. Legalization would, moreover, abrogate the position taken in 1961 by the United States and 114 other nations in ratifying the United Nations Single Convention on Narcotic Drugs. The impact of drug reform merits an unbiased study by an independent agency. Until that time, pediatricians should inform themselves of the arguments for and against drug reform and be prepared to educate patients and their families about the issue.

In vitro tests for drug hypersensitivity reactions: an ENDA/EAACI Drug Allergy Interest Group position paper.

PubMed

Mayorga, C; Celik, G; Rouzaire, P; Whitaker, P; Bonadonna, P; Rodrigues-Cernadas, J; Vultaggio, A; Brockow, K; Caubet, J C; Makowska, J; Nakonechna, A; Romano, A; Montañez, M I; Laguna, J J; Zanoni, G; Gueant, J L; Oude Elberink, H; Fernandez, J; Viel, S; Demoly, P; Torres, M J

2016-08-01

Drug hypersensitivity reactions (DHRs) are a matter of great concern, both for outpatient and in hospital care. The evaluation of these patients is complex, because in vivo tests have a suboptimal sensitivity and can be time-consuming, expensive and potentially risky, especially drug provocation tests. There are several currently available in vitro methods that can be classified into two main groups: those that help to characterize the active phase of the reaction and those that help to identify the culprit drug. The utility of these in vitro methods depends on the mechanisms involved, meaning that they cannot be used for the evaluation of all types of DHRs. Moreover, their effectiveness has not been defined by a consensus agreement between experts in the field. Thus, the European Network on Drug Allergy and Drug Allergy Interest Group of the European Academy of Allergy and Clinical Immunology has organized a task force to provide data and recommendations regarding the available in vitro methods for DHR diagnosis. We have found that although there are many in vitro tests, few of them can be given a recommendation of grade B or above mainly because there is a lack of well-controlled studies, most information comes from small studies with few subjects and results are not always confirmed in later studies. Therefore, it is necessary to validate the currently available in vitro tests in a large series of well-characterized patients with DHR and to develop new tests for diagnosis. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Safe syringe disposal is related to safe syringe access among HIV-positive injection drug users.

PubMed

Coffin, Phillip O; Latka, Mary H; Latkin, Carl; Wu, Yingfeng; Purcell, David W; Metsch, Lisa; Gomez, Cynthia; Gourevitch, Marc N

2007-09-01

We evaluated the effect of syringe acquisition on syringe disposal among HIV-positive injection drug users (IDUs) in Baltimore, New York City, and San Francisco (N = 680; mean age 42 years, 62% male, 59% African-American, 21% Hispanic, 12% White). Independent predictors of safe disposal were acquiring syringes through a safe source and ever visiting a syringe exchange program. Weaker predictors included living in San Francisco, living in the area longer, less frequent binge drinking, injecting with an HIV+ partner, peer norms supporting safe injection, and self-empowerment. Independent predictors of safe "handling"-both acquiring and disposing of syringes safely-also included being from New York and being older. HIV-positive IDUs who obtain syringes from a safe source are more likely to safely dispose; peer norms contribute to both acquisition and disposal. Interventions to improve disposal should include expanding sites of safe syringe acquisition while enhancing disposal messages, alternatives, and convenience.

Making drugs accessible.

PubMed

1999-01-01

Making drugs accessible for common HIV-associated illnesses in West Africa is discussed. HIV-positive people in Ouagadougou, Burkina Faso, could not afford drugs for treating their illnesses; thus, volunteers from La Bergerie-FUC, a Christian organization, have established a day care center for HIV-positive people. A French church supplies the drugs; oral rehydration salts are provided through the Ministry of Health. Since the organization did not have enough drugs to meet the needs of all its patients, two strategies were developed to improve its drug supply. The first strategy was to raise money to buy drugs through the support of a local NGO, the Initiative Privee et Communautaire de lutte contre le SIDA (IPC). IPC initially refused to support them, but, eventually agreed to fund drug purchasing as a pilot project. The second strategy was to look at ways of reducing the cost of drugs, which resulted in a list of essential drugs for HIV-associated infections. The list was approved by Care and Support Committee of the national AIDS program for use by other organizations. The organizations have created a national network to improve the delivery of community-based care and support services in Burkina Faso. Recently, the national AIDS program has asked this network to help them change the national essential drugs list to include essential drugs for treating common HIV-associated infections.

Does random urine drug testing reduce illicit drug use in chronic pain patients receiving opioids?

PubMed

Manchikanti, Laxmaiah; Manchukonda, Rajeev; Pampati, Vidyasagar; Damron, Kim S; Brandon, Doris E; Cash, Kim A; McManus, Carla D

2006-04-01

Prescription drug abuse and illicit drug use are common in chronic pain patients. Adherence monitoring with screening tests, and urine drug testing, periodic monitoring with prescription monitoring programs, has become a common practice in recent years. Random drug testing for appropriate use of opioids and use of illicit drugs is often used in pain management practices. Thus, it is expected that random urine drug testing will deter use of illicit drugs, and also improve compliance. To study the prevalence of illicit drug use in patients receiving opioids for chronic pain management and to compare the results of illicit drug use with the results from a previous study. A prospective, consecutive study. Interventional pain management practice setting in the United States. A total of 500 consecutive patients on opioids, considered to be receiving stable doses of opioids supplemental to their interventional techniques, were studied by random drug testing. Testing was performed by rapid drug screen. Results were considered positive if one or more of the monitored illicit drugs including cocaine, marijuana (THC), methamphetamine or amphetamines were present. Illicit drug use was evident in 80 patients, or 16%, with marijuana in 11%, cocaine in 5%, and methamphetamine and/or amphetamines in 2%. When compared with previous data, the overall illicit drug use was significantly less. Illicit drug use in elderly patients was absent. The prevalence of illicit drug abuse in patients with chronic pain receiving opioids continues to be a common occurence. This study showed significant reductions in overall illicit drug use with adherence monitoring combined with random urine drug testing.

Schiff base derived from thiosemicarbazone and anthracene showed high potential in overcoming multidrug resistance in vitro with low drug resistance index.

PubMed

Bai, Jie; Wang, Rui-Hui; Qiao, Yan; Wang, Aidong; Fang, Chen-Jie

2017-01-01

Multidrug resistance (MDR) is a huge obstacle in cancer chemotherapeutics. Overcoming MDR is a great challenge for anticancer drug discovery. Here, DNA binding and cytotoxicity of Schiff base L1 and L2 were explored to assess their efficiency in fighting cancer and overcoming the MDR. L1 and L2 could treat extremely chemoresistant MCF-7/ADR cell as drug-sensitive cell, with drug resistance index (DRI) <2.13, showing high potential in overcoming the MDR. The apoptotic ratio induced by L1 and L2 was low for both MCF-7 and MCF-7/ADR cells. L1 and L2 induced an impairment of cell cycle progression of MCF-7 and MCF-7/ADR cell lines and suppressed cell growth by perturbing progress through the G0/G1 phase, with L2 causing more profound effect, which might account for lower drug resistance after L2 treatment. The molecular docking revealed weak interaction between L1/L2 and P-glycoprotein (P-gp), the most important drug efflux pump and intracellular Rhodamine 123 accumulation indicated that the activity of P-gp was not inhibited by L1 and L2. Combined with the cellular uptake results, it implied that L1 and L2 could bypass P-gp efflux to exert anticancer activity.

Drugs in injured drivers in Denmark.

PubMed

Bernhoft, I M; Steentoft, A; Johansen, S S; Klitgaard, N A; Larsen, L B; Hansen, L B

2005-06-10

As part of the project Impaired Motorists, Methods of Roadside Testing and Assessment for Licensing (IMMORTAL) under the European Commission's Transport RTD Programme of the 5th Framework Programme [I.M. Bernhoft, Drugs in accidents involved drivers in Denmark, D-R4.3 of the project Impaired Motorists, Methods Of Roadside Testing and Assessment for Licensing (IMMORTAL), , 2005], a study regarding drugs in accident-involved drivers was carried out in Denmark. The main objectives of this study were: (1) to collect and analyse samples from injured drivers for the presence of drugs; (2) to give an indication whether drugs may have contributed to traffic accidents; and (3) to get information on the drug-positive drivers and their drug use. This paper focuses on objective 1. Injured drivers who were treated in hospital were asked to give a saliva sample, a blood sample or both. The samples were screened for the following substances: opiates, amphetamines, methamphetamines, incl. MDMA (ecstasy), cannabinoids and metabolites, cocaine and metabolites and benzodiazepines. Screenings were carried out by means of Cozart Microplate EIA kit. Positive screenings were confirmation analysed by gas chromatography-mass spectrometry (GC-MS) or liquid chromatography/tandem mass spectrometry (LC/MS/MS). In total, 26 out of 330 patients were confirmed positive for one or more of the six drug groups. However, three patients were excluded from the survey for various reasons. Of the remaining 23 drug-positive patients 15 were found positive for one drug group, and in five of these cases alcohol was present in a concentration over the legal limit in Denmark (0.05%). The other eight patients were found positive for two drug groups, and in four of these cases, alcohol was also present in a concentration over the legal limit. Alcohol was found both in combinations with medicinal drugs, with illegal drugs and with both. Based on the saliva or blood concentrations, we estimate that there is a

Sex matters: females in proestrus show greater diazepam anxiolysis and brain-derived neurotrophin factor- and parvalbumin-positive neurons than males.

PubMed

Ravenelle, Rebecca; Berman, Ariel K; La, Jeffrey; Mason, Briana; Asumadu, Evans; Yelleswarapu, Chandra; Donaldson, S Tiffany

2018-04-01

In humans and animal models, sex differences are reported for anxiety-like behavior and response to anxiogenic stimuli. In the current work, we studied anxiety-like behavior and response to the prototypical anti-anxiety drug, diazepam. We used 6th generation outbred lines of adult Long Evans rats with high and low anxiety-like behavior phenotypes to investigate the impact of proestrus on the baseline and diazepam-induced behavior. At three doses of diazepam (0, 0.1, and 1.0 mg/kg, i.p.), we measured anxiogenic responses on the elevated plus maze of adult male and female rats. We assessed parvalbumin and brain-derived neurotrophin protein levels in forebrain and limbic structures implicated in anxiety/stress using immunohistochemistry. At baseline, we saw significant differences between anxiety lines, with high anxiety lines displaying less time on the open arms of the elevated plus maze, and less open arm entries, regardless of sex. During proestrus, high anxiety females showed less anxiety-like behavior at 0.1 mg/kg, while low anxiety females displayed less anxiety-like behavior at 0.1 and 1.0 doses, relative to males. Brain-derived neurotrophin protein was elevated in females in the medial prefrontal cortex and central amygdala, while parvalbumin-immunoreactive cells were greater in males in the medial prefrontal cortex. Parvalbumin-positive cells in high anxiety females were higher in CA2 and dentate gyrus relative to males from the same line. In sum, when tested in proestrus, females showed greater anxiolytic effects of diazepam relative to males, and this correlated with increases in neurotrophin and parvalbumin neuron density in corticolimbic structures. © 2018 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Active and latent tuberculosis among HIV-positive injecting drug users in Indonesia

PubMed Central

Meijerink, Hinta; Wisaksana, Rudi; Lestari, Mery; Meilana, Intan; Chaidir, Lydia; van der Ven, Andre JAM; Alisjahbana, Bachti; van Crevel, Reinout

2015-01-01

Introduction Injecting drug use (IDU) is associated with tuberculosis but few data are available from low-income settings. We examined IDU in relation to active and latent tuberculosis (LTBI) among HIV-positive individuals in Indonesia, which has a high burden of tuberculosis and a rapidly growing HIV epidemic strongly driven by IDU. Methods Active tuberculosis was measured prospectively among 1900 consecutive antiretroviral treatment (ART)-naïve adult patients entering care in a clinic in West Java. Prevalence of LTBI was determined cross-sectionally in a subset of 518 ART-experienced patients using an interferon-gamma release assay. Results Patients with a history of IDU (53.1%) more often reported a history of tuberculosis treatment (34.8% vs. 21.9%, p<0.001), more often received tuberculosis treatment during follow-up (adjusted HR=1.71; 95% CI: 1.25–2.35) and more often had bacteriologically confirmed tuberculosis (OR=1.67; 95% CI: 0.94–2.96). LTBI was equally prevalent among people with and without a history of IDU (29.1 vs. 30.4%, NS). The risk estimates did not change after adjustment for CD4 cell count or ART. Conclusions HIV-positive individuals with a history of IDU in Indonesia have more active tuberculosis, with similar rates of LTBI. Within the HIV clinic, LTBI screening and isoniazid preventive therapy may be prioritized to patients with a history of IDU. PMID:25690530

Entry time effects and follow-on drug competition.

PubMed

Andrade, Luiz Flavio; Sermet, Catherine; Pichetti, Sylvain

2016-01-01

Pharmaceutical firms have been criticized for concentrating efforts of R&D on the so-called me-too or follow-on drugs. There have been many comments for and against the dissemination of these incremental innovations but few papers have broached the subject from an econometric point of view, possibly because identification of me-too or follow-on drugs is not so obvious. This paper focuses on the impact of entry order on follow-on drug competition in the French market between the years 2001 and 2007. More precisely, this study examines the effects on market share of first entrants in the follow-on drug market and how this possible competitive advantage changes over time. First results are coherent with theoretical microeconomic issues concerning the importance of being first. We find evidence that first movers in the follow-on drug market have the ability to capture and maintain greater market share for a long period of time. The hierarchical market position of follow-on drugs does not seem to be affected by generic drug emergence. From a dynamic perspective, our analysis shows that market share is positively correlated with the ability of follow-on drugs to set prices higher than the average follow-on drug prices in a specific therapeutic class, which means that market power remains considerably important for first movers. Moreover, we found that the optimum level of innovation to maximize market share is the highest one.

[Myonecrosis in users of injecting drugs (a clinical case)].

PubMed

Shestakova, I V; Iushchuk, N D; Tishkevich, O L

2010-01-01

Myonecrosis remains one of the severest manifestations of skin and soft tissue infections. Clostridia (C. perfringens, C. novyi, C. septicum, C. sordellii, C. histolyticum) are dominant and Staphylococcus aureus, Streptococcus pyogenes, Bacillus cereus, and Bacteriodes fragilis are much less in the etiology of myonecrosis. Cases of gas gangrene have recently become more frequent among injection drug users all over the world. Russia has become the largest opiate market in Europe and consumption of these narcotic drugs is annually growing. In the Russian Federation, a larger number of injection drug users uniquely results in a rise of cases of Clostridium- and mixed flora-induced myonecrosis. Gas gangrene in HIV-positive drug abusers seems to rapidly progress to multiple organ failure and to show high death rates, rather than to develop a localized form. The analyzed case of mixed flora-induced gas gangrene is of interest to physicians of any specialties who can encounter this wound infection in HIV-positive patients.

A positive cannabinoids workplace drug test following the ingestion of commercially available hemp seed oil.

PubMed

Struempler, R E; Nelson, G; Urry, F M

1997-01-01

A commercially available health food product of cold-pressed hemp seed oil ingested by one volunteer twice a day for 4 1/2 days (135 mL total). Urine specimens collected from the volunteer were subjected to standard workplace urine drug testing procedures, and the following concentrations of 11-nor-delta9- tetrahydrocannabinol carboxylic acid (9-THCA) were detected: 41 ng/mL 9-THCA at 45 h, 49 ng/mL at 69 h, and 55 ng/mL at 93 h. Ingestion was discontinued after 93 h, and the following concentrations were detected: 68 ng/mL at 108 h, 57 ng/mL at 117 h, 31 ng/mL at 126 h, and 20 ng/mL at 142 h. The first specimen that tested negative (50 ng/mL initial immunoassay test, 15 ng/mL confirmatory gas chromatographic-mass spectrometric test) was at 146 h, which was 53 h after the last hemp seed oil ingestion. Four subsequent specimens taken to 177 h were also negative. This study indicates that a workplace urine drug test positive for cannabinoids may arise from the consumption of commercially available cold-pressed hemp seed oil.

Effects of Drugs and Alcohol on Behavior, Job Performance, and Workplace Safety

ERIC Educational Resources Information Center

Elliott, Karen; Shelley, Kyna

2006-01-01

A study of records for 1 large U.S. company revealed that employees with positive drug screens were fired, whereas workers who self-disclosed drug/alcohol problems remained employed. Both groups were offered substance abuse intervention, and some previously fired workers were rehired after they received treatment. Accident results showed that…

An Outreach Program in Drug Education; Teaching a Rational Approach to Drug Use

ERIC Educational Resources Information Center

Sorensen, James L.; Joffe, Stephen J.

1975-01-01

Aimed at encouraging rational decision making about drug use, a peer oriented drug education program was conducted in a community youth project. Youth and leaders shared feelings and knowledge about drugs. Compared with four program dropouts, six participants exhibited more positive attitudes toward the drug group, its leaders and themselves.…

Microfluidic device for drug delivery

NASA Technical Reports Server (NTRS)

MacDonald, Michael J. (Inventor); Eddington, David T. (Inventor); Beebe, David J. (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.

Correlates of lending needles/syringes among HIV-seropositive injection drug users.

PubMed

Metsch, Lisa R; Pereyra, Margaret; Purcell, David W; Latkin, Carl A; Malow, Robert; Gómez, Cynthia A; Latka, Mary H

2007-11-01

Among HIV-positive injection drug users (IDUs), we examined the correlates of lending needles/syringes with HIV-negative and unknown status injection partners. HIV-positive IDUs (N=738) from 4 cities in the United States who reported injection drug use with other IDUs in the past 3 months participated in an audio computer-assisted self-administered interview. Eighteen percent of study participants self-reported having lent their needles to HIV-negative or unknown status injection partners. Multivariate analyses showed that 6 variables were significantly associated with this high-risk injecting practice. Older IDUs, high school graduates, and those reporting more supportive peer norms for safer drug use were less likely to lend needles/syringes. Admission to a hospital for drug treatment in the past 6 months, having injected with >1 person in the past 3 months, and having more psychiatric symptoms were all associated with more risk. These findings underscore the need for a continued prevention focus on HIV-positive IDUs that recognizes the combination of drug use, mental health factors, and social factors that might affect this high-risk injecting practice, which could be associated with HIV and hepatitis C transmission.

Detection of drugs in the urine of body-packers.

PubMed

Gherardi, R K; Baud, F J; Leporc, P; Marc, B; Dupeyron, J P; Diamant-Berger, O

1988-05-14

The presence of opiates and benzoylecgonine, the major metabolite of cocaine, in the urine was detected by means of enzyme immunoassay in a series of 120 smugglers who had either ingested or inserted into their rectum cocaine or heroin packaged for transportation. There was a striking relation between the presence of drugs in the urine and swallowing of drug-filled bundles (cocaine 49 of 50 cases, heroin 9 of 10). The proportion of positive results was also high in cases of rectal insertion (cocaine 2 of 2, heroin 35 of 58). In 30 cases of cocaine-packet ingestion, serial measurements showed that the accuracy of the test progressively decreased with respect to the detection of residual packets in the body. Drug detection in the urine of suspected body-packers seems to be a useful test, positive results justifying subsequent radiological investigations.

A Synthetic Dual Drug Sideromycin Induces Gram-Negative Bacteria To Commit Suicide with a Gram-Positive Antibiotic.

PubMed

Liu, Rui; Miller, Patricia A; Vakulenko, Sergei B; Stewart, Nichole K; Boggess, William C; Miller, Marvin J

2018-05-10

Many antibiotics lack activity against Gram-negative bacteria because they cannot permeate the outer membrane or suffer from efflux and, in the case of β-lactams, are degraded by β-lactamases. Herein, we describe the synthesis and studies of a dual drug conjugate (1) of a siderophore linked to a cephalosporin with an attached oxazolidinone. The cephalosporin component of 1 is rapidly hydrolyzed by purified ADC-1 β-lactamase to release the oxazolidinone. Conjugate 1 is active against clinical isolates of Acinetobacter baumannii as well as strains producing large amounts of ADC-1 β-lactamase. Overall, the results are consistent with siderophore-mediated active uptake, inherent activity of the delivered dual drug, and in the presence of β-lactamases, intracellular release of the oxazolidinone upon cleavage of the cephalosporin to allow the freed oxazolidinone to inactivate its target. The ultimate result demonstrates that Gram-positive oxazolidinone antibiotics can be made to be effective against Gram-negative bacteria by β-lactamase triggered release.

Survey results show that adults are willing to pay higher insurance premiums for generous coverage of specialty drugs.

PubMed

Romley, John A; Sanchez, Yuri; Penrod, John R; Goldman, Dana P

2012-04-01

Generous coverage of specialty drugs for cancer and other diseases may be valuable not only for sick patients currently using these drugs, but also for healthy people who recognize the potential need for them in the future. This study estimated how healthy people value insurance coverage of specialty drugs, defined as high-cost drugs that treat cancer and other serious health conditions like multiple sclerosis, by quantifying willingness to pay via a survey. US adults were estimated to be willing to pay an extra $12.94 on average in insurance premiums per month for generous specialty-drug coverage--in effect, $2.58 for every dollar in out-of-pocket costs that they would expect to pay with a less generous insurance plan. Given the value that people assign to generous coverage of specialty drugs, having high cost sharing on these drugs seemingly runs contrary to what people value in their health insurance.

Emergence of cocaine and methamphetamine injection among HIV-positive injection drug users in Northern and Western India

PubMed Central

Mehta, Shruti H.; Srikrishnan, Aylur K; Noble, Eva; Vasudevan, Canjeevaram K; Solomon, Suniti; Kumar, M Suresh; Solomon, Sunil S

2014-01-01

Background Little is known regarding the epidemiology of drug injection and risk behaviors among injection drug users (IDUs) across India. In particular, there is limited data on the prevalence of stimulant injection. Methods We sampled 801 HIV positive IDUs from 14 locations throughout India to represent the geography of India as well as the diversity in IDU epidemic stage (established epidemics, emerging epidemics and large cities). All participants underwent a behavioral survey and blood draw. Given prior associations with stimulant injection and HIV risk, we compared stimulant injectors (cocaine and/or methamphetamine) to those who injected opiates and/or pharmaceuticals only. Results The median age was 33; 86% were male. The primary drugs injected were heroin, buprenorphine and other pharmaceuticals. In all but four sites, >50% of those actively injecting reported needle sharing. Stimulant injection was most common in emerging epidemics. Compared to exclusive opiate injectors, stimulant injectors were significantly younger, more likely to be educated and employed, more likely to report non-injection use of heroin, crack/cocaine and amphetamines, heavy alcohol use, recent needle sharing (71% vs. 57%), sex with a casual partner (57% vs. 31%) and men having sex with other men (33% vs. 9%; p<0.01 for all). Conclusions Emerging IDU epidemics have a drug/sexual risk profile not previously been observed in India. Given the high prevalence of stimulant injection in these populations, HIV prevention/treatment programs may need to be redesigned to maximize effectiveness. The high levels of injection sharing overall reinforce the need to ensure access to harm-reduction services for all. PMID:24382362

Technology transfer through performance management: the effects of graphical feedback and positive reinforcement on drug treatment counselors' behavior.

PubMed

Andrzejewski, M E; Kirby, K C; Morral, A R; Iguchi, M Y

2001-07-01

After drug treatment counselors at a community-based methadone treatment clinic were trained in implementing a contingency management (CM) intervention, baseline measures of performance revealed that, on average, counselors were meeting the performance criteria specified by the treatment protocol about 42% of the time. Counselors were exposed to graphical feedback and a drawing for cash prizes in an additive within-subjects design to assess the effectiveness of these interventions in improving protocol adherence. Counselor performance measures increased to 71% during the graphical feedback condition, and to 81% during the drawing. Each counselor's performance improved during the intervention conditions. Additional analyses suggested that counselors did not have skill deficits that hindered implementation. Rather, protocol implementation occurred more frequently when consequences were added, thereby increasing the overall proportion of criteria met. Generalizations, however, may be limited due to a small sample size and possible confounding of time and intervention effects. Nonetheless, present results show promise that feedback and positive reinforcement could be used to improve technology transfer of behavioral interventions into community clinic settings.

The great American medicine show revisited.

PubMed

Tomes, Nancy

2005-01-01

Since the late 1800s, changes in the advertising and marketing of medicinal drugs have produced heated debates in the United States. With the emergence of the modern prescription drug between 1938 and 1951, concerns that once focused primarily on patients' use of over-the-counter drugs were broadened to include physicians and their "doctors' drugs" as well. The medical profession's growing control over their patients' drug choices inevitably heightened the scrutiny of their own performance as consumers. Although deeply divided over issues of the patient's role in medical decision making, consumer activists and physician reformers expressed similar concerns about the impact of aggressive pharmaceutical marketing and advertising on the doctor-patient relationship, and starting in the late 1950s they employed strikingly similar strategies to counter the new corporate "medicine show." Yet their efforts to promote a more rational use of prescription drugs have usually been too little and too late to offset the effectiveness of pharmaceutical advertising and mar-keting activities.

Treatment Outcomes for Extensively Drug-Resistant Tuberculosis and HIV Co-infection

PubMed Central

Padayatchi, Nesri; Kvasnovsky, Charlotte; Werner, Lise; Master, Iqbal; Horsburgh, C. Robert

2013-01-01

High mortality rates have been reported for patients co-infected with extensively drug-resistant tuberculosis (XDR-TB) and HIV, but treatment outcomes have not been reported. We report treatment outcomes for adult XDR TB patients in KwaZulu-Natal Province, South Africa. Initial data were obtained retrospectively, and outcomes were obtained prospectively during 24 months of treatment. A total of 114 XDR TB patients were treated (median 6 drugs, range 3–9 drugs); 82 (73%) were HIV positive and 50 (61%) were receiving antiretroviral therapy. After receiving treatment for 24 months, 48 (42%) of 114 patients died, 25 (22%) were cured or successfully completed treatment, 19 (17%) withdrew from the study, and 22 (19%) showed treatment failure. A higher number of deaths occurred among HIV-positive patients not receiving antiretroviral therapy and among patients who did not show sputum culture conversion. Culture conversion was a major predictor of survival but was poorly predictive (51%) of successful treatment outcome. PMID:23622055

Preclinical study shows drug has extreme potency against multidrug-resistant HIV variants | Center for Cancer Research

Cancer.gov

CCR investigators and colleagues have developed an anti-HIV drug, GRL-142, which at low concentrations block the replication of various wild-type and multidrug-resistant HIV strains. The drug also reaches high concentrations in a rat’s brain, suggesting it may prevent HIV-associated neurocognitive disorders. Read more…

Head shop compound abuse amongst attendees of the Drug Treatment Centre Board.

PubMed

McNamara, S; Stokes, S; Coleman, N

2010-05-01

The use of "Head Shop" compounds has received much media attention lately. There is very little research in the current literature with regard to the extent of the usage of these substances amongst the drug using population in Ireland. We conducted a study to examine the extent of the usage of Mephedrone, Methylone and BZP amongst attendees of Methadone maintenance programs at the DTCB. Two hundred and nine samples in total were tested. The results showed significant usage of these compounds amongst this cohort of drug users, with 29 (13.9%) of samples tested being positive for Mephedrone, 7 (3.3%) positive for Methylone and 1 (0.5%) positive for BZP.

Defining a reference set to support methodological research in drug safety.

PubMed

Ryan, Patrick B; Schuemie, Martijn J; Welebob, Emily; Duke, Jon; Valentine, Sarah; Hartzema, Abraham G

2013-10-01

Methodological research to evaluate the performance of methods requires a benchmark to serve as a referent comparison. In drug safety, the performance of analyses of spontaneous adverse event reporting databases and observational healthcare data, such as administrative claims and electronic health records, has been limited by the lack of such standards. To establish a reference set of test cases that contain both positive and negative controls, which can serve the basis for methodological research in evaluating methods performance in identifying drug safety issues. Systematic literature review and natural language processing of structured product labeling was performed to identify evidence to support the classification of drugs as either positive controls or negative controls for four outcomes: acute liver injury, acute kidney injury, acute myocardial infarction, and upper gastrointestinal bleeding. Three-hundred and ninety-nine test cases comprised of 165 positive controls and 234 negative controls were identified across the four outcomes. The majority of positive controls for acute kidney injury and upper gastrointestinal bleeding were supported by randomized clinical trial evidence, while the majority of positive controls for acute liver injury and acute myocardial infarction were only supported based on published case reports. Literature estimates for the positive controls shows substantial variability that limits the ability to establish a reference set with known effect sizes. A reference set of test cases can be established to facilitate methodological research in drug safety. Creating a sufficient sample of drug-outcome pairs with binary classification of having no effect (negative controls) or having an increased effect (positive controls) is possible and can enable estimation of predictive accuracy through discrimination. Since the magnitude of the positive effects cannot be reliably obtained and the quality of evidence may vary across outcomes

Young people's attitudes towards illicit drugs: A population-based study.

PubMed

Friis, Karina; Østergaard, Jeanette; Reese, Sidsel; Lasgaard, Mathias

2017-12-01

Previous studies indicate that young people who have positive attitudes towards illicit drugs are more inclined to experiment with them. The first aim of our study was to identify the sociodemographic and risk behaviour characteristics of young people (16-24 years) with positive attitudes towards illicit drug use. The second aim was to identify the characteristics of young people with positive attitudes towards illicit drugs among those who had never tried drugs, those who had tried cannabis but no other illicit drugs, and those who regularly used cannabis and/or had tried other illicit drugs. The analysis was based on a population-based survey from 2013 ( N = 3812). Multiple logistic regression was used to analyse the association between sociodemographic and risk behaviour characteristics and positive attitudes towards illicit drugs. Young men had twice the odds of having positive attitudes towards illicit drug use compared with young women (AOR = 2.1). Also, young age, being single, being employed, smoking tobacco, practising unprotected sex, and experimental cannabis use were associated with positive attitudes towards illicit drug use. Finally, use of cannabis at least 10 times during the previous year and/or use of other illicit drugs had the strongest association with positive attitudes to illicit drug use (AOR = 6.0). Young people who have positive attitudes towards illicit drug use are characterized by a broad range of risky behaviours. These findings may help to identify young people at risk of initiating illicit drug use and thereby support the development and implementation of prevention programmes.

Materials and methods for delivery of biological drugs

NASA Astrophysics Data System (ADS)

Zelikin, Alexander N.; Ehrhardt, Carsten; Healy, Anne Marie

2016-11-01

Biological drugs generated via recombinant techniques are uniquely positioned due to their high potency and high selectivity of action. The major drawback of this class of therapeutics, however, is their poor stability upon oral administration and during subsequent circulation. As a result, biological drugs have very low bioavailability and short therapeutic half-lives. Fortunately, tools of chemistry and biotechnology have been developed into an elaborate arsenal, which can be applied to improve the pharmacokinetics of biological drugs. Depot-type release systems are available to achieve sustained release of drugs over time. Conjugation to synthetic or biological polymers affords long circulating formulations. Administration of biological drugs through non-parenteral routes shows excellent performance and the first products have reached the market. This Review presents the main accomplishments in this field and illustrates the materials and methods behind existing and upcoming successful formulations and delivery strategies for biological drugs.

21 CFR 892.5780 - Light beam patient position indicator.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Light beam patient position indicator. 892.5780 Section 892.5780 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES RADIOLOGY DEVICES Therapeutic Devices § 892.5780 Light beam patient position...

10 CFR 707.8 - Applicant drug testing.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 10 Energy 4 2011-01-01 2011-01-01 false Applicant drug testing. 707.8 Section 707.8 Energy... testing. An applicant for a testing designated position will be tested for the use of illegal drugs before... contractors from conducting drug testing on applicants for employment in any position. ...

10 CFR 707.8 - Applicant drug testing.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 10 Energy 4 2012-01-01 2012-01-01 false Applicant drug testing. 707.8 Section 707.8 Energy... testing. An applicant for a testing designated position will be tested for the use of illegal drugs before... contractors from conducting drug testing on applicants for employment in any position. ...

Antimicrobial drug use and resistance in dogs

PubMed Central

Prescott, John F.; Hanna, W. J. Brad; Reid-Smith, Richard; Drost, Kelli

2002-01-01

Fifteen years (1984–1998) of records from a Veterinary Teaching Hospital were analyzed to determine whether antimicrobial drug resistance in coagulase-positive Staphylococcus spp. (S. aureus, S. intermedius) isolated from clinical infections in dogs has increased, and whether there has been a change in the species of bacteria isolated from urinary tract infections in dogs. In coagulase-positive Staphylococcus spp., a complex pattern showing both increases and decreases of resistance to different classes of antimicrobial drugs was observed, reflecting the changing use of different antimicrobial drug classes in the hospital over a similar period (1990–1999). In canine urinary tract infections identified from 1984 to 1998, an increase in the incidence of multiresistant Enterococcus spp. was apparent, with marginal increases also in incidence in Enterobacter spp. and in Pseudomonas aeruginosa, both of which, like Enterococcus spp., are innately antimicrobial-resistant bacteria. A survey of directors of veterinary teaching hospitals in Canada and the United States identified only 3 hospitals that had any policy on use of “last resort” antimicrobial drugs (amikacin, imipenem, vancomycin). Evidence is briefly reviewed that owners may be at risk when dogs are treated with antimicrobial drugs, as well as evidence that some resistant bacteria may be acquired by dogs as a result of antimicrobial drug use in agriculture. Based in part on gaps in our knowledge, recommendations are made on prudent use of antimicrobial drugs in companion animals, as well as on the need to develop science-based infection control programs in veterinary hospitals. PMID:11842592

Utility of patch testing for patients with drug eruption.

PubMed

Ohtoshi, S; Kitami, Y; Sueki, H; Nakada, T

2014-04-01

Patch testing is less dangerous than oral provocation testing for identification of the causative drug for patients with drug eruption; however, its usefulness for such identification is controversial. To clarify the rates of positive patch testing for patients with drug eruption, classified by causative drugs and clinical features. We analysed results during the period 1990-2010 for 444 patients (151 men, 293 women; mean ± SD age 49.9 ± 18.6 years) who were tested for drug eruption. In the patient group, there were 309 people (69.1%) with maculopapular eruption and 31 (6.9%) with severe drug eruption. The test materials were applied to the back and left for 2 days under occlusion, then results were assessed by the International Contact Dermatitis Research Group (ICDRG) scoring system 3 days after application. Reactions of + to +++ were regarded as positive. Of the 444 patients, 100 (22.4%) had a positive patch test result to a suspected drug. Positive rates were 23.6% and 20.0% for maculopapular eruption and fixed drug eruption, respectively. The class of materials to which most patients reacted positively was contrast medium (n = 53; 41.1%), followed by drugs acting on the central nervous system (n = 18; 28.6%). In the latter group, 16 of the 18 patients were positive to antiepileptics. Positive rates depend on the causative drug rather than the clinical features of the drug eruption. Patch testing is useful when contrast medium or antiepileptics are suspected to be the causative drugs. However, standardization of patch test materials and method of reading is needed, as well as guidelines regarding when testing should be performed. Although patch testing for drug eruption has significant potential, it requires further validation. © 2014 The Authors. Clinical and Experimental Dermatology published by John Wiley & Sons Ltd on behalf of British Association of Dermatologists.

Academic Detailing Has a Positive Effect on Prescribing and Decreasing Prescription Drug Costs: A Health Plan's Perspective

PubMed Central

Ndefo, Uche Anadu; Norman, Rolicia; Henry, Andrea

2017-01-01

Background When initiated by a health plan, academic detailing can be used to change prescribing practices, which can lead to increased safety and savings. Objective To evaluate the impact of academic detailing on prescribing and prescription drug costs of cefixime to a health plan. Methods A prospective intervention study was carried out that evaluated the prescribing practices and prescription drug costs of cefixime. A total of 11 prescribers were detailed by 1 pharmacist between August 2014 and March 2015. Two of the 11 prescribers did not respond to the academic detailing and were not followed up. The physicians' prescribing habits and prescription costs were compared before and after detailing to evaluate the effectiveness of the intervention. Data were collected for approximately 5 months before and after the intervention. Each prescriber served as his or her own control. Results Overall, an approximate 36% reduction in the number of cefixime prescriptions written and an approximate 20% decrease in prescription costs was seen with academic detailing compared with the year before the intervention. In 9 of 11 (82%) prescribers, intervention with academic detailing was successful and resulted in fewer prescriptions for cefixime during the study period. Conclusion Academic detailing had a positive impact on prescribing, by decreasing the number of cefixime prescriptions and lowering the drug costs to the health plan. PMID:28626509

Importance of Urinary Drug Screening in the Multiple Sleep Latency Test and Maintenance of Wakefulness Test.

PubMed

Anniss, Angela M; Young, Alan; O'Driscoll, Denise M

2016-12-15

Multiple sleep latency testing (MSLT) and the maintenance of wakefulness test (MWT) are gold-standard objective tests of daytime sleepiness and alertness; however, there is marked variability in their interpretation and practice. This study aimed to determine the incidence of positive drug screens and their influence on MSLT, MWT, and polysomnographic variables. All patients attending Eastern Health Sleep Laboratory for MSLT or MWT over a 21-mo period were included in the study. Urinary drug screening for amphetamines, barbiturates, benzodiazepines, cannabinoids, cocaine, methadone, and opiates was performed following overnight polysomnography (PSG). Demographics and PSG variables were compared. Of 69 studies, MSLT (43) and MWT (26), 16% of patients had positive urinary drug screening (7 MSLT; 4 MWT). Drugs detected included amphetamines, cannabinoids, opiates, and benzodiazepines. No patient self-reported use of these medications prior to testing. No demographic, MSLT or MWT PSG data or overnight PSG data showed any statistical differences between positive and negative drug screen groups. Of seven MSLT patients testing positive for drug use, one met criteria for the diagnosis of narcolepsy and five for idiopathic hypersomnia. On MWT, three of the four drug-positive patients had a history of a motor vehicle accident and two patients were occupational drivers. These findings indicate drug use is present in patients attending for daytime testing of objective sleepiness and wakefulness. These data support routine urinary drug screening in all patients undergoing MSLT or MWT studies to ensure accurate interpretation in the context of illicit and prescription drug use. © 2016 American Academy of Sleep Medicine

Sexual violence from police and HIV risk behaviours among HIV-positive women who inject drugs in St. Petersburg, Russia - a mixed methods study.

PubMed

Lunze, Karsten; Raj, Anita; Cheng, Debbie M; Quinn, Emily K; Lunze, Fatima I; Liebschutz, Jane M; Bridden, Carly; Walley, Alexander Y; Blokhina, Elena; Krupitsky, Evgeny; Samet, Jeffrey H

2016-01-01

Police violence against people who inject drugs (PWID) is common in Russia and associated with HIV risk behaviours. Sexual violence from police against women who use drugs has been reported anecdotally in Russia. This mixed-methods study aimed to evaluate sexual violence from police against women who inject drugs via quantitative assessment of its prevalence and HIV risk correlates, and through qualitative interviews with police, substance users and their providers in St. Petersburg, Russia. Cross-sectional analyses with HIV-positive women who inject drugs (N=228) assessed the associations between sexual violence from police (i.e. having been forced to have sex with a police officer) and the following behaviours: current drug use, needle sharing and injection frequency using multiple regression models. We also conducted in-depth interviews with 23 key informants, including PWID, police, civil society organization workers, and other stakeholders, to explore qualitatively the phenomenon of sexual violence from police in Russia and strategies to address it. We analyzed qualitative data using content analysis. Approximately one in four women in our quantitative study (24.1%; 95% CI, 18.6%, 29.7%) reported sexual violence perpetrated by police. Affected women reported more transactional sex for drugs or money than those who were not; however, the majority of those reporting sexual violence from police were not involved in these forms of transactional sex. Sexual violence from police was not significantly associated with current drug use or needle sharing but with more frequent drug injections (adjusted incidence rate ratio 1.43, 95% CI 1.04, 1.95). Qualitative data suggested that sexual violence and coercion by police appear to be entrenched as a norm and are perceived insurmountable because of the seemingly absolute power of police. They systematically add to the risk environment of women who use drugs in Russia. Sexual violence from police was common in this cohort of

Bioanalysis of antibody-drug conjugates: American Association of Pharmaceutical Scientists Antibody-Drug Conjugate Working Group position paper.

PubMed

Gorovits, Boris; Alley, Stephen C; Bilic, Sanela; Booth, Brian; Kaur, Surinder; Oldfield, Phillip; Purushothama, Shobha; Rao, Chetana; Shord, Stacy; Siguenza, Patricia

2013-05-01

Antibody-drug conjugates (ADCs) typically consist of a cytotoxic drug covalently bound to an antibody by a linker. These conjugates have the potential to substantially improve efficacy and reduce toxicity compared with cytotoxic small-molecule drugs. Since ADCs are generally complex heterogeneous mixtures of multiple species, these novel therapeutic products present unique bioanalytical challenges. The growing number of ADCs being developed across the industry suggests the need for alignment of the bioanalytical methods or approaches used to assess the multiple species and facilitate consistent interpretation of the bioanalytical data. With limited clinical data, the current strategies that can be used to provide insight into the relationship between the multiple species and the observed clinical safety and efficacy are still evolving. Considerations of the bioanalytical strategies for ADCs based on the current industry practices that take into account the complexity and heterogeneity of ADCs are discussed.

Drugs and Alcohol: Their Relative Crash Risk

PubMed Central

Romano, Eduardo; Torres-Saavedra, Pedro; Voas, Robert B.; Lacey, John H.

2014-01-01

Objective: The purpose of this study was to determine (a) whether among sober (blood alcohol concentration [BAC] = .00%) drivers, being drug positive increases the drivers' risk of being killed in a fatal crash; (b) whether among drinking (BAC > .00%) drivers, being drug positive increases the drivers' risk of being killed in a fatal crash; and (c) whether alcohol and other drugs interact in increasing crash risk. Method: We compared BACs for the 2006, 2007, and 2008 crash cases drawn from the U.S. Fatality Analysis Reporting System (FARS) with control drug and blood alcohol data from participants in the 2007 U.S. National Roadside Survey. Only FARS drivers from states with drug information on 80% or more of the drivers who also participated in the 2007 National Roadside Survey were selected. Results: For both sober and drinking drivers, being positive for a drug was found to increase the risk of being fatally injured. When the drug-positive variable was separated into marijuana and other drugs, only the latter was found to contribute significantly to crash risk. In all cases, the contribution of drugs other than alcohol to crash risk was significantly lower than that produced by alcohol. Conclusions: Although overall, drugs contribute to crash risk regardless of the presence of alcohol, such a contribution is much lower than that by alcohol. The lower contribution of drugs other than alcohol to crash risk relative to that of alcohol suggests caution in focusing too much on drugged driving, potentially diverting scarce resources from curbing drunk driving. PMID:24411797

49 CFR 655.46 - Return to duty following refusal to submit to a test, verified positive drug test result and/or...

Code of Federal Regulations, 2010 CFR

2010-10-01

... 49 Transportation 7 2010-10-01 2010-10-01 false Return to duty following refusal to submit to a test, verified positive drug test result and/or breath alcohol test result of 0.04 or greater. 655.46 Section 655.46 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL TRANSIT ADMINISTRATION, DEPARTMENT OF TRANSPORTATION...

49 CFR 655.46 - Return to duty following refusal to submit to a test, verified positive drug test result and/or...

Code of Federal Regulations, 2011 CFR

2011-10-01

... 49 Transportation 7 2011-10-01 2011-10-01 false Return to duty following refusal to submit to a test, verified positive drug test result and/or breath alcohol test result of 0.04 or greater. 655.46 Section 655.46 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL TRANSIT ADMINISTRATION, DEPARTMENT OF TRANSPORTATION...

49 CFR 655.46 - Return to duty following refusal to submit to a test, verified positive drug test result and/or...

Code of Federal Regulations, 2012 CFR

2012-10-01

... 49 Transportation 7 2012-10-01 2012-10-01 false Return to duty following refusal to submit to a test, verified positive drug test result and/or breath alcohol test result of 0.04 or greater. 655.46 Section 655.46 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL TRANSIT ADMINISTRATION, DEPARTMENT OF TRANSPORTATION...

49 CFR 655.46 - Return to duty following refusal to submit to a test, verified positive drug test result and/or...

Code of Federal Regulations, 2013 CFR

2013-10-01

... 49 Transportation 7 2013-10-01 2013-10-01 false Return to duty following refusal to submit to a test, verified positive drug test result and/or breath alcohol test result of 0.04 or greater. 655.46 Section 655.46 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL TRANSIT ADMINISTRATION, DEPARTMENT OF TRANSPORTATION...

49 CFR 655.46 - Return to duty following refusal to submit to a test, verified positive drug test result and/or...

Code of Federal Regulations, 2014 CFR

2014-10-01

... 49 Transportation 7 2014-10-01 2014-10-01 false Return to duty following refusal to submit to a test, verified positive drug test result and/or breath alcohol test result of 0.04 or greater. 655.46 Section 655.46 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL TRANSIT ADMINISTRATION, DEPARTMENT OF TRANSPORTATION...

Symmetrical drug-related intertriginous and flexural exanthema.

PubMed

Tan, Sze-Chin; Tan, Justina W-L

2011-08-01

Symmetrical drug-related intertriginous and flexural exanthema (SDRIFE), previously termed drug-related baboon syndrome, is a benign and self-limiting type IV hypersensitivity reaction characterized by symmetrical erythema involving the gluteal and intertriginous areas in the absence of systemic involvement. It may also occur in the absence of previous drug exposure. Antibiotics, in particular beta-lactams, comprise the majority of causes of SDRIFE. Other drugs which have been implicated include antihypertensives, radiocontrast media, chemotherapeutic agents, and biologics. Histology of lesional skin is variable with predominance of superficial perivascular inflammatory cell infiltrates. Outcomes of allergy tests are variable with positive delayed intradermal tests reported for penicillin V, allopurinol; positive patch tests for erythromycin, mitomycin, nystatin, pseudoephdrine; positive lymphocyte transformation tests for erythromycin; and positive drug provocation tests for clindamycin, cimetidine, corticosteroids, terbinafine, and valacyclovir. Diagnosis of SDRIFE is dependent upon recognition of the clinical morphology and distribution of the rash, and its temporal relationship to the use of the suspected drug. Outcomes of in-vivo and in-vitro tests have been inconsistent, and thus may not be useful in the identification of the putative drug.

Drug use, travel and HIV risk.

PubMed

Lee, D; Bell, D C; Hinojosa, M

2002-08-01

A study was conducted to examine the travel experiences of a community sample of 160 drug users and 44 non-users recruited as part of a study of HIV risk. Of the sample, 47% (96/204) reported intercity travel in the previous ten years. Results showed that men were more likely to travel than women, Anglos more than minorities, and young persons more than old. When travellers testing HIV-seropositive (n = 13) were compared with seronegative travellers, HIV-positive travellers reported more sex while travelling than HIV-negative persons, but virtually all of the difference reported involved sex with condoms. There were no significant differences in sex risk behaviours while travelling between drug users and non-drug users, or in sex risk behaviors between drug injectors and non-injectors. Travellers had fewer injection partners while travelling than they had while at home. There was also a significant difference in number of sex partners with whom a condom was not used, with fewer sex partners while travelling.

Bone effects of biologic drugs in rheumatoid arthritis.

PubMed

Corrado, Addolorata; Neve, Anna; Maruotti, Nicola; Cantatore, Francesco Paolo

2013-01-01

Biologic agents used in the treatment of rheumatoid arthritis (RA) are able to reduce both disease activity and radiographic progression of joint disease. These drugs are directed against several proinflammatory cytokines (TNF α , IL-6, and IL-1) which are involved both in the pathogenesis of chronic inflammation and progression of joint structural damage and in systemic and local bone loss typically observed in RA. However, the role of biologic drugs in preventing bone loss in clinical practice has not yet clearly assessed. Many clinical studies showed a trend to a positive effect of biologic agents in preventing systemic bone loss observed in RA. Although the suppression of inflammation is the main goal in the treatment of RA and the anti-inflammatory effects of biologic drugs exert a positive effect on bone metabolism, the exact relationship between the prevention of bone loss and control of inflammation has not been clearly established, and if the available biologic drugs against TNF α , IL-1, and IL-6 can exert their effect on systemic and local bone loss also through a direct mechanism on bone cell metabolism is still to be clearly defined.

Simultaneous quantification of four antiretroviral drugs in breast milk samples from HIV-positive women by an ultra-high performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method

PubMed Central

Rodríguez-Delgado, Rosa Georgina; Figueroa-Damián, Ricardo; Domínguez-Castro, Mauricio; López-Martínez, Margarita; Flores-García, Zayra

2018-01-01

The primary strategy to avoid mother-to-child transmission of human immunodeficiency virus (HIV) through breastfeeding is administration of highly active antiretroviral therapy (HAART) to HIV-positive pregnant women. Because significant changes in the pharmacokinetics of antiretroviral (ARV) drugs occur during pregnancy, quantifying HAART and the viral load in breast milk in this population is essential. Here, we developed an analytical assay for the simultaneous quantification of four ARV drugs in breast milk using ultra-performance liquid chromatography coupled to tandem mass spectrometry. We validated this method following Mexican and international guidelines. ARV drugs. We extracted the ARV drugs from 200 μL samples of breast milk and detected these drugs in a triple quadrupole mass spectrometer with positive electrospray ionization. The validated concentration ranges (ng/mL) for zidovudine, lamivudine, lopinavir, and ritonavir were 12.5–750, 50–2500, 100–5000 and 5 to 250, respectively. Additionally, the absolute recovery percentages (and matrix effects) were 91.4 (8.39), 88.78 (28.75), 91.38 (11.77) and 89.78 (12.37), respectively. We determined that ARV drugs are stable for 24 h at 8°C and 24°C for 15 days at –80°C. This methodology had the capacity for simultaneous detection; separation; and accurate, precise quantification of ARV drugs in human breast milk samples according to Mexican standard laws and United States Food and Drug Administration guidelines. PMID:29351333

Schizophrenia Spectrum Disorders Show Reduced Specificity and Less Positive Events in Mental Time Travel

PubMed Central

Chen, Xing-jie; Liu, Lu-lu; Cui, Ji-fang; Wang, Ya; Chen, An-tao; Li, Feng-hua; Wang, Wei-hong; Zheng, Han-feng; Gan, Ming-yuan; Li, Chun-qiu; Shum, David H. K.; Chan, Raymond C. K.

2016-01-01

Mental time travel refers to the ability to recall past events and to imagine possible future events. Schizophrenia (SCZ) patients have problems in remembering specific personal experiences in the past and imagining what will happen in the future. This study aimed to examine episodic past and future thinking in SCZ spectrum disorders including SCZ patients and individuals with schizotypal personality disorder (SPD) proneness who are at risk for developing SCZ. Thirty-two SCZ patients, 30 SPD proneness individuals, and 33 healthy controls participated in the study. The Sentence Completion for Events from the Past Test (SCEPT) and the Sentence Completion for Events in the Future Test were used to measure past and future thinking abilities. Results showed that SCZ patients showed significantly reduced specificity in recalling past and imagining future events, they generated less proportion of specific and extended events compared to healthy controls. SPD proneness individuals only generated less extended events compared to healthy controls. The reduced specificity was mainly manifested in imagining future events. Both SCZ patients and SPD proneness individuals generated less positive events than controls. These results suggest that mental time travel impairments in SCZ spectrum disorders and have implications for understanding their cognitive and emotional deficits. PMID:27507958

Micro-Fluidic Device for Drug Delivery

NASA Technical Reports Server (NTRS)

Beebe, David J. (Inventor); Eddington, David T. (Inventor); MacDonald, Michael J. (Inventor); Mensing, Glennys A. (Inventor)

2014-01-01

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.

False positive 18FDG PET-CT results due to exogenous lipoid pneumonia secondary to oily drug inhalation: A case report.

PubMed

Chardin, David; Nivaggioni, Guillaume; Viau, Philippe; Butori, Caherine; Padovani, Bernard; Grangeaon, Caroline; Razzouk-Cadet, Micheline

2017-06-01

Exogenous lipoid pneumonia is a rare condition due to abnormal presence of oily substances in the lungs. It is a rarely known cause for false positive FDG PET-CT results and can sometimes lead to invasive investigations. Searching and finding the source of the oily substance is one of the keys to the diagnosis. Inhalation of oily drugs during snorting has rarely been described. A patient with well controlled HIV infection was referred for an FDG PET-CT to assess extension of Kaposi's disease, recently removed from his right foot. The patient had no particular symptoms. Abnormal uptake of FDG was found in a suspicious lung nodule. An experienced radiologist thought the nodule was due to lipoid pneumonia. Bronchoalveolar lavage fluid did not contain lipid-laden macrophages but bronchoscopy showed violet lesions resembling Kaposi's disease lesions. Lobectomy was performed after a multidisciplinary discussion. Anatomopathological analysis revealed the nodule was due to lipoid pneumonia. The patient's quality of life did not diminish after the operation and he is still in good health. The source of the oily substance causing lipoid pneumonia was found after the surgery: the patient used to snort oily drugs. The presence of a suspicious lung nodule possibly due to lipoid pneumonia in a patient with known Kaposi's disease was difficult to untangle and lead to invasive surgery. It is possible that if a source of exogenous lipoid pneumonia had been found beforehand, surgery could have been prevented.

Use of illicit drugs by truck drivers arriving at Paranaguá port terminal, Brazil.

PubMed

Peixe, Tiago Severo; de Almeida, Rafael Menck; Girotto, Edmarlon; de Andrade, Selma Maffei; Mesas, Arthur Eumann

2014-01-01

The purpose of this study was to estimate the prevalence of recent use of illicit drugs among truck drivers who had parked their vehicles at the terminal port in Paranaguá City at Paraná State, southern Brazil. This cross-sectional study was part of a larger research project conducted among drivers at a regional Brazilian port. Data on professional characteristics, involvement in road traffic injuries, sleep, and use of alcohol and illicit drugs were collected using a questionnaire. Urine samples were collected and analyzed for amphetamines, cocaine, and cannabis using gas chromatography with mass spectrometric detection. Sixty-two drivers were included in the study. Toxicological analyses showed that 8.1 percent (95% confidence interval [CI], 2.7-17.8%) of the urine samples were positive for drugs (4.8% for cocaine, 1.6% for amphetamine, and 1.6% for both); 8.1 percent reported drug use during the preceding 30 days in the questionnaire and only one tested positive for the drug in the urine sample. No sample was positive for cannabinoids. In total, at least 14.5 percent (95% CI, 6.9-25.8%) had used illicit drugs during the preceding 30 days based on self-reports and urine testing. Drivers who reported involvement in traffic injuries the year before more often tested positive for drugs in biological samples (P <.05). This research provides preliminary evidence that the use of illicit stimulants was common among professional truck drivers transporting grain loads. Thus, actions are needed to reduce drug use among truck drivers in order to prevent drug-related road traffic injuries.

Hepatitis C infection and other drug-related harms among inpatients who injected drugs in Turkey.

PubMed

Alaei, A; Alaei, K; Waye, K; Tracy, M; Nalbandyan, M; Mutlu, E; Cetin, M K

2017-06-01

Hepatitis C virus (HCV) is easily spread among those who share drug injection equipment. Due to the ease of contraction and growing prevalence of HCV in Eastern Europe, the aims of this study focused on describing risky injection practices as well as the prevalence of HCV, HIV and hepatitis B virus (HBV) among people who inject drugs (PWID) who were admitted to public and private drug treatment centres in Turkey from 2012 to 2013. Other aims included identifying correlates of needle sharing and HCV infection. Of the 4694 inpatients who ever injected drugs and the 3914 who injected in the past 30 days, nearly all (98%) reported heroin as their drug of choice, the vast majority reported ever sharing a needle (73.4% and 79.3%), and the mean age at first injection was 23 years. Of current PWID, 51.9% were HCV-positive, 5.9% were HBV-positive and only 0.34% of lifetime PWID were HIV-positive. Predictors of increased needle sharing include younger age, being unemployed, having lesser education and reporting heroin as a drug of choice. Significant predictors of HCV infection included being 40 years or older, receiving treatment in the Mediterranean region of Turkey, reporting heroin as a primary substance, a longer duration of drug use and sharing needles. With this information, it is essential to improve access to clean injection equipment in Turkey, to focus on improving education on clean injection practices and to enhance efforts in testing and treating HCV-positive PWID. © 2016 John Wiley & Sons Ltd.

49 CFR 655.61 - Action when an employee has a verified positive drug test result or has a confirmed alcohol test...

Code of Federal Regulations, 2014 CFR

2014-10-01

... 49 Transportation 7 2014-10-01 2014-10-01 false Action when an employee has a verified positive drug test result or has a confirmed alcohol test result of 0.04 or greater, or refuses to submit to a test. 655.61 Section 655.61 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL TRANSIT ADMINISTRATION, DEPARTMENT OF...

49 CFR 655.61 - Action when an employee has a verified positive drug test result or has a confirmed alcohol test...

Code of Federal Regulations, 2010 CFR

2010-10-01

... 49 Transportation 7 2010-10-01 2010-10-01 false Action when an employee has a verified positive drug test result or has a confirmed alcohol test result of 0.04 or greater, or refuses to submit to a test. 655.61 Section 655.61 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL TRANSIT ADMINISTRATION, DEPARTMENT OF...

49 CFR 655.61 - Action when an employee has a verified positive drug test result or has a confirmed alcohol test...

Code of Federal Regulations, 2011 CFR

2011-10-01

... 49 Transportation 7 2011-10-01 2011-10-01 false Action when an employee has a verified positive drug test result or has a confirmed alcohol test result of 0.04 or greater, or refuses to submit to a test. 655.61 Section 655.61 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL TRANSIT ADMINISTRATION, DEPARTMENT OF...

49 CFR 655.61 - Action when an employee has a verified positive drug test result or has a confirmed alcohol test...

Code of Federal Regulations, 2013 CFR

2013-10-01

... 49 Transportation 7 2013-10-01 2013-10-01 false Action when an employee has a verified positive drug test result or has a confirmed alcohol test result of 0.04 or greater, or refuses to submit to a test. 655.61 Section 655.61 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL TRANSIT ADMINISTRATION, DEPARTMENT OF...

49 CFR 655.61 - Action when an employee has a verified positive drug test result or has a confirmed alcohol test...

Code of Federal Regulations, 2012 CFR

2012-10-01

... 49 Transportation 7 2012-10-01 2012-10-01 false Action when an employee has a verified positive drug test result or has a confirmed alcohol test result of 0.04 or greater, or refuses to submit to a test. 655.61 Section 655.61 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL TRANSIT ADMINISTRATION, DEPARTMENT OF...

Positive relationship between dietary fat, ethanol intake, triglycerides, and hypothalamic peptides: counteraction by lipid-lowering drugs.

PubMed

Barson, Jessica R; Karatayev, Olga; Chang, Guo-Qing; Johnson, Deanne F; Bocarsly, Miriam E; Hoebel, Bartley G; Leibowitz, Sarah F

2009-09-01

Studies in both humans and animals suggest a positive relationship between the intake of ethanol and intake of fat, which may contribute to alcohol abuse. This relationship may be mediated, in part, by hypothalamic orexigenic peptides such as orexin (OX), which stimulate both consumption of ethanol and fat, and circulating triglycerides (TGs), which stimulate these peptides and promote consummatory behavior. The present study investigated this vicious cycle between ethanol and fat, to further characterize its relation to TGs and to test the effects of lowering TG levels. In Experiment 1, the behavioral relationship between fat intake and ethanol was confirmed. Adult male Sprague-Dawley rats, chronically injected intraperitoneally with ethanol (1g/kg) and tested in terms of their preference for a high-fat diet (HFD) compared with low-fat diet (LFD), showed a significant increase in their fat preference, compared with rats injected with saline, in measures of 2h and 24h intake. Experiment 2 tested the relationship of circulating TGs in this positive association between ethanol and fat, in rats chronically consuming 9% ethanol versus water and given acute meal tests (25kcal) of a HFD versus LFD. Levels of TGs were elevated in response to both chronic drinking of ethanol versus water and acute eating of a high-fat versus low-fat meal. Most importantly, ethanol and a HFD showed an interaction effect, whereby their combination produced a considerably larger increase in TG levels (+172%) compared to ethanol with a LFD (+111%). In Experiment 3, a direct manipulation of TG levels was found to affect ethanol intake. After intragastric administration of gemfibrozil (50mg/kg) compared with vehicle, TG levels were lowered by 37%, and ethanol intake was significantly reduced. In Experiment 4, the TG-lowering drug gemfibrozil also caused a significant reduction in the expression of the orexigenic peptide, OX, in the perifornical lateral hypothalamus. These results support the

Positive relationship between dietary fat, ethanol intake, triglycerides and hypothalamic peptides: Counteraction by lipid-lowering drugs

PubMed Central

Barson, Jessica R.; Karatayev, Olga; Chang, Guo-Qing; Johnson, Deanne F.; Bocarsly, Miriam E.; Hoebel, Bartley G.; Leibowitz, Sarah F.

2009-01-01

Studies in both humans and animals suggest a positive relationship between the intake of ethanol and intake of fat, which may contribute to alcohol abuse. This relationship may be mediated, in part, by hypothalamic orexigenic peptides such as orexin (OX), which stimulate both consumption of ethanol and fat, and circulating triglycerides (TG), which stimulate these peptides and promote consummatory behavior. The present study investigated this vicious cycle between ethanol and fat, to further characterize its relation to TG and to test the effects of lowering TG levels. In Experiment 1, the behavioral relationship between fat intake and ethanol was confirmed. Adult male Sprague-Dawley rats, chronically injected with ethanol (1 g/kg i.p.) and tested in terms of their preference for a high-fat compared to low-fat diet, showed a significant increase in their fat preference, compared to rats injected with saline, in measures of 2 h and 24 h intake. Experiment 2 tested the relationship of circulating TG in this positive association between ethanol and fat, in rats chronically consuming 9% ethanol vs. water and given acute meal tests (25 kcal) of a high-fat vs. low-fat diet. Levels of TG were elevated in response to both chronic drinking of ethanol vs. water and acute eating of a high-fat vs. low-fat meal. Most importantly, ethanol and a high-fat diet showed an interaction effect, whereby their combination produced a considerably larger increase in TG levels (+172%) compared to ethanol with a low-fat diet (+111%). In Experiment 3, a direct manipulation of TG levels was found to affect ethanol intake. After administration of gemfibrozil (50 mg/kg i.g.) compared to vehicle, TG levels were lowered by 37%, and ethanol intake was significantly reduced. In Experiment 4, the TG-lowering drug gemfibrozil also caused a significant reduction in the expression of the orexigenic peptide OX, in the perifornical lateral hypothalamus. These results support the existence of a vicious

Risk Behaviors Among HIV-Positive Gay and Bisexual Men at Party-Oriented Vacations

PubMed Central

Fisher, Michael P.; Ramchand, Rajeev; Bana, Sarah; Iguchi, Martin Y.

2013-01-01

Objective: This study examined substance use (intended and actual), unprotected sex, and HIV disclosure practices (disclosure and questioning) among HIV-positive men who have sex with men (MSM) at two party-oriented vacations, where substance use and sexual risk may be heightened. Method: A random sample of 489 MSM attending one of two party-oriented vacations participated in PartyIntents, a short-term longitudinal survey. Nearly half (47%) completed a follow-up assessment at the event or online for up to 2 weeks after the event. We examined rates of baseline intentions to use substances, actual substance use, and unprotected intercourse among HIV-positive men in attendance.Rates among HIV-negative men were estimated for comparison. Multiple logistic regression was used to assess the impact of illegal drug use and HIV status on unprotected anal intercourse (UAI). Results: HIV-positive attendees (17%) were significantly more likely than HIV-negative attendees to use nitrite inhalants (or “poppers”) (24.3% vs. 10.7%). HIV-positive attendees were also significantly more likely to have insertive UAI (64.3% vs. 34.1%) and receptive UAI (68.8% vs. 22.2%). Multivariate models showed associations between HIV status and illegal drug use with UAI (for HIV status, odds ratio [OR] = 4.5, p = .001; for any illegal drug use, OR = 16.4, p < .001). There was no evidence that the influence of drug use moderated risk by HIV status. Rates of HIV disclosure and questioning did not differ by HIV status. Conclusions: HIV-positive men attending these events engaged in higher rates of illegal drug use and sexual risk than HIV-negative men. Prevention campaigns targeting MSM at high-risk events should include messages geared toward HIV-positive men. PMID:23200162

Resolving anaphoras for the extraction of drug-drug interactions in pharmacological documents

PubMed Central

2010-01-01

Background Drug-drug interactions are frequently reported in the increasing amount of biomedical literature. Information Extraction (IE) techniques have been devised as a useful instrument to manage this knowledge. Nevertheless, IE at the sentence level has a limited effect because of the frequent references to previous entities in the discourse, a phenomenon known as 'anaphora'. DrugNerAR, a drug anaphora resolution system is presented to address the problem of co-referring expressions in pharmacological literature. This development is part of a larger and innovative study about automatic drug-drug interaction extraction. Methods The system uses a set of linguistic rules drawn by Centering Theory over the analysis provided by a biomedical syntactic parser. Semantic information provided by the Unified Medical Language System (UMLS) is also integrated in order to improve the recognition and the resolution of nominal drug anaphors. Besides, a corpus has been developed in order to analyze the phenomena and evaluate the current approach. Each possible case of anaphoric expression was looked into to determine the most effective way of resolution. Results An F-score of 0.76 in anaphora resolution was achieved, outperforming significantly the baseline by almost 73%. This ad-hoc reference line was developed to check the results as there is no previous work on anaphora resolution in pharmalogical documents. The obtained results resemble those found in related-semantic domains. Conclusions The present approach shows very promising results in the challenge of accounting for anaphoric expressions in pharmacological texts. DrugNerAr obtains similar results to other approaches dealing with anaphora resolution in the biomedical domain, but, unlike these approaches, it focuses on documents reflecting drug interactions. The Centering Theory has proved being effective at the selection of antecedents in anaphora resolution. A key component in the success of this framework is the

Tunable drug loading and release from polypeptide multilayer nanofilms

PubMed Central

Jiang, Bingbing; Li, Bingyun

2009-01-01

Polypeptide multilayer nanofilms were prepared using electrostatic layer-by-layer self-assembly nanotechnology. Small charged drug molecules (eg, cefazolin, gentamicin, and methylene blue) were loaded in polypeptide multilayer nanofilms. Their loading and release were found to be pH-dependent and could also be controlled by changing the number of film layers and drug incubation time, and applying heat-treatment after film formation. Antibioticloaded polypeptide multilayer nanofilms showed controllable antibacterial properties against Staphylococcus aureus. The developed biodegradable polypeptide multilayer nanofilms are capable of loading both positively- and negatively-charged drug molecules and promise to serve as drug delivery systems on biomedical devices for preventing biomedical device-associated infection, which is a significant clinical complication for both civilian and military patients. PMID:19421369

Patterns of Drugs and Drug Metabolites Observed in Meconium: What Do They Mean?

PubMed

McMillin, Gwendolyn A; Wood, Kelly E; Strathmann, Frederick G; Krasowski, Matthew D

2015-10-01

Meconium drug testing is performed to detect potentially harmful drug exposures in a newborn. Interpretation of meconium drug testing results can be complicated based on the patterns and proportional concentrations of the drug(s) and/or drug metabolite(s) detected. The objective of this study was to analyze meconium drug testing patterns in a de-identified dataset from a national reference laboratory (n = 76,631) and in a subset of the data, wherein specimens originated at a single academic medical center for which detailed chart review was possible (n = 3635). Meconium testing was performed using 11 immunoassay-based drug screens. Specimens that were positive for one or more drug screens were reflexed to corresponding confirmation tests performed by gas chromatography or liquid chromatography with mass spectrometric detection, targeted to identify and quantitate specific parent drug(s) and metabolite(s). The positivity rate was the highest for the cannabis metabolite 11-nor-9-carboxy-delta-9-tetrahydrocannabinol (25.2%, n = 18,643), followed by opiates/oxycodone (23.2%, n = 17,778), amphetamine/methamphetamine (6.7%, n = 5134), cocaine metabolites (5.5%, n = 4205), methadone (5.3%, n = 4093), benzodiazepines (3.4%, n = 2603), barbiturates (1.1%, n = 834), propoxyphene (1.0%, n = 749), and phencyclidine (0.1%, n = 44). Based on documented pharmacy history, drugs administered to either the mother or newborn during the birth hospitalization were detected in meconium, providing evidence that drugs can be incorporated into meconium rapidly. Drugs administered directly to the newborn after birth were recovered in meconium as both parent drug and metabolites, providing evidence of neonatal metabolism. Overall, patterns observed in meconium exhibited many similarities to those patterns commonly reported with urine drug testing. Interpretation of meconium drug testing results requires comparison of results with clinical and analytical expectations, including maternal

[Value of positive auto controls in the gel centrifugation method].

PubMed

Eichler, H; Kretschmer, V

1994-01-01

We studied 97 samples of patients being positive in the autocontrol of the indirect antiglobulin test (IAT) in the gel system (DiaMed). In 83.2%, retesting with monospecific anti-IgG serum gave also positive results, due to a specific phenomenon caused, for example, by drug-specific antibodies (AB), warm auto-AB or allo-AB. In contrast, only 52.9% of the samples retested by the standard tube technique with polyspecific antiglobulin serum reacted positive. Only in 6 patients slightly increased cold agglutinins could be detected. None of the investigated patients showed any clinical or laboratory signs of hemolysis except one with pernicious anemia. We conclude that positive results of the autocontrol in the gel IAT should be confirmed by an additional DAT in the tube technique. If this second test shows a negative result, transfusions can take place without any restrictions.

Systems pharmacology augments drug safety surveillance

PubMed Central

Lorberbaum, Tal; Nasir, Mavra; Keiser, Michael J.; Vilar, Santiago; Hripcsak, George; Tatonetti, Nicholas P.

2014-01-01

Small molecule drugs are the foundation of modern medical practice yet their use is limited by the onset of unexpected and severe adverse events (AEs). Regulatory agencies rely on post-marketing surveillance to monitor safety once drugs are approved for clinical use. Despite advances in pharmacovigilance methods that address issues of confounding bias, clinical data of AEs are inherently noisy. Systems pharmacology– the integration of systems biology and chemical genomics – can illuminate drug mechanisms of action. We hypothesize that these data can improve drug safety surveillance by highlighting drugs with a mechanistic connection to the target phenotype (enriching true positives) and filtering those that do not (depleting false positives). We present an algorithm, the modular assembly of drug safety subnetworks (MADSS), to combine systems pharmacology and pharmacovigilance data and significantly improve drug safety monitoring for four clinically relevant adverse drug reactions. PMID:25670520

Patents Associated with High-Cost Drugs in Australia

PubMed Central

Christie, Andrew F.; Dent, Chris; McIntyre, Peter; Wilson, Lachlan; Studdert, David M.

2013-01-01

Australia, like most countries, faces high and rapidly-rising drug costs. There are longstanding concerns about pharmaceutical companies inappropriately extending their monopoly position by “evergreening” blockbuster drugs, through misuse of the patent system. There is, however, very little empirical information about this behaviour. We fill the gap by analysing all of the patents associated with 15 of the costliest drugs in Australia over the last 20 years. Specifically, we search the patent register to identify all the granted patents that cover the active pharmaceutical ingredient of the high-cost drugs. Then, we classify the patents by type, and identify their owners. We find a mean of 49 patents associated with each drug. Three-quarters of these patents are owned by companies other than the drug's originator. Surprisingly, the majority of all patents are owned by companies that do not have a record of developing top-selling drugs. Our findings show that a multitude of players seek monopoly control over innovations to blockbuster drugs. Consequently, attempts to control drug costs by mitigating misuse of the patent system are likely to miss the mark if they focus only on the patenting activities of originators. PMID:23577165

Targeted Therapy Larotrectinib Shows Promise in Early Trials

Cancer.gov

The drug larotrectinib shrank tumors in patients with 13 different cancer types, results from three small clinical trials show. The drug, which targets tumors with TRK fusions, was effective in children and adults, this Cancer Currents post explains.

Evolution of drug resistance in multiple distinct lineages of H5N1 avian influenza.

PubMed

Hill, Andrew W; Guralnick, Robert P; Wilson, Meredith J C; Habib, Farhat; Janies, Daniel

2009-03-01

Some predict that influenza A H5N1 will be the cause of a pandemic among humans. In preparation for such an event, many governments and organizations have stockpiled antiviral drugs such as oseltamivir (Tamiflu). However, it is known that multiple lineages of H5N1 are already resistant to another class of drugs, adamantane derivatives, and a few lineages are resistant to oseltamivir. What is less well understood is the evolutionary history of the mutations that confer drug resistance in the H5N1 population. In order to address this gap, we conducted phylogenetic analyses of 676 genomic sequences of H5N1 and used the resulting hypotheses as a basis for asking 3 molecular evolutionary questions: (1) Have drug-resistant genotypes arisen in distinct lineages of H5N1 through point mutation or through reassortment? (2) Is there evidence for positive selection on the codons that lead to drug resistance? (3) Is there evidence for covariation between positions in the genome that confer resistance to drugs and other positions, unrelated to drug resistance, that may be under selection for other phenotypes? We also examine how drug-resistant lineages proliferate across the landscape by projecting or phylogenetic analysis onto a virtual globe. Our results for H5N1 show that in most cases drug resistance has arisen by independent point mutations rather than reassortment or covariation. Furthermore, we found that some codons that mediate resistance to adamantane derivatives are under positive selection, but did not find positive selection on codons that mediate resistance to oseltamivir. Together, our phylogenetic methods, molecular evolutionary analyses, and geographic visualization provide a framework for analysis of globally distributed genomic data that can be used to monitor the evolution of drug resistance.

Morphology effect of nano-hydroxyapatite as a drug carrier of methotrexate.

PubMed

Sun, Haina; Liu, Shanshan; Zeng, Xiongfeng; Meng, Xianguang; Zhao, Lina; Wan, Yizao; Zuo, Guifu

2017-09-13

In this study, morphology effect of nano-hydroxyapatite as a drug carrier was investigated for the first time. Hydroxyapatite/methotrexate (HAp/MTX) hybrids with different morphologies were successfully prepared in situ using polyethylene glycol (PEG) as a template. SEM, TEM, XRD and FTIR results confirmed that the hybrids of different morphologies (laminated, rod-like and spherical) with similar phase composition and functional groups were obtained by changing the preparation parameters. UV-Vis spectroscopy was used to identify the drug loading capacity and drug release mechanism of the three hybrids with different morphologies. It is concluded that the laminated hybrid exhibits a higher drug loading capacity compared to the other two hybrids, and all the three hybrids showed a sustained slow release which were fitted well by Bhaskar equation. Additionally, the result of in vitro bioassay test confirms that the inhibition efficacy of the three hybrids showed a positive correlation to the drug loading capacity.

HIV infection in females dependent on drugs.

PubMed

Wai, B H; Singh, S; Varma, S L

1996-03-01

One hundred and seventy-one drug-dependent females in a drug rehabilitation centre were studied to estimate the prevalence of HIV infection among them. Twenty-four (14%) were positive on the Western Blot test. The presence of HIV infection was significantly correlated with syphilis (p < 0.03) and age (p < 0.001); 83% of those who were HIV positive were intravenous drug users. The need for harm reduction programmes to prevent spread of HIV infection among injecting drug users is stressed.

Biosimilar drugs in Mexico: position of the Mexican College of Rheumatology, 2012.

PubMed

Espinosa Morales, Rolando; Díaz Borjón, Alejandro; Barile Fabris, Leonor Adriana; Esquivel Valerio, Jorge Antonio; Medrano Ramírez, Gabriel; Arce Salinas, César Alejandro; Barreira Mercado, Eduardo Rubén; Cardiel Ríos, Mario Humberto; Díaz Jouanen, Efraín; Flores Murrieta, Francisco Javier; Fraga Mouret, Antonio; Garza Elizondo, Mario Alberto; Luján Estrada, Miguel; Muñoz Barradas, Francisco José; Talavera Piña, Juan Osvaldo; Vera Lastra, Olga Lidia

2013-01-01

Biotechnological drugs (BTDs) are complex molecules whose manufacturing process precludes the ability to identically reproduce the structure of the original product, and therefore there cannot be an absolute equivalence between the original (innovative) medication and its biosimilar counterpart. BTDs have been proven useful in the treatment of several rheumatic diseases, however their high cost has prevented their use in many patients. Several BTD patents have expired or are close to expire, triggering the development of structurally similar drugs with efficacy and safety profiles comparable to the innovative compound; however, these must be evaluated through evidence based medicine. The Mexican General Health Law contemplates the registry of these biosimilar drugs for their use in our country. This document is a forethought from members of the Mexican College of Rheumatology, pharmacologists, and epidemiologists, in accordance with Mexican health authorities regarding the necessary scientific evidence required to evaluate the efficacy and safety of biosimilar drugs before and after their arrival to the Mexican market. Copyright © 2012 Elsevier España, S.L. All rights reserved.

Investigating the correlation between wastewater analysis and roadside drug testing in South Australia.

PubMed

Bade, Richard; Tscharke, Benjamin J; Longo, Marie; Cooke, Richard; White, Jason M; Gerber, Cobus

2018-06-01

The societal impact of drug use is well known. An example is when drug-intoxicated drivers increase the burden on policing and healthcare services. This work presents the correlation of wastewater analysis (using UHPLC-MS/MS) and positive roadside drug testing results for methamphetamine, 3,4-methylenedioxymethamphetamine (MDMA) and cannabis from December 2011-December 2016 in South Australia. Methamphetamine and MDMA showed similar trends between the data sources with matching increases and decreases, respectively. Cannabis was relatively steady based on wastewater analysis, but the roadside drug testing data started to diverge in the final part of the measurement period. The ability to triangulate data as shown here validates both wastewater analysis and roadside drug testing. This suggests that changes in overall population drug use revealed by WWA is consistent and proportional with changes in drug-driving behaviours. The results show that, at higher levels of drug use as measured by wastewater analysis, there is an increase in drug driving in the community and therefore more strain on health services and police. Copyright © 2018 Elsevier B.V. All rights reserved.

Pseudoephedrine may cause "pigmenting" fixed drug eruption.

PubMed

Ozkaya, Esen; Elinç-Aslan, Meryem Sevinç

2011-05-01

Fixed drug eruption (FDE) is a distinctive drug eruption characterized by recurrent well-defined lesions in the same location each time the responsible drug is taken. Two different clinical forms have been described: the common classic pigmenting form and the rare nonpigmenting form. Nonpigmenting FDE is mainly characterized by symmetrical large erythematous plaques and the dermal histopathologic reaction pattern. Pseudoephedrine is known as the major inducer of nonpigmenting FDE. Pigmenting FDE from pseudoephedrine has not been reported previously. Here, the first case of pseudoephedrine-induced pigmenting FDE is reported, showing the characteristic features of classic pigmenting FDE such as asymmetry, normal-sized lesions, and the epidermodermal histopathologic reaction pattern. Moreover, a positive occlusive patch-test reaction to pseudoephedrine could be demonstrated on postlesional FDE skin for the first time.

21 CFR 890.3110 - Electric positioning chair.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Electric positioning chair. 890.3110 Section 890.3110 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES PHYSICAL MEDICINE DEVICES Physical Medicine Prosthetic Devices § 890.3110 Electric...

21 CFR 890.3110 - Electric positioning chair.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Electric positioning chair. 890.3110 Section 890.3110 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES PHYSICAL MEDICINE DEVICES Physical Medicine Prosthetic Devices § 890.3110 Electric...

21 CFR 890.3110 - Electric positioning chair.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Electric positioning chair. 890.3110 Section 890.3110 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES PHYSICAL MEDICINE DEVICES Physical Medicine Prosthetic Devices § 890.3110 Electric...

21 CFR 890.3110 - Electric positioning chair.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Electric positioning chair. 890.3110 Section 890.3110 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES PHYSICAL MEDICINE DEVICES Physical Medicine Prosthetic Devices § 890.3110 Electric...

21 CFR 890.3110 - Electric positioning chair.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Electric positioning chair. 890.3110 Section 890.3110 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES PHYSICAL MEDICINE DEVICES Physical Medicine Prosthetic Devices § 890.3110 Electric...

Homelessness and drug misuse in developing countries: A mathematical approach

NASA Astrophysics Data System (ADS)

Bhunu, C. P.

2014-06-01

Homelessness and drug-misuse are known to exist like siamese twins. We present a model to capture the dynamics in the growth in the number of homeless (street kids and street adults) and drug misusers. The reproduction numbers of the model are determined and analyzed. Results from this study suggests that adult peer pressure plays a more significant role in the growth of drug-misuse and the number of street kids. This result suggests that in resource constrained settings intervention strategies should be tailor made to target adults whose behaviour influence others to misuse drugs and abuse children. Furthermore, numerical simulations show that homelessness and drug-misuse positively enhances, the growth of each other. Thus, to effectively control these two social problems require strategies targeting both of them.

The Effects of Opioid Substitution Treatment and Highly Active Antiretroviral Therapy on the Cause-Specific Risk of Mortality Among HIV-Positive People Who Inject Drugs.

PubMed

Nosyk, Bohdan; Min, Jeong E; Evans, Elizabeth; Li, Libo; Liu, Lei; Lima, Viviane D; Wood, Evan; Montaner, Julio S G

2015-10-01

Prior studies indicated opioid substitution treatment (OST) reduces mortality risk and improves the odds of accessing highly active antiretroviral therapy (HAART); however, the relative effects of these treatments for human immunodeficiency virus (HIV)-positive people who inject drugs (PWID) are unclear. We determine the independent and joint effects of OST and HAART on mortality, by cause, within a population of HIV-positive PWID initiating HAART. Using a linked population-level database for British Columbia, Canada, we used time-to-event analytic methods, including competing risks models, proportional hazards models with time-varying covariates, and marginal structural models, to identify the independent and joint effects of OST and HAART on all-cause as well as drug- and HIV-related mortality, controlling for covariates. Among 1727 HIV-positive PWID, 493 (28.5%) died during a median 5.1 years (interquartile range, 2.1-9.1) of follow-up: 18.7% due to drug-related causes, 55.8% due to HIV-related causes, and 25.6% due to other causes. Standardized mortality ratios were 12.2 (95% confidence interval [CI], 9.8, 15.0) during OST and 30.0 (27.1, 33.1) during periods out of OST. Both OST (adjusted hazard, 0.34; 95% CI, .23, .49) and HAART (0.39 [0.31, 0.48]) decreased the hazard of all-cause mortality; however, individuals were at lowest risk of death when these medications were used jointly (0.16 [0.10, 0.26]). Both OST and HAART independently protected against HIV-related death, drug-related death and death due to other causes. While both OST and HAART are life-saving treatments, joint administration is urgently needed to protect against both drug- and HIV-related mortality. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Reducing the Risk of Drug Involvement among Early Adolescents: An Evaluation of Drug Abuse Resistance Education (DARE).

ERIC Educational Resources Information Center

Harmon, Michele Alicia

1993-01-01

DARE's effectiveness in Charleston County (South Carolina) was studied by comparing 341 DARE to 367 non-DARE fifth-grade students. DARE teaches students to recognize and resist social pressures to use drugs. DARE has positive impacts on anti-substance abuse attitudes, assertiveness, positive peer association, association with drug-using peers, and…

Audit of intrathecal drug delivery for patients with difficult-to-control cancer pain shows a sustained reduction in pain severity scores over a 6-month period.

PubMed

Mitchell, Alison; McGhie, Jonathan; Owen, Margaret; McGinn, Gordon

2015-06-01

Intrathecal drug delivery is known to be effective in alleviating cancer pain in patients for whom the conventional World Health Organization approach has proved insufficient. A multidisciplinary interventional cancer pain service was established in the West of Scotland in 2008 with the aim of providing a safe and effective intrathecal drug delivery service for patients with difficult-to-control cancer pain. The aim of the intrathecal drug delivery service is to improve pain scores as evaluated by pain scores before and after insertion of an intrathecal drug delivery device. Pain is monitored before and after intrathecal drug delivery implantation using the Brief Pain Inventory. Following implantation, pumps are refilled fortnightly and repeat Brief Pain Inventory assessments are undertaken. This prospective case series analyses change in Brief Pain Inventory domains for patients who had an intrathecal drug delivery implanted using a paired sample t-test. Data are presented from 2008-2013 for 22 patients receiving an intrathecal drug delivery system who experienced an immediate improvement in their pain that was both clinically and statistically significant. One week after insertion, the average pain score on the Brief Pain Inventory fell from 6.8 (pre-intrathecal drug delivery) to 3.0 (post-intrathecal drug delivery). Improvement in pain scores was sustained over a 6-month period. Evaluation of results of this case series shows that with the appropriate use of intrathecal drug delivery systems, patients with difficult-to-control cancer pain can benefit from effective pain relief for many months. © The Author(s) 2015.

Compulsory drug detention and injection drug use cessation and relapse in Bangkok, Thailand.

PubMed

Fairbairn, Nadia; Hayashi, Kanna; Ti, Lianping; Kaplan, Karyn; Suwannawong, Paisan; Wood, Evan; Kerr, Thomas

2015-01-01

Strategies to promote the reduction and cessation of injection drug use are central to human immunodeficiency virus prevention and treatment efforts globally. Though drug use cessation is a major focus of drug policy in Thailand, little is known about factors associated with injection cessation and relapse in this setting. A cross-sectional study was conducted between July and October 2011 of a community-recruited sample of people who inject drugs in Bangkok, Thailand. Using multivariate logistic regression, we examined the prevalence and correlates of injection drug use cessation with subsequent relapse. Among 422 participants, 209 (49.5%) reported a period of injection drug use cessation of at least one year. In multivariate analyses, incarceration (adjusted odds ratio [AOR] 13.07), voluntary drug treatment (AOR 2.75), midazolam injection (AOR 2.48) and number of years since first injection (AOR 1.07) were positively associated with injection cessation of duration greater than a year (all P < 0.05). Exposure to compulsory drug detention was positively associated (AOR 2.61) and methadone treatment was negatively associated (AOR 0.38) with short-term cessation only. Injection drug use cessation was most often due to incarceration (74%), and relapse was associated with release from prison (66%). Half of the study participants had previously stopped injecting drugs for more than a year, and this was strongly associated with incarceration. Compulsory drug detention was associated with short-term cessation and relapse. A range of evidence-based strategies should be made available to facilitate sustained cessation of injection drug use in Thailand. © 2014 Australasian Professional Society on Alcohol and other Drugs.

Glutamatergic transmission in drug reward: implications for drug addiction.

PubMed

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, there has been an increasing focus on the role of the excitatory neurotransmitter glutamate in drug addiction. In this review, pharmacological and genetic evidence supporting the role of glutamate in mediating the rewarding effects of the above described drugs of abuse will be discussed. Further, the review will discuss the role of glutamate transmission in two complex heterogeneous brain regions, namely the nucleus accumbens (NAcc) and the ventral tegmental area (VTA), which mediate the rewarding effects of drugs of abuse. In addition, several medications approved by the Food and Drug Administration that act by blocking glutamate transmission will be discussed in the context of drug reward. Finally, this review will discuss future studies needed to address currently unanswered gaps in knowledge, which will further elucidate the role of glutamate in the rewarding effects of drugs of abuse.

Cost-offsets of prescription drug expenditures: data analysis via a copula-based bivariate dynamic hurdle model.

PubMed

Deb, Partha; Trivedi, Pravin K; Zimmer, David M

2014-10-01

In this paper, we estimate a copula-based bivariate dynamic hurdle model of prescription drug and nondrug expenditures to test the cost-offset hypothesis, which posits that increased expenditures on prescription drugs are offset by reductions in other nondrug expenditures. We apply the proposed methodology to data from the Medical Expenditure Panel Survey, which have the following features: (i) the observed bivariate outcomes are a mixture of zeros and continuously measured positives; (ii) both the zero and positive outcomes show state dependence and inter-temporal interdependence; and (iii) the zeros and the positives display contemporaneous association. The point mass at zero is accommodated using a hurdle or a two-part approach. The copula-based approach to generating joint distributions is appealing because the contemporaneous association involves asymmetric dependence. The paper studies samples categorized by four health conditions: arthritis, diabetes, heart disease, and mental illness. There is evidence of greater than dollar-for-dollar cost-offsets of expenditures on prescribed drugs for relatively low levels of spending on drugs and less than dollar-for-dollar cost-offsets at higher levels of drug expenditures. Copyright © 2013 John Wiley & Sons, Ltd.

Assessment of drug-drug interaction potential between ceritinib and proton pump inhibitors in healthy subjects and in patients with ALK-positive non-small cell lung cancer.

PubMed

Lau, Yvonne Y; Gu, Wen; Lin, Tiffany; Viraswami-Appanna, Kalyanee; Cai, Can; Scott, Jeffrey W; Shi, Michael

2017-06-01

The impact of proton pump inhibitors (PPIs) on the pharmacokinetics (PK) and efficacy of ceritinib was evaluated. A healthy subject drug-drug interaction (DDI) study was conducted to assess the effect of esomeprazole on the PK of a single 750 mg dose of ceritinib. To further investigate the impact of PPIs on the PK and efficacy of ceritinib in ALK-positive cancer patients, two subgroup analyses were performed. Analysis 1 evaluated ceritinib steady-state trough concentration (C trough,ss ) and overall response rate (ORR) by concomitant use of PPIs in patients from the ASCEND-1, -2, and -3 studies; analysis 2 evaluated ceritinib single-dose and steady-state AUC 0-24h and C max by concomitant PPI use in patients from ASCEND-1 using a definition of PPI usage similar to that used in the healthy subject study. In the healthy subject study, co-administration of a single 750 mg dose of ceritinib with esomeprazole 40 mg for 6 days decreased ceritinib AUC 0-∞ by 76% and C max by 79%. However, based on subgroup analysis 1, patients had similar C trough,ss and ORR regardless of concomitant PPI usage. Based on analysis 2, co-administration of a single 750 mg ceritinib dose with PPIs for 6 days in patients suggested less effect on ceritinib exposure than that observed in healthy subjects as AUC 0-24h decreased by 30% and C max decreased by 25%. No clinically meaningful effect on steady-state exposure was observed after daily dosing. Long-term administration of ceritinib with PPIs does not adversely affect the PK and efficacy of ceritinib in ALK-positive cancer patients.

Prevalence of multi-drug resistant organisms in stool of paediatric patients with acute leukaemia and correlation with blood culture positivity: A single institution experience.

PubMed

Shankar, Krupa; Radhakrishnan, Venkatraman; Vijayakumar, Varalakskmi; Ramamoorthy, Jaikumar; Ganesan, Prasanth; Dhanushkodi, Manikandan; Ganesan, T S; Sagar, T G

2018-01-01

Multi-drug resistant (MDR) bacteria are associated with increased morbidity and mortality in children with acute leukaemia. The present study was conducted to assess the prevalence of MDR bacteria in stool cultures of patients with acute leukaemia at presentation to the hospital. The results were then correlated with blood cultures when patients developed septicaemia. The study involved analysis of case records of patients with newly diagnosed acute leukaemia less than 18 years of age treated at our centre from January 2015 to December 2015. Stool cultures were sent within 72 hr of hospital admission and blood cultures were sent when clinically indicated. MDR was defined as resistance to at least one antibiotic in three or more following antimicrobial groups: cephalosporins, β-lactam/β-lactamase inhibitor, carbapenems, fluoroquinolones and aminoglycosides. The analysis included 85 patients with acute leukaemia, among whom 48 of 85 (56%) patients had positive stool cultures and 42 of 85 (50%) patients were positive for MDR bacteria. Blood cultures were positive in 13 of 48 patients (27%, seven MDR and six non-MDR) with positive stool cultures and three of 37 patients (8%, one MDR and two non-MDR) with negative stool cultures (P = 0.01). The concordance between stool and blood culture for similar organism was 61%. There were seven deaths in 48 stool culture positive patients and two deaths in 37 stool culture negative patients. This study shows the high prevalence of MDR bacteria in newly diagnosed children with acute leukaemia. Colonisation with MDR bacteria in stools is associated with increased positivity of blood cultures and mortality. © 2017 Wiley Periodicals, Inc.

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

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

Nadanaciva, Sashi; Aleo, Michael D.; Strock, Christopher J.

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)more » 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.« less

Alcohol and drug involvement in motorcycle driver injuries in the city of Sao Paulo, Brazil: Analysis of crash culpability and other associated factors.

PubMed

de Carvalho, Heraclito Barbosa; Andreuccetti, Gabriel; Rezende, Marcelo Rosa; Bernini, Celso; Silva, Jorge Santos; Leyton, Vilma; D'Andréa Greve, Julia Maria

2016-05-01

Earlier studies have already identified that a greater proportion of injured drivers are under the effects of illicit drugs than alcohol in Brazil, but the crash risk attributable to each substance is still unknown. Injured motorcycle drivers who were involved in traffic accidents in the West Zone of the city of Sao Paulo were recruited for a cross-sectional study based on crash culpability analysis. Alcohol and drug positivity among drivers was evaluated according to their responsibility for the crash. Culpability ratios were generated based on the proportion of drivers who were deemed culpable in relation to those considered not culpable according to the use of drugs and alcohol. Of the 273 drivers recruited, 10.6% tested positive for alcohol. Among those who were also tested for drugs (n=232), 20.3% had consumed either alcohol and/or other drugs, 15.5% of whom were positive only for drugs other than alcohol, specifically cannabis and cocaine. Drivers who tested positive for alcohol were significantly less likely to possess a valid driver's license and to report driving professionally, whereas those who had consumed only drugs were more likely to drive professionally. The culpability ratio estimated for alcohol-positive drivers was three times higher than that for alcohol-free drivers, showing a superior ratio than drivers who had consumed only drugs other than alcohol, who presented a 1.7 times higher culpability ratio than drug-free drivers. Substance use was overrepresented among culpable motorcycle drivers, with alcohol showing a greater contribution to crash culpability than other drugs. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

The regional drug information service: a factor in health care?

PubMed Central

Leach, F N

1978-01-01

Most regional health authorities throughout the United Kingdom have established drug information units to provide health service staff with a wide range of information about drugs and drug use. The units, which are staffed by drug information pharmacists, provide their service mainly by answering inquiries, although some disseminate information more positively through lectures and bulletins. An analysis of inquiries received by regional information units during 1976 showed that most were submitted by hospital doctors or pharmacists; comparatively few were received from general practitioners. Topics of inquiry included adverse effects of drugs, source of supply and identification, current treatment, dosage, route, precautions, and pharmaceutical problems such as stability or formulation of drug preparations. A more detailed analysis of the inquiries received by the North-western Regional Drug Information Service at Manchester over three years showed that the number of inquiries gradually increased and that more were received from general practitioners after a programme of lectures had been introduced to tell them about the service. The North-western service also received more requests from hospital pharmacists than other units, though many originated from clinicians. The regional drug information units consulted widely with clinical and other specialists in answering questions, but about a quarter of all inquiries were pharmaceutical, relating to stability and incompatibility. A multidisciplinary approach therefore seems necessary to provide a comprehensive and advisory drug information service. PMID:630339

High HIV Prevalence, Suboptimal HIV Testing, and Low Knowledge of HIV-Positive Serostatus Among Injection Drug Users in St. Petersburg, Russia

PubMed Central

Toussova, Olga V.; Verevochkin, Sergei V.; Barbour, Russell; Heimer, Robert; Kozlov, Andrei P.

2011-01-01

The purpose of this analysis was to estimate human immunodeficiency virus (HIV) prevalence and testing patterns among injection drug users (IDUs) in St. Petersburg, Russia. HIV prevalence among 387 IDUs in the sample was 50%. Correlates of HIV-positive serostatus included unemployment, recent unsafe injections, and history/current sexually transmitted infection. Seventy-six percent had been HIV tested, but only 22% of those who did not report HIV-positive serostatus had been tested in the past 12 months and received their test result. Correlates of this measure included recent doctor visit and having been in prison or jail among men. Among the 193 HIV-infected participants, 36% were aware of their HIV-positive serostatus. HIV prevalence is high and continuing to increase in this population. Adequate coverage of HIV testing has not been achieved, resulting in poor knowledge of positive serostatus. Efforts are needed to better understand motivating and deterring factors for HIV testing in this setting. PMID:18843531

Amoxicillin rash in patients with infectious mononucleosis: evidence of true drug sensitization.

PubMed

Ónodi-Nagy, Katinka; Kinyó, Ágnes; Meszes, Angéla; Garaczi, Edina; Kemény, Lajos; Bata-Csörgő, Zsuzsanna

2015-01-01

It hasn't been clearly understood yet whether sensitization to antibiotics, the virus itself or transient loss of drug tolerance due to the virus, is responsible for the development of maculopapular exanthems following amoxicillin intake in patients with infectious mononucleosis. We aimed to examine whether sensitization to penicillin developed among patients with skin rash following amoxicillin treatment within infectious mononucleosis. Ten patients were investigated for drug sensitization by lymphocyte transformation test and six patients were further tested by prick-, intradermal and patch tests employing the penicillin's main antigens. Lymphocyte transformation test showed negative results with amoxicillin, while one patient had positive reaction to cefixime. Six patients with suspected sensitization to amoxicillin were then investigated by in vivo tests. Prick tests were negative in all six patients, but the intradermal tests showed positive reactions in four patients. Our data demonstrate that in vitro testing is not sensitive enough in determining drug sensitization to penicillin. In vivo tests should be performed to detect sensitization and indeed with skin tests our results confirmed that sensitization to aminopenicillin may develop within infectious mononucleosis.

The effect of banning MDPV on the incidence of MDPV-positive findings among users of illegal drugs and on court decisions in traffic cases in Finland.

PubMed

Kriikku, Pirkko; Rintatalo, Janne; Pihlainen, Katja; Hurme, Jukka; Ojanperä, Ilkka

2015-07-01

In this study, we sought to determine what impact the banning of 3, 4- methylenedioxypyrovalerone (MDPV) had on the incidence of MDPV-positive findings and on user profiles in driving under the influence of drugs (DUID) and postmortem (PM) investigations in Finland. All MDPV-positive cases and a selection of corresponding court cases between 2009 and 2012 were examined. The median serum concentration of MDPV in DUID cases was 0.030 mg/L and in PM blood 0.12 mg/L. The number of MDPV-positive cases decreased both in DUID and PM investigations after the drug was banned. The decrease in the mean monthly numbers of MDPV-positive DUID cases was 51.1%. In court cases, MDPV was rarely mentioned until banned and frequently mentioned thereafter. Of the convicted, 37% were without a fixed abode, 98% had other charges besides that of DUID, and 13% appeared in the study material more than once. In MDPV-positive PM cases, the proportion of suicides was very high (24%). Research on new psychoactive substances is required not only to support banning decisions but more importantly to be able to provide a scientific assessment of the risks of these new substances to the public and potential users.

Drug resistance of Mycobacterium tuberculosis in Malawi: a cross-sectional survey

PubMed Central

Abouyannis, Michael; Dacombe, Russell; Dambe, Isaias; Mpunga, James; Faragher, Brian; Gausi, Francis; Ndhlovu, Henry; Kachiza, Chifundo; Suarez, Pedro; Mundy, Catherine; Banda, Hastings T; Nyasulu, Ishmael

2014-01-01

Abstract Objective To document the prevalence of multidrug resistance among people newly diagnosed with – and those retreated for – tuberculosis in Malawi. Methods We conducted a nationally representative survey of people with sputum-smear-positive tuberculosis between 2010 and 2011. For all consenting participants, we collected demographic and clinical data, two sputum samples and tested for human immunodeficiency virus (HIV).The samples underwent resistance testing at the Central Reference Laboratory in Lilongwe, Malawi. All Mycobacterium tuberculosis isolates found to be multidrug-resistant were retested for resistance to first-line drugs – and tested for resistance to second-line drugs – at a Supranational Tuberculosis Reference Laboratory in South Africa. Findings Overall, M. tuberculosis was isolated from 1777 (83.8%) of the 2120 smear-positive tuberculosis patients. Multidrug resistance was identified in five (0.4%) of 1196 isolates from new cases and 28 (4.8%) of 581 isolates from people undergoing retreatment. Of the 31 isolates from retreatment cases who had previously failed treatment, nine (29.0%) showed multidrug resistance. Although resistance to second-line drugs was found, no cases of extensive drug-resistant tuberculosis were detected. HIV testing of people from whom M. tuberculosis isolates were obtained showed that 577 (48.2%) of people newly diagnosed and 386 (66.4%) of people undergoing retreatment were positive. Conclusion The prevalence of multidrug resistance among people with smear-positive tuberculosis was low for sub-Saharan Africa – probably reflecting the strength of Malawi’s tuberculosis control programme. The relatively high prevalence of such resistance observed among those with previous treatment failure may highlight a need for a change in the national policy for retreating this subgroup of people with tuberculosis. PMID:25378741

Drug repositioning for enzyme modulator based on human metabolite-likeness.

PubMed

Lee, Yoon Hyeok; Choi, Hojae; Park, Seongyong; Lee, Boah; Yi, Gwan-Su

2017-05-31

Recently, the metabolite-likeness of the drug space has emerged and has opened a new possibility for exploring human metabolite-like candidates in drug discovery. However, the applicability of metabolite-likeness in drug discovery has been largely unexplored. Moreover, there are no reports on its applications for the repositioning of drugs to possible enzyme modulators, although enzyme-drug relations could be directly inferred from the similarity relationships between enzyme's metabolites and drugs. We constructed a drug-metabolite structural similarity matrix, which contains 1,861 FDA-approved drugs and 1,110 human intermediary metabolites scored with the Tanimoto similarity. To verify the metabolite-likeness measure for drug repositioning, we analyzed 17 known antimetabolite drugs that resemble the innate metabolites of their eleven target enzymes as the gold standard positives. Highly scored drugs were selected as possible modulators of enzymes for their corresponding metabolites. Then, we assessed the performance of metabolite-likeness with a receiver operating characteristic analysis and compared it with other drug-target prediction methods. We set the similarity threshold for drug repositioning candidates of new enzyme modulators based on maximization of the Youden's index. We also carried out literature surveys for supporting the drug repositioning results based on the metabolite-likeness. In this paper, we applied metabolite-likeness to repurpose FDA-approved drugs to disease-associated enzyme modulators that resemble human innate metabolites. All antimetabolite drugs were mapped with their known 11 target enzymes with statistically significant similarity values to the corresponding metabolites. The comparison with other drug-target prediction methods showed the higher performance of metabolite-likeness for predicting enzyme modulators. After that, the drugs scored higher than similarity score of 0.654 were selected as possible modulators of enzymes for

Ribonucleotide reductase as a drug target against drug resistance Mycobacterium leprae: A molecular docking study.

PubMed

Mohanty, Partha Sarathi; Bansal, Avi Kumar; Naaz, Farah; Gupta, Umesh Datta; Dwivedi, Vivek Dhar; Yadava, Umesh

2018-06-01

Leprosy is a chronic infection of skin and nerve caused by Mycobacterium leprae. The treatment is based on standard multi drug therapy consisting of dapsone, rifampicin and clofazamine. The use of rifampicin alone or with dapsone led to the emergence of rifampicin-resistant Mycobacterium leprae strains. The emergence of drug-resistant leprosy put a hurdle in the leprosy eradication programme. The present study aimed to predict the molecular model of ribonucleotide reductase (RNR), the enzyme responsible for biosynthesis of nucleotides, to screen new drugs for treatment of drug-resistant leprosy. The study was conducted by retrieving RNR of M. leprae from GenBank. A molecular 3D model of M. leprae was predicted using homology modelling and validated. A total of 325 characters were included in the analysis. The predicted 3D model of RNR showed that the ϕ and φ angles of 251 (96.9%) residues were positioned in the most favoured regions. It was also conferred that 18 α-helices, 6 β turns, 2 γ turns and 48 helix-helix interactions contributed to the predicted 3D structure. Virtual screening of Food and Drug Administration approved drug molecules recovered 1829 drugs of which three molecules, viz., lincomycin, novobiocin and telithromycin, were taken for the docking study. It was observed that the selected drug molecules had a strong affinity towards the modelled protein RNR. This was evident from the binding energy of the drug molecules towards the modelled protein RNR (-6.10, -6.25 and -7.10). Three FDA-approved drugs, viz., lincomycin, novobiocin and telithromycin, could be taken for further clinical studies to find their efficacy against drug resistant leprosy. Copyright © 2018 Elsevier B.V. All rights reserved.

Illicit drugs in Emergency Department patients injured in road traffic accidents.

PubMed

Papa, Pietro; Rocchi, Loretta; Rolandi, Laura Maria; Di Tuccio, Marcello; Biffi, Marco; Valli, Antonella

2017-01-01

Urine and blood samples from 1730 drivers involved in road accidents (July 2012 - December 2015) were analyzed for the evaluation of driving under influence of drug of abuse according to the Lombardia Region guideline. The 22.5% (95% CI 20.5 to 24.5) of urine screenings tested positive for at least one class of drugs. 10.6% (95% CI 9.2 to 12.1) of the 1730 drivers were under the influence of drug, being blood concentration above the cut-off limit for at least one active substance; the proportion of illicit drugs in blood was cocaine 5.7 % (95% CI 4.7 to 6.9), cannabinoids 3.7 % (95% CI 2.9 to 4.7), opiates 1.4% (95% CI 0.9 to 2.1), methadone 1.4% (95% CI 0.9 to 2.1), amphetamines 0.2% (95% CI 0.04 to 0.5). Trend in proportion showed similar percentage (about 5%) of cocaine and cannabinoids consumption in the last two years. Poly-drug of abuse consumption emerged in the 10.4% (95% CI 6.4 to 15.7) of the positive blood and alcohol was above the legal limit in 47% (95% CI 39.6 to 54.5) of the subjects driving under the influence of drugs.

Molecularly precise dendrimer-drug conjugates with tunable drug release for cancer therapy.

PubMed

Zhou, Zhuxian; Ma, Xinpeng; Murphy, Caitlin J; Jin, Erlei; Sun, Qihang; Shen, Youqing; Van Kirk, Edward A; Murdoch, William J

2014-10-06

The structural preciseness of dendrimers makes them perfect drug delivery carriers, particularly in the form of dendrimer-drug conjugates. Current dendrimer-drug conjugates are synthesized by anchoring drug and functional moieties onto the dendrimer peripheral surface. However, functional groups exhibiting the same reactivity make it impossible to precisely control the number and the position of the functional groups and drug molecules anchored to the dendrimer surface. This structural heterogeneity causes variable pharmacokinetics, preventing such conjugates to be translational. Furthermore, the highly hydrophobic drug molecules anchored on the dendrimer periphery can interact with blood components and alter the pharmacokinetic behavior. To address these problems, we herein report molecularly precise dendrimer-drug conjugates with drug moieties buried inside the dendrimers. Surprisingly, the drug release rates of these conjugates were tailorable by the dendrimer generation, surface chemistry, and acidity. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Psychophysiological prediction of choice: relevance to insight and drug addiction

PubMed Central

Moeller, Scott J.; Hajcak, Greg; Parvaz, Muhammad A.; Dunning, Jonathan P.; Volkow, Nora D.

2012-01-01

An important goal of addiction research and treatment is to predict behavioural responses to drug-related stimuli. This goal is especially important for patients with impaired insight, which can interfere with therapeutic interventions and potentially invalidate self-report questionnaires. This research tested (i) whether event-related potentials, specifically the late positive potential, predict choice to view cocaine images in cocaine addiction; and (ii) whether such behaviour prediction differs by insight (operationalized in this study as self-awareness of image choice). Fifty-nine cocaine abusers and 32 healthy controls provided data for the following laboratory components that were completed in a fixed-sequence (to establish prediction): (i) event-related potential recordings while passively viewing pleasant, unpleasant, neutral and cocaine images, during which early (400–1000 ms) and late (1000–2000 ms) window late positive potentials were collected; (ii) self-reported arousal ratings for each picture; and (iii) two previously validated tasks: one to assess choice for viewing these same images, and the other to group cocaine abusers by insight. Results showed that pleasant-related late positive potentials and arousal ratings predicted pleasant choice (the choice to view pleasant pictures) in all subjects, validating the method. In the cocaine abusers, the predictive ability of the late positive potentials and arousal ratings depended on insight. Cocaine-related late positive potentials better predicted cocaine image choice in cocaine abusers with impaired insight. Another emotion-relevant event-related potential component (the early posterior negativity) did not show these results, indicating specificity of the late positive potential. In contrast, arousal ratings better predicted respective cocaine image choice (and actual cocaine use severity) in cocaine abusers with intact insight. Taken together, the late positive potential could serve as a biomarker

Supramolecular "Trojan Horse" for Nuclear Delivery of Dual Anticancer Drugs.

PubMed

Cai, Yanbin; Shen, Haosheng; Zhan, Jie; Lin, Mingliang; Dai, Liuhan; Ren, Chunhua; Shi, Yang; Liu, Jianfeng; Gao, Jie; Yang, Zhimou

2017-03-01

Nuclear delivery and accumulation are very important for many anticancer drugs that interact with DNA or its associated enzymes in the nucleus. However, it is very difficult for neutrally and negatively charged anticancer drugs such as 10-hydroxycamptothecine (HCPT). Here we report a simple strategy to construct supramolecular nanomedicines for nuclear delivery of dual synergistic anticancer drugs. Our strategy utilizes the coassembly of a negatively charged HCPT-peptide amphiphile and the positively charged cisplatin. The resulting nanomaterials behave as the "Trojan Horse" that transported soldiers (anticancer drugs) across the walls of the castle (cell and nucleus membranes). Therefore, they show improved inhibition capacity to cancer cells including the drug resistant cancer cell and promote the synergistic tumor suppression property in vivo. We envision that our strategy of constructing nanomaterials by metal chelation would offer new opportunities to develop nanomedicines for combination chemotherapy.

Sexual violence from police and HIV risk behaviours among HIV-positive women who inject drugs in St. Petersburg, Russia – a mixed methods study

PubMed Central

Lunze, Karsten; Raj, Anita; Cheng, Debbie M; Quinn, Emily K; Lunze, Fatima I; Liebschutz, Jane M; Bridden, Carly; Walley, Alexander Y; Blokhina, Elena; Krupitsky, Evgeny; Samet, Jeffrey H

2016-01-01

Introduction Police violence against people who inject drugs (PWID) is common in Russia and associated with HIV risk behaviours. Sexual violence from police against women who use drugs has been reported anecdotally in Russia. This mixed-methods study aimed to evaluate sexual violence from police against women who inject drugs via quantitative assessment of its prevalence and HIV risk correlates, and through qualitative interviews with police, substance users and their providers in St. Petersburg, Russia. Methods Cross-sectional analyses with HIV-positive women who inject drugs (N=228) assessed the associations between sexual violence from police (i.e. having been forced to have sex with a police officer) and the following behaviours: current drug use, needle sharing and injection frequency using multiple regression models. We also conducted in-depth interviews with 23 key informants, including PWID, police, civil society organization workers, and other stakeholders, to explore qualitatively the phenomenon of sexual violence from police in Russia and strategies to address it. We analyzed qualitative data using content analysis. Results Approximately one in four women in our quantitative study (24.1%; 95% CI, 18.6%, 29.7%) reported sexual violence perpetrated by police. Affected women reported more transactional sex for drugs or money than those who were not; however, the majority of those reporting sexual violence from police were not involved in these forms of transactional sex. Sexual violence from police was not significantly associated with current drug use or needle sharing but with more frequent drug injections (adjusted incidence rate ratio 1.43, 95% CI 1.04, 1.95). Qualitative data suggested that sexual violence and coercion by police appear to be entrenched as a norm and are perceived insurmountable because of the seemingly absolute power of police. They systematically add to the risk environment of women who use drugs in Russia. Conclusions Sexual violence

[Clinical evaluation of triage as drug-of-abuse test kit].

PubMed

Yoshioka, Toshiharu; Kohriyama, Kazuaki; Kondo, Rumiko; Goto, Kyoko; Yashiki, Mikio

2003-01-01

There are about 60,000 chemical substances which may cause poisoning. Identifying the cause substances is, therefore, very important for patient at emergency department. Triage is an immunoassay kit for the qualitative test for the metabolites of 8 major abuse drugs in urine. We assessed the usefullness of Triage on two patient groups. The first Group consists of the patients considered having not taken substances at initial diagnosis; the second Group consists of the patients considered having taken substances. The result are as follows. 1) The rate of Triage positive patients in the first Group were: attempt-suicide 23%, coma 24%, shock 10%, trauma 7%, respectively. Except for the habitually used medicine, narcotic and stimulant drugs were detected. In the first Group, negative result of Triage was effective in diagnosing the patients as not poisoned, excluding the possitivity of 8 major drugs usage. 2) The rate of Triage positive patients in the second Group were very high: attempt-suicide 77%, coma 51%, shock 57%, trauma 30%, respectively, showing mostly any of 8 major drugs were the cause of poisoning. In the second Group, positive result of Triage was effective in diagnosing the patient as poisoning or as coexisting poisoning with other diseases. 3) The specificity of Triage diagnosis in the first Group was 80% (113/142). The specificity and the sensitivity in the second Group were 64% (50/78) and 97% (74/76), respectively. These results means that Triage is very useful for diagnosis on 8 major drugs poisoning. 4) Triage is efficient for identifying the cause substances in drug poisoning and, therefore, can save medical expense. Triage is a very useful test kit at emergency department.

Frequency and structure of stimulant designer drug consumption among suspected drug users in Budapest and South-East Hungary in 2012-2013.

PubMed

Institóris, László; Árok, Zsófia; Seprenyi, Katalin; Varga, Tibor; Sára-Klausz, Gabriella; Keller, Éva; Tóth, Réka A; Sala, Leonardo; Kereszty, Éva; Róna, Kálmán

2015-03-01

Identification of abuse and frequency patterns of stimulant designer drugs (SDDs) provides important information for their risk assessment and legislative control. In the present study urine and/or blood samples of suspected drug users in criminal cases were analysed by GC-MS for 38 SDDs, and for the most frequent illicit and psychoactive licit drugs in Hungary. Between July 2012 and June 2013, 2744 suspected drug users were sampled in Budapest and during 2012 and 2013, 774 persons were sampled in South-East Hungary (Csongrád County - neighbour the Romanian and Serbian borders). In Budapest 71.4% of cases, and in South-East Hungary 61% of cases were positive for at least one substance. Pentedrone was the most frequent SDD in both regions; however, the frequency distribution of the remaining drugs was highly diverse. SDDs were frequently present in combination with other drugs - generally with amphetamine or other stimulants, cannabis and/or benzodiazepines. The quarterly distribution of positive samples indicated remarkable seasonal changes in the frequency and pattern of consumption. Substances placed on the list of illicit drugs (mephedrone, 4-fluoro-amphetamine, MDPV, methylone, 4-MEC) showed a subsequent drop in frequency and were replaced by other SDDs (pentedrone, 3-MMC, methiopropamine, etc.). Newly identified compounds from seized materials were added to the list of new psychoactive substances ("Schedule C"). While the risk assessment of substances listed in Schedule C has to be performed within 2 years after scheduling, continuous monitoring of their presence and frequency among drug users is essential. In summary, our results suggest which substances should be dropped from the list of SDDs measured in biological samples; while the appearance of new substances from seized materials indicate the need for developing adequate standard analytical methods. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

21 CFR 868.6820 - Patient position support.

Code of Federal Regulations, 2010 CFR

2010-04-01

...) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Miscellaneous § 868.6820 Patient position support. (a) Identification. A patient position support is a device intended to maintain the position of an anesthetized... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Patient position support. 868.6820 Section 868...

Repurposing Clinical Molecule Ebselen to Combat Drug Resistant Pathogens.

PubMed

Thangamani, Shankar; Younis, Waleed; Seleem, Mohamed N

2015-01-01

Without a doubt, our current antimicrobials are losing the battle in the fight against newly-emerged multidrug-resistant pathogens. There is a pressing, unmet need for novel antimicrobials and novel approaches to develop them; however, it is becoming increasingly difficult and costly to develop new antimicrobials. One strategy to reduce the time and cost associated with antimicrobial innovation is drug repurposing, which is to find new applications outside the scope of the original medical indication of the drug. Ebselen, an organoselenium clinical molecule, possesses potent antimicrobial activity against clinical multidrug-resistant Gram-positive pathogens, including Staphylococcus, Streptococcus, and Enterococcus, but not against Gram-negative pathogens. Moreover, the activity of ebselen against Gram-positive pathogens exceeded those activities determined for vancomycin and linezolid, drugs of choice for treatment of Enterococcus and Staphylococcus infections. The minimum inhibitory concentrations of ebselen at which 90% of clinical isolates of Enterococcus and Staphylococcus were inhibited (MIC90) were found to be 0.5 and 0.25 mg/L, respectively. Ebselen showed significant clearance of intracellular methicillin-resistant S. aureus (MRSA) in comparison to vancomycin and linezolid. We demonstrated that ebselen inhibits the bacterial translation process without affecting mitochondrial biogenesis. Additionally, ebselen was found to exhibit excellent activity in vivo in a Caenorhabditis elegans MRSA-infected whole animal model. Finally, ebselen showed synergistic activities with conventional antimicrobials against MRSA. Taken together, our results demonstrate that ebselen, with its potent antimicrobial activity and safety profiles, can be potentially used to treat multidrug resistant Gram-positive bacterial infections alone or in combination with other antibiotics and should be further clinically evaluated.

Drug Violations and Aviation Accidents: Findings from the U.S. Mandatory Drug Testing Programs

PubMed Central

Li, Guohua; Baker, Susan P.; Zhao, Qi; Brady, Joanne E.; Lang, Barbara H.; Rebok, George W.; DiMaggio, Charles

2012-01-01

Aims To assess the role of drug violations in aviation accidents. Design Case-control analysis. Setting Commercial aviation in the United States. Participants Aviation employees who were tested for drugs during 1995 through 2005 under the post-accident testing program (cases, n=4,977) or under the random testing program (controls, n=1,129,922). Measurements Point prevalence of drug violations, odds ratio of accident involvement, and attributable risk in the population. A drug violation was defined as a confirmed positive test for marijuana (≥ 50 ng/ml), cocaine (≥ 300 ng/ml), amphetamines (≥1000 ng/ml), opiates (≥ 2000 ng/ml), or phencyclidine (≥ 25 ng/ml). Findings The prevalence of drug violations was 0.64% [95% confidence interval (CI), 0.62–0.65%] in random drug tests and 1.82% (95% CI, 1.47–2.24%) in post-accident tests. The odds of accident involvement for employees who tested positive for drugs was almost three times the odds for those who tested negative (odds ratio 2.90, 95% CI, 2.35–3.57), with an estimated attributable risk of 1.2%. Marijuana accounted for 67.3% of the illicit drugs detected. The proportion of illicit drugs represented by amphetamines increased progressively during the study period, from 3.4% in 1995 to 10.3% in 2005 (p<0.0001). Conclusions Use of illicit drugs by aviation employees is associated with a significantly increased risk of accident involvement. Due to the very low prevalence, drug violations contribute to only a small fraction of aviation accidents. PMID:21306594

[Uniform analyzes of drugs in urine needed for rule of law].

PubMed

Hansson, Therese; Helander, Anders; Beck, Olof; Elmgren, Anders; Kugelberg, Fredrik; Kronstrand, Robert

2015-09-22

Drugs of abuse testing is used in various areas of society for detection and follow-up of drug use. In routine laboratory drug testing, immunoassays are employed for initial screening of specimens to indicate the presence of drugs. To confirm a positive screening test, a secondary analysis by mass spectrometry is performed. The "cut-off" is the pre-defined concentration threshold of a drug or drug metabolite above which the sample is considered positive. A reading below this level implies a negative test result. Swedish drug testing laboratories currently employ varying cut-offs to distinguish between a positive and a negative test result. Because a positive drug test may have serious legal consequences to the individual, it is of importance that testing is performed and judged equally, regardless of where it is performed. A national harmonization of cut-offs is therefore warranted. Based on data from four major Swedish drug testing laboratories, and considering the recommendations in international guidelines, a proposal for national harmonization of urine cut-offs for the most common set of drugs of abuse is presented.

Can biochemistry drive drug discovery beyond simple potency measurements?

PubMed

Chène, Patrick

2012-04-01

Among the fields of expertise required to develop drugs successfully, biochemistry holds a key position in drug discovery at the interface between chemistry, structural biology and cell biology. However, taking the example of protein kinases, it appears that biochemical assays are mostly used in the pharmaceutical industry to measure compound potency and/or selectivity. This limited use of biochemistry is surprising, given that detailed biochemical analyses are commonly used in academia to unravel molecular recognition processes. In this article, I show that biochemistry can provide invaluable information on the dynamics and energetics of compound-target interactions that cannot be obtained on the basis of potency measurements and structural data. Therefore, an extensive use of biochemistry in drug discovery could facilitate the identification and/or development of new drugs. Copyright © 2012 Elsevier Ltd. All rights reserved.

The synthesis and application of heparin-based smart drug carrier.

PubMed

Li, Qingxuan; Gan, Lu; Tao, Hong; Wang, Qian; Ye, Lin; Zhang, Aiying; Feng, Zengguo

2016-04-20

Heparin based polymer drug which could self-assemble into sphere micelle in water was firstly prepared by grafting paclitaxel (PTX) into the hydroxyl of heparin via aconitic bond as pH sensitive spacer. Positive charged drug DOX·HCl and cationic folic acid (CFA) can be further loaded into the polymer drug via electrostatic interaction in aqueous solution so as to prepare smart drug carrier. The drug carrier was able to release more PTX and DOX at pH 4.8 than that at pH 7.4, exhibiting pH sensitivity for two drugs. Furthermore, tumor cell cytotoxicity test proved it possessed significant cytotoxicity against tumor cells MDA-MB-231 as well as its active tumor targeting ability resulting from the loading of CFA. Cellular uptake and intracellular distribution were further revealed by confocal laser scanning microscopy (CLSM). In conclusion, this paper not only provided a simple strategy but also indicated heparin is a versatile platform for the design of smart drug carrier. The as-prepared drug carrier also showed promising potential in chemotherapy. Copyright © 2015 Elsevier Ltd. All rights reserved.

Neurobiology of dysregulated motivational systems in drug addiction

PubMed Central

Edwards, Scott; Koob, George F

2010-01-01

The progression from recreational drug use to drug addiction impacts multiple neurobiological processes and can be conceptualized as a transition from positive to negative reinforcement mechanisms driving both drug-taking and drug-seeking behaviors. Neurobiological mechanisms for negative reinforcement, defined as drug taking that alleviates a negative emotional state, involve changes in the brain reward system and recruitment of brain stress (or antireward) systems within forebrain structures, including the extended amygdala. These systems are hypothesized to be dysregulated by excessive drug intake and to contribute to allostatic changes in reinforcement mechanisms associated with addiction. Points of intersection between positive and negative motivational circuitry may further drive the compulsivity of drug addiction but also provide a rich neurobiological substrate for therapeutic intervention. PMID:20563312

Proton pump inhibitors while belonging to the same family of generic drugs show different anti-tumor effect.

PubMed

Lugini, Luana; Federici, Cristina; Borghi, Martina; Azzarito, Tommaso; Marino, Maria Lucia; Cesolini, Albino; Spugnini, Enrico Pierluigi; Fais, Stefano

2016-08-01

Tumor acidity represents a major cause of chemoresistance. Proton pump inhibitors (PPIs) can neutralize tumor acidity, sensitizing cancer cells to chemotherapy. To compare the anti-tumor efficacy of different PPIs in vitro and in vivo. In vitro experiments PPIs anti-tumor efficacy in terms of cell proliferation and cell death/apoptosis/necrosis evaluation were performed. In vivo PPIs efficacy experiments were carried out using melanoma xenograft model in SCID mice. Lansoprazole showed higher anti-tumor effect when compared to the other PPIs. The lansoprazole effect lasted even upon drug removal from the cell culture medium and it was independent from the lipophilicity of the PPIs formulation. These PPIs have shown different anti-tumoral efficacy, and the most effective at low dose was lansoprazole. The possibility to contrast tumor acidity by off-label using PPIs opens a new field of oncology investigation.

Pattern of secondary acquired drug resistance to antituberculosis drug in Mumbai, India--1991-1995.

PubMed

Chowgule, R V; Deodhar, L

1998-01-01

A retrospective observational study was conducted to find out whether secondary acquired drug resistance to isoniazid and ethambutol is high and to rifamycin and pyrazinamide is low, as is commonly believed in India. There were 2033 patients, whose sputum samples (6099) were reviewed from a specimen registry of the microbiology laboratory for the years 1991 to 1995. Of these, 521 (25.6%) patients [335 males and 186 females; age ranged from 11 to 75 years] had sputum positive culture and sensitivity for acid-fast bacilli (AFB). The drug resistance patterns in our study were: isoniazid (H) 15%, rifamycin (R) 66.8%, pyrazinamide (Z) 72.2%, ethambutol (E) 8.4%, streptomycin (S) 53.6%, cycloserine (C) 39.2% kanamycin (K) 25.1% and ethionamide (Eth) 65.3%. The resistance to streptomycin showed a significant fall over a year while there was a rise in resistance to cycloserine and kanamycin which is significant. The rate of secondary acquired resistance of isoniazid and ethambutol was low, and the rate of secondary acquired resistance to rifamycin and pyrazinamide was high, which is contarary to the common belief regarding these drugs in India. This implies that isoniazid is still a valuable drug in the treatment of multidrug resistance in India.

Cellulose Nanocrystal Membranes as Excipients for Drug Delivery Systems

PubMed Central

Barbosa, Ananda M.; Robles, Eduardo; Ribeiro, Juliana S.; Lund, Rafael G.; Carreño, Neftali L. V.; Labidi, Jalel

2016-01-01

In this work, cellulose nanocrystals (CNCs) were obtained from flax fibers by an acid hydrolysis assisted by sonochemistry in order to reduce reaction times. The cavitation inducted during hydrolysis resulted in CNC with uniform shapes, and thus further pretreatments into the cellulose are not required. The obtained CNC exhibited a homogeneous morphology and high crystallinity, as well as typical values for surface charge. Additionally, CNC membranes were developed from CNC solution to evaluation as a drug delivery system by the incorporation of a model drug. The drug delivery studies were carried out using chlorhexidine (CHX) as a drug and the antimicrobial efficiency of the CNC membrane loaded with CHX was examined against Gram-positive bacteria Staphylococcus aureus (S. Aureus). The release of CHX from the CNC membranes is determined by UV-Vis. The obtaining methodology of the membranes proved to be simple, and these early studies showed a potential use in antibiotic drug delivery systems due to the release kinetics and the satisfactory antimicrobial activity. PMID:28774122

Predominance of alcohol and illicit drugs among traffic accidents fatalities in an urban area of Brazil.

PubMed

Pelição, Fabrício Souza; Peres, Mariana Dadalto; Pissinate, Jauber Fornaciari; de Paula, Daniela Mendes Louzada; de Faria, Maria das Graças Corrêa; Nakamura-Palacios, Ester Miyuki; De Martinis, Bruno Spinosa

2016-10-02

The objective of this study was to determine the prevalence of alcohol and illicit drug use among victims of fatal traffic accidents in the Metropolitan Region of Vitória, Brazil, during the period 2011-2012. Blood samples were collected and analyzed for the presence of drugs from 391 deceased victims of traffic crashes that occurred in the Metropolitan Region of Vitória, Brazil. The victims included drivers, passengers, and pedestrians. Sociodemographic variables such as age, gender, day of the week, and period of the year in which the accidents occurred were recorded. The analyses were performed by a gas chromatography-flame ionization method for alcohol and by a gas chromatography-mass spectrometry for amphetamines, cocaine, and cannabis. The results showed that 44.8% (n = 175) of all cases were positive for alcohol and/or illicit drugs. The detection of alcohol and/or drugs was more frequent in young males, aged 17 to 34, whose samples were positive in 46.8% of cases. Small differences among drivers, passengers, and pedestrians were observed (drivers = 45.9%, passengers = 46.4%, and pedestrians = 45.6%). In general, the most prevalent drug was alcohol, with 141 positive cases (36.1%), followed by cocaine, with 47 positive cases (12%). Amphetamines and cannabis had positivity rates of 4.1 and 4.3%, with 16 and 17 positive cases, respectively. The combined use of alcohol and other drugs was found in 36 cases (9.2%). Crack cocaine use was observed in 27.7% of the positive cases for cocaine. For the effective reduction of traffic accidents related to driving under influence of drugs (DUID), we suggest the intensification of enforcement actions against the use of alcohol by drivers, the definition of which illicit drugs should be surveyed, as well the cutoff values, the promotion of changing legislation to oblige drivers to provide samples for toxicological testing, and the establishment of public information programs and specific actions aimed at young drivers to

Computer-delivered indirect screening and brief intervention for drug use in the perinatal period: A randomized trial.

PubMed

Ondersma, Steven J; Svikis, Dace S; Thacker, Casey; Resnicow, Ken; Beatty, Jessica R; Janisse, James; Puder, Karoline

2018-04-01

Under-reporting of drug use in the perinatal period is well-documented, and significantly limits the reach of proactive intervention approaches. The Wayne Indirect Drug Use Screener (WIDUS) focuses on correlates of drug use rather than use itself. This trial tested a computer-delivered, brief intervention designed for use with indirect screen-positive cases, seeking to motivate reductions in drug use without presuming its presence. Randomized clinical trial with 500 WIDUS-positive postpartum women recruited between August 14, 2012 and November 19, 2014. Participants were randomly assigned to either a time control condition or a single-session, tailored, indirect brief intervention. The primary outcome was days of drug use over the 6-month follow-up period; secondary outcomes included urine and hair analyses results at 3- and 6-month follow-up. All outcomes were measured by blinded evaluators. Of the 500 participants (252 intervention and 248 control), 36.1% of participants acknowledged drug use in the 3 months prior to pregnancy, but 89% tested positive at the 6-month follow-up. Participants rated the intervention as easy to use (4.9/5) and helpful (4.4/5). Analyses revealed no between-group differences in drug use (52% in the intervention group, vs. 53% among controls; OR 1.03). Exploratory analyses also showed that intervention effects were not moderated by baseline severity, WIDUS score, or readiness to change. The present trial showed no evidence of efficacy for an indirect, single-session, computer-delivered, brief intervention designed as a complement to indirect screening. More direct approaches that still do not presume active drug use may be possible and appropriate. Copyright © 2018 Elsevier B.V. All rights reserved.

Isolation and Structural Elucidation of Brevibacillin, an Antimicrobial Lipopeptide from Brevibacillus laterosporus That Combats Drug-Resistant Gram-Positive Bacteria.

PubMed

Yang, Xu; Huang, En; Yuan, Chunhua; Zhang, Liwen; Yousef, Ahmed E

2016-05-01

A new environmental bacterial strain exhibited strong antimicrobial characteristics against methicillin-resistant Staphylococcus aureus, vancomycin-resistant strains of Enterococcus faecalis and Lactobacillus plantarum, and other Gram-positive bacteria. The producer strain, designated OSY-I1, was determined to be Brevibacillus laterosporusvia morphological, biochemical, and genetic analyses. The antimicrobial agent was extracted from cells of OSY-I1 with isopropanol, purified by high-performance liquid chromatography, and structurally analyzed using mass spectrometry (MS) and nuclear magnetic resonance (NMR). The MS and NMR results, taken together, uncovered a linear lipopeptide consisting of 13 amino acids and an N-terminal C6 fatty acid (FA) chain, 2-hydroxy-3-methylpentanoic acid. The lipopeptide (FA-Dhb-Leu-Orn-Ile-Ile-Val-Lys-Val-Val-Lys-Tyr-Leu-valinol, where Dhb is α,β-didehydrobutyric acid and valinol is 2-amino-3-methyl-1-butanol) has a molecular mass of 1,583.0794 Da and contains three modified amino acid residues: α,β-didehydrobutyric acid, ornithine, and valinol. The compound, designated brevibacillin, was determined to be a member of a cationic lipopeptide antibiotic family. In addition to its potency against drug-resistant bacteria, brevibacillin also exhibited low MICs (1 to 8 μg/ml) against selected foodborne pathogenic and spoilage bacteria, such as Listeria monocytogenes,Bacillus cereus, and Alicyclobacillus acidoterrestris Purified brevibacillin showed no sign of degradation when it was held at 80 °C for 60 min, and it retained at least 50% of its antimicrobial activity when it was held for 22 h under acidic or alkaline conditions. On the basis of these findings, brevibacillin is a potent antimicrobial lipopeptide which is potentially useful to combat drug-resistant bacterial pathogens and foodborne pathogenic and spoilage bacteria. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Associations of health insurance coverage, mental health problems, and drug use with mental health service use in US adults: an analysis of 2013 National Survey on Drug Use and Health.

PubMed

Wang, Nianyang; Xie, Xin

2018-02-22

To estimate the prevalence of mental health service use among US adults, examine the associations of mental health service use with health insurance coverage, mental health problems and drug use, and detect health disparities. This was a cross-sectional study with 5,434 adults receiving mental health service out of 37,424 adult respondents from the 2013 National Survey on Drug Use and Health. Weighted univariate and multiple logistic regression analyses were used to estimate the associations of potential factors with mental health service use. The overall prevalence of mental health services use was 14.7%. Our results showed that being female, aging, having a major depressive episode, serious psychological distress, and illicit drug or alcohol abuse/dependence were positively associated with mental health service use; whereas being African American, Asian or Hispanic ethnicity, married, and having any form of insurance were negatively associated with mental health service use . Stratified analysis by insurance types showed that Medicaid/CHIP, CHAMPUS, and other insurance were positively associated with mental health service use. Health insurance coverage, mental health problems, and drug abuse or dependence were associated with mental health service use in US adults. Furthermore, adults with different insurances had disparities in access of mental health service.

Identification of precision treatment strategies for relapsed/refractory multiple myeloma by functional drug sensitivity testing.

PubMed

Majumder, Muntasir Mamun; Silvennoinen, Raija; Anttila, Pekka; Tamborero, David; Eldfors, Samuli; Yadav, Bhagwan; Karjalainen, Riikka; Kuusanmäki, Heikki; Lievonen, Juha; Parsons, Alun; Suvela, Minna; Jantunen, Esa; Porkka, Kimmo; Heckman, Caroline A

2017-08-22

Novel agents have increased survival of multiple myeloma (MM) patients, however high-risk and relapsed/refractory patients remain challenging to treat and their outcome is poor. To identify novel therapies and aid treatment selection for MM, we assessed the ex vivo sensitivity of 50 MM patient samples to 308 approved and investigational drugs. With the results we i) classified patients based on their ex vivo drug response profile; ii) identified and matched potential drug candidates to recurrent cytogenetic alterations; and iii) correlated ex vivo drug sensitivity to patient outcome. Based on their drug sensitivity profiles, MM patients were stratified into four distinct subgroups with varied survival outcomes. Patients with progressive disease and poor survival clustered in a drug response group exhibiting high sensitivity to signal transduction inhibitors. Del(17p) positive samples were resistant to most drugs tested with the exception of histone deacetylase and BCL2 inhibitors. Samples positive for t(4;14) were highly sensitive to immunomodulatory drugs, proteasome inhibitors and several targeted drugs. Three patients treated based on the ex vivo results showed good response to the selected treatments. Our results demonstrate that ex vivo drug testing may potentially be applied to optimize treatment selection and achieve therapeutic benefit for relapsed/refractory MM.

How excluding some benefits from value assessment of new drugs impacts innovation.

PubMed

Cook, Joseph P; Golec, Joseph

2017-12-01

Payers often assess the benefits of new drugs relative to costs for reimbursement purposes, but they frequently exclude some drugs' option-related benefits, reducing their reimbursement chances, and making them less attractive R&D investments. We develop and test a real options model of R&D investment that shows that excluding option-related benefits heightens drug developers' incentives to avoid high-risk (volatile) R&D investments and instead encourages them to focus on "safer" (positively skewed) investments. Our model and empirical results could partly explain the decline in the number of risky new molecular entities. Copyright © 2017 John Wiley & Sons, Ltd.

Correlation between octanol/water and liposome/water distribution coefficients and drug absorption of a set of pharmacologically active compounds.

PubMed

Esteves, Freddy; Moutinho, Carla; Matos, Carla

2013-06-01

Absorption and consequent therapeutic action are key issues in the development of new drugs by the pharmaceutical industry. In this sense, different models can be used to simulate biological membranes to predict the absorption of a drug. This work compared the octanol/water and the liposome/water models. The parameters used to relate the two models were the distribution coefficients between liposomes and water and octanol and water and the fraction of drug orally absorbed. For this study, 66 drugs were collected from literature sources and divided into four groups according to charge and ionization degree: neutral; positively charged; negatively charged; and partially ionized/zwitterionic. The results show a satisfactory linear correlation between the octanol and liposome systems for the neutral (R²= 0.9324) and partially ionized compounds (R²= 0.9367), contrary to the positive (R²= 0.4684) and negatively charged compounds (R²= 0.1487). In the case of neutral drugs, results were similar in both models because of the high fraction orally absorbed. However, for the charged drugs (positively, negatively, and partially ionized/zwitterionic), the liposomal model has a more-appropriate correlation with absorption than the octanol model. These results show that the neutral compounds only interact with membranes through hydrophobic bonds, whereas charged drugs favor electrostatic interactions established with the liposomes. With this work, we concluded that liposomes may be a more-appropriate biomembrane model than octanol for charged compounds.

Cartilage-targeting drug delivery: can electrostatic interactions help?

PubMed

Bajpayee, Ambika G; Grodzinsky, Alan J

2017-03-01

Current intra-articular drug delivery methods do not guarantee sufficient drug penetration into cartilage tissue to reach cell and matrix targets at the concentrations necessary to elicit the desired biological response. Here, we provide our perspective on the utilization of charge-charge (electrostatic) interactions to enhance drug penetration and transport into cartilage, and to enable sustained binding of drugs within the tissue's highly negatively charged extracellular matrix. By coupling drugs to positively charged nanocarriers that have optimal size and charge, cartilage can be converted from a drug barrier into a drug reservoir for sustained intra-tissue delivery. Alternatively, a wide variety of drugs themselves can be made cartilage-penetrating by functionalizing them with specialized positively charged protein domains. Finally, we emphasize that appropriate animal models, with cartilage thickness similar to that of humans, must be used for the study of drug transport and retention in cartilage.

Chronic Myeloid Leukemia Patients Sensitive and Resistant to Imatinib Treatment Show Different Metabolic Responses

PubMed Central

Wang, Guangji; Yan, Bei; Zhang, Sujiang; Huang, Qing; Ni, Lingna; Zha, Weibin; Liu, Linsheng; Cao, Bei; Hong, Ming; Wu, Hanxin; Lu, Hua; Shi, Jian; Li, Mengjie; Li, Jianyong

2010-01-01

The BCR-ABL tyrosine kinase inhibitor imatinib is highly effective for chronic myeloid leukemia (CML). However, some patients gradually develop resistance to imatinib, resulting in therapeutic failure. Metabonomic and genomic profiling of patients' responses to drug interventions can provide novel information about the in vivo metabolism of low-molecular-weight compounds and extend our insight into the mechanism of drug resistance. Based on a multi-platform of high-throughput metabonomics, SNP array analysis, karyotype and mutation, the metabolic phenotypes and genomic polymorphisms of CML patients and their diverse responses to imatinib were characterized. The untreated CML patients (UCML) showed different metabolic patterns from those of healthy controls, and the discriminatory metabolites suggested the perturbed metabolism of the urea cycle, tricarboxylic acid cycle, lipid metabolism, and amino acid turnover in UCML. After imatinib treatment, patients sensitive to imatinib (SCML) and patients resistant to imatinib (RCML) had similar metabolic phenotypes to those of healthy controls and UCML, respectively. SCML showed a significant metabolic response to imatinib, with marked restoration of the perturbed metabolism. Most of the metabolites characterizing CML were adjusted to normal levels, including the intermediates of the urea cycle and tricarboxylic acid cycle (TCA). In contrast, neither cytogenetic nor metabonomic analysis indicated any positive response to imatinib in RCML. We report for the first time the associated genetic and metabonomic responses of CML patients to imatinib and show that the perturbed in vivo metabolism of UCML is independent of imatinib treatment in resistant patients. Thus, metabonomics can potentially characterize patients' sensitivity or resistance to drug intervention. PMID:20949032

Understanding drugs in breast cancer through drug sensitivity screening.

PubMed

Uhr, Katharina; Prager-van der Smissen, Wendy J C; Heine, Anouk A J; Ozturk, Bahar; Smid, Marcel; Göhlmann, Hinrich W H; Jager, Agnes; Foekens, John A; Martens, John W M

2015-01-01

With substantial numbers of breast tumors showing or acquiring treatment resistance, it is of utmost importance to develop new agents for the treatment of the disease, to know their effectiveness against breast cancer and to understand their relationships with other drugs to best assign the right drug to the right patient. To achieve this goal drug screenings on breast cancer cell lines are a promising approach. In this study a large-scale drug screening of 37 compounds was performed on a panel of 42 breast cancer cell lines representing the main breast cancer subtypes. Clustering, correlation and pathway analyses were used for data analysis. We found that compounds with a related mechanism of action had correlated IC50 values and thus grouped together when the cell lines were hierarchically clustered based on IC50 values. In total we found six clusters of drugs of which five consisted of drugs with related mode of action and one cluster with two drugs not previously connected. In total, 25 correlated and four anti-correlated drug sensitivities were revealed of which only one drug, Sirolimus, showed significantly lower IC50 values in the luminal/ERBB2 breast cancer subtype. We found expected interactions but also discovered new relationships between drugs which might have implications for cancer treatment regimens.

C8-Linked Pyrrolobenzodiazepine Monomers with Inverted Building Blocks Show Selective Activity against Multidrug Resistant Gram-Positive Bacteria.

PubMed

Andriollo, Paolo; Hind, Charlotte K; Picconi, Pietro; Nahar, Kazi S; Jamshidi, Shirin; Varsha, Amrit; Clifford, Melanie; Sutton, J Mark; Rahman, Khondaker Miraz

2018-02-09

Antimicrobial resistance has become a major global concern. Development of novel antimicrobial agents for the treatment of infections caused by multidrug resistant (MDR) pathogens is an urgent priority. Pyrrolobenzodiazepines (PBDs) are a promising class of antibacterial agents initially discovered and isolated from natural sources. Recently, C8-linked PBD biaryl conjugates have been shown to be active against some MDR Gram-positive strains. To explore the role of building block orientations on antibacterial activity and obtain structure activity relationship (SAR) information, four novel structures were synthesized in which the building blocks of previously reported compounds were inverted, and their antibacterial activity was studied. The compounds showed minimum inhibitory concentrations (MICs) in the range of 0.125-32 μg/mL against MDR Gram-positive strains with a bactericidal mode of action. The results showed that a single inversion of amide bonds reduces the activity while the double inversion restores the activity against MDR pathogens. All inverted compounds did not stabilize DNA and lacked eukaryotic toxicity. The compounds inhibit DNA gyrase in vitro, and the most potent compound was equally active against both wild-type and mutant DNA gyrase in a biochemical assay. The observed activity of the compounds against methicillin resistant S. aureus (MRSA) strains with equivalent gyrase mutations is consistent with gyrase inhibition being the mechanism of action in vivo, although this has not been definitively confirmed in whole cells. This conclusion is supported by a molecular modeling study showing interaction of the compounds with wild-type and mutant gyrases. This study provides important SAR information about this new class of antibacterial agents.

False-positive results in pharmacoepidemiology and pharmacovigilance.

PubMed

Bezin, Julien; Bosco-Levy, Pauline; Pariente, Antoine

2017-09-01

False-positive constitute an important issue in scientific research. In the domain of drug evaluation, it affects all phases of drug development and assessment, from the very early preclinical studies to the late post-marketing evaluations. The core concern associated with this false-positive is the lack of replicability of the results. Aside from fraud or misconducts, false-positive is often envisioned from the statistical angle, which considers them as a price to pay for type I error in statistical testing, and its inflation in the context of multiple testing. If envisioning this problematic in the context of pharmacoepidemiology and pharmacovigilance however, that both evaluate drugs in an observational settings, information brought by statistical testing and the significance of such should only be considered as additional to the estimates provided and their confidence interval, in a context where differences have to be a clinically meaningful upon everything, and the results appear robust to the biases likely to have affected the studies. In the following article, we consequently illustrate these biases and their consequences in generating false-positive results, through studies and associations between drug use and health outcomes that have been widely disputed. Copyright © 2017 Société française de pharmacologie et de thérapeutique. Published by Elsevier Masson SAS. All rights reserved.

Gratitude and Drug Misuse: Role of Coping as Mediator.

PubMed

Leung, Chi-Ching; Tong, Eddie M W

2017-12-06

Positive emotions, such as gratitude has been found to be beneficial to both physical and mental well-being but so far, drug misuse research has yet to identify important emotive predictors related to drug use. This study aimed to examine the relationship between gratitude and drug use among a group of drug misusers. It was hypothesized that greater dispositional gratitude was associated with lesser drug use through greater use of adaptive coping methods and lesser use of maladaptive coping methods. This study utilized a cross-sectional design to examine the relationship between gratitude, coping, and drug use among a sample of drug misusers (N = 105) at a drug rehabilitation center. Participants completed the gratitude questionnaire (GQ-6), the joy subscale of the Dispositional Positive Emotion Scale (DPES), the Brief COPE, and a questionnaire on their drug use. Data were collected in 2015. Mediation analysis supported the hypothesis and found that adaptive coping mediated the relationship between gratitude and drug use. However, mediation was not found for maladaptive coping. Additional analysis found that adaptive coping as a mediator was not found for joy. Results suggested that gratitude has utility in reducing drug use through the use of more adaptive coping strategies and this relationship was not simply due to positive affect. Interventions targeting drug use behavior could consider introducing gratitude to increase adaptive coping abilities to reduce drug use.

Incarceration and injection drug use in Baltimore, Maryland.

PubMed

Genberg, Becky L; Astemborski, Jacquie; Vlahov, David; Kirk, Gregory D; Mehta, Shruti H

2015-07-01

There is limited longitudinal research examining incarceration and subsequent changes in drug use among people who inject drugs (PWID) in the United States. The objective of the current study was to characterize the frequency of incarceration and estimate the association between incarceration and subsequent injection drug use among current and former PWIDs in one US city. ALIVE (AIDS Linked to the Intravenous Experience) is a prospective cohort study of current and former PWIDs, with semi-annual follow-up occurring since 1988. Baltimore, Maryland, USA. A total of 3245 participants with 48 738 study visits were included. Participants enrolled from 1988 to 2012 with a median of 13 follow-up visits per participant (Interquartile range = 7-25). Incarcerations were defined as any self-reported jail or prison stays in the previous 6 months that were ≥7 days or longer. The primary outcome was defined as any self-reported injection drug use in the previous 6 months. At baseline, 29% were female, 90% African American and 33% HIV-positive. Fifty-seven per cent of participants experienced at least one incarceration episode. After adjusting for confounders, there was a positive association between incarceration and subsequent injection drug use [adjusted odds ratio (AOR) = 1.48, 95% confidence interval (CI) = 1.37-1.59]; however, stratified analysis showed that the effect was restricted to those who were not injecting at the time of incarceration (AOR = 2.11, 95% CI = 1.88-2.37). In the United States, incarceration of people who had previously stopped injecting drugs appears to be associated with an increased risk of subsequent injecting. © 2015 Society for the Study of Addiction.

Successful management of drug-induced hypercapnic acidosis with naloxone and noninvasive positive pressure ventilation.

PubMed

Agrafiotis, Michalis; Tryfon, Stavros; Siopi, Demetra; Chassapidou, Georgia; Galanou, Artemis; Tsara, Venetia

2015-02-01

A 74-year-old man was referred to our hospital due to deteriorating level of consciousness and desaturation. His Glasgow Coma Scale was 6, and his pupils were constricted but responded to light. Chest radiograph was negative for significant findings. Arterial blood gas evaluation on supplemental oxygen revealed severe acute on chronic respiratory acidosis: pH 7.15; PCO2, 133 mm Hg; PO2,64 mm Hg; and HCO3, 31 mmol/L. He regained full consciousness (Glasgow Coma Scale, 15) after receiving a 0.4 mg dose of naloxone, but because of persistent severe respiratory acidosis (pH 7.21; PCO2, 105 mm Hg), he was immediately commenced on noninvasive positive pressure ventilation (NIV) displaying a remarkable improvement in arterial blood gas values within the next few hours. However, in the days that followed, he remained dependent on NIV, and he was finally discharged on a home mechanical ventilation prescription. In cases of drug-induced respiratory depression, NIV should be regarded as an acceptable treatment, as it can provide ventilatory support without the increased risks associated with invasive mechanical ventilation.

Drug policy constellations: A Habermasian approach for understanding English drug policy.

PubMed

Stevens, Alex; Zampini, Giulia Federica

2018-07-01

It is increasingly accepted that a view of policy as a rational process of fitting evidence-based means to rationally justified ends is inadequate for understanding the actual processes of drug policy making. We aim to provide a better description and explanation of recent English drug policy decisions. We develop the policy constellation concept from the work of Habermas, in dialogue with data from two contemporary debates in English policy; on decriminalisation of drug possession and on recovery in drug treatment. We collect data on these debates through long-term participant observation, stakeholder interviews (n = 15) and documentary analysis. We show the importance of social asymmetries in power in enabling structurally advantaged groups to achieve the institutionalisation of their moral preferences as well as the reproduction of their social and economic power through the deployment of policies that reflect their material interests and normative beliefs. The most influential actors in English drug policy come together in a 'medico-penal constellation', in which the aims and practices of public health and social control overlap. Formal decriminalisation of possession has not occurred, despite the efforts of members of a challenging constellation which supports it. Recovery was put forward as the aim of drug treatment by members of a more powerfully connected constellation. It has been absorbed into the practice of 'recovery-oriented' drug treatment in a way that maintains the power of public health professionals to determine the form of treatment. Actors who share interests and norms come together in policy constellations. Strategic action within and between constellations creates policies that may not take the form that was intended by any individual actor. These policies do not result from purely rational deliberation, but are produced through 'systematically distorted communication'. They enable the most structurally favoured actors to institutionalise

Positional Asphyxia: Death Due to Unusual Head-Down Position in a Narrow Space.

PubMed

Chaudhari, Vinod Ashok; Ghodake, Dattatray G; Kharat, Rajesh D

2016-06-01

Death due to a head-down position with hyperflexion of the neck is a rare event. A person accidentally falling into a narrow space and remaining in an upside-down position with no timely recovery may experience positional or postural asphyxia. It is a critical condition arising out of particular body positions, leading to mechanical obstruction of respiration. The precipitating factors are intoxication due to alcohol, drugs, obesity, psychiatric illnesses, and injuries. A 30-year-old unmarried woman, weighing 82 kg and with a body mass index of 31.24, was found in a narrow space between the bed and the wall in a naked state and in a head-down position with hyperflexion of the neck. The distribution of lividity was consistent with the position of the body at the scene. Blood was oozing from the mouth and nostrils, and signs of asphyxia were present. The toxicological analyses of viscera, blood, and urine were negative for alcohol, drugs, and poisons. Glucose levels in the blood (86 mg/dL) as well as urine and vitreous humor levels (68 mg/dL) were within normal limits. On microscopic examination, there were no findings of coronary atherosclerosis, whereas the brain and lung were edematous. After meticulous examination, we ruled out sexual assault, autoerotic asphyxia, epilepsy, psychiatric illness, diabetes, toxicity, and coronary artery disease. Death was attributed to the accidental fall of the obese individual being stuck in a narrow space, resulting in positional asphyxia. It is imperative to recognize the precipitating or risk factors before labeling positional asphyxia as a cause of death.

The Influence of Drug Testing and Benefit-Based Distribution of Opioid Substitution Therapy on Drug Abstinence.

PubMed

Gabrovec, Branko

2015-01-01

The objective of our research was to discover whether the new approach to urine drug testing has a positive effect on users' abstinence, users' treatment, and their cooperation, while remaining user-friendly, and whether this approach is more cost-effective. The centers are focused on providing high-quality treatment within a cost-efficient program. In this study, we focus on the influence of drug testing and benefit-based distribution of opioid substitution therapy (BBDOST) on drug abstinence. The purpose of this study was to find any possible positive effect of modified distribution of the therapy and illicit drug testing on the number of users who are abstinent from illicit drugs and users who are not abstinent from illicit drugs as well as the users' opinion on BBDOST and testing. We are also interested in a difference in abstinence rates between those on BBDOST and those not receiving BBDOST. In 2010, the method of drug testing at the center was changed (less frequent and random drug testing) to enable its users faster access to BBDOST (take-home therapy). It was found that the number of drug-abstinent program participants has increased from initial 44.5% (2010) to 54.1% (2014). According to the program participants, the new method allows them to achieve and maintain abstinence from drugs more easily. In addition, they are also satisfied with the modified way of drug testing. This opinion does not change with age, gender, and acquired benefits.

The fading affect bias shows positive outcomes at the general but not the individual level of analysis in the context of social media.

PubMed

Gibbons, Jeffrey A; Horowitz, Kyle A; Dunlap, Spencer M

2017-08-01

Unpleasant affect fades faster than pleasant affect (e.g., Walker, Vogl, & Thompson, 1997); this effect is referred to as the Fading Affect Bias (FAB; Walker, Skowronski, Gibbons, Vogl, & Thompson, 2003a). Research shows that the FAB is consistently related to positive/healthy outcomes at a general but not at a specific level of analysis based on event types and individual differences (e.g., Gibbons et al., 2013). Based on the positive outcomes for FAB and negative outcomes for social media (Bolton et al., 2013; Huang, 2010), the current study examined FAB in the context of social media events along with related individual differences. General positive outcomes were shown in the form of robust FAB effects across social media and non-social media events, a larger FAB for non-social media events than for social media events, negative correlations of FAB with depression, anxiety, and stress as well as a positive correlation of FAB with self-esteem. However, the lack of a negative correlation between FAB and anxiety for social media events in a 3-way interaction did not show positive outcomes at a specific level of analysis. Rehearsal ratings mediated the 3-way interaction. Implications are discussed. Copyright © 2017 Elsevier Inc. All rights reserved.

Controllable drug uptake and nongenomic response through estrogen-anchored cyclodextrin drug complex

PubMed Central

Yin, Juan-Juan; Shumyak, Stepan P; Burgess, Christopher; Zhou, Zhi-Wei; He, Zhi-Xu; Zhang, Xue-Ji; Pan, Shu-Ting; Yang, Tian-Xin; Duan, Wei; Qiu, Jia-Xuan; Zhou, Shu-Feng

2015-01-01

Breast cancer is a leading killer of women worldwide. Cyclodextrin-based estrogen receptor-targeting drug-delivery systems represent a promising direction in cancer therapy but have rarely been investigated. To seek new targeting therapies for membrane estrogen receptor-positive breast cancer, an estrogen-anchored cyclodextrin encapsulating a doxorubicin derivative Ada-DOX (CDE1-Ada-DOX) has been synthesized and evaluated in human breast cancer MCF-7 cells. First, we synthesized estrone-conjugated cyclodextrin (CDE1), which formed the complex CDE1-Ada-DOX via molecular recognition with the derivative adamantane-doxorubicin (Ada-DOX) (Kd =1,617 M−1). The structure of the targeting vector CDE1 was fully characterized using 1H- and 13C-nuclear magnetic resonance, mass spectrometry, and electron microscopy. CDE1-Ada-DOX showed two-phase drug-release kinetics with much slower release than Ada-DOX. The fluorescence polarization analysis reveals that CDE1-Ada-DOX binds to recombinant human estrogen receptor α fragments with a Kd of 0.027 µM. Competition assay of the drug complex with estrogen ligands demonstrated that estrone and tamoxifen competed with CDE1-Ada-DOX for membrane estrogen receptor binding in MCF-7 cells. Intermolecular self-assembly of CDE1 molecules were observed, showing tail-in-bucket and wire-like structures confirmed by transmission electronic microscopy. CDE1-Ada-DOX had an unexpected lower drug uptake (when the host–guest ratio was >1) than non-targeting drugs in MCF-7 cells due to ensconced ligands in cyclodextrins cavities resulting from the intermolecular self-assembly. The uptake of CDE1-Ada-DOX was significantly increased when the host–guest ratio was adjusted to be less than half at the concentration of CDE1 over 5 µM due to the release of the estrone residues. CDE1 elicited rapid activation of mitogen-activated protein kinases (p44/42 MAPK, Erk1/2) in minutes through phosphorylation of Thr202/Tyr204 in MCF-7 cells. These results

Bio-fabricated silver nanoparticles preferentially targets Gram positive depending on cell surface charge.

PubMed

Mandal, Debasis; Kumar Dash, Sandeep; Das, Balaram; Chattopadhyay, Sourav; Ghosh, Totan; Das, Debasis; Roy, Somenath

2016-10-01

Recently bio-inspired experimental processes for synthesis of nanoparticles are receiving significant attention in nanobiotechnology. Silver nanoparticles (Ag NPs) have been used very frequently in recent times to the wounds, burns and bacterial infections caused by drug-resistant microorganisms. Though, the antibacterial effects of Ag NPs on some multi drug-resistant bacteria specially against Gram positive bacteria has been established, but further investigation is needed to elicit its effectiveness against Gram negatives and to identify the probable mechanism of action. Thus, the present study was conducted to synthesize Ag NPs using Andrographis paniculata leaf extract and to investigate its antibacterial efficacy. After synthesis process the biosynthesized nanoparticles were purified and characterized with the help of various physical measurement techniques which raveled their purity, stability and small size range. The antimicrobial activity of Ag NPs was determined against both Gram-positive Enterococcus faecalis and Gram-negative Proteus vulgaris. Results showed comparatively higher antibacterial efficacy of Ag NPs against Gram positive Enterococcus faecalis strains. It was found that greater difference in zeta potential values between Gram positive bacteria and Ag NPs triggers better internalization of the particles. Thus the cell surface charge played vital role in cell killing which was confirmed by surface zeta potential study. Finally it may be concluded that green synthesized Ag NPs using Andrographis paniculata leaf extract can be very useful against both multi drug resistant Gram-positive and Gram-negative bacteria. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Drugs of abuse detection in saliva based on actuated optical method

NASA Astrophysics Data System (ADS)

Shao, Jie; Li, Zhenyu; Jiang, Hong; Wang, Wenlong; Wu, Yixuan

2014-12-01

There has been a considerable increase in the abuse of drugs during the past decade. Combing drug use with driving is very dangerous. More than 11% of drivers in a roadside survey tested positive for drugs, while 18% of drivers killed in accidents tested positive for drugs as reported in USA, 2007. Toward developing a rapid drug screening device, we use saliva as the sample, and combining the traditional immunoassays method with optical magnetic technology. There were several methods for magnetic nanoparticles detection, such as magnetic coils, SQUID, microscopic imaging, and Hall sensors. All of these methods were not suitable for our demands. By developing a novel optical scheme, we demonstrate high-sensitivity detection in saliva. Drugs of abuse are detected at sub-nano gram per milliliter levels in less than 120 seconds. Evanescent wave principle has been applied to sensitively monitor the presence of magnetic nanoparticles on the binding surface. Like the total internal reflection fluorescence microscope (TIRFM), evanescent optical field is generated at the plastic/fluid interface, which decays exponentially and penetrates into the fluid by only a sub-wavelength distance. By disturbance total internal reflection with magnetic nanoparticles, the optical intensity would be influenced. We then detected optical output by imaging the sensor surface onto a CCD camera. We tested four drugs tetrahydrocannabinol (THC), methamphetamine (MAMP), ketamine (KET), morphine (OPI), using this technology. 100 ng mL-1 sensitivity was achieved, and obvious evidence showed that this results could be improved in further researches.

Lack of cross-reactivity of Ambien (zolpidem) with drugs in standard urine drug screens.

PubMed

Piergies, A A; Sainati, S; Roth-Schechter, B

1997-04-01

To determine in healthy volunteers (men and women; 18 to 40 years old) the potential cross-reactivity of Ambien (zolpidem) and/or its metabolites with drugs that are screened by the Syva EMIT II and the Abbott ADx urine drug screens assays. Open-label, fixed-treatment sequence of 1 night each of treatment with zolpidem (10 mg) and temazepam (15 mg). Clinical Pharmacology Unit within a teaching hospital. Over a 24-hour period, presence or absence of positive results on the Syva EMIT II or the Abbott ADx urine drug assay system, each performed at two different laboratory assay sites. Following ingestion of zolpidem, no subject had any positive response in either laboratory to the Syva EMIT II or the Abbott ADx urine drug screen assays at 0, 4, 8, 12, and 24 hours postdose. During the same time period, all subjects had measurable zolpidem plasma concentrations at 1.5 and 8 hours postdose, with mean concentrations of 115.2 ng/mL and 30.1 ng/mL, respectively (in agreement with its half-life of 2.5 hours). The positive response rate at 10 hours after ingestion of Restoril (temazepam) among the four laboratory/assay combinations ranged from 36.8% to 73.7%, a range that is within the reported response rates for these tests. These data indicate that zolpidem will not cross-react in standard urine drug screens with benzodiazepines, opiates, barbiturates, cocaine, cannabinoids, or amphetamines.

High-Intensity Cannabis Use And HIV Clinical Outcomes Among HIV-Positive People Who Use Illicit Drugs in Vancouver, Canada

PubMed Central

Lake, Stephanie; Kerr, Thomas; Capler, Rielle; Shoveller, Jeannie; Montaner, Julio; Milloy, M-J

2017-01-01

Background Reforms to the legal status of medical and non-medical cannabis are underway in many jurisdictions, including Canada, as are renewed efforts to scale-up HIV treatment-as-prevention (TasP) initiatives. It has been suggested that high-intensity cannabis use may be associated with sub-optimal HIV treatment outcomes. Thus, using data from a setting with a community-wide treatment-as-prevention (TasP) initiative coinciding with increasing access to medical cannabis, we sought to investigate the possible impact of high-intensity cannabis use on HIV clinical outcomes. Methods Data was derived from the ACCESS study, a prospective cohort of HIV-positive people who use illicit drugs (PWUD) in Vancouver, Canada. Cohort data was confidentially linked to comprehensive clinical profiles, including records of all antiretroviral therapy (ART) dispensations and longitudinal plasma HIV-1 RNA viral load (VL) monitoring. We used generalized estimating equations (GEEs) to estimate the longitudinal bivariable and multivariable relationships between at least daily cannabis use and two key clinical outcomes: overall engagement in ART care, and achieving a non-detectable VL among ART-exposed participants. Results Between December 2005 and June 2015, 874 HIV-positive PWUD (304 [35%] non-male) were included in this study. In total, 788 (90%) were engaged in HIV care at least once over the study period, of whom 670 (85%) achieved non-detectable VL at least once. In multivariable analyses, ≥ daily cannabis use did not predict lower odds of ART care (Adjusted Odds Ratio [AOR]: 1.02, 95% confidence interval [CI]: 0.77–1.36) or VL non-detectability among ART-exposed (AOR: 0.96, 95% CI: 0.75–1.21). Conclusion Our results showed no statistically significant impact of daily cannabis use on the likelihood of ART care or VL non-detectability among ART-exposed HIV-positive PWUD. These findings are reassuring in light of the impending legalization of cannabis in Canada and ongoing

Medicinal and illegal drugs among Danish car drivers.

PubMed

Behrensdorff, Inge; Steentoft, Anni

2003-11-01

The objective of this study was to get an insight into the prevalence of medicinal and illegal drugs among car drivers in a Danish rural area. The police randomly stopped about 1000 car drivers and asked them to deliver a saliva sample and gave them a questionnaire to fill in at home. Laboratory analyses by specific methods of samples, which a screening found positive, confirmed that 2% were positive for benzodiazepines or illegal drugs (amphetamine, cannabis, cocaine or opiates): 1.3% were positive for illegal drugs and 0.7% for benzodiazepines. Questionnaire statements from some of the drivers confirm that occasionally some of these drive despite a suspicion to be under the influence of an illegal drug (2.8%), an illegal drug including alcohol (4%), a hazardous medicinal drug including alcohol (8.5%), or alcohol alone above the legal limit (24.5%). These results are considered reliable for the survey area and may not reflect national conditions. The overall results indicate that in this study driving under the influence of illegal drugs or alcohol seems to be associated to especially men, aged 22-44 years. Driving under the influence of hazardous medicinal drugs seems to be associated to middle-aged/elderly drivers, both men and women.

Anxiety sensitivity and self-reported reasons for drug use.

PubMed

Stewart, S H; Karp, J; Pihl, R O; Peterson, R A

1997-01-01

Two studies examined the relationships between anxiety sensitivity (AS), drug use, and reasons for drug use. In Study 1, 229 university students (57% F) completed the Anxiety Sensitivity Index (ASI) and a drug use survey, assessing use of a variety of drugs within the last month, and coping reasons for drug use. Consistent with a modified tension-reduction hypothesis, ASI scores were positively correlated with the number of both anxiety- and depression-related reasons for drug use endorsed. In Study 2, 219 university students (74% F) completed the ASI and a drug use survey, assessing use of several drugs (e.g., alcohol, cigarettes, caffeine, and marijuana/hashish) within the last year, and primary reasons (coping, affiliative, or enhancement) for the use of each drug. Marijuana/hashish users reported lower ASI scores than non-users supporting a negative relation between AS and the use of cannabis. ASI scores were positively correlated with the use of alcohol primarily to cope, and negatively correlated with the use of alcohol primarily to affiliate, among both gender groups, and ASI scores were positively correlated with the use of nicotine primarily to cope among the females. Implications of these findings for understanding risk for abuse of stress-response-dampening drugs by high AS individuals are discussed.

Lesser snow goose helminths show recurring and positive parasite infection-diversity relations.

PubMed

Dargent, Felipe; Morrill, André; Alisauskas, Ray T; McLaughlin, J Daniel; Shutler, Dave; Forbes, Mark R

2017-04-01

The patterns and mechanisms by which biological diversity is associated with parasite infection risk are important to study because of their potential implications for wildlife population's conservation and management. Almost all research in this area has focused on host species diversity and has neglected parasite diversity, despite evidence that parasites are important drivers of community structure and ecosystem processes. Here, we assessed whether presence or abundance of each of nine helminth species parasitizing lesser snow geese ( Chen caerulescens ) was associated with indices of parasite diversity (i.e. species richness and Shannon's Diversity Index). We found repeated instances of focal parasite presence and abundance having significant positive co-variation with diversity measures of other parasites. These results occurred both within individual samples and for combinations of all samples. Whereas host condition and parasite facilitation could be drivers of the patterns we observed, other host- or parasite-level effects, such as age or sex class of host or taxon of parasite, were discounted as explanatory variables. Our findings of recurring and positive associations between focal parasite abundance and diversity underscore the importance of moving beyond pairwise species interactions and contexts, and of including the oft-neglected parasite species diversity in infection-diversity studies.

Drug-Path: a database for drug-induced pathways

PubMed Central

Zeng, Hui; Cui, Qinghua

2015-01-01

Some databases for drug-associated pathways have been built and are publicly available. However, the pathways curated in most of these databases are drug-action or drug-metabolism pathways. In recent years, high-throughput technologies such as microarray and RNA-sequencing have produced lots of drug-induced gene expression profiles. Interestingly, drug-induced gene expression profile frequently show distinct patterns, indicating that drugs normally induce the activation or repression of distinct pathways. Therefore, these pathways contribute to study the mechanisms of drugs and drug-repurposing. Here, we present Drug-Path, a database of drug-induced pathways, which was generated by KEGG pathway enrichment analysis for drug-induced upregulated genes and downregulated genes based on drug-induced gene expression datasets in Connectivity Map. Drug-Path provides user-friendly interfaces to retrieve, visualize and download the drug-induced pathway data in the database. In addition, the genes deregulated by a given drug are highlighted in the pathways. All data were organized using SQLite. The web site was implemented using Django, a Python web framework. Finally, we believe that this database will be useful for related researches. Database URL: http://www.cuilab.cn/drugpath PMID:26130661

Drug-Path: a database for drug-induced pathways.

PubMed

Zeng, Hui; Qiu, Chengxiang; Cui, Qinghua

2015-01-01

Some databases for drug-associated pathways have been built and are publicly available. However, the pathways curated in most of these databases are drug-action or drug-metabolism pathways. In recent years, high-throughput technologies such as microarray and RNA-sequencing have produced lots of drug-induced gene expression profiles. Interestingly, drug-induced gene expression profile frequently show distinct patterns, indicating that drugs normally induce the activation or repression of distinct pathways. Therefore, these pathways contribute to study the mechanisms of drugs and drug-repurposing. Here, we present Drug-Path, a database of drug-induced pathways, which was generated by KEGG pathway enrichment analysis for drug-induced upregulated genes and downregulated genes based on drug-induced gene expression datasets in Connectivity Map. Drug-Path provides user-friendly interfaces to retrieve, visualize and download the drug-induced pathway data in the database. In addition, the genes deregulated by a given drug are highlighted in the pathways. All data were organized using SQLite. The web site was implemented using Django, a Python web framework. Finally, we believe that this database will be useful for related researches. © The Author(s) 2015. Published by Oxford University Press.

The runway model of drug self-administration

PubMed Central

Ettenberg, Aaron

2009-01-01

Behavioral scientists have employed operant runways as a means of investigating the motivational impact of incentive stimuli for the better part of the past 100 years. In this task, the speed with which a trained animal traverses a long straight alley for positive incentive stimuli, like food or water, provides a reliable index of the subject’s motivation to seek those stimuli. The runway is therefore a particularly appropriate tool for investigating the drug-seeking behavior of animals working for drugs of abuse. The current review describes our laboratory’s work over the past twenty years developing and implementing an operant runway model of drug self-administration. Procedures are described that methodologically dissociate the antecedent motivational processes that induce an animal to seek a drug, from the positive reinforcing consequences of actually earning the drug. Additional work is reviewed on the use of the runway method as a means of modeling the factors that often result in a “relapse” of drug self-administration after a period of abstinence (i.e., a response reinstatement test), as are runway studies that revealed the presence of opposing positive and negative consequences of self-administered cocaine. This body of work suggests that the runway method has served as a powerful behavioral tool for the study of the behavioral and neurobiological basis of drug self-administration. PMID:19032964

"It is easier for me to shoot up": stigma, abandonment, and why HIV-positive drug users in Russia fail to link to HIV care.

PubMed

Kiriazova, Tetiana; Lunze, Karsten; Raj, Anita; Bushara, Natalia; Blokhina, Elena; Krupitsky, Evgeny; Bridden, Carly; Lioznov, Dmitry; Samet, Jeffrey H; Gifford, Allen L

2017-05-01

Many HIV-positive people who inject drugs (PWID) globally are not receiving HIV care. This represents a major challenge among key populations to end the global HIV epidemic. This qualitative study explored the process and associated barriers of linking HIV-positive PWID who are in addiction treatment to HIV care in St. Petersburg, Russia. We conducted three focus groups and seven semi-structured interviews with participants in the LINC ("Linking Infectious and Narcology Care") project at addiction and HIV hospitals in St. Petersburg. The sample consisted of 25 HIV-infected patients with opioid dependence and seven health-care providers, including addiction and infectious disease physicians and case managers. A variety of intertwining factors influence effective engagement of PWID with HIV treatment. Stigma, problematic patient-provider relationships, and fragmented health care were the main challenges for HIV care initiation by PWID, which were further exacerbated by injection drug use. Effective linkage of PWID to HIV care requires acknowledging and addressing stigma's role and different perspectives of patients and providers.

Association of serum brain derived neurotropic factor with duration of drug-naive period and positive-negative symptom scores in drug naive schizophrenia.

PubMed

Bakirhan, Abdurrahim; Yalcin Sahiner, Safak; Sahiner, Ismail Volkan; Safak, Yasir; Goka, Erol

2017-01-01

The aim of this study was to compare the serum brain derived neurotropic factor (BNDF) levels of patients with schizophrenia who had never received an antipsychotic treatment with those of a control group. Also, to analyze the relationship between the Positive and Negative Symptom Scale (PANSS) scores and BDNF levels of the patients during the period they were drug-naive. The sample of the study comprised patients who presentedto the Psychiatry Clinic and were admitted after a distinctive schizophrenia diagnosis was made in accordance with the fourth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR) diagnosis classification and who were not using and never had any antipsychotic medicine. A total of 160 participants were included in the study, 80 of whom had schizophrenia patients and 80 constituted the age- and sex-matched healthy control group. Before the start of the treatment, the serum samples to be checked for the BDNF levels were collected from the patients. The difference between the average BDNF levels of the groups were statistically significant (t = -5.25; p˂.001). An analysis as to whether there was a relation between the BDNF levels and the drug-naïve duration indicated no correlations. An examination of the relationship between PANSS scores and BDNF levels of the patients yielded no correlations. Serum BDNF levels seem to be one of the indicators of schizophrenia and its progress; nevertheless, we still do not have sufficient information about this neurotropic factor. In light of our study, the neurodevelopmental changes that occur at disease onset of the illness prominently affect the progress of the illness, which highlights the importance of the treatment in the early stages.

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

PubMed

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

2017-10-10

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

Syndemic vulnerability, sexual and injection risk behaviors, and HIV continuum of care outcomes in HIV-positive injection drug users

PubMed Central

Mizuno, Yuko; Purcell, David W.; Knowlton, Amy R.; Wilkinson, James D.; Gourevitch, Marc N.; Knight, Kelly R.

2015-01-01

Limited investigations have been conducted on syndemics and HIV continuum of care outcomes. Using baseline data from a multi-site, randomized controlled study of HIV-positive injection drug users (n=1052), we examined whether psychosocial factors co-occurred, and whether these factors were additively associated with behavioral and HIV continuum of care outcomes. Experiencing one type of psychosocial problem was significantly (p<0.05) associated with an increased odds of experiencing another type of problem. Persons with 3 or more psychosocial problems were significantly more likely to report sexual and injection risk behaviors and were less likely to be adherent to HIV medications. Persons with 4 or more problems were less likely to be virally suppressed. Reporting any problems was associated with not currently taking HIV medications. Our findings highlight the association of syndemics not only with risk behaviors, but also with outcomes related to the continuum of care for HIV-positive persons. PMID:25249392

Multifunctional High Drug Loading Nanocarriers for Cancer Drug Delivery

NASA Astrophysics Data System (ADS)

Jin, Erlei

2011-12-01

Most anticancer drugs have poor water-solubility, rapid blood clearance, low tumor-selectivity and severe systemic toxicity to healthy tissues. Thus, polymeric nanocarriers have been widely explored for anticancer drugs to solve these problems. However, polymer nanocarriers developed to date still suffer drawbacks including low drug loading contents, premature drug release, slow cellular internalization, slow intracellular drug release and thereby low therapeutic efficiency in cancer thermotherapy. Accordingly, in this dissertation, functional nanocapsules and nanoparticles including high drug loading liposome-like nanocapsules, high drug loading phospholipid-mimic nanocapsules with fast intracellular drug release, high drug loading charge-reversal nanocapsules, TAT based long blood circulation nanoparticles and charge-reversal nuclear targeted nanoparticles are designed and synthesized. These functional carriers have advantages such as high drug loading contents without premature drug release, fast cellular internalization and intracellular drug release, nuclear targeted delivery and long blood circulation. As a result, all these drug carriers show much higher in vitro and in vivo anti-cancer activities.

Significant drug-nutrient interactions.

PubMed

Kirk, J K

1995-04-01

Many nutrients substantially interfere with pharmacotherapeutic goals. The presence of certain nutrients in the gastrointestinal tract affects the bioavailability and disposition of many oral medications. Drug-nutrient interactions can also have positive effects that result in increased drug absorption or reduced gastrointestinal irritation. Knowing the significant drug-nutrient interactions can help the clinician identify the nutrients to avoid with certain medications, as well as the therapeutic agents that should be administered with food. This information can be used to educate patients and optimize pharmacotherapy.

Relationship between hunger, adherence to antiretroviral therapy and plasma HIV RNA suppression among HIV-positive illicit drug users in a Canadian setting.

PubMed

Anema, Aranka; Kerr, Thomas; Milloy, M-J; Feng, Cindy; Montaner, Julio S G; Wood, Evan

2014-04-01

Food insecurity may be a barrier to achieving optimal HIV treatment-related outcomes among illicit drug users. This study therefore, aimed to assess the impact of severe food insecurity, or hunger, on plasma HIV RNA suppression among illicit drug users receiving antiretroviral therapy (ART). A cross-sectional Multivariate logistic regression model was used to assess the potential relationship between hunger and plasma HIV RNA suppression. A sample of n = 406 adults was derived from a community-recruited open prospective cohort of HIV-positive illicit drug users, in Vancouver, British Columbia (BC), Canada. A total of 235 (63.7%) reported "being hungry and unable to afford enough food," and 241 (59.4%) had plasma HIV RNA < 50 copies/ml. In unadjusted analyses, self-reported hunger was associated with lower odds of plasma HIV RNA suppression (Odds Ratio = 0.59, 95% confidence interval [CI]: 0.39-0.90, p = 0.015). In multivariate analyses, this association was no longer significant after controlling for socio-demographic, behavioral, and clinical characteristics, including 95% adherence (Adjusted Odds Ratio [AOR] = 0.65, 95% CI: 0.37-1.10, p = 0.105). Multivariate models stratified by 95% adherence found that the direction and magnitude of this association was not significantly altered by the adherence level. Hunger was common among illicit drug users in this setting. Although, there was an association between hunger and lower likelihood of plasma HIV RNA suppression, this did not persist in adjusted analyses. Further research is warranted to understand the social-structural, policy, and physical factors shaping the HIV outcomes of illicit drug users.

Injecting drug use is associated with a more rapid CD4 cell decline among treatment naïve HIV-positive patients in Indonesia

PubMed Central

Meijerink, Hinta; Wisaksana, Rudi; Iskandar, Shelly; den Heijer, Martin; van der Ven, Andre J A M; Alisjahbana, Bachti; van Crevel, Reinout

2014-01-01

Background It remains unclear whether the natural course of human immunodeficiency virus (HIV) differs in subjects infected through injecting drug use (IDU) and no data have been published from low- or middle-income countries. We addressed this question in an urban cohort in Indonesia, which is experiencing a rapidly growing HIV epidemic strongly driven by IDU. Methods All antiretroviral treatment (ART) naïve HIV-positive patients who had at least two subsequent CD4 cell counts available before starting ART were included in this study. We examined the association between IDU and CD4 cell decline using a linear mixed model, with adjustment for possible confounders such as HIV viral load and hepatitis C antibodies. Results Among 284 HIV-positive ART naïve patients, the majority were male (56%) with a history of IDU (79% among men). People with a history of IDU had a statistically significant faster decline in CD4 cells (p<0.001). Based on our data, patients with a history of IDU would have an average 33% decline in CD4 cells after one year without ART, compared with a 22% decline among non-users. At two years, the decline would average 66 and 40%, respectively. No other factor was significantly associated with CD4 cell decline. Conclusions We show that a history of IDU is associated with a more rapid CD4 cell natural decline among HIV-positive individuals in Indonesia. These findings have implications for monitoring ART naïve patients with a history of IDU and for starting ART in this group. PMID:24388495

Phenotypic drug profiling in droplet microfluidics for better targeting of drug-resistant tumors.

PubMed

Sarkar, S; Cohen, N; Sabhachandani, P; Konry, T

2015-12-07

Acquired drug resistance is a key factor in the failure of chemotherapy. Due to intratumoral heterogeneity, cancer cells depict variations in intracellular drug uptake and efflux at the single cell level, which may not be detectable in bulk assays. In this study we present a droplet microfluidics-based approach to assess the dynamics of drug uptake, efflux and cytotoxicity in drug-sensitive and drug-resistant breast cancer cells. An integrated droplet generation and docking microarray was utilized to encapsulate single cells as well as homotypic cell aggregates. Drug-sensitive cells showed greater death in the presence or absence of Doxorubicin (Dox) compared to the drug-resistant cells. We observed heterogeneous Dox uptake in individual drug-sensitive cells while the drug-resistant cells showed uniformly low uptake and retention. Dox-resistant cells were classified into distinct subsets based on their efflux properties. Cells that showed longer retention of extracellular reagents also demonstrated maximal death. We further observed homotypic fusion of both cell types in droplets, which resulted in increased cell survival in the presence of high doses of Dox. Our results establish the applicability of this microfluidic platform for quantitative drug screening in single cells and multicellular interactions.

Oral fluid vs. Urine Analysis to Monitor Synthetic Cannabinoids and Classic Drugs Recent Exposure

PubMed Central

Blandino, Vincent; Wetzel, Jillian; Kim, Jiyoung; Haxhi, Petrit; Curtis, Richard; Concheiro, Marta

2018-01-01

Background Urine is a common biological sample to monitor recent drug exposure, and oral fluid is an alternative matrix of increasing interest in clinical and forensic toxicology. Limited data are available about oral fluid vs. urine drug disposition, especially for synthetic cannabinoids. Objective To compare urine and oral fluid as biological matrices to monitor recent drug exposure among HIV-infected homeless individuals. Methods Seventy matched urine and oral fluid samples were collected from 13 participants. Cannabis, amphetamines, benzodiazepines, cocaine and opiates were analyzed in urine by the enzyme-multiplied-immunoassay-technique and in oral fluid by liquid chromatography tandem mass spectrometry (LC-MSMS). Eleven synthetic cannabinoids were analyzed in urine and in oral fluid by LC-MSMS. Results Five oral fluid samples were positive for AB-FUBINACA. In urine, 4 samples tested positive for synthetic cannabinoids PB-22, 5-Fluoro-PB-22, AB-FUBINACA, and metabolites UR-144 5-pentanoic acid and UR-144 4-hydroxypentyl. In only one case, oral fluid and urine results matched, both specimens being AB-FUBINACA positive. For cannabis, 40 samples tested positive in urine and 30 in oral fluid (85.7% match). For cocaine, 37 urine and 52 oral fluid samples were positive (75.7% match). Twenty-four urine samples were positive for opiates, and 25 in oral fluid (81.4% match). For benzodiazepines, 23 samples were positive in urine and 25 in oral fluid (85.7% match). Conclusion/Discussion These results offer new information about drugs disposition between urine and oral fluid. Oral fluid is a good alternative matrix to urine for monitoring cannabis, cocaine, opiates and benzodiazepines recent use; however, synthetic cannabinoids showed mixed results. PMID:29173162

Oral Fluid vs. Urine Analysis to Monitor Synthetic Cannabinoids and Classic Drugs Recent Exposure.

PubMed

Blandino, Vincent; Wetzel, Jillian; Kim, Jiyoung; Haxhi, Petrit; Curtis, Richard; Concheiro, Marta

2017-01-01

Urine is a common biological sample to monitor recent drug exposure, and oral fluid is an alternative matrix of increasing interest in clinical and forensic toxicology. Limited data are available about oral fluid vs. urine drug disposition, especially for synthetic cannabinoids. To compare urine and oral fluid as biological matrices to monitor recent drug exposure among HIV-infected homeless individuals. Seventy matched urine and oral fluid samples were collected from 13 participants. Cannabis, amphetamines, benzodiazepines, cocaine and opiates were analyzed in urine by the enzyme-multipliedimmunoassay- technique and in oral fluid by liquid chromatography tandem mass spectrometry (LCMSMS). Eleven synthetic cannabinoids were analyzed in urine and in oral fluid by LC-MSMS. Five oral fluid samples were positive for AB-FUBINACA. In urine, 4 samples tested positive for synthetic cannabinoids PB-22, 5-Fluoro-PB-22, AB-FUBINACA, and metabolites UR-144 5-pentanoic acid and UR-144 4-hydroxypentyl. In only one case, oral fluid and urine results matched, both specimens being AB-FUBINACA positive. For cannabis, 40 samples tested positive in urine and 30 in oral fluid (85.7% match). For cocaine, 37 urine and 52 oral fluid samples were positive (75.7% match). Twenty-four urine samples were positive for opiates, and 25 in oral fluid (81.4% match). For benzodiazepines, 23 samples were positive in urine and 25 in oral fluid (85.7% match). These results offer new information about drugs disposition between urine and oral fluid. Oral fluid is a good alternative matrix to urine for monitoring cannabis, cocaine, opiates and benzodiazepines recent use; however, synthetic cannabinoids showed mixed results. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Drug-related stigma and access to care among people who inject drugs in Vietnam.

PubMed

Lan, Chiao-Wen; Lin, Chunqing; Thanh, Duong Cong; Li, Li

2018-03-01

There are considerable challenges faced by people with a history of injecting drug use (PWID) in Vietnam, including drug-related stigma and lack of access to healthcare. Seeking and utilising healthcare, as well as harm reduction programs for PWID, are often hampered by drug-related stigma. This study aimed to examine the impacts of drug-related stigma on access to care and utilisation of harm reduction programs among PWID in Vietnam. A cross-sectional study was conducted in two provinces in Vietnam, Phú Thọ and Vinh Phúc. The study participants completed the survey by using Audio Computer-Assisted Self-Interview between late 2014 and early 2015. Linear multiple regression models and logistic regression models were used to assess the relationship among drug-related stigma, access to care and utilisation of harm reduction programs, including methadone maintenance treatment (MMT) and needle exchange programs (NEP). A total of 900 PWID participated in this study. Drug-related stigma was significantly associated with lower level of access to care, but not with utilisation of MMT or NEP. Older age was positively associated with higher levels of access to care. Levels of education were positively correlated with access to care, as well as utilisation of MMT and NEP. This study underscores the need for future interventions to reduce drug-related stigma in society and in health-care settings to improve PWID's utilisation of care services. Special attention should be paid to younger PWID and those with lower levels of education. © 2017 Australasian Professional Society on Alcohol and other Drugs.

Amphiphilic Peptide Nanorods Based on Oligo-Phenylalanine as a Biocompatible Drug Carrier.

PubMed

Song, Su Jeong; Lee, Seulgi; Ryu, Kyoung-Seok; Choi, Joon Sig

2017-09-20

Peptide nanostructure has been widely explored for drug-delivery systems in recent studies. Peptides possess comparatively lower cytotoxicity and are more efficient than polymeric carriers. Here, we propose a peptide nanorod system, composed of an amphiphilic oligo-peptide RH 3 F 8 (Arg-His 3 -Phe 8 ), as a drug-delivery carrier. Arginine is an essential amino acid in typical cell-penetration peptides, and histidine induces endo- and lysosomal escape because of its proton sponge effect. Phenylalanine is introduced to provide rich hydrophobicity for stable self-assembly and drug encapsulation. The self-assembled structure of RH 3 F 8 showed nanorod-shaped morphology, positive surface charge, and retained formation in water for 35 days. RH 3 F 8 , labeled with Nile Red, showed high cellar uptake and accumulation in both cytoplasm and nucleus. The RH 3 F 8 nanorods demonstrated negligible cytotoxicity, as shown by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), lactate dehydrogenase (LDH), and hemolysis assays. To confirm the efficiency of drug delivery, curcumin was encapsulated in the RH 3 F 8 nanorod system (RH 3 F 8 -Cur). RH 3 F 8 -Cur showed high encapsulation efficiency (24.63%) under the conditions of 200 μM curcumin. The RH 3 F 8 -Cur retained nanoscale size and positive surface charge, similar to those of the empty RH 3 F 8 nanorods. RH 3 F 8 -Cur displayed a robust anticancer effect in HeLa and A549 cells, and inhibited the proliferation of cancer cells in a zebrafish model. These results indicate that the RH 3 F 8 nanorods may be a promising candidate for a safe and effective drug-delivery system.

Illicit drug exposure in patients evaluated for alleged child abuse and neglect.

PubMed

Oral, Resmiye; Bayman, Levent; Assad, Abraham; Wibbenmeyer, Lucy; Buhrow, Jakob; Austin, Andrea; Bayman, Emine O

2011-06-01

Substantiation of drug exposure in cases with alleged maltreatment is important to provide proper treatment and services to these children and their families. A study performed at University of Iowa Hospitals and Clinics showed that 30% of pediatric patients with burn injuries, which were due to child maltreatment, were also exposed to illicit drugs. The children presenting to the University of Iowa Hospitals and Clinics with alleged maltreatment have been tested for illicit substances since 2004. The objective of this study was to analyze the presence of illicit drug exposure in the pediatric subpopulation admitted to pediatric inpatient and outpatient units for an evaluation for abuse/neglect. The study design is a retrospective chart review. Using hospital databases, every pediatric chart with a child abuse/neglect allegation was retrieved. The association between risk factors and clinical presentation and illicit drug test result was assessed. Excel and SAS were used for statistical analysis. Institutional review board approval was obtained to conduct this study. Six hundred sixty-five charts met study inclusion criteria for child abuse/neglect allegation. Of those, 232 cases were tested for illicit drugs between 2004 and 2008 per the testing protocol. Thirty-four cases (14.7%) tested positive on a drug test. Positive test rates based on clinical presentation were 28.6% (18/63) in neglect cases, 16.1% (5/31) in cases with soft tissue injuries, 14.3% (4/28) in burn injuries, 10.0% (2/20) in cases with sexual abuse, 7.1% (2/28) in cases with fractures, and 4.8% (3/62) in abusive head trauma cases. There were long-term abuse findings in 129 children (55.6%). Logistic regression analysis revealed that positive drug testing was most significantly associated with clinical symptoms suggesting physical abuse or neglect versus sexual abuse (odds ratio [OR] = 6.70; 95% confidence interval [CI], 1.26-35.49; P = 0.026), no or public health insurance versus those with

Patterns of drug use in fatal crashes.

PubMed

Romano, Eduardo; Pollini, Robin A

2013-08-01

To characterize drug prevalence among fatally injured drivers, identify significant associations (i.e. day of week, time of day, age, gender), and compare findings with those for alcohol. Descriptive and logistic mixed-model regression analyses of Fatality Analysis Reporting System data. US states with drug test results for >80% of fatally injured drivers, 1998-2010. Drivers killed in single-vehicle crashes on public roads who died at the scene of the crash (n = 16 942). Drug test results, blood alcohol concentration (BAC), gender, age and day and time of crash. Overall, 45.1% of fatally injured drivers tested positive for alcohol (39.9% BAC ≥ 0.08) and 25.9% for drugs. The most common drugs present were stimulants (7.2%) and cannabinols (7.1%), followed by 'other' drugs (4.1%), multiple drugs (4.1%), narcotics (2.1%) and depressants (1.5%). Drug-involved crashes occurred with relative uniformity throughout the day while alcohol-involved crashes were more common at night (P < 0.01). The odds of testing positive for drugs varied depending upon drug class, driver characteristics, time of day and the presence of alcohol. Fatal single-vehicle crashes involving drugs are less common than those involving alcohol and the characteristics of drug-involved crashes differ, depending upon drug class and whether alcohol is present. Concerns about drug-impaired driving should not detract from the current law enforcement focus on alcohol-impaired driving. © 2013 Society for the Study of Addiction.

Teens and Prescription Drugs: An Analysis of Recent Trends on the Emerging Drug Threat

ERIC Educational Resources Information Center

Office of National Drug Control Policy, 2007

2007-01-01

This report synthesizes a number of national studies that show the intentional abuse of prescription drugs to get high is a growing concern, particularly among teens. The analysis shows that teens are turning away from street drugs and using prescription drugs to get high. New users of prescription drugs have caught up with new users of marijuana.…

Beyond Cue Reactivity: Non-Drug-Related Motivationally Relevant Stimuli Are Necessary to Understand Reactivity to Drug-Related Cues.

PubMed

Versace, Francesco; Engelmann, Jeffrey M; Deweese, Menton M; Robinson, Jason D; Green, Charles E; Lam, Cho Y; Minnix, Jennifer A; Karam-Hage, Maher A; Wetter, David W; Schembre, Susan M; Cinciripini, Paul M

2017-06-01

Neurobiological models of addiction posit that drug use can alter reward processes in two ways: (1) by increasing the motivational relevance of drugs and drug-related cues and (2) by reducing the motivational relevance of non-drug-related rewards. Here, we discuss the results from a series of neuroimaging studies in which we assessed the extent to which these hypotheses apply to nicotine dependence. In these studies, we recorded smokers’ and nonsmokers’ brain responses to a wide array of motivationally relevant visual stimuli that included pleasant, unpleasant, cigarette-related, and neutral images. Based on these findings, we highlight the flaws of the traditional cue reactivity paradigm and we conclude that responses to non-drug-related motivationally relevant stimuli should be used to appropriately gauge the motivational relevance of cigarette-related cues and to identify smokers attributing higher motivational relevance to drug-related cues than to non-drug-related rewards. Identifying these individuals is clinically relevant as they achieve lower rates of long-term smoking abstinence when attempting to quit. Finally, we show how this approach may be extended beyond nicotine dependence to inform theoretical and clinical research in the study of obesity. The cue reactivity paradigm (ie, comparing responses evoked by drug-related cues to those evoked by neutral cues) cannot provide conclusive information about the motivational relevance of drug-related cues. Responses to non-drug-related motivationally relevant stimuli should be used to appropriately gauge the level of motivational relevance that substance-dependent individuals attribute to drug-related cues. © The Author 2017. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Application of drug testing using exhaled breath for compliance monitoring of drug addicts in treatment.

PubMed

Carlsson, Sten; Olsson, Robert; Lindkvist, Irene; Beck, Olof

2015-04-01

Exhaled breath has recently been identified as a possible matrix for drug testing. This study explored the potential of this new method for compliance monitoring of patients being treated for dependence disorders. Outpatients in treatment programs were recruited for this study. Urine was collected as part of clinical routine and a breath sample was collected in parallel together with a questionnaire about their views of the testing procedure. Urine was analyzed for amphetamines, benzodiazepines, cannabis, cocaine, buprenorphine, methadone and opiates using CEDIA immunochemical screening and mass spectrometry confirmation. The exhaled breath was collected using the SensAbues device and analyzed by mass spectrometry for amphetamine, methamphetamine, diazepam, oxazepam, tetrahydrocannabinol, cocaine, benzoylecgonine, buprenorphine, methadone, morphine, codeine and 6-acetylmorphine. A total of 122 cases with parallel urine and breath samples were collected; 34 of these were negative both in urine and breath. Out of 88 cases with positive urine samples 51 (58%) were also positive in breath. Among the patients on methadone treatment, all were positive for methadone in urine and 83% were positive in breath. Among patients in treatment with buprenorphine, 92% were positive in urine and among those 80% were also positive in breath. The questionnaire response documented that in general, patients accepted drug testing well and that the breath sampling procedure was preferred. Compliance testing for the intake of prescribed and unprescribed drugs among patients in treatment for dependence disorders using the exhaled breath sampling technique is a viable method and deserves future attention.

Prevalence of gabapentin in drug overdose postmortem toxicology testing results.

PubMed

Slavova, Svetla; Miller, Alison; Bunn, Terry L; White, Jessica R; Kirschke, David; Light, Tom; Christy, Daniel; Thompson, Gary; Winecker, Ruth

2018-05-01

The goal of this study was to establish and compare baseline data on the prevalence of gabapentin identified through postmortem toxicology testing among drug overdose decedents in several geographically diverse states/jurisdictions with differing levels of drug overdose fatality burdens in 2015. Death certificates and postmortem toxicology result reports from five U.S. jurisdictions were used to identify residents who died from drug overdoses in year 2015 and to calculate prevalence rates of gabapentin in postmortem toxicology by jurisdiction. On average, 22% of all drug overdose decedents in our study tested positive for gabapentin. The percentage of gabapentin-positive overdose deaths varied significantly among jurisdictions: 4% in Northeast Tennessee, 7% in Maricopa County, 15% in West Virginia, 20% in North Carolina, and 41% in Kentucky (p < 0.0001). Among the drug overdose decedents who tested positive for opioids (including heroin), 26% also tested positive for gabapentin, with significant variation among states/jurisdictions (p < 0.0001). There was a significant difference in the gender distribution among drug overdose decedents who tested positive for gabapentin (46% male) vs. those who tested negative for gabapentin (65% male) (p < 0.0001). In Kentucky, gabapentin was listed as a contributing drug on the death certificate in 40% of the overdose deaths with gabapentin-positive toxicology; in North Carolina this percentage was 57%. Routine gabapentin postmortem testing and linking of death certificate, medical examiner, coroner, toxicology, and prescription history data will provide more reliable information on the extent of gabapentin misuse, diversion, and implications for clinical care. Copyright © 2018 Elsevier B.V. All rights reserved.

Prevalence of hepatitis C virus infection and associated factors among male illicit drug users in Cuiabá, Mato Grosso, Brazil.

PubMed

Novais, Antônia Carlos Magalhães; Lopes, Carmen Luci Rodrigues; Reis, Nádia Rúbia da Silva; Silva, Agabo Macêdo Costa E; Martins, Regina Maria Bringel; Souto, Francisco José Dutra

2009-09-01

Intravenous drug injection has been reported as the main risk factor for hepatitis C virus (HCV) infection. The aim of the present study was to describe the prevalence and the epidemiological profile of HCV infection among abusers of illegal injected and non-injected drugs in Cuiabá, state of Mato Grosso, Central Brazil. A cross-sectional study including 314 male drug users from eight detoxification centres was performed. Out of 314 subjects studied, 48 (15.2%) were intravenous drug users. Participants were interviewed and had blood samples taken and tested for the presence of anti-HCV antibodies. Positive samples were tested for the presence of HCV RNA. Genotyping was performed on HCV RNA-positive samples. The overall prevalence of anti-HCV antibodies was 6.4% (n = 20). Out of 20 anti-HCV antibody-positive subjects, 16 (80%) were also HCV RNA-positive. Genotype 1 predominated (75%), followed by 3a (25%). Subtype 1a was more common than 1b. HCV infection was more prevalent among intravenous drug users (33%) than non-injecting users (1.5%). Logistic regression analyses showed independent associations between HCV infection and intravenous drug use, imprisonment and increasing age. In the present study, injecting drug use was the factor most strongly associated to HCV infection and inhaling or sniffing did not represent an increased susceptibility to infection.

Patch testing and cross sensitivity study of adverse cutaneous drug reactions due to anticonvulsants: A preliminary report.

PubMed

Shiny, T N; Mahajan, Vikram K; Mehta, Karaninder S; Chauhan, Pushpinder S; Rawat, Ritu; Sharma, Rajni

2017-03-26

To evaluate the utility of patch test and cross-sensitivity patterns in patients with adverse cutaneous drug reactions (ACDR) from common anticonvulsants. Twenty-four (M:F = 13:11) patients aged 18-75 years with ACDR from anticonvulsants were patch tested 3-27 mo after complete recovery using carbamazepine, phenytoin, phenobarbitone, lamotrigine, and sodium valproate in 10%, 20% and 30% conc. in pet. after informed consent. Positive reactions persisting on D3 and D4 were considered significant. Clinical patterns were exanthematous drug rash with or without systemic involvement (DRESS) in 18 (75%), Stevens-Johnsons syndrome/toxic epidermal necrolysis (SJS/TEN) overlap and TEN in 2 (8.3%) patients each, SJS and lichenoid drug eruption in 1 (4.2%) patient each, respectively. The implicated drugs were phenytoin in 14 (58.3%), carbamazepine in 9 (37.5%), phenobarbitone in 2 (8.3%), and lamotrigine in 1 (4.7%) patients, respectively. Twelve (50%) patients elicited positive reactions to implicated drugs; carbamazepine in 6 (50%), phenytoin alone in 4 (33.3%), phenobarbitone alone in 1 (8.3%), and both phenytoin and phenobarbitone in 1 (8.33%) patients, respectively. Cross-reactions occurred in 11 (92%) patients. Six patients with carbamazepine positive patch test reaction showed cross sensitivity with phenobarbitone, sodium valproate and/or lamotrigine. Three (75%) patients among positive phenytoin patch test reactions had cross reactions with phenobarbitone, lamotrigine, and/or valproate. Carbamazepine remains the commonest anticonvulsant causing ACDRs and cross-reactions with other anticonvulsants are possible. Drug patch testing appears useful in DRESS for drug imputability and cross-reactions established clinically.

Patch testing and cross sensitivity study of adverse cutaneous drug reactions due to anticonvulsants: A preliminary report

PubMed Central

Shiny, T N; Mahajan, Vikram K; Mehta, Karaninder S; Chauhan, Pushpinder S; Rawat, Ritu; Sharma, Rajni

2017-01-01

AIM To evaluate the utility of patch test and cross-sensitivity patterns in patients with adverse cutaneous drug reactions (ACDR) from common anticonvulsants. METHODS Twenty-four (M:F = 13:11) patients aged 18-75 years with ACDR from anticonvulsants were patch tested 3-27 mo after complete recovery using carbamazepine, phenytoin, phenobarbitone, lamotrigine, and sodium valproate in 10%, 20% and 30% conc. in pet. after informed consent. Positive reactions persisting on D3 and D4 were considered significant. RESULTS Clinical patterns were exanthematous drug rash with or without systemic involvement (DRESS) in 18 (75%), Stevens-Johnsons syndrome/toxic epidermal necrolysis (SJS/TEN) overlap and TEN in 2 (8.3%) patients each, SJS and lichenoid drug eruption in 1 (4.2%) patient each, respectively. The implicated drugs were phenytoin in 14 (58.3%), carbamazepine in 9 (37.5%), phenobarbitone in 2 (8.3%), and lamotrigine in 1 (4.7%) patients, respectively. Twelve (50%) patients elicited positive reactions to implicated drugs; carbamazepine in 6 (50%), phenytoin alone in 4 (33.3%), phenobarbitone alone in 1 (8.3%), and both phenytoin and phenobarbitone in 1 (8.33%) patients, respectively. Cross-reactions occurred in 11 (92%) patients. Six patients with carbamazepine positive patch test reaction showed cross sensitivity with phenobarbitone, sodium valproate and/or lamotrigine. Three (75%) patients among positive phenytoin patch test reactions had cross reactions with phenobarbitone, lamotrigine, and/or valproate. CONCLUSION Carbamazepine remains the commonest anticonvulsant causing ACDRs and cross-reactions with other anticonvulsants are possible. Drug patch testing appears useful in DRESS for drug imputability and cross-reactions established clinically. PMID:28396847

Antimicrobial Activities of Methanol, Ethanol and Supercritical CO2 Extracts of Philippine Piper betle L. on Clinical Isolates of Gram Positive and Gram Negative Bacteria with Transferable Multiple Drug Resistance

PubMed Central

Valle, Demetrio L.; Cabrera, Esperanza C.; Puzon, Juliana Janet M.; Rivera, Windell L.

2016-01-01

Piper betle L. has traditionally been used in alternative medicine in different countries for various therapeutic purposes, including as an anti-infective agent. However, studies reported in the literature are mainly on its activities on drug susceptible bacterial strains. This study determined the antimicrobial activities of its ethanol, methanol, and supercritical CO2 extracts on clinical isolates of multiple drug resistant bacteria which have been identified by the Infectious Disease Society of America as among the currently more challenging strains in clinical management. Assay methods included the standard disc diffusion method and the broth microdilution method for the determination of the minimum inhibitory concentration (MIC) and the minimum bactericidal concentrations (MBC) of the extracts for the test microorganisms. This study revealed the bactericidal activities of all the P. betle leaf crude extracts on methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus (VRE), extended spectrum β-lactamase-producing Enterobacteriaceae, carbapenem-resistant Enterobacteriaceae, and metallo-β-lactamase-producing Pseudomonas aeruginosa and Acinetobacter baumannii, with minimum bactericidal concentrations that ranged from 19μg/ml to 1250 μg/ml. The extracts proved to be more potent against the Gram positive MRSA and VRE than for the Gram negative test bacteria. VRE isolates were more susceptible to all the extracts than the MRSA isolates. Generally, the ethanol extracts proved to be more potent than the methanol extracts and supercritical CO2 extracts as shown by their lower MICs for both the Gram positive and Gram negative MDRs. MTT cytotoxicity assay showed that the highest concentration (100 μg/ml) of P. betle ethanol extract tested was not toxic to normal human dermal fibroblasts (HDFn). Data from the study firmly established P. betle as an alternative source of anti-infectives against multiple drug resistant bacteria. PMID

Antimicrobial Activities of Methanol, Ethanol and Supercritical CO2 Extracts of Philippine Piper betle L. on Clinical Isolates of Gram Positive and Gram Negative Bacteria with Transferable Multiple Drug Resistance.

PubMed

Valle, Demetrio L; Cabrera, Esperanza C; Puzon, Juliana Janet M; Rivera, Windell L

2016-01-01

Piper betle L. has traditionally been used in alternative medicine in different countries for various therapeutic purposes, including as an anti-infective agent. However, studies reported in the literature are mainly on its activities on drug susceptible bacterial strains. This study determined the antimicrobial activities of its ethanol, methanol, and supercritical CO2 extracts on clinical isolates of multiple drug resistant bacteria which have been identified by the Infectious Disease Society of America as among the currently more challenging strains in clinical management. Assay methods included the standard disc diffusion method and the broth microdilution method for the determination of the minimum inhibitory concentration (MIC) and the minimum bactericidal concentrations (MBC) of the extracts for the test microorganisms. This study revealed the bactericidal activities of all the P. betle leaf crude extracts on methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus (VRE), extended spectrum β-lactamase-producing Enterobacteriaceae, carbapenem-resistant Enterobacteriaceae, and metallo-β-lactamase-producing Pseudomonas aeruginosa and Acinetobacter baumannii, with minimum bactericidal concentrations that ranged from 19μg/ml to 1250 μg/ml. The extracts proved to be more potent against the Gram positive MRSA and VRE than for the Gram negative test bacteria. VRE isolates were more susceptible to all the extracts than the MRSA isolates. Generally, the ethanol extracts proved to be more potent than the methanol extracts and supercritical CO2 extracts as shown by their lower MICs for both the Gram positive and Gram negative MDRs. MTT cytotoxicity assay showed that the highest concentration (100 μg/ml) of P. betle ethanol extract tested was not toxic to normal human dermal fibroblasts (HDFn). Data from the study firmly established P. betle as an alternative source of anti-infectives against multiple drug resistant bacteria.

Magnetically Actuated Soft Capsule With the Multimodal Drug Release Function

PubMed Central

Yim, Sehyuk; Goyal, Kartik; Sitti, Metin

2014-01-01

In this paper, we present a magnetically actuated multimodal drug release mechanism using a tetherless soft capsule endoscope for the treatment of gastric disease. Because the designed capsule has a drug chamber between both magnetic heads, if it is compressed by the external magnetic field, the capsule could release a drug in a specific position locally. The capsule is designed to release a drug in two modes according to the situation. In the first mode, a small amount of drug is continuously released by a series of pulse type magnetic field (0.01–0.03 T). The experimental results show that the drug release can be controlled by the frequency of the external magnetic pulse. In the second mode, about 800 mm3 of drug is released by the external magnetic field of 0.07 T, which induces a stronger magnetic attraction than the critical force for capsule’s collapsing. As a result, a polymeric coating is formed around the capsule. The coated area is dependent on the drug viscosity. This paper presents simulations and various experiments to evaluate the magnetically actuated multimodal drug release capability. The proposed soft capsules could be used as minimally invasive tetherless medical devices with therapeutic capability for the next generation capsule endoscopy. PMID:25378896

Validity of suspected alcohol and drug violations in aviation employees.

PubMed

Li, Guohua; Brady, Joanne E; DiMaggio, Charles; Baker, Susan P; Rebok, George W

2010-10-01

In the United States, transportation employees who are suspected of using alcohol and drugs are subject to reasonable-cause testing. This study aims to assess the validity of suspected alcohol and drug violations in aviation employees. Using reasonable-cause testing and random testing data from the Federal Aviation Administration for the years 1995-2005, we calculated the positive predictive value (PPV) and positive likelihood ratio (LR+) of suspected alcohol and drug violations. The true status of violations was based on testing results, with an alcohol violation being defined as a blood alcohol concentration of ≥0.04 mg/dl and a drug violation as a test positive for marijuana, cocaine, amphetamines, phencyclidine or opiates. During the 11-year study period, a total of 2284 alcohol tests and 2015 drug tests were performed under the reasonable-cause testing program. The PPV was 37.7% [95% confidence interval (CI), 35.7-39.7%] for suspected alcohol violations and 12.6% (95% CI, 11.2-14.1%) for suspected drug violations. Random testing revealed an overall prevalence of 0.09% for alcohol violations and 0.6% for drug violations. The LR+ was 653.6 (95% CI, 581.7-734.3) for suspected alcohol violations and 22.5 (95% CI, 19.6-25.7) for suspected drug violations. The discriminative power of reasonable-cause testing suggests that, despite its limited positive predictive value, physical and behavioral observation represents an efficient screening method for detecting alcohol and drug violations. The limited positive predictive value of reasonable-cause testing in aviation employees is due in part to the very low prevalence of alcohol and drug violations. © 2010 The Authors, Addiction © 2010 Society for the Study of Addiction.

Validity of Suspected Alcohol and Drug Violations in Aviation Employees

PubMed Central

Li, Guohua; Brady, Joanne E.; DiMaggio, Charles; Baker, Susan P.; Rebok, George W.

2012-01-01

Introduction In the United States, transportation employees who are suspected of using alcohol and drugs are subject to reasonable-cause testing. This study aims to assess the validity of suspected alcohol and drug violations in aviation employees. Methods Using reasonable-cause testing and random testing data from the Federal Aviation Administration for the years 1995 through 2005, we calculated the positive predictive value (PPV) and positive likelihood ratio (LR+) of suspected alcohol and drug violations. The true status of violations was based on testing results, with an alcohol violation being defined as a blood alcohol concentration of ≥40 mg/dL and a drug violation as a test positive for marijuana, cocaine, amphetamines, phencyclidine, or opiates. Results During the 11-year study period, a total of 2,284 alcohol tests and 2,015 drug tests were performed under the reasonable-cause testing program. The PPV was 37.7% [95% confidence interval (CI), 35.7–39.7%] for suspected alcohol violations and 12.6% (95% CI, 11.2–14.1%) for suspected drug violations. Random testing revealed an overall prevalence of 0.09% (601/649,796) for alcohol violations and 0.6% (7,211/1,130,922) for drug violations. The LR+ was 653.6 (95% CI, 581.7–734.3) for suspected alcohol violations and 22.5 (95% CI, 19.6–25.7) for suspected drug violations. Discussion The discriminative power of reasonable-cause testing suggests that, despite its limited positive predictive value, physical and behavioral observation represents an efficient screening method for detecting alcohol and drug violations. The limited positive predictive value of reasonable-cause testing in aviation employees is due in part to the very low prevalence of alcohol and drug violations. PMID:20712820

Self-association and cyclodextrin solubilization of drugs.

PubMed

Loftsson, Thorsteinn; Magnúsdóttir, Auethur; Másson, Már; Sigurjónsdóttir, Jóhanna F

2002-11-01

Phase-solubility diagrams are frequently used to calculate stoichiometry of drug/cyclodextrin complexes. Linear diagrams (A(L)-type systems) are thought to indicate that the complexes are first order with respect to cyclodextrin and first or higher order with respect to the drug. Positive deviation from linearity (A(P)-type systems) are thought to indicate formation of complexes that are first order with respect to the drug but second or higher order with respect to cyclodextrin. The phase solubility of several different compounds, i.e., cholesterol, ibuprofen, diflunisal, alprazolam, 17beta-estradiol and diethylstilbestrol, and various charged and uncharged cyclodextrins was investigated. Phase-solubility diagrams of cholesterol in aqueous cyclodextrin solutions were all of A(P) type. However, the phase-solubility diagrams obtained with charged cyclodextrins could not be fitted to complexes of second or higher order with respect to cyclodextrin. The phase-solubility diagrams of ibuprofen and diflunisal were of A(L) type with slope greater than unity indicating formation of 2:1 drug/cyclodextrin complexes. However, Job's plots and space filling docking studies indicated that 1:1 complexes were formed. These and other observations show that stoichiometry of drug/cyclodextrin complexes cannot be derived from simple phase-solubility studies. Furthermore, the results indicate that drug/cyclodextrin complexes can self-associate to form water-soluble aggregates, which then can further solubilize the drug through non-inclusion complexation. Copyright 2002 Wiley-Liss, Inc. and the American Pharmaceutical Association J Pharm Sci 91:2307-2316, 2002

Influence of drugs of abuse and alcohol upon patients admitted to acute psychiatric wards: physician's assessment compared to blood drug concentrations.

PubMed

Mordal, Jon; Medhus, Sigrid; Holm, Bjørn; Mørland, Jørg; Bramness, Jørgen G

2013-06-01

In acute psychiatric services, rapid and accurate detection of psychoactive substance intake may be required for appropriate diagnosis and intervention. The aim of this study was to investigate the relationship between (a) drug influence as assessed by physicians and (b) blood drug concentrations among patients admitted to acute psychiatric wards. We also explored the possible effects of age, sex, and psychotic symptoms on physician's assessment of drug influence. In a cross-sectional study, the sample comprised 271 consecutive admissions from 2 acute psychiatric wards. At admission, the physician on call performed an overall judgment of drug influence. Psychotic symptoms were assessed with the positive subscale of the Positive and Negative Syndrome Scale. Blood samples were screened for a wide range of psychoactive substances, and quantitative results were used to calculate blood drug concentration scores. Patients were judged as being under the influence of drugs and/or alcohol in 28% of the 271 admissions. Psychoactive substances were detected in 56% of the blood samples. Altogether, 15 different substances were found; up to 8 substances were found in samples from 1 patient. Markedly elevated blood drug concentration scores were estimated for 15% of the patients. Physician's assessment was positively related to the blood drug concentration scores (r = 0.52; P < 0.001), to symptoms of excitement, and to the detection of alcohol, cannabis, and amphetamines. The study demonstrates the major impact of alcohol and drugs in acute psychiatric settings and illustrates the challenging nature of the initial clinical assessment.

Prison rights: mandatory drugs tests and performance indicators for prisons.

PubMed Central

Gore, S. M.; Bird, A. G.; Ross, A. J.

1996-01-01

Mandatory drugs testing of prisoners applies throughout England and Wales. Data from the 1995 pilot study in eight prisons show that the proportion testing positive for opiates or benzodiazepines rose from 4.1% to 7.4% between the first and second phase of random testing and that there was a 20% increase over 1993-4 in the provisional total of assaults for 1995. Interpretation of these data is difficult, but this is no excuse for prevarication over the danger that this policy may induce inmates to switch from cannabis (which has a negligible public health risk) to injectable class A drugs (a serious public health risk) in prison. The performance indicators for misuse of drugs that are based on the random mandatory drugs testing programme lack relevant covariate information about the individuals tested and are not reliable or timely for individual prisons. PMID:8646103

21 CFR 892.5780 - Light beam patient position indicator.

Code of Federal Regulations, 2011 CFR

2011-04-01

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

21 CFR 892.5780 - Light beam patient position indicator.

Code of Federal Regulations, 2013 CFR

2013-04-01

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

21 CFR 892.5780 - Light beam patient position indicator.

Code of Federal Regulations, 2014 CFR

2014-04-01

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

21 CFR 892.5780 - Light beam patient position indicator.

Code of Federal Regulations, 2012 CFR

2012-04-01

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

Current position of high-resolution MS for drug quantification in clinical & forensic toxicology.

PubMed

Meyer, Markus R; Helfer, Andreas G; Maurer, Hans H

2014-08-01

This paper reviews high-resolution MS approaches published from January 2011 until March 2014 for the quantification of drugs (of abuse) and/or their metabolites in biosamples using LC-MS with time-of-flight or Orbitrap™ mass analyzers. Corresponding approaches are discussed including sample preparation and mass spectral settings. The advantages and limitations of high-resolution MS for drug quantification, as well as the demand for a certain resolution or a specific mass accuracy are also explored.

Membrane-destabilizing activity of pH-responsive cationic lysine-based surfactants: role of charge position and alkyl chain length.

PubMed

Nogueira, Daniele Rubert; Mitjans, Montserrat; Morán, M Carmen; Pérez, Lourdes; Vinardell, M Pilar

2012-09-01

Many strategies for treating diseases require the delivery of drugs into the cell cytoplasm following internalization within endosomal vesicles. Thus, compounds triggered by low pH to disrupt membranes and release endosomal contents into the cytosol are of particular interest. Here, we report novel cationic lysine-based surfactants (hydrochloride salts of N(ε)- and N(α)-acyl lysine methyl ester) that differ in the position of the positive charge and the length of the alkyl chain. Amino acid-based surfactants could be promising novel biomaterials in drug delivery systems, given their biocompatible properties and low cytotoxic potential. We examined their ability to disrupt the cell membrane in a range of pH values, concentrations and incubation times, using a standard hemolysis assay as a model of endosomal membranes. Furthermore, we addressed the mechanism of surfactant-mediated membrane destabilization, including the effects of each surfactant on erythrocyte morphology as a function of pH. We found that only surfactants with the positive charge on the α-amino group of lysine showed pH-sensitive hemolytic activity and improved kinetics within the endosomal pH range, indicating that the positive charge position is critical for pH-responsive behavior. Moreover, our results showed that an increase in the alkyl chain length from 14 to 16 carbon atoms was associated with a lower ability to disrupt cell membranes. Knowledge on modulating surfactant-lipid bilayer interactions may help us to develop more efficient biocompatible amino acid-based drug delivery devices.

A Study on the Reliability of an On-Site Oral Fluid Drug Test in a Recreational Context

PubMed Central

Gentili, Stefano; Tittarelli, Roberta; Mannocchi, Giulio

2016-01-01

The reliability of DrugWipe 5A on site test for principal drugs of abuse (cannabis, amphetamines, cocaine, and opiates) detection in oral fluid was assessed by comparing the on-site results with headspace solid-phase microextraction (HS-SPME) gas chromatography-mass spectrometry (GC-MS) analysis on samples extracted by the device collection pad. Oral fluid samples were collected at recreational settings (e.g., discos, pubs, and music bars) of Rome metropolitan area. Eighty-three club goers underwent the on-site drug screening test with one device. Independently from the result obtained, a second device was used just to collect another oral fluid sample subsequently extracted and analyzed in the laboratory following HS-SPME procedure, gas chromatographic separation by a capillary column, and MS detection by electron impact ionization. DrugWipe 5A on-site test showed 54 samples (65.1%) positive to one or more drugs of abuse, whereas 75 samples (90.4%) tested positive for one or more substances following GC-MS assay. Comparing the obtained results, the device showed sensitivity, specificity, and accuracy around 80% for amphetamines class. Sensitivity (67 and 50%) was obtained for cocaine and opiates, while both sensitivity and accuracy were unsuccessful (29 and 53%, resp.) for cannabis, underlying the limitation of the device for this latter drug class. PMID:27610266

Prevalence of HIV-1 Subtypes and Drug Resistance-Associated Mutations in HIV-1-Positive Treatment-Naive Pregnant Women in Pointe Noire, Republic of the Congo (Kento-Mwana Project).

PubMed

Bruzzone, Bianca; Saladini, Francesco; Sticchi, Laura; Mayinda Mboungou, Franc A; Barresi, Renata; Caligiuri, Patrizia; Calzi, Anna; Zazzi, Maurizio; Icardi, Giancarlo; Viscoli, Claudio; Bisio, Francesca

2015-08-01

The Kento-Mwana project was carried out in Pointe Noire, Republic of the Congo, to prevent mother-to-child HIV-1 transmission. To determine the prevalence of different subtypes and transmitted drug resistance-associated mutations, 95 plasma samples were collected at baseline from HIV-1-positive naive pregnant women enrolled in the project during the years 2005-2008. Full protease and partial reverse transcriptase sequencing was performed and 68/95 (71.6%) samples were successfully sequenced. Major mutations to nucleoside reverse transcriptase inhibitors, nonnucleoside reverse transcriptase inhibitors, and protease inhibitors were detected in 4/68 (5.9%), 3/68 (4.4%), and 2/68 (2.9%) samples, respectively. Phylogenetic analysis of HIV-1 isolates showed a high prevalence of unique recombinant forms (24/68, 35%), followed by CRF45_cpx (7/68, 10.3%) and subsubtype A3 and subtype G (6/68 each, 8.8%). Although the prevalence of transmitted drug resistance mutations appears to be currently limited, baseline HIV-1 genotyping is highly advisable in conjunction with antiretroviral therapy scale-up in resource-limited settings to optimize treatment and prevent perinatal transmission.

Fast screening tests for the simultaneous detection of 11 drugs of abuse in urine specimens. A forensic epidemiology study of 28,298 cases in Tunisia.

PubMed

Moslah, B; Araoud, M; Nouioui, M A; Najjar, S; Amira, D; Ben Salah, N; Hedhili, A

2018-02-01

Forensic investigation performed on people suspected to be drug abusers covering all Tunisian cities was conducted by monitoring an epidemiological study of human urine samples surveying positive rates of consumption for drugs of abuse. The forensic investigations were conducted on a total of 28,298 arrested individuals suspected to be drug addicts during five years (January 2010-December 2015). An immunoassay screening tests to detect elevated levels of drugs classes in urine samples was performed. These screening assays provide a preliminary qualitative test result. Only positives urine specimens were analyzed with GC-MS for confirmation. Except for cannabis, the results showed insignificant number of positive cases for cocaine, ecstasy (MDMA) and amphetamine consumptions (<1%). Copyright © 2017 Elsevier B.V. All rights reserved.

Hydrophobic Drug-Loaded PEGylated Magnetic Liposomes for Drug-Controlled Release

NASA Astrophysics Data System (ADS)

Hardiansyah, Andri; Yang, Ming-Chien; Liu, Ting-Yu; Kuo, Chih-Yu; Huang, Li-Ying; Chan, Tzu-Yi

2017-05-01

Less targeted and limited solubility of hydrophobic-based drug are one of the serious obstacles in drug delivery system. Thus, new strategies to enhance the solubility of hydrophobic drug and controlled release behaviors would be developed. Herein, curcumin, a model of hydrophobic drug, has been loaded into PEGylated magnetic liposomes as a drug carrier platform for drug controlled release system. Inductive magnetic heating (hyperthermia)-stimulated drug release, in vitro cellular cytotoxicity assay of curcumin-loaded PEGylated magnetic liposomes and cellular internalization-induced by magnetic guidance would be investigated. The resultant of drug carriers could disperse homogeneously in aqueous solution, showing a superparamagnetic characteristic and could inductive magnetic heating with external high-frequency magnetic field (HFMF). In vitro curcumin release studies confirmed that the drug carriers exhibited no significant release at 37 °C, whereas exhibited rapid releasing at 45 °C. However, it would display enormous (three times higher) curcumin releasing under the HFMF exposure, compared with that without HFMF exposure at 45 °C. In vitro cytotoxicity test shows that curcumin-loaded PEGylated magnetic liposomes could efficiently kill MCF-7 cells in parallel with increasing curcumin concentration. Fluorescence microscopy observed that these drug carriers could internalize efficiently into the cellular compartment of MCF-7 cells. Thus, it would be anticipated that the novel hydrophobic drug-loaded PEGylated magnetic liposomes in combination with inductive magnetic heating are promising to apply in the combination of chemotherapy and thermotherapy for cancer therapy.

Need for Affect and Attitudes Toward Drugs: The Mediating Role of Values.

PubMed

Lins de Holanda Coelho, Gabriel; H P Hanel, Paul; Vilar, Roosevelt; P Monteiro, Renan; Gouveia, Valdiney V; R Maio, Gregory

2018-05-04

Human values and affective traits were found to predict attitudes toward the use of different types of drugs (e.g., alcohol, marijuana, and other illegal drugs). In this study (N = 196, M age = 23.09), we aimed to gain a more comprehensive understanding of those predictors of attitudes toward drug use in a mediated structural equation model, providing a better overview of a possible motivational path that drives to such a risky behavior. Specifically, we predicted and found that the relations between need for affect and attitudes toward drug use were mediated by excitement values. Also, results showed that excitement values and need for affect positively predicted attitudes toward the use of drugs, whereas normative values predicted it negatively. The pattern of results remained the same when we investigated attitudes toward alcohol, marijuana, or illegal drugs separately. Overall, the findings indicate that emotions operate via excitement and normative values to influence risk behavior.

Development of Metronidazole-Loaded Colon-Targeted Microparticulate Drug Delivery System.

PubMed

Kumar, Manoj; Awasthi, Rajendra

2015-01-01

Crohn’s disease and ulcerative colitis are the main autoimmune inflammatory bowel diseases. Metronidazole is the most commonly used drug for the treatment of Crohn’s disease. However, the pharmacokinetic profile of this drug indicates that the largest amount of the drug is absorbed from the upper part of the intestines and very little concentration of the drugs reaches the colon.Objectives: The aim of this investigation was to formulate metronidazole loaded microspheres for the efficient therapy of inflammatory bowel diseases.Material and Methods: Microspheres were prepared using the emulsification-solvent evaporation method. The effect of Eudragit S100 concentration and the ratio of liquid paraffin (light: heavy) on percentage yield, particle size, morphology, drug encapsulation and in vitro drug release was examined. Drug-polymer interaction was investigated using Fourier Transformed Infrared Spectroscopy (FTIR). The results showed that the particle had good flow properties, encapsulation efficiency (56.11 ・} 1.51–81.02 ・} 2.14%)and cumulative drug release (64.14 ・} 0.83–79.69 ・} 2.45%) in a phosphate buffer (pH 6.8) after 10 h of the dissolution study.An increased particle size was observed with an increasing polymer concentration. It was observed that the Eudragit had a positive effect on the drug encapsulation and negative effect on drug release. Aggregation of drug-polymer droplets was observed at a lower level of magnesium stearate during microsphere preparation. The results of FTIR spectroscopy revealed the absence of any drug-polymer interactions. However, slight peak shifting and suppression in peak height was observed.This might be due to the minor ionic interactions. The microspheres were discrete, spherical and free-flowing. The spherical shape of the microspheres was confirmed from SEM photomicrographs. The developed microspheres showed a controlled drug release and were found to follow Higuchi’s model. The release mechanism of

Manipulation of the mouse genome: a multiple impact resource for drug discovery and development.

PubMed

Prosser, Haydn; Rastan, Sohaila

2003-05-01

Few would deny that the pharmaceutical industry's investment in genomics throughout the 1990s has yet to deliver in terms of drugs on the market. The reasons are complex and beyond the scope of this review. The unique ability to manipulate the mouse genome, however, has already had a positive impact on all stages of the drug discovery process and, increasingly, on the drug development process too. We give an overview of some recent applications of so-called 'transgenic' mouse technology in pharmaceutical research and development. We show how genetic manipulation in the mouse can be employed at multiple points in the drug discovery and development process, providing new solutions to old problems.

10 CFR 707.8 - Applicant drug testing.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 10 Energy 4 2014-01-01 2014-01-01 false Applicant drug testing. 707.8 Section 707.8 Energy DEPARTMENT OF ENERGY WORKPLACE SUBSTANCE ABUSE PROGRAMS AT DOE SITES Procedures § 707.8 Applicant drug testing. An applicant for a testing designated position will be tested for the use of illegal drugs before...

10 CFR 707.8 - Applicant drug testing.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 10 Energy 4 2013-01-01 2013-01-01 false Applicant drug testing. 707.8 Section 707.8 Energy DEPARTMENT OF ENERGY WORKPLACE SUBSTANCE ABUSE PROGRAMS AT DOE SITES Procedures § 707.8 Applicant drug testing. An applicant for a testing designated position will be tested for the use of illegal drugs before...

10 CFR 707.8 - Applicant drug testing.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 10 Energy 4 2010-01-01 2010-01-01 false Applicant drug testing. 707.8 Section 707.8 Energy DEPARTMENT OF ENERGY WORKPLACE SUBSTANCE ABUSE PROGRAMS AT DOE SITES Procedures § 707.8 Applicant drug testing. An applicant for a testing designated position will be tested for the use of illegal drugs before...

Therapeutic community drug treatment success in Peru: a follow-up outcome study

PubMed Central

Johnson, Knowlton; Pan, Zhenfeng; Young, Linda; Vanderhoff, Jude; Shamblen, Steve; Browne, Thom; Linfield, Ken; Suresh, Geetha

2008-01-01

Background The purpose of this study was to assess the impact of drug abuse treatment in Peru that used the therapeutic community (TC) model. Program directors and several staff members from all study treatment facilities received two to eight weeks of in-country training on how to implement the TC treatment model prior to the follow-up study. Methods This outcome study involved 33 TC treatment facilities and 509 former clients in Lima and other cities in five providences across Peru. A retrospective pre-test (RPT) follow-up design was employed in which 30-day use of illegal drugs and alcohol to intoxication was measured at baseline retrospectively, at the same time of the six-month follow-up. In-person interview data were collected from directors of 73 percent of the eligible TC organizations in January and February 2003 and from former 58 percent of the eligible TC former clients between October 2003 and October 2004. Drug testing was conducted on a small sample of former clients to increase the accuracy of the self-reported drug use data. Results Medium to large positive treatment effects were found when comparing 30-day illegal drug and alcohol use to intoxication before and six months after receiving treatment. As a supplemental analysis, we assumed the 42 percent of the former clients who were not interviewed at the six month assessment had returned to drugs. These results showed medium treatment effects as well. Hierarchical Generalized Linear Modeling (HGLM) results showed higher implementation fidelity, less stigma after leaving treatment, and older clients, singly or in combination are key predictors of treatment success. Conclusion This study found that former clients of drug and alcohol treatment in facilities using the TC model reported substantial positive change in use of illegal drugs and alcohol to intoxication at a six-month follow-up. The unique contribution of this study is that the results also suggest attention should be placed on the

[Drug innovation and reverse thinking].

PubMed

Guo, Zong-ru

2016-03-01

Drug innovation involves an individual molecular operation, and every new molecular entity features a hard-duplicated track of R&D. The transformation from an active compound to a new medicine carries out almost in a chaotic system devoid of regularity and periodic alteration. Since new millennium the dominant position in drug innovation has been occupied by the first-in-class drugs, yet the number of launched follow-on drugs has been distinctly decreased. The innovation of first-in-class drugs is characterized by a high risk throughout the whole process. To achieve initiative and uniqueness of drug discovery, the strategy and method of the inverse thinking might be a feasible way, because the inertial and conformity thinkings in drug discovery normally lead to ensemble with similar drug category. However, the study from the flipside or opposite of things(e.g. targets or effects) brand new routes might be opened. This article is to describe the strategy of reverse thinking in drug discovery by some examples including opioid receptor antagonist eluxadoline, HSP90 activator, h ERG channel agonist, covalent drugs, and ultra-small drugs.

Diagnosis of Pulmonary Tuberculosis in HIV-Positive Patients by Microscopic Observation Drug Susceptibility Assay ▿

PubMed Central

Ha, Dang Thi Minh; Lan, Nguyen Thi Ngoc; Kiet, Vo Sy; Wolbers, Marcel; Hang, Hoang Thi Thanh; Day, Jeremy; Hien, Nguyen Quang; Tien, Nguyen Anh; An, Pham Thuy; Anh, Truong Thi; Oanh, Do Thi Tuong; Hoa, Chau Luong; Chau, Nguyen Thi Minh; Hai, Nguyen Ngoc; Binh, Ngo Thanh; Ngoc, Le Hong; Phuong, Doan Thanh; Quyet, Tran Van; Tuyen, Nguyen Thi Bich; Ha, Vo Thi; Nho, Nguyen Thi; Hoa, Dai Viet; Anh, Phan Thi Hoang; Dung, Nguyen Huy; Farrar, Jeremy; Caws, Maxine

2010-01-01

The microscopic observation drug susceptibility assay (MODS) is a novel and promising test for the early diagnosis of tuberculosis (TB). We evaluated the MODS assay for the early diagnosis of TB in HIV-positive patients presenting to Pham Ngoc Thach Hospital for Tuberculosis and Lung Diseases in southern Vietnam. A total of 738 consecutive sputum samples collected from 307 HIV-positive individuals suspected of TB were tested by smear, MODS, and the mycobacteria growth indicator tube method (MGIT). The diagnostic sensitivity and specificity of MODS compared to the microbiological gold standard (either smear or MGIT) were 87 and 93%, respectively. The sensitivities of smear, MODS, and MGIT were 57, 71, and 75%, respectively, against clinical gold standard (MODS versus smear, P < 0.001; MODS versus MGIT, P = 0.03). The clinical gold standard was defined as patients who had a clinical examination and treatment consistent with TB, with or without microbiological confirmation. For the diagnosis of smear-negative patients, the sensitivities of MODS and MGIT were 38 and 45%, respectively (P = 0.08). The median times to detection using MODS and MGIT were 8 and 11 days, respectively, and they were 11 and 17 days, respectively, for smear-negative samples. The original bacterial/fungal contamination rate of MODS was 1.1%, while it was 2.6% for MGIT. The cross-contamination rate of MODS was 4.7%. In conclusion, MODS is a sensitive, specific, and rapid test that is appropriate for the detection of HIV-associated TB; its cost and ease of use make it particularly useful in resource-limited settings. PMID:20926704

Positioning as Not-Understanding: The Value of Showing Uncertainty for Engaging in Science

ERIC Educational Resources Information Center

Watkins, Jessica; Hammer, David; Radoff, Jennifer; Jaber, Lama Z.; Phillips, Anna M.

2018-01-01

Not understanding is central to scientific work: what scientists do is learn about the natural world, which involves seeking out what they do not know. In classrooms, however, the position of not-understanding is generally a liability; confusion is an unfortunate condition to resolve as quickly as possible, or to conceal. In this article, we argue…

Comparison of Attitudes, Knowledge and Drug Abuse Among Military Offenders

ERIC Educational Resources Information Center

Ratliff, Bascom W.

1977-01-01

Military offenders' (N=69) attitudes towards drugs, knowledge about drugs, and reported drug abuse histories were analyzed. Results indicated a significantly positive relationship between all three variables. Military offenders who had drug use histories also had more liberal attitudes toward drug use and a greater degree of knowledge about drugs.…

Predicting early positive change in multisystemic therapy with youth exhibiting antisocial behaviors.

PubMed

Tiernan, Kristine; Foster, Sharon L; Cunningham, Phillippe B; Brennan, Patricia; Whitmore, Elizabeth

2015-03-01

This study examined individual and family characteristics that predicted early positive change in the context of Multisystemic Therapy (MST). Families (n = 185; 65% male; average youth age 15 years) receiving MST in community settings completed assessments at the outset of treatment and 6-12 weeks into treatment. Early positive changes in youth antisocial behavior were assessed using the caregiver report on the Child Behavior Checklist Externalizing Behaviors subscale and youth report on the Self-Report Delinquency Scale. Overall, families showed significant positive changes by 6-12 weeks into treatment; these early changes were maintained into midtreatment 6-12 weeks later. Families who exhibited clinically significant gains early in treatment were more likely to terminate treatment successfully compared with those who did not show these gains. Low youth internalizing behaviors and absence of youth drug use predicted early positive changes in MST. High levels of parental monitoring and low levels of affiliation with deviant peers (mechanisms known to be associated with MST success) were also associated with early positive change. (PsycINFO Database Record (c) 2015 APA, all rights reserved).

Air Quality Inside Police Drug Safes and Drug Storage Areas.

PubMed

Doran, Gregory S; Deans, Ralph; De Filippis, Carlo; Kostakis, Chris; Howitt, Julia A

2018-06-01

Storage of drug-based evidence inside sealed safes may allow chemical vapors to accumulate, creating concerns of drug exposure by inhalation, or the possibility of cross-contamination of drug evidence. Air samples were taken from inside eight drug safes and one small storage room at nine city and country police stations, as well as a large centralized drug evidence storage vault, in New South Wales (NSW), Australia. Sorbent tubes containing charcoal were used to determine whether any drug residues could be detected in the air, and to identify the types of chemicals present. Carbon traps were extracted and analyzed by LC-MS-MS for a suite of 22 licit and illicit drug residues and 2 metabolites. Carbon traps and SPME fibers were also analyzed by GC-MS for general volatile organic compound (VOC) residues. No detectable drug residues, either as airborne dust or vapor, were found in the safes, the storage room or the large central repository vault. No drugs were detected in any of the 34 urine samples collected at 8 of the 10 sampling locations, while only one of the five hair samples was positive for cocaine (9 pg/mg) provided by police exhibit officers at 3 of the 10 sampling locations. VOC analysis identified a variety of solvents associated with drug manufacture, plasticisers, personal care products and volatiles associated with plants such as cannabis. The results indicate that strong chemical odours emanating from drug safes are unlikely to be drug residues due to low volatility of drugs, and are more likely VOCs associated with their manufacture or from plant growing operations. Consideration should be given to the quality of air flow in rooms in which safes are housed and the use of air filtering inside safes to reduce the likelihood of VOC accumulation, and therefore the risk of human exposure.

Bacterial Contamination of Anaesthetic and Vasopressor Drugs in the Operating Theatres

PubMed Central

Rueangchira-Urai, Rongrong; Rujirojindakul, Panthila; Geater, Alan Frederick; McNeil, Edward

2017-01-01

Objective The aim of this study was to determine the incidence of bacterial and fungal contamination in anaesthetic and vasopressor drugs before and after use in operating theatres. Methods A cross-sectional study was conducted in the operating theatres of a university hospital. We collected 945 samples of three different drugs, namely, propofol, vecuronium and ephedrine, from 20 operating rooms and refrigerators where the unused drugs were stored. Each drug was divided into two groups, the pre-use group and the post-use group. The pre-use drugs were cultured before the patient received the drug. The post-use drugs were cultured after the patient had received the drug or after the drugs had been transferred to other syringes. The culture results were reported as either positive or negative. Results Out of the 945 drug samples, 26 (2.8%, 95% confidence interval=1.8%–4.0%) gave a positive culture. Of the 317 propofol samples, 20 (6.3%) were found to have bacterial contamination, 11 in the pre-use group and 9 in the post-use group. Of the 318 ephedrine samples, 6 (1.9%) were found to be positive on culture, one in the pre-use group and five in the post-use group. Vecuronium gave no positive cultures. All organisms were non-pathogenic, and no fungal contamination was found. Conclusion The incidence of bacterial contamination in anaesthetic and vasopressor drugs was 2.8%. Anaesthetic teams must be aware of contamination issues in anaesthetic drugs that have been prepared for later use and, in order to reduce the risk of contamination, they must improve the methods of administering drugs to patients. PMID:28377840

Surface Proteins of Gram-Positive Pathogens: Using Crystallography to Uncover Novel Features in Drug and Vaccine Candidates

NASA Astrophysics Data System (ADS)

Baker, Edward N.; Proft, Thomas; Kang, Haejoo

Proteins displayed on the cell surfaces of pathogenic organisms are the front-line troops of bacterial attack, playing critical roles in colonization, infection and virulence. Although such proteins can often be recognized from genome sequence data, through characteristic sequence motifs, their functions are often unknown. One such group of surface proteins is attached to the cell surface of Gram-positive pathogens through the action of sortase enzymes. Some of these proteins are now known to form pili: long filamentous structures that mediate attachment to human cells. Crystallographic analyses of these and other cell surface proteins have uncovered novel features in their structure, assembly and stability, including the presence of inter- and intramolecular isopeptide crosslinks. This improved understanding of structures on the bacterial cell surface offers opportunities for the development of some new drug targets and for novel approaches to vaccine design.

SELF-BLM: Prediction of drug-target interactions via self-training SVM.

PubMed

Keum, Jongsoo; Nam, Hojung

2017-01-01

Predicting drug-target interactions is important for the development of novel drugs and the repositioning of drugs. To predict such interactions, there are a number of methods based on drug and target protein similarity. Although these methods, such as the bipartite local model (BLM), show promise, they often categorize unknown interactions as negative interaction. Therefore, these methods are not ideal for finding potential drug-target interactions that have not yet been validated as positive interactions. Thus, here we propose a method that integrates machine learning techniques, such as self-training support vector machine (SVM) and BLM, to develop a self-training bipartite local model (SELF-BLM) that facilitates the identification of potential interactions. The method first categorizes unlabeled interactions and negative interactions among unknown interactions using a clustering method. Then, using the BLM method and self-training SVM, the unlabeled interactions are self-trained and final local classification models are constructed. When applied to four classes of proteins that include enzymes, G-protein coupled receptors (GPCRs), ion channels, and nuclear receptors, SELF-BLM showed the best performance for predicting not only known interactions but also potential interactions in three protein classes compare to other related studies. The implemented software and supporting data are available at https://github.com/GIST-CSBL/SELF-BLM.

In silico modeling to predict drug-induced phospholipidosis

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

Choi, Sydney S.; Kim, Jae S.; Valerio, Luis G., E-mail: luis.valerio@fda.hhs.gov

2013-06-01

Drug-induced phospholipidosis (DIPL) is a preclinical finding during pharmaceutical drug development that has implications on the course of drug development and regulatory safety review. A principal characteristic of drugs inducing DIPL is known to be a cationic amphiphilic structure. This provides evidence for a structure-based explanation and opportunity to analyze properties and structures of drugs with the histopathologic findings for DIPL. In previous work from the FDA, in silico quantitative structure–activity relationship (QSAR) modeling using machine learning approaches has shown promise with a large dataset of drugs but included unconfirmed data as well. In this study, we report the constructionmore » and validation of a battery of complementary in silico QSAR models using the FDA's updated database on phospholipidosis, new algorithms and predictive technologies, and in particular, we address high performance with a high-confidence dataset. The results of our modeling for DIPL include rigorous external validation tests showing 80–81% concordance. Furthermore, the predictive performance characteristics include models with high sensitivity and specificity, in most cases above ≥ 80% leading to desired high negative and positive predictivity. These models are intended to be utilized for regulatory toxicology applied science needs in screening new drugs for DIPL. - Highlights: • New in silico models for predicting drug-induced phospholipidosis (DIPL) are described. • The training set data in the models is derived from the FDA's phospholipidosis database. • We find excellent predictivity values of the models based on external validation. • The models can support drug screening and regulatory decision-making on DIPL.« less

Review of HIV and HCV infection among drug users in China.

PubMed

Bao, Yan-ping; Liu, Zhi-min; Lu, Lin

2010-05-01

Drug abuse has resulted in a huge public health and economic burden in China, especially the rapid spread of HIV/AIDS and hepatitis C virus (HCV) infection. Multiple HIV and HCV subtypes were detected among drug users in China, this study reviews the molecular distribution of HIV and HCV among injection drug users (IDUs) and explores new epidemiologic trends of HIV and HCV among drug users in China. The 2009 National Narcotic Control Commission report showed that the percentage of users of 'new-type drugs', including amphetamine-type stimulants (ATS: methamphetamine and MDMA/ecstasy) and ketamine, was about 27% of total drug users. The pooled data from published papers showed that CRF07BC was the predominant HIV-1 subtype, which accounted for 38.8%, and it was followed by AE, which accounted for 22.7% among HIV-positive IDUs. Following these, the CRF08BC, B' and C subtypes accounted for about 10.8%, 9.9% and 9.2%, respectively. Subtype 6a was the predominant HCV subtype, accounting for 36.7%, and subtypes 3b, 1a, 3a and 1b were the next most predominant subtypes. With the increase of 'new-type drugs' use and AE HIV-1 subtype infection among IDUs, the situation regarding HIV/AIDS and HCV infection has become complicated. More comprehensive prevention and intervention strategies should be instigated for the extensive high-risk populations in China.

Potential drug-drug interactions between anti-cancer agents and community pharmacy dispensed drugs.

PubMed

Voll, Marsha L; Yap, Kim D; Terpstra, Wim E; Crul, Mirjam

2010-10-01

community pharmacy. It shows us there is need for an optimal medication surveillance mechanism to detect potential drug-drug interactions between these two groups of medication, especially because of the high toxicity of anticancer drugs and thus the severe consequences these interactions can have for the patient.

Considering the context: social factors in responses to drugs in humans.

PubMed

de Wit, Harriet; Sayette, Michael

2018-04-01

Drugs are typically used in social settings. Here, we consider two factors that may contribute to this observation: (i) the presence of other people may enhance the positive mood effects of a drug, and conversely, (ii) drugs may enhance the value of social stimuli. We review evidence from controlled laboratory studies with human volunteers, which investigated either of these interactions between social factors and responses to drugs. We examine the bidirectional effects of social stimuli and single doses of alcohol, stimulants, opioids, and cannabis. All four classes of drugs interact with social contexts, but the nature of these interactions varies across drugs, and depends on whether the context is positive or negative. Alcohol and stimulant drugs enhance the attractiveness of social stimuli and the desire to socialize, and social contexts, in turn, enhance these drugs' effects. In contrast, opioids and cannabis have subtler effects on social interactions and their effects are less influenced by the presence of others. Overall, there is stronger evidence that drugs enhance positive social contexts than that they dampen the negativity of unpleasant social settings. Controlled research is needed to understand the interactions between drugs of abuse and social contexts, to model and understand the determinants of drug use outside the laboratory.

Determination of different recreational drugs in sweat by headspace solid-phase microextraction gas chromatography mass spectrometry (HS-SPME GC/MS): Application to drugged drivers.

PubMed

Gentili, Stefano; Mortali, Claudia; Mastrobattista, Luisa; Berretta, Paolo; Zaami, Simona

2016-09-10

A procedure based on headspace solid-phase microextraction (HS-SPME) coupled with gas chromatography/mass spectrometry (GC/MS) has been developed for the determination of most commonly used drugs of abuse in sweat of drivers stopped during roadside controls. DrugWipe 5A sweat screening device was used to collect sweat by a specific pad rubbed gently over forehead skin surface. The procedure involved an acid hydrolysis, a HS-SPME extraction for drugs of abuse but Δ(9)-tetrahydrocannabinol, which was directly extracted in alkaline medium HS-SPME conditions, a GC separation of analytes by a capillary column and MS detection by electron impact ionisation. The method was linear from the limit of quantification (LOQ) to 50ng drug per pad (r(2)≥0.99), with an intra- and inter-assay precision and accuracy always less than 15% and an analytical recovery between 95.1% and 102.8%, depending on the considered analyte. Using the validated method, sweat from 60 apparently intoxicated drivers were found positive to one or more drugs of abuse, showing sweat patches testing as a viable economic and simple alternative to conventional (blood and/or urine) and non conventional (oral fluid) testing of drugs of abuse in drugged drivers. Copyright © 2016 Elsevier B.V. All rights reserved.

Automatic signal extraction, prioritizing and filtering approaches in detecting post-marketing cardiovascular events associated with targeted cancer drugs from the FDA Adverse Event Reporting System (FAERS).

PubMed

Xu, Rong; Wang, Quanqiu

2014-02-01

Targeted drugs dramatically improve the treatment outcomes in cancer patients; however, these innovative drugs are often associated with unexpectedly high cardiovascular toxicity. Currently, cardiovascular safety represents both a challenging issue for drug developers, regulators, researchers, and clinicians and a concern for patients. While FDA drug labels have captured many of these events, spontaneous reporting systems are a main source for post-marketing drug safety surveillance in 'real-world' (outside of clinical trials) cancer patients. In this study, we present approaches to extracting, prioritizing, filtering, and confirming cardiovascular events associated with targeted cancer drugs from the FDA Adverse Event Reporting System (FAERS). The dataset includes records of 4,285,097 patients from FAERS. We first extracted drug-cardiovascular event (drug-CV) pairs from FAERS through named entity recognition and mapping processes. We then compared six ranking algorithms in prioritizing true positive signals among extracted pairs using known drug-CV pairs derived from FDA drug labels. We also developed three filtering algorithms to further improve precision. Finally, we manually validated extracted drug-CV pairs using 21 million published MEDLINE records. We extracted a total of 11,173 drug-CV pairs from FAERS. We showed that ranking by frequency is significantly more effective than by the five standard signal detection methods (246% improvement in precision for top-ranked pairs). The filtering algorithm we developed further improved overall precision by 91.3%. By manual curation using literature evidence, we show that about 51.9% of the 617 drug-CV pairs that appeared in both FAERS and MEDLINE sentences are true positives. In addition, 80.6% of these positive pairs have not been captured by FDA drug labeling. The unique drug-CV association dataset that we created based on FAERS could facilitate our understanding and prediction of cardiotoxic events associated with

Towards better patient care: drugs to avoid.

PubMed

2013-04-01

Common sense dictates that one should choose tried and tested drugs with proven, concrete benefits that outweigh their adverse effects. Many new drugs are approved each year, often despite a lack of solid evidence that they are any better than existing treatments. Worse, some are approved despite being less effective or more harmful than current options. Massive promotion is used to ensure that such drugs achieve a positive image in the eyes of healthcare professionals and patients. Renowned "opinion leaders" intervene in their favour at conferences and in specialist media, and their opinions are further propagated by specialists in the field. Finally, campaigns in the lay media are used to highlight the target illness, encouraging patients to request a prescription. New data sometimes show that older, initially promising drugs are less effective or more harmful than first thought. For all these reasons, many drugs that are now present on the market are more harmful than beneficial and should be avoided. Unfortunately, negative assessment data and warnings are often drowned in the flood of promotion and advertising. Front-line healthcare professionals who are determined to act in their patients' best interests can find themselves swimming against a tide of specialist opinion, marketing authorisation, and reimbursement decisions. By leaving drugs that are more harmful than beneficial on the market and contenting themselves with simple half-measures, healthcare authorities are failing in their duty to protect patients. Prescrire, a journal funded solely by its subscribers, does not seek to do the work of health authorities, and does not have the means to do so. Prescrire's goal is simply to help healthcare professionals provide better care. The following text lists the principal drugs that we consider more harmful than beneficial, based on our reviews published between 2010 and 2012 in our French edition. These drugs should not be used. Patients and healthcare

Drug expenditure and new drug introductions: the Swedish experience.

PubMed

Gerdtham, U G; Johannesson, M; Jönsson, B

1993-09-01

This article measures the impact of the switch to new and more expensive drugs on the aggregate drug expenditure (both prescription and nonprescription) in Sweden during the period 1974 to 1991, and also on the disaggregated expenditure for 3 medical areas: asthma, hypertension and peptic ulcer disease. During the period studied, nominal drug expenditure increased 6-fold. The retail price index of drugs and the number of prescribed drugs accounted for 51.6 and 5.8% of this increase, respectively. The remaining residual amount accounted for 42.6%. Since the price index of drugs increased more slowly than the overall net price index of goods and services, the relative price of drugs decreased dramatically by about 30%. This means that increases in prices of drugs cannot explain the increase in real inflation-adjusted drug expenditure. We also show that the residual increase can be partly explained by the introduction of new and more expensive drugs. It is therefore argued that economic evaluations which compare the extra costs induced by new drugs with the extra benefits should be undertaken to guide decisions about the prescription of new and more expensive drugs.

Drug-Drug Interactions, Effectiveness, and Safety of Hormonal Contraceptives in Women Living with HIV.

PubMed

Scarsi, Kimberly K; Darin, Kristin M; Chappell, Catherine A; Nitz, Stephanie M; Lamorde, Mohammed

2016-11-01

Family planning options, including hormonal contraceptives, are essential for improving reproductive health among the more than 17 million women living with HIV worldwide. For these women, prevention of unintended pregnancy decreases maternal and child mortality, as well as reduces the risk of perinatal HIV transmission. Similarly, treatment of HIV with antiretroviral therapy (ART) is essential for reducing morbidity and mortality among HIV-positive individuals, as well as preventing HIV transmission between sexual partners or from mother to child. Importantly, despite the benefits of hormonal contraceptives, barriers to effective family planning methods exist for HIV-positive women. Specifically, drug-drug interactions can occur between some antiretroviral medications and some hormonal contraceptives, which may influence both contraceptive efficacy and tolerability. In addition, safety concerns have been raised about the impact of hormonal contraceptives on HIV disease progression, tolerability, and the risk of female-to-male HIV transmission. This review article summarizes the potential for drug-drug interactions, tolerability, and contraceptive effectiveness when hormonal contraceptives are combined with ART. In addition, the evidence surrounding the influence of hormonal contraceptives on HIV transmission and HIV disease progression in women living with HIV are summarized.

Drug concentration heterogeneity facilitates the evolution of drug resistance.

PubMed

Kepler, T B; Perelson, A S

1998-09-29

Pathogenic microorganisms use Darwinian processes to circumvent attempts at their control through chemotherapy. In the case of HIV-1 infection, in which drug resistance is a continuing problem, we show that in one-compartment systems, there is a relatively narrow window of drug concentrations that allows evolution of resistant variants. When the system is enlarged to two spatially distinct compartments held at different drug concentrations with transport of virus between them, the range of average drug concentrations that allow evolution of resistance is significantly increased. For high average drug concentrations, resistance is very unlikely to arise without spatial heterogeneity. We argue that a quantitative understanding of the role played by heterogeneity in drug levels and pathogen transport is crucial for attempts to control re-emergent infectious disease.

Evaluation of deoxyhypusine synthase inhibitors targeting BCR-ABL positive leukemias.

PubMed

Ziegler, Patrick; Chahoud, Tuhama; Wilhelm, Thomas; Pällman, Nora; Braig, Melanie; Wiehle, Valeska; Ziegler, Susanne; Schröder, Marcus; Meier, Chris; Kolodzik, Adrian; Rarey, Matthias; Panse, Jens; Hauber, Joachim; Balabanov, Stefan; Brümmendorf, Tim H

2012-12-01

Effective inhibition of BCR-ABL tyrosine kinase activity with Imatinib represents a breakthrough in the treatment of patients with chronic myeloid leukemia (CML). However, more than 30 % of patients with CML in chronic phase do not respond adequately to Imatinib and the drug seems not to affect the quiescent pool of BCR-ABL positive leukemic stem and progenitor cells. Therefore, despite encouraging clinical results, Imatinib can still not be considered a curative treatment option in CML. We recently reported downregulation of eukaryotic initiation factor 5A (eIF5A) in Imatinib treated K562 cells. Furthermore, the inhibition of eIF5A by siRNA in combination with Imatinib has been shown to exert synergistic cytotoxic effects on BCR-ABL positive cell lines. Based on the structure of known deoxyhypusine synthase (DHS) inhibitors such as CNI-1493, a drug design approach was applied to develop potential compounds targeting DHS. Here we report the biological evaluation of selected novel (DHSI-15) as compared to established (CNI-1493, deoxyspergualin) DHS inhibitors. We show that upon the compounds tested, DHSI-15 and deoxyspergualin exert strongest antiproliferative effects on BCR-ABL cells including Imatinib resistant mutants. However, this effect did not seem to be restricted to BCR-ABL positive cell lines or primary cells. Both compounds are able to induce apoptosis/necrosis during long term incubation of BCR-ABL positive BA/F3 derivates. Pharmacological synergism can be observed for deoxyspergualin and Imatinib, but not for DHSI-15 and Imatinib. Finally we show that deoxyspergualin is able to inhibit proliferation of CD34+ progenitor cells from CML patients. We conclude that inhibition of deoxyhypusine synthase (DHS) can be supportive for the anti-proliferative treatment of leukemia and merits further investigation including other cancers.

GABAA receptor: Positive and negative allosteric modulators.

PubMed

Olsen, Richard W

2018-01-31

gamma-Aminobutyric acid (GABA)-mediated inhibitory neurotransmission and the gene products involved were discovered during the mid-twentieth century. Historically, myriad existing nervous system drugs act as positive and negative allosteric modulators of these proteins, making GABA a major component of modern neuropharmacology, and suggesting that many potential drugs will be found that share these targets. Although some of these drugs act on proteins involved in synthesis, degradation, and membrane transport of GABA, the GABA receptors Type A (GABA A R) and Type B (GABA B R) are the targets of the great majority of GABAergic drugs. This discovery is due in no small part to Professor Norman Bowery. Whereas the topic of GABA B R is appropriately emphasized in this special issue, Norman Bowery also made many insights into GABA A R pharmacology, the topic of this article. GABA A R are members of the ligand-gated ion channel receptor superfamily, a chloride channel family of a dozen or more heteropentameric subtypes containing 19 possible different subunits. These subtypes show different brain regional and subcellular localization, age-dependent expression, and potential for plastic changes with experience including drug exposure. Not only are GABA A R the targets of agonist depressants and antagonist convulsants, but most GABA A R drugs act at other (allosteric) binding sites on the GABA A R proteins. Some anxiolytic and sedative drugs, like benzodiazepine and related drugs, act on GABA A R subtype-dependent extracellular domain sites. General anesthetics including alcohols and neurosteroids act at GABA A R subunit-interface trans-membrane sites. Ethanol at high anesthetic doses acts on GABA A R subtype-dependent trans-membrane domain sites. Ethanol at low intoxicating doses acts at GABA A R subtype-dependent extracellular domain sites. Thus GABA A R subtypes possess pharmacologically specific receptor binding sites for a large group of different chemical classes of

Focused use of drug screening in overdose patients increases impact on management.

PubMed

Erdmann, Andreas; Werner, Dominique; Hugli, Olivier; Yersin, Bertrand

2015-01-01

Drug poisoning is a common cause for attendance in the emergency department. Several toxicology centres suggest performing urinary drug screens, even though they rarely influence patient management. Measuring the impact on patient management, in a University Emergency Department with approximately 40 000 admissions annually, of a rapid urinary drug screening test using specifically focused indications. Drug screening was restricted to patients having a first psychotic episode or cases demonstrating respiratory failure, coma, seizures, a sympathomimetic toxidrome, severe opiate overdose necessitating naloxone, hypotension, ventricular arrhythmia, acquired long QT or QRS >100 ms, and high-degree heart block. Retrospective analysis of Triage® TOX drug screen tests performed between September 2009 and November 2011, and between January 2013 and March 2014. A total of 262 patients were included, mean age 35 ± 14.6 (standard deviation) years, 63% men; 29% poisoning with alcohol, and 2.3% deaths. Indications for testing were as follows: 34% were first psychotic episodes; 20% had acute respiratory failure; 16% coma; 8% seizures; 8% sympathomimetic toxidromes; 7% severe opioid toxidromes; 4% hypotension; 3% ventricular arrhythmias or acquired long QT intervals on electrocardiogram. A total of 78% of the tests were positive (median two substances, maximum five). The test resulted in drug-specific therapy in 6.1%, drug specific diagnostic tests in 13.3 %, prolonged monitoring in 10.7% of methadone-positive tests, and psychiatric admission in 4.2%. Overall, 34.3% tests influenced patient management. In contrast to previous studies showing modest effects of toxicological testing, restricted use of rapid urinary drug testing increases the impact on management of suspected overdose patients in the ED.

Drug therapy smartens up

NASA Astrophysics Data System (ADS)

Martin, Christian

2015-11-01

The submission of the first 'smart pill' for market approval, combined with progress in the European nanomedicine landscape, illustrates the positive outlook for drug therapy and health monitoring, explains Christian Martin.

[Drug consumption and occupational violence in working women of Monterrey, N. L., Mexico].

PubMed

Alonso Castillo, Maria Magdalena; Caufield, Catherine; Gómez Meza, Marco Vinicio

2005-01-01

The purpose of this study was to explore drug consumption and occupational violence in a sample of 669 adult women, working and living in 13 basic geostatistical areas of Monterrey, Nuevo León, México, using a descriptive correlational design with a qualitative approach. Results indicated that 37.1% of women consumed alcohol, 29.1% tobacco, 0.4% marihuana, 0.1% inhalants, and, among medical drugs, 5% consumed tranquilizers, and 1% other substances (barbiturates, antidepressive agents, Tylenol/codeine). The c2 test found no significant difference between sociodemographic and occupational factors and drug consumption (p<.05), except for the work form (c2=18.08, gl=4, p=.001). However, violence rate showed a positive association with drug consumption (p<.05). This study found 126 cases of violence, 34 of which narrated their experience. Drug consumption and violence perception was identified in 2 categories: Conceptualization of Occupational Violence and Relationship between Violence and Drug Consumption.

A Randomized Pilot Study of the Engaging Moms Program for Family Drug Court

PubMed Central

Dakof, Gayle A.; Cohen, Jeri B.; Henderson, Craig E.; Duarte, Eliette; Boustani, Maya; Blackburn, Audra; Venzer, Ellen; Hawes, Sam

2010-01-01

In response to the need for effective drug court interventions, the effectiveness of the Engaging Moms Program (EMP) versus intensive case management services (ICMS) on multiple outcomes for mothers enrolled in family drug court was investigated. In this intent-to-treat study, mothers (N = 62) were randomly assigned to either usual drug court care or the Engaging Moms drug court program. Mothers were assessed at intake, and 3, 6, 12, and 18 months following intake. Results indicated that at 18 months post drug court enrollment, 77% of mothers assigned to EMP versus 55% of mothers assigned to ICMS had positive child welfare dispositions. There were statistically significant time effects for both intervention groups on multiple outcomes including substance use, mental health, parenting practices, and family functioning. EMP showed equal or better improvement than ICMS on all outcomes. The results suggest that EMP in family drug court is a viable and promising intervention approach to reduce maternal addiction and child maltreatment. PMID:20116961

Safety Management Status among Nurses Handling Anticancer Drugs: Nurse Awareness and Performance Following Safety Regulations.

PubMed

Jeong, Kyeong Weon; Lee, Bo-Young; Kwon, Myung Soon; Jang, Ji-Hye

2015-01-01

This study identified the actual conditions for safe anticancer drug management among nurses and the relationship between level of awareness and performance of anticancer drug safety regulations in terms of preparation, administration, and disposal. The respondents were 236 nurses working with chemotherapy in wards and outpatient clinics in five hospitals in and near Seoul. Safety regulations provided for the anticancer drug the Occupational Safety Health Administration (OSHA, 1999), as modified for an earlier study, were used. The results showed that the level of awareness and performance on the anticancer drug safety regulations indicate their preparation (3.38±0.55, 2.38±0.98), administration (3.52±0.46, 3.17±0.70), general handling and disposal (3.33±0.54, 2.42±0.90) on a scale 0 to 5. Also, there were significant differences in job positions, work experience, type of preparation, and continuing education and a positive relationship between the level of awareness and nursing performance. Thus, nurses should receive continuing education on the handling of anticancer drugs to improve the level of performance following safety regulations.

[Analysis of tools, methods and results of toxicological screening for detection of drug abuse in Italian professional drivers].

PubMed

Rosso, G L

2013-01-01

Three years after a protocol agreement between the State and the Regions came into force in 2008 (drug testing at the workplace Law) a large number of studies have been conducted to analyse and test the efficacy of on-site screening tests for detection of drug consumption (opiates, cocaine, cannabinoids, amphetamine and methamphetamine, MDMA and methadone), which are frequently used by the occupational health physician, and also to present data resulting from workplace drug testing obtained during health surveillance programmes. The aim of the present study was to verify whether the features of sensitivity and specificity of the most common on-site testing ensure correct application of the provisions of current Italian legislation and also to analyse published studies showing the frequency of positive drug testing. A review of Italian and international literature was carried out aimed at identifying studies relating to: (1) performance of on-site screening tests frequently used by the occupational health physician, (2) prevalence of drug use/abuse among Italian public and commercial transport drivers. A comparison between the studies was then carried out. Several rapid on-site screening tests are commercially available (Italian law does not provide standards for the technical specifications of the tests), the sensitivity and specificity of which varies depending on the model and the substance tested. The sensitivity of these tools is poor when used for the detection of low concentrations of drugs and/or their metabolites in urine (close to the cut-off). Studies are lacking that compare on-site tests performed by the occupational health physician and confirmative tests in specialized laboratories (with particular regard to false positives found by the occupational health physician). The major studies in terms of methods and/or size reported a positive rate (confirmed at the first level) between 1.6% and 1.9%. The drugs most frequently used/abused were cannabis and

21 CFR 872.1850 - Lead-lined position indicator.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Lead-lined position indicator. 872.1850 Section... (CONTINUED) MEDICAL DEVICES DENTAL DEVICES Diagnostic Devices § 872.1850 Lead-lined position indicator. (a) Identification. A lead-lined position indicator is a cone-shaped device lined with lead that is attached to a...

21 CFR 872.1850 - Lead-lined position indicator.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Lead-lined position indicator. 872.1850 Section... (CONTINUED) MEDICAL DEVICES DENTAL DEVICES Diagnostic Devices § 872.1850 Lead-lined position indicator. (a) Identification. A lead-lined position indicator is a cone-shaped device lined with lead that is attached to a...

21 CFR 872.1850 - Lead-lined position indicator.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Lead-lined position indicator. 872.1850 Section... (CONTINUED) MEDICAL DEVICES DENTAL DEVICES Diagnostic Devices § 872.1850 Lead-lined position indicator. (a) Identification. A lead-lined position indicator is a cone-shaped device lined with lead that is attached to a...

21 CFR 872.1850 - Lead-lined position indicator.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Lead-lined position indicator. 872.1850 Section... (CONTINUED) MEDICAL DEVICES DENTAL DEVICES Diagnostic Devices § 872.1850 Lead-lined position indicator. (a) Identification. A lead-lined position indicator is a cone-shaped device lined with lead that is attached to a...

Risky decision making and the anterior cingulate cortex in abstinent drug abusers and nonusers.

PubMed

Fishbein, Diana H; Eldreth, Diana L; Hyde, Christopher; Matochik, John A; London, Edythe D; Contoreggi, Carlo; Kurian, Varughese; Kimes, Alane S; Breeden, Andrew; Grant, Steven

2005-04-01

Risky decision making is a hallmark behavioral phenotype of drug abuse; thus, an understanding of its biological bases may inform efforts to develop therapies for addictive disorders. A neurocognitive task that measures this function (Rogers Decision-Making Task; RDMT) was paired with measures of regional cerebral perfusion to identify brain regions that may underlie deficits in risky decision making in drug abusers. Subjects were abstinent drug abusers (> or =3 months) and healthy controls who underwent positron emission tomography scans with H(2)(15)O. Drug abusers showed greater risk taking and heightened sensitivity to rewards than control subjects. Both drug abusers and controls exhibited significant activations in a widespread network of brain regions, primarily in the frontal cortex, previously implicated in decision-making tasks. The only significant group difference in brain activation, however, was found in the left pregenual anterior cingulate cortex, with drug abusers exhibiting less task-related activation than control subjects. There were no significant correlations between neural activity and task performance within the control group. In the drug abuse group, on the other hand, increased risky choices on the RDMT negatively correlated with activation in the right hippocampus, left anterior cingulate gyrus, left medial orbitofrontal cortex, and left parietal lobule, and positively correlated with activation in the right insula. Drug abuse severity was related positively to right medial orbitofrontal activity. Attenuated activation of the pregenual ACC in the drug abusers relative to the controls during performance on the RDMT may underlie the abusers' tendency to choose risky outcomes.

Walking on thin ice! Identifying methamphetamine "drug mules" on digital plain radiography.

PubMed

Abdul Rashid, S N; Mohamad Saini, S B; Abdul Hamid, S; Muhammad, S J; Mahmud, R; Thali, M J; Flach, P M

2014-04-01

The purpose of this study was to retrospectively evaluate the sensitivity, specificity and accuracy of identifying methamphetamine (MA) internal payloads in "drug mules" by plain abdominal digital radiography (DR). The study consisted of 35 individuals suspected of internal MA drug containers. A total of 59 supine digital radiographs were collected. An overall calculation regarding the diagnostic accuracy for all "drug mules" and a specific evaluation concerning the radiological appearance of drug packs as well as the rate of clearance and complications in correlation with the reader's experience were performed. The gold standard was the presence of secured drug packs in the faeces. There were 16 true-positive "drug mules" identified. DR of all drug carriers for Group 1 (forensic imaging experienced readers, n = 2) exhibited a sensitivity of 100%, a mean specificity of 76.3%, positive predictive value (PPV) of 78.5%, negative predictive value (NPV) of 100% and a mean accuracy 87.2%. Group 2 (inexperienced readers, n = 3) showed a lower sensitivity (93.7%), a mean specificity of 86%, a PPV of 86.5%, an NPV of 94.1% and a mean accuracy of 89.5%. The interrater agreement within Group 1 was 0.72 and within Group 2 averaged to 0.79, indicating a fair to very good agreement. DR is a valuable screening tool in cases of MA body packers with huge internal payloads being associated with a high diagnostic insecurity. Diagnostic insecurity on plain films may be overcome by low-dose CT as a cross-sectional imaging modality and addressed by improved radiological education in reporting drug carriers on imaging. Diagnostic signs (double-condom and halo signs) on digital plain radiography are specific in MA "drug mules", although DR is associated with high diagnostic insecurity and underreports the total internal payload.

The Impact of Trauma on Drug Users' Identities

ERIC Educational Resources Information Center

Etherington, Kim

2007-01-01

This article addresses drug users' identity construction, and invites counsellors, psychotherapists, researchers and others who work with drug misusers to notice how cultural and societal discourses can shape drug misusers' stories, and the positions from which helpers listen and respond to them. By representing and analysing parts of two life…

Effect of peers on employment and implications for drug treatment.

PubMed

Montoya, Isaac D

2005-01-01

We examined the effect peers have on Temporary Assistance to Needy Families (TANF) recipients' employment behavior. Nondrug using and chronic drug using TANF recipients (n=433) participating in a study funded by the National Institute on Drug Abuse were asked how many of the people they regularly spent time with over the past 4 months had jobs and how many of them encouraged the individual to look for work. Results of a path analysis showed that age, education, and chronic drug use were significantly related to the nature of peer relationships. A significant and positive association between the number of peers that worked and the number of hours worked in the following 4 months was observed. Examining the effect of peers on labor force participation by TANF recipients is necessary to assist recipients in securing and maintaining employment.

Polypharmacy, drug-drug interactions, and potentially inappropriate medications in older adults with human immunodeficiency virus infection.

PubMed

Greene, Meredith; Steinman, Michael A; McNicholl, Ian R; Valcour, Victor

2014-03-01

To describe the frequency of medication-related problems in older adults with human immunodeficiency virus (HIV) infection. Retrospective chart review. Community. HIV-positive individuals aged 60 and older and age- and sex-matched HIV-negative individuals. Total number of medications, potentially inappropriate medications (PIMs) according to the modified Beers Criteria, anticholinergic drug burden according to the Anticholinergic Risk Scale (ARS), and drug-drug interactions using the Lexi-Interact online drug interactions database. Of 89 HIV-positive participants, most were Caucasian (91%) and male (94%), with a median age of 64 (range 60-82). Common comorbidities included hyperlipidemia, hypertension, and depression. Participants were taking a median of 13 medications (range 2-38), of which only a median of four were antiretrovirals. At least one PIM was prescribed in 46 participants (52%). Sixty-two (70%) participants had at least one Category D (consider therapy modification) drug-drug interaction, and 10 (11%) had a Category X (avoid combination) interaction. One-third of these interactions were between two nonantiretroviral medications. Fifteen participants (17%) had an ARS score of 3 or greater. In contrast, HIV-negative participants were taking a median of six medications, 29% had at least one PIM, and 4% had an ARS score of 3 or greater (P < .05 for each comparison, except P = .07 for anticholinergic burden). HIV-positive older adults have a high frequency of medication-related problems, of which a large portion is due to medications used to treat comorbid diseases. These medication issues were substantially higher than HIV-negative participants. Attention to the principles of geriatric prescribing is needed as this population ages in order to minimize complications from multiple medication use. © Published 2014. This article is a U.S. Government work and is in the public domain in the U.S.A.

Solid Lipid Nanoparticles of Guggul Lipid as Drug Carrier for Transdermal Drug Delivery

PubMed Central

Gaur, Praveen Kumar; Mishra, Shikha; Purohit, Suresh

2013-01-01

Diclofenac sodium loaded solid lipid nanoparticles (SLNs) were formulated using guggul lipid as major lipid component and analyzed for physical parameters, permeation profile, and anti-inflammatory activity. The SLNs were prepared using melt-emulsion sonication/low temperature-solidification method and characterized for physical parameters, in vitro drug release, and accelerated stability studies, and formulated into gel. Respective gels were compared with a commercial emulgel (CEG) and plain carbopol gel containing drug (CG) for ex vivo and in vivo drug permeation and anti-inflammatory activity. The SLNs were stable with optimum physical parameters. GMS nanoparticle 1 (GMN-1) and stearic acid nanoparticle 1 (SAN-1) gave the highest in vitro drug release. Guggul lipid nanoparticle gel 3 (GLNG-3) showed 104.68 times higher drug content than CEG in receptor fluid. The enhancement ratio of GLNG-3 was 39.43 with respect to CG. GLNG-3 showed almost 8.12 times higher C max than CEG at 4 hours. The AUC value of GLNG-3 was 15.28 times higher than the AUC of CEG. GLNG-3 showed edema inhibition up to 69.47% in the first hour. Physicochemical properties of major lipid component govern the properties of SLN. SLN made up of guggul lipid showed good physical properties with acceptable stability. Furthermore, it showed a controlled drug release profile along with a promising permeation profile. PMID:24058913

Therapeutic approaches for HER2-positive brain metastases: Circumventing the blood–brain barrier

PubMed Central

Mehta, Ankit I.; Brufsky, Adam M.; Sampson, John H.

2015-01-01

We aim to summarize data from studies of trastuzumab in patients with human epidermal growth factor receptor 2 (HER2)–positive metastatic breast cancer (MBC) and brain metastasis and to describe novel methods being developed to circumvent the blood–brain barrier (BBB). A literature search was conducted to obtain data on the clinical efficacy of trastuzumab and lapatinib in patients with HER2-positive MBC and brain metastasis, as well as the transport of therapeutic molecules across the BBB. Trastuzumab-based therapy is the standard of care for patients with HER2-positive MBC. Post hoc and retrospective analyses show that trastuzumab significantly prolongs overall survival when given after the diagnosis of central nervous system (CNS) metastasis; this is probably attributable to its control of extracranial disease, although trastuzumab may have a direct effect on CNS disease in patients with local or general perturbation of the BBB. In patients without a compromised BBB, trastuzumab is thought to have limited access to the brain, because of its relatively large molecular size. Several approaches are being developed to enhance the delivery of therapeutic agents to the brain. These include physical or pharmacologic disruption of the BBB, direct intracerebral drug delivery, drug manipulation, and coupling drugs to transport vectors. Available data suggest that trastuzumab extends survival in patients with HER2-positive MBC and brain metastasis. Novel methods for delivery of therapeutic agents into the brain could be used in the future to enhance access to the CNS by trastuzumab, thereby improving its efficacy in this setting. PMID:22727691

Test implementation of a school-oriented drug prevention program "Study without Drugs": pre- and post-testing for effectiveness.

PubMed

Ishaak, Fariel; de Vries, Nanne Karel; van der Wolf, Kees

2014-06-11

In this article, the test implementation of a school-oriented drug prevention program "Study without Drugs" is discussed. The aims of this study were to determine the results of the process evaluation and to determine whether the proposed school-oriented drug prevention program during a pilot project was effective for the participating pupils. Sixty second-grade pupils at a junior high school in Paramaribo, Suriname participated in the test implementation. They were divided into two classes. For the process evaluation the students completed a structured questionnaire focusing on content and teaching method after every lesson. Lessons were qualified with a score from 0-10. The process was also evaluated by the teachers through structured interviews. Attention was paid to reach, dose delivered, dose received, fidelity, connection, achieved effects/observed behaviors, areas for improvement, and lesson strengths. The effect evaluation was conducted by using the General Liniair Model (repeated measure). The research (-design) was a pre-experimental design with pre-and post-test. No class or sex differences were detected among the pupils with regard to the assessment of content, methodology, and qualification of the lessons. Post-testing showed that participating pupils obtained an increased knowledge of drugs, their drug-resisting skills were enhanced, and behavior determinants (attitude, subjective norm, self-efficacy, and intention) became more negative towards drugs. From the results of the test implementation can be cautiously concluded that the program "Study without Drugs" may yield positive results when applied in schools). Thus, this pilot program can be considered a step towards the development and implementation of an evidence-based school-oriented program for pupils in Suriname.

"Quenchbodies": quench-based antibody probes that show antigen-dependent fluorescence.

PubMed

Abe, Ryoji; Ohashi, Hiroyuki; Iijima, Issei; Ihara, Masaki; Takagi, Hiroaki; Hohsaka, Takahiro; Ueda, Hiroshi

2011-11-02

Here, we describe a novel reagentless fluorescent biosensor strategy based on the antigen-dependent removal of a quenching effect on a fluorophore attached to antibody domains. Using a cell-free translation-mediated position-specific protein labeling system, we found that an antibody single chain variable region (scFv) that had been fluorolabeled at the N-terminal region showed a significant antigen-dependent fluorescence enhancement. Investigation of the enhancement mechanism by mutagenesis of the carboxytetramethylrhodamine (TAMRA)-labeled anti-osteocalcin scFv showed that antigen-dependency was dependent on semiconserved tryptophan residues near the V(H)/V(L) interface. This suggested that the binding of the antigen led to the interruption of a quenching effect caused by the proximity of tryptophan residues to the linker-tagged fluorophore. Using TAMRA-scFv, many targets including peptides, proteins, and haptens including morphine-related drugs could be quantified. Similar or higher sensitivities to those observed in competitive ELISA were obtained, even in human plasma. Because of its versatility, this "quenchbody" is expected to have a range of applications, from in vitro diagnostics, to imaging of various targets in situ.

[Drug Exposed Infants and Their Families.

ERIC Educational Resources Information Center

Fenichel, Emily, Ed.

1992-01-01

This bulletin issue addresses the theme of drug-exposed infants and the services required by these infants and their families. "Cocaine-Exposed Infants: Myths and Misunderstandings" (Barbara J. Myers and others) comments on the negative accounts of drug-exposed babies presented by mass media and reviews the mix of positive and negative…

Parent ads in the National Youth Anti-Drug Media Campaign.

PubMed

Stephenson, Michael T; Quick, Brian L

2005-12-01

The National Youth Anti-Drug Media Campaign aims not only to reduce drug use by teens and preteens, but also to arm parents with knowledge about specific parenting practices known to reduce the risk of teen drug use. Among the documented successes of the campaign to date was a small, but direct effect on some parenting practices, including parent-child discussions about drug use. To reach a deeper understanding about the substance of the parental ads, we content analyzed the message strategies employed in the campaign's parent ads over the inaugural 5 years of the campaign. Each ad was coded for its major theme, minor subtheme, and featured drug. Among seven possible major themes, the parental anti-drug ads largely featured four: enhance the risk of their child's drug use, encourage monitoring practices, promote parent-child discussions about drug use, or advocate positive involvement behaviors. Moreover, most parental messages addressed marijuana use or addressed drug use in general. Marijuana and inhalant ads largely were risk based, while general drug messages focused on monitoring, parent-child discussions or positive involvement practices.

[Cost-benefit analysis of the implementation of automated drug-dispensing systems in Critical Care and Emergency Units].

PubMed

Poveda Andrés, J L; García Gómez, C; Hernández Sansalvador, M; Valladolid Walsh, A

2003-01-01

To determine monetary impact when traditional drug floor stocks are replaced by Automated Drug Dispensing Systems (ADDS) in the Medical Intensive Care Unit, Surgical Intensive Care Unit and the Emergency Room. We analysed four different flows considered to be determinant when implementing ADDS in a hospital environment: capital investment, staff costs, inventory costs and costs related to drug use policies. Costs were estimated by calculation of the current net value. Its analysis shows that those expenses derived from initial investment are compensated by the three remaining flows, with costs related to drug use policies showing the most substantial savings. Five years after initial investment, global cash-flows have been estimated at 300.525 euros. Replacement of traditional floor stocks by ADDS in the Medical Intensive Care Unit, Surgery Intensive Care Unit and the Emergency Room produces a positive benefit/cost ratio (1.95).

Employee Drug Testing. A Single Agency is Needed to Manage Federal Employee Drug Testing

DTIC Science & Technology

1991-02-19

The executive order requires the head of each executive agency to establish a program to test employees in sensitive positions for the use of illegal...that although several agencies were responsible for helping to design employee drug testing programs , there is no federal agency responsible for... EMPLOYEES ARE NOT BEING TREATED EQUITABLY Because the head of each agency is responsible for implementing a drug testing program , the extent to which

Nano-Advantage in Enhanced Drug Delivery with Biodegradable Nanoparticles: Contribution of Reduced Clearance

PubMed Central

Kadam, Rajendra S.; Bourne, David W. A.

2012-01-01

The aim of this study was to investigate the contribution of reduced apparent clearance to the enhanced exposure reported for biodegradable nanoparticles after extravascular and intravascular routes of administration. Plasma concentration profiles for drug and nanoparticle formulations after administration by intravenous, intraduodenal, and oral routes were extracted from the literature. Data were fit to pharmacokinetic models using BOOMER. The compartmental pharmacokinetic analysis of literature data for six drugs (camptothecin, 9-nitrocamptothecin, epirubicin, vinpocetine, clozapine, and cyclosporine) showed that the encapsulation of drug molecules in nanoparticles significantly reduced the apparent clearance and prolonged the apparent circulation half-life compared with those for the plain drug. Positively charged nanoparticles assessed in this study had lower apparent clearance, lower elimination rate constant values, and longer apparent circulation half-life than neutral and negatively charged nanoparticles. After oral administration, a reduction in apparent clearance contributed substantially to elevations in plasma drug exposure with nanoparticles. For the drugs and delivery systems examined, the nano-advantage in drug delivery enhancement can be explained, in part, by reduced clearance. PMID:22498894

Influence networks based on coexpression improve drug target discovery for the development of novel cancer therapeutics.

PubMed

Penrod, Nadia M; Moore, Jason H

2014-02-05

The demand for novel molecularly targeted drugs will continue to rise as we move forward toward the goal of personalizing cancer treatment to the molecular signature of individual tumors. However, the identification of targets and combinations of targets that can be safely and effectively modulated is one of the greatest challenges facing the drug discovery process. A promising approach is to use biological networks to prioritize targets based on their relative positions to one another, a property that affects their ability to maintain network integrity and propagate information-flow. Here, we introduce influence networks and demonstrate how they can be used to generate influence scores as a network-based metric to rank genes as potential drug targets. We use this approach to prioritize genes as drug target candidates in a set of ER⁺ breast tumor samples collected during the course of neoadjuvant treatment with the aromatase inhibitor letrozole. We show that influential genes, those with high influence scores, tend to be essential and include a higher proportion of essential genes than those prioritized based on their position (i.e. hubs or bottlenecks) within the same network. Additionally, we show that influential genes represent novel biologically relevant drug targets for the treatment of ER⁺ breast cancers. Moreover, we demonstrate that gene influence differs between untreated tumors and residual tumors that have adapted to drug treatment. In this way, influence scores capture the context-dependent functions of genes and present the opportunity to design combination treatment strategies that take advantage of the tumor adaptation process. Influence networks efficiently find essential genes as promising drug targets and combinations of targets to inform the development of molecularly targeted drugs and their use.

Influence networks based on coexpression improve drug target discovery for the development of novel cancer therapeutics

PubMed Central

2014-01-01

Background The demand for novel molecularly targeted drugs will continue to rise as we move forward toward the goal of personalizing cancer treatment to the molecular signature of individual tumors. However, the identification of targets and combinations of targets that can be safely and effectively modulated is one of the greatest challenges facing the drug discovery process. A promising approach is to use biological networks to prioritize targets based on their relative positions to one another, a property that affects their ability to maintain network integrity and propagate information-flow. Here, we introduce influence networks and demonstrate how they can be used to generate influence scores as a network-based metric to rank genes as potential drug targets. Results We use this approach to prioritize genes as drug target candidates in a set of ER + breast tumor samples collected during the course of neoadjuvant treatment with the aromatase inhibitor letrozole. We show that influential genes, those with high influence scores, tend to be essential and include a higher proportion of essential genes than those prioritized based on their position (i.e. hubs or bottlenecks) within the same network. Additionally, we show that influential genes represent novel biologically relevant drug targets for the treatment of ER + breast cancers. Moreover, we demonstrate that gene influence differs between untreated tumors and residual tumors that have adapted to drug treatment. In this way, influence scores capture the context-dependent functions of genes and present the opportunity to design combination treatment strategies that take advantage of the tumor adaptation process. Conclusions Influence networks efficiently find essential genes as promising drug targets and combinations of targets to inform the development of molecularly targeted drugs and their use. PMID:24495353

Surveillance of drug abuse in Hong Kong by hair analysis using LC-MS/MS.

PubMed

Leung, K Wing; Wong, Zack C F; Ho, Janet Y M; Yip, Ada W S; Cheung, Jerry K H; Ho, Karen K L; Duan, Ran; Tsim, Karl W K

2018-06-01

The aim of this study is to reveal the habits of drug abusers in hair samples from drug rehabilitation units in Hong Kong. With the application of liquid chromatography-tandem mass spectrometry (LC-MS/MS) technology, a total of 1771 hair samples were analyzed during the period of hair testing service (January 2012 to March 2016) provided to 14 drug rehabilitation units including non-governmental organizations (NGOs), rehabilitation centers, and medical clinics. Hair samples were analyzed for abused drugs and their metabolites simultaneously, including ketamine, norketamine, cocaine, benzoylecgonine, cocaethylene, norcocaine, codeine, MDMA, MDA, MDEA, amphetamine, methamphetamine, morphine, 6-acetylmorphine, phencyclidine, and methadone. The results showed that ketamine (77.2%), cocaine (21.3%), and methamphetamine (16.5%) were the frequently detected drugs among those drug abusers, which is consistent with the reported data. In addition, the usage of multiple drugs was also observed in the hair samples. About 29% of drug-positive samples were detected with multiple drug use. Our studies prove that our locally developed hair drug-testing method and service can be a valid tool to monitor the use of abused drugs, and which could facilitate rehabilitation program management. Copyright © 2017 John Wiley & Sons, Ltd.

Prediction of Drug-Target Interactions and Drug Repositioning via Network-Based Inference

PubMed Central

Jiang, Jing; Lu, Weiqiang; Li, Weihua; Liu, Guixia; Zhou, Weixing; Huang, Jin; Tang, Yun

2012-01-01

Drug-target interaction (DTI) is the basis of drug discovery and design. It is time consuming and costly to determine DTI experimentally. Hence, it is necessary to develop computational methods for the prediction of potential DTI. Based on complex network theory, three supervised inference methods were developed here to predict DTI and used for drug repositioning, namely drug-based similarity inference (DBSI), target-based similarity inference (TBSI) and network-based inference (NBI). Among them, NBI performed best on four benchmark data sets. Then a drug-target network was created with NBI based on 12,483 FDA-approved and experimental drug-target binary links, and some new DTIs were further predicted. In vitro assays confirmed that five old drugs, namely montelukast, diclofenac, simvastatin, ketoconazole, and itraconazole, showed polypharmacological features on estrogen receptors or dipeptidyl peptidase-IV with half maximal inhibitory or effective concentration ranged from 0.2 to 10 µM. Moreover, simvastatin and ketoconazole showed potent antiproliferative activities on human MDA-MB-231 breast cancer cell line in MTT assays. The results indicated that these methods could be powerful tools in prediction of DTIs and drug repositioning. PMID:22589709

FAT10 IS AN EPIGENETIC MARKER FOR LIVER PRENEOPLASIA IN A DRUG-PRIMED MOUSE MODEL OF TUMORIGENESIS

PubMed Central

Oliva, Joan; Bardag-Gorce, Fawzia; French, Barbara A; Li, Jun; McPhaul, Laron; Amidi, Fataneh; Dedes, Jeniffer; Habibi, Amir; Nguyen, Sheila; French, Samuel W

2010-01-01

There is clinical evidence that chronic liver diseases in which MDBs (Mallory Denk Bodies) form progress to hepatocellular carcinoma. The present study provides evidence that links MDB formation induced by chronic drug injury, with preneoplasia and later to the formation of tumors, which develop long after drug withdrawal. Evidence indicated that this link was due to an epigenetic cellular memory induced by chronic drug ingestion. Microarray analysis showed that the expressions of many markers of preneoplasia (UBD, Alpha Fetoprotein, KLF6 and Glutathione-S-Transferase mu2) were increased together when the drug DDC was refed. These changes were suppressed by S-adenosylmethionine feeding, indicating that the drug was affecting DNA and histones methylation in an epigenetic manner. The link between MDB formation and neoplasia formation was likely due to the over expression of UBD (also called FAT10), which is up regulated in 90% of human hepatocellular carcinomas. Immunohistochemical staining of drug primed mouse livers showed that FAT10 positive liver cells persisted up to 4 months after drug withdrawal and they were still found in the livers of mice, 14 months after drug withdrawal. The refeeding of DDC increased the percent of FAT10 hepatocytes. PMID:18280469

Illicit drug policy in Spain: the opinion of health and legal professionals.

PubMed

Rossi, Paola; Blay, Ester; Costela, Víctor; Torrens, Marta

2018-01-01

The high frequency of criminal behaviour and related legal problems associated with substance addiction generates a field of interaction between legal and healthcare systems. This study was developed as a multicentre project to investigate the opinions of professionals from legal and healthcare systems about policies on illegal drugs and their implementation in practice. A multiple choice questionnaire designed ad hoc was administered to a sample of 230 professionals from legal and healthcare fields working in the cities of Barcelona, Granada and Bilbao. The questionnaire included sociodemographic and work-related data, and assessed interviewees' information about the response to drug-related crime and opinion on drug policy issues. This article presents the results from Spain. The main results showed that both groups of professionals value alternative measures to imprisonment (AMI) as useful tools to prevent offenses related to drug use and claim a broader application of AMI. They also evaluated positively the regulations on cannabis use in effect. Though the attitude of healthcare professionals towards the application of AMI is more permissive, both groups favour restricting these sanctions in cases of recidivism. Both groups show mild satisfaction with the current addiction healthcare system and express dissatisfaction with actual drug policies in Spain.

[Drug delivery systems using nano-sized drug carriers].

PubMed

Nakayama, Masamichi; Okano, Teruo

2005-07-01

Nanotechnology has attracted great attention all over the world in recent several years and has led to the establishment of the novel technical field of "nanomedicine" through collaboration with advanced medical technology. Particularly, site-specific drug targeting using particle drug carrier systems has made substantial progress and been actively developed. This review explains the essential factors (size and chemical character) of drug carriers to allow long circulation in the bloodstream avoiding the reticuloendothelial system, and shows the present status and future perspective of several types of nano-carrier systems (water-soluble polymer, liposome and polymeric micelle). We also introduce the novel concept of multi-targeting system (combination of two or more targeting methodologies) for ideal drug therapies.

Decriminalization of drug use.

PubMed

Vicknasingam, Balasingam; Narayanan, Suresh; Singh, Darshan; Chawarski, Marek

2018-05-08

To review the literature on decriminalization of drug use from 2016 to 2017 and suggest the way forward. The systematic review of the literature on decriminalization resulted in seven articles that discuss decriminalization as compared with 57 published articles on legalization. Decriminalization of drug use did not have an effect on the age of onset of drug use and the prices of drugs did not decrease after the implementation of drug decriminalization. Policy-based studies on decriminalization suggest shifting from criminal sanctions to a public health approach, which was endorsed by the United Nations (UN) that viewed drug addiction as a preventable and treatable health disorder. One study preferred decriminalization only for cannabis and cautioned against regulating cannabis like alcohol. Another study indicated that general medical practitioners in Ireland did not favour the decriminalization of cannabis. Scientific evidence supporting drug addiction as a health disorder and the endorsement by the UN strengthen the case for decriminalization. However, studies reporting on the positive outcomes of decriminalization remain scarce. The evidence needs to be more widespread in order to support the case for decriminalization. Furthermore, the endorsement by the UN needs to be acted upon by individual member states.

Detection of Illicit Drugs by Trained Honeybees (Apis mellifera).

PubMed

Schott, Matthias; Klein, Birgit; Vilcinskas, Andreas

2015-01-01

Illegal drugs exacerbate global social challenges such as substance addiction, mental health issues and violent crime. Police and customs officials often rely on specially-trained sniffer dogs, which act as sensitive biological detectors to find concealed illegal drugs. However, the dog "alert" is no longer sufficient evidence to allow a search without a warrant or additional probable cause because cannabis has been legalized in two US states and is decriminalized in many others. Retraining dogs to recognize a narrower spectrum of drugs is difficult and training new dogs is time consuming, yet there are no analytical devices with the portability and sensitivity necessary to detect substance-specific chemical signatures. This means there is currently no substitute for sniffer dogs. Here we describe an insect screening procedure showing that the western honeybee (Apis mellifera) can sense volatiles associated with pure samples of heroin and cocaine. We developed a portable electroantennographic device for the on-site measurement of volatile perception by these insects, and found a positive correlation between honeybee antennal responses and the concentration of specific drugs in test samples. Furthermore, we tested the ability of honeybees to learn the scent of heroin and trained them to show a reliable behavioral response in the presence of a highly-diluted scent of pure heroin. Trained honeybees could therefore be used to complement or replace the role of sniffer dogs as part of an automated drug detection system. Insects are highly sensitive to volatile compounds and provide an untapped resource for the development of biosensors. Automated conditioning as presented in this study could be developed as a platform for the practical detection of illicit drugs using insect-based sensors.

Detection of Illicit Drugs by Trained Honeybees (Apis mellifera)

PubMed Central

Schott, Matthias; Klein, Birgit; Vilcinskas, Andreas

2015-01-01

Illegal drugs exacerbate global social challenges such as substance addiction, mental health issues and violent crime. Police and customs officials often rely on specially-trained sniffer dogs, which act as sensitive biological detectors to find concealed illegal drugs. However, the dog “alert” is no longer sufficient evidence to allow a search without a warrant or additional probable cause because cannabis has been legalized in two US states and is decriminalized in many others. Retraining dogs to recognize a narrower spectrum of drugs is difficult and training new dogs is time consuming, yet there are no analytical devices with the portability and sensitivity necessary to detect substance-specific chemical signatures. This means there is currently no substitute for sniffer dogs. Here we describe an insect screening procedure showing that the western honeybee (Apis mellifera) can sense volatiles associated with pure samples of heroin and cocaine. We developed a portable electroantennographic device for the on-site measurement of volatile perception by these insects, and found a positive correlation between honeybee antennal responses and the concentration of specific drugs in test samples. Furthermore, we tested the ability of honeybees to learn the scent of heroin and trained them to show a reliable behavioral response in the presence of a highly-diluted scent of pure heroin. Trained honeybees could therefore be used to complement or replace the role of sniffer dogs as part of an automated drug detection system. Insects are highly sensitive to volatile compounds and provide an untapped resource for the development of biosensors. Automated conditioning as presented in this study could be developed as a platform for the practical detection of illicit drugs using insect-based sensors. PMID:26083377

Allosteric cross-talk in chromatin can mediate drug-drug synergy

NASA Astrophysics Data System (ADS)

Adhireksan, Zenita; Palermo, Giulia; Riedel, Tina; Ma, Zhujun; Muhammad, Reyhan; Rothlisberger, Ursula; Dyson, Paul J.; Davey, Curt A.

2017-03-01

Exploitation of drug-drug synergism and allostery could yield superior therapies by capitalizing on the immensely diverse, but highly specific, potential associated with the biological macromolecular landscape. Here we describe a drug-drug synergy mediated by allosteric cross-talk in chromatin, whereby the binding of one drug alters the activity of the second. We found two unrelated drugs, RAPTA-T and auranofin, that yield a synergistic activity in killing cancer cells, which coincides with a substantially greater number of chromatin adducts formed by one of the compounds when adducts from the other agent are also present. We show that this occurs through an allosteric mechanism within the nucleosome, whereby defined histone adducts of one drug promote reaction of the other drug at a distant, specific histone site. This opens up possibilities for epigenetic targeting and suggests that allosteric modulation in nucleosomes may have biological relevance and potential for therapeutic interventions.

Reduction of non-specific adsorption of drugs to plastic containers used in bioassays or analyses.

PubMed

Fukazawa, Tominaga; Yamazaki, Yuri; Miyamoto, Yohei

2010-01-01

Non-specific adsorption (NSA) of drugs to plastic or glass containers used in clinical use is well known, but methods for reducing NSA have been rarely reported. We assessed the NSA to various containers and then investigated methods to reduce NSA. Probe drugs (methotrexate, warfarin, chloroquine, propranolol, verapamil, digoxin and paclitaxel) dissolved in water were incubated in conventional or low-adsorption containers for 4h at 4 degrees C and the NSA was determined by HPLC. They were also dissolved in aqueous methanol or acetonitrile and the NSA to a conventional polypropylene microplate was determined. Finally, tissue culture microplates were coated with silane coupling agents and the effects of the coatings were evaluated. Hydrophobic drugs (paclitaxel, verapamil and digoxin) were highly adsorbed to conventional plastic microplates, but in addition to hydrophobic drugs, positively charged drugs were well adsorbed to the tissue culture microplate. Low-adsorption microplates could reduce NSA below 15%, but positively charged or neutral hydrophobic drugs showed relatively higher adsorption. Acetonitrile showed stronger NSA inhibition than that of methanol, but the peak shapes of methotrexate and chloroquine were broadened and split. Among the silane coupling agents, GPTMS suppressed the NSA below 10%. Also, AATMS resembled the NSA pattern of GPTMS, but it increased the adsorption of methotrexate to 29%. On conventional plastic microplates, NSA is mainly driven by hydrophobic interactions, but on tissue culture microplates and low-adsorption microplates, in addition to hydrophobic interactions, ionic interactions play a role in the NSA. Therefore, to reduce the NSA to plastic containers, both hydrophobic and ionic interactions should be reduced using amphiphilic organic solvents or neutral and hydrophilic coatings. 2010 Elsevier Inc. All rights reserved.

Club Drug Use in Hispanic College Students

PubMed Central

Resor, Michelle R.; Cooper, Theodore V.

2010-01-01

Club drug use and correlates were examined among 251 Hispanic college students on the Texas - México border. Participants completed questionnaires on substance use, club drug attitudes and beliefs, sexual risk-taking behaviors, depressive symptoms, and acculturation. One-quarter of participants reported club drug use. Regression analyses demonstrated that frequency and history of lifetime use were consistently associated with more permissive drug attitudes and other substance use but not sexual risk-taking, depression symptoms, or acculturation. Acculturation was negatively associated with frequency of club drug use, yet positively associated with use of other illicit substances. Avenues for future studies are suggested. PMID:20653638

Drug use and abuse: the ethical issues.

PubMed

Almond, B

1992-01-01

Drug abuse is both a personal and a public issue, raising questions about individual rights and the boundaries of law, as well as about national sovereignty and international control. Ethical issues that arise under these headings may be related to certain broad ethical positions. The implications of adopting utilitarian assumptions may be contrasted with basing ethics on a theory of individual rights, closely related to a theory of human nature. Neither position justifies a libertarian presumption against control, for, first, an individual decision to expose one's mind and personality to the control of drugs cannot be ethically justified and, second, there are no ethical reasons, nor any compelling arguments from social and political theory, for decriminalizing non-medical drug use.

Outbreak of mastitis in sheep caused by multi-drug resistant Enterococcus faecalis in Sardinia, Italy.

PubMed

Sanciu, G; Marogna, G; Paglietti, B; Cappuccinelli, P; Leori, G; Rappelli, P

2013-03-01

An outbreak of infective mastitis due to Enterococcus faecalis occurred in an intensive sheep farm in north Sardinia (Italy). E. faecalis, which is only rarely isolated from sheep milk, was unexpectedly found in 22·3% of positive samples at microbiological examination. Forty-five out of the 48 E. faecalis isolates showed the same multi-drug resistance pattern (cloxacillin, streptomycin, kanamycin, clindamycin, oxytetracycline). E. faecalis isolates were analysed by pulsed-field gel electrophoresis, and all 45 multi-drug resistant strains showed an indistinguishable macrorestiction profile, indicating their clonal origin. To our knowledge, this is the first report of an outbreak of mastitis in sheep caused by E. faecalis.

Drug Discovery Prospect from Untapped Species: Indications from Approved Natural Product Drugs

PubMed Central

Qin, Chu; Tao, Lin; Liu, Xin; Shi, Zhe; Zhang, Cun Long; Tan, Chun Yan; Chen, Yu Zong; Jiang, Yu Yang

2012-01-01

Due to extensive bioprospecting efforts of the past and technology factors, there have been questions about drug discovery prospect from untapped species. We analyzed recent trends of approved drugs derived from previously untapped species, which show no sign of untapped drug-productive species being near extinction and suggest high probability of deriving new drugs from new species in existing drug-productive species families and clusters. Case histories of recently approved drugs reveal useful strategies for deriving new drugs from the scaffolds and pharmacophores of the natural product leads of these untapped species. New technologies such as cryptic gene-cluster exploration may generate novel natural products with highly anticipated potential impact on drug discovery. PMID:22808057

Simple, direct drug susceptibility testing technique for diagnosis of drug-resistant tuberculosis in resource-poor settings.

PubMed

Kim, C-K; Joo, Y-T; Lee, E P; Park, Y K; Kim, H-J; Kim, S J

2013-09-01

The Korean Institute of Tuberculosis, Seoul, Republic of Korea. To develop a simple, direct drug susceptibility testing (DST) technique using Kudoh-modified Ogawa (KMO) medium. The critical concentrations of isoniazid (INH), rifampicin (RMP), kanamycin (KM) and ofloxacin (OFX) for KMO medium were calibrated by comparing the minimal inhibitory concentrations (MICs) against clinical isolates of Mycobacterium tuberculosis on KMO with those on Löwenstein-Jensen (LJ). The performance of the direct KMO DST technique was evaluated on 186 smear-positive sputum specimens and compared with indirect LJ DST. Agreement of MICs on direct vs. indirect DST was high for INH, RMP and OFX. KM MICs on KMO were ∼10 g/ml higher than those on LJ. The critical concentrations of INH, RMP, OFX and KM for KMO were therefore set at 0.2, 40.0, 2.0, and 40.0 g/ml. The evaluation of direct DST of smear-positive sputum specimens showed 100% agreement with indirect LJ DST for INH and RMP. However, the respective susceptible and resistant predictive values were 98.8% and 100% for OFX, and 100% and 80% for KM. Direct DST using KMO is useful, with clear advantages of a shorter turnaround time, procedural simplicity and low cost compared to indirect DST. It may be most indicated in resource-poor settings for programmatic management of drug-resistant tuberculosis.

Incidence of multidrug-resistant, extensively drug-resistant and pan-drug-resistant bacteria in children hospitalized at Dr. Hasan Sadikin general hospital Bandung Indonesia

NASA Astrophysics Data System (ADS)

Adrizain, R.; Suryaningrat, F.; Alam, A.; Setiabudi, D.

2018-03-01

Antibiotic resistance has become a global issue, with 700,000 deaths attributable to multidrug-resistance (MDR) occurring each year. Centers for Disease Control and Prevention (CDC) show rapidly increasing rates of infection due to antibiotic-resistant bacteria. The aim of the study isto describe the incidence of MDR, extensively drug-resistant (XDR) and pan drug-resistant (PDR) in Enterococcus spp., Staphylococcus aureus, K. pneumonia, Acinetobacter baumanii, P. aeruginosin, and Enterobacter spp. (ESKAPE) pathogens in children admitted to Dr. Hasan Sadikin Hospital. All pediatric patients having blood culture drawn from January 2015 to December 2016 were retrospectively studied. Data include the number of drawn blood culture, number of positive results, type of bacteria, sensitivity pattern. International standard definitions for acquired resistance by ECDC and CDC was used as definitions for MDR, XDR and PDR bacteria. From January 2015 to December 2016, 299 from 2.542 (11.7%) blood culture was positive, with Staphylococcus aureus, Enterococcus spp., Enterobacteriaceae, Pseudomonas aeruginosa, Acinetobacter spp., respectively 5, 6, 24, 5, 20 with total 60 (20%). The MDR and XDR pathogen found were 47 and 13 patients, respectively.

Hepatitis C infection among intravenous drug users attending therapy programs in Cyprus.

PubMed

Demetriou, Victoria L; van de Vijver, David A M C; Hezka, Johana; Kostrikis, Leondios G; Kostrikis, Leondios G

2010-02-01

The most high-risk population for HCV transmission worldwide today are intravenous drug users. HCV genotypes in the general population in Cyprus demonstrate a polyphyletic infection and include subtypes associated with intravenous drug users. The prevalence of HCV, HBV, and HIV infection, HCV genotypes and risk factors among intravenous drug users in Cyprus were investigated here for the first time. Blood samples and interviews were obtained from 40 consenting users in treatment centers, and were tested for HCV, HBV, and HIV antibodies. On the HCV-positive samples, viral RNA extraction, RT-PCR and sequencing were performed. Phylogenetic analysis determined subtype and any relationships with database sequences and statistical analysis determined any correlation of risk factors with HCV infection. The prevalence of HCV infection was 50%, but no HBV or HIV infections were found. Of the PCR-positive samples, eight (57%) were genotype 3a, and six (43%) were 1b. No other subtypes, recombinant strains or mixed infections were observed. The phylogenetic analysis of the injecting drug users' strains against database sequences observed no clustering, which does not allow determination of transmission route, possibly due to a limitation of sequences in the database. However, three clusters were discovered among the drug users' sequences, revealing small groups who possibly share injecting equipment. Statistical analysis showed the risk factor associated with HCV infection is drug use duration. Overall, the polyphyletic nature of HCV infection in Cyprus is confirmed, but the transmission route remains unknown. These findings highlight the need for harm-reduction strategies to reduce HCV transmission. (c) 2009 Wiley-Liss, Inc.

Factors associated with reported hepatitis C and HIV among injecting drug users in ten European cities.

PubMed

March, Joan Carles; Oviedo-Joekes, Eugenia; Romero, Manuel

2007-02-01

To analyze self-reported prevalence of HCV and HIV in a sample of socially excluded injecting drug users, as well as factors associated with the presence of these diseases. Cross-sectional study. Data were collected with a structured, face-to-face questionnaire by outreach workers and privileged access interviewers in 1131 participants who had injected heroin and/or cocaine over the past year (71.5% men; mean age, 30 years) from Seville and Granada, Spain; Cologne, Germany; Vienna, Austria; Brussels, Belgium; Athens, Greece; Dublin, Ireland; London, England; Lisbon, Portugal and Perugia, Italy. Among the total sample, 595 (52.6%) participants reported HCV-positive status and 143 (12.6%) HIV-positive status. Multivariate analysis for HCV showed that women are at less risk than men, and that longer drug use, injecting while in prison, sharing needles, and reported positive status for tuberculosis, HBV, HIV or sexually-transmitted disease are positively associated with HCV. Participants reporting positive HIV status were generally older, had injected drugs while in prison, had completed less than 8 years of schooling, were divorced, had no regular employment, and declared infection with tuberculosis, sexually-transmitted disease and HCV. The highest incidences of HCV and HIV were reported by participants in a poorer social and health situation. Drug addicts must cope not only with their addiction but also with the process of social exclusion they are immersed in. To the greatest extent possible, any course of action for this group should be built into integrated, coordinated plans that take a broad approach to the main issues involved.

Modeling antibiotic treatment in hospitals: A systematic approach shows benefits of combination therapy over cycling, mixing, and mono-drug therapies.

PubMed

Tepekule, Burcu; Uecker, Hildegard; Derungs, Isabel; Frenoy, Antoine; Bonhoeffer, Sebastian

2017-09-01

Multiple treatment strategies are available for empiric antibiotic therapy in hospitals, but neither clinical studies nor theoretical investigations have yielded a clear picture when which strategy is optimal and why. Extending earlier work of others and us, we present a mathematical model capturing treatment strategies using two drugs, i.e the multi-drug therapies referred to as cycling, mixing, and combination therapy, as well as monotherapy with either drug. We randomly sample a large parameter space to determine the conditions determining success or failure of these strategies. We find that combination therapy tends to outperform the other treatment strategies. By using linear discriminant analysis and particle swarm optimization, we find that the most important parameters determining success or failure of combination therapy relative to the other treatment strategies are the de novo rate of emergence of double resistance in patients infected with sensitive bacteria and the fitness costs associated with double resistance. The rate at which double resistance is imported into the hospital via patients admitted from the outside community has little influence, as all treatment strategies are affected equally. The parameter sets for which combination therapy fails tend to fall into areas with low biological plausibility as they are characterised by very high rates of de novo emergence of resistance to both drugs compared to a single drug, and the cost of double resistance is considerably smaller than the sum of the costs of single resistance.

Studies on drug metabolism by fungi colonizing decomposing human cadavers. Part II: biotransformation of five model drugs by fungi isolated from post-mortem material.

PubMed

Martínez-Ramírez, Jorge A; Walther, Grit; Peters, Frank T

2015-04-01

The present study investigated the in vitro metabolic capacity of 28 fungal strains isolated from post-mortem material towards five model drugs: amitriptyline, metoprolol, mirtazapine, promethazine, and zolpidem. Each fungal strain was incubated at 25 °C for up to 120 h with each of the five models drugs. Cunninghamella elegans was used as positive control. Aliquots of the incubation mixture were centrifuged and 50 μL of the supernatants were diluted and directly analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) with product ion scanning. The remaining mixture was analyzed by full scan gas chromatography-mass spectrometry (GC-MS) after liquid-liquid extraction and acetylation. The metabolic activity was evaluated through the total number of detected metabolites (NDM) produced in each model and fungal strains and the percentage of parent drug remaining (%RPD) after up to five days of incubation. All the tested fungal strains were capable of forming mammalian phase I metabolites. Fungi from the normal fungal flora of the human body such as Candida sp., Geotrichum candidum, and Trichosporon asahii) formed up to seven metabolites at %RPD values greater than 52% but no new fungal metabolites (NFM). In contrast, some airborne fungal strains like Bjerkandera adusta, Chaetomium sp, Coriolopsis sp., Fusarium solani and Mucor plumbeus showed NDM values exceeding those of the positive control, complete metabolism of the parent drug in some models and formation of NFM. NFM (numbers in brackets) were detected in four of the five model drugs: amitriptyline (18), metoprolol (4), mirtazapine (8), and zolpidem (2). The latter NFM are potential candidates for marker substances indicating post-mortem fungal metabolism. Copyright © 2014 John Wiley & Sons, Ltd.

Weakening of negative relative to positive associations with cocaine-paired cues contributes to cue-induced responding after drug removal.

PubMed

Su, Zu-In; Kichaev, Gleb; Wenzel, Jennifer; Ben-Shahar, Osnat; Ettenberg, Aaron

2012-01-01

Cocaine has been shown to have initial positive (euphoric) and delayed negative (anxiogenic) effects in both humans and animals. Cocaine-paired cues are consequently imbued with mixed positive and negative associations. The current study examines the relative roles of these dual associations in the enhanced drug-seeking observed upon presentation of cocaine-paired cues. Rats ran a straight alley once/day for a single i.v. injection of cocaine (1.0 mg/kg/inj) in the presence of a distinctive olfactory cue (scented cotton swabs placed under the apparatus). An alternate scent was presented in a separate cage 2-h prior to runway testing. After 15 trials/days, the scents and cocaine reinforcer were removed and a series of extinction trials (lasting for 1 or 3 weeks) was initiated. Immediately following extinction, runway responding was tested during a single trial in the presence of the cocaine-paired or non-paired cue. As previously reported, while subjects initiated responding faster over trials (reduced latencies to leave the start box), they exhibited a progressive increase in approach-avoidance conflict behavior ("retreats") regarding goal-box entry, reflecting cocaine's dual positive+negative effects. Once established, retreat behaviors persisted over the course of 1 or 3 weeks days of extinction. However, both run times and retreats decreased in response to presentation of the cocaine-paired but not the non-paired scent. These data suggest that, after reinforcer removal, cue-induced cocaine-seeking stems in part from a reduction in approach-avoidance conflict; i.e., a greater weakening of the negative relative to the positive associations that animals form with cocaine-paired stimuli. Copyright © 2011 Elsevier Inc. All rights reserved.