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Sample records for drug utilization

  1. Rural drug users: factors associated with substance abuse treatment utilization.

    PubMed

    Oser, Carrie B; Leukefeld, Carl G; Tindall, Michele Staton; Garrity, Thomas F; Carlson, Robert G; Falck, Russel; Wang, Jichuan; Booth, Brenda M

    2011-06-01

    The purpose of this study is to use a modified version of Andersen's Behavioral Model of Health Services Use to identify the correlates of the number of substance abuse treatment episodes received by rural drug users. Data were collected from face-to-face interviews with 711 drug users in rural areas of Ohio, Arkansas, and Kentucky. Descriptive analyses examine rural drug users' substance use histories and retrospective substance abuse treatment service utilization patterns. A negative binomial regression model indicated that selected predisposing, historical health, and enabling factors were significantly associated with the utilization of substance abuse treatment among rural drug users. Despite high levels of recent and lifetime self-reported substance use among these rural drug users, treatment services were underutilized. Future studies are needed to examine the impact of the health care system and characteristics of the external environment associated with rural substance abuse treatment in order to increase utilization among drug users.

  2. The anticipatory effects of Medicare Part D on drug utilization.

    PubMed

    Alpert, Abby

    2016-09-01

    While health care policies are frequently signed into law well before they are implemented, such lags are ignored in most empirical work. This paper demonstrates the importance of implementation lags in the context of Medicare Part D, the prescription drug benefit that took effect two years after it was signed into law. Exploiting the differential responses of chronic and acute drugs to anticipated future prices, I show that individuals reduced drug utilization for chronic but not acute drugs in anticipation of Part D's implementation. Accounting for this anticipatory response substantially reduces the estimated total treatment effect of Part D. PMID:27372577

  3. Drug utilization and teratogenicity risk categories during pregnancy.

    PubMed

    Basgül, Alin; Akici, Ahmet; Uzuner, Arzu; Kalaça, Sibel; Kavak, Zehra N; Tural, Alper; Oktay, Sule

    2007-01-01

    A limited number of studies have investigated in detail the use of drugs during pregnancy. Researchers in the present study investigated the details of drug utilization in pregnant women during the month before pregnancy, at the time that they became aware of the pregnancy, and during the first trimester. Face-to-face interviews were conducted with 359 pregnant women who were admitted to the fetal medicine unit at a university hospital for diagnosis and follow-up. A questionnaire was used to document sociodemographic characteristics and details of drug use. Drugs were categorized according to the US Food and Drug Administration fetal risk classification. Mean maternal age was 29.9+/-5.1 y, and mean gestational age was 19.6+/-9.5 wk. Many of the pregnant women studied (46.6%) were university graduates, and most (61.9%) had a relatively high annual income. Mean gestational age when participants first learned of their pregnancy was 39.8+/-16.4 d. One hundred seventeen participants (32.6%) used drugs during the month before conception, 54 (15%) at the time when they learned of their pregnancy, 180 (50.1%) at the time of the interview, and 289 (80.5%) during the first trimester. The percentages of drugs in categories D and X used by these subjects were 14%, 13.5%, 2.9%, and 5.9%, respectively. Most of the drugs were hormones. The total rate of drug utilization was not high before and during the first trimester of pregnancy. A considerable number of women were using drugs from the D and X categories; however, these numbers decreased significantly when women learned of their pregnancies. Intake of folic acid, vitamins, and iron was very low during the preconception period and was not high enough during the first trimester; this suggests that particular attention should be paid to the use of beneficial "safe" drugs during the preconception and early pregnancy periods.

  4. Socioeconomic factors, morbidity and drug utilization--an ecological study.

    PubMed

    Henricson, K; Stenberg, P; Rametsteiner, G; Ranstam, J; Hanson, B S; Melander, A

    1998-07-01

    The aim of the present study was to elucidate the relations between demographic and socioeconomic factors, morbidity and the utilization of major drug groups in an urban Swedish population. The study was performed as an ecological analysis during November 1991 in the 17 different districts of Malmö, the third largest Swedish city (235,000 inhabitants). The material comprised 86,228 ACT-coded drug items which corresponded to 76% of all prescriptions dispensed during the study month. Of these, 43,032, dispensed to patients aged 15-64 years, were analysed in the present work. Age standardized drug utilization was expressed as the number of dispensed Defined Daily Doses per 1000 inhabitants per day. Morbidity was measured in terms of reimbursed days on sick leave. The sociodemographic parameters used were socioeconomic status (SES), employment rate, median income per family, households on social allowance, and ethnicity. For four of the five major pharmacological groups (ATC-groups A, C, J, N and R, i.e. alimentation, circulation, infectious diseases, nervous system and respiration), most pronouncedly group N and least so group R, utilization correlated positively with not only the extent of morbidity but also with an unfavourable socioeconomic situation, high proportion of immigrants, and households on social allowance or with low income and/or with a low employment rate. The utilization of antibiotics (group J), however, instead correlated negatively with these parameters. For all five drug groups, these trends were similar among men and women, albeit with varying strength. In conclusion, socioeconomic factors may have a profound influence on the utilization of several major drug groups. At least in the case of antibiotics, the consequence of this influence is irrational drug use. PMID:15073988

  5. Forecasting drug utilization and expenditure in a metropolitan health region

    PubMed Central

    2010-01-01

    Background New pharmacological therapies are challenging the healthcare systems, and there is an increasing need to assess their therapeutic value in relation to existing alternatives as well as their potential budget impact. Consequently, new models to introduce drugs in healthcare are urgently needed. In the metropolitan health region of Stockholm, Sweden, a model has been developed including early warning (horizon scanning), forecasting of drug utilization and expenditure, critical drug evaluation as well as structured programs for the introduction and follow-up of new drugs. The aim of this paper is to present the forecasting model and the predicted growth in all therapeutic areas in 2010 and 2011. Methods Linear regression analysis was applied to aggregate sales data on hospital sales and dispensed drugs in ambulatory care, including both reimbursed expenditure and patient co-payment. The linear regression was applied on each pharmacological group based on four observations 2006-2009, and the crude predictions estimated for the coming two years 2010-2011. The crude predictions were then adjusted for factors likely to increase or decrease future utilization and expenditure, such as patent expiries, new drugs to be launched or new guidelines from national bodies or the regional Drug and Therapeutics Committee. The assessment included a close collaboration with clinical, clinical pharmacological and pharmaceutical experts from the regional Drug and Therapeutics Committee. Results The annual increase in total expenditure for prescription and hospital drugs was predicted to be 2.0% in 2010 and 4.0% in 2011. Expenditures will increase in most therapeutic areas, but most predominantly for antineoplastic and immune modulating agents as well as drugs for the nervous system, infectious diseases, and blood and blood-forming organs. Conclusions The utilisation and expenditure of drugs is difficult to forecast due to uncertainties about the rate of adoption of new

  6. Medical cost offsets from prescription drug utilization among Medicare beneficiaries.

    PubMed

    Roebuck, M Christopher

    2014-10-01

    This brief commentary extends earlier work on the value of adherence to derive medical cost offset estimates from prescription drug utilization. Among seniors with chronic vascular disease, 1% increases in condition-specific medication use were associated with significant (P  less than  0.001) reductions in gross nonpharmacy medical costs in the amounts of 0.63% for dyslipidemia, 0.77% for congestive heart failure, 0.83% for diabetes, and 1.17% for hypertension. PMID:25278321

  7. [Development of topical drug delivery systems utilizing polymeric materials].

    PubMed

    Machida, Y

    1993-05-01

    Topical drug delivery is important from the view points of improvement of therapeutic effect and reduction of systemic side effects. Utilization of polymeric materials seemed to be as a key for the development of new topical dosage forms including targeting drug delivery systems. Adriamycin ointment for local chemotherapy to breast cancer prepared using polyethylene glycol, ammonium polyacrylate and hydroxypropyl cellulose (HPC) according to an optimum formulation showed an excellent clinical effect in spite of a decreased drug content. Double-layered mucoadhesive sticks for the treatment of uterine cervix cancer were prepared by direct compression of powder mixture of bleomycin, HPC and carboxyvinyl polymer (CP). Drug release property of the sticks could be controlled by the weight of outer layer, drug combining ratio to each layer and coating of core layer. The results suggested a possibility of a "once-a-week" treatment that is preferable for the patients. Magnetic granules for the treatment of esophageal cancer were prepared using ferrite, HPC and CP. Magnetic guidance and retainment of the granules on esophageal mucosa were confirmed using rabbits in vivo. Buoyant sustained release preparations were prepared using chitosan, soybean protein, HPC and other polymers. Usefulness of the buoyant preparations was suggested from the results in vitro and in vivo. Insulin microspheres (IMS) for targeting delivery to the small intestine were prepared by the newly developed method. Employment of enteric coating material (Eudragit) and combination of protease inhibitor protected insulin from enzymatic attack and gave decreased levels of blood glucose by oral administration.

  8. Emergency department utilization and subsequent prescription drug overdose death

    PubMed Central

    Brady, Joanne E.; DiMaggio, Charles J.; Keyes, Katherine M.; Doyle, John J.; Richardson, Lynne D.; Li, Guohua

    2015-01-01

    Purpose Prescription drug overdose (PDO) deaths are a critical public health problem in the United States. This study aims to assess the association between emergency department (ED) utilization patterns in a cohort of ED patients and the risk of subsequent unintentional PDO mortality. Methods Using data from the New York Statewide Planning and Research Cooperative System for 2006–2010, a nested case-control design was used to examine the relationship between ED utilization patterns in New York State residents of age 18–64 years and subsequent PDO death. Results The study sample consisted of 2732 case patients who died of PDO and 2732 control ED patients who were selected through incidence density sampling. With adjustment for demographic characteristics, and diagnoses of pain, substance abuse, and psychiatric disorders, the estimated odds ratios of PDO death relative to one ED visit or less in the previous year were 4.90 (95% confidence interval [CI]: 4.50–5.34) for those with two ED visits, 16.61 (95% CI: 14.72–18.75) for those with three ED visits, and 48.24 (95% CI: 43.23–53.83) for those with four ED visits or more. Conclusions Frequency of ED visits is strongly associated with the risk of subsequent PDO death. Intervention programs targeting frequent ED users are warranted to reduce PDO mortality. PMID:25935710

  9. An informatics approach to assess pediatric pharmacotherapy: design and implementation of a hospital drug utilization system.

    PubMed

    Zuppa, Athena; Vijayakumar, Sundararajan; Jayaraman, Bhuvana; Patel, Dimple; Narayan, Mahesh; Vijayakumar, Kalpana; Mondick, John T; Barrett, Jeffrey S

    2007-09-01

    Drug utilization in the inpatient setting can provide a mechanism to assess drug prescribing trends, efficiency, and cost-effectiveness of hospital formularies and examine subpopulations for which prescribing habits may be different. Such data can be used to correlate trends with time-dependent or seasonal changes in clinical event rates or the introduction of new pharmaceuticals. It is now possible to provide a robust, dynamic analysis of drug utilization in a large pediatric inpatient setting through the creation of a Web-based hospital drug utilization system that retrieves source data from our accounting database. The production implementation provides a dynamic and historical account of drug utilization at the authors' institution. The existing application can easily be extended to accommodate a multi-institution environment. The creation of a national or even global drug utilization network would facilitate the examination of geographical and/or socioeconomic influences in drug utilization and prescribing practices in general. PMID:17656617

  10. Can Walmart make us healthier? Prescription drug prices and health care utilization.

    PubMed

    Borrescio-Higa, Florencia

    2015-12-01

    This paper analyzes how prices in the retail pharmaceutical market affect health care utilization. Specifically, I study the impact of Walmart's $4 Prescription Drug Program on utilization of antihypertensive drugs and on hospitalizations for conditions amenable to drug therapy. Identification relies on the change in the availability of cheap drugs introduced by Walmart's program, exploiting variation in the distance to the nearest Walmart across ZIP codes in a difference-in-differences framework. I find that living close to a source of cheap drugs increases utilization of antihypertensive medications by 7 percent and decreases the probability of an avoidable hospitalization by 6.2 percent.

  11. Reservoir-Based Drug Delivery Systems Utilizing Microtechnology

    PubMed Central

    Stevenson, Cynthia L.; Santini, John T.; Langer, Robert

    2012-01-01

    This review covers reservoir-based drug delivery systems that incorporate microtechnology, with an emphasis on oral, dermal, and implantable systems. Key features of each technology are highlighted such as working principles, fabrication methods, dimensional constraints, and performance criteria. Reservoir-based systems include a subset of microfabricated drug delivery systems and provide unique advantages. Reservoirs, whether external to the body or implanted, provide a well-controlled environment for a drug formulation, allowing increased drug stability and prolonged delivery times. Reservoir systems have the flexibility to accommodate various delivery schemes, including zero order, pulsatile, and on demand dosing, as opposed to a standard sustained release profile. Furthermore, the development of reservoir-based systems for targeted delivery for difficult to treat applications (e.g., ocular) has resulted in potential platforms for patient therapy. PMID:22465783

  12. [Drug utilization in renal transplant patients: medication practices and representations].

    PubMed

    de Arruda, Guilherme Oliveira; Renovato, Rogério Dias

    2012-12-01

    Qualitative research approach, descriptive and exploratory with objective of to know the practices and representations of medication on the use of drugs by people transplanted kidney. 18 people participated in the Dourados (MS), through semistructured interview. The theoretical contributions of medication practices were Peter Conrad and representation of Stuart Hall. The definition of the categories of theoretical analysis was Michel Foucault. Respondents had a mean age of 53.5 years, 13 males and 5 females, with median time to transplant eight years. The medications predominantly used were immunosuppresssive. We developed three categories of analysis: the drug as part of everyday life, the central role of the drug and correlation with rejection, and medicine and the autonomy of the transplanted kidney. The drugs are part of everyday life and the representations of autonomy and quality enhance your daily use.

  13. Prescription drug monitoring program utilization in Kentucky community pharmacies

    PubMed Central

    Wixson, Sarah E.; Blumenschein, Karen; Goodin, Amie J.; Talbert, Jeffery; Freeman, Patricia R.

    2014-01-01

    Objective: Identify characteristics of Kentucky community pharmacists and community pharmacists’ practice environment associated with utilization of the Kentucky All Schedule Prescription Electronic Reporting Program (KASPER). Methods: Surveys were mailed to all 1,018 Kentucky pharmacists with a KASPER account and an additional 1,000 licensed pharmacists without an account. Bivariate analyses examined the association between KASPER utilization and practice type (independent or chain) and practice location (rural or urban). A multivariate Poisson regression model with robust error variance estimated risk ratios (RR) of KASPER utilization by characteristics of pharmacists’ practice environment. Results: Responses were received from 563 pharmacists (response rate 27.9%). Of these, 402 responses from community pharmacists were included in the analyses. A majority of responding pharmacists (84%) indicated they or someone in their pharmacy had requested a patient’s controlled substance history since KASPER’s inception. Bivariate results showed that pharmacists who practiced in independent pharmacies reported greater KASPER utilization (94%) than pharmacists in chain pharmacies (75%; p<0.001). Multivariate regression results found utilization of KASPER varied significantly among practice environments of community pharmacists with those who practiced in an urban location (RR: 1.11; [1.01–1.21]) or at an independent pharmacy (RR: 1.27; [1.14–1.40]) having an increased likelihood of KASPER utilization. Conclusion: Utilization of KASPER differs by community pharmacists’ practice environment, predominantly by practice type and location. Understanding characteristics of community pharmacists and community pharmacists’ practice environment associated with PDMP use is necessary to remove barriers to access and increase utilization thereby increasing PDMP effectiveness. PMID:26131042

  14. Drug utilization study in medical emergency unit of a tertiary care hospital in north India.

    PubMed

    Kaur, Sharonjeet; Rajagopalan, Sujit; Kaur, Navjot; Shafiq, Nusrat; Bhalla, Ashish; Pandhi, Promila; Malhotra, Samir

    2014-01-01

    Objective. To generate data on the drug utilization pattern and cost of drug treatment and to determine the rationality of prescriptions. Methods. A retrospective cross-sectional drug utilization study was conducted in the medical emergency unit of our hospital. Patient case records were reviewed to extract data on the pattern of drug use. Cost of drug treatment for the emergency visit was calculated by referring to the cost mentioned in Monthly Index of Medical Specialties and the rationality of prescriptions was evaluated using WHO core indicators of drug utilization. Results. 1100 case records were reviewed. Majority of patients received proton pump inhibitors followed by multivitamins. The median cost per prescription was 119.23$ (7.32$-7663.46$). Majority (49.9%) of drug cost was driven by antibiotics alone. An average of 4.9 drugs was prescribed per prescription. There were 14.89% encounters with antibiotics. 75.17% of the drugs were given as injectables and only 29.27% of the drugs were prescribed as generics. Conclusion. There is need to rationalize the drug therapy in terms of increasing prescribing of drugs by generic name and to avoid overuse of PPIs and multivitamins in emergency unit. Also the hospital pharmacy should be encouraged to procure more cost effective alternative antibiotics in future. PMID:24883208

  15. Drug utilization in selected health facilities of South West Shoa Zone, Oromia Region, Ethiopia

    PubMed Central

    Kebede, Mengistu; Kebebe Borga, Dereje; Mulisa Bobasa, Eshetu

    2015-01-01

    Background Sustaining the availability and rational use of safe and effective drugs is a major problem in developing countries. Irrational drug use affects quality of health care more than accessibility of drugs. Objective To assess drug utilization in selected health facilities of South West Shoa Zone, Oromia Region, Ethiopia. Methods A cross-sectional study was conducted in selected health facilities of South West Shoa Zone from January 21–28, 2012 by using structured questionnaires. Results Of 50 prescribers and 30 dispensers, 58% and 83.3% were males, respectively. The result showed that majority of prescribers agreed on availability of essential drugs (72%) and had access to up-to-date drug information (76%). However, 43.3% of dispensers didn’t get access to up-to-date drug information. 86% and 88% of prescribers note cost of drugs and stick to standard treatment guidelines of Ethiopia during prescription, respectively. All drug dispensers check the name of the drug (100%), age of the patient (90%), the dosage form of drug (96.7%), the route of administration (90%), the duration of therapy (86.7%), and frequency of administration (86.7%) for prescription papers. Conclusion In general, drug utilization at the study sites was found to be good, although there are major deviations from the concept of rational drug use. PMID:26229506

  16. A Proposal for Better Drug Utilization and Education in Tompkins County (New York)

    ERIC Educational Resources Information Center

    Rivkin, Lawrence S.

    1976-01-01

    This proposal contains a mechanism to provide the population with useful drug information at the time of purchase. This mechanism may also provide the system with useful information concerning drug utilization by the consuming public. Such information is vital to health planners and others interested in health care delivery. (Author)

  17. Utilizing ambulatory blood pressure recordings to evaluate antihypertensive drug therapy.

    PubMed

    White, W B

    1992-04-30

    Until recently, the efficacy and pharmacodynamics of antihypertensive agents were assessed by resting blood pressure measurements in the doctor's office or a research clinic. The limitations of the office or clinic blood pressure measurement include the lack of representation (from recording only 1 point of time in the dosing schedule), the effects of the doctor's office on the patient's blood pressure, and, perhaps more relevant, observer bias. Ambulatory monitoring of the blood pressure has gained worldwide acceptance as an alternative method to assess antihypertensive drug efficacy and the time-effect relation of a drug. The ambulatory monitoring devices have been refined and are smaller, more precise, and more reliable than earlier recording models. Although there are no reference standards for analysis of ambulatory blood pressure data, international consensus groups are presently addressing this problem. Key roles for ambulatory blood pressure recordings in clinical trials of antihypertensive agents now include determination of the entry criteria for patients, improving the assessment of peak/trough pharmacodynamics in the patient's own environment (including nocturnal/sleep readings), and evaluating efficacy through calculation of the hypertensive burden, or blood pressure load. PMID:1575177

  18. 42 CFR 423.153 - Drug utilization management, quality assurance, and medication therapy management programs (MTMPs).

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ...-utilization and under-utilization of prescribed medications; and (3) Provides CMS with information concerning... examination of claims data and other records, through computerized drug claims processing and information retrieval systems, in order to identify patterns of inappropriate or medically unnecessary care...

  19. Utilizing diversity-oriented synthesis in antimicrobial drug discovery.

    PubMed

    Comer, Eamon; Duvall, Jeremy R; duPont Lee, Maurice

    2014-01-01

    The development of resistance to existing antimicrobials has created a threat to human health that is not being addressed through our current drug pipeline. Limitations with the use of commercial vendor libraries and natural products have created a need for new types of small molecules to be screened in antimicrobial assays. Diversity oriented synthesis (DOS) is a strategy for the efficient generation of compound collections with a high degree of structural diversity. Diversity-oriented synthesis molecules occupy the middle ground of both complexity and efficiency of synthesis between natural products and commercial libraries. In this review we focus upon the use of diversity-oriented synthesis compound collections for the discovery of new antimicrobial agents. PMID:25495985

  20. Drug utilization of clarithromycin for gastrointestinal disease treatment

    PubMed Central

    Zhou, Quan; Zhu, Ling-Ling; Yan, Xiao-Feng; Pan, Wen-Sheng; Zeng, Su

    2008-01-01

    AIM: To evaluate the patterns of use of clarithromycin for gastrointestinal disease treatment and promote its rational use. METHODS: Using a structured pro forma, we conducted a two-month survey of the electronic prescriptions containing immediate-release (IR) or sustained-release (SR) product of clarithromycin for outpatients with gastrointestinal diseases in a 2200-bed general hospital. Suitability of the prescription was audited retrospectively. RESULTS: One hundred and sixty-four prescriptions of SR product and 110 prescriptions of IR product were prescribed for gastrointestinal disease treatment. Among prescriptions for anti-Helicobacter pylori (H pylori) therapy, triple therapy take the dominant position (91.8%), followed by quadruple therapy (4.3%) and dual therapy (3.9%). Amoxicillin was the most frequently co-prescribed antibiotic. Furazolidone and levofloxacin are used more widely than metronidazole or tinidazole. Clarithromycin SR was administered at inappropriate time points in all prescriptions. Fifty percent of all prescriptions of clarithromycin SR, and 6.4% of prescriptions of clarithromycin IR, were prescribed at inappropriate dosing intervals. Surprisingly, disconcordance between diagnoses and indications was observed in all prescriptions of clarithromycin SR which has not been approved for treating H pylori infection although off-label use for this purpose was reported in literature. On the contrary, only one prescription (0.9%) of clarithromycin IR was prescribed for unapproved indication (i.e. gastro-oesophageal reflux disease). 1.4% of prescriptions for chronic gastritis or peptic ulcer treatment were irrational in that clarithromycin was not co-prescribed with gastric acid inhibitors. Clinical significant CYP3A based drug interactions with clarithromycin were identified. CONCLUSION: There is a great scope to improve the quality of clarithromycin prescribing in patients with gastrointestinal disease, especially with regard to administration

  1. Methods for comparing drug policies--the utility of composite drug harm indexes.

    PubMed

    Ritter, Alison

    2009-11-01

    One of the challenges for drug policy research is being able to compare policy options and outcomes. The development of indexes, such as the UK Drug Harm Index or the UNODC Illicit Drug Index is a way to systematically enable such comparisons. An Index is a single common metric that represents the diverse outcomes or consequences of drug use. An Index may be used for performance monitoring within one country/region over time; to establish societal benefit of drug policies as expressed in social costs saved; to compare countries or regions; or for comparative policy analysis. Clarity of purpose is important in how an Index is used. The consequences or outcomes that can be combined into a single Index include health consequences, crime consequences, public amenity, pain and suffering, labour market outcomes, and drug manufacture and trafficking activity. The choice of outcomes for inclusion is driven by the purpose but also often by practical considerations, such as data availability. The weighting of the consequences is an important consideration in translating the outcomes into a common metric. A monetary unit has a number of advantages: it is a unit that can be measured across diverse impacts; it gives implicit "weighting" of harms; and it is intuitive for policy makers and community. On the other hand, it represents an economic perspective. No one Index will be regarded as suitable and appropriate by every stakeholder and ongoing research effort on Indexes is an important foundational research activity to advance illicit drug policy. PMID:19356915

  2. Comparative study of paediatric prescription drug utilization between the spanish and immigrant population

    PubMed Central

    2009-01-01

    Background The immigrant population has increased greatly in Spain in recent years to the point where immigrants made up 12% of the infant population in 2008. There is little information available on the profile of this group with regard to prescription drug utilization in universal public health care systems such as that operating in Spain. This work studies the overall and specific differences in prescription drug utilization between the immigrant and Spanish population. Methods Use was made of the Aragonese Health Service databases for 2006. The studied population comprises 159,908 children aged 0-14 years, 13.6% of whom are foreign nationals. Different utilization variables were calculated for each group. Prescription-drug consumption is measured in Defined Daily Doses (DDD) and DDD/1000 persons/day/(DID). Results A total of 833,223 prescriptions were studied. Utilization is lower for immigrant children than in Spanish children for both DID (66.27 v. 113.67) and average annual expense (€21.55 v. €41.14). Immigrant children consume fewer prescription drugs than Spanish children in all of the therapy groups, with the most prescribed (in DID) being: respiratory system, anti-infectives for systemic use, nervous system, sensory organs. Significant differences were observed in relation to the type of drugs and the geographical background of immigrants. Conclusion Prescription drug utilization is much greater in Spanish children than in immigrant children, particularly with reference to bronchodilators (montelukast and terbutaline) and attention-disorder hyperactivity drugs such as methylphenidate. There are important differences regarding drug type and depending on immigrants' geographical backgrounds that suggest there are social, cultural and access factors underlying these disparities. PMID:19995453

  3. Utility of population pharmacokinetic modeling in the assessment of therapeutic protein-drug interactions.

    PubMed

    Chow, Andrew T; Earp, Justin C; Gupta, Manish; Hanley, William; Hu, Chuanpu; Wang, Diane D; Zajic, Stefan; Zhu, Min

    2014-05-01

    Assessment of pharmacokinetic (PK) based drug-drug interactions (DDI) is essential for ensuring patient safety and drug efficacy. With the substantial increase in therapeutic proteins (TP) entering the market and drug development, evaluation of TP-drug interaction (TPDI) has become increasingly important. Unlike for small molecule (e.g., chemical-based) drugs, conducting TPDI studies often presents logistical challenges, while the population PK (PPK) modeling may be a viable approach dealing with the issues. A working group was formed with members from the pharmaceutical industry and the FDA to assess the utility of PPK-based TPDI assessment including study designs, data analysis methods, and implementation strategy. This paper summarizes key issues for consideration as well as a proposed strategy with focuses on (1) PPK approach for exploratory assessment; (2) PPK approach for confirmatory assessment; (3) importance of data quality; (4) implementation strategy; and (5) potential regulatory implications. Advantages and limitations of the approach are also discussed.

  4. Drug and alcohol abuse: the bases for employee assistance programs in the nuclear-utility industry

    SciTech Connect

    Radford, L.R.; Rankin, W.L.; Barnes, V.; McGuire, M.V.; Hope, A.M.

    1983-07-01

    This report describes the nature, prevalence, and trends of drug and alcohol abuse among members of the US adult population and among personnel in non-nuclear industries. Analogous data specific to the nuclear utility industry are not available, so these data were gathered in order to provide a basis for regulatory planning. The nature, prevalence, and trend inforamtion was gathered using a computerized literature, telephone discussions with experts, and interviews with employee assistance program representatives from the Seattle area. This report also evaluates the possible impacts that drugs and alcohol might have on nuclear-related job performance, based on currently available nuclear utility job descriptions and on the scientific literature regarding the impairing effects of drugs and alcohol on human performance. Employee assistance programs, which can be used to minimize or eliminate job performance decrements resulting from drug or alcohol abuse, are also discussed.

  5. Drug utilization and morbidity statistics for the evaluation of drug safety in Sweden.

    PubMed

    Wiholm, B E; Westerholm, B

    1984-01-01

    For a continuous monitoring and evaluation of drug safety problems in Sweden, the Department of Drugs of the National Board of Health and Welfare has access to a number of computerised patient-, drug-, and disease-oriented registers. The usefulness and limitations of these registers are presented by examples. A recent increase in asthma deaths is presently being analysed by comparing information from death certificates and case records with drug sales and prescription data. A recent analysis of the cancer register showed no increased risk of malignant thyroid tumors after diagnostic or therapeutic doses of I 131. Similarly no increased risk of malformations after occupational exposure to hexachlorophene could be detected by analysing the malformation and medical birth-record registers in relation to hospital hexachlorophene use. The register of patient discharge diagnoses has been repeatedly used to analyse the incidence and pattern of drug induced blood dyscrasias and thromboembolism associated with oral contraceptives (OC). These analyses have resulted i.a. in the withdrawal of dipyrone and tenalidine and a decrease of the estrogen-content of OCs. At the same time about 1/3 of these serious adverse drug reactions (ADR) was found to have been reported to the ADR-register. By combining sales and prescription data with ADR-reports the risk of inducing lactic acidosis was found to be significantly higher for phenformin than for metformin. Also the incidence of tardive dyskinesia from longterm use of metoclopramide was found to be much higher than hitherto recognized. By use of these registers it is possible to obtain valuable information about the safety of drugs. The raw data must, however, be interpreted with care and often be supplemented with in depth studies of the various problems. PMID:6430038

  6. ChEMBL web services: streamlining access to drug discovery data and utilities.

    PubMed

    Davies, Mark; Nowotka, Michał; Papadatos, George; Dedman, Nathan; Gaulton, Anna; Atkinson, Francis; Bellis, Louisa; Overington, John P

    2015-07-01

    ChEMBL is now a well-established resource in the fields of drug discovery and medicinal chemistry research. The ChEMBL database curates and stores standardized bioactivity, molecule, target and drug data extracted from multiple sources, including the primary medicinal chemistry literature. Programmatic access to ChEMBL data has been improved by a recent update to the ChEMBL web services (version 2.0.x, https://www.ebi.ac.uk/chembl/api/data/docs), which exposes significantly more data from the underlying database and introduces new functionality. To complement the data-focused services, a utility service (version 1.0.x, https://www.ebi.ac.uk/chembl/api/utils/docs), which provides RESTful access to commonly used cheminformatics methods, has also been concurrently developed. The ChEMBL web services can be used together or independently to build applications and data processing workflows relevant to drug discovery and chemical biology.

  7. Internalized HIV and Drug Stigmas: Interacting Forces Threatening Health Status and Health Service Utilization Among People with HIV Who Inject Drugs in St. Petersburg, Russia.

    PubMed

    Calabrese, Sarah K; Burke, Sara E; Dovidio, John F; Levina, Olga S; Uusküla, Anneli; Niccolai, Linda M; Heimer, Robert

    2016-01-01

    Marked overlap between the HIV and injection drug use epidemics in St. Petersburg, Russia, puts many people in need of health services at risk for stigmatization based on both characteristics simultaneously. The current study examined the independent and interactive effects of internalized HIV and drug stigmas on health status and health service utilization among 383 people with HIV who inject drugs in St. Petersburg. Participants self-reported internalized HIV stigma, internalized drug stigma, health status (subjective rating and symptom count), health service utilization (HIV care and drug treatment), sociodemographic characteristics, and health/behavioral history. For both forms of internalized stigma, greater stigma was correlated with poorer health and lower likelihood of service utilization. HIV and drug stigmas interacted to predict symptom count, HIV care, and drug treatment such that individuals internalizing high levels of both stigmas were at elevated risk for experiencing poor health and less likely to access health services.

  8. Utilizing the protein corona around silica nanoparticles for dual drug loading and release

    NASA Astrophysics Data System (ADS)

    Shahabi, Shakiba; Treccani, Laura; Dringen, Ralf; Rezwan, Kurosch

    2015-10-01

    A protein corona forms spontaneously around silica nanoparticles (SNPs) in serum-containing media. To test whether this protein corona can be utilized for the loading and release of anticancer drugs we incorporated the hydrophilic doxorubicin, the hydrophobic meloxicam as well as their combination in the corona around SNPs. The application of corona-covered SNPs to osteosarcoma cells revealed that drug-free particles did not affect the cell viability. In contrast, SNPs carrying a protein corona with doxorubicin or meloxicam lowered the cell proliferation in a concentration-dependent manner. In addition, these particles had an even greater antiproliferative potential than the respective concentrations of free drugs. The best antiproliferative effects were observed for SNPs containing both doxorubicin and meloxicam in their corona. Co-localization studies revealed the presence of doxorubicin fluorescence in the nucleus and lysosomes of cells exposed to doxorubicin-containing coated SNPs, suggesting that endocytotic uptake of the SNPs facilitates the cellular accumulation of the drug. Our data demonstrate that the protein corona, which spontaneously forms around nanoparticles, can be efficiently exploited for loading the particles with multiple drugs for therapeutic purposes. As drugs are efficiently released from such particles they may have a great potential for nanomedical applications.A protein corona forms spontaneously around silica nanoparticles (SNPs) in serum-containing media. To test whether this protein corona can be utilized for the loading and release of anticancer drugs we incorporated the hydrophilic doxorubicin, the hydrophobic meloxicam as well as their combination in the corona around SNPs. The application of corona-covered SNPs to osteosarcoma cells revealed that drug-free particles did not affect the cell viability. In contrast, SNPs carrying a protein corona with doxorubicin or meloxicam lowered the cell proliferation in a concentration

  9. Evaluation of utility of pharmacokinetic studies in phase I trials of two oncology drugs

    PubMed Central

    Wu, Kehua; House, Larry; Ramírez, Jacqueline; Seminerio, Michael J.; Ratain, Mark J.

    2013-01-01

    Purpose There are many phase I trials of oncology drug combinations, very few of which report clinically significant pharmacokinetic interactions. We hypothesized that the utility of such pharmacokinetic drug-drug interaction (DDI) studies is low in the absence of a mechanistic hypothesis. Experimental Design We retrospectively reviewed 152 phase I (2 drug) combination studies published in 2007–2011. Results Only 28 (18%) studies had an implicit or explicit rationale, either inhibition/induction of a drug metabolizing enzyme or transporter, co-substrates for the same enzyme or transporter, potential for end-organ toxicity, or protein binding. Only 12 (8%) studies demonstrated a statistically significant DDI, based on change in clearance (or area under the curve) of parent drug and/or active metabolite. There was a strong association between a rationale and a demonstrable drug interaction, as only 2% of studies without a rationale demonstrated a DDI, compared to 32% of studies with a rationale (Fisher’s exact test, p<10−6). Conclusion DDI studies should not be routinely performed as part of phase I trials of oncology combinations. PMID:24056785

  10. Study of drug utilization pattern in dental OPD at tertiary care teaching hospital.

    PubMed

    Rehan, H S; Singh, C; Tripathi, C D; Kela, A K

    2001-01-01

    Irrational prescribing is a global phenomenon. The objective of the study was to find out the prescribing practices of dental prescribers in a tertiary care teaching hospital with special emphasis on the utilization of antimicrobial agents. A prospective study was conducted in the month of March 2000. A total of 491 prescriptions were collected randomly. Prescribing pattern was analyzed using WHO basic drug indicators. The average number of drugs for prescription was 2.4. 78.8% of all prescriptions contained antimicrobial agents. It was most commonly prescribed (40.37%) group of drugs followed by anti-inflammatory and analgesics (33.8%). Fixed dose combination of ampicillin and cloxacillin was most commonly prescribed antimicrobial agents. Prophylactic use of AMA (78%) was more than therapeutic purpose (21.9%). Prophylactic use of antimicrobial agents was irrational in all the cases as duration for the use of antimicrobial agents was 5.1 +/- 0.5 days. Fixed dose combinations (45%), drugs by brand name (98.5%) were frequently used. Drug prescribed from Essential Drug List was maximum when one drug was prescribed. Results indicate that there is a scope for improving prescribing habits and minimizing the use of antimicrobial agents. This could be facilitated by periodic education to the prescribers.

  11. Utility of Ion Mobility Mass Spectrometry for Drug-to-Antibody Ratio Measurements in Antibody-Drug Conjugates

    NASA Astrophysics Data System (ADS)

    Huang, Richard Y.-C.; Deyanova, Ekaterina G.; Passmore, David; Rangan, Vangipuram; Deshpande, Shrikant; Tymiak, Adrienne A.; Chen, Guodong

    2015-06-01

    Antibody-drug conjugates (ADCs) are emerging modalities in the pharmaceutical industry. Characterization of ADC's drug-to-antibody ratio (DAR) becomes a key assessment because of its importance in ADC efficacy and safety. DAR characterization by conventional intact protein MS analysis, however, is challenging because of high heterogeneity of ADC samples. The analysis often requires protein deglycosylation, disulfide-bond reduction, or partial fragmentation. In this study, we illustrate the practical utility of ion mobility mass spectrometry (IM-MS) in a routine LC/MS workflow for DAR measurements. This strategy allows analyte "cleanup" in the gas phase, providing significant improvement of signal-to-noise ratios of ADC intact mass spectra for accurate DAR measurements. In addition, protein drift time analysis offers a new dimension in monitoring the changes of DAR in lot-to-lot analysis.

  12. Medical and psychosocial services in drug abuse treatment: do stronger linkages promote client utilization?

    PubMed Central

    Friedmann, P D; D'Aunno, T A; Jin, L; Alexander, J A

    2000-01-01

    OBJECTIVE: To examine the extent to which linkage mechanisms (on-site delivery, external arrangements, case management, and transportation assistance) are associated with increased utilization of medical and psychosocial services in outpatient drug abuse treatment units. DATA SOURCES: Survey of administrative directors and clinical supervisors from a nationally representative sample of 597 outpatient drug abuse treatment units in 1995. STUDY DESIGN: We generated separate two-stage multivariate generalized linear models to evaluate the correlation of on-site service delivery, formal external arrangements (joint program/venture or contract), referral agreements, case management, and transportation with the percentage of clients reported to have utilized eight services: physical examinations, routine medical care, tuberculosis screening, HIV treatment, mental health care, employment counseling, housing assistance, and financial counseling services. PRINCIPAL FINDINGS: On-site service delivery and transportation assistance were significantly associated with higher levels of client utilization of ancillary services. Referral agreements and formal external arrangements had no detectable relationship to most service utilization. On-site case management was related to increased clients' use of routine medical care, financial counseling, and housing assistance, but off-site case management was not correlated with utilization of most services. CONCLUSIONS: On-site service delivery appears to be the most reliable mechanism to link drug abuse treatment clients to ancillary services, while referral agreements and formal external mechanisms offer little detectable advantage over ad hoc referral. On-site case management might facilitate utilization of some services, but transportation seems a more important linkage mechanism overall. These findings imply that initiatives and policies to promote linkage of such clients to medical and psychosocial services should emphasize on

  13. Applicability, Commercial Utility and Recent Patents on Starch and Starch Derivative as Pharmaceutical Drug Delivery Carrier.

    PubMed

    Pandey, Shreya; Malviya, Rishabha; Sharma, Pramod K

    2015-01-01

    Natural polymers are widely utilized in pharmaceutical and food industries. Starch, a major carbohydrate is a staple food in human and animal diets which is simply extractable from various sources, like potato, maize, corn, wheat, etc. It is widely used as a raw material in various food and non food industries as well as in paper, textile and other industries. This article summarizes the starch and modification of starch and to produce a novel molecule with various applications in industries including number of advances in pharmaceutical industry. The unique characteristics of starch and their modified form can be successfully used as drug delivery carriers in various pharmaceutical preparations. It is widely used as controlled and sustained release polymer, tablet disintegrant, drug delivery carrier, plasma volume expander and also finds its applicability in bone tissue engineering and in artificial red cells. It also includes the patents related to starch and modified starch based products and their commercial utility. PMID:26205680

  14. Legitimacy and modernity via policy transfer: the utility of the 2003 Afghan National Drug Control Strategy.

    PubMed

    Bewley-Taylor, David R

    2014-09-01

    Very much an exercise in historical reconstruction, this article is concerned with the development of the first version of the Afghan NDCS. It is hoped that this domain of enquiry will contribute to discussions around the 'governance of drug policy' in this special issue of the International Journal of Drug Policy by focusing on how different policy actors operate in influencing the policy process; or parts thereof. More specifically, exploration of the formulation of the Strategy does much to help us understand not only the origins and shifting nature of ownership of drug policy within Afghanistan but also the relationship between the NDCS and the broader normative expectations of what has been referred to as the global drug prohibition regime (Andreas & Nadelmann, 2006, p. 38). As will be discussed, while indisputably the product of a process of policy transfer involving a number of non-Afghan actors - and as such arguably not always appropriate to the peculiarities of the drug market within the country - it can be argued that the 2003 National Drug Control Strategy fulfilled a useful functional role that in many ways exceeded its utility as a guiding document beyond the confines of Kabul.

  15. Utilizing the protein corona around silica nanoparticles for dual drug loading and release.

    PubMed

    Shahabi, Shakiba; Treccani, Laura; Dringen, Ralf; Rezwan, Kurosch

    2015-10-21

    A protein corona forms spontaneously around silica nanoparticles (SNPs) in serum-containing media. To test whether this protein corona can be utilized for the loading and release of anticancer drugs we incorporated the hydrophilic doxorubicin, the hydrophobic meloxicam as well as their combination in the corona around SNPs. The application of corona-covered SNPs to osteosarcoma cells revealed that drug-free particles did not affect the cell viability. In contrast, SNPs carrying a protein corona with doxorubicin or meloxicam lowered the cell proliferation in a concentration-dependent manner. In addition, these particles had an even greater antiproliferative potential than the respective concentrations of free drugs. The best antiproliferative effects were observed for SNPs containing both doxorubicin and meloxicam in their corona. Co-localization studies revealed the presence of doxorubicin fluorescence in the nucleus and lysosomes of cells exposed to doxorubicin-containing coated SNPs, suggesting that endocytotic uptake of the SNPs facilitates the cellular accumulation of the drug. Our data demonstrate that the protein corona, which spontaneously forms around nanoparticles, can be efficiently exploited for loading the particles with multiple drugs for therapeutic purposes. As drugs are efficiently released from such particles they may have a great potential for nanomedical applications.

  16. Exploring the limits and utility of operant conditioning in the treatment of drug addiction.

    PubMed

    Silverman, Kenneth

    2004-01-01

    This article describes a research program to develop an operant treatment for cocaine addiction in low-income, treatment-resistant methadone patients. The treatment's central feature is an abstinence reinforcement contingency in which patients earn monetary reinforcement for providing cocaine-free urine samples. Success and failure of this contingency appear to be an orderly function of familiar parameters of operant conditioning. Increasing reinforcement magnitude and duration can increase effectiveness, and sustaining the contingency can prevent relapse. Initial development of a potentially practical application of this technology suggests that it may be possible to integrate abstinence reinforcement into employment settings using salary for work to reinforce drug abstinence. This research illustrates the potential utility and current limitations of an operant approach to the treatment of drug addiction. Similar research programs are needed to explore the limits of the operant approach and to develop practical applications that can be used widely in society for the treatment of drug addiction.

  17. Watching the monitors: "PAID" prescriptions, fiscal intermediaries and drug-utilization review.

    PubMed

    Morgan, J P

    1977-02-01

    Prescription monitoring evolved from the need of drug firms to obtain marketing information. Today, extensive monitoring is also done by fiscal intermediaries who administer prepaid drug benefit plans, both private and governmental, particularly Medicaid. The most important such agent is PAID Prescriptions. Under various contracts, PAID monitors physician, pharmacy, and patient behavior related to prescriptions and uses review processes that evaluate certain kinds of behavior for appropriateness. The criteria of appropriateness are essentially those that save money. PAID negotiates a program fee with the insurer (public or private) and applies constraints so that prescription and administrative costs do not overrun that fee. PAID and other monitors have contemplated expansion into the realm of defining and encouraging appropriate prescribing under the concept of "drugutilization review." The actual practices of PAID, particularly the background of fiscal enforcement, may impede the development of an actual drug-utilization review process.

  18. Profile of drug utilization in the elderly living in Porto Alegre, Brazil

    PubMed Central

    Tôrres Faggiani, Fabiana; Schroeter, Guilherme; Luz Pacheco, Sandro; Araújo De Souza, Antônio Carlos; Werlang, Maria Cristina; Attílio De Carli, Geraldo; Bueno Morrone, Fernanda

    The elderly population is one of the most rapidly increasing populations in the world. Physiological alterations induced by the aging process make these individuals more susceptible to chronic diseases and, consequently, to increased drug utilization. Objective To describe the profile of drug utilization in the elderly living in Porto Alegre, RS, Brazil. Methods An observational and cross-sectional population-based study to investigate the characteristics of the population, sources of information and types of drugs used by the elderly was performed. Four hundred and eighty patients were recruited from data supplied by the City Hall of Porto Alegre. The elderly were interviewed individually during the period from January to May 2006 by trained interviewers. A validated pharmacotherapy questionnaire was used for data collection and data were tabulated and analyzed by the SPSS 11.5 computer program. Results Of the 480 patients interviewed, 13.8% did not use any medication. Cardiovascular system drugs represented the pharmacological class most used by the elderly (64.0%). When ill, 71.9% of these individuals visited the doctor, while 36.9% self-medicated. For the majority (50.2%), drugs were identified by their labels. Only 41.2% of the elderly understood medical prescriptions and 68.3% of the patients studied obtained the necessary information for the appropriate use of therapy from their doctors. Conclusions The present study suggests that a pharmaceutical care program for the treatment, prevention, and use of medications may provide a higher efficiency to elderly drug therapy. PMID:25170356

  19. Utility of coloured hair for the detection of drugs and alcohol.

    PubMed

    Agius, Ronald

    2014-06-01

    The aim of this paper is to assess the utility of coloured hair for the detection of drugs and alcohol in a large statistically significant population. The positivity rate, the 1st, 5th, 50th, 95th, and 99th percentiles of five amphetamines, cannabinoids, cocaine, four opiates, methadone, buprenorphine, seven benzodiazepines, and ethyl glucuronide (EtG) in 9488 non-treated and 1026 cosmetically treated (dyed or bleached) authentic hair samples was compared. Analytical methods used were accredited for forensic purposes at the cut-offs defined by the German driving licence re-granting medical and psychological assessment (MPA) guidelines. Considering only the drug classes for which at least 10 positive samples were detected, the positivity rate in non-treated hair was highest for alcohol (4.50%; measured using EtG at concentrations ≥ 7 pg/mg hair), followed by THC (2.00%), cocaine (1.75%), and amphetamine (0.59%). While the 1st to 99th percentile range was significantly lower for drugs in treated, compared to non-treated hair, no significant change was observed for EtG. Additionally, no significant difference in the positivity rate was observed between treated hair and non-treated hair for both drugs and EtG. This study is the first attempt to evaluate the influence of cosmetic treatment, mainly dying, on the positivity rate for both drugs and EtG in hair samples submitted routinely for abstinence testing and the first to indicate that dyed and eventually bleached hair is not necessarily useless in detecting drugs and/or alcohol consumption, thus making coloured hair analysis still useful, often being the only possibility to prove such misuse. PMID:24817056

  20. The utilization of Arabic online drug information among adults in Saudi Arabia.

    PubMed

    Abanmy, Norah O; Al-Quait, Nouf A; Alami, Amani H; Al-Juhani, Meshaal H; Al-Aqeel, Sinaa

    2012-10-01

    In Saudi Arabia, the utilization of the world wide web has become increasingly popular. However, the exact figure of such use is unknown. This study aimed to determine the percentage of, and experience with, online Arabic drug information by Arabic-speaking adults in Saudi Arabia. A web based questionnaire was used. The questionnaire language was Arabic. Public were invited to participate in the survey through e-mails, Twitter, WhatsApp and Facebook in March 2012. The survey included 17 items examining the types of accessed Arabic drug information, the respondent's demographics, their ability to easily find and understand Arabic drug-related information, and their trustfulness and dependency on such information websites. Of the 422 Arabic speaking adults who answered the questionnaire, 88% stated that they used Arabic websites to answer drug-related questions. Of the respondents, 50% had a bachelor's degree, 44% were young adults, over half were female (60%), and 72% of them have a chronic disease. The ease of retrieving online information was the most common reason (69%) for consulting such websites. Google as a search engine was the most frequently (86%) accessible website. Although respondents reported different drug-related topics in their online searching, the search for adverse effects was the most common (68%). Respondents claimed that they could easily find (65%) and understand (49%) the drug-related information. Although a good number of respondents qualified this type of information as good, double-checking of information on other websites was highly recommended. Trustfulness was one of the important parameters to measure and 205 respondents (55%) claimed that they only trusted half of the information cited. Moreover, around 48% of respondents considered that finding the same information on more than one website increased its trustfulness. Surprisingly, 54% of respondents did not depend on Arabic information websites when making decisions on drug use

  1. A facile nanoaggregation strategy for oral delivery of hydrophobic drugs by utilizing acid base neutralization reactions

    NASA Astrophysics Data System (ADS)

    Chen, Huabing; Wan, Jiangling; Wang, Yirui; Mou, Dongsheng; Liu, Hongbin; Xu, Huibi; Yang, Xiangliang

    2008-09-01

    Nanonization strategies have been used to enhance the oral availability of numerous drugs that are poorly soluble in water. Exploring a facile nanonization strategy with highly practical potential is an attractive focus. Here, we report a novel facile nanoaggregation strategy for constructing drug nanoparticles of poorly soluble drugs with pH-dependent solubility by utilizing acid-base neutralization in aqueous solution, thus facilitating the exploration of nanonization in oral delivery for general applicability. We demonstrate that hydrophobic itraconazole dissolved in acid solution formed a growing core and aggregated into nanoparticles in the presence of stabilizers. The nanoparticles, with an average diameter of 279.3 nm and polydispersity index of 0.116, showed a higher dissolution rate when compared with the marketed formulation; the average dissolution was about 91.3%. The in vivo pharmacokinetic studies revealed that the nanoparticles had a rapid absorption and enhanced oral availability. The diet state also showed insignificant impact on the absorption of itraconazole from nanoparticles. This nanoaggregation strategy is a promising nanonization method with a facile process and avoidance of toxic organic solvents for oral delivery of poorly soluble drugs with pH-dependent solubility and reveals a highly practical potential in the pharmaceutical and chemical industries.

  2. The Association between Stimulant, Opioid, and Multiple Drug Use on Behavioral Healthcare Utilization in a Safety-Net Health System

    PubMed Central

    Calcaterra, Susan L; Keniston, Angela; Blum, Joshua; Crume, Tessa; Binswanger, Ingrid A

    2016-01-01

    Background Prior studies show an association between drug use and healthcare utilization. The relationship between specific drug type and emergent/urgent, inpatient, outpatient and behavioral healthcare utilization has not been examined. We aimed to determine if multiple drug use was associated with increased utilization of behavioral healthcare. Methods To assess healthcare utilization, we conducted a retrospective cohort study of patients who accessed healthcare at a safety-net medical center and affiliated clinics. Using electronic health records, we categorized patients who used stimulants, opioids, or multiple drugs based on urine toxicology screening tests and/or International Classification of Diseases, 9th Revision (ICD-9). Remaining patients were categorized as patients without identified drug use. Healthcare utilization by drug use group and visit type was determined using a negative binomial regression model. Associations were reported as incidence rate ratios. Utilization was described by rates of healthcare-related visits for inpatient, emergent/urgent, outpatient, and behavioral healthcare among patients who used drugs, categorized by drug types, compared to patients without identified drug use. Results Of 95,198 index visits, 4.6% (n=4,340) were by patients who used drugs. Opioid and multiple drug users had significantly higher rates of behavioral healthcare visits than patients without identified drug use (opioid incidence rate ratio [IRR]=7.2; 95% confidence interval [CI] 3.8–13.8; multiple drug use IRR=5.6, 95% CI 3.3–9.7). Patients who used stimulants were less likely to use behavioral health services (IRR=1.3, 95% CI 0.9–2.0) when compared to opioid and multiple drug users, but were more likely to use inpatient (IRR=1.6, 95% CI 1.4–1.8) and emergent/urgent care (IRR=1.4, 95% CI 1.3–1.5) services as compared to patients without identified drug use. Conclusions Integrated medical and mental healthcare and drug treatment may reduce

  3. Expanding Medicaid drug formulary coverage. Effects on utilization of related services.

    PubMed

    Kozma, C M; Reeder, C E; Lingle, E W

    1990-10-01

    Effects on utilization and expenditures occurring concurrently with an expansion of coverage in the South Carolina Medicaid drug formulary were investigated. Data were collected for prescriptions, physician office visits, and outpatient and inpatient hospital visits. Data were evaluated for a cohort of 12,139 individuals who had at least one prescription claim and were continuously eligible for benefits during the two-year study. A repeated measures design was employed to control the differences between subjects. A multivariate analysis of variance was used to detect overall differences in utilization and expenditures. A priori comparisons of means were performed to detect changes in levels and rates of expenditures and utilization for each service. Increases were observed in the number of prescriptions, physician visits, and outpatient visits per person while the number of inpatient hospital admissions declined. Similarly, expenditures increased for all service areas except the inpatient hospital service. The proportion of variance explained by the formulary change was small in all service areas, but would be of practical significance because of the large number of Medicaid recipients affected. From a theoretical perspective, an association of a reduction in inpatient hospital use and expenditures following the elimination of drug formulary restrictions is particularly noteworthy. These findings support the thesis that medical care services should not be viewed in isolation but rather as a system of interrelated activities. Interventions in one portion of the system are mirrored by changes in utilization of other components. Frequently, private and public medical care programs are managed with organizationally distinct benefit budgets, which are controlled independently. In view of the results of this study, this organizational approach may lead to a suboptimal allocation of resources. PMID:2232926

  4. Quantification of cell viability and rapid screening anti-cancer drug utilizing nanomechanical fluctuation.

    PubMed

    Wu, Shangquan; Liu, Xiaoli; Zhou, Xiarong; Liang, Xin M; Gao, Dayong; Liu, Hong; Zhao, Gang; Zhang, Qingchuan; Wu, Xiaoping

    2016-03-15

    Cancer is a serious threat to human health. Although numerous anti-cancer drugs are available clinically, many have shown toxic side effects due to poor tumor-selectivity, and reduced effectiveness due to cancers rapid development of resistance to treatment. The development of new highly efficient and practical methods to quantify cell viability and its change under drug treatment is thus of significant importance in both understanding of anti-cancer mechanism and anti-cancer drug screening. Here, we present an approach of utilizing a nanomechanical fluctuation based highly sensitive microcantilever sensor, which is capable of characterizing the viability of cells and quantitatively screening (within tens of minutes) their responses to a drug with the obvious advantages of a rapid, label-free, quantitative, noninvasive, real-time and in-situ assay. The microcantilever sensor operated in fluctuation mode was used in evaluating the paclitaxel effectiveness on breast cancer cell line MCF-7. This study demonstrated that the nanomechanical fluctuations of the microcantilever sensor are sensitive enough to detect the dynamic variation in cellular force which is provided by the cytoskeleton, using cell metabolism as its energy source, and the dynamic instability of microtubules plays an important role in the generation of the force. We propose that cell viability consists of two parts: biological viability and mechanical viability. Our experimental results suggest that paclitaxel has little effect on biological viability, but has a significant effect on mechanical viability. This new method provides a new concept and strategy for the evaluation of cell viability and the screening of anti-cancer drugs.

  5. Quantification of cell viability and rapid screening anti-cancer drug utilizing nanomechanical fluctuation.

    PubMed

    Wu, Shangquan; Liu, Xiaoli; Zhou, Xiarong; Liang, Xin M; Gao, Dayong; Liu, Hong; Zhao, Gang; Zhang, Qingchuan; Wu, Xiaoping

    2016-03-15

    Cancer is a serious threat to human health. Although numerous anti-cancer drugs are available clinically, many have shown toxic side effects due to poor tumor-selectivity, and reduced effectiveness due to cancers rapid development of resistance to treatment. The development of new highly efficient and practical methods to quantify cell viability and its change under drug treatment is thus of significant importance in both understanding of anti-cancer mechanism and anti-cancer drug screening. Here, we present an approach of utilizing a nanomechanical fluctuation based highly sensitive microcantilever sensor, which is capable of characterizing the viability of cells and quantitatively screening (within tens of minutes) their responses to a drug with the obvious advantages of a rapid, label-free, quantitative, noninvasive, real-time and in-situ assay. The microcantilever sensor operated in fluctuation mode was used in evaluating the paclitaxel effectiveness on breast cancer cell line MCF-7. This study demonstrated that the nanomechanical fluctuations of the microcantilever sensor are sensitive enough to detect the dynamic variation in cellular force which is provided by the cytoskeleton, using cell metabolism as its energy source, and the dynamic instability of microtubules plays an important role in the generation of the force. We propose that cell viability consists of two parts: biological viability and mechanical viability. Our experimental results suggest that paclitaxel has little effect on biological viability, but has a significant effect on mechanical viability. This new method provides a new concept and strategy for the evaluation of cell viability and the screening of anti-cancer drugs. PMID:26406457

  6. Torsadogenic Risk of Antipsychotics: Combining Adverse Event Reports with Drug Utilization Data across Europe

    PubMed Central

    Raschi, Emanuel; Poluzzi, Elisabetta; Godman, Brian; Koci, Ariola; Moretti, Ugo; Kalaba, Marija; Bennie, Marion; Barbui, Corrado; Wettermark, Bjorn; Sturkenboom, Miriam; De Ponti, Fabrizio

    2013-01-01

    Background Antipsychotics (APs) have been associated with risk of torsade de Pointes (TdP). This has important public health implications. Therefore, (a) we exploited the public FDA Adverse Event Reporting System (FAERS) to characterize their torsadogenic profile; (b) we collected drug utilization data from 12 European Countries to assess the population exposure over the 2005-2010 period. Methods FAERS data (2004-2010) were analyzed based on the following criteria: (1) ≥4 cases of TdP/QT abnormalities; (2) Significant Reporting Odds Ratio, ROR [Lower Limit of the 95% confidence interval>1], for TdP/QT abnormalities, adjusted and stratified (Arizona CERT drugs as effect modifiers); (3) ≥4 cases of ventricular arrhythmia/sudden cardiac death (VA/SCD); (4) Significant ROR for VA/SCD; (5) Significant ROR, combined by aggregating TdP/QT abnormalities with VA and SCD. Torsadogenic signals were characterized in terms of signal strength: from Group A (very strong torsadogenic signal: all criteria fulfilled) to group E (unclear/uncertain signal: only 2/5 criteria). Consumption data were retrieved from 12 European Countries and expressed as defined daily doses per 1,000 inhabitants per day (DID). Results Thirty-five antipsychotics met at least one criterium: 9 agents were classified in Group A (amisulpride, chlorpromazine, clozapine, cyamemazine, haloperidol, olanzapine, quetiapine, risperidone, ziprasidone). In 2010, the overall exposure to antipsychotics varied from 5.94 DID (Estonia) to 13.99 (France, 2009). Considerable increment of Group A agents was found in several Countries (+3.47 in France): the exposure to olanzapine increased across all Countries (+1.84 in France) and peaked 2.96 in Norway; cyamemazine was typically used only in France (2.81 in 2009). Among Group B drugs, levomepromazine peaked 3.78 (Serbia); fluphenazine 1.61 (Slovenia). Conclusions This parallel approach through spontaneous reporting and drug utilization analyses highlighted drug- and

  7. Identification of novel, in vivo active Chk1 inhibitors utilizing structure guided drug design.

    PubMed

    Massey, Andrew J; Stokes, Stephen; Browne, Helen; Foloppe, Nicolas; Fiumana, Andreá; Scrace, Simon; Fallowfield, Mandy; Bedford, Simon; Webb, Paul; Baker, Lisa; Christie, Mark; Drysdale, Martin J; Wood, Mike

    2015-11-01

    Chk1 kinase is a critical component of the DNA damage response checkpoint especially in cancer cells and targeting Chk1 is a potential therapeutic opportunity for potentiating the anti-tumor activity of DNA damaging chemotherapy drugs. Fragment elaboration by structure guided design was utilized to identify and develop a novel series of Chk1 inhibitors culminating in the identification of V158411, a potent ATP-competitive inhibitor of the Chk1 and Chk2 kinases. V158411 abrogated gemcitabine and camptothecin induced cell cycle checkpoints, resulting in the expected modulation of cell cycle proteins and increased cell death in cancer cells. V158411 potentiated the cytotoxicity of gemcitabine, cisplatin, SN38 and camptothecin in a variety of p53 deficient human tumor cell lines in vitro, p53 proficient cells were unaffected. In nude mice, V158411 showed minimal toxicity as a single agent and in combination with irinotecan. In tumor bearing animals, V158411 was detected at high levels in the tumor with a long elimination half-life; no pharmacologically significant in vivo drug-drug interactions with irinotecan were identified through analysis of the pharmacokinetic profiles. V158411 potentiated the anti-tumor activity of irinotecan in a variety of human colon tumor xenograft models without additional systemic toxicity. These results demonstrate the opportunity for combining V158411 with standard of care chemotherapeutic agents to potentiate the therapeutic efficacy of these agents without increasing their toxicity to normal cells. Thus, V158411 would warrant further clinical evaluation. PMID:26437226

  8. Use of proton-pump inhibitors among adults: a Danish nationwide drug utilization study

    PubMed Central

    Pottegård, Anton; Broe, Anne; Hallas, Jesper; de Muckadell, Ove B. Schaffalitzky; Lassen, Annmarie T.; Lødrup, Anders B.

    2016-01-01

    Background: The use of proton-pump inhibitors (PPIs) has increased over the last decade. The objective of this study was to provide detailed utilization data on PPI use over time, with special emphasis on duration of PPI use and concomitant use of ulcerogenic drugs. Methods: Using the nationwide Danish Prescription Registry, we identified all Danish adults filling a PPI between 2002 and 2014. Using descriptive statistics, we reported (i) the distribution of use between single PPI entities, (ii) the development in incidence and prevalence of use over time, (iii) measures of duration and intensity of treatment, and (iv) the prevalence of use of ulcerogenic drugs among users of PPIs. Results: We identified 1,617,614 adults using PPIs during the study period. The prevalence of PPI use increased fourfold during the study period to 7.4% of all Danish adults in 2014. PPI use showed strong age dependency, reaching more than 20% among those aged at least 80 years. The proportion of users maintaining treatment over time increased with increasing age, with less than10% of those aged 18–39 years using PPIs 2 years after their first prescription, compared with about 40% among those aged at least 80 years. The overall use of ulcerogenic drugs among PPI users increased moderately, from 35% of users of PPI in 2002 to 45% in 2014. Conclusions: The use of PPIs is extensive and increasing rapidly, especially among the elderly. PMID:27582879

  9. Identification of novel, in vivo active Chk1 inhibitors utilizing structure guided drug design

    PubMed Central

    Massey, Andrew J.; Stokes, Stephen; Browne, Helen; Foloppe, Nicolas; Fiumana, Andreá; Scrace, Simon; Fallowfield, Mandy; Bedford, Simon; Webb, Paul; Baker, Lisa; Christie, Mark; Drysdale, Martin J.; Wood, Mike

    2015-01-01

    Chk1 kinase is a critical component of the DNA damage response checkpoint especially in cancer cells and targeting Chk1 is a potential therapeutic opportunity for potentiating the anti-tumor activity of DNA damaging chemotherapy drugs. Fragment elaboration by structure guided design was utilized to identify and develop a novel series of Chk1 inhibitors culminating in the identification of V158411, a potent ATP-competitive inhibitor of the Chk1 and Chk2 kinases. V158411 abrogated gemcitabine and camptothecin induced cell cycle checkpoints, resulting in the expected modulation of cell cycle proteins and increased cell death in cancer cells. V158411 potentiated the cytotoxicity of gemcitabine, cisplatin, SN38 and camptothecin in a variety of p53 deficient human tumor cell lines in vitro, p53 proficient cells were unaffected. In nude mice, V158411 showed minimal toxicity as a single agent and in combination with irinotecan. In tumor bearing animals, V158411 was detected at high levels in the tumor with a long elimination half-life; no pharmacologically significant in vivo drug-drug interactions with irinotecan were identified through analysis of the pharmacokinetic profiles. V158411 potentiated the anti-tumor activity of irinotecan in a variety of human colon tumor xenograft models without additional systemic toxicity. These results demonstrate the opportunity for combining V158411 with standard of care chemotherapeutic agents to potentiate the therapeutic efficacy of these agents without increasing their toxicity to normal cells. Thus, V158411 would warrant further clinical evaluation. PMID:26437226

  10. Utilizing Chemical Genomics to Identify Cytochrome b as a Novel Drug Target for Chagas Disease

    PubMed Central

    Khare, Shilpi; Roach, Steven L.; Barnes, S. Whitney; Hoepfner, Dominic; Walker, John R.; Chatterjee, Arnab K.; Neitz, R. Jeffrey; Arkin, Michelle R.; McNamara, Case W.; Ballard, Jaime; Lai, Yin; Fu, Yue; Molteni, Valentina; Yeh, Vince; McKerrow, James H.; Glynne, Richard J.; Supek, Frantisek

    2015-01-01

    Unbiased phenotypic screens enable identification of small molecules that inhibit pathogen growth by unanticipated mechanisms. These small molecules can be used as starting points for drug discovery programs that target such mechanisms. A major challenge of the approach is the identification of the cellular targets. Here we report GNF7686, a small molecule inhibitor of Trypanosoma cruzi, the causative agent of Chagas disease, and identification of cytochrome b as its target. Following discovery of GNF7686 in a parasite growth inhibition high throughput screen, we were able to evolve a GNF7686-resistant culture of T. cruzi epimastigotes. Clones from this culture bore a mutation coding for a substitution of leucine by phenylalanine at amino acid position 197 in cytochrome b. Cytochrome b is a component of complex III (cytochrome bc1) in the mitochondrial electron transport chain and catalyzes the transfer of electrons from ubiquinol to cytochrome c by a mechanism that utilizes two distinct catalytic sites, QN and QP. The L197F mutation is located in the QN site and confers resistance to GNF7686 in both parasite cell growth and biochemical cytochrome b assays. Additionally, the mutant cytochrome b confers resistance to antimycin A, another QN site inhibitor, but not to strobilurin or myxothiazol, which target the QP site. GNF7686 represents a promising starting point for Chagas disease drug discovery as it potently inhibits growth of intracellular T. cruzi amastigotes with a half maximal effective concentration (EC50) of 0.15 µM, and is highly specific for T. cruzi cytochrome b. No effect on the mammalian respiratory chain or mammalian cell proliferation was observed with up to 25 µM of GNF7686. Our approach, which combines T. cruzi chemical genetics with biochemical target validation, can be broadly applied to the discovery of additional novel drug targets and drug leads for Chagas disease. PMID:26186534

  11. Impact of Pharmacy Benefit Design on Prescription Drug Utilization: A Fixed Effects Analysis of Plan Sponsor Data

    PubMed Central

    Roebuck, M Christopher; Liberman, Joshua N

    2009-01-01

    Objective To study the impact of various elements of pharmacy benefit design on both the absolute and relative utilization of generics, brands, retail pharmacy, and mail service. Data Source Panel data on 1,074 plan sponsors covering 21.6 million individuals over 12 calendar quarters (2005–2007). Study Design A retrospective analysis of pharmacy claims. Statistical Methods To control for potential endogeneity, linear fixed effects models were estimated for each of six dependent variables: the generic utilization rate, the brand utilization rate, the generic dispensing rate (GDR), the retail pharmacy utilization rate, the mail service utilization rate, and the mail distribution rate. Principal Findings Most member cost-share variables were nonlinearly associated with changes in prescription drug utilization. Marginal effects were generally greater in magnitude for brand out-of-pocket costs than for generic out-of-pocket costs. Time dummies, as well as other pharmacy benefit design elements, also yielded significant results. Conclusions Prior estimates of the effect of member cost sharing on prescription drug utilization may be biased if complex benefit designs, mail service fulfillment, and unmeasured factors such as pharmaceutical pipelines are not accounted for. Commonly cited relative utilization metrics, such as GDR, may be misleading if not examined alongside absolute prescription drug utilization. PMID:19187183

  12. Chemical and genetic validation of thiamine utilization as an antimalarial drug target.

    PubMed

    Chan, Xie Wah Audrey; Wrenger, Carsten; Stahl, Katharina; Bergmann, Bärbel; Winterberg, Markus; Müller, Ingrid B; Saliba, Kevin J

    2013-01-01

    Thiamine is metabolized into an essential cofactor for several enzymes. Here we show that oxythiamine, a thiamine analog, inhibits proliferation of the malaria parasite Plasmodium falciparum in vitro via a thiamine-related pathway and significantly reduces parasite growth in a mouse malaria model. Overexpression of thiamine pyrophosphokinase (the enzyme that converts thiamine into its active form, thiamine pyrophosphate) hypersensitizes parasites to oxythiamine by up to 1,700-fold, consistent with oxythiamine being a substrate for thiamine pyrophosphokinase and its conversion into an antimetabolite. We show that parasites overexpressing the thiamine pyrophosphate-dependent enzymes oxoglutarate dehydrogenase and pyruvate dehydrogenase are up to 15-fold more resistant to oxythiamine, consistent with the antimetabolite inactivating thiamine pyrophosphate-dependent enzymes. Our studies therefore validate thiamine utilization as an antimalarial drug target and demonstrate that a single antimalarial can simultaneously target several enzymes located within distinct organelles.

  13. The Affordable Care Act, health care reform, prescription drug formularies and utilization management tools.

    PubMed

    Ung, Brian L; Mullins, C Daniel

    2015-01-01

    The U.S. Patient Protection and Affordable Care Act (hence, Affordable Care Act, or ACA) was signed into law on March 23, 2010. Goals of the ACA include decreasing the number of uninsured people, controlling cost and spending on health care, increasing the quality of care provided, and increasing insurance coverage benefits. This manuscript focuses on how the ACA affects pharmacy benefit managers and consumers when they have prescriptions dispensed. PBMs use formularies and utilization control tools to steer drug usage toward cost-effective and efficacious agents. A logic model was developed to explain the effects of the new legislation. The model draws from peer-reviewed and gray literature commentary about current and future U.S. healthcare reform. Outcomes were identified as desired and undesired effects, and expected unintended consequences. The ACA extends health insurance benefits to almost 32 million people and provides financial assistance to those up to 400% of the poverty level. Increased access to care leads to a similar increase in overall health care demand and usage. This short-term increase is projected to decrease downstream spending on disease treatment and stunt the continued growth of health care costs, but may unintentionally exacerbate the current primary care physician shortage. The ACA eliminates limitations on insurance and increases the scope of benefits. Online health care insurance exchanges give patients a central location with multiple insurance options. Problems with prescription drug affordability and control utilization tools used by PBMs were not addressed by the ACA. Improving communication within the U.S. healthcare system either by innovative health care delivery models or increased usage of health information technology will help alleviate problems of health care spending and affordability. PMID:25217142

  14. The Affordable Care Act, health care reform, prescription drug formularies and utilization management tools.

    PubMed

    Ung, Brian L; Mullins, C Daniel

    2015-01-01

    The U.S. Patient Protection and Affordable Care Act (hence, Affordable Care Act, or ACA) was signed into law on March 23, 2010. Goals of the ACA include decreasing the number of uninsured people, controlling cost and spending on health care, increasing the quality of care provided, and increasing insurance coverage benefits. This manuscript focuses on how the ACA affects pharmacy benefit managers and consumers when they have prescriptions dispensed. PBMs use formularies and utilization control tools to steer drug usage toward cost-effective and efficacious agents. A logic model was developed to explain the effects of the new legislation. The model draws from peer-reviewed and gray literature commentary about current and future U.S. healthcare reform. Outcomes were identified as desired and undesired effects, and expected unintended consequences. The ACA extends health insurance benefits to almost 32 million people and provides financial assistance to those up to 400% of the poverty level. Increased access to care leads to a similar increase in overall health care demand and usage. This short-term increase is projected to decrease downstream spending on disease treatment and stunt the continued growth of health care costs, but may unintentionally exacerbate the current primary care physician shortage. The ACA eliminates limitations on insurance and increases the scope of benefits. Online health care insurance exchanges give patients a central location with multiple insurance options. Problems with prescription drug affordability and control utilization tools used by PBMs were not addressed by the ACA. Improving communication within the U.S. healthcare system either by innovative health care delivery models or increased usage of health information technology will help alleviate problems of health care spending and affordability.

  15. A Case Report of Clonazepam Dependence: Utilization of Therapeutic Drug Monitoring During Withdrawal Period.

    PubMed

    Kacirova, Ivana; Grundmann, Milan; Silhan, Petr; Brozmanova, Hana

    2016-03-01

    Clonazepam is long-acting benzodiazepine agonist used in short-acting benzodiazepine withdrawal; however, recent observations suggest the existence of its abuse. We demonstrate a 40-year-old man with a 20-year history of psychiatric care with recently benzodiazepine dependence (daily intake of ∼60 mg of clonazepam and 10 mg of alprazolam). High serum levels of both drugs were analyzed 3 weeks before admission to hospitalization (clonazepam 543.9 ng/mL, alprazolam 110 ng/mL) and at the time of admission (clonazepam 286.2 ng/mL, alprazolam 140 ng/mL) without any signs of benzodiazepine intoxication. Gradual withdrawal of clonazepam with monitoring of its serum levels and increase of gabapentin dose were used to minimize physical signs and symptoms of clonazepam withdrawal. Alprazolam was discontinued promptly. Clinical consequences of the treatment were controllable tension, intermittent headache, and rarely insomia. It is the first case report showing utilization of therapeutic drug monitoring during withdrawal period in the patient with extreme toleration to severe benzodiazepine dependence. PMID:26945373

  16. Effects of gamma-aminobutyric acid agonist and antagonist drugs on local cerebral glucose utilization

    SciTech Connect

    Palacios, J.M.; Kuhar, M.J.; Rapoport, S.I.; London, E.D.

    1982-07-01

    The (/sup 14/C)2-deoxy-D-glucose method of Sokoloff et al. was used to study local cerebral glucose utilization (LCGU) in rats treated with gamma-aminobutyric acid (GABA) agonist (muscimol and 4,5,6,7-tetrahydroisoxazolo(5,4-C)pyridin-3-ol, THIP) and antagonist (bicuculline) drugs. It was of interest to determine if the pattern of LCGU responses to GABA agonists and antagonists administered systemically in vivo would reflect the known distributions of markers for central GABAergic synapses. The patterns of LCGU responses to muscimol and THIP generally were similar. Most brain regions showed dose-dependent decreases in LCGU; others showed no effects; but the red nucleus showed an increase. The GABA antagonist bicuculline produced convulsions and variable LCGU responses, depending on the time of administration. Bicuculline also partially antagonized the depressant effects of muscimol of LCGU. The magnitudes and distribution of in vivo cerebral metabolic responses to specific GABA agonists were not correlated simply with markers for GABAergic synapses. This lack of correlation indicates that additional factors, such as neural circuitry, regulate the LCGU responses to GABAergic drugs.

  17. Utility of cerebrospinal fluid drug concentration as a surrogate for unbound brain concentration in nonhuman primates.

    PubMed

    Nagaya, Yoko; Nozaki, Yoshitane; Kobayashi, Kazumasa; Takenaka, Osamu; Nakatani, Yosuke; Kusano, Kazutomi; Yoshimura, Tsutomu; Kusuhara, Hiroyuki

    2014-01-01

    In central nervous system drug discovery, cerebrospinal fluid (CSF) drug concentration (C(CSF)) has been widely used as a surrogate for unbound brain concentrations (C(u,brain)). However, previous rodent studies demonstrated that when drugs undergo active efflux by transporters, such as P-glycoprotein (P-gp), at the blood-brain barrier, the C(CSF) overestimates the corresponding C(u,brain). To investigate the utility of C(CSF) as a surrogate for interstitial fluid (ISF) concentration (C(ISF)) in nonhuman primates, this study simultaneously determined the C(CSF) and C(ISF) of 12 compounds, including P-gp substrates, under steady-state conditions in cynomolgus monkeys using intracerebral microdialysis coupled with cisternal CSF sampling. Unbound plasma concentrations of non- or weak P-gp substrates were within 2.2-fold of the C(ISF) or C(CSF), whereas typical P-gp substrates (risperidone, verapamil, desloratadine, and quinidine) showed ISF-to-plasma unbound (K(p,uu,ISF)) and CSF-to-plasma unbound concentration ratios (K(p,uu,CSF)) that were appreciably lower than unity. Although the K(p,uu,CSF) of quinidine, verapamil, and desloratadine showed a trend of overestimating the K(p,uu,ISF), K(p,uu,CSF) showed a good agreement with K(p,uu,ISF) within 3-fold variations for all compounds examined. C(u,brain) of some basic compounds, as determined using brain homogenates, overestimated the C(ISF) and C(CSF). Therefore, C(CSF) could be used as a surrogate for C(ISF) in nonhuman primates.

  18. Recent Advances in Ligand-Based Drug Design: Relevance and Utility of the Conformationally Sampled Pharmacophore Approach

    PubMed Central

    Acharya, Chayan; Coop, Andrew; Polli, James E.; MacKerell, Alexander D.

    2010-01-01

    In the absence of three-dimensional (3D) structures of potential drug targets, ligand-based drug design is one of the popular approaches for drug discovery and lead optimization. 3D structure-activity relationships (3D QSAR) and pharmacophore modeling are the most important and widely used tools in ligand-based drug design that can provide crucial insights into the nature of the interactions between drug target and ligand molecule and provide predictive models suitable for lead compound optimization. This review article will briefly discuss the features and potential application of recent advances in ligand-based drug design, with emphasis on a detailed description of a novel 3D QSAR method based on the conformationally sample pharmacophore (CSP) approach (denoted CSP-SAR). In addition, data from a published study is used to compare the CSP-SAR approach to the Catalyst method, emphasizing the utility of the CSP approach for ligand-based model development. PMID:20807187

  19. 42 CFR 423.153 - Drug utilization management, quality assurance, and medication therapy management programs (MTMPs).

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ...) Screening for potential drug therapy problems due to therapeutic duplication. (ii) Age/gender-related... dosage or duration of drug therapy. (vi) Drug-allergy contraindications. (vii) Clinical abuse/misuse....

  20. Cost-utility analyses of drug therapies in breast cancer: a systematic review.

    PubMed

    Nerich, Virginie; Saing, Sopany; Gamper, Eva Maria; Kemmler, Georg; Daval, Franck; Pivot, Xavier; Holzner, Bernhard

    2016-10-01

    The economic evaluation (EE) of health care products has become a necessity. Their quality must be high in order to trust the results and make informed decisions. While cost-utility analyses (CUAs) should be preferred to cost-effectiveness analyses in the oncology area, the quality of breast cancer (BC)-related CUA has been given little attention so far. Thus, firstly, a systematic review of published CUA related to drug therapies for BC, gene expression profiling, and HER2 status testing was performed. Secondly, the quality of selected CUA was assessed and the factors associated with a high-quality CUA identified. The systematic literature search was conducted in PubMed, MEDLINE/EMBASE, and Cochrane to identify published CUA between 2000 and 2014. After screening and data extraction, the quality of each selected CUA was assessed by two independent reviewers, using the checklist proposed by Drummond et al. The analysis of factors associated with a high-quality CUA (defined as a Drummond score ≥7) was performed using a two-step approach. Our systematic review was based on 140 CUAs and showed a wide variety of methodological approaches, including differences in the perspective adopted, the time horizon, measurement of cost and effectiveness, and more specially health-state utility values (HSUVs). The median Drummond score was 7 [range 3-10]. Only one in two of the CUA (n = 74) had a Drummond score ≥7, synonymous of "high quality." The statistically significant predictors of a high-quality CUA were article with "gene expression profiling" topic (p = 0.001), consulting or pharmaceutical company as main location of first author (p = 0.004), and articles with both incremental cost-utility ratio and incremental cost-effectiveness ratio as outcomes of EE (p = 0.02). Our systematic review identified only 140 CUAs published over the past 15 years with one in two of high quality. It showed a wide variety of methodological approaches, especially focused on HSUVs. A

  1. Cost-utility analyses of drug therapies in breast cancer: a systematic review.

    PubMed

    Nerich, Virginie; Saing, Sopany; Gamper, Eva Maria; Kemmler, Georg; Daval, Franck; Pivot, Xavier; Holzner, Bernhard

    2016-10-01

    The economic evaluation (EE) of health care products has become a necessity. Their quality must be high in order to trust the results and make informed decisions. While cost-utility analyses (CUAs) should be preferred to cost-effectiveness analyses in the oncology area, the quality of breast cancer (BC)-related CUA has been given little attention so far. Thus, firstly, a systematic review of published CUA related to drug therapies for BC, gene expression profiling, and HER2 status testing was performed. Secondly, the quality of selected CUA was assessed and the factors associated with a high-quality CUA identified. The systematic literature search was conducted in PubMed, MEDLINE/EMBASE, and Cochrane to identify published CUA between 2000 and 2014. After screening and data extraction, the quality of each selected CUA was assessed by two independent reviewers, using the checklist proposed by Drummond et al. The analysis of factors associated with a high-quality CUA (defined as a Drummond score ≥7) was performed using a two-step approach. Our systematic review was based on 140 CUAs and showed a wide variety of methodological approaches, including differences in the perspective adopted, the time horizon, measurement of cost and effectiveness, and more specially health-state utility values (HSUVs). The median Drummond score was 7 [range 3-10]. Only one in two of the CUA (n = 74) had a Drummond score ≥7, synonymous of "high quality." The statistically significant predictors of a high-quality CUA were article with "gene expression profiling" topic (p = 0.001), consulting or pharmaceutical company as main location of first author (p = 0.004), and articles with both incremental cost-utility ratio and incremental cost-effectiveness ratio as outcomes of EE (p = 0.02). Our systematic review identified only 140 CUAs published over the past 15 years with one in two of high quality. It showed a wide variety of methodological approaches, especially focused on HSUVs. A

  2. Catanionic mixtures involving a drug: a rather general concept that can be utilized for prolonged drug release from gels.

    PubMed

    Bramer, Tobias; Dew, Noel; Edsman, Katarina

    2006-04-01

    The aim of this work was to study at what extent mixtures of drug substances and oppositely charged surfactants form catanionic aggregates and to apply these as a means of obtaining prolonged drug release from a gel. The properties of traditional catanionic mixtures are relatively well known, but only recently we found that not only traditional surfactants form these mixtures, but also structurally more complex surface active drug compounds. In this study, several different compositions of catanionic mixtures were studied visually, by cryogenic transmission electron microscopy (cryo-TEM) and rheologically using a Bohlin VOR Rheometer. Some of the catanionic vesicle and micelle phases were incorporated in and released from gels using the USP paddle method. The drug compounds investigated were lidocaine, ibuprofen, naproxen, alprenolol, propranolol, and orphenadrine. Of the six drug molecules used in this study, five, both positively and negatively charged, were capable of forming catanionic vesicles and/or micelles with oppositely charged surfactants. The drug release studies show that catanionic drug surfactant mixtures are beneficial for obtaining prolonged release from gels, as the drug release using catanionic vesicles and micelles was prolonged between 10 and 100 times compared to the release of pure drug substance from the gel.

  3. Integration and utilization of different visualization methods and devices in a structure-based drug design process

    NASA Astrophysics Data System (ADS)

    Grohn, Matti T.; Nyronen, Tommi N.

    2003-05-01

    Molecular visualization techniques are used in various stages in the computer-aided drug design process. Here, we report on utilization of a four wall immersive virtual room in the visualization of protein - drug complexes. The advantage of a virtual room compared to desktop graphics is that it provides a high-resolution large field of view, helping the observers of the visualization to dissect the individual important structural features more easily than while using only conventional molecular graphics visualizations.

  4. Hospital Utilization for Injection Drug Use-Related Soft Tissue Infections in Urban versus Rural Counties in California

    PubMed Central

    Etzioni, David A.; Hurley, Brian; Holtom, Paul; Bluthenthal, Ricky N.; Asch, Steven M.

    2006-01-01

    Drug related-soft tissue infections (DR-STIs) are a significant source of hospital utilization in inner-city urban areas where injection drug use is common but the magnitude of hospital utilization for DR-STIs outside of inner-city urban areas is not known. We described the magnitude and characteristics of hospital utilization for DR-STIs in urban versus rural counties in California. All discharges from all nonfederal hospitals in California in 2000 with ICD-9 codes for a soft tissue infection and for drug dependence/abuse were abstracted from the California Office of Statewide Health Planning and Development discharge database. There were 4,152 DR-STI discharges in 2000 from hospitals in 49 of California's 58 counties. Residents of 12 large metropolitan counties accounted for 3,598 discharges (87% of total). The majority of DR-STI discharges were from urban safety net hospitals with county indigent programs and Medicaid as the expected payment source and opiate related discharge diagnoses. Hospital utilization for DR-STIs in California is highest in large urban metropolitan counties, although DR-STI discharges are widespread. Increased access to harm reduction services and drug treatment may reduce government health care expenditures by preventing unnecessary hospital utilization for DR-STIs. PMID:16736367

  5. Prescription patterns of antihypertensives in a community health centre in Mexico City: a drug utilization study.

    PubMed

    Alba-Leonel, Adela; Carvajal, Alfonso; Fierro, Immaculada; Castillo-Nájera, Fernando; Campos-Ramos, Oscar; Villa-Romero, Antonio; Molina-Guarneros, Juan

    2016-06-01

    Hypertension is highly prevalent; in Mexico, the 2012 National Health and Nutrition Survey reported a prevalence of hypertension of 31.5% in the adult population. Pharmacological treatment is the commonest intervention and has been shown to reduce cardiovascular mortality and morbidity, and total mortality. Accordingly, the type and number of antihypertensives used and the outcome - in terms of blood pressure (BP) control - are important. Therefore, our purpose is to learn the pattern of antihypertensive drug prescription and explore the determinants of BP control in an urban population in Mexico. A retrospective cross-sectional drug utilization study was conducted. Medical records from a community health centre were searched to identify those corresponding to patients diagnosed with hypertension; information upon antihypertensives used and control of the disease was carefully retrieved. A logistic regression model was built to know the main determinants of BP control. A sample of 345 clinical records of interest was identified. Most patients received antihypertensives (86.4%); the leading medications used were angiotensin-converting enzyme inhibitors, 63.8%; beta-blockers (26.5%), diuretics (19.8%), angiotensin-receptor blockers (15.8%) and calcium-channel blockers (6.4%). Only the age (≥55 years) and BMI (>30) of the patients, and the age of the doctors (≥55 years), had an important influence on BP control. Obesity is a particular and important determinant of uncontrolled hypertension; it is worth to act on body weight, on an individual basis. As lack of control has been also tied to elderly doctors, an education programme could be envisaged. PMID:26787266

  6. Prescription patterns of antihypertensives in a community health centre in Mexico City: a drug utilization study.

    PubMed

    Alba-Leonel, Adela; Carvajal, Alfonso; Fierro, Immaculada; Castillo-Nájera, Fernando; Campos-Ramos, Oscar; Villa-Romero, Antonio; Molina-Guarneros, Juan

    2016-06-01

    Hypertension is highly prevalent; in Mexico, the 2012 National Health and Nutrition Survey reported a prevalence of hypertension of 31.5% in the adult population. Pharmacological treatment is the commonest intervention and has been shown to reduce cardiovascular mortality and morbidity, and total mortality. Accordingly, the type and number of antihypertensives used and the outcome - in terms of blood pressure (BP) control - are important. Therefore, our purpose is to learn the pattern of antihypertensive drug prescription and explore the determinants of BP control in an urban population in Mexico. A retrospective cross-sectional drug utilization study was conducted. Medical records from a community health centre were searched to identify those corresponding to patients diagnosed with hypertension; information upon antihypertensives used and control of the disease was carefully retrieved. A logistic regression model was built to know the main determinants of BP control. A sample of 345 clinical records of interest was identified. Most patients received antihypertensives (86.4%); the leading medications used were angiotensin-converting enzyme inhibitors, 63.8%; beta-blockers (26.5%), diuretics (19.8%), angiotensin-receptor blockers (15.8%) and calcium-channel blockers (6.4%). Only the age (≥55 years) and BMI (>30) of the patients, and the age of the doctors (≥55 years), had an important influence on BP control. Obesity is a particular and important determinant of uncontrolled hypertension; it is worth to act on body weight, on an individual basis. As lack of control has been also tied to elderly doctors, an education programme could be envisaged.

  7. Mental Health Service and Drug Treatment Utilization: Adolescents with Substance Use/Mental Disorders and Dual Diagnosis

    ERIC Educational Resources Information Center

    Cheng, Tyrone C.; Lo, Celia C.

    2010-01-01

    This research is a secondary data analysis of the impact of adolescents' mental/substance-use disorders and dual diagnosis on their utilization of drug treatment and mental health services. By analyzing the same teenagers who participated in the NIMH Methods for the Epidemiology of Child and Adolescent Mental Disorders (MECA) study, logistic…

  8. Management of postoperative pain in abdominal surgery in Spain. A multicentre drug utilization study

    PubMed Central

    Vallano, Antonio; Aguilera, Cristina; Arnau, Josep Maria; Baños, Josep-Eladi; Laporte, Joan-Ramon

    1999-01-01

    Participating centres: Hospital Universitario San Juan, Alicante: Maria Jesús Olaso, Javier Agulló, Clara Faura. Hospital Torrecárdenas, Almería: Carmen Fernández Sánchez, Miguel Lorenzo Campos, Juan Manuel Rodríguez Alonso. Hospital Quirúrgic Adriano, Barcelona: Carmen Alerany Pardo, Paquita Alvarez González, Teresa Martín Benito. Hospital Universitari del Mar-IMIM, Barcelona: Magí Farré, Maite Terán. Corporació Sanitària Parc Taulí, Sabadell: Montserrat Cañellas, Sergio Zavala, Josep Planell. Hospital Universitari de la Santa Creu i Sant Pau: Gonzalo Calvo, Rosa Morros, Silvia Mateo. Hospital General Vall d’Hebron, Barcelona: Carmen Bosch, María José Martínez. Hospital Universitario Virgen de la Victoria, Málaga: Maribel Lucena, José Antonio González, Gabriel Carranque. Hospital Clínico Universitario San Carlos, Madrid: Emilio Vargas, Amparo Gil López-Oliva, Míriam García Mateos. Hospital Universitario Marqués de Valdecilla, Santander: Mario González, Antonio Cuadrado. Hospital Universitario Virgen de la Macarena, Sevilla: Juan Antonio Durán, Pilar Máyquez, María Isabel Serrano. Hospital Universitario Virgen del Rocío, Sevilla: Jaume Torelló, Juan Ramón Castillo, María de las Nieves Merino. Aims Postoperative pain is common in hospital-admitted patients. Its management is determined by different therapeutic traditions and by the attitudes of health professionals in each hospital. The aim of this study was to describe the patterns of prescription and administration of analgesic drugs used for postoperative pain after abdominal surgery in Spanish hospitals, to know the prevalence and the severity of postoperative pain, and to determine the extent of variability in the management of postoperative pain among the participating centres. Methods The study was a multicentre descriptive cross-sectional drug utilization study in 12 Spanish hospitals. The subjects were an unselected sample of consecutive patients undergoing abdominal

  9. Changes in Drug Utilization during a Gap in Insurance Coverage: An Examination of the Medicare Part D Coverage Gap

    PubMed Central

    Polinski, Jennifer M.; Shrank, William H.; Huskamp, Haiden A.; Glynn, Robert J.; Liberman, Joshua N.; Schneeweiss, Sebastian

    2011-01-01

    but not switching drugs in 2006 and 2007. Blunt cost-containment features such as the coverage gap have an adverse impact on drug utilization that may conceivably affect health outcomes. Please see later in the article for the Editors' Summary PMID:21857811

  10. Short-term Efficacy of a Brief Intervention to Reduce Drug Misuse and Increase Drug Treatment Utilization Among Adult Emergency Department Patients

    PubMed Central

    Merchant, Roland C.; Baird, Janette R.; Liu, Tao

    2016-01-01

    Objectives Although brief interventions (BIs) have shown some success for smoking cessation and alcohol misuse, it is not known if they can be applied in the emergency department (ED) to drug use and misuse. The objectives of this investigation were to assess the 3-month efficacy of a BI to reduce drug use and misuse, increase drug treatment services utilization among adult ED patients, and identify subgroups more likely to benefit from the BI. Methods This randomized, controlled trial enrolled 18- to 64-year-old English- or Spanish-speaking patients from two urban, academic EDs whose responses to the Alcohol, Smoking, and Substance Involvement Screening Test indicated a need for a brief or intensive intervention. Treatment participants received a tailored BI, while control participants only completed the study questionnaires. At the 3-month follow-up, each participant’s past 3-month drug use and misuse and treatment utilization were compared to his or her baseline enrollment data. Regression modeling was used to identify subgroups of patients (per demographic and clinical factors) more likely to stop or reduce their drug use or misuse or engage in drug treatment by the 3-month follow-up assessment. Results Of the 1,030 participants, the median age was 30 years (interquartile range = 24 to 42 years), and 46% were female; 57% were white/non-Hispanic, 24.9% were black/non-Hispanic, and 15% were Hispanic. The most commonly misused drugs were marijuana, prescription opioids, cocaine/crack, and benzodiazepines. Although at follow-up the proportions of participants reporting any past 3-month drug misuse had decreased in both study arms (control 84% vs. treatment 78%), the decreases were similar between the two study arms (Δ−6.3%; 95% confidence interval [CI] = −13.0% to 0.0). In addition, at follow-up there were no differences between study arms in those who were currently receiving drug treatment (Δ1.8; 95% CI = −3.5 to 6.8), who had received treatment during

  11. New developments in the treatment of drug-resistant tuberculosis: clinical utility of bedaquiline and delamanid

    PubMed Central

    Brigden, Grania; Hewison, Cathy; Varaine, Francis

    2015-01-01

    The current treatment for drug-resistant tuberculosis (TB) is long, complex, and associated with severe and life-threatening side effects and poor outcomes. For the first time in nearly 50 years, there have been two new drugs registered for use in multidrug-resistant TB (MDR-TB). Bedaquiline, a diarylquinoline, and delamanid, a nitromidoxazole, have received conditional stringent regulatory approval and have World Health Organization interim policy guidance for their use. As countries improve and scale up their diagnostic services, increasing number of patients with MDR-TB and extensively drug-resistant TB are identified. These two new drugs offer a real opportunity to improve the outcomes of these patients. This article reviews the evidence for these two new drugs and discusses the clinical questions raised as they are used outside clinical trial settings. It also reviews the importance of the accompanying drugs used with these new drugs. It is important that barriers hindering the use of these two new drugs are addressed and that the existing clinical experience in using these drugs is shared, such that their routine-use programmatic conditions is scaled up, ensuring maximum benefit for patients and countries battling the MDR-TB crisis. PMID:26586956

  12. Study of warfarin utilization in hospitalized patients: analysis of possible drug interactions.

    PubMed

    Guidoni, Camilo Molino; Camargo, Helen Palmira Miranda; Obreli-Neto, Paulo Roque; Girotto, Edmarlon; Pereira, Leonardo Regis Leira

    2016-10-01

    Background Drug-drug interactions in patients taking warfarin may contribute to a higher risk of adverse events. Objective To identify and evaluate the prevalence and characteristics of potential DDIs with warfarin. Methods A cross-sectional study was performed in a Brazilian tertiary hospital. The electronic prescriptions of the patients receiving warfarin between January 2004 and December 2010 were analyzed. Socio-demographic, clinical, and therapeutic variables were collected. Warfarin drug-drug interactions were classified as either risk A, B, C, D, or X according to the Lexi-Interact™ Online database. Results A total of 3048 patients were identified who were prescribed warfarin. Of the 154,161 total drug prescriptions issued, 42,120 (27.3 %) were for warfarin. Evaluation of the prescriptions showed that 63.1 and 0.1 % of patients received concomitant drugs classified as having class D or X risk. It was found that 20,539 (48.7 %) prescriptions had at least one drug with a D or X risk. Patients were prescribed an average of 1.4 (±0.4) concomitant medications with a class D or X warfarin-DDI risk, the most frequent being acetylsalicylic acid and amiodarone. Conclusion The results demonstrate a high prevalence of concomitant drug prescriptions with the potential for clinically relevant DDIs with warfarin, the most frequent being acetylsalicylic acid and amiodarone. PMID:27365092

  13. Study of Drug Utilization Pattern for Skin Diseases in Dermatology OPD of an Indian Tertiary Care Hospital - A Prescription Survey

    PubMed Central

    Pathak, Anuj Kumar; Kumar, Subodh; Kumar, Manish; Dikshit, Harihar

    2016-01-01

    Introduction Skin diseases are the major contributors of disease burden in society. It affects individuals of all ages, neonates to elderly. Owing to its chronic nature, it causes serious impact on quality of life and financial status of the sufferer and his family. The problem gets compounded with the inappropriate and irrational use of medicines. Periodic prescription audit in form of drug utilization study is a way to improve the quality of prescription and curb the menace of irrational prescribing which has become a global phenomenon. Aim This study aims to determine the drug utilization pattern and assess the economic burden of the patient with skin disease. Materials and Methods It was a prospective, cross-sectional study conducted over a period of three months from January to March 2015 in newly diagnosed cases attending outpatient department of Skin and VD, IGIMS, Patna. The prescriptions were analysed with the help of descriptive statistics and results were expressed in percentage. Results Total 752 prescriptions were analysed during the study. Male patients were lesser as compared to female as male to female ratio was 0.88. Over 50% of patients were in adolescent age group i.e. 21-40 years. Acne (17.95%) was most common disease in the study population followed by eczema and Dermatophytosis. Among the drugs, antihistaminics (24.13%) were prescribed most frequently followed by antifungals and antibiotics. Topical agents constituted almost 60% of the total prescription and average number of drugs per prescription was 5.13, irrespective of the dosage forms prescribed. Conclusion This drug utilization study provides an insight to the prescriber regarding various issues related to polypharmacy, cost analysis and prevalent disease pattern in the region. This study also suggests periodic evaluation of prescription pattern to monitor and improve quality of prescription in other departments of the hospital. PMID:27042479

  14. Trends in utilization of FDA expedited drug development and approval programs, 1987-2014: cohort study

    PubMed Central

    Wang, Bo; Franklin, Jessica M; Darrow, Jonathan J

    2015-01-01

    Objective To evaluate the use of special expedited development and review pathways at the US Food and Drug Administration over the past two decades. Design Cohort study. Setting FDA approved novel therapeutics between 1987 and 2014. Population Publicly available sources provided each drug’s year of approval, their innovativeness (first in class versus not first in class), World Health Organization Anatomic Therapeutic Classification, and which (if any) of the FDA’s four primary expedited development and review programs or designations were associated with each drug: orphan drug, fast track, accelerated approval, and priority review. Main outcome measures Logistic regression models evaluated trends in the proportion of drugs associated with each of the four expedited development and review programs. To evaluate the number of programs associated with each approved drug over time, Poisson models were employed, with the number of programs as the dependent variable and a linear term for year of approval. The difference in trends was compared between drugs that were first in class and those that were not. Results The FDA approved 774 drugs during the study period, with one third representing first in class agents. Priority review (43%) was the most prevalent of the four programs, with accelerated approval (9%) the least common. There was a significant increase of 2.6% per year in the number of expedited review and approval programs granted to each newly approved agent (incidence rate ratio 1.026, 95% confidence interval 1.017 to 1.035, P<0.001), and a 2.4% increase in the proportion of drugs associated with at least one such program (odds ratio 1.024, 95% confidence interval 1.006 to 1.043, P=0.009). Driving this trend was an increase in the proportion of approved, non-first in class drugs associated with at least one program for drugs (P=0.03 for interaction). Conclusions In the past two decades, drugs newly approved by the FDA have been associated with an

  15. Ophthalmic drug delivery utilizing two-photon absorption: a novel approach to treat posterior capsule opacification

    NASA Astrophysics Data System (ADS)

    Kim, H.-C.; Träger, J.; Zorn, M.; Haberkorn, N.; Hampp, N.

    2007-07-01

    Intraocular lens (IOL) implantation is the standard technique to treat cataract. Despite recent progress in surgical procedures, posterior capsule opacification is one of the sill remaining postoperative complications of cataract surgery. We present a novel strategy to reduce the incidence of posterior capsule opacification. A drug delivery polymer suitable for manufacturing intraocular lenses has been developed which enables repeated drug release in a non-invasive and controlled manner. The therapeutic molecules are attached through a UV light sensitive linkage to the polymer backbone which is mainly responsible for the optical properties of the intraocular lenses. However, UV light can not trigger the release of drug from the polymer due to the high absorption of the cornea. We developed linkers which enable drug release by two-photon absorption induced cleavage of the linker structure. Since the two-photon absorption requires high photon densities, this does not occur in ambient light conditions in daily life, but is easily triggered by focused laser beams from a pulsed laser. In this proof-of-principle study we have employed a cyclobutane type linker and investigated the properties of the therapeutic system with the approved drugs 5-fluorouracil and chlorambucil. The controlled drug delivery was successfully demonstrated in vitro and additional cell tests confirmed that the device itself shows no cytotoxicity until photochemical activation. This presented concept can provide a powerful method in ophthalmic drug delivery.

  16. Illicit Drugs: Contaminants in the Environment and Utility in Forensic Epidemiology

    EPA Science Inventory

    The published literature surrounding the origin, occurrence, fate, and effects of illicit drug ingredients (IDIs) in the environment is examined. Similarities exist with medical pharmaceuticals, particularly with regard to the basic processes by which these ingredients enter the ...

  17. Utility of drug-eluting stents in complex lesions and high-risk patients.

    PubMed

    Nikolsky, Eugenia; Stone, Gregg W

    2007-02-01

    Drug-eluting stents represent a breakthrough technology designed to deliver high concentrations of a bioactive agent locally to an atherosclerotic lesion, thereby minimizing systemic side effects of the drug. The safety and efficacy of drug-eluting stents have clearly been demonstrated in noncomplex lesions. This article presents an evidence-based analysis of the current experience with CYPHER sirolimus-eluting stents (Cordis Corp., Miami Lakes, FL) and TAXUS paclitaxel-eluting stents (Boston Scientific, Natick, MA) in a broad spectrum of high-risk and/or complex subsets of patients and lesions, including those with diabetes mellitus, multivessel disease, diffuse disease, very small vessels, lesions in saphenous vein grafts, chronic total occlusions, in-stent restenosis, ostial and bifurcation lesions, unprotected left main disease, and acute myocardial infarction. Emerging data in several of these subsets suggest that drug-eluting stents are safe and effective, and their use may currently be recommended, whereas in other groups of patients and lesions the efficacy and/or safety of drug-eluting stents remains to be determined, thus warranting caution. It is anticipated that penetration of drug-eluting stents will continue to increase, and fewer patients will require surgical revascularization to achieve sustained event-free survival.

  18. Drug utilization patterns and reported health status in ethnic German migrants (Aussiedler) in Germany: a cross-sectional study

    PubMed Central

    2011-01-01

    Background Inadequate utilization of healthcare services by migrant populations is an important public health concern. Inadequate drug consumption and poor compliance to the therapeutic regimen are common manifestations of low health-care seeking behavior present in migrants even in the countries with well-established healthcare systems. There are few studies on the use of medicines among the different groups of migrants in Germany. The objective of this study is to investigate drug consumption patterns of ethnic German migrants (Aussiedler) and their current health status. Methods A cross-sectional study nested into a cohort of 18,621 individuals aged 20-70 years who migrated to Germany from the former Soviet Union between 1990 and 2005 was conducted. Data on consumption of drugs, drug handling, major health risk factors, and one-year disease prevalence were obtained for 114 individuals through a self-administered questionnaire and phone interviews. Results were compared to the data on the German population derived from the Disease Analyzer database and Robert Koch Institute (RKI) annual reports. Direct age standardization, test of differences, Chi-square test, and descriptive statistics were applied as appropriate. For drug classification the Anatomical Therapeutic Chemical (ATC) system was used. Results Of the respondents, 97% reported to have at least one disease within a 12-month period. The one-year prevalence of asthma (6.9%), hypertension (26.7%), chronic bronchitis (8.6%), and diabetes (4.9%) in migrants was similar to the general German population. 51% regularly took either over-the-counter (OTC) medication or prescription medicines. Six ATC groups were analyzed. The highest drug consumption was reported for the ATC cardiovascular (22%), nervous (9%), and muskulo-skeletal system (8%). 30% used OTC medicines obtained in the country of origin. Difficulties with drug handling were rare. Alcohol consumption did not differ from the German population (p = 0

  19. 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

  20. Health Services Utilization and Payments in Patients With Cancer Pain: A Comparison of Intrathecal Drug Delivery vs. Conventional Medical Management

    PubMed Central

    Stearns, Lisa J.; Hammond, Krisstin; Berryman, Eric; Janjan, Nora A.

    2016-01-01

    Introduction To compare health services utilization and payments for cancer patients who received an implantable intrathecal drug delivery (IDD) system, consisting of a pump and catheter, vs. conventional medical management (CMM) for the treatment of cancer‐related pain. Methods This retrospective claims‐data analysis compared health services utilization and payments in a population of patients receiving either IDD or CMM for treatment of cancer pain. Patients were propensity score‐matched 1:1 based on characteristics including, but not limited to, age, gender, cancer type, comorbid conditions, and health care utilization and payments. Results From a sample of 142 IDD patients and 3188 CMM patients who met all inclusion/exclusion criteria, 73 matched pairs were obtained. In the year following implant, IDD patients had a consistent trend of lower medical utilization, and total payments that were $3195 lower compared to CMM. Conclusions Despite the high initial cost of IDD, this analysis suggests that patients with IDD incur lower medical utilization and payments over the first year post‐implant. Further analysis comprised of a larger, longitudinal sample would contribute to health economics and outcomes research, and assist with future practice guideline development. PMID:26816205

  1. Trends in prescribing and utilization of statins and other lipid lowering drugs across Europe 1997–2003

    PubMed Central

    Walley, T; Folino-Gallo, P; Stephens, P; Van Ganse, E

    2005-01-01

    Aims To describe trends in utilization and prescribing of statins and other lipid lowering drugs across Europe from data in routine administrative databases. Methods Observational study in EU member states and Norway. Comparison of annual utilization data for lipid lowering agents by class and drug from national administrative databases for reimbursement over the period 1997–2003, measured in DDDs per 1000 inhabitants/day. Prescribed daily doses (PDD) of statins obtained from a commercial database (IMS Health) for 2000 and 2003, and used to calculate numbers of ‘patient treatment days’ (PTD) in each country in each year. Analysis of PTD to explain increased utilization of statins. Results Use of lipid lowering agents varied among countries (in 2003, highest in Ireland and Norway, and lowest in Italy), but increased in all countries studied (between 2000 and 2003 by 274%in Ireland and by 56%in France). This increase was entirely due to increases in statin use. Prescribed daily doses of statins increased in all countries for which data was available between 2000 and 2003, but still usually fell below the doses used in the major trials of statins. As a result, the numbers of PTDs increased to a lesser extent than suggested by utilization (e.g. by 192% in Ireland and by 35% in France). One-third of the total rise in utilization was explained by increased PDD, and two-thirds by an increase in numbers of PTDs. Statins dominated the markets in all countries, although fibrates remained strong in France and Belgium (approximately 25% of all lipid lowering agents) and to a lesser extent Germany (10%). Conclusions Use of statins across Europe has increased hugely over the study period. Some of the increase in use is due to higher prescribed daily doses, but two-thirds is due to increases in numbers of patient days of treatment, either due to more patients treated or less likely to better compliance. PMID:16236045

  2. Utilizing Business, University, and Community Resources to Target Adolescent Prescription Drug Abuse

    ERIC Educational Resources Information Center

    Wade-Mdivanian, R.; Anderson-Butcher, D.; Hale, K.; Kwiek, N.; Smock, J.; Radigan, D.; Lineberger, J.

    2012-01-01

    "Generation Rx" is a prescription drug abuse prevention strategy which includes a "toolkit" designed to be used with youth. Developed by Cardinal Health Foundation and the Ohio State University, it provides health care providers (especially pharmacists), parents, teachers, youth workers, and other community leaders with interactive tools and…

  3. Dynamic SIMS utilizing SF 5+ polyatomic primary ion beams for drug delivery applications

    NASA Astrophysics Data System (ADS)

    Mahoney, Christine M.; Roberson, Sonya; Gillen, Greg

    2004-06-01

    The behavior of various biodegradable polymer films (e.g. polylactic acid, polyglycolic acid and polycaprolactone) as well as some model drugs (theophylline and 4-acetamidophenol) under dynamic SF 5+ primary ion bombardment is explored. A series of polylactic acid films containing varying concentrations of 4-acetamidophenol are also analyzed under similar conditions. The resultant molecular depth profiles obtained from these polymer films doped with drug show very little degradation in molecular signal as a function of SF 5+ primary ion dose, and it was found that the molecular ion signals of both polymer and drug remained constant for ion doses up to ˜5×10 15 ions/cm 2. In addition, the polymer film/Si interface was well defined which may imply that sputter-induced topography formation was not a significant limitation. These results suggest that the structure of the biodegradable polymers studied here which all have the common main chain structural unit, RCOOR, allows for a greater ability to depth profile due to ease of bond cleavage. Most importantly, however, these results indicate that in these particular polymer systems, the distribution of the drug as a function of depth can be monitored.

  4. Health-related service utilization and HIV risk behaviors among HIV infected injection drug users and crack smokers.

    PubMed

    Booth, R E; Kwiatkowski, C F; Weissman, G

    1999-06-01

    This study was designed to assess utilization of health-related services and HIV risk related behaviors by HIV infected drug users one year prior to and two years following the availability of Ryan White Title I funding. Using a cross-sectional design, a total of 777 drug injectors and crack smokers from five US cities were surveyed, over three waves of data collection, about their use of drug treatment, medical services, housing, mental health, and case management and about their sex and drug-related risk behaviors. For all service categories and in each wave, including the year prior to Title I funding, HIV risk behaviors were lower among those who used health-related services, with the exception of housing. Use of services did not increase significantly following the disbursement of Title I funds except for housing and case management. These findings suggest that it may be necessary to increase the attractiveness of health-related services, not just funding for services, for HIV infected substance abusers. PMID:10402151

  5. Cost-Utility Analysis of IEV Drug Regimen Versus ESHAP Drug Regimen for the Patients With Relapsed and Refractory Hodgkin and Non-Hodgkin’s Lymphoma in Iran

    PubMed Central

    Hatam, Nahid; Dehghani, Mehdi; Habibian, Mostafa; Jafari, Abdosaleh

    2015-01-01

    Background: Chemotherapy for lymph nodes cancer is often composed of several drugs that are used in a treatment program. Objectives: The aim of this study was to perform a cost-utility analysis of IEV regimen (ifosfamide, epirubicin and etoposide) versus ESHAP regimen (etoposide, methylprednisolone, high-dose cytarabine, and cisplatin) in patients with lymphoma in the south of Iran. Patients and Methods: This was a cost-utility analysis done as a cross-sectional study in the south of Iran. Using decision tree, expected costs, quality -adjusted life years (QALYs) and the incremental cost-effectiveness ratio (ICER) were estimated. In addition, the robustness of results was examined by sensitivity analysis. Results: The results of this study indicated that the total lymphoma patients were about 65 people that 27 patients received IEV regimen and 38 patients ESHAP (43 patients with Hodgkin’s and 22 with non-Hodgkin lymphoma). The results of decision tree showed that in the IEV arm, the expected cost was $20952.93 and the expected QALYs was 3.89 and in the ESHAP arm, the expected cost was $31691.74 and the expected QALYs was 3.86. Based on the results of the study, IEV regimen was cost-effective alternative to the ESHAP regimen. Conclusions: According to the results of this study, it is recommended that oncologists use IEV instead of ESHAP in the treatment of patients with lymphoma and because of high costs of IEV drug costs, it is suggested that IEV drugs should be covered by insurance. PMID:26634115

  6. Turning the gun on cancer: Utilizing lysosomal P-glycoprotein as a new strategy to overcome multi-drug resistance.

    PubMed

    Seebacher, Nicole; Lane, Darius J R; Richardson, Des R; Jansson, Patric J

    2016-07-01

    Oxidative stress plays a role in the development of drug resistance in cancer cells. Cancer cells must constantly and rapidly adapt to changes in the tumor microenvironment, due to alterations in the availability of nutrients, such as glucose, oxygen and key transition metals (e.g., iron and copper). This nutrient flux is typically a consequence of rapid growth, poor vascularization and necrosis. It has been demonstrated that stress factors, such as hypoxia and glucose deprivation up-regulate master transcription factors, namely hypoxia inducible factor-1α (HIF-1α), which transcriptionally regulate the multi-drug resistance (MDR), transmembrane drug efflux transporter, P-glycoprotein (Pgp). Interestingly, in addition to the established role of plasma membrane Pgp in MDR, a new paradigm of intracellular resistance has emerged that is premised on the ability of lysosomal Pgp to transport cytotoxic agents into this organelle. This mechanism is enabled by the topological inversion of Pgp via endocytosis resulting in the transporter actively pumping agents into the lysosome. In this way, classical Pgp substrates, such as doxorubicin (DOX), can be actively transported into this organelle. Within the lysosome, DOX becomes protonated upon acidification of the lysosomal lumen, causing its accumulation. This mechanism efficiently traps DOX, preventing its cytotoxic interaction with nuclear DNA. This review discusses these effects and highlights a novel mechanism by which redox-active and protonatable Pgp substrates can utilize lysosomal Pgp to gain access to this compartment, resulting in catastrophic lysosomal membrane permeabilization and cell death. Hence, a key MDR mechanism that utilizes Pgp (the "gun") to sequester protonatable drug substrates safely within lysosomes can be "turned on" MDR cancer cells to destroy them from within.

  7. Turning the gun on cancer: Utilizing lysosomal P-glycoprotein as a new strategy to overcome multi-drug resistance.

    PubMed

    Seebacher, Nicole; Lane, Darius J R; Richardson, Des R; Jansson, Patric J

    2016-07-01

    Oxidative stress plays a role in the development of drug resistance in cancer cells. Cancer cells must constantly and rapidly adapt to changes in the tumor microenvironment, due to alterations in the availability of nutrients, such as glucose, oxygen and key transition metals (e.g., iron and copper). This nutrient flux is typically a consequence of rapid growth, poor vascularization and necrosis. It has been demonstrated that stress factors, such as hypoxia and glucose deprivation up-regulate master transcription factors, namely hypoxia inducible factor-1α (HIF-1α), which transcriptionally regulate the multi-drug resistance (MDR), transmembrane drug efflux transporter, P-glycoprotein (Pgp). Interestingly, in addition to the established role of plasma membrane Pgp in MDR, a new paradigm of intracellular resistance has emerged that is premised on the ability of lysosomal Pgp to transport cytotoxic agents into this organelle. This mechanism is enabled by the topological inversion of Pgp via endocytosis resulting in the transporter actively pumping agents into the lysosome. In this way, classical Pgp substrates, such as doxorubicin (DOX), can be actively transported into this organelle. Within the lysosome, DOX becomes protonated upon acidification of the lysosomal lumen, causing its accumulation. This mechanism efficiently traps DOX, preventing its cytotoxic interaction with nuclear DNA. This review discusses these effects and highlights a novel mechanism by which redox-active and protonatable Pgp substrates can utilize lysosomal Pgp to gain access to this compartment, resulting in catastrophic lysosomal membrane permeabilization and cell death. Hence, a key MDR mechanism that utilizes Pgp (the "gun") to sequester protonatable drug substrates safely within lysosomes can be "turned on" MDR cancer cells to destroy them from within. PMID:27154979

  8. Illicit drugs: contaminants in the environment and utility in forensic epidemiology.

    PubMed

    Daughton, Christian G

    2011-01-01

    The published literature that addresses the many facets of pharmaceutical ingredients as environmental contaminants has grown exponentially since the 1990s. Although there are several thousand active ingredients used in medical pharmaceuticals worldwide, illicit drug ingredients (IDIs) have generally been excluded from consideration. Medicinal and illicit drugs have been treated separately in environmental research even though they pose many of the same concerns regarding the potential for both human and ecological exposure. The overview presented here covers the state of knowledge up until mid-2010 regarding the origin, occurrence, fate, and potential for biological effects of IDIs in the environment. Similarities exist with medical pharmaceuticals, particularly with regard to the basic processes by which these ingredients enter the environment--excretion of unmetabolized residues (including via sweat), bathing, disposal, and manufacturing. The features of illicit drugs that distinguish them from medical pharmaceuticals are discussed. Demarcations between the two are not always clear, and a certain degree of overlap adds additional confusion as to what exactly defines an illicit drug; indeed, medical pharmaceuticals diverted from the legal market or used for non-medicinal purposes ar also captured in discussions of illicit drugs. Also needing consideration as par tof the universe of IDIs are the numerous adulterants and synthesis impurities often encountered in these very impure preparations. many of these extraneous chemicals have high biological activity themselves. In contract to medical pharmaceuticals, comparatively little is know about the fate and effects of IDIs in the environment. Environmental surveys for IDIs have revealed their presence in sewage wastewaters, raw sewage sludge and processed sludge (biosolids), and drinking water. Nearly nothing is known, however, regarding wildlife exposure to IDIs, especially aquatic exposure such as indicated by

  9. Drug Utilization Pattern in Patients with Different Types of Dementia in Western India

    PubMed Central

    Patel, Mansi; Joshi, Anuradha; Suthar, Jalpa; Desai, Soaham

    2014-01-01

    Background. Dementia is one of the most frequent disorders among elderly patients, reaching to epidemic proportions with an estimated 4.6 million new cases globally annually. Partially effective treatments are available for dementia. Aims & Objectives. We aim to study drugs used in dementia and find out frequency of types of Dementia. Method. This was an observational study conducted at rurally based tertiary care hospital. Prospective data was collected from outpatient department, while retrospective data was collected from medical records. Descriptive statistics were used to analyze data. Result. Total 125 prescriptions of patients diagnosed with dementia were analyzed. Alzheimer's dementia was most common (65.6%), followed by vascular dementia (21.6%), and frontotemporal dementia (10.4%), with the rarest being Lewy body dementia in (2.4%) cases. 60.57% of patients were males. Mini Mental Score Examination mean score was 15.93 ± 1.37. Frontal Battery Assessment mean score was 4.75 ± 1.01. Prescribed drugs were Donepezil (68.49%), Rivastigmine (13.63%), Donepezil + Memantine (6.43%) and Galantamine (12.83%), Quetiapine (38.46%), Lorazepam (23.07%), Clozapine (11.53%), Escitalopram (10.25%), Haloperidol (3.84%), Zolpidem, Sertraline, Olanzepine (2.56%), Nitrazepine, Lamotrigine, Fluoxetine, Tianeptine (1.28%), Folic acid, and Vitamin B12, respectively. Conclusion. Alzheimer's is the most common type of dementia while Donepezil was the most frequent drug. PMID:25243092

  10. Drug utilization pattern in patients with different types of dementia in Western India.

    PubMed

    Patel, Mansi; Joshi, Anuradha; Suthar, Jalpa; Desai, Soaham

    2014-01-01

    Background. Dementia is one of the most frequent disorders among elderly patients, reaching to epidemic proportions with an estimated 4.6 million new cases globally annually. Partially effective treatments are available for dementia. Aims & Objectives. We aim to study drugs used in dementia and find out frequency of types of Dementia. Method. This was an observational study conducted at rurally based tertiary care hospital. Prospective data was collected from outpatient department, while retrospective data was collected from medical records. Descriptive statistics were used to analyze data. Result. Total 125 prescriptions of patients diagnosed with dementia were analyzed. Alzheimer's dementia was most common (65.6%), followed by vascular dementia (21.6%), and frontotemporal dementia (10.4%), with the rarest being Lewy body dementia in (2.4%) cases. 60.57% of patients were males. Mini Mental Score Examination mean score was 15.93 ± 1.37. Frontal Battery Assessment mean score was 4.75 ± 1.01. Prescribed drugs were Donepezil (68.49%), Rivastigmine (13.63%), Donepezil + Memantine (6.43%) and Galantamine (12.83%), Quetiapine (38.46%), Lorazepam (23.07%), Clozapine (11.53%), Escitalopram (10.25%), Haloperidol (3.84%), Zolpidem, Sertraline, Olanzepine (2.56%), Nitrazepine, Lamotrigine, Fluoxetine, Tianeptine (1.28%), Folic acid, and Vitamin B12, respectively. Conclusion. Alzheimer's is the most common type of dementia while Donepezil was the most frequent drug. PMID:25243092

  11. Antiepileptic drug utilization in Bangladesh: experience from Dhaka Medical College Hospital

    PubMed Central

    2013-01-01

    Background Epilepsy is a common health problem which carries a huge medical social psychological and economic impact for a developing country. The aim of this hospital-based study was to get an insight into the effectiveness and tolerability of low cost antiepileptic drugs (AEDs) in Bangladeshi people with epilepsy. Methods This retrospective chart review was done from hospital records in weekly Epilepsy outdoor clinic of Department of Neurology, Dhaka Medical College Hospital (DMCH) from October 1998 to February 2013. A total of 854 epilepsy patients met the eligibility criteria (had a complete record of two years of follow up data) from hospital database. A checklist was used to take demographics (age and gender), epilepsy treatment and adverse event related data. At least two years of follow up data were considered for analysis. Results Out of 854 patients selected, majority of the patients attending outdoor clinic were >11-30 years age group (55.2%) with a mean age of 20.3 ± 9 years and with a male (53%) predominance. Focal epilepsy were more common (53%), among whom secondary generalized epilepsy was the most frequent diagnosis (67%) followed by complex partial seizure (21%). Among those with Idiopathic Generalized Epilepsy (46%), generalized tonic clonic seizure was encountered in 74% and absence seizure was observed in 13%. The number of patients on monotherapy and dual AED therapy were 67% and 24% respectively and polytherapy (i.e. >3 AEDs) was used only in 9%. CBZ (67%) was the most frequently prescribed AED, followed by VPA (43%), PHB (17%), and PHT (8%). CBZ was prescribed in 37% patients as monotherapy followed by VPA in 21% and PHB in 8% patients. Newer generation drugs eg lemotrigine and topiramate were used only as add on therapy in combination with CBZ and VPA in only 2% patients. The treatment retention rates over the follow up period for the AEDs in monotherapy varied between 86 and 91% and were highest for CBZ, followed by VPA. Most of the

  12. Synthesis of a drug delivery vehicle for cancer treatment utilizing DNA-functionalized gold nanoparticles

    NASA Astrophysics Data System (ADS)

    Brann, Tyler

    The treatment of cancer with chemotherapeutic agents has made great strides in the last few decades but still introduces major systemic side effects. The potent drugs needed to kill cancer cells often cause irreparable damage to otherwise healthy organs leading to further morbidity and mortality. A therapy with intrinsic selective properties and/or an inducible activation has the potential to change the way cancer can be treated. Gold nanoparticles (GNPs) are biocompatible and chemically versatile tools that can be readily functionalized to serve as molecular vehicles. The ability of these particles to strongly absorb light with wavelengths in the therapeutic window combined with the heating effect of surface plasmon resonance makes them uniquely suited for noninvasive heating in biologic applications. Specially designed DNA aptamers have shown their ability to serve as drug carriers through intercalation as well as directly acting as therapeutic agents. By combining these separate molecules a multifaceted drug delivery vehicle can be created with great potential as a selective and controllable treatment for cancer. Oligonucleotide-coated GNPs have been created using spherical GNPs but little work has been reported using gold nanoplates in this way. Using the Diasynth method gold nanoplates were produced to absorb strongly in the therapeutic near infrared (nIR) window. These particles were functionalized with two DNA oligonucleotides: one serving as an intercalation site for doxorubicin, and another, AS1411, serving directly as an anticancer targeting/therapeutic agent. These functional particles were fully synthesized and processed along with confirmation of DNA functionalization and doxorubicin intercalation. Doxorubicin is released via denaturation of the DNA structure into which doxorubicin is intercalated upon the heating of the gold nanoplate well above the DNA melting temperature. This temperature increase, due to light stimulation of surface plasmon

  13. The search for novel drug leads for predominately antitumor therapies by utilizing mother nature's pharmacophoric libraries.

    PubMed

    Kingston, David G I; Newman, David J

    2005-03-01

    Recent advances in the use of natural products and compounds derivedfrom natural products as agents for the treatment of cancer and other diseases are reviewed. The antitumor agents discussed include tubulin interactive agents, inhibitors of topoisomerases I and II, caspase activators, proteasome inhibitors, histone deacetylase inhibitors, heat shock protein 90 inhibitors, protein kinase inhibitors, and inhibitors of hypoxia inducible factor 1. It can be concluded that, despite a perceived lack of popularity in recent years, the use of natural product scaffolds in searching for drug leads is still being practiced.

  14. Design and utilization of the drug-excipient chemical compatibility automated system.

    PubMed

    Thomas, V Hayden; Naath, Maryanne

    2008-07-01

    To accelerate clinical formulation development, an excipient compatibility screen should be conducted as early as possible and it must be rapid, robust and resource sparing. This however, does not describe the traditional excipient compatibility testing approach, requiring many tedious and labor intensive manual operations. This study focused on transforming traditional practices into a completely automated screening process to increase sample throughput and realign resources to more urgent areas, while maintaining quality. Using the developed system, a complete on-line performance study was conducted whereby drug-excipient mixtures were weighed, blended and subjected to accelerated stress stability for up to 1 month, followed by sample extraction and HPLC analysis. Compared to off-line traditional study protocols, the system provided similar relative rank order results with equivalent precision and accuracy, while increasing sample throughput. The designed system offers a resource sparing primary screen for drug-excipient chemical compatibility for solid dosage form development. This approach allows risk assessment analysis, based upon formulation complexity, to be conducted prior to the commitment of resources and candidate selection for clinical development. PMID:18486368

  15. The Utility of a Rodent Model in Detecting Pediatric Drug-Induced Nephrotoxicity

    PubMed Central

    Espandiari, Parvaneh; Zhang, Jun; Rosenzweig, Barry A.; Vaidya, Vishal S.; Sun, Jinchun; Schnackenberg, Laura; Herman, Eugene H.; Knapton, Alan; Bonventre, Joseph V.; Beger, Richard D.; Thompson, Karol L.; Hanig, Joseph

    2009-01-01

    A multi-age rat model was used to identify potential age-related differences in renal injury following exposure to gentamicin (GM). In this study, 10-, 25-, 40-, and 80-day-old Sprague-Dawley rats were dosed with GM at 0, 50, or 100 mg kg-1 body weight per day (mkd) sc for 6 or 14 days. Urine samples were collected up to 72 h after initial dosing. The maximum tolerated dose was lower in 10-day-old rats than for other ages (none survived 11 days of treatment). Eighty-day-old rats given the highest dose showed a diminished rate of growth and an increase in serum creatinine, blood urea nitrogen (BUN), urinary kidney injury molecule-1 (Kim-1), and renal pathology. Ten- and 40-day-old rats given 100 mkd of GM for 6- or 14 days also had increased levels of serum BUN and Cr and renal pathology, whereas only mild renal alterations were found in 25-day-old rats. After 6 days of treatment with 100 mkd GM, significant increases in Havcr-1 (Kim-1) gene expression were detected only in 10- and 80-day-old rats. In urine samples, nuclear magnetic resonance and ultra performance liquid chromatography/mass spectrometry analysis detected changes related to GM efficacy (e.g., hippurate) and increases in metabolites related to antioxidant activity, which was greatest in the 80-day-old rats. The magnitude of the genomic, metabonomic, and serum chemistry changes appeared to correlate with the degree of nephropathy. These findings indicate that an experimental animal model that includes several developmental stages can detect age-related differences in drug-induced organ toxicities and may be a useful predictor of pediatric drug safety in preclinical studies. PMID:17636248

  16. The utility of a rodent model in detecting pediatric drug-induced nephrotoxicity.

    PubMed

    Espandiari, Parvaneh; Zhang, Jun; Rosenzweig, Barry A; Vaidya, Vishal S; Sun, Jinchun; Schnackenberg, Laura; Herman, Eugene H; Knapton, Alan; Bonventre, Joseph V; Beger, Richard D; Thompson, Karol L; Hanig, Joseph

    2007-10-01

    A multi-age rat model was used to identify potential age-related differences in renal injury following exposure to gentamicin (GM). In this study, 10-, 25-, 40-, and 80-day-old Sprague-Dawley rats were dosed with GM at 0, 50, or 100 mg kg(-1) body weight per day (mkd) sc for 6 or 14 days. Urine samples were collected up to 72 h after initial dosing. The maximum tolerated dose was lower in 10-day-old rats than for other ages (none survived 11 days of treatment). Eighty-day-old rats given the highest dose showed a diminished rate of growth and an increase in serum creatinine, blood urea nitrogen (BUN), urinary kidney injury molecule-1 (Kim-1), and renal pathology. Ten- and 40-day-old rats given 100 mkd of GM for 6- or 14 days also had increased levels of serum BUN and Cr and renal pathology, whereas only mild renal alterations were found in 25-day-old rats. After 6 days of treatment with 100 mkd GM, significant increases in Havcr-1 (Kim-1) gene expression were detected only in 10- and 80-day-old rats. In urine samples, nuclear magnetic resonance and ultra performance liquid chromatography/mass spectrometry analysis detected changes related to GM efficacy (e.g., hippurate) and increases in metabolites related to antioxidant activity, which was greatest in the 80-day-old rats. The magnitude of the genomic, metabonomic, and serum chemistry changes appeared to correlate with the degree of nephropathy. These findings indicate that an experimental animal model that includes several developmental stages can detect age-related differences in drug-induced organ toxicities and may be a useful predictor of pediatric drug safety in preclinical studies.

  17. Very large virtual compound spaces: construction, storage and utility in drug discovery.

    PubMed

    Peng, Zhengwei

    2013-09-01

    Recent activities in the construction, storage and exploration of very large virtual compound spaces are reviewed by this report. As expected, the systematic exploration of compound spaces at the highest resolution (individual atoms and bonds) is intrinsically intractable. By contrast, by staying within a finite number of reactions and a finite number of reactants or fragments, several virtual compound spaces have been constructed in a combinatorial fashion with sizes ranging from 10(11)11 to 10(20)20 compounds. Multiple search methods have been developed to perform searches (e.g. similarity, exact and substructure) into those compound spaces without the need for full enumeration. The up-front investment spent on synthetic feasibility during the construction of some of those virtual compound spaces enables a wider adoption by medicinal chemists to design and synthesize important compounds for drug discovery. Recent activities in the area of exploring virtual compound spaces via the evolutionary approach based on Genetic Algorithm also suggests a positive shift of focus from method development to workflow, integration and ease of use, all of which are required for this approach to be widely adopted by medicinal chemists.

  18. Differences in utilization of drug-eluting stents by race and payer.

    PubMed

    Hannan, Edward L; Racz, Michael; Walford, Gary; Clark, Luther T; Holmes, David R; King, Spencer B; Sharma, Samin

    2007-10-15

    Numerous disparities in access to health care by race and gender have been identified in the literature. This study examines differences in the use of drug-eluting stents (DES) versus bare-metal stents (BMS) by race, payer, and income level. Data from New York State's Percutaneous Coronary Intervention Reporting System from July 2003 to December 2004 were used to examine use of DES (20,165 patients) relative to BMS (4,547 patients) by race, payer, and annual income level, controlling for a variety of patient and hospital characteristics. African-Americans were found to be less likely to receive DES than other races between July 2003 and March 2004 (adjusted odds ratio [OR] 0.56, 95% confidence interval [CI] 0.50 to 0.65) and between April 2004 and December 2004 (adjusted OR 0.74, 95% CI 0.61 to 0.90). These disparities were reduced (respective adjusted ORs 0.67, 95% CI 0.58 to 0.77 and 0.81, 95% CI 0.66 to 0.91) when controlling for admitting hospital and hospital volume, but were still significant. Medicaid/self-pay patients, and patients living in zip codes with median annual incomes between $20,000 and $30,000 were also less likely to receive DES in the first time period (adjusted respective ORs 0.80, 95% CI 0.68 to 0.93) and 0.85, 95% CI 0.75 to 0.96). In conclusion, African-Americans and low income groups receive DES less frequently than their counterparts compared with BMS. This is related to the hospitals where they are admitted, but not entirely.

  19. Pro-Arrhythmic Potential of Oral Antihistamines (H1): Combining Adverse Event Reports with Drug Utilization Data across Europe

    PubMed Central

    Poluzzi, Elisabetta; Raschi, Emanuel; Godman, Brian; Koci, Ariola; Moretti, Ugo; Kalaba, Marija; Wettermark, Bjorn; Sturkenboom, Miriam; De Ponti, Fabrizio

    2015-01-01

    Background There is appreciable utilisation of antihistamines (H1) in European countries, either prescribed by physician and purchased by patients for self-medication. Terfenadine and astemizole underwent regulatory restrictions in ’90 because of their cardiac toxicity, but only scarce clinical data are available on other antihistamines. Aim To investigate the pro-arrhythmic potential of antihistamines by combining safety reports of the FDA Adverse Event Reporting System (FAERS) with drug utilization data from 13 European Countries. Methods We identified signals of antihistamine arrhythmogenic potential by analyzing FAERS database for all cases of Torsades de Pointes (TdP), QT abnormalities (QTabn), ventricular arrhythmia (VA) and sudden cardiac death/cardiac arrest (SCD/CA). Number of cases ≥3 and disproportionality were used to define alert signals: TdP and QTabn identified stronger signals, whereas SCD/CA identified weaker signals. Drug utilization data from 2005 to 2010 were collected from administrative databases through health authorities and insurance. Results Antihistamines were reported in 109 cases of TdP/QT prolongation, 278 VA and 610 SCD/CA. Five agents resulted in stronger signals (cetirizine, desloratadine, diphenhydramine, fexofenadine, loratadine) and 6 in weaker signals (alimemazine, carbinoxamine, cyclizine, cyproeptadine, dexchlorpheniramine and doxylamine). Exposure to antihistamines with stronger signal was markedly different across European countries and was at least 40% in each Country. Cetirizine was >29 Defined Daily Doses per 1000 inhabitants per day (DID) in Norway, desloratadine >11 DID in France and loratadine >9 DID in Sweden and Croatia. Drugs with weaker signals accounted for no more than 10% (in Sweden) and in most European countries their use was negligible. Conclusions Some second-generation antihistamines are associated with signal of torsadogenicity and largely used in most European countries. Although confirmation by

  20. Ten-Year Trends in the Morbidity of Diabetes Mellitus and Antidiabetic Drug Utilization in Croatia: A Study Based on Routinely Collected Data.

    PubMed

    Pavlov, Renata; Topličan, Ivančica; Vrcić Keglević, Mladenka

    2016-01-01

    Objectives. To investigate trends of diabetes mellitus (DM) morbidity and antidiabetic drug utilization in Croatian primary health care (PHC) from 2005 to 2014. Method. Routinely collected morbidity data from all PHC units, presented in Croatian health-statistics yearbooks, were retrieved. Data on drug utilization were retrieved from the Annual Reports of the Croatian Agency for Medicinal Products and Medical Devices (ATC/DDD, antidiabetic, A10). Results. Total morbidity increased by 33.3% and DM increased by 65.6%, mostly in patients over age 65 (from 50% to 57%). Estimated DM prevalence in adults increased from 3.9% to 6.4%. Increased morbidity was followed by an even higher increase in drug utilization (120%). Metformin was first, with a constant increase (from 18% to 39%), followed by glimepiride, while glibenclamide use decreased. Total utilization of insulin increased even more, mostly for aspart (600%) and newly introduced glargine and detemir, while human insulin usage sharply decreased. Spending also increased, mostly for aspart (from 21% to 61% of total). Conclusions. Increased DM is followed by a higher increase in antidiabetic drug utilization; this trend will continue in the future. In Croatian PHC, metformin has primacy along with insulin analogues. PMID:27462470

  1. Ten-Year Trends in the Morbidity of Diabetes Mellitus and Antidiabetic Drug Utilization in Croatia: A Study Based on Routinely Collected Data

    PubMed Central

    Topličan, Ivančica; Vrcić Keglević, Mladenka

    2016-01-01

    Objectives. To investigate trends of diabetes mellitus (DM) morbidity and antidiabetic drug utilization in Croatian primary health care (PHC) from 2005 to 2014. Method. Routinely collected morbidity data from all PHC units, presented in Croatian health-statistics yearbooks, were retrieved. Data on drug utilization were retrieved from the Annual Reports of the Croatian Agency for Medicinal Products and Medical Devices (ATC/DDD, antidiabetic, A10). Results. Total morbidity increased by 33.3% and DM increased by 65.6%, mostly in patients over age 65 (from 50% to 57%). Estimated DM prevalence in adults increased from 3.9% to 6.4%. Increased morbidity was followed by an even higher increase in drug utilization (120%). Metformin was first, with a constant increase (from 18% to 39%), followed by glimepiride, while glibenclamide use decreased. Total utilization of insulin increased even more, mostly for aspart (600%) and newly introduced glargine and detemir, while human insulin usage sharply decreased. Spending also increased, mostly for aspart (from 21% to 61% of total). Conclusions. Increased DM is followed by a higher increase in antidiabetic drug utilization; this trend will continue in the future. In Croatian PHC, metformin has primacy along with insulin analogues. PMID:27462470

  2. The utility of the zebrafish model in conditioned place preference to assess the rewarding effects of drugs.

    PubMed

    Collier, Adam D; Echevarria, David J

    2013-09-01

    Substance abuse is a significant public health concern both domestically and worldwide. The persistent use of substances regardless of aversive consequences forces the user to give higher priority to the drug than to normal activities and obligations. The harmful and hazardous use of psychoactive substances can lead to a dependence syndrome. In this regard, the genetic and neurobiological underpinnings of reward-seeking behavior need to be fully understood in order to develop effective pharmacotherapies and other methods of treatment. Animal models are often implemented in preclinical screening for testing the efficacy of novel treatments. Several paradigms exist that model various facets of addiction including sensitization, tolerance, withdrawal, drug seeking, extinction, and relapse. Self-administration and, most notably, conditioned place preference (CPP) are relatively simple tests that serve as indicators of the aforementioned aspects of addiction by means of behavioral quantification. CPP is a commonly used technique to evaluate the motivational effects of compounds and experiences that have been associated with a positive or negative reward, which capitalizes on the basic principles of Pavlovian conditioning. During training, the unconditioned stimulus is consistently paired with a neutral set of environmental stimuli, which obtain, during conditioning, secondary motivational properties that elicit approach behavior in the absence of the unconditioned stimulus. For over 50 years, rodents have been the primary test subjects. However, the zebrafish (Danio rerio) is gaining favor as a valuable model organism in the fields of biology, genetics, and behavioral neuroscience. This paper presents a discussion on the merits, advantages, and limitations of the zebrafish model and its utility in relation to CPP.

  3. Patterns of finasteride use in the male populations of four Nordic countries: A cross-national drug utilization study.

    PubMed

    Kjærulff, T M; Ersbøll, A K; Green, A; Emneus, M; Pukkala, E; Bolin, K; Stavem, K; Iversen, P; Brasso, K; Hallas, J; Thygesen, L C

    2016-06-01

    Objective Finasteride 5 mg is a drug used to treat prostate hyperplasia. Little is known about its pattern of usage. This cross-national analysis of individual-level data from Denmark, Finland, Norway and Sweden was undertaken to appraise its usage and describe cross-national differences. Materials and methods Individual-level data from nationwide prescription registers in Denmark (1995-2009), Finland (1997-2010), Norway (2004-2009) and Sweden (July 2005-2011) were used to examine cross-national finasteride utilization patterns in the adult male population (≥15 years). The study presents period prevalences, incidence rates, waiting time distributions and Lorenz curves. Results During the study period, 295,620 men had at least one prescription redemption of finasteride 5 mg, and there were approximately 3 million dispensing events of finasteride prescriptions in the four Nordic countries. Different patterns of finasteride use were observed among the four Nordic countries. The period prevalence was markedly higher in Finland and Sweden than in Denmark and Norway. In 2009, period prevalences were 18.2/1000 males in Finland and 12.0/1000 males in Sweden compared to 6.7/1000 males in Norway and 4.9/1000 males in Denmark. Incidence rates of finasteride use for Finland, Norway and Sweden were about three times that for Denmark in 2008-2009. Long-term use of finasteride was found in all four Nordic countries with a high ratio between prevalent and incident users. Conclusion Despite resemblances regarding political systems and healthcare services in the Nordic countries, differences in finasteride utilization were found across Denmark, Finland, Norway and Sweden. PMID:26901820

  4. Drugs.

    ERIC Educational Resources Information Center

    Hurst, Hunter, Ed.; And Others

    1984-01-01

    This document contains the third volume of "Today's Delinquent," an annual publication of the National Center for Juvenile Justice. This volume deals with the issue of drugs and includes articles by leading authorities in delinquency and substance abuse who share their views on causes and cures for the drug problem among youth in this country.…

  5. Impact of drug price adjustments on utilization of and expenditures on angiotensin-converting enzyme inhibitors and angiotensin receptor blockers in Taiwan

    PubMed Central

    2012-01-01

    Background A previous study has suggested that drug price adjustments allow physicians in Taiwan to gain greater profit by prescribing generic drugs. To better understand the effect of price adjustments on physician choice, this study used renin-angiotensin drugs (including angiotensin-converting enzyme inhibitors [ACEIs] and angiotensin receptor blockers [ARBs]) to examine the impact of price adjustments on utilization of and expenditures on patented and off-patent drugs with the same therapeutic indication. Methods Using the Taiwan’s Longitudinal Health Insurance Database (2005), we identified 147,157 patients received ACEIs and/or ARBs between 1997 and 2008. The annual incident and prevalent users of ACEIs, ARBs and overall renin-angiotensin drugs were examined. Box-Tiao intervention analysis was applied to assess the impact of price adjustments on monthly utilization of and expenditures on these drugs. ACEIs were divided into patented and off-patent drugs, off-patent ACEIs were further divided into original brands and generics, and subgroup analyses were performed. Results The number of incident renin-angiotensin drug users decreased over the study period. The number of prevalent ARB users increased and exceeded the cumulative number of first-time renin-angiotensin drug users starting on ARBs, implying that some patients switched from ACEIs to ARBs. After price adjustments, long term trend increases in utilization were observed for patented ACEIs and ARBs; a long-term trend decrease was observed for off-patent ACEIs; long-term trend change was not significant for overall renin-angiotensin drugs. Significant long-term trend increases in expenditures were observed for patented ACEIs after price adjustment in 2007 (200.9%, p = 0.0088) and in ARBs after price adjustments in 2001 (173.4%, p < 0.0001) and 2007 (146.3%, p < 0.0001). A significant long-term trend decrease in expenditures was observed for off-patent ACEIs after 2004 price adjustment (

  6. Inpatient drug utilization in Europe: nationwide data sources and a review of publications on a selected group of medicines (PROTECT project).

    PubMed

    Sabaté, Mònica; Ferrer, Pili; Ballarín, Elena; Rottenkolber, Marietta; Amelio, Justyne; Schmiedl, Sven; Reynolds, Robert; Klungel, Olaf; Ibáñez, Luisa

    2015-03-01

    Drug utilization (DU) studies in inpatient settings at a national level are rarely conducted. The main objective of this study was to review the general information on hospital medicine management in Europe and to report on the availability and characteristics of nationwide administrative drug consumption databases. A secondary objective was to perform a review of published studies on hospital DU of a group of selected drugs, focusing on methodological characteristics (ATC/DDD). General information on hospital drug management was retrieved from several websites, nationwide administrative drug consumption databases and reports published by governmental organizations. A PubMed search was conducted using keywords related to the selected group of drugs AND 'hospital drug utilization'. The data sources for hospital DU information varied widely and included 14 databases from 25 reviewed countries. Bulgaria, Croatia, Denmark, Estonia, Finland, France, Hungary, Iceland, Latvia, Norway and Sweden obtain information on inpatient DU at a national level from wholesalers/manufacturers. In Belgium, Italy and Portugal, drugs dispensed to patients in hospitals are registered at a national level. Data are freely available online only for Denmark and Iceland. From the PubMed search, of a total of 868 retrieved studies, only 13 studies used the ATC/DDD methodology. Although the number of DDD/100 bed-days was used in four studies, other units of measure were also used. The type of information provided for the inpatient sector allowed primarily for conducting DU research at an aggregated data level. The existence of national administrative structures to monitor hospital DU would contribute to promoting the rational use of medicines and improving the safety and quality of prescribing. PMID:25420967

  7. Age- and Sex-related Prevalence and Drug Utilization Pattern in the Management of Type 2 Diabetes Mellitus and its Comorbidity with Cardiovascular Diseases: A Comparative Study.

    PubMed

    Das, S; Haroled Peter, P L; Bhavani, M Lakshmi; Naresh, P; Ramana, M V

    2015-01-01

    A cross-sectional study of 250 cases of type 2 diabetes management was conducted in a governmental tertiary care hospital of urban south India to determine the comparative prevalence of type 2 diabetes and its comorbidity with cardiovascular diseases in diabetic population, core drug use indicators and drug utilization pattern in the management of diabetics entirely and with cardiovascular diseases. Highest prevalent age group for type 2 diabetes/cardiovascular diseases (greater incidence in female than male) was 51-60 years. The 62.8% prevalence of cardiovascular diseases in the diabetic population ascertained in the study could provide an evidence-based rationale for the World Health Organization guidelines for the management of hypertension in type 2 diabetics. Incidence of polypharmacy (6.06, the mean number of total drug products prescribed); 59.26% of encounters prescribed antibiotics; 17.6 and 18.5 min of average consultation and dispensing time, respectively; 100% of drugs actually dispensed and adequately labeled; 81.26% of patients having knowledge of correct dosage and average drug cost of Indian Rupees 145.54 per prescription were the core drug use indicators found mainly. Moreover, drugs prescribed from the Essential Drug List were more than 90% and thereby indicated the drug use in this set-up quite rational. Around 71.09% of cardiovascular agents prescribed by generic name revealed the cost effective medical care. Among the agents in type 2 diabetes management, Actrapid(®) (35.43%) was the highest. Among the cardiovascular agents prescribed, lasix (19.37%) was the highest. Cardiovascular agents prescribed orally by 76.48% signified the good prescription habit indicating the improved patients' adherence to the treatment. The present study emphasizes the need of early detection of hypertension as a preliminary diagnostic parameter of cardiovascular diseases in diabetics and appropriate management through concomitant therapy of cardiovascular drugs to

  8. Age- and Sex-related Prevalence and Drug Utilization Pattern in the Management of Type 2 Diabetes Mellitus and its Comorbidity with Cardiovascular Diseases: A Comparative Study.

    PubMed

    Das, S; Haroled Peter, P L; Bhavani, M Lakshmi; Naresh, P; Ramana, M V

    2015-01-01

    A cross-sectional study of 250 cases of type 2 diabetes management was conducted in a governmental tertiary care hospital of urban south India to determine the comparative prevalence of type 2 diabetes and its comorbidity with cardiovascular diseases in diabetic population, core drug use indicators and drug utilization pattern in the management of diabetics entirely and with cardiovascular diseases. Highest prevalent age group for type 2 diabetes/cardiovascular diseases (greater incidence in female than male) was 51-60 years. The 62.8% prevalence of cardiovascular diseases in the diabetic population ascertained in the study could provide an evidence-based rationale for the World Health Organization guidelines for the management of hypertension in type 2 diabetics. Incidence of polypharmacy (6.06, the mean number of total drug products prescribed); 59.26% of encounters prescribed antibiotics; 17.6 and 18.5 min of average consultation and dispensing time, respectively; 100% of drugs actually dispensed and adequately labeled; 81.26% of patients having knowledge of correct dosage and average drug cost of Indian Rupees 145.54 per prescription were the core drug use indicators found mainly. Moreover, drugs prescribed from the Essential Drug List were more than 90% and thereby indicated the drug use in this set-up quite rational. Around 71.09% of cardiovascular agents prescribed by generic name revealed the cost effective medical care. Among the agents in type 2 diabetes management, Actrapid(®) (35.43%) was the highest. Among the cardiovascular agents prescribed, lasix (19.37%) was the highest. Cardiovascular agents prescribed orally by 76.48% signified the good prescription habit indicating the improved patients' adherence to the treatment. The present study emphasizes the need of early detection of hypertension as a preliminary diagnostic parameter of cardiovascular diseases in diabetics and appropriate management through concomitant therapy of cardiovascular drugs to

  9. Utilization of H-bond interaction of nucleobase Uralic with antitumor methotrexate to design drug carrier with ultrahigh loading efficiency and pH-responsive drug release

    PubMed Central

    Cai, Teng-Teng; Lei, Qi; Yang, Bin; Jia, Hui-Zhen; Cheng, Hong; Liu, Li-Han; Zeng, Xuan; Feng, Jun; Zhuo, Ren-Xi; Zhang, Xian-Zheng

    2014-01-01

    A novel Uralic (U)-rich linear-hyperbranched mono-methoxy poly (ethylene glycol)-hyperbranched polyglycerol-graft-Uralic (mPEG-HPG-g-U) nanoparticle (NP) was prepared as drug carrier for antitumor methotrexate (MTX). Due to the H-bond interaction of U with MTX and hydrophobic interaction, this NP exhibited high drug loading efficiency of up to 40%, which was significantly higher than that of traditional NPs based on U-absent copolymers (<15%). In addition, MTX-loaded mPEG-HPG-g-U NPs also demonstrated an acidity-accelerated drug release behavior. PMID:26816622

  10. Utilization of H-bond interaction of nucleobase Uralic with antitumor methotrexate to design drug carrier with ultrahigh loading efficiency and pH-responsive drug release.

    PubMed

    Cai, Teng-Teng; Lei, Qi; Yang, Bin; Jia, Hui-Zhen; Cheng, Hong; Liu, Li-Han; Zeng, Xuan; Feng, Jun; Zhuo, Ren-Xi; Zhang, Xian-Zheng

    2014-11-01

    A novel Uralic (U)-rich linear-hyperbranched mono-methoxy poly (ethylene glycol)-hyperbranched polyglycerol-graft-Uralic (mPEG-HPG-g-U) nanoparticle (NP) was prepared as drug carrier for antitumor methotrexate (MTX). Due to the H-bond interaction of U with MTX and hydrophobic interaction, this NP exhibited high drug loading efficiency of up to 40%, which was significantly higher than that of traditional NPs based on U-absent copolymers (<15%). In addition, MTX-loaded mPEG-HPG-g-U NPs also demonstrated an acidity-accelerated drug release behavior.

  11. Utilization of formal and informal home care by AIDS patients in Boston: a comparison of intravenous drug users and homosexual males.

    PubMed

    Ettner, S L; Weissman, J

    1994-05-01

    The assumption that intravenous (i.v.) drug users have weaker informal support networks than homosexual men has led to opposing policy recommendations: one emphasizes outreach and more formal (paid) home care for i.v. drug users, whereas the other maintains that formal home care programs are less effective for this risk group due to the lack of informal (unpaid) caregivers to coordinate efforts. Data from interviews with a sample of 231 persons with AIDS in the Boston area were used to compare the use of formal and informal home care between the two largest risk groups, homosexual men and i.v. drug users. Multivariate regression analysis was also employed to adjust estimates and to determine the significance of population characteristics in explaining utilization differences. IV drug users received about twice as much formal and informal home care as homosexual men. Controlling for functional status, income and assets, insurance and potential caregiver supply, i.v. drug users obtained significantly fewer formal home care services, but more informal care. Overall, i.v. drug users received a greater number of adjusted home care hours. These findings cast doubt upon the previous assumptions of the literature and suggest that members of both risk groups are appropriate candidates for formal home care services.

  12. Drug utilization and prescribing patterns in a skilled nursing facility: the need for a rational approach to therapeutics.

    PubMed

    Segal, J L; Thompson, J F; Floyd, R A

    1979-03-01

    A study was made of 50 patients drawn at random from a Skilled Nursing Facility (SNF) attended by seven physicians. For 59 percent of these patients, polypharmacy was practiced but no substantiating diagnoses were recorded. Approximately half of the drugs were administered pro re nata. More drugs were prescribed in potentially toxic dosages than in subtherapeutic dosages. The risk of an adverse drug reaction (ADR) was most often associated with anticholinergic agents, sedative-hypnotic drugs, and neuroleptics (thioridazine and chlorpromazine), particularly when prescribed concurrently. Risk of an ADR was highest when a drug was prescribed without recording a definite diagnostic indication. Lack of consistency by individual physicians in their approaches to the therapy of similar disease entities in comparable patients tended to support the concept of peer review in SNFs and also the need for teaching a rational approach to therapeutics in SNFs based on clinical pharmacology as applied to the elderly. PMID:429730

  13. A challenge for diagnosing acute liver injury with concomitant/sequential exposure to multiple drugs: can causality assessment scales be utilized to identify the offending drug?

    PubMed

    Lim, Roxanne; Choudry, Hassan; Conner, Kim; Karnsakul, Wikrom

    2014-01-01

    Drug-induced hepatotoxicity most commonly manifests as an acute hepatitis syndrome and remains the leading cause of drug-induced death/mortality and the primary reason for withdrawal of drugs from the pharmaceutical market. We report a case of acute liver injury in a 12-year-old Hispanic boy, who received a series of five antibiotics (amoxicillin, ceftriaxone, vancomycin, ampicillin/sulbactam, and clindamycin) for cervical lymphadenitis/retropharyngeal cellulitis. Histopathology of the liver biopsy specimen revealed acute cholestatic hepatitis. All known causes of acute liver injury were appropriately excluded and (only) drug-induced liver injury was left as a cause of his cholestasis. Liver-specific causality assessment scales such as Council for the International Organization of Medical Sciences/Roussel Uclaf Causality Assessment Method scoring system (CIOMS/RUCAM), Maria and Victorino scale, and Digestive Disease Week-Japan were applied to seek the most likely offending drug. Although clindamycin is the most likely cause by clinical diagnosis, none of causality assessment scales aid in the diagnosis.

  14. The Utility of Impulsive Bias and Altered Decision Making as Predictors of Drug Efficacy and Target Selection: Rethinking Behavioral Screening for Antidepressant Drugs.

    PubMed

    Marek, Gerard J; Day, Mark; Hudzik, Thomas J

    2016-03-01

    Cognitive dysfunction may be a core feature of major depressive disorder, including affective processing bias, abnormal response to negative feedback, changes in decision making, and increased impulsivity. Accordingly, a translational medicine paradigm predicts clinical action of novel antidepressants by examining drug-induced changes in affective processing bias. With some exceptions, these concepts have not been systematically applied to preclinical models to test new chemical entities. The purpose of this review is to examine whether an empirically derived behavioral screen for antidepressant drugs may screen for compounds, at least in part, by modulating an impulsive biasing of responding and altered decision making. The differential-reinforcement-of-low-rate (DRL) 72-second schedule is an operant schedule with a documented fidelity for discriminating antidepressant drugs from nonantidepressant drugs. However, a theoretical basis for this empirical relationship has been lacking. Therefore, this review will discuss whether response bias toward impulsive behavior may be a critical screening characteristic of DRL behavior requiring long inter-response times to obtain rewards. This review will compare and contrast DRL behavior with the five-choice serial reaction time task, a test specifically designed for assessing motoric impulsivity, with respect to psychopharmacological testing and the neural basis of distributed macrocircuits underlying these tasks. This comparison suggests that the existing empirical basis for the DRL 72-second schedule as a pharmacological screen for antidepressant drugs is complemented by a novel hypothesis that altering impulsive response bias for rodents trained on this operant schedule is a previously unrecognized theoretical cornerstone for this screening paradigm. PMID:26699144

  15. Development, validation and utility of an in vitro technique for assessment of potential clinical drug-drug interactions involving P-glycoprotein.

    PubMed

    Keogh, John P; Kunta, Jeevan R

    2006-04-01

    Regulatory interest is increasing for drug transporters generally and P-glycoprotein (Pgp) in particular, primarily in the area of drug-drug interactions. To aid in both identifying and discharging the potential liabilities associated with drug-transporter interactions, the pharmaceutical industry has a growing requirement for routine and robust non-clinical assays. An assay was designed, optimised and validated to determine the in vitro inhibitory potency of new chemical entities (NCEs) towards human Pgp-mediated transport. [3H]-Digoxin was established as a suitable probe substrate by investigating its characteristics in the in vitro system (MDCKII-MDR1 cells grown in 24-multiwell inserts). The inhibitory potencies (apparent IC50) of known Pgp inhibitors astemizole, GF120918, ketoconazole, itraconazole, quinidine, verapamil and quinine were determined over at least a 1000-fold concentration range. Validation was carried out using manual and automatic techniques. [3H]-Digoxin was found to be stable and have good mass balance in the system. In contrast to [A-->B] transport, [3H]-digoxin [B-->A] transport rates were readily measured with good reproducibility. There was no evidence of saturation of transport up to 10 microM digoxin and 30 nM digoxin was selected for routine assay use, reflecting clinical therapeutic concentrations. IC50 values ranged over approximately 100-fold with excellent reproducibility. Results from manual and automated versions were in close agreement. This method is suitable for routine use to assess the in vitro inhibitory potency of NCEs on Pgp-mediated digoxin transport. Comparison of IC50 values against clinical interaction profiles for the probe inhibitors indicated the in vitro assay is predictive of clinical digoxin-drug interactions mediated via Pgp.

  16. Utility of spatially-resolved atmospheric pressure surface sampling and ionization techniques as alternatives to mass spectrometric imaging (MSI) in drug metabolism

    SciTech Connect

    Blatherwick, Eleanor Q.; Van Berkel, Gary J; Pickup, Kathryn; Johansson, Maria K.; Beaudoin, Marie-Eve; Cole, Roderic; Day, Jennifer M.; Iverson, Suzanne; Wilson, Ian D.; Scrivens, James H.; Weston, Daniel J.

    2011-01-01

    1. Tissue distribution studies of drug molecules play an essential role in the pharmaceutical industry and are commonly undertaken using quantitative whole body autoradiography (QWBA) methods. 2. The growing need for complementary methods to address some scientific gaps around radiography methods has led to increased use of mass spectrometric imaging (MSI) technology over the last 5 to 10 years. More recently, the development of novel mass spectrometric techniques for ambient surface sampling has redefined what can be regarded as fit-for-purpose for MSI in a drug metabolism and disposition arena. 3. Together with a review of these novel alternatives, this paper details the use of two liquid microjunction (LMJ)- based mass spectrometric surface sampling technologies. These approaches are used to provide qualitative determination of parent drug in rat liver tissue slices using liquid extraction surface analysis (LESA) and to assess the performance of a LMJ surface sampling probe (LMJ-SSP) interface for quantitative assessment of parent drug in brain, liver and muscle tissue slices. 4. An assessment of the utility of these spatially-resolved sampling methods is given, showing interdependence between mass spectrometric and QWBA methods, in particular there emerges a reason to question typical MSI workflows for drug metabolism; suggesting the expedient use of profile or region analysis may be more appropriate, rather than generating time-intensive molecular images of the entire tissue section.

  17. Dabigatran - a continuing exemplar case history demonstrating the need for comprehensive models to optimize the utilization of new drugs

    PubMed Central

    Godman, Brian; Malmström, Rickard E.; Diogene, Eduardo; Jayathissa, Sisira; McTaggart, Stuart; Cars, Thomas; Alvarez-Madrazo, Samantha; Baumgärtel, Christoph; Brzezinska, Anna; Bucsics, Anna; Campbell, Stephen; Eriksson, Irene; Finlayson, Alexander; Fürst, Jurij; Garuoliene, Kristina; Gutiérrez-Ibarluzea, Iñaki; Hviding, Krystyna; Herholz, Harald; Joppi, Roberta; Kalaba, Marija; Laius, Ott; Malinowska, Kamila; Pedersen, Hanne B.; Markovic-Pekovic, Vanda; Piessnegger, Jutta; Selke, Gisbert; Sermet, Catherine; Spillane, Susan; Tomek, Dominik; Vončina, Luka; Vlahović-Palčevski, Vera; Wale, Janet; Wladysiuk, Magdalena; van Woerkom, Menno; Zara, Corinne; Gustafsson, Lars L.

    2014-01-01

    Background: There are potential conflicts between authorities and companies to fund new premium priced drugs especially where there are effectiveness, safety and/or budget concerns. Dabigatran, a new oral anticoagulant for the prevention of stroke in patients with non-valvular atrial fibrillation (AF), exemplifies this issue. Whilst new effective treatments are needed, there are issues in the elderly with dabigatran due to variable drug concentrations, no known antidote and dependence on renal elimination. Published studies showed dabigatran to be cost-effective but there are budget concerns given the prevalence of AF. These concerns resulted in extensive activities pre- to post-launch to manage its introduction. Objective: To (i) review authority activities across countries, (ii) use the findings to develop new models to better manage the entry of new drugs, and (iii) review the implications based on post-launch activities. Methodology: (i) Descriptive review and appraisal of activities regarding dabigatran, (ii) development of guidance for key stakeholder groups through an iterative process, (iii) refining guidance following post launch studies. Results: Plethora of activities to manage dabigatran including extensive pre-launch activities, risk sharing arrangements, prescribing restrictions and monitoring of prescribing post launch. Reimbursement has been denied in some countries due to concerns with its budget impact and/or excessive bleeding. Development of a new model and future guidance is proposed to better manage the entry of new drugs, centering on three pillars of pre-, peri-, and post-launch activities. Post-launch activities include increasing use of patient registries to monitor the safety and effectiveness of new drugs in clinical practice. Conclusion: Models for introducing new drugs are essential to optimize their prescribing especially where concerns. Without such models, new drugs may be withdrawn prematurely and/or struggle for funding. PMID

  18. Utilizing a novel tandem oral dosing strategy to enhance exposure of low-solubility drug candidates in a preclinical setting.

    PubMed

    Chiang, Po-Chang; South, Sarah A; Foster, Kimberly A; Daniels, J Scott; Wene, Steve P; Albin, Lesley A; Thompson, David C

    2010-07-01

    Time and resource constraints necessitate increasingly early decision making to accelerate or stop preclinical drug discovery programs. Early discovery drug candidates may be potent inhibitors of new targets, but all too often exhibit poor pharmaceutical and pharmacokinetic properties that limit the in vivo exposure. Low solubility of a drug candidate often leads to poor oral bioavailability and poor dose linearity that creates an issue for efficacy and target safety studies, where high drug exposures are desired. When solubility issues are encountered, enabling formulations are often used to improve the exposure. However, this approach often requires a substantial and lengthy investment to develop the formulation. In our study, two drug candidates with poor aqueous solubility were dosed in rats as simple suspension formulations using a novel tandem dosing strategy, which employs dosing orally in 2.5 h increments up to three times to simulate an oral infusion by avoiding saturation of absorption associated with bolus dosing. These compounds were also dosed using the same suspension formulations and a standard dosing strategy. The resulting in vivo exposures were compared. It was found that this novel tandem dosing strategy significantly improved the in vivo exposures.

  19. Clinical utility of the Food and Drug Administration Electrocardiogram Warehouse: a paradigm for the critical pathway initiative.

    PubMed

    Cabell, Christopher H; Noto, Tory C; Krucoff, Mitchell W

    2005-10-01

    Although there are rising public expectations about the prospects for new therapies based on advances in biomedical discoveries, the rate of new product submissions to the Food and Drug Administration (FDA) has not been increasing. Alarmingly, over the past 6 years, there has been a 30% decline in submissions. The reasons for this are multifactorial and include new science not at its full potential, mergers/business arrangements have decreased candidates, chronic disease is harder to study, the failure rate has not improved, and rapidly escalating costs and complexity. Notably, societal investment in research and development to improve the drug approval process has been lacking in contrast to the large investments, both private and public, in basic research and specific product advances. The Critical Path Initiative has been developed by the FDA to combat many of these issues. This initiative is designed to be collaborative between government, academic, industry, and patient groups. The partnership is designed to expand product opportunities by sharing existing knowledge and data, allowing the development of enabling standards, to improve drug development and approval. A central tenant of Critical Path is a focus on the evaluative science of the drug approval process, including both efficacy and safety measures. The FDA Electrocardiogram Warehouse is 1 example where a government resource could be used by a confluence of groups to improve the science surrounding important components of the drug approval process such as cardiac safety evaluation.

  20. Rapid and facile detection of four date rape drugs in different beverages utilizing proton transfer reaction mass spectrometry (PTR-MS).

    PubMed

    Jürschik, Simone; Agarwal, Bishu; Kassebacher, Thomas; Sulzer, Philipp; Mayhew, Christopher A; Märk, Tilmann D

    2012-09-01

    In this work, we illustrate the application of proton transfer reaction mass spectrometry (PTR-MS) in the field of food and drink safety. We present proof-of-principle measurements of four different drinks (water, tea, red wine and white wine) each spiked separately with four different date rape drugs (chloral hydrate, tricholorethanol, γ-butyrolactone and butanediol). At first, the ideal PTR-MS operating conditions (reduced electric field strength and monitoring the most abundant [fragment] ion) for detection of the drugs were determined utilizing a time-of-flight-based PTR-MS instrument. We then dissolved small quantities of the drugs (below the activation threshold for effects on humans) into the various types of drinks and detected them using a quadrupole-based PTR-MS instrument via two different sampling methods: (1) dynamic headspace sampling and (2) direct liquid injection. Both methods have their advantages and drawbacks. Only with dynamic headspace sampling can rape drug contaminations be detected within a timeframe of seconds, and therefore, this method is the most promising use of PTR-MS as a fast, sensitive and selective monitor for the detection of food and drink contamination. PMID:22972776

  1. A Review: The Current In Vivo Models for the Discovery and Utility of New Anti-leishmanial Drugs Targeting Cutaneous Leishmaniasis

    PubMed Central

    Mears, Emily Rose; Modabber, Farrokh; Don, Robert; Johnson, George E.

    2015-01-01

    The current in vivo models for the utility and discovery of new potential anti-leishmanial drugs targeting Cutaneous Leishmaniasis (CL) differ vastly in their immunological responses to the disease and clinical presentation of symptoms. Animal models that show similarities to the human form of CL after infection with Leishmania should be more representative as to the effect of the parasite within a human. Thus, these models are used to evaluate the efficacy of new anti-leishmanial compounds before human clinical trials. Current animal models aim to investigate (i) host–parasite interactions, (ii) pathogenesis, (iii) biochemical changes/pathways, (iv) in vivo maintenance of parasites, and (v) clinical evaluation of drug candidates. This review focuses on the trends of infection observed between Leishmania parasites, the predictability of different strains, and the determination of parasite load. These factors were used to investigate the overall effectiveness of the current animal models. The main aim was to assess the efficacy and limitations of the various CL models and their potential for drug discovery and evaluation. In conclusion, we found that the following models are the most suitable for the assessment of anti-leishmanial drugs: L. major–C57BL/6 mice (or–vervet monkey, or–rhesus monkeys), L. tropica–CsS-16 mice, L. amazonensis–CBA mice, L. braziliensis–golden hamster (or–rhesus monkey). We also provide in-depth guidance for which models are not suitable for these investigations. PMID:26334763

  2. A Review: The Current In Vivo Models for the Discovery and Utility of New Anti-leishmanial Drugs Targeting Cutaneous Leishmaniasis.

    PubMed

    Mears, Emily Rose; Modabber, Farrokh; Don, Robert; Johnson, George E

    2015-01-01

    The current in vivo models for the utility and discovery of new potential anti-leishmanial drugs targeting Cutaneous Leishmaniasis (CL) differ vastly in their immunological responses to the disease and clinical presentation of symptoms. Animal models that show similarities to the human form of CL after infection with Leishmania should be more representative as to the effect of the parasite within a human. Thus, these models are used to evaluate the efficacy of new anti-leishmanial compounds before human clinical trials. Current animal models aim to investigate (i) host-parasite interactions, (ii) pathogenesis, (iii) biochemical changes/pathways, (iv) in vivo maintenance of parasites, and (v) clinical evaluation of drug candidates. This review focuses on the trends of infection observed between Leishmania parasites, the predictability of different strains, and the determination of parasite load. These factors were used to investigate the overall effectiveness of the current animal models. The main aim was to assess the efficacy and limitations of the various CL models and their potential for drug discovery and evaluation. In conclusion, we found that the following models are the most suitable for the assessment of anti-leishmanial drugs: L. major-C57BL/6 mice (or-vervet monkey, or-rhesus monkeys), L. tropica-CsS-16 mice, L. amazonensis-CBA mice, L. braziliensis-golden hamster (or-rhesus monkey). We also provide in-depth guidance for which models are not suitable for these investigations. PMID:26334763

  3. New Alert Override Codes for the Drug Utilization Review System Derived from Outpatient Prescription Data from a Tertiary Teaching Hospital in Korea

    PubMed Central

    Yoo, Ki-Bong; Kim, Woojae; Park, Man Young; Ahn, Eun Kyoung; Park, Rae Woong

    2016-01-01

    Objectives This paper proposes new alert override reason codes that are improvements on existing Drug Utilization Review (DUR) codes based on an analysis of DUR alert override cases in a tertiary medical institution. Methods Data were obtained from a tertiary teaching hospital covering the period from April 1, 2012 to January 15, 2013. We analyzed cases in which doctors had used the 11 overlapping prescription codes provided by the Health Insurance Review and Assessment Service (HIRA) or had provided free-text reasons. Results We identified 27,955 alert override cases. Among these, 7,772 (27.8%) utilized the HIRA codes, and 20,183 (72.2%) utilized free-text reasons. According to the free-text content analysis, 8,646 cases (42.8%) could be classified using the 11 HIRA codes, and 11,537 (57.2%) could not. In the unclassifiable cases, we identified the need for codes for "prescription relating to operation" and "emergency situations." Two overlapping prescription codes required removal because they were not used. Codes A, C, F, H, I, and J (for drug non-administration cases) explained surrounding situations in too much detail, making differentiation between them difficult. These 6 codes were merged into code J4: "patient was not taking/will not take the medications involved in the DDI." Of the 11 HIRA codes, 6 were merged into a single code, 2 were removed, and 2 were added, yielding 6 alert override codes. We could codify 23,550 (84.2%) alert override cases using these codes. Conclusions These new codes will facilitate the use of the drug–drug interactions alert override in the current DUR system. For further study, an appropriate evaluation should be conducted with prescribing clinicians. PMID:26893949

  4. Epoetin alfa and darbepoetin alfa for the treatment of chemotherapy-related anemia in cancer patients in Sweden: comparative analysis of drug utilization, costs, and hematologic response.

    PubMed

    Persson, Ulf; Borg, Sixten; Jansson, Sandra; Ekman, Tor; Franksson, Lars; Friesland, Signe; Larsson, Anna-Maria

    2005-01-01

    A retrospective chart review was performed at 3 Swedish hospitals to evaluate the utilization, outcomes, and cost of using epoetin alfa or darbepoetin alfa to treat cancer patients with chemotherapy-related anemia. Data on dosage, duration of treatment, hematologic response, red blood cell transfusions, and healthcare resource consumption were collected and analyzed at various time points following the initiation of drug therapy. A significantly faster hematologic response and increase in hemoglobin were observed in patients treated with epoetin alfa. Dosages used in clinical practice appeared to be lower than those recommended by Swedish treatment guidelines. There were no significant differences in resource utilization or healthcare costs between the 2 treatment groups. By day 112, the mean treatment cost per patient, in Swedish kronors (SEK), was SEK74,701 (approximately US$9800 or approximately 8300) with epoetin alfa and SEK85,285 (approximately US$11,000 or approximately 9500) with darbepoetin alfa. Drug acquisition and administration accounted for 81% and 67% of the total cost of epoetin alfa and darbepoetin alfa therapy, respectively; the remainder of the total cost was for hospitalization and transfusions.

  5. A New Screen for Tuberculosis Drug Candidates Utilizing a Luciferase-Expressing Recombinant Mycobacterium bovis Bacillus Calmette-Guéren

    PubMed Central

    Igarashi, Masayuki; Doe, Matsumi; Tamaru, Aki; Kinoshita, Naoko; Ogura, Yoshitoshi; Iwamoto, Tomotada; Sawa, Ryuichi; Umekita, Maya; Enany, Shymaa; Nishiuchi, Yukiko; Osada-Oka, Mayuko; Hayashi, Tetsuya; Niki, Mamiko; Tateishi, Yoshitaka; Hatano, Masaki

    2015-01-01

    Tuberculosis (TB) is a serious infectious disease caused by a bacterial pathogen. Mortality from tuberculosis was estimated at 1.5 million deaths worldwide in 2013. Development of new TB drugs is needed to not only to shorten the medication period but also to treat multi-drug resistant and extensively drug-resistant TB. Mycobacterium tuberculosis (Mtb) grows slowly and only multiplies once or twice per day. Therefore, conventional drug screening takes more than 3 weeks. Additionally, a biosafety level-3 (BSL-3) facility is required. Thus, we developed a new screening method to identify TB drug candidates by utilizing luciferase-expressing recombinant Mycobacterium bovis bacillus Calmette-Guéren (rBCG). Using this method, we identified several candidates in 4 days in a non-BSL-3 facility. We screened 10,080 individual crude extracts derived from Actinomyces and Streptomyces and identified 137 extracts which possessed suppressive activity to the luciferase of rBCG. Among them, 41 compounds inhibited the growth of both Mtb H37Rv and the extensively drug-resistant Mtb (XDR-Mtb) strains. We purified the active substance of the 1904–1 extract, which possessed strong activity toward rBCG, Mtb H37Rv, and XDR-Mtb but was harmless to the host eukaryotic cells. The MIC of this substance was 0.13 μg/ml, 0.5 μg/ml, and 2.0–7.5 μg/ml against rBCG, H37Rv, and 2 XDR-strains, respectively. Its efficacy was specific to acid-fast bacterium except for the Mycobacterium avium intracellular complex. Mass spectrometry and nuclear magnetic resonance analyses revealed that the active substance of 1904–1 was cyclomarin A. To confirm the mode of action of the 1904-1-derived compound, resistant BCG clones were used. Whole genome DNA sequence analysis showed that these clones contained a mutation in the clpc gene which encodes caseinolytic protein, an essential component of an ATP-dependent proteinase, and the likely target of the active substance of 1904–1. Our method provides a

  6. Screening and determination of drugs in human saliva utilizing microextraction by packed sorbent and liquid chromatography-tandem mass spectrometry.

    PubMed

    Abdel-Rehim, Abbi; Abdel-Rehim, Mohamed

    2013-09-01

    This study presents a new method for collecting and handling saliva samples using an automated analytical microsyringe and microextraction by packed syringe (MEPS). The screening and determination of lidocaine in human saliva samples utilizing MEPS and liquid chromatography-tandem mass spectrometry (LC-MS/MS) were carried out. An exact volume of saliva could be collected. The MEPS C8 -cartridge could be used for 50 extractions before it was discarded. The extraction recovery was about 60%. The pharmacokinetic curve of lidocaine in saliva using MEPS-LC-MS/MS is reported.

  7. Drug Utilization Review of Potassium Chloride Injection Formulations Available in a Private Hospital in Kuching, Sarawak, Malaysia

    PubMed Central

    MELISSA, Mohammad Hirman; AZMI, Sarriff

    2013-01-01

    Background: The concentrated potassium chloride injection is a high-alert medication and replacing it with a pre-mixed formulation can reduce the risks associated with its use. The aim of this study was to determine the clinical characteristics of patients receiving different potassium chloride formulations available at a private institution. The study also assessed the effectiveness and safety of pre-mixed formulations in the correction of hypokalaemia. Methods: This was a retrospective observational study consisting of 296 cases using concentrated and pre-mixed potassium chloride injections in 2011 in a private hospital in Kuching, Sarawak, Malaysia. Results: There were 135 (45.6%) cases that received concentrated potassium chloride, and 161 (54.4%) cases that received pre-mixed formulations. The patients’ clinical characteristics that were significantly related to the utilization of the different formulations were diagnosis (P < 0.001), potassium serum blood concentration (P < 0.05), and fluid overload risk (P < 0.05). The difference observed for the cases that achieved or maintained normokalaemia was statistically insignificant (P = 0.172). Infusion-related adverse effects were seen more in pre-mixes compared to concentrated formulations (6.8% versus 2.2%, P < 0.05). Conclusion: This study provides insight into the utilization of potassium chloride injections at this specific institution. The results support current recommendations to use pre-mixed formulations whenever possible. PMID:24043996

  8. Can utilizing a computerized provider order entry (CPOE) system prevent hospital medical errors and adverse drug events?

    PubMed

    Charles, Krista; Cannon, Margaret; Hall, Robert; Coustasse, Alberto

    2014-01-01

    Computerized provider order entry (CPOE) systems allow physicians to prescribe patient services electronically. In hospitals, CPOE essentially eliminates the need for handwritten paper orders and achieves cost savings through increased efficiency. The purpose of this research study was to examine the benefits of and barriers to CPOE adoption in hospitals to determine the effects on medical errors and adverse drug events (ADEs) and examine cost and savings associated with the implementation of this newly mandated technology. This study followed a methodology using the basic principles of a systematic review and referenced 50 sources. CPOE systems in hospitals were found to be capable of reducing medical errors and ADEs, especially when CPOE systems are bundled with clinical decision support systems designed to alert physicians and other healthcare providers of pending lab or medical errors. However, CPOE systems face major barriers associated with adoption in a hospital system, mainly high implementation costs and physicians' resistance to change.

  9. Can Utilizing a Computerized Provider Order Entry (CPOE) System Prevent Hospital Medical Errors and Adverse Drug Events?

    PubMed Central

    Charles, Krista; Cannon, Margaret; Hall, Robert; Coustasse, Alberto

    2014-01-01

    Computerized provider order entry (CPOE) systems allow physicians to prescribe patient services electronically. In hospitals, CPOE essentially eliminates the need for handwritten paper orders and achieves cost savings through increased efficiency. The purpose of this research study was to examine the benefits of and barriers to CPOE adoption in hospitals to determine the effects on medical errors and adverse drug events (ADEs) and examine cost and savings associated with the implementation of this newly mandated technology. This study followed a methodology using the basic principles of a systematic review and referenced 50 sources. CPOE systems in hospitals were found to be capable of reducing medical errors and ADEs, especially when CPOE systems are bundled with clinical decision support systems designed to alert physicians and other healthcare providers of pending lab or medical errors. However, CPOE systems face major barriers associated with adoption in a hospital system, mainly high implementation costs and physicians’ resistance to change. PMID:25593568

  10. The utility of self-emulsifying oil formulation to improve the poor solubility of the anti HIV drug CSIC

    PubMed Central

    2013-01-01

    Background CSIC (5-chloro-3-phenylsulfonylindole-2-carboxamide), a non-nucleoside reverse transcriptase inhibitor (NNRTI) has not been advanced as a therapeutic anti-HIV candidate drug due to its low aqueous solubility and poor bioavailability. Objective The objective of this work was to formulate CSIC into self-emulsifying oil formulations for the purpose of improving its aqueous solubility and evaluating in vitro antiretroviral activity. Methods CSIC self-emulsifying oil formulations (SEFs) were formulated and evaluated for droplet size, zeta potential, polydispersity index (PDI), viscosity, emulsification time, stability and bioactivity. Results Results showed significantly improved solubility of CSIC in the SEFs.The concentration of co-surfactant affected the droplet size, zeta potential and polydispersity index. In vitro bioactivity studies showed that the CSIC SEFs retained full anti-HIV activity. Conclusion The in vitro data from this first attempt to formulate CSIC SEFs suggest that improvement on the aqueous solubility of CSIC through this delivery system may accentuate its antiretroviral effectiveness in vivo via bioavailability enhancement. The formulation is therefore intended as an oral anti-HIV agent for prophylactic and therapeutic uses. PMID:23721408

  11. Drug Interactions

    PubMed Central

    Tong Logan, Angela; Silverman, Andrew

    2012-01-01

    One of the most clinically significant complications related to the use of pharmacotherapy is the potential for drug-drug or drug-disease interactions. The gastrointestinal system plays a large role in the pharmacokinetic profile of most medications, and many medications utilized in gastroenterology have clinically significant drug interactions. This review will discuss the impact of alterations of intestinal pH, interactions mediated by phase I hepatic metabolism enzymes and P-glycoprotein, the impact of liver disease on drug metabolism, and interactions seen with commonly utilized gastrointestinal medications. PMID:22933873

  12. Utilization of bio-degradable fermented tapioca to synthesized low toxicity of carbon nanotubes for drug delivery applications

    NASA Astrophysics Data System (ADS)

    Nurulhuda, I.; Poh, R.; Mazatulikhma, M. Z.; Salman, A. H. A.; Haseeb, A. K.; Rusop, M.

    2016-07-01

    Carbon nanotubes (CNT) have potential biomedical applications, and investigations are shifting towards the production of such nanotubes using renewable natural sources. CNTs were synthesized at various temperatures of 700, 750, 800, 850 and 900 °C, respectively, using a local fermented food known as "tapai ubi" or fermented tapioca as a precursor. The liquid part of this fermented food was heated separately at 80°C and channeled directly into the furnace system that employs the thermal chemical vapor deposition (CVD) method. Ferrocene, which was the catalyst was placed in furnace 1 in the thermal CVD process. The resulting CNTs produced from the process were studied using field emission scanning electron microscopy (FESEM) and raman spectroscopy. The FESEM images showed the growth morphology of the CNTs at the different temperatures employed. It was observed that the higher the synthesis temperature up to a point, the diameter of CNTs produced, after which the diameter increased. CNTs with helical structures were observed at 700 °C with a diameter range of 111 - 143 nm. A more straightened structure was observed at 750 °C with a diameter range of 59 - 121 nm. From 800 °C onwards, the diameters of the CNTs were less than 60 nm. Raman analysis revealed the present of D, G and G' peak were observed at 1227-1358, 1565-1582, and 2678-2695 cm-1, respectively. The highest degree of crystallity of the carbon nanotubes synthesized were obtained at 800 °C. The radial breathing mode (RBM) were in range between 212-220 and 279-292 cm-1. Carbon nanotubes also being functionalized with Polyethylene bis(amine) Mw2000 (PEG 2000-NH2) and showed highly cells viability compared to non-functionalized CNT. The nanotubes synthesized will be applied as drug delivery in future study.

  13. EMERGENCY DEPARTMENT UTILIZATION AMONG A COHORT OF HIV-POSITIVE INJECTING DRUG USERS IN A CANADIAN SETTING

    PubMed Central

    Fairbairn, Nadia; Milloy, M-J; Zhang, Ruth; Lai, Calvin; Grafstein, Eric; Kerr, Thomas; Wood, Evan

    2011-01-01

    Background HIV-positive injection drug users (IDU) are known to be at risk for multiple medical problems that may necessitate emergency department (ED) use, however, the relative contribution of HIV disease versus injection-related complications have not been well described. Objectives We examined factors associated with ED use among a prospective cohort of HIV-positive IDU in a Canadian setting. Methods We enrolled HIV-positive IDU into a community-recruited prospective cohort study. We modeled factors associated with the time to first ED visit using Cox regression to determine factors independently associated with ED use. In sub-analyses, we examined ED diagnoses and subsequent hospital admission rates. Results Between December 5, 2005, and April 30, 2008, 428 HIV-positive IDU were enrolled, among whom the cumulative incidence of ED use was 63.7% (95% Confidence Interval [CI]: 59.1% – 68.3%) at 12 months after enrollment. Factors independently associated with time to first ED visit included: unstable housing (Hazard Ratio [HR] = 1.5, 95% CI: 1.1–2.0) and reporting being unable to obtain needed health care services (HR = 2.2, 95% CI: 1.2–4.1), whereas CD4 count and viral load were non-significant. Skin and soft tissue infections (SSTIs) accounted for the greatest proportion of ED visits (17%). Of the 2461 visits to the ED, 419 (17%) were admitted to hospital. Conclusions High rates of ED use were observed among HIV-positive IDU, a behavior that was predicted by unstable housing and limited access to primary care. Factors other than HIV infection appear to be driving ED use among this population in the post-HAART era. PMID:21719229

  14. Utility of in vitro systems and preclinical data for the prediction of human intestinal first-pass metabolism during drug discovery and preclinical development.

    PubMed

    Karlsson, Fredrik H; Bouchene, Salim; Hilgendorf, Constanze; Dolgos, Hugues; Peters, Sheila Annie

    2013-12-01

    A growing awareness of the risks associated with extensive intestinal metabolism has triggered an interest in developing robust methods for its quantitative assessment. This study explored the utility of intestinal S9 fractions, human liver microsomes, and recombinant cytochromes P450 to quantify CYP3A-mediated intestinal extraction in humans for a selection of marketed drugs that are predominantly metabolized by CYP3A4. A simple competing rates model is used to estimate the fraction of drug escaping gut wall metabolism (fg) from in vitro intrinsic clearance in humans. The fg values extrapolated from the three in vitro systems used in this study, together with literature-derived fg from human intestinal microsomes, were validated against fg extracted from human in vivo pharmacokinetic (PK) profiles using a generic whole-body physiologically-based pharmacokinetic (PBPK) model. The utility of the rat as a model for human CYP3A-mediated intestinal metabolism was also evaluated. Human fg from PBPK compares well with that from the grapefruit juice method, justifying its use for the evaluation of human in vitro systems. Predictive performance of all human in vitro systems was comparable [root mean square error (RMSE) = 0.22-0.27; n = 10]. Rat fg derived from in vivo PK profiles using PBPK has the lowest RMSE (0.19; n = 11) for the prediction of human fg for the selected compounds, most of which have a fraction absorbed close to 1. On the basis of these evaluations, the combined use of fg from human in vitro systems and rats is recommended for the estimation of CYP3A4-mediated intestinal metabolism in lead optimization and preclinical development phases.

  15. Development of a simple system for screening anti-hepatitis C virus drugs utilizing mutants capable of vigorous replication.

    PubMed

    Yu, Lijuan; Aoki, Chie; Shimizu, Yohko; Shimizu, Kazufumi; Hou, Wei; Yagyu, Fumihiro; Wen, Xianzi; Oshima, Masamichi; Iwamoto, Aikichi; Gao, Bin; Liu, Wenjun; Gao, George Fu; Kitamura, Yoshihiro

    2010-11-01

    Replication of infectious hepatitis C virus in Huh7 cells, a human hepatocyte cell line, has become possible due to the unique properties of the JFH1 isolate. Developing reporter virus systems for a simple titration has been attempted by integrating heterologous reporter genes into the JFH1 genome, resulting in a big infectivity reduction that limits the usefulness of such reporter systems. To overcome this problem, JFH1-infected Huh7 cells were cultured continuously for 2 years to obtain Huh7-adapted JFH1 variants capable of yielding up to 1000-fold higher titers. Sequence analysis of variant genome RNA suggested that this adapted population consisted mainly of two variants. By joining the 5'-half of the obtained representative viral complementary DNA (cDNA) fragments of the variants with the 3'-half of the wild-type's, two prototype clones, A/WT and B/WT, were constructed. Replication of A/WT and B/WT viruses in Huh7 cells showed up to 100-1000-fold higher titers than the wild-type. A Renilla luciferase cDNA was inserted into the Nonstructural Protein 5A region of the A/WT and B/WT cDNA to generate A/WT-Rluc and B/WT-Rluc, respectively. Transfection of Huh7 cells with in vitro-transcribed A/WT-Rluc and B/WT-Rluc RNA resulted in production of infectious viruses with approximately 15- and 25-fold higher titers, respectively, than the wild-type RNA. The replication of A/WT-Rluc and B/WT-Rluc viruses was more vigorous than the wild-type even with insertion of the luciferase cDNA showing a good correlation of luciferase activities with infectious titers. Furthermore, interferon-alpha inhibited the replication of A/WT-Rluc and B/WT-Rluc viruses in a dose-dependent manner as determined by a luciferase assay. These results imply that our system is potentially a tool useful for screening anti-hepatitis C virus drugs in a simple and time/cost-saving manner.

  16. Isolation and Physical Property Optimization of an Amorphous Drug Substance Utilizing a High Surface Area Magnesium Aluminometasilicate (Neusilin(®) US2).

    PubMed

    Allgeier, Matthew C; Piper, Jared L; Hinds, Jeremy; Yates, Matthew H; Kolodsick, Kevin J; Meury, Richard; Shaw, Bruce; Kulkarni, Mehuli R; Remick, David M

    2016-10-01

    Control and optimization of the physical properties of a drug substance (DS) are critical to the development of robust drug product manufacturing processes and performance. A lack of isolatable, for example, crystalline, DS solid forms can present challenges to achieving this control. In this study, an isolation scheme for an amorphous DS was developed and integrated into the synthetic route producing DS with optimized properties. An inert absorbent excipient (Neusilin® US2) was used to isolate the DS via a novel antisolvent scheme as the final step of the route. Isolation was executed at kilogram scale utilizing conventional equipment. The resulting 50 wt% DS:Neusilin complex had improved physical stability and exceptional micromeritic and tableting properties. Improved dissolution was observed and attributed to enhanced dispersion and increased surface area. Characterization data suggest a high degree of penetration of the DS into the Neusilin, with DS occupying 70% of mesopore and 12% of macropore volume. This approach has application in the isolation and particle engineering of difficult to isolate DS without additional unit operation, such as spray drying, and has the potential for a high degree of optimization and control of physical properties over the course of DS development. PMID:27492963

  17. Impact of potential pregabalin or duloxetine drug–drug interactions on health care costs and utilization among Medicare members with fibromyalgia

    PubMed Central

    Ellis, Jeffrey J; Sadosky, Alesia B; Ten Eyck, Laura L; Cappelleri, Joseph C; Brown, Courtney R; Suehs, Brandon T; Parsons, Bruce

    2014-01-01

    Purpose To examine the impact of newly initiated pregabalin or duloxetine treatment on fibromyalgia (FM) patients’ encounters with potential drug–drug interactions (DDIs), the health care cost and utilization consequences of those interactions, and the impact of treatment on opioid utilization. Patients and methods Subjects included those with an FM diagnosis, a pregabalin or duloxetine prescription claim (index event), ≥1 inpatient or ≥2 outpatient medical claims, and ≥12 months preindex and ≥6 postindex enrollment. Propensity score matching was used to help balance the pregabalin and duloxetine cohorts on baseline demographics and comorbidities. Potential DDIs were defined based on Micromedex 2.0 software and were identified by prescription claims. Results No significant differences in baseline characteristics were found between matched pregabalin (n=794) and duloxetine cohorts (n=794). Potential DDI prevalence was significantly greater (P<0.0001) among duloxetine subjects (71.9%) than among pregabalin subjects (4.0%). There were no significant differences in all-cause health care utilization or costs between pregabalin subjects with and without a potential DDI. By contrast, duloxetine subjects with a potential DDI had higher mean all-cause costs ($9,373 versus $7,228; P<0.0001) and higher mean number of outpatient visits/member (16.0 versus 13.0; P=0.0009) in comparison to duloxetine subjects without a potential DDI. There was a trend toward a statistically significant difference between pregabalin and duloxetine subjects in their respective pre- versus post-differences in use of ≥1 long-acting opioids (1.6% and 3.4%, respectively; P=0.077). Conclusion The significantly higher prevalence of potential DDIs and potential cost impact found in FM duloxetine subjects, relative to pregabalin subjects, underscore the importance of considering DDIs when selecting a treatment. PMID:25339847

  18. Medication Use and Medical Comorbidity in Patients with Chronic Hepatitis C from a U.S. Commercial Claims Database: High Utilization of Drugs with Interaction Potential

    PubMed Central

    Lauffenburger, Julie C.; Mayer, Christina L.; Hawke, Roy L.; Brouwer, Kim L. R.; Fried, Michael W.; Farley, Joel F.

    2014-01-01

    Background With the advent of the direct-acting antiviral agents (DAAs), significant drug-drug interaction (DDI) potential now exists for patients treated for chronic hepatitis C virus (HCV) infection. However, little is known about how often patients with HCV use medications that may interact with newer HCV treatments, especially those with CYP3A DDI potential. Methods Using a large United States commercial insurance database, medication use and comorbidity burden was examined among adult patients with a chronic HCV diagnosis from 2006-2010. Medications were examined by total number of prescription claims, proportion of patients exposed, and DDI potential with prototypical CYP3A DAAs, boceprevir and telaprevir, for which data were available. Results Patient comorbidity burden was high and increased over the study period. Medication use was investigated in 53,461 patients with chronic HCV. Twenty-one (53%) of the top 40 most utilized medications were classified as having interaction potential, with 62% of patients received at least one of the top 22 interacting medications by exposure. Of these, 59% and 41% were listed in a common DDI resource but not in medication prescribing information, 77% and 77% had not been investigated in DDI studies, 32% and 27% did not have clear recommendations for DDI management, and only 14% and 23% carried a recommendation to avoid coadministration for boceprevir and telaprevir, respectively. Conclusion Practitioners may expect a medication with CYP3A DDI potential in two-thirds of patients with HCV and almost one-half of the most frequently used medications. However, DDI potential may not be reflected in prescribing information. PMID:25014625

  19. Epidemiology of contact allergy: an estimation of morbidity employing the clinical epidemiology and drug-utilization research (CE-DUR) approach.

    PubMed

    Schnuch, A; Uter, W; Geier, J; Gefeller, O

    2002-07-01

    Clinical epidemiology (CE) is considered unable to estimate morbidity concerning either contact sensitization (CS) or allergic contact dermatitis (ACD) at the population level. Drug-utilization research (DUR) methods estimate the morbidity of suitable diseases based on prescription data for disease-specific drugs. Our objective was to estimate population figures for incidence and prevalence of ACD and CS based on sales data for patch test material in Germany and on patient data from the Information Network of Departments of Dermatology (IVDK). Approximately 600000 standard series are sold per year in Germany, according to the 2 main manufacturers. This raw sales figure was corrected for certain effects (discarded preparations, proportion of formerly patch-tested patients, proportion of patients with ACD seeking medical advice) to obtain an estimate of the denominator of patients eligible for patch testing annually, and combined with patch test results from the Information Network of Departments of Dermatology (IVDK). In 17.8% (of 9266 IVDK patients) ACD was established. Extrapolated to the general population, an incidence of ACD of between 1.7 and 7 per 1000 per year was estimated, depending on whether conservative or more liberal assumptions concerning the above effects were made. Of 78067 IVDK patients tested between 1992 and 2000, 46.8% had at least 1 positive reaction (+ to + + +), and 22.7% had at least 1 stronger positive reaction (+ + or + + +). The 9-year prevalence of CS was estimated to lie between 4.0% and 16.6% for the first outcome, and between 2.0% and 8.1% for the second. Concerning single allergens, 1.9-4.5 million individuals are probably sensitized to nickel, and 1.4-3.4 million to fragrance mix among the German population of 82 million inhabitants. The morbidity data found in this study are in good accordance with data from population-based epidemiological studies. In comparison to these, the CE-DUR approach seems to be an economically feasible

  20. Pathways of colicin import: utilization of BtuB, OmpF porin and the TolC drug-export protein.

    PubMed

    Zakharov, Stanislav D; Sharma, Onkar; Zhalnina, Mariya; Yamashita, Eiki; Cramer, William A

    2012-12-01

    Pathway I. Group A nuclease colicins parasitize and bind tightly (Kd ≤ 10(-9) M) to the vitamin B12 receptor on which they diffuse laterally in the OM (outer membrane) and use their long (≥100 Å; 1 Å=0.1 nm) receptor-binding domain as a 'fishing pole' to locate the OmpF porin channel for translocation. Crystal structures of OmpF imply that a disordered N-terminal segment of the colicin T-domain initiates insertion. Pathway II. Colicin N does not possess a 'fishing pole' receptor-binding domain. Instead, it uses OmpF as the Omp (outer membrane protein) for reception and translocation, processes in which LPS (lipopolysaccharide) may also serve. Keio collection experiments defined the LPS core that is used. Pathway III. Colicin E1 utilizes the drug-export protein TolC for import. CD spectra and thermal-melting analysis predict: (i) N-terminal translocation (T) and central receptor (BtuB) -binding (R) domains are predominantly α-helical; and (ii) helical coiled-coil conformation of the R-domain is similar to that of colicins E3 and Ia. Recombinant colicin peptides spanning the N-terminal translocation domain defined TolC-binding site(s). The N-terminal 40-residue segment lacks the ordered secondary structure. Peptide 41-190 is helical (78%), co-elutes with TolC and occluded TolC channels. Driven by a trans-negative potential, peptides 82-140 and 141-190 occluded TolC channels. The use of TolC for colicin E1 import implies that the interaction of this colicin with the other Tol proteins does not occur in the periplasmic space, but rather through Tol domains in the cytoplasmic membrane, thus explaining colicin E1 cytotoxicity towards a strain in which a 234 residue periplasmic TolA segment is deleted.

  1. Utilization of human nuclear receptors as an early counter screen for off-target activity: a case study with a compendium of 615 known drugs.

    PubMed

    Fan, Fan; Hu, Rong; Munzli, Anke; Chen, Yuan; Dunn, Robert T; Weikl, Kerstin; Strauch, Simone; Schwandner, Ralf; Afshari, Cynthia A; Hamadeh, Hisham; Nioi, Paul

    2015-06-01

    Off-target effects of drugs on nuclear hormone receptors (NHRs) may result in adverse effects in multiple organs/physiological processes. Reliable assessments of the NHR activities for drug candidates are therefore crucial for drug development. However, the highly permissive structures of NHRs for vastly different ligands make it challenging to predict interactions by examining the chemical structures of the ligands. Here, we report a detailed investigation on the agonistic and antagonistic activities of 615 known drugs or drug candidates against a panel of 6 NHRs: androgen, progesterone, estrogen α/β, and thyroid hormone α/β receptors. Our study revealed that 4.7 and 12.4% compounds have agonistic and antagonistic activities, respectively, against this panel of NHRs. Nonetheless, potent, unintended NHR hits are relatively rare among the known drugs, indicating that such interactions are perhaps not tolerated during drug development. However, we uncovered examples of compounds that unintentionally agonize or antagonize NHRs. In addition, a number of compounds showed multi-NHR activities, suggesting that the cross-talk between multiple NHRs co-operate to elicit in vivo effects. These data highlight the merits of counter screening drug candidate against NHRs during drug discovery/development.

  2. Boston Collaborative Drug Surveillance Program

    Cancer.gov

    The Boston Collaborative Drug Surveillance Program started in 1966 and conducted epidemiologic research to quantify the potential adverse effects of prescription drugs, utilizing in-hospital monitoring.

  3. Acceptability of Rapid Point-of-Care Hepatitis C Tests Among People Who Inject Drugs and Utilize Syringe-Exchange Programs.

    PubMed

    Barocas, Joshua A; Linas, Benjamin P; Kim, Arthur Y; Fangman, John; Westergaard, Ryan P

    2016-03-01

    People who inject drugs may benefit from point-of-care hepatitis C virus (HCV) testing offered at syringe exchanges. We sought to understand whether this population would be willing to undergo rapid HCV testing. We found that there was broad support for rapid HCV testing, especially among younger people who inject drugs with high perceived risk. PMID:27191007

  4. Acceptability of Rapid Point-of-Care Hepatitis C Tests Among People Who Inject Drugs and Utilize Syringe-Exchange Programs

    PubMed Central

    Barocas, Joshua A.; Linas, Benjamin P.; Kim, Arthur Y.; Fangman, John; Westergaard, Ryan P.

    2016-01-01

    People who inject drugs may benefit from point-of-care hepatitis C virus (HCV) testing offered at syringe exchanges. We sought to understand whether this population would be willing to undergo rapid HCV testing. We found that there was broad support for rapid HCV testing, especially among younger people who inject drugs with high perceived risk. PMID:27191007

  5. [Drug dependence and psychotropic drugs].

    PubMed

    Giraud, M J; Lemonnier, E; Bigot, T

    1994-11-01

    Although the utility of psychotropic drugs has been well demonstrated, caution must still be exercised in their use. Among their potential risks, drug dependency must be kept in mind. This risk is well accepted with regard to benzodiazepines, and it appeared useful to study the potential risk for antidepressants, neuroleptics and thymoregulatory agents. Whatever the drug, the predominant factor appears to be psychological dependency. Prevention of drug dependency is most often achieved by informing the patient, limiting the length of use of the drug, making regular reevaluation of symptoms and of drug indication, and frequently be establishing a "treatment contract". The importance of the patient-physician relationship in the prescription of such treatment must be underlined. PMID:7984941

  6. Health Plans and Drug Companies Dip Their Toes Into Value-Based Pricing: The Pressure Is on P&T Committees to Monitor Utilization.

    PubMed

    Barlas, Stephen

    2016-01-01

    The agreement between Harvard Pilgrim and Amgen on a "pay for performance" deal involving evolocumab could encourage other manufacturers, health plans, and policy-makers to press for value-based pricing as drug costs continue to escalate. PMID:26766890

  7. A new high-throughput method utilizing porous silica-based nano-composites for the determination of partition coefficients of drug candidates.

    PubMed

    Yu, Chih H; Tam, Kin; Tsang, Shik C

    2011-09-01

    We show that highly porous silica-based nanoparticles prepared via micro-emulsion and sol-gel techniques are stable colloids in aqueous solution. By incorporating a magnetic core into the porous silica nano-composite, it is found that the material can be rapidly separated (precipitated) upon exposure to an external magnetic field. Alternatively, the porous silica nanoparticles without magnetic cores can be equally separated from solution by applying a high-speed centrifugation. Using these silica-based nanostructures a new high-throughput method for the determination of partition coefficient for water/n-octanol is hereby described. First, a tiny quantity of n-octanol phase is pre-absorbed in the porous silica nano-composite colloids, which allows an establishment of interface at nano-scale between the adsorbed n-octanol with the bulk aqueous phase. Organic compounds added to the mixture can therefore undergo a rapid partition between the two phases. The concentration of drug compound in the supernatant in a small vial can be determined by UV-visible absorption spectroscopy. With the adaptation of a robotic liquid handler, a high-throughput technology for the determination of partition coefficients of drug candidates can be employed for drug screening in the industry based on these nano-separation skills. The experimental results clearly suggest that this new method can provide partition coefficient values of potential drug candidates comparable to the conventional shake-flask method but requires much shorter analytical time and lesser quantity of chemicals.

  8. A new high-throughput method utilizing porous silica-based nano-composites for the determination of partition coefficients of drug candidates.

    PubMed

    Yu, Chih H; Tam, Kin; Tsang, Shik C

    2011-09-01

    We show that highly porous silica-based nanoparticles prepared via micro-emulsion and sol-gel techniques are stable colloids in aqueous solution. By incorporating a magnetic core into the porous silica nano-composite, it is found that the material can be rapidly separated (precipitated) upon exposure to an external magnetic field. Alternatively, the porous silica nanoparticles without magnetic cores can be equally separated from solution by applying a high-speed centrifugation. Using these silica-based nanostructures a new high-throughput method for the determination of partition coefficient for water/n-octanol is hereby described. First, a tiny quantity of n-octanol phase is pre-absorbed in the porous silica nano-composite colloids, which allows an establishment of interface at nano-scale between the adsorbed n-octanol with the bulk aqueous phase. Organic compounds added to the mixture can therefore undergo a rapid partition between the two phases. The concentration of drug compound in the supernatant in a small vial can be determined by UV-visible absorption spectroscopy. With the adaptation of a robotic liquid handler, a high-throughput technology for the determination of partition coefficients of drug candidates can be employed for drug screening in the industry based on these nano-separation skills. The experimental results clearly suggest that this new method can provide partition coefficient values of potential drug candidates comparable to the conventional shake-flask method but requires much shorter analytical time and lesser quantity of chemicals. PMID:21780284

  9. The Methylene Alkoxy Carbamate Self-Immolative Unit: Utilization for the Targeted Delivery of Alcohol-Containing Payloads with Antibody-Drug Conjugates.

    PubMed

    Kolakowski, Robert V; Haelsig, Karl T; Emmerton, Kim K; Leiske, Chris I; Miyamoto, Jamie B; Cochran, Julia H; Lyon, Robert P; Senter, Peter D; Jeffrey, Scott C

    2016-07-01

    A strategy for the conjugation of alcohol-containing payloads to antibodies has been developed and involves the methylene alkoxy carbamate (MAC) self-immolative unit. A series of MAC β-glucuronide model constructs were prepared to evaluate stability and enzymatic release, and the results demonstrated high stability at physiological pH in a substitution-dependent manner. All the MAC model compounds efficiently released alcohol drug surrogates under the action of β-glucuronidase. To assess the MAC technology for ADCs, the potent microtubule-disrupting agent auristatin E (AE) was incorporated through the norephedrine alcohol. Conjugation of the MAC β-glucuronide AE drug linker to the anti-CD30 antibody cAC10, and an IgG control antibody, gave potent and immunologically specific activities in vitro and in vivo. These studies validate the MAC self-immolative unit for alcohol-containing payloads within ADCs, a class that has not been widely exploited. PMID:27198854

  10. A concise review of the bioanalytical methods for the quantitation of sitagliptin, an important dipeptidyl peptidase-4 (DPP4) inhibitor, utilized for the characterization of the drug.

    PubMed

    Suresh, P S; Srinivas, Nuggehally R; Mullangi, Ramesh

    2016-05-01

    Inhibition of dipeptidyl peptidase-4 (DPP4) is an emerging therapeutic approach for treating type 2 diabetes and has revolutionized the concept of diabetes management. Sitagliptin is the first approved orally active, potent, selective and nonpeptidomimetic DPP4 inhibitor. Incidence of hypoglycemia and weight gain is negligible with sitagliptin treatment. It is used as monotherapy or in combination with other anti-diabetic drugs to treat type 2 diabetes. There are numerous bioanalytical methods published for the analysis of sitagliptin in preclinical and clinical samples. This review focuses on the various HPLC and LC-MS/MS methods that have been used to analyze sitagliptin in various biological matrices. A small section is devoted to the bioanalysis of other DPP4 inhibitors such as vildagliptin, saxagliptin and linagliptin. This review provides key information in a concise manner regarding sample processing options, chromatographic/detection conditions and validation parameters of the chosen methods for sitagliptin and other DPP4 inhibitors. PMID:26873580

  11. Labview utilities

    2011-09-30

    The software package provides several utilities written in LabView. These utilities don't form independent programs, but rather can be used as a library or controls in other labview programs. The utilities include several new controls (xcontrols), VIs for input and output routines, as well as other 'helper'-functions not provided in the standard LabView environment.

  12. Utilization of an automated pipetting system in the cell line-based screening of the activity of a DNA-damaging anti-tumour drug.

    PubMed

    Suchánková, T; Ovesná, P; Samadder, P; Souček, K

    2014-01-01

    The principles of large screening strategies, which are developed by industrial companies, have been recently adopted by researchers in the fields of molecular biology and oncology as invaluable tools for translational medicine. The declining costs of laboratory robotic machines have allowed high-throughput screening to become more available to academic centres with limited resources. Here, we describe how a robotic conventional liquid handling system could be used on a daily basis in laboratories to obtain consistent and reproducible results. Our approach allowed us to quickly screen a panel of more than 20 tumorigenic and non-tumorigenic cell lines for their responses to hydroxyurea, which is a DNA-damaging anticancer therapeutic drug. The format of 384-well microplates was used for manual cell seeding, and the effect of hydroxyurea was screened at multiple concentrations. The fluorescence-based CyQuant assay was employed as the readout method to analyse the cellular DNA content. The effectiveness of our approach was demonstrated in the experimental results.

  13. Investigation of utility of cerebrospinal fluid drug concentration as a surrogate for interstitial fluid concentration using microdialysis coupled with cisternal cerebrospinal fluid sampling in wild-type and Mdr1a(-/-) rats.

    PubMed

    Nagaya, Yoko; Nozaki, Yoshitane; Takenaka, Osamu; Watari, Ryuji; Kusano, Kazutomi; Yoshimura, Tsutomu; Kusuhara, Hiroyuki

    2016-02-01

    In drug discovery, the cerebrospinal fluid (CSF) drug concentration (CCSF) has been used as a surrogate for the interstitial fluid (ISF) concentration (CISF). However, the CCSF-to-CISF gradient suggested for P-glycoprotein (P-gp) substrates in rodents causes uncertainty in CISF estimations and subsequent pharmacokinetic-pharmacodynamic analyses. To evaluate the utility of CCSF as a surrogate for CISF, this study directly compared the CCSF with the CISF of 12 compounds, including P-gp substrates, under steady-state conditions in wild-type and Mdr1a(-/-) rats using microdialysis coupled with cisternal CSF sampling. In wild-type rats, the ISF-to-unbound plasma (Kp,uu,ISF) and CSF-to-unbound plasma (Kp,uu,CSF) concentration ratios of the P-gp substrates, except for metoclopramide, were lower than those of the non-P-gp substrates, and the Kp,uu,CSF values were within or close to 3-fold of the Kp,uu,ISF values for all the compounds examined. The Kp,uu,CSF values of the selected P-gp substrates increased in Mdr1a(-/-) rats with a similar magnitude to the Kp,uu,ISF values, resulting in the Kp,uu,CSF-to-Kp,uu,ISF ratios being unchanged. These results suggested that P-gp-mediated active efflux at the blood-brain barrier is a major determinant not only for CISF, but also for CCSF, and that CCSF can be used as a surrogate for CISF even for P-gp substrates in rats.

  14. Food-Drug Interactions

    PubMed Central

    Bushra, Rabia; Aslam, Nousheen; Khan, Arshad Yar

    2011-01-01

    The effect of drug on a person may be different than expected because that drug interacts with another drug the person is taking (drug-drug interaction), food, beverages, dietary supplements the person is consuming (drug-nutrient/food interaction) or another disease the person has (drug-disease interaction). A drug interaction is a situation in which a substance affects the activity of a drug, i.e. the effects are increased or decreased, or they produce a new effect that neither produces on its own. These interactions may occur out of accidental misuse or due to lack of knowledge about the active ingredients involved in the relevant substances. Regarding food-drug interactions physicians and pharmacists recognize that some foods and drugs, when taken simultaneously, can alter the body's ability to utilize a particular food or drug, or cause serious side effects. Clinically significant drug interactions, which pose potential harm to the patient, may result from changes in pharmaceutical, pharmacokinetic, or pharmacodynamic properties. Some may be taken advantage of, to the benefit of patients, but more commonly drug interactions result in adverse drug events. Therefore it is advisable for patients to follow the physician and doctors instructions to obtain maximum benefits with least food-drug interactions. The literature survey was conducted by extracting data from different review and original articles on general or specific drug interactions with food. This review gives information about various interactions between different foods and drugs and will help physicians and pharmacists prescribe drugs cautiously with only suitable food supplement to get maximum benefit for the patient. PMID:22043389

  15. Club Drugs

    MedlinePlus

    ... Rohypnol, ketamine, as well as MDMA (ecstasy) and methamphetamine ( Drug Facts: Club Drugs , National Institute on Drug ... Club Drugs , National Institute on Drug Abuse, 2010). Methamphetamine is a powerfully addictive stimulant associated with serious ...

  16. Lighting Utilization.

    ERIC Educational Resources Information Center

    Crank, Ron

    This instructional unit is one of 10 developed by students on various energy-related areas that deals specifically with lighting utilization. Its objective is for the student to be able to outline the development of lighting use and conservation and identify major types and operating characteristics of lamps used in electric lighting. Some topics…

  17. Club Drugs. The DAWN Report.

    ERIC Educational Resources Information Center

    Substance Abuse and Mental Health Services Administration (DHHS/PHS), Rockville, MD. Office of Applied Studies.

    This report was prepared in response to requests from the media, law enforcement, and community leaders for information about club drugs. By being able to utilize statistics from hospital emergency departments and by compiling statistics on drug-related deaths, the Drug Abuse Warning Network (DAWN) is able to alert parents, educators, and others…

  18. Drug allergies

    MedlinePlus

    Allergic reaction - drug (medication); Drug hypersensitivity; Medication hypersensitivity ... A drug allergy involves an immune response in the body that produces an allergic reaction to a medicine. The ...

  19. 78 FR 31943 - Draft Guidance for Industry on Contract Manufacturing Arrangements for Drugs: Quality Agreements...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-05-28

    ... Arrangements for Drugs: Quality Agreements; Availability AGENCY: Food and Drug Administration, HHS. ACTION... guidance for industry entitled ``Contract Manufacturing Arrangements for Drugs: Quality Agreements.'' This... drugs can utilize Quality Agreements to delineate their responsibilities and assure drug quality,...

  20. Drug Safety

    MedlinePlus

    ... over-the-counter drug. The FDA evaluates the safety of a drug by looking at Side effects ... clinical trials The FDA also monitors a drug's safety after approval. For you, drug safety means buying ...

  1. Drug-drug interactions between clopidogrel and novel cardiovascular drugs.

    PubMed

    Pelliccia, Francesco; Rollini, Fabiana; Marazzi, Giuseppe; Greco, Cesare; Gaudio, Carlo; Angiolillo, Dominick J

    2015-10-15

    The combination of aspirin and the thienopyridine clopidogrel is a cornerstone in the prevention of atherothrombotic events. These two agents act in concert to ameliorate the prothrombotic processes stimulated by plaque rupture and vessel injury complicating cardiovascular disease. Guidelines recommend the use of clopidogrel in patients with acute coronary syndromes and in those undergoing percutaneous coronary intervention, and the drug remains the most utilized P2Y12 receptor inhibitor despite the fact that newer antiplatelet agents are now available. In recent years, numerous studies have shown inconsistency in the efficacy of clopidogrel to prevent atherothrombotic events. Studies of platelet function testing have shown variability in the response to clopidogrel. One of the major reason for this phenomenon lies in the interaction between clopidogrel and other drugs that may affect clopidogrel absorption, metabolism, and ultimately its antiplatelet action. Importantly, these drug-drug interactions have prognostic implications, since patients with high on-treatment platelet reactivity associated with reduced clopidogrel metabolism have an increased risk of ischemia. Previous systematic reviews have focused on drug-drug interactions between clopidogrel and specific pharmacologic classes, such as proton pump inhibitors, calcium channel blockers, and statins. However, more recent pieces of scientific evidence show that clopidogrel may also interact with newer drugs that are now available for the treatment of cardiovascular patients. Accordingly, the aim of this review is to highlight and discuss recent data on drug-drug interactions between clopidogrel and third-generation proton pump inhibitors, pantoprazole and lansoprazole, statins, pitavastatin, and antianginal drug, ranolazine. PMID:26341013

  2. 42 CFR 456.714 - DUR/surveillance and utilization review relationship.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL ASSISTANCE PROGRAMS UTILIZATION CONTROL Drug Use Review (DUR) Program and Electronic Claims Management System for Outpatient Drug Claims § 456.714...

  3. Pharmacogenetic testing: current evidence of clinical utility

    PubMed Central

    Haga, Susanne B.

    2013-01-01

    Over the last decade, the number of clinical pharmacogenetic tests has steadily increased as understanding of the role of genes in drug response has grown. However, uptake of these tests has been slow, due in large part to the lack of robust evidence demonstrating clinical utility. We review the evidence behind four pharmacogenetic tests and discuss the barriers and facilitators to uptake: (1) warfarin (drug safety and efficacy); (2) clopidogrel (drug efficacy); (3) codeine (drug safety and efficacy); and (4) abacavir (drug safety). Future efforts should be directed toward addressing these issues and considering additional approaches to generating evidence basis to support clinical use of pharmacogenetic tests. PMID:24020014

  4. Drug Resistance

    MedlinePlus

    HIV Treatment Drug Resistance (Last updated 3/1/2016; last reviewed 3/1/2016) Key Points As HIV multiplies in the ... the risk of drug resistance. What is HIV drug resistance? Once a person becomes infected with HIV, ...

  5. Drug Abuse

    MedlinePlus

    ... as drugged driving, violence, stress, and child abuse. Drug abuse can lead to homelessness, crime, and missed work or problems with keeping a job. It harms unborn babies and destroys families. There are different types of treatment for drug abuse. But the best is to prevent drug ...

  6. Controlled drugs.

    PubMed

    2016-05-18

    Essential facts Controlled drugs are defined and governed by the Misuse of Drugs Act 1971 and associated regulations. Examples of controlled drugs include morphine, pethidine and methadone. Since 2012, appropriately qualified nurses and midwives can prescribe controlled drugs for medical conditions within their competence. There are some exceptions when treating addiction. PMID:27191427

  7. Nanosize drug delivery system.

    PubMed

    Mukherjee, Biswajit

    2013-01-01

    Nanosize materials provide hopes, speculations and chances for an unprecedented change in drug delivery in near future. Nanotechnology is an emerging field to produce nanomaterials for drug delivery that can offer a new tool, opportunities and scope to provide more focused and fine-tuned treatment of diseases at a molecular level, enhancing the therapeutic potential of drugs so that they become less toxic and more effective. Nanodimensional drug delivery systems are of great scientific interest as they project their tremendous utility because of their capability of altering biodistribution of therapeutic agents so that they can concentrate more in the target tissues. Nanosize drug delivery systems generally focus on formulating bioactive molecules in biocompatible nanosystems such as nanocrystals, solid lipid nanoparticles, nanostructure lipid carriers, lipid drug conjugates, nanoliposomes, dendrimers, nanoshells, emulsions, nanotubes, quantum dots etc. Extensively versatile molecules like synthetic chemicals to naturally occurring complex macromolecules such as nucleic acids and proteins could be dispensed in such formulations maintaining their stability and efficacy. Empty viral capsids are being tried to deliver drug as these uniformly sized bionanomaterials can be utilized to load drug to improve solubility, reduce toxicity and provide site specific targeting. Nanomedicines offer a wide scope for delivery of smart materials from tissue engineering to more recently artificial RBCs. Nanocomposites are the future hope for tailored and personalized medicines as well as for bone repairing and rectification of cartilage impairment. Nanosize drug delivery systems are addressing the challenges to overcome the delivery problems of wide ranges of drugs through their narrow submicron particle size range, easily manipulatable surface characteristics in achievement of versatile tissue targeting (includes active and passive drug targeting), controlled and sustained drug

  8. Pharmacy utilization and the Medicare Modernization Act.

    PubMed

    Maio, Vittorio; Pizzi, Laura; Roumm, Adam R; Clarke, Janice; Goldfarb, Neil I; Nash, David B; Chess, David

    2005-01-01

    To control expenditures and use medications appropriately, the Medicare drug coverage program has established pharmacy utilization management (PUM) measures. This article assesses the effects of these strategies on the care of seniors. The literature suggests that although caps on drug benefits lower pharmaceutical costs, they may also increase the use of other health care services and hurt health outcomes. Our review raises concerns regarding the potential unintended effects of the Medicare drug program's PUM policies for beneficiaries. Therefore, the economic and clinical impact of PUM measures on seniors should be studied further to help policymakers design better drug benefit plans. PMID:15787955

  9. 42 CFR 456.705 - Prospective drug review.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... (CONTINUED) MEDICAL ASSISTANCE PROGRAMS UTILIZATION CONTROL Drug Use Review (DUR) Program and Electronic... potential for, or the occurrence of— (i) An undesirable alteration of the therapeutic effect of a given drug... adverse effect of the drug on the patient's disease condition. (3) Adverse drug-drug interaction, that...

  10. 42 CFR 456.705 - Prospective drug review.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... (CONTINUED) MEDICAL ASSISTANCE PROGRAMS UTILIZATION CONTROL Drug Use Review (DUR) Program and Electronic... potential for, or the occurrence of— (i) An undesirable alteration of the therapeutic effect of a given drug... adverse effect of the drug on the patient's disease condition. (3) Adverse drug-drug interaction, that...

  11. 42 CFR 456.705 - Prospective drug review.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... (CONTINUED) MEDICAL ASSISTANCE PROGRAMS UTILIZATION CONTROL Drug Use Review (DUR) Program and Electronic... potential for, or the occurrence of— (i) An undesirable alteration of the therapeutic effect of a given drug... adverse effect of the drug on the patient's disease condition. (3) Adverse drug-drug interaction, that...

  12. 42 CFR 456.705 - Prospective drug review.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... (CONTINUED) MEDICAL ASSISTANCE PROGRAMS UTILIZATION CONTROL Drug Use Review (DUR) Program and Electronic... potential for, or the occurrence of— (i) An undesirable alteration of the therapeutic effect of a given drug... adverse effect of the drug on the patient's disease condition. (3) Adverse drug-drug interaction, that...

  13. Automated Drug Identification for Urban Hospitals

    NASA Technical Reports Server (NTRS)

    Shirley, Donna L.

    1971-01-01

    Many urban hospitals are becoming overloaded with drug abuse cases requiring chemical analysis for identification of drugs. In this paper, the requirements for chemical analysis of body fluids for drugs are determined and a system model for automated drug analysis is selected. The system as modeled, would perform chemical preparation of samples, gas-liquid chromatographic separation of drugs in the chemically prepared samples, infrared spectrophotometric analysis of the drugs, and would utilize automatic data processing and control for drug identification. Requirements of cost, maintainability, reliability, flexibility, and operability are considered.

  14. Drug Debacle.

    PubMed

    Sorrel, Amy Lynn

    2016-01-01

    Medicaid's Vendor Drug Program is under examination by the Texas Legislature. TMA's Physicians Medicaid Congress is seizing the opportunity to call for an administrative overhaul of a drug benefit physicians describe as unnecessarily complicated and confusing. PMID:27441421

  15. Drug Debacle.

    PubMed

    Sorrel, Amy Lynn

    2016-07-01

    Medicaid's Vendor Drug Program is under examination by the Texas Legislature. TMA's Physicians Medicaid Congress is seizing the opportunity to call for an administrative overhaul of a drug benefit physicians describe as unnecessarily complicated and confusing.

  16. Drugged Driving

    MedlinePlus

    ... Infographics » Drugged Driving Drugged Driving Email Facebook Twitter Text Description of Infographic Top Right Figure : In 2009, ... crash than those who don't smoke. Bottom Text: Develop Social Strategies Offer to be a designated ...

  17. Drug Control

    ERIC Educational Resources Information Center

    Leviton, Harvey S.

    1975-01-01

    This article attempts to assemble pertinent information about the drug problem, particularily marihuana. It also focuses on the need for an educational program for drug control with the public schools as the main arena. (Author/HMV)

  18. Generic Drugs

    MedlinePlus

    ... drugs. There are a few other differences— like color, shape, size, or taste—but they do not ... different . Brand-name drugs are often advertised by color and shape. Remember the ads for the “purple ...

  19. [Drug therapy and the most common drugs for childhood psychiatric disorders].

    PubMed

    Puustjärvi, Anita; Raunio, Hannu; Lecklin, Anne; Kumpulainen, Kirsti

    2016-01-01

    Psychotropic drugs are more commonly prescribed for children, although scientific evidence about psychotrophic medication and long-term effects thereof in children is scarce. The drugs are often used off-label. ADHD drugs, antipsychotics and antidepressants and melatonin are the most commonly used drugs. ADHD medication possesses the most established status. Antipsychotic drugs are utilized for the treatment of psychoses, bipolar disorder, and conduct disorder symptoms in particular. Antidepressants are utilized for the treatment of childhood depression and anxiety disorders, melatonin for the treatment of children's sleep problems. Drug therapy should always be carried out as part of other psychiatric therapy. PMID:27382830

  20. Innovative Recruitment Using Online Networks: Lessons Learned From an Online Study of Alcohol and Other Drug Use Utilizing a Web-Based, Respondent-Driven Sampling (webRDS) Strategy

    PubMed Central

    Bauermeister, José A.; Zimmerman, Marc A.; Johns, Michelle M.; Glowacki, Pietreck; Stoddard, Sarah; Volz, Erik

    2012-01-01

    Objective: We used a web version of Respondent-Driven Sampling (webRDS) to recruit a sample of young adults (ages 18–24) and examined whether this strategy would result in alcohol and other drug (AOD) prevalence estimates comparable to national estimates (National Survey on Drug Use and Health [NSDUH]). Method: We recruited 22 initial participants (seeds) via Facebook to complete a web survey examining AOD risk correlates. Sequential, incentivized recruitment continued until our desired sample size was achieved. After correcting for webRDS clustering effects, we contrasted our AOD prevalence estimates (past 30 days) to NSDUH estimates by comparing the 95% confidence intervals of prevalence estimates. Results: We found comparable AOD prevalence estimates between our sample and NSDUH for the past 30 days for alcohol, marijuana, cocaine, Ecstasy (3,4-methylenedioxymethamphetamine, or MDMA), and hallucinogens. Cigarette use was lower than NSDUH estimates. Conclusions: WebRDS may be a suitable strategy to recruit young adults online. We discuss the unique strengths and challenges that may be encountered by public health researchers using webRDS methods. PMID:22846248

  1. Spirocyclic sulfamides as β-secretase 1 (BACE-1) inhibitors for the treatment of Alzheimer's disease: utilization of structure based drug design, WaterMap, and CNS penetration studies to identify centrally efficacious inhibitors.

    PubMed

    Brodney, Michael A; Barreiro, Gabriela; Ogilvie, Kevin; Hajos-Korcsok, Eva; Murray, John; Vajdos, Felix; Ambroise, Claude; Christoffersen, Curt; Fisher, Katherine; Lanyon, Lorraine; Liu, Jianhua; Nolan, Charles E; Withka, Jane M; Borzilleri, Kris A; Efremov, Ivan; Oborski, Christine E; Varghese, Alison; O'Neill, Brian T

    2012-11-01

    β-Secretase 1 (BACE-1) is an attractive therapeutic target for the treatment and prevention of Alzheimer's disease (AD). Herein, we describe the discovery of a novel class of BACE-1 inhibitors represented by sulfamide 14g, using a medicinal chemistry strategy to optimize central nervous system (CNS) penetration by minimizing hydrogen bond donors (HBDs) and reducing P-glycoprotein (P-gp) mediated efflux. We have also taken advantage of the combination of structure based drug design (SBDD) to guide the optimization of the sulfamide analogues and the in silico tool WaterMap to explain the observed SAR. Compound 14g is a potent inhibitor of BACE-1 with excellent permeability and a moderate P-gp liability. Administration of 14g to mice produced a significant, dose-dependent reduction in central Aβ(X-40) levels at a free drug exposure equivalent to the whole cell IC(50) (100 nM). Furthermore, studies of the P-gp knockout mouse provided evidence that efflux transporters affected the amount of Aβ lowering versus that observed in wild-type (WT) mouse at an equivalent dose. PMID:22984865

  2. Utilizing Structures of CYP2D6 and BACE1 Complexes To Reduce Risk of Drug–Drug Interactions with a Novel Series of Centrally Efficacious BACE1 Inhibitors

    PubMed Central

    2016-01-01

    In recent years, the first generation of β-secretase (BACE1) inhibitors advanced into clinical development for the treatment of Alzheimer’s disease (AD). However, the alignment of drug-like properties and selectivity remains a major challenge. Herein, we describe the discovery of a novel class of potent, low clearance, CNS penetrant BACE1 inhibitors represented by thioamidine 5. Further profiling suggested that a high fraction of the metabolism (>95%) was due to CYP2D6, increasing the potential risk for victim-based drug–drug interactions (DDI) and variable exposure in the clinic due to the polymorphic nature of this enzyme. To guide future design, we solved crystal structures of CYP2D6 complexes with substrate 5 and its corresponding metabolic product pyrazole 6, which provided insight into the binding mode and movements between substrate/inhibitor complexes. Guided by the BACE1 and CYP2D6 crystal structures, we designed and synthesized analogues with reduced risk for DDI, central efficacy, and improved hERG therapeutic margins. PMID:25781223

  3. Microdosing of protein drugs.

    PubMed

    Rowland, M

    2016-02-01

    Poor pharmacokinetics (PK) can seriously limit clinical utility. Knowing early whether a new compound is likely to have the desired PK profile at therapeutic doses is therefore important. One approach, microdosing, has shown high success with small molecular weight compounds, despite early skepticism. Vlaming et al. report the first, and successful, clinical application of a microdose of a humanized recombinant protein. But what is the likely success for this class of drugs more generally?

  4. COPD - control drugs

    MedlinePlus

    Chronic obstructive pulmonary disease - control drugs; Bronchodilators - COPD - control drugs; Beta agonist inhaler - COPD - control drugs; Anticholinergic inhaler - COPD - control drugs; Long-acting inhaler - COPD - control drugs; ...

  5. Cell-Based Selection Expands the Utility of DNA-Encoded Small-Molecule Library Technology to Cell Surface Drug Targets: Identification of Novel Antagonists of the NK3 Tachykinin Receptor.

    PubMed

    Wu, Zining; Graybill, Todd L; Zeng, Xin; Platchek, Michael; Zhang, Jean; Bodmer, Vera Q; Wisnoski, David D; Deng, Jianghe; Coppo, Frank T; Yao, Gang; Tamburino, Alex; Scavello, Genaro; Franklin, G Joseph; Mataruse, Sibongile; Bedard, Katie L; Ding, Yun; Chai, Jing; Summerfield, Jennifer; Centrella, Paolo A; Messer, Jeffrey A; Pope, Andrew J; Israel, David I

    2015-12-14

    DNA-encoded small-molecule library technology has recently emerged as a new paradigm for identifying ligands against drug targets. To date, this technology has been used with soluble protein targets that are produced and used in a purified state. Here, we describe a cell-based method for identifying small-molecule ligands from DNA-encoded libraries against integral membrane protein targets. We use this method to identify novel, potent, and specific inhibitors of NK3, a member of the tachykinin family of G-protein coupled receptors (GPCRs). The method is simple and broadly applicable to other GPCRs and integral membrane proteins. We have extended the application of DNA-encoded library technology to membrane-associated targets and demonstrate the feasibility of selecting DNA-tagged, small-molecule ligands from complex combinatorial libraries against targets in a heterogeneous milieu, such as the surface of a cell.

  6. Drug Research

    NASA Technical Reports Server (NTRS)

    1989-01-01

    NBOD2, a program developed at Goddard Space Flight Center to solve equations of motion coupled N-body systems is used by E.I. DuPont de Nemours & Co. to model potential drugs as a series of elements. The program analyses the vibrational and static motions of independent components in drugs. Information generated from this process is used to design specific drugs to interact with enzymes in designated ways.

  7. Controlling Your Utility Rates.

    ERIC Educational Resources Information Center

    Lucht, Ray; Dembowski, Frederick L.

    1985-01-01

    A cost-effective alternative to high utility bills for middle-sized and smaller utility users is the service of utility rate consultants. The consultants analyze utility invoices for the previous 12 months to locate available refunds or credits. (MLF)

  8. [30 years in the history of drugs and drug therapy].

    PubMed

    Taboulet, F

    1994-01-01

    The last three decades have been undoubtedly a "revolutionary time" in the life of pharmaceuticals. Progress in scientific knowledge and medical practice have fueled tremendous change in the drug universe. The "drug chain" has been totally transformed, from the early conception through evaluation by the public authorities to end up with the utilization by the patient. The article describes all these transformations in the French context.

  9. [30 years in the history of drugs and drug therapy].

    PubMed

    Taboulet, F

    1994-01-01

    The last three decades have been undoubtedly a "revolutionary time" in the life of pharmaceuticals. Progress in scientific knowledge and medical practice have fueled tremendous change in the drug universe. The "drug chain" has been totally transformed, from the early conception through evaluation by the public authorities to end up with the utilization by the patient. The article describes all these transformations in the French context. PMID:7736313

  10. 21 CFR 14.171 - Utilization of an advisory committee on the initiative of FDA.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... Human Prescription Drugs § 14.171 Utilization of an advisory committee on the initiative of FDA. (a) Any matter involving a human prescription drug under review within the agency may, in the discretion of the... 21 Food and Drugs 1 2010-04-01 2010-04-01 false Utilization of an advisory committee on...

  11. Drug Education.

    ERIC Educational Resources Information Center

    Sardana, Raj K.

    This autoinstructional lesson deals with the study of such drugs as marijuana and LSD, with emphasis on drug abuse. It is suggested that it can be used in science classes at the middle level of school. No prerequisites are suggested. The teacher's guide lists the behavioral objectives, the equipment needed to complete the experience and suggests…

  12. Antineoplastic Drugs

    NASA Astrophysics Data System (ADS)

    Sadée, Wolfgang; El Sayed, Yousry Mahmoud

    The limited scope of therapeutic drug-level monitoring in cancer chemotherapy results from the often complex biochemical mechanisms that contribute to antineoplastic activity and obscure the relationships among drug serum levels and therapeutic benefits. Moreover, new agents for cancer chemotherapy are being introduced at a more rapid rate than for the treatment of other diseases, although the successful application of therapeutic drug-level monitoring may require several years of intensive study of the significance of serum drug levels. However, drug level monitoring can be of considerable value during phase I clinical trials of new antineoplastic agents in order to assess drug metabolism, bioavailability, and intersubject variability; these are important parameters in the interpretation of clinical studies, but have no immediate benefit to the patient. High performance liquid chromatography (HPLC) probably represents the most versatile and easily adaptable analytical technique for drug metabolite screening (1). HPLC may therefore now be the method of choice during phase I clinical trials of antineoplastic drugs. For example, within a single week we developed an HPLC assay—using a C18 reverse-phase column, UV detection, and direct serum injection after protein precipitation—for the new radiosensitizer, misonidazole (2).

  13. 42 CFR 456.703 - Drug use review program.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 42 Public Health 4 2012-10-01 2012-10-01 false Drug use review program. 456.703 Section 456.703... (CONTINUED) MEDICAL ASSISTANCE PROGRAMS UTILIZATION CONTROL Drug Use Review (DUR) Program and Electronic Claims Management System for Outpatient Drug Claims § 456.703 Drug use review program. (a)...

  14. 42 CFR 456.703 - Drug use review program.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 42 Public Health 4 2013-10-01 2013-10-01 false Drug use review program. 456.703 Section 456.703... (CONTINUED) MEDICAL ASSISTANCE PROGRAMS UTILIZATION CONTROL Drug Use Review (DUR) Program and Electronic Claims Management System for Outpatient Drug Claims § 456.703 Drug use review program. (a)...

  15. 42 CFR 456.709 - Retrospective drug use review.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 42 Public Health 4 2013-10-01 2013-10-01 false Retrospective drug use review. 456.709 Section 456... (CONTINUED) MEDICAL ASSISTANCE PROGRAMS UTILIZATION CONTROL Drug Use Review (DUR) Program and Electronic Claims Management System for Outpatient Drug Claims § 456.709 Retrospective drug use review. (a)...

  16. 42 CFR 456.709 - Retrospective drug use review.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 42 Public Health 4 2014-10-01 2014-10-01 false Retrospective drug use review. 456.709 Section 456... (CONTINUED) MEDICAL ASSISTANCE PROGRAMS UTILIZATION CONTROL Drug Use Review (DUR) Program and Electronic Claims Management System for Outpatient Drug Claims § 456.709 Retrospective drug use review. (a)...

  17. 42 CFR 456.703 - Drug use review program.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 42 Public Health 4 2014-10-01 2014-10-01 false Drug use review program. 456.703 Section 456.703... (CONTINUED) MEDICAL ASSISTANCE PROGRAMS UTILIZATION CONTROL Drug Use Review (DUR) Program and Electronic Claims Management System for Outpatient Drug Claims § 456.703 Drug use review program. (a)...

  18. 42 CFR 456.709 - Retrospective drug use review.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 42 Public Health 4 2011-10-01 2011-10-01 false Retrospective drug use review. 456.709 Section 456... (CONTINUED) MEDICAL ASSISTANCE PROGRAMS UTILIZATION CONTROL Drug Use Review (DUR) Program and Electronic Claims Management System for Outpatient Drug Claims § 456.709 Retrospective drug use review. (a)...

  19. 42 CFR 456.709 - Retrospective drug use review.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 42 Public Health 4 2012-10-01 2012-10-01 false Retrospective drug use review. 456.709 Section 456... (CONTINUED) MEDICAL ASSISTANCE PROGRAMS UTILIZATION CONTROL Drug Use Review (DUR) Program and Electronic Claims Management System for Outpatient Drug Claims § 456.709 Retrospective drug use review. (a)...

  20. 42 CFR 456.703 - Drug use review program.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 42 Public Health 4 2011-10-01 2011-10-01 false Drug use review program. 456.703 Section 456.703... (CONTINUED) MEDICAL ASSISTANCE PROGRAMS UTILIZATION CONTROL Drug Use Review (DUR) Program and Electronic Claims Management System for Outpatient Drug Claims § 456.703 Drug use review program. (a)...

  1. Old drugs, novel ways out: Drug resistance toward cytotoxic chemotherapeutics.

    PubMed

    Wijdeven, Ruud H; Pang, Baoxu; Assaraf, Yehuda G; Neefjes, Jacques

    2016-09-01

    Efficacy of chemotherapy in the treatment of distinct malignancies is often hampered by drug resistance arising in the tumor. Understanding the molecular basis of drug resistance and translating this knowledge into personalized treatment decisions can enhance therapeutic efficacy and even curative outcome. Over the years, multiple drug resistance mechanisms have been identified that enable tumors to cope with the damage instigated by a specific drug or group of anti-tumor agents. Here we provide an overview of the molecular pathways leading to resistance against conventional anti-cancer drugs, with emphasis on the utility of these pathways for rational selection of treatments for individual cancer patients. We further complement the review by discussing the pitfalls and difficulties in translating these findings into novel treatment strategies for cancer patients. PMID:27620955

  2. Street Drugs and Pregnancy

    MedlinePlus

    ... drugs that are abused How can street drugs harm your pregnancy? Using street drugs can cause problems ... drugs that are abused How can street drugs harm your pregnancy? Using street drugs can cause problems ...

  3. Prescription Drugs

    MedlinePlus

    ... body, especially in brain areas involved in the perception of pain and pleasure. Prescription stimulants , such as ... of drug that causes changes in your mood, perceptions, and behavior can affect judgment and willingness to ...

  4. Antiretroviral drugs.

    PubMed

    De Clercq, Erik

    2010-10-01

    In October 2010, it will be exactly 25 years ago that the first antiretroviral drug, AZT (zidovudine, 3'-azido-2',3'-dideoxythymidine), was described. It was the first of 25 antiretroviral drugs that in the past 25 years have been formally licensed for clinical use. These antiretroviral drugs fall into seven categories [nucleoside reverse transcriptase inhibitors (NRTIs), nucleotide reverse transcriptase inhibitors (NtRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors (PIs), fusion inhibitors (FIs), co-receptor inhibitors (CRIs) and integrase inhibitors (INIs). The INIs (i.e. raltegravir) represent the most recent advance in the search for effective and selective anti-HIV agents. Combination of several anti-HIV drugs [often referred to as highly active antiretroviral therapy (HAART)] has drastically altered AIDS from an almost uniformly fatal disease to a chronic manageable one.

  5. Drug Reactions

    MedlinePlus

    ... or diabetes. But medicines can also cause unwanted reactions. One problem is interactions, which may occur between ... more serious. Drug allergies are another type of reaction. They can be mild or life-threatening. Skin ...

  6. Club Drugs

    MedlinePlus

    Skip to main content En español Researchers Medical & Health Professionals Patients & ... Cold Medicines Steroids (Anabolic) Synthetic Cannabinoids (K2/Spice) Synthetic Cathinones (Bath Salts) Tobacco/Nicotine Other Drugs ...

  7. Drugged Driving

    MedlinePlus

    ... Charts Emerging Trends and Alerts Alcohol Club Drugs Cocaine Hallucinogens Heroin Inhalants Marijuana MDMA (Ecstasy/Molly) Methamphetamine ... distance, and decrease coordination. Drivers who have used cocaine or methamphetamine can be aggressive and reckless when ...

  8. Drug Interactions

    MedlinePlus

    ... not be taken at the same time as antacids. WHAT CAUSES THE MOST INTERACTIONS WITH HIV MEDICATIONS? ... azole” Some antibiotics (names end in “mycin”) The antacid cimetidine (Tagamet) Some drugs that prevent convulsions, including ...

  9. Club Drugs

    MedlinePlus

    ... also known as Ecstasy XTC, X, E, Adam, Molly, Hug Beans, and Love Drug Gamma-hydroxybutyrate (GHB), also known as G, Liquid Ecstasy, and Soap Ketamine, also known as Special K, K, Vitamin K, and Jet Rohypnol, also known ...

  10. A Global Information Utility.

    ERIC Educational Resources Information Center

    Block, Robert S.

    1984-01-01

    High-powered satellites, along with other existing technologies, make possible a world information utility that could distribute virtually limitless information to every point on earth. The utility could distribute information for business, government, education, and entertainment. How the utility would work is discussed. (RM)

  11. Drug allergy

    PubMed Central

    Warrington, Richard

    2012-01-01

    Allergic drug reactions occur when a drug, usually a low molecular weight molecule, has the ability to stimulate an immune response. This can be done in one of two ways. The first is by binding covalently to a self-protein, to produce a haptenated molecule that can be processed and presented to the adaptive immune system to induce an immune response. Sometimes the drug itself cannot do this but a reactive breakdown product of the drug is able to bind covalently to the requisite self-protein or peptide. The second way in which drugs can stimulate an immune response is by binding non-covalently to antigen presenting or antigen recognition molecules such as the major histocompatibility complex (MHC) or the T cell receptor. This is known as the p-I or pharmacological interaction hypothesis. The drug binding in this situation is reversible and stimulation of the response may occur on first exposure, not requiring previous sensitization. There is probably a dependence on the presence of certain MHC alleles and T cell receptor structures for this type of reaction to occur. PMID:22922763

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

    ERIC Educational Resources Information Center

    Gold, Robert S.; Duncan, David F.

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

  13. Drug misuse.

    PubMed Central

    Waller, T.

    1992-01-01

    1. Assessment by history and examination should include: a history of all drugs taken during each day for the previous 7 days (including alcohol), length of drug use and route (including the sharing of needles or syringes), the possibility of pregnancy if female, previous psychiatric history and treatment of drug misuse, social factors (including employment, family, friends, involvement in prostitution, legal problems), medical problems, including evidence of hepatitis, injection abscesses and other infections, suicide attempts, and weight loss. 2. Notification to the Chief Medical Officer of the Drug Branch of the Home Office is a legal obligation. 3. Investigations include: liver function tests (LFTs), hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (HBsAb), hepatitis C antibody, full blood count (FBC), and urine for drug screening. Consider HIV testing if at risk but it is usually better arranged at a later stage. 4. Prescribing may be considered for a variety of drugs but objectives will differ according to drug type and individual. 5. In the case of opioid users, prescribing may be useful to stabilize their lives and to promote attendance for professional help. It may reduce high risk behaviour for contracting and spreading HIV. 6. If medication is given to opioid users, methadone mixture 1 mg/ml given once a day is the prescription of choice. Dispensing should be on a daily basis and the blue prescription form FP10 (MDA) allows the chemist to dispense daily for up to 14 days. A maximum ceiling of 100 mg methadone/day should not be exceeded. The initial dose will depend on the amount of opioid consumed in the previous week.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1345155

  14. Prime Drug Interplay in Dental Practice.

    PubMed

    Mohan, Sumedha; Govila, Vivek; Saini, Ashish; Verma, Sunil Chandra

    2016-03-01

    Drug interaction is a negative representation of pharmacotherapy. In order to provide the best patient care possible, a thorough knowledge of how the drug interactions occur is needed for proper application in practice. Possible interactions among current medication and drugs being prescribed should be considered always. A thorough understanding of the mechanism of interactions among drugs is a must for the health care practitioner. Considering the astounding number of drugs patients may be taking, this task seems discouraging. The count of possible interactions in dental practice are less due to few number of drugs utilized and brief period of therapy, but still notable number are to be considered. The aim of present preview is to consider the manifold and multiplex nature of pharmacological drug-drug interaction in the general dental practice setting. PMID:27135021

  15. Prime Drug Interplay in Dental Practice

    PubMed Central

    Govila, Vivek; Saini, Ashish; Verma, Sunil Chandra

    2016-01-01

    Drug interaction is a negative representation of pharmacotherapy. In order to provide the best patient care possible, a thorough knowledge of how the drug interactions occur is needed for proper application in practice. Possible interactions among current medication and drugs being prescribed should be considered always. A thorough understanding of the mechanism of interactions among drugs is a must for the health care practitioner. Considering the astounding number of drugs patients may be taking, this task seems discouraging. The count of possible interactions in dental practice are less due to few number of drugs utilized and brief period of therapy, but still notable number are to be considered. The aim of present preview is to consider the manifold and multiplex nature of pharmacological drug-drug interaction in the general dental practice setting. PMID:27135021

  16. Narcotic Drug Control in New York State.

    ERIC Educational Resources Information Center

    New York State Legislature, Albany.

    This report concentrates on the analysis and evaluation of programs utilized by New York State's Narcotics Addiction Control Commission (NACC) and concerned with control of narcotic drugs and with those individuals who abuse them. The three key premises, basic to the narcotic drug control programs approved by the state legislature, are: (1) there…

  17. Drug watch.

    PubMed

    Whitson, S

    1999-01-01

    Recent developments on new anti-HIV agents and drugs for opportunistic infections are highlighted. Information is provided on the infusion inhibitor T-20; DuPont's second generation non-nukes, DPC 961 and DPC 963; Papirine (PEN203) for the human papilloma virus; Sporanox for treating fungal infections; and the antiretroviral protein, lysozyme. In addition, information is given on a plant found in the Bolivian rainforest that may contain compounds to prevent HIV infection by blocking the enzyme, integrase. Other promising new drugs addressed at the 6th Conference on Retroviruses and Opportunistic Infections are listed in a table. Contact information for US clinical trials is provided.

  18. Drug Allergy.

    PubMed

    Waheed, Abdul; Hill, Tiffany; Dhawan, Nidhi

    2016-09-01

    An adverse drug reaction relates to an undesired response to administration of a drug. Type A reactions are common and are predictable to administration, dose response, or interaction with other medications. Type B reactions are uncommon with occurrences that are not predictable. Appropriate diagnosis, classification, and entry into the chart are important to avoid future problems. The diagnosis is made with careful history, physical examination, and possibly allergy testing. It is recommended that help from allergy immunology specialists should be sought where necessary and that routine prescription of Epi pen should be given to patients with multiple allergy syndromes. PMID:27545730

  19. [Ureter drugs].

    PubMed

    Raynal, G; Bellan, J; Saint, F; Tillou, X; Petit, J

    2008-03-01

    Many improvements have been made recently in the field of the ureteral smooth muscle pharmacology. After a brief summary on physiological basis, we review what is known about effects on ureter of different drugs class. In a second part, we review clinical applications for renal colic analgesia, calculi expulsive medical therapy, ESWL adjuvant treatment and preoperative treatment before retrograde access. There are now sufficient data on NSAID and alpha-blockers. beta-agonists, especially for beta3 selective ones, and topical drugs before retrograde access are interesting and should be further evaluated.

  20. Participatory design for drug-drug interaction alerts.

    PubMed

    Luna, Daniel; Otero, Carlos; Almerares, Alfredo; Stanziola, Enrique; Risk, Marcelo; González Bernaldo de Quirós, Fernán

    2015-01-01

    The utilization of decision support systems, in the point of care, to alert drug-drug interactions has been shown to improve quality of care. Still, the use of these systems has not been as expected, it is believed, because of the difficulties in their knowledge databases; errors in the generation of the alerts and the lack of a suitable design. This study expands on the development of alerts using participatory design techniques based on user centered design process. This work was undertaken in three stages (inquiry, participatory design and usability testing) it showed that the use of these techniques improves satisfaction, effectiveness and efficiency in an alert system for drug-drug interactions, a fact that was evident in specific situations such as the decrease of errors to meet the specified task, the time, the workload optimization and users overall satisfaction in the system.

  1. Participatory design for drug-drug interaction alerts.

    PubMed

    Luna, Daniel; Otero, Carlos; Almerares, Alfredo; Stanziola, Enrique; Risk, Marcelo; González Bernaldo de Quirós, Fernán

    2015-01-01

    The utilization of decision support systems, in the point of care, to alert drug-drug interactions has been shown to improve quality of care. Still, the use of these systems has not been as expected, it is believed, because of the difficulties in their knowledge databases; errors in the generation of the alerts and the lack of a suitable design. This study expands on the development of alerts using participatory design techniques based on user centered design process. This work was undertaken in three stages (inquiry, participatory design and usability testing) it showed that the use of these techniques improves satisfaction, effectiveness and efficiency in an alert system for drug-drug interactions, a fact that was evident in specific situations such as the decrease of errors to meet the specified task, the time, the workload optimization and users overall satisfaction in the system. PMID:25991099

  2. Utilities weather the storm

    SciTech Connect

    Lihach, N.

    1984-11-01

    Utilities must restore power to storm-damaged transmission and distribution systems, even if it means going out in ice storms or during lightning and hurricane conditions. Weather forecasting helps utilities plan for possible damage as well as alerting them to long-term trends. Storm planning includes having trained repair personnel available and adjusting the system so that less power imports are needed. Storm damage response requires teamwork and cooperation between utilities. Utilities can strengthen equipment in storm-prone or vulnerable areas, but good data are necessary to document the incidence of lighning strikes, hurricanes, etc. 2 references, 8 figures.

  3. Antineoplastic Drugs.

    ERIC Educational Resources Information Center

    Morris, Sara; Michael, Nancy, Ed.

    This module on antineoplastic drugs is intended for use in inservice or continuing education programs for persons who administer medications in long-term care facilities. Instructor information, including teaching suggestions, and a listing of recommended audiovisual materials and their sources appear first. The module goal and objectives are then…

  4. Drug development to protozoan diseases.

    PubMed

    Monzote, Lianet; Siddiq, Afshan

    2011-01-01

    The diseases caused by protozoan parasite are responsible for considerable mortality and morbidity, affecting more than 500 million of people in the world. The epidemiological control of protozoan is unsatisfactory due to difficulties of vector and reservoir control; while the progress in the development of vaccine tends to be slow and arduous. Currently, the chemotherapy remains essential component of both clinical management and disease control programmer in endemic areas. The drugs in use as anti-protozoan agents were discovered over 50 years and a number of factors limit their utility such as: high cost, poor compliance, drug resistance, low efficacy and poor safety. In the recent years, the searches about the development of new drugs against protozoa parasite have been increased. This special issue of The Open Medicinal Chemistry Journal will present some of developments in this field with the aim to shown the significant advances in the discovery of new anti-protozoan drugs.

  5. Trojan Microparticles for Drug Delivery

    PubMed Central

    Anton, Nicolas; Jakhmola, Anshuman; Vandamme, Thierry F.

    2012-01-01

    During the last decade, the US Food and Drug Administration (FDA) have regulated a wide range of products, (foods, cosmetics, drugs, devices, veterinary, and tobacco) which may utilize micro and nanotechnology or contain nanomaterials. Nanotechnology allows scientists to create, explore, and manipulate materials in nano-regime. Such materials have chemical, physical, and biological properties that are quite different from their bulk counterparts. For pharmaceutical applications and in order to improve their administration (oral, pulmonary and dermal), the nanocarriers can be spread into microparticles. These supramolecular associations can also modulate the kinetic releases of drugs entrapped in the nanoparticles. Different strategies to produce these hybrid particles and to optimize the release kinetics of encapsulated drugs are discussed in this review. PMID:24300177

  6. Drugs derived from phage display

    PubMed Central

    Nixon, Andrew E; Sexton, Daniel J; Ladner, Robert C

    2014-01-01

    Phage display, one of today’s fundamental drug discovery technologies, allows identification of a broad range of biological drugs, including peptides, antibodies and other proteins, with the ability to tailor critical characteristics such as potency, specificity and cross-species binding. Further, unlike in vivo technologies, generating phage display-derived antibodies is not restricted by immunological tolerance. Although more than 20 phage display-derived antibody and peptides are currently in late-stage clinical trials or approved, there is little literature addressing the specific challenges and successes in the clinical development of phage-derived drugs. This review uses case studies, from candidate identification through clinical development, to illustrate the utility of phage display as a drug discovery tool, and offers a perspective for future developments of phage display technology. PMID:24262785

  7. Instructional Facility Utilization.

    ERIC Educational Resources Information Center

    Kalamazoo Valley Community Coll., MI.

    Data describing campus facility use for instructional and related purposes for one week of activity in Fall 1978 were collected and evaluated at Kalamazoo Valley Community College. Four measures of space utilization were used: (1) percent of available time used; (2) percent of available space used; (3) percent of scheduled space utilized; and (4)…

  8. Teuchos Utility Package

    2004-03-01

    Teuchos is designed to provide portable, object-oriented tools for Trillnos developers and users. This includes templated wrappers to BLAS/LAPACK, a serial dense matrix class, a parameter list, XML parsing utilities, reference counted pointer (smart pointer) utilities, and more. These tools are designed to run on both serial and parallel computers.

  9. Tribal water utility management

    SciTech Connect

    Not Available

    1993-03-01

    Contents: primacy program (what is primacy, advantages and disadvantages, treatment as a state, grant applications and funding); safe drinking water act (sampling requirements, coliform standard, public notification, surface water treatment rule impacts, uic and wellhead protection programs, lead/copper rule); water utility management (how is the utility program evaluated, who's responsible, what is the board and tribal council role).

  10. Therapeutic drug monitoring: antiarrhythmic drugs.

    PubMed

    Campbell, T J; Williams, K M

    2001-01-01

    Antiarrhythmic agents are traditionally classified according to Vaughan Williams into four classes of action. Class I antiarrhythmic agents include most of the drugs traditionally thought of as antiarrhythmics, and have as a common action, blockade of the fast-inward sodium channel on myocardium. These agents have a very significant toxicity, and while they are being used less, therapeutic drug monitoring (TDM) does significantly increase the safety with which they can be administered. Class II agents are antisympathetic drugs, particularly the b-adrenoceptor blockers. These are generally safe agents which do not normally require TDM. Class III antiarrhythmic agents include sotalol and amiodarone. TDM can be useful in the case of amiodarone to monitor compliance and toxicity but is generally of little value for sotalol. Class IV antiarrhythmic drugs are the calcium channel blockers verapamil and diltiazem. These are normally monitored by haemodynamic effects, rather than using TDM. Other agents which do not fall neatly into the Vaughan Williams classification include digoxin and perhexiline. TDM is very useful for monitoring the administration (and particularly the safety) of both of these agents.

  11. Therapeutic drug monitoring: antiarrhythmic drugs

    PubMed Central

    Campbell, T J; Williams, K M

    2001-01-01

    Antiarrhythmic agents are traditionally classified according to Vaughan Williams into four classes of action. Class I antiarrhythmic agents include most of the drugs traditionally thought of as antiarrhythmics, and have as a common action, blockade of the fast-inward sodium channel on myocardium. These agents have a very significant toxicity, and while they are being used less, therapeutic drug monitoring (TDM) does significantly increase the safety with which they can be administered. Class II agents are antisympathetic drugs, particularly the b-adrenoceptor blockers. These are generally safe agents which do not normally require TDM. Class III antiarrhythmic agents include sotalol and amiodarone. TDM can be useful in the case of amiodarone to monitor compliance and toxicity but is generally of little value for sotalol. Class IV antiarrhythmic drugs are the calcium channel blockers verapamil and diltiazem. These are normally monitored by haemodynamic effects, rather than using TDM. Other agents which do not fall neatly into the Vaughan Williams classification include digoxin and perhexiline. TDM is very useful for monitoring the administration (and particularly the safety) of both of these agents. PMID:11564050

  12. Part I---Evaluating Effects of Oligomer Formation on Cytochrome P450 2C9 Electron Transfer and Drug Metabolism, Part II---Utilizing Molecular Modeling Techniques to Study the Src-Interacting Proteins Actin Filament Associated Protein of 110 kDa (AFAP-110) and Cortactin

    NASA Astrophysics Data System (ADS)

    Jett, John Edward, Jr.

    The dissertation has been divided into two parts to accurately reflect the two distinct areas of interest pursued during my matriculation in the School of Pharmacy at West Virginia University. In Part I, I discuss research probing the nature of electron transfer in the Cytochrome P450 family of proteins, a group of proteins well-known for their role in drug metabolism. In Part II, I focus on in silico and in vitro work developed in concert to probe protein structure and protein-protein interactions involved in actin filament reorganization and cellular motility. Part I. Cytochrome P450s (P450s) are an important class of enzymes known to metabolize a variety of endogenous and xenobiotic compounds. P450s are most commonly found in liver and intestinal endothelial cells and are responsible for the metabolism of approximately 75% of pharmaceutical drugs on the market. CYP2C9---one of the six major P450 isoforms---is responsible for ˜20% of drug metabolism. Elucidation of the factors that affect in vitro drug metabolism is crucial to the accurate prediction of in vivo drug metabolism kinetics. Currently, the two major techniques for studying in vitro drug metabolism are solution-based. However, it is known that the results of solution-based studies can vary from in vivo drug metabolism. One reason suggested to account for this variation is the state of P450 oligomer formation in solution compared to the in vivo environment, where P450s are membrane-bound. To understand the details of how oligomer formation affects in vitro drug metabolism, it is imperative that techniques be developed which will allow for the unequivocal control of oligomer formation without altering other experimental parameters. Our long term goal of this research is to develop methods to more accurately predict in vivo drug metabolism from in vitro data. This section of the dissertation will discuss the development of a platform consisting of a doped silicon surface containing a large array of gold

  13. 21 CFR 14.172 - Utilization of an advisory committee at the request of an interested person.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... Committees for Human Prescription Drugs § 14.172 Utilization of an advisory committee at the request of an... 21 Food and Drugs 1 2010-04-01 2010-04-01 false Utilization of an advisory committee at the... particular human prescription drug be submitted to an appropriate advisory committee for a hearing and...

  14. SINGLE DRUG THERAPY IN NETRAROGA

    PubMed Central

    Gayathri, M.B.; Kareem, M. Abdul; Sarneswar; Unnikrishnan, P.M.

    1996-01-01

    The non-availability of reliable and standardized drugs, their high cost, and ambiguity in the identity of the ingredients used are a few of the major problems encountered today in the utilization of compound drugs in Ayurveda. There is thus an urgent need to reemphasize the use of single plant drug formulations recorded in the classical texts. The present study is an attempt to list out all the single plant drugs mentioned in the treatment of various Netrarogas from the classical texts of Ayurveda and to fix their proper botanical identity. The study of 7 classical texts has revealed that there are 41 single plant drugs in 80 preparations for treating 9 lakshanas and 29 rogas. They have been correlated with their botanical identities based on nomenclature correlation studies published over the last century. The drugs are arranged alphabetically with their botanical names, habit, indications, parts used, method of preparation, mode of administration and the reference, A primary analysis has also been made on the nomenclature, qualities and applications of the drugs. PMID:22556780

  15. Drug watch.

    PubMed

    Whitson, S

    1999-01-01

    Current research findings and treatment issues related to a number of drugs are briefly outlined. Topics include T-20, a reformulation of ddI, PMPA, chicoric acid, Omniferon (alpha leukoferon), and Mepron. Also discussed is a non-nucleoside reverse transcriptase inhibitor called calanolide A, which is synthesized from a tree native to Malaysian rain forests. An update is provided on Panretin, a gel which is used to treat KS lesions. Contact information is provided.

  16. QSAR Modeling and Prediction of Drug-Drug Interactions.

    PubMed

    Zakharov, Alexey V; Varlamova, Ekaterina V; Lagunin, Alexey A; Dmitriev, Alexander V; Muratov, Eugene N; Fourches, Denis; Kuz'min, Victor E; Poroikov, Vladimir V; Tropsha, Alexander; Nicklaus, Marc C

    2016-02-01

    Severe adverse drug reactions (ADRs) are the fourth leading cause of fatality in the U.S. with more than 100,000 deaths per year. As up to 30% of all ADRs are believed to be caused by drug-drug interactions (DDIs), typically mediated by cytochrome P450s, possibilities to predict DDIs from existing knowledge are important. We collected data from public sources on 1485, 2628, 4371, and 27,966 possible DDIs mediated by four cytochrome P450 isoforms 1A2, 2C9, 2D6, and 3A4 for 55, 73, 94, and 237 drugs, respectively. For each of these data sets, we developed and validated QSAR models for the prediction of DDIs. As a unique feature of our approach, the interacting drug pairs were represented as binary chemical mixtures in a 1:1 ratio. We used two types of chemical descriptors: quantitative neighborhoods of atoms (QNA) and simplex descriptors. Radial basis functions with self-consistent regression (RBF-SCR) and random forest (RF) were utilized to build QSAR models predicting the likelihood of DDIs for any pair of drug molecules. Our models showed balanced accuracy of 72-79% for the external test sets with a coverage of 81.36-100% when a conservative threshold for the model's applicability domain was applied. We generated virtually all possible binary combinations of marketed drugs and employed our models to identify drug pairs predicted to be instances of DDI. More than 4500 of these predicted DDIs that were not found in our training sets were confirmed by data from the DrugBank database. PMID:26669717

  17. Drug Rash (Unclassified Drug Eruption) in Children

    MedlinePlus

    ... rash and rashes clinical tools newsletter | contact Share | Drug Eruption, Unclassified (Pediatric) A parent's guide to condition ... lesions coming together into larger lesions typical of drug rashes (eruptions). Overview A drug eruption, also known ...

  18. Asthma - control drugs

    MedlinePlus

    Asthma - inhaled corticosteroids; Asthma - long-acting beta-agonists; Asthma - leukotriene modifiers; Asthma - cromolyn; Bronchial asthma-control drugs; Wheezing - control drugs; Reactive airway disease - control drugs

  19. Reporting of Drug Expenditures in the MCBS

    PubMed Central

    Poisal, John A.

    2003-01-01

    Comparing data from both the 1999 MCBS and drug utilization data supplied by the survey respondents' pharmacies, the author details the methods used to determine the level of misreporting of drug expenditures in the MCBS. Findings suggest that prescription drug expenditures are underreported by 17 percent and the number of prescriptions used is underreported by 17.7 percent. The data also identify demographic factors that predict a beneficiary's likelihood to either overreport or underreport his or her medications, as well as the extent to which beneficiaries misreport their drug use and spending. PMID:15124375

  20. PAM stack test utility

    2007-08-22

    The pamtest utility calls the normal PAM hooks using a service and username supplied on the command line. This allows an administratory to test any one of many configured PAM stacks as any existing user on the machine.

  1. Understanding the Utilities.

    ERIC Educational Resources Information Center

    Matthews, Joseph R.

    1980-01-01

    Briefly describes the origin and development of some major online bibliographic utilities, including the Ohio College Library Center (OCLC), the Research Libraries Information Network (RLIN), the University of Toronto Library Automation Systems (UTLAS), and the Washington Library Network (WLN). (FM)

  2. Measuring Resource Utilization

    PubMed Central

    Leggett, Laura E.; Khadaroo, Rachel G.; Holroyd-Leduc, Jayna; Lorenzetti, Diane L.; Hanson, Heather; Wagg, Adrian; Padwal, Raj; Clement, Fiona

    2016-01-01

    Abstract A variety of methods may be used to obtain costing data. Although administrative data are most commonly used, the data available in these datasets are often limited. An alternative method of obtaining costing is through self-reported questionnaires. Currently, there are no systematic reviews that summarize self-reported resource utilization instruments from the published literature. The aim of the study was to identify validated self-report healthcare resource use instruments and to map their attributes. A systematic review was conducted. The search identified articles using terms like “healthcare utilization” and “questionnaire.” All abstracts and full texts were considered in duplicate. For inclusion, studies had to assess the validity of a self-reported resource use questionnaire, to report original data, include adult populations, and the questionnaire had to be publically available. Data such as type of resource utilization assessed by each questionnaire, and validation findings were extracted from each study. In all, 2343 unique citations were retrieved; 2297 were excluded during abstract review. Forty-six studies were reviewed in full text, and 15 studies were included in this systematic review. Six assessed resource utilization of patients with chronic conditions; 5 assessed mental health service utilization; 3 assessed resource utilization by a general population; and 1 assessed utilization in older populations. The most frequently measured resources included visits to general practitioners and inpatient stays; nonmedical resources were least frequently measured. Self-reported questionnaires on resource utilization had good agreement with administrative data, although, visits to general practitioners, outpatient days, and nurse visits had poorer agreement. Self-reported questionnaires are a valid method of collecting data on healthcare resource utilization. PMID:26962773

  3. Utility straight sections

    SciTech Connect

    Leemann, B.; Peggs, S.; Peterson, J.

    1985-10-01

    Utility straight sections are insertions in the SSC lattice to provide relatively free space to facilitate various beam manipulations. These uses include beam-abort, injection (and conceivably ejection), space for the rf system, and collimation. A typical utility straight section is 1500 meters in overall length (ranging from 500 to 1200 meters). It has zero dispersion and high values of the beta functions. The betatron phase shift across the insertion is about 90{degrees} in each plane.

  4. Drug Utilisation Study in a Tertiary Care Center: Recommendations for Improving Hospital Drug Dispensing Policies

    PubMed Central

    Mittal, Niti; Mittal, R.; Singh, I.; Shafiq, Nusrat; Malhotra, S.

    2014-01-01

    Drug therapy accounts for a major portion of health expenditure. A useful strategy for achieving cost efficient healthcare is drug utilisation research as it forms the basis for making amendments in drug policies and helps in rational drug use. The present observational study was conducted to generate data on drug utilization in inpatients of our tertiary care hospital to identify potential targets for improving drug prescribing patterns. Data was collected retrospectively from randomly selected 231 medical records of patients admitted in various wards of the hospital. WHO Anatomical Therapeutic Chemical/Defined Daily Dose methodology was used to assess drug utilisation data and drug prescriptions were analysed by WHO core drug indicators. Antibiotics were prescribed most frequently and also accounted for majority of drug costs. The prescribed daily dose for most of the antibiotics corresponded to defined daily dose reflecting adherence to international recommendations. Brand name prescribing and polypharmacy was very common.78% of the total drugs prescribed were from the National List of Essential Medicines 2003. Restricting the use of newer and costlier antibiotics, branded drugs and number of drugs per prescription could be considered as targets to cut down the cost of drug therapysignificantly. PMID:25284928

  5. Antiplatelet Drugs

    PubMed Central

    Hirsh, Jack; Spencer, Frederick A.; Baglin, Trevor P.; Weitz, Jeffrey I.

    2012-01-01

    The article describes the mechanisms of action, pharmacokinetics, and pharmacodynamics of aspirin, dipyridamole, cilostazol, the thienopyridines, and the glycoprotein IIb/IIIa antagonists. The relationships among dose, efficacy, and safety are discussed along with a mechanistic overview of results of randomized clinical trials. The article does not provide specific management recommendations but highlights important practical aspects of antiplatelet therapy, including optimal dosing, the variable balance between benefits and risks when antiplatelet therapies are used alone or in combination with other antiplatelet drugs in different clinical settings, and the implications of persistently high platelet reactivity despite such treatment. PMID:22315278

  6. Drugs Approved for Neuroblastoma

    Cancer.gov

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for neuroblastoma. The list includes generic names and brand names. The drug names link to NCI's Cancer Drug Information summaries.

  7. Drugs Approved for Retinoblastoma

    Cancer.gov

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for retinoblastoma. The list includes generic names and brand names. The drug names link to NCI’s Cancer Drug Information summaries.

  8. Drugs Approved for Leukemia

    Cancer.gov

    This page lists cancer drugs approved by the FDA for use in leukemia. The drug names link to NCI's Cancer Drug Information summaries. The list includes generic names, brand names, and common drug combinations, which are shown in capital letters.

  9. Drug Plan Coverage Rules

    MedlinePlus

    ... works with other insurance Find health & drug plans Drug plan coverage rules Note Call your Medicare drug ... shingles vaccine) when medically necessary to prevent illness. Drugs you get in hospital outpatient settings In most ...

  10. Therapeutic Drug Monitoring

    MedlinePlus

    ... be limited. Home Visit Global Sites Search Help? Therapeutic Drug Monitoring Share this page: Was this page ... Monitored Drugs | Common Questions | Related Pages What is therapeutic drug monitoring? Therapeutic drug monitoring is the measurement ...

  11. [Drug poisoning].

    PubMed

    Gainza, I; Nogué, S; Martínez Velasco, C; Hoffman, R S; Burillo-Putze, G; Dueñas, A; Gómez, J; Pinillos, M A

    2003-01-01

    A review is made of acute poisoning by opiates and its treatment in the emergency services, bearing in mind the progressive decline in the number of cases presented with the arrival of new forms of their administration, as well as the presence of new addictive drugs that have resulted in a shift in consumption habits. Reference is also made to the way in which the different types of existing substances originated, with the aim of achieving a better understanding of their use and in order to administer the most suitable treatment when poisoning occurs. Cocaine poisoning is discussed, with reference to its clinical picture, diagnosis and treatment. The consumption of illegal drugs in our country has undergone a notable change in recent years, with heroin being relegated and the incorporation of cocaine, amphetamine derivatives such as "ecstasy" (MDMA), "liquid ecstasy" (GHB) and, to a lesser extent, ketamine. A review is made of cannabis and its derivates, from the history of its consumption and the preparations employed to the effects produced in the different bodily systems. A brief explanation is also given of its metabolites and its principal mechanisms of action. Finally, we comment on the effects of LSD and hallucinogenic mushrooms.

  12. Utility terrestrial biodiversity issues

    SciTech Connect

    Breece, G.A.; Ward, B.J.

    1996-11-01

    Results from a survey of power utility biologists indicate that terrestrial biodiversity is considered a major issued by only a few utilities; however, a majority believe it may be a future issue. Over half of the respondents indicated that their company is involved in some management for biodiversity, and nearly all feel that it should be a goal for resource management. Only a few utilities are funding biodiversity research, but a majority felt more research was needed. Generally, larger utilities with extensive land holdings had greater opportunities and resources for biodiversity management. Biodiversity will most likely be a concern with transmission rights-of-way construction and maintenance, endangered species issues and general land resource management, including mining reclamation and hydro relicensing commitments. Over half of the companies surveyed have established voluntary partnerships with management groups, and biodiversity is a goal in nearly all the joint projects. Endangered species management and protection, prevention of forest fragmentation, wetland protection, and habitat creation and protection are the most common partnerships involving utility companies. Common management practices and unique approaches are presented, along with details of the survey. 4 refs.

  13. Drugs and the Brain.

    ERIC Educational Resources Information Center

    National Institutes of Health (DHHS), Bethesda, MD.

    This booklet explores various aspects of drug addiction, with a special focus on drugs' effects on the brain. A brief introduction presents information on the rampant use of drugs in society and elaborates the distinction between drug abuse and drug addiction. Next, a detailed analysis of the brain and its functions is given. Drugs target the more…

  14. Photovoltaics and electric utilities

    NASA Astrophysics Data System (ADS)

    Bright, R.; Leigh, R.; Sills, T.

    1981-12-01

    The long term value of grid connected, residential photovoltaic (PV) systems is determined. The value of the PV electricity is defined as the full avoided cost in accordance with the Public Utilities Regulatory Policies Act of 1978. The avoided cost is computed using a long range utility planning approach to measure revenue requirement changes in response to the time phased introduction of PV systems into the grid. A case study approach to three utility systems is used. The changing value of PV electricity over a twenty year period from 1985 is presented, and the fuel and capital savings due to FY are analyzed. These values are translated into measures of breakeven capital investment under several options of power interchange and pricing.

  15. Deregulation of electric utilities

    SciTech Connect

    Zaccour, G.

    1998-07-01

    This volume is a collection of fourteen, mainly applied, economic papers examining electric utility deregulation in many parts of the world. These papers were presented at the International Workshop on Deregulation of Electric Utilities held in Montreal, Canada in September 1997. As the title suggests, these papers cover a broad range of topics. Despite the book's scattershot approach, a small subset of contributors asks a fundamental question: Is the industry sufficiently deregulated? This book succeeds in providing some concrete and well-analyzed examples that examine this important question.

  16. Male Adolescent Contraceptive Utilization.

    ERIC Educational Resources Information Center

    Finkel, Madelon Lubin; Finkel, David J.

    1978-01-01

    The contraceptive utilization of a sample of sexually active, urban, high school males (Black, Hispanic, and White) was examined by anonymous questionnaire. Contraceptive use was haphazard, but White males tended to be more effective contraceptors than the other two groups. Reasons for nonuse were also studied. (Author/SJL)

  17. Module utilization committee

    NASA Technical Reports Server (NTRS)

    Volkmer, K.; Praver, G.

    1984-01-01

    Photovoltaic collector modules were declared surplus to the needs of the U.S. Dept. of Energy. The Module Utilization Committee was formed to make appropriate disposition of the surplus modules on a national basis and to act as a broker for requests for these modules originating outside of the National Photovoltaics Program.

  18. Administrative Utility Analysis: Appendices.

    ERIC Educational Resources Information Center

    Peat, Marwick, Mitchell and Co., San Juan, Puerto Rico.

    Appendixes to a study on administrative utility analysis and vocational education programs for the Area of Vocational and Technical Education (AVTE) in the Puerto Rico Department of Education contain the planning and budgeting system elements, position descriptions, and information on the growth of vocational education in Puerto Rico. The elements…

  19. Technology utilization program report

    NASA Technical Reports Server (NTRS)

    1974-01-01

    The application of aerospace technology to the solution of public health and industrial problems is reported. Data cover: (1) development of an externally rechargeable cardiac pacemaker, (2) utilization of ferrofluids-colloidal suspensions of ferrite particles - in the efficient separation of nonferrous metals as Ni, Zn, Cu, and Al from shredded automobile scrap, and (3) development of a breathing system for fire fighters.

  20. A Classroom Mathematics Utility.

    ERIC Educational Resources Information Center

    Williams, Michael

    1984-01-01

    Reviews CATUSPLOT, a mathematics utility aimed at high school algebra through college-level calculus. Basic program capabilities include plotting, tabulating, integrating, and locating of intersections of functions composed of combinations of polynomial, trigonometric, and exponential functions. Rated excellent on all areas examined…

  1. Utilities. [univac computer programs

    NASA Technical Reports Server (NTRS)

    Colquitt, W. N.

    1976-01-01

    Several sets of related Adage utility programs are described. A general description of the software group, instructions on how to use the programs, and a programmers description of the theory of operation are given along with a printed example of the program in use and a listing of the program.

  2. Employment Tax Credit Utilization.

    ERIC Educational Resources Information Center

    Parkinson, Jan

    Utilizing data collected through a national survey of employers, the impact of federal tax credit programs for employers of Work Incentive Program (WIN) participants and Aid to Families with Dependent Children (AFDC) recipients was assessed. Six major questions were addressed: (1) What differences there were in the use of the WIN and welfare tax…

  3. Classroom Use and Utilization.

    ERIC Educational Resources Information Center

    Fink, Ira

    2002-01-01

    Discusses how classrooms are distributed by size on a campus, how well they are used, and how their use changes with faculty and student needs and desires. Details how to analyze classroom space, use, and utilization, taking into account such factors as scheduling and classroom stations. (EV)

  4. NASA technology utilization house

    NASA Technical Reports Server (NTRS)

    1977-01-01

    Following systems and features, which are predicted to save approximately $20,000 in utility costs over twenty year period, are incorporated into single-level, contemporarily designed, energy efficient residential structure: solar heating and cooling; energy efficient appliances; water recycling; security, smoke, and tornado detectors; and flat conductor electrical wiring.

  5. Readability: Computer Utilization.

    ERIC Educational Resources Information Center

    Felsenthal, Helen

    Textual Analysis of Language Samples (TEXAN) is a computer program which can count a number of variables needed for use in readability formulas. Three studies which utilize TEXAN are reported in this paper: (1) In 1972, Norman and Helen Felsenthal randomly selected 20 books from the 1306 in Eakin's "Good Books for Children" and calculated their…

  6. A weighted and integrated drug-target interactome: drug repurposing for schizophrenia as a use case

    PubMed Central

    2015-01-01

    Background Computational pharmacology can uniquely address some issues in the process of drug development by providing a macroscopic view and a deeper understanding of drug action. Specifically, network-assisted approach is promising for the inference of drug repurposing. However, the drug-target associations coming from different sources and various assays have much noise, leading to an inflation of the inference errors. To reduce the inference errors, it is necessary and critical to create a comprehensive and weighted data set of drug-target associations. Results In this study, we created a weighted and integrated drug-target interactome (WinDTome) to provide a comprehensive resource of drug-target associations for computational pharmacology. We first collected drug-target interactions from six commonly used drug-target centered data sources including DrugBank, KEGG, TTD, MATADOR, PDSP Ki Database, and BindingDB. Then, we employed the record linkage method to normalize drugs and targets to the unique identifiers by utilizing the public data sources including PubChem, Entrez Gene, and UniProt. To assess the reliability of the drug-target associations, we assigned two scores (Score_S and Score_R) to each drug-target association based on their data sources and publication references. Consequently, the WinDTome contains 546,196 drug-target associations among 303,018 compounds and 4,113 genes. To assess the application of the WinDTome, we designed a network-based approach for drug repurposing using mental disorder schizophrenia (SCZ) as a case. Starting from 41 known SCZ drugs and their targets, we inferred a total of 264 potential SCZ drugs through the associations of drug-target with Score_S higher than two in WinDTome and human protein-protein interactions. Among the 264 SCZ-related drugs, 39 drugs have been investigated in clinical trials for SCZ treatment and 74 drugs for the treatment of other mental disorders, respectively. Compared with the results using other

  7. Genetically engineered nanocarriers for drug delivery

    PubMed Central

    Shi, Pu; Gustafson, Joshua A; MacKay, J Andrew

    2014-01-01

    Cytotoxicity, low water solubility, rapid clearance from circulation, and off-target side-effects are common drawbacks of conventional small-molecule drugs. To overcome these shortcomings, many multifunctional nanocarriers have been proposed to enhance drug delivery. In concept, multifunctional nanoparticles might carry multiple agents, control release rate, biodegrade, and utilize target-mediated drug delivery; however, the design of these particles presents many challenges at the stage of pharmaceutical development. An emerging solution to improve control over these particles is to turn to genetic engineering. Genetically engineered nanocarriers are precisely controlled in size and structure and can provide specific control over sites for chemical attachment of drugs. Genetically engineered drug carriers that assemble nanostructures including nanoparticles and nanofibers can be polymeric or non-polymeric. This review summarizes the recent development of applications in drug and gene delivery utilizing nanostructures of polymeric genetically engineered drug carriers such as elastin-like polypeptides, silk-like polypeptides, and silk-elastin-like protein polymers, and non-polymeric genetically engineered drug carriers such as vault proteins and viral proteins. PMID:24741309

  8. Thermodynamic Studies for Drug Design and Screening

    PubMed Central

    Garbett, Nichola C.; Chaires, Jonathan B.

    2012-01-01

    Introduction A key part of drug design and development is the optimization of molecular interactions between an engineered drug candidate and its binding target. Thermodynamic characterization provides information about the balance of energetic forces driving binding interactions and is essential for understanding and optimizing molecular interactions. Areas covered This review discusses the information that can be obtained from thermodynamic measurements and how this can be applied to the drug development process. Current approaches for the measurement and optimization of thermodynamic parameters are presented, specifically higher throughput and calorimetric methods. Relevant literature for this review was identified in part by bibliographic searches for the period 2004 – 2011 using the Science Citation Index and PUBMED and the keywords listed below. Expert opinion The most effective drug design and development platform comes from an integrated process utilizing all available information from structural, thermodynamic and biological studies. Continuing evolution in our understanding of the energetic basis of molecular interactions and advances in thermodynamic methods for widespread application are essential to realize the goal of thermodynamically-driven drug design. Comprehensive thermodynamic evaluation is vital early in the drug development process to speed drug development towards an optimal energetic interaction profile while retaining good pharmacological properties. Practical thermodynamic approaches, such as enthalpic optimization, thermodynamic optimization plots and the enthalpic efficiency index, have now matured to provide proven utility in design process. Improved throughput in calorimetric methods remains essential for even greater integration of thermodynamics into drug design. PMID:22458502

  9. Clinically significant drug interactions.

    PubMed

    Ament, P W; Bertolino, J G; Liszewski, J L

    2000-03-15

    A large number of drugs are introduced every year, and new interactions between medications are increasingly reported. Consequently, it is no longer practical for physicians to rely on memory alone to avoid potential drug interactions. Multiple drug regimens carry the risk of adverse interactions. Precipitant drugs modify the object drug's absorption, distribution, metabolism, excretion or actual clinical effect. Nonsteroidal anti-inflammatory drugs, antibiotics and, in particular, rifampin are common precipitant drugs prescribed in primary care practice. Drugs with a narrow therapeutic range or low therapeutic index are more likely to be the objects for serious drug interactions. Object drugs in common use include warfarin, fluoroquinolones, antiepileptic drugs, oral contraceptives, cisapride and 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors. Many other drugs, act as precipitants or objects, and a number of drugs act as both. Regularly updated manuals of drug interactions and CD-ROM-formatted programs are useful office references. PMID:10750880

  10. Personality, Drug Preference, Drug Use, and Drug Availability

    ERIC Educational Resources Information Center

    Feldman, Marc; Boyer, Bret; Kumar, V. K.; Prout, Maurice

    2011-01-01

    This study examined the relationship between drug preference, drug use, drug availability, and personality among individuals (n = 100) in treatment for substance abuse in an effort to replicate the results of an earlier study (Feldman, Kumar, Angelini, Pekala, & Porter, 2007) designed to test prediction derived from Eysenck's (1957, 1967)…

  11. MTV Utility Library

    2008-02-29

    The MSV Java Utility Library contains software developed over many years for many sponsors. (This work is not a derivative of CB-EMIS), but rather support to the CB-EMIS software). Projects that have used and contributed to code in this library: CB-EMIS (PROTECT), BWIC, Fort Future, Teva, Integrated Oceans, ENKIMDU, RCW, JEMS, JWACS, EPA watershed, and many others. This library will continue to be used in other non-CB-EMIS related projects. The components include: Spatial components: Multi-coordinatemore » system spatial objects. 2D spatial indexing system, and polygon griding system. Data translation: Allows import and export of file based data to and from object oriented systems. Multi-platform data streams: Allows platform specific data streams to operate on any support platform. Other items include printing, custom GUI components, support for NIMA Raster Product Format, program logging utilities and others.« less

  12. MTV Utility Library

    SciTech Connect

    Lurie, Gordon; Taxon, Thomas; Kehrer, Michelle; Simunich, Kathy Lee

    2008-02-29

    The MSV Java Utility Library contains software developed over many years for many sponsors. (This work is not a derivative of CB-EMIS), but rather support to the CB-EMIS software). Projects that have used and contributed to code in this library: CB-EMIS (PROTECT), BWIC, Fort Future, Teva, Integrated Oceans, ENKIMDU, RCW, JEMS, JWACS, EPA watershed, and many others. This library will continue to be used in other non-CB-EMIS related projects. The components include: Spatial components: Multi-coordinate system spatial objects. 2D spatial indexing system, and polygon griding system. Data translation: Allows import and export of file based data to and from object oriented systems. Multi-platform data streams: Allows platform specific data streams to operate on any support platform. Other items include printing, custom GUI components, support for NIMA Raster Product Format, program logging utilities and others.

  13. MVUSRS utility reference manual

    SciTech Connect

    Brengle, T.A.

    1985-11-01

    The MVUSRS utility assists in the moving of TOPS-10/20 user accounts to VMS systems. MVUSRS runs on the source TOPS-10/20 system and combines user account information from the TOPS system (from REACT on TOPS-10 or from DLUSER on TOPS-20) with input from the operator of the utility to generate a VMS DCL COM file. This COM file can then be shipped to the target VMS system and executed. MVUSRS is known to work with TOPS-10 Version 4.01, TOPS-20 Version 5.1, and VMS Version 4.1. Other versions may work, but have not been tested. In particular, it is unlikely that MVUSRS will work with versions of VMS prior to 4.0 since much has been made of the enhanced user account information available in Version 4.0. The MVUSRS source listing is provided. (DWL)

  14. NASA's Technology Utilization Program.

    NASA Technical Reports Server (NTRS)

    Farley, C. F.

    1972-01-01

    NASA's Technology Utilization Program is described, illustrating how it can be useful in achieving improved productivity, providing more jobs, solving public sector challenges, and strengthening the international competitive situation. Underlying the program is the fact that research and development conducted in NASA's aeronautics and space programs have generated much technical information concerning processes, products, or techniques which may be useful to engineers, doctors, or to others. The program is based on acquisition and publication, working with the user, and applications engineering.

  15. Utility avoids cooling tower

    SciTech Connect

    1994-08-01

    After more than four years of often rancorous debate, New Jersey late last month approved a plan that permits the state`s largest utility to reclaim and restore Delaware Bay marshland instead of constructing a costly cooling tower for two nuclear power units. Environmental interests say they`ll appeal the wetlands proposal, calling it an {open_quotes}unproven experiment{close_quotes} that violates Clean Water Act provisions.

  16. Seasat data utilization project

    NASA Technical Reports Server (NTRS)

    Born, G. H.; Held, D. N.; Lame, D. B.; Lipes, R. G.; Montgomery, D. R.; Rygh, P. J.; Scott, J. F.

    1981-01-01

    During the three months of orbital operations, the satellite returned data from the world's oceans. Dozens of tropical storms, hurricanes and typhoons were observed, and two planned major intensive surface truth experiments were conducted. The utility of the Seasat-A microwave sensors as oceanographic tools was determined. Sensor and geophysical evaluations are discussed, including surface observations, and evaluation summaries of an altimeter, a scatterometer, a scanning multichannel microwave radiometer, a synthetic aperture radar, and a visible and infrared radiometer.

  17. Energy utilization in phonation

    NASA Astrophysics Data System (ADS)

    Krane, Michael

    2015-11-01

    A control volume analysis of energy utilization in phonation is presented. Conversion of subglottal airstream potential energy into work done vibrating the vocal folds, air flowing through the glottis, and radiating sound are described. An approximate numerical model is used to compute the contributions of each of these mechanisms, as a function of subglottal pressure, for normal phonation. An efficiency measure for each energy conversion mechanism is proposed. Acknowledge NIH grant 2R01 2R01DC005642.

  18. Ethics for electic utilities

    SciTech Connect

    Powers, C.W.; Toffler, B.L. )

    1991-05-15

    This article examines the ethical challenges of remaining honest and fair when the playing field of competition does not appear to be level. Topics discussed include measuring performance, monitoring use of services, public opinion of utility integrity and commitment to service, making ethical concerns and language a part of the management decision process, and communication of moral issues to a place where resolution can occur.

  19. 99 Films on Drugs.

    ERIC Educational Resources Information Center

    Weber, David O., Ed.

    This catalog describes and evaluates 16-millimeter films about various aspects of drug use. Among the subjects covered by the 99 films are the composition and effects of different drugs, reasons why people use drugs, life in the drug culture, the problem of law enforcement, and various means of dealing with drug users. Each film is synopsized. Two…

  20. Superhydrophobic materials for drug delivery

    NASA Astrophysics Data System (ADS)

    Yohe, Stefan Thomas

    Superhydrophobicity is a property of material surfaces reflecting the ability to maintain air at the solid-liquid interface when in contact with water. These surfaces have characteristically high apparent contact angles, by definition exceeding 150°, as a result of the composite material-air surface formed under an applied water droplet. Superhydrophobic surfaces were first discovered on naturally occurring substrates, and have subsequently been fabricated in the last several decades to harness these favorable surface properties for a number of emerging applications, including their use in biomedical settings. This work describes fabrication and characterization of superhydrophobic 3D materials, as well as their use as drug delivery devices. Superhydrophobic 3D materials are distinct from 2D superhydrophobic surfaces in that air is maintained not just at the surface of the material, but also within the bulk. When the superhydrophobic 3D materials are submerged in water, water infiltrates slowly and continuously as a new water-air-material interface is formed with controlled displacement of air. Electrospinning and electrospraying are used to fabricate superhydrophobic 3D materials utilizing blends of the biocompatible polymers poly(epsilon-caprolactone) and poly(caprolactone-co-glycerol monostearate) (PGC-C18). PGC-C18 is significantly more hydrophobic than PCL (contact angle of 116° versus 83° for flat materials), and further additions of PGC-C18 into electrospun meshes and electrosprayed coatings affords increased stability of the entrapped air layer. For example, PCL meshes alone (500 mum thick) take 10 days to fully wet, and with 10% or 30% PGC-C18 addition wetting rates are dramatically slowed to 60% wetted by 77 days and 4% by 75 days, respectively. Stability of the superhydrophobic materials can be further probed with a variety of physio-chemical techniques, including pressure, surfactant containing solutions, and solvents of varying surface tension

  1. Testing for Drug Hypersensitivity Syndromes

    PubMed Central

    Rive, Craig M; Bourke, Jack; Phillips, Elizabeth J

    2013-01-01

    Adverse drug reactions are a common cause of patient morbidity and mortality. Type B drug reactions comprise only 20% of all drug reactions but they tend to be primarily immunologically mediated and less dependent on the drug’s pharmacological action and dose. Common Type B reactions seen in clinical practice are those of the immediate, IgE, Gell-Coombs Type I reactions, and the delayed, T-cell mediated, Type IV reactions. Management of these types of reactions, once they have occurred, requires careful consideration and recognition of the utility of routine diagnostic tests followed by ancillary specialised diagnostic testing. For Type I, IgE mediated reactions this includes prick/intradermal skin testing and oral provocation. For Type IV, T-cell mediated reactions this includes a variety of in vivo (patch testing) and ex vivo tests, many of which are currently mainly used in highly specialised research laboratories. The recent association of many serious delayed (Type IV) hypersensitivity reactions to specific drugs with HLA class I and II alleles has created the opportunity for HLA screening to exclude high risk populations from exposure to the implicated drug and hence prevent clinical reactions. For example, the 100% negative predictive value of HLA-B*5701 for true immunologically mediated abacavir hypersensitivity and the development of feasible, inexpensive DNA-based molecular tests has led to incorporation of HLA-B*5701 screening in routine HIV clinical practice. The mechanism by which drugs specifically interact with HLA has been recently characterised and promises to lead to strategies for pre-clinical screening to inform drug development and design. PMID:23592889

  2. Prediction of Drug Combinations by Integrating Molecular and Pharmacological Data

    PubMed Central

    Zhao, Xing-Ming; Iskar, Murat; Zeller, Georg; Kuhn, Michael; van Noort, Vera; Bork, Peer

    2011-01-01

    Combinatorial therapy is a promising strategy for combating complex disorders due to improved efficacy and reduced side effects. However, screening new drug combinations exhaustively is impractical considering all possible combinations between drugs. Here, we present a novel computational approach to predict drug combinations by integrating molecular and pharmacological data. Specifically, drugs are represented by a set of their properties, such as their targets or indications. By integrating several of these features, we show that feature patterns enriched in approved drug combinations are not only predictive for new drug combinations but also provide insights into mechanisms underlying combinatorial therapy. Further analysis confirmed that among our top ranked predictions of effective combinations, 69% are supported by literature, while the others represent novel potential drug combinations. We believe that our proposed approach can help to limit the search space of drug combinations and provide a new way to effectively utilize existing drugs for new purposes. PMID:22219721

  3. Molecular science for drug development and biomedicine.

    PubMed

    Zhong, Wei-Zhu; Zhou, Shu-Feng

    2014-01-01

    With the avalanche of biological sequences generated in the postgenomic age, molecular science is facing an unprecedented challenge, i.e., how to timely utilize the huge amount of data to benefit human beings. Stimulated by such a challenge, a rapid development has taken place in molecular science, particularly in the areas associated with drug development and biomedicine, both experimental and theoretical. The current thematic issue was launched with the focus on the topic of "Molecular Science for Drug Development and Biomedicine", in hopes to further stimulate more useful techniques and findings from various approaches of molecular science for drug development and biomedicine.[...].

  4. Magnetic polymer nanospheres for anticancer drug targeting

    NASA Astrophysics Data System (ADS)

    Juríková, A.; Csach, K.; Koneracká, M.; Závišová, V.; Múčková, M.; Tomašovičová, N.; Lancz, G.; Kopčanský, P.; Timko, M.; Miškuf, J.

    2010-01-01

    Poly(D,L-lactide-co-glycolide) polymer (PLGA) nanospheres loaded with biocom-patible magnetic fluid as a magnetic carrier and anticancer drug Taxol were prepared by the modified nanoprecipitation method with size of 200-250 nm in diameter. The PLGA polymer was utilized as a capsulation material due to its biodegradability and biocompatibility. Taxol as an important anticancer drug was chosen for its significant role against a wide range of tumours. Thermal properties of the drug-polymer system were characterized using thermal analysis methods. It was determined the solubility of Taxol in PLGA nanospheres. Magnetic properties investigated using SQUID magnetometry showed superparamagnetism of the prepared magnetic polymer nanospheres.

  5. [Ilicit drugs frequently used by drug addicts].

    PubMed

    Cirriez, J P

    2015-03-01

    Drugs stimulate the brain causing mental and physical effects. The effects of drugs can be stimulating, narcotic or mind-altering. This article briefly discusses some commonly used illicit drugs, namely heroin, cocaine, cannabis, ecstasy, amphetamines, LSD, psilocybin mushrooms and poppers. PMID:26571792

  6. 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.

  7. Drug Use by Students of Drug Abuse

    ERIC Educational Resources Information Center

    Linder, Ronald; And Others

    1973-01-01

    The purpose of this study was to determine the significance of differences in the use of certain psychoactive drugs among students who enrolled for an elective drug abuse course and students not enrolled, or who have not previously taken a drug abuse course. (Author)

  8. Discontinued drugs in 2008: cardiovascular drugs.

    PubMed

    Zhang, Xu-Song; Xiang, Bing-Ren

    2009-07-01

    This perspective is part of an annual series of papers discussing drugs dropped from clinical development in the previous year. Specifically, this paper focuses on the 16 cardiovascular drugs discontinued in 2008. Information for this perspective was derived from a search of the Pharmaprojects database for drugs discontinued after reaching Phase I-III clinical trials. PMID:19548849

  9. Access to Investigational Drugs

    MedlinePlus

    ... drug if the supply is limited and the demand is high. Are all investigational drugs available through ... be limited in part by drug supply, patient demand, or other factors. What is NCI’s role in ...

  10. Drug Development Process

    MedlinePlus

    ... Approvals The Drug Development Process The Drug Development Process Share Tweet Linkedin Pin it More sharing options ... public. More Information More in The Drug Development Process Step 1: Discovery and Development Step 2: Preclinical ...

  11. Drugs Approved for Leukemia

    MedlinePlus

    ... Ask about Your Treatment Research Drugs Approved for Leukemia This page lists cancer drugs approved by the ... not listed here. Drugs Approved for Acute Lymphoblastic Leukemia (ALL) Abitrexate (Methotrexate) Arranon (Nelarabine) Asparaginase Erwinia chrysanthemi ...

  12. Drug Retention Times

    SciTech Connect

    Center for Human Reliability Studies

    2007-05-01

    The purpose of this monograph is to provide information on drug retention times in the human body. The information provided is based on plausible illegal drug use activities that might be engaged in by a recreational drug user.

  13. Drug Retention Times

    SciTech Connect

    Center for Human Reliability Studies

    2007-05-01

    The purpose of this monograph is to provide information on drug retention times in the human body. The information provided is based on plausible illegal drug use activities that might be engaged in by a recreational drug user

  14. Drug-induced hepatitis

    MedlinePlus

    Toxic hepatitis ... to get liver damage. Some drugs can cause hepatitis with small doses, even if the liver breakdown ... liver. Many different drugs can cause drug-induced hepatitis. Painkillers and fever reducers that contain acetaminophen are ...

  15. Nanocrystal technology, drug delivery and clinical applications

    PubMed Central

    Junghanns, Jens-Uwe A H; Müller, Rainer H

    2008-01-01

    Nanotechnology will affect our lives tremendously over the next decade in very different fields, including medicine and pharmacy. Transfer of materials into the nanodimension changes their physical properties which were used in pharmaceutics to develop a new innovative formulation principle for poorly soluble drugs: the drug nanocrystals. The drug nanocrystals do not belong to the future; the first products are already on the market. The industrially relevant production technologies, pearl milling and high pressure homogenization, are reviewed. The physics behind the drug nanocrystals and changes of their physical properties are discussed. The marketed products are presented and the special physical effects of nanocrystals explained which are utilized in each market product. Examples of products in the development pipelines (clinical phases) are presented and the benefits for in vivo administration of drug nanocrystals are summarized in an overview. PMID:18990939

  16. Designing Drug Trials: Considerations for Pregnant Women

    PubMed Central

    Sheffield, Jeanne S.; Siegel, David; Mirochnick, Mark; Heine, R. Phillips; Nguyen, Christine; Bergman, Kimberly L.; Savic, Rada M.; Long, Jill; Dooley, Kelly E.; Nesin, Mirjana

    2014-01-01

    Clinical pharmacology studies that describe the pharmacokinetics and pharmacodynamics of drugs in pregnant women are critical for informing on the safe and effective use of drugs during pregnancy. That being said, multiple factors have hindered the ability to study drugs in pregnant patients. These include concerns for maternal and fetal safety, ethical considerations, the difficulty in designing appropriate trials to assess the study objectives, and funding limitations. This document summarizes the recommendations of a panel of experts convened by the Division of Microbiology and Infectious Diseases at the National Institute of Allergy and Infectious Diseases, National Institutes of Health. These experts were charged with reviewing the issues related to the development of preclinical and clinical drug studies in pregnant women and to develop strategies for addressing these issues. These findings may also be utilized in the development of future drug studies involving pregnant women and their fetus/neonate. PMID:25425722

  17. Drug-induced impairment of renal function

    PubMed Central

    Pazhayattil, George Sunny; Shirali, Anushree C

    2014-01-01

    Pharmaceutical agents provide diagnostic and therapeutic utility that are central to patient care. However, all agents also carry adverse drug effect profiles. While most of these are clinically insignificant, some drugs may cause unacceptable toxicity that impacts negatively on patient morbidity and mortality. Recognizing adverse effects is important for administering appropriate drug doses, instituting preventive strategies, and withdrawing the offending agent due to toxicity. In the present article, we will review those drugs that are associated with impaired renal function. By focusing on pharmaceutical agents that are currently in clinical practice, we will provide an overview of nephrotoxic drugs that a treating physician is most likely to encounter. In doing so, we will summarize risk factors for nephrotoxicity, describe clinical manifestations, and address preventive and treatment strategies. PMID:25540591

  18. Role of computer-aided drug design in modern drug discovery.

    PubMed

    Macalino, Stephani Joy Y; Gosu, Vijayakumar; Hong, Sunhye; Choi, Sun

    2015-09-01

    Drug discovery utilizes chemical biology and computational drug design approaches for the efficient identification and optimization of lead compounds. Chemical biology is mostly involved in the elucidation of the biological function of a target and the mechanism of action of a chemical modulator. On the other hand, computer-aided drug design makes use of the structural knowledge of either the target (structure-based) or known ligands with bioactivity (ligand-based) to facilitate the determination of promising candidate drugs. Various virtual screening techniques are now being used by both pharmaceutical companies and academic research groups to reduce the cost and time required for the discovery of a potent drug. Despite the rapid advances in these methods, continuous improvements are critical for future drug discovery tools. Advantages presented by structure-based and ligand-based drug design suggest that their complementary use, as well as their integration with experimental routines, has a powerful impact on rational drug design. In this article, we give an overview of the current computational drug design and their application in integrated rational drug development to aid in the progress of drug discovery research.

  19. Time Functions as Utilities

    NASA Astrophysics Data System (ADS)

    Minguzzi, E.

    2010-09-01

    Every time function on spacetime gives a (continuous) total preordering of the spacetime events which respects the notion of causal precedence. The problem of the existence of a (semi-)time function on spacetime and the problem of recovering the causal structure starting from the set of time functions are studied. It is pointed out that these problems have an analog in the field of microeconomics known as utility theory. In a chronological spacetime the semi-time functions correspond to the utilities for the chronological relation, while in a K-causal (stably causal) spacetime the time functions correspond to the utilities for the K + relation (Seifert’s relation). By exploiting this analogy, we are able to import some mathematical results, most notably Peleg’s and Levin’s theorems, to the spacetime framework. As a consequence, we prove that a K-causal (i.e. stably causal) spacetime admits a time function and that the time or temporal functions can be used to recover the K + (or Seifert) relation which indeed turns out to be the intersection of the time or temporal orderings. This result tells us in which circumstances it is possible to recover the chronological or causal relation starting from the set of time or temporal functions allowed by the spacetime. Moreover, it is proved that a chronological spacetime in which the closure of the causal relation is transitive (for instance a reflective spacetime) admits a semi-time function. Along the way a new proof avoiding smoothing techniques is given that the existence of a time function implies stable causality, and a new short proof of the equivalence between K-causality and stable causality is given which takes advantage of Levin’s theorem and smoothing techniques.

  20. Raman Barcode for Counterfeit Drug Product Detection.

    PubMed

    Lawson, Latevi S; Rodriguez, Jason D

    2016-05-01

    Potential infiltration of counterfeit drug products-containing the wrong or no active pharmaceutical ingredient (API)-into the bona fide drug supply poses a significant threat to consumers worldwide. Raman spectroscopy offers a rapid, nondestructive avenue to screen a high throughput of samples. Traditional qualitative Raman identification is typically done with spectral correlation methods that compare the spectrum of a reference sample to an unknown. This is often effective for pure materials but is quite challenging when dealing with drug products that contain different formulations of active and inactive ingredients. Typically, reliable identification of drug products using common spectral correlation algorithms can only be made if the specific product under study is present in the library of reference spectra, thereby limiting the scope of products that can be screened. In this paper, we introduce the concept of the Raman barcode for identification of drug products by comparing the known peaks in the API reference spectrum to the peaks present in the finished drug product under study. This method requires the transformation of the Raman spectra of both API and finished drug products into a barcode representation by assigning zero intensity to every spectral frequency except the frequencies that correspond to Raman peaks. By comparing the percentage of nonzero overlap between the expected API barcode and finished drug product barcode, the identity of API present can be confirmed. In this study, 18 approved finished drug products and nine simulated counterfeits were successfully identified with 100% accuracy utilizing this method. PMID:27043140

  1. Cost-utility analysis in schizophrenia.

    PubMed

    Awad, A G; Voruganti, L P

    1999-01-01

    Estimation of quality of life is important to the study of the pharmacoeconomics of schizophrenia. The subject has gained popularity among policymakers, clinicians, and patients and their families, since the advent of new antipsychotic medications that are more expensive than older drugs yet have been shown to cause fewer side effects. Quantifying quality of life has been difficult, since studies often inconsistently define the concept or use rating scales that are inappropriate for the patient population. Utility analysis is a procedure that calculates subjects' preferences regarding living with various health states, given such options as trading more years of life at a lowered health state for dying sooner but having a strong health state during the last years of life. The feasibility of performing utility analysis among patients with schizophrenia was recently examined in a study carried out by the authors. This article reflects initial observations from that study of utility analysis and includes a discussion of problems still facing the study of quality of life and utility analysis.

  2. ORAL ADVERSE DRUG REACTIONS TO CARDIOVASCULAR DRUGS.

    PubMed

    Torpet, Lis Andersen; Kragelund, Camilla; Reibel, Jesper; Nauntofte, Birgitte

    2004-01-01

    A great many cardiovascular drugs (CVDs) have the potential to induce adverse reactions in the mouth. The prevalence of such reactions is not known, however, since many are asymptomatic and therefore are believed to go unreported. As more drugs are marketed and the population includes an increasing number of elderly, the number of drug prescriptions is also expected to increase. Accordingly, it can be predicted that the occurrence of adverse drug reactions (ADRs), including the oral ones (ODRs), will continue to increase. ODRs affect the oral mucous membrane, saliva production, and taste. The pathogenesis of these reactions, especially the mucosal ones, is largely unknown and appears to involve complex interactions among the drug in question, other medications, the patient's underlying disease, genetics, and life-style factors. Along this line, there is a growing interest in the association between pharmacogenetic polymorphism and ADRs. Research focusing on polymorphism of the cytochrome P450 system (CYPs) has become increasingly important and has highlighted the intra- and inter-individual responses to drug exposure. This system has recently been suggested to be an underlying candidate regarding the pathogenesis of ADRs in the oral mucous membrane. This review focuses on those CVDs reported to induce ODRs. In addition, it will provide data on specific drugs or drug classes, and outline and discuss recent research on possible mechanisms linking ADRs to drug metabolism patterns. Abbreviations used will be as follows: ACEI, ACE inhibitor; ADR, adverse drug reaction; ANA, antinuclear antigen; ARB, angiotensin II receptor blocker; BAB, beta-adrenergic blocker; CCB, calcium-channel blocker; CDR, cutaneous drug reaction; CVD, cardiovascular drug; CYP, cytochrome P450 enzyme; EM, erythema multiforme; FDE, fixed drug eruption; I, inhibitor of CYP isoform activity; HMG-CoA, hydroxymethyl-glutaryl coenzyme A; NAT, N-acetyltransferase; ODR, oral drug reaction; RDM, reactive

  3. Coming utility squeeze play

    SciTech Connect

    Stoiaken, L.N.

    1988-02-01

    Like a sleeping giant, utilities are waking up and preparing to participate in the increasingly competitive power production industry. Some are establishing subsidiaries to participate in join venture deals with independents. Others are competing by offering lucrative discount or deferral rates to important industrial and commercial customers considering cogeneration. And now, a third approach is beginning to shape up- the disaggregation of generation assets into a separate generation company, or genco. This article briefly discusses these three and also devotes brief sections to functional segmentation and The regulatory arena.

  4. Tribal Utility Feasibility Study

    SciTech Connect

    Engel, R. A.; Zoellick, J. J.

    2007-06-30

    The Schatz Energy Research Center (SERC) assisted the Yurok Tribe in investigating the feasibility of creating a permanent energy services program for the Tribe. The original purpose of the DOE grant that funded this project was to determine the feasibility of creating a full-blown Yurok Tribal electric utility to buy and sell electric power and own and maintain all electric power infrastructure on the Reservation. The original project consultant found this opportunity to be infeasible for the Tribe. When SERC took over as project consultant, we took a different approach. We explored opportunities for the Tribe to develop its own renewable energy resources for use on the Reservation and/or off-Reservation sales as a means of generating revenue for the Tribe. We also looked at ways the Tribe can provide energy services to its members and how to fund such efforts. We identified opportunities for the development of renewable energy resources and energy services on the Yurok Reservation that fall into five basic categories: • Demand-side management – This refers to efforts to reduce energy use through energy efficiency and conservation measures. • Off-grid, facility and household scale renewable energy systems – These systems can provide electricity to individual homes and Tribal facilities in areas of the Reservation that do not currently have access to the electric utility grid. • Village scale, micro-grid renewable energy systems - These are larger scale systems that can provide electricity to interconnected groups of homes and Tribal facilities in areas of the Reservation that do not have access to the conventional electric grid. This will require the development of miniature electric grids to serve these interconnected facilities. • Medium to large scale renewable energy development for sale to the grid – In areas where viable renewable energy resources exist and there is access to the conventional electric utility grid, these resources can be

  5. Classical subjective expected utility.

    PubMed

    Cerreia-Vioglio, Simone; Maccheroni, Fabio; Marinacci, Massimo; Montrucchio, Luigi

    2013-04-23

    We consider decision makers who know that payoff-relevant observations are generated by a process that belongs to a given class M, as postulated in Wald [Wald A (1950) Statistical Decision Functions (Wiley, New York)]. We incorporate this Waldean piece of objective information within an otherwise subjective setting à la Savage [Savage LJ (1954) The Foundations of Statistics (Wiley, New York)] and show that this leads to a two-stage subjective expected utility model that accounts for both state and model uncertainty. PMID:23559375

  6. TRW utility demonstration unit

    SciTech Connect

    Not Available

    1990-01-01

    The TRW Advanced Entrained Coal Combustor Demonstration Project consists of retrofitting Orange and Rockland (O R) Utility Corporation's Lovett Plant Unit No. 3 with four (4) slagging combustors which will allow the gas/oil unit to fire 2.5% sulfur coal. The slagging combustor process will provide NO{sub x} and SO{sub x} emissions that meet NSPS and New York State Environmental Standards. During this report period, activity continued to address the total program funding shortfall. Ideas and responsibilities for further evaluation have been put forward to reduce the shortfall. In addition, an effort aimed at gaining additional program sponsorships, was initiated.

  7. Space Resources Utilization Roundtable

    NASA Technical Reports Server (NTRS)

    1999-01-01

    This volume contains abstracts that have been accepted for presentation at the Space Resources Utilization Roundtable, October 27-29, 1999, in Golden, Colorado. The program committee consisted of M. B. Duke (Lunar and Planetary Institute), G. Baughman (Colorado School of Mines), D. Criswell (University of Houston), C. Graham (Canadian Mining Industry Research Organization), H. H. Schmitt (Apollo Astronaut), W. Sharp (Colorado School of Mines), L. Taylor (University of Tennessee), and a space manufacturing representative. Administration and publications support for this meeting were provided by the staff of the Publications and Program Services Department at the Lunar and Planetary Institute.

  8. Biogas: Production and utilization

    NASA Astrophysics Data System (ADS)

    Price, E. C.; Cheremisinoff, P. N.

    Among the aspects of biogas production and utilization covered are: (1) the microbiology and biochemistry of the acid and methane production stages in the anaerobic process; (2) factors affecting the process, such as temperature, acidity and alkalinity, nutrients, and cations; (3) denitrification processes and systems; and (4) the process kinetics of suspended growth systems, packed columns, and fluidized beds. Also considered are such issues in the application of this technology as the digestion of municipal treatment plant sludges, animal wastes, food processing wastes and energy crops. Attention is in addition given to anaerobic digester design, offgas measurement of anaerobic digesters, and sludge treatment through soil conditioning and composting.

  9. Resource recovery utility

    SciTech Connect

    Jones, R.L.

    1987-02-17

    This patent describes a resource recovery utility comprising: (i) a landfill; (ii) a continuous wall surrounding the perimeter of the landfill; (iii) a containment structure extending completely over the landfill and affixed to the continuous wall; (iv) means for introducing refuse into the landfill; (v) means for compacting the refuse; (vi) means for removing and recovering methane generated by anaerobic bacterial digestion of organic materials contained in the refuse; and (vii) means for removing at least a portion of the compacted refuse from the landfill.

  10. [Drug-induced dementia].

    PubMed

    Kojima, Taro; Akishita, Masahiro

    2016-03-01

    Many drugs have been reported to induce not only delirium but also cognitive impairment. Some types of drugs are reported to induce dementia, and prolonged hypotension or hypoglycemia induced by overuse of antihypertensive drugs or oral antidiabetic drugs could result in dementia. Recently, taking multiple drugs with anticholinergic activity are reported to cause cognitive decline and anticholinergic burden should be avoided especially in patients with dementia. Drug-induced dementia can be prevented by avoiding polypharmacy and adhering to the saying 'start low and go slow' . Early diagnosis of drug-induced dementia and withdrawal of the offending drug is essential to improve cognitive function. PMID:27025096

  11. Nanoencapsulation for drug delivery

    PubMed Central

    Kumari, Avnesh; Singla, Rubbel; Guliani, Anika; Yadav, Sudesh Kumar

    2014-01-01

    Nanoencapsulation of drug/small molecules in nanocarriers (NCs) is a very promising approach for development of nanomedicine. Modern drug encapsulation methods allow efficient loading of drug molecules inside the NCs thereby reducing systemic toxicity associated with drugs. Targeting of NCs can enhance the accumulation of nanonencapsulated drug at the diseased site. This article focussed on the synthesis methods, drug loading, drug release mechanism and cellular response of nanoencapsulated drugs on liposomes, micelles, carbon nanotubes, dendrimers, and magnetic NCs. Also the uses of these various NCs have been highlighted in the field of nanotechnology. PMID:26417260

  12. Predictors of Illicit Drug/s Use Among University Students in Northern Ireland, Wales and England

    PubMed Central

    Ansari, Walid El; Vallentin-Holbech, Lotte; Stock, Christiane

    2015-01-01

    Introduction: The use of illicit drug/s among university students is a public health concern. Nevertheless, many UK studies investigated a narrow spectrum of variables to explore their association/s with illicit drug/s use. Methods: We assessed the associations between a wide range of socio-demographic, health and wellbeing variables (independent variables) and having used illicit drug/s regularly, occasionally or never in life (dependent variables). Data (3706 students) were collected from seven universities in England, Wales, and Northern Ireland, using a self-administered questionnaire. Results: About 5% of the sample had regularly used illicit drug/s, 25% occasionally, and 70% never. Regular drug use (RDU) was significantly more likely among males aged 21-29 years, daily smokers, those with heavy episodic drinking or possible alcohol dependency (CAGE test), and those who perceived their academic performance better than their peers. RDU was less likely among students with high health awareness and those living with parents. The predictors of occasional drug use (ODU) were similar to those of RDU. However, in addition, students with higher perceived stress were less likely, and students who felt financial burden/s were more likely to report ODU, while no association with academic performance was found. Never use of illicit drug/s was inversely associated with most of the variables listed above, and was positively associated with religiosity. Illicit drug/s use goes along with other substance use (alcohol and smoking). The finding that illicit drug/s use was higher among students reporting good academic performance was surprising and raises the question of whether illicit drug/s may be used as performance enhancing drugs. Conclusion: The factors identified with illicit drug/s use in this study could be utilized to develop appropriate public health policies and preventive measures for the health of students. Multilevel, value based, comprehensive, and strategic

  13. Nuclear Receptors in Drug Metabolism, Drug Response and Drug Interactions

    PubMed Central

    Prakash, Chandra; Zuniga, Baltazar; Song, Chung Seog; Jiang, Shoulei; Cropper, Jodie; Park, Sulgi; Chatterjee, Bandana

    2016-01-01

    Orally delivered small-molecule therapeutics are metabolized in the liver and intestine by phase I and phase II drug-metabolizing enzymes (DMEs), and transport proteins coordinate drug influx (phase 0) and drug/drug-metabolite efflux (phase III). Genes involved in drug metabolism and disposition are induced by xenobiotic-activated nuclear receptors (NRs), i.e. PXR (pregnane X receptor) and CAR (constitutive androstane receptor), and by the 1α, 25-dihydroxy vitamin D3-activated vitamin D receptor (VDR), due to transactivation of xenobiotic-response elements (XREs) present in phase 0-III genes. Additional NRs, like HNF4-α, FXR, LXR-α play important roles in drug metabolism in certain settings, such as in relation to cholesterol and bile acid metabolism. The phase I enzymes CYP3A4/A5, CYP2D6, CYP2B6, CYP2C9, CYP2C19, CYP1A2, CYP2C8, CYP2A6, CYP2J2, and CYP2E1 metabolize >90% of all prescription drugs, and phase II conjugation of hydrophilic functional groups (with/without phase I modification) facilitates drug clearance. The conjugation step is mediated by broad-specificity transferases like UGTs, SULTs, GSTs. This review delves into our current understanding of PXR/CAR/VDR-mediated regulation of DME and transporter expression, as well as effects of single nucleotide polymorphism (SNP) and epigenome (specified by promoter methylation, histone modification, microRNAs, long non coding RNAs) on the expression of PXR/CAR/VDR and phase 0-III mediators, and their impacts on variable drug response. Therapeutic agents that target epigenetic regulation and the molecular basis and consequences (overdosing, underdosing, or beneficial outcome) of drug-drug/drug-food/drug-herb interactions are also discussed. Precision medicine requires understanding of a drug’s impact on DME and transporter activity and their NR-regulated expression in order to achieve optimal drug efficacy without adverse drug reactions. In future drug screening, new tools such as humanized mouse models and

  14. Utility Static Generation Reliability

    1993-03-05

    PICES (Probabilistic Investigation of Capacity and Energy Shortages) was developed for estimating an electric utility''s expected frequency and duration of capacity deficiencies on a daily on and off-peak basis. In addition to the system loss-of-load probability (LOLP) and loss-of-load expectation (LOLE) indices, PICES calculates the expected frequency and duration of system capacity deficiencies and the probability, expectation, and expected frequency and duration of a range of system reserve margin states. Results are aggregated and printedmore » on a weekly, monthly, or annual basis. The program employs hourly load data and either the two-state (on/off) or a more sophisticated three-state (on/partially on/fully off) generating unit representation. Unit maintenance schedules are determined on a weekly, levelized reserve margin basis. In addition to the 8760-hour annual load record, the user provides the following information for each unit: plant capacity, annual maintenance requirement, two or three-state unit failure and repair rates, and for three-state models, the partial state capacity deficiency. PICES can also supply default failure and repair rate values, based on the Edison Electric Institute''s 1979 Report on Equipment Availability for the Ten-Year Period 1968 Through 1977, for many common plant types. Multi-year analysis can be performed by specifying as input data the annual peak load growth rates and plant addition and retirement schedules for each year in the study.« less

  15. Lunar construction utility vehicle

    NASA Technical Reports Server (NTRS)

    1989-01-01

    The lunar construction utility vehicle (LCUV) is an all-purpose construction vehicle which will aid in the robotic assembly of a lunar outpost. The LCUV will have the following capabilities: (1) must be self supporting including repairs; (2) must offload itself from a lunar lander; (3) must be telerobotic and semi-autonomous; (4) must be able to transport one space station common module; (5) must allow for man-rated operation; and (6) must be able to move lunar regolith for site preparation. This study recommends the use of an elastic tracked vehicle. Detailed material analyses of most of the LCUV components were accomplished. The body frame, made of pinned truss elements, was stress analyzed using NASTRAN. A track connection system was developed; however, kinematic and stress analyses are still required. This design recommends the use of hydrogen-oxygen fuel cells for power. Thermal control has proven to be a problem which may be the most challenging technically. A tentative solution has been proposed which utilizes an onboard and towable radiator. Detailed study of the heat dissipation requirements is needed to finalize radiator sizing. Preliminary work on a man-rated cabin has begun; however, this is not required during the first mission phase of the LCUV. Finally, still in the conceptual phases, are the communication, navigation and mechanical arm systems.

  16. Stable isotope method to measure drug release from nanomedicines.

    PubMed

    Skoczen, Sarah; McNeil, Scott E; Stern, Stephan T

    2015-12-28

    Existing methods to measure nanomedicine drug release in biological matrices are inadequate. A novel drug release method utilizing a stable isotope tracer has been developed. Stable isotope-labeled drug is spiked into plasma containing nanomedicine. The labeled drug equilibrates with plasma components identical to the normoisotopic drug released from the nanomedicine formulation. Therefore, the ultrafilterable fraction of the isotope-labeled drug represents a reliable measure of free normoisotopic drug fraction in plasma, and can be used to calculate nanomedicine encapsulated and unencapsulated drug fractions. To demonstrate the utility of this method, we performed a plasma drug release study with both a fast releasing commercial docetaxel formulation, Taxotere®, and a delayed releasing nanomicellar formulation of a docetaxel prodrug, Procet 8. The instability of the unencapsulated prodrug in plasma allowed us to compare our calculated prodrug release and docetaxel conversion with the actual docetaxel concentration measured directly without fractionation. Drug release estimates for the fast releasing Taxotere formulation demonstrated accuracy deviation and precision (%CV) of <15%. For the controlled release Procet 8 formulation, we calculated a slow release and conversion of the prodrug in rat plasma that was highly correlated with the direct docetaxel measurement (R(2)=0.98). We believe that this method will have tremendous utility in the development and regulatory evaluation of nanomedicines, and aid in determination of generic bioequivalence.

  17. Teratogenic mechanisms of medical drugs.

    PubMed

    van Gelder, Marleen M H J; van Rooij, Iris A L M; Miller, Richard K; Zielhuis, Gerhard A; de Jong-van den Berg, Lolkje T W; Roeleveld, Nel

    2010-01-01

    BACKGROUND Although prescription drug use is common during pregnancy, the human teratogenic risks are undetermined for more than 90% of drug treatments approved in the USA during the past decades. A particular birth defect may have its origins through multiple mechanisms and possible exposures, including medications. A specific pathogenic process may result in different outcomes depending upon factors such as embryonic age at which a drug is administered, duration and dose of exposure and genetic susceptibility. This review focuses on the teratogenic mechanisms associated with a number of medications. METHODS We used three methods to identify the teratogenic mechanisms of medications: the MEDLINE and EMBASE databases, two recent books on teratogenic agents and a list of drugs classified as U.S. Food and Drug Administration class D or X. Mechanisms were included only if they are associated with major structural birth defects and medications that are used relatively frequently by women of reproductive age. RESULTS We identified six teratogenic mechanisms associated with medication use: folate antagonism, neural crest cell disruption, endocrine disruption, oxidative stress, vascular disruption and specific receptor- or enzyme-mediated teratogenesis. Many medications classified as class X are associated with at least one of these mechanisms. CONCLUSIONS Identifying teratogenic mechanisms may not only be relevant for etiologic and post-marketing research, but may also have implications for drug development and prescribing behavior for women of reproductive age, especially since combinations of seemingly unrelated prescription and over the counter medications may utilize similar teratogenic mechanisms with a resultant increased risk of birth defects. PMID:20061329

  18. Student Drug Usage and Self-Alienation.

    ERIC Educational Resources Information Center

    Fischler, Michael L.

    Utilizing responses (a self administered, 15 item questionnaire) of a rural northeastern New England sample of junior high, senior high, and college students, correlation between legal and illegal drug use and perceived self-alienation was examined. Comparison was also made between users and nonusers. Legal users were defined as those who made at…

  19. Pharmacogenomic Biomarkers: an FDA Perspective on Utilization in Biological Product Labeling.

    PubMed

    Schuck, Robert N; Grillo, Joseph A

    2016-05-01

    Precision medicine promises to improve both the efficacy and safety of therapeutic products by better informing why some patients respond well to a drug, and some experience adverse reactions, while others do not. Pharmacogenomics is a key component of precision medicine and can be utilized to select optimal doses for patients, more precisely identify individuals who will respond to a treatment and avoid serious drug-related toxicities. Since pharmacogenomic biomarker information can help inform drug dosing, efficacy, and safety, pharmacogenomic data are critically reviewed by FDA staff to ensure effective use of pharmacogenomic strategies in drug development and appropriate incorporation into product labels. Pharmacogenomic information may be provided in drug or biological product labeling to inform health care providers about the impact of genotype on response to a drug through description of relevant genomic markers, functional effects of genomic variants, dosing recommendations based on genotype, and other applicable genomic information. The format and content of labeling for biologic drugs will generally follow that of small molecule drugs; however, there are notable differences in pharmacogenomic information that might be considered useful for biologic drugs in comparison to small molecule drugs. Furthermore, the rapid entry of biologic drugs for treatment of rare genetic diseases and molecularly defined subsets of common diseases will likely lead to increased use of pharmacogenomic information in biologic drug labels in the near future. In this review, we outline the general principles of therapeutic product labeling and discuss the utilization of pharmacogenomic information in biologic drug labels. PMID:26912182

  20. Pharmacogenomic Biomarkers: an FDA Perspective on Utilization in Biological Product Labeling.

    PubMed

    Schuck, Robert N; Grillo, Joseph A

    2016-05-01

    Precision medicine promises to improve both the efficacy and safety of therapeutic products by better informing why some patients respond well to a drug, and some experience adverse reactions, while others do not. Pharmacogenomics is a key component of precision medicine and can be utilized to select optimal doses for patients, more precisely identify individuals who will respond to a treatment and avoid serious drug-related toxicities. Since pharmacogenomic biomarker information can help inform drug dosing, efficacy, and safety, pharmacogenomic data are critically reviewed by FDA staff to ensure effective use of pharmacogenomic strategies in drug development and appropriate incorporation into product labels. Pharmacogenomic information may be provided in drug or biological product labeling to inform health care providers about the impact of genotype on response to a drug through description of relevant genomic markers, functional effects of genomic variants, dosing recommendations based on genotype, and other applicable genomic information. The format and content of labeling for biologic drugs will generally follow that of small molecule drugs; however, there are notable differences in pharmacogenomic information that might be considered useful for biologic drugs in comparison to small molecule drugs. Furthermore, the rapid entry of biologic drugs for treatment of rare genetic diseases and molecularly defined subsets of common diseases will likely lead to increased use of pharmacogenomic information in biologic drug labels in the near future. In this review, we outline the general principles of therapeutic product labeling and discuss the utilization of pharmacogenomic information in biologic drug labels.

  1. Nanoparticles for Brain Drug Delivery

    PubMed Central

    Masserini, Massimo

    2013-01-01

    The central nervous system, one of the most delicate microenvironments of the body, is protected by the blood-brain barrier (BBB) regulating its homeostasis. BBB is a highly complex structure that tightly regulates the movement of ions of a limited number of small molecules and of an even more restricted number of macromolecules from the blood to the brain, protecting it from injuries and diseases. However, the BBB also significantly precludes the delivery of drugs to the brain, thus, preventing the therapy of a number of neurological disorders. As a consequence, several strategies are currently being sought after to enhance the delivery of drugs across the BBB. Within this review, the recently born strategy of brain drug delivery based on the use of nanoparticles, multifunctional drug delivery systems with size in the order of one-billionth of meters, is described. The review also includes a brief description of the structural and physiological features of the barrier and of the most utilized nanoparticles for medical use. Finally, the potential neurotoxicity of nanoparticles is discussed, and future technological approaches are described. The strong efforts to allow the translation from preclinical to concrete clinical applications are worth the economic investments. PMID:25937958

  2. Polymeric conjugates for drug delivery

    PubMed Central

    Larson, Nate; Ghandehari, Hamidreza

    2012-01-01

    The field of polymer therapeutics has evolved over the past decade and has resulted in the development of polymer-drug conjugates with a wide variety of architectures and chemical properties. Whereas traditional non-degradable polymeric carriers such as poly(ethylene glycol) (PEG) and N-(2-hydroxypropyl methacrylamide) (HPMA) copolymers have been translated to use in the clinic, functionalized polymer-drug conjugates are increasingly being utilized to obtain biodegradable, stimuli-sensitive, and targeted systems in an attempt to further enhance localized drug delivery and ease of elimination. In addition, the study of conjugates bearing both therapeutic and diagnostic agents has resulted in multifunctional carriers with the potential to both “see and treat” patients. In this paper, the rational design of polymer-drug conjugates will be discussed followed by a review of different classes of conjugates currently under investigation. The design and chemistry used for the synthesis of various conjugates will be presented with additional comments on their potential applications and current developmental status. PMID:22707853

  3. Optimal Electric Utility Expansion

    1989-10-10

    SAGE-WASP is designed to find the optimal generation expansion policy for an electrical utility system. New units can be automatically selected from a user-supplied list of expansion candidates which can include hydroelectric and pumped storage projects. The existing system is modeled. The calculational procedure takes into account user restrictions to limit generation configurations to an area of economic interest. The optimization program reports whether the restrictions acted as a constraint on the solution. All expansionmore » configurations considered are required to pass a user supplied reliability criterion. The discount rate and escalation rate are treated separately for each expansion candidate and for each fuel type. All expenditures are separated into local and foreign accounts, and a weighting factor can be applied to foreign expenditures.« less

  4. Asteroid exploration and utilization

    NASA Technical Reports Server (NTRS)

    Radovich, Brian M.; Carlson, Alan E.; Date, Medha D.; Duarte, Manny G.; Erian, Neil F.; Gafka, George K.; Kappler, Peter H.; Patano, Scott J.; Perez, Martin; Ponce, Edgar

    1992-01-01

    The Earth is nearing depletion of its natural resources at a time when human beings are rapidly expanding the frontiers of space. The resources possessed by asteroids have enormous potential for aiding and enhancing human space exploration as well as life on Earth. Project STONER (Systematic Transfer of Near Earth Resources) is based on mining an asteroid and transporting raw materials back to Earth. The asteroid explorer/sample return mission is designed in the context of both scenarios and is the first phase of a long range plan for humans to utilize asteroid resources. Project STONER is divided into two parts: asteroid selection and explorer spacecraft design. The spacecraft design team is responsible for the selection and integration of the subsystems: GNC, communications, automation, propulsion, power, structures, thermal systems, scientific instruments, and mechanisms used on the surface to retrieve and store asteroid regolith. The sample return mission scenario consists of eight primary phases that are critical to the mission.

  5. Proteomics: capacity versus utility.

    PubMed

    Harry, J L; Wilkins, M R; Herbert, B R; Packer, N H; Gooley, A A; Williams, K L

    2000-04-01

    Until recently scientists studied genes or proteins one at a time. With improvements in technology, new tools have become available to study the complex interactions that occur in biological systems. Global studies are required to do this, and these will involve genomic and proteomic approaches. High-throughput methods are necessary in each case because the number of genes and proteins in even the simplest of organisms are immense. In the developmental phase of genomics, the emphasis was on the generation and assembly of large amounts of nucleic acid sequence data. Proteomics is currently in a phase of technological development and establishment, and demonstrating the capacity for high throughput is a major challenge. However, funding bodies (both in the public and private sector) are increasingly focused on the usefulness of this capacity. Here we review the current state of proteome research in terms of capacity and utility.

  6. RFID Tag Helix Antenna Sensors for Wireless Drug Dosage Monitoring.

    PubMed

    Huang, Haiyu; Zhao, Peisen; Chen, Pai-Yen; Ren, Yong; Liu, Xuewu; Ferrari, Mauro; Hu, Ye; Akinwande, Deji

    2014-01-01

    Miniaturized helix antennas are integrated with drug reservoirs to function as RFID wireless tag sensors for real-time drug dosage monitoring. The general design procedure of this type of biomedical antenna sensors is proposed based on electromagnetic theory and finite element simulation. A cost effective fabrication process is utilized to encapsulate the antenna sensor within a biocompatible package layer using PDMS material, and at the same time form a drug storage or drug delivery unit inside the sensor. The in vitro experiment on two prototypes of antenna sensor-drug reservoir assembly have shown the ability to monitor the drug dosage by tracking antenna resonant frequency shift from 2.4-2.5-GHz ISM band with realized sensitivity of 1.27 [Formula: see text] for transdermal drug delivery monitoring and 2.76-[Formula: see text] sensitivity for implanted drug delivery monitoring. PMID:27170865

  7. Fighting the Drug War.

    ERIC Educational Resources Information Center

    The Journal of State Government, 1990

    1990-01-01

    All nine articles in this periodical issue focus on the theme of the war against illegal drug use, approaching the topic from a variety of perspectives. The articles are: "The Drug War: Meeting the Challenge" (Stanley E. Morris); "Ways to Fight Drug Abuse" (Bruce A. Feldman); "Treatment Key to Fighting Drugs" (Stan Lundine); "Patience and…

  8. What Are Drugs?

    ERIC Educational Resources Information Center

    Minnesota Police and Peace Officers Association.

    This guide for parents presents, in Laotian and English, information about drugs, drug use and abuse, and treatment for drug use. Most of the information is presented in question and answer form to give parents the information they need to answer their children's questions and help prevent drug use. The following sections are included: (1)…

  9. Drugs and Young People

    MedlinePlus

    Drug abuse is a serious public health problem. It affects almost every community and family in some way. Drug abuse in children and teenagers may pose a ... of young people may be more susceptible to drug abuse and addiction than adult brains. Abused drugs ...

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

    PubMed Central

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

    2015-01-01

    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. PMID:26456240

  11. Nano- and microfabrication for overcoming drug delivery challenges

    PubMed Central

    Kam, Kimberly R.

    2013-01-01

    This highlight article describes current nano- and microfabrication techniques for creating drug delivery devices. We first review the main physiological barriers to delivering therapeutic agents. Then, we describe how novel fabrication methods can be utilized to combine many features into a single physiologically relevant device to overcome drug delivery challenges. PMID:23730504

  12. The tuberculosis drug discovery and development pipeline and emerging drug targets.

    PubMed

    Mdluli, Khisimuzi; Kaneko, Takushi; Upton, Anna

    2015-06-01

    The recent accelerated approval for use in extensively drug-resistant and multidrug-resistant-tuberculosis (MDR-TB) of two first-in-class TB drugs, bedaquiline and delamanid, has reinvigorated the TB drug discovery and development field. However, although several promising clinical development programs are ongoing to evaluate new TB drugs and regimens, the number of novel series represented is few. The global early-development pipeline is also woefully thin. To have a chance of achieving the goal of better, shorter, safer TB drug regimens with utility against drug-sensitive and drug-resistant disease, a robust and diverse global TB drug discovery pipeline is key, including innovative approaches that make use of recently acquired knowledge on the biology of TB. Fortunately, drug discovery for TB has resurged in recent years, generating compounds with varying potential for progression into developable leads. In parallel, advances have been made in understanding TB pathogenesis. It is now possible to apply the lessons learned from recent TB hit generation efforts and newly validated TB drug targets to generate the next wave of TB drug leads. Use of currently underexploited sources of chemical matter and lead-optimization strategies may also improve the efficiency of future TB drug discovery. Novel TB drug regimens with shorter treatment durations must target all subpopulations of Mycobacterium tuberculosis existing in an infection, including those responsible for the protracted TB treatment duration. This review summarizes the current TB drug development pipeline and proposes strategies for generating improved hits and leads in the discovery phase that could help achieve this goal. PMID:25635061

  13. Pharmacogenomics and adverse drug reactions in children

    PubMed Central

    Rieder, Michael J.; Carleton, Bruce

    2014-01-01

    Adverse drug reactions are a common and important complication of drug therapy in children. Over the past decade it has become increasingly apparent that genetically controlled variations in drug disposition and response are important determinants of adverse events for many important adverse events associated with drug therapy in children. While this research has been difficult to conduct over the past decade technical and ethical evolution has greatly facilitated the ability of investigators to conduct pharmacogenomic studies in children. Some of this research has already resulted in changes in public policy and clinical practice, for example in the case of codeine use by mothers and children. It is likely that the use of pharmacogenomics to enhance drug safety will first be realized among selected groups of children with high rates of drug use such as children with cancer, but it also likely that this research will be extended to other groups of children who have high rates of drug utilization and as well as providing insights into the mechanisms and pathophysiology of adverse drug reactions in children. PMID:24795743

  14. A wireless actuating drug delivery system

    NASA Astrophysics Data System (ADS)

    Jo, Won-Jun; Baek, Seung-Ki; Park, Jung-Hwan

    2015-04-01

    A wireless actuating drug delivery system was devised. The system is based on induction heating for drug delivery. In this study, thermally generated nitrogen gas produced by induction heating of azobisisobutyronitrile (AIBN) was utilized for pressure-driven release of the drug. The delivery device consists of an actuator chamber, a drug reservoir, and a microchannel. A semicircular copper disc (5 and 6 mm in diameter and 100 µm thick), and thermal conductive tape were integrated as the heating element in the actuator chamber. The final device was 2.7 mm thick. 28 µl of drug solution were placed in the reservoir and the device released the drug quickly at the rate of 6 µl s-1 by induction heating at 160 µT of magnetic intensity. The entire drug solution was released and dispersed after subcutaneous implantation under identical experimental condition. This study demonstrates that the device was simply prepared and drug delivery could be achieved by wireless actuation of a thin, pressure-driven actuator.

  15. Electroresponsive nanoparticles for drug delivery on demand

    NASA Astrophysics Data System (ADS)

    Samanta, Devleena; Hosseini-Nassab, Niloufar; Zare, Richard N.

    2016-04-01

    The potential of electroresponsive conducting polymer nanoparticles to be used as general drug delivery systems that allow electrically pulsed, linearly scalable, and on demand release of incorporated drugs is demonstrated. As examples, facile release from polypyrrole nanoparticles is shown for fluorescein, a highly water-soluble model compound, piroxicam, a lipophilic small molecule drug, and insulin, a large hydrophilic peptide hormone. The drug loading is about 13 wt% and release is accomplished in a few seconds by applying a weak constant current or voltage. To identify the parameters that should be finely tuned to tailor the carrier system for the release of the therapeutic molecule of interest, a systematic study of the factors that affect drug delivery is performed, using fluorescein as a model compound. The parameters studied include current, time, voltage, pH, temperature, particle concentration, and ionic strength. Results indicate that there are several degrees of freedom that can be optimized for efficient drug delivery. The ability to modulate linearly drug release from conducting polymers with the applied stimulus can be utilized to design programmable and minimally invasive drug delivery devices.

  16. Electroresponsive nanoparticles for drug delivery on demand.

    PubMed

    Samanta, Devleena; Hosseini-Nassab, Niloufar; Zare, Richard N

    2016-04-28

    The potential of electroresponsive conducting polymer nanoparticles to be used as general drug delivery systems that allow electrically pulsed, linearly scalable, and on demand release of incorporated drugs is demonstrated. As examples, facile release from polypyrrole nanoparticles is shown for fluorescein, a highly water-soluble model compound, piroxicam, a lipophilic small molecule drug, and insulin, a large hydrophilic peptide hormone. The drug loading is about 13 wt% and release is accomplished in a few seconds by applying a weak constant current or voltage. To identify the parameters that should be finely tuned to tailor the carrier system for the release of the therapeutic molecule of interest, a systematic study of the factors that affect drug delivery is performed, using fluorescein as a model compound. The parameters studied include current, time, voltage, pH, temperature, particle concentration, and ionic strength. Results indicate that there are several degrees of freedom that can be optimized for efficient drug delivery. The ability to modulate linearly drug release from conducting polymers with the applied stimulus can be utilized to design programmable and minimally invasive drug delivery devices. PMID:27088543

  17. Nanotransporters for drug delivery.

    PubMed

    Lühmann, Tessa; Meinel, Lorenz

    2016-06-01

    Soluble nanotransporters for drugs can be profiled for targeted delivery particularly to maximize the efficacy of highly potent drugs while minimizing off target effects. This article outlines on the use of biological carrier molecules with a focus on albumin, various drug linkers for site specific release of the drug payload from the nanotransporter and strategies to combine these in various ways to meet different drug delivery demands particularly the optimization of the payload per nanotransporter.

  18. Do national medicinal drug policies and essential drug programs improve drug use?: a review of experiences in developing countries.

    PubMed

    Ratanawijitrasin, S; Soumerai, S B; Weerasuriya, K

    2001-10-01

    Increasing concerns regarding access to and appropriateness of medicinal drug use have led many governments in developing countries to develop national policies and regulations intended to increase the affordability, supply, safety, and rational use of pharmaceuticals. However, little is known about the intended and unintended impacts of these social experiments on actual drug use. We conducted a critical review and synthesis of the international literature in an attempt to define the current state of knowledge regarding drug policy effects on drug use, and to extract from the evidence important lessons for future policy and research. Literature sources included the archives and computerized databases, articles published in medical and pharmacy journals, as well as published annotated bibliographies. The evaluated interventions included three broad categories: (1) multi-component national drug policies including essential drug programs; (2) drug supply and cost-sharing programs; and (3) regulatory measures. Most of these studies utilized weak research designs that evaluated programs solely on the basis of post-intervention measures. Only two studies measured pre-policy utilization, but did not include a control group. Thus, none of the results are conclusive, and the findings represent, at best, hypotheses for more rigorous studies of policy impacts. Some suggestive findings include an association between increases in the supply of essential drugs (combined with training) and more appropriate use of medications in primary care settings. In addition, preliminary data suggest some unintended effects of de-registration of drugs or upward reclassification of specific medicines. Similarly, loosening restrictions have sometimes been accompanied by increased dispensing of specific drugs by unqualified personnel. The available studies focused only on a few categories of national and regulatory policies. Because of poor study design, the results do not provide valid data to

  19. Towards drug repositioning: a unified computational framework for integrating multiple aspects of drug similarity and disease similarity.

    PubMed

    Zhang, Ping; Wang, Fei; Hu, Jianying

    2014-01-01

    In response to the high cost and high risk associated with traditional de novo drug discovery, investigation of potential additional uses for existing drugs, also known as drug repositioning, has attracted increasing attention from both the pharmaceutical industry and the research community. In this paper, we propose a unified computational framework, called DDR, to predict novel drug-disease associations. DDR formulates the task of hypothesis generation for drug repositioning as a constrained nonlinear optimization problem. It utilizes multiple drug similarity networks, multiple disease similarity networks, and known drug-disease associations to explore potential new associations among drugs and diseases with no known links. A large-scale study was conducted using 799 drugs against 719 diseases. Experimental results demonstrated the effectiveness of the approach. In addition, DDR ranked drug and disease information sources based on their contributions to the prediction, thus paving the way for prioritizing multiple data sources and building more reliable drug repositioning models. Particularly, some of our novel predictions of drug-disease associations were supported by clinical trials databases, showing that DDR could serve as a useful tool in drug discovery to efficiently identify potential novel uses for existing drugs. PMID:25954437

  20. Towards Drug Repositioning: A Unified Computational Framework for Integrating Multiple Aspects of Drug Similarity and Disease Similarity

    PubMed Central

    Zhang, Ping; Wang, Fei; Hu, Jianying

    2014-01-01

    In response to the high cost and high risk associated with traditional de novo drug discovery, investigation of potential additional uses for existing drugs, also known as drug repositioning, has attracted increasing attention from both the pharmaceutical industry and the research community. In this paper, we propose a unified computational framework, called DDR, to predict novel drug-disease associations. DDR formulates the task of hypothesis generation for drug repositioning as a constrained nonlinear optimization problem. It utilizes multiple drug similarity networks, multiple disease similarity networks, and known drug-disease associations to explore potential new associations among drugs and diseases with no known links. A large-scale study was conducted using 799 drugs against 719 diseases. Experimental results demonstrated the effectiveness of the approach. In addition, DDR ranked drug and disease information sources based on their contributions to the prediction, thus paving the way for prioritizing multiple data sources and building more reliable drug repositioning models. Particularly, some of our novel predictions of drug-disease associations were supported by clinical trials databases, showing that DDR could serve as a useful tool in drug discovery to efficiently identify potential novel uses for existing drugs. PMID:25954437

  1. Towards drug repositioning: a unified computational framework for integrating multiple aspects of drug similarity and disease similarity.

    PubMed

    Zhang, Ping; Wang, Fei; Hu, Jianying

    2014-01-01

    In response to the high cost and high risk associated with traditional de novo drug discovery, investigation of potential additional uses for existing drugs, also known as drug repositioning, has attracted increasing attention from both the pharmaceutical industry and the research community. In this paper, we propose a unified computational framework, called DDR, to predict novel drug-disease associations. DDR formulates the task of hypothesis generation for drug repositioning as a constrained nonlinear optimization problem. It utilizes multiple drug similarity networks, multiple disease similarity networks, and known drug-disease associations to explore potential new associations among drugs and diseases with no known links. A large-scale study was conducted using 799 drugs against 719 diseases. Experimental results demonstrated the effectiveness of the approach. In addition, DDR ranked drug and disease information sources based on their contributions to the prediction, thus paving the way for prioritizing multiple data sources and building more reliable drug repositioning models. Particularly, some of our novel predictions of drug-disease associations were supported by clinical trials databases, showing that DDR could serve as a useful tool in drug discovery to efficiently identify potential novel uses for existing drugs.

  2. YEAR 2 BIOMASS UTILIZATION

    SciTech Connect

    Christopher J. Zygarlicke

    2004-11-01

    This Energy & Environmental Research Center (EERC) Year 2 Biomass Utilization Final Technical Report summarizes multiple projects in biopower or bioenergy, transportation biofuels, and bioproducts. A prototype of a novel advanced power system, termed the high-temperature air furnace (HITAF), was tested for performance while converting biomass and coal blends to energy. Three biomass fuels--wood residue or hog fuel, corn stover, and switchgrass--and Wyoming subbituminous coal were acquired for combustion tests in the 3-million-Btu/hr system. Blend levels were 20% biomass--80% coal on a heat basis. Hog fuel was prepared for the upcoming combustion test by air-drying and processing through a hammer mill and screen. A K-Tron biomass feeder capable of operating in both gravimetric and volumetric modes was selected as the HITAF feed system. Two oxide dispersion-strengthened (ODS) alloys that would be used in the HITAF high-temperature heat exchanger were tested for slag corrosion rates. An alumina layer formed on one particular alloy, which was more corrosion-resistant than a chromia layer that formed on the other alloy. Research activities were completed in the development of an atmospheric pressure, fluidized-bed pyrolysis-type system called the controlled spontaneous reactor (CSR), which is used to process and condition biomass. Tree trimmings were physically and chemically altered by the CSR process, resulting in a fuel that was very suitable for feeding into a coal combustion or gasification system with little or no feed system modifications required. Experimental procedures were successful for producing hydrogen from biomass using the bacteria Thermotoga, a deep-ocean thermal vent organism. Analytical procedures for hydrogen were evaluated, a gas chromatography (GC) method was derived for measuring hydrogen yields, and adaptation culturing and protocols for mutagenesis were initiated to better develop strains that can use biomass cellulose. Fly ash derived from

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

    PubMed

    Lee, Juliet P; Antin, Tamar M J

    2012-01-01

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

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

    PubMed Central

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

    2011-01-01

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

  5. Immunotherapy for Drug Abuse

    PubMed Central

    Shen, Xiaoyun; Kosten, Thomas R.

    2013-01-01

    Substance use disorders continue to be major medical and social problems worldwide. Current medications for substance use disorders have many limitations such as cost, availability, medication compliance, dependence, diversion of some to illicit use and relapse to addiction after discontinuing their use. Immunotherapies using either passive monoclonal antibodies or active vaccines have distinctly different mechanisms and therapeutic utility from small molecule approaches to treatment. They have great potential to help the patient achieve and sustain abstinence and have fewer of the above limitations. This review covers the cocaine vaccine development in detail and provides an overview of directions for developing anti-addiction vaccines against the abuse of other substances. The notable success of the first placebo-controlled clinical trial of a cocaine vaccine, TA-CD, has led to an ongoing multi-site, Phase IIb clinical trial in 300 subjects. The results from these trials are encouarging further development of the cocaine vacine as one of the first anti-addiction vaccines to go forward to the U.S. Food and Drug Administration for review and approval for human use. PMID:22229313

  6. National Utility Rate Database: Preprint

    SciTech Connect

    Ong, S.; McKeel, R.

    2012-08-01

    When modeling solar energy technologies and other distributed energy systems, using high-quality expansive electricity rates is essential. The National Renewable Energy Laboratory (NREL) developed a utility rate platform for entering, storing, updating, and accessing a large collection of utility rates from around the United States. This utility rate platform lives on the Open Energy Information (OpenEI) website, OpenEI.org, allowing the data to be programmatically accessed from a web browser, using an application programming interface (API). The semantic-based utility rate platform currently has record of 1,885 utility rates and covers over 85% of the electricity consumption in the United States.

  7. Utilization management in anatomic pathology.

    PubMed

    Lewandrowski, Kent; Black-Schaffer, Steven

    2014-01-01

    There is relatively little published literature concerning utilization management in anatomic pathology. Nonetheless there are many utilization management opportunities that currently exist and are well recognized. Some of these impact only the cost structure within the pathology department itself whereas others reduce charges for third party payers. Utilization management may result in medical legal liabilities for breaching the standard of care. For this reason it will be important for pathology professional societies to develop national utilization guidelines to assist individual practices in implementing a medically sound approach to utilization management.

  8. Herb-drug, food-drug, nutrient-drug, and drug-drug interactions: mechanisms involved and their medical implications.

    PubMed

    Sørensen, Janina Maria

    2002-06-01

    Adverse drug reactions (ADRs) and iatrogenic diseases have been identified as significant factors responsible for patient morbidity and mortality. Significant studies on drug metabolism in humans have been published during the last few years, offering a deeper comprehension of the mechanisms underlying adverse drug reactions and interactions. More understanding of these mechanisms, and of recent advances in laboratory technology, can help to evaluate potential drug interactions when drugs are prescribed concurrently. Increasing knowledge of interindividual variation in drug breakdown capacity and recent findings concerning the influence of environment, diet, nutrients, and herbal products can be used to reduce ADRs and iatrogenic diseases. Reviewed data suggest that drug treatment should be increasingly custom tailored to suit the individual patient and that appropriately co-prescribed diet and herbal remedies, could increase drug efficacy and lessen drug toxicity. This review focuses mainly on recently published research material. The cytochrome p450 enzymes, their role in metabolism, and their mechanisms of action are reviewed, and their role in drug-drug interactions are discussed. Drug-food and drug-herb interactions have garnered attention. Interdisciplinary communication among medical herbalists, medical doctors, and dietetic experts needs to be improved and encouraged. Internet resources for obtaining current information regarding drug-drug, drug-herb, and drug-nutrient interactions are provided. PMID:12165187

  9. PFBC Utility Demonstration Project

    SciTech Connect

    Not Available

    1992-11-01

    This report provides a summary of activities by American Electric Power Service Corporation during the first budget period of the PFBC Utility Demonstration Project. In April 1990, AEP signed a Cooperative Agreement with the US Department of Energy to repower the Philip Sporn Plant, Units 3 4 in New Haven, West Virginia, with a 330 KW PFBC plant. The purpose of the program was to demonstrate and verify PFBC in a full-scale commercial plant. The technical and cost baselines of the Cooperative Agreement were based on a preliminary engineering and design and a cost estimate developed by AEP subsequent to AEP's proposal submittal in May 1988, and prior to the signing of the Cooperative Agreement. The Statement of Work in the first budget period of the Cooperative Agreement included a task to develop a preliminary design and cost estimate for erecting a Greenfield plant and to conduct a comparison with the repowering option. The comparative assessment of the options concluded that erecting a Greenfield plant rather than repowering the existing Sporn Plant could be the technically and economically superior alternative. The Greenfield plant would have a capacity of 340 MW. The ten additional MW output is due to the ability to better match the steam cycle to the PFBC system with a new balance of plant design. In addition to this study, the conceptual design of the Sporn Repowering led to several items which warranted optimization studies with the goal to develop a more cost effective design.

  10. Wind power utilization guide

    NASA Astrophysics Data System (ADS)

    Pal, D.

    1981-09-01

    This report presents general information covering site wind potential and characteristics, specific design, system design, and siting requirements for utilization of wind energy conversion systems (WECS) at Navy installations. The objective of this report is also to provide a method for performing economic analysis to plan and justify a WECS in a particular Navy application. The information presented here is sufficient to enable an engineer to prepare a system's design to conduct a feasibility study for a given application of WECS. Most Navy applications of wind power will involve generation of electricity using small wind turbine generators (less than 60 kW size), with or without storage, located at remote Navy sites. Larger (over 100 kW size) WECS will, generally, be integrated with a base grid located on remote overseas or CONUS bases. This report, however, deals only with guidance for applying small WECS at Navy installations. The subject matter is divided into five parts dealing respectively with wind behavior and its determination with wind-driven turbines, power conditioning requirements, siting requirements, and the economics of wind power under different conditions. Three examples are given to demonstrate use of these sections in developing the required feasibility or design information for a given application.

  11. Space Resources Utilization Roundtable

    NASA Astrophysics Data System (ADS)

    1999-01-01

    This volume contains abstracts on various topics. These topics include; Economics of Lunar Mineral Exploration; Lunar Solar Power System and Lunar Development; Space Resource Roundtable Rationale; Successfully Mining Asteroids and Comets; Lunar Polar Ice: Method for Mining the New Resource for Exploration; Acoustic Shaping: Enabling Technology for a Space-based Economy; Return to the Moon: A New Strategic Evaluation; Spacewatch Discovery and Study of Accessible Asteroids; Role of Mining in Space Development; A Commercial/Lunar Resources Exploration Concept; Radar Reconnaissance of Near-Earth Asteroids; Solar Energy Conversion Using In Situ Lunar Soil; The Application of Thermal Plasmas to Ore Reduction for In Situ Resource Utilization; Prospecting Near-Earth Asteroids from the Ground; Some Implications of Space Tourism for Extraterrestrial Resources; An Overview of NASA's Current In Situ Consumable Production (ISCP) Development Activities and Goals; Prospectives on Lunar Helium-3; Self-Propagating High-Temperature Synthesis for In Situ Materials Processing; Subsurface Exploration from Lander and Rover Platforms with Seismic Surface Waves; Space Weathering and the Formation of Lunar Soil: The Moon as the Model for all Airless Bodies in the Solar System; and Acoustic Shaping in Microgravity: Technology Issues.

  12. Utilization of hospital resources.

    PubMed

    Black, C D; Roos, N P; Burchill, C A

    1995-12-01

    A population-based approach was used to analyze the utilization patterns of hospital care by Manitoba residents during the fiscal year 1991/1992. Patterns were analyzed for eight administrative regions, with use assigned to the patient's region of residence, regardless of the location of the hospitalization. Regional boundaries consistent with those used for presentation of data on health status and socioeconomic risk permitted integration of findings across the Population Health Information System. Marked differences in acute hospital use were found. Residents of the urban Winnipeg ("good health") region had the lowest rates of use of acute care overall, and northern rural ("poor health") regions had significantly higher rates of use. However, almost one half of hospital days by Winnipeg residents were used in long-stay care (60+ days), while rural residents were more likely to use short-stay hospital care. Despite a concentration of surgical specialists in Winnipeg, there were only small regional differences in overall rates of surgery. PMID:7500670

  13. Gas utilization technologies

    SciTech Connect

    Biljetina, R.

    1994-09-01

    One of the constant challenges facing the research community is the identification of technology needs 5 to 15 years from now. A look back into history indicates that the forces driving natural gas research have changed from decade to decade. In the 1970s research was driven by concerns for adequate supply; in the 1980s research was aimed at creating new markets for natural gas. What then are the driving forces for the 1990s? Recent reports from the natural gas industry have helped define a new direction driven primarily by market demand for natural gas. A study prepared by the Interstate Natural Gas Association of America Foundation entitled ``Survey of Natural Research, Development, and Demonstration RD&D Priorities`` indicated that in the 1990s the highest research priority should be for natural gas utilization and that technology development efforts should not only address efficiency and cost, but environmental and regulatory issues as well. This study and others, such as the report by the American Gas Association (A.G.A.) entitled ``Strategic Vision for Natural Gas Through the Year 2000,`` clearly identify the market sectors driving today`s technology development needs. The biggest driver is the power generation market followed by the industrial, transportation, appliance, and gas cooling markets. This is best illustrated by the GRI 1994 Baseline Projection on market growth in various sectors between the year 1992 and 2010. This paper highlights some of the recent technology developments in each one of these sectors.

  14. Do drug offences matter?

    PubMed

    Gordon, A M

    1978-07-15

    Drug offences in addicts are often thought to indicate little more than continued dependency. In a four-year follow-up study of 60 men attending a drug clinic a history of repeated convictions for drug offences was found to be strongly related to patterns of delinquency. The following variables were associated with a history of repeated drug offences: a higher conviction rate for "non-drug" offences; younger age at first conviction; conviction preceding drug use; convictions for offences of sex and violence; longer prison sentences; and regular narcotic use and continued dependency at follow-up. Receiving a clinic prescription was not associated with a lower incidence of drug offences. Repeated drug offences identified a subgroup of drug users who were characterised by extensive sociopathic behaviour. Such offences should not be dismissed as an unavoidable, unimportant part of addiction. PMID:678840

  15. Microneedle Coating Techniques for Transdermal Drug Delivery

    PubMed Central

    Haj-Ahmad, Rita; Khan, Hashim; Arshad, Muhammad Sohail; Rasekh, Manoochehr; Hussain, Amjad; Walsh, Susannah; Li, Xiang; Chang, Ming-Wei; Ahmad, Zeeshan

    2015-01-01

    Drug administration via the transdermal route is an evolving field that provides an alternative to oral and parenteral routes of therapy. Several microneedle (MN) based approaches have been developed. Among these, coated MNs (typically where drug is deposited on MN tips) are a minimally invasive method to deliver drugs and vaccines through the skin. In this review, we describe several processes to coat MNs. These include dip coating, gas jet drying, spray coating, electrohydrodynamic atomisation (EHDA) based processes and piezoelectric inkjet printing. Examples of process mechanisms, conditions and tested formulations are provided. As these processes are independent techniques, modifications to facilitate MN coatings are elucidated. In summary, the outcomes and potential value for each technique provides opportunities to overcome formulation or dosage form limitations. While there are significant developments in solid degradable MNs, coated MNs (through the various techniques described) have potential to be utilized in personalized drug delivery via controlled deposition onto MN templates. PMID:26556364

  16. Drugs and drug administration in extreme environments.

    PubMed

    Küpper, Thomas E A H; Schraut, Bettina; Rieke, Burkhard; Hemmerling, Arnica-Verena; Schöffl, Volker; Steffgen, Juergen

    2006-01-01

    Emergency medicine must often cope with harsh climates far below freezing point or high temperatures, and sometimes, an alternative to the normal route of drug administration is necessary. Most of this information is not yet published. Therefore, we summarized the information about these topics for most drugs used in medical emergencies by combining literature research with extensive personal communications with the heads of the drug safety departments of the companies producing these drugs. Most drugs can be used after temperature stress of limited duration. Nevertheless, we recommend replacing them at least once per year or after extreme heat. Knowledge about drugs used in extreme environments will be of increasing importance for medical personnel because in an increasingly mobile society, more and more people, and especially elderly -often with individual medical risks-travel to extreme regions such as tropical or arctic regions or to high altitude, and some of them need medical care during these activities. Because of this increasing need to use drugs in harsh climates (tourism, expeditions, peace corps, military, etc) the actual International Congress of Harmonization recommendations should be added with stability tests at +50 degrees C, freezing and oscillating temperatures, and UV exposure to simulate the storage of the drugs at "outdoor conditions." PMID:16412107

  17. Discontinued drugs in 2010: cardiovascular drugs.

    PubMed

    Zhao, Hong-ping; Zhang, Xu-song; Xiang, Bing-ren

    2011-10-01

    This perspective is a paper discussing drugs dropped from clinical development in the previous years. Specifically, this paper focuses on 16 cardiovascular drugs discontinued in 2010 after reaching Phase I - III clinical trials. Information for this perspective is mainly derived from a search of Pharmaprojects. PMID:21870899

  18. Utility Computing: Reality and Beyond

    NASA Astrophysics Data System (ADS)

    Ivanov, Ivan I.

    Utility Computing is not a new concept. It involves organizing and providing a wide range of computing-related services as public utilities. Much like water, gas, electricity and telecommunications, the concept of computing as public utility was announced in 1955. Utility Computing remained a concept for near 50 years. Now some models and forms of Utility Computing are emerging such as storage and server virtualization, grid computing, and automated provisioning. Recent trends in Utility Computing as a complex technology involve business procedures that could profoundly transform the nature of companies' IT services, organizational IT strategies and technology infrastructure, and business models. In the ultimate Utility Computing models, organizations will be able to acquire as much IT services as they need, whenever and wherever they need them. Based on networked businesses and new secure online applications, Utility Computing would facilitate "agility-integration" of IT resources and services within and between virtual companies. With the application of Utility Computing there could be concealment of the complexity of IT, reduction of operational expenses, and converting of IT costs to variable `on-demand' services. How far should technology, business and society go to adopt Utility Computing forms, modes and models?

  19. 21 CFR 200.10 - Contract facilities (including consulting laboratories) utilized as extramural facilities by...

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... laboratories) utilized as extramural facilities by pharmaceutical manufacturers. 200.10 Section 200.10 Food and... extramural facilities by pharmaceutical manufacturers. (a) Section 704(a) of the Federal Food, Drug, and...) The Food and Drug Administration is aware that many manufacturers of pharmaceutical products...

  20. 21 CFR 200.10 - Contract facilities (including consulting laboratories) utilized as extramural facilities by...

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... laboratories) utilized as extramural facilities by pharmaceutical manufacturers. 200.10 Section 200.10 Food and... extramural facilities by pharmaceutical manufacturers. (a) Section 704(a) of the Federal Food, Drug, and...) The Food and Drug Administration is aware that many manufacturers of pharmaceutical products...

  1. 21 CFR 200.10 - Contract facilities (including consulting laboratories) utilized as extramural facilities by...

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... laboratories) utilized as extramural facilities by pharmaceutical manufacturers. 200.10 Section 200.10 Food and... extramural facilities by pharmaceutical manufacturers. (a) Section 704(a) of the Federal Food, Drug, and...) The Food and Drug Administration is aware that many manufacturers of pharmaceutical products...

  2. 21 CFR 200.10 - Contract facilities (including consulting laboratories) utilized as extramural facilities by...

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... laboratories) utilized as extramural facilities by pharmaceutical manufacturers. 200.10 Section 200.10 Food and... extramural facilities by pharmaceutical manufacturers. (a) Section 704(a) of the Federal Food, Drug, and...) The Food and Drug Administration is aware that many manufacturers of pharmaceutical products...

  3. 21 CFR 200.10 - Contract facilities (including consulting laboratories) utilized as extramural facilities by...

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... laboratories) utilized as extramural facilities by pharmaceutical manufacturers. 200.10 Section 200.10 Food and... extramural facilities by pharmaceutical manufacturers. (a) Section 704(a) of the Federal Food, Drug, and...) The Food and Drug Administration is aware that many manufacturers of pharmaceutical products...

  4. Quantitative structure-activity relationship models for predicting drug-induced liver injury based on FDA-approved drug labeling annotation and using a large collection of drugs.

    PubMed

    Chen, Minjun; Hong, Huixiao; Fang, Hong; Kelly, Reagan; Zhou, Guangxu; Borlak, Jürgen; Tong, Weida

    2013-11-01

    Drug-induced liver injury (DILI) is one of the leading causes of the termination of drug development programs. Consequently, identifying the risk of DILI in humans for drug candidates during the early stages of the development process would greatly reduce the drug attrition rate in the pharmaceutical industry but would require the implementation of new research and development strategies. In this regard, several in silico models have been proposed as alternative means in prioritizing drug candidates. Because the accuracy and utility of a predictive model rests largely on how to annotate the potential of a drug to cause DILI in a reliable and consistent way, the Food and Drug Administration-approved drug labeling was given prominence. Out of 387 drugs annotated, 197 drugs were used to develop a quantitative structure-activity relationship (QSAR) model and the model was subsequently challenged by the left of drugs serving as an external validation set with an overall prediction accuracy of 68.9%. The performance of the model was further assessed by the use of 2 additional independent validation sets, and the 3 validation data sets have a total of 483 unique drugs. We observed that the QSAR model's performance varied for drugs with different therapeutic uses; however, it achieved a better estimated accuracy (73.6%) as well as negative predictive value (77.0%) when focusing only on these therapeutic categories with high prediction confidence. Thus, the model's applicability domain was defined. Taken collectively, the developed QSAR model has the potential utility to prioritize compound's risk for DILI in humans, particularly for the high-confidence therapeutic subgroups like analgesics, antibacterial agents, and antihistamines.

  5. Plasmon resonant liposomes for controlled drug delivery

    NASA Astrophysics Data System (ADS)

    Knights-Mitchell, Shellie S.; Romanowski, Marek

    2015-03-01

    Nanotechnology use in drug delivery promotes a reduction in systemic toxicity, improved pharmacokinetics, and better drug bioavailability. Liposomes continue to be extensively researched as drug delivery systems (DDS) with formulations such as Doxil® and Ambisome® approved by FDA and successfully marketed in the United States. However, the limited ability to precisely control release of active ingredients from these vesicles continues to challenge the broad implementation of this technology. Moreover, the full potential of the carrier to sequester drugs until it can reach its intended target has yet to be realized. Here, we describe a liposomal DDS that releases therapeutic doses of an anticancer drug in response to external stimulus. Earlier, we introduced degradable plasmon resonant liposomes. These constructs, obtained by reducing gold on the liposome surface, facilitate spatial and temporal release of drugs upon laser light illumination that ultimately induces an increase in temperature. In this work, plasmon resonant liposomes have been developed to stably encapsulate and retain doxorubicin at physiological conditions represented by isotonic saline at 37o C and pH 7.4. Subsequently, they are stimulated to release contents either by a 5o C increase in temperature or by laser illumination (760 nm and 88 mW/cm2 power density). Successful development of degradable plasmon resonant liposomes responsive to near-infrared light or moderate hyperthermia can provide a new delivery method for multiple lipophilic and hydrophilic drugs with pharmacokinetic profiles that limit clinical utility.

  6. LC/MS applications in drug development.

    PubMed

    Lee, M S; Kerns, E H

    1999-01-01

    The combination of high-performance liquid chromatography and mass spectrometry (LC/MS) has had a significant impact on drug development over the past decade. Continual improvements in LC/MS interface technologies combined with powerful features for structure analysis, qualitative and quantitative, have resulted in a widened scope of application. These improvements coincided with breakthroughs in combinatorial chemistry, molecular biology, and an overall industry trend of accelerated development. New technologies have created a situation where the rate of sample generation far exceeds the rate of sample analysis. As a result, new paradigms for the analysis of drugs and related substances have been developed. The growth in LC/MS applications has been extensive, with retention time and molecular weight emerging as essential analytical features from drug target to product. LC/MS-based methodologies that involve automation, predictive or surrogate models, and open access systems have become a permanent fixture in the drug development landscape. An iterative cycle of "what is it?" and "how much is there?" continues to fuel the tremendous growth of LC/MS in the pharmaceutical industry. During this time, LC/MS has become widely accepted as an integral part of the drug development process. This review describes the utility of LC/MS techniques for accelerated drug development and provides a perspective on the significant changes in strategies for pharmaceutical analysis. Future applications of LC/MS technologies for accelerated drug development and emerging industry trends are also discussed.

  7. Continuous drug release by sea anemone Nematostella vectensis stinging microcapsules.

    PubMed

    Tal, Yossi; Ayalon, Ari; Sharaev, Agnesa; Kazir, Zoya; Brekhman, Vera; Lotan, Tamar

    2014-01-27

    Transdermal delivery is an attractive option for drug delivery. Nevertheless, the skin is a tough barrier and only a limited number of drugs can be delivered through it. The most difficult to deliver are hydrophilic drugs. The stinging mechanism of the cnidarians is a sophisticated injection system consisting of microcapsular nematocysts, which utilize built-in high osmotic pressures to inject a submicron tubule that penetrates and delivers their contents to the prey. Here we show, for the first time, that the nematocysts of the starlet sea anemone Nematostella vectensis can be isolated and incorporated into a topical formulation for continuous drug delivery. We demonstrate quantitative delivery of nicotinamide and lidocaine hydrochloride as a function of microcapsular dose or drug exposure. We also show how the released submicron tubules can be exploited as a skin penetration enhancer prior to and independently of drug application. The microcapsules are non-irritant and may offer an attractive alternative for hydrophilic transdermal drug delivery.

  8. Continuous drug release by sea anemone Nematostella vectensis stinging microcapsules.

    PubMed

    Tal, Yossi; Ayalon, Ari; Sharaev, Agnesa; Kazir, Zoya; Brekhman, Vera; Lotan, Tamar

    2014-02-01

    Transdermal delivery is an attractive option for drug delivery. Nevertheless, the skin is a tough barrier and only a limited number of drugs can be delivered through it. The most difficult to deliver are hydrophilic drugs. The stinging mechanism of the cnidarians is a sophisticated injection system consisting of microcapsular nematocysts, which utilize built-in high osmotic pressures to inject a submicron tubule that penetrates and delivers their contents to the prey. Here we show, for the first time, that the nematocysts of the starlet sea anemone Nematostella vectensis can be isolated and incorporated into a topical formulation for continuous drug delivery. We demonstrate quantitative delivery of nicotinamide and lidocaine hydrochloride as a function of microcapsular dose or drug exposure. We also show how the released submicron tubules can be exploited as a skin penetration enhancer prior to and independently of drug application. The microcapsules are non-irritant and may offer an attractive alternative for hydrophilic transdermal drug delivery. PMID:24473172

  9. Continuous Drug Release by Sea Anemone Nematostella vectensis Stinging Microcapsules

    PubMed Central

    Tal, Yossi; Ayalon, Ari; Sharaev, Agnesa; Kazir, Zoya; Brekhman, Vera; Lotan, Tamar

    2014-01-01

    Transdermal delivery is an attractive option for drug delivery. Nevertheless, the skin is a tough barrier and only a limited number of drugs can be delivered through it. The most difficult to deliver are hydrophilic drugs. The stinging mechanism of the cnidarians is a sophisticated injection system consisting of microcapsular nematocysts, which utilize built-in high osmotic pressures to inject a submicron tubule that penetrates and delivers their contents to the prey. Here we show, for the first time, that the nematocysts of the starlet sea anemone Nematostella vectensis can be isolated and incorporated into a topical formulation for continuous drug delivery. We demonstrate quantitative delivery of nicotinamide and lidocaine hydrochloride as a function of microcapsular dose or drug exposure. We also show how the released submicron tubules can be exploited as a skin penetration enhancer prior to and independently of drug application. The microcapsules are non-irritant and may offer an attractive alternative for hydrophilic transdermal drug delivery. PMID:24473172

  10. Adverse drug reactions in veterinary patients associated with drug transporters.

    PubMed

    Mealey, Katrina L

    2013-09-01

    For many drugs used in veterinary practice, plasma and tissue concentrations are highly dependent on the activity of drug transporters. This article describes how functional changes in drug transporters, whether mediated by genetic variability or drug-drug interactions, affect drug disposition and, ultimately, drug safety and efficacy in veterinary patients. A greater understanding of species, breed, and individual (genetic) differences in drug transporter function, as well as drug-drug interactions involving drug transporters, will result in improved strategies for drug design and will enable veterinarians to incorporate individualized medicine in their practices.

  11. Adverse drug reactions in veterinary patients associated with drug transporters.

    PubMed

    Mealey, Katrina L

    2013-09-01

    For many drugs used in veterinary practice, plasma and tissue concentrations are highly dependent on the activity of drug transporters. This article describes how functional changes in drug transporters, whether mediated by genetic variability or drug-drug interactions, affect drug disposition and, ultimately, drug safety and efficacy in veterinary patients. A greater understanding of species, breed, and individual (genetic) differences in drug transporter function, as well as drug-drug interactions involving drug transporters, will result in improved strategies for drug design and will enable veterinarians to incorporate individualized medicine in their practices. PMID:23890239

  12. Students and Drug Abuse

    ERIC Educational Resources Information Center

    Todays Educ, 1969

    1969-01-01

    Introduction to "Students and Drug Abuse, prepared by the Public Information Branch and Center for Studies of Narcotic and Drug Abuse, National Institute of Mental Health, in cooperation with the staff of Today's Education.

  13. Antidiarrheal drug overdose

    MedlinePlus

    ... class of drugs that includes morphine and other narcotics. Use of prescription opioids for nonmedical reasons is ... tracing) Intravenous fluids (given through a vein) Laxative Narcotic-counteracting drug (antagonist), approximately every 30 minutes Tube ...

  14. What Are Narcotic Drugs?

    ERIC Educational Resources Information Center

    Todays Educ, 1969

    1969-01-01

    Part of "Students and Drug Abuse, prepared by the Public Information Branch and Center for Studies of Narcotic and Drug Abuse, National Institute of Mental Health, in cooperation with the staff of Today's Education.

  15. The Drug Education Gap

    ERIC Educational Resources Information Center

    Reynolds, John C., Jr.

    1976-01-01

    Examines the problems of alcoholism, smoking and drug addiction and their influence on students. Suggests that intermediate and secondary schools can assist in alcohol and tobacco (the two legal drugs) programs through improved educational methods. (Author/RK)

  16. Therapeutic drug levels

    MedlinePlus

    ... medlineplus.gov/ency/article/003430.htm Therapeutic drug levels To use the sharing features on this page, please enable JavaScript. Therapeutic drug levels are lab tests to look for the presence ...

  17. Alcoholism, Alcohol, and Drugs

    ERIC Educational Resources Information Center

    Rubin, Emanuel; Lieber, Charles S.

    1971-01-01

    Describes research on synergistic effects of alcohol and other drugs, particularly barbiturates. Proposes biochemical mechanisms to explain alcoholics' tolerance of other drugs when sober, and increased sensitivity when drunk. (AL)

  18. Drug discovery in academia.

    PubMed

    Shamas-Din, Aisha; Schimmer, Aaron D

    2015-08-01

    Participation of academic centers in aspects of drug discovery and development beyond target identification and clinical trials is rapidly increasing. Yet many academic drug discovery projects continue to stall at the level of chemical probes, and they infrequently progress to drugs suitable for clinical trials. This gap poses a major hurdle for academic groups engaged in drug discovery. A number of approaches have been pursued to overcome this gap, including stopping at the production of high-quality chemical probes, establishing the resources in-house to advance select projects toward clinical trials, partnering with not-for-profit groups to bring the necessary resources and expertise to develop probes into drugs, and drug repurposing, whereby known drugs are advanced into clinical trials for new indications. In this review, we consider the role of academia in anticancer drug discovery and development, as well as the strategies used by academic groups to overcome barriers in this process.

  19. Animal Drug Safety FAQs

    MedlinePlus

    ... the top How do you determine if a veterinary drug is safe to market? As mandated by the ... to the top How does CVM remove unsafe veterinary drugs from the market? See Withdrawal of New Animal ...

  20. Drug Interaction and Pharmacist

    PubMed Central

    Ansari, JA

    2010-01-01

    The topic of drug–drug interactions has received a great deal of recent attention from the regulatory, scientific, and health care communities worldwide. Nonsteroidal anti-inflammatory drugs, antibiotics and, in particular, rifampin are common precipitant drugs prescribed in primary care practice. Drugs with a narrow therapeutic range or low therapeutic index are more likely to be the objects for serious drug interactions. Object drugs in common use include warfarin, fluoroquinolones, antiepileptic drugs, oral contraceptives, cisapride, and 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors. The pharmacist, along with the prescriber has a duty to ensure that patients are aware of the risk of side effects and a suitable course of action should they occur. With their detailed knowledge of medicine, pharmacists have the ability to relate unexpected symptoms experienced by patients to possible adverse effects of their drug therapy. PMID:21042495

  1. Prescription Drug Abuse

    MedlinePlus

    ... what the doctor prescribed, it is called prescription drug abuse. It could be Taking a medicine that ... purpose, such as getting high Abusing some prescription drugs can lead to addiction. These include narcotic painkillers, ...

  2. Treating Prescription Drug Addiction

    MedlinePlus

    ... Trends and Alerts Alcohol Club Drugs Cocaine Hallucinogens Heroin Inhalants Marijuana MDMA (Ecstasy/Molly) Methamphetamine Opioids Prescription ... View all ​Research Reports Opioids: The Prescription Drug & Heroin Overdose Epidemic (HHS website) NIDA Home Site Map ...

  3. Surrogacy in antiviral drug development

    PubMed Central

    Shaunak, Sunil; Davies, Donald S

    2002-01-01

    The coming of age of molecular biology has resulted in an explosion in our understanding of the pathogenesis of virus related diseases. New pathogens have been identified and characterized as being responsible for old diseases. Empirical clinical evaluation of morbidity and mortality as outcome measures after a therapeutic intervention have started to give way to the use of an increasing number of surrogate markers. Using a combination of these markers, it is now possible to measure and monitor the pathogen as well as the host's response. Nowhere is this better exemplified in virology than in the field of AIDS. We have utilized the advances in pathogenesis and new antiretroviral drug development to: develop a new class of drugs which block the entry of HIV-1 into cells.develop a new approach for effectively delivering these drugs to those tissues in which most viral replication takes place. Over the last 10 years, our work has progressed from concept to clinical trial. Our laboratory based evaluation of the new molecules developed as well as our clinical evaluation of their safety and efficacy have had to respond and adapt to the rapid changes taking place in AIDS research. This paper discusses the problems encountered and the lessons learnt. PMID:12100230

  4. Black Youths and Illegal Drugs.

    ERIC Educational Resources Information Center

    Joseph, Janice; Pearson, Patricia G.

    2002-01-01

    Examines the effect of drugs on black youths, discussing different types of drug involvement, reasons for drug involvement, extent and nature of involvement, drugs and crime, drugs and health issues, drug control strategies, and prevention. Policy implications include prioritizing drug prevention among black youths, providing alternatives to drug…

  5. Contemporary drugs of abuse.

    PubMed

    Giannini, A J; Price, W A; Giannini, M C

    1986-03-01

    The physician needs to know the signs, symptoms and recommended treatments of drug overdoses. Overdose of hallucinogens usually does not require drug therapy. Overdose of amphetamines ("uppers") may be complicated by the presence of PCP, a dissociative substance. It is important for the physician to be familiar with the street terminology for contemporary drugs of abuse and to be aware of how users obtain these drugs.

  6. siRNA Genome Screening Approaches to Therapeutic Drug Repositioning

    PubMed Central

    Perwitasari, Olivia; Bakre, Abhijeet; Tompkins, S. Mark; Tripp, Ralph A.

    2013-01-01

    Bridging high-throughput screening (HTS) with RNA interference (RNAi) has allowed for rapid discovery of the molecular basis of many diseases, and identification of potential pathways for developing safe and effective treatments. These features have identified new host gene targets for existing drugs paving the pathway for therapeutic drug repositioning. Using RNAi to discover and help validate new drug targets has also provided a means to filter and prioritize promising therapeutics. This review summarizes these approaches across a spectrum of methods and targets in the host response to pathogens. Particular attention is given to the utility of drug repurposing utilizing the promiscuous nature of some drugs that affect multiple molecules or pathways, and how these biological pathways can be targeted to regulate disease outcome. PMID:24275945

  7. Polypharmacology in a single drug: multitarget drugs.

    PubMed

    Bolognesi, M L

    2013-01-01

    Polypharmacology offers a model for the way drug discovery must evolve to develop therapies most suited to treating currently incurable diseases. It is driven by a worldwide demand for safer, more effective, and affordable medicines against the most complex diseases, and by the failures of modern drug discovery to provide these. Polypharmacology can involve combinations and/or multitarget drugs (MTD). Although not mutually exclusive, my premise is that MTDs have inherent advantages over combinations. This review article focuses on MTDs from a medicinal chemistry perspective. I will explore their use in current clinical practice, their likely application in the future, and the challenges to be overcome to achieve this goal.

  8. Mathematical modeling of coupled drug and drug-encapsulated nanoparticle transport in patient-specific coronary artery walls

    NASA Astrophysics Data System (ADS)

    Hossain, Shaolie S.; Hossainy, Syed F. A.; Bazilevs, Yuri; Calo, Victor M.; Hughes, Thomas J. R.

    2012-02-01

    The majority of heart attacks occur when there is a sudden rupture of atherosclerotic plaque, exposing prothrombotic emboli to coronary blood flow, forming clots that can cause blockages of the arterial lumen. Diseased arteries can be treated with drugs delivered locally to vulnerable plaques. The objective of this work was to develop a computational tool-set to support the design and analysis of a catheter-based nanoparticulate drug delivery system to treat vulnerable plaques and diffuse atherosclerosis. A three-dimensional mathematical model of coupled mass transport of drug and drug-encapsulated nanoparticles was developed and solved numerically utilizing isogeometric finite element analysis. Simulations were run on a patient-specific multilayered coronary artery wall segment with a vulnerable plaque and the effect of artery and plaque inhomogeneity was analyzed. The method captured trends observed in local drug delivery and demonstrated potential for optimizing drug design parameters, including delivery location, nanoparticle surface properties, and drug release rate.

  9. Drug Enforcement Administration.

    ERIC Educational Resources Information Center

    Department of Justice, Washington, DC.

    This fact sheet contains information relating to drug abuse and abusers; drug traffic legislation; law enforcement; and descriptions of commonly used narcotics, stimulants, depressants, and hallucinogens. Also included is a short but explicit listing of audiovisual aids, an annotated bibliography, and drug identification pictures. The booklet…

  10. Educating against Drug Abuse.

    ERIC Educational Resources Information Center

    United Nations Educational, Scientific, and Cultural Organization, Paris (France).

    This book is a compilation of drug education and drug abuse prevention materials collected by United Nations Educational, Scientific and Cultural Organization (UNESCO) along with example of activities carried out by various countries. It opens with four introductory papers by separate authors: (1) "Prevention of Drug Dependence: A Utopian Dream?"…

  11. Other Drugs of Abuse

    MedlinePlus

    ... can make you pass out. It's called a "date rape" drug because someone can secretly put it in your ... you without your permission. Rohypnol (roofies) is a date rape pill and can ... about these drugs . Bath Salts are drugs made with chemicals like ...

  12. Strategies against Drugs.

    ERIC Educational Resources Information Center

    Metzler, Birgit

    1996-01-01

    The main private organization in Germany dedicated to combatting drug addition--the DHS and the Federal Health Information Agency (BzGA) jointly estimate the number of persons addicted to "illegal" drugs in Germany at around 200,000. Yet, people may grow up immune to drug addiction if they acquire a stable basis for self-confidence and…

  13. Keeping Youth Drug Free.

    ERIC Educational Resources Information Center

    Substance Abuse and Mental Health Services Administration (DHHS/PHS), Rockville, MD. Center for Substance Abuse Prevention.

    This guide is designed to help caregivers prevent children from getting involved in drugs. It details six key prevention principles, including actions caregivers can take that can help their child make healthy choices. Each section includes language to use with children, activities to do, information about drugs, statistics about youth drug use,…

  14. Drugs and the Coach.

    ERIC Educational Resources Information Center

    Clarke, Kenneth S., Ed.

    This volume is based on the premise that professional preparation for coaching should include viable experiences in drug education, with particular reference to coping with drug-related problems. The first section provides general information on the purposes and effects of drugs, controls, and concepts of doping. The second section deals with four…

  15. Drugs of Abuse.

    ERIC Educational Resources Information Center

    Joseph, Donald E., Ed.

    This Drug Enforcement Administration publication delivers clear, scientific information about drugs in a factual, straightforward way, combined with precise photographs shot to scale. The publication is intended to serve as an A to Z guide for drug history, effects, and identification information. Chapters are included on the Controlled Substances…

  16. Issues In-Depth: Advancing Understanding of Drug Addiction and Treatment

    ERIC Educational Resources Information Center

    Miller, Roxanne Greitz

    2009-01-01

    While most school districts utilize a drug abuse resistance curriculum, as science teachers, it is our responsibility to understand the science behind drug addiction in order to most effectively educate our students against drug abuse. In the last two decades, increases in scientific technology have permitted significant discoveries surrounding…

  17. Laser-induced enhancement of drug cytotoxicity: a new approach to cancer therapy

    NASA Astrophysics Data System (ADS)

    Flotte, Thomas J.; Anderson, T.; McAuliffe, Daniel J., Sr.; Hasan, Tayyaba; Doukas, Apostolos G.

    1993-07-01

    A new approach to drug delivery has been developed at the Wellman Laboratories of Photomedicine that is analogous to photodynamic therapy except that it utilizes high pressure impulse waves to increase the effectiveness of a variety of drugs rather than light activated drugs. This therapeutic modality offers a generic technology that can be used in a variety of conditions including infections, abscesses, and cancer.

  18. [Rational drug use: an economic approach to decision making].

    PubMed

    Mota, Daniel Marques; da Silva, Marcelo Gurgel Carlos; Sudo, Elisa Cazue; Ortún, Vicente

    2008-04-01

    The present article approaches rational drug use (RDU) from the economical point of view. The implementation of RDU implies in costs and involves acquisition of knowledge and behavioral changes of several agents. The difficulties in implementing RDU may be due to shortage problems, information asymmetry, lack of information, uncertain clinical decisions, externalities, time-price, incentives for drug prescribers and dispensers, drug prescriber preferences and marginal utility. Health authorities, among other agencies, must therefore regularize, rationalize and control drug use to minimize inefficiency in pharmaceutical care and to prevent exposing the population to unnecessary health risks.

  19. The exuberant planet: A global look at the role of utilities in protecting biodiversity

    SciTech Connect

    Yeager, K.E.

    1996-11-01

    Biodiversity is a critical environmental issue. Biodiverse species as a source of unique genetic information, for example, continues to provide society with lifesaving drugs and important industrial chemicals. Since US utilities are substantial landholders and virtually every aspect of utility industry step forward as a leader. This paper details the past, present, and future role that utilities have played and need to play in the very important arena of biodiversity. 13 refs.

  20. Drug companies, UNAIDS make drugs available.

    PubMed

    1998-01-01

    The United Nations AIDS (UNAIDS) initiative is working with several drug companies and four countries on a pilot program to build a health infrastructure that provides affordable drugs to insure that combination therapies are used appropriately. The countries involved in the program are Uganda, Chile, Vietnam and Cote d'Ivoire, and the drug companies are Glaxo Wellcome, Hoffmann-La Roche, and Virco NV. Each country agreed to form national HIV/AIDS drug advisory boards, and non-profit companies will act as clearinghouses. Financing will come from the pharmaceutical companies, local health ministries, and a $1 million grant from UNAIDS. The program will be evaluated in terms of improvements to overall health care delivery, number of people treated, the impact on emergency care, and the rate of illness and death.

  1. Drug Rash (Unclassified Drug Eruption) in Adults

    MedlinePlus

    ... microscope by a specially trained physician (dermatopathologist). In addition, your doctor may want to perform blood work to look for signs of an allergic reaction. The best treatment for a drug rash is ...

  2. Drug abuse and addiction.

    PubMed

    Nessa, A; Latif, S A; Siddiqui, N I; Hussain, M A; Hossain, M A

    2008-07-01

    Among the social and medical ills of the twentieth century, substance abuse ranks as on one of the most devastating and costly. The drug problem today is a major global concern including Bangladesh. Almost all addictive drugs over stimulate the reward system of the brain, flooding it with the neurotransmitter dopamine. That produces euphoria and that heightened pleasure can be so compelling that the brain wants that feeling back again and again. However repetitive exposure induces widespread adaptive changes in the brain. As a consequence drug use may become compulsive. An estimated 4.7% of the global population aged 15 to 64 or 184 million people, consume illicit drug annually. Heroin use alone is responsible for the epidemic number of new cases of HIV/AIDS, Hepatitis and drug addicted infant born each year. Department of narcotic control (DNC) in Bangladesh reported in June 2008 that about 5 million drug addicts in the country & addicts spend at least 17 (Seventeen) billion on drugs per year. Among these drug addicts, 91% are young and adolescents population. Heroin is the most widely abused drugs in Bangladesh. For geographical reason like India, Pakistan and Myanmar; Bangladesh is also an important transit root for internationally trafficking of illicit drug. Drug abuse is responsible for decreased job productivity and attendance increased health care costs, and escalations of domestic violence and violent crimes. Drug addiction is a preventable disease. Through scientific advances we now know much more about how exactly drugs work in the brain, and we also know that drug addiction can be successfully treated to help people stop abusing drugs and resume their productive lives. Most countries have legislation designed to criminalize some drugs. To decrease the prevalence of this problem in our setting; increase awareness, promoting additional research on abused and addictive drugs, and exact implementation of existing laws are strongly recommended. We should

  3. Drug discovery in jeopardy

    PubMed Central

    Cuatrecasas, Pedro

    2006-01-01

    Despite striking advances in the biomedical sciences, the flow of new drugs has slowed to a trickle, impairing therapeutic advances as well as the commercial success of drug companies. Reduced productivity in the drug industry is caused mainly by corporate policies that discourage innovation. This is compounded by various consequences of mega-mergers, the obsession for blockbuster drugs, the shift of control of research from scientists to marketers, the need for fast sales growth, and the discontinuation of development compounds for nontechnical reasons. Lessons from the past indicate that these problems can be overcome, and herein, new and improved directions for drug discovery are suggested. PMID:17080187

  4. Drug Facts Chat Day: NIH Experts Answer Students' Drug Questions

    MedlinePlus

    ... Home Current Issue Past Issues Drug Facts Chat Day: NIH Experts Answer Students' Drug Questions Past Issues / ... Drug Abuse during their first Drug Facts Chat Day. Photo courtesy of NIDA The questions poured in… ...

  5. Drug Delivery to the Ischemic Brain

    PubMed Central

    Thompson, Brandon J.; Ronaldson, Patrick T.

    2014-01-01

    Cerebral ischemia occurs when blood flow to the brain is insufficient to meet metabolic demand. This can result from cerebral artery occlusion that interrupts blood flow, limits CNS supply of oxygen and glucose, and causes an infarction/ischemic stroke. Ischemia initiates a cascade of molecular events inneurons and cerebrovascular endothelial cells including energy depletion, dissipation of ion gradients, calcium overload, excitotoxicity, oxidative stress, and accumulation of ions and fluid. Blood-brain barrier (BBB) disruption is associated with cerebral ischemia and leads to vasogenic edema, a primary cause of stroke-associated mortality. To date, only a single drug has received US Food and Drug Administration (FDA) approval for acute ischemic stroke treatment, recombinant tissue plasminogen activator (rt-PA). While rt-PA therapy restores perfusion to ischemic brain, considerable tissue damage occurs when cerebral blood flow is re-established. Therefore, there is a critical need for novel therapeutic approaches that can “rescue” salvageable brain tissue and/or protect BBB integrity during ischemic stroke. One class of drugs that may enable neural cell rescue following cerebral ischemia/reperfusion injury is the HMG-CoA reductase inhibitors (i.e., statins). Understanding potential CNS drug delivery pathways for statins is critical to their utility in ischemic stroke. Here, we review molecular pathways associated with cerebral ischemia and novel approaches for delivering drugs to treat ischemic disease. Specifically, we discuss utility of endogenous BBB drug uptake transporters such as organic anion transporting polypeptides (OATPs/Oatps) and nanotechnology-based carriers for optimization of CNS drug delivery. Overall, this chapter highlights state-of-the-art technologies that may improve pharmacotherapy of cerebral ischemia. PMID:25307217

  6. Xylose utilization in recombinant Zymomonas

    DOEpatents

    Kahsay, Robel Y; Qi, Min; Tao, Luan; Viitanen, Paul V; Yang, Jianjun

    2013-01-07

    Zymomonas expressing xylose isomerase from A. missouriensis was found to have improved xylose utilization, growth, and ethanol production when grown in media containing xylose. Xylose isomerases related to that of A. missouriensis were identified structurally through molecular phylogenetic and Profile Hidden Markov Model analyses, providing xylose isomerases that may be used to improve xylose utilization.

  7. Acid rain & electric utilities II

    SciTech Connect

    1997-12-31

    This document presents reports which were presented at the Acid Rain and Electric Utilities Conference. Topics include environmental issues and electric utilities; acid rain program overview; global climate change and carbon dioxide; emissions data management; compliance; emissions control; allowance and trading; nitrogen oxides; and assessment. Individual reports have been processed separately for the United States Department of Energy databases.

  8. Xylose utilization in recombinant zymomonas

    DOEpatents

    Caimi, Perry G; McCole, Laura; Tao, Luan; Tomb, Jean-Francois; Viitanen, Paul V

    2014-03-25

    Xylose-utilizing Zymomonas strains studied were found to accumulate ribulose when grown in xylose-containing media. Engineering these strains to increase ribose-5-phosphate isomerase activity led to reduced ribulose accumulation, improved growth, improved xylose utilization, and increased ethanol production.

  9. Drug Interactions and Antiretroviral Drug Monitoring

    PubMed Central

    Foy, Matthew; Sperati, C. John; Lucas, Gregory M.

    2014-01-01

    Due to the improved longevity afforded by combination antiretroviral therapy (cART), HIV-infected individuals are developing several non-AIDS related comorbid conditions. Consequently, medical management of the HIV-infected population is increasingly complex, with a growing list of potential drug-drug interactions (DDIs). This article reviews some of the most relevant and emerging potential interactions between antiretroviral medications and other agents. The most common DDIs are those involving protease inhibitors or non-nucleoside reverse transcriptase inhibitors which alter the cytochrome P450 enzyme system and/or drug transporters such as p-glycoprotein. Of note are the new agents for the treatment of chronic hepatitis C virus infection. These new classes of drugs and others drugs which are increasingly used in this patient population represent a significant challenge with regard to achieving the goals of effective HIV suppression and minimization of drug-related toxicities. Awareness of DDIs and a multidisciplinary approach are imperative in reaching these goals. PMID:24950731

  10. Intracranial Self-Stimulation to Evaluate Abuse Potential of Drugs

    PubMed Central

    Miller, Laurence L.

    2014-01-01

    Intracranial self-stimulation (ICSS) is a behavioral procedure in which operant responding is maintained by pulses of electrical brain stimulation. In research to study abuse-related drug effects, ICSS relies on electrode placements that target the medial forebrain bundle at the level of the lateral hypothalamus, and experimental sessions manipulate frequency or amplitude of stimulation to engender a wide range of baseline response rates or response probabilities. Under these conditions, drug-induced increases in low rates/probabilities of responding maintained by low frequencies/amplitudes of stimulation are interpreted as an abuse-related effect. Conversely, drug-induced decreases in high rates/probabilities of responding maintained by high frequencies/amplitudes of stimulation can be interpreted as an abuse-limiting effect. Overall abuse potential can be inferred from the relative expression of abuse-related and abuse-limiting effects. The sensitivity and selectivity of ICSS to detect abuse potential of many classes of abused drugs is similar to the sensitivity and selectivity of drug self-administration procedures. Moreover, similar to progressive-ratio drug self-administration procedures, ICSS data can be used to rank the relative abuse potential of different drugs. Strengths of ICSS in comparison with drug self-administration include 1) potential for simultaneous evaluation of both abuse-related and abuse-limiting effects, 2) flexibility for use with various routes of drug administration or drug vehicles, 3) utility for studies in drug-naive subjects as well as in subjects with controlled levels of prior drug exposure, and 4) utility for studies of drug time course. Taken together, these considerations suggest that ICSS can make significant contributions to the practice of abuse potential testing. PMID:24973197

  11. Hualapai Tribal Utility Development Project

    SciTech Connect

    Hualapai Tribal Nation

    2008-05-25

    The first phase of the Hualapai Tribal Utility Development Project (Project) studied the feasibility of establishing a tribally operated utility to provide electric service to tribal customers at Grand Canyon West (see objective 1 below). The project was successful in completing the analysis of the energy production from the solar power systems at Grand Canyon West and developing a financial model, based on rates to be charged to Grand Canyon West customers connected to the solar systems, that would provide sufficient revenue for a Tribal Utility Authority to operate and maintain those systems. The objective to establish a central power grid over which the TUA would have authority and responsibility had to be modified because the construction schedule of GCW facilities, specifically the new air terminal, did not match up with the construction schedule for the solar power system. Therefore, two distributed systems were constructed instead of one central system with a high voltage distribution network. The Hualapai Tribal Council has not taken the action necessary to establish the Tribal Utility Authority that could be responsible for the electric service at GCW. The creation of a Tribal Utility Authority (TUA) was the subject of the second objective of the project. The second phase of the project examined the feasibility and strategy for establishing a tribal utility to serve the remainder of the Hualapai Reservation and the feasibility of including wind energy from a tribal wind generator in the energy resource portfolio of the tribal utility (see objective 2 below). It is currently unknown when the Tribal Council will consider the implementation of the results of the study. Objective 1 - Develop the basic organizational structure and operational strategy for a tribally controlled utility to operate at the Tribe’s tourism enterprise district, Grand Canyon West. Coordinate the development of the Tribal Utility structure with the development of the Grand Canyon

  12. Drugs Approved for Wilms Tumor

    Cancer.gov

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for Wilms tumor and other childhood kidney cancers. The list includes generic names and brand names. The drug names link to NCI's Cancer Drug Information summaries.

  13. Drugs Approved for Kaposi Sarcoma

    Cancer.gov

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for Kaposi sarcoma. The list includes generic names and brand names. The drug names link to NCI's Cancer Drug Information summaries.

  14. Drugs Approved for Malignant Mesothelioma

    Cancer.gov

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for malignant mesothelioma. The list includes generic names and brand names. The drug names link to NCI's Cancer Drug Information summaries.

  15. How to Read Drug Labels

    MedlinePlus

    ... and alternative medicine Healthy Aging How to read drug labels Printer-friendly version How to Read Drug ... read drug labels How to read a prescription drug label View a text version of this picture. ...

  16. COPD - quick-relief drugs

    MedlinePlus

    COPD - quick-relief drugs; Chronic obstructive pulmonary disease - control drugs; Chronic obstructive airways disease - quick-relief drugs; Chronic obstructive lung disease - quick-relief drugs; Chronic bronchitis - quick-relief ...

  17. Drugs Approved for Skin Cancer

    Cancer.gov

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for skin cancer. The list includes generic names and brand names. The drug names link to NCI's Cancer Drug Information summaries.

  18. Drugs Approved for Vaginal Cancer

    Cancer.gov

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) to prevent vaginal cancer. The list includes generic names and brand names. The drug names link to NCI’s Cancer Drug Information summaries.

  19. DEA Multimedia Drug Library: Marijuana

    MedlinePlus

    ... OPERATIONS Diversion Control Programs Most Wanted Fugitives Training Intelligence Submit a Tip DRUG INFO Drug Fact Sheets ... Operations Diversion Control Programs Most Wanted Fugitives Training Intelligence Submit a Tip Drug Info Drug Fact Sheets ...

  20. Drugs Approved for Penile Cancer

    Cancer.gov

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for penile cancer. The list includes generic names and brand names. The drug names link to NCI’s Cancer Drug Information summaries.

  1. Drugs Approved for Vulvar Cancer

    Cancer.gov

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for vulvar cancer. The list includes generic names and brand names. The drug names link to NCI's Cancer Drug Information summaries.

  2. Drugs Approved for Liver Cancer

    Cancer.gov

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for liver cancer. The list includes generic names and brand names. The drug names link to NCI’s Cancer Drug Information summaries.

  3. Drugs Approved for Bone Cancer

    Cancer.gov

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for bone cancer. The list includes generic names and brand names. The drug names link to NCI's Cancer Drug Information summaries.

  4. Drugs Approved for Esophageal Cancer

    Cancer.gov

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for esophageal cancer. The list includes generic names and brand names. The drug names link to NCI's Cancer Drug Information summaries.

  5. Drugs Approved for Endometrial Cancer

    Cancer.gov

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for endometrial cancer. The list includes generic names and brand names. The drug names link to NCI's Cancer Drug Information summaries.

  6. ATP-triggered anticancer drug delivery

    NASA Astrophysics Data System (ADS)

    Mo, Ran; Jiang, Tianyue; Disanto, Rocco; Tai, Wanyi; Gu, Zhen

    2014-03-01

    Stimuli-triggered drug delivery systems have been increasingly used to promote physiological specificity and on-demand therapeutic efficacy of anticancer drugs. Here we utilize adenosine-5'-triphosphate (ATP) as a trigger for the controlled release of anticancer drugs. We demonstrate that polymeric nanocarriers functionalized with an ATP-binding aptamer-incorporated DNA motif can selectively release the intercalating doxorubicin via a conformational switch when in an ATP-rich environment. The half-maximal inhibitory concentration of ATP-responsive nanovehicles is 0.24 μM in MDA-MB-231 cells, a 3.6-fold increase in the cytotoxicity compared with that of non-ATP-responsive nanovehicles. Equipped with an outer shell crosslinked by hyaluronic acid, a specific tumour-targeting ligand, the ATP-responsive nanocarriers present an improvement in the chemotherapeutic inhibition of tumour growth using xenograft MDA-MB-231 tumour-bearing mice. This ATP-triggered drug release system provides a more sophisticated drug delivery system, which can differentiate ATP levels to facilitate the selective release of drugs.

  7. Model-based Utility Functions

    NASA Astrophysics Data System (ADS)

    Hibbard, Bill

    2012-05-01

    Orseau and Ring, as well as Dewey, have recently described problems, including self-delusion, with the behavior of agents using various definitions of utility functions. An agent's utility function is defined in terms of the agent's history of interactions with its environment. This paper argues, via two examples, that the behavior problems can be avoided by formulating the utility function in two steps: 1) inferring a model of the environment from interactions, and 2) computing utility as a function of the environment model. Basing a utility function on a model that the agent must learn implies that the utility function must initially be expressed in terms of specifications to be matched to structures in the learned model. These specifications constitute prior assumptions about the environment so this approach will not work with arbitrary environments. But the approach should work for agents designed by humans to act in the physical world. The paper also addresses the issue of self-modifying agents and shows that if provided with the possibility to modify their utility functions agents will not choose to do so, under some usual assumptions.

  8. Drug-induced hyperkalemia.

    PubMed

    Ben Salem, Chaker; Badreddine, Atef; Fathallah, Neila; Slim, Raoudha; Hmouda, Houssem

    2014-09-01

    Hyperkalemia is a common clinical condition that can be defined as a serum potassium concentration exceeding 5.0 mmol/L. Drug-induced hyperkalemia is the most important cause of increased potassium levels in everyday clinical practice. Drug-induced hyperkalemia may be asymptomatic. However, it may be dramatic and life threatening, posing diagnostic and management problems. A wide range of drugs can cause hyperkalemia by a variety of mechanisms. Drugs can interfere with potassium homoeostasis either by promoting transcellular potassium shift or by impairing renal potassium excretion. Drugs may also increase potassium supply. The reduction in renal potassium excretion due to inhibition of the renin-angiotensin-aldosterone system represents the most important mechanism by which drugs are known to cause hyperkalemia. Medications that alter transmembrane potassium movement include amino acids, beta-blockers, calcium channel blockers, suxamethonium, and mannitol. Drugs that impair renal potassium excretion are mainly represented by angiotensin-converting enzyme inhibitors, angiotensin-II receptor blockers, direct renin inhibitors, nonsteroidal anti-inflammatory drugs, calcineurin inhibitors, heparin and derivatives, aldosterone antagonists, potassium-sparing diuretics, trimethoprim, and pentamidine. Potassium-containing agents represent another group of medications causing hyperkalemia. Increased awareness of drugs that can induce hyperkalemia, and monitoring and prevention are key elements for reducing the number of hospital admissions, morbidity, and mortality related to drug-induced hyperkalemia.

  9. Drug abuse and reproduction.

    PubMed

    Smith, C G; Asch, R H

    1987-09-01

    It is clear that a number of CNS agents, including drugs of abuse, can inhibit reproductive function. Figure 1 shows the chemical diversity of some of the drug groups that affect reproductive hormones. Their structural dissimilarity to the steroid hormones is also readily apparent in the figure. These chemically diverse drugs share an important pharmacologic property: they are highly potent neuroactive drugs, and they can disrupt hypothalamic-pituitary function. Although it is frequently difficult to distinguish between direct drug actions on the hypothalamic-pituitary axis and subsequent effects on gonadal hormones and sex accessory gland function, the distinction is an important one. Most neuroactive drugs produce only transient effects on the central nervous pathways necessary for normal gonadotropin secretion. The disruptive effects of these drugs are likely to be transient and completely reversible, and tolerance to the inhibitory drug effects may occur even with continued drug use. Under these circumstances, normal adults may experience only subtle changes in sexual function. However, individuals with compromised reproductive function may exhibit major problems. It is also likely that adolescents may be at substantial risk for reproductive damage from these neuroactive drugs since the endocrine events associated with puberty are dependent on the normal development of the hypothalamic-pituitary axis.

  10. Ocular drug delivery.

    PubMed

    Gaudana, Ripal; Ananthula, Hari Krishna; Parenky, Ashwin; Mitra, Ashim K

    2010-09-01

    Ocular drug delivery has been a major challenge to pharmacologists and drug delivery scientists due to its unique anatomy and physiology. Static barriers (different layers of cornea, sclera, and retina including blood aqueous and blood-retinal barriers), dynamic barriers (choroidal and conjunctival blood flow, lymphatic clearance, and tear dilution), and efflux pumps in conjunction pose a significant challenge for delivery of a drug alone or in a dosage form, especially to the posterior segment. Identification of influx transporters on various ocular tissues and designing a transporter-targeted delivery of a parent drug has gathered momentum in recent years. Parallelly, colloidal dosage forms such as nanoparticles, nanomicelles, liposomes, and microemulsions have been widely explored to overcome various static and dynamic barriers. Novel drug delivery strategies such as bioadhesive gels and fibrin sealant-based approaches were developed to sustain drug levels at the target site. Designing noninvasive sustained drug delivery systems and exploring the feasibility of topical application to deliver drugs to the posterior segment may drastically improve drug delivery in the years to come. Current developments in the field of ophthalmic drug delivery promise a significant improvement in overcoming the challenges posed by various anterior and posterior segment diseases. PMID:20437123

  11. Ocular drug delivery.

    PubMed

    Gaudana, Ripal; Ananthula, Hari Krishna; Parenky, Ashwin; Mitra, Ashim K

    2010-09-01

    Ocular drug delivery has been a major challenge to pharmacologists and drug delivery scientists due to its unique anatomy and physiology. Static barriers (different layers of cornea, sclera, and retina including blood aqueous and blood-retinal barriers), dynamic barriers (choroidal and conjunctival blood flow, lymphatic clearance, and tear dilution), and efflux pumps in conjunction pose a significant challenge for delivery of a drug alone or in a dosage form, especially to the posterior segment. Identification of influx transporters on various ocular tissues and designing a transporter-targeted delivery of a parent drug has gathered momentum in recent years. Parallelly, colloidal dosage forms such as nanoparticles, nanomicelles, liposomes, and microemulsions have been widely explored to overcome various static and dynamic barriers. Novel drug delivery strategies such as bioadhesive gels and fibrin sealant-based approaches were developed to sustain drug levels at the target site. Designing noninvasive sustained drug delivery systems and exploring the feasibility of topical application to deliver drugs to the posterior segment may drastically improve drug delivery in the years to come. Current developments in the field of ophthalmic drug delivery promise a significant improvement in overcoming the challenges posed by various anterior and posterior segment diseases.

  12. Utilization of Orimulsion{reg_sign} in utility boilers

    SciTech Connect

    Woodworth, L.

    1994-08-01

    Orimulsion{reg_sign}, a bitumen-in-water emulsion with excellent combustion characteristics, abundantly available from Venezuela, is being increasingly considered a a reliable economical fuel for relatively low cost conversion of utility boilers. Given the increasing deregulation of power generation both in the United States and worldwide, the economics and related advantages of Orimulsion{reg_sign} applications may provide opportunities for electric utilities to compete in power markets and do so in an environmentally acceptable manner.

  13. Pathway-based drug repositioning using causal inference

    PubMed Central

    2013-01-01

    Background Recent in vivo studies showed new hopes of drug repositioning through causality inference from drugs to disease. Inspired by their success, here we present an in silico method for building a causal network (CauseNet) between drugs and diseases, in an attempt to systematically identify new therapeutic uses of existing drugs. Methods Unlike the traditional 'one drug-one target-one disease' causal model, we simultaneously consider all possible causal chains connecting drugs to diseases via target- and gene-involved pathways based on rich information in several expert-curated knowledge-bases. With statistical learning, our method estimates transition likelihood of each causal chain in the network based on known drug-disease treatment associations (e.g. bexarotene treats skin cancer). Results To demonstrate its validity, our method showed high performance (AUC = 0.859) in cross validation. Moreover, our top scored prediction results are highly enriched in literature and clinical trials. As a showcase of its utility, we show several drugs for potential re-use in Crohn's Disease. Conclusions We successfully developed a computational method for discovering new uses of existing drugs based on casual inference in a layered drug-target-pathway-gene- disease network. The results showed that our proposed method enables hypothesis generation from public accessible biological data for drug repositioning. PMID:24564553

  14. Making Connections: New Orleans Evacuees’ Experiences in Obtaining Drugs1

    PubMed Central

    Dunlap, Eloise; Johnson, Bruce D.; Kotarba, Joseph; Fackler, Jennifer

    2009-01-01

    Between August 29 and September 7, 2005, almost all New Orleans residents were evacuated from the area in the aftermath of Hurricane Katrina. News reports indicate that almost 130,000 New Orleans Evacuees (NOEs) were evacuated to Houston, Texas, the largest recipient of the civilian population from New Orleans. Many of these NOEs were active participants in the illicit drug market in New Orleans prior to the hurricane. Their displacement to Houston and other locations provided a unique opportunity to study what occurs when illicit drug markets are disrupted. The period between the flooding and nearly complete evacuation of New Orleans provided a unique opportunity to systematically learn about the disruption of illicit drug markets since populations of illicit drug users and purchasers could no longer routinely obtain their drugs in predictable ways. Utilizing qualitative data from in-depth interviews and focus groups, this article describes the ways NOEs (1) managed their drug acquisition and use following evacuation; (2) located new sources of drugs in Houston and elsewhere by tapping into shared drug culture; and (3) gained access to and learned the argot for drugs in the local drug market in new settings. This report contributes to the nascent literature on disrupted drug markets. PMID:19999675

  15. Regional intestinal drug permeation: biopharmaceutics and drug development.

    PubMed

    Lennernäs, Hans

    2014-06-16

    Over the last 25 years, profound changes have been seen in both the development and regulation of pharmaceutical dosage forms, due primarily to the extensive use of the biopharmaceutical classification system (BCS) in both academia and industry. The BCS and the FDA scale-up and post-approval change guidelines were both developed during the 1990s and both are currently widely used to claim biowaivers. The development of the BCS and its wide acceptance were important steps in pharmaceutical science that contributed to the more rational development of oral dosage forms. The effective permeation (Peff) of drugs through the intestine often depends on the combined outcomes of passive diffusion and multiple parallel transport processes. Site-specific jejunal Peff cannot reflect the permeability of the whole intestinal tract, since this varies along the length of the intestine, but is a useful approximation of the fraction of the oral dose that is absorbed. It appears that drugs with a jejunal Peff>1.5×10(-4)cm/s will be completely absorbed no matter which transport mechanisms are utilized. In this paper, historical clinical data originating from earlier open, single-pass perfusion studies have been used to calculate the Peff of different substances from sites in the jejunum and ileum. More exploratory in vivo studies are required in order to obtain reliable data on regional intestinal drug absorption. The development of experimental and theoretical methods of assessing drug absorption from both small intestine and various sites in the colon is encouraged. Some of the existing human in vivo data are discussed in relation to commonly used cell culture models. It is crucial to accurately determine the input parameters, such as the regional intestinal Peff, as these will form the basis for the expected increase in modeling and simulation of all the processes involved in GI drug absorption, thus facilitating successful pharmaceutical development in the future. It is suggested

  16. Role of Molecular Dynamics and Related Methods in Drug Discovery.

    PubMed

    De Vivo, Marco; Masetti, Matteo; Bottegoni, Giovanni; Cavalli, Andrea

    2016-05-12

    Molecular dynamics (MD) and related methods are close to becoming routine computational tools for drug discovery. Their main advantage is in explicitly treating structural flexibility and entropic effects. This allows a more accurate estimate of the thermodynamics and kinetics associated with drug-target recognition and binding, as better algorithms and hardware architectures increase their use. Here, we review the theoretical background of MD and enhanced sampling methods, focusing on free-energy perturbation, metadynamics, steered MD, and other methods most consistently used to study drug-target binding. We discuss unbiased MD simulations that nowadays allow the observation of unsupervised ligand-target binding, assessing how these approaches help optimizing target affinity and drug residence time toward improved drug efficacy. Further issues discussed include allosteric modulation and the role of water molecules in ligand binding and optimization. We conclude by calling for more prospective studies to attest to these methods' utility in discovering novel drug candidates. PMID:26807648

  17. Diamond: shedding light on structure-based drug discovery.

    PubMed

    Brown, David G; Shotton, Elizabeth J

    2015-03-01

    Structure-based drug design has become a key tool for the development of novel drugs. The process involves elucidating the three-dimensional structure of the potential drug molecule bound to the target protein that has been identified as playing a key role in the disease state. Using this three-dimensional information facilitates the process of making improvements to the potential drug molecule by highlighting existing and possible new interactions within the binding site. This knowledge is used to inform increases in potency and selectivity of the molecules as well as to help improve other drug-like properties. The speed and numbers of samples that can be studied, combined with the improved resolution of the structures that can be obtained using synchrotron radiation, have had a significant impact on the utilization of crystallography in the drug discovery process. PMID:25624512

  18. Opioid pharmacokinetic drug-drug interactions.

    PubMed

    Overholser, Brian R; Foster, David R

    2011-09-01

    Pharmacokinetic drug-drug interactions (DDIs) involving opioid analgesics can be problematic. Opioids are widely used, have a narrow therapeutic index, and can be associated with severe toxicity. The purpose of this review is to describe pharmacokinetic DDIs associated with opioids frequently encountered in managed care settings (morphine, codeine, oxycodone, oxymorphone, hydrocodone, hydromorphone, fentanyl, tramadol, and methadone). An introduction to the pharmacokinetic basis of DDIs is provided, and potential DDIs associated with opioids are reviewed. Opioids metabolized by the drug metabolizing enzymes of the cytochrome P450 (CYP450) system (codeine, oxycodone, hydrocodone, fentanyl, tramadol, and methadone) are associated with numerous DDIs that can result in either a reduction in opioid effect or excess opioid effects. Conversely, opioids that are not metabolized by that system (morphine, oxymorphone, and hydromorphone) tend to be involved in fewer CYP450-associated pharmacokinetic DDIs.

  19. Informatics confronts drug-drug interactions.

    PubMed

    Percha, Bethany; Altman, Russ B

    2013-03-01

    Drug-drug interactions (DDIs) are an emerging threat to public health. Recent estimates indicate that DDIs cause nearly 74000 emergency room visits and 195000 hospitalizations each year in the USA. Current approaches to DDI discovery, which include Phase IV clinical trials and post-marketing surveillance, are insufficient for detecting many DDIs and do not alert the public to potentially dangerous DDIs before a drug enters the market. Recent work has applied state-of-the-art computational and statistical methods to the problem of DDIs. Here we review recent developments that encompass a range of informatics approaches in this domain, from the construction of databases for efficient searching of known DDIs to the prediction of novel DDIs based on data from electronic medical records, adverse event reports, scientific abstracts, and other sources. We also explore why DDIs are so difficult to detect and what the future holds for informatics-based approaches to DDI discovery. PMID:23414686

  20. Discontinued drugs in 2012: cardiovascular drugs.

    PubMed

    Zhao, Hong-Ping; Jiang, Hong-Min; Xiang, Bing-Ren

    2013-11-01

    The continued high rate of cardiovascular morbidity and mortality has attracted wide concern and great attention of pharmaceutical industry. In order to reduce the attrition of cardiovascular drug R&D, it might be helpful recapitulating previous failures and identifying the potential factors to success. This perspective mainly analyses the 30 cardiovascular drugs dropped from clinical development in 2012. Reasons causing the termination of the cardiovascular drugs in the past 5 years are also tabulated and analysed. The analysis shows that the attrition is highest in Phase II trials and financial and strategic factors and lack of clinical efficacy are the principal reasons for these disappointments. To solve the four problems (The 'better than the Beatles' problem, the 'cautious regulator' problem, the 'throw money at it' tendency and the 'basic researchbrute force' bias) is recommended as the main measure to increase the number and quality of approvable products. PMID:23992034

  1. New Antithrombotic Drugs

    PubMed Central

    Eikelboom, John W.; Samama, Meyer Michel

    2012-01-01

    This article focuses on new antithrombotic drugs that are in or are entering phase 3 clinical testing. Development of these new agents was prompted by the limitations of existing antiplatelet, anticoagulant, or fibrinolytic drugs. Addressing these unmet needs, this article (1) outlines the rationale for development of new antithrombotic agents; (2) describes the new antiplatelet, anticoagulant, and fibrinolytic drugs; and (3) provides clinical perspectives on the opportunities and challenges faced by these novel agents. PMID:22315258

  2. [Safety nonsteroidal antiinflammatory drugs].

    PubMed

    Oscanoa-Espinoza, Teodoro Julio

    2015-01-01

    The choice of a specific medication belonging to a drug class is under the criteria of efficacy, safety, cost and suitability. NSAIDs currently constitute one of the most consumed drug in the world, so it is very important review of the safety aspects of this drug class. This review has the objective of analyze the safety of NSAIDs on 3 main criteria: gastrolesivity, cardiotoxicity and nephrotoxicity.

  3. Grapefruit and drug interactions.

    PubMed

    2012-12-01

    Since the late 1980s, grapefruit juice has been known to affect the metabolism of certain drugs. Several serious adverse effects involving drug interactions with grapefruit juice have been published in detail. The components of grapefruit juice vary considerably depending on the variety, maturity and origin of the fruit, local climatic conditions, and the manufacturing process. No single component accounts for all observed interactions. Other grapefruit products are also occasionally implicated, including preserves, lyophylised grapefruit juice, powdered whole grapefruit, grapefruit seed extract, and zest. Clinical reports of drug interactions with grapefruit juice are supported by pharmacokinetic studies, each usually involving about 10 healthy volunteers, in which the probable clinical consequences were extrapolated from the observed plasma concentrations. Grapefruit juice inhibits CYP3A4, the cytochrome P450 isoenzyme most often involved in drug metabolism. This increases plasma concentrations of the drugs concerned, creating a risk of overdose and dose-dependent adverse effects. Grapefruit juice also inhibits several other cytochrome P450 isoenzymes, but they are less frequently implicated in interactions with clinical consequences. Drugs interacting with grapefruit and inducing serious clinical consequences (confirmed or very probable) include: immunosuppressants, some statins, benzodiazepines, most calcium channel blockers, indinavir and carbamazepine. There are large inter-individual differences in enzyme efficiency. Along with the variable composition of grapefruit juice, this makes it difficult to predict the magnitude and clinical consequences of drug interactions with grapefruit juice in a given patient. There is increasing evidence that transporter proteins such as organic anion transporters and P-glycoprotein are involved in interactions between drugs and grapefruit juice. In practice, numerous drugs interact with grapefruit juice. Although only a few

  4. Grapefruit and drug interactions.

    PubMed

    2012-12-01

    Since the late 1980s, grapefruit juice has been known to affect the metabolism of certain drugs. Several serious adverse effects involving drug interactions with grapefruit juice have been published in detail. The components of grapefruit juice vary considerably depending on the variety, maturity and origin of the fruit, local climatic conditions, and the manufacturing process. No single component accounts for all observed interactions. Other grapefruit products are also occasionally implicated, including preserves, lyophylised grapefruit juice, powdered whole grapefruit, grapefruit seed extract, and zest. Clinical reports of drug interactions with grapefruit juice are supported by pharmacokinetic studies, each usually involving about 10 healthy volunteers, in which the probable clinical consequences were extrapolated from the observed plasma concentrations. Grapefruit juice inhibits CYP3A4, the cytochrome P450 isoenzyme most often involved in drug metabolism. This increases plasma concentrations of the drugs concerned, creating a risk of overdose and dose-dependent adverse effects. Grapefruit juice also inhibits several other cytochrome P450 isoenzymes, but they are less frequently implicated in interactions with clinical consequences. Drugs interacting with grapefruit and inducing serious clinical consequences (confirmed or very probable) include: immunosuppressants, some statins, benzodiazepines, most calcium channel blockers, indinavir and carbamazepine. There are large inter-individual differences in enzyme efficiency. Along with the variable composition of grapefruit juice, this makes it difficult to predict the magnitude and clinical consequences of drug interactions with grapefruit juice in a given patient. There is increasing evidence that transporter proteins such as organic anion transporters and P-glycoprotein are involved in interactions between drugs and grapefruit juice. In practice, numerous drugs interact with grapefruit juice. Although only a few

  5. Vaccines for Drug Abuse

    PubMed Central

    Shen, Xiaoyun; Orson, Frank M.; Kosten, Thomas R.

    2012-01-01

    Current medications for drug abuse have had only limited success. Anti-addiction vaccines to elicit antibodies that block the pharmacological effects of drugs have great potential for treating drug abuse. We review the status for two vaccines that are undergoing clinical trials (cocaine and nicotine) and two that are still in pre-clinical development (methamphetamine and heroin). We also outline the challenges and ethical concerns for anti-addiction vaccine development and their use as future therapeutics. PMID:22130115

  6. IDENTIFYING VULNERABLE SURFACE WATER UTILITIES

    EPA Science Inventory

    This study was conducted to provide a mechanism and framework with which utility managers could analyze the effects of upstream discharges on source waters. Specific components of the project included selection, implementation, and demonstration of a microcomputer-based commerci...

  7. Energy Conservation Through Effective Utilization

    ERIC Educational Resources Information Center

    Berg, Charles A.

    1973-01-01

    Discusses various ways in which the demand for energy could be decreased, focusing not so much on discouraging demand by increasing prices, as on reducing energy consumption by improving efficiency of energy utilization in buildings and in industry. (JR)

  8. Designer Drugs: A Synthetic Catastrophe

    PubMed Central

    Fratantonio, James; Andrade, Lawrence; Febo, Marcelo

    2016-01-01

    Synthetic stimulants can cause hallucinations, aggressive behaviors, death and are sometimes legal. These substances are sold as plant food and bath salts that are “Not for Human Consumption”, therefore skirting the 1986 Federal Analogue Act and giving a false pretense of safety. Studies have proved that these substances are toxic, have a high abuse potential, and are becoming extremely prevalent in the United States. This creates a dilemma for law enforcement agents, hospitals, and substance use disorder treatment centers. Urine Drug Testing is utilized as a clinical diagnostic tool in substance use disorder treatment centers, and the furious pace at which new synthetic stimulants are introduced to the black market are making the detection via urine increasingly difficult. This article will discuss the prevalence, pharmacology and difficulty developing laboratory assays to detect synthetic stimulants. PMID:27617301

  9. Nanodisks: hydrophobic drug delivery vehicles.

    PubMed

    Ryan, Robert O

    2008-03-01

    Members of the class of exchangeable apolipoproteins possess the unique capacity to transform phospholipid vesicle substrates into nanoscale disk-shaped bilayers. This reaction can proceed in the presence of exogenous hydrophobic biomolecules, resulting in the formation of novel transport vehicles termed nanodisks (NDs). The objective of this study is to describe the structural organization of NDs and evaluate the utility of these complexes as hydrophobic biomolecule transport vehicles. The topics presented focus on two distinct water insoluble drugs, amphotericin B (AMB) and all trans retinoic acid (ATRA). In vitro and in vivo studies reveal that AMB-ND display potent anti-fungal and anti-protozoal activity, while ATRA-ND show promise in the treatment of cancer. The versatility conferred by the presence of a polypeptide component provides opportunities for targeted delivery of ND to cells.

  10. Fragment-based drug design.

    PubMed

    Feyfant, Eric; Cross, Jason B; Paris, Kevin; Tsao, Désirée H H

    2011-01-01

    Fragment-based drug design (FBDD), which is comprised of both fragment screening and the use of fragment hits to design leads, began more than 15 years ago and has been steadily gaining in popularity and utility. Its origin lies on the fact that the coverage of chemical space and the binding efficiency of hits are directly related to the size of the compounds screened. Nevertheless, FBDD still faces challenges, among them developing fragment screening libraries that ensure optimal coverage of chemical space, physical properties and chemical tractability. Fragment screening also requires sensitive assays, often biophysical in nature, to detect weak binders. In this chapter we will introduce the technologies used to address these challenges and outline the experimental advantages that make FBDD one of the most popular new hit-to-lead process. PMID:20981527

  11. Burnout and health care utilization.

    PubMed

    Jackson, C N; Manning, M R

    1995-01-01

    This study explores the relationship between burnout and health care utilization of 238 employed adults. Burnout was measured by the Maslach Burnout Inventory and health care utilization by insurance company records regarding these employees' health care costs and number of times they accessed health care services over a one year period. ANOVAs were conducted using Golembiewski and Munzenrider's approach to define the burnout phase. Significant differences in health care costs were found. PMID:10152340

  12. Photovoltaics: New opportunities for utilities

    NASA Astrophysics Data System (ADS)

    1991-07-01

    This publication presents information on photovoltaics. The following topics are discussed: residential photovoltaics- the New England experience builds confidence in PV; Austin's 300-kW Photovoltaic Power Station- evaluating the breakeven costs; residential photovoltaics- the lessons learned; photovoltaics for electric utility use; least-cost planning- the environmental link; photovoltaics in the distribution system; photovoltaic systems for the rural consumer; the issues of utility-intertied photovoltaics; and photovoltaics for large-scale use- costs ready to drop again.

  13. Enduring values of municipal utilities

    SciTech Connect

    Telly, C.S.; Grove, J.F.

    1981-05-01

    The value of municipal utilities is assessed in terms of their social responsibility, the political responsiveness of the owners, and pricing policy - issues which conflict with the traditional concept of corporate responsibility to the shareholder and which reveal a growing demand for accountability. Although municipal utilities are only a small part of the economic, legal, and political setting, they contribute as a small, locally-controlled natural monopoly to the American goals of democracy and self-determination. (DCK)

  14. Facilities Utilization Program Implementation Handbook

    NASA Technical Reports Server (NTRS)

    1987-01-01

    This Facilities Utilization Program Implementation Handbook (FUPIH) prescribes procedures for the review and the reporting on the utilization of NASA facilities. The Directors of NASA Field Installations should designate an Installation Official responsible for coordinating the assignment of buildings space and implementing the facilities utilization reviews and annual report preparation. The individual designated shall be known as the 'Facilities Utilization Officer (FUO).' Functional responsibilities of the FUO are detailed in NASA Management Instruction (NMI) 7234.1. It is recognized that titles used in the implementation of the Facilities Utilization Program may vary between field installations. The Facilities Utilization Program (FUP) is designed to provide a uniform and orderly process for meeting or addressing the following objectives: the establishment of sound facilities requirements to meet NASA's programmatic and institutional needs; the optimum allocation of available facilities and related resources to meet these requirements; and the early identification and request for required additional facilities resources. The detailed review and reporting system enacted by NMI 7234.1 should encourage more comprehensive utilization planning for all NASA facilities and ensure, to the maximum extent practicable, that all such facilities are put to their highest and best use consistent with NASA programmatic and institutional priorities. A principal purpose of the FUP is the early identification of NASA facilities which may be or may become underutilized or excess to NASA needs and to provide a timely reference point from which corrective actions (i.e., consolidation, elimination of duplication, improved utilization of disposal) may be taken. Because the supply of this handbook is limited, distribution should be controlled at the field installation level.

  15. Photovoltaics: New opportunities for utilities

    SciTech Connect

    Not Available

    1991-07-01

    This publication presents information on photovoltaics. The following topics are discussed: Residential Photovoltaics: The New England Experience Builds Confidence in PV; Austin's 300-kW Photovoltaic Power Station: Evaluating the Breakeven Costs; Residential Photovoltaics: The Lessons Learned; Photovoltaics for Electric Utility Use; Least-Cost Planning: The Environmental Link; Photovoltaics in the Distribution System; Photovoltaic Systems for the Rural Consumer; The Issues of Utility-Intertied Photovoltaics; and Photovoltaics for Large-Scale Use: Costs Ready to Drop Again.

  16. Regulatory reform and public utilities

    SciTech Connect

    Crew, M.A.

    1982-01-01

    This book results from two seminars regarding the subject title that were held at Rutgers the State University, New Brunswick, NJ on October 30, 1981 and March 26, 1982. The seminars received financial support from leading New Jersey utilities. The introductory chapter (by the editor) and the other nine chapters are all written within the context of the pressures facing regulated utilities and their regulators. A separate abstract was prepared for each chapter.

  17. Antimicrobial (Drug) Resistance

    MedlinePlus

    ... Antimicrobial (Drug) Resistance Antibiotic-Resistant Mycobacterium tuberculosis (TB) Methicillin-Resistant Staphylococcus aureus (MRSA) Vancomycin-Resistant Enterococci (VRE) Multidrug-Resistant Neisseria ...

  18. Newer drugs for arthritis.

    PubMed

    McGillivray, D C

    1977-01-01

    The major area of new drug discoveries for the treatment of arthritis is in non-steroidal anti-inflammatory agents (NSAIA). Unfortunately, as yet no new and safe drug of major significance has appeared. Aspirin still ranks high beside the newcomers. Indomethacin, ibuprofen, naproxen, fenoprofen and tolmetin are described and their roles in therapy are discussed. A further group of older drugs receiving new application in the treatment of arthritis is presented. These include penicillamine and the immunosuppressive drugs. Gold and chloroquin are also discussed to put these agents in their proper perspective.

  19. [The importance of therapeutic drug monitoring for psychotropic drugs].

    PubMed

    Messer, Thomas; Schmauss, Max

    2006-05-15

    The goal of therapeutic drug monitoring (TDM) is the optimization of the psychiatric pharmacotherapy. Above all, TDM is absolutely indicated for the prevention of adverse drug effects or poisoning. TDM is well-established for therapies with antidepressants, antipsychotic drugs and mood stabilizers. For anti-dementia drugs, anxiolytic drugs, hypnotic drugs and medications for treating addiction, monitoring is currently applied to the interpretation of side effects, drug interactions and to forensic questions. PMID:20104722

  20. Neuroimaging and Drug Taking in Primates Abbreviated title: Neuroimaging and Drug taking

    PubMed Central

    Murnane, Kevin S.; Howell, Leonard L.

    2011-01-01

    Rationale Neuroimaging techniques have led to significant advances in our understanding of the neurobiology of drug-taking and the treatment of drug addiction in humans. Neuroimaging approaches provide a powerful translational approach that can link findings from humans and laboratory animals. Objective This review describes the utility of neuroimaging toward understanding the neurobiological basis of drug taking, and documents the close concordance that can be achieved among neuroimaging, neurochemical and behavioral endpoints. Results The study of drug interactions with dopamine and serotonin transporters in vivo has identified pharmacological mechanisms of action associated with the abuse liability of stimulants. Neuroimaging has identified the extended limbic system, including the prefrontal cortex and anterior cingulate, as important neuronal circuitry that underlies drug taking. The ability to conduct within-subject, longitudinal assessments of brain chemistry and neuronal function has enhanced our efforts to document long-term changes in dopamine D2 receptors, monoamine transporters, and prefrontal metabolism due to chronic drug exposure. Dysregulation of dopamine function and brain metabolic changes in areas involved in reward circuitry have been linked to drug-taking behavior, cognitive impairment and treatment response. Conclusions Experimental designs employing neuroimaging should consider well-documented determinants of drug taking, including pharmacokinetic considerations, subject history and environmental variables. Methodological issues to consider include limited molecular probes, lack of neurochemical specificity in brain activation studies, and the potential influence of anesthetics in animal studies. Nevertheless, these integrative approaches should have important implications for understanding drug-taking behavior and the treatment of drug addiction. PMID:21360099

  1. Oral Drug Delivery Systems Comprising Altered Geometric Configurations for Controlled Drug Delivery

    PubMed Central

    Moodley, Kovanya; Pillay, Viness; Choonara, Yahya E.; du Toit, Lisa C.; Ndesendo, Valence M. K.; Kumar, Pradeep; Cooppan, Shivaan; Bawa, Priya

    2012-01-01

    Recent pharmaceutical research has focused on controlled drug delivery having an advantage over conventional methods. Adequate controlled plasma drug levels, reduced side effects as well as improved patient compliance are some of the benefits that these systems may offer. Controlled delivery systems that can provide zero-order drug delivery have the potential for maximizing efficacy while minimizing dose frequency and toxicity. Thus, zero-order drug release is ideal in a large area of drug delivery which has therefore led to the development of various technologies with such drug release patterns. Systems such as multilayered tablets and other geometrically altered devices have been created to perform this function. One of the principles of multilayered tablets involves creating a constant surface area for release. Polymeric materials play an important role in the functioning of these systems. Technologies developed to date include among others: Geomatrix® multilayered tablets, which utilizes specific polymers that may act as barriers to control drug release; Procise®, which has a core with an aperture that can be modified to achieve various types of drug release; core-in-cup tablets, where the core matrix is coated on one surface while the circumference forms a cup around it; donut-shaped devices, which possess a centrally-placed aperture hole and Dome Matrix® as well as “release modules assemblage”, which can offer alternating drug release patterns. This review discusses the novel altered geometric system technologies that have been developed to provide controlled drug release, also focusing on polymers that have been employed in such developments. PMID:22312236

  2. Ultrasound mediated nanoparticle drug delivery

    NASA Astrophysics Data System (ADS)

    Mullin, Lee B.

    Ultrasound is not only a powerful diagnostic tool, but also a promising therapeutic technology that can be used to improve localized drug delivery. Microbubble contrast agents are micron sized encapsulated gas filled bubbles that are administered intravenously. Originally developed to enhance ultrasound images, microbubbles are highly echogenic due to the gas core that provides a detectable impedance difference from the surrounding medium. The core also allows for controlled response of the microbubbles to ultrasound pulses. Microbubbles can be pushed using acoustic radiation force and ruptured using high pressures. Destruction of microbubbles can increase permeability at the cellular and vascular level, which can be advantageous for drug delivery. Advances in drug delivery methods have been seen with the introduction of nanoparticles, nanometer sized objects often carrying a drug payload. In chemotherapy, nanoparticles can deliver drugs to tumors while limiting systemic exposure due to abnormalities in tumor vasculature such large gaps between endothelial cells that allow nanoparticles to enter into the interstitial space; this is referred to as the enhanced permeability and retention (EPR) effect. However, this effect may be overestimated in many tumors. Additionally, only a small percentage of the injected dose accumulates in the tumor, which most the nanoparticles accumulating in the liver and spleen. It is hypothesized that combining the acoustic activity of an ultrasound contrast agent with the high payload and extravasation ability of a nanoparticle, localized delivery to the tumor with reduced systemic toxicity can be achieved. This method can be accomplished by either loading nanoparticles onto the shell of the microbubble or through a coadministration method of both nanoparticles and microbubbles. The work presented in this dissertation utilizes novel and commercial nanoparticle formulations, combined with microbubbles and a variety of ultrasound systems

  3. Drug Repositioning for Cancer Therapy Based on Large-Scale Drug-Induced Transcriptional Signatures.

    PubMed

    Lee, Haeseung; Kang, Seungmin; Kim, Wankyu

    2016-01-01

    An in silico chemical genomics approach is developed to predict drug repositioning (DR) candidates for three types of cancer: glioblastoma, lung cancer, and breast cancer. It is based on a recent large-scale dataset of ~20,000 drug-induced expression profiles in multiple cancer cell lines, which provides i) a global impact of transcriptional perturbation of both known targets and unknown off-targets, and ii) rich information on drug's mode-of-action. First, the drug-induced expression profile is shown more effective than other information, such as the drug structure or known target, using multiple HTS datasets as unbiased benchmarks. Particularly, the utility of our method was robustly demonstrated in identifying novel DR candidates. Second, we predicted 14 high-scoring DR candidates solely based on expression signatures. Eight of the fourteen drugs showed significant anti-proliferative activity against glioblastoma; i.e., ivermectin, trifluridine, astemizole, amlodipine, maprotiline, apomorphine, mometasone, and nortriptyline. Our DR score strongly correlated with that of cell-based experimental results; the top seven DR candidates were positive, corresponding to an approximately 20-fold enrichment compared with conventional HTS. Despite diverse original indications and known targets, the perturbed pathways of active DR candidates show five distinct patterns that form tight clusters together with one or more known cancer drugs, suggesting common transcriptome-level mechanisms of anti-proliferative activity. PMID:26954019

  4. Employment, employment-related problems, and drug use at drug court entry.

    PubMed

    Leukefeld, Carl; McDonald, Hope Smiley; Staton, Michele; Mateyoke-Scrivner, Allison

    2004-01-01

    The literature indicates that employment may be an important factor for retaining substance misusing clients in treatment. Given the link between employment problems and treatment retention for Drug Court clients, the current project builds upon the existing services provided by Drug Courts in order to develop and implement an innovative model that focuses on obtaining, maintaining, and upgrading employment for Drug Court participants. The purpose of this article is to (1) describe the employment intervention used in Kentucky Drug Courts, which is grounded in established job readiness and life skill training approaches; and (2) profile those participants who were employed full-time prior to Drug Court and those who were not. Findings suggest that those employed full-time were more likely to have higher incomes and more earned income from legitimate job sources, although there were no differences in the types of employment (major jobs included food service and construction). In addition, study findings suggest that full-time employment was not "protective" since there were few differences in drug use and criminal activity by employment status. Employment interventions need to be examined to determine their utility for enhancing employment and keeping drug users in treatment. This article focuses on the initial 400 participants, who began entering the study in March, 2000.

  5. PREDICTING DRUG DISPOSITION, ABSORPTION / ELIMINATION / TRANSPORTER INTERPLAY AND THE ROLE OF FOOD ON DRUG ABSORPTION

    PubMed Central

    Custodio, Joseph M.; Wu, Chi-Yuan; Benet, Leslie Z.

    2008-01-01

    The ability to predict drug disposition involves concurrent consideration of many chemical and physiological variables and the effect of food on the rate and extent of availability adds further complexity due to postprandial changes in the gastrointestinal (GI) tract. A system that allows for the assessment of the multivariate interplay occurring following administration of an oral dose, in the presence or absence of meal, would greatly benefit the early stages of drug development. This is particularly true in an era when the majority of new molecular entities are highly permeable, poorly soluble, extensively metabolized compounds (BDDCS Class 2), which present the most complicated relationship in defining the impact of transporters due to the marked effects of transporter-enzyme interplay. This review evaluates the GI luminal environment by taking into account the absorption / transport / elimination interplay and evaluates the physiochemical property issues by taking into account the importance of solubility, permeability and metabolism. We concentrate on the BDDCS and its utility in predicting drug disposition. Furthermore, we focus on the effect of food on the extent of drug availability (F), which appears to follow closely what might be expected if a significant effect of high fat meals is inhibition of transporters. That is, high fat meals and lipidic excipients would be expected to have little effect on F for Class 1 drugs; they would increase F of Class 2 drugs, while decreasing F for Class 3 drugs. PMID:18199522

  6. June`s jolt: A utility`s perspective

    SciTech Connect

    Fayne, H.

    1998-10-01

    The unprecedented Midwest market turmoil in late June was an anomalous situation stemming from a confluence of four key conditions. Claims of inappropriate behavior by utilities and other market participants are unfounded, and a retreat to re-regulation would be a serious mistake. During the week of June 22, the Midwestern United States saw a convergence of events that severely stretched the physical capabilities of the interconnected electric utility system and its supporting power generation. These events, added to an already tight capacity situation, included a significant amount of Midwestern power generation that went out of service, hotter than expected weather over a large area of the region, and various transmission constraints. Further complications resulted when some market participants defaulted on contracts. A number of utilities were forced into the hourly spot market to meet their load obligations. The utilities were forced into the market because their suppliers curtailed deliveries, they (the utilities) did not have sufficient capabilities, or their contracted resources were insufficient to cover their load requirements.

  7. Silk-Based Biomaterials for Sustained Drug Delivery

    PubMed Central

    Yucel, Tuna; Lovett, Michael L.; Kaplan, David L.

    2014-01-01

    Silk presents a rare combination of desirable properties for sustained drug delivery, including aqueous-based purification and processing options without chemical cross-linkers, compatibility with common sterilization methods, controllable and surface-mediated biodegradation into non-inflammatory by-products, biocompatibility, utility in drug stabilization, and robust mechanical properties. A versatile silk-based toolkit is currently available for sustained drug delivery formulations of small molecule through macromolecular drugs, with a promise to mitigate several drawbacks associated with other degradable sustained delivery technologies in the market. Silk-based formulations utilize silk’s well-defined nano- through microscale structural hierarchy, stimuli-responsive self-assembly pathways and crystal polymorphism, as well as sequence and genetic modification options towards targeted pharmaceutical outcomes. Furthermore, by manipulating the interactions between silk and drug molecules, near-zero order sustained release may be achieved through diffusion- and degradation-based release mechanisms. Because of these desirable properties, there has been increasing industrial interest in silk-based drug delivery systems currently at various stages of the developmental pipeline from pre-clinical to FDA-approved products. Here, we discuss the unique aspects of silk technology as a sustained drug delivery platform and highlight the current state of the art in silk-based drug delivery. We also offer a potential early development pathway for silk-based sustained delivery products. PMID:24910193

  8. Utilization

    NASA Astrophysics Data System (ADS)

    Lu, Guozhi; Zhang, Ting-An; Zhu, Xiaofeng; Liu, Yan; Wang, Yanxiu; Guo, Fangfang; Zhao, Qiuyue; Zheng, Chaozhen

    2014-09-01

    In this study, a calcification-carbonation method is proposed to change the equilibrium structure of red mud produced from the Bayer process. The thermodynamics of both calcification and carbonation processes has been elucidated. In addition, the non-isothermal kinetics involved in the calcification process and the effects of different parameters on the hydrogarnet synthesis and carbonation decomposition are experimentally investigated using pure reagents. The results indicate that through a two-step carbonation treatment of calcified slag by the new method, the mass ratio of alumina to silica ( A/S) of the modified red mud has decreased to 0.44 and the Na2O content drops to 0.12 wt.% at the carbonation temperature of 120°C under the CO2 pressure of 1.2 MPa. The newly modified red mud could be directly used in the cement industry.

  9. Recommunalizing Drug Offenders: The "Drug Peace" Agenda.

    ERIC Educational Resources Information Center

    Arrigo, Bruce A.

    1997-01-01

    Examines the manner in which substance-using shelter tenants, many of them ex-offenders, who lived in an urban, single- room-occupancy neighborhood, engaged in the process of recommunalization. Identifies and describes eight developmental stages of recommunalization, and links recommunalization to proposals for solving the war on drugs. (RJM)

  10. Drugs and Drug Abuse: A Bibliography.

    ERIC Educational Resources Information Center

    State Univ. of New York, Stony Brook.

    For a relatively new field of research and interest, the bibliographic control of drug literature (indexing and recording for retrieval) is remarkable. Public and private agencies have taken the initiative in compiling catalogs, bibliographies and indexes which, although often duplicatory, nonetheless ensure access to the many aspects of the drug…

  11. The Drug War.

    ERIC Educational Resources Information Center

    DeCrosta, Anthony

    1989-01-01

    The role of teachers in helping fight against drug abuse is discussed stressing the teacher's ability to see changes in the students and the potential for positive influence. A vital school role involves teaching life skills and wellness principles. Information on commonly abused drugs and their effects is presented. (SM)

  12. Drug and Substance Abuse

    MedlinePlus

    ... Latest Research Getting More Help Related Topics Anxiety COPD Delirium Depression Pain Management Prevention Related News Older Adults Who Drink Alcohol at Risk for Drug Interactions Monday, November 23, 2015 Join our e-newsletter! Aging & Health A to Z Drug and Substance Abuse ...

  13. Dimensions of Drug Information

    ERIC Educational Resources Information Center

    Sharp, Mark E.

    2011-01-01

    The high number, heterogeneity, and inadequate integration of drug information resources constitute barriers to many drug information usage scenarios. In the biomedical domain there is a rich legacy of knowledge representation in ontology-like structures that allows us to connect this problem both to the very mature field of library and…

  14. Drug effects on spermatogenesis.

    PubMed

    Amory, John K

    2007-10-01

    Many drugs can adversely affect spermatogenesis. These effects can occur either by directly inhibiting sperm or testicular function or indirectly by impairing the hypothalamic pituitary testicular axis. In this paper, we will review the drugs that are known to adversely impact spermatogenesis, and/or sperm function and detail what is known about the mechanisms through which these compounds impair fertility in men.

  15. Drugs and Personal Values.

    ERIC Educational Resources Information Center

    Blum, Richard H.

    Drug use and abuse have two major motivations: the medical or curative, and the religious or supplementary. The author discusses the expanding use of drugs for both purposes, suggesting a possible connection between increased medical use and confidence, and increased religious or pleasure use. He outlines many problems of definition and public…

  16. Enhancing Drug Court Success

    ERIC Educational Resources Information Center

    Deschenes, Elizabeth Piper; Ireland, Connie; Kleinpeter, Christine B.

    2009-01-01

    This study evaluates the impact of enhanced drug court services in a large county in Southern California. These enhanced services, including specialty counseling groups, educational/employment resources, and increased Residential Treatment (RT) beds, were designed to increase program retention and successful completion (graduation) of drug court.…

  17. Automated drug identification system

    NASA Technical Reports Server (NTRS)

    Campen, C. F., Jr.

    1974-01-01

    System speeds up analysis of blood and urine and is capable of identifying 100 commonly abused drugs. System includes computer that controls entire analytical process by ordering various steps in specific sequences. Computer processes data output and has readout of identified drugs.

  18. Drug Testing. Research Brief

    ERIC Educational Resources Information Center

    Walker, Karen

    2007-01-01

    In 2002, the United States Supreme Court confirmed that in the school's role of in loco parentis, drug testing of students who were involved in athletics and extracurricular activities was constitutional. In a state of the union address, George W. Bush stated that drug testing in schools had been effective and was part of "our aggressive…

  19. Drugs, Alcohol & Pregnancy.

    ERIC Educational Resources Information Center

    Dye, Christina

    Expectant parents are introduced to the effects of a variety of drugs on the unborn baby. Material is divided into seven sections. Section 1 deals with the most frequently used recreational drugs, including alcohol, marijuana, narcotics, depressants, stimulants, inhalants, and hallucinogens. Sections 2 and 3 focus on the effects of prescription…

  20. Alternative drugs of abuse.

    PubMed

    Sutter, M E; Chenoweth, J; Albertson, T E

    2014-02-01

    The incidence of drug abuse with alternative agents is increasing. The term "alternative drugs of abuse" is a catch-all term for abused chemicals that do not fit into one of the classic categories of drugs of abuse. The most common age group abusing these agents range from 17 to 25 years old and are often associated with group settings. Due to their diverse pharmacological nature, legislative efforts to classify these chemicals as a schedule I drug have lagged behind the development of new alternative agents. The potential reason for abuse of these agents is their hallucinogenic, dissociative, stimulant, anti-muscarinic, or sedative properties. Some of these drugs are easily obtainable such as Datura stramonium (Jimson Weed) or Lophophora williamsii (Peyote) because they are natural plants indigenous to certain regions. The diverse pharmacology and clinical effects of these agents are so broad that they do not produce a universal constellation of signs and symptoms. Detailed physical exams are essential for identifying clues leading one to suspect an alternative drug of abuse. Testing for the presence of these agents is often limited, and even when available, the results do not return in a timely fashion. Intoxications from these agents pose unique challenges for health care providers. Physician knowledge of the physiological effects of these alternative agents and the local patterns of drug of abuse are important for the accurate diagnosis and optimal care of poisoned patients. This review summarizes the current knowledge of alternative drugs of abuse and highlights their clinical presentations. PMID:23636733

  1. Interoception and Drug Addiction

    PubMed Central

    Paulus, Martin P.; Stewart, Jennifer L.

    2013-01-01

    The role of interoception and its neural basis with relevance to drug addiction is reviewed. Interoception consists of the receiving, processing, and integrating body-relevant signals with external stimuli to affect ongoing motivated behavior. The insular cortex is the central nervous system hub to process and integrate these signals. Interoception is an important component of several addiction relevant constructs including arousal, attention, stress, reward, and conditioning. Imaging studies with drug-addicted individuals show that the insular cortex is hypo-active during cognitive control processes but hyperactive during cue reactivity and drug-specific, reward-related processes. It is proposed that interoception contributes to drug addiction by incorporating an “embodied” experience of drug uses together with the individual’s predicted versus actual internal state to modulate approach or avoidance behavior, i.e. whether to take or not to take drugs. This opens the possibility of two types of interventions. First, one may be able to modulate the embodied experience by enhancing insula reactivity where necessary, e.g. when engaging in drug seeking behavior, or attenuating insula when exposed to drug-relevant cues. Second, one may be able to reduce the urge to act by increasing the frontal control network, i.e. inhibiting the urge to use by employing cognitive training. PMID:23855999

  2. Prescription Drug Abuse

    MedlinePlus

    ... Fitness Diseases & Conditions Infections Q&A School & Jobs Drugs & Alcohol Staying Safe Recipes En Español Making a Change – Your Personal Plan Hot Topics Meningitis Choosing Your Mood Prescription Drug Abuse Healthy School Lunch Planner How Can I ...

  3. Newer antithrombotic drugs

    PubMed Central

    Sikka, Pranav; Bindra, V. K.

    2010-01-01

    Thromboembolic disorders are one of the disorders for which we are still on the look out for a safe and efficient drug. Despite the widespread use of antithrombotic drugs for the prevention and treatment of arterial and venous thrombosis, thromboembolic diseases continue to be a major cause of death and disability worldwide. This shows our inefficiency in searching efficacious and safe antithrombotic drugs. We have reached the basic mechanism of thrombus formation and by interrupting various steps of this mechanism, we can prevent as well as treat thromboembolic disorders. In continuation of Aspirin, now, we are using Clopidogrel, Ticlopidine and GpIIb/IIIa inhibitors (Abciximab, Tirofiban and Eptifibatide). Warfarin is an old antithrombotic drug which is still being used; but due to various side effects and drug interactions, we are bound to use newer drugs. Newer antiplatelet drugs include Prasugrel, Ticagrelor and Cangrelor, whereas newer thrombin inhibitors are Ximelgatran and Dabigatran. Apixaban is also a newer entry in this category as factor Xa inhibitor. Idrabiotaparinux is an indirect inhibitor of Xa as it accelerates the activity of antithrombin. Moreover, researches and trials for better and safe drugs are ongoing. PMID:21572750

  4. PRESERVATION OF DRUGS

    PubMed Central

    Rao, R. Bhima; Natarajan, R.K.; Sarma, P.S. Nataraja; Purushothaman, K.K.

    1982-01-01

    In this article the factors likely to cause spoilage of the drugs of the Indian systems of medicine are reviewed. Methods for the prevention of spoilage are discussed. The results of a limited study carried out on the stability of a few selected drug preparations representing the main dosage forms are also presented PMID:22556951

  5. Implantable Drug Dispenser

    NASA Technical Reports Server (NTRS)

    Collins, E. R. J.

    1983-01-01

    Drugs such as insulin are injected as needed directly into bloodstream by compact implantable dispensing unit. Two vapor cavities produce opposing forces on drug-chamber diaphragm. Heaters in cavities allow control of direction and rate of motion of bellows. Dispensing capsule fitted with coil so batteries can be recharged by induction.

  6. Single compartment drug delivery

    PubMed Central

    Cima, Michael J.; Lee, Heejin; Daniel, Karen; Tanenbaum, Laura M.; Mantzavinou, Aikaterini; Spencer, Kevin C.; Ong, Qunya; Sy, Jay C.; Santini, John; Schoellhammer, Carl M.; Blankschtein, Daniel; Langer, Robert S.

    2014-01-01

    Drug design is built on the concept that key molecular targets of disease are isolated in the diseased tissue. Systemic drug administration would be sufficient for targeting in such a case. It is, however, common for enzymes or receptors that are integral to disease to be structurally similar or identical to those that play important biological roles in normal tissues of the body. Additionally, systemic administration may not lead to local drug concentrations high enough to yield disease modification because of rapid systemic metabolism or lack of sufficient partitioning into the diseased tissue compartment. This review focuses on drug delivery methods that physically target drugs to individual compartments of the body. Compartments such as the bladder, peritoneum, brain, eye and skin are often sites of disease and can sometimes be viewed as “privileged,” since they intrinsically hinder partitioning of systemically administered agents. These compartments have become the focus of a wide array of procedures and devices for direct administration of drugs. We discuss the rationale behind single compartment drug delivery for each of these compartments, and give an overview of examples at different development stages, from the lab bench to phase III clinical trials to clinical practice. We approach single compartment drug delivery from both a translational and a technological perspective. PMID:24798478

  7. Drug Testing. Research Brief

    ERIC Educational Resources Information Center

    Walker, Karen

    2005-01-01

    The Vernonia School District v. Acton Supreme Court decision in 1995, forever changed the landscape of the legality of drug testing in schools. This decision stated that students who were involved in athletic programs could be drug tested as long as the student's privacy was not invaded. According to some in the medical profession, there are two…

  8. Alternative drugs of abuse.

    PubMed

    Sutter, M E; Chenoweth, J; Albertson, T E

    2014-02-01

    The incidence of drug abuse with alternative agents is increasing. The term "alternative drugs of abuse" is a catch-all term for abused chemicals that do not fit into one of the classic categories of drugs of abuse. The most common age group abusing these agents range from 17 to 25 years old and are often associated with group settings. Due to their diverse pharmacological nature, legislative efforts to classify these chemicals as a schedule I drug have lagged behind the development of new alternative agents. The potential reason for abuse of these agents is their hallucinogenic, dissociative, stimulant, anti-muscarinic, or sedative properties. Some of these drugs are easily obtainable such as Datura stramonium (Jimson Weed) or Lophophora williamsii (Peyote) because they are natural plants indigenous to certain regions. The diverse pharmacology and clinical effects of these agents are so broad that they do not produce a universal constellation of signs and symptoms. Detailed physical exams are essential for identifying clues leading one to suspect an alternative drug of abuse. Testing for the presence of these agents is often limited, and even when available, the results do not return in a timely fashion. Intoxications from these agents pose unique challenges for health care providers. Physician knowledge of the physiological effects of these alternative agents and the local patterns of drug of abuse are important for the accurate diagnosis and optimal care of poisoned patients. This review summarizes the current knowledge of alternative drugs of abuse and highlights their clinical presentations.

  9. Drug-induced lupus.

    PubMed

    Rubin, Robert L

    2005-04-15

    Autoantibodies and, less commonly, systemic rheumatic symptoms are associated with treatment with numerous medications and other types of ingested compounds. Distinct syndromes can be distinguished, based on clinical and laboratory features, as well as exposure history. Drug-induced lupus has been reported as a side-effect of long-term therapy with over 40 medications. Its clinical and laboratory features are similar to systemic lupus erythematosus, except that patients fully recover after the offending medication is discontinued. This syndrome differs from typical drug hypersensitivity reactions in that drug-specific T-cells or antibodies are not involved in induction of autoimmunity, it usually requires many months to years of drug exposure, is drug dose-dependent and generally does not result in immune sensitization to the drug. Circumstantial evidence strongly suggests that oxidative metabolites of the parent compound trigger autoimmunity. Several mechanisms for induction of autoimmunity will be discussed, including bystander activation of autoreactive lymphocytes due to drug-specific immunity or to non-specific activation of lymphocytes, direct cytotoxicity with release of autoantigens and disruption of central T-cell tolerance. The latter hypothesis will be supported by a mouse model in which a reactive metabolite of procainamide introduced into the thymus results in lupus-like autoantibody induction. These findings, as well as evidence for thymic function in drug-induced lupus patients, support the concept that abnormalities during T-cell selection in the thymus initiate autoimmunity.

  10. Drugs and Addictions.

    ERIC Educational Resources Information Center

    Smith, S. Mae; Miller, Eva

    The effects of drug abuse and dependence vary, depending on the type of drug, polydrug use, and characteristics of the user. The influence of genetic, neurochemical, neuropsyiological, sociocultural, and economic factors suggest that the etiology of substance abuse and dependence is multiply determined. Models explaining the causation of substance…

  11. Medicare Prescription Drug Coverage

    MedlinePlus

    ... people also have to pay an additional monthly cost. Private companies provide Medicare prescription drug coverage. You choose the drug plan you like best. Whether or not you should sign up depends on how good your current coverage is. You need to sign up as ...

  12. Ayurvedic drug discovery.

    PubMed

    Balachandran, Premalatha; Govindarajan, Rajgopal

    2007-12-01

    Ayurveda is a major traditional system of Indian medicine that is still being successfully used in many countries. Recapitulation and adaptation of the older science to modern drug discovery processes can bring renewed interest to the pharmaceutical world and offer unique therapeutic solutions for a wide range of human disorders. Eventhough time-tested evidences vouch immense therapeutic benefits for ayurvedic herbs and formulations, several important issues are required to be resolved for successful implementation of ayurvedic principles to present drug discovery methodologies. Additionally, clinical examination in the extent of efficacy, safety and drug interactions of newly developed ayurvedic drugs and formulations are required to be carefully evaluated. Ayurvedic experts suggest a reverse-pharmacology approach focusing on the potential targets for which ayurvedic herbs and herbal products could bring tremendous leads to ayurvedic drug discovery. Although several novel leads and drug molecules have already been discovered from ayurvedic medicinal herbs, further scientific explorations in this arena along with customization of present technologies to ayurvedic drug manufacturing principles would greatly facilitate a standardized ayurvedic drug discovery.

  13. Safety of obesity drugs.

    PubMed

    Greenway, Frank L; Caruso, Mary K

    2005-11-01

    The safety of obesity drugs has historically been poor. This and the stigmatisation of obesity in society ensured that a higher standard of safety for obesity drugs must be met. The authors review the safety disasters of obesity drugs that were withdrawn. The authors then review the safety of presently available drugs--benzphetamine, phendimetrazine, diethylpropion, phentermine, sibutramine and orlistat. The safety of rimonabant, a drug with a pending new drug application that has an independent effect on metabolic syndrome, is also reviewed. The authors compare the stage of obesity drug development to that of hypertension in the 1950s. As new and safer drugs with more downstream mechanisms are developed that have independent effects on the cardiovascular risks associated with obesity, third party reimbursement for obesity medicine is likely to improve. This may lead to obesity being treated like hypertension and other chronic diseases with long-term medication. With improved technological tools, the authors believe this process will be more rapid for obesity than it was for hypertension.

  14. Drug Dependence in Michigan Including A Study of Attitudes and Actions of the Young People of Michigan.

    ERIC Educational Resources Information Center

    Bogg, Richard A.; And Others

    A 1968 study was undertaken in Michigan with the following objectives: 1) to determine drug utilization rates for public high school seniors; 2) to determine demographic, sociological, and social-psychological correlates of drug utilization; and 3) to acquire information relevant to present and future health education programs. A questionnaire…

  15. Evaluation of enzyme inhibition kinetics in drug-drug interactions.

    PubMed

    Chen, Ang; Qin, Xuan; Tang, Yu; Liu, Mingyao; Wang, Xin

    2014-10-01

    Inhibition of CYP enzymes is thought to be the most common cause of drug-drug and/or herb-drug interactions. To characterize the inhibition of CYP enzymes activities by chemicals, enzyme inhibition kinetic experiments are usually carried out. The purpose of this letter is to call attention to evaluate the enzyme inhibition kinetics in drug-drug interactions.

  16. The exuberant planet: A global look at the role of utilities in protecting biodiversity

    NASA Astrophysics Data System (ADS)

    Yeager, Kurt E.

    1996-11-01

    Biodiversity is a critical environmental issue. Biodiverse species as a source of unique genetic information, for example, continues to provide society with lifesaving drugs and important industrial chemicals. Since US utilities are substantial landholders and virtually every aspect of utility operations are in some way tied to environmental/biodiversity issues, it is important and essential that the utility industry step forward as a leader. This paper details the past, present, and future role that utilities have played and need to play in the very important arena of biodiversity.

  17. Novel Approaches in Formulation and Drug Delivery using Contact Lenses.

    PubMed

    Singh, Kishan; Nair, Anroop B; Kumar, Ashok; Kumria, Rachna

    2011-03-01

    The success of ocular delivery relies on the potential to enhance the drug bioavailability by controlled and extended release of drug on the eye surface. Several new approaches have been attempted to augment the competence and diminish the intrinsic side effects of existing ocular drug delivery systems. In this contest, progress has been made to develop drug-eluting contact lens using different techniques, which have the potential to control and sustain the delivery of drug. Further, the availability of novel polymers have facilitated and promoted the utility of contact lenses in ocular drug delivery. Several research groups have already explored the feasibility and potential of contact lens using conventional drugs for the treatment of periocular and intraocular diseases. Contact lenses formulated using modern technology exhibits high loading, controlled drug release, apposite thickness, water content, superior mechanical and optical properties as compared to commercial lenses. In general, this review discus various factors and approaches designed and explored for the successful delivery of ophthalmic drugs using contact lenses as drug delivery device.

  18. Novel Approaches in Formulation and Drug Delivery using Contact Lenses

    PubMed Central

    Singh, Kishan; Nair, Anroop B; Kumar, Ashok; Kumria, Rachna

    2011-01-01

    The success of ocular delivery relies on the potential to enhance the drug bioavailability by controlled and extended release of drug on the eye surface. Several new approaches have been attempted to augment the competence and diminish the intrinsic side effects of existing ocular drug delivery systems. In this contest, progress has been made to develop drug-eluting contact lens using different techniques, which have the potential to control and sustain the delivery of drug. Further, the availability of novel polymers have facilitated and promoted the utility of contact lenses in ocular drug delivery. Several research groups have already explored the feasibility and potential of contact lens using conventional drugs for the treatment of periocular and intraocular diseases. Contact lenses formulated using modern technology exhibits high loading, controlled drug release, apposite thickness, water content, superior mechanical and optical properties as compared to commercial lenses. In general, this review discus various factors and approaches designed and explored for the successful delivery of ophthalmic drugs using contact lenses as drug delivery device PMID:24826007

  19. Making connections: New Orleans Evacuees' experiences in obtaining drugs.

    PubMed

    Dunlap, Eloise; Johnson, Bruce D; Kotarba, Joseph A; Fackler, Jennifer

    2009-09-01

    Between August 29 and September 7, 2005, almost all New Orleans residents were evacuated from the area in the aftermath of Hurricane Katrina. News reports indicate that almost 130,000 New Orleans Evacuees (NOEs) were evacuated to Houston, Texas, the largest recipient of the civilian population from New Orleans. Some of these NOEs were active participants in the illicit drug market in New Orleans prior to the hurricane. The period between the flooding and the nearly complete evacuation of New Orleans as well as their subsequent displacement to Houston and other locations provided unique opportunities to study what occurs when illicit drug markets are disrupted, since populations of illicit drug users and purchasers could no longer routinely obtain their drugs in predictable ways. Utilizing qualitative data from in-depth interviews and focus groups, this article describes the ways NOEs (1) managed their drug acquisition and use following evacuation; (2) located new sources of drugs in Houston and elsewhere by tapping into shared drug culture; and (3) gained access to and learned the argot for drugs in the local drug market in new settings. This report contributes to the nascent literature on disrupted drug markets.

  20. Utility Solar Generation Valuation Methods

    SciTech Connect

    Hansen, Thomas N.; Dion, Phillip J.

    2009-06-30

    Tucson Electric Power (TEP) developed, tested and verified the results of a new and appropriate method for accurately evaluating the capacity credit of time variant solar generating sources and reviewed new methods to appropriately and fairly evaluate the value of solar generation to electric utilities. The project also reviewed general integrated approaches for adequately compensating owners of solar generation for their benefits to utilities. However, given the limited funding support and time duration of this project combined with the significant differences between utilities regarding rate structures, solar resource availability and coincidence of solar generation with peak load periods, it is well beyond the scope of this project to develop specific rate, rebate, and interconnection approaches to capture utility benefits for all possible utilities. The project developed computer software based evaluation method models to compare solar generation production data measured in very short term time increments called Sample Intervals over a typical utility Dispatch Cycle during an Evaluation Period against utility system load data. Ten second resolution generation production data from the SGSSS and actual one minute resolution TEP system load data for 2006 and 2007, along with data from the Pennington Street Garage 60 kW DC capacity solar unit installed in downtown Tucson will be applied to the model for testing and verification of the evaluation method. Data was provided by other utilities, but critical time periods of data were missing making results derived from that data inaccurate. The algorithms are based on previous analysis and review of specific 2005 and 2006 SGSSS production data. The model was built, tested and verified by in house TEP personnel. For this phase of the project, TEP communicated with, shared solar production data with and collaborated on the development of solar generation valuation tools with other utilities, including Arizona Public