Drug utilization review: mechanisms to improve its effectiveness and broaden its scope. The U.S. Pharmacopeia Drug Utilization Review Advisory Panel.

PubMed

2000-01-01

To address important problems and needed changes in online and retrospective drug utilization review (DUR) programs. Emphasis is placed on reliability of DUR criteria and the shift of traditional retrospective DUR programs toward disease management and health care outcomes. Published literature evaluating the role of online and retrospective DUR programs. Particular attention was given to studies assessing DUR criteria reliability and new interventions with retrospective DUR programs. A literature review was conducted along with an expert summary from the U.S. Pharmacopeia Drug Utilization Review Advisory Panel. Studies have revealed variations in DUR criteria that could be affecting clinical practice and patient care. Appropriate formal methodologies and use of consistent procedures in developing online prospective DUR programs and systems could help resolve these problems. Traditional retrospective DUR is also shifting to incorporate disease management and methodologies from health outcomes and pharmacoeconomics studies. Refinements are needed to improve the reliability and validity of online DUR criteria and to minimize false positive messages. Databases created as a result of DUR efforts have been used in new and innovative ways to incorporate health outcomes data and disease management interventions. Additional outcomes data, combined with quality assurance efforts, should increase the utility of DUR/disease management efforts in evaluating health systems while improving the effectiveness and efficiency of pharmacists' health care interventions.

Out-of-pocket drug costs and drug utilization patterns of postmenopausal Medicare beneficiaries with osteoporosis.

PubMed

Conwell, Leslie Jackson; Esposito, Dominick; Garavaglia, Susan; Meadows, Eric S; Colby, Margaret; Herrera, Vivian; Goldfarb, Seth; Ball, Daniel; Marciniak, Martin

2011-08-01

The Medicare Part D coverage gap has been associated with lower adherence and drug utilization and higher discontinuation. Because osteoporosis has a relatively high prevalence among Medicare-eligible postmenopausal women, we examined changes in utilization of osteoporosis medications during this coverage gap. The purpose of this study was to investigate changes in out-of-pocket (OOP) drug costs and utilization associated with the Medicare Part D coverage gap among postmenopausal beneficiaries with osteoporosis. This retrospective analysis of 2007 pharmacy claims focuses on postmenopausal female Medicare beneficiaries enrolled in full-, partial-, or no-gap exposure standard or Medicare Advantage prescription drug plans (PDPs), retiree drug subsidy (RDS) plans, or the low-income subsidy program. We compared beneficiaries with osteoporosis who were taking teriparatide (Eli Lilly and Company, Indianapolis, Indiana) (n = 5657) with matched samples of beneficiaries who were taking nonteriparatide osteoporosis medications (NTO; n = 16,971) or who had other chronic conditions (OCC; n = 16,971). We measured average monthly prescription drug fills and OOP costs, medication discontinuation, and skipping. More than half the sample reached the coverage gap; OOP costs then rose for teriparatide users enrolled in partial- or full-gap exposure plans (increase of 121% and 186%; $300 and $349) but fell for those in no-gap exposure PDPs or RDS plans (decrease of 49% and 30%; $131 and $40). OOP costs for beneficiaries in partial- or full-gap exposure PDPs increased >120% (increase of $144 and $176) in the NTO group and nearly doubled for the OCC group (increase of $124 and $151); these OOP costs were substantially lower than those for teriparatide users. Both teriparatide users and NTO group members discontinued or skipped medications more often than persons in the OCC group, regardless of plan or benefit design. Medication discontinuation and OOP costs among beneficiaries with

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

Interrupted time series analysis in drug utilization research is increasing: systematic review and recommendations.

PubMed

Jandoc, Racquel; Burden, Andrea M; Mamdani, Muhammad; Lévesque, Linda E; Cadarette, Suzanne M

2015-08-01

To describe the use and reporting of interrupted time series methods in drug utilization research. We completed a systematic search of MEDLINE, Web of Science, and reference lists to identify English language articles through to December 2013 that used interrupted time series methods in drug utilization research. We tabulated the number of studies by publication year and summarized methodological detail. We identified 220 eligible empirical applications since 1984. Only 17 (8%) were published before 2000, and 90 (41%) were published since 2010. Segmented regression was the most commonly applied interrupted time series method (67%). Most studies assessed drug policy changes (51%, n = 112); 22% (n = 48) examined the impact of new evidence, 18% (n = 39) examined safety advisories, and 16% (n = 35) examined quality improvement interventions. Autocorrelation was considered in 66% of studies, 31% reported adjusting for seasonality, and 15% accounted for nonstationarity. Use of interrupted time series methods in drug utilization research has increased, particularly in recent years. Despite methodological recommendations, there is large variation in reporting of analytic methods. Developing methodological and reporting standards for interrupted time series analysis is important to improve its application in drug utilization research, and we provide recommendations for consideration. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Drug utilization pattern during pregnancy in North India.

PubMed

Sharma, Rashmi; Kapoor, Bhuvneshvar; Verma, Ujala

2006-07-01

Pregnancy is a special physiological condition, where drug treatment presents a special concern. To evaluate the drug utilization pattern during pregnancy and to evaluate the effect of the educational and economic status on it.. The retrospective cross-sectional study. The postgraduate Department of Pharmacology and Therapeutics of a medical college. and the antenatal clinic of the institution. Medical students filled 405 questionnaires after interviewing pregnant women (243 primigravida and 152 multigravida). All the collected questionnaires were analysed for various study parameters. Inter-group comparison was done using chi-square test. P value < 0.05 was considered statistically significant. A total of 700, 1086 and 686 drugs, with an average of 1.73, 2.89 and 2.49 drugs per pregnant women, were used during first, second and third trimester of pregnancy, respectively. A majority of the drugs used, were from category-A, followed by category-B and category-D. However, category C and X drugs constituted 2.90 (20) and 5.71% (40) of drugs used during the third trimester and first trimester, respectively. Herbal/homeopathic drugs constituted 6.42 (45), 3.68 (40) and 1.46% (10) of the drugs used in the first, second and third trimester of pregnancy, respectively (P=649). 33.33% (135) women believed that drug use during pregnancy is dangerous to both mother and child and 37.03% (150) believed that drugs are dangerous throughout pregnancy. 55.55% (225) females advocated the use of iron/folic acid during pregnancy. 24.69% (100) of women had knowledge about barrier contraceptives. Self-medication and homeopathic/ herbal drugs use was found more in graduates than in undergraduates; as well as, it was more in the higher socioeconomic group than the lower socioeconomic group. There is a need to educate and counsel women of child-bearing age, regarding the advantages and disadvantages of drug use during pregnancies, with special reference to alternative therapies and self-medication.

The clinical utility index as a practical multiattribute approach to drug development decisions.

PubMed

Poland, B; Hodge, F L; Khan, A; Clemen, R T; Wagner, J A; Dykstra, K; Krishna, R

2009-07-01

We identify some innovative approaches to predicting overall patient benefit from investigational drugs to support development decisions. We then illustrate calculation of a probabilistic clinical utility index (CUI), an implementation of multiattribute utility that focuses on clinical attributes. We recommend use of the CUI for the support of early drug development decisions because of its practicality, reasonable accuracy, and transparency to decision makers, at stages in which financial factors that may dominate later-phase decisions are less critical.

Drug therapy problems and medication discrepancies during care transitions in super-utilizers.

PubMed

Surbhi, Satya; Munshi, Kiraat D; Bell, Paula C; Bailey, James E

First, to investigate the prevalence and types of drug therapy problems and medication discrepancies among super-utilizers, and associated patient characteristics. Second, to examine the outcomes of pharmacist recommendations and estimated cost avoidance through care transitions support focused on medication management. Retrospective analysis of the pharmacist-led interventions as part of the SafeMed Program. A large nonprofit health care system serving the major medically underserved areas in Memphis, Tennessee. Three hundred seventy-four super-utilizing SafeMed participants with multiple chronic conditions and polypharmacy. Comprehensive medication review, medication therapy management, enhanced discharge planning, home visits, telephone follow-up, postdischarge medication reconciliation, and care coordination with physicians. Types of drug therapy problems, outcomes of pharmacist recommendations, estimated cost avoided, medication discrepancies, and self-reported medication adherence. Prevalence of drug therapy problems and postdischarge medication discrepancies was 80.7% and 75.4%, respectively. The most frequently occurring drug therapy problems were enrollee not receiving needed medications (33.4%), underuse of medications (16.9%), and insufficient dose or duration (11.2%). Overall 50.8% of the pharmacist recommendations were accepted by physicians and patients, resulting in an estimated cost avoidance of $293.30 per drug therapy problem identified. Multivariate analysis indicated that participants with a higher number of comorbidities were more likely to have medication discrepancies (odds ratio 1.23 [95% CI 1.05-1.44]). Additional contributors to postdischarge medication discrepancies were difficulty picking up and paying for medications and not being given necessary prescriptions before discharge. Drug therapy problems and medication discrepancies are common in super-utilizers with multiple chronic conditions and polypharmacy during transitions of care

Generic antiepileptic drugs and associated medical resource utilization in the United States.

PubMed

Labiner, D M; Paradis, P E; Manjunath, R; Duh, M S; Lafeuille, M-H; Latrémouille-Viau, D; Lefebvre, P; Helmers, S L

2010-05-18

To evaluate whether generic substitution was associated with any difference in medical resource utilization for 5 widely used antiepileptic drugs (AEDs) in the United States. Health insurance claims from PharMetrics Database, representing over 90 health plans between January 2000 and October 2007, were analyzed. Adult patients with epilepsy, continuously treated with carbamazepine, gabapentin, phenytoin, primidone, or zonisamide, were selected. An open-cohort design was used to classify patients into mutually exclusive periods of brand vs generic use of AEDs. Pharmacy and medical utilization were compared between the 2 periods with multivariate regression analyses. Results were stratified into epilepsy-related medical services, and stable (< or = 2 outpatient visits per year and no emergency room visit) vs unstable epilepsy. Time-to-event analyses were also performed for all services and epilepsy-related endpoints. A total of 18,125 patients were observed in the stable group and 15,500 patients in the unstable group. After adjustment of covariates, periods of generic AED treatment were associated with increased use of all prescription drugs (incidence rate ratio [IRR] [95% confidence interval (CI)] = 1.13 [1.13-1.14]) and higher epilepsy-related medical utilization rates (hospitalizations: IRR [95% CI] = 1.24 [1.19-1.30]; outpatient visits: IRR [95% CI] = 1.14 [1.13-1.16]; lengths of hospital stays: IRR [95% CI] = 1.29 [1.27-1.32]). Generic-use periods were associated with increased utilization rates in stable and unstable patients and with 20% increased risk of injury, compared to periods with brand use of AEDs. Generic antiepileptic drug use was associated with significantly greater medical utilization and risk of epilepsy-related medical events, compared to brand use. This relationship was observed even in patients characterized as stable. AED = antiepileptic drug; CI = confidence interval; ER = emergency room; HR = hazard ratio; ICD = International

Prescription Drug Utilization and Reimbursement Increased Following State Medicaid Expansion in 2014.

PubMed

Mahendraratnam, Nirosha; Dusetzina, Stacie B; Farley, Joel F

2017-03-01

The Affordable Care Act (ACA) expanded health care and medication insurance coverage through Medicaid expansion in select states. Expansion has the potential to increase the availability of health services to patients, including prescription medications. However, limited studies have examined how expansion affected prescription drug utilization and reimbursement. To compare prescription drug utilization (number of prescriptions filled) and reimbursement trends between states that did and did not expand Medicaid coverage in 2014, while accounting for known effects of expansion on Medicaid enrollment. We conducted a comparative interrupted time series using retrospective Medicaid state drug utilization data from 2011 to 2014. After inclusion/exclusion criteria, 8 states that expanded Medicaid in 2014 and 10 states that did not expand Medicaid were studied. Primary outcomes were changes in quarterly prescription drug utilization and quarterly total prescription drug reimbursement before and after expansion. To account for increases in enrollment in expansion states, secondary outcomes were per-member-per-quarter (PMPQ) utilization and reimbursement before and after expansion. Expansion states experienced a 1.4 million prescriptions per quarter and $163 million per quarter increase in utilization and reimbursement above the change in rates observed in nonexpansion states after expansion (P < 0.001). Specifically, 1 year after ACA implementation, expansion states used 17.0% more prescriptions and spent 36.1% more in reimbursement than the quarter preceding expansion. Expansion and nonexpansion states experienced significant drops in PMPQ prescriptions immediately after expansion (P < 0.001), but PMPQ prescriptions and reimbursement trends increased by the end of the postexpansion period in expansion states (P < 0.029 and P < 0.001, respectively). Study results suggest that Medicaid expansion offers vulnerable patients who were previously uninsured increased access to

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 Central

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. PMID:26050155

Health plan utilization and costs of specialty drugs within 4 chronic conditions.

PubMed

Gleason, Patrick P; Alexander, G Caleb; Starner, Catherine I; Ritter, Stephen T; Van Houten, Holly K; Gunderson, Brent W; Shah, Nilay D

2013-09-01

Drugs are most typically defined as specialty because they are expensive; however, other criteria used to define a drug as specialty include biologic drugs, the need to inject or infuse the drug, the requirement for special handling, or drug availability only via a limited distribution network. Specialty drugs play an increasingly important role in the treatment of chronic conditions such as multiple sclerosis (MS), rheumatoid arthritis (RA), psoriasis, and inflammatory bowel disease (IBD), yet little is known regarding the comprehensive medical and pharmacy benefit utilization and cost trends for these conditions. To describe MS, RA, psoriasis, and IBD trends for condition prevalence, treatment with specialty drugs, specialty costs, nonspecialty costs, and total direct costs of care within the medical and pharmacy benefits. This was a descriptive analysis of a commercially insured population made up of 1 million members, using integrated medical and pharmacy administrative claims data from 2008 to 2010. Analyses were limited to continuously enrolled commercially insured individuals less than 65 years of age. Condition-specific cohorts for MS, RA, psoriasis, and IBD were defined using standardized criteria. Trends in condition prevalence, specialty drug use for the conditions, and direct total cost of care were analyzed. The direct costs were subcategorized into the following: medical benefit specialty drug costs, medical benefit all other costs, pharmacy benefit specialty drug costs, and pharmacy benefit all other costs. Trends and compound annual growth rates were calculated for the total cost of care and subcategory costs from 2008 through 2010. Condition prevalence ranged from a low of 1,720 per million members for MS to a high of 4,489 per million members for RA. Psoriasis and MS condition prevalence rates were unchanged over the 3 years; however, IBD prevalence increased 7.0%, and RA prevalence increased 9.7%. The rate of specialty drug use was lowest for IBD

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

PubMed Central

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

2015-01-01

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. PMID:25883136

How good is "evidence" from clinical studies of drug effects and why might such evidence fail in the prediction of the clinical utility of drugs?

PubMed

Naci, Huseyin; Ioannidis, John P A

2015-01-01

Promising evidence from clinical studies of drug effects does not always translate to improvements in patient outcomes. In this review, we discuss why early evidence is often ill suited to the task of predicting the clinical utility of drugs. The current gap between initially described drug effects and their subsequent clinical utility results from deficits in the design, conduct, analysis, reporting, and synthesis of clinical studies-often creating conditions that generate favorable, but ultimately incorrect, conclusions regarding drug effects. There are potential solutions that could improve the relevance of clinical evidence in predicting the real-world effectiveness of drugs. What is needed is a new emphasis on clinical utility, with nonconflicted entities playing a greater role in the generation, synthesis, and interpretation of clinical evidence. Clinical studies should adopt strong design features, reflect clinical practice, and evaluate outcomes and comparisons that are meaningful to patients. Transformative changes to the research agenda may generate more meaningful and accurate evidence on drug effects to guide clinical decision making.

Microemulsion utility in pharmaceuticals: Implications for multi-drug delivery.

PubMed

Callender, Shannon P; Mathews, Jessica A; Kobernyk, Katherine; Wettig, Shawn D

2017-06-30

Emulsion technology has been utilized extensively in the pharmaceutical industry. This article presents a comprehensive review of the literature on an important subcategory of emulsions, microemulsions. Microemulsions are optically transparent, thermodynamically stable colloidal systems, 10-100nm diameter, that form spontaneously upon mixing of oil, water and emulsifier. This review is the first to address advantages and disadvantages, as well as considerations and challenges in multi-drug delivery. For the period 1 January 2011-30 April 2016, 431 publications related to microemulsion drug delivery were identified and screened according to microemulsion, drug classification, and surfactant types. Results indicate the use of microemulsions predominantly in lipophilic drug delivery (79.4%) via oil-in-water microemulsions and non-ionic surfactants (90%) for oral or topical administration. Cancer is the disease state most targeted followed by inflammatory diseases, microbial infections and cardiovascular disease. Key generalizations from this analysis include: 1) microemulsion formulation is largely based on trial-and-error despite over 1200 publications related to microemulsion drug delivery since their discovery in 1943; 2) characterization using methods including interfacial tension, droplet size, electrical conductivity, turbidity and viscosity may provide additional information for greater predictability; 3) microemulsion drug delivery publications arise primarily from China (27%) and India (21%) suggesting additional research opportunities elsewhere. Copyright © 2017 Elsevier B.V. All rights reserved.

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. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

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)

Impact of pharmacy benefit design on prescription drug utilization: a fixed effects analysis of plan sponsor data.

PubMed

Roebuck, M Christopher; Liberman, Joshua N

2009-06-01

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. Panel data on 1,074 plan sponsors covering 21.6 million individuals over 12 calendar quarters (2005-2007). A retrospective analysis of pharmacy claims. 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. 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. 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.

Regulatory perspective on remaining challenges for utilization of pharmacogenomics-guided drug developments.

PubMed

Otsubo, Yasuto; Ishiguro, Akihiro; Uyama, Yoshiaki

2013-01-01

Pharmacogenomics-guided drug development has been implemented in practice in the last decade, resulting in increased labeling of drugs with pharmacogenomic information. However, there are still many challenges remaining in utilizing this process. Here, we describe such remaining challenges from the regulatory perspective, specifically focusing on sample collection, biomarker qualification, ethnic factors, codevelopment of companion diagnostics and means to provide drugs for off-target patients. To improve the situation, it is important to strengthen international harmonization and collaboration among academia, industries and regulatory agencies, followed by the establishment of an international guideline on this topic. Communication with a regulatory agency from an early stage of drug development is also a key to success.

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

PubMed

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

2015-01-01

Prior studies show an association between drug use and health care utilization. The relationship between specific drug type and emergent/urgent, inpatient, outpatient, and behavioral health care utilization has not been examined. We aimed to determine if multiple drug use was associated with increased utilization of behavioral health care. To assess health care utilization, we conducted a retrospective cohort study of patients who accessed health care 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. Health care 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 health care-related visits for inpatient, emergent/urgent, outpatient, and behavioral health care among patients who used drugs, categorized by drug types, compared with patients without identified drug use. Of 95,198 index visits, 4.6% (n=4340) were by patients who used drugs. Opioid and multiple drug users had significantly higher rates of behavioral health care 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 with 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 with patients without identified drug use. Integrated medical and mental health care and drug treatment may reduce utilization of costly health care

Strategies for Utilizing Neuroimaging Biomarkers in CNS Drug Discovery and Development: CINP/JSNP Working Group Report.

PubMed

Suhara, Tetsuya; Chaki, Shigeyuki; Kimura, Haruhide; Furusawa, Makoto; Matsumoto, Mitsuyuki; Ogura, Hiroo; Negishi, Takaaki; Saijo, Takeaki; Higuchi, Makoto; Omura, Tomohiro; Watanabe, Rira; Miyoshi, Sosuke; Nakatani, Noriaki; Yamamoto, Noboru; Liou, Shyh-Yuh; Takado, Yuhei; Maeda, Jun; Okamoto, Yasumasa; Okubo, Yoshiaki; Yamada, Makiko; Ito, Hiroshi; Walton, Noah M; Yamawaki, Shigeto

2017-04-01

Despite large unmet medical needs in the field for several decades, CNS drug discovery and development has been largely unsuccessful. Biomarkers, particularly those utilizing neuroimaging, have played important roles in aiding CNS drug development, including dosing determination of investigational new drugs (INDs). A recent working group was organized jointly by CINP and Japanese Society of Neuropsychopharmacology (JSNP) to discuss the utility of biomarkers as tools to overcome issues of CNS drug development.The consensus statement from the working group aimed at creating more nuanced criteria for employing biomarkers as tools to overcome issues surrounding CNS drug development. To accomplish this, a reverse engineering approach was adopted, in which criteria for the utilization of biomarkers were created in response to current challenges in the processes of drug discovery and development for CNS disorders. Based on this analysis, we propose a new paradigm containing 5 distinct tiers to further clarify the use of biomarkers and establish new strategies for decision-making in the context of CNS drug development. Specifically, we discuss more rational ways to incorporate biomarker data to determine optimal dosing for INDs with novel mechanisms and targets, and propose additional categorization criteria to further the use of biomarkers in patient stratification and clinical efficacy prediction. Finally, we propose validation and development of new neuroimaging biomarkers through public-private partnerships to further facilitate drug discovery and development for CNS disorders. © The Author 2016. Published by Oxford University Press on behalf of CINP.

Dynamic effects among patients' treatment needs, beliefs, and utilization: a prospective study of adolescents in drug treatment.

PubMed

Schell, Terry L; Orlando, Maria; Morral, Andrew R

2005-08-01

To document the prospective, reciprocal relationships among substance use problems, utilization of drug treatment, and predisposing beliefs thought to increase treatment utilization. Persistent Effects of Treatment Study-Adolescent (PETS-A), conducted by the Center on Substance Abuse Treatment. This was a longitudinal study of youths originally participating in one of two CSAT studies; one sample included 476 youths receiving residential drug treatment, and the other included 519 youths receiving outpatient treatment. This study uses five waves of data collected over a 12-month period to examine the temporal relationships among four variables: treatment dose, substance use problems, drug resistance self-efficacy, and perceived need for treatment (PNT). Data from this longitudinal study were analyzed using cross-lagged panel models, and structural equation modeling techniques were used to estimate the prospective, reciprocal relationships among these four variables in each of the two samples, while controlling for several covariates. Both PNT and low drug resistance self-efficacy led to higher levels of subsequent treatment. However, low self-efficacy presaged increases in drug problems while PNT predicted decreases. Understanding the role of psychological variables in the utilization of health services is complicated for psychological disorders because beliefs that affect treatment can also influence the disorder itself. Efforts to keep adolescents in drug treatment should focus on convincing youth that treatment can help them with their problems, rather than convincing them that they cannot resist drugs on their own. While both messages increase treatment utilization, the latter belief undermines the effects of treatment.

Dynamic Effects among Patients' Treatment Needs, Beliefs, and Utilization: A Prospective Study of Adolescents in Drug Treatment

PubMed Central

Schell, Terry L; Orlando, Maria; Morral, Andrew R

2005-01-01

Objective To document the prospective, reciprocal relationships among substance use problems, utilization of drug treatment, and predisposing beliefs thought to increase treatment utilization. Data Source Persistent Effects of Treatment Study-Adolescent (PETS-A), conducted by the Center on Substance Abuse Treatment. This was a longitudinal study of youths originally participating in one of two CSAT studies; one sample included 476 youths receiving residential drug treatment, and the other included 519 youths receiving outpatient treatment. Study Design This study uses five waves of data collected over a 12-month period to examine the temporal relationships among four variables: treatment dose, substance use problems, drug resistance self-efficacy, and perceived need for treatment (PNT). Data from this longitudinal study were analyzed using cross-lagged panel models, and structural equation modeling techniques were used to estimate the prospective, reciprocal relationships among these four variables in each of the two samples, while controlling for several covariates. Principal Findings Both PNT and low drug resistance self-efficacy led to higher levels of subsequent treatment. However, low self-efficacy presaged increases in drug problems while PNT predicted decreases. Conclusions Understanding the role of psychological variables in the utilization of health services is complicated for psychological disorders because beliefs that affect treatment can also influence the disorder itself. Efforts to keep adolescents in drug treatment should focus on convincing youth that treatment can help them with their problems, rather than convincing them that they cannot resist drugs on their own. While both messages increase treatment utilization, the latter belief undermines the effects of treatment. PMID:16033496

The effect of incentive-based formularies on prescription-drug utilization and spending.

PubMed

Huskamp, Haiden A; Deverka, Patricia A; Epstein, Arnold M; Epstein, Robert S; McGuigan, Kimberly A; Frank, Richard G

2003-12-04

Many employers and health plans have adopted incentive-based formularies in an attempt to control prescription-drug costs. We used claims data to compare the utilization of and spending on drugs in two employer-sponsored health plans that implemented changes in formulary administration with those in comparison groups of enrollees covered by the same insurers. One plan simultaneously switched from a one-tier to a three-tier formulary and increased all enrollee copayments for medications. The second switched from a two-tier to a three-tier formulary, changing only the copayments for tier-3 drugs. We examined the utilization of angiotensin-converting-enzyme (ACE) inhibitors, proton-pump inhibitors, and 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins). Enrollees covered by the employer that implemented more dramatic changes experienced slower growth than the comparison group in the probability of the use of a drug and a major shift in spending from the plan to the enrollee. Among the enrollees who were initially taking tier-3 statins, more enrollees in the intervention group than in the comparison group switched to tier-1 or tier-2 medications (49 percent vs. 17 percent, P<0.001) or stopped taking statins entirely (21 percent vs. 11 percent, P=0.04). Patterns were similar for ACE inhibitors and proton-pump inhibitors. The enrollees covered by the employer that implemented more moderate changes were more likely than the comparison enrollees to switch to tier-1 or tier-2 medications but not to stop taking a given class of medications altogether. Different changes in formulary administration may have dramatically different effects on utilization and spending and may in some instances lead enrollees to discontinue therapy. The associated changes in copayments can substantially alter out-of-pocket spending by enrollees, the continuation of the use of medications, and possibly the quality of care. Copyright 2003 Massachusetts Medical Society

Teaching exercise of drug utilization by medical students.

PubMed

Das, B P; Sethi, A; Nutan, K; Gunjan

2005-01-01

The prescription is a vital written document communicating between the physician, the patient and the pharmacist. The audit of prescribing pattern is a component of medical audit, which seeks monitoring, evaluation and necessary modifications in the prescribing practices of prescribers to achieve rational and cost effective medical care for the patients, The present drug utilization study was conducted by fourth year MBBs students during their research posting in the department of Pharmacology at B.P. Koirala Institute of Health Sciences (BPKIHS), Dharan. The prescriptions were randomly collected from BPKIHS pharmacy over a period of 3 weeks. The auditing was done in the form of a semi structured performa containing the patients particulars with regard to age, sex, and residence, the details of the illness and prescribed drug information. The data was analyzed at the end of the study. The study points out that the maximum (27.5%) prescriptions were from General Outpatient Department (GOPD) followed by ENT (16.5%), Internal medicine (15.5%) and General surgery (10%). This indicates the distribution of patient load in hospital and the dominant areas to be targeted for intervention. Further, the proportion of antimicrobial agents (AMAs) i.e. 26.03% use was low and was prescribed empirically in most of the cases. There was use of expensive AMAs and irrational prescribing of combinations of AMAs in some prescriptions. Other prevailing drugs which were prescribed were analgesics. The usage of nimesulide and rofecoxib. withdrawn by FDA were used recurrently in this setup. There was greater use of dubious drugs of unproven benefit like vitamins, calcium etc. The diagnosis of the disease were not mentioned in 32.5% of prescriptions, The dose, frequency and duration of drugs were unascertained in majority of prescriptions that might lead to health hazards. This exercise might change the behavior of existing prescribers and also of the future doctors.

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

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

Radford, L.R.; Rankin, W.L.; Barnes, V.

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 nuclearmore » 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.« less

Impact of cost sharing on specialty drug utilization and outcomes: a review of the evidence and future directions.

PubMed

Doshi, Jalpa A; Li, Pengxiang; Ladage, Vrushabh P; Pettit, Amy R; Taylor, Erin A

2016-03-01

Specialty drugs often represent major medical advances for patients with few other effective options available, but high costs have attracted the attention of both payers and policy makers. We reviewed the evidence regarding the impact of cost sharing on utilization of specialty drugs indicated for rheumatoid arthritis (RA), multiple sclerosis (MS), and cancer, and on the use of nondrug medical services, health outcomes, and spending. Systematic review of Medline-indexed studies identified via an OVID search for articles published in English from 1995 to 2014, using combinations of terms for cost sharing and specialty drugs, and/or our 3 conditions of interest. We identified additional studies from reference lists. We identified 19 articles focusing on specialty drugs indicated for MS (n = 9), cancer (n = 8), and RA (n = 8). Studies examined prescription abandonment (n = 3), initiation or any utilization (n = 8), adherence (n = 9), persistence/discontinuation (n = 7), number of claims (n = 1), and drug spending (n = 1). Findings varied by disease, but generally indicated stronger effects for noninitiation or abandonment of a prescription at the pharmacy and somewhat smaller effects for refill behavior and drug spending once patients initiated therapy. Studies have not examined specialty tier cost sharing seen under Medicare Part D or health insurance exchanges, nor effects on medical utilization, spending, or health outcomes. Evidence to date generally indicates reductions in specialty drug utilization associated with higher cost sharing; effects have varied by type of disease and specialty drug use outcome. We draw upon our findings and the gaps in evidence to summarize future directions for research and policy.

[Pharmacoeconomic indicators of cardiovascular drug utilization in the Republic of Croatia and city of Zagreb in 2008].

PubMed

Stimac, Danijela; Stambuk, Ivanka

2010-12-01

In comparison with original drugs, generic drugs have the same efficacy but considerably lower price and should therefore be preferred to original drugs on prescribing. The aim of the present study was to assess outpatient utilization and rationality of cardiovascular drug prescribing in the City of Zagreb and Republic of Croatia based on the generic to original drug prescribing ratio. Data on the financial indicators and number of cardiovascular drug packages issued in 2008 were obtained from the Croatian Institute of Health Insurance. These data were used to calculate the number of defined daily doses (DDD) and number of DDD per 1000 inhabitants per day (DDD/1000/day). The index of generic/original drug utilization was determined for Zagreb and Croatia as a measure for assessment of prescribing rationality; the significance of difference was determined by X2-test. The rate of prescribing original cardiovascular drugs was significantly higher in Zagreb as compared with Croatia as a whole. The index of prescribing generic versus original drugs was 1.20 (249/208 DDD/1000/day) in Zagreb and 1.65 (249/151 DDD/1000/day) in Croatia. Difference in the utilization of generic drugs between Zagreb and Croatia as determined by X2-test (the level of statistical significance was set at P<0.05) was statistically significant (P=0.021). The highest differences were recorded in the most widely prescribed drug groups, i.e. ACE inhibitors with the generic/original drug index of 1.38 in Zagreb and 2.02 in Croatia; and hypolipemics with the generic/original drug index of 0.96 in Zagreb and 1.34 in Croatia. According to financial indicators, the generic/original drug index was 1.44 in Croatia and only 0.96 in Zagreb. The significantly greater influence of pharmaceutical industry marketing in Zagreb entailed the significantly higher rate of original drug prescribing, which is associated with considerably greater drug expenses. Measures to stimulate prescribing generic drugs should be

[High utilization of health insurance services by the elderly--analysis of hospital and drug utilization data].

PubMed

Nordheim, Johanna; Maaz, Asja; Winter, Maik H J; Kuhlmey, Adelheid; Hofmann, Werner

2006-01-01

The present contribution discusses the utilization of the healthcare system by elderly patients in Germany. First, the paper focuses on the detailed characterization of a group of people aged 60 years or more (N = 73,454). Second, the objective is to analyze the data for high utilization of healthcare services by older men and women. The analysis is based on data regularly recorded by a German health insurance agency for the year 2000. High utilization is operationalized by a 10% cutoff for users with the highest number of treatments, highest costs and/or other criteria depending on the respective health service sector. The insured group investigated received approximately 1.4 million prescriptions, producing costs of 42 million E. High utilizers account for 32% of all prescriptions and 44% of the costs, respectively. At the same time, the age groups with the highest prescription rates do not cause the highest costs: So the relationship between age and prescription drug expenses as well as between age and prescription rates does not display an arithmetically increasing pattern. Within the timeframe investigated 26,000 hospital treatments were accounted for by 21.75% of the elderly under research. In total, they caused expenses of 88 million E. High utilization in the hospital sector was operationalized by four criteria. Sex- and age-specific analysis of high utilization of hospital treatment revealed that the four different criteria apply to different insured groups. In summary, the high utilization of healthcare services appears to be a multidimensional phenomenon.

Methods in pharmacoepidemiology: a review of statistical analyses and data reporting in pediatric drug utilization studies.

PubMed

Sequi, Marco; Campi, Rita; Clavenna, Antonio; Bonati, Maurizio

2013-03-01

To evaluate the quality of data reporting and statistical methods performed in drug utilization studies in the pediatric population. Drug utilization studies evaluating all drug prescriptions to children and adolescents published between January 1994 and December 2011 were retrieved and analyzed. For each study, information on measures of exposure/consumption, the covariates considered, descriptive and inferential analyses, statistical tests, and methods of data reporting was extracted. An overall quality score was created for each study using a 12-item checklist that took into account the presence of outcome measures, covariates of measures, descriptive measures, statistical tests, and graphical representation. A total of 22 studies were reviewed and analyzed. Of these, 20 studies reported at least one descriptive measure. The mean was the most commonly used measure (18 studies), but only five of these also reported the standard deviation. Statistical analyses were performed in 12 studies, with the chi-square test being the most commonly performed test. Graphs were presented in 14 papers. Sixteen papers reported the number of drug prescriptions and/or packages, and ten reported the prevalence of the drug prescription. The mean quality score was 8 (median 9). Only seven of the 22 studies received a score of ≥10, while four studies received a score of <6. Our findings document that only a few of the studies reviewed applied statistical methods and reported data in a satisfactory manner. We therefore conclude that the methodology of drug utilization studies needs to be improved.

Drug utilization according to reason for prescribing: a pharmacoepidemiologic method based on an indication hierarchy.

PubMed

Wallach Kildemoes, Helle; Hendriksen, Carsten; Andersen, Morten

2012-10-01

To develop a pharmacoepidemiologic method for drug utilization analysis according to indication, gender, and age by means of register-based information. Statin utilization in 2005 was applied as an example. Following the recommendations for statin therapy, we constructed an indication hierarchy with eight mutually exclusive levels of register markers of cardiovascular disease and diabetes. Danish residents, as of January 1, 1996, were followed at the individual level in nationwide registers with respect to dispensed prescriptions of cardiovascular drugs and antidiabetics (1996-2005) along with discharge diagnoses and surgical procedures (1977-2005). The highest current possible indication level was assigned to all cohort members. Stratified by indication, gender, and age, statin treatment prevalence and incidence were calculated. Statin treatment prevalence was highest among individuals with myocardial infarction and tended to be higher among men with indications in the upper part of the hierarchy, but it was higher among women (especially the elderly) in the lower part of the hierarchy. Treatment incidence rates followed roughly the same pattern. Women with no register marker or primary hypertension accounted for almost 50% of all incident female users; among men, the figure was 35%. The proportion of incident users with ischemic heart disease or myocardial infarction increased with age. The proposed indication hierarchy provided new insight into prescription patterns of statins. The method can be implemented for other drug categories and could be useful for studying trends in drug utilization, differential drug adherence, and cross-national comparisons. Copyright © 2011 John Wiley & Sons, Ltd.

Trends in the Outpatient Utilization of Antipsychotic Drugs in the City of Zagreb in the Ten-Year Period as a Tool to Assess Drug Prescribing Rationality.

PubMed

Polić-Vižintin, Marina; Tripković, Ingrid; Štimac, Danijela; Šostar, Zvonimir; Orban, Mirjana

2016-12-01

The aim was to determine distribution and trends in the outpatient utilization of antipsychotics to evaluate the rationality of antipsychotic drug prescribing during the ten year period. The epidemiological method of descriptive and analytical observation was used. Data on drug utilization from Zagreb Municipal Pharmacy were used to calculate the number of defined daily doses (DDD) and DDD per 1000 inhabitants per day (DDD/TID) using the World Health Organization Anatomical-Therapeutic-Chemical methodology. The ratio of typical versus atypical antipsychotics served as an indicator on assessing the rationality of the utilization. Data on the use of anticholinergics in the treatment of neuroleptic side effects were also included. Outpatient utilization of antipsychotics showed a declining pattern from 14.17 in 2001 to 8.42 DDD/TID in 2010. The utilization of atypical antipsychotics increased by 60% (from 3.68 to 5.89 DDD/TID), while the utilization of typical antipsychotics decreased by 76% (from 10.49 to 2.53 DDD/TID). The drugs showing the largest increase were olanzapine (from 1.21 to 2.78 DDD/TID) and quetiapine (from 0 to 0.68 DDD/TID). The typical/atypical antipsychotic ratio changed from 1:0.4 in 2001 to 1:2.3 in 2010. A 2.3-fold decrease was recorded in the utilization of anticholinergics (from 2.05 to 0.91 DDD/TID). Total consumption of neuroleptics significantly decreased. A decrease was also recorded in the utilization of anticholinergics. Study results pointed to two favorable features, i.e. low use of typical antipsychotics and the ratio of typical and atypical antipsychotics. Implementation of the new clinical guidelines for nervous system disorders and updating of the list of reimbursable drugs with the addition of new ones contributed to the observed improvement in the prescribing patterns during the study period. Using the WHO ATC/DDD methodology and rationality indicators in the assessment of trends in the outpatient utilization of

What is known about the cost-effectiveness of orphan drugs? Evidence from cost-utility analyses.

PubMed

Picavet, E; Cassiman, D; Simoens, S

2015-06-01

In times of financial and economic hardship, governments are looking to contain pharmaceutical expenditure by focusing on cost-effective drugs. Because of their high prices and difficulties in demonstrating effectiveness in small patient populations, orphan drugs are often perceived as not able to meet traditional reimbursement threshold value for money. The aim of this study was to provide an overview of the available evidence on the cost-effectiveness of orphan drugs. All orphan drugs listed as authorized on the website of the European Medicines Agency on 21 November 2013 were included in the analysis. Cost-utility analyses (CUAs) were identified by searching the Tufts Medical Center Cost-Effectiveness Analysis Registry and Embase. For each CUA, a number of variables were collected. The search identified 23 articles on the Tufts registry and 167 articles on Embase. The final analysis included 45 CUAs and 61 incremental cost-utility ratios (ICURs) for 19 orphan drugs. Of all ICURS, 16·3% were related to dominant drugs (i.e. more effective and less expensive than the comparator), 70·5% were related to drugs that are more effective, but at a higher cost, and 13·1% were related to dominated drugs (i.e. less effective and more expensive than the comparator). The median overall ICUR was €40 242 per quality-adjusted life year (QALY) with a minimum ICUR of €6311/QALY and a maximum ICUR of €974,917/QALY. This study demonstrates that orphan drugs can meet traditional reimbursement thresholds. Considering a threshold of £30,000/QALY, in this study, ten (52·6%) of a total of 19 orphan drugs for which data were available meet the threshold. As much as fifteen orphan drugs (78·9%) are eligible for reimbursement if a threshold of €80,000/QALY is considered. © 2015 John Wiley & Sons Ltd.

Posaconazole exposure-response relationship: evaluating the utility of therapeutic drug monitoring.

PubMed

Dolton, Michael J; Ray, John E; Marriott, Deborah; McLachlan, Andrew J

2012-06-01

Posaconazole has become an important part of the antifungal armamentarium in the prophylaxis and salvage treatment of invasive fungal infections (IFIs). Structurally related to itraconazole, posaconazole displays low oral bioavailability due to poor solubility, with significant drug interactions and gastrointestinal disease also contributing to the generally low posaconazole plasma concentrations observed in patients. While therapeutic drug monitoring (TDM) of plasma concentrations is widely accepted for other triazole antifungal agents such as voriconazole, the utility of TDM for posaconazole is controversial due to debate over the relationship between posaconazole exposure in plasma and clinical response to therapy. This review examines the available evidence for a relationship between plasma concentration and clinical efficacy for posaconazole, as well as evaluating the utility of TDM and providing provisional target concentrations for posaconazole therapy. Increasing evidence supports an exposure-response relationship for plasma posaconazole concentrations for prophylaxis and treatment of IFIs; a clear relationship has not been identified between posaconazole concentration and toxicity. Intracellular and intrapulmonary concentrations have been studied for posaconazole but have not been correlated to clinical outcomes. In view of the high mortality and cost associated with the treatment of IFIs, increasing evidence of an exposure-response relationship for posaconazole efficacy in the prevention and treatment of IFIs, and the common finding of low posaconazole concentrations in patients, TDM for posaconazole is likely to be of significant clinical utility. In patients with subtherapeutic posaconazole concentrations, increased dose frequency, administration with high-fat meals, and withdrawal of interacting medications from therapy are useful strategies to improve systemic absorption.

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

Drug Treatment Service Utilization and Outcomes for Hispanic and White Methamphetamine Abusers

PubMed Central

Niv, Noosha; Hser, Yih-Ing

2006-01-01

Objective To examine differences in drug treatment service needs, utilization, satisfaction, and outcomes between Hispanic and white methamphetamine (meth) abusers. Data Sources Intake assessments and follow-up interviews of 128 Hispanic and 371 non-Hispanic white meth abusers admitted during 2000–2001 to 43 drug treatment programs in 13 counties across California. Study Design A prospective longitudinal study comparing ethnic differences in problem severity during pre- and posttreatment periods, as well as in services received during treatment. Data Collection/Extraction Methods The Addiction Severity Index (ASI) was administered at both intake and the 9-month follow-up to assess clients' problem severity in a number of domains. Service utilization and satisfaction were assessed 3 months following treatment admission. Principal Findings Hispanics were less educated and reported more employment difficulties than whites. Whites were more likely to be treated in residential programs than Hispanics despite similar severity in drug and alcohol use, legal, medical and family/social problems, and psychiatric status. Significantly more whites than Hispanics received psychiatric services, likely because more of them were treated in residential programs. Whites also reported receiving greater numbers of total services and services addressing alcohol and psychiatric problems. While no ethnic differences were found in treatment satisfaction and several other outcomes, Hispanics demonstrated better family and social outcomes than whites. Conclusions Both Hispanic and white meth abusers improved after treatment, although benefits from treatment can be further enhanced if services underscore different facets of their psychosocial problems. PMID:16899005

Employment services utilization and outcomes among substance abusing offenders participating in California's proposition 36 drug treatment initiative.

PubMed

Evans, Elizabeth; Hser, Yih-Ing; Huang, David

2010-10-01

California drug treatment programs may use funds to address barriers to work faced by Proposition 36 offenders, most of whom are not working at treatment entry, but employment services utilization and related behavioral outcomes have never been studied. This study examined primary data collected on 1,453 offenders by 30 programs during 2004 to explore the characteristics, employment services utilization, and outcomes of those who did and did not receive employment services while in drug treatment. One-year outcomes were mostly similar across groups, however, increases in the proportion of offenders employed, receiving income from employment and family or friends, and being paid for work were significantly greater among the received-employment-services group, and a greater proportion of this group also completed drug treatment. Employment services utilization was less likely for persons recruited from outpatient settings and more likely with greater severity of family/social problems and desire for services. Odds of employment one-year post-treatment entry were higher for those of Hispanic race/ethnicity (vs. White) and for those with treatment completion/longer retention but lower for those who were older, lived in specific counties, had greater employment problem severity at intake, and received other income-related services. Strategies for improving employment services utilization and outcomes among Proposition 36 offenders are discussed.

Utilization of self-medication and prescription drugs among 15-year-old children from the German GINIplus birth cohort.

PubMed

Italia, Salvatore; Brand, Helmut; Heinrich, Joachim; Berdel, Dietrich; von Berg, Andrea; Wolfenstetter, Silke Britta

2015-11-01

The objective was to analyse paediatric drug utilization in relation to self-medication, prescription drugs, and the most reported therapeutic drug categories. Data were collected for 3013 children on their utilization of drugs (4-week prevalence) from a German birth cohort study (GINIplus, 15-year follow-up) using a self-administered questionnaire. The drugs were grouped into over-the-counter drugs and prescription drugs, and were classified according to the anatomical therapeutic chemical classification system. Predictors were analysed using a logistic regression model with four independent variables (gender, study area, maternal education, and parental income). Some 69% of the reported 2489 drugs were over-the-counter drugs, and 31% were prescription drugs. The 4-week prevalence for using any type of drug was 41.0%. Drug categories with high prevalence rates of use were antiinflammatory drugs (10.3%), analgesics (7.1%), and antiallergics (5.0%). Factors associated with higher use of over-the-counter drugs were female gender (OR = 1.56, p < 0.0001) and higher maternal education (OR = 1.60, p = 0.0021; university degree vs. secondary high school). Maternal education was correlated with the use of prescribed or self-medicated antiallergics (positive association) and contraceptives (negative association). The use of antibiotics, methylphenidate, and drugs for thyroid therapy was associated with lower parental income. The use of over-the-counter drugs in 15-year-old children from the GINIplus birth cohort is very common and is predicted by socioeconomic factors such as maternal education. This has to be considered by health care managers when deciding about the exclusion of over-the-counter drugs (normally used for self-medication) from reimbursement or the deregulation of drug sales. Copyright © 2015 John Wiley & Sons, Ltd.

Variability in utilization of drug eluting stents in United States: Insights from nationwide inpatient sample.

PubMed

Panaich, Sidakpal S; Badheka, Apurva O; Arora, Shilpkumar; Patel, Nileshkumar J; Thakkar, Badal; Patel, Nilay; Singh, Vikas; Chothani, Ankit; Deshmukh, Abhishek; Agnihotri, Kanishk; Jhamnani, Sunny; Lahewala, Sopan; Manvar, Sohilkumar; Panchal, Vinaykumar; Patel, Achint; Patel, Neil; Bhatt, Parth; Savani, Chirag; Patel, Jay; Savani, Ghanshyambhai T; Solanki, Shantanu; Patel, Samir; Kaki, Amir; Mohamad, Tamam; Elder, Mahir; Kondur, Ashok; Cleman, Michael; Forrest, John K; Schreiber, Theodore; Grines, Cindy

2016-01-01

We studied the trends and predictors of drug eluting stent (DES) utilization from 2006 to 2011 to further expound the inter-hospital variability in their utilization. We queried the Healthcare Cost and Utilization Project's Nationwide Inpatient Sample (NIS) between 2006 and 2011 using ICD-9-CM procedure code, 36.06 (bare metal stent) or 36.07 (drug eluting stents) for Percutaneous Coronary Intervention (PCI). Annual hospital volume was calculated using unique identification numbers and divided into quartiles for analysis. We built a hierarchical two level model adjusted for multiple confounding factors, with hospital ID incorporated as random effects in the model. About 665,804 procedures (weighted n = 3,277,884) were analyzed. Safety concerns arising in 2006 reduced utilization DES from 90% of all PCIs performed in 2006 to a nadir of 69% in 2008 followed by increase (76% of all stents in 2009) and plateau (75% in 2011). Significant between-hospital variation was noted in DES utilization irrespective of patient or hospital characteristics. Independent patient level predictors of DES were (OR, 95% CI, P-value) age (0.99, 0.98-0.99, <0.001), female(1.12, 1.09-1.15, <0.001), acute myocardial infarction(0.75, 0.71-0.79, <0.001), shock (0.53, 0.49-0.58, <0.001), Charlson Co-morbidity index (0.81,0.77-0.86, <0.001), private insurance/HMO (1.27, 1.20-1.34, <0.001), and elective admission (1.16, 1.05-1.29, <0.001). Highest quartile hospital (1.64, 1.25-2.16, <0.001) volume was associated with higher DES placement. There is significant between-hospital variation in DES utilization and a higher annual hospital volume is associated with higher utilization rate of DES. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

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. Copyright © 2014 John Wiley & Sons, Ltd.

Temporal Changes in Prescription of Neuropharmacologic Drugs and Utilization of Resources Related to Neurologic Morbidity in Mechanically Ventilated Children With Bronchiolitis.

PubMed

Shein, Steven L; Slain, Katherine; Wilson-Costello, Deanne; McKee, Bryan; Rotta, Alexandre T

2017-12-01

Critically ill children with bronchiolitis may require neuropharmacologic medications and support for neuro-functional sequelae, but current practices are not well described. We aimed to describe recent trends in neuropharmacology and utilization of neuro-rehabilitation resources in mechanically ventilated children with bronchiolitis. Analysis of the multicenter Pediatric Health Information System database. Forty-seven U.S. children's hospitals. PICU patients less than 2 years old with bronchiolitis undergoing mechanical ventilation between 2006 and 2015. None. Annual rates of utilization of neuropharmacologic medications (sedatives, analgesics, etc) and of neuro-rehabilitation services (physical therapy, neurologic consultation, etc) over the 10-year study period were compared. Neuropharmacologic medications prescribed on greater than or equal to 2 days were extracted. Utilization of MRI of the brain, neurologic consultation, swallow evaluation, occupational therapy, and physical therapy was also extracted. Among 12,508 subjects, the median age was 2.8 months, ~50% had comorbid conditions, and the median duration of mechanical ventilation was 7 days. The percentage of children prescribed greater than or equal to five drugs/drug classes increased over the study period from 36.5% to 55.8% (p < 0.001). There were significant increases over time in utilization of 10 of the 15 individual drugs/drug classes analyzed. More than half of subjects (6,294 [50.3%]) received at least one service that evaluates/treats neurologic morbidity. There were significant increases in the use of greater than or equal to one service (36.3% in 2006 to 59.6% in 2015; p < 0.001) and in the use of greater than or equal to two services (20.8% to 34.8%; p < 0.001). Utilization of each of the five individual resources increased significantly during the study period, but use of vasoactive medications and mortality did not. Prescription of neuropharmacologic agents increased over time using

Impact of decentralization on health services in Uganda: a look at facility utilization, prescribing and availability of essential drugs.

PubMed

Anokbonggo, W W; Ogwal-Okeng, J W; Obua, C; Aupont, O; Ross-Degnan, D

2004-02-01

Uganda began implementation of a structural adjustment programme (SAP) in July 1994 in order to improve social services. The decentralization of health services administration to district level was intended to improve the quality of health services and pharmaceutical supplies in the hospitals, with resultant increase in the level of utilization of health facilities. This study evaluated the impact of the decentralization policy on health facility utilization; availability of essential drugs, and prescribing patterns for acute respiratory infections (ARI), diarrhoea, and malaria in two district hospitals in Uganda. Mixed method evaluation design, involving both quantitative and qualitative methods. Time series analyses of data from utilization, pharmacy stock, and prescription records before and after the policy change. Key informant interviews and focus group discussions to obtain information on perceptions and attitude of stakeholders on the process of the policy implementation. STUDY SETTING AND POPULATION: The study was conducted in two district hospitals in northern Uganda. A total of seven years of utilization and pharmacy stock data including 5040 patient records from the hospitals were analysed retrospectively. In-depth interviews were conducted among 11 politicians from each district; 100 open-ended questionnaires were administered to patients in each hospital; 86 health care workers were interviewed using semi-structured questionnaires; and focus group discussions were conducted with 23 health care providers. Facility utilization was evaluated by average monthly attendance in the outpatient department and paediatric ward admissions. Availability was assessed as average number of drugs per month. Prescribing indicator outcomes included: for malaria, percent chloroquine tablets and percent chloroquine injection; for ARI, percent receiving antibiotics or injections; for diarrhoea, use of oral rehydration salts (ORS), antidiarrhoeal mixtures, and antibiotics

The effect of new and continuing prescription drug use on cost: a longitudinal analysis of chronic and seasonal utilization.

PubMed

Fairman, K A

2000-05-01

To provide basic information about 2 factors contributing to rising prescription drug costs--utilization trends and product selection. Prescription drug costs have risen sharply in recent years, and continued growth is expected. There is little consensus about appropriate cost-management strategies, in part because quantitative data on the causes and implications of increased drug costs are lacking. This study followed 463,820 continuously enrolled adult (> or = 18 years of age on January 1, 1996) utilizers of 15 chronic or seasonal therapeutic classes for 2.5 years (January 1996 through June 1998) using a pharmacy benefit manager's multiple-payer claims database. Outcome measures included (1) change in utilization rate, (2) relationship between new use and utilization growth, (3) stability of the treated population (ie, mostly long-term use vs high rates of turnover), and (4) product mix changes (ie, cost per dispensed day for 1996 vs 1997 and for new vs continuing users, controlling for inflation). Of the 463,820 utilizers, 97% were commercially insured and 3% enrolled in Medicare risk plans; 40% were enrolled in managed care and the remainder covered by indemnity insurance. Rates of growth and turnover varied substantially by class. The highest 2-year utilization rate change was 66.7% for antihyperlipidemic agents; change was < 10% in only 3 classes. Across classes, an average of 38.7% of 1997 users were new (ie, no use in 1996) and an average of 34.0% of 1996 users were dropouts (ie, no use in 1997). Utilization growth depended heavily on treatment continuation; classes with high dropout rates (eg, antirheumatic, antiasthmatic) did not have high growth rates, even with high rates of new use. In most classes, costs were not higher for new than for continuing users. In some classes, however (eg, antipsychotic, antidiabetic), both new and continuing users increased their use of newer, more expensive products. Because factors underlying rising prescription drug

Comparing the Medicaid Retrospective Drug Utilization Review Program Cost-Savings Methods Used by State Agencies.

PubMed

Prada, Sergio I

2017-12-01

The Medicaid Drug Utilization Review (DUR) program is a 2-phase process conducted by Medicaid state agencies. The first phase is a prospective DUR and involves electronically monitoring prescription drug claims to identify prescription-related problems, such as therapeutic duplication, contraindications, incorrect dosage, or duration of treatment. The second phase is a retrospective DUR and involves ongoing and periodic examinations of claims data to identify patterns of fraud, abuse, underutilization, drug-drug interaction, or medically unnecessary care, implementing corrective actions when needed. The Centers for Medicare & Medicaid Services requires each state to measure prescription drug cost-savings generated from its DUR programs on an annual basis, but it provides no guidance or unified methodology for doing so. To describe and synthesize the methodologies used by states to measure cost-savings using their Medicaid retrospective DUR program in federal fiscal years 2014 and 2015. For each state, the cost-savings methodologies included in the Medicaid DUR 2014 and 2015 reports were downloaded from Medicaid's website. The reports were then reviewed and synthesized. Methods described by the states were classified according to research designs often described in evaluation textbooks. In 2014, the most often used prescription drugs cost-savings estimation methodology for the Medicaid retrospective DUR program was a simple pre-post intervention method, without a comparison group (ie, 12 states). In 2015, the most common methodology used was a pre-post intervention method, with a comparison group (ie, 14 states). Comparisons of savings attributed to the program among states are still unreliable, because of a lack of a common methodology available for measuring cost-savings. There is great variation among states in the methods used to measure prescription drug utilization cost-savings. This analysis suggests that there is still room for improvement in terms of

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

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

Comparing the Medicaid Retrospective Drug Utilization Review Program Cost-Savings Methods Used by State Agencies

PubMed Central

Prada, Sergio I.

2017-01-01

Background The Medicaid Drug Utilization Review (DUR) program is a 2-phase process conducted by Medicaid state agencies. The first phase is a prospective DUR and involves electronically monitoring prescription drug claims to identify prescription-related problems, such as therapeutic duplication, contraindications, incorrect dosage, or duration of treatment. The second phase is a retrospective DUR and involves ongoing and periodic examinations of claims data to identify patterns of fraud, abuse, underutilization, drug–drug interaction, or medically unnecessary care, implementing corrective actions when needed. The Centers for Medicare & Medicaid Services requires each state to measure prescription drug cost-savings generated from its DUR programs on an annual basis, but it provides no guidance or unified methodology for doing so. Objectives To describe and synthesize the methodologies used by states to measure cost-savings using their Medicaid retrospective DUR program in federal fiscal years 2014 and 2015. Method For each state, the cost-savings methodologies included in the Medicaid DUR 2014 and 2015 reports were downloaded from Medicaid's website. The reports were then reviewed and synthesized. Methods described by the states were classified according to research designs often described in evaluation textbooks. Discussion In 2014, the most often used prescription drugs cost-savings estimation methodology for the Medicaid retrospective DUR program was a simple pre-post intervention method, without a comparison group (ie, 12 states). In 2015, the most common methodology used was a pre-post intervention method, with a comparison group (ie, 14 states). Comparisons of savings attributed to the program among states are still unreliable, because of a lack of a common methodology available for measuring cost-savings. Conclusion There is great variation among states in the methods used to measure prescription drug utilization cost-savings. This analysis suggests that

Awareness of Mothers and Doctors about Drug Utilization Pattern for Illnesses Encountered during Pregnancy.

PubMed

Kureshee, Nargis Ibrahim; Dhande, Priti Pravin

2013-11-01

Careful consideration of the benefit to the mother and risk to the foetus, is required, while prescribing drugs during pregnancy. To assess the pattern of drug utilization during pregnancy and to explore the knowledge, attitude and awareness on drug use by the antenatal mother in a tertiary care hospital setup in western India. Observational, cross-sectional study involved holding interviews on 501 pregnant women, in OPD and IPD of Obstetrics-Gynaecology Department using a pilot-based questionnaire, was done. Data from prescriptions and case-files were also collected. Drugs were classified pharmacologically and according to teratogenic potential using U.S.FDA classification. Study population was classified according to the trimester of pregnancy and educational and socioeconomic status. Intergroup comparison was done using Chi-square test. Majority of the drugs were from Category A(71.2%) and Category B (16.5%), followed by those from Categories C(9.09%), D(1.12%) and X(0.7%). Category A drugs were significantly used more in first trimester, while Category C and D drugs were used in the last two trimesters (p<0.0001) for pregnancy associated complications. Only 24.55% of the women believed that drug use in pregnancy could be harmful to both mother and baby, while 35.52% believed that drug use could be dangerous throughout pregnancy. Patients' educational and socio-economic statuses influenced their compliance for nutritional supplements prescribed during pregnancy and their awareness on common contraceptive methods. Higher education and socioeconomic class provided information on safety of barrier contraception during pregnancy. Study revealed careful prescribing behaviour of physicians. Lack of awareness on safety of drugs in pregnancy and contraceptive use advocates a need for educating and counselling women of child bearing ages.

Adverse drug effects in hospitalized elderly: Data from the Healthcare Cost and Utilization Project

PubMed Central

Shamliyan, Tatyana

2010-01-01

We aimed to analyze trends in hospital admissions due to adverse drug effects between the years 2000 to 2007 among the elderly using the National Inpatient Sample (NIS) of the Healthcare Cost and Utilization Project. We identified the discharges with the principal and all listed diagnoses related to adverse drug effects and associated hospital charges using the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9) codes. Between 2000 and 2007, 321,057 patients over 65 years were discharged with a principal diagnosis related to an adverse drug effect. Hospital charges were $5,329,276,300 or $666,159,537 annual cost. The number of discharges and total hospital charges did not change over the examined years, while mean charge per discharge increased on average by $1064 ± 384 per year. Total hospital charges for drug-induced gastritis with hemorrhage increased the most by $11,206,555 per year among those 66–84 years old and by $8,646,456 per year among those older than 85 years. During 2007, 791,931 elderly had adverse treatment effects among all listed diagnoses with hospital charges of $937,795,690. Effective drug management interventions are needed to improve safety of treatments in the elderly. PMID:22291486

Trends in prescription drug utilization and spending for the Department of Defense, 2002-2007.

PubMed

Devine, Joshua W; Trice, Shana; Spridgen, Stacia L; Bacon, Thomas A

2009-09-01

Examine trends in U.S. Department of Defense (DoD) outpatient drug spending and utilization between 2002 and 2007. We analyzed pharmacy claims data from the U.S. Military Health System (MHS), using a cross-sectional analysis at the prescription and patient-year level and measuring utilization in 30-day equivalent prescriptions and expenditures in dollars. Pharmaceutical spending more than doubled in DoD, from $3 billion in FY02 to $6.5 billion in FY07. The largest increase occurred in the DoD community pharmacy network, where utilization grew from 6 million 30-day equivalent prescriptions in the first quarter of FY02 to more than 16 million in the last quarter of FY07. The smallest increase in annual spending occurred in FY07 (5.5%), down from a high of 27.5% in FY03. The MHS has experienced rapid growth in pharmaceutical spending since FY02. However, there are signs that growth in pharmaceutical spending may be slowing.

e-Learning for the elderly on drug utilization: A pilot study.

PubMed

Throfast, Victoria; Hellström, Lina; Hovstadius, Bo; Petersson, Göran; Ericson, Lisa

2017-05-01

This study explores the attitudes of elderly people to the use of electronic educational technology (e-learning) on drug utilization, with particular emphasis on the layout, usability, content, and level of knowledge in the tool. e-Learning modules were evaluated by a group of elderly people (aged ⩾65 years, n = 16) via a questionnaire comprising closed and open-ended questions. Both qualitative and quantitative analyses of the responses showed mostly positive reviews. The results indicate that the e-learning modules are a suitable tool for distributing information and education and that they can be managed by elderly individuals who are familiar with computers, allowing them to learn more about medication use.

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…

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

Treatment Utilization Among Adolescent Substance Users: Findings from the 2002 to 2013 National Survey on Drug Use and Health.

PubMed

Haughwout, Sarah P; Harford, Thomas C; Castle, I-Jen P; Grant, Bridget F

2016-08-01

Adolescent substance users face serious health and social consequences and benefit from early diagnosis and treatment. The objectives of this study were to observe trends in treatment utilization; examine correlates of treatment utilization and treatment types/settings among adolescent substance users with and without substance use disorder (SUD); and assess gender differences. National Survey on Drug Use and Health data were pooled across 2002 to 2013, with a combined sample of 79,885 past-year substance users ages 12 to 17 (17,510 with SUD and 62,375 without SUD). Treatment was defined as receiving treatment or counseling for use of alcohol or any drug, not counting cigarettes. Trends were assessed by joinpoint linear regression, and multivariable logistic regression assessed odds ratios of treatment utilization. Percentages of past-year treatment use did not change in 2002 to 2013. Treatment utilization was more prevalent among adolescents with SUD than without (11.4% vs. 1.4%) and among males than females. Among adolescents with and without SUD, criminal justice involvement and perceiving a need for treatment increased adolescent treatment utilization, while SUDs other than alcohol abuse, older age, and talking to parents increased treatment use among adolescents with SUD, and polysubstance use and male gender increased treatment among those without SUD. Treatment gaps persisted among non-Hispanic Blacks for both groups with and without SUD, male Hispanics with SUD, female non-Hispanic Asians without SUD, and private insurance coverages. Gender differences were observed in SUD, race/ethnicity, and insurance coverage. Most adolescents received treatment for both alcohol and drug use, and self-help group and outpatient rehabilitation facility were the most used treatment settings. Treatment utilization among adolescents with past-year substance use remained low and unimproved in 2002 to 2013. Treatment gaps among minority populations, insurance coverage, and in

Association between switching antiepileptic drug products and healthcare utilization: A systematic review.

PubMed

Kwan, Patrick; Palmini, André

2017-08-01

There is ongoing concern whether switching between different antiepileptic drug (AED) products may compromise patient care. We systematically reviewed changes in healthcare utilization following AED switch. We searched MEDLINE and EMBASE databases (1980-October 2016) for studies that assessed the effect of AED switching in patients with epilepsy on outpatient visits, emergency room visits, hospitalization and hospital stay duration. A total of 14 articles met the inclusion criteria. All were retrospective studies. Four provided findings for specific AEDs only (lamotrigine, topiramate, phenytoin and divalproex), 9 presented pooled findings from multiple AEDs, and 1 study provided both specific (lamotrigine, topiramate, oxcarbazepine, and levetiracetam) and pooled findings. Three studies found an association between a switch of topiramate and an increase in healthcare utilization. Another three studies found that a brand-to-generic lamotrigine switch was not associated with an increased risk of emergently treated events (ambulance use, ER visits or hospitalization). The outcomes of the pooled AED switch studies were inconsistent; 5 studies reported an increased healthcare utilization while 5 studies did not. Studies that have examined the association between an AED switch and a change in healthcare utilization report conflicting findings. Factors that may explain these inconsistent outcomes include inter-study differences in the type of analysis undertaken (pooled vs individual AED data), the covariates used for data adjustment, and the type of switch examined. Future medical claim database studies employing a prospective design are encouraged to address these and other factors in order to enhance inter-study comparability and extrapolation of findings. Copyright © 2017 Elsevier Inc. All rights reserved.

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.

Clinical utility of therapeutic drug monitoring in biological disease modifying anti-rheumatic drug treatment of rheumatic disorders: a systematic narrative review.

PubMed

Van Herwaarden, Noortje; Van Den Bemt, Bart J F; Wientjes, Maike H M; Kramers, Cornelis; Den Broeder, Alfons A

2017-08-01

Biological Disease Modifying Anti-Rheumatic Drugs (bDMARDs) have improved the treatment outcomes of inflammatory rheumatic diseases including Rheumatoid Arthritis and spondyloarthropathies. Inter-individual variation exists in (maintenance of) response to bDMARDs. Therapeutic Drug Monitoring (TDM) of bDMARDs could potentially help in optimizing treatment for the individual patient. Areas covered: Evidence of clinical utility of TDM in bDMARD treatment is reviewed. Different clinical scenarios will be discussed, including: prediction of response after start of treatment, prediction of response to a next bDMARD in case of treatment failure of the first, prediction of successful dose reduction or discontinuation in case of low disease activity, prediction of response to dose-escalation in case of active disease and prediction of response to bDMARD in case of flare in disease activity. Expert opinion: The limited available evidence does often not report important outcomes for diagnostic studies, such as sensitivity and specificity. In most clinical relevant scenarios, predictive value of serum (anti-) drug levels is absent, therefore the use of TDM of bDMARDs cannot be advocated. Well-designed prospective studies should be done to further investigate the promising scenarios to determine the place of TDM in clinical practice.

Psychosocial Correlates of Clinicians' Prescription Drug Monitoring Program Utilization.

PubMed

Pugliese, John A; Wintemute, Garen J; Henry, Stephen G

2018-05-01

The purpose of this study is to extend prior research on barriers to use of a prescription drug monitoring program by examining psychosocial correlates of intended use among physicians and pharmacists. Overall, 1,904 California physicians and pharmacists responded to a statewide survey (24.1% response rate) from August 2016 to January 2017. Participants completed an online survey examining attitudes toward prescription drug misuse and abuse, prescribing practices, prescription drug monitoring program design and ease of use, professional obligations, and normative beliefs regarding prescription drug monitoring program use. Data were analyzed in 2017. Perceived prescription drug monitoring program usefulness and normative beliefs fully mediated the relationship between concern about prescription drug abuse and intentions to use the prescription drug monitoring program. Clinicians' sense of professional and moral obligation to use the prescription drug monitoring program was unrelated to intention to use the prescription drug monitoring program despite a positive relationship with concern about misuse and abuse. Compared with physicians, pharmacists reported greater concern about prescription drug misuse, greater professional and moral obligation to use prescription drug monitoring program, and greater rating of prescription drug monitoring program usefulness. Interventions that target normative beliefs surrounding prescription drug monitoring program use and how to use prescription drug monitoring programs effectively are likely to be more effective than those that target professional obligations or moralize to the medical community. Published by Elsevier Inc.

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

Patterns of prescription antihypertensive drug utilization and adherence to treatment guidelines in the city of Novi Sad.

PubMed

Tomas, Ana; Tomić, Zdenko; Milijasević, Boris; Ban, Milica; Horvat, Olga; Vukmirović, Sasa; Sabo, Ana

2016-06-01

Hypertension is one of the leading causes of cardiovascular morbidity and mortality and more than a half of all health insurance expenditures for reimbursed medicines are allocated to antihypertensive drugs in Serbia. The aim of this study was to identify the antihypertensive drug utilization patterns among hypertensive outpatients in the city of Novi Sad, Serbia, determine the adherence to clinical guidelines and address the economic aspects of current prescribing practices. This retrospective observational study was conducted in Novi Sad over a period of six months. The data on the number of packages, size their, and retail price of antihypertensives issued on prescription in outpatients with the diagnosis of essential arterial hypertension was collected from all state-owned pharmacies in Novi Sad. Drug consumption was analyzed using the Anatomical Therapeutic Chemical (ATC)/ defined daily dose (DDD) methodology. Total consumption of antihypertensives issued on prescription over a 6-month period in the city of Novi sad, Serbia was 283.48 DDD per 1,000 inhabitans per day (DID). Angiotensin converting enzyme inhibitors (ACEi) were most commonly prescribed drugs, and were used 3 times more often than calcium channel blockers and 5 times more than beta-blockers. The consumption of diuretics and angiotensin receptor antagonists was low within all the groups of outpatients. Both national and international guidelines state superiority and effectiveness of diuretics in treatment of hypertension in the elderly, but their consumption was unreasonable low despite the fact that over 70% of all antihypertensive drugs in the city of Novi Sad were dispensed in people aged > 60. The use of more expensive ACEi was observed despite the guidelines deeming all the drugs of this class equally effective in treatment of hypertension. Large differences in utilization of different groups of antihypertensive agents were noted in this study. Underutilization of valuable, efficacious, and

Drug utilization, prescription errors and potential drug-drug interactions: an experience in rural Sri Lanka.

PubMed

Rathish, Devarajan; Bahini, Sivaswamy; Sivakumar, Thanikai; Thiranagama, Thilani; Abarajithan, Tharmarajah; Wijerathne, Buddhika; Jayasumana, Channa; Siribaddana, Sisira

2016-06-25

Prescription writing is a process which transfers the therapeutic message from the prescriber to the patient through the pharmacist. Prescribing errors, drug duplication and potential drug-drug interactions (pDDI) in prescriptions lead to medication error. Assessment of the above was made in prescriptions dispensed at State Pharmaceutical Corporation (SPC), Anuradhapura, Sri Lanka. A cross sectional study was conducted. Drugs were classified according to the WHO anatomical, therapeutic chemical classification system. A three point Likert scale, a checklist and Medscape online drug interaction checker were used to assess legibility, completeness and pDDIs respectively. Thousand prescriptions were collected. Majority were hand written (99.8 %) and from the private sector (73 %). The most frequently prescribed substance and subgroup were atorvastatin (4 %, n = 3668) and proton pump inhibitors (7 %, n = 3668) respectively. Out of the substances prescribed from the government and private sectors, 59 and 50 % respectively were available in the national list of essential medicines, Sri Lanka. Patients address (5 %), Sri Lanka Medical Council (SLMC) registration number (35 %), route (7 %), generic name (16 %), treatment symbol (48 %), diagnosis (41 %) and refill information (6 %) were seen in less than half of the prescriptions. Most were legible with effort (65 %) and illegibility was seen in 9 %. There was significant difference in omission and/or errors of generic name (P = 0.000), dose (P = 0.000), SLMC registration number (P = 0.000), and in evidence of pDDI (P = 0.009) with regards to the sector of prescribing. The commonest subgroup involved in duplication was non-steroidal anti-inflammatory drugs (NSAIDs) (43 %; 56/130). There were 1376 potential drug interactions (466/887 prescriptions). Most common pair causing pDDI was aspirin with losartan (4 %, n = 1376). Atorvastatin was the most frequently prescribed substance

Race/ethnic disparities in the utilization of treatment for drug dependent inmates in U.S. state correctional facilities.

PubMed

Nowotny, Kathryn M

2015-01-01

Research has documented racial and ethnic disparities in utilization, access, continuity, and quality of care for psychiatric disorders including treatment for substance use disorders among those with similar need in the general community. Currently, the extent of racial and ethnic disparities in treatment within U.S. correctional facilities is unknown. This study examines race/ethnic disparities in treatment for drug dependent inmates using the 2004 Survey of Inmates in State Correctional Facilities. Fixed effects logistic regression is used to analyze treatment outcomes for 5180 inmates housed within 286 prisons. The analysis accounts for differences in background characteristics (i.e., age, gender, marital status, foreign born status, veteran status), socioeconomic characteristics (i.e., education, employment prior to incarceration), mental health (i.e., diagnosis with a serious mental illness), and incarceration experiences (i.e., current conviction, previous incarceration episodes, time served, additional sentencing requirements, external social support, disciplinary violations). The findings identify a remarkable unmet need among drug dependent inmates in that less than one-half of drug dependent inmates had received any type of treatment in prison at the time of the interview with the most common treatment type being self-help groups. Compared to whites, drug dependent Latino inmates have significantly lower odds of utilizing treatment, yet there are no significant black--white disparities found. The current study suggests that treatment for drug dependent inmates needs to be expanded to include clinically or medically based treatment since the failure to address addictions in the criminal legal system has been identified as the single most significant reason for rearrest and recidivism once released. Copyright © 2014 Elsevier Ltd. All rights reserved.

[Prescribing and drug utilization at community health centers].

PubMed

Diawara, A; Sangho, H; Maiga, D; Kone, A B D; Maiga, M D; Simaga, S Y

2007-01-01

The rationalization of the prescription and the good use of the drugs generally constitute a major problem in the health facilities. The present survey led in November 2002 in Mali assessed the practices of prescription and the use of the drugs by the populations. The indicators of drugs use rational have been measured from 600 drawn prescriptions randomly select at the level of 20 community health center (CSCOM) retained at random in the regions of Ségou, Sikasso, Mopti and the District of Bamako. The means of drugs by order (2.8), the percentages of prescription with antibiotic (61.6%) and injectable drugs (35%) are raised in relation to the normative values of WHO (Wold Health Organization). The rate of conformity to the treatments standardized estimated on exploitation of consultations registers in the centers is estimated to 0.5% for the simple diarrhoea, 13.5% for the acute respiratory infections (ARI) without pneumonia and 60.5% for the pneumonia. On 293 patients in the households our survey permitted to estimate to 84.6% the observance of the treatment by the persons having bought the prescribed drugs totality. The percentage of antibiotics prescription and injectable drugs, and the big insufficiency in the non respect of the treatment standard constitutes some practices potentially to high risk justifying the necessity of an urgent training to the rational prescription.

Cost effectiveness of drug eluting coronary artery stenting in a UK setting: cost-utility study.

PubMed

Bagust, A; Grayson, A D; Palmer, N D; Perry, R A; Walley, T

2006-01-01

To assess the cost effectiveness of drug eluting stents (DES) compared with conventional stents for treatment of symptomatic coronary artery disease in the UK. Cost-utility analysis of audit based patient subgroups by means of a simple economic model. Tertiary care. 12 month audit data for 2884 patients receiving percutaneous coronary intervention with stenting at the Cardiothoracic Centre Liverpool between January 2000 and December 2002. Risk of repeat revascularisation within 12 months of index procedure and reduction in risk from use of DES. Economic modelling was used to estimate the cost-utility ratio and threshold price premium. Four factors were identified for patients undergoing elective surgery (n = 1951) and two for non-elective surgery (n = 933) to predict risk of repeat revascularisation within 12 months. Most patients fell within the subgroup with lowest risk (57% of the elective surgery group with 5.6% risk and 91% of the non-elective surgery group with 9.9% risk). Modelled cost-utility ratios were acceptable for only one group of high risk patients undergoing non-elective surgery (only one patient in audit data). Restricting the number of DES for each patient improved results marginally: 4% of stents could then be drug eluting on economic grounds. The threshold price premium justifying 90% substitution of conventional stents was estimated to be 112 pound sterling (212 USD, 162 pound sterling) (sirolimus stents) or 89 pound sterling (167 USD, 130 pound sterling) (paclitaxel stents). At current UK prices, DES are not cost effective compared with conventional stents except for a small minority of patients. Although the technology is clearly effective, general substitution is not justified unless the price premium falls substantially.

High-throughput screening of PLGA thin films utilizing hydrophobic fluorescent dyes for hydrophobic drug compounds.

PubMed

Steele, Terry W J; Huang, Charlotte L; Kumar, Saranya; Widjaja, Effendi; Chiang Boey, Freddy Yin; Loo, Joachim S C; Venkatraman, Subbu S

2011-10-01

Hydrophobic, antirestenotic drugs such as paclitaxel (PCTX) and rapamycin are often incorporated into thin film coatings for local delivery using implantable medical devices and polymers such as drug-eluting stents and balloons. Selecting the optimum coating formulation through screening the release profile of these drugs in thin films is time consuming and labor intensive. We describe here a high-throughput assay utilizing three model hydrophobic fluorescent compounds: fluorescein diacetate (FDAc), coumarin-6, and rhodamine 6G that were incorporated into poly(d,l-lactide-co-glycolide) (PLGA) and PLGA-polyethylene glycol films. Raman microscopy determined the hydrophobic fluorescent dye distribution within the PLGA thin films in comparison with that of PCTX. Their subsequent release was screened in a high-throughput assay and directly compared with HPLC quantification of PCTX release. It was observed that PCTX controlled-release kinetics could be mimicked by a hydrophobic dye that had similar octanol-water partition coefficient values and homogeneous dissolution in a PLGA matrix as the drug. In particular, FDAc was found to be the optimal hydrophobic dye at modeling the burst release as well as the total amount of PCTX released over a period of 30 days. Copyright © 2011 Wiley-Liss, Inc.

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

PubMed Central

2014-01-01

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

Utility of patch testing for patients with drug eruption.

PubMed

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

2014-04-01

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

Can Untargeted Metabolomics Be Utilized in Drug Discovery/Development?

PubMed

Caldwell, Gary W; Leo, Gregory C

2017-01-01

Untargeted metabolomics is a promising approach for reducing the significant attrition rate for discovering and developing drugs in the pharmaceutical industry. This review aims to highlight the practical decision-making value of untargeted metabolomics for the advancement of drug candidates in drug discovery/development including potentially identifying and validating novel therapeutic targets, creating alternative screening paradigms, facilitating the selection of specific and translational metabolite biomarkers, identifying metabolite signatures for the drug efficacy mechanism of action, and understanding potential drug-induced toxicity. The review provides an overview of the pharmaceutical process workflow to discover and develop new small molecule drugs followed by the metabolomics process workflow that is involved in conducting metabolomics studies. The pros and cons of the major components of the pharmaceutical and metabolomics workflows are reviewed and discussed. Finally, selected untargeted metabolomics literature examples, from primarily 2010 to 2016, are used to illustrate why, how, and where untargeted metabolomics can be integrated into the drug discovery/preclinical drug development process. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Race/Ethnic Disparities in the Utilization of Treatment for Drug Dependent Inmates in U.S. State Correctional Facilities

PubMed Central

Nowotny, Kathryn M.

2014-01-01

This study examines race/ethnic disparities in treatment for drug dependent inmates in state correctional facilities. The data come from the 2004 Survey of Inmates in State Correctional Facilities. Fixed effects logistic regression is used to analyze treatment outcomes for 5,180 inmates housed within 286 prisons. The analysis accounts for differences in background characteristics (i.e., age, gender, marital status, foreign born status, veteran status), socioeconomic characteristics (i.e., education, employment prior to incarceration), mental health (i.e., diagnosis with a serious mental illness), and incarceration experiences (i.e., current conviction, previous incarceration episodes, time served, additional sentencing requirements, external social support, disciplinary violations). The findings identify a remarkable unmet need among drug dependent inmates in that less than one-half of drug dependent inmates had received any type of treatment in prison at the time of the interview with the most common treatment type being self-help groups. Compared to whites, drug dependent Latino inmates have significantly lower odds of utilizing treatment, yet there are no significant black-white disparities found. Implications for drug treatment within prisons are discussed. PMID:25270722

Prescription Drugs: HCFA’s Proposed Drug Utilization Review System Ignores Quality of Care Issues

DTIC Science & Technology

1989-07-13

Parkinsonism , 32,000 with hip fractures attributable to dOfg-induced falls, 163,000 with drug-induced memory loss or impaired thinking, and 243,000...year there are approximately 61,000 older adults with drug-induced Parkinsonism , 32,000 with hip fractures attributable to drug-induced falls, 163,000...particu- larly phenytoin and warfarin). A drug in one category may interact with a drug in another category to raise the concentration of the drugs in the

An overview of herbal supplement utilization with particular emphasis on possible interactions with dental drugs and oral manifestations.

PubMed

Abebe, Worku

2003-01-01

Herbal medication in the United States is a popular form of therapy. This paper provides an overview of the utilization of herbal supplements with particular emphasis on possible interactions with oral health drugs and oral manifestations. Herbal supplements are regulated by the Dietary Supplement Health and Education Act (DSHEA), which limits their regulation by the U.S Food and Drug Administration (FDA). A number of studies indicate that there is a progressive increase in the utilization of herbal supplements. The majority of consumers of these products are white, middle-aged women who have some college education. Many of the consumers use pharmaceutical drugs concurrently, but most do not inform their health-care providers about their use of herbal supplements. Various herbal supplements have been reported or are suspected to interact with certain oral health drugs, the most important one being 1) bromelain, cayenne, chamomile, feverfew, dong quai, eleuthro/Seberian ginseng, garlic, ginkgo, ginger, ginseng and licorice interacting with aspirin; 2) aloe latex, ephedra, ginseng, rhubarb, cascara sagrada, licorice, and senna interacting with corticosteriods; 3) kava, St. John's wort, chamomile, and valerian interacting with central nervous system (CNS) depressant drugs; and 4) herbs acting on the gastrointestinal system, altering the absorption of several orally administered drugs. Further, the use of some herbal supplements has been reported to be associated with oral manifestations, including aphthous ulcers, lip and tongue irritation, and swelling with feverfew; gingival bleeding with feverfew and ginkgo; tongue numbness with echinacea; xerostomia with St. John's wort; oral and lingual dyskinesia with kava; and salivation with yohimbe. These potential effects of herbal supplements in conjunction with factors related to regulation restrictions suggest that the use of these products may be associated with various adverse reactions that can affect oral health and

Trends in Florida's Prescription Drug Monitoring Program registration and utilization: Implications for increasing voluntary use.

PubMed

Delcher, Chris; Wang, Yanning; Young, Henry W; Goldberger, Bruce A; Schmidt, Siegfried; Reisfield, Gary M

Effective use of state prescription drug monitoring programs (PDMPs) to track controlled substance prescribing and dispensing may help mitigate the current opioid crisis. Our objective was to examine trends in registration for and use of Florida's PDMP by physicians and pharmacists, from 2013 to 2016. We discuss implications for PDMP uptake and policy. Key measures, such as cumulative number of registrants per license type and monthly utilization intensity, are presented. A time series forecasting approach was used to (1) model the monthly count of new PDMP registrants and users from January 2013 to December 2016 and (2) estimate cumulative registration totals after 1 year. Florida. As of November 2016, there were 16,498 physicians (representing 31 percent of Drug Enforcement Administration licensees) and 17,241 pharmacists registered with the PDMP, representing 21 and 57 percent of professional licensees, respectively. Of note, the PDMP's designation as a "specialized registry" for electronic medical record "meaningful use" criteria led to a nearly sevenfold increase in physician registrations in a single month. In November 2016, pharmacists displayed a higher past-month PDMP utilization rate (52.2 percent vs 30.1 percent), while physicians displayed a higher past-month PDMP utilization intensity (58.1 vs. 36.1 queries per user). Approximately 25,000 physicians and 31,000 pharmacists must register by the end of 2017 to meet national policy goals. PDMP registration among physicians and pharmacists is limited, and the use of the PDMP among registrants is more limited still. Our findings suggest that Florida will not meet national policy goals for registrants by the end of 2017, although new initiatives may alter this trend. Allowing the PDMP to help prescribers meet other professional needs, such as "meaningful use" or similar efforts, may be effective in increasing PDMP use.

Utilization of the Arkansas Prescription Monitoring Program to combat prescription drug abuse

PubMed Central

Rittenhouse, Rebecca; Wei, Feifei; Robertson, Denise; Ryan, Kevin

2015-01-01

Objective The Arkansas Prescription Monitoring Program (AR PMP) was implemented in 2013 to combat prescription drug abuse. All enrollees were invited to participate in a user survey available in February 2014, to identify makeup of users, utilization of the program, and changes made to health care practices after implementation of the program. Methods Of the 3694 individual enrollees invited to participate, 1541 (41.7%) completed the survey. Data collected were analyzed to identify changes in health care practices by program frequency of use and user profession. Results Medical doctors, advanced practice nurses, and pharmacists are the professions who use the program most frequently. Daily AR PMP users are considerably more likely than infrequent users to be prompted to access the program by the involvement of a controlled substance (CS) prescription or by office/facility policy requirements. Increased frequency of use of the AR PMP results in positive impacts on CS prescribing and dispensing practices. Conclusion Compelling more users of the AR PMP to be prompted to access the program by the involvement of a CS prescription or by requirements per office/facility policy may increase frequency of use of the program and thereby changes in health care practices to combat prescription drug abuse. PMID:26191489

The utilization of drug-polymer interactions for improving the chemical stability of hot-melt extruded solid dispersions.

PubMed

Guo, Zhefei; Lu, Ming; Li, Yongcheng; Pang, Huishi; Lin, Ling; Liu, Xu; Wu, Chuanbin

2014-02-01

Interactions between drugs and polymers were utilized to lower the processing temperature of hot-melt extrusion (HME), and thus minimize the thermal degradation of heat-sensitive drugs during preparation of amorphous solid dispersions. Diflunisal (DIF), which would degrade upon melting, was selected as a model drug. Hydrogen bonds between DIF and polymeric carriers (PVP K30, PVP VA64, hydroxypropyl methylcellulose and Soluplus) were revealed by differential scanning calorimetry and Fourier transform infrared spectroscopy. The hot-melt extruded solid dispersion was characterized by powder X-ray diffraction (XRD), scanning electron microscopy (SEM) and high-performance liquid chromatography (HPLC). The results of hot-stage polar microscopy indicated that DIF was dissolved in molten polymers at 160°C, much lower than the melting point of DIF (215°C). At this temperature, amorphous solid dispersions were successfully produced by HME, as confirmed by XRD and SEM. The related impurities in amorphous solid dispersions detected by HPLC were lower than 0.3%, indicating that thermal degradation was effectively minimized. The dissolution of DIF from amorphous solid dispersions was significantly enhanced as compared with the pure crystalline drug. This technique based on drug-polymer interactions to prepare chemically stable amorphous solid dispersions by HME provides an attractive opportunity for development of heat-sensitive drugs. © 2013 Royal Pharmaceutical Society.

Effect of a therapeutic maximum allowable cost (MAC) program on the cost and utilization of proton pump inhibitors in an employer-sponsored drug plan in Canada.

PubMed

Mabasa, Vincent H; Ma, Johnny

2006-06-01

Therapeutic maximum allowable cost (MAC) is a managed care intervention that uses reference pricing in a therapeutic class or category of drugs or an indication (e.g., heartburn). Therapeutic MAC has not been studied in Canada or the United States. The proton pump inhibitor (PPI) rabeprazole was used as the reference drug in this therapeutic MAC program based on prices for PPIs in the province of Ontario. No PPI is available over the counter in Canada. To evaluate the utilization and anticipated drug cost savings for PPIs in an employer-sponsored drug plan in Canada that implemented a therapeutic MAC program for PPIs. An employer group with an average of 6,300 covered members, which adopted the MAC program for PPIs in June 2003, was compared with a comparison group comprising the book of business throughout Canada (approximately 5 million lives) without a PPI MAC program (non-MAC group). Pharmacy claims for PPIs were identified using the first 6 characters of the generic product identifier (GPI 492700) for a 36-month period from June 1, 2002, through May 31, 2005. The primary comparison was the year prior to the intervention (from June 1, 2002, through May 31, 2003) and the first full year following the intervention (June 1, 2004, through May 31, 2005). Drug utilization was evaluated by comparing the market share of each of the PPIs for the 2 time periods and by the days of PPI therapy per patient per year (PPPY) and days of therapy per prescription (Rx). Drug cost was defined as the cost of the drug (ingredient cost), including allowable provincial pharmacy markup but excluding pharmacy dispense fee. Cost savings were calculated from the allowed drug cost per claim, allowed cost per day, and allowed cost PPPY. (All amounts are in Canadian dollars.) The MAC intervention group experienced an 11.7% reduction in the average cost per day of PPI drug therapy, from 2.14 US dollars in the preperiod to 1.89 US dollars in the postperiod, compared with a 3.7% reduction in

Regenerated cellulose capsules for controlled drug delivery: Part III. Developing a fabrication method and evaluating extemporaneous utility for controlled-release.

PubMed

Bhatt, Bhavik; Kumar, Vijay

2016-08-25

In this article, we describe a method to utilize cellulose dissolved in dimethyl sulfoxide and paraformaldehyde solvent system to fabricate two-piece regenerated cellulose hard shell capsules for their potential use as an oral controlled drug delivery a priori vehicle. A systematic evaluation of solution rheology as well as resulting capsule mechanical, visual and thermal analysis was performed to develop a suitable method to repeatedly fabricate RC hard shell capsule halves. Because of the viscoelastic nature of the cellulose solution, a combination of dip-coating and casting method, herein referred to as dip-casting method, was developed. The dip-casting method was formalized by utilizing two-stage 2(2) full factorial design approach in order to determine a suitable approach to fabricate capsules with minimal variability. Thermal annealing is responsible for imparting shape rigidity of the capsules. Proof-of-concept analysis for the utility of these capsules in controlled drug delivery was performed by evaluating the release of KCl from them as well as from commercially available USP equivalent formulations. Release of KCl from cellulose capsules was comparable to extended release capsule formulation. Copyright © 2016 Elsevier B.V. All rights reserved.

Pediatric Asthma Mortality and Hospitalization Trends Across Asia Pacific Relationship With Asthma Drug Utilization Patterns

PubMed Central

2009-01-01

Background The wide variability in prevalence of childhood asthma across Asia Pacific is well documented, but less is known about its trends in mortality and hospitalization. Objectives To examine pediatric asthma mortality and hospitalization trends of selected countries across Asia Pacific, and also patterns of asthma drug utilization. Materials and Methods Mortality and population data were sourced from the World Health Organization's mortality database. Data on hospitalization were obtained by direct inquiry and from government and scientific publications. Drug use for asthma was expressed as a controller-to-reliever (C:R) ratio (ie, units of inhaled corticosteroids/units of short-acting β-agonists, sold in each country). Time-series regression analyses were used to examine temporal patterns and study association between deaths, hospitalizations, and drug use. Results Japan showed a decreasing trend in pediatric asthma mortality whereas an increase was observed in Thailand. Hospitalizations decreased in Australia and Singapore but increased in Taiwan, Republic of China. C:R ratios increased significantly across the countries. Conclusions Mixed trends in pediatric asthma mortality and hospitalization rates were observed, which coincided with a uniform increase in C:R ratios. This may reflect importance of other aspects of asthma management besides pharmacotherapy. PMID:23283014

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. Copyright © 2016 Elsevier Inc. All rights reserved.

Effect of educational and policy interventions on institutional utilization of wet nebulization respiratory drugs and portable inhalers.

PubMed

Lowe, Donna O; Lummis, Heather; Zhang, Ying; Sketris, Ingrid S

2008-01-01

Asthma and chronic obstructive pulmonary disease treatment guidelines support the preferential use of portable inhalers (PIs) over wet nebulization (WN) respiratory therapy. Hospital- and community-based educational initiatives and a community-based provincial drug program policy change were previously implemented to promote the conversion of WN therapy to PI and spacer device use in Nova Scotia. To examine the effect of these interventions on salbutamol, ipratropium bromide, and spacer device (Aerochamber) use at the Queen Elizabeth II Health Sciences Centre (QEII HSC). We conducted a time-series analysis of drug utilization data from August 1998 to July 2005. We used two intervention phases compared to the pre-intervention phase to determine whether the educational and policy interventions were associated with significant changes in monthly drug and spacer device utilization rates at the QEII HSC (1000-bed teaching hospital; Halifax, Nova Scotia). Salbutamol and ipratropium bromide PI use significantly increased in both intervention phases, compared to the pre-intervention phase. Mean (SD) defined daily doses/100 bed-days for salbutamol PI increased from 30.4 (0.4) in the pre-intervention phase to 34.6 (0.9) and 37.0 (0.4) in intervention phases I and II respectively (p<0.001 for both), and ipratropium bromide PI increased from 27.3 (3.5) to 32.8 (2.5) in intervention phase I (p=0.004) and 35.6 (3.5) in intervention phase II (p<0.001). However, a significant corresponding decrease was observed with salbutamol WN only. Mean (SD) Aerochamber units/100 bed-days significantly increased. Educational and policy interventions had limited effects on converting WN to PI use at the QEII HSC.

CLINICALLY SIGNIFICANT PSYCHOTROPIC DRUG-DRUG INTERACTIONS IN THE PRIMARY CARE SETTING

PubMed Central

English, Brett A.; Dortch, Marcus; Ereshefsky, Larry; Jhee, Stanford

2014-01-01

In recent years, the growing numbers of patients seeking care for a wide range of psychiatric illnesses in the primary care setting has resulted in an increase in the number of psychotropic medications prescribed. Along with the increased utilization of psychotropic medications, considerable variability is noted in the prescribing patterns of primary care providers and psychiatrists. Because psychiatric patients also suffer from a number of additional medical comorbidities, the increased utilization of psychotropic medications presents an elevated risk of clinically significant drug interactions in these patients. While life-threatening drug interactions are rare, clinically significant drug interactions impacting drug response or appearance of serious adverse drug reactions have been documented and can impact long-term outcomes. Additionally, the impact of genetic variability on the psychotropic drug’s pharmacodynamics and/or pharmacokinetics may further complicate drug therapy. Increased awareness of clinically relevant psychotropic drug interactions can aid clinicians to achieve optimal therapeutic outcomes in patients in the primary care setting. PMID:22707017

Medication adherence, healthcare costs and utilization associated with acne drugs in Medicaid enrollees with acne vulgaris.

PubMed

Tan, Xi; Al-Dabagh, Amir; Davis, Scott A; Lin, Hsien-Chang; Balkrishnan, Rajesh; Chang, Jongwha; Feldman, Steven R

2013-06-01

Acne vulgaris is a common chronic disease that may require long-term treatment. Medication adherence is critical to acne management; non-adherence is a common reason for treatment failure and can lead to poor quality of life. The aim of the study was to examine medication adherence, healthcare costs, and utilization associated with acne drugs among acne patients in the USA. This was a retrospective cohort study from January 2004 to December 2007 using the Marketscan Medicaid Database, a national healthcare claims database. The study followed acne patients aged 0-64 years for 90 days after the first acne drug prescription to measure acne medication adherence, acne-related outpatient visits, and total acne-related healthcare costs. Adherence was measured among different acne drug classes using medication possession ratio (MPR). Multivariate regression analyses were conducted to assess the outcomes. The study included 24,438 eligible patients, of whom 89.39 % were under 18 years old. The average adherence rate to acne drugs (MPR) was 0.34, and only 11.74 % of the patients were adherent (MPR ≥0.80). Patients with drug refills had a higher adherence rate (MPR = 0.74) than who those without refills (MPR = 0.27). Factors significantly associated with adherence were age, comorbidity, gender, number of drug refills and number of drug classes used. Patients were more adherent to oral retinoids than any other acne drug classes (MPR = 0.78, 57 % adherent). Patients were less adherent to oral antibiotics (MPR = 0.21) and topical retinoids (MPR = 0.31). After controlling for medication use behavior, the use of oral antibiotics decreased the number of acne-related outpatient visits by 50.9 % (p < 0.001) and lowered acne-related total costs by 51.7 % (p < 0.001). Medication non-adherence is generally prevalent among young acne patients enrolled in Medicaid. The combination of a topical retinoid and an antibiotic agent may be a good choice given their associated healthcare

Gastroprotection during the administration of non-steroidal anti-inflammatory drugs. A drug-utilization study.

PubMed

Carvajal, Alfonso; Arias, Luis H Martín; Vega, Eva; Sánchez, José Antonio García; Rodríguez, Igor Martín; Ortega, Pilar García; del Pozo, Javier García

2004-08-01

There has been an increase of anti-ulcer drug consumption in Spain. A high proportion of this consumption may be due to the use of those drugs as gastroprotective agents when co-prescribed with non-steroidal anti-inflammatory drugs (NSAIDs). The aim of this study was to learn how these treatments are being used: the prevalence of use, the type of drug and the main features of patients. A sample of patients going to pharmacies with a NSAID prescription, with or without a gastroprotective agent, was obtained. A survey questionnaire was distributed to learn clinical and demographic data of the patients. Of the 942 patients interviewed, 41.6% were co-treated with a gastroprotective agent in addition to the NSAID. Most of these patients received proton-pump inhibitors and, to a lesser extent, histamine-2-receptor antagonists, antacids and prostaglandin analogues. The use of gastroprotective agents increased with age, treatment duration and illness chronicity; specialists prescribed a higher proportion of those co-treatments than did general practitioners. There was a high prescription rate of gastroprotective agents; in general, these were used according to recommendations. However, the type of gastroprotective agents being used does not seem to be justified by the current guidelines: histamine-2-receptor antagonists and antacid drugs have not proved their efficacy in this indication. The fact that one in four treatments with gastroprotective drugs was issued to patients without associated risk factors identifies a possible problem where an intervention could be appropriate.

Identifying Programmatic Gaps: Inequities in Harm Reduction Service Utilization among Male and Female Drug Users in Dar es Salaam, Tanzania

PubMed Central

Lambdin, Barrot H.; Bruce, R. Douglas; Chang, Olivia; Nyandindi, Cassian; Sabuni, Norman; Zamudio-Haas, Sophia; McCurdy, Sheryl; Masao, Frank; Ivo, Yovin; Msami, Amani; Ubuguy, Omar; Mbwambo, Jessie

2013-01-01

Introduction Current estimates suggest an HIV prevalence of 42% among people who inject drugs (PWIDs) in Dar es Salaam, while HIV prevalence is estimated to be 8.8% among the general population in the city. To address the HIV epidemic in this population, the government of Tanzania began establishing HIV prevention, treatment and care services including outreach and medication assisted treatment (MAT) for PWIDs in 2010. We assessed gender inequities in utilization of outreach and MAT services and evaluated differences in HIV risk behaviors between female and male PWIDs. Materials and Methods Routine outreach data between December 2010 to mid-August 2012 and baseline data on clients enrolling in methadone from February 2011 to August 2012 were utilized. Binomial regression was used to estimate adjusted relative risk estimates comparing females to males. Results From December 2010 to August 2012, 8,578 contacts were made to drug users; among them 1,898 were injectors. A total of 453 injectors were eligible and referred to MAT, of which, 443 enrolled in treatment. However, regarding total outreach contacts, outreach to PWID, referral to MAT and enrollment in MAT, 8% or less of drug users accessing services were women. In contrast, weighted estimations from surveys suggest that 34% of PWIDs are female, and this approximation is similar to recent population size estimations. Overall, 43% of traditional outreach workers conducting outreach with drug users were female. Though reporting higher levels of condom usage, female PWID were more likely to report multiple sex partners, anal sex, commercial sex work and struggle under a higher burden of addiction, mental disorders and abuse. Conclusions Services have not been mobilized adequately to address the clear needs of females who inject drugs. A clear and urgent need exists for women-centered strategies that effectively engage female PWID into HIV prevention services. PMID:23825620

Do drug formulary policies reflect evidence of value?

PubMed

Neumann, Peter J; Lin, Pei-Jung; Greenberg, Dan; Berger, Marc; Teutsch, Steven; Mansley, Edward; Weinstein, Milton C; Rosen, Allison B

2006-01-01

To investigate the extent to which preferred drug lists and tiered formularies reflect evidence of value, as measured in published cost-utility analyses (CUAs). Using 1998-2001 data from a large registry of cost-effectiveness analyses, we examined the 2004 Florida Medicaid preferred drug list and the 2004 Harvard Pilgrim Pharmacy Program 3-tier formulary, and compared cost-utility ratios (standardized to 2002 US dollars) of drugs with preferred and nonpreferred status. Few drugs on the formularies had any cost-utility data available. Of those that did, median cost-utility ratios were somewhat higher (less favorable) for Florida's preferred drugs compared with the nonpreferred drugs (25,465 dollars vs 13,085 dollars; P = .09). Ratios did not differ for drugs on tiers 1 and 2 of the Harvard Pilgrim formulary, although they were higher for tier 3 and for excluded drugs (18,309 dollars, 18,846 dollars, 52,119 dollars, and 22,580 dollars, respectively; P = .01). Among therapies reported to be cost-saving or to have cost-utility ratios below 50,000 dollars, 77% had favored status in Florida Medicaid and 73% in Harvard Pilgrim. Among dominated drug interventions (reported to be more costly and less effective than alternatives), 95% had favored status in Florida Medicaid and 56% in Harvard Pilgrim. This study underscores the paucity of published cost-utility data available to formulary committees. Some discrepancies prevail between the value of drugs, as reflected in published cost-utility ratios, and the formulary placement policies of 2 large health plans.

In-home drug storage and utilization habits: a Sudanese study.

PubMed

Yousif, M A

2002-01-01

Community drug-use habits were studied in 469 household units in different areas of Sudan. About 97.7% of the investigated families had at least one drug product stored at home. The study revealed a high rate of self-medication (46.9%), repeated use of unfinished stored drugs (55.0%), a high rate of drug exchange among families (59.3%) and poor compliance (71.2%). In Sudan there is still a great need to educate and to motivate the general public regarding the principles of rational drug use in order to safeguard health and avoid economic losses.

Changes in drug utilization during a gap in insurance coverage: an examination of the medicare Part D coverage gap.

PubMed

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

2011-08-01

-containment features such as the coverage gap have an adverse impact on drug utilization that may conceivably affect health outcomes.

[Improvement and prediction of intestinal drug absorption].

PubMed

Miyake, Masateru

2013-01-01

The suppository preparation, which can improve the absorption of poorly absorbable drugs safer than commercially available suppositories, was developed by utilizing sodium laurate and taurine. Additionally, the novel oral absorption-improving system was also established by utilizing polyamines and bile acids. Furthermore, to evaluate the efficacy of these new formulations and estimate the absorbability of new drug candidates in humans, the in vitro prediction system utilizing an isolated human intestinal tissues was developed and successfully predicted the fraction of dose absorbed for several model drugs. These findings would contribute to the development of new dosage forms and new drugs for oral administration.

Healthcare resource utilization following switch or discontinuation in multiple sclerosis patients on disease modifying drugs.

PubMed

Reynolds, Matthew W; Stephen, Reejis; Seaman, Chris; Rajagopalan, Kitty

2010-03-01

The objective of this study was to explore the cost and utilization in the period following discontinuations or switches of disease modifying drugs (DMDs) for patients with multiple sclerosis (MS). Secondary objectives included an assessment of the time to switch or discontinuation from index DMD treatment. Cases were defined as a billed MS diagnosis in continuously enrolled patients initiated with interferon-beta1a IM, interferon-beta1b SC, glatiramer acetate, and interferon-beta1a SC found in the PharMetrics Patient-Centric Database. Information on patient demographics, diagnoses, procedures, pharmacy-dispensed drugs, and costs was extracted; reasons for discontinuation and expenses outside of the healthcare system were not available. Treatment discontinuations and switches between study drugs were defined using pharmacy prescription patterns and analyzed by descriptive and regression methods. The non-pharmacy medical costs in the 18 months following switching or discontinuation were compared to the costs in a randomly selected similar period for those patients who did not switch or discontinue these agents. A total of 5,772 MS patients were continuously enrolled and were treated with one or more of the four drugs of interest, and about half of these patients switched drugs or discontinued treatment for at least 90 days. Patients initiated with interferon-beta1b SC were more likely to discontinue treatment compared to interferon-beta1a IM users. Non-pharmaceutical medical costs were highest for those switching treatments followed by those discontinuing DMDs in the 18 months following a switch or discontinuation, compared to persistent users of these drugs. Interferon beta1b SC initiators had higher costs following changes or discontinuations, while glatiramer acetate and interferon-beta1a SC users had lower subsequent costs compared to interferon-beta1a IM users. Unfortunately, the reasons for stopping the initial treatment cannot be determined from analysis of

Drug utilization review of cephalosporins in a secondary care hospital in United Arab Emirates.

PubMed

Abou-Shaaban, Mohammad; Ali, Areeg Anwer; Rao, Padma G M; Majid, Asif

2016-12-01

Background Cephalosporins are one of the most commonly used antibiotics in United Arab Emirates (UAE). Few studies have been carried out to evaluate the antibiotic utilization pattern in UAE in spite of the obvious increase in cephalosporins resistance during the past decade. Objective To assess the prescriptions pattern of cephalosporins among physicians at a secondary care hospital in Ras Al Khaimah, UAE. Method This observational prospective study was carried out during October 2013 to April 2014. The data of in patients were documented in the predesigned patient profile form and was analyzed for patient's, drug's and drug's therapy related parameters. Results The 3rd generation cephalosporins constituted 83.6 % of the prescriptions, with ceftriaxone being the most commonly used one (81.1 %). They were mainly prescribed for the treatment of the lower respiratory tract infections (60.2 %). Seven (3.5 %) different ADRs linked to cephalosporin use were observed ranging from oral thrush to clostridium difficile infection. A total of 1039 antimicrobial and nonantimicrobial medications were prescribed concomitantly with cephalosporins. Conclusion The 3rd generation cephalosporins were commonly prescribed by parenteral route. Thus, there is a strong need for rationalizing their use to preserve their efficacy and prevent the development of resistance in the region.

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

PubMed Central

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

2011-01-01

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

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

PubMed

Lee, Juliet P; Antin, Tamar M J

2012-01-01

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

Effects of electronic prescribing on formulary compliance and generic drug utilization in the ambulatory care setting: a retrospective analysis of administrative claims data.

PubMed

Ross, S Michael; Papshev, Diana; Murphy, Erin L; Sternberg, David J; Taylor, Jeffrey; Barg, Ronald

2005-06-01

Electronic prescribing (e-prescribing) provides formulary information at the point of care. The objective of this study was to assess the effects of e-prescribing on formulary compliance and generic utilization. This was a retrospective analysis of pharmacy claims data from a large national managed care organization. A sample of 95 providers using predominantly e-prescribing was randomly selected (e-prescriber group). A matched sample of 95 traditional prescribers was selected (traditional prescriber group), matched to the e-prescriber group by zip code and medical specialty. A total of 110,975 paid pharmacy claims, for the 12 months from August 1, 2001, through July 31, 2002, were analyzed to assess the effect of e-prescribing on formulary compliance and generic utilization. All paid pharmacy claims were examined for each group; for the e-prescriber group, this included all claims, not just those prescribed using an e-prescribing device. A written qualitative survey was distributed to physicians and office managers to assess e-prescribing usage, sources of formulary information, and effects of e-prescribing on office resources. Both predominantly e-prescribers and traditional prescribers demonstrated high levels of formulary compliance, 83.2% versus 82.8%, respectively (P=0.32). Formulary compliance for these groups did not differ from the overall prescriber population (82.0%). There was not a difference in generic drug utilization rates between e-prescribers and traditional prescribers (absolute rates 37.3% versus 36.9%, P=0.18). Qualitative survey responses supported previously reported research indicating reductions in calls both to and from pharmacies for prescription orders. An examination of paid pharmacy claims from a large, national managed care organization demonstrated no differences between predominantly e-prescribers and traditional prescribers in measures of formulary compliance or generic drug utilization. Future studies should examine keystroke data

Use of multiattribute utility theory for formulary management in a health system.

PubMed

Chung, Seonyoung; Kim, Sooyon; Kim, Jeongmee; Sohn, Kieho

2010-01-15

The application, utility, and flexibility of the multiattribute utility theory (MAUT) when used as a formulary decision methodology in a Korean medical center were evaluated. A drug analysis model using MAUT consisting of 10 steps was designed for two drug classes of dihydropyridine calcium channel blockers (CCBs) and angiotensin II receptor blockers (ARBs). These two drug classes contain the most diverse agents among cardiovascular drugs on Samsung Medical Center's drug formulary. The attributes identified for inclusion in the drug analysis model were effectiveness, safety, patient convenience, and cost, with relative weights of 50%, 30%, 10%, and 10%, respectively. The factors were incorporated into the model to quantify the contribution of each attribute. For each factor, a utility scale of 0-100 was established, and the total utility score for each alternative was calculated. An attempt was made to make the model adaptable to changing health care and regulatory circumstances. The analysis revealed amlodipine besylate to be an alternative agent, with the highest total utility score among the dihydropyridine CCBs, while barnidipine hydrochloride had the lowest score. For ARBs, losartan potassium had the greatest total utility score, while olmesartan medoxomil had the lowest. A drug analysis model based on the MAUT was successfully developed and used in making formulary decisions for dihydropyridine CCBs and ARBs for a Korean health system. The model incorporates sufficient utility and flexibility of a drug's attributes and can be used as an alternative decision-making tool for formulary management in health systems.

Therapeutic Drug Monitoring of the Newer Anti-Epilepsy Medications

PubMed Central

Krasowski, Matthew D.

2010-01-01

In the past twenty years, 14 new antiepileptic drugs have been approved for use in the United States and/or Europe. These drugs are eslicarbazepine acetate, felbamate, gabapentin, lacosamide, lamotrigine, levetiracetam, oxcarbazepine, pregabalin, rufinamide, stiripentol, tiagabine, topiramate, vigabatrin and zonisamide. In general, the clinical utility of therapeutic drug monitoring has not been established in clinical trials for these new anticonvulsants, and clear guidelines for drug monitoring have yet to be defined. The antiepileptic drugs with the strongest justifications for drug monitoring are lamotrigine, oxcarbazepine, stiripentol, and zonisamide. Stiripentol and tiagabine are strongly protein bound and are candidates for free drug monitoring. Therapeutic drug monitoring has lower utility for gabapentin, pregabalin, and vigabatrin. Measurement of salivary drug concentrations has potential utility for therapeutic drug monitoring of lamotrigine, levetiracetam, and topiramate. Therapeutic drug monitoring of the new antiepileptic drugs will be discussed in managing patients with epilepsy. PMID:20640233

Racial and ethnic disparities in antidepressant drug use.

PubMed

Chen, Jie; Rizzo, John A

2008-12-01

Little is known about racial and ethnic disparities in health care utilization, expenditures and drug choice in the antidepressant market. This study investigates factors associated with the racial and ethnic disparities in antidepressant drug use. We seek to determine the extent to which disparities reflect differences in observable population characteristics versus heterogeneity across racial and ethnic groups. Among the population characteristics, we are interested in identifying which factors are most important in accounting for racial and ethnic disparities in antidepressant drug use. Using Medical Expenditure Panel Survey (MEPS) data from 1996-2003, we have an available sample of 10,416 Caucasian, 1,089 African American and 1,539 Hispanic antidepressant drug users aged 18 to 64 years. We estimate individual out-of-pocket payments, total prescription drug expenditures, drug utilization, the probability of taking generic versus brand name antidepressants, and the share of drugs that are older types of antidepressants (e.g., TCAs and MAOIs) for these individuals during a calendar year. Blinder-Oaxaca decomposition techniques are employed to determine the extent to which disparities reflect differences in observable population characteristics versus unobserved heterogeneity across racial and ethnic groups. Caucasians have the highest antidepressant drug expenditures and utilization. African-Americans have the lowest drug expenditures and Hispanics have the lowest drug utilization. Relative to Caucasians and Hispanics, African-Americans are more likely to purchase generics and use a higher share of older drugs (e.g., TCAs and MAOIs). Differences in observable characteristics explain most of the racial/ethnic differences in these outcomes, with the exception of drug utilization. Differences in health insurance and education levels are particularly important factors in explaining disparities. In contrast, differences in drug utilization largely reflect unobserved

Patterns and predictors of analgesic use in pregnancy: a longitudinal drug utilization study with special focus on women with migraine.

PubMed

Harris, Gerd-Marie Eskerud; Wood, Mollie; Eberhard-Gran, Malin; Lundqvist, Christofer; Nordeng, Hedvig

2017-07-14

Few studies have investigated the drug utilization patterns and factors predicting drug use in pregnant women with migraine. This longitudinal drug utilization study aimed to describe patterns of analgesic use in a sample of Norwegian pregnant women according to their migraine history, and to identify predictors for analgesic use among these women. Pregnant women giving birth at Akershus University Hospital between 2008 and 2010 were recruited at ultrasound examination in gestational week 17. Data were collected by questionnaires in gestational weeks 17 and 32, and at 8 weeks postpartum, and linked to birth records. Women were grouped into four categories according to migraine history: no migraine history, previous migraine history, recent migraine history (within 1 year prior to pregnancy) and migraine in pregnancy. Patterns of use of analgesics were analyzed descriptively. Multivariable logistic regression was used to identify factors predicting analgesic use. Out of 1981 women, 5.0% reported having migraine in pregnancy, 13.2% had a recent history of migraine, 11.5% had a previous history of migraine, and 68.8% reported no history of migraine. Analgesic use declined during pregnancy. Many women switched from triptans and non-steroidal anti-inflammatory drugs to paracetamol, which constituted most of the analgesic use. Factors associated with analgesic use included recent migraine history (OR 1.6, 95% CI 1.2-2.2), more severe headache intensity (OR 1.3, 95% CI 1.3-1.4), smoking (OR 1.9, 95% CI 1.1-3.3) and multiparity (OR 1.4, 95% CI 1.1-1.7). Women with migraine stop or switch medications during pregnancy. Analgesic use in pregnancy is affected by migraine characteristics and intensity, and also by socio-demographic factors. Clinicians should bear this in mind when giving advice on adequate management of migraine in pregnancy and safe analgesic use.

Drug Courts and Adolescents.

ERIC Educational Resources Information Center

Schwebel, Robert

2002-01-01

The narrow preoccupation with abstinence causes many substance-abusing youth to react either with dishonesty or resistance. Drug education and treatment programs need to help youth rethink their use of drugs, rather than utilize harshly confrontational tactics. Drug courts can provide sanctions, while treatment interventions such as the Seven…

Drug-nutrient interactions.

PubMed

Trovato, A; Nuhlicek, D N; Midtling, J E

1991-11-01

Drug-nutrient interactions are a commonly overlooked aspect of the prescribing practices of physicians. As more pharmaceutical agents become available, attention should be focused on interactions of drugs with foods and nutrients. Although drug-nutrient interactions are not as common as drug-drug interactions, they can have an impact on therapeutic outcome. Drugs can affect nutritional status by altering nutrient absorption, metabolism, utilization or excretion. Food, beverages and mineral or vitamin supplements can affect the absorption and effectiveness of drugs. Knowledge of drug-nutrient interactions can help reduce the incidence of these effects. Physicians should question patients about their dietary habits so that patients can be informed about possible interactions between a prescribed drug and foods and nutrients.

Moving on From Representativeness: Testing the Utility of the Global Drug Survey.

PubMed

Barratt, Monica J; Ferris, Jason A; Zahnow, Renee; Palamar, Joseph J; Maier, Larissa J; Winstock, Adam R

2017-01-01

A decline in response rates in traditional household surveys, combined with increased internet coverage and decreased research budgets, has resulted in increased attractiveness of web survey research designs based on purposive and voluntary opt-in sampling strategies. In the study of hidden or stigmatised behaviours, such as cannabis use, web survey methods are increasingly common. However, opt-in web surveys are often heavily criticised due to their lack of sampling frame and unknown representativeness. In this article, we outline the current state of the debate about the relevance of pursuing representativeness, the state of probability sampling methods, and the utility of non-probability, web survey methods especially for accessing hidden or minority populations. Our article has two aims: (1) to present a comprehensive description of the methodology we use at Global Drug Survey (GDS), an annual cross-sectional web survey and (2) to compare the age and sex distributions of cannabis users who voluntarily completed (a) a household survey or (b) a large web-based purposive survey (GDS), across three countries: Australia, the United States, and Switzerland. We find that within each set of country comparisons, the demographic distributions among recent cannabis users are broadly similar, demonstrating that the age and sex distributions of those who volunteer to be surveyed are not vastly different between these non-probability and probability methods. We conclude that opt-in web surveys of hard-to-reach populations are an efficient way of gaining in-depth understanding of stigmatised behaviours and are appropriate, as long as they are not used to estimate drug use prevalence of the general population.

Moving on From Representativeness: Testing the Utility of the Global Drug Survey

PubMed Central

Barratt, Monica J; Ferris, Jason A; Zahnow, Renee; Palamar, Joseph J; Maier, Larissa J; Winstock, Adam R

2017-01-01

A decline in response rates in traditional household surveys, combined with increased internet coverage and decreased research budgets, has resulted in increased attractiveness of web survey research designs based on purposive and voluntary opt-in sampling strategies. In the study of hidden or stigmatised behaviours, such as cannabis use, web survey methods are increasingly common. However, opt-in web surveys are often heavily criticised due to their lack of sampling frame and unknown representativeness. In this article, we outline the current state of the debate about the relevance of pursuing representativeness, the state of probability sampling methods, and the utility of non-probability, web survey methods especially for accessing hidden or minority populations. Our article has two aims: (1) to present a comprehensive description of the methodology we use at Global Drug Survey (GDS), an annual cross-sectional web survey and (2) to compare the age and sex distributions of cannabis users who voluntarily completed (a) a household survey or (b) a large web-based purposive survey (GDS), across three countries: Australia, the United States, and Switzerland. We find that within each set of country comparisons, the demographic distributions among recent cannabis users are broadly similar, demonstrating that the age and sex distributions of those who volunteer to be surveyed are not vastly different between these non-probability and probability methods. We conclude that opt-in web surveys of hard-to-reach populations are an efficient way of gaining in-depth understanding of stigmatised behaviours and are appropriate, as long as they are not used to estimate drug use prevalence of the general population. PMID:28924351

Differential effects of ibogaine on local cerebral glucose utilization in drug-naive and morphine-dependent rats.

PubMed

Levant, Beth; Pazdernik, Thomas L

2004-04-02

Ibogaine, a hallucinogenic indole alkaloid, has been proposed as a treatment for addiction to opioids and other drugs of abuse. The mechanism for its putative anti-addictive effects is unknown. In this study, the effects of ibogaine on local cerebral glucose utilization (LCGU) were determined in freely moving, drug-naive, or morphine-dependent adult, male, Sprague-Dawley rats using the [(14)C]2-deoxyglucose (2-DG) method. Morphine-dependent rats were treated with increasing doses of morphine (5-25 mg/kg, s.c., b.i.d.) and then maintained at 25 mg/kg (b.i.d.) for 4-7 days. For the 2-DG procedure, rats were injected with saline or ibogaine (40 mg/kg, i.p.). 2-DG was administered 1 h after administration of ibogaine. The rate of LCGU was determined by quantitative autoradiography in 46 brain regions. In drug-naive animals, ibogaine produced significant increases in LCGU in the parietal, cingulate, and occipital cortices and cerebellum compared to controls consistent with its activity as a hallucinogen and a tremorogen. Morphine-dependent rats had only minor alterations in LCGU at the time assessed in this experiment. However, in morphine-dependent animals, ibogaine produced a global decrease in LCGU that was greatest in brain regions such as the lateral and medial preoptic areas, nucleus of the diagonal band, nucleus accumbens shell, inferior colliculus, locus coeruleus, and flocculus compared to morphine-dependent animals treated with saline. These findings indicate that ibogaine produces distinctly different effects on LCGU in drug-naive and morphine-dependent rats. This suggests that different mechanisms may underlie ibogaine's hallucinogenic and anti-addictive effects.

Comparative Resuscitation Measures for Drug Toxicities Utilizing Lipid Emulsions

DTIC Science & Technology

2015-01-13

experimental, mixed research design Methods: For each drug studied, seven swine were assigned to eight ACLS or BLS protocol resuscitation groups ...studied drug overdose. For example, with bupivacaine, seventy- one percent of the epinephrine/lipid group survived compared to 19% of all the groups ...surviving. The Epinephrine only group yielded three survivors and the Lipid emulsion only group yielded one survivor. No swine in the CPR only or

Drug metabolism and hypersensitivity reactions to drugs.

PubMed

Agúndez, José A G; Mayorga, Cristobalina; García-Martin, Elena

2015-08-01

The aim of the present review was to discuss recent advances supporting a role of drug metabolism, and particularly of the generation of reactive metabolites, in hypersensitivity reactions to drugs. The development of novel mass-spectrometry procedures has allowed the identification of reactive metabolites from drugs known to be involved in hypersensitivity reactions, including amoxicillin and nonsteroidal antiinflammatory drugs such as aspirin, diclofenac or metamizole. Recent studies demonstrated that reactive metabolites may efficiently bind plasma proteins, thus suggesting that drug metabolites, rather than - or in addition to - parent drugs, may elicit an immune response. As drug metabolic profiles are often determined by variability in the genes coding for drug-metabolizing enzymes, it is conceivable that an altered drug metabolism may predispose to the generation of reactive drug metabolites and hence to hypersensitivity reactions. These findings support the potential for the use of pharmacogenomics tests in hypersensitivity (type B) adverse reactions, in addition to the well known utility of these tests in type A adverse reactions. Growing evidence supports a link between genetically determined drug metabolism, altered metabolic profiles, generation of highly reactive metabolites and haptenization. Additional research is required to developing robust biomarkers for drug-induced hypersensitivity reactions.

Outpatient utilization of psychopharmaceuticals in the City of Zagreb 2001-2006.

PubMed

Stimac, Danijela; Culig, Josip

2009-03-01

A comprehensive insight into drug utilization as an economic and primarily a public health issue can only be acquired in the context of overall health state of the respective population. The objectives of the study were: 1) to determine the real outpatient utilization of psychopharmaceuticals in Zagreb, 2) to determine the psychopharmaceutical prescribing quality during the study period; and 3) to propose appropriate interventions in Zagreb on the basis of the results obtained. Data on drug utilization were obtained from all Zagreb pharmacies. The number of defined daily doses (DDD) and number of DDD per 1000 inhabitants per day (DDD/1000/day) were calculated from the number of particular drug packages. The Drug Utilization 90% (DU90%) method was used as a criterion of prescribing quality. Outpatient utilization of psychopharmaceuticals showed a declining pattern from 115.40 DDD/1000/day in 2001 to 93.15 DDD/1000/day in 2006. Anxiolytics accounted for the majority of this drug group utilization in the City of Zagreb, although the anxiolytic/antidepressant ratio decreased from 7.19 in 2001 to 3.86 in 2006. The utilization of selective serotonin reuptake inhibitors showed a 2.5-fold increase and accounted for 90% of overall antidepressant utilization. A 2.5-fold decrease was recorded in the utilization of antipsychotics, while the atypical/typical antipsychotic ratio changed from 1:2 in 2001 to 1.1:1 in 2006. Despite some improvement observed in the prescribing quality, the predominance of benzodiazepines in the utilization of psychopharmaceuticals points to the need of additional rationalization in the field.

Pharmacogenomic biomarker information in drug labels approved by the United States food and drug administration: prevalence of related drug use.

PubMed

Frueh, Felix W; Amur, Shashi; Mummaneni, Padmaja; Epstein, Robert S; Aubert, Ronald E; DeLuca, Teresa M; Verbrugge, Robert R; Burckart, Gilbert J; Lesko, Lawrence J

2008-08-01

To review the labels of United States Food and Drug Administration (FDA)-approved drugs to identify those that contain pharmacogenomic biomarker information, and to collect prevalence information on the use of those drugs for which pharmacogenomic information is included in the drug labeling. Retrospective analysis. The Physicians' Desk Reference Web site, Drugs@FDA Web site, and manufacturers' Web sites were used to identify drug labels containing pharmacogenomic information, and the prescription claims database of a large pharmacy benefits manager (insuring > 55 million individuals in the United States) was used to obtain drug utilization data. Pharmacogenomic biomarkers were defined, FDA-approved drug labels containing this information were identified, and utilization of these drugs was determined. Of 1200 drug labels reviewed for the years 1945-2005, 121 drug labels contained pharmacogenomic information based on a key word search and follow-up screening. Of those, 69 labels referred to human genomic biomarkers, and 52 referred to microbial genomic biomarkers. Of the labels referring to human biomarkers, 43 (62%) pertained to polymorphisms in cytochrome P450 (CYP) enzyme metabolism, with CYP2D6 being most common. Of 36.1 million patients whose prescriptions were processed by a large pharmacy benefits manager in 2006, about 8.8 million (24.3%) received one or more drugs with human genomic biomarker information in the drug label. Nearly one fourth of all outpatients received one or more drugs that have pharmacogenomic information in the label for that drug. The incorporation and appropriate use of pharmacogenomic information in drug labels should be tested for its ability to improve drug use and safety in the United States.

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.

Clinical evidence supporting pharmacogenomic biomarker testing provided in US Food and Drug Administration drug labels.

PubMed

Wang, Bo; Canestaro, William J; Choudhry, Niteesh K

2014-12-01

Genetic biomarkers that predict a drug's efficacy or likelihood of toxicity are assuming increasingly important roles in the personalization of pharmacotherapy, but concern exists that evidence that links use of some biomarkers to clinical benefit is insufficient. Nevertheless, information about the use of biomarkers appears in the labels of many prescription drugs, which may add confusion to the clinical decision-making process. To evaluate the evidence that supports pharmacogenomic biomarker testing in drug labels and how frequently testing is recommended. Publicly available US Food and Drug Administration databases. We identified drug labels that described the use of a biomarker and evaluated whether the label contained or referenced convincing evidence of its clinical validity (ie, the ability to predict phenotype) and clinical utility (ie, the ability to improve clinical outcomes) using guidelines published by the Evaluation of Genomic Applications in Practice and Prevention Working Group. We graded the completeness of the citation of supporting studies and determined whether the label recommended incorporation of biomarker test results in therapeutic decision making. Of the 119 drug-biomarker combinations, only 43 (36.1%) had labels that provided convincing clinical validity evidence, whereas 18 (15.1%) provided convincing evidence of clinical utility. Sixty-one labels (51.3%) made recommendations about how clinical decisions should be based on the results of a biomarker test; 36 (30.3%) of these contained convincing clinical utility data. A full description of supporting studies was included in 13 labels (10.9%). Fewer than one-sixth of drug labels contained or referenced convincing evidence of clinical utility of biomarker testing, whereas more than half made recommendations based on biomarker test results. It may be premature to include biomarker testing recommendations in drug labels when convincing data that link testing to patient outcomes do not exist.

Resource utilization with insulin pump therapy for type 2 diabetes mellitus.

PubMed

Lynch, Peter M; Riedel, Aylin Altan; Samant, Navendu; Fan, Ying; Peoples, Tim; Levinson, Jennifer; Lee, Scott W

2010-01-01

To evaluate the effects of switching from multiple daily injection (MDI) therapy to insulin pump therapy, also called continuous subcutaneous insulin infusion (CSII), on antidiabetic drug and healthcare resource utilization. This study was a retrospective analysis of administrative claims data from a large geographically diverse health plan in the United States from January 1, 2005, through April 30, 2008. Changes in antidiabetic drug use, antidiabetic drug switching and augmentation, and healthcare utilization during the baseline period and after CSII initiation were assessed using paired t test. There were 3649 possible subjects, of whom 943 met the criteria for analysis. The mean number of antidiabetic drugs used decreased by 46% after CSII initiation, and the mean reduction in antidiabetic drug utilization was 0.67; both were statistically significant. More than one-third of subjects who were taking antidiabetic drugs before CSII initiation discontinued oral therapy after CSII initiation. The number of subjects using multiple antidiabetic drugs significantly decreased after CSII initiation by 58%, and rates of switching or augmenting significantly decreased from 42% at baseline to 25% after CSII initiation.The rates of emergency department visits and inpatient admissions significantly decreased, and the rate of ambulatory visits significantly increased. CSII was associated with significant decreases in antidiabetic drug and healthcare resource utilization, contributing to stability of care. The evidence from this study indicates that CSII should be considered as an option for patients with type 2 diabetes mellitus who are using MDI and are experiencing a high degree of antidiabetic drug and healthcare resource utilization.

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

Utility and importance of animal data in drug product labels.

PubMed

Baldrick, Paul

2014-08-01

Information on the use and safety of medicines to assist prescription by healthcare professionals occurs in drug labels (Summary of Product Characteristics in Europe and Package Insert in the USA). Animal data (notably genotoxicity, reproduction toxicity and carcinogenicity and/or repeat dose toxicity testing) comprise an important component of the information (having a vital role in giving assurance that an extensive safety assessment for the medicinal product has occurred) and regulatory guidance is available to help inform on its input into drug labels. However, an evaluation of animal data for the 27 new drugs approved in the USA in 2013 (and the same drugs if available in Europe) shows great variability in detail and level of information presented within and across regions and/or the possibility of confusion on interpretation of some of the presented animal study findings. It is concluded that it may be time to revisit what animal data are presented in drug product labels (although bearing in mind current regional regulatory guidance requirements), not only to allow within and across region consistency on information given but to present it in a way that fully assists healthcare professions when prescribing a medicine. Copyright © 2014 Elsevier Inc. All rights reserved.

Utility of Phenotypic and Genotypic Testing in the Study of Mycobacterium tuberculosis Resistance to First-Line Anti-Tuberculosis drugs.

PubMed

Alba Álvarez, Luz María; García García, José María; Pérez Hernández, M Dolores; Martínez González, Susana; Palacios Gutiérrez, Juan José

2017-04-01

To determine the utility of molecular techniques in the diagnosis of resistance and the extent of resistance to first-line drugs in our region. From 2004 to 2013, 1,889 strains of Mycobacterium tuberculosis complex isolated in Asturias, Spain, were studied using phenotypic (Clinical and Laboratory Standards Institute guidelines) and molecular (INNOLiPA RIF-TB © ; GenotypeMDRplus © ; GenotypeMDRsl © ) sensitivity tests. 1,759 strains (94.52%) were sensitive to all first-line drugs, and 102 strains (5.48%) showed some resistance: 81 strains (4.35%) were resistant to 1 single drug, 14 (0.75%) were polyresistant, and 7 (0.37%) were multiresistant (resistant to rifampicin and isoniazid). In total, 137 resistances were identified: 60 to isoniazid (3.22%), 7 to rifampicin (0.37%), 9 to pyrazinamide (0.48%), 11 to ethambutol (0.59%), and 50 to streptomycin (2.68%). Of the mutations detected, 75.9% (63/83) correlated with resistance, while 24.09% of mutations detected (20/83) were not associated with resistance; 16 of these involved a silent mutation at codon 514 of the rpoB gene. Between 0 and 90% of strains, depending on the drug under consideration, were resistant even when no gene mutations were detected using marketed systems. Molecular techniques are very useful, particularly for obtaining rapid results, but these must be confirmed with standard phenotypic sensitivity testing. The rate of resistance in our region is low and multi-drug resistantcases (0.37%) are sporadic. Copyright © 2016 SEPAR. Publicado por Elsevier España, S.L.U. All rights reserved.

The impact of physician-level drug budgets on prescribing behavior.

PubMed

Fischer, Katharina Elisabeth; Koch, Taika; Kostev, Karel; Stargardt, Tom

2018-03-01

To contain pharmaceutical spending, drug budgets have been introduced across health systems. Apart from analyzing whether drug budgets fulfill their overall goal of reducing spending, changes in the cost and quality of prescribing and the enforcement mechanisms put in place need evaluation to assess the effectiveness of drug budgets at the physician level. In this study, we aim to analyze the cost and quality of prescribing conditional on the level of utilization of the drug budget and in view of varying levels of enforcement in cases of overspending. We observed drug budget utilization in a panel of 440 physicians in three federal states of Germany from 2005 to 2011. At the physician level, we retrospectively calculated drug budgets, the level of drug budget utilization, and differentiated by varying levels of enforcement where physicians overspent their budgets (i.e., more than 115/125% of the drug budget). Using lagged dependent-variable regression models, we analyzed whether the level of drug budget utilization in the previous year affected current prescribing in terms of various indicators to describe the cost and quality of prescribing. We controlled for patient and physician characteristics. The mean drug budget utilization is 92.3%. The level of drug budget utilization influences selected dimensions of cost and quality of prescribing (i.e., generic share (estimate 0.000215; p = 0.0246), concentration of generic brands (estimate 0.000585; p = 0.0056) and therapeutic substances (estimate -0.000060; p < 0.0001) and the share of potentially inappropriate medicines in the elderly (estimate 0.001; p < 0.0001)), whereas the level of enforcement does not. Physicians seem to gradually adjust their prescription patterns, especially in terms of generic substitution.

Indolealkylamines: biotransformations and potential drug-drug interactions.

PubMed

Yu, Ai-Ming

2008-06-01

Indolealkylamine (IAA) drugs are 5-hydroxytryptamine (5-HT or serotonin) analogs that mainly act on the serotonin system. Some IAAs are clinically utilized for antimigraine therapy, whereas other substances are notable as drugs of abuse. In the clinical evaluation of antimigraine triptan drugs, studies on their biotransformations and pharmacokinetics would facilitate the understanding and prevention of unwanted drug-drug interactions (DDIs). A stable, principal metabolite of an IAA drug of abuse could serve as a useful biomarker in assessing intoxication of the IAA substance. Studies on the metabolism of IAA drugs of abuse including lysergic acid amides, tryptamine derivatives and beta-carbolines are therefore emerging. An important role for polymorphic cytochrome P450 2D6 (CYP2D6) in the metabolism of IAA drugs of abuse has been revealed by recent studies, suggesting that variations in IAA metabolism, pharmaco- or toxicokinetics and dynamics can arise from distinct CYP2D6 status, and CYP2D6 polymorphism may represent an additional risk factor in the use of these IAA drugs. Furthermore, DDIs with IAA agents could occur additively at the pharmaco/toxicokinetic and dynamic levels, leading to severe or even fatal serotonin toxicity. In this review, the metabolism and potential DDIs of these therapeutic and abused IAA drugs are described.

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…

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

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 1 2010-04-01 2010-04-01 false Utilization of an advisory committee on the initiative of FDA. 14.171 Section 14.171 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH... Human Prescription Drugs § 14.171 Utilization of an advisory committee on the initiative of FDA. (a) Any...

Drug-Target Kinetics in Drug Discovery.

PubMed

Tonge, Peter J

2018-01-17

The development of therapies for the treatment of neurological cancer faces a number of major challenges including the synthesis of small molecule agents that can penetrate the blood-brain barrier (BBB). Given the likelihood that in many cases drug exposure will be lower in the CNS than in systemic circulation, it follows that strategies should be employed that can sustain target engagement at low drug concentration. Time dependent target occupancy is a function of both the drug and target concentration as well as the thermodynamic and kinetic parameters that describe the binding reaction coordinate, and sustained target occupancy can be achieved through structural modifications that increase target (re)binding and/or that decrease the rate of drug dissociation. The discovery and deployment of compounds with optimized kinetic effects requires information on the structure-kinetic relationships that modulate the kinetics of binding, and the molecular factors that control the translation of drug-target kinetics to time-dependent drug activity in the disease state. This Review first introduces the potential benefits of drug-target kinetics, such as the ability to delineate both thermodynamic and kinetic selectivity, and then describes factors, such as target vulnerability, that impact the utility of kinetic selectivity. The Review concludes with a description of a mechanistic PK/PD model that integrates drug-target kinetics into predictions of drug activity.

University of Michigan Drug Education Questionnaire.

ERIC Educational Resources Information Center

Francis, John Bruce; Patch, David J.

This questionnaire assesses attitudes toward potential drug education programs and drug use practices in college students. The 87 items (multiple choice or free response) pertain to the history and extent of usage of 27 different drugs, including two non-existent drugs which may be utilized as a validity check; attitude toward the content, format,…

Genetically engineered nanocarriers for drug delivery.

PubMed

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.

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

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

PubMed

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

2011-08-01

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. 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. 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. 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.

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.

Patterns of harm reduction service utilization and HIV incidence among people who inject drugs in Ukraine: A two-part latent profile analysis.

PubMed

Ompad, Danielle C; Wang, Jiayu; Dumchev, Konstantin; Barska, Julia; Samko, Maria; Zeziulin, Oleksandr; Saliuk, Tetiana; Varetska, Olga; DeHovitz, Jack

2017-05-01

Program utilization patterns are described within a large network of harm reduction service providers in Ukraine. The relationship between utilization patterns and HIV incidence is determined among people who inject drugs (PWID) controlling for oblast-level HIV incidence and treatment/syringe coverage. Data were extracted from the network's monitoring and evaluation database (January 2011-September 2014, n=327,758 clients). Latent profile analysis was used to determine harm reduction utilization patterns using the number of HIV tests received annually and the number of condoms, syringes, and services (i.e., information and counseling sessions) received monthly over a year. Cox proportional hazards regression determined the relations between HIV seroconversion and utilization class membership. In the final 4-class model, class 1 (34.0% of clients) received 0.1 HIV tests, 1.3 syringes, 0.6 condom and minimal counseling and information sessions per month; class 2 (33.6%) received 8.6 syringes, 3.2 condoms, and 0.5 HIV tests and counseling and information sessions; class 3 (19.1%) received 1 HIV test, 11.9 syringes, 4.3 condoms, and 0.7 information and counseling sessions; class 4 (13.3%) received 1 HIV test, 26.1 syringes, 10.3 condoms, and 1.8 information and 1.9 counseling sessions. Class 4 clients had significantly decreased risk for HIV seroconversion as compared to those in class 1 after controlling for oblast-level characteristics. Injection drug use continues to be a major mode of HIV transmission in Ukraine, making evaluation of harm reduction efforts in reducing HIV incidence among PWID critical. These analyses suggest that receiving more syringes and condoms decreased risk of HIV. Scaling up HIV testing and harm reduction services is warranted. Copyright © 2016. Published by Elsevier B.V.

Cost-utility analysis of competing treatment strategies for drug-resistant epilepsy in children with Tuberous Sclerosis Complex.

PubMed

Fallah, Aria; Weil, Alexander G; Wang, Shelly; Lewis, Evan; Baca, Christine B; Mathern, Gary W

2016-10-01

The management of drug-resistant epilepsy in children with Tuberous Sclerosis Complex (TSC) is challenging because of the multitude of treatment options, wide range of associated costs, and uncertainty of seizure outcomes. The most cost-effective approach for children whose epilepsy has failed to improve with first-line medical therapy is uncertain. A review of MEDLINE from 1990 to 2015 was conducted. A cost-utility analysis, from a third-party payer perspective, was performed for children with drug-resistant epilepsy that had failed to improve with 2 antiseizure drugs (ASDs) and that was amenable to resective epilepsy surgery, across a time-horizon of 5years. Four strategies were included: (1) resective epilepsy surgery, (2) vagus nerve stimulator (VNS) implantation, (3) ketogenic diet, and (4) addition of a third ASD (specifically, carbamazepine). The incremental cost per quality-adjusted life year (QALY) gained was analyzed. Given a willingness-to-pay (WTP) of $100,000 per QALY, the addition of a third ASD ($6600 for a gain of 4.14 QALYs) was the most cost-effective treatment strategy. In a secondary analysis, if the child whose epilepsy had failed to improve with 3 ASDs, ketogenic diet, addition of a fourth ASD, and resective epilepsy surgery were incrementally cost-effective treatment strategies. Vagus nerve stimulator implantation was more expensive yet less effective than alternative strategies and should not be prioritized. The addition of a third ASD is a universally cost-effective treatment option in the management of children with drug-resistant epilepsy that has failed to improve with 2 ASDs. For children whose epilepsy has failed to improve with 3 ASDs, the most cost-effective treatment depends on the health-care resources available reflected by the WTP. Copyright © 2016 Elsevier Inc. All rights reserved.

42 CFR 456.705 - Prospective drug review.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 42 Public Health 4 2012-10-01 2012-10-01 false Prospective drug review. 456.705 Section 456.705... (CONTINUED) MEDICAL ASSISTANCE PROGRAMS UTILIZATION CONTROL Drug Use Review (DUR) Program and Electronic Claims Management System for Outpatient Drug Claims § 456.705 Prospective drug review. (a) General...

42 CFR 456.705 - Prospective drug review.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 42 Public Health 4 2013-10-01 2013-10-01 false Prospective drug review. 456.705 Section 456.705... (CONTINUED) MEDICAL ASSISTANCE PROGRAMS UTILIZATION CONTROL Drug Use Review (DUR) Program and Electronic Claims Management System for Outpatient Drug Claims § 456.705 Prospective drug review. (a) General...

42 CFR 456.705 - Prospective drug review.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 42 Public Health 4 2011-10-01 2011-10-01 false Prospective drug review. 456.705 Section 456.705... (CONTINUED) MEDICAL ASSISTANCE PROGRAMS UTILIZATION CONTROL Drug Use Review (DUR) Program and Electronic Claims Management System for Outpatient Drug Claims § 456.705 Prospective drug review. (a) General...

42 CFR 456.705 - Prospective drug review.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 42 Public Health 4 2014-10-01 2014-10-01 false Prospective drug review. 456.705 Section 456.705... (CONTINUED) MEDICAL ASSISTANCE PROGRAMS UTILIZATION CONTROL Drug Use Review (DUR) Program and Electronic Claims Management System for Outpatient Drug Claims § 456.705 Prospective drug review. (a) General...

Drug Use, the Drug Environment, and Child Physical Abuse and Neglect.

PubMed

Freisthler, Bridget; Wolf, Jennifer Price; Wiegmann, Wendy; Kepple, Nancy J

2017-08-01

Although drug use is considered a risk factor for child maltreatment, very little work has examined how the drug environment may affect physical abuse and neglect by parents. Utilizing information from a telephone survey with 2,597 respondents from 43 cities with valid police data on narcotics incidents, we analyzed the relationship between drug use, drug availability, and child maltreatment using multilevel models. City-level rates of drug abuse and dependence were related to more frequent physical abuse. Parents who use drugs in areas with greater availability of drugs reported more physical abuse and physical neglect. Emotional support was protective of all types of maltreatment. While most child welfare interventions focus on reducing parental drug use in order to reduce child abuse, these findings suggest environmental prevention or neighborhood strengthening approaches designed to reduce the supply of illicit drugs may also reduce child abuse through multiple mechanisms.

Nucleoside Derived Antibiotics to Fight Microbial Drug Resistance: New Utilities for an Established Class of Drugs?

PubMed

Serpi, Michaela; Ferrari, Valentina; Pertusati, Fabrizio

2016-12-08

Novel antibiotics are urgently needed to combat the rise of infections due to drug-resistant microorganisms. Numerous natural nucleosides and their synthetically modified analogues have been reported to have moderate to good antibiotic activity against different bacterial and fungal strains. Nucleoside-based compounds target several crucial processes of bacterial and fungal cells such as nucleoside metabolism and cell wall, nucleic acid, and protein biosynthesis. Nucleoside analogues have also been shown to target many other bacterial and fungal cellular processes although these are not well characterized and may therefore represent opportunities to discover new drugs with unique mechanisms of action. In this Perspective, we demonstrate that nucleoside analogues, cornerstones of anticancer and antiviral treatments, also have great potential to be repurposed as antibiotics so that an old drug can learn new tricks.

"A'ole" Drugs! Cultural Practices and Drug Resistance of Rural Hawai'ian Youths

ERIC Educational Resources Information Center

Po'A-Kekuawela, Ka'Ohinani; Okamoto, Scott K.; Nebre, La Risa H.; Helm, Susana; Chin, Coralee I. H.

2009-01-01

This qualitative study examined how Native Hawai'ian youths from rural communities utilized cultural practices to promote drug resistance and/or abstinence. Forty-seven students from five different middle schools participated in gender-specific focus groups that focused on the cultural and environmental contexts of drug use for Native Hawai'ian…

Drug transporters in tissues and cells relevant to sexual transmission of HIV: Implications for drug delivery.

PubMed

Hu, Minlu; Patel, Sravan Kumar; Zhou, Tian; Rohan, Lisa C

2015-12-10

Efflux and uptake transporters of drugs are key regulators of the pharmacokinetics of many antiretroviral drugs. A growing body of literature has revealed the expression and functionality of multiple transporters in female genital tract (FGT), colorectal tissue, and immune cells. Drug transporters could play a significant role in the efficacy of preventative strategies for HIV-1 acquisition. Pre-exposure prophylaxis (PrEP) is a promising strategy, which utilizes topically (vaginally or rectally), orally or other systemically administered antiretroviral drugs to prevent the sexual transmission of HIV to receptive partners. The drug concentration in the receptive mucosal tissues and target immune cells for HIV is critical for PrEP effectiveness. Hence, there is an emerging interest in utilizing transporter information to explain tissue disposition patterns of PrEP drugs, to interpret inter-individual variability in PrEP drug pharmacokinetics and effectiveness, and to improve tissue drug exposure through modulation of the cervicovaginal, colorectal, or immune cell transporters. In this review, the existing literature on transporter expression, functionality and regulation in the transmission-related tissues and cells is summarized. In addition, the relevance of transporter function for drug delivery and strategies that could exploit transporters for increased drug concentration at target locales is discussed. The overall goal is to facilitate an understanding of drug transporters for PrEP optimization. Copyright © 2015 Elsevier B.V. All rights reserved.

Firm- and drug-specific patterns of generic drug payments by US medicaid programs: 1991-2008.

PubMed

Kelton, Christina M L; Chang, Lenisa V; Guo, Jeff J; Yu, Yan; Berry, Edmund A; Bian, Boyang; Heaton, Pamela C

2014-04-01

The entry of generic drugs into markets previously monopolized by patented, branded drugs often represents large potential savings for healthcare payers in the USA. Our objectives were to describe and explain the trends in drug reimbursement by public Medicaid programmes post-generic entry for as many drug markets and for as long a time period as possible. The data were the Medicaid State Drug Utilization Data maintained by the Centers for Medicare and Medicaid Services. Quarterly utilization and expenditure data from 1991 to 2008 were extracted for 83 drugs, produced by 229 firms, that experienced initial generic entry between 1992 and 2004. A relative 'price' for a specific drug, firm and quarter was constructed as Medicaid reimbursement per unit (e.g. tablet, capsule or vial) divided by average reimbursement per unit for the branded drug the year before entry. Fixed-effects models controlling for time-, firm- and drug-specific differences were estimated to explain reimbursement. Twelve quarters after generic entry, 18 % of drugs had average per-unit reimbursement less than 50 % of the original branded-drug reimbursement. For each additional firm manufacturing the drug, reimbursement per unit, relative to the pre-generic-entry branded-drug reimbursement, was estimated to fall by 17 (p < 0.01) and 3 (p < 0.01) percentage points for generic and branded-drug companies, respectively. Each additional quarter post-generic entry brought a 2 (p < 0.01) percentage point drop in relative reimbursement. State Medicaid programmes generally have been able to obtain relief from high drug prices following patent expirations for many branded-drug medications by adjusting reimbursement following the expanded competition in the pharmaceutical market.

Clinical utility of genetic testing in pediatric drug-resistant epilepsy: a pilot study.

PubMed

Ream, Margie A; Mikati, Mohamad A

2014-08-01

The utility of genetic testing in pediatric drug-resistant epilepsy (PDRE), its yield in "real life" clinical practice, and the practical implications of such testing are yet to be determined. To start to address the above gaps in our knowledge as they apply to a patient population seen in a tertiary care center. We retrospectively reviewed our experience with the use of clinically available genetic tests in the diagnosis and management of PDRE in one clinic over one year. Genetic testing included, depending on clinical judgment, one or more of the following: karyotype, chromosomal microarray, single gene sequencing, gene sequencing panels, and/or whole exome sequencing (WES). We were more likely to perform genetic testing in patients with developmental delay, epileptic encephalopathy, and generalized epilepsy. In our unique population, the yield of specific genetic diagnosis was relatively high: karyotype 14.3%, microarray 16.7%, targeted single gene sequencing 15.4%, gene panels 46.2%, and WES 16.7%. Overall yield of diagnosis from at least one of the above tests was 34.5%. Disease-causing mutations that were not clinically suspected based on the patients' phenotypes and representing novel phenotypes were found in 6.9% (2/29), with an additional 17.2% (5/29) demonstrating pharmacologic variants. Three patients were incidentally found to be carriers of recessive neurologic diseases (10.3%). Variants of unknown significance (VUSs) were identified in 34.5% (10/29). We conclude that genetic testing had at least some utility in our patient population of PDRE, that future similar larger studies in various populations are warranted, and that clinics offering such tests must be prepared to address the complicated questions raised by the results of such testing. Copyright © 2014. Published by Elsevier Inc.

[Quality assessment of drug use in the elderly].

PubMed

Mosegui, G B; Rozenfeld, S; Veras, R P; Vianna, C M

1999-10-01

The objective is to evaluate the quality of medication utilization through the analysis of the pattern of usage, the degree of compliance to essential drug lists, therapeutic value and by drug interactions found among women over 60 years of age. Six hundred thirty-four women enrolled at the Open University of the Third Age were studied. Data was collected through pattern-oriented, tested questionnaires. The variables examined were related to drugs and to drug utilization. The units of analysis used were the drugs and the individual. Of 634 women that participated in the study, 9,1% did not use drugs. The number of medications taken vary from 1 to 17. The average is 4,0 drugs/woman. Among the 2.510 pharmaceutical specialties mentioned by the interviewed, 538 different substances were identified. About 26% of the medications were in agreement with the recommendations of the World Health Organization and 17% with recommendations of the "Relação Nacional de Medicamentos Essenciais". Seventeen percent of the drugs are inappropriate for use in seniors; 14,1% of the women may suffer consequences for taking drugs of the same therapeutic class, and 15, 5% are exposed to interactions. The data suggest that the pattern of the medication utilization is considerably influenced by the medical prescription and that their quality is harmed by the low selectiveness of the pharmaceutical market

46 CFR 16.113 - Chemical drug testing.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 46 Shipping 1 2010-10-01 2010-10-01 false Chemical drug testing. 16.113 Section 16.113 Shipping... General § 16.113 Chemical drug testing. (a) Drug testing programs required by this part must be conducted... should be consulted to determine the specific procedures which must be established and utilized. Drug...

46 CFR 16.113 - Chemical drug testing.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 46 Shipping 1 2014-10-01 2014-10-01 false Chemical drug testing. 16.113 Section 16.113 Shipping... General § 16.113 Chemical drug testing. (a) Drug testing programs required by this part must be conducted... should be consulted to determine the specific procedures which must be established and utilized. Drug...

46 CFR 16.113 - Chemical drug testing.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 46 Shipping 1 2012-10-01 2012-10-01 false Chemical drug testing. 16.113 Section 16.113 Shipping... General § 16.113 Chemical drug testing. (a) Drug testing programs required by this part must be conducted... should be consulted to determine the specific procedures which must be established and utilized. Drug...

46 CFR 16.113 - Chemical drug testing.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 46 Shipping 1 2013-10-01 2013-10-01 false Chemical drug testing. 16.113 Section 16.113 Shipping... General § 16.113 Chemical drug testing. (a) Drug testing programs required by this part must be conducted... should be consulted to determine the specific procedures which must be established and utilized. Drug...

46 CFR 16.113 - Chemical drug testing.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 46 Shipping 1 2011-10-01 2011-10-01 false Chemical drug testing. 16.113 Section 16.113 Shipping... General § 16.113 Chemical drug testing. (a) Drug testing programs required by this part must be conducted... should be consulted to determine the specific procedures which must be established and utilized. Drug...

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.

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

PubMed

Ozeki, Yuriko; 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; Matsumoto, Sohkichi

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 rapid and

Decomposition of Economic Inequality in Needle and Syringe Programs Utilization to its Determinants among Men Who Inject Drugs in Tehran using Blinder-Oaxaca Decomposition Method.

PubMed

Noroozi, Mehdi; Rahimi, Ebrahim; Ghisvand, Hessam; Qorbani, Mostafa; Sharifi, Hamid; Noroozi, Alireza; Farhoudian, Ali; Marshall, Brandon D L; Jorjoran Shoshtari, Zahra; Karimi, Salah Eddin; Rezaei, Omid; Armoon, Bahram

2018-06-07

According to latest available data there are more of 300,000 people injects drug users (PWID) in Iran. In this study, we used a Blinder-Oaxaca (BO) decomposition to explore the relative contributions of inequality in utilization of NSPs and to decompose it to its determinants in Teheran. We used data from a cross-sectional survey using snowball sampling to recruit 500 PWID from June to July 2016 in Tehran. Participants were reported injecting drug use in the past month, were able to speak and comprehend Farsi enough to respond to survey questions, and were able to provide informed consent to complete the interview. We used a BO method to decompose the role of economic inequality on utilization of needle and syringe programs. A total 520 of clients participated in the study of which data was fully complete for 500. The selected predictor variables (age, education level, marital status, homelessness, HIV risk perception, and HIV knowledge) together explain 54% (8.5% out of 16%) of total inequality in utilization of needle and syringe programs and the remaining 46% constitute the unexplained residual. HIV risk perception status contributed about 38% (3.3% out of 8.5%) to the total health inequality, followed by HIV knowledge (26%) and education level were contributed 20% each, respectively. The results showed that contribution of economic inequalities in utilization of NSPs was primarily explained by the differential effects of HIV risk perception and HIV knowledge among PWID. Reducing HIV risk perception and increasing HIV knowledge might be essential to efforts to eliminate inequalities in access to NSPs among PWID.

Hospital ownership and drug utilization under a global budget: a quantile regression analysis.

PubMed

Zhang, Jing Hua; Chou, Shin-Yi; Deily, Mary E; Lien, Hsien-Ming

2014-03-01

A global budgeting system helps control the growth of healthcare spending by setting expenditure ceilings. However, the hospital global budget implemented in Taiwan in 2002 included a special provision: drug expenditures are reimbursed at face value, while other expenditures are subject to discounting. That gives hospitals, particularly those that are for-profit, an incentive to increase drug expenditures in treating patients. We calculated monthly drug expenditures by hospital departments from January 1997 to June 2006, using a sample of 348 193 patient claims to Taiwan National Health Insurance. To allow for variation among responses by departments with differing reliance on drugs and among hospitals of different ownerships, we used quantile regression to identify the effect of the hospital global budget on drug expenditures. Although drug expenditure increased in all hospital departments after the enactment of the hospital global budget, departments in for-profit hospitals that rely more heavily on drug treatments increased drug spending more, relative to public hospitals. Our findings suggest that a global budgeting system with special reimbursement provisions for certain treatment categories may alter treatment decisions and may undermine cost-containment goals, particularly among for-profit hospitals.

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

Opportunities and Challenges for Niosomes as Drug Delivery Systems.

PubMed

Thakkar, Miloni; Brijesh, S

2016-01-01

With the increase in drug resistance observed in most infectious diseases as well as some forms of cancer, and with the chances of development of new drug molecules to address this issue looking bleak, one of the most plausible ways to disease treatment is combination therapy. Combination therapy would ensure delay in drug resistance, if utilized rationally. However, the biggest difficulty in employing combination therapy are adverse effects due to potential drug-drug interactions and patient compliance due to multiple routes of administration or multiple dosing that may be required. To overcome these issues, researchers have utilized nanoparticle-based systems that can hold multiple drugs in a single carrier. There are several nanocarrier systems available for such purposes. However, the focus of this review will be non-ionic surfactant-based systems (niosomes) for delivery of multiple therapeutic agents. Niosomes are artificially prepared drug delivery carriers. They are structurally similar to liposomes albeit more stable than them. Literature pertaining to combination drug delivery and various drug delivery systems was reviewed. It was conceptualized that many of the methods used to prepare various types of carriers for combination delivery of drugs may be used for niosomal systems as well. We envisage that niosomes may effectively be utilized to package older drugs in newer ways. The review will thus focus on techniques that may be used for the formulation of niosomes, ways to encapsulate multiple-drug moieties, and challenges associated in preparing and optimizing such systems.

Preclinical Determinants of Drug Choice under Concurrent Schedules of Drug Self-Administration

PubMed Central

Banks, Matthew L.; Negus, S. Stevens

2012-01-01

Drug self-administration procedures have played a critical role in the experimental analysis of psychoactive compounds, such as cocaine, for over 50 years. While there are numerous permutations of this procedure, this paper will specifically focus on choice procedures using concurrent schedules of intravenous drug self-administration. The aims of this paper are to first highlight the evolution of drug choice procedures and then review the subsequent preclinical body of literature utilizing these choice procedures to understand the environmental, pharmacological, and biological determinants of the reinforcing stimulus effects of drugs. A main rationale for this paper is our proposition that choice schedules are underutilized in investigating the reinforcing effects of drugs in assays of drug self-administration. Moreover, we will conclude with potential future directions and unexplored scientific space for the use of drug choice procedures. PMID:23243420

42 CFR 456.703 - Drug use review program.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 42 Public Health 4 2010-10-01 2010-10-01 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) General...

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) General...

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) General...

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) General...

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) General...

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) General...

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) General...

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) General...

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) General...

Effects of a consumer driven health plan on pharmaceutical spending and utilization.

PubMed

Parente, Stephen T; Feldman, Roger; Chen, Song

2008-10-01

To compare pharmaceutical spending and utilization in a consumer driven health plan (CDHP) with a three-tier pharmacy benefit design, and to examine whether the CDHP creates incentives to reduce pharmaceutical spending and utilization for chronically ill patients, generic or brand name drugs, and mail-order drugs. Retrospective insurance claims analysis from a large employer that introduced a CDHP in 2001 in addition to a point of service (POS) plan and a preferred provider organization (PPO), both of which used a three-tier pharmacy benefit. Difference-in-differences regression models were estimated for drug spending and utilization. Control variables included the employee's income, age, and gender, number of covered lives per contract, election of flexible spending account, health status, concurrent health shock, cohort, and time trend. Results. CDHP pharmaceutical expenditures were lower than those in the POS cohort in 1 year without differences in the use of brand name drugs. We find limited evidence of less drug consumption by CDHP enrollees with chronic illnesses, and some evidence of less generic drug use and more mail-order drug use among CDHP members. The CDHP is cost-neutral or cost-saving to both the employer and the employee compared with three-tier benefits with no differences in brand name drug use. © Health Research and Educational Trust.

A critical assessment of antipsychotic drug monitoring.

PubMed

Waraska, J; Nagle, J D

1987-06-01

Analytic problems associated with monitoring antipsychotic drug levels have largely been resolved. Despite the establishment of target values for some drugs, the clinical utility of such levels remains to be determined.

Utilization of the Bridging Strategy for the Development of New Drugs in Oncology to Avoid Drug Lag.

PubMed

Kogure, Seiji; Koyama, Nobuyuki; Hidaka, Shinji

2017-11-01

Global trial (GT) strategy and bridging (BG) strategy are currently the main clinical development strategies of oncology drugs in Japan, but the relationship between development style and drug lag and how the bridging strategy has contributed to the solution of drug lag have not been clear. We investigated the potential factors that influenced submission lag (SL), and also compared the differences in SL among early-initiation BG strategy, late-initiation BG strategy, and GT strategy. A stepwise linear regression analysis identified the potential factors that shorten SL: development start lag and development style. Comparison of the differences in SL among the strategies also indicated that the SL in the GT strategy and that in the early-initiation BG strategy were significantly shorter than that in the late-initiation BG strategy. The findings in our study suggest that the late-initiation BG strategy may not contribute to shortening drug lag. Because the number of late-initiation BG studies has not decreased, we propose first that pharmaceutical companies should initiate clinical development as early as possible in Japan so that they can choose the GT strategy as a first option at the next step, and second when they cannot choose the GT strategy after investigating differences in exposure between Japanese and non-Japanese in a phase 1 study, they should select the early BG strategy to avoid future drug lag. It is also important for the regulatory authorities to provide reasonable guidance to have a positive impact on strategic decisions, even for foreign-capital companies. © 2017, The American College of Clinical Pharmacology.

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

Liability and ophthalmic drug use.

PubMed

Classé, J G

1992-01-01

Ophthalmic drug use has been an aspect of optometry for more than two decades. Although utilization of these drugs has produced significant changes in the clinical and legal responsibilities of optometrists, the liability posture of the profession has remained unaltered. Studies of malpractice claims against optometrists and ophthalmologists have demonstrated that ophthalmologists are much more likely to be charged with negligence for adverse drug reactions and that drug-related malpractice claims are not a liability issue for optometrists. Based on the experiences of both professions, this paper describes the adverse effects of common ophthalmic drugs, with emphasis on those drug reactions that have resulted in litigation.

7 CFR 1710.127 - Drug free workplace.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 7 Agriculture 11 2012-01-01 2012-01-01 false Drug free workplace. 1710.127 Section 1710.127 Agriculture Regulations of the Department of Agriculture (Continued) RURAL UTILITIES SERVICE, DEPARTMENT OF... and Basic Policies § 1710.127 Drug free workplace. Borrowers are required to comply with the Drug Free...

7 CFR 1710.127 - Drug free workplace.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 7 Agriculture 11 2014-01-01 2014-01-01 false Drug free workplace. 1710.127 Section 1710.127 Agriculture Regulations of the Department of Agriculture (Continued) RURAL UTILITIES SERVICE, DEPARTMENT OF... and Basic Policies § 1710.127 Drug free workplace. Borrowers are required to comply with the Drug Free...

7 CFR 1710.127 - Drug free workplace.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 7 Agriculture 11 2013-01-01 2013-01-01 false Drug free workplace. 1710.127 Section 1710.127 Agriculture Regulations of the Department of Agriculture (Continued) RURAL UTILITIES SERVICE, DEPARTMENT OF... and Basic Policies § 1710.127 Drug free workplace. Borrowers are required to comply with the Drug Free...

7 CFR 1710.127 - Drug free workplace.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 7 Agriculture 11 2011-01-01 2011-01-01 false Drug free workplace. 1710.127 Section 1710.127 Agriculture Regulations of the Department of Agriculture (Continued) RURAL UTILITIES SERVICE, DEPARTMENT OF... and Basic Policies § 1710.127 Drug free workplace. Borrowers are required to comply with the Drug Free...

Physician drug dispensing in Switzerland: association on health care expenditures and utilization.

PubMed

Trottmann, Maria; Frueh, Mathias; Telser, Harry; Reich, Oliver

2016-07-08

Several countries recently reassessed the roles of drug prescribing and dispensing, either by enlarging pharmacists' rights to prescribe (e.g. the US and the United Kingdom) or by limiting physicians' rights to dispense (e.g. Taiwan and South Korea). While integrating the two roles might increase supply and be convenient for patients, concern is that drug mark-ups incite providers to prescribe unnecessary drugs. We aimed to assess the association of physician dispensing (PD) in Switzerland on various outcomes. We performed a retrospective cohort study, using health care claims data for patients in the year 2013. The analysis of the association of PD was perfomed using a large patient level dataset and several target variables, including the number of different chemical agents, share of generic drugs, number of visits to physicians and expenditures. Different multivariate econometric models were applied in order to capture the association PD on the target variables. A total of 101'784 patients were enrolled in 2013, whereas 54 % were PD patients. We find that PD is associated with lower pharmaceutical expenditure per patient, which can be explained by an increased use of generic drugs. The decrease is compensated by higher use of physician services. We find no significant impact of physician dispensing on total health care expenditure. Our study offers insights for policy makers who are (re-)considering the separation between drug prescribing and dispensing, either by allowing physicians to dispense or pharmacists to prescribe certain drugs. In terms of total health care expenditures, we find no difference between the two systems, so we are doubtful that changing dispensing rights are a good measure to contain cost, at least in Switzerland.

Impact of Doctors' Resistance on Success of Drug Utilization Review System

PubMed Central

Choi, Jong Soo; Yun, Seong Hyeon; Kim, Dongsoo

2014-01-01

Objectives The drug utilization review (DUR) system, which checks any conflict event of medications, contributes to improve patient safety. One of the important barriers in its adoption is doctors' resistance. This study aimed to analyze the impacts of doctors' resistance on the success of the DUR system. Methods This study adopted an augmented the DeLone and McLean Information System (D&M IS) Success Model (2003), which used doctors' resistance as a socio-technological measure. This study framework is the same as that of the D&M IS Success Model in that it is based on qualities, such as system, information, and services. The major difference is that this study excluded the variable 'use' because it was not statistically significant for mandatory systems. A survey of doctors who used computers to enter prescriptions was conducted at a Korean tertiary hospital in February 2012. Results This study is very meaningful in that it is the first study to explore the success factors of the DUR system associated with doctors' resistance. Doctors' resistance to the DUR system was not statistically associated with user usefulness, whereas it affected user satisfaction. Conclusions The results indicate that doctors still complain of discomfort in using the DUR system in the outpatient clinical setting, even though they admit that it contributes to patient safety. To mitigate doctors' resistance and raise user satisfaction, more opinions from doctors regarding the DUR system have to be considered and have to be reflected in the system. PMID:24872908

Comparison of MDCK-MDR1 and Caco-2 cell based permeability assays for anti-malarial drug screening and drug investigations.

PubMed

Jin, Xiannu; Luong, Thu-Lan; Reese, Necole; Gaona, Heather; Collazo-Velez, Vanessa; Vuong, Chau; Potter, Brittney; Sousa, Jason C; Olmeda, Raul; Li, Qigui; Xie, Lisa; Zhang, Jing; Zhang, Ping; Reichard, Greg; Melendez, Victor; Marcsisin, Sean R; Pybus, Brandon S

2014-01-01

Malaria is a major health concern and affects over 300million people a year. Accordingly, there is an urgent need for new efficacious anti-malarial drugs. A major challenge in developing new anti-malarial drugs is to design active molecules that have preferable drug-like characteristics. These "drug-like" characteristics include physiochemical properties that affect drug absorption, distribution, metabolism, and excretion (ADME). Compounds with poor ADME profiles will likely fail in vivo due to poor pharmacokinetics and/or other drug delivery related issues. There have been numerous assays developed in order to pre-screen compounds that would likely fail in further development due to poor absorption properties including PAMPA, Caco-2, and MDCK permeability assays. The use of cell-based permeability assays such as Caco-2 and MDCK serve as surrogate indicators of drug absorption and transport, with the two approaches often used interchangeably. We sought to evaluate both approaches in support of anti-malarial drug development. Accordingly, a comparison of both assays was conducted utilizing apparent permeability coefficient (Papp) values determined from liquid chromatography/tandem mass spectrometry (LC-MS) analyses. Both Caco-2 and MDCK permeability assays produced similar Papp results for potential anti-malarial compounds with low and medium permeability. Differences were observed for compounds with high permeability and compounds that were P-gp substrates. Additionally, the utility of MDCK-MDR1 permeability measurements was demonstrated in probing the role of P-glycoprotein transport in Primaquine-Chloroquine drug-drug interactions in comparison with in vivo pharmacokinetic changes. This study provides an in-depth comparison of the Caco-2 and MDCK-MDR1 cell based permeability assays and illustrates the utility of cell-based permeability assays in anti-malarial drug screening/development in regard to understanding transporter mediated changes in drug absorption

Botanical drugs in Ayurveda and Traditional Chinese Medicine.

PubMed

Jaiswal, Yogini; Liang, Zhitao; Zhao, Zhongzhen

2016-12-24

China and India have a long history in the therapeutic application of botanical drugs in traditional medicine. Traditional Chinese Medicine (TCM) and Ayurveda are considered as two of the most ancient systems of medicine, with history of more than two millennia. Medicinal plants are the principal medicinal materials used in both these systems. This review discusses about the histories of Ayurveda and TCM, the common medicinal plants species, the drug processing strategies used, and the current statuses of these traditional systems of medicine (TSM). Through the views presented in this article, we aim to provide a new perspective to herbal drug researchers for expanding and improving the utilization of botanical drugs and their therapeutic applications. A bibliographic investigation of Chinese and Indian pharmacopoeias, monographs and official websites was performed. Furthermore, information was obtained from scientific databases on ethnobotany and ethno medicines. The review of Ayurveda and TCM ethno medicine indicates that both these systems have many medicinal materials in common. The studies carried out by the authors for comparison of plants from same genus from both these TSM's have been discussed to further bring focus to the utilization of "qualitatively" similar species which can be utilized and substituted for endangered or economically valued species. The overview of ancient literature and scientific findings for drugs in both these systems suggests that, the botanical drugs used in common and their processing methods can be explored further for extensive utilization in traditional medicine. This review describes the histories, common medicinal plant species, their processing methods and therapeutic applications in Ayurveda and TCM. The insights provided through this article may be used by herbal drug researchers and pharmacologists for further exploration of botanical drugs from these two traditional systems of medicine. Copyright © 2016. Published by

Pharmacy Utilization and the Medicare Modernization Act

PubMed Central

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

Effects of managerial intervention on drug utilization pattern at King Chulalongkorn Memorial Hospital.

PubMed

Limpanasithikul, Wacharee; Wangsaturaka, Danai; Nantawan, Patra; Itthipanichapong, Chandhanee; Thamaree, Sopit; Wittayalertpanya, Supeecha; Ketcharoen, Aurawan; Taworn, Nongnuch; Kemsri, Wandee; Kusolsomboon, Thammarat; Tangphao, Oranee

2002-06-01

The economic crisis in Thailand since 1997 has a major impact on all sections of the country including health care. There were several suggestions for reducing the drug expenditure budget including restriction of hospital formulary, generic prescribing and generic dispensing. At King Chulalongkorn Memorial hospital, the new hospital formulary was established and implemented in March 1998. The generic dispensing policy was also in place at the same time. This study aimed to evaluate the impact of the new implementation by comparing the prescription patterns in out patient departments (OPDs) of the hospital before and after the new hospital formulary implementation. The prescriptions from several OPDs were systematically stratified samplings 5 weeks before and 5 weeks after March 1st, 1998. The information from the prescriptions including drug category, drug name, amount of dispensed drug, drug cost, etc. was collected and analyzed. The total number of prescriptions and the average number of drug items/prescription before and after the implementation were similar (2,049 vs 2,052, and 2.52 +/- 0.048 vs 2.45 +/- 0.03 respectively). The total cost of the prescription, the cost/prescription and the cost/item seemed to be different (1,690,484 baht vs 1,282,343 baht, 844 +/- 54.04 vs 633 +/- 41.11 and 332.58 +/- 29.59 vs 255.29 +/- 19.98 respectively). After the implementation, physicians in the hospital increasingly prescribed drugs by generic name (37.1% vs 44.85%). Locally made drugs were also prescribed by physicians and received by patients more than before (9.56% vs 84.27% and 28.15% vs 60.72%, respectively). Anti-infective agents were studied in depth as they contribute to significant amount of drug expenditure. The total cost of prescribed anti-infective agents and the cost/prescription were increased after the implementation (223,529 vs 274,435 Baht and 585.38 +/- 102.84 vs 772.71 +/- 147.59). The increased cost mainly came from the cost of anti-HIV drugs. Our

Clinical Utility of LC3 and p62 Immunohistochemistry in Diagnosis of Drug-Induced Autophagic Vacuolar Myopathies: A Case-Control Study

PubMed Central

Lee, Han S.; Daniels, Brianne H.; Salas, Eduardo; Bollen, Andrew W.; Debnath, Jayanta; Margeta, Marta

2012-01-01

Background Some patients treated with chloroquine, hydroxychloroquine, or colchicine develop autophagic vacuolar myopathy, the diagnosis of which currently requires electron microscopy. The goal of the current study was to develop an immunohistochemical diagnostic marker for this pathologic entity. Methodology Microtubule-associated protein light chain 3 (LC3) has emerged as a robust marker of autophagosomes. LC3 binds p62/SQSTM1, an adapter protein that is selectively degraded via autophagy. In this study, we evaluated the utility of immunohistochemical stains for LC3 and p62 as diagnostic markers of drug-induced autophagic vacuolar myopathy. The staining was performed on archival muscle biopsy material, with subject assignment to normal control, drug-treated control, and autophagic myopathy groups based on history of drug use and morphologic criteria. Principal Findings In all drug-treated subjects, but not in normal controls, LC3 and p62 showed punctate staining characteristic of autophagosome buildup. In the autophagic myopathy subjects, puncta were coarser and tended to coalesce into linear structures aligned with the longitudinal axis of the fiber, often in the vicinity of vacuoles. The percentage of LC3- and p62-positive fibers was significantly higher in the autophagic myopathy group compared to either the normal control (p<0.001) or the drug-treated control group (p<0.05). With the diagnostic threshold set between 8% and 15% positive fibers (depending on the desired level of sensitivity and specificity), immunohistochemical staining for either LC3 or p62 could be used to identify subjects with autophagic vacuolar myopathy within the drug-treated subject group (p≤0.001). Significance Immunohistochemistry for LC3 and p62 can facilitate tissue-based diagnosis of drug-induced autophagic vacuolar myopathies. By limiting the need for electron microscopy (a time consuming and costly technique with high specificity, but low sensitivity), clinical use of these

Clinical utility of LC3 and p62 immunohistochemistry in diagnosis of drug-induced autophagic vacuolar myopathies: a case-control study.

PubMed

Lee, Han S; Daniels, Brianne H; Salas, Eduardo; Bollen, Andrew W; Debnath, Jayanta; Margeta, Marta

2012-01-01

Some patients treated with chloroquine, hydroxychloroquine, or colchicine develop autophagic vacuolar myopathy, the diagnosis of which currently requires electron microscopy. The goal of the current study was to develop an immunohistochemical diagnostic marker for this pathologic entity. Microtubule-associated protein light chain 3 (LC3) has emerged as a robust marker of autophagosomes. LC3 binds p62/SQSTM1, an adapter protein that is selectively degraded via autophagy. In this study, we evaluated the utility of immunohistochemical stains for LC3 and p62 as diagnostic markers of drug-induced autophagic vacuolar myopathy. The staining was performed on archival muscle biopsy material, with subject assignment to normal control, drug-treated control, and autophagic myopathy groups based on history of drug use and morphologic criteria. In all drug-treated subjects, but not in normal controls, LC3 and p62 showed punctate staining characteristic of autophagosome buildup. In the autophagic myopathy subjects, puncta were coarser and tended to coalesce into linear structures aligned with the longitudinal axis of the fiber, often in the vicinity of vacuoles. The percentage of LC3- and p62-positive fibers was significantly higher in the autophagic myopathy group compared to either the normal control (p<0.001) or the drug-treated control group (p<0.05). With the diagnostic threshold set between 8% and 15% positive fibers (depending on the desired level of sensitivity and specificity), immunohistochemical staining for either LC3 or p62 could be used to identify subjects with autophagic vacuolar myopathy within the drug-treated subject group (p ≤ 0.001). Immunohistochemistry for LC3 and p62 can facilitate tissue-based diagnosis of drug-induced autophagic vacuolar myopathies. By limiting the need for electron microscopy (a time consuming and costly technique with high specificity, but low sensitivity), clinical use of these markers will improve the speed and accuracy of

Impact of China's Public Hospital Reform on Healthcare Expenditures and Utilization: A Case Study in ZJ Province

PubMed Central

Zhang, Hao; Hu, Huimei; Wu, Christina; Yu, Hai; Dong, Hengjin

2015-01-01

Background High drug costs due to supplier-induced demand (SID) obstruct healthcare accessibility in China. Drug prescriptions can generate markup-related profits, and the low prices of other medical services can lead to labor-force underestimations; therefore, physicians are keen to prescribe drugs rather than services. Thus, in China, a public hospital reform has been instituted to cancel markups and increase service prices. Methods A retrospective pre/post-reform study was conducted in ZJ province to assess the impact of the reform on healthcare expenditures and utilization, ultimately to inform policy development and decision-making. The main indicators are healthcare expenditures and utilization. Results Post-reform, drug expenditures per visit decreased by 8.2% and 15.36% in outpatient and inpatient care, respectively; service expenditures per visit increased by 23.03% and 27.69% in outpatient and inpatient care, respectively. Drug utilization per visit increased by 5.58% in outpatient care and underwent no significant change in inpatient care. Both were lower than the theoretical drug-utilization level, which may move along the demand curve because of patient-initiated demand (PID); this indicates that SID-promoted drug utilization may decrease. Finally, service utilization per visit increased by 6% in outpatient care and by 13.10% in inpatient care; both were higher than the theoretical level moving along the demand curve, and this indicates that SID-promoted service utilization may increase. Conclusion The reform reduces drug-prescription profits by eliminating drug markups; additionally, it compensates for service costs by increasing service prices. Post-reform, the SID of drug prescriptions decreased, which may reduce drug-resource waste. The SID of services increased, with potentially positive and negative effects: accessibility to services may be promoted when physicians provide more services, but the risk of resource waste may also increase. This

Impact of China's Public Hospital Reform on Healthcare Expenditures and Utilization: A Case Study in ZJ Province.

PubMed

Zhang, Hao; Hu, Huimei; Wu, Christina; Yu, Hai; Dong, Hengjin

2015-01-01

High drug costs due to supplier-induced demand (SID) obstruct healthcare accessibility in China. Drug prescriptions can generate markup-related profits, and the low prices of other medical services can lead to labor-force underestimations; therefore, physicians are keen to prescribe drugs rather than services. Thus, in China, a public hospital reform has been instituted to cancel markups and increase service prices. A retrospective pre/post-reform study was conducted in ZJ province to assess the impact of the reform on healthcare expenditures and utilization, ultimately to inform policy development and decision-making. The main indicators are healthcare expenditures and utilization. Post-reform, drug expenditures per visit decreased by 8.2% and 15.36% in outpatient and inpatient care, respectively; service expenditures per visit increased by 23.03% and 27.69% in outpatient and inpatient care, respectively. Drug utilization per visit increased by 5.58% in outpatient care and underwent no significant change in inpatient care. Both were lower than the theoretical drug-utilization level, which may move along the demand curve because of patient-initiated demand (PID); this indicates that SID-promoted drug utilization may decrease. Finally, service utilization per visit increased by 6% in outpatient care and by 13.10% in inpatient care; both were higher than the theoretical level moving along the demand curve, and this indicates that SID-promoted service utilization may increase. The reform reduces drug-prescription profits by eliminating drug markups; additionally, it compensates for service costs by increasing service prices. Post-reform, the SID of drug prescriptions decreased, which may reduce drug-resource waste. The SID of services increased, with potentially positive and negative effects: accessibility to services may be promoted when physicians provide more services, but the risk of resource waste may also increase. This warrants further research. It is

The Therapeutic Utility of Employment in Treating Drug Addiction: Science to Application.

PubMed

Silverman, Kenneth; Holtyn, August F; Morrison, Reed

2016-06-01

Research on a model Therapeutic Workplace has allowed for evaluation of the use of employment in the treatment of drug addiction. Under the Therapeutic Workplace intervention, adults with histories of drug addiction are hired and paid to work. To promote drug abstinence or adherence to addiction medications, participants are required to provide drug-free urine samples or take prescribed addiction medications, respectively, to gain access to the workplace and/or to maintain their maximum rate of pay. Research has shown that the Therapeutic Workplace intervention is effective in promoting and maintaining abstinence from heroin, cocaine and alcohol and in promoting adherence to naltrexone. Three models could be used to implement and maintain employment-based reinforcement in the treatment of drug addiction: A Social Business model, a Cooperative Employer model, and a Wage Supplement model. Under all models, participants initiate abstinence in a training and abstinence initiation phase (Phase 1). Under the Social Business model, Phase 1 graduates are hired as employees in a social business and required to maintain abstinence to maintain employment and/or maximum pay. Under the Cooperative Employer model, cooperating community employers hire graduates of Phase 1 and require them to maintain abstinence to maintain employment and/or maximum pay. Under the Wage Supplement Model, graduates of Phase 1 are offered abstinence-contingent wage supplements if they maintain competitive employment in a community job. Given the severity and persistence of the problem of drug addiction and the lack of treatments that can produce lasting effects, continued development of the Therapeutic Workplace is warranted.

Examination of psychosocial predictors of Virginia pharmacists' intention to utilize a prescription drug monitoring program using the theory of planned behavior.

PubMed

Gavaza, Paul; Fleming, Marc; Barner, Jamie C

2014-01-01

Little is known about the main drivers of pharmacists' intention to utilize prescription drug monitoring programs (PDMPs) when making care decisions and the actual contribution of these factors in explaining intention and behavior. This study examined what theory of planned behavior (TPB) model constructs (i.e., attitude, subjective norm [SN], perceived behavioral control [PBC]), past utilization behavior (PUB) and perceived moral obligation (PMO) were significant predictors of Virginia community pharmacists' intention to utilize a PDMP. A cover letter with a link to a 28-item online survey was e-mailed to 600 members of the Virginia Pharmacists Association. Multiple regression analyses were used to determine the association between pharmacists' intention to utilize the PDMP database and attitude, SN, PBC, PUB and PMO. Ninety-seven usable responses were received, for a response rate of 16.2%. A majority of the respondents were Caucasian (96.4%), female (50.5%), working in independent community pharmacies (60.4%) with an average age of 49.5 ± 13.4 years. Overall, pharmacists intended to utilize a PDMP (mean = 5.3 ± 4.6; possible range: -9 to 9), had a positive attitude toward utilizing PDMP (mean = 6.3 ± 5.3; possible range: -12 to 12), perceived that others wanted them to utilize a PDMP (SN score = 3.7 ± 2.4; range: -6 to 6), and believed that they had control over utilization behavior (PBC score = 4.5 ± 4.0; range: -9 to 9). Attitude (β = 0.723, P < 0.001), SN (β = 0.230, P = 0.014) and PBC (β = -0.215, P = 0.026) significantly predicted pharmacists' intent, accounting for 56.7% of the variance in intention to utilize the PDMP database (P < 0.001). The addition of PMO (P < 0.001) significantly contributed to explaining the variance in intention but PUB did not. Members of the Virginia Pharmacists Association who responded to the survey showed a strong positive intent to utilize PDMP database. Pharmacists' attitudes, subjective norm, perceived behavioral

Effect of Prescription Drug Coupons on Statin Utilization and Expenditures: A Retrospective Cohort Study.

PubMed

Daubresse, Matthew; Andersen, Martin; Riggs, Kevin R; Alexander, G Caleb

2017-01-01

Drug coupons are widely used, but their effects are not well understood. To quantify the effect of coupons on statin use and expenditures. Retrospective cohort analysis of IMS Health LRx LifeLink database. U.S. retail pharmacy transactions. Incident statin users who initiated branded atorvastatin or rosuvastatin between June 2006 and February 2013. Monthly statin utilization (pill-days of therapy), switching (filling a different statin), termination (failure to refill statin for 6 mo), and out-of-pocket and total costs. Of 1.1 million incident atorvastatin and rosuvastatin users, 2% used a coupon for at least one statin fill. At 1 year, compared with noncoupon users, those who used a statin coupon on their first fill were dispensed an equal number of monthly pill-days (23.7 vs 23.8), were less likely to switch statins (14.4% vs 16.3%), and were less likely to have terminated statin therapy (31.3% vs 39.2%). At 4 years, coupon users were more likely to have switched (45.5% vs 40.8%) and less likely to have terminated statin therapy (50.6% vs 61.1%) compared with noncoupon users. Those who used greater numbers of coupons were substantially less likely to switch and terminate statin therapies. Monthly out-of-pocket costs were lower among coupon than noncoupon users at 1 year ($9.7 vs $15.1), but total monthly costs were qualitatively similar ($115.5 vs $116.9). At 4 years, monthly out-of-pocket costs among coupon users remained lower ($14.3 vs $16.6) compared with noncoupon users. Sensitivity analyses supported the main results. Coupons for branded statins are associated with higher utilization and lower rates of discontinuation and short-term switching to other statin products. © 2016 Pharmacotherapy Publications, Inc.

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…

Drug Use among Seniors on Public Drug Programs in Canada, 2012.

PubMed

Proulx, Jeff; Hunt, Jordan

2015-01-01

Seniors take more drugs than younger Canadians because, on average, they have a higher number of chronic conditions. Although taking multiple medications may be necessary to manage these conditions, it is important to consider the benefits and risks of each medication and the therapeutic goals of the patient. This article provides an in-depth look at the number and types of drugs used by seniors using drug claims data from the CIHI's National Prescription Drug Utilization Information System Database, representing approximately 70% of seniors in Canada. In 2012, almost two-thirds (65.9%) of seniors on public drug programs had claims for five or more drug classes, while 27.2% had claims for 10 or more, and 8.6% had claims for 15 or more. The most commonly used drug class was statins, used by nearly half (46.6%) of seniors. Nearly two-thirds (60.9%) of seniors living in long-term care (LTC) facilities had claims for 10 or more drug classes. Proton pump inhibitors were the most commonly used drug class among seniors living in LTC facilities (used by 37.0% of seniors in LTC facilities), while statins ranked seventh (29.8%).

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

Drugs as instruments: a new framework for non-addictive psychoactive drug use.

PubMed

Müller, Christian P; Schumann, Gunter

2011-12-01

Most people who are regular consumers of psychoactive drugs are not drug addicts, nor will they ever become addicts. In neurobiological theories, non-addictive drug consumption is acknowledged only as a "necessary" prerequisite for addiction, but not as a stable and widespread behavior in its own right. This target article proposes a new neurobiological framework theory for non-addictive psychoactive drug consumption, introducing the concept of "drug instrumentalization." Psychoactive drugs are consumed for their effects on mental states. Humans are able to learn that mental states can be changed on purpose by drugs, in order to facilitate other, non-drug-related behaviors. We discuss specific "instrumentalization goals" and outline neurobiological mechanisms of how major classes of psychoactive drugs change mental states and serve non-drug-related behaviors. We argue that drug instrumentalization behavior may provide a functional adaptation to modern environments based on a historical selection for learning mechanisms that allow the dynamic modification of consummatory behavior. It is assumed that in order to effectively instrumentalize psychoactive drugs, the establishment of and retrieval from a drug memory is required. Here, we propose a new classification of different drug memory subtypes and discuss how they interact during drug instrumentalization learning and retrieval. Understanding the everyday utility and the learning mechanisms of non-addictive psychotropic drug use may help to prevent abuse and the transition to drug addiction in the future.

FDA drug labeling: rich resources to facilitate precision medicine, drug safety, and regulatory science.

PubMed

Fang, Hong; Harris, Stephen C; Liu, Zhichao; Zhou, Guangxu; Zhang, Guoping; Xu, Joshua; Rosario, Lilliam; Howard, Paul C; Tong, Weida

2016-10-01

Here, we provide a concise overview of US Food and Drug Administration (FDA) drug labeling, which details drug products, drug-drug interactions, adverse drug reactions (ADRs), and more. Labeling data have been collected over several decades by the FDA and are an important resource for regulatory research and decision making. However, navigating through this data is challenging. To aid such navigation, the FDALabel database was developed, which contains a set of approximately 80000 labeling data. The full-text searching capability of FDALabel and querying based on any combination of specific sections, document types, market categories, market date, and other labeling information makes it a powerful and attractive tool for a variety of applications. Here, we illustrate the utility of FDALabel using case scenarios in pharmacogenomics biomarkers and ADR studies. Published by Elsevier Ltd.

Recent advances in the diagnosis of drug allergy.

PubMed

Primeau, M N; Adkinson, N F

2001-08-01

The diagnosis of immunologic drug reactions is based primarily on a detailed clinical history and historical data on relative immunogenicity of the culprit drugs. Except for a few standardized skin tests, most of the other methods for diagnosing drug allergy have unproven diagnostic or predictive clinical utility. Many tests for drug-specific immune responses are suggestive if positive, but have unknown negative predictive values. The present review addresses the most recent published literature regarding the diagnosis of drug allergy. Recent advances in the use of the lymphocyte transformation test, and delayed intradermal skin tests and patch tests for the diagnosis of delayed cutaneous reactions to penicillins suggest that these tests may have clinical utility, although confirmatory reports are still missing. For the diagnosis of acute vaccine reactions, gelatin-specific IgE as measured by radioallergosorbent test has now been shown to be reliably associated with allergic reactions to gelatin-containing vaccines.

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.

Underexplored Opportunities for Natural Products in Drug Discovery.

PubMed

DeCorte, Bart L

2016-10-27

The importance of natural products in the treatment of human disease is well documented. While natural products continue to have a profound impact on human health, chemists have succeeded in generating semisynthetic analogues that sometimes overshadow the original natural product in terms of clinical significance. Synthetic efforts based on natural products have primarily focused on improving their drug-like features while targeting utility in the same biological space. A less documented phenomenon is that natural products can serve as powerful starting materials to generate drug substances with novel therapeutic utility that is unrelated to the biological space of the natural product starting material. In this Perspective, examples of natural product derived marketed drugs with therapeutic utility in clinical space that is different from the biological profile of the starting material are presented, demonstrating that this is not merely a theoretical concept but both a clinical reality and an underexplored opportunity.

The anti-hepatitis drug use effect and inventory management optimization from the perspective of hospital drug supply chain.

PubMed

Liu, Zhanyu

2017-09-01

By analyzing the current hospital anti hepatitis drug use, dosage, indications and drug resistance, this article studied the drug inventory management and cost optimization. The author used drug utilization evaluation method, analyzed the amount and kind distribution of anti hepatitis drugs and made dynamic monitoring of inventory. At the same time, the author puts forward an effective scheme of drug classification management, uses the ABC classification method to classify the drugs according to the average daily dose of drugs, and implements the automatic replenishment plan. The design of pharmaceutical services supply chain includes drug procurement platform, warehouse management system and connect to the hospital system through data exchange. Through the statistical analysis of drug inventory, we put forward the countermeasures of drug logistics optimization. The results showed that drug replenishment plan can effectively improve drugs inventory efficiency.

Dendrimers for Drug Delivery.

PubMed

Chauhan, Abhay Singh

2018-04-18

Dendrimers have come a long way in the last 25 years since their inception. Originally created as a wonder molecule of chemistry, dendrimer is now in the fourth class of polymers. Dr. Donald Tomalia first published his seminal work on Poly(amidoamine) (PAMAM) dendrimers in 1985. Application of dendrimers as a drug delivery system started in late 1990s. Dendrimers for drug delivery are employed using two approaches: (i) formulation and (ii) nanoconstruct. In the formulation approach, drugs are physically entrapped in a dendrimer using non-covalent interactions, whereas drugs are covalently coupled on dendrimers in the nanoconstruct approach. We have demonstrated the utility of PAMAM dendrimers for enhancing solubility, stability and oral bioavailability of various drugs. Drug entrapment and drug release from dendrimers can be controlled by modifying dendrimer surfaces and generations. PAMAM dendrimers are also shown to increase transdermal permeation and specific drug targeting. Dendrimer platforms can be engineered to attach targeting ligands and imaging molecules to create a nanodevice. Dendrimer nanotechnology, due to its multifunctional ability, has the potential to create next generation nanodevices.

[Prescribed and reported drug use during pregnancy].

PubMed

Osorio-de-Castro, Claudia Garcia Serpa; Pepe, Vera Lucia Edais; Luiza, Vera Lucia; Cosendey, Marly Aparecida Elias; Freitas, Aline Matias de; Miranda, Frederico Fonseca; Bermudez, Jorge Antonio Zepeda; Leal, Maria do Carmo

2004-01-01

Few studies describe drug utilization in pregnancy focusing on prescribing practices. This study is part of a larger survey on perinatal care in the City of Rio de Janeiro, Brazil. The type of hospital (public, contracted out by the Unified National Health System, or private) determined the stratification of 10,072 hospitalized post-partum women, who were asked about medication used during pregnancy. Hospital records supplied information on drugs prescribed during labor. Drugs were classified according to the Anatomical Therapeutic Chemical (ATC) system. Another system was used for specific cases of referred use. A mean of 2.08 drugs was prescribed during labor, and a mean of 2.3 was reported during pregnancy. Anesthetics, antibiotics, oxytocin, and analgesics were the most frequently prescribed during labor, with significant differences between strata. Ferrous sulfate, vitamins, scopolamine, and acetaminophen were the main drugs reported during pregnancy. Women who had attempted abortion referred use of various kinds of tea (49.7%) and misoprostol (9.2%). The drug utilization pattern was consistent with the literature. This study offers knowledge on prescribing patterns during labor and self-reported use during pregnancy in both the public and private sectors.

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

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

PubMed

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

2015-12-07

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

Utilizing Social Action Theory as a Framework to Determine Correlates of Illicit Drug Use Among Young Men Who Have Sex with Men

PubMed Central

Traube, Dorian E.; Holloway, Ian W.; Schrager, Sheree M.; Kipke, Michele D.

2011-01-01

Background Young men who have sex with men (YMSM) continue to be at elevated risk for substance use; however, models explaining this phenomenon have often focused on a limited array of explanatory constructs. Purpose This study utilizes Social Action Theory (SAT) as a framework to address gaps in research by documenting the social, behavioral, and demographic risk factors associated with illicit drug use among YMSM. Methods Structural equation modeling was used to apply SAT to a cross-sectional sample of 526 men from the Healthy Young Men Study, a longitudinal study of substance use and sexual risk behavior among YMSM in Los Angeles. Results The final model possessed very good fit statistics (CFI = 0.936, TLI = 0.925, RMSEA = 0.040) indicating that SAT is appropriate for use with YMSM. Conclusions Substance use interventions for YMSM could be enhanced by employing SAT as conceptualized in this study and using a multi-targeted strategy for impacting illicit drug use. PMID:21644802

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

Drug-nutrient interactions: a case and clinical guide.

PubMed

Plotnikoff, Gregory A

2011-10-01

Advances in pharmacokinetics and pharmacodynamics require new competencies related to pharmaceutical prescribing. First, both physicians and pharmacists need to recognize the potential negative impact of nutrients and dietary supplements on the absorption, metabolism, and utilization of prescription drugs. Second, physicians, even more than pharmacists, need to recognize the potential negative effects of pharmaceuticals on the absorption, metabolism, and utilization of nutrients. This article discusses common drug-nutrient interactions and presents a case that illustrates how unrecognized nutrient disruption may negatively affect a patient's health and potentially result in unnecessary prescribing of medications. In presenting the case, we also provide a conceptual framework for assessing and treating this patient and a summary of current knowledge regarding drug-nutrient interactions.

Characterization of drug-induced transcriptional modules: towards drug repositioning and functional understanding

PubMed Central

Iskar, Murat; Zeller, Georg; Blattmann, Peter; Campillos, Monica; Kuhn, Michael; Kaminska, Katarzyna H; Runz, Heiko; Gavin, Anne-Claude; Pepperkok, Rainer; van Noort, Vera; Bork, Peer

2013-01-01

In pharmacology, it is crucial to understand the complex biological responses that drugs elicit in the human organism and how well they can be inferred from model organisms. We therefore identified a large set of drug-induced transcriptional modules from genome-wide microarray data of drug-treated human cell lines and rat liver, and first characterized their conservation. Over 70% of these modules were common for multiple cell lines and 15% were conserved between the human in vitro and the rat in vivo system. We then illustrate the utility of conserved and cell-type-specific drug-induced modules by predicting and experimentally validating (i) gene functions, e.g., 10 novel regulators of cellular cholesterol homeostasis and (ii) new mechanisms of action for existing drugs, thereby providing a starting point for drug repositioning, e.g., novel cell cycle inhibitors and new modulators of α-adrenergic receptor, peroxisome proliferator-activated receptor and estrogen receptor. Taken together, the identified modules reveal the conservation of transcriptional responses towards drugs across cell types and organisms, and improve our understanding of both the molecular basis of drug action and human biology. PMID:23632384

Use of Pregabalin - A Nationwide Pharmacoepidemiological Drug Utilization Study with Focus on Abuse Potential.

PubMed

Schjerning, O; Pottegård, A; Damkier, P; Rosenzweig, M; Nielsen, J

2016-07-01

Pregabalin is currently approved for the treatment of epilepsy, generalized anxiety disorder and neuropathic pain with a licensed dosage range of 150 mg to 600 mg/day. Growing concern about the abuse potential of pregabalin is partly based on reports of pregabalin being used in dosages that exceed the approved therapeutic range. To identify predictors of pregabalin use above recommended dosage, we conducted a pharmacoepidemological drug utilization study using the Danish nationwide registers. We deployed 4 measures of abuse: high use (≥600 mg/day) or very high use (≥1 200 mg/day) over a 6- or 12-month period, respectively. Multiple logistic regression was used to identify patient and treatment characteristics that were associated with either abuse marker. Out of 42 520 pregabalin users 4 090 (9.6%) were treated with more than 600 mg/day for 6 months and 2 765 (6.5%) for more than 12 months. Male gender and prescription of antipsychotics and benzodiazepines were associated with increased risk of use of above the recommended dosage. Use of pregabalin above recommended dosages was rare but abuse may occur in susceptible patients. © Georg Thieme Verlag KG Stuttgart · New York.

The Tuberculosis Drug Discovery and Development Pipeline and Emerging Drug Targets

PubMed Central

Mdluli, Khisimuzi; Kaneko, Takushi; Upton, Anna

2015-01-01

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

An explanatory model for state Medicaid per capita prescription drug expenditures.

PubMed

Roy, Sanjoy; Madhavan, S Suresh

2012-01-01

Rising prescription drug expenditure is a growing concern for publicly funded drug benefit programs like Medicaid. To be able to contain drug expenditures in Medicaid, it is important that cause(s) for such increases are identified. This study attempts to establish an explanatory model for Medicaid prescription drugs expenditure based on the impacts of key influencers/predictors identified using a comprehensive framework of drug utilization. A modified Andersen's behavior model of health services utilization is employed to identify potential determinants of pharmaceutical expenditures in state Medicaid programs. Level of federal matching funds, access to primary care, severity of diseases, unemployment, and education levels were found to be key influencers of Medicaid prescription drug expenditure. Increases in all, except education levels, were found to result in increases in drug expenditures. Findings from this study could better inform intervention policies and cost-containment strategies for state Medicaid drug benefit programs.

Outpatient utilization of psychopharmaceuticals: comparison between the cities of Zagreb and Sarajevo (2006-2009).

PubMed

Catić, Tarik; Stimac, Danijela; Zivković, Krešimir; Zelić, Ana

2012-08-01

To determine the real outpatient utilization of psychiatric drugs in Zagreb (Croatia) and Sarajevo (Bosnia and Herzegovina) and to compare the outpatient utilization of psychiatric drugs between this two cities. Data on the outpatient utilization of psycholpetics and psychoanaleptics (N05 and N06) in both cities were received from pharmacies and collected during 2006-2009. Based on the data obtained, a number of DDD and DDD per 1000 inhabitants perday (DDD/1000/day) has been calculated. The data in Zagreb were received from all pharmacies in Zagreb, whereas only 50% of pharmacies in Sarajevo participated, thus an extrapolation of data for Sarajevo was required and accomplished. All drugs were classified according to the ATC system. Based on the data obtained, a number of DDD and DDD/1000/day was calculated for all N05 and N06 drugs. Overall utilization trend was similar between the cities Sarajevo and Zagreb and followed trends in other neighbouring countries. Total consumption of psycholeptics and psychoanaleptics in Sarajevo was 22.6% (on average) lower than in Zagreb, during the 4-year period. During the 2006-2009 period the total consumption of psychopharmaceuticals showed increasing trend with peak in 2008 with similar trend between Zagreb and Sarajevo. It is necessary to implement systematic approach to drug utilization monitoring in Sarajevo and Bosnia and Herzegovina in general in order to improve prescribing quality as it is done in Croatia.

Gratitude and Drug Misuse: Role of Coping as Mediator.

PubMed

Leung, Chi-Ching; Tong, Eddie M W

2017-12-06

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

Drug-to-antibody determination for an antibody-drug-conjugate utilizing cathepsin B digestion coupled with reversed-phase high-pressure liquid chromatography analysis.

PubMed

Adamo, Michael; Sun, Guoyong; Qiu, Difei; Valente, Joseph; Lan, Wenkui; Song, Hangtian; Bolgar, Mark; Katiyar, Amit; Krishnamurthy, Girija

2017-01-20

Antibody drug conjugates or ADCs are currently being evaluated for their effectiveness as targeted chemotherapeutic agents across the pharmaceutical industry. Due to the complexity arising from the choice of antibody, drug and linker; analytical methods for release and stability testing are required to provide a detailed understanding of both the antibody and the drug during manufacturing and storage. The ADC analyzed in this work consists of a tubulysin drug analogue that is randomly conjugated to lysine residues in a human IgG1 antibody. The drug is attached to the lysine residue through a peptidic, hydrolytically stable, cathepsin B cleavable linker. The random lysine conjugation produces a heterogeneous mixture of conjugated species with a variable drug-to-antibody ratio (DAR), therefore, the average amount of drug attached to the antibody is a critical parameter that needs to be monitored. In this work we have developed a universal method for determining DAR in ADCs that employ a cathepsin B cleavable linker. The ADC is first cleaved at the hinge region and then mildly reduced prior to treatment with the cathepsin B enzyme to release the drug from the antibody fragments. This pre-treatment allows the cathepsin B enzyme unrestricted access to the cleavage sites and ensures optimal conditions for the cathepsin B to cleave all the drug from the ADC molecule. The cleaved drug is then separated from the protein components by reversed phase high performance liquid chromatography (RP-HPLC) and quantitated using UV absorbance. This method affords superior cleavage efficiency to other methods that only employ a cathepsin digestion step as confirmed by mass spectrometry analysis. This method was shown to be accurate and precise for the quantitation of the DAR for two different random lysine conjugated ADC molecules. Copyright © 2016 Elsevier B.V. All rights reserved.

Selection and utilization of assessment instruments in substance abuse treatment trials: the National Drug Abuse Treatment Clinical Trials Network experience.

PubMed

Rosa, Carmen; Ghitza, Udi; Tai, Betty

2012-07-17

Based on recommendations from a US Institute of Medicine report, the National Institute on Drug Abuse established the National Drug Abuse Treatment Clinical Trials Network (CTN) in 1999, to accelerate the translation of science-based addiction treatment research into community-based practice, and to improve the quality of addiction treatment, using science as the vehicle. One of the CTN's primary tasks is to serve as a platform to forge bi-directional communications and collaborations between providers and scientists, to enhance the relevance of research, which generates empirical results that impact practice. Among many obstacles in moving research into real-world settings, this commentary mainly describes challenges and iterative experiences in regard to how the CTN develops its research protocols, with focus on how the CTN study teams select and utilize assessment instruments, which can reasonably balance the interests of both research scientists and practicing providers when applied in CTN trials. This commentary also discusses the process by which the CTN further selects a core set of common assessment instruments that may be applied across all trials, to allow easier cross-study analyses of comparable data.

Iontophoresis: A Potential Emergence of a Transdermal Drug Delivery System

PubMed Central

Dhote, Vinod; Bhatnagar, Punit; Mishra, Pradyumna K.; Mahajan, Suresh C.; Mishra, Dinesh K.

2012-01-01

The delivery of drugs into systemic circulation via skin has generated much attention during the last decade. Transdermal therapeutic systems propound controlled release of active ingredients through the skin and into the systemic circulation in a predictive manner. Drugs administered through these systems escape first-pass metabolism and maintain a steady state scenario similar to a continuous intravenous infusion for up to several days. However, the excellent impervious nature of the skin offers the greatest challenge for successful delivery of drug molecules by utilizing the concepts of iontophoresis. The present review deals with the principles and the recent innovations in the field of iontophoretic drug delivery system together with factors affecting the system. This delivery system utilizes electric current as a driving force for permeation of ionic and non-ionic medications. The rationale behind using this technique is to reversibly alter the barrier properties of skin, which could possibly improve the penetration of drugs such as proteins, peptides and other macromolecules to increase the systemic delivery of high molecular weight compounds with controlled input kinetics and minimum inter-subject variability. Although iontophoresis seems to be an ideal candidate to overcome the limitations associated with the delivery of ionic drugs, further extrapolation of this technique is imperative for translational utility and mass human application. PMID:22396901

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

PubMed

Kesselheim, Aaron S; Wang, Bo; Franklin, Jessica M; Darrow, Jonathan J

2015-09-23

To evaluate the use of special expedited development and review pathways at the US Food and Drug Administration over the past two decades. Cohort study. FDA approved novel therapeutics between 1987 and 2014. 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. 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. 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). In the past two decades, drugs newly approved by the FDA have been associated with an increasing number of expedited development or review programs. Though expedited programs

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.

The Impact of Patient Complexity on Healthcare Utilization

ClinicalTrials.gov

2017-10-27

Primary Care Quality Metrics; Well Child Visits in First 15 Months of Life NQF 1392; Diabetes Mellitus NQF 0059; Colorectal Cancer Screening NQF 0034; Emergency Department Utilization; Alcohol and Drug Screening

Engineered Polymers for Advanced Drug Delivery

PubMed Central

Kim, Sungwon; Kim, Jong-Ho; Jeon, Oju; Kwon, Ick Chan; Park, Kinam

2009-01-01

Engineered polymers have been utilized for developing advanced drug delivery systems. The development of such polymers has caused advances in polymer chemistry, which, in turn, has resulted in smart polymers that can respond to changes in environmental condition, such as temperature, pH, and biomolecules. The responses vary widely from swelling/deswelling to degradation. Drug-polymer conjugates and drug-containing nano/micro-particles have been used for drug targeting. Engineered polymers and polymeric systems have also been used in new areas, such as molecular imaging as well as in nanotechnology. This review examines the engineered polymers that have been used as traditional drug delivery and as more recent applications in nanotechnology. PMID:18977434

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

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

PubMed

Habib, Mansur; Khan, Sharif Uddin; Hoque, Azhahul; Mondal, Badrul Alam; Hasan, A T M Hasibul; Chowdhury, Rajib Nayan; Haque, Badrul; Rahman, Kazi Mohibur; Chowdhury, Ahmed Hossain; Ghose, Swapon Kumar; Mohammad, Quazi Deen

2013-11-18

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. 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. 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 combination regimens had a

Access to linked administrative healthcare utilization data for pharmacoepidemiology and pharmacoeconomics research in Canada: anti-viral drugs as an example.

PubMed

Rawson, Nigel S B

2009-11-01

Administrative healthcare utilization data from Canadian provinces have been used for pharmacoepidemiology and pharmacoeconomics research, but limited transparency exists about opportunities for data access, who can access them, and processes to obtain data. An attempt was made to obtain data from all 10 provinces to evaluate access and its complexity. An initial enquiry about the process and requirements to obtain data on individual, anonymized patients dispensed any of four anti-viral drugs in the ambulatory setting, linked with data from hospital and physician service claims, was sent to each province. Where a response was encouraging, a technical description of the data of interest was submitted. Data were unavailable from the provinces of New Brunswick, Newfoundland and Labrador, and Prince Edward Island, and inaccessible from British Columbia, Manitoba and Ontario due to policies that prohibit collaborative work with pharmaceutical industry researchers. In Nova Scotia, patient-level data were available but only on site. Data were accessible in Alberta, Quebec and Saskatchewan, although variation exists in the currency of the data, time to obtain data, approval requirements and insurance coverage eligibility. As Canada moves towards a life-cycle management approach to drug regulation, more post-marketing studies will be required, potentially using administrative data. Linked patient-level drug and healthcare data are presently accessible to pharmaceutical industry researchers in four provinces, although only logistically realistic in three and limited to seniors and low-income individuals in two. Collaborative endeavours to improve access to provincial data and to create other data resources should be encouraged. (c) 2009 John Wiley & Sons, Ltd.

DrugQuest - a text mining workflow for drug association discovery.

PubMed

Papanikolaou, Nikolas; Pavlopoulos, Georgios A; Theodosiou, Theodosios; Vizirianakis, Ioannis S; Iliopoulos, Ioannis

2016-06-06

Text mining and data integration methods are gaining ground in the field of health sciences due to the exponential growth of bio-medical literature and information stored in biological databases. While such methods mostly try to extract bioentity associations from PubMed, very few of them are dedicated in mining other types of repositories such as chemical databases. Herein, we apply a text mining approach on the DrugBank database in order to explore drug associations based on the DrugBank "Description", "Indication", "Pharmacodynamics" and "Mechanism of Action" text fields. We apply Name Entity Recognition (NER) techniques on these fields to identify chemicals, proteins, genes, pathways, diseases, and we utilize the TextQuest algorithm to find additional biologically significant words. Using a plethora of similarity and partitional clustering techniques, we group the DrugBank records based on their common terms and investigate possible scenarios why these records are clustered together. Different views such as clustered chemicals based on their textual information, tag clouds consisting of Significant Terms along with the terms that were used for clustering are delivered to the user through a user-friendly web interface. DrugQuest is a text mining tool for knowledge discovery: it is designed to cluster DrugBank records based on text attributes in order to find new associations between drugs. The service is freely available at http://bioinformatics.med.uoc.gr/drugquest .

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.

Computer-Aided Drug Design Methods.

PubMed

Yu, Wenbo; MacKerell, Alexander D

2017-01-01

Computational approaches are useful tools to interpret and guide experiments to expedite the antibiotic drug design process. Structure-based drug design (SBDD) and ligand-based drug design (LBDD) are the two general types of computer-aided drug design (CADD) approaches in existence. SBDD methods analyze macromolecular target 3-dimensional structural information, typically of proteins or RNA, to identify key sites and interactions that are important for their respective biological functions. Such information can then be utilized to design antibiotic drugs that can compete with essential interactions involving the target and thus interrupt the biological pathways essential for survival of the microorganism(s). LBDD methods focus on known antibiotic ligands for a target to establish a relationship between their physiochemical properties and antibiotic activities, referred to as a structure-activity relationship (SAR), information that can be used for optimization of known drugs or guide the design of new drugs with improved activity. In this chapter, standard CADD protocols for both SBDD and LBDD will be presented with a special focus on methodologies and targets routinely studied in our laboratory for antibiotic drug discoveries.

Review of Utilization of Cardiovascular Medicines by Daily Defined Dose in the Czech Republic and Slovak Republic.

PubMed

Szilágyiová, Petra; Slušná, Jana; Babela, Robert

2017-11-01

To the Editor, Drug utilization is an important field of drug policy and an integral part of public health internationally. This area of research attracts increasing interest but the pioneering work was done 50 years ago when the first drug consumption report from six European countries for the period of 1966-1967 showed great differences in drug utilization between population groups (WHO, 1968). These results gave important stimulus for creation of Anatomical Therapeutic Chemical (ATC) classification and technical unit of measurement called the Defined Daily Dose (DDD) which is specified as "the assumed average maintenance dose per day for a drug used for its main indication in adults" that dealt with the objections against traditional units of measurement in drug utilization studies (WHO, 2016). The ATC/DDD methodology has in the meantime proved its suitability in drug utilization monitoring and research. As mentioned previously, consumption of pharmaceuticals is often used as a basis for comparison between countries. Based on our professional expertise, we decided to analyze the consumption of cardiovascular medicines by DDD in the Czech Republic and Slovak Republic within all ATC groups reported to OECD (OECD, 2016a). According to OECD indicator results, the Slovak Republic showed in 2014 a higher pharmaceutical consumption by DDD in ATC group C (cardiovascular system) compared to the Czech Republic (OECD, 2016a).

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…

Family Therapy for the Drug User: Conceptual and Practical Considerations

ERIC Educational Resources Information Center

Davis, Donald I.; And Others

1978-01-01

National surveys suggest that many drug treatment programs are utilizing family therapy. It is frequently the choice of treatment. Controlled studies of family therapy in drug abuse are sparce but encouraging. (MFD)

Network pharmacology: reigning in drug attrition?

PubMed

Alian, Osama M; Shah, Minjel; Mohammad, Momin; Mohammad, Ramzi M

2013-06-01

In the process of drug development, there has been an exceptionally high attrition rate in oncological compounds entering late phases of testing. This has seen a concurrent reduction in approved NCEs (new chemical entities) reaching patients. Network pharmacology has become a valuable tool in understanding the fine details of drug-target interactions as well as painting a more practical picture of phenotype relationships to patients and drugs. By utilizing all the tools achieved through molecular medicine and combining it with high throughput data analysis, interactions and mechanisms can be elucidated and treatments reasonably tailored to patients expressing specific phenotypes (or genotypes) of disease, essentially reigning in the phenomenon of drug attrition.

Near-infrared imaging spectroscopy for counterfeit drug detection

NASA Astrophysics Data System (ADS)

Arnold, Thomas; De Biasio, Martin; Leitner, Raimund

2011-06-01

Pharmaceutical counterfeiting is a significant issue in the healthcare community as well as for the pharmaceutical industry worldwide. The use of counterfeit medicines can result in treatment failure or even death. A rapid screening technique such as near infrared (NIR) spectroscopy could aid in the search for and identification of counterfeit drugs. This work presents a comparison of two laboratory NIR imaging systems and the chemometric analysis of the acquired spectroscopic image data. The first imaging system utilizes a NIR liquid crystal tuneable filter and is designed for the investigation of stationary objects. The second imaging system utilizes a NIR imaging spectrograph and is designed for the fast analysis of moving objects on a conveyor belt. Several drugs in form of tablets and capsules were analyzed. Spectral unmixing techniques were applied to the mixed reflectance spectra to identify constituent parts of the investigated drugs. The results show that NIR spectroscopic imaging can be used for contact-less detection and identification of a variety of counterfeit drugs.

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

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 1 2011-04-01 2011-04-01 false Utilization of an advisory committee at the... Committees for Human Prescription Drugs § 14.172 Utilization of an advisory committee at the request of an... should be submitted for a hearing at that time. The Commissioner may grant or deny the request. ...

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

... 21 Food and Drugs 1 2010-04-01 2010-04-01 false Utilization of an advisory committee at the... Committees for Human Prescription Drugs § 14.172 Utilization of an advisory committee at the request of an... should be submitted for a hearing at that time. The Commissioner may grant or deny the request. ...

Determinants of NSAID choice in rheumatoid arthritis--a drug utilization study.

PubMed

Inotai, András; Mészáros, Agnes

2012-01-01

Long term nonsteroidal anti-inflammatory drug (NSAID) medication is associated with gastrointestinal (GI) adverse events. This paper aimed to depict main determinants of NSAID drug choice (GI safe/traditional NSAIDs) in a rheumatoid arthritis (RA) patient sample (n=143). According to our logistic regression model, current/prior GI adverse events in the anamnesis was the only significant determinant of GI safer NSAID use (OR 3.1, p = 0.01). There was significant difference regarding most NSAIDs between the RA study sample and the total Hungarian population, suggesting that chronic administration could also influence the NSAID choice. GI safe NSAIDs were much preferred in the RA study sample than in the total population. In conclusion, the NSAID medication of the observed 143 patients was considered to be reasonable regarding both cardiovascular and GI safety.

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. © 2016 The Authors Fundamental & Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of Société Française de Pharmacologie et de Thérapeutique.

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

Drug Testing of Public Employees: Anatomy of a Statute.

ERIC Educational Resources Information Center

Thompson, David C.; Shoop, Robert J.

1989-01-01

The recently enacted public employee drug testing policy in Kansas is utilized as a basis to speculate on the future of drug screening in education and to offer guidelines to public school districts considering implementation of voluntary or required testing. (MLF)

Urine drug screening in the medical setting.

PubMed

Hammett-Stabler, Catherine A; Pesce, Amadeo J; Cannon, Donald J

2002-01-01

The term drug screen is a misnomer since it implies screening for all drugs, which is not possible. Current practice is to limit the testing to the examination of serum for several drugs such as ethanol, acetaminophen, salicylate, and of urine for several specific drugs or classes of drugs. In the emergency setting the screen should be performed in less than one hour. Controversies continue to exist regarding the value of urine drug testing in the medical setting. The reasons for these include the drugs involved, the sample, the methods utilized to perform the tests, and the level of understanding of the physician using the data, all of which are closely related to the other. Current automated methods provide rapid results demanded in emergency situations, but are often designed for, or adapted from, workplace testing and are not necessarily optimized for clinical applications. Furthermore, the use of these methods without consideration of the frequency in which the drugs are found in a given area is not cost-effective. The laboratory must understand the limitations of the assays used and provide this information to the physician. Additionally, the laboratory and the physicians using the data must cooperate to determine which drugs are appropriate and necessary to measure for their institution and clinical setting. In doing so it should be remembered that for many drugs, the sample, urine, contains the end product(s) of drug metabolism, not the parent drug. Furthermore, it is necessary to understand the pharmacokinetic parameters of the drug of interest when interpreting data. Finally, while testing for some drugs may not appear cost-effective, the prevention or reduction of morbidity and mortality may offset any laboratory costs. While the literature is replete with studies concerning new methods and a few regarding physician understanding, there are none that we could find that thoroughly, objectively, and fully addressed the issues of utility and cost-effectiveness.

Tolerability and Healthcare Utilization in Maintenance Hemodialysis Patients Undergoing Treatment for Tuberculosis-Related Conditions.

PubMed

Hamadah, Abdurrahman M; Beaulieu, Lynn M; Wilson, John W; Aksamit, Timothy R; Gregoire, James R; Williams, Amy W; Dillon, John J; Albright, Robert C; Onuigbo, Macaulay; Iyer, Venkateshwaran K; Hickson, LaTonya J

2016-01-01

The incidence of tuberculosis (TB) in end-stage renal disease is significantly higher than that in the general population. Among those with kidney dysfunction, anti-TB treatment is associated with increased side effects, but the effect on healthcare utilization is unknown. Methods/Aim: To assess patient-reported symptoms, adverse effects and describe changes in healthcare utilization patterns during treatment for TB, we conducted a case series (n = 12) of patients receiving maintenance hemodialysis (HD) from Mayo Clinic Dialysis Services and concurrent drug therapy for TB from January 2002 through May 2014. Healthcare utilization (hospitalizations and emergency department (ED) visits independent of hospital admission) was compared before and during treatment. Patients were treated for latent (n = 7) or active (n = 5) TB. The majority of patients with latent disease were treated with isoniazid (n = 5, 71%), while active-disease patients received a 4-drug regimen. Adverse effects were reported in 83% of patients. Compared to measurements prior to drug initiation, serum albumin and dialysis weights were similar at 3 months. Commonly reported anti-TB drug toxicities were described. More than half (58%) of the patients were hospitalized at least once. No ED or hospital admissions occurred in the period prior to drug therapy, but healthcare utilization increased during treatment in the latent disease group (hospitalization rate per person-month: pre 0 vs. post 1). Among HD patients, anti-TB therapy is associated with frequently reported symptoms and increased healthcare utilization. Among this subset, patients receiving treatment for latent disease may be those with greatest increase in healthcare use. Careful monitoring and early complication detection may help optimize medication adherence and minimize hospitalizations. © 2016 S. Karger AG, Basel.

Tolerability and Healthcare Utilization in Maintenance Hemodialysis Patients Undergoing Treatment for Tuberculosis-Related Conditions

PubMed Central

Hamadah, Abdurrahman M.; Beaulieu, Lynn M.; Wilson, John W.; Aksamit, Timothy R.; Gregoire, James R.; Williams, Amy W.; Dillon, John J.; Albright, Robert C.; Onuigbo, Macaulay; Iyer, Venkateshwaran K.; Hickson, LaTonya J.

2016-01-01

Background The incidence of tuberculosis in end-stage renal disease is significantly higher than the general population. Among those with kidney dysfunction, anti-tuberculosis treatment is associated with increased side effects, but the effect on healthcare utilization is unknown. Methods/Aim To assess patient-reported symptoms, adverse effects and describe changes in healthcare utilization patterns during treatment for tuberculosis, we conducted a case series (n=12) of patients receiving maintenance hemodialysis from Mayo Clinic Dialysis Services and concurrent drug therapy for tuberculosis from January 2002 through May 2014. Healthcare utilization (hospitalizations and emergency department visits independent of hospital admission) was compared before and during treatment. Results Patients were treated for latent (n=7) or active (n=5) tuberculosis. The majority of patients with latent disease were treated with isoniazid (n=5, 71%), while active-disease patients received a 4-drug regimen. Adverse effects were reported in 83% of patients. Compared to measurements prior to drug initiation, serum albumin and dialysis weights were similar at 3 months. Commonly reported anti-tuberculosis drug toxicities were described. More than half (58%) of patients were hospitalized at least once. No emergency department or hospital admissions occurred in the period prior to drug therapy, but healthcare utilization increased during treatment in the latent disease group (hospitalization rate per person-month: pre, 0 vs. post, 1). Conclusions Among hemodialysis patients, anti-tuberculosis therapy is associated with frequent patient-reported symptoms and increased healthcare utilization. Patients receiving treatment for latent disease may have the greatest increase in healthcare use. Careful monitoring and early complication detection may help optimize medication adherence and minimize hospitalizations. PMID:26859893

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.

Racial and ethnic disparities in the financial burden of prescription drugs among older Americans.

PubMed

Xu, K Tom; Borders, Tyrone F

2007-01-01

This study examines racial and ethnic disparities in the financial burden of prescription drugs among older Americans using a market and an egalitarian model. A nationally representative data set, the Medical Expenditure Panel Survey 2002, was used. The financial burden of prescription drugs was measured by the out-of-pocket expenditure and proportion. In the market model (utilization adjustment)., utilization was measured at the annual aggregate level by the total number of prescription drugs, the average refills and the average quantity per prescription drug. In the egalitarian model (need adjustment)., health was measured by 15 chronic and costly diseases and the SF-12. Individuals 65 years or older were included. Nationally representative estimates were calculated. Raw racial and ethnic disparities were observed in the bivariate analyses between non-Hispanic whites and Hispanics in the out-of-pocket expenditure and proportion, and between non-Hispanic whites and non-Hispanic blacks in the out-of-pocket proportion. However, these disparities disappeared after controlling for utilization or health needs. Insurance status contributed the most to the disparities in the financial burden of prescription drugs. In conclusion, The disparities in the financial burden of prescription drugs between non-Hispanic elderly whites and Hispanics may be attributable to differences in utilization patterns. However, whether health disparities contribute to disparities in the financial burden of prescription drugs requires studies of specific diseases.

Pharmacogenetics/pharmacogenomics and antirheumatic drugs in rheumatology.

PubMed

Ferraccioli, Gianfranco; De Santis, Maria; Tolusso, Barbara

2004-12-01

Genomic medicine has raised many expectations with regard to individualized therapies. Drug response is a complex function of many genes interacting with environmental and behavioral factors. In addition, poor prescribing, interactions between drugs and an incomplete understanding of the metabolism of many drugs, which are administered simultaneously to treat concomitant morbidities, are leading causes of the occurrence of adverse drug reactions in chronic non-inflammatory and autoimmune rheumatic diseases. Symptomatic non-steroidal anti-inflammatory drugs, as well as disease-modifying drugs, are complicated by drop-outs (poor patient compliance) in a large percentage of patients. Even though intensive and careful monitoring is always clearly advisable, preliminary data suggest that typing of genes controlling the effects, metabolism and response of drugs might be of clinical utility to define the 'at-risk' genotype.

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 ...

Drug Licenses: A Better Model for Pharmaceutical Pricing

PubMed Central

Goldman, Dana P.; Jena, Anupam B.; Philipson, Tomas; Sun, Eric

2013-01-01

High drug prices are a substantial barrier to patient access and compliance. Yet, low drug prices are often argued to provide inadequate incentives for innovation. We propose a “drug-licensing” model for health care which has the promise of increasing drug utilization without altering patient out-of-pocket spending, health plan costs, or pharmaceutical profits. In such a model, individuals purchase annual drug licenses which guarantee unfettered access to a clinically optimal number of prescriptions over the course of a year. For the case of statins, we illustrate how such a model may be implemented in practice. PMID:18180487

Inkjet Printing of Drug-Loaded Mesoporous Silica Nanoparticles-A Platform for Drug Development.

PubMed

Wickström, Henrika; Hilgert, Ellen; Nyman, Johan O; Desai, Diti; Şen Karaman, Didem; de Beer, Thomas; Sandler, Niklas; Rosenholm, Jessica M

2017-11-21

Mesoporous silica nanoparticles (MSNs) have shown great potential in improving drug delivery of poorly water soluble (BCS class II, IV) and poorly permeable (BCS class III, IV) drugs, as well as facilitating successful delivery of unstable compounds. The nanoparticle technology would allow improved treatment by reducing adverse reactions of currently approved drugs and possibly reintroducing previously discarded compounds from the drug development pipeline. This study aims to highlight important aspects in mesoporous silica nanoparticle (MSN) ink formulation development for digital inkjet printing technology and to advice on choosing a method (2D/3D) for nanoparticle print deposit characterization. The results show that both unfunctionalized and polyethyeleneimine (PEI) surface functionalized MSNs, as well as drug-free and drug-loaded MSN-PEI suspensions, can be successfully inkjet-printed. Furthermore, the model BCS class IV drug remained incorporated in the MSNs and the suspension remained physically stable during the processing time and steps. This proof-of-concept study suggests that inkjet printing technology would be a flexible deposition method of pharmaceutical MSN suspensions to generate patterns according to predefined designs. The concept could be utilized as a versatile drug screening platform in the future due to the possibility of accurately depositing controlled volumes of MSN suspensions on various materials.

Identifying genomic and developmental causes of adverse drug reactions in children

PubMed Central

Becker, Mara L; Leeder, J Steven

2011-01-01

Adverse drug reactions are a concern for all clinicians who utilize medications to treat adults and children; however, the frequency of adult and pediatric adverse drug reactions is likely to be under-reported. In this age of genomics and personalized medicine, identifying genetic variation that results in differences in drug biotransformation and response has contributed to significant advances in the utilization of several commonly used medications in adults. In order to better understand the variability of drug response in children however, we must not only consider differences in genotype, but also variation in gene expression during growth and development, namely ontogeny. In this article, recommendations for systematically approaching pharmacogenomic studies in children are discussed, and several examples of studies that investigate the genomic and developmental contribution to adverse drug reactions in children are reviewed. PMID:21121777

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

Drugs foresight 2020: a Delphi expert panel study.

PubMed

Lintonen, Tomi; Konu, Anne; Rönkä, Sanna; Kotovirta, Elina

2014-05-03

Historically substance misuse has been relatively common in western countries, but comparatively few Finns report drug use. The Drugs 2020 study aimed at foreseeing changes in the drug situation in Finland by the year 2020. The Delphi method was used, utilizing drug experts of the EU national network in Finland. Marked growth was foreseen in drug use, especially in synthetic designer drugs and misuse of medicinal drugs. Significant increase was also expected in growing cannabis at home. However, the control of drug market was expected to shift more into the hands of organized crime. No consensus was reached on how drug prices will develop in the time period. Drug use is likely to remain punishable although the use and possession of cannabis may be treated less severely. It seems likely that health and social services resources will be directed towards medicinal treatment. Foresight can be utilized in preparing for the future; desirable developments can be fostered, and measures can be taken to curb probable but undesirable lines of development. Based on the results of this study, the experts' view is that it is highly likely that the Finnish society will have to prepare for an increase in the demand for drug-related care, both in terms of content of the care and financing the services. Also, the forecasted increase in the role of legal prescription medicine used as intoxicants will call for efforts not only in changing prescription practices but in border and police control measures, as well. Parallel developments have been foreseen in the UK and Sweden, and it is likely that similar trends will actualize also in other western countries.

DrugBank 5.0: a major update to the DrugBank database for 2018.

PubMed

Wishart, David S; Feunang, Yannick D; Guo, An C; Lo, Elvis J; Marcu, Ana; Grant, Jason R; Sajed, Tanvir; Johnson, Daniel; Li, Carin; Sayeeda, Zinat; Assempour, Nazanin; Iynkkaran, Ithayavani; Liu, Yifeng; Maciejewski, Adam; Gale, Nicola; Wilson, Alex; Chin, Lucy; Cummings, Ryan; Le, Diana; Pon, Allison; Knox, Craig; Wilson, Michael

2018-01-04

DrugBank (www.drugbank.ca) is a web-enabled database containing comprehensive molecular information about drugs, their mechanisms, their interactions and their targets. First described in 2006, DrugBank has continued to evolve over the past 12 years in response to marked improvements to web standards and changing needs for drug research and development. This year's update, DrugBank 5.0, represents the most significant upgrade to the database in more than 10 years. In many cases, existing data content has grown by 100% or more over the last update. For instance, the total number of investigational drugs in the database has grown by almost 300%, the number of drug-drug interactions has grown by nearly 600% and the number of SNP-associated drug effects has grown more than 3000%. Significant improvements have been made to the quantity, quality and consistency of drug indications, drug binding data as well as drug-drug and drug-food interactions. A great deal of brand new data have also been added to DrugBank 5.0. This includes information on the influence of hundreds of drugs on metabolite levels (pharmacometabolomics), gene expression levels (pharmacotranscriptomics) and protein expression levels (pharmacoprotoemics). New data have also been added on the status of hundreds of new drug clinical trials and existing drug repurposing trials. Many other important improvements in the content, interface and performance of the DrugBank website have been made and these should greatly enhance its ease of use, utility and potential applications in many areas of pharmacological research, pharmaceutical science and drug education. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

Validation of a microdose probe drug cocktail for clinical drug interaction assessments for drug transporters and CYP3A.

PubMed

Prueksaritanont, T; Tatosian, D A; Chu, X; Railkar, R; Evers, R; Chavez-Eng, C; Lutz, R; Zeng, W; Yabut, J; Chan, G H; Cai, X; Latham, A H; Hehman, J; Stypinski, D; Brejda, J; Zhou, C; Thornton, B; Bateman, K P; Fraser, I; Stoch, S A

2017-04-01

A microdose cocktail containing midazolam, dabigatran etexilate, pitavastatin, rosuvastatin, and atorvastatin has been established to allow simultaneous assessment of a perpetrator impact on the most common drug metabolizing enzyme, cytochrome P450 (CYP)3A, and the major transporters organic anion-transporting polypeptides (OATP)1B, breast cancer resistance protein (BCRP), and MDR1 P-glycoprotein (P-gp). The clinical utility of these microdose cocktail probe substrates was qualified by conducting clinical drug interaction studies with three inhibitors with different in vitro inhibitory profiles (rifampin, itraconazole, and clarithromycin). Generally, the pharmacokinetic profiles of the probe substrates, in the absence and presence of the inhibitors, were comparable to their reported corresponding pharmacological doses, and/or in agreement with theoretical expectations. The exception was dabigatran, which resulted in an approximately twofold higher magnitude for microdose compared to conventional dosing, and, thus, can be used to flag a worst-case scenario for P-gp. Broader application of the microdose cocktail will facilitate a more comprehensive understanding of the roles of drug transporters in drug disposition and drug interactions. © 2016 American Society for Clinical Pharmacology and Therapeutics.

Application of PBPK modelling in drug discovery and development at Pfizer.

PubMed

Jones, Hannah M; Dickins, Maurice; Youdim, Kuresh; Gosset, James R; Attkins, Neil J; Hay, Tanya L; Gurrell, Ian K; Logan, Y Raj; Bungay, Peter J; Jones, Barry C; Gardner, Iain B

2012-01-01

Early prediction of human pharmacokinetics (PK) and drug-drug interactions (DDI) in drug discovery and development allows for more informed decision making. Physiologically based pharmacokinetic (PBPK) modelling can be used to answer a number of questions throughout the process of drug discovery and development and is thus becoming a very popular tool. PBPK models provide the opportunity to integrate key input parameters from different sources to not only estimate PK parameters and plasma concentration-time profiles, but also to gain mechanistic insight into compound properties. Using examples from the literature and our own company, we have shown how PBPK techniques can be utilized through the stages of drug discovery and development to increase efficiency, reduce the need for animal studies, replace clinical trials and to increase PK understanding. Given the mechanistic nature of these models, the future use of PBPK modelling in drug discovery and development is promising, however, some limitations need to be addressed to realize its application and utility more broadly.

Potential Drug-Drug Interactions among Patients prescriptions collected from Medicine Out-patient Setting.

PubMed

Farooqui, Riffat; Hoor, Talea; Karim, Nasim; Muneer, Mehtab

2018-01-01

To identify and evaluate the frequency, severity, mechanism and common pairs of drug-drug interactions (DDIs) in prescriptions by consultants in medicine outpatient department. This cross sectional descriptive study was done by Pharmacology department of Bahria University Medical & Dental College (BUMDC) in medicine outpatient department (OPD) of a private hospital in Karachi from December 2015 to January 2016. A total of 220 prescriptions written by consultants were collected. Medications given with patient's diagnosis were recorded. Drugs were analyzed for interactions by utilizing Medscape drug interaction checker, drugs.com checker and stockley`s drug interactions index. Two hundred eleven prescriptions were selected while remaining were excluded from the study because of unavailability of the prescribed drugs in the drug interaction checkers. In 211 prescriptions, two common diagnoses were diabetes mellitus (28.43%) and hypertension (27.96%). A total of 978 medications were given. Mean number of medications per prescription was 4.6. A total of 369 drug-drug interactions were identified in 211 prescriptions (175%). They were serious 4.33%, significant 66.12% and minor 29.53%. Pharmacokinetic and pharmacodynamic interactions were 37.94% and 51.21% respectively while 10.84% had unknown mechanism. Number wise common pairs of DDIs were Omeprazole-Losartan (S), Gabapentine- Acetaminophen (M), Losartan-Diclofenac (S). The frequency of DDIs is found to be too high in prescriptions of consultants from medicine OPD of a private hospital in Karachi. Significant drug-drug interactions were more and mostly caused by Pharmacodynamic mechanism. Number wise evaluation showed three common pairs of drugs involved in interactions.

Potential Drug-Drug Interactions among Patients prescriptions collected from Medicine Out-patient Setting

PubMed Central

Farooqui, Riffat; Hoor, Talea; Karim, Nasim; Muneer, Mehtab

2018-01-01

Objective: To identify and evaluate the frequency, severity, mechanism and common pairs of drug-drug interactions (DDIs) in prescriptions by consultants in medicine outpatient department. Methods: This cross sectional descriptive study was done by Pharmacology department of Bahria University Medical & Dental College (BUMDC) in medicine outpatient department (OPD) of a private hospital in Karachi from December 2015 to January 2016. A total of 220 prescriptions written by consultants were collected. Medications given with patient's diagnosis were recorded. Drugs were analyzed for interactions by utilizing Medscape drug interaction checker, drugs.com checker and stockley`s drug interactions index. Two hundred eleven prescriptions were selected while remaining were excluded from the study because of unavailability of the prescribed drugs in the drug interaction checkers. Results: In 211 prescriptions, two common diagnoses were diabetes mellitus (28.43%) and hypertension (27.96%). A total of 978 medications were given. Mean number of medications per prescription was 4.6. A total of 369 drug-drug interactions were identified in 211 prescriptions (175%). They were serious 4.33%, significant 66.12% and minor 29.53%. Pharmacokinetic and pharmacodynamic interactions were 37.94% and 51.21% respectively while 10.84% had unknown mechanism. Number wise common pairs of DDIs were Omeprazole-Losartan (S), Gabapentine- Acetaminophen (M), Losartan-Diclofenac (S). Conclusion: The frequency of DDIs is found to be too high in prescriptions of consultants from medicine OPD of a private hospital in Karachi. Significant drug-drug interactions were more and mostly caused by Pharmacodynamic mechanism. Number wise evaluation showed three common pairs of drugs involved in interactions. PMID:29643896

Projecting future drug expenditures--2006.

PubMed

Hoffman, James M; Shah, Nilay D; Vermeulen, Lee C; Schumock, Glen T; Grim, Penny; Hunkler, Robert J; Hontz, Karrie M

2006-01-15

Drug expenditure trends in 2004 and 2005, projected drug expenditures for 2006, and factors likely to influence drug costs are discussed. Various factors are likely to affect drug costs, including drug prices, drugs in development, and generic drugs. In 2004 there was a continued moderation of the increase in drug expenditures. Drug expenditures increased by 8.7% from 2003 to 2004. Through the first nine months of 2005, expenditures increased by only 8.1% compared with 2004. This moderation can be attributed to several factors, including the continued trend toward higher prescription drug cost sharing for insured consumers, growing availability of generic drugs, and lack of "blockbuster" new drugs in recent years. Drug expenditures in 2006 will likely be influenced by similar factors, with few costly new products reaching the market, increased concern over product safety slowing the diffusion of those new agents that do reach the market, and several important patent expirations, leading to slower growth in expenditures. Forecasting and managing rising drug expenditures remains a challenge. Pharmacy managers must remain vigilant in monitoring drug costs in their health system and take a proactive role in pursuing efficient drug utilization. The dynamic health policy environment further complicates drug budgeting and must be considered, especially in integrated health systems responsible for managing inpatient, outpatient, and clinic drug costs. The comparison of health-system-specific data and trends with the national information presented in this article may provide a useful context when presenting institutional drug costs to senior management.

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.

Defining drug response for stratified medicine.

PubMed

Lonergan, Mike; Senn, Stephen J; McNamee, Christine; Daly, Ann K; Sutton, Robert; Hattersley, Andrew; Pearson, Ewan; Pirmohamed, Munir

2017-01-01

The premise for stratified medicine is that drug efficacy, drug safety, or both, vary between groups of patients, and biomarkers can be used to facilitate more targeted prescribing, with the aim of improving the benefit:risk ratio of treatment. However, many factors can contribute to the variability in response to drug treatment. Inadequate characterisation of the nature and degree of variability can lead to the identification of biomarkers that have limited utility in clinical settings. Here, we discuss the complexities associated with the investigation of variability in drug efficacy and drug safety, and how consideration of these issues a priori, together with standardisation of phenotypes, can increase both the efficiency of stratification procedures and identification of biomarkers with the potential for clinical impact. Copyright © 2016 Elsevier Ltd. All rights reserved.

Female Ex-Offender Perspectives on Drug Initiation, Relapse, and Desire to Remain Drug Free

PubMed Central

Nyamathi, Adeline M.; Srivastava, Neha; Salem, Benissa E.; Wall, Sarah; Kwon, Jordan; Ekstrand, Maria; Hall, Elizabeth; Turner, Susan F.; Faucette, Mark

2016-01-01

Recently-released homeless women residing in temporary residential drug treatment programs are at a critical juncture in the process of recovery, transition and reentry. The purpose of this study was to explore factors influencing initial use of drugs and relapse triggers among a sample of incarcerated women exiting jails and prisons, and who are residing in a residential drug treatment (RDT) program and preparing for reentry into their communities. Among this population, relapse to drug use and recidivism are common. A qualitative study was conducted utilizing focus groups to understand the perspectives of formerly incarcerated, currently homeless women residing in a RDT program. Content analysis generated the development of three broad categories: a) factors associated with first drug use; b) factors involved in relapse; c) factors influencing desire to remain drug free. A discussion follows highlighting the importance of targeted interventions at RDT sites that integrate physical, psychological and social needs to optimize reentry into communities. This would include a focus on building self-esteem, life skills, and providing access to resources such as housing, employment, and healthcare. PMID:27195929

Controlling prescription drug expenditures: a report of success.

PubMed

Miller, David P; Furberg, Curt D; Small, Ronald H; Millman, Franklyn M; Ambrosius, Walter T; Harshbarger, Julia S; Ohl, Christopher A

2007-08-01

To determine whether a multi-interventional program can limit increases in prescription drug expenditures while maintaining utilization of needed medications. Quasi-experimental, pre-post design. The program included formulary changes, quantity limits, and mandatory pill splitting for select drugs implemented in phases. We assessed the short-term effects of each intervention by comparing class-specific drug spending and generic medication use before and after benefit changes. Long-term effects were determined by comparing overall spending with projected spending estimates, and by examining changes in the planwide use of generic medications over time. Effects on medication utilization were assessed by examining members' use of selected classes of chronic medications before and after the policy changes. Over 3 years, the plan and members saved $6.6 million attributed to the interventions. Most of the savings were due to the reclassification of select brand-name drugs to nonpreferred status (estimated annual savings, $941,000), followed by the removal of nonsedating antihistamines from the formulary (annual savings, $565,000), and the introduction of pill splitting (annual savings, $342,000). Limiting quantities of select medications had the smallest impact (annual savings, $135,000). Members' use of generic medications steadily increased from 40% to 57%. Although 17.5% of members stopped using at least 1 class of selected medications, members' total use of chronic medications remained constant. A combination of interventions can successfully manage prescription drug spending while preserving utilization of chronic medications. Additional studies are needed to determine the effect of these cost-control interventions on other health outcomes.

Self-assembled hydrogels utilizing polymer-nanoparticle interactions

NASA Astrophysics Data System (ADS)

Appel, Eric A.; Tibbitt, Mark W.; Webber, Matthew J.; Mattix, Bradley A.; Veiseh, Omid; Langer, Robert

2015-02-01

Mouldable hydrogels that flow on applied stress and rapidly self-heal are increasingly utilized as they afford minimally invasive delivery and conformal application. Here we report a new paradigm for the fabrication of self-assembled hydrogels with shear-thinning and self-healing properties employing rationally engineered polymer-nanoparticle (NP) interactions. Biopolymer derivatives are linked together by selective adsorption to NPs. The transient and reversible interactions between biopolymers and NPs enable flow under applied shear stress, followed by rapid self-healing when the stress is relaxed. We develop a physical description of polymer-NP gel formation that is utilized to design biocompatible gels for drug delivery. Owing to the hierarchical structure of the gel, both hydrophilic and hydrophobic drugs can be entrapped and delivered with differential release profiles, both in vitro and in vivo. The work introduces a facile and generalizable class of mouldable hydrogels amenable to a range of biomedical and industrial applications.

[Multilateral Strategies Utilizing Exosomes for Cancer Therapy].

PubMed

Nishida-Aoki, Nao; Ochiya, Takahiro

2017-05-01

Exosomes are nano-sized extracellular vesicles which transfer their components such as RNA, DNA, and proteins from one cell to another cell. The components are released to the cytoplasm of the recipient cells, having an effect on the cells. Cancerderived exosomes promote cancer progression, invasion, gain of drug resistance, and metastasis. Recently, according to their characteristics, it is expected to apply exosomes to cancer therapies, such as utilizing exosomes as drug delivery systems(DDS) for anticancer drugs and as cancer vaccines to enhance immunity to cancer cells. More, as the cancer-derived exosomes have cancer-promoting effects on multiple stages, inhibiting the function of the cancer-derived exosomes would be helpful to cancer therapies by suppressing cancer progression. DDS and cancer vaccines utilizing exosomes are now undergoing clinical studies, although DDS is suffering from loading efficiency. Treatments by inhibiting the functions of cancer-derived exosomes have still only few reports at experimental levels. Recently, we showed in a mouse model that disruption of cancer-derived exosomes by antibodies could suppress lung metastasis of the human breast cancer cells. Exosomes will provide us the multiple strategies to fight with cancer, which can be applied to cancers from many organs. It is important to confirm safety and overcome technical problems to bring exosomes in practical use.

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

Prescription Drug Benefits: Cost Management Issues for Medicare

PubMed Central

Fox, Peter D.

2003-01-01

Little attention has been devoted in policy circles as to how Medicare would manage an outpatient prescription drug benefit. This article, first, discusses the role of the pharmacy benefits manager (PBM), the entity that processes claims and otherwise helps administer the benefit. It then discusses the major decisions that will be necessary regarding such matters as: which drugs should be covered; how broad should the pharmacy network be; whether there should be incentives to obtain generic rather than brand-name drugs when available; for drugs with no generic equivalent, should there be incentives to obtain less expensive, medically appropriate brand-name drugs; and how should prescription drug utilization be managed. PMID:15124374

Diabetes diagnosis, resource utilization, and health outcomes.

PubMed

Gulliford, Martin C; Latinovic, Radoslav; Charlton, Judith

2008-01-01

To determine the effect of a clinical diagnosis of diabetes mellitus (DM) on healthcare utilization and health outcomes. Cohort study. A total of 197 United Kingdom family practices with 4974 subjects (mean age, 62.8 years; 52.2% men) with type 2 DM and 9948 matched nondiabetic control subjects. Healthcare utilization and the occurrence of complications were estimated from 2 years before to 2 years after the first clinical diagnosis of DM. From 24 months before the DM diagnosis, primary care consultations were increased in prediagnosis cases compared with controls (relative rate [RR], 1.31; 95% confidence interval [CI], 1.27-1.35), as were emergency and hospital care consultations, hospital specialist referrals, and prescription drug items. At diagnosis of DM, utilization of all forms of healthcare was increased (RR, 4.27; 95% CI, 4.17-4.36 for primary care consultations; RR, 2.49; 95% CI, 2.46-2.52 for prescription drug items). In the quarter following diagnosis, healthcare utilization was increased for acute myocardial infarction (RR, 6.29; 95% CI, 2.69-14.73), cerebrovascular disease (RR, 5.14; 95% CI, 3.37-7.84), ischemic heart disease (RR, 3.65; 95% CI, 2.77-4.80), and peripheral nerve disorders (RR, 5.01; 95% CI, 2.81-8.95). First diagnoses of myocardial infarction, cerebrovascular disease, and peripheral nerve disorders were increased during the period from 6 months before to 6 months after diagnosis. Clinical diagnosis of DM is often the end of a process leading to established complications and is associated with greatly increased utilization of care. This adds to the justification of strategies for earlier detection of hyperglycemic states.

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

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

The impact of China's retail drug price control policy on hospital expenditures: a case study in two Shandong hospitals.

PubMed

Meng, Qingyue; Cheng, Gang; Silver, Lynn; Sun, Xiaojie; Rehnberg, Clas; Tomson, Göran

2005-05-01

In China, 44.4% of total health expenditures in 2001 were for pharmaceuticals. Containment of pharmaceutical expenditures is a top priority for policy intervention. Control of drug retail prices was adopted by the Chinese government for this purpose. This study aims to examine the impact of this policy on the containment of hospital drug expenditures, and to analyze contributing factors. This is a retrospective pre/post-reform case study in two public hospitals. Financial records were reviewed to analyze changes in drug expenditures for all patients. A tracer condition, cerebral infarction, was selected for in-depth examination of changes in prices, utilization, expenditures and rationality of drugs. In the two hospitals, a total of 104 and 109 cerebral infarction cases, hospitalized respectively before and after the reform, were selected. Prescribed daily dose (PDD) was used for measuring drug utilization, and the contribution of price and utilization to changes in drug expenditures were decomposed. Rationality of drug use post-reform was reviewed based on published literature. Drug expenditures for all patients still increased rapidly in the two hospitals after implementation of the pricing policy. In the provincial hospital, drug expenditures per patient for cerebral infarction cases declined, but not significantly. This was mainly attributable to reduced utilization. In the municipal hospital, drug expenditure per patient increased by 50.1% after the reform, mainly due to greater drug utilization. Three to five fold higher drug expenditure per inpatient day in the provincial hospital was due to use of more expensive drugs. Of the top 15 drugs for treating cerebral infarction cases after the reform, 19.5% and 46.5% of the expenditures, in the provincial and municipal hospitals, respectively, were spent on drugs with prices set by the government. A large proportion of expenditures for the top 15 drugs, at least 65% and 41% in the provincial and municipal

Direct-to-consumer advertising of prescription drugs.

PubMed

Frosch, Dominick L; Grande, David

2010-01-01

In 2007, the pharmaceutical industry spent more than $4.9 billion on direct-to-consumer advertising (DTCA) of prescription drugs in the U.S. Controversy over DTCA has grown since the Food and Drug Administration liberalized its regulations in 1997. Proponents claim that such advertising educates consumers, promotes patient participation in clinical decisions, and improves patient adherence to medication instructions. Opponents argue that such advertising is meant to persuade, not educate, and that it promotes inappropriate use of prescription drugs, or diverts consumers from better alternatives. This Issue Brief summarizes the evidence about the effects of DTCA, and proposes guidelines for improving the utility of prescription drug advertising.

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.

Effects of a recovery management intervention on Chinese heroin users' community recovery through the mediation effect of enhanced service utilization

PubMed Central

Wu, F.; Fu, L.M.; Hser, Y.H.

2015-01-01

Background This study investigates whether a recovery management intervention (RMI) can improve the utilization of community drug treatment and wraparound services among heroin users in China and subsequently lead to positive recovery outcomes. Methods Secondary analysis was conducted drawing data from a randomized controlled trial; 100 heroin users with no severe mental health problems were recruited in two Shanghai districts (Hongkou and Yangpu) upon their release from compulsory rehabilitation facilities. A latent variable modeling approach was utilized to test whether the RMI influences heroin users' perceived motivation and readiness for treatment, enhances treatment and wraparound service participation, and, in turn, predicts better recovery outcomes. Results Enrollment in drug treatment and other social service utilization increased significantly as a result of RMI rather than an individual drug user's motivation and readiness for treatment. Increased service utilization thus led to more positive individual recovery outcomes. In addition to this mediation effect through service utilization, the RMI also improved participants' community recovery directly. Conclusions Findings suggest that better drug treatment enrollment, community service utilization and recovery outcomes can be potentially achieved among heroin users in China with carefully designed case management interventions. PMID:24990956

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

Code of Federal Regulations, 2014 CFR

2014-04-01

... initiative of FDA. 14.171 Section 14.171 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH... Human Prescription Drugs § 14.171 Utilization of an advisory committee on the initiative of FDA. (a) Any... monitoring of the matter and consultation with FDA on behalf of the committee. The member or consultant may...

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

Code of Federal Regulations, 2011 CFR

2011-04-01

... initiative of FDA. 14.171 Section 14.171 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH... Human Prescription Drugs § 14.171 Utilization of an advisory committee on the initiative of FDA. (a) Any... monitoring of the matter and consultation with FDA on behalf of the committee. The member or consultant may...

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

Code of Federal Regulations, 2012 CFR

2012-04-01

... initiative of FDA. 14.171 Section 14.171 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH... Human Prescription Drugs § 14.171 Utilization of an advisory committee on the initiative of FDA. (a) Any... monitoring of the matter and consultation with FDA on behalf of the committee. The member or consultant may...

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

Code of Federal Regulations, 2013 CFR

2013-04-01

... initiative of FDA. 14.171 Section 14.171 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH... Human Prescription Drugs § 14.171 Utilization of an advisory committee on the initiative of FDA. (a) Any... monitoring of the matter and consultation with FDA on behalf of the committee. The member or consultant may...

Is there a relationship between patient beliefs or communication about generic drugs and medication utilization?

PubMed

Shrank, William H; Cadarette, Suzanne M; Cox, Emily; Fischer, Michael A; Mehta, Jyotsna; Brookhart, Alan M; Avorn, Jerry; Choudhry, Niteesh K

2009-03-01

Insurers and policymakers strive to stimulate more cost-effective prescribing and, increasingly, are educating beneficiaries about generics. To evaluate the relationship between patient beliefs and communication about generic drugs and actual drug use. We performed a national mailed survey of a random sample of 2500 commercially-insured adults. Patient responses were linked to pharmacy claims data to assess actual generic medication use. We used factor analysis to develop 5 multi-item scales from patient survey responses that measured: (1) general preferences for generics, (2) generic safety/effectiveness, (3) generic cost/value, (4) comfort with generic substitution, and (5) communication with providers about generics. The relationship between each scale and the proportion of prescriptions filled for generics was assessed using linear regression, controlling for demographic, health, and insurance characteristics. Separate models were created for each scale and then all 5 scales were included simultaneously in a fully-adjusted model. The usable response rate was 48%. When evaluated independently, a 1 SD increase in each of the 5 scales was associated with a 3.1% to 6.3% increase in generic drug use (P < 0.05 for each). In the fully adjusted model, only 2 scales were significantly associated with generic drug use: comfort with generic substitution (P = 0.021) and communication with providers about generic drugs (P = 0.012). Generic drug use is most closely associated with the 2 actionable items we evaluated: communication with providers about generics and comfort with generic substitution. Educational campaigns that focus on these 2 domains may be most effective at influencing generic drug use.

Unique and potent effects of acute ibogaine on zebrafish: the developing utility of novel aquatic models for hallucinogenic drug research.

PubMed

Cachat, Jonathan; Kyzar, Evan J; Collins, Christopher; Gaikwad, Siddharth; Green, Jeremy; Roth, Andrew; El-Ounsi, Mohamed; Davis, Ari; Pham, Mimi; Landsman, Samuel; Stewart, Adam Michael; Kalueff, Allan V

2013-01-01

An indole alkaloid, ibogaine is the principal psychoactive component of the iboga plant, used by indigenous peoples in West Africa for centuries. Modulating multiple neurotransmitter systems, the drug is a potent hallucinogen in humans, although its psychotropic effects remain poorly understood. Expanding the range of model species is an important strategy for translational neuroscience research. Here we exposed adult zebrafish (Danio rerio) to 10 and 20mg/L of ibogaine, testing them in the novel tank, light-dark box, open field, mirror stimulation, social preference and shoaling tests. In the novel tank test, the zebrafish natural diving response (geotaxis) was reversed by ibogaine, inducing initial top swimming followed by bottom dwelling. Ibogaine also attenuated the innate preference for dark environments (scototaxis) in the light-dark box test. While it did not exert overt locomotor or thigmotaxic responses in the open field test, the drug altered spatiotemporal exploration of novel environment, inducing clear preference of some areas over others. Ibogaine also promoted 'mirror' exploration in the mirror stimulation test, disrupted group cohesion in the shoaling test, and evoked strong coloration responses due to melanophore aggregation, but did not alter brain c-fos expression or whole-body cortisol levels. Overall, our results support the complex pharmacological profile of ibogaine and its high sensitivity in zebrafish models, dose-dependently affecting multiple behavioral domains. While future investigations in zebrafish may help elucidate the mechanisms underlying these unique behavioral effects, our study strongly supports the developing utility of aquatic models in hallucinogenic drug research. High sensitivity of three-dimensional phenotyping approaches applied here to behavioral effects of ibogaine in zebrafish provides further evidence of how 3D reconstructions of zebrafish swimming paths may be useful for high-throughput pharmacological screening

Applications of nanodiamonds in drug delivery and catalysis.

PubMed

Moosa, Basem; Fhayli, Karim; Li, Song; Julfakyan, Khatchatur; Ezzeddine, Alaa; Khashab, Niveen M

2014-01-01

The interest of researchers in utilizing nanomaterials as carriers for a wide spectrum of molecules has exploded in the last two decades. Nanodiamonds are one class of carbon-based nanomaterials that have emerged as promising drug delivery vehicles and imaging probes. Their ease of functionalization also led to the generation of stimuli-responsive nanodiamonds that deliver drugs on demand in a controlled manner. The ample surface area of NDs allowed for a higher loading of not only small molecules but also macromolecules like genes and proteins. Recently, the unique surface of NDs has attracted more attention as catalyst support in a huge range of organic modification and C-C bond formation reactions. Herein, recent advances in the utilization of nanodiamonds as a drug delivery vehicle and catalytical support are highlighted and summarized to illustrate the potential and versatility of this cheap and commercially available nanomaterial.

Genomic Indicators in the blood predict drug-induced liver injury

EPA Science Inventory

Hepatotoxicity and other forms of liver injury stemming from exposure to toxicants and idiosyncratic drug reactions are major concerns during the drug discovery process. Animal model systems have been utilized in an attempt to extrapolate the risk of harmful agents to humans and...

Non-steroidal anti-inflammatory drug administration after coronary artery bypass surgery: utilization persists despite the boxed warning.

PubMed

Kulik, Alexander; Bykov, Katsiaryna; Choudhry, Niteesh K; Bateman, Brian T

2015-06-01

In 2005, the US Food and Drug Administration (FDA) issued a boxed warning against the administration of non-steroidal anti-inflammatory drugs (NSAIDs) after coronary artery bypass graft (CABG) surgery because of cardiovascular safety concerns. We assessed utilization rates before and after the advisory and evaluated predictors of NSAID administration following CABG. We assembled a cohort of 277,576 patients who underwent CABG from 2004 to 2010. Temporal trends in NSAID exposure were evaluated, and predictors of postoperative NSAID use were identified using generalized estimating equations. Over the study period, 92,938 CABG patients (33.5%) received NSAIDs following surgery. The frequency of NSAID administration declined steadily over time, from a peak of 38.9% in 2004 to a low of 29.0% in 2010 (p < 0.0007). Ketorolac was the most frequent NSAID prescribed, commonly on the first postoperative day. Surgery performed after the boxed warning was independently associated with a 20% lower odds of NSAID administration [odds ratio (OR): 0.80; p = 0.0003]. Other factors that predicted a lower odds of NSAID use following surgery included a history of renal disease (OR: 0.33; p < 0.0001) and liver disease (OR: 0.66; p < 0.0001), and the need for concurrent valve surgery (OR: 0.78; p < 0.0001). A mammary graft at the time of surgery increased the odds of NSAID administration (OR: 1.23; p < 0.0001). The frequency of NSAID administration after CABG has declined since the FDA advisory, yet many patients continue to receive them in recent years. Our data highlight the need for future research initiatives to further define the risks associated with NSAID use in this population. Copyright © 2015 John Wiley & Sons, Ltd.

Photomedicine with laser drug delivery technologies

NASA Astrophysics Data System (ADS)

Zharov, Vladimir P.; Latyshev, Alexei S.; Leviev, Dmitry O.

1999-07-01

This paper presents a new technology, which consists in utilizing laser drug delivery methods for the purposes of photodrug therapy. According to this technology, photosensitizer is applied onto the treated surface and then the solution is either impregnated or injected into the medium, with it being suggested to employ laser drug delivery techniques for the impregnation and injection of the photosensitizer. After introducing the photosensitizer, the area is illuminated by a matrix of light-emission diodes.

Demand for prescription drugs under non-linear pricing in Medicare Part D.

PubMed

Jung, Kyoungrae; Feldman, Roger; McBean, A Marshall

2014-03-01

We estimate the price elasticity of prescription drug use in Medicare Part D, which features a non-linear price schedule due to a coverage gap. We analyze patterns of drug utilization prior to the coverage gap, where the "effective price" is higher than the actual copayment for drugs because consumers anticipate that more spending will make them more likely to reach the gap. We find that enrollees' total pre-gap drug spending is sensitive to their effective prices: the estimated price elasticity of drug spending ranges between [Formula: see text]0.14 and [Formula: see text]0.36. This finding suggests that filling in the coverage gap, as mandated by the health care reform legislation passed in 2010, will influence drug utilization prior to the gap. A simulation analysis indicates that closing the gap could increase Part D spending by a larger amount than projected, with additional pre-gap costs among those who do not hit the gap.

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

PubMed

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

2017-06-05

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

Acute care hospital utilization among medical inpatients discharged with a substance use disorder diagnosis.

PubMed

Walley, Alexander Y; Paasche-Orlow, Michael; Lee, Eugene C; Forsythe, Shaula; Chetty, Veerappa K; Mitchell, Suzanne; Jack, Brian W

2012-03-01

Hospital discharge may be an opportunity to intervene among patients with substance use disorders to reduce subsequent hospital utilization. This study determined whether having a substance use disorder diagnosis was associated with subsequent acute care hospital utilization. We conducted an observational cohort study among 738 patients on a general medical service at an urban, academic, safety-net hospital. The main outcomes were rate and risk of acute care hospital utilization (emergency department visit or hospitalization) within 30 days of discharge. The main independent variable was presence of a substance use disorder primary or secondary discharge diagnosis code at the index hospitalization. At discharge, 17% of subjects had a substance use disorder diagnosis. These patients had higher rates of recurrent acute care hospital utilization than patients without substance use disorder diagnoses (0.63 vs 0.32 events per subject at 30 days, P < 0.01) and increased risk of any recurrent acute care hospital utilization (33% vs 22% at 30 days, P < 0.05). In adjusted Poisson regression models, the incident rate ratio at 30 days was 1.49 (95% confidence interval, 1.12-1.98) for patients with substance use disorder diagnoses compared with those without. In subgroup analyses, higher utilization was attributable to those with drug diagnoses or a combination of drug and alcohol diagnoses, but not to those with exclusively alcohol diagnoses. Medical patients with substance use disorder diagnoses, specifically those with drug use-related diagnoses, have higher rates of recurrent acute care hospital utilization than those without substance use disorder diagnoses.

Is There a Relationship Between Patient Beliefs or Communication About Generic Drugs and Medication Utilization?

PubMed Central

Shrank, William H.; Cadarette, Suzanne M.; Cox, Emily; Fischer, Michael A.; Mehta, Jyotsna; Brookhart, Alan M.; Avorn, Jerry; Choudhry, Niteesh K.

2009-01-01

Background Insurers and policymakers strive to stimulate more cost-effective prescribing and, increasingly, are educating beneficiaries about generics. Objectives To evaluate the relationship between patient beliefs and communication about generic drugs and actual drug use. Research Design and Subjects We performed a national mailed survey of a random sample of 2500 commercially-insured adults. Patient responses were linked to pharmacy claims data to assess actual generic medication use. Measures We used factor analysis to develop 5 multi-item scales from patient survey responses that measured: (1) general preferences for generics, (2) generic safety/effectiveness, (3) generic cost/value, (4) comfort with generic substitution, and (5) communication with providers about generics. The relationship between each scale and the proportion of prescriptions filled for generics was assessed using linear regression, controlling for demographic, health, and insurance characteristics. Separate models were created for each scale and then all 5 scales were included simultaneously in a fully-adjusted model. Results The usable response rate was 48%. When evaluated independently, a 1 SD increase in each of the 5 scales was associated with a 3.1% to 6.3% increase in generic drug use (P < 0.05 for each). In the fully adjusted model, only 2 scales were significantly associated with generic drug use: comfort with generic substitution (P = 0.021) and communication with providers about generic drugs (P = 0.012). Conclusions Generic drug use is most closely associated with the 2 actionable items we evaluated: communication with providers about generics and comfort with generic substitution. Educational campaigns that focus on these 2 domains may be most effective at influencing generic drug use. PMID:19194329

Cartilage-targeting drug delivery: can electrostatic interactions help?

PubMed

Bajpayee, Ambika G; Grodzinsky, Alan J

2017-03-01

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

The Multi-Billion Dollar Drug-Sensitive Spending Opportunity.

PubMed

Easter, Jon C; Thorpe, Kenneth

2018-01-01

Chronic diseases increase utilization and avoidable drug-sensitive spending, but little is done to optimize medication use and drive value. Value-based approaches to health care financing should shift focus to drug-sensitive spending to balance patient access and quality improvement with cost containment. ©2018 by the North Carolina Institute of Medicine and The Duke Endowment. All rights reserved.

[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.

Cost-utility analysis of varenicline, an oral smoking-cessation drug, in Japan.

PubMed

Igarashi, Ataru; Takuma, Hiroki; Fukuda, Takashi; Tsutani, Kiichiro

2009-01-01

To conduct a cost-utility analysis of two 12-week smoking-cessation interventions in Japan: smoking-cessation counselling by a physician compared with use of varenicline, an oral smoking-cessation drug, in addition to counselling. A Markov model was constructed to analyse lifetime medical costs and QALYs from the perspective of the healthcare payer. The cycle length was 5 years. Both costs and QALYs were discounted at 3% annually. The cohort of smokers was classified by sex and age, and we assumed that smokers started smoking at the age of 20 years and received smoking-cessation therapy at the ages of 30, 40, 50, 60 or 70 years (five separate models were run). The healthcare costs and QALYs were calculated throughout the term until the age of 90 years. In the base-case analysis, success rates of varenicline plus counselling and counselling alone were assumed to be 37.9% and 25.5%, respectively, in male smokers, and 22.2% and 16.1%, respectively, in female smokers, based on a randomized controlled trial conducted in Japan. Both univariate and probabilistic sensitivity analyses were conducted. Prescribed varenicline was shown to be more effective and less costly than smoking-cessation counselling alone. Varenicline would save direct medical costs of Japanese Yen (yen)43 846 ($US381; $US1 = yen115; Oct 2007) and generate an increase of 0.094 QALYs in male smokers. In females the incremental cost-effectiveness ratio was yen346 143 per QALY gained. Varenicline is estimated to save yen23.7 billion ($US206 million) of the medical costs for tobacco-associated diseases for the whole population. Overall savings are yen9.5 billion. Sensitivity analyses suggested the robustness of the results. As with any data of this nature, there is some uncertainty in the results and further research is warranted. However, based on the results of this pharmacoeconomic evaluation, varenicline, the first non-nicotine, oral treatment developed for smoking cessation, appears to be cost

Structure based drug discovery for designing leads for the non-toxic metabolic targets in multi drug resistant Mycobacterium tuberculosis.

PubMed

Kaur, Divneet; Mathew, Shalu; Nair, Chinchu G S; Begum, Azitha; Jainanarayan, Ashwin K; Sharma, Mukta; Brahmachari, Samir K

2017-12-21

The problem of drug resistance and bacterial persistence in tuberculosis is a cause of global alarm. Although, the UN's Sustainable Development Goals for 2030 has targeted a Tb free world, the treatment gap exists and only a few new drug candidates are in the pipeline. In spite of large information from medicinal chemistry to 'omics' data, there has been a little effort from pharmaceutical companies to generate pipelines for the development of novel drug candidates against the multi drug resistant Mycobacterium tuberculosis. In the present study, we describe an integrated methodology; utilizing systems level information to optimize ligand selection to lower the failure rates at the pre-clinical and clinical levels. In the present study, metabolic targets (Rv2763c, Rv3247c, Rv1094, Rv3607c, Rv3048c, Rv2965c, Rv2361c, Rv0865, Rv0321, Rv0098, Rv0390, Rv3588c, Rv2244, Rv2465c and Rv2607) in M. tuberculosis, identified using our previous Systems Biology and data-intensive genome level analysis, have been used to design potential lead molecules, which are likely to be non-toxic. Various in silico drug discovery tools have been utilized to generate small molecular leads for each of the 15 targets with available crystal structures. The present study resulted in identification of 20 novel lead molecules including 4 FDA approved drugs (droxidropa, tetroxoprim, domperidone and nemonapride) which can be further taken for drug repurposing. This comprehensive integrated methodology, with both experimental and in silico approaches, has the potential to not only tackle the MDR form of Mtb but also the most important persister population of the bacterium, with a potential to reduce the failures in the Tb drug discovery. We propose an integrated approach of systems and structural biology for identifying targets that address the high attrition rate issue in lead identification and drug development We expect that this system level analysis will be applicable for identification of drug

Effects of a recovery management intervention on Chinese heroin users' community recovery through the mediation effect of enhanced service utilization.

PubMed

Wu, F; Fu, L M; Hser, Y H

2015-09-01

This study investigates whether a recovery management intervention (RMI) can improve the utilization of community drug treatment and wraparound services among heroin users in China and subsequently lead to positive recovery outcomes. Secondary analysis was conducted drawing data from a randomized controlled trial; 100 heroin users with no severe mental health problems were recruited in two Shanghai districts (Hongkou and Yangpu) upon their release from compulsory rehabilitation facilities. A latent variable modeling approach was utilized to test whether the RMI influences heroin users' perceived motivation and readiness for treatment, enhances treatment and wraparound service participation, and, in turn, predicts better recovery outcomes. Enrollment in drug treatment and other social service utilization increased significantly as a result of RMI rather than an individual drug user's motivation and readiness for treatment. Increased service utilization thus led to more positive individual recovery outcomes. In addition to this mediation effect through service utilization, the RMI also improved participants' community recovery directly. Findings suggest that better drug treatment enrollment, community service utilization and recovery outcomes can be potentially achieved among heroin users in China with carefully designed case management interventions. © The Author 2014. Published by Oxford University Press on behalf of Faculty of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Molecular science for drug development and biomedicine.

PubMed

Zhong, Wei-Zhu; Zhou, Shu-Feng

2014-11-04

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.[...].

National Drug Formulary review of statin therapeutic group using the multiattribute scoring tool

PubMed Central

Ramli, Azuana; Aljunid, Syed Mohamed; Sulong, Saperi; Md Yusof, Faridah Aryani

2013-01-01

Purpose HMG-CoA reductase inhibitors (statins) are extensively used in treating hypercholesterolemia. The statins available in Malaysia include atorvastatin, lovastatin, pravastatin, rosuvastatin, simvastatin, and fluvastatin. Over the years, they have accumulated in the National Drug Formulary; hence, the need for review. Effective selection of the best drugs to remain in the formulary can become complex due to the multiple drug attributes involved, and is made worse by the limited time and resources available. The multiattribute scoring tool (MAST) systematizes the evaluation of the drug attributes to facilitate the drug selection process. In this study, a MAST framework was developed to rank the statins based on their utilities or benefits. Methods Published literature on multicriteria decision analysis (MCDA) were studied and five sessions of expert group discussions were conducted to build the MAST framework and to review the evidence. The attributes identified and selected for analysis were efficacy (clinical efficacy, clinical endpoints), safety (drug interactions, serious side effects and documentation), drug applicability (drug strength/formulation, indications, dose frequency, side effects, food–drug interactions, and dose adjustments), and cost. The average weights assigned by the members for efficacy, safety, drug applicability and cost were 32.6%, 26.2%, 24.1%, and 17.1%, respectively. The utility values of the attributes were scored based on the published evidence or/and agreements during the group discussions. The attribute scores were added up to provide the total utility score. Results Using the MAST, the six statins under review were successfully scored and ranked. Atorvastatin scored the highest total utility score (TUS) of 84.48, followed by simvastatin (83.11). Atorvastatin and simvastatin scored consistently high, even before drug costs were included. The low scores on the side effects for atorvastatin were compensated for by the higher

Method Development for Clinical Comprehensive Evaluation of Pediatric Drugs Based on Multi-Criteria Decision Analysis: Application to Inhaled Corticosteroids for Children with Asthma.

PubMed

Yu, Yuncui; Jia, Lulu; Meng, Yao; Hu, Lihua; Liu, Yiwei; Nie, Xiaolu; Zhang, Meng; Zhang, Xuan; Han, Sheng; Peng, Xiaoxia; Wang, Xiaoling

2018-04-01

Establishing a comprehensive clinical evaluation system is critical in enacting national drug policy and promoting rational drug use. In China, the 'Clinical Comprehensive Evaluation System for Pediatric Drugs' (CCES-P) project, which aims to compare drugs based on clinical efficacy and cost effectiveness to help decision makers, was recently proposed; therefore, a systematic and objective method is required to guide the process. An evidence-based multi-criteria decision analysis model that involved an analytic hierarchy process (AHP) was developed, consisting of nine steps: (1) select the drugs to be reviewed; (2) establish the evaluation criterion system; (3) determine the criterion weight based on the AHP; (4) construct the evidence body for each drug under evaluation; (5) select comparative measures and calculate the original utility score; (6) place a common utility scale and calculate the standardized utility score; (7) calculate the comprehensive utility score; (8) rank the drugs; and (9) perform a sensitivity analysis. The model was applied to the evaluation of three different inhaled corticosteroids (ICSs) used for asthma management in children (a total of 16 drugs with different dosage forms and strengths or different manufacturers). By applying the drug analysis model, the 16 ICSs under review were successfully scored and evaluated. Budesonide suspension for inhalation (drug ID number: 7) ranked the highest, with comprehensive utility score of 80.23, followed by fluticasone propionate inhaled aerosol (drug ID number: 16), with a score of 79.59, and budesonide inhalation powder (drug ID number: 6), with a score of 78.98. In the sensitivity analysis, the ranking of the top five and lowest five drugs remains unchanged, suggesting this model is generally robust. An evidence-based drug evaluation model based on AHP was successfully developed. The model incorporates sufficient utility and flexibility for aiding the decision-making process, and can be a useful

Leukocytes as carriers for targeted cancer drug delivery.

PubMed

Mitchell, Michael J; King, Michael R

2015-03-01

Metastasis contributes to over 90% of cancer-related deaths. Numerous nanoparticle platforms have been developed to target and treat cancer, yet efficient delivery of these systems to the appropriate site remains challenging. Leukocytes, which share similarities to tumor cells in terms of their transport and migration through the body, are well suited to serve as carriers of drug delivery systems to target cancer sites. This review focuses on the use and functionalization of leukocytes for therapeutic targeting of metastatic cancer. Tumor cell and leukocyte extravasation, margination in the bloodstream, and migration into soft tissue are discussed, along with the potential to exploit these functional similarities to effectively deliver drugs. Current nanoparticle-based drug formulations for the treatment of cancer are reviewed, along with methods to functionalize delivery vehicles to leukocytes, either on the surface and/or within the cell. Recent progress in this area, both in vitro and in vivo, is also discussed, with a particular emphasis on targeting cancer cells in the bloodstream as a means to interrupt the metastatic process. Leukocytes interact with cancer cells both in the bloodstream and at the site of solid tumors. These interactions can be utilized to effectively deliver drugs to targeted areas, which can reduce both the amount of drug required and various nonspecific cytotoxic effects within the body. If drug delivery vehicle functionalization does not interfere with leukocyte function, this approach may be utilized to neutralize tumor cells in the bloodstream to prevent the formation of new metastases, and also to deliver drugs to metastatic sites within tissues.

Patterns of drug treatment entry by Latino male injection drug users from different national/geographical backgrounds.

PubMed

Reynoso-Vallejo, Humberto; Chassler, Deborah; Witas, Julie; Lundgren, Lena M

2008-02-01

This study examined patterns of treatment entry by Puerto Rican, Central American, Dominican, and other Latino male injection drug users (IDUs) in the state of Massachusetts over the time period 1996-2002. Specifically, it explored whether these populations had different patterns relative to three paths: entry into detoxification only, entry into residential treatment, or entry into methadone maintenance. Using a state-level MIS dataset on all substance abuse treatment entries to all licensed treatment programs, bi-variate and logistic regression methods were employed to examine patterns of drug treatment utilization among Latino men residing in Massachusetts. Three logistic regression models, which controlled for age, education, homelessness, employment, history of mental health treatment, health insurance, criminal justice involvement, having injected drugs in the past month, and number of treatment entries, indicated that Puerto Rican men were significantly less likely to only use detoxification services and residential treatment services, and significantly more likely to enter methadone maintenance compared to Latino men from Central American, Dominican, or other Latino backgrounds. For example, Central American men were 2.4 times more likely to enter only detoxification programs and 54% less likely to enter methadone maintenance programs than Puerto Rican male IDUs. For program planning, include the need to (a) develop varied drug treatment services to meet the needs of non-homogenous Latino groups within the population, (b) tailor outreach efforts to effectively reach all Latino groups, and (c) increase awareness among practitioners of differential patterns of treatment utilization.

Parsing interindividual drug variability: an emerging role for systems pharmacology

PubMed Central

Turner, Richard M; Park, B Kevin; Pirmohamed, Munir

2015-01-01

There is notable interindividual heterogeneity in drug response, affecting both drug efficacy and toxicity, resulting in patient harm and the inefficient utilization of limited healthcare resources. Pharmacogenomics is at the forefront of research to understand interindividual drug response variability, but although many genotype-drug response associations have been identified, translation of pharmacogenomic associations into clinical practice has been hampered by inconsistent findings and inadequate predictive values. These limitations are in part due to the complex interplay between drug-specific, human body and environmental factors influencing drug response and therefore pharmacogenomics, whilst intrinsically necessary, is by itself unlikely to adequately parse drug variability. The emergent, interdisciplinary and rapidly developing field of systems pharmacology, which incorporates but goes beyond pharmacogenomics, holds significant potential to further parse interindividual drug variability. Systems pharmacology broadly encompasses two distinct research efforts, pharmacologically-orientated systems biology and pharmacometrics. Pharmacologically-orientated systems biology utilizes high throughput omics technologies, including next-generation sequencing, transcriptomics and proteomics, to identify factors associated with differential drug response within the different levels of biological organization in the hierarchical human body. Increasingly complex pharmacometric models are being developed that quantitatively integrate factors associated with drug response. Although distinct, these research areas complement one another and continual development can be facilitated by iterating between dynamic experimental and computational findings. Ultimately, quantitative data-derived models of sufficient detail will be required to help realize the goal of precision medicine. WIREs Syst Biol Med 2015, 7:221–241. doi: 10.1002/wsbm.1302 PMID:25950758

A Study of Outpatient Pharmacy Utilization at Naval Hospital, Camp Lejeune

DTIC Science & Technology

2002-07-01

5,468.87 LAMOTRIGINE 19 $4,907.53 ROSIGLITAZONE MALEATE 43 $4,849.93 ATORVASTATIN CALCIUM 47 $4,761.28 Table 10. Pharmacy Utilization 45 The Top 20 NHCL... ATORVASTATIN CALCIUM 246 $19,647.89 OXYCODONE HCL 132 $17,217.78 LANSOPRAZOLE 118 $16,499.98 PIOGLITAZONE HCL 83 $11,250.99 LORATADINE 150 $10,138.27...2,564.48 ATORVASTATIN CALCIUM 17 $2,276.93 LANSOPRAZOLE 13 $2,268.28 Table 13. Pharmacy Utilization 48 The Top 20 Drugs Utilized by NHCL Non-Prime

Microfluidics‐based 3D cell culture models: Utility in novel drug discovery and delivery research

PubMed Central

Gupta, Nilesh; Liu, Jeffrey R.; Patel, Brijeshkumar; Solomon, Deepak E.; Vaidya, Bhuvaneshwar

2016-01-01

Abstract The implementation of microfluidic devices within life sciences has furthered the possibilities of both academic and industrial applications such as rapid genome sequencing, predictive drug studies, and single cell manipulation. In contrast to the preferred two‐dimensional cell‐based screening, three‐dimensional (3D) systems have more in vivo relevance as well as ability to perform as a predictive tool for the success or failure of a drug screening campaign. 3D cell culture has shown an adaptive response to the recent advancements in microfluidic technologies which has allowed better control over spheroid sizes and subsequent drug screening studies. In this review, we highlight the most significant developments in the field of microfluidic 3D culture over the past half‐decade with a special focus on their benefits and challenges down the lane. With the newer technologies emerging, implementation of microfluidic 3D culture systems into the drug discovery pipeline is right around the bend. PMID:29313007

Drug policy: making effective drugs available without bankrupting the healthcare system.

PubMed

Laupacis, Andreas; Anderson, Geoffrey; O'Brien, Bernie

2002-01-01

To the extent possible, drug policy should be based upon good quality evidence. This must extend beyond the traditional focus on efficacy and safety in carefully selected patients, to evidence about real-world effectiveness, cost-effectiveness and safety of drugs. This paper will consider methods of improving the quality of the evidence currently available, and the implications of requiring that evidence. Historically, there has been a direct link between research evidence and policy at the level of licensing - drugs are only made available after they have been shown to be safe and efficacious in well-designed and independently assessed research studies. We propose that this reliance on evidence be logically extended to cover the formulary inclusion and post-marketing surveillance aspects of modern prescription drug policy. More specifically we propose that the decision to initially list a drug on a benefit formulary be based on evidence from relevant head-to-head comparisons and well-designed cost-effectiveness analyses. This evidence would be produced by industry in cooperation with independent peer-reviewed funding agencies. Drugs could only be added to a formulary if they met specific predetermined criteria, and drugs could be removed as superior alternatives became available. The provincial governments are monopsony buyers of medicines, and they wield the power to determine public payer "market access'for medicines. This power (within and across provinces) could be used more effectively to negotiate price in the context of reimbursement. The effect of different methods of influencing prescribing (e.g., 'limited access?) upon drug utilization and patient outcomes should be rigorously assessed, including the randomization of groups of patients or communities to different strategies. We also propose that all drugs on the formulary would be subject to a well-designed post-marketing surveillance program. This program would build on the existing passive reporting of

Economics of new oncology drug development.

PubMed

DiMasi, Joseph A; Grabowski, Henry G

2007-01-10

Review existing studies and provide new results on the development, regulatory, and market aspects of new oncology drug development. We utilized data from the US Food and Drug Administration (FDA), company surveys, and publicly available commercial business intelligence databases on new oncology drugs approved in the United States and on investigational oncology drugs to estimate average development and regulatory approval times, clinical approval success rates, first-in-class status, and global market diffusion. We found that approved new oncology drugs to have a disproportionately high share of FDA priority review ratings, of orphan drug designations at approval, and of drugs that were granted inclusion in at least one of the FDA's expedited access programs. US regulatory approval times were shorter, on average, for oncology drugs (0.5 years), but US clinical development times were longer on average (1.5 years). Clinical approval success rates were similar for oncology and other drugs, but proportionately more of the oncology failures reached expensive late-stage clinical testing before being abandoned. In relation to other drugs, new oncology drug approvals were more often first-in-class and diffused more widely across important international markets. The market success of oncology drugs has induced a substantial amount of investment in oncology drug development in the last decade or so. However, given the great need for further progress, the extent to which efforts to develop new oncology drugs will grow depends on future public-sector investment in basic research, developments in translational medicine, and regulatory reforms that advance drug-development science.

Comprehensive Urine Drug Screen by Gas Chromatography/Mass Spectrometry (GC/MS).

PubMed

Ramoo, Bheemraj; Funke, Melissa; Frazee, Clint; Garg, Uttam

2016-01-01

Drug screening is an essential component of clinical toxicology laboratory service. Some laboratories use only automated chemistry analyzers for limited screening of drugs of abuse and few other drugs. Other laboratories use a combination of various techniques such as immunoassays, colorimetric tests, and mass spectrometry to provide more detailed comprehensive drug screening. Mass spectrometry, gas or liquid, can screen for hundreds of drugs and is often considered the gold standard for comprehensive drug screening. We describe an efficient and rapid gas chromatography/mass spectrometry (GC/MS) method for comprehensive drug screening in urine which utilizes a liquid-liquid extraction, sample concentration, and analysis by GC/MS.

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…

[Polymeric drug carriers activated by ultrasounds energy].

PubMed

Kik, Krzysztof; Lwow, Felicja; Szmigiero, Leszek

2007-01-01

In the last two decades an extensive research on the employment of ultrasounds in anticancer therapy has been noticed. So far ultrasounds have been widely used in medicine for diagnostic purposes (ultrasonography), but their great therapeutic potential and the development of polymer based antineoplastic drug carriers have persuaded many investigators to start research on the employment of ultrasounds in anticancer therapy. A new therapeutic concept based on the controlled drug's molecules release from their transporting polymer carriers has been proposed. Cavitation, a phenomenon characteristic for the action of ultrasounds, is used to destroy polymeric drug carriers and for drug release in target sites. The sonodynamic therapy (SDT) which utilizes ultrasonic waves for "acoustic drug activation" leading to the enhancement of cytotoxic activity of some drugs has also been developed. Furthermore, a long standing research on ultrasounds resulted in a new concept based on hyperthermia. This method of cancer treatment does not require any chemotherapeutic agent to be applied.

Cost-Utility of Video-Electroencephalography Monitoring Followed by Surgery in Adults with Drug-Resistant Focal Epilepsy in Thailand.

PubMed

Kitwitee, Pimprapa; Unnwongse, Kanjana; Srikijvilaikul, Teeradej; Yadee, Tinonkorn; Limwattananon, Chulaporn

2017-02-01

This study assessed whether video-electroencephalography (VEEG) monitoring followed by surgery was cost-effective in adult patients with drug-resistant focal epilepsy under Thai health care context, as compared with continued medical treatment without VEEG. The total cost (in Thai Baht, THB) and effectiveness (in quality-adjusted life years, QALYs) were estimated over a lifetime horizon, using a decision tree and a Markov model. Data on short-term surgical outcomes, direct health care costs, and utilities were collected from Thai patients in a specialized hospital. Long-term outcomes and relative effectiveness of the surgery over medical treatment were derived, using systematic reviews of published literature. Seizure-free rates at years 1 and 2 after surgery were 79.4% and 77.8%, respectively. Costs of VEEG and surgery plus 1-year follow-up care were 216,782 THB, of which the VEEG and other necessary investigations were the main cost drivers (42.8%). On the basis of societal perspective, the total cost over a 40-year horizon accrued to 1,168,679 THB for the VEEG option, 64,939 THB higher than that for no VEEG. The VEEG option contributed to an additional 1.50 QALYs over no VEEG, resulting in an incremental cost-effectiveness ratio of 43,251 THB (USD 1236) per 1 QALY gained. Changes in key parameters had a minimal impact on the incremental cost-effectiveness ratio. Accounting for uncertainty, there was an 84% probability that the VEEG option was cost-effective on the basis of Thailand's cost-effective threshold of 160,000 THB/QALY. For patients with drug-resistant epilepsy, VEEG monitoring followed by epilepsy surgery was cost-effective in Thailand. Therefore it should be recommended for health insurance coverage. Copyright © 2016 Elsevier Inc. All rights reserved.

Hair drug testing results and self-reported drug use among primary care patients with moderate-risk illicit drug use.

PubMed

Gryczynski, Jan; Schwartz, Robert P; Mitchell, Shannon Gwin; O'Grady, Kevin E; Ondersma, Steven J

2014-08-01

This study sought to examine the utility of hair testing as a research measure of drug use among individuals with moderate-risk drug use based on the internationally validated Alcohol, Smoking, and Substance Involvement Screening Test (ASSIST). This study is a secondary analysis using baseline data from a randomized trial of brief intervention for drug misuse, in which 360 adults with moderate-risk drug use were recruited from two community clinics in New Mexico, USA. The current study compared self-reported drug use on the ASSIST with laboratory analysis of hair samples using a standard commercially available 5-panel test with assay screening and gas chromatography/mass spectrometry (GC/MS) confirmation. Both self-report and hair testing covered a 3-month period. Overall concordance between hair testing and self-report was 57.5% (marijuana), 86.5% (cocaine), 85.8% (amphetamines), and 74.3% (opioids). Specificity of hair testing at standard laboratory cut-offs exceeded 90% for all drugs, but sensitivity of hair testing relative to self-report was low, identifying only 52.3% (127/243) of self-disclosed marijuana users, 65.2% (30/46) of cocaine users, 24.2% (8/33) of amphetamine users, and 2.9% (2/68) of opioid users. Among participants who disclosed using marijuana or cocaine in the past 3 months, participants with a negative hair test tended to report lower-frequency use of those drugs (p<.001 for marijuana and cocaine). Hair testing can be useful in studies with moderate-risk drug users, but the potential for under-identification of low-frequency use suggests that researchers should consider employing low detection cut-offs and using hair testing in conjunction with self-report. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Hair Drug Testing Results and Self-reported Drug Use among Primary Care Patients with Moderate-risk Illicit Drug Use

PubMed Central

Gryczynski, Jan; Schwartz, Robert P.; Mitchell, Shannon Gwin; O’Grady, Kevin E.; Ondersma, Steven J.

2014-01-01

Background This study sought to examine the utility of hair testing as a research measure of drug use among individuals with moderate-risk drug use based on the internationally-validated Alcohol, Smoking, and Substance Involvement Screening Test (ASSIST). Methods This study is a secondary analysis using baseline data from a randomized trial of brief intervention for drug misuse, in which 360 adults with moderate-risk drug use were recruited from two community clinics in New Mexico, USA. The current study compared self-reported drug use on the ASSIST with laboratory analysis of hair samples using a standard commercially-available 5-panel test with assay screening and gas chromatography/mass spectrometry (GC/MS) confirmation. Both self-report and hair testing covered a 3 month period. Results Overall concordance between hair testing and self-report was 57.5% (marijuana), 86.5% (cocaine), 85.8% (amphetamines), and 74.3% (opioids). Specificity of hair testing at standard laboratory cut-offs exceeded 90% for all drugs, but sensitivity of hair testing relative to self-report was low, identifying only 52.3% (127/243) of self-disclosed marijuana users, 65.2% (30/46) of cocaine users, 24.2% (8/33) of amphetamine users, and 2.9% (2/68) of opioid users. Among participants who disclosed using marijuana or cocaine in the past 3 months, participants with a negative hair test tended to report lower-frequency use of those drugs (p< .001 for marijuana and cocaine). Conclusions Hair testing can be useful in studies with moderate-risk drug users, but the potential for under-identification of low-frequency use suggests that researchers should consider employing low detection cut-offs and using hair testing in conjunction with self-report. PMID:24932945

Health care service utilization and associated factors among heroin users in northern Taiwan.

PubMed

Chen, Yi-Chih; Chen, Chih-Ken; Lin, Shih-Ku; Chiang, Shu-Chuan; Su, Lien-Wen; Wang, Liang-Jen

2013-11-01

Due to the needs of medical care, the probability of using health care service from heroin users is high. This cross-sectional study investigated the frequency and correlates of health service utilization among heroin users. From June to September 2006, 124 heroin users (110 males and 14 females, mean age: 34.2 ± 8.3 years) who entered two psychiatric hospitals (N = 83) and a detention center (N = 41) in northern Taiwan received a face-to-face interview. Therefore, socio-demographic characteristics, patterns of drug use, psychiatric comorbidities, blood-borne infectious diseases and health service utilization were recorded. The behaviors of health service utilization were classified into the frequency of out-patient department visit and hospitalization, as well as the purchase of over-the-counter drugs. During 12 months prior to interview, 79.8% of the participants attended health care service at least once. The rate of having any event in out-patients service visit, hospitalization, and over-the-counter drugs were 66.1%, 29.8% and 25.8% respectively. The frequency of health service utilization was associated with numerous factors. Among these factors, patients who were recruited from hospital and having a mood disorder were conjoint predictors of out-patient department visit, hospitalization and purchase of over-the-counter drugs. According to the results of this study, social education and routine screening for mood disorders can help heroin users to obtain adequate health care service. The findings of this study are useful references for targeting the heroin users for whom a successful intervention represents the greatest cost benefit. © 2013 Elsevier Ltd. All rights reserved.

Nanobiotechnology-based drug delivery in brain targeting.

PubMed

Dinda, Subas C; Pattnaik, Gurudutta

2013-01-01

Blood brain barrier (BBB) found to act as rate limiting factor in drug delivery to brain in combating the central nervous system (CNS) disorders. Such limiting physiological factors include the reticuloendothelial system and protein opsonization, which present across BBB, play major role in reducing the passage of drug. Several approaches employed to improve the drug delivery across the BBB. Nanoparticles (NP) are the solid colloidal particle ranges from 1 to 1000 nm in size utilized as career for drug delivery. At present NPs are found to play a significant advantage over the other methods of available drug delivery systems to deliver the drug across the BBB. Nanoparticles may be because of its size and functionalization characteristics able to penetrate and facilitate the drug delivery through the barrier. There are number of mechanisms and strategies found to be involved in this process, which are based on the type of nanomaterials used and its combination with therapeutic agents, such materials include liposomes, polymeric nanoparticles and non-viral vectors of nano-sizes for CNS gene therapy, etc. Nanotechnology is expected to reduce the need for invasive procedures for delivery of therapeutics to the CNS. Some devices such as implanted catheters and reservoirs however will still be needed to overcome the problems in effective drug delivery to the CNS. Nanomaterials are found to improve the safety and efficacy level of drug delivery devices in brain targeting. Nanoegineered devices are found to be delivering the drugs at cellular levels through nono-fluidic channels. Different drug delivery systems such as liposomes, microspheres, nanoparticles, nonogels and nonobiocapsules have been used to improve the bioavailability of the drug in the brain, but microchips and biodegradable polymeric nanoparticulate careers are found to be more effective therapeutically in treating brain tumor. The physiological approaches also utilized to improve the transcytosis capacity

Predicting new drug indications from network analysis

NASA Astrophysics Data System (ADS)

Mohd Ali, Yousoff Effendy; Kwa, Kiam Heong; Ratnavelu, Kurunathan

This work adapts centrality measures commonly used in social network analysis to identify drugs with better positions in drug-side effect network and drug-indication network for the purpose of drug repositioning. Our basic hypothesis is that drugs having similar phenotypic profiles such as side effects may also share similar therapeutic properties based on related mechanism of action and vice versa. The networks were constructed from Side Effect Resource (SIDER) 4.1 which contains 1430 unique drugs with side effects and 1437 unique drugs with indications. Within the giant components of these networks, drugs were ranked based on their centrality scores whereby 18 prominent drugs from the drug-side effect network and 15 prominent drugs from the drug-indication network were identified. Indications and side effects of prominent drugs were deduced from the profiles of their neighbors in the networks and compared to existing clinical studies while an optimum threshold of similarity among drugs was sought for. The threshold can then be utilized for predicting indications and side effects of all drugs. Similarities of drugs were measured by the extent to which they share phenotypic profiles and neighbors. To improve the likelihood of accurate predictions, only profiles such as side effects of common or very common frequencies were considered. In summary, our work is an attempt to offer an alternative approach to drug repositioning using centrality measures commonly used for analyzing social networks.

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.

Leukocytes as carriers for targeted cancer drug delivery

PubMed Central

Mitchell, Michael J

2017-01-01

Introduction Metastasis contributes to over 90% of cancer-related deaths. Numerous nanoparticle platforms have been developed to target and treat cancer, yet efficient delivery of these systems to the appropriate site remains challenging. Leukocytes, which share similarities to tumor cells in terms of their transport and migration through the body, are well suited to serve as carriers of drug delivery systems to target cancer sites. Areas covered This review focuses on the use and functionalization of leukocytes for therapeutic targeting of metastatic cancer. Tumor cell and leukocyte extravasation, margination in the bloodstream, and migration into soft tissue are discussed, along with the potential to exploit these functional similarities to effectively deliver drugs. Current nanoparticle-based drug formulations for the treatment of cancer are reviewed, along with methods to functionalize delivery vehicles to leukocytes, either on the surface and/or within the cell. Recent progress in this area, both in vitro and in vivo, is also discussed, with a particular emphasis on targeting cancer cells in the bloodstream as a means to interrupt the metastatic process. Expert opinion Leukocytes interact with cancer cells both in the bloodstream and at the site of solid tumors. These interactions can be utilized to effectively deliver drugs to targeted areas, which can reduce both the amount of drug required and various nonspecific cytotoxic effects within the body. If drug delivery vehicle functionalization does not interfere with leukocyte function, this approach may be utilized to neutralize tumor cells in the bloodstream to prevent the formation of new metastases, and also to deliver drugs to metastatic sites within tissues. PMID:25270379

Examining the Feasibility and Utility of Estimating Partial Expected Value of Perfect Information (via a Nonparametric Approach) as Part of the Reimbursement Decision-Making Process in Ireland: Application to Drugs for Cancer.

PubMed

McCullagh, Laura; Schmitz, Susanne; Barry, Michael; Walsh, Cathal

2017-11-01

In Ireland, all new drugs for which reimbursement by the healthcare payer is sought undergo a health technology assessment by the National Centre for Pharmacoeconomics. The National Centre for Pharmacoeconomics estimate expected value of perfect information but not partial expected value of perfect information (owing to computational expense associated with typical methodologies). The objective of this study was to examine the feasibility and utility of estimating partial expected value of perfect information via a computationally efficient, non-parametric regression approach. This was a retrospective analysis of evaluations on drugs for cancer that had been submitted to the National Centre for Pharmacoeconomics (January 2010 to December 2014 inclusive). Drugs were excluded if cost effective at the submitted price. Drugs were excluded if concerns existed regarding the validity of the applicants' submission or if cost-effectiveness model functionality did not allow required modifications to be made. For each included drug (n = 14), value of information was estimated at the final reimbursement price, at a threshold equivalent to the incremental cost-effectiveness ratio at that price. The expected value of perfect information was estimated from probabilistic analysis. Partial expected value of perfect information was estimated via a non-parametric approach. Input parameters with a population value at least €1 million were identified as potential targets for research. All partial estimates were determined within minutes. Thirty parameters (across nine models) each had a value of at least €1 million. These were categorised. Collectively, survival analysis parameters were valued at €19.32 million, health state utility parameters at €15.81 million and parameters associated with the cost of treating adverse effects at €6.64 million. Those associated with drug acquisition costs and with the cost of care were valued at €6.51 million and €5.71�

Utility of NBD-Cl for the spectrophotometric determination of some skeletal muscle relaxant and antihistaminic drugs

NASA Astrophysics Data System (ADS)

Saleh, Hanaa M.; EL-Henawee, Magda M.; Ragab, Gamal H.; El-Hay, Soad S. Abd

2007-08-01

A simple, accurate, precise and sensitive colorimetric method for the determination of some skeletal muscle relaxant drugs, namely orphenadrine citrate ( I), baclofen ( II), antihistaminic drugs as acrivastine ( III) and fexofenadine hydrochloride ( IV) is described. This method is based on the formation of charge transfer complex with 4-chloro-7-nitro-2,1,3-benzoxadiazole (NBD-Cl) in non-aqueous medium. The orange color products were measured at 472, 465, 475 and 469 nm for drugs I, II, III and IV, respectively. The optimization of various experimental conditions was described. Beer's Law was obeyed in the range (2.5-17.5), (5-70), (2.5-25) and (10-50) μg/ml for drugs I, II, III and IV, respectively. The molar absorptivity ( ɛ), sandell sensitivity, detection (LOD) and quantitation limits (LOQ) are calculated. The procedure was favorably applied for determination of certain pharmaceutical dosage forms containing the studied drugs. The obtained results were compared with the official and reported methods. There were no significant differences between proposed, reported and the official methods.

Zebrafish models in neuropsychopharmacology and CNS drug discovery.

PubMed

Khan, Kanza M; Collier, Adam D; Meshalkina, Darya A; Kysil, Elana V; Khatsko, Sergey L; Kolesnikova, Tatyana; Morzherin, Yury Yu; Warnick, Jason E; Kalueff, Allan V; Echevarria, David J

2017-07-01

Despite the high prevalence of neuropsychiatric disorders, their aetiology and molecular mechanisms remain poorly understood. The zebrafish (Danio rerio) is increasingly utilized as a powerful animal model in neuropharmacology research and in vivo drug screening. Collectively, this makes zebrafish a useful tool for drug discovery and the identification of disordered molecular pathways. Here, we discuss zebrafish models of selected human neuropsychiatric disorders and drug-induced phenotypes. As well as covering a broad range of brain disorders (from anxiety and psychoses to neurodegeneration), we also summarize recent developments in zebrafish genetics and small molecule screening, which markedly enhance the disease modelling and the discovery of novel drug targets. © 2017 The British Pharmacological Society.

A biotin-drug extraction and acid dissociation (BEAD) procedure to eliminate matrix and drug interference in a protein complex anti-drug antibody (ADA) isotype specific assay.

PubMed

Niu, Hongmei; Klem, Thomas; Yang, Jinsong; Qiu, Yongchang; Pan, Luying

2017-07-01

Monitoring anti-drug antibody (ADA) responses in patients receiving protein therapeutics treatment is an important safety assessment for regulatory agencies, drug manufacturers, clinicians and patients. Recombinant human IGF-1/IGFBP-3 (rhIGF-1/rhIGFBP-3) is a 1:1 formulation of naturally occurring protein complex. The individual IGF-1 and IGFBP-3 proteins have multiple binding partners in serum matrix with high binding affinity to each other, which presents challenges in ADA assay development. We have developed a biotin-drug extraction with acid dissociation (BEAD) procedure followed by an electrochemiluminescence (ECL) direct assay to overcome matrix and drug interference. The method utilizes two step acid dissociation and excess biotin-drug to extract total ADA, which are further captured by soluble biotin-drug and detected in an ECL semi-homogeneous direct assay format. The pre-treatment method effectively eliminates interference by serum matrix and free drug, and enhances assay sensitivity. The assays passed acceptance criteria for all validation parameters, and have been used for clinical sample Ab testing. This method principle exemplifies a new approach for anti-isotype ADA assays, and could be an effective strategy for neutralizing antibody (NAb), pharmacokinetic (PK) and biomarker analysis in need of overcoming interference factors. Copyright © 2017 Elsevier B.V. All rights reserved.

Work-related injuries in a state trauma registry: relationship between industry and drug screening.

PubMed

Bunn, Terry L; Slavova, Svetla; Bernard, Andrew C

2014-08-01

Work-related injuries exert a great financial and economic burden on the US population. The study objectives were to identify the industries and occupations associated with worker injuries and to determine the predictors for injured worker drug screening in trauma centers. Work-related injury cases were selected using three criteria (expected payer source of workers' compensation, industry-related e-codes, and work-related indicator) from the Kentucky Trauma Registry data set for years 2008 to 2012. Descriptive analyses and multiple logistic regression were performed on the work-related injury cases. The "other services" and construction industry sectors accounted for the highest number of work-related cases. Drugs were detected in 55% of all drug-screened work-related trauma cases. Higher percentages of injured workers tested positive for drugs in the natural resources and mining, transportation and public utilities, and construction industries. In comparison, higher percentages of injured workers in the other services as well as transportation and public utilities industries were drug screened. Treatment at Level I trauma centers and Glasgow Coma Scale (GCS) scores indicating a coma or severe brain injury were both significant independent predictors for being screened for drugs; industry was not a significant predictor for being drug screened. The injured worker was more likely to be drug screened if the worker had a greater than mild injury, regardless of whether the worker was an interfacility transfer. These findings indicate that there may be elevated drug use or abuse in natural resources and mining, transportation and public utilities, as well as construction industry workers; improved identification of the specific drug types in positive drug screen results of injured workers is needed to better target prevention efforts. Epidemiologic study, level III.

Real-world utilization of molecular diagnostic testing and matched drug therapies in the treatment of metastatic cancers.

PubMed

Chawla, Anita; Peeples, Miranda; Li, Nanxin; Anhorn, Rachel; Ryan, Jason; Signorovitch, James

2018-06-01

To assess the frequency of biopsies and molecular diagnostic testing (human DNA/RNA analysis), anti-cancer drug use (genomically-matched targeted therapy [GMTT], unmatched targeted therapy [UTT], endocrine therapy [ET], and chemotherapy [CT]), and medical service costs among adults with metastatic cancer. Adults diagnosed with metastatic breast, non-small cell lung (NSCLC), colorectal, head and neck, ovarian, and uterine cancer (2010Q1-2015Q1) were identified in the OptumHealth Care Solutions claims database and followed from first metastatic diagnosis for ≥1 month and until the end of data availability. Utilization was assessed for each cancer cohort (all and patients aged ≥65 years); per-patient-per-month (PPPM) medical service costs were assessed for all patients. Testing frequency estimates were applied to Surveillance, Epidemiology, and End Results Program data to estimate the number of untested patients (2010-2014). Patients with metastatic cancer (n = 8,193; breast [n = 3,414], NSCLC [n = 2,231], colorectal [n = 1,611], head and neck [n = 511], ovarian [n = 275], and uterine [n = 151]) were 63 years old (mean), with 11.1-22.2 months of observation. Biopsy and molecular diagnostic testing frequencies ranged from 7% (uterine) to 73% (ovarian), and from 34% (head and neck) to 52% (breast), respectively. Few were treated with GMTT (breast, 11%; NSCLC, 9%; colorectal, 6%). Treatment with UTT ranged from 0.7% (uterine) to 21% (colorectal). Biopsy, diagnostic testing, and anti-cancer drug therapy were less frequent for those ≥65 years. Medical service costs (PPPM, mean) ranged from $6,618 (head and neck) to $9,940 (ovarian). The estimated number of untested new patients with metastatic cancer was 636,369 (all) and 341,397 (≥65). In addition to the limitations of claims analyses, diagnostic testing frequency may be under-estimated if patients underwent testing prior to study inclusion. The low frequency of molecular diagnostic

[Placental transfer of drugs].

PubMed

Evain-Brion, Danièle; Berveiller, Paul; Gil, Sophie

2014-01-01

With more than 830,000 live births in France, a great number of pregnant women are concerned by a treatment during pregnancy and many questions revolve around appreciating medication-related risks during pregnancy. The human placenta is the interface between mother and fetus and remains difficult to study for ethical reasons. Placental transfer of drugs from mother to fetus is dependent on their physicochemical properties, maternal and fetal factors and placental factors. The human placental perfusion model is the only experimental model to study human placental transfer of drugs in organized placental tissue. In vitro models utilizing cell cultures are mostly limited to the investigation of cellular toxicity along pregnancy or specific transfer mechanisms, such as their interaction with transporters. Taking advantage of the complementarity of these models, it will be possible to develop a rational use of drugs during this period. © 2014 Société Française de Pharmacologie et de Thérapeutique.

Identification of drug-resistant subpopulations in canine hemangiosarcoma.

PubMed

Khammanivong, A; Gorden, B H; Frantz, A M; Graef, A J; Dickerson, E B

2016-09-01

Canine hemangiosarcoma is a rapidly progressive disease that is poorly responsive to conventional chemotherapy. Despite numerous attempts to advance treatment options and improve outcomes, drug resistance remains a hurdle to successful therapy. To address this problem, we used recently characterized progenitor cell populations derived from canine hemangiosarcoma cell lines and grown as non-adherent spheres to identify potential drug resistance mechanisms as well as drug-resistant cell populations. Cells from sphere-forming cultures displayed enhanced resistance to chemotherapy drugs, expansion of dye-excluding side populations and altered ATP-binding cassette (ABC) transporter expression. Invasion studies demonstrated variability between cell lines as well as between sphere and monolayer cell populations. Collectively, our results suggest that sphere cell populations contain distinct subpopulations of drug-resistant cells that utilize multiple mechanisms to evade cytotoxic drugs. Our approach represents a new tool for the study of drug resistance in hemangiosarcoma, which could alter approaches for treating this disease. © 2014 John Wiley & Sons Ltd.

Identification of drug-resistant subpopulations in canine hemangiosarcoma

PubMed Central

Khammanivong, A.; Gorden, B. H.; Frantz, A. M.; Graef, A. J.; Dickerson, E. B.

2017-01-01

Canine hemangiosarcoma is a rapidly progressive disease that is poorly responsive to conventional chemotherapy. Despite numerous attempts to advance treatment options and improve outcomes, drug resistance remains a hurdle to successful therapy. To address this problem, we used recently characterized progenitor cell populations derived from canine hemangiosarcoma cell lines and grown as non-adherent spheres to identify potential drug resistance mechanisms as well as drug-resistant cell populations. Cells from sphere-forming cultures displayed enhanced resistance to chemotherapy drugs, expansion of dye-excluding side populations and altered ATP-binding cassette (ABC) transporter expression. Invasion studies demonstrated variability between cell lines as well as between sphere and monolayer cell populations. Collectively, our results suggest that sphere cell populations contain distinct subpopulations of drug-resistant cells that utilize multiple mechanisms to evade cytotoxic drugs. Our approach represents a new tool for the study of drug resistance in hemangiosarcoma, which could alter approaches for treating this disease. PMID:25112808

Nanoparticle-Delivered Chemotherapy: Old Drugs in New Packages.

PubMed

Lee, Michael S; Dees, E Claire; Wang, Andrew Z

2017-03-15

Cytotoxic chemotherapies have a narrow therapeutic window, with high peaks and troughs of plasma concentration. Novel nanoparticle formulations of cytotoxic chemotherapy drugs can enhance pharmacokinetic characteristics and facilitate passive targeting of drugs to tumors via the enhanced permeability and retention effect, thus mitigating toxicity. Nanoparticle vehicles currently in clinical use or undergoing clinical investigation for anticancer therapies include liposomes, polymeric micelles, protein-drug nanoparticles, and dendrimers. Multiple nanoparticle formulations of existing cytotoxic chemotherapies are approved for use in several indications, with clinical data indeed showing optimization of pharmacokinetics and different toxicity profiles compared with their parent drugs. There are also many new nanoparticle drug formulations in development and undergoing early- and late-phase clinical trials, including several that utilize active targeting or triggered release based on environmental stimuli. Here, we review the rationale for nanoparticle formulations of existing or previously investigated cytotoxic drugs, describe currently approved nanoparticle formulations of drugs, and discuss some of the most promising clinical trials currently underway.

Advanced cell culture techniques for cancer drug discovery.

PubMed

Lovitt, Carrie J; Shelper, Todd B; Avery, Vicky M

2014-05-30

Human cancer cell lines are an integral part of drug discovery practices. However, modeling the complexity of cancer utilizing these cell lines on standard plastic substrata, does not accurately represent the tumor microenvironment. Research into developing advanced tumor cell culture models in a three-dimensional (3D) architecture that more prescisely characterizes the disease state have been undertaken by a number of laboratories around the world. These 3D cell culture models are particularly beneficial for investigating mechanistic processes and drug resistance in tumor cells. In addition, a range of molecular mechanisms deconstructed by studying cancer cells in 3D models suggest that tumor cells cultured in two-dimensional monolayer conditions do not respond to cancer therapeutics/compounds in a similar manner. Recent studies have demonstrated the potential of utilizing 3D cell culture models in drug discovery programs; however, it is evident that further research is required for the development of more complex models that incorporate the majority of the cellular and physical properties of a tumor.

Advanced Cell Culture Techniques for Cancer Drug Discovery

PubMed Central

Lovitt, Carrie J.; Shelper, Todd B.; Avery, Vicky M.

2014-01-01

Human cancer cell lines are an integral part of drug discovery practices. However, modeling the complexity of cancer utilizing these cell lines on standard plastic substrata, does not accurately represent the tumor microenvironment. Research into developing advanced tumor cell culture models in a three-dimensional (3D) architecture that more prescisely characterizes the disease state have been undertaken by a number of laboratories around the world. These 3D cell culture models are particularly beneficial for investigating mechanistic processes and drug resistance in tumor cells. In addition, a range of molecular mechanisms deconstructed by studying cancer cells in 3D models suggest that tumor cells cultured in two-dimensional monolayer conditions do not respond to cancer therapeutics/compounds in a similar manner. Recent studies have demonstrated the potential of utilizing 3D cell culture models in drug discovery programs; however, it is evident that further research is required for the development of more complex models that incorporate the majority of the cellular and physical properties of a tumor. PMID:24887773

Prescription copay reduction program for diabetic employees: impact on medication compliance and healthcare costs and utilization.

PubMed

Nair, Kavita V; Miller, Kerri; Saseen, Joseph; Wolfe, Pamela; Allen, Richard Read; Park, Jinhee

2009-01-01

To examine the impact of a value-based benefit design on utilization and expenditures. This benefit design involved all diabetes-related drugs and testing supplies placed on the lowest copay tier for 1 employer group. The sample of diabetic members were enrolled from a 9-month preperiod and for 2 years after the benefit design was implemented. Measured outcomes included prescription drug utilization for diabetes and medical utilization. Generalized measures were used to estimate differences between years 1 and 2 and the preperiod adjusting for age, gender, and comorbidity risk. Diabetes prescription drug use increased by 9.5% in year 1 and by 5.5% in year 2, and mean adherence increased by 7% to 8% in year 1 and fell slightly in year 2 compared with the preperiod. Pharmacy expenditures increased by 47% and 53% and expenditures for diabetes services increased by 16% and 32% in years 1 and 2, respectively. Increases in adherence and use of diabetes medications were observed. There were no compensatory cost-savings for the employer through lower utilization of medical expenditures in the first 2 years. Adherent patients had fewer emergency department visits than nonadherent patients after the implementation of this benefit design.

Drugs and the dance music scene: a survey of current drug use patterns among a sample of dance music enthusiasts in the UK.

PubMed

Winstock, A R; Griffiths, P; Stewart, D

2001-09-01

This study explores the utility of a self-completion survey method to quickly and cheaply generate information on patterns and trends among regular "recreational" drug consumers. Data is reported here from 1151 subjects accessed through a dance music publication. In keeping with previous studies of drug use within the dance scene polysubstance use was the norm. Many of those reporting use of "ecstasy" were regularly using multiple tablets often consumed in combination with other substances thus exposing themselves to serious health risks, in particular the risk of dose related neurotoxic effects. Seventy percent were drinking alcohol at hazardous levels. Subjects' patterns of drug purchasing also put them at risk of severe criminal sanction. Data supported evidence that cocaine use had become increasing popular in the UK, but contrasted with some commentators' views that ecstasy use was in decline. The utility of this method and how the results should be interpreted is discussed, as are the data's implications for harm and risk reduction activities.

Chronic Health Outcomes and Prescription Drug Copayments in Medicaid.

PubMed

Kostova, Deliana; Fox, Jared

2017-05-01

Prescription drug copayments and cost-sharing have been linked to reductions in prescription drug use and expenditures. However, little is known about their effect on specific health outcomes. To evaluate the association between prescription drug copayments and uncontrolled hypertension, uncontrolled hypercholesterolemia, and prescription drug utilization among Medicaid beneficiaries with these conditions. Select adults aged 20-64 from NHANES 1999-2012 in 18 states. Uncontrolled hypertension, uncontrolled hypercholesterolemia, and taking medication for each of these conditions. A differencing regression model was used to evaluate health outcomes among Medicaid beneficiaries in 4 states that introduced copayments during the study period, relative to 2 comparison groups-Medicaid beneficiaries in 14 states unaffected by shifts in copayment policy, and a within-state counterfactual group of low-income adults not on Medicaid, while controlling for individual demographic factors and unobserved state-level characteristics. Although uncontrolled hypertension and hypercholesterolemia declined among all low-income persons during the study period, the trend was less pronounced in Medicaid beneficiaries affected by copayments. After netting out concurrent trends in health outcomes of low-income persons unaffected by Medicaid copayment changes, we estimated that introduction of drug copayments in Medicaid was associated with an average rise in uncontrolled hypertension and uncontrolled hypercholesterolemia of 7.7 and 13.2 percentage points, respectively, and with reduced drug utilization for hypercholesterolemia. As Medicaid programs change in the years following the Affordable Care Act, prescription drug copayments may play a role as a lever for controlling hypertension and hypercholesterolemia at the population level.

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 Central

Lim, Roxanne; 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. PMID:25506455

Nanomaterials in cancer-therapy drug delivery system.

PubMed

Zhang, Gen; Zeng, Xin; Li, Ping

2013-05-01

Nanomaterials can enhance the delivery and treatment efficiency of anti-cancer drugs, and the mechanisms of the tumor-reducing activity of nanomaterials with cancer drug have been investigated. The task for drug to reach pathological areas has facilitated rapid advances in nanomedicine. Herein, we summarize promising findings with respect to cancer therapeutics based on nano-drug delivery vectors. Relatively high toxicity of uncoated nanoparticles restricts the use of these materials in humans. In order to reduce toxicity, many approaches have focused on the encapsulation of nanoparticles with biocompatible materials. Efficient delivery systems have been developed that utilized nanoparticles loaded with high dose of cancer drug in the presence of bilayer molecules. Well-established nanotechnologies have been designed for drug delivery with specific bonding. Surface-modified nanoparticles as vehicles for drug delivery system that contains multiple nano-components, each specially designed to achieve aimed task for the emerging application delivery of therapeutics. Drug-coated polymer nanoparticles could efficiently increase the intracellular accumulation of anti-cancer drugs. This review also introduces the nanomaterials with drug on the induction of apoptosis in cancer cells in vitro and in vivo. Direct interactions between the particles and cellular molecules to cause adverse biological responses are also discussed.

An investigation of the representativity of neuropsychiatrists and their patients in a drug utilization observation study on fluoxetine.

PubMed

Schaaf, B; Linden, M; Weber, H J

1997-01-01

This study presents a methodological approach to an expost facto investigation of sample bias in drug utilization observation (DUO) studies using the example of a DUO with the nontricyclic antidepressant fluoxetine. A total of 479 psychiatrists and neurologists and 2,401 patients were investigated. The purpose of the study was to judge the representativeness of our DUO sample for two populations: first, for all psychiatrics and neurologists prescribing fluoxetine or all patients being treated with fluoxetine in Germany and, second, for all psychiatrists and neurologists prescribing antidepressants or all patients being treated with antidepressants in Germany. Criteria for the representativeness test were physician variables (gender, size of community where practicing, federal state, age, volume of prescriptions) and patient variables (gender, age, prescription-related diagnosis, concurrent illnesses, concomitant medications). The study shows that the DUO sample can rightfully claim representativeness in the majority of parameters for the psychiatrists and neurologists prescribing fluoxetine and for the patients being treated with fluoxetine. There are more noticeable discrepancies with regard to the psychiatrists and neurologists in general and to the patients being treated with antidepressants in general. The methodological problems of pharmacoepidemiological investigation of representativeness are discussed.

Guidelines and methodological reviews concerning drug abuse liability assessment.

PubMed

Balster, Robert L; Bigelow, George E

2003-06-05

Regulatory control of drugs with abuse liability is an important component of drug control policy and is believed to help prevent nonmedical use. To be maximally effective, this requires a scientific assessment of abuse liability of drugs considered for regulatory control. These assessments have relied extensively on laboratory-based animal and human testing, but also utilize information from clinical trials, actual abuse and other sources. Here, we discuss recommendations and guidelines that have been proposed for abuse liability assessment and describe important review papers and conference proceedings that have addressed this matter, focusing primarily on drugs with medical usefulness. Historically, there is substantial consensus about how to approach abuse liability evaluation of drugs with actions similar to those of abused opiates, stimulants, depressants, and to a somewhat lesser extent, cannabinoids and hallucinogens, and much of what has been recommended for abuse potential assessment in the past remains valid and useful. On the other hand, novel CNS-active medications which cannot be readily classified with these traditional drugs of abuse are increasingly under development. In addition, advances in the science of abuse liability assessment need to be incorporated into future guidelines and recommendations on this subject. Developers of new medications need guidance on how to utilize scientific research to maximize therapeutic benefit while minimizing risk for abuse. Thus, another goal of this review has been to identify areas where critical thinking and new guideline development are needed.

FDA-approved drugs that are spermatotoxic in animals and the utility of animal testing for human risk prediction.

PubMed

Rayburn, Elizabeth R; Gao, Liang; Ding, Jiayi; Ding, Hongxia; Shao, Jun; Li, Haibo

2018-02-01

This study reviews FDA-approved drugs that negatively impact spermatozoa in animals, as well as how these findings reflect on observations in human male gametes. The FDA drug warning labels included in the DailyMed database and the peer-reviewed literature in the PubMed database were searched for information to identify single-ingredient, FDA-approved prescription drugs with spermatotoxic effects. A total of 235 unique, single-ingredient, FDA-approved drugs reported to be spermatotoxic in animals were identified in the drug labels. Forty-nine of these had documented negative effects on humans in either the drug label or literature, while 31 had no effect or a positive impact on human sperm. For the other 155 drugs that were spermatotoxic in animals, no human data was available. The current animal models are not very effective for predicting human spermatotoxicity, and there is limited information available about the impact of many drugs on human spermatozoa. New approaches should be designed that more accurately reflect the findings in men, including more studies on human sperm in vitro and studies using other systems (ex vivo tissue culture, xenograft models, in silico studies, etc.). In addition, the present data is often incomplete or reported in a manner that prevents interpretation of their clinical relevance. Changes should be made to the requirements for pre-clinical testing, drug surveillance, and the warning labels of drugs to ensure that the potential risks to human fertility are clearly indicated.

Development of description framework of pharmacodynamics ontology and its application to possible drug-drug interaction reasoning.

PubMed

Imai, Takeshi; Hayakawa, Masayo; Ohe, Kazuhiko

2013-01-01

Prediction of synergistic or antagonistic effects of drug-drug interaction (DDI) in vivo has been of considerable interest over the years. Formal representation of pharmacological knowledge such as ontology is indispensable for machine reasoning of possible DDIs. However, current pharmacology knowledge bases are not sufficient to provide formal representation of DDI information. With this background, this paper presents: (1) a description framework of pharmacodynamics ontology; and (2) a methodology to utilize pharmacodynamics ontology to detect different types of possible DDI pairs with supporting information such as underlying pharmacodynamics mechanisms. We also evaluated our methodology in the field of drugs related to noradrenaline signal transduction process and 11 different types of possible DDI pairs were detected. The main features of our methodology are the explanation capability of the reason for possible DDIs and the distinguishability of different types of DDIs. These features will not only be useful for providing supporting information to prescribers, but also for large-scale monitoring of drug safety.

The impact of South Korea's new drug-pricing policy on market competition among off-patent drugs.

PubMed

Kwon, Hye-Young; Kim, Hyungmin; Godman, Brian; Reich, Michael R

2015-01-01

A new pricing policy was introduced in Korea in April 2012 with the aim of strengthening competition among off-patent drugs by eliminating price gaps between originators and generics. Examine the effect of newly implemented pricing policy. Retrospectively examining the effects through extracting from the National Health Insurance claims data a 30-month panel dataset (January 2011-June 2013) containing consumption data in four major therapeutic classes (antihypertensives, lipid-lowering drugs, antiulcerants and antidepressants). Proxies for market competition were examined before and after the policy. The new pricing policy did not enhance competition among off-patent drugs. In fact, price dispersion significantly decreased as opposed to the expected change. Originator-to-generic utilization increased 6.12 times (p = 0.000) after the new policy. The new pricing policy made no impact on competition among off-patent drugs. Competition in the off-patent market cannot be enhanced unless both supply and demand side measures are coordinated.

41 CFR 101-42.1102-5 - Drugs, biologicals, and reagents other than controlled substances.

Code of Federal Regulations, 2012 CFR

2012-07-01

... UTILIZATION AND DISPOSAL 42-UTILIZATION AND DISPOSAL OF HAZARDOUS MATERIALS AND CERTAIN CATEGORIES OF PROPERTY... are subject to the provisions of § 101-42.1102-3. (a) Utilization requirements. Excess drugs... Scientific Coordination Staff, ACFA-CF-30, located in the appropriate FDA district office, of surplus...

Utilization of gastroprotective strategies for nonsteroidal anti-inflammatory drug-induced gastrointestinal events in a major teaching hospital

PubMed Central

Lee, Hooi Leng; Chua, Siew Siang; Mahadeva, Sanjiv

2016-01-01

Background and purpose Clinical guidelines recommend the prescribing of gastroprotective strategies in nonsteroidal anti-inflammatory drug (NSAID) users with risk factors for gastrointestinal (GI) ulcer or ulcer complications. However, these guidelines are not often translated into clinical practice. Therefore, the aim of this study was to investigate the utilization of gastroprotective strategies for NSAID-induced upper GI events in at-risk users in a major teaching hospital. Patients and methods A cross-sectional, observational, pharmacy-based study was conducted in a major Asian institution with both primary and secondary health care services. This study involved the screening of prescriptions for regular NSAIDs, and patients who met the inclusion criteria were recruited and interviewed using a questionnaire. Results Of the 409 participants recruited, 83.1% had at least one GI risk factor, of whom 70.3% did not receive appropriate gastroprotection. The most common GI risk factor was the use of high-dose NSAIDs (69.2%), followed by participants aged 65 years and older (22%) and concomitant use of low-dose aspirin (11.7%). Appropriate gastroprotective strategies utilized consisted of the use of a cyclooxygenase (COX)-2 inhibitor alone or a nonselective NSAID plus a proton pump inhibitor (PPI) in the moderate-risk group and a COX-2 inhibitor plus a PPI in the high-risk group. Gastroprotective strategies were underutilized in 67.1% of at-risk participants and overutilized in 59.4% of those without risk factors. Co-prescription of a histamine-2 receptor antagonist at lower-than-recommended doses constituted 59% of the inappropriate gastroprotective agents used. Logistic regression analysis revealed patients aged 65 years and older (odds ratio, 1.89; 95% CI =1.15–3.09) as a predictor for the prescribing of gastroprotection by the clinicians. Conclusion Approximately 70% of at-risk NSAID users, mainly on high-dose NSAIDs, were not prescribed appropriate

Outcome of the first Medicines Utilization Research in Africa group meeting to promote sustainable and rational medicine use in Africa.

PubMed

Massele, Amos; Burger, Johanita; Katende-Kyenda, Norah L; Kalemeera, Francis; Kenaope, Thatoyaone; Kibuule, Dan; Mbachu, Ogochukwu; Mubita, Mwangana; Oluka, Margaret; Olusanya, Adedunni; Paramadhas, Bene D Anand; van Zyl, Paulina; Godman, Brian

2015-01-01

The first Medicines Utilization Research in Africa group workshop and symposium brought researchers together from across Africa to improve their knowledge on drug utilization methodologies as well as exchange ideas. As a result, progress was made on drug utilization research and formulating future strategies to enhance the rational use of medicines in Africa. Anti-infectives were the principal theme for the 1-day symposium following the workshops. This included presentations on the inappropriate use of antibiotics as well as ways to address this. Concerns with adverse drug reactions and adherence to anti-retroviral medicines were also discussed, with poor adherence remaining a challenge. There were also concerns with the underutilization of generics. These discussions resulted in a number of agreed activities before the next conference in 2016.

Drug Usage and Health Characteristics in Non-Institutionalized Mexican-American Elderly.

ERIC Educational Resources Information Center

Vener, A. M.; And Others

1980-01-01

Results of in-depth interviews with 32 elderly Mexican Americans revealed minimal potential hazardous drug interactions. Mexican Americans showed a disinclination to utilize over-the-counter drugs to alleviate minor ailments. Professionals involved in health care delivery systems for the aging should become aware of the special needs of ethnic…

The effect of garlic supplements and phytochemicals on the ADMET properties of drugs.

PubMed

Berginc, Katja; Kristl, Albin

2012-03-01

Garlic supplements have received wide public attention because of their health-beneficial effects. Although these products are considered as innocuous, several case reports and studies have shown the capacity of individual garlic phytochemicals/supplements to interfere with drug pharmacokinetics. This review covers recently published literature on garlic chemistry and composition, and provides a thorough review of published studies evaluating drug-garlic interactions. The authors illustrate the mechanisms underlying pharmacokinetic interactions, which could serve as important highlights in further research to explain results for drugs with narrow therapeutic indices or for drugs, utilizing multiple absorption, distribution and metabolism pathways. To increase the relevance of further research on safety and efficacy of garlic supplements and phytochemicals, their composition should be addressed before conducting in vitro or in vivo research. It is also strongly recommended to characterize in vitro formulation performance to assess the rate and extent of garlic phytochemical release in order to anticipate the in vivo impact on the pharmacokinetics of concomitantly consumed drugs. The main conclusion of this review is that the impact of garlic on different stages of pharmacokinetics, especially on drug absorption and metabolism, is drug specific and dependent on the type/quality of utilized supplement.

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

Predictors of illicit drug/s use among university students in Northern Ireland, Wales and England.

PubMed

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

2014-12-16

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. 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. 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. 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 long-term intervention plans are required. This

Formulary Drug Review: Betrixaban.

PubMed

Baker, Danial E

2018-02-01

Each month, subscribers to The Formulary Monograph Service receive 5 to 6 well-documented monographs on drugs that are newly released or are in late phase 3 trials. The monographs are targeted to Pharmacy & Therapeutics Committees. Subscribers also receive monthly 1-page summary monographs on agents that are useful for agendas and pharmacy/nursing in-services. A comprehensive target drug utilization evaluation/medication use evaluation (DUE/MUE) is also provided each month. With a subscription, the monographs are available online to subscribers. Monographs can be customized to meet the needs of a facility. Through the cooperation of The Formulary, Hospital Pharmacy publishes selected reviews in this column. For more information about The Formulary Monograph Service , contact Wolters Kluwer customer service at 866-397-3433.

Formulary Drug Review: Ocrelizumab.

PubMed

Ali, Zaynah K; Baker, Danial E

2017-10-01

Each month, subscribers to The Formulary Monograph Service receive 5 to 6 well-documented monographs on drugs that are newly released or are in late phase 3 trials. The monographs are targeted to Pharmacy & Therapeutics Committees. Subscribers also receive monthly 1-page summary monographs on agents that are useful for agendas and pharmacy/nursing in-services. A comprehensive target drug utilization evaluation/medication use evaluation (DUE/MUE) is also provided each month. With a subscription, the monographs are available online to subscribers. Monographs can be customized to meet the needs of a facility. Through the cooperation of The Formulary, Hospital Pharmacy publishes selected reviews in this column. For more information about The Formulary Monograph Service , contact Wolters Kluwer customer service at 866-397-3433.

Formulary Drug Review: Edaravone.

PubMed

Ali, Zaynah K; Baker, Danial E

2017-12-01

Each month, subscribers to The Formulary Monograph Service receive 5 to 6 well-documented monographs on drugs that are newly released or are in late phase 3 trials. The monographs are targeted to Pharmacy & Therapeutics Committees. Subscribers also receive monthly 1-page summary monographs on agents that are useful for agendas and pharmacy/nursing in-services. A comprehensive target drug utilization evaluation/medication use evaluation (DUE/MUE) is also provided each month. With a subscription, the monographs are available online to subscribers. Monographs can be customized to meet the needs of a facility. Through the cooperation of The Formulary, Hospital Pharmacy publishes selected reviews in this column. For more information about The Formulary Monograph Service , contact Wolters Kluwer customer service at 866-397-3433.

Comparison of Psychotropic Drug Prescribing Quality between Zagreb, Croatia and Sarajevo, B&H.

PubMed

Polić-Vižintin, Marina; Štimac, Danijela; Čatić, Tarik; Šostar, Zvonimir; Zelić, Ana; Živković, Krešimir; Draganić, Pero

2014-12-01

The purpose of this paper was to compare outpatient consumption and quality of psychotropic drug prescribing between Croatia and Bosnia & Herzegovina 2006-2010. Data on drug utilization from Zagreb Municipal Pharmacy and Sarajevo Public Pharmacy were used to calculate the number of defined daily doses (DDD) and DDD per 1000 inhabitants per day (DDD/TID) using the WHO Anatomical-Therapeutic-Chemical methodology. Total utilization of psychopharmaceuticals increased in both cities; however, it was higher in Zagreb than in Sarajevo throughout the study period. The utilization of psycholeptics increased in Zagreb by 2.4% (from 74.5 to 76.3 DDD/TID) and in Sarajevo by 3.8% (from 62.4 to 64.8 DDD/TID). The utilization of anxiolytics decreased in Zagreb by 2.1% and in Sarajevo by even 18.7%. The utilization of antidepressants increased in both cities with predominance of SSRI over TCA utilization, greater in Sarajevo (96.6%) than in Zagreb (10.2%). The anxiolytic/antidepressant ratio decreased by 11.1% in Zagreb (from 2.87 to 2.55) and by 58.7% in Sarajevo (from 5.66 to 2.34). Outpatient utilization of antipsychotics increased significantly in Sarajevo, predominated by typical ones, whereas in Zagreb the utilization of antipsychotics was stable, predominated by atypical ones. In Croatia and Bosnia & Herzegovina, there was an obvious tendency to follow western trends in drug prescribing, as demonstrated by the increased use of antidepressants and reduced use of anxiolytics. Despite some improvement observed in the prescribing quality, high use of antipsychotics with dominance of typical antipsychotics in Sarajevo points to the need of prescribing guidelines for antipsychotics.

The role of fMRI in drug development

PubMed Central

Carmichael, Owen; Schwarz, Adam J.; Chatham, Christopher H.; Scott, David; Turner, Jessica A.; Upadhyay, Jaymin; Coimbra, Alexandre; Goodman, James A.; Baumgartner, Richard; English, Brett A.; Apolzan, John W.; Shankapal, Preetham; Hawkins, Keely R.

2017-01-01

Functional magnetic resonance imaging (fMRI) has been known for over a decade to have the potential to greatly enhance the process of developing novel therapeutic drugs for prevalent health conditions. However, the use of fMRI in drug development continues to be relatively limited because of a variety of technical, biological, and strategic barriers that continue to limit progress. Here, we briefly review the roles that fMRI can have in the drug development process and the requirements it must meet to be useful in this setting. We then provide an update on our current understanding of the strengths and limitations of fMRI as a tool for drug developers and recommend activities to enhance its utility. PMID:29154758

[Drug Repositioning Research Utilizing a Large-scale Medical Claims Database to Improve Survival Rates after Cardiopulmonary Arrest].

PubMed

Zamami, Yoshito; Niimura, Takahiro; Takechi, Kenshi; Imanishi, Masaki; Koyama, Toshihiro; Ishizawa, Keisuke

2017-01-01

 Approximately 100000 people suffer cardiopulmonary arrest in Japan every year, and the aging of society means that this number is expected to increase. Worldwide, approximately 100 million develop cardiac arrest annually, making it an international issue. Although survival has improved thanks to advances in cardiopulmonary resuscitation, there is a high rate of postresuscitation encephalopathy after the return of spontaneous circulation, and the proportion of patients who can return to normal life is extremely low. Treatment for postresuscitation encephalopathy is long term, and if sequelae persist then nursing care is required, causing immeasurable economic burdens as a result of ballooning medical costs. As at present there is no drug treatment to improve postresuscitation encephalopathy as a complication of cardiopulmonary arrest, the development of novel drug treatments is desirable. In recent years, new efficacy for existing drugs used in the clinical setting has been discovered, and drug repositioning has been proposed as a strategy for developing those drugs as therapeutic agents for different diseases. This review describes a large-scale database study carried out following a discovery strategy for drug repositioning with the objective of improving survival rates after cardiopulmonary arrest and discusses future repositioning prospects.

Financial Burden of Cancer Drug Treatment in Lebanon.

PubMed

Elias, Fadia; Khuri, Fadlo R; Adib, Salim M; Karam, Rita; Harb, Hilda; Awar, May; Zalloua, Pierre; Ammar, Walid

2016-01-01

The Ministry of Public Health (MOPH) in Lebanon provides cancer drugs free of charge for uninsured patients who account for more than half the total caseload. Other categories of cancer care are subsidized under more stringent eligibility criteria. MOPH's large database offers an excellent opportunity to analyze the cost of cancer treatment in Lebanon. Using utilization and spending data accumulated at MOPH during 20082013, the cost to the public budget of cancer drugs was assessed per case and per drug type. The average annual cost of cancer drugs was 6,475$ per patient. Total cancer drug costs were highest for breast cancer, followed by chronic myeloid leukemia (CML), colorectal cancer, lung cancer, and NonHodgkin's lymphoma (NHL), which together represented 74% of total MOPH cancer drug expenditure. The annual average cancer drug cost per case was highest for CML ($31,037), followed by NHL ($11,566). Trastuzumab represented 26% and Imatinib 15% of total MOPH cancer drug expenditure over six years. Sustained increase in cancer drug cost threatens the sustainability of MOPH coverage, so crucial for socially vulnerable citizens. To enhance the bargaining position with pharmaceutical firms for drug cost containment in a small market like Lebanon, drug price comparisons with neighboring countries which have already obtained lower prices may succeed in lowering drug costs.

Molecular Networking As a Drug Discovery, Drug Metabolism, and Precision Medicine Strategy.

PubMed

Quinn, Robert A; Nothias, Louis-Felix; Vining, Oliver; Meehan, Michael; Esquenazi, Eduardo; Dorrestein, Pieter C

2017-02-01

Molecular networking is a tandem mass spectrometry (MS/MS) data organizational approach that has been recently introduced in the drug discovery, metabolomics, and medical fields. The chemistry of molecules dictates how they will be fragmented by MS/MS in the gas phase and, therefore, two related molecules are likely to display similar fragment ion spectra. Molecular networking organizes the MS/MS data as a relational spectral network thereby mapping the chemistry that was detected in an MS/MS-based metabolomics experiment. Although the wider utility of molecular networking is just beginning to be recognized, in this review we highlight the principles behind molecular networking and its use for the discovery of therapeutic leads, monitoring drug metabolism, clinical diagnostics, and emerging applications in precision medicine. Copyright © 2016. Published by Elsevier Ltd.

The Impact of Global Budgets on Pharmaceutical Spending and Utilization

PubMed Central

Fendrick, A. Mark; Song, Zirui; Landon, Bruce E.; Safran, Dana Gelb; Mechanic, Robert E.; Chernew, Michael E.

2014-01-01

In 2009, Blue Cross Blue Shield of Massachusetts implemented a global budget-based payment system, the Alternative Quality Contract (AQC), in which provider groups assumed accountability for spending. We investigate the impact of global budgets on the utilization of prescription drugs and related expenditures. Our analyses indicate no statistically significant evidence that the AQC reduced the use of drugs. Although the impact may change over time, early evidence suggests that it is premature to conclude that global budget systems may reduce access to medications. PMID:25500751

Utility of preclinical drug versus food choice procedures to evaluate candidate medications for methamphetamine use disorder.

PubMed

Banks, Matthew L

2017-04-01

Substance use disorders are diagnosed as a manifestation of inappropriate behavioral allocation toward abused drugs and away from other behaviors maintained by more adaptive nondrug reinforcers (e.g., money and social relationships). Substance use disorder treatment goals include not only decreasing drug-maintained behavior but also promoting behavioral reallocation toward these socially adaptive alternative reinforcers. Preclinical drug self-administration procedures that offer concurrent access to both drug and nondrug reinforcers provide a translationally relevant dependent measure of behavioral allocation that may be useful for candidate medication evaluation. In contrast to other abused drugs, such as heroin or cocaine, preclinical methamphetamine versus food choice procedures have been a more recent development. We hypothesize that preclinical to clinical translatability would be improved by the evaluation of repeated pharmacological treatment effects on methamphetamine self-administration under a methamphetamine versus food choice procedure. In support of this hypothesis, a literature review suggests strong concordance between preclinical pharmacological treatment effects on methamphetamine versus food choice in nonhuman primates and clinical medication treatment effects on methamphetamine self-administration in human laboratory studies or methamphetamine abuse metrics in clinical trials. In conclusion, this literature suggests preclinical methamphetamine versus food choice procedures may be useful in developing innovative pharmacotherapies for methamphetamine use disorder. © 2016 New York Academy of Sciences.

Utility of preclinical drug versus food choice procedures to evaluate candidate medications for methamphetamine use disorder

PubMed Central

Banks, Matthew L.

2016-01-01

Substance use disorders are diagnosed as a manifestation of inappropriate behavioral allocation towards abused drugs and away from other behaviors maintained by more adaptive nondrug reinforcers (e.g., work and social relationships). Substance use disorder treatment goals include not only decreasing drug-maintained behavior but also promoting behavioral reallocation toward these socially adaptive alternative reinforcers. Preclinical drug self-administration procedures that offer concurrent access to both drug and nondrug reinforcers provide a translationally relevant dependent measure of behavioral allocation that may be useful for candidate medication evaluation. In contrast to other abused drugs, such as heroin or cocaine, preclinical methamphetamine versus food choice procedures have been a more recent development. We hypothesize that preclinical to clinical translatability would be improved by the evaluation of repeated pharmacological treatment effects on methamphetamine self-administration under a methamphetamine versus food choice procedure. In support of this hypothesis, a literature review suggests strong concordance between preclinical pharmacological treatment effects on methamphetamine versus food choice in nonhuman primates and clinical medication treatment effects on methamphetamine self-administration in human laboratory studies or methamphetamine abuse metrics in clinical trials. In conclusion, this literature suggests preclinical methamphetamine versus food choice procedures may be useful in developing innovative pharmacotherapies for methamphetamine use disorder. PMID:27936284

The Prediction of Drug-Disease Correlation Based on Gene Expression Data.

PubMed

Cui, Hui; Zhang, Menghuan; Yang, Qingmin; Li, Xiangyi; Liebman, Michael; Yu, Ying; Xie, Lu

2018-01-01

The explosive growth of high-throughput experimental methods and resulting data yields both opportunity and challenge for selecting the correct drug to treat both a specific patient and their individual disease. Ideally, it would be useful and efficient if computational approaches could be applied to help achieve optimal drug-patient-disease matching but current efforts have met with limited success. Current approaches have primarily utilized the measureable effect of a specific drug on target tissue or cell lines to identify the potential biological effect of such treatment. While these efforts have met with some level of success, there exists much opportunity for improvement. This specifically follows the observation that, for many diseases in light of actual patient response, there is increasing need for treatment with combinations of drugs rather than single drug therapies. Only a few previous studies have yielded computational approaches for predicting the synergy of drug combinations by analyzing high-throughput molecular datasets. However, these computational approaches focused on the characteristics of the drug itself, without fully accounting for disease factors. Here, we propose an algorithm to specifically predict synergistic effects of drug combinations on various diseases, by integrating the data characteristics of disease-related gene expression profiles with drug-treated gene expression profiles. We have demonstrated utility through its application to transcriptome data, including microarray and RNASeq data, and the drug-disease prediction results were validated using existing publications and drug databases. It is also applicable to other quantitative profiling data such as proteomics data. We also provide an interactive web interface to allow our Prediction of Drug-Disease method to be readily applied to user data. While our studies represent a preliminary exploration of this critical problem, we believe that the algorithm can provide the basis for

Availability of new drugs and Americans' ability to work.

PubMed

Lichtenberg, Frank R

2005-04-01

The objective of this work was the investigation of the extent to which the introduction of new drugs has increased society's ability to produce goods and services by increasing the number of hours worked per member of the working-age population. Econometric models of ability-to-work measures from data on approximately 200,000 individuals with 47 major chronic conditions observed throughout a 15-year period (1982-1996) were estimated. Under very conservative assumptions, the estimates indicate that the value of the increase in ability to work attributable to new drugs is 2.5 times as great as expenditure on new drugs. The potential of drugs to increase employee productivity should be considered in the design of drug-reimbursement policies. Conversely, policies that broadly reduce the development and utilization of new drugs may ultimately reduce our ability to produce other goods and services.

Modulated evaluation metrics for drug-based ontologies.

PubMed

Amith, Muhammad; Tao, Cui

2017-04-24

Research for ontology evaluation is scarce. If biomedical ontological datasets and knowledgebases are to be widely used, there needs to be quality control and evaluation for the content and structure of the ontology. This paper introduces how to effectively utilize a semiotic-inspired approach to ontology evaluation, specifically towards drug-related ontologies hosted on the National Center for Biomedical Ontology BioPortal. Using the semiotic-based evaluation framework for drug-based ontologies, we adjusted the quality metrics based on the semiotic features of drug ontologies. Then, we compared the quality scores before and after tailoring. The scores revealed a more precise measurement and a closer distribution compared to the before-tailoring. The results of this study reveal that a tailored semiotic evaluation produced a more meaningful and accurate assessment of drug-based ontologies, lending to the possible usefulness of semiotics in ontology evaluation.

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…

Targeted prodrugs in oral drug delivery: the modern molecular biopharmaceutical approach.

PubMed

Dahan, Arik; Khamis, Mustafa; Agbaria, Riad; Karaman, Rafik

2012-08-01

The molecular revolution greatly impacted the field of drug design and delivery in general, and the utilization of the prodrug approach in particular. The increasing understanding of membrane transporters has promoted a novel 'targeted-prodrug' approach utilizing carrier-mediated transport to increase intestinal permeability, as well as specific enzymes to promote activation to the parent drug. This article provides the reader with a concise overview of this modern approach to prodrug design. Targeting the oligopeptide transporter PEPT1 for absorption and the serine hydrolase valacyclovirase for activation will be presented as examples for the successful utilization of this approach. Additionally, the use of computational approaches, such as DFT and ab initio molecular orbital methods, in modern prodrugs design will be discussed. Overall, in the coming years, more and more information will undoubtedly become available regarding intestinal transporters and potential enzymes that may be exploited for the targeted modern prodrug approach. Hence, the concept of prodrug design can no longer be viewed as merely a chemical modification to solve problems associated with parent compounds. Rather, it opens promising opportunities for precise and efficient drug delivery, as well as enhancement of treatment options and therapeutic efficacy.

Systemic fluoroquinolone prescriptions for hospitalized children in Belgium, results of a multicenter retrospective drug utilization study.

PubMed

Meesters, Kevin; Mauel, Reiner; Dhont, Evelyn; Walle, Johan Vande; De Bruyne, Pauline

2018-02-23

Fluoroquinolones (FQ) are increasingly prescribed for children, despite being labeled for only a limited number of labeled pediatric indications. In this multicenter retrospective drug utilization study, we analyzed indications for systemic FQ prescriptions in hospitalized children and the appropriateness of the prescribed dose. Using data obtained from electronic medical files, the study included all children who received a systemic FQ prescription in two Belgian university children's hospitals between 2010 and 2013. Two authors reviewed prescribed daily doses. Univariate and multivariate logistic regression models were used to analyze risk factors for inadequately dosing. Results262 FQ prescriptions for individual patients were included for analysis. 16.8% of these prescriptions were for labeled indications, and 35.1% were guided by bacteriological findings. Prescribed daily dose was considered to be inappropriate in 79 prescriptions (30.2%). Other FQ than ciprofloxacin accounted for 9 prescriptions (3.4%), of which 8 were correctly dosed. Underdosing represented 45 (56.9%) dosing errors. Infants and preschool children were at particular risk for dosing errors, with associated adjusted OR of 0.263 (0.097-0.701) and 0.254 (0.106-0.588) respectively. FQ were often prescribed off-label and not guided by bacteriological findings in our study population. Dosing errors were common, particularly in infants and preschool children. FQ prescriptions for children should be improved by specific pediatric antimicrobial stewardship teams. Furthermore, pharmacokinetic studies should optimise dosing recommendations for children.

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. Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.

Large-scale prediction of adverse drug reactions using chemical, biological, and phenotypic properties of drugs.

PubMed

Liu, Mei; Wu, Yonghui; Chen, Yukun; Sun, Jingchun; Zhao, Zhongming; Chen, Xue-wen; Matheny, Michael Edwin; Xu, Hua

2012-06-01

Adverse drug reaction (ADR) is one of the major causes of failure in drug development. Severe ADRs that go undetected until the post-marketing phase of a drug often lead to patient morbidity. Accurate prediction of potential ADRs is required in the entire life cycle of a drug, including early stages of drug design, different phases of clinical trials, and post-marketing surveillance. Many studies have utilized either chemical structures or molecular pathways of the drugs to predict ADRs. Here, the authors propose a machine-learning-based approach for ADR prediction by integrating the phenotypic characteristics of a drug, including indications and other known ADRs, with the drug's chemical structures and biological properties, including protein targets and pathway information. A large-scale study was conducted to predict 1385 known ADRs of 832 approved drugs, and five machine-learning algorithms for this task were compared. This evaluation, based on a fivefold cross-validation, showed that the support vector machine algorithm outperformed the others. Of the three types of information, phenotypic data were the most informative for ADR prediction. When biological and phenotypic features were added to the baseline chemical information, the ADR prediction model achieved significant improvements in area under the curve (from 0.9054 to 0.9524), precision (from 43.37% to 66.17%), and recall (from 49.25% to 63.06%). Most importantly, the proposed model successfully predicted the ADRs associated with withdrawal of rofecoxib and cerivastatin. The results suggest that phenotypic information on drugs is valuable for ADR prediction. Moreover, they demonstrate that different models that combine chemical, biological, or phenotypic information can be built from approved drugs, and they have the potential to detect clinically important ADRs in both preclinical and post-marketing phases.

Nanotechnology controlled drug delivery for treating bone diseases.

PubMed

Yang, Lei; Webster, Thomas J

2009-08-01

Rapid developments at the intersection of nanotechnology and controlled drug delivery have triggered exceptional growth in treating various bone diseases. As a result, over the past decade, nanotechnology has contributed tremendously to controlling drug delivery for treating various bone diseases, and in many cases, has led to increased bone regeneration. In this review paper, the recent experimental progress towards using nanotechnology to treat bone-specific diseases is reviewed. Novel applications of different types of nanomaterials (from nanoparticles to 3D nanostructured scaffolds) for treating bone diseases are summarized. In addition, fundamental principles for utilizing nanomaterials to create better drug delivery systems, especially for treating bone diseases and regenerating bone, are emphasized.

Applications of SHAPES screening in drug discovery.

PubMed

Lepre, Christopher A; Peng, Jeffrey; Fejzo, Jasna; Abdul-Manan, Norzehan; Pocas, Jennifer; Jacobs, Marc; Xie, Xiaoling; Moore, Jonathan M

2002-12-01

The SHAPES strategy combines nuclear magnetic resonance (NMR) screening of a library of small drug-like molecules with a variety of complementary methods, such as virtual screening, high throughput enzymatic assays, combinatorial chemistry, X-ray crystallography, and molecular modeling, in a directed search for new medicinal chemistry leads. In the past few years, the SHAPES strategy has found widespread utility in pharmaceutical research. To illustrate a variety of different implementations of the method, we will focus in this review on recent applications of the SHAPES strategy in several drug discovery programs at Vertex Pharmaceuticals.

Experimental design and statistical analysis for three-drug combination studies.

PubMed

Fang, Hong-Bin; Chen, Xuerong; Pei, Xin-Yan; Grant, Steven; Tan, Ming

2017-06-01

Drug combination is a critically important therapeutic approach for complex diseases such as cancer and HIV due to its potential for efficacy at lower, less toxic doses and the need to move new therapies rapidly into clinical trials. One of the key issues is to identify which combinations are additive, synergistic, or antagonistic. While the value of multidrug combinations has been well recognized in the cancer research community, to our best knowledge, all existing experimental studies rely on fixing the dose of one drug to reduce the dimensionality, e.g. looking at pairwise two-drug combinations, a suboptimal design. Hence, there is an urgent need to develop experimental design and analysis methods for studying multidrug combinations directly. Because the complexity of the problem increases exponentially with the number of constituent drugs, there has been little progress in the development of methods for the design and analysis of high-dimensional drug combinations. In fact, contrary to common mathematical reasoning, the case of three-drug combinations is fundamentally more difficult than two-drug combinations. Apparently, finding doses of the combination, number of combinations, and replicates needed to detect departures from additivity depends on dose-response shapes of individual constituent drugs. Thus, different classes of drugs of different dose-response shapes need to be treated as a separate case. Our application and case studies develop dose finding and sample size method for detecting departures from additivity with several common (linear and log-linear) classes of single dose-response curves. Furthermore, utilizing the geometric features of the interaction index, we propose a nonparametric model to estimate the interaction index surface by B-spine approximation and derive its asymptotic properties. Utilizing the method, we designed and analyzed a combination study of three anticancer drugs, PD184, HA14-1, and CEP3891 inhibiting myeloma H929 cell line

The Prescription Drug User Fee Act: Cause for Concern?

PubMed

Gabay, Michael

2018-04-01

The Prescription Drug User Fee Act (PDUFA) was originally enacted into law in 1992. PDUFA provides the Food and Drug Administration (FDA) with needed revenue in the form of various fees paid by drug and biologic manufacturers. The FDA utilizes this revenue to streamline the review and approval process for medications. Since the enactment of PDUFA, the median approval time for priority new drug applications and biologics license applications has reduced significantly. The FDA views PDUFA as a successful program that provides a consistent revenue stream to the agency, improves access to medications for patients, and allows industry to have a more predictable product review timeline. However, critics of PDUFA cite concerns including the potential for a lack of FDA independence and medication safety issues involving drugs approved after the existence of PDUFA.

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

DrugBank: a knowledgebase for drugs, drug actions and drug targets

PubMed Central

Wishart, David S.; Knox, Craig; Guo, An Chi; Cheng, Dean; Shrivastava, Savita; Tzur, Dan; Gautam, Bijaya; Hassanali, Murtaza

2008-01-01

DrugBank is a richly annotated resource that combines detailed drug data with comprehensive drug target and drug action information. Since its first release in 2006, DrugBank has been widely used to facilitate in silico drug target discovery, drug design, drug docking or screening, drug metabolism prediction, drug interaction prediction and general pharmaceutical education. The latest version of DrugBank (release 2.0) has been expanded significantly over the previous release. With ∼4900 drug entries, it now contains 60% more FDA-approved small molecule and biotech drugs including 10% more ‘experimental’ drugs. Significantly, more protein target data has also been added to the database, with the latest version of DrugBank containing three times as many non-redundant protein or drug target sequences as before (1565 versus 524). Each DrugCard entry now contains more than 100 data fields with half of the information being devoted to drug/chemical data and the other half devoted to pharmacological, pharmacogenomic and molecular biological data. A number of new data fields, including food–drug interactions, drug–drug interactions and experimental ADME data have been added in response to numerous user requests. DrugBank has also significantly improved the power and simplicity of its structure query and text query searches. DrugBank is available at http://www.drugbank.ca PMID:18048412

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

PubMed

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

2016-07-05

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

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

PubMed Central

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

2016-01-01

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

Impacts of generic competition and benefit management practices on spending for prescription drugs: evidence from Medicare's Part D benefit.

PubMed

Sheingold, Steven; Nguyen, Nguyen Xuan

2014-01-01

This study estimates the effects of generic competition, increased cost-sharing, and benefit practices on utilization and spending for prescription drugs. We examined changes in Medicare price and utilization from 2007 to 2009 of all drugs in 28 therapeutic classes. The classes accounted for 80% of Medicare Part D spending in 2009 and included the 6 protected classes and 6 classes with practically no generic competition. All variables were constructed to measure each drug relative to its class at a specific plan sponsor. We estimated that the shift toward generic utilization had cut in half the rate of increase in the price of a prescription during 2007-2009. Specifically, the results showed that (1) rapid generic penetration had significantly held down costs per prescription, (2) copayment and other benefit practices shifted utilization to generics and favored brands, and (3) price increases were generally greater in less competitive classes of drugs. In many ways, Part D was implemented at a fortuitous time; since 2006, there have been relatively few new blockbuster drugs introduced, and many existing high-volume drugs used by beneficiaries were in therapeutic classes with multiple brands and generic alternatives. Under these conditions, our paper showed that plan sponsors have been able to contain costs by encouraging use of generics or drugs offering greater value within therapeutic classes. It is less clear what will happen to future Part D costs if a number of new and effective drugs for beneficiaries enter the market with no real competitors.

Etiologic features and utilization of antiepileptic drugs in people with chronic epilepsy in China: Report from the Epilepsy Cohort of Huashan Hospital (ECoH).

PubMed

Ge, Yan; Yu, Peimin; Ding, Ding; Wang, Ping; Shi, Yunbo; Zhao, Ting; Tang, Xinghua; Hong, Zhen

2015-10-01

Chronic epilepsy is estimated to affect more than 2 million people in China. However, data of its clinical characteristics was rarely reported in China. In the present study, we summarized the etiologic features and utilization patterns of antiepileptic drugs (AEDs) in people with chronic epilepsy in a tertiary medical center in China. We prospectively recruited people with chronic epilepsy treated at the Epilepsy Outpatient Clinic of Huashan Hospital during October 2009 to August 2013. Demographic data, clinical characteristics, AED treatment, epilepsy-associated risk factors and medical history, and results of supplementary examinations of each participant were collected retrospectively via an interviewer-administered questionnaire and confirmed by the medical records. Among 554 people with chronic epilepsy, 58.0% of them were male, 66.8% had focal seizure, and 29.2% had symptomatic cause. Developmental anomalies of cerebral structure (16.7%) and cerebral trauma (16.7%) shared the leading cause of symptomatic epilepsy among children with epilepsy. While cerebral trauma (29.1%) and cerebrovascular disorder (36.4%) were the most common causes in groups of adults and elderly. Fifty percent of participants were taking AED monotherapy. Proportions of people with idiopathic, cryptogenic and symptomatic epilepsy treated by multitherapy were 35%, 46% and 45.6%, respectively. Valproic acid (VPA) was the most frequently utilized AED as monotherapy (32.7%) and within multitherapy (62.5%). This hospital-based study reported that etiologic features were diverse in different age groups of people with chronic epilepsy. VPA was widely utilized to treat chronic epilepsy in mainland China. Copyright © 2015 Elsevier B.V. All rights reserved.

Development of Bone Targeting Drugs.

PubMed

Stapleton, Molly; Sawamoto, Kazuki; Alméciga-Díaz, Carlos J; Mackenzie, William G; Mason, Robert W; Orii, Tadao; Tomatsu, Shunji

2017-06-23

The skeletal system, comprising bones, ligaments, cartilage and their connective tissues, is critical for the structure and support of the body. Diseases that affect the skeletal system can be difficult to treat, mainly because of the avascular cartilage region. Targeting drugs to the site of action can not only increase efficacy but also reduce toxicity. Bone-targeting drugs are designed with either of two general targeting moieties, aimed at the entire skeletal system or a specific cell type. Most bone-targeting drugs utilize an affinity to hydroxyapatite, a major component of the bone matrix that includes a high concentration of positively-charged Ca 2+ . The strategies for designing such targeting moieties can involve synthetic and/or biological components including negatively-charged amino acid peptides or bisphosphonates. Efficient delivery of bone-specific drugs provides significant impact in the treatment of skeletal related disorders including infectious diseases (osteoarthritis, osteomyelitis, etc.), osteoporosis, and metabolic skeletal dysplasia. Despite recent advances, however, both delivering the drug to its target without losing activity and avoiding adverse local effects remain a challenge. In this review, we investigate the current development of bone-targeting moieties, their efficacy and limitations, and discuss future directions for the development of these specific targeted treatments.

Development of Bone Targeting Drugs

PubMed Central

Stapleton, Molly; Sawamoto, Kazuki; Alméciga-Díaz, Carlos J.; Mackenzie, William G.; Mason, Robert W.; Orii, Tadao; Tomatsu, Shunji

2017-01-01

The skeletal system, comprising bones, ligaments, cartilage and their connective tissues, is critical for the structure and support of the body. Diseases that affect the skeletal system can be difficult to treat, mainly because of the avascular cartilage region. Targeting drugs to the site of action can not only increase efficacy but also reduce toxicity. Bone-targeting drugs are designed with either of two general targeting moieties, aimed at the entire skeletal system or a specific cell type. Most bone-targeting drugs utilize an affinity to hydroxyapatite, a major component of the bone matrix that includes a high concentration of positively-charged Ca2+. The strategies for designing such targeting moieties can involve synthetic and/or biological components including negatively-charged amino acid peptides or bisphosphonates. Efficient delivery of bone-specific drugs provides significant impact in the treatment of skeletal related disorders including infectious diseases (osteoarthritis, osteomyelitis, etc.), osteoporosis, and metabolic skeletal dysplasia. Despite recent advances, however, both delivering the drug to its target without losing activity and avoiding adverse local effects remain a challenge. In this review, we investigate the current development of bone-targeting moieties, their efficacy and limitations, and discuss future directions for the development of these specific targeted treatments. PMID:28644392

Pharmacology of Antisense Drugs.

PubMed

Bennett, C Frank; Baker, Brenda F; Pham, Nguyen; Swayze, Eric; Geary, Richard S

2017-01-06

Recent studies have led to a greater appreciation of the diverse roles RNAs play in maintaining normal cellular function and how they contribute to disease pathology, broadening the number of potential therapeutic targets. Antisense oligonucleotides are the most direct means to target RNA in a selective manner and have become an established platform technology for drug discovery. There are multiple molecular mechanisms by which antisense oligonucleotides can be used to modulate RNAs in cells, including promoting the degradation of the targeted RNA or modulating RNA function without degradation. Antisense drugs utilizing various antisense mechanisms are demonstrating therapeutic potential for the treatment of a broad variety of diseases. This review focuses on some of the advances that have taken place in translating antisense technology from the bench to the clinic.

Pharmacogenetics in drug regulation: promise, potential and pitfalls

PubMed Central

Shah, Rashmi R

2005-01-01

Pharmacogenetic factors operate at pharmacokinetic as well as pharmacodynamic levels—the two components of the dose–response curve of a drug. Polymorphisms in drug metabolizing enzymes, transporters and/or pharmacological targets of drugs may profoundly influence the dose–response relationship between individuals. For some drugs, although retrospective data from case studies suggests that these polymorphisms are frequently associated with adverse drug reactions or failure of efficacy, the clinical utility of such data remains unproven. There is, therefore, an urgent need for prospective data to determine whether pre-treatment genotyping can improve therapy. Various regulatory guidelines already recommend exploration of the role of genetic factors when investigating a drug for its pharmacokinetics, pharmacodynamics, dose–response relationship and drug interaction potential. Arising from the global heterogeneity in the frequency of variant alleles, regulatory guidelines also require the sponsors to provide additional information, usually pharmacogenetic bridging data, to determine whether data from one ethnic population can be extrapolated to another. At present, sponsors explore pharmacogenetic influences in early clinical pharmacokinetic studies but rarely do they carry the findings forward when designing dose–response studies or pivotal studies. When appropriate, regulatory authorities include genotype-specific recommendations in the prescribing information. Sometimes, this may include the need to adjust a dose in some genotypes under specific circumstances. Detailed references to pharmacogenetics in prescribing information and pharmacogenetically based prescribing in routine therapeutics will require robust prospective data from well-designed studies. With greater integration of pharmacogenetics in drug development, regulatory authorities expect to receive more detailed genetic data. This is likely to complicate the drug evaluation process as well as

The Impact of Private Insurance Coverage on Prescription Drug Use in Ontario, Canada.

PubMed

Kratzer, Jillian; Cheng, Lucy; Allin, Sara; Law, Michael R

2015-05-01

Canadians obtain prescription drug coverage through a patchwork of public insurance, private benefit plans and out-of-pocket payments. Prior evidence suggests that insurance coverage, in general, leads to higher utilization rates of essential medicines; it is unclear whether individuals with private insurance have better access to medicines. Using data from the 2008 Canadian Community Health Survey, we identified cohorts from Ontario who reported having been diagnosed by a physician with asthma, high blood pressure or diabetes. Using propensity score stratification techniques, we compared drug utilization of individuals holding private insurance with that of individuals holding either public insurance (for those aged over 65 years) or no insurance (aged under 65 years). In five out of six comparisons, individuals with private insurance were more likely to take prescribed drugs than those without. Raw differences in the percentage of patients taking medicines ranged from 0.1 to 8.1%. Ontarians with chronic conditions holding private drug insurance are more likely to use prescription drugs than those who do not. Whether these inequities result in health outcome differences remains unknown. Copyright © 2015 Longwoods Publishing.

The Impact of Private Insurance Coverage on Prescription Drug Use in Ontario, Canada

PubMed Central

Kratzer, Jillian; Cheng, Lucy; Allin, Sara

2015-01-01

Canadians obtain prescription drug coverage through a patchwork of public insurance, private benefit plans and out-of-pocket payments. Prior evidence suggests that insurance coverage, in general, leads to higher utilization rates of essential medicines; it is unclear whether individuals with private insurance have better access to medicines. Using data from the 2008 Canadian Community Health Survey, we identified cohorts from Ontario who reported having been diagnosed by a physician with asthma, high blood pressure or diabetes. Using propensity score stratification techniques, we compared drug utilization of individuals holding private insurance with that of individuals holding either public insurance (for those aged over 65 years) or no insurance (aged under 65 years). In five out of six comparisons, individuals with private insurance were more likely to take prescribed drugs than those without. Raw differences in the percentage of patients taking medicines ranged from 0.1 to 8.1%. Ontarians with chronic conditions holding private drug insurance are more likely to use prescription drugs than those who do not. Whether these inequities result in health outcome differences remains unknown. PMID:26142359

Effects of the Affordable Care Act's young adult insurance expansion on prescription drug insurance coverage, utilization, and expenditures.

PubMed

Look, Kevin A; Arora, Prachi

2016-01-01

The US Affordable Care Act (ACA) extended the age of eligibility for young adults to remain on their parents' health insurance plans in order to address the disproportionate number of uninsured young adults in the United States. Effective September 23, 2010, the ACA has required all private health insurance plans to cover dependents until the age of 26. However, it is unknown whether the ACA dependent coverage expansion had an impact on prescription drug insurance or the use of prescription drugs. To evaluate short-term changes in prescription health insurance coverage, prescription drug insurance coverage, prescription drug use, and prescription drug expenditures following implementation of the ACA young adult insurance expansion using national data from 2009 and 2011. Full-year health insurance coverage increased 4.9 percentage points during the study period, which was mainly due to increases in private health insurance among middle- and high-income young adults. In contrast, full-year prescription drug insurance coverage increased 5.5 percentage points and was primarily concentrated among high-income young adults. Although no significant short-term changes in overall prescription drug use were observed, a 30% decrease in out-of-pocket expenditures was seen among young adults. While the main goal of the ACA's young adult insurance expansion was to increase health insurance coverage among young adults, it also had the unintended positive effect of increasing coverage for prescription drug insurance. Additionally, young adults experienced substantial decreases in out-of-pocket spending for prescription drugs. It is important for evaluations of health care policies to assess both intended and unintended outcomes to better understand the implications for the broader health system. Copyright © 2015 Elsevier Inc. All rights reserved.

HIV and injecting drug use in Indonesia: epidemiology and national response.

PubMed

Afriandi, Irvan; Aditama, Tjandra Yoga; Mustikawati, Dyah; Oktavia, Martiani; Alisjahbana, Bachti; Riono, Pandu

2009-07-01

Indonesia is facing one of the most rapidly growing HIV-epidemics in Asia. Risk behaviour associated with injecting drug use, such as sharing contaminated needles, is the main risk factor for HIV infection. Among the general population the prevalence of HIV-infection is still low (0.2%), but up to 50% or more of the estimated 145.000 - 170.000 injecting drug users are already HIV-positive. Overrepresentation of injecting drug users and continued risk behavior inside Indonesian prisons contribute to spread of HIV. Through sexual contacts, HIV is transmitted from current or previous injecting drug users to their non-injecting sexual partners; 10-20% of this group may already be infected. The national response targeted to limit spread of HIV through injecting drug use has included needle and syringe program (NSP), methadone maintenance treatment (MMT), voluntary counseling and testing (VCT), and outreach program as priority programs. However coverage and utilization of the harm reduction services is still limited, but effective integration with HIV testing and treatment is expanding. By 2008, there were 110 service points for NSP and 24 operational MMT clinics. Nevertheless, utilization of these services has been less satisfactory and their effectiveness has been questioned. Besides effective prevention, HIV- testing and earlier treatment of HIV-seropositve individuals, including those with a history of injecting drug use, will help control the growing HIV-epidemic in Indonesia.

The Food and Drug Administration advisory committees and panels: how they are applied to the drug regulatory process.

PubMed

Ciociola, Arthur A; Karlstadt, Robyn G; Pambianco, Daniel J; Woods, Karen L; Ehrenpreis, Eli D

2014-10-01

Food and Drug Administration (FDA) advisory panels and committees play a critical role in advising the FDA on the safety and efficacy of medical devices and drugs marketed in the US. Advisory panel recommendations are used by the FDA to make decisions regarding medical products. Currently, the FDA utilizes over 50 advisory panels that serve the three major FDA centers, including the Centers for Biologics, Drugs and Device Products. Members of an advisory panel typically include academicians, clinicians, consumers, patients, and industry representatives. The FDA establishes the schedules for advisory panel meetings on an annual basis and a panel usually meets several times a year for two consecutive days in Washington, DC. Typically, the advisory panel discusses issues highlighted by the FDA and is then asked to vote a response to the questions posed in advance by the FDA. Advisory panel recommendations have a strong influence on FDA's decision to approve a product, as evidenced by the 214 Advisory Panels FDA convened between January 2008 to November 2012, during which advisory panel members voted to approve the product (or use of the product) ∼74% of the time, with FDA ultimately approving the medical product (or use of the product) ∼79% of the time. The ACG membership are encouraged to consider serving the public's interest by participating in an FDA advisory panel utilizing their expertise for the evaluation of a new drug or medical device, and providing advice about whether the product should be sold in the US.

Cost-utility and budget impact analysis of drug treatments in pulmonary arterial hypertension associated with congenital heart diseases in Thailand.

PubMed

Thongsri, Watsamon; Bussabawalai, Thanaporn; Leelahavarong, Pattara; Wanitkun, Suthep; Durongpisitkul, Kritvikrom; Chaikledkaew, Usa; Teerawattananon, Yot

2016-08-01

This study aims to compare the lifetime costs and health outcomes of both first-line and sequential combination treatments with standard treatment for pulmonary arterial hypertension (PAH) associated with congenital heart disease (CHD) (PAH-CHD) patients. A cost-utility analysis was performed using a Markov model based on a societal perspective. One-way and probabilistic sensitivity analyses were performed to investigate the effect of parameter uncertainty. As first-line treatments, both beraprost (incremental cost-effectiveness ratio (ICER) = 192,752 and 201,308 Thai baht (THB) per quality-adjusted life year (QALY) gained) and sildenafil (ICER = 249,770 and 226,802 THB per QALY gained) seemed cost-effective for PAH-CHD patients aged ≤30 years in functional classes II and III, respectively, while no treatment was cost-effective for the sequential combination therapy. Sildenafil should be included in the National Drug List of Essential Medicines as the first-line treatment for PAH-CHD, and its price per dose should be negotiated to be reduced by 43-57%.

Glutamate-Modulating Drugs as a Potential Therapeutic Strategy in Obsessive-Compulsive Disorder

PubMed Central

Marinova, Zoya; Chuang, De-Maw; Fineberg, Naomi

2017-01-01

Objective: Abstract: Obsessive-compulsive disorder (OCD) is a mental disease commonly associated with severe distress and impairment of social functioning. Serotonin reuptake inhibitors and/or cognitive behavioural therapy are the therapy of choice, however up to 40% of patients do not respond to treatment. Glutamatergic signalling has also been implicated in OCD. The aim of the current study was to review the clinical evidence for therapeutic utility of glutamate-modulating drugs as an augmentation or monotherapy in OCD patients. Methods: We conducted a search of the MEDLINE database for clinical studies evaluating the effect of glutamate-modulating drugs in OCD. Results: Memantine is the compound most consistently showing a positive effect as an augmentation therapy in OCD. Anti-convulsant drugs (lamotrigine, topiramate) and riluzole may also provide therapeutic benefit to some OCD patients. Finally, ketamine may be of interest due to its potential for a rapid onset of action. Conclusion: Further randomized placebo-controlled trials in larger study populations are necessary in order to draw definitive conclusions on the utility of glutamate-modulating drugs in OCD. Furthermore, genetic and epigenetic factors, clinical symptoms and subtypes predicting treatment response to glutamate-modulating drugs need to be investigated systematically. PMID:28322166

UniDrug-target: a computational tool to identify unique drug targets in pathogenic bacteria.

PubMed

Chanumolu, Sree Krishna; Rout, Chittaranjan; Chauhan, Rajinder S

2012-01-01

Targeting conserved proteins of bacteria through antibacterial medications has resulted in both the development of resistant strains and changes to human health by destroying beneficial microbes which eventually become breeding grounds for the evolution of resistances. Despite the availability of more than 800 genomes sequences, 430 pathways, 4743 enzymes, 9257 metabolic reactions and protein (three-dimensional) 3D structures in bacteria, no pathogen-specific computational drug target identification tool has been developed. A web server, UniDrug-Target, which combines bacterial biological information and computational methods to stringently identify pathogen-specific proteins as drug targets, has been designed. Besides predicting pathogen-specific proteins essentiality, chokepoint property, etc., three new algorithms were developed and implemented by using protein sequences, domains, structures, and metabolic reactions for construction of partial metabolic networks (PMNs), determination of conservation in critical residues, and variation analysis of residues forming similar cavities in proteins sequences. First, PMNs are constructed to determine the extent of disturbances in metabolite production by targeting a protein as drug target. Conservation of pathogen-specific protein's critical residues involved in cavity formation and biological function determined at domain-level with low-matching sequences. Last, variation analysis of residues forming similar cavities in proteins sequences from pathogenic versus non-pathogenic bacteria and humans is performed. The server is capable of predicting drug targets for any sequenced pathogenic bacteria having fasta sequences and annotated information. The utility of UniDrug-Target server was demonstrated for Mycobacterium tuberculosis (H37Rv). The UniDrug-Target identified 265 mycobacteria pathogen-specific proteins, including 17 essential proteins which can be potential drug targets. UniDrug-Target is expected to accelerate

Drug–Target Kinetics in Drug Discovery

PubMed Central

2017-01-01

The development of therapies for the treatment of neurological cancer faces a number of major challenges including the synthesis of small molecule agents that can penetrate the blood-brain barrier (BBB). Given the likelihood that in many cases drug exposure will be lower in the CNS than in systemic circulation, it follows that strategies should be employed that can sustain target engagement at low drug concentration. Time dependent target occupancy is a function of both the drug and target concentration as well as the thermodynamic and kinetic parameters that describe the binding reaction coordinate, and sustained target occupancy can be achieved through structural modifications that increase target (re)binding and/or that decrease the rate of drug dissociation. The discovery and deployment of compounds with optimized kinetic effects requires information on the structure–kinetic relationships that modulate the kinetics of binding, and the molecular factors that control the translation of drug–target kinetics to time-dependent drug activity in the disease state. This Review first introduces the potential benefits of drug-target kinetics, such as the ability to delineate both thermodynamic and kinetic selectivity, and then describes factors, such as target vulnerability, that impact the utility of kinetic selectivity. The Review concludes with a description of a mechanistic PK/PD model that integrates drug–target kinetics into predictions of drug activity. PMID:28640596

Drugp-Induced Rhabdomyolysis Atlas (DIRA) for idiosyncratic adverse drug reaction management.

PubMed

Wen, Zhining; Liang, Yu; Hao, Yingyi; Delavan, Brian; Huang, Ruili; Mikailov, Mike; Tong, Weida; Li, Menglong; Liu, Zhichao

2018-06-11

Drug-induced rhabdomyolysis (DIR) is an idiosyncratic and fatal adverse drug reaction (ADR) characterized in severe muscle injuries accompanied by multiple-organ failure. Limited knowledge regarding the pathophysiology of rhabdomyolysis is the main obstacle to developing early biomarkers and prevention strategies. Given the lack of a centralized data resource to curate, organize, and standardize widespread DIR information, here we present a Drug-Induced Rhabdomyolysis Atlas (DIRA) that provides DIR-related information, including: a classification scheme for DIR based on drug labeling information; postmarketing surveillance data of DIR; and DIR drug property information. To elucidate the utility of DIRA, we used precision dosing, concomitant use of DIR drugs, and predictive modeling development to exemplify strategies for idiosyncratic ADR (IADR) management. Published by Elsevier Ltd.

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.

Advanced systems biology methods in drug discovery and translational biomedicine.

PubMed

Zou, Jun; Zheng, Ming-Wu; Li, Gen; Su, Zhi-Guang

2013-01-01

Systems biology is in an exponential development stage in recent years and has been widely utilized in biomedicine to better understand the molecular basis of human disease and the mechanism of drug action. Here, we discuss the fundamental concept of systems biology and its two computational methods that have been commonly used, that is, network analysis and dynamical modeling. The applications of systems biology in elucidating human disease are highlighted, consisting of human disease networks, treatment response prediction, investigation of disease mechanisms, and disease-associated gene prediction. In addition, important advances in drug discovery, to which systems biology makes significant contributions, are discussed, including drug-target networks, prediction of drug-target interactions, investigation of drug adverse effects, drug repositioning, and drug combination prediction. The systems biology methods and applications covered in this review provide a framework for addressing disease mechanism and approaching drug discovery, which will facilitate the translation of research findings into clinical benefits such as novel biomarkers and promising therapies.

Patterns of pre-treatment drug abuse, drug treatment history and characteristics of addicts in methadone maintenance treatment in Iran

PubMed Central

2012-01-01

Background Opiates are the main drugs of abuse, and Methadone Maintenance Treatment (MMT) is the most widely administered drug addiction treatment program in Iran. Our study aimed to investigate patterns of pre-treatment drug abuse, addiction treatment history and characteristics of patients in MMT in Tehran. Methods We applied a stratified cluster random sampling technique and conducted a cross-sectional survey utilizing a standard patient characteristic and addiction history form with patients (n = 810) in MMT. The Chi-square test and t-test served for statistical analyses. Results A clear majority of the participants were men (96%), more than 60% of whom were between 25 and 44 years of age, educated (89% had more than elementary education), and employed (>70%). The most commonly reported main drugs of abuse prior to MMT entry were opium (69%) and crystalline heroin (24%). The patients’ lifetime drug experience included opium (92%), crystalline heroin (28%), cannabis (16%), amphetamines (15%), and other drugs (33%). Crystalline heroin abusers were younger than opium users, had begun abusing drugs earlier, and reported a shorter history of opiate addiction. Conclusion Opium and crystalline heroin were the main drugs of abuse. A high rate of addiction using more dangerous opiate drugs such as crystalline heroin calls for more preventive efforts, especially among young men. PMID:22676557