Reliability and Validity of the Alcohol Short Index of Problems and a Newly Constructed Drug Short Index of Problems*

PubMed Central

Alterman, Arthur I.; Cacciola, John S.; Ivey, Megan A.; Lynch, Kevin G.

2009-01-01

Objective: This study evaluated the psychometric properties of the 15-item alcohol Short Index of Problems (SIP) instrument and those of a newly constructed 15-item drug Short Index of Problems (SIP-D) instrument in 277 newly entered substance-abuse patients. Method: The SIP is derived from the longer, 50-item Drinker Inventory of Consequences (DrInC), which was designed to assess adverse consequences of alcohol use. The SIP-D was constructed by substituting the term “drug use” for the term “drinking” in each SIP item. A 3-month recall interval was employed. Results: Factor analyses of each of the instruments revealed similar solutions, with only one main factor accounting for the majority of variance. Nonparametric item response theory methods produced the same finding. Internal consistency reliability estimates for the SIP and SIP-D total scores were .98 and .97, respectively. Concurrent validity was demonstrated by examining the correlations of the total scores for each of the instruments with the recent summary indexes of the newly revised Addiction Severity Index (ASI-Version 6): alcohol, drug, medical, economic, legal, family/social, and psychiatric problems. Conclusions: This study is the first to confirm the psychometric validity of the SIP when used as an independent instrument unembedded within the DrInC. The study also supports the use of the SIP-D as a brief measure of adverse consequences of drug use. The findings strongly support the unidimensional structure of both measures. PMID:19261243

Drug-related problems in type 2 diabetes mellitus patients with dyslipidemia

PubMed Central

2013-01-01

Background Drug-Related Problems (DRPs) commonly occur among type 2 diabetes mellitus (T2DM) patients. However, few studies have been performed on T2DM patients with dyslipidemia. This purpose of this study was to assess drug-related problems (DRPs) and factors associated with its occurrence. Methods The retrospective study involved 208 T2DM in-patients and out-patients with dyslipidemia, and was conducted at a tertiary hospital in Malaysia from January 2009 to December 2011. The identification and assessment of DRPs were based on the Pharmaceutical Care Network Europe (PCNE) tool version 5.01. The potentially inappropriate medication use in older adults was assessed based on the American Geriatrics Society updated Beers Criteria. Results A total of 406 DRPs were identified. Among these patients, 91.8% had at least one DRP, averaging 1.94 ± 1.10 problems per patient. The majority of T2DM patients with dyslipidemia (91.8%) had at least one DRP. The most frequent types of DRP were potential drug-drug interaction (18.0%), drug not taken or administered (14.3%) and insufficient awareness of health and diseases (11.8%). Anti-hypertensive, lipid-modifying and anti-diabetic agents were the drug classes that were most likely to be associated with DRPs. Male gender, renal impairment, polypharmacy and poor lipid control were factors that were significantly associated with DRP in diabetic dyslipidemia patients. Conclusion Early identification of DRPs and factors associated with them are essential to prevent and resolve DRPs in T2DM patients with dyslipidemia. PMID:24341672

Racial discrimination, post-traumatic stress and prescription drug problems among Aboriginal Canadians.

PubMed

Currie, Cheryl; Wild, T Cameron; Schopflocher, Donald; Laing, Lory

2015-06-24

1) To examine associations between racial discrimination and drug problems among urban-based Aboriginal adults; and 2) to determine whether these associations are best explained by symptoms of psychological stress, distress or post-traumatic stress disorder (PTSD). Data were collected through in-person surveys with a community-based sample of Aboriginal adults (N = 372) living in a mid-sized city in western Canada in 2010. Associations were examined using bootstrapped linear regression models adjusted for confounders, with continuous prescription and illicit drug problem scores as outcomes. Mediation was examined using the cross-products of coefficients method. More than 80% of Aboriginal adults had experienced racial discrimination in the past year, with the majority reporting high levels in that period. Past-year discrimination was a risk factor for PTSD symptoms and prescription drug problems in models adjusted for confounders and other forms of psychological trauma. In mediation models, PTSD symptoms explained the association between discrimination and prescription drug problems; psychological stress and distress did not. PTSD symptoms also explained this association when the covariance between mediators was controlled. The results also indicate that participation in Aboriginal cultural traditions was associated with increased discrimination. Most efforts to address Aboriginal health inequities in Canada have focused on the role Aboriginal people play in these disparities. The current findings combine with others to call for an expanded focus. Non-Aboriginal Canadians may also play a role in the health inequities observed. The findings of this study suggest efforts to reduce discrimination experienced by Aboriginal adults in cities may reduce PTSD symptomology and prescription drug problems in these populations.

Preventing Alcohol and Other Drug Problems through Drug Education. Policy Bulletin No. 3.

ERIC Educational Resources Information Center

Bailey, William J.

Public schools have a responsibility to educate students about drug abuse, and states have a responsibility to assist schools in their efforts. Properly designed and implemented drug education programs are the most cost-effective means of preventing alcohol and other drug problems. Poorly designed and implemented programs, on the other hand, can…

Crystallization Methods for Preparation of Nanocrystals for Drug Delivery System.

PubMed

Gao, Yuan; Wang, Jingkang; Wang, Yongli; Yin, Qiuxiang; Glennon, Brian; Zhong, Jian; Ouyang, Jinbo; Huang, Xin; Hao, Hongxun

2015-01-01

Low water solubility of drug products causes delivery problems such as low bioavailability. The reduced particle size and increased surface area of nanocrystals lead to the increasing of the dissolution rate. The formulation of drug nanocrystals is a robust approach and has been widely applied to drug delivery system (DDS) due to the significant development of nanoscience and nanotechnology. It can be used to improve drug efficacy, provide targeted delivery and minimize side-effects. Crystallization is the main and efficient unit operation to produce nanocrystals. Both traditional crystallization methods such as reactive crystallization, anti-solvent crystallization and new crystallization methods such as supercritical fluid crystallization, high-gravity controlled precipitation can be used to produce nanocrystals. The current mini-review outlines the main crystallization methods addressed in literature. The advantages and disadvantages of each method were summarized and compared.

Early Twentieth Century Responses to the Drug Problem.

ERIC Educational Resources Information Center

Pfennig, Dennis Joseph

1991-01-01

Describes early twentieth-century responses to the drug problem in the United States. Discusses pressure from the media and reformers to control the availability of drugs such as opium and cocaine that were widely available in over-the-counter medications. Focuses on New York State, which took the lead in enacting drug control legislation. (DK)

Prescription drug abuse: problem, policies, and implications.

PubMed

Phillips, Janice

2013-01-01

This article provides an overview on prescription drug abuse and highlights a number of related legislative bills introduced during the 112th Congress in response to this growing epidemic. Prescription drug abuse has emerged as the nation's fastest growing drug problem. Although prescription drugs have been used effectively and appropriately for decades, deaths from prescription pain medicine in particular have reached epidemic proportions. Bills related to prescription drug abuse introduced during the 112th Congress focus on strengthening provider and consumer education, tracking and monitoring prescription drug abuse, improving data collection on drug overdose fatalities, combating fraud and abuse in Medicare and Medicaid programs, reclassifying drugs to make them more difficult to prescribe and obtain, and enforcing stricter penalties for individuals who operate scam pain clinics and sell pain pills illegitimately. This article underscores the importance of a multifaceted approach to combating prescription drug abuse and concludes with implications for nursing. Copyright © 2013. Published by Mosby, Inc.

Policy Issues and the Drug Abuse Problem in America: Overview, Critique, and Recommendations.

ERIC Educational Resources Information Center

Johnston, Lloyd D.

The so-called "drug abuse problem" in America is really a constellation of separate but related problems; since a variety of drugs are illicitly used, and drug abuse leads to many derivative problems, both within and outside the United States. This monograph begins by assessing the current state of the drug abuse problem in America, and analyzing…

Testing the effects of brief intervention in primary care for problem drug use in a randomized controlled trial: rationale, design, and methods.

PubMed

Krupski, Antoinette; Joesch, Jutta M; Dunn, Chris; Donovan, Dennis; Bumgardner, Kristin; Lord, Sarah Peregrine; Ries, Richard; Roy-Byrne, Peter

2012-12-14

A substantial body of research has established the effectiveness of brief interventions for problem alcohol use. Following these studies, national dissemination projects of screening, brief intervention (BI), and referral to treatment (SBIRT) for alcohol and drugs have been implemented on a widespread scale in multiple states despite little existing evidence for the impact of BI on drug use for non-treatment seekers. This article describes the design of a study testing the impact of SBIRT on individuals with drug problems, its contributions to the existing literature, and its potential to inform drug policy. The study is a randomized controlled trial of an SBIRT intervention carried out in a primary care setting within a safety net system of care. Approximately 1,000 individuals presenting for scheduled medical care at one of seven designated primary care clinics who endorse problematic drug use when screened are randomized in a 1:1 ratio to BI versus enhanced care as usual (ECAU). Individuals in both groups are reassessed at 3, 6, 9, and 12 months after baseline. Self-reported drug use and other psychosocial measures collected at each data point are supplemented by urine analysis and public health-related data from administrative databases. This study will contribute to the existing literature by providing evidence for the impact of BI on problem drug use based on a broad range of measures including self-reported drug use, urine analysis, admission to drug abuse treatment, and changes in utilization and costs of health care services, arrests, and death with the intent of informing policy and program planning for problem drug use at the local, state, and national levels. ClinicalTrials.gov NCT00877331.

Drug problems in contemporary China: a profile of Chinese drug users in a metropolitan area.

PubMed

Huang, Kaicheng; Zhang, Lening; Liu, Jianhong

2011-03-01

Drug problems are reemerging in China since the nation implemented economic reform and an "open door" policy in the early 1980s. This is causing both national and international concern. However, knowledge and understanding of the Chinese drug problem is fairly limited because of the nation's unique social and political history. In response to this shortage of information, our study presents a profile of Chinese drug users. Data were collected from a survey of drug users attending mandatory treatment centres in a large city in 2009. We present a demographic profile of the drug users, describe their patterns of drug use, their access to drugs and their history of drug treatment. Chinese drug users, like those from the U.S., are likely to be unemployed and have a low level of education. However, they are more likely than those in the U.S. to use heroin, Bingdu (methamphetamine) and Maguo (a derivative of methamphetamine), and they pay less for their drugs. This profile of drug users is informative and valuable for drug prevention, intervention, and treatment in the Chinese setting because knowing and understanding the drug population is essential for effective control. Copyright © 2010 Elsevier B.V. All rights reserved.

Drug-related visits to the emergency department: how big is the problem?

PubMed

Patel, Payal; Zed, Peter J

2002-07-01

To review the literature concerning drug-related problems that result in emergency department visits, estimate the frequency of these problems and the rates of hospital admissions, and identify patient risk factors and drugs that are associated with the greatest risk. A systematic search of MEDLINE (January 1966-December 2001), EMBASE (January 1980-December 2001), and PubMed (January 1966-December 2001) databases for full reports published in English was performed. The Ottawa Valley Regional Drug Information Service database of nonindexed pharmacy journals also was searched. Data from eight retrospective and four prospective trials retrieved indicated that as many as 28% of all emergency department visits were drug related. Of these, 70% were preventable, and as many as 24% resulted in hospital admission. Drug classes often implicated in drug-related visits to an emergency department were nonsteroidal antiinflammatory drugs, anticonvulsants, antidiabetic drugs, antibiotics, respiratory drugs, hormones, central nervous system drugs, and cardiovascular drugs. Common drug-related problems resulting in emergency department visits were adverse drug reactions, noncompliance, and inappropriate prescribing. Drug-related problems are a significant cause of emergency department visits and subsequent resource use. Primary caregivers, such as family physicians and pharmacists, should collaborate more closely to provide and reinforce care plans and monitor patients to prevent drug-related visits to the emergency department and subsequent morbidity and mortality.

[Adverse reactions and other drug-related problems in an emergency service department].

PubMed

Güemes Artiles, M; Sanz Alvarez, E; Garcia Sánchez-Colomer, M

1999-01-01

Adverse Drug Reactions (ADR) and Drug-Related Problems (DRP's) are a frequency cause of hospital emergency room visits and require better assessment. An analysis was made of 1097 consecutive admission to the emergency room at the Nuestra Senora de los Volcanes, Hospital (currently the General Hospital of Lanzarote) in Arrecife de Lanzarote (Canary Islands) over a three-month period in order to detect any possible DAR or any other drug-related problems. Nineteen (19) of the 1097 admissions were due to Adverse Drug Reactions (ADR) (1.73%; 95% IC:0.96%-2.5%). Some of the most outstanding of the other "Drug-Related Problems" (DRP's) were medication overdose, which was diagnosed in 5 (0.45%) of the patients; the worsening of the symptoms due to ceasing to take the medication was involved in 8 (0.72%), and incorrect treatments which involved medical care at the emergency room totaled 11 (1.0%). The number of drug-related problems (DRP's) in the sample totaled 43 (3.9%). The drug-related problems (DRP's) led to hospitalization in 1.9% of the cases seen in the emergency room and led to hospitalization in 9.6% of all of hospital admission through the emergency room for the period of time under study. The ADR led to 4.1% of the hospital admissions. Drug-related problems are a frequent, major problem which has not been well-analyzed in the emergency rooms. Additionally, emergency rooms can function as the first point of detection of a ADR among an outpatient population.

[The Swiss population and drug problems: perception of the problems and proposals for solutions].

PubMed

Leuthold, A; Cattaneo, M; Dubois-Arber, F

1993-01-01

The aim of this study is to investigate which problems in relation with drug abuse are considered to be the most important by the Swiss population and which measures do they support to reduce them. Base for this study are the results of a representative telephone survey realized in october 1991 with 1004 Swiss residents. People are mostly concerned with problems related to the danger for youth and those concerning public order but also with the human condition of addicts. Drug addicts are considered as people who have lost the sense of live, as sick but also as dangerous and less truthful. Supported are overall prevention, offers for therapies, the repression of trafficking and money-laundering but not of drug users as well as measures going in the direction of harm-minimisation (shooting rooms, medical prescription of drugs). Younger people, those with higher education and the german-speaking population have a more positive view of drug addicts and support measures in the sense of harm-minimisation. Elder people and the french-speaking population have a rather negative view of drug addicts and don't favour measures for harm-minimisation.

Reliability and validity of the alcohol short index of problems and a newly constructed drug short index of problems.

PubMed

Alterman, Arthur I; Cacciola, John S; Ivey, Megan A; Habing, Brian; Lynch, Kevin G

2009-03-01

This study evaluated the psychometric properties of the 15-item alcohol Short Index of Problems (SIP) instrument and those of a newly constructed 15-item drug Short Index of Problems (SIP-D) instrument in 277 newly entered substance-abuse patients. The SIP is derived from the longer, 50-item Drinker Inventory of Consequences (DrInC), which was designed to assess adverse consequences of alcohol use. The SIP-D was constructed by substituting the term "drug use" for the term "drinking" in each SIP item. A 3-month recall interval was employed. Factor analyses of each of the instruments revealed similar solutions, with only one main factor accounting for the majority of variance. Nonparametric item response theory methods produced the same finding. Internal consistency reliability estimates for the SIP and SIP-D total scores were .98 and .97, respectively. Concurrent validity was demonstrated by examining the correlations of the total scores for each of the instruments with the recent summary indexes of the newly revised Addiction Severity Index (ASI-Version 6): alcohol, drug, medical, economic, legal, family/social, and psychiatric problems. This study is the first to confirm the psychometric validity of the SIP when used as an independent instrument unembedded within the DrInC. The study also supports the use of the SIP-D as a brief measure of adverse consequences of drug use. The findings strongly support the unidimensional structure of both measures.

A guided interview process to improve student pharmacists' identification of drug therapy problems.

PubMed

Rovers, John; Miller, Michael J; Koenigsfeld, Carrie; Haack, Sally; Hegge, Karly; McCleeary, Erin

2011-02-10

To measure agreement between advanced pharmacy practice experience students using a guided interview process and experienced clinical pharmacists using standard practices to identify drug therapy problems. Student pharmacists enrolled in an advanced pharmacy practice experience (APPE) and clinical pharmacists conducted medication therapy management interviews to identify drug therapy problems in elderly patients recruited from the community. Student pharmacists used a guided interview tool, while clinical pharmacists' interviews were conducted using their usual and customary practices. Student pharmacists also were surveyed to determine their perceptions of the interview tool. Fair to moderate agreement was observed on student and clinical pharmacists' identification of 4 of 7 drug therapy problems. Of those, agreement was significantly higher than chance for 3 drug therapy problems (adverse drug reaction, dosage too high, and needs additional drug therapy) and not significant for 1 (unnecessary drug therapy). Students strongly agreed that the interview tool was useful but agreed less strongly on recommending its use in practice. The guided interview process served as a useful teaching aid to assist student pharmacists to identify drug therapy problems.

Problem drug use the public health imperative: what some of the literature says.

PubMed

Bevan, Gez

2009-12-16

With more than 200,000 problem drug users is contact with structured treatment services in England the public health imperative behind drug treatment is great. Problem drug use for many is a chronic and relapsing condition, where "cure" is often neither a reasonable or appropriate expectation and it can further be argued that in these circumstances problem drug use is no different from any number of chronic and enduring health conditions that are managed in the health care system and therefore should be conceptualised as such. A public health approach to drug treatment emphasises the need for drug users in or accessing treatment, to reduce their harmful drug use, reduce drug use related risks such as sepsis and overdose and stay alive for longer. However a public health perspective in relation to problem drug use isn't always either apparent or readily understood and to that end there is still a significant need to continue the arguments and debate that treatment and interventions for problem and dependent drug users need to extend beyond an individualistic approach. For the purposes of discussion in this article public and population health will be used interchangeably. A recognition and acceptance that a public and population health approach to the management of problem drug users is sound public health policy also then requires a long term commitment in terms of staffing and resources where service delivery mirrors that of chronic condition management.

49 CFR 40.199 - What problems always cause a drug test to be cancelled?

Code of Federal Regulations, 2013 CFR

2013-10-01

... 49 Transportation 1 2013-10-01 2013-10-01 false What problems always cause a drug test to be cancelled? 40.199 Section 40.199 Transportation Office of the Secretary of Transportation PROCEDURES FOR TRANSPORTATION WORKPLACE DRUG AND ALCOHOL TESTING PROGRAMS Problems in Drug Tests § 40.199 What problems always cause a drug test to be cancelled? (a...

Medical problems related to recreational drug use at nocturnal dance parties.

PubMed

Van Sassenbroeck, Diederik K; Calle, Paul A; Rousseau, Filip M; Verstraete, Alain G; Belpaire, Frans M; Monsieurs, Koenraad G; Haentjens, Raoul; Allonsius, Jacques; Van Brantegem, Jean; Haenen, Wim; Buylaert, Walter A

2003-12-01

During 'I love techno' (edition 2001), an indoor rave party attended by 37 000 people, data about medical problems (especially drug-related problems) were collected. To place these data in a wider perspective, a similar registration was done during 'De Nacht', a traditional New Year's Eve dance party held at the same location and attended by 12 000 people. Furthermore, a prospective study on the time course of the level of consciousness (Glasgow Coma Score) and blood concentrations of illicit drugs, especially gamma-hydroxybutyrate was set up. The results revealed that during 'I love techno' the incidence of medical problems was high (66.5/10 000 attendees), but not higher than during 'De Nacht' (70.0/10 000 attendees). At 'I love techno', however, mainly illicit drugs were used, more frequently leading to severe drug-related medical problems. The observations in patients with a drug-related medical problem who had taken gamma-hydroxybutyrate showed that for a given level of consciousness the gamma-hydroxybutyrate concentrations may show important differences, that the transition from coma (Glasgow Coma Score < or =7) to full recovery (Glasgow Coma Score 15) takes only 30-60 min (and only a small decrease in gamma-hydroxybutyrate concentrations), and that the time it takes before a comatose patient reaches the above-mentioned 'transition area' may be a few hours.

The Drug Problem in Black Communities. Working Paper 87-01-01.

ERIC Educational Resources Information Center

Ferguson, Ronald F.

The drug problem among blacks in the United States is analyzed, focusing on low-income communities and the involvement of children. Interviews with more than 30 community-based black professionals in Washington (District of Columbia), Cleveland (Ohio), and San Francisco (California), whose jobs place them in daily contact with the drug problem,…

The Commissioning and Provision of Advocacy for Problem Drug Users in English DATS: A Cross-Sectional Survey

ERIC Educational Resources Information Center

Cargill, Tamsin; Weaver, Tim D.; Patterson, Sue

2012-01-01

Aims: This study investigated the commissioning and delivery of advocacy for problem drug users. We aimed to quantify provision, describe the commissioning of advocacy services in Drug Action Teams (DATs) and to identify factors influencing advocacy provision. Methods: A cross-sectional survey of a randomly selected sample of 50 English DATs. The…

Drug use, mental health and problems related to crime and violence: cross-sectional study1

PubMed Central

Claro, Heloísa Garcia; de Oliveira, Márcia Aparecida Ferreira; Bourdreaux, Janet Titus; Fernandes, Ivan Filipe de Almeida Lopes; Pinho, Paula Hayasi; Tarifa, Rosana Ribeiro

2015-01-01

Objective: to investigate the correlation between disorders related to the use of alcohol and other drugs and symptoms of mental disorders, problems related to crime and violence and to age and gender. Methods: cross-sectional descriptive study carried out with 128 users of a Psychosocial Care Center for Alcohol and other Drugs, in the city of São Paulo, interviewed by means of the instrument entitled Global Appraisal of Individual Needs - Short Screener. Univariate and multiple linear regression models were used to verify the correlation between the variables. Results: using univariate regression models, internalizing and externalizing symptoms and problems related to crime/violence proved significant and were included in the multiple model, in which only the internalizing symptoms and problems related to crime and violence remained significant. Conclusions: there is a correlation between the severity of problems related to alcohol use and severity of mental health symptoms and crime and violence in the study sample. The results emphasize the need for an interdisciplinary and intersectional character of attention to users of alcohol and other drugs, since they live in a socially vulnerable environment. PMID:26626010

Selective Prevention: Addressing Vulnerability to Problem Drug Use in Europe

ERIC Educational Resources Information Center

Burkhart, Gregor; Gyarmathy, V. Anna; Bo, Alessandra

2011-01-01

Following the 2003 publication of the European Union (EU) Council Recommendations and the 2005-2008 and 2009-2012 EU Drugs Action Plans, increasing attention has been given in EU member states' drug policies to populations that are vulnerable to problem drug use (PDU). Monitoring data reported to the EMCDDA by designated agencies from 30 countries…

2010 drug packaging review: identifying problems to prevent errors.

PubMed

2011-06-01

Prescrire's analyses showed that the quality of drug packaging in 2010 still left much to be desired. Potentially dangerous packaging remains a significant problem: unclear labelling is source of medication errors; dosing devices for some psychotropic drugs create a risk of overdose; child-proof caps are often lacking; and too many patient information leaflets are misleading or difficult to understand. Everything that is needed for safe drug packaging is available; it is now up to regulatory agencies and drug companies to act responsibly. In the meantime, health professionals can help their patients by learning to identify the pitfalls of drug packaging and providing safe information to help prevent medication errors.

Prisoners' views about the drugs problem in prisons, and the new Prison Service drug strategy.

PubMed

Gore, S M; Bird, A G; Cassidy, J

1999-09-01

Three hundred and seventy-five out of 575 prisoners (222/299 drug users and 153/267 non-users) who responded to a self-completion health care questionnaire at two prisons in 1997 commented on drugs in prisons. One hundred and forty-eight out of 176 responses expressed negative opinions about mandatory drugs testing (MDT), and 107 said that MDT promoted switching to or increased use of heroin/hard drugs'. Sixty-two prisoners suggested that more help/counselling was needed for drug users, 52 segregation of drug users/drug-free wings, and 50 more security on visits/in corridors after medication. The new Prison Service drug strategy has revised random MDT. It targets those who supply drugs, and supports those who want to stop using drugs, and accords with prisoners' views about the heroin problem in prisons.

[Analysis of drug-related problems in a tertiary university hospital in Barcelona (Spain)].

PubMed

Ferrández, Olivia; Casañ, Borja; Grau, Santiago; Louro, Javier; Salas, Esther; Castells, Xavier; Sala, Maria

2018-05-07

To describe drug-related problems identified in hospitalized patients and to assess physicians' acceptance rate of pharmacists' recommendations. Retrospective observational study that included all drug-related problems detected in hospitalized patients during 2014-2015. Statistical analysis included a descriptive analysis of the data and a multivariate logistic regression to evaluate the association between pharmacists' recommendation acceptance rate and the variable of interest. During the study period 4587 drug-related problems were identified in 44,870 hospitalized patients. Main drug-related problems were prescription errors due to incorrect use of the computerized physician order entry (18.1%), inappropriate drug-drug combination (13.3%) and dose adjustment by renal and/or hepatic function (11.5%). Acceptance rate of pharmacist therapy advice in evaluable cases was 81.0%. Medical versus surgical admitting department, specific types of intervention (addition of a new drug, drug discontinuation and correction of a prescription error) and oral communication of the recommendation were associated with a higher acceptance rate. The results of this study allow areas to be identified on which to implement optimization strategies. These include training courses for physicians on the computerized physician order entry, on drugs that need dose adjustment with renal impairment, and on relevant drug interactions. Copyright © 2018 SESPAS. Publicado por Elsevier España, S.L.U. All rights reserved.

Handbook for the Prevention and Control of Drug Problems.

ERIC Educational Resources Information Center

Parsippany - Troy Hills Board of Education, Parsippany, NJ.

Guidelines for teachers relative to drug abuse are developed in this handbook offering special steps necessary in attempting to prevent and/or guide students with a drug problem. Stress is placed on helping each student individually understand the forces affecting him, and in helping him form the necessary positive attitudes to cope with each…

Solving Drug-Related Problems in the Professional Experience Program.

ERIC Educational Resources Information Center

Kane, Michael P.; And Others

1993-01-01

A study investigated the effectiveness of using the Pharmacist's Work-up of Drug Therapy (PWDT) in teaching 91 pharmacy students in a clinical clerkship program to identify and solve drug-related problems. Because the instructional technique was recently implemented, the study looked at effects of 3 different quantities of training (0, 1, and 3…

Computational methods in drug discovery

PubMed Central

Leelananda, Sumudu P

2016-01-01

The process for drug discovery and development is challenging, time consuming and expensive. Computer-aided drug discovery (CADD) tools can act as a virtual shortcut, assisting in the expedition of this long process and potentially reducing the cost of research and development. Today CADD has become an effective and indispensable tool in therapeutic development. The human genome project has made available a substantial amount of sequence data that can be used in various drug discovery projects. Additionally, increasing knowledge of biological structures, as well as increasing computer power have made it possible to use computational methods effectively in various phases of the drug discovery and development pipeline. The importance of in silico tools is greater than ever before and has advanced pharmaceutical research. Here we present an overview of computational methods used in different facets of drug discovery and highlight some of the recent successes. In this review, both structure-based and ligand-based drug discovery methods are discussed. Advances in virtual high-throughput screening, protein structure prediction methods, protein–ligand docking, pharmacophore modeling and QSAR techniques are reviewed. PMID:28144341

Computational methods in drug discovery.

PubMed

Leelananda, Sumudu P; Lindert, Steffen

2016-01-01

The process for drug discovery and development is challenging, time consuming and expensive. Computer-aided drug discovery (CADD) tools can act as a virtual shortcut, assisting in the expedition of this long process and potentially reducing the cost of research and development. Today CADD has become an effective and indispensable tool in therapeutic development. The human genome project has made available a substantial amount of sequence data that can be used in various drug discovery projects. Additionally, increasing knowledge of biological structures, as well as increasing computer power have made it possible to use computational methods effectively in various phases of the drug discovery and development pipeline. The importance of in silico tools is greater than ever before and has advanced pharmaceutical research. Here we present an overview of computational methods used in different facets of drug discovery and highlight some of the recent successes. In this review, both structure-based and ligand-based drug discovery methods are discussed. Advances in virtual high-throughput screening, protein structure prediction methods, protein-ligand docking, pharmacophore modeling and QSAR techniques are reviewed.

Child abuse, drug addiction and mental health problems of incarcerated women in Israel.

PubMed

Chen, Gila; Gueta, Keren

2015-01-01

The mental health problems and pathways to drug addiction and crime among female inmates have long been of interest to researchers and practitioners. The purpose of the current study was to examine the possible association between multiple types of childhood abuse, mental health problems, and drug addiction and the incarceration of 50 Israeli women in prison. The findings indicated that female inmates come from risky families with a high prevalence of family mental health problems, parental drug addiction and crime, and sibling drug addiction and crime. Furthermore, they revealed that incarcerated women from risky families were victims of multiple types of childhood abuse and neglect by their parents, as well as their siblings. Overall, the results suggest that the adverse consequences of a family's mental health problems are much more dramatic than we assumed to date, and that women are more likely than men to be the victims of multiple types of childhood abuse and neglect, as well as suffering more severe psychiatric problems, depression, and drug addiction. The implications of these findings are discussed. Copyright © 2015 Elsevier Ltd. All rights reserved.

Coexisting social conditions and health problems among clients seeking treatment for illicit drug use in Finland: The HUUTI study

PubMed Central

2013-01-01

Background Illicit drug use is an important public health problem. Identifying conditions that coexist with illicit drug use is necessary for planning health services. This study described the prevalence and factors associated with social and health problems among clients seeking treatment for illicit drug use. Methods We carried out cross-sectional analyses of baseline data of 2526 clients who sought treatment for illicit drug use at Helsinki Deaconess Institute between 2001 and 2008. At the clients’ first visit, trained clinicians conducted face-to-face interviews using a structured questionnaire. Logistic regression was used to compute adjusted odds ratios (AORs) and 95% confidence intervals (CIs) for factors associated with social and health problems. Results The mean age of the clients was 25 years, 21% (n = 519) were homeless, 54% (n = 1363) were unemployed and 7% (n = 183) had experienced threats of violence. Half of the clients (50%, n = 1258) were self-referred and 31% (n = 788) used opiates as their primary drugs of abuse. Hepatitis C (25%, n = 630) was more prevalent than other infectious diseases and depressive symptoms (59%, n = 1490) were the most prevalent psychological problems. Clients who were self-referred to treatment were most likely than others to report social problems (AOR = 1.86; 95% CI = 1.50–2.30) and psychological problems (AOR = 1.51; 95% CI = 1.23–1.85). Using opiates as primary drugs of abuse was the strongest factor associated with infectious diseases (AOR = 3.89; 95% CI = 1.32–11.46) and for reporting a combination of social and health problems (AOR = 3.24; 95% CI = 1.58–6.65). Conclusion The existence of illicit drug use with other social and health problems could lead to increased utilisation and cost of healthcare services. Coexisting social and health problems may interfere with clients’ treatment response. Our findings support the call for integration of

Development and validation of a Client Problem Profile and Index for drug treatment.

PubMed

Joe, George W; Simpson, D Dwayne; Greener, Jack M; Rowan-Szal, Grace A

2004-08-01

The development of the Client Problem Profile and Index are described, and initial concurrent and predictive validity data are presented for a sample of 547 patients in outpatient methadone treatment. Derived from the TCU Brief Intake for drug treatment admissions, the profile covers 14 problem areas related to drug use (particularly cocaine, heroin/opiate, marijuana, other illegal drugs, and multiple drug use), HIV risks, psychosocial-functioning, health, employment, and criminality. Analyses of predictive validity show the profile and its index (number of problem areas) were significantly related to therapeutic engagement, during-treatment performance, and posttreatment follow-up outcomes. Low moderate to high moderate effect sizes were observed in analyses of the index's discrimination.

Drug problem in southeast and southwest Asia.

PubMed

Kulsudjarit, Kongpetch

2004-10-01

In 2002, the drug problem in Southeast and Southwest Asia was serious, particularly in the production of opium and heroin in Afghanistan, Myanmar, and Laos, the three largest producers of illicit opium in the world. The increasing illicit manufacture of ATS, particularly methamphetamine, in Southeast Asia, mainly in China and Myanmar, was also a major concern. Some reports indicated that ephedrine, used for illicitly producing methamphetamine in Southeast Asia, is diverted and smuggled out of China and India, whereas caffeine, the adulterant used for producing methamphetamine tablets, is mainly smuggled into Myanmar through its border with Thailand. Seizure data showed a dramatic increase in trafficking in MDMA through Southeast Asia. In terms of the drug epidemic, in 2002, cannabis remained overall the main drug of abuse in all of the countries of Southeast and Southwest Asia. Opiates, mainly opium and heroin, were also the drugs of choice except in Thailand, where opiate abuse declined, but ATS was the main drug of abuse due to its low cost and availability. A significant increase in ATS abuse, amphetamine, methamphetamine, and MDMA among the youth who smoked, sniffed, and inhaled them was reported in Cambodia, China, Indonesia, Laos, Myanmar, the Philippines, and Thailand. Injecting drug use among opiate abusers has been identified as the prime cause of the rapid spread of HIV/AIDS in Southeast and Southwest Asia.

Effects of Motivation and Problem Severity on Court-Based Drug Treatment

ERIC Educational Resources Information Center

Cosden, Merith; Basch, Janice E.; Campos, Emily; Greenwell, Ashley; Barazani, Sivan; Walker, Sara

2006-01-01

This study addresses the effects of motivation and problem severity on outcomes in two court-based drug treatment programs. Data were examined for 578 offenders served by a drug court and 223 served by a drug treatment court mandated through California's Substance Abuse Crime Prevention Act (SACPA). It was hypothesized that client-reported…

Alzheimer’s Disease Drug Development in 2008 and Beyond: Problems and Opportunities

PubMed Central

Becker, Robert E.; Greig, Nigel H.

2008-01-01

Recently, a number of Alzheimer’s disease (AD) multi-center clinical trials (CT) have failed to provide statistically significant evidence of drug efficacy. To test for possible design or execution flaws we analyzed in detail CTs for two failed drugs that were strongly supported by preclinical evidence and by proven CT AD efficacy for other drugs in their class. Studies of the failed commercial trials suggest that methodological flaws may contribute to the failures and that these flaws lurk within current drug development practices ready to impact other AD drug development [1]. To identify and counter risks we considered the relevance to AD drug development of the following factors: (1) effective dosing of the drug product, (2) reliable evaluations of research subjects, (3) effective implementation of quality controls over data at research sites, (4) resources for practitioners to effectively use CT results in patient care, (5) effective disease modeling, (6) effective research designs. New drugs currently under development for AD address a variety of specific mechanistic targets. Mechanistic targets provide AD drug development opportunities to escape from many of the factors that currently undermine AD clinical pharmacology, especially the problems of inaccuracy and imprecision associated with using rated outcomes. In this paper we conclude that many of the current problems encountered in AD drug development can be avoided by changing practices. Current problems with human errors in clinical trials make it difficult to differentiate drugs that fail to evidence efficacy from apparent failures due to Type II errors. This uncertainty and the lack of publication of negative data impede researchers’ abilities to improve methodologies in clinical pharmacology and to develop a sound body of knowledge about drug actions. We consider the identification of molecular targets as offering further opportunities for overcoming current failures in drug development. PMID

Use of refractometry and colorimetry as field methods to rapidly assess antimalarial drug quality.

PubMed

Green, Michael D; Nettey, Henry; Villalva Rojas, Ofelia; Pamanivong, Chansapha; Khounsaknalath, Lamphet; Grande Ortiz, Miguel; Newton, Paul N; Fernández, Facundo M; Vongsack, Latsamy; Manolin, Ot

2007-01-04

The proliferation of counterfeit and poor-quality drugs is a major public health problem; especially in developing countries lacking adequate resources to effectively monitor their prevalence. Simple and affordable field methods provide a practical means of rapidly monitoring drug quality in circumstances where more advanced techniques are not available. Therefore, we have evaluated refractometry, colorimetry and a technique combining both processes as simple and accurate field assays to rapidly test the quality of the commonly available antimalarial drugs; artesunate, chloroquine, quinine, and sulfadoxine. Method bias, sensitivity, specificity and accuracy relative to high-performance liquid chromatographic (HPLC) analysis of drugs collected in the Lao PDR were assessed for each technique. The HPLC method for each drug was evaluated in terms of assay variability and accuracy. The accuracy of the combined method ranged from 0.96 to 1.00 for artesunate tablets, chloroquine injectables, quinine capsules, and sulfadoxine tablets while the accuracy was 0.78 for enterically coated chloroquine tablets. These techniques provide a generally accurate, yet simple and affordable means to assess drug quality in resource-poor settings.

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.

Least bad solutions to the 'drugs problem'.

PubMed

Mugford, S

1991-01-01

This paper examines the current difficulties being faced in Australia by policy-makers attempting to regulate the non-medical use of illegal drugs, and it is suggested that the difficulties centre upon two aspects. First, existing prohibitions are unsuccessful, with use levels rising and, in some arenas (e.g. cocaine use in the USA), quite out of control. On the other hand, a move towards decriminalization or legalization is difficult because past propaganda has been so vehement that a change now apparently risks sending the wrong messages to young people. This dilemma means that there is no solution, including inertia, which is risk-free, nor is there one free of difficulties. It is thus relevant to think in terms of 'least bad' rather than 'best' when formulating a system to face these problems. The exploration of what this least bad solution might be begins with the examination of the prominent myths (such as 'the drug-free society', 'the evil pusher', 'the user as victim' and 'the young person as cultural dope') that hinder our reasoning. Secondly, by suggesting that, in a climate of increasing crime related to drugs, inability of prohibitions to control that use and escalating health risks attendant on use (including the AIDS problem), the central policy thrust must be harm reduction and damage minimization rather than illusory goals such as widespread abstinence. The paper concludes with a discussion of some relevant evidence on alternative options.

The menu-setting problem and subsidized prices: drug formulary illustration.

PubMed

Olmstead, T; Zeckhauser, R

1999-10-01

The menu-setting problem (MSP) determines the goods and services an institution offers and the prices charged. It appears widely in health care, from choosing the services an insurance arrangement offers, to selecting the health plans an employer proffers. The challenge arises because purchases are subsidized, and consumers (or their physician agents) may make cost-ineffective choices. The intuitively comprehensible MSP model--readily solved by computer using actual data--helps structure thinking and support decision making about such problems. The analysis uses drug formularies--lists of approved drugs in a plan or institution--to illustrate the framework.

The Problem of Confounding in Studies of the Effect of Maternal Drug Use on Pregnancy Outcome

PubMed Central

Källén, Bengt

2012-01-01

In most epidemilogical studies, the problem of confounding adds to the uncertainty in conclusions drawn. This is also true for studies on the effect of maternal drug use on birth defect risks. This paper describes various types of such confounders and discusses methods to identify and adjust for them. Such confounders can be found in maternal characteristics like age, parity, smoking, use of alcohol, and body mass index, subfertility, and previous pregnancies including previous birth of a malformed child, socioeconomy, race/ethnicity, or country of birth. Confounding by concomitant maternal drug use may occur. A geographical or seasonal confounding can exist. In rare instances, infant sex and multiple birth can appear as confounders. The most difficult problem to solve is often confounding by indication. The problem of confounding is less important for congenital malformations than for many other pregnancy outcomes. PMID:22190949

An all-embracing problem description. The Swedish drug issue as a political catalyst 1982-2000.

PubMed

Edman, Johan

2013-11-01

This article examines the political formulation and ideological solution of the Swedish drug problem in 1982-2000. How was the drug problem described in the Swedish parliament at the time? How serious was the problem and what solutions were proposed? What were the ideological implications of the problem description, and how was the general political and ideological solution formulated? The empirical basis for the textual analysis consists of parliamentary bills, government bills and parliamentary records discussing the drug issue during the years 1982-2000. In the prevailing spirit of consensus in the Swedish parliament at the time, both left-wing and right-wing parties portrayed drugs as a threat to the nation, people and the welfare state. Still, as the ideological dimension kept growing stronger, the drug question functioned even better as an arena for political discussions and ideological positions than in the 1970s. Compared to previous decades, the problem description broadened during the 1980s and 1990s, and the drug problem could be used to support arguments on almost any topic. The drug problem became a highly politicized issue about whom or what to change when the individual and the society clashed, but also about what the individual and/or society should be changed into. Copyright © 2013 Elsevier B.V. All rights reserved.

Computational Methods in Drug Discovery

PubMed Central

Sliwoski, Gregory; Kothiwale, Sandeepkumar; Meiler, Jens

2014-01-01

Computer-aided drug discovery/design methods have played a major role in the development of therapeutically important small molecules for over three decades. These methods are broadly classified as either structure-based or ligand-based methods. Structure-based methods are in principle analogous to high-throughput screening in that both target and ligand structure information is imperative. Structure-based approaches include ligand docking, pharmacophore, and ligand design methods. The article discusses theory behind the most important methods and recent successful applications. Ligand-based methods use only ligand information for predicting activity depending on its similarity/dissimilarity to previously known active ligands. We review widely used ligand-based methods such as ligand-based pharmacophores, molecular descriptors, and quantitative structure-activity relationships. In addition, important tools such as target/ligand data bases, homology modeling, ligand fingerprint methods, etc., necessary for successful implementation of various computer-aided drug discovery/design methods in a drug discovery campaign are discussed. Finally, computational methods for toxicity prediction and optimization for favorable physiologic properties are discussed with successful examples from literature. PMID:24381236

Illicit and prescription drug problems among urban Aboriginal adults in Canada: the role of traditional culture in protection and resilience.

PubMed

Currie, Cheryl L; Wild, T Cameron; Schopflocher, Donald P; Laing, Lory; Veugelers, Paul

2013-07-01

Illicit and prescription drug use disorders are two to four times more prevalent among Aboriginal peoples in North America than the general population. Research suggests Aboriginal cultural participation may be protective against substance use problems in rural and remote Aboriginal communities. As Aboriginal peoples continue to urbanize rapidly around the globe, the role traditional Aboriginal beliefs and practices may play in reducing or even preventing substance use problems in cities is becoming increasingly relevant, and is the focus of the present study. Mainstream acculturation was also examined. Data were collected via in-person surveys with a community-based sample of Aboriginal adults living in a mid-sized city in western Canada (N = 381) in 2010. Associations were analysed using two sets of bootstrapped linear regression models adjusted for confounders with continuous illicit and prescription drug problem scores as outcomes. Psychological mechanisms that may explain why traditional culture is protective for Aboriginal peoples were examined using the cross-products of coefficients mediation method. The extent to which culture served as a resilience factor was examined via interaction testing. Results indicate Aboriginal enculturation was a protective factor associated with reduced 12-month illicit drug problems and 12-month prescription drug problems among Aboriginal adults in an urban setting. Increased self-esteem partially explained why cultural participation was protective. Cultural participation also promoted resilience by reducing the effects of high school incompletion on drug problems. In contrast, mainstream acculturation was not associated with illicit drug problems and served as a risk factor for prescription drug problems in this urban sample. Findings encourage the growth of programs and services that support Aboriginal peoples who strive to maintain their cultural traditions within cities, and further studies that examine how Aboriginal

[The problem of post-marketing surveillance planning on drugs for infectious disease].

PubMed

Sato, J

2001-12-01

In principle, a new drug is approved via the assessments of safety and efficacy by the Ministry of Health, Labor and Welfare (MHLW). After approval, conduct of post-marketing surveillance is requested by law in order to assess the safety and efficacy of the drug in a large number of patients. Before initiating a surveillance, submission to MHLW of a document on the plan of survey is necessary in the purpose of inspection if it includes any ethical or regulatory problem or not. Through the inspections of the plans submitted during the period of April 1998 and March 2000, many problems have been pointed out. In this report, the author introduces some of the concrete problems noted in the plans on drugs for infectious diseases and shows some of the guidance made by the authority how to improve them. It is expected that such practical analyses of cases may be useful for future planning of post-marketing surveillance on drugs for infectious diseases.

Identifying and Preventing Health Problems among Young Drug-Misusing Offenders

ERIC Educational Resources Information Center

Bennett, Trevor; Holloway, Katy

2008-01-01

Purpose: The purpose of this paper is to identify the health problems and treatment needs of drug-misusing offenders and to draw out the implications of the findings for health education and prevention. Design/methodology/approach: This analysis is based on data collected as part of the New English and Welsh Arrestee Drug Abuse Monitoring…

Potential and problems in ultrasound-responsive drug delivery systems

PubMed Central

Zhao, Ying-Zheng; Du, Li-Na; Lu, Cui-Tao; Jin, Yi-Guang; Ge, Shu-Ping

2013-01-01

Ultrasound is an important local stimulus for triggering drug release at the target tissue. Ultrasound-responsive drug delivery systems (URDDS) have become an important research focus in targeted therapy. URDDS include many different formulations, such as microbubbles, nanobubbles, nanodroplets, liposomes, emulsions, and micelles. Drugs that can be loaded into URDDS include small molecules, biomacromolecules, and inorganic substances. Fields of clinical application include anticancer therapy, treatment of ischemic myocardium, induction of an immune response, cartilage tissue engineering, transdermal drug delivery, treatment of Huntington’s disease, thrombolysis, and disruption of the blood–brain barrier. This review focuses on recent advances in URDDS, and discusses their formulations, clinical application, and problems, as well as a perspective on their potential use in the future. PMID:23637531

Comprehensive Substance Abuse Services for Homeless Persons with Alcohol and Other Drug Problems.

ERIC Educational Resources Information Center

Kirby, Michael W., Jr.; Braucht, G. Nicholas

Homeless people with alcohol and other drug problems present the traditional substance abuse services delivery provider with special challenges. This paper discusses the optimal designs of comprehensive treatment services for homeless persons with alcohol and other drug problems. Most importantly, the homeless must have immediate access to a safe…

Adverse drug events and medication problems in "Hospital at Home" patients.

PubMed

Mann, Elizabeth; Zepeda, Orlando; Soones, Tacara; Federman, Alex; Leff, Bruce; Siu, Albert; Boockvar, Kenneth

2018-03-26

"Hospital at Home(HaH)" programs provide an alternative to traditional hospitalization. However, the incidence of adverse drug events in these programs is unknown. This study describes adverse drug events and potential adverse drug events in a new HaH program. We examined the charts of the first 50 patients admitted. We found 45 potential adverse drug events and 14 adverse drug events from admission to 30 days after HaH discharge. None of the adverse drug events were severe. Some events, like problems with medication administration, may be unique to the hospital at home setting. Monitoring for adverse drug events is feasible and important for hospital at home programs.

The Drug Problem.

ERIC Educational Resources Information Center

Gose, Ben

1995-01-01

Drug law violations have risen sharply on college campuses, but officials disagree on the reason. Some students feel administrators are invading their privacy. The trend is attributed to several factors, including changes in how violations are counted, reduced tolerance of increased drug use by non-drug-using students, and more vigorous…

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

[Effects of the new comprehensive system for designating illegal drug components on the abuse of designer drugs and future problems based on an online questionnaire].

PubMed

Morino, Taichi; Okazaki, Mitsuhiro; Toda, Takaki; Yokoyama, Takashi

2015-12-01

Recently, the abuse of designer drugs has become a social problem. Designer drugs are created by modifying part of the chemical structure of drugs that have already been categorized as illegal, thereby creating a different chemical compound in order to evade Pharmaceutical Affairs Law regulations. The new comprehensive system for designating illegal drug components has been in effect since March 2013, and many designer drugs can now be regulated. We conducted an online questionnaire survey of people with a history of designer drug use to elucidate the effects of the new system on the abuse of designer drugs and to identify potential future problems. Over half the subjects obtained designer drugs only before the new system was implemented. Awareness of the system was significantly lower among subjects who obtained designer drugs for the first time after its introduction than those who obtained the drugs only before its implementation. Due to the new system, all methods of acquiring designer drugs saw decreases in activity. However, the ratio of the acquisition of designer drugs via the Internet increased. Since over 50% of the subjects never obtained designer drugs after the new system was introduced, goals that aimed to make drug procurement more difficult were achieved. However, awareness of the new system among subjects who obtained designer drugs after the new system was introduced was significantly low. Therefore, fostering greater public awareness of the new system is necessary. The results of the questionnaire also suggested that acquiring designer drugs through the Internet has hardly been affected by the new system. We strongly hope that there will be a greater push to restrict the sale of designer drugs on the Internet in the near future.

Analyzing HIV/AIDS and Alcohol and Other Drug Use as a Social Problem

PubMed Central

PATTERSON, DAVID A.; Wolf (Adelv unegv Waya), Silver

2012-01-01

Most prevention and intervention activities directed toward HIV/AIDS and alcohol and other drug use separately as well as the combining of the two (e.g., those who are both HIV/AIDS and using alcohol and other drugs) comes in the form of specific, individualized therapies without consideration of social influences that may have a greater impact on this population. Approaching this social problem from the narrowed view of individualized, mi-cro solutions disregards the larger social conditions that affect or perhaps even are at the root of the problem. This paper analyzes the social problem of HIV/AIDS and alcohol and other drug abuse using three sociological perspectives—social construction theory, ethnomethodology, and conflict theory—informing the reader of the broader influences accompanying this problem. PMID:23264724

Educational Policy and the Drug Problem--A Redistributive Politics Issue

ERIC Educational Resources Information Center

Caliguri, Joseph P.

1975-01-01

The drug problem exists as a cluster of problems affecting broad interests or groups. The issues are redistributive in that everything relates to everything else. It seems apparent that a cluster of policies and programs need development as well as genuine citizen participation in the formulation of these policies. (Author)

49 CFR 40.203 - What problems cause a drug test to be cancelled unless they are corrected?

Code of Federal Regulations, 2013 CFR

2013-10-01

... 49 Transportation 1 2013-10-01 2013-10-01 false What problems cause a drug test to be cancelled unless they are corrected? 40.203 Section 40.203 Transportation Office of the Secretary of Transportation PROCEDURES FOR TRANSPORTATION WORKPLACE DRUG AND ALCOHOL TESTING PROGRAMS Problems in Drug Tests § 40.203 What problems cause a drug test to be...

Potential drug related problems detected by electronic expert support system in patients with multi-dose drug dispensing.

PubMed

Tora, Hammar; Bo, Hovstadius; Bodil, Lidström; Göran, Petersson; Birgit, Eiermann

2014-10-01

Background Drug related problems (DRPs) are frequent and cause suffering for patients and substantial costs for society. Multi-dose drug dispensing (MDDD) is a service by which patients receive their medication packed in bags with one unit for each dose occasion. The clinical decision support system (CDSS) electronic expert support (EES) analyses patients' prescriptions in the Swedish national e-prescription repository and provides alerts if potential DRPs are detected, i.e. drug-drug interactions, duplicate therapy, drug-disease contraindications, high dose, gender warnings, geriatric, and paediatric alerts. Objective To analyse potential DRPs in patients with MDDD, detected by means of EES. Setting A register study of all electronically stored prescriptions for patients with MDDD in Sweden (n = 180,059) March 5-June 5, 2013. Method Drug use and potential DRPs detected in the study population during the 3 month study period by EES were analysed. The potential DRPs were analysed in relation to patients' age, gender, number of drugs, and type of medication. Main outcome measure Prevalence of potential DRPs measured as EES alerts. Results The study population was on average 75.8 years of age (± 17.5, range 1-110) and had 10.0 different medications (± 4.7, range 1-53). EES alerted for potential DRPs in 76 % of the population with a mean of 2.2 alerts per patient (± 2.4, range 0-27). The older patients received a lower number of alerts compared to younger patients despite having a higher number of drugs. The most frequent alert categories were drug-drug interactions (37 % of all alerts), duplicate therapy (30 %), and geriatric warnings for high dose or inappropriate drugs (23 %). Psycholeptics, psychoanaleptics, antithrombotic agents, anti-epileptics, renin-angiotensin system agents, and analgesics represented 71 % of all drugs involved in alerts. Conclusions EES detected potential DRPs in the majority of patients with MDDD. The number of potential DRPs was

Developing natural product drugs: Supply problems and how they have been overcome.

PubMed

Newman, David J

2016-06-01

The development of natural product-derived drugs has some unique problems associated with the process, which can be best described as the "problem of supply". In this short review, four examples are given demonstrating how the "supply problem" was overcome using as examples the development of Picato® from a plant, Kyprolis® modified from a microbial metabolite, Halaven® a totally synthetic compound based on a marine sponge metabolite and Yondelis® isolated from a marine tunicate and now known to be from an as yet uncultured microbe in the tunicate. The methods used are described in each case and show how all scientific disciplines are necessary to succeed. All of these are antitumor agents and the time involved ranged from a low of 13years to greater than 29years from the initial identification of an active compound. Copyright © 2015 Elsevier Inc. All rights reserved.

Drug Craving Terminology among Opiate Dependents; A Mixed Method Study

PubMed Central

Maarefvand, Masoomeh; Ghiasvand, Hamid Reza

2013-01-01

Objective Drug craving is defined as an urge to continue substance abuse. Drug dependents use different terms to express their subjective feeling of craving. This study was an attempt to generate an understanding of craving terminology among different groups of Persian speaking Iranian opiate dependents. Method Terms used for the meaning of drug craving were listed by 36 ex-opiate dependents in focus group discussion meetings in the first phase of the study. These terms were composed from Craving Terms Questionnaire. In the second phase, 120 subjects in 3 groups of opiate dependents and a group of Current Opiate Abusers rated usage frequency of each term in the questionnaire under a Twelve-Step Program, Methadone Maintenance, and Other Abstinence-based Programs. Results Eighty nine terms were categorized in stimulation and triggering, attention bias and obsession, decision making difficulty, information processing impairment, withdrawal induction, drug euphoric experience, mental urge, motor control problem, negative valancing and stigmatizing. Terms for the three categories of mental urge, attention bias and obsession and motor control problem were used more than others. Patients in Methadone Maintenance Treatment (MMT) group used different categories of craving terms in comparison to other groups. Abstinent cases reported higher total score for craving terms in comparison to other groups in Twelve-Step Program and other abstinence-based programs. Conclusion Each craving-related term is associated with some aspects of the multidimensional concept of craving. A drug-craving thesaurus could provide a better understanding of craving nature from a drug dependent point of view. There are differences among abstinence vs. maintenance based treated opiate dependents in using craving terms. Addiction therapists will benefit from accessing drug dependents’ lexicon to assess and create therapeutic alliance with their clients. PMID:24130609

The Relationship of Social Problem-Solving Skills and Dysfunctional Attitudes with Risk of Drug Abuse among Dormitory Students at Isfahan University of Medical Sciences

PubMed Central

Nasrazadani, Ehteram; Maghsoudi, Jahangir; Mahrabi, Tayebeh

2017-01-01

Background: Dormitory students encounter multiple social factors which cause pressure, such as new social relationships, fear of the future, and separation from family, which could cause serious problems such as tendency toward drug abuse. This research was conducted with the goal to determine social problem-solving skills, dysfunctional attitudes, and risk of drug abuse among dormitory students of Isfahan University of Medical Sciences, Iran. Materials and Methods: This was a descriptive-analytical, correlational, and cross-sectional research. The research sample consisted of 211 students living in dormitories. The participants were selected using randomized quota sampling method. The data collection tools included the Social Problem-Solving Inventory (SPSI), Dysfunctional Attitude Scale (DAS), and Identifying People at Risk of Addiction Questionnaire. Results: The results indicated an inverse relationship between social problem-solving skills and risk of drug abuse (P = 0.0002), a direct relationship between dysfunctional attitude and risk of drug abuse (P = 0.030), and an inverse relationship between social problem-solving skills and dysfunctional attitude among students (P = 0.0004). Conclusions: Social problem-solving skills have a correlation with dysfunctional attitudes. As a result, teaching these skills and the way to create efficient attitudes should be considered in dormitory students. PMID:28904539

Annual Report on the State of the Drugs Problem in the European Union, 2000.

ERIC Educational Resources Information Center

European Monitoring Centre for Drugs and Drug Addiction, Lisbon (Portugal).

This report presents an overview of the drug phenomenon in Europe at the start of the new millennium. The first chapter begins with a discussion of overall drug trends. Specifically, it examines trends in drug use and the consequences including multiple drug use; problem drug use and demand for treatment; drug-related deaths; drug-related…

Comparison of Homeless and Non-Homeless Problem Drug Users Recruited from Primary Care Safety-Net Clinics.

PubMed

Krupski, Antoinette; Graves, Meredith C; Bumgardner, Kristin; Roy-Byrne, Peter

2015-11-01

The present study of homeless non-treatment-seeking problem drug users was designed to complement and extend previous studies which focused exclusively on treatment-seeking homeless problem drug users. Data were available for 866 primary care patients with drug problems, 30% homeless and 70% housed. In the 2 years prior to baseline, homeless participants had less chronic medical co-morbidity than problem drug users who were housed yet were significantly more likely to have used emergency department services, to have used them more frequently, and at higher cost. Compared to their housed counterparts, homeless participants were also more likely to have been admitted to specialized chemical dependency treatment and/or detoxification services, to have been arrested for a felony or gross misdemeanor, and to report having psychiatric problems in the prior 30 days. Additional support may be necessary for homeless patients presenting in primary care to benefit from substance abuse treatment given their more severe drug use problems coupled with their co-morbid health, psychiatric, and psychosocial problems. Copyright © 2015 Elsevier Inc. All rights reserved.

The Tentative Drug Use Scale: A Quick and Relatively Problem Free Outcome Measure for Drug Abuse Prevention Projects

ERIC Educational Resources Information Center

Horan, John J.; Williams, John M.

1975-01-01

Difficulties involved with the evaluation of drug abuse prevention programs are numerous. Tentative Drug Use Scale (TDUS) was designed in response to a number of specific problems associated with obtaining behavioral data. Advantages of this scale over others are discussed. Reliability and validity information are provided. (Author)

Alternative Solutions to the Workplace Drug Problem: Results of a Survey of Personnel Managers.

ERIC Educational Resources Information Center

Rosse, Joseph G.; And Others

1990-01-01

Surveyed personnel managers (N=127) to learn more about the prevalence of employee drug use and employer substance abuse programs. Results indicated companies' responses to the drug problem included drug use policies, drug education, employee assistance programs, and drug testing. Recommendations based on findings are discussed. (Author/TE)

Drug-Target Interactions: Prediction Methods and Applications.

PubMed

Anusuya, Shanmugam; Kesherwani, Manish; Priya, K Vishnu; Vimala, Antonydhason; Shanmugam, Gnanendra; Velmurugan, Devadasan; Gromiha, M Michael

2018-01-01

Identifying the interactions between drugs and target proteins is a key step in drug discovery. This not only aids to understand the disease mechanism, but also helps to identify unexpected therapeutic activity or adverse side effects of drugs. Hence, drug-target interaction prediction becomes an essential tool in the field of drug repurposing. The availability of heterogeneous biological data on known drug-target interactions enabled many researchers to develop various computational methods to decipher unknown drug-target interactions. This review provides an overview on these computational methods for predicting drug-target interactions along with available webservers and databases for drug-target interactions. Further, the applicability of drug-target interactions in various diseases for identifying lead compounds has been outlined. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Differential Effects of Parent and Grandparent Drug Use on Behavior Problems of Male and Female Children.

ERIC Educational Resources Information Center

Stein, Judith A.; And Others

1993-01-01

Grandparents' and mothers' drug use predicted hyperactivity, psychosomatic complaints, and social problems for boys, and acting-out behaviors for boys and girls. Maternal drug use predicted fearfulness, hyperactivity, and social problems for boys, and developmental problems for boys and girls. (BC)

Drug trajectories among youth undergoing treatment: the influence of psychological problems and delinquency.

PubMed

Brunelle, Natacha; Bertrand, Karine; Beaudoin, Isabelle; Ledoux, Cinthia; Gendron, Annie; Arseneault, Catherine

2013-08-01

Previous research has documented associations of addiction with delinquency and psychological problems. However, few studies have evaluated their influence on adolescent's drug use trajectories. The current study aims to examine the influence of these factors on the recovery trajectories of 199 youths aged 15.6 years on average admitted to inpatient and outpatient addiction treatment centers, followed up three and six months later. Results indicate that youth who show higher severity of drug abuse exhibit greater improvement than youth with a lower severity of drug abuse at the onset of treatment. Although psychological problems were associated with baseline drug use, they did not influence drug use trajectory over time. Only delinquency influenced the recovery trajectories of these youth. Results suggest that a high level of delinquency can have a significant effect on the drug recovery process of adolescents and that interventions should attempt to reduce both drug use and delinquency. Copyright © 2013 The Foundation for Professionals in Services for Adolescents. Published by Elsevier Ltd. All rights reserved.

Undocumented Immigration, Drug Problems, and Driving Under the Influence in the United States, 1990-2014.

PubMed

Light, Michael T; Miller, Ty; Kelly, Brian C

2017-09-01

To examine the influence of undocumented immigration in the United States on 4 different metrics of drug and alcohol problems: drug arrests, drug overdose fatalities, driving under the influence (DUI) arrests, and DUI deaths. We combined newly developed state-level estimates of the undocumented population between 1990 and 2014 from the Center for Migration Studies with arrest data from the Federal Bureau of Investigation Uniform Crime Reports and fatality information from the Fatality Analysis Reporting System and the Centers for Disease Control and Prevention Underlying Cause of Death database. We used fixed-effects regression models to examine the longitudinal association between increased undocumented immigration and drug problems and drunk driving. Increased undocumented immigration was significantly associated with reductions in drug arrests, drug overdose deaths, and DUI arrests, net of other factors. There was no significant relationship between increased undocumented immigration and DUI deaths. This study provides evidence that undocumented immigration has not increased the prevalence of drug or alcohol problems, but may be associated with reductions in these public health concerns.

Information on actual medication use and drug-related problems in older patients: questionnaire or interview?

PubMed

Willeboordse, Floor; Grundeken, Lucienne H; van den Eijkel, Lisanne P; Schellevis, François G; Elders, Petra J M; Hugtenburg, Jacqueline G

2016-04-01

Information on medication use and drug-related problems is important in the preparation of clinical medication reviews. Critical information can only be provided by patients themselves, but interviewing patients is time-consuming. Alternatively, patient information could be obtained with a questionnaire. In this study the agreement between patient information on medication use and drug-related problems in older patients obtained with a questionnaire was compared with information obtained during an interview. General practice in The Netherlands. A questionnaire was developed to obtain information on actual medication use and drug-related problems. Two patient groups ≥65 years were selected based on general practitioner electronic medical records in nine practices; I. polypharmacy and II. ≥1 predefined general geriatric problems. Eligible patients were asked to complete the questionnaire and were interviewed afterwards. Agreement on information on medication use and drug-related problems collected with the questionnaire and interview was calculated. Ninety-seven patients participated. Of all medications used, 87.6 % (95 % CI 84.7-90.5) was reported identically in the questionnaire and interview. Agreement for the complete medication list was found for 45.4 % (95 % CI 35.8-55.3) of the patients. On drug-related problem level, agreement between questionnaire and interview was 75 %. Agreement tended to be lower in vulnerable patients characterized by ≥4 chronic diseases, ≥10 medications used and low health literacy. Information from a questionnaire showed reasonable agreement compared with interviewing. The patients reported more medications and drug-related problems in the interview than the questionnaire. Taking the limitations into account, a questionnaire seems a suitable tool for medication reviews that may replace an interview for most patients.

Heterogeneous Costs of Alcohol and Drug Problems Across Cities and Counties in California

PubMed Central

Miller, Ted R.; Nygaard, Peter; Gaidus, Andrew; Grube, Joel W.; Ponicki, William R.; Lawrence, Bruce A.; Gruenewald, Paul J.

2017-01-01

Background Estimates of economic and social costs related to alcohol and other drug (AOD) use and abuse are usually made at state and national levels. Ecological analyses demonstrate, however, that substantial variations exist in the incidence and prevalence of AOD use and problems including impaired driving, violence, and chronic disease between smaller geopolitical units like counties and cities. This study examines the ranges of these costs across counties and cities in California. Methods We used estimates of the incidence and prevalence of AOD use, abuse and related problems to calculate costs in 2010 dollars for all 58 counties and an ecological sample of 50 cities with populations between 50,000 and 500,000 persons in California. The estimates were built from archival and public-use survey data collected at state, county and city-levels over the years from 2009 to 2010. Results Costs related to alcohol use and related problems exceeded those related to illegal drugs across all counties and most cities in the study. Substantial heterogeneities in costs were observed between cities within counties. Conclusions AOD costs are heterogeneously distributed across counties and cities, reflecting the degree to which different populations are engaged in use and abuse across the state. These findings provide a strong argument for the distribution of treatment and prevention resources proportional to need. PMID:28208210

Child maltreatment, parent alcohol and drug-related problems, polydrug problems, and parenting practices: a test of gender differences and four theoretical perspectives.

PubMed

Locke, Thomas F; Newcomb, Michael

2004-03-01

The authors tested how adverse childhood experiences (child maltreatment and parent alcohol- and drug-related problems) and adult polydrug use (as a mediator) predict poor parenting in a community sample (237 mothers and 81 fathers). These relationships were framed within several theoretical perspectives, including observational learning, impaired functioning, self-medication, and parentification-pseudomaturity. Structural models revealed that child maltreatment predicted poor parenting practices among mothers. Parent alcohol- and drug-related problems had an indirect detrimental influence on mothers' parenting and practices through self-drug problems. Among fathers, emotional neglect experienced as a child predicted lack of parental warmth more parental neglect, and sexual abuse experienced as a child predicted a rejecting style of parenting.

Prevalence of skin problems and leg ulceration in a sample of young injecting drug users.

PubMed

Coull, Alison F; Atherton, Iain; Taylor, Avril; Watterson, Andrew E

2014-08-13

Drug users suffer harm from the injecting process, and clinical services are reporting increasing numbers presenting with skin-related problems such as abscesses and leg ulcers. Skin breakdown can lead to long-term health problems and increased service costs and is often the first indication of serious systemic ill health. The extent of skin problems in injecting drug users has not previously been quantified empirically, and there is a dearth of robust topical literature. Where skin problems have been reported, this is often without clear definition and generic terms such as 'soft tissue infection' are used which lack specificity. The aim of this study was to identify the range and extent of skin problems including leg ulceration in a sample of injecting drug users. Definitions of skin problems were developed and applied to descriptions from drug users to improve rigour. Data were collected in needle exchanges and methadone clinics across Glasgow, Scotland, from both current and former drug injectors using face-to-face interviews. Two hundred participants were recruited, of which 74% (n = 148) were males and 26% (n = 52) were females. The age range was 21-44 years (mean 35 years). Just under two thirds (64%, n = 127) were currently injecting or had injected within the last 6 months, and 36% (n = 73) had previously injected and had not injected for more than 6 months.Sixty per cent (n = 120) of the sample had experienced a skin problem, and the majority reported more than one problem. Most common were abscesses, lumps, track marks and leg ulcers. Fifteen per cent (n = 30) of all participants reported having had a leg ulcer. This is an original empirical study which demonstrated unique findings of a high prevalence of skin disease (60%) and surprisingly high rates of leg ulceration (15%). Skin disease in injecting drug users is clearly widespread. Leg ulceration in particular is a chronic recurring condition that is costly to treat and has

Protective factors can mitigate behavior problems after prenatal cocaine and other drug exposures.

PubMed

Bada, Henrietta S; Bann, Carla M; Whitaker, Toni M; Bauer, Charles R; Shankaran, Seetha; Lagasse, Linda; Lester, Barry M; Hammond, Jane; Higgins, Rosemary

2012-12-01

We determined the role of risk and protective factors on the trajectories of behavior problems associated with high prenatal cocaine exposure (PCE)/polydrug exposure. The Maternal Lifestyle Study enrolled 1388 children with or without PCE, assessed through age 15 years. Because most women using cocaine during pregnancy also used other substances, we analyzed for the effects of 4 categories of prenatal drug exposure: high PCE/other drugs (OD), some PCE/OD, OD/no PCE, and no PCE/no OD. Risks and protective factors at individual, family, and community levels that may be associated with behavior outcomes were entered stepwise into latent growth curve models, then replaced by cumulative risk and protective indexes, and finally by a combination of levels of risk and protective indexes. Main outcome measures were the trajectories of externalizing, internalizing, total behavior, and attention problems scores from the Child Behavior Checklist (parent). A total of 1022 (73.6%) children had known outcomes. High PCE/OD significantly predicted externalizing, total, and attention problems when considering the balance between risk and protective indexes. Some PCE/OD predicted externalizing and attention problems. OD/no PCE also predicted behavior outcomes except for internalizing behavior. High level of protective factors was associated with declining trajectories of problem behavior scores over time, independent of drug exposure and risk index scores. High PCE/OD is a significant risk for behavior problems in adolescence; protective factors may attenuate its detrimental effects. Clinical practice and public health policies should consider enhancing protective factors while minimizing risks to improve outcomes of drug-exposed children.

Access to generic drugs in the 1950s: the politics of a social problem.

PubMed Central

Facchinetti, N J; Dickson, W M

1982-01-01

From the published literature of the 1950s, the social history of anti-substitution law is analyzed in terms of sociological theory on the construction of social problems. The analysis reveals how the substitution of generic drugs for prescribed brands came to be recognized as a social problem in need of remedial legislation. The most influential party in the process was the brand-drug industry which centered the debate on matters of public health and professionalism instead of industrial profitability. The industry was able to form a coalition of interests and establish the saliency and legitimacy of the problem, even though there was no objective evidence to establish brand substitution as a hazard to health. The case fits well into the theory of social problem construction. Other issues in health care, particularly drug issues can be studied from this same perspective. PMID:7065335

A Focus on Problems of National Interest in the College General Chemistry Laboratory: The Effects of the Problem-Oriented Method Compared with Those of the Traditional Approach.

ERIC Educational Resources Information Center

Neman, Robert Lynn

This study was designed to assess the effects of the problem-oriented method compared to those of the traditional approach in general chemistry at the college level. The problem-oriented course included topics such as air and water pollution, drug addiction and analysis, tetraethyl-lead additives, insecticides in the environment, and recycling of…

Alcohol and other drug problems in Australia: the urgent need for nurse education.

PubMed

de Crespigny, C

1996-07-01

The economic, social and health costs associated with alcohol and other drug use, including medicines, impact on the Australian community profoundly. Many Australians use alcohol and other drugs (AODs) on a regular basis and a significant number experience problems at some time. There are about 25,000 drug-related deaths annually, the majority of which are related to alcohol and tobacco use. Many young people die or are injured as a direct result of alcohol intoxication, accidental overdose and related problems, and significant numbers of elderly people are hospitalised, permanently incapacitated or suffer avoidable trauma through adverse drug reactions and side-effects of medications. It is estimated that at least 25 per cent of acute hospital beds hold patients with alcohol-related problems directly associated with the medical diagnosis, and there are comparable numbers of people needing social and other forms of assistance at some time. Despite the preventative nature of many AOD problems and the call for harm reduction, timely intervention and support for the thousands of Australians attending hospitals, community health and mental health services, nurses are yet to effectively assist the community in preventing and responding to the range of AOD problems. Nursing policy, guidelines and clinical expertise are required to assist the community in addressing this issue. Undergraduate, postgraduate and continuing education have a vital role to play in providing the profession with the knowledge, skills and research base to meet this challenge.

Multigrid method for stability problems

NASA Technical Reports Server (NTRS)

Ta'asan, Shlomo

1988-01-01

The problem of calculating the stability of steady state solutions of differential equations is addressed. Leading eigenvalues of large matrices that arise from discretization are calculated, and an efficient multigrid method for solving these problems is presented. The resulting grid functions are used as initial approximations for appropriate eigenvalue problems. The method employs local relaxation on all levels together with a global change on the coarsest level only, which is designed to separate the different eigenfunctions as well as to update their corresponding eigenvalues. Coarsening is done using the FAS formulation in a nonstandard way in which the right-hand side of the coarse grid equations involves unknown parameters to be solved on the coarse grid. This leads to a new multigrid method for calculating the eigenvalues of symmetric problems. Numerical experiments with a model problem are presented which demonstrate the effectiveness of the method.

Relationship of drug-addicted patients' personality disorders to social problem-solving changes during the rehabilitation process.

PubMed

Kolesnikova, Jelena; Miezitis, Solveiga; Osis, Guntars

2013-08-01

Drug-addicted patients exhibit various personality disorders that interfere with their adaptation to society, as well as their ability to participate in the rehabilitation process. The Latvian Rehabilitation Programme for drug addicts includes social problem-solving training to help patients reintegrate into society. However, the role of personality disorders has not been investigated in relation to this process. The aim of the study is to assess whether personality disorders predict changes in dimensions of social problem-solving after 6 months of rehabilitation for drug-addicted patients. The sample of this study consists of 31 drug-addicted patients from the Latvian rehabilitation centres aged 21-35 (females 21%, males 79%). Two inventories are used: the Social Problem-Solving Inventory--Revised (SPSI-R) and Millon(TM) Clinical Multiaxial Inventory--III (MCMI-III) adapted into Russian. Results of the study indicated that some MCMI-III personality disorders (Schizoid and Histrionic) negatively predicted SPSI-R Positive problem orientation, and narcissistic disorder positively predicted SPSI-R Avoidance style after 6 months in the Latvian Rehabilitation Programme. The other personality disorders did not predict social problem-solving dimensions. The results of the study suggest that some personality disorders are related to changes in social problem-solving dimensions for drug-addicted patients. Hence, it is important to consider the implications of particular personality disorders to facilitate the implementation of social problem-solving rehabilitation programmes.

Mothers' alcohol and other drug problems and their punitiveness toward their children.

PubMed

Miller, B A; Smyth, N J; Mudar, P J

1999-09-01

The relationship between mothers' alcohol or other drug (AOD) problems and their punitiveness toward their children is examined in this study. Women (N = 170) were recruited from five different sources, including clinical interventions and the community. Women's punitiveness toward their children was assessed by three different maternal self-report measures: Conflict Tactics Scale, Parental Punitiveness Scale and Child Abuse Potential Inventory. Women's histories of AOD problems, violent victimization and hostility were assessed using standardized assessment tools. Women were categorized by their AOD problems as follows: current problem (22.4%), past only problem (44.7%) or no problems (32.9%). Results indicate that mothers with current or past AOD problems are more punitive toward their children, controlling for potentially confounding demographic factors. Mothers' histories of partner violence and parental violence also predicted higher levels of mother-to-child punitiveness. However, histories of childhood sexual abuse predicted lower levels of mothers' punitiveness. Hostility served as a predictor of mothers' punitiveness and moderated some of the relationships between their AOD problems and their punitiveness. Findings suggest that women with AOD problems are more likely to be punitive toward their children, but other factors may also contribute to this risk. Treatment and prevention interventions need to be developed to decrease the risk of violent victimization among children whose mothers have alcohol and other drug problems.

Influence of gender and race/ethnicity on perceived barriers to help-seeking for alcohol or drug problems.

PubMed

Verissimo, Angie Denisse Otiniano; Grella, Christine E

2017-04-01

This study examines reasons why people do not seek help for alcohol or drug problems by gender and race/ethnicity using data from the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC), a nationally representative survey. Multivariate models were fit for 3 barriers to seeking help (structural, attitudinal, and readiness for change) for either alcohol or drug problems, controlling for socio-demographic characteristics and problem severity. Predicted probabilities were generated to evaluate gender differences by racial/ethnic subgroups. Over three quarters of the samples endorsed attitudinal barriers related to either alcohol or drug use. Generally, women were less likely to endorse attitudinal barriers for alcohol problems. African Americans and Latina/os were less likely than Whites to endorse attitudinal barriers for alcohol problems, Latina/os were less likely than Whites to endorse readiness for change barriers for alcohol and drug problems, however, African Americans were more likely to endorse structural barriers for alcohol problems. Comparisons within racial/ethnic subgroups by gender revealed more complex findings, although across all racial/ethnic groups women endorsed attitudinal barriers for alcohol problems more than men. Study findings suggest the need to tailor interventions to increase access to help for alcohol and drug problems that take into consideration both attitudinal and structural barriers and how these vary across groups. Copyright © 2017 Elsevier Inc. All rights reserved.

Influence of Gender and Race/Ethnicity on Perceived Barriers to Help-Seeking for Alcohol or Drug Problems

PubMed Central

Verissimo, Angie Denisse Otiniano

2017-01-01

This study examines reasons why people do not seek help for alcohol or drug problems by gender and race/ethnicity using data from the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC), a nationally representative survey. Multivariate models were fit for 3 barriers to seeking help (structural, attitudinal, and readiness for change) for either alcohol or drug problems, controlling for socio-demographic characteristics and problem severity. Predicted probabilities were generated to evaluate gender differences by racial/ethnic subgroups. Over three quarters of the samples endorsed attitudinal barriers related to either alcohol or drug use. Generally, women were less likely to endorse attitudinal barriers for alcohol problems. African Americans and Latina/os were less likely than Whites to endorse attitudinal barriers for alcohol problems, Latina/os were less likely than Whites to endorse readiness for change barriers for alcohol and drug problems, however, African Americans were more likely to endorse structural barriers for alcohol problems. Comparisons within racial/ethnic subgroups by gender revealed more complex findings, although across all racial/ethnic groups women endorsed attitudinal barriers for alcohol problems more than men. Study findings suggest the need to tailor interventions to increase access to help for alcohol and drug problems that take into consideration both attitudinal and structural barriers and how these vary across groups. PMID:28237055

The Relationship of Social Problem-Solving Skills and Dysfunctional Attitudes with Risk of Drug Abuse among Dormitory Students at Isfahan University of Medical Sciences.

PubMed

Nasrazadani, Ehteram; Maghsoudi, Jahangir; Mahrabi, Tayebeh

2017-01-01

Dormitory students encounter multiple social factors which cause pressure, such as new social relationships, fear of the future, and separation from family, which could cause serious problems such as tendency toward drug abuse. This research was conducted with the goal to determine social problem-solving skills, dysfunctional attitudes, and risk of drug abuse among dormitory students of Isfahan University of Medical Sciences, Iran. This was a descriptive-analytical, correlational, and cross-sectional research. The research sample consisted of 211 students living in dormitories. The participants were selected using randomized quota sampling method. The data collection tools included the Social Problem-Solving Inventory (SPSI), Dysfunctional Attitude Scale (DAS), and Identifying People at Risk of Addiction Questionnaire. The results indicated an inverse relationship between social problem-solving skills and risk of drug abuse ( P = 0.0002), a direct relationship between dysfunctional attitude and risk of drug abuse ( P = 0.030), and an inverse relationship between social problem-solving skills and dysfunctional attitude among students ( P = 0.0004). Social problem-solving skills have a correlation with dysfunctional attitudes. As a result, teaching these skills and the way to create efficient attitudes should be considered in dormitory students.

Reasons behind Greek problem drug users’ decisions to quit using drugs and engage in treatment of their own volition: sense of self and the Greek filotimo.

PubMed

Fotopoulou, Maria

2014-04-01

The aim of this study was to explore Greek problem drug users’ perceptions of the reasons that led them to quit using drugs and engage in treatment of their own volition. Qualitative semi-structured in-depth interviews. Two state drug agencies in Thessaloniki, Greece. A total of 40 adult problem drug-using men and women participated in the study. Participants were asked to reflect on their decisions to wean themselves from drugs and enter treatment. Findings Participants reported that their decisions centred on the re-conceptualization of the drug-using community and their membership in it, the desire to restore aspects of identities thatwere deemed to be spoiled, and finally memories of their drug-free selves. The importance of the distinctively Greek notion of filotimo in this discussion is highlighted. Primarily in relation to filotimo (a concept that represents a complex array of virtues that regulates behaviour towards one’s family), the desire to restore one’s spoiled identity plays a pivotal role in Greek problem drug users’ decisions to cease drug use and engage in treatment.

Preventive education to cope with the drug problems of Latin America.

PubMed

Massun, E

1990-01-01

Insufficient resources, services, staff, facilities and attention at the policymaking level are devoted to demand reduction measures, especially preventive education for young persons. Instead, emphasis is placed on and disproportionate resources are allocated to supply reduction measures and activities such as suppressing and/or limiting the availability of illicit drugs. Prevention policy constitutes a viable approach to solving the problem of illicit drug trafficking and consumption. The crux of the problem is not the availability of illicit drugs, but the demand of consumers for the substances. Preventive education for the young is an indispensable ingredient of effective prevention policy. The school environment can be instrumental in developing systematic and lasting preventive education. An essential condition, which, according to the author, is lacking in Latin America, is that educators should be provided with the training and training tools needed to enable them to perform properly as agents of prevention policy. A number of recommendations to reduce illicit drug demand and consumption through prevention are made, including giving priority to a comprehensive and systematically applied prevention policy focusing on the young and involving an educational approach and tools that are progressive and highly specialized, as well as research that is intensified and of better quality.

Alcohol and Other Drugs on Campus: The Scope of the Problem. Infofacts/Resources

ERIC Educational Resources Information Center

Kapner, Daniel Ari

2008-01-01

The most widespread health problem on college and university campuses in the United States is high-risk alcohol and other drug (AOD) use. Recent reports confirm that the nation's campuses continue to encounter significant consequences as a result of this problem. This "Infofacts/Resources" offers an overview of the problem and highlights effective…

Producing alcohol and other drugs as a policy 'problem': A critical analysis of South Africa's 'National Drug Master Plan' (2013-2017).

PubMed

Pienaar, Kiran; Savic, Michael

2016-04-01

The strong symbolic value of illicit drug use makes it a contested issue, which attracts mixed public opinion, intense media attention and close political scrutiny. This means that the formulation of plausible, authoritative policies governing illicit drugs must navigate fraught political terrain. In a country like South Africa with its long unique history of institutionalised oppression of the black majority, the issues confronting drug policy are particularly complex and the need for carefully formulated policy responses especially urgent. Yet despite this, the area of drug policy development in South Africa has received little scholarly attention to date. This paper explores the complexities of policymaking in the South African context by drawing on feminist scholar Carol Bacchi's poststructuralist approach to policy analysis, which focuses on how policy helps to produce the problems it purports to solve. Taking as its empirical focus, South Africa's current drug policy, the third National Drug Master Plan (NDMP), 2013-2017, the paper analyses how the policy constitutes the 'problem of alcohol and other drugs' (AODs). We identify three central policy proposals through which specific problematisations emerge: (1) the proposal that drug use is a global issue requiring a coordinated policy response, (2) appeals to evidence-based policy proposals and (3) the proposal that AOD 'use' and 'abuse' be treated interchangeably. We suggest that these proposals reveal a tendency towards inflating the 'problem of AODs' and thus work to justify punitive policy measures. In an effort to explore the implications of particular problematisations for effecting social change, we clarify the ways in which the policy may work to undermine the interests of those it seeks to aid by reinforcing stigma and marginalisation. Copyright © 2015 Elsevier B.V. All rights reserved.

Program Administrator's Handbook. Strategies for Preventing Alcohol and Other Drug Problems. The College Series.

ERIC Educational Resources Information Center

CSR, Inc., Washington, DC.

This handbook is for administrators of programs in higher education settings which deal with alcohol and other drug (AOD) related problems. Chapter 1, "Defining the Problem, Issues, and Trends" examines the problem from various perspectives and presents the latest statistics on the extent of AOD use on campuses, specific problems affecting…

Prenatal alcohol use: the role of lifetime problems with alcohol, drugs, depression, and violence.

PubMed

Flynn, Heather A; Chermack, Stephen T

2008-07-01

The purpose of this study was to examine a broader array of lifetime factors that theoretically may be associated with prenatal alcohol use than have previously been studied together, including family history of alcohol-use problems, history of physical or sexual abuse, lifetime major depressive disorder, alcohol-use disorder, illicit-drug-use problems, and partner violence. A total of 186 pregnant women, all of whom used alcohol in the year before pregnancy, were initially recruited in prenatal care settings. Women who reported no prenatal alcohol use (n = 96) were compared with women who drank 1-10 standard drinks during pregnancy (n = 75) and with women who drank more than 10 standard drinks during pregnancy (n = 13), considered to be a higher risk group, on the lifetime risk variables. Because of the public health implications, secondary analyses compared women who abstained during pregnancy with those who used any alcohol. Significant intercorrelations were found among most of the lifetime risk factors studied. Multivariate analyses showed that drug-use problems and partner violence were most strongly associated with prenatal alcohol use than any other variable studied. Consistent with a life span risk framework for alcohol-use problems, results of this study show that childhood abuse, familial alcoholism, lifetime major depressive disorder, and alcohol- and drug-use problems are interrelated. However, when considered together, only lifetime partner violence and drug use are significantly related to various levels of prenatal alcohol use. Identification, assessment, and intervention efforts should integrate these important factors.

Home visits during pregnancy and after birth for women with an alcohol or drug problem.

PubMed

Turnbull, Catherine; Osborn, David A

2012-01-18

One potential method of improving outcome for pregnant or postpartum women with a drug or alcohol problem is with home visits. To determine the effects of home visits during pregnancy and/or after birth for women with a drug or alcohol problem. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (30 November 2011), CENTRAL (The Cochrane Library 2011, Issue 4 of 4), MEDLINE (1966 to 30 November 2011), EMBASE (1980 to 30 November 2011), CINAHL (1982 to 30 November 2011) and PsycINFO (1974 to 30 November 2011) supplemented by searches of citations from previous reviews and trials and contact with experts. Studies using random or quasi-random allocation of pregnant or postpartum women with a drug or alcohol problem to home visits. Trials enrolling high-risk women of whom more than 50% were reported to use drugs or alcohol were also eligible. Review authors performed assessments of trials independently. We performed statistical analyses using fixed-effect and random-effects models where appropriate. Seven studies (reporting 803 mother-infant pairs) compared home visits mostly after birth with no home visits. Visitors included community health nurses, paediatric nurses, trained counsellors, paraprofessional advocates, midwives and lay African-American women. Several studies had significant methodological limitations. There was no significant difference in continued illicit drug use (three studies, 384 women; risk ratio (RR) 1.05, 95% confidence interval (CI) 0.89 to 1.24), continued alcohol use (three studies, 379 women; RR 1.18, 95% CI 0.96 to 1.46), failure to enrol in a drug treatment program (two studies, 211 women; RR 0.45, 95% CI 0.10 to 1.94), not breastfeeding at six months (two studies, 260 infants; RR 0.95, 95% CI 0.83 to 1.10), incomplete six-month infant vaccination schedule (two studies, 260 infants; RR 1.09, 95% CI 0.91 to 1.32), the Bayley Mental Development Index (three studies, 199 infants; mean difference 2.89, 95% CI -1.17 to 6

What to Do If Your Teen or Young Adult Has a Problem with Drugs

MedlinePlus

... Teen or Young Adult Has a Problem with Drugs Email Facebook Twitter Revised January 2016 Expand All ... may be addicted. Anyone Can Become Addicted to Drugs YouTube embedded video: https://www.youtube-nocookie.com/ ...

Computerized pharmacy surveillance and alert system for drug-related problems.

PubMed

Ferrández, O; Urbina, O; Grau, S; Mateu-de-Antonio, J; Marin-Casino, M; Portabella, J; Mojal, S; Riu, M; Salas, E

2017-04-01

Because of the impact of drug-related problems (DRPs) on morbidity and mortality, there is a need for computerized strategies to increase drug safety. The detection and identification of the causes of potential DRPs can be facilitated by the incorporation of a pharmacy warning system (PWS) in the computerized prescriber order entry (CPOE) and its application in the routine validation of inpatient drug therapy. A limited number of studies have evaluated a clinical decision support system to monitor drug treatment. Most of these applications have utilized a small range of drugs with alerts and/or types of alert. The objective of this study was to describe the implementation of a PWS integrated in the electronic medical record (EMR). The PWS was developed in 2003-2004. Pharmacological information to generate drug alerts was entered on demographic data, drug dosage, laboratory tests related to the prescribed drug and drug combinations (interactions, duplications and necessary combinations). The PWS was applied in the prescription reviews conducted in patients admitted to the hospital in 2012. Information on 83% of the drugs included in the pharmacopeia was introduced into the PWS, allowing detection of 2808 potential DRPs, representing 79·1% of all potential DRPs detected during the study period. Twenty per cent of PWS DRPs were clinically relevant, requiring pharmacist intervention. The PWS detected most potential DRPs, thus increasing inpatient safety. The detection ability of the PWS was higher than that reported for other tools described in the literature. © 2017 John Wiley & Sons Ltd.

International aspects of problems associated with the use of psychoactive drugs.

PubMed

Chruściel, T L

1976-01-01

Problems of terminology, use and consumption, advertising, effectiveness and appropriate information and education on psychoactive drugs are outlined and advantages of international collaboration in attempts to establish standards for controlled clinical trials in psychopharmacology are discussed.

Multigrid method for stability problems

NASA Technical Reports Server (NTRS)

Taasan, Shlomo

1988-01-01

The problem of calculating the stability of steady state solutions of differential equations is treated. Leading eigenvalues (i.e., having maximal real part) of large matrices that arise from discretization are to be calculated. An efficient multigrid method for solving these problems is presented. The method begins by obtaining an initial approximation for the dominant subspace on a coarse level using a damped Jacobi relaxation. This proceeds until enough accuracy for the dominant subspace has been obtained. The resulting grid functions are then used as an initial approximation for appropriate eigenvalue problems. These problems are being solved first on coarse levels, followed by refinement until a desired accuracy for the eigenvalues has been achieved. The method employs local relaxation on all levels together with a global change on the coarsest level only, which is designed to separate the different eigenfunctions as well as to update their corresponding eigenvalues. Coarsening is done using the FAS formulation in a non-standard way in which the right hand side of the coarse grid equations involves unknown parameters to be solved for on the coarse grid. This in particular leads to a new multigrid method for calculating the eigenvalues of symmetric problems. Numerical experiments with a model problem demonstrate the effectiveness of the method proposed. Using an FMG algorithm a solution to the level of discretization errors is obtained in just a few work units (less than 10), where a work unit is the work involved in one Jacobi relization on the finest level.

Solid dispersion of poorly water-soluble drugs: early promises, subsequent problems, and recent breakthroughs.

PubMed

Serajuddin, A T

1999-10-01

Although there was a great interest in solid dispersion systems during the past four decades to increase dissolution rate and bioavailability of poorly water-soluble drugs, their commercial use has been very limited, primarily because of manufacturing difficulties and stability problems. Solid dispersions of drugs were generally produced by melt or solvent evaporation methods. The materials, which were usually semisolid and waxy in nature, were hardened by cooling to very low temperatures. They were then pulverized, sieved, mixed with relatively large amounts of excipients, and encapsulated into hard gelatin capsules or compressed into tablets. These operations were difficult to scale up for the manufacture of dosage forms. The situation has, however, been changing in recent years because of the availability of surface-active and self-emulsifying carriers and the development of technologies to encapsulate solid dispersions directly into hard gelatin capsules as melts. Solid plugs are formed inside the capsules when the melts are cooled to room temperature. Because of surface activity of carriers used, complete dissolution of drug from such solid dispersions can be obtained without the need for pulverization, sieving, mixing with excipients, etc. Equipment is available for large-scale manufacturing of such capsules. Some practical limitations of dosage form development might be the inadequate solubility of drugs in carriers and the instability of drugs and carriers at elevated temperatures necessary to manufacture capsules.

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

PubMed

Vozeh, S; Steimer, J L

1985-01-01

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

Are therapeutic vaccines an answer to the global problem of drug and alcohol abuse?

PubMed

Brashier, Dick B S; Sharma, Ashok Kumar; Akhoon, Neha

2016-01-01

Drug Abuse has become a major challenging problem for the society. It effects people of all countries economical strata's and all ages. According. Monetary loss all over the world regarding drug abuse is in million dollars, it not only has an impact on human productivity and healthcare cost but also on cost of crimes conducted by these drugs and alcohol abuse. Therapeutic vaccine has come as new approach to deal with this problem, after failures in search for a pharmaceutical agent to deal with drug of abuse and alcohol. Research in field of nicotine abuse has gone a way ahead with number of vaccines being tried clinically followed by cocaine, opioids, methamphetamine, phencyclidine and alcohol. All of them have a common mechanism of action by antibody production whereas alcohol acts by genetic intervention. None have being approved yet due to poor results in phase II trials, possibly due to not able to trigger an adequate immunological response. But still quest is on for cracking the ice by developing first successful vaccine against drug of abuse, that would follow for other drugs too. It would be great step in field of therapeutic vaccines for drug abuse after similar successful vaccines being approved for other diseases like cancer.

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

PubMed

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

2008-10-03

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

Drugs and Mental Health Problems among the Roma: Protective Factors Promoted by the Iglesia Evangélica Filadelfia

PubMed Central

López, Jelen Amador; García, Ramón Flecha; Martí, Teresa Sordé

2018-01-01

Background: High incidences of drug consumption and mental health problems are found among the Roma population in Spain, a reality that remains understudied. Past studies have indicated the positive role played by the Iglesia Evangélica Filadelfia (IEF) in promoting rehabilitation and prevention of these practices. Objective: In this article, authors analyze in which ways the IEF favors processes of drug rehabilitation and mental health recovery as well as the prevention of these problems among its Roma members. Methods: A communicative qualitative approach was developed. It was communicative because new knowledge was created by dialogically contrasting the existing state of the art with study participants. It was qualitative because everyday life stories were collected, gathering the experiences, perceptions and interpretations of Roma people who are actively involved in three different IEF churches based in Barcelona. Results: This article identifies these protective factors: anti-drug discourse, a supportive environment, new social relations, role model status, the promotion of interactions, the revaluation of oneself, spiritual activities and the improvement of the feeling of belonging and the creation of meaning. Conclusion: The present research contributes new evidence to the current understanding of the role played by the IEF in improving Roma health status and how the identified protective factors can contribute to rehabilitation and recovery from such problems in other contexts. PMID:29443877

Drugs and Mental Health Problems among the Roma: Protective Factors Promoted by the Iglesia Evangélica Filadelfia.

PubMed

López, Jelen Amador; García, Ramón Flecha; Martí, Teresa Sordé

2018-02-14

Background: High incidences of drug consumption and mental health problems are found among the Roma population in Spain, a reality that remains understudied. Past studies have indicated the positive role played by the Iglesia Evangélica Filadelfia (IEF) in promoting rehabilitation and prevention of these practices. Objective: In this article, authors analyze in which ways the IEF favors processes of drug rehabilitation and mental health recovery as well as the prevention of these problems among its Roma members. Methods: A communicative qualitative approach was developed. It was communicative because new knowledge was created by dialogically contrasting the existing state of the art with study participants. It was qualitative because everyday life stories were collected, gathering the experiences, perceptions and interpretations of Roma people who are actively involved in three different IEF churches based in Barcelona. Results: This article identifies these protective factors: anti-drug discourse, a supportive environment, new social relations, role model status, the promotion of interactions, the revaluation of oneself, spiritual activities and the improvement of the feeling of belonging and the creation of meaning. Conclusion: The present research contributes new evidence to the current understanding of the role played by the IEF in improving Roma health status and how the identified protective factors can contribute to rehabilitation and recovery from such problems in other contexts.

What to Do If Your Adult Friend or Loved One Has a Problem with Drugs

MedlinePlus

... Friend or Loved One Has a Problem with Drugs Email Facebook Twitter Revised January 2016 Expand All ... NIDA's video, below. Anyone Can Become Addicted to Drugs YouTube embedded video: https://www.youtube-nocookie.com/ ...

Drug and alcohol abuse: The pattern and magnitude of the problem

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

Ajayi, P.A.

In the last 12 months, many more cases of alcohol and drug (substance) abuse in the workplace were seen in the Escravos operations of Chevron Nigeria Limited than in previous years. This called the attention to the rising prevalence of drug and alcohol abuse in contradistinction to reports from similar organizations in other parts of the world. Chevron Nigeria has a written Drug and Alcohol Policy which has been dormant for some time because of the apparent rarity of the problem of substance abuse in the workplace. This Policy is being reviewed to broaden its scope and make it moremore » effective. A total of 30 employees were tested for drugs and alcohol .6 exceeded the legal limits of Blood Alcohol Concentration (BAC) and 5 tested positive for drugs. Tests were mainly post-accident, reasonable cause and random. The common substances abused were alcohol, cannabis, cocaine and morphine in that order. The findings are compared with those of similar organizations in UK and USA. Efforts to control substance abuse in the workplace are being put into place.« less

Dealing with Drug Problems: Preventing and Treating Drug Abuse

MedlinePlus

... a drug even though you know it’s harmful is the hallmark of addiction. A drug doesn’t have to be illegal to cause this effect. People can become addicted to alcohol, nicotine, or even prescription drugs when they use them ...

Links between Alcohol and Other Drug Problems and Maltreatment among Adolescent Girls: Perceived Discrimination, Ethnic Identity, and Ethnic Orientation as Moderators

ERIC Educational Resources Information Center

Gray, Calonie M. K.; Montgomery, Marilyn J.

2012-01-01

Objectives: This study examined the links between maltreatment, posttraumatic stress symptoms, ethnicity-specific factors (i.e., perceived discrimination, ethnic identity, and ethnic orientation), and alcohol and/or other drug (AOD) problems among adolescent girls. Methods: These relations were examined using archived data from a community sample…

[Alcohol and drugs in Central Europe--problems and possible solutions].

PubMed

Nespor, K; Cs emy, L

1994-08-22

The high alcohol consumption and increasing abuse of other addictive inducing substances in Central Europe calls for broadley conceived preventive programmes and cheap and widely applicable therapeutic strategies (early treatment at the first contact level, self-help manuals, self-aid organizations). Social instability along with greater availability of alcohol and drugs create a dangerous combination. In addition to strategies of stress prevention at the societal level also strategy at the individual level is important (e.g. relaxation training, yoga, psychotherapy). It is also important to change the "image" of western society and commercial interests of those who make profits on alcohol and drugs should be under control and advertising should be greatly restricted if not prohibited. Prevention of problems caused by alcohol and drugs in particular in youths must be combined and really effective strategies should be used such as peer programmes. The authors mention also their own preventive programme FIT IN and print materials oriented specifically on certain population groups.

Dose Equivalents for Antipsychotic Drugs: The DDD Method.

PubMed

Leucht, Stefan; Samara, Myrto; Heres, Stephan; Davis, John M

2016-07-01

Dose equivalents of antipsychotics are an important but difficult to define concept, because all methods have weaknesses and strongholds. We calculated dose equivalents based on defined daily doses (DDDs) presented by the World Health Organisation's Collaborative Center for Drug Statistics Methodology. Doses equivalent to 1mg olanzapine, 1mg risperidone, 1mg haloperidol, and 100mg chlorpromazine were presented and compared with the results of 3 other methods to define dose equivalence (the "minimum effective dose method," the "classical mean dose method," and an international consensus statement). We presented dose equivalents for 57 first-generation and second-generation antipsychotic drugs, available as oral, parenteral, or depot formulations. Overall, the identified equivalent doses were comparable with those of the other methods, but there were also outliers. The major strength of this method to define dose response is that DDDs are available for most drugs, including old antipsychotics, that they are based on a variety of sources, and that DDDs are an internationally accepted measure. The major limitations are that the information used to estimate DDDS is likely to differ between the drugs. Moreover, this information is not publicly available, so that it cannot be reviewed. The WHO stresses that DDDs are mainly a standardized measure of drug consumption, and their use as a measure of dose equivalence can therefore be misleading. We, therefore, recommend that if alternative, more "scientific" dose equivalence methods are available for a drug they should be preferred to DDDs. Moreover, our summary can be a useful resource for pharmacovigilance studies. © The Author 2016. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.

49 CFR 40.203 - What problems cause a drug test to be cancelled unless they are corrected?

Code of Federal Regulations, 2010 CFR

2010-10-01

... 49 Transportation 1 2010-10-01 2010-10-01 false What problems cause a drug test to be cancelled... What problems cause a drug test to be cancelled unless they are corrected? (a) As the MRO, when a... the CCF, you must cancel the test unless the flaw is corrected. (d) The following are correctable...

A Predictive Model for Toxicity Effects Assessment of Biotransformed Hepatic Drugs Using Iterative Sampling Method.

PubMed

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

2016-12-09

Measuring toxicity is one of the main steps in drug development. Hence, there is a high demand for computational models to predict the toxicity effects of the potential drugs. In this study, we used a dataset, which consists of four toxicity effects:mutagenic, tumorigenic, irritant and reproductive effects. The proposed model consists of three phases. In the first phase, rough set-based methods are used to select the most discriminative features for reducing the classification time and improving the classification performance. Due to the imbalanced class distribution, in the second phase, different sampling methods such as Random Under-Sampling, Random Over-Sampling and Synthetic Minority Oversampling Technique are used to solve the problem of imbalanced datasets. ITerative Sampling (ITS) method is proposed to avoid the limitations of those methods. ITS method has two steps. The first step (sampling step) iteratively modifies the prior distribution of the minority and majority classes. In the second step, a data cleaning method is used to remove the overlapping that is produced from the first step. In the third phase, Bagging classifier is used to classify an unknown drug into toxic or non-toxic. The experimental results proved that the proposed model performed well in classifying the unknown samples according to all toxic effects in the imbalanced datasets.

The Drug Education Gap

ERIC Educational Resources Information Center

Reynolds, John C., Jr.

1976-01-01

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

Recovery from Problem Drug Use: What Can We Learn from the Dociologist Erving Goffman?

ERIC Educational Resources Information Center

Neale, Joanne; Nettleton, Sarah; Pickering, Lucy

2011-01-01

In this commentary, we critically review the contribution of the sociologist Erving Goffman (1922-1982) to understanding recovery from problem drug use. Previous research has indicated that drug users have a "spoiled identity" and must restore a "normal" or "unspoiled" identity in order to recover. This argument has been linked to Goffman's…

Drug-Related-Problem Outcomes and Program Satisfaction from a Comprehensive Brown Bag Medication Review.

PubMed

O'Connell, Mary Beth; Chang, Feng; Tocco, Ashley; Mills, Megan E; Hwang, Jamie M; Garwood, Candice L; Khreizat, Hanan S; Gupta, Nishi S

2015-09-01

To classify and quantify drug-related problems (DRPs), determine acceptance of DRP recommendations, and assess medication review satisfaction. Comprehensive brown bag medication reviews. Six senior centers and three senior high-rises. Individuals aged 60 and older (mean age 75.9 ± 8.5) taking five or more medications (n = 85). Two investigators independently classified DRPs using modified Pharmaceutical Care Network Europe classification scheme and severity of medication error and value of service scales. Two other investigators adjudicated classification differences. Satisfaction surveys were administered immediately and 3 months after review. A DRP recommendation implementation survey was completed at least 3 months after the review. Participants had a mean of 4.3 ± 2.8 DRPs (range 0-10). DRPs were classified as adverse reactions (30%), treatment effectiveness (28%), treatment costs (13%), information need (8%), and other (21%). Causes included drug selection (40%), wrong dosage (23%), participant problems (e.g., adherence, lack of medication knowledge, 16%), drug use process problems (12%), drug formulation (0.5%), treatment duration (0.5%), and other (7%). Interventions required drug changes (44%), prescriber input (37%), individual counseling (18%), or other (1%). DRP severities were significant (59%) or minor (35%). Participants expressed satisfaction with the program because they were able to ask questions, trusted the answers, and knew more about their medications. After 3 months, they had implemented 63% of the DRP recommendations. Older adults found the medication review helpful and implemented 63% of the DRP recommendations. © 2015, Copyright the Authors Journal compilation © 2015, The American Geriatrics Society.

Drug-related problems and pharmacist interventions in a cohort of patients with asthma and chronic obstructive pulmonary disease.

PubMed

Apikoglu-Rabus, Sule; Yesilyaprak, Gozde; Izzettin, Fikret Vehbi

2016-11-01

Asthma and chronic obstructive pulmonary disease are preventable and treatable chronic airway diseases with high incidence and prevalence. Pharmacists and clinical pharmacy based pharmaceutical care services have positive impact on therapy outcomes. The aim of this study is to describe drug related problems in a cohort of patients with asthma and chronic obstructive pulmonary disease and to assess interventions provided by the pharmacist to address these problems in a community pharmacy. Study population consisted of patients with asthma and chronic obstructive pulmonary disease older than 18 years who visited the study pharmacy during the pre-determined six-month period. The patients whose disease control states were "not fully controlled" were included in our study for further steps. On the first interview, present and potential drug related problems were addressed, interventions were provided. Follow-up interviews were held one month and two months later than the first interview. For the 44 patients with asthma, 59 drug-related problems and 134 causes for these problems were identified. Eighty-four interventions were made to resolve the problems; and 54.2% of the problems were resolved. For the 37 patients with chronic obstructive pulmonary disease, 60 drug-related problems and 128 causes for these problems were identified. Ninety-five interventions were made to resolve the problems; and 63.3% of the problems were resolved. Pharmacists taking part in therapy and management of asthma and chronic obstructive pulmonary disease can help patients be more educated about their disease and medications; and improve disease control and therapy outcomes. Copyright © 2016 Elsevier Ltd. All rights reserved.

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

PubMed

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

2015-04-01

An aging population and the increasing prevalence of chronic diseases have led to the increased use of medicines. Portugal is one of the European countries where more medicines are consumed and the associated expense is higher. Medicines are associated with enormous health benefits but also with the potential to cause illness and death. A drug related problem (DRP) is an "an event or circumstance involving drug therapy that actually or potentially interferes with desired health outcomes". In the U.S., they represent the 4th-6th leading cause of death and have an estimated cost of 130 billion dollars. Moreover, many of these DRP can be avoided. Elderly are at increased risk of DRP due to multiple factors: pluripathology and consequent polypharmacy, complex dosing regimens, pharmacokinetic/pharmacodynamic and functional/cognitive changes. Therefore, this population would be the one who would benefit most from the prevention, detection and control of DRP. The role of the pharmacist as an integral element of health care has been recognized by various international and European organizations. Providing pharmaceutical care as a patient-centered activity, focusing on their needs related to pharmacotherapy, contributes to guarantee that drug expenditure is a good investment, with benefits that outweigh potential risks. To evaluate the need for pharmaceutical care implementation in institutionalized, polymedicated elderly. Descriptive observational cross-sectional study carried out in six Portuguese nursing homes, selected by convenience, in November-December 2013. Each institution selected up to six patients, according to the following inclusion criteria: age ≥65 years, number of medications ≥5 and ability to respond to an interview. All participants signed an informed consent form. Pharmacists carried out a structured interview with each patient and consulted patient medical records to gather demographic data and information on health problems and medications used. To

Postmortem Presence of Drugs and Method of Violent Suicide

PubMed Central

Sheehan, Connor M.; Rogers, Richard G.; Boardman, Jason D.

2016-01-01

The link between substance use and suicide is well established. However, little research analyzes how substance use is related to the method of suicide. This paper analyzes how specific drugs are associated with method of suicide, a critical topic because drug use bears on the etiology of suicide and may lead to policies aimed at deterring suicide. We use the COVDRS and logistic regression to examine postmortem presence of drugs among 3,389 hanging and firearm suicides in Colorado from 2004–2009. Net of demographic controls, we find that opiates are positively associated with firearms (OR: 1.92, 95% L: 1.27, 95% U: 2.86]) while antidepressants are positively associated with hanging (OR: 1.45, 95% L: 1.04, 95% U: 2.03). For cocaine and opiates, the association between drug use and violent method vary by educational attainment. Importantly, knowledge of the presence and type of specific drug is strongly associated with the method of suicide. PMID:27239069

[Simple method for precognition of drug interaction between oral iron and phenolic hydroxyl group-containing drugs].

PubMed

Sunagane, Nobuyoshi; Yoshinobu, Etsuko; Murayama, Nobuko; Terawaki, Yasufumi; Kamimura, Naoki; Uruno, Tsutomu

2005-02-01

In the present study, we devised a simple method for detecting the drug interaction between oral iron preparations and phenolic hydroxyl group-containing drugs, using the coloring reaction as indicator, due to the formation of complexes or chelates. In the method, oral iron preparations and test drugs in amounts as much as single dose for adults were added to 10 ml of purified water to make sample suspensions for testing. Thirty minutes after mixing an oral iron suspension and a test drug suspension, the change of color in the mixture was observed macroscopically and graded as 0 to 3, with a marked color change judged as grade 3 and no color change as grade 0. Screening of 14 test drugs commonly used orally was carried out. When using sodium ferrous citrate preparations as oral iron, 5 were classified as grade 3, 2 as grade 2, 4 as grade 1, and 3 as grade 0, respectively. To verify usefulness of the method, the interactions suggested by screening were pharmacokinetically assessed by measuring serum concentrations of the drug in mice. When a levodopa or droxidopa preparation, judged as grade 3 in screening, was concomitantly administered with an iron preparation, a significant reduction in bioavailability of the test drug was observed, indicating possible drug interaction between the test drug and oral iron. Combined administration of an acetaminophen preparation, judged as grade 1, and oral iron preparation showed no influence on the bioavailability of the test drug, implying no detectable interactions between them. In conclusion, the simple method devised in the present study is useful for precognition of drug interactions between oral iron preparations and phenolic hydroxyl group-containing drugs, and the drugs with a higher grade in screening may induce drug interactions with oral iron.

Iterative methods for tomography problems: implementation to a cross-well tomography problem

NASA Astrophysics Data System (ADS)

Karadeniz, M. F.; Weber, G. W.

2018-01-01

The velocity distribution between two boreholes is reconstructed by cross-well tomography, which is commonly used in geology. In this paper, iterative methods, Kaczmarz’s algorithm, algebraic reconstruction technique (ART), and simultaneous iterative reconstruction technique (SIRT), are implemented to a specific cross-well tomography problem. Convergence to the solution of these methods and their CPU time for the cross-well tomography problem are compared. Furthermore, these three methods for this problem are compared for different tolerance values.

A Bright Future for Evolutionary Methods in Drug Design.

PubMed

Le, Tu C; Winkler, David A

2015-08-01

Most medicinal chemists understand that chemical space is extremely large, essentially infinite. Although high-throughput experimental methods allow exploration of drug-like space more rapidly, they are still insufficient to fully exploit the opportunities that such large chemical space offers. Evolutionary methods can synergistically blend automated synthesis and characterization methods with computational design to identify promising regions of chemical space more efficiently. We describe how evolutionary methods are implemented, and provide examples of published drug development research in which these methods have generated molecules with increased efficacy. We anticipate that evolutionary methods will play an important role in future drug discovery. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Toward better drug repositioning: prioritizing and integrating existing methods into efficient pipelines.

PubMed

Jin, Guangxu; Wong, Stephen T C

2014-05-01

Recycling old drugs, rescuing shelved drugs and extending patents' lives make drug repositioning an attractive form of drug discovery. Drug repositioning accounts for approximately 30% of the newly US Food and Drug Administration (FDA)-approved drugs and vaccines in recent years. The prevalence of drug-repositioning studies has resulted in a variety of innovative computational methods for the identification of new opportunities for the use of old drugs. Questions often arise from customizing or optimizing these methods into efficient drug-repositioning pipelines for alternative applications. It requires a comprehensive understanding of the available methods gained by evaluating both biological and pharmaceutical knowledge and the elucidated mechanism-of-action of drugs. Here, we provide guidance for prioritizing and integrating drug-repositioning methods for specific drug-repositioning pipelines. Copyright © 2013 Elsevier Ltd. All rights reserved.

Automated method for study of drug metabolism

NASA Technical Reports Server (NTRS)

Furner, R. L.; Feller, D. D.

1973-01-01

Commercially available equipment can be modified to provide automated system for assaying drug metabolism by continuous flow-through. System includes steps and devices for mixing drug with enzyme and cofactor in the presence of pure oxygen, dialyzing resulting metabolite against buffer, and determining amount of metabolite by colorimetric method.

Prevalence and Psychosocial Correlates of Party-Drug Use and Associated Problems among University Students in the Netherlands.

PubMed

Kunst, Laura E; Gebhardt, Winifred A

2018-04-18

Recent developments in drug use patterns call for an investigation of current party-drug use and associated problems among college students, who appear to be an important target population for harm reduction interventions. In addition to reporting on party-drug use prevalence, we investigated whether initial use and continuation of party-drug use among students was associated with demographic, personality and psychosocial factors. An online questionnaire was administered to 446 students from a Dutch university, inquiring about party-drug use, demographic characteristics, social norms and personality (big five, impulsiveness, aggression). Univariate and multivariate bootstrapped linear regression analyses were used. Of all students, 22.9% indicated having used party-drugs at least once, with a notable sex difference (39.2% of men vs. 16.2% of women). In contrast to the reported trends in Dutch nightlife, GHB was used rarely (lifetime 1.6%) and new psychoactive substances (NPS; 6.7%) appeared almost equally popular as amphetamines (7.6%) and cocaine (7%). Mild health/psychosocial problems (e.g., doing embarrassing things, feeling unwell) were common (65%), whereas serious problems (e.g., being hospitalized) were rare. Neuroticism, extraversion, conscientiousness and impulsiveness were associated with lifetime but not regular party-drug use. Of all predictors, lifetime and regular party-drug use were most strongly related to lenient injunctive and descriptive norms in friends, and a low motivation to comply with parents. Our findings indicate that harm reduction/preventive interventions might profit from focusing on social norms, and targeting students who are highly involved in a pro-party-drug environment while experiencing less parental influence.

Current HPLC Methods for Assay of Nano Drug Delivery Systems.

PubMed

Tekkeli, Serife Evrim Kepekci; Kiziltas, Mustafa Volkan

2017-01-01

In nano drug formulations the mechanism of release is a critical process to recognize controlled and targeted drug delivery systems. In order to gain high bioavailability and specificity from the drug to reach its therapeutic goal, the active substance must be loaded into the nanoparticles efficiently. Therefore, the amount in biological fluids or tissues and the remaining amount in nano carriers are very important parameters to understand the potential of the nano drug delivery systems. For this aim, suitable and validated quantitation methods are required to determine released drug concentrations from nano pharmaceutical formulations. HPLC (High Performance Liquid Chromatography) is one of the most common techniques used for determination of released drug content out of nano drug formulations, in different physical conditions, over different periods of time. Since there are many types of HPLC methods depending on detector and column types, it is a challenge for the researchers to choose a suitable method that is simple, fast and validated HPLC techniques for their nano drug delivery systems. This review's goal is to compare HPLC methods that are currently used in different nano drug delivery systems in order to provide detailed and useful information for researchers. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

The Visibility of Illicit Drugs: Implications for Community-Based Drug Control Strategies

PubMed Central

Saxe, Leonard; Kadushin, Charles; Beveridge, Andrew; Livert, David; Tighe, Elizabeth; Rindskopf, David; Ford, Julie; Brodsky, Archie

2001-01-01

Objectives. This study examined differences between the visibility of drugs and drug use in more than 2100 neighborhoods, challenging an assumption about drug use in poor, minority, and urban communities. Methods. A telephone survey assessed substance use and attitudes across 41 communities in an evaluation of a national community-based demand reduction program. Three waves of data were collected from more than 42 000 respondents. Results. Measures of neighborhood disadvantage, population density, and proportion of minority residents explained more than 57% of the variance between census tracts in visibility of drug sales but less than 10% of tract-to-tract variance in drug use. Visible drug sales were 6.3 times more likely to be reported in the most disadvantaged neighborhoods than in the least disadvantaged, while illicit drug use was only 1.3 times more likely. Conclusions. The most disadvantaged neighborhoods have the most visible drug problems, but drug use is nearly equally distributed across all communities. Thus, efforts to address drug-related problems in poorer areas need to take into account the broader drug market served by these neighborhoods. PMID:11726381

DrugE-Rank: improving drug-target interaction prediction of new candidate drugs or targets by ensemble learning to rank.

PubMed

Yuan, Qingjun; Gao, Junning; Wu, Dongliang; Zhang, Shihua; Mamitsuka, Hiroshi; Zhu, Shanfeng

2016-06-15

Identifying drug-target interactions is an important task in drug discovery. To reduce heavy time and financial cost in experimental way, many computational approaches have been proposed. Although these approaches have used many different principles, their performance is far from satisfactory, especially in predicting drug-target interactions of new candidate drugs or targets. Approaches based on machine learning for this problem can be divided into two types: feature-based and similarity-based methods. Learning to rank is the most powerful technique in the feature-based methods. Similarity-based methods are well accepted, due to their idea of connecting the chemical and genomic spaces, represented by drug and target similarities, respectively. We propose a new method, DrugE-Rank, to improve the prediction performance by nicely combining the advantages of the two different types of methods. That is, DrugE-Rank uses LTR, for which multiple well-known similarity-based methods can be used as components of ensemble learning. The performance of DrugE-Rank is thoroughly examined by three main experiments using data from DrugBank: (i) cross-validation on FDA (US Food and Drug Administration) approved drugs before March 2014; (ii) independent test on FDA approved drugs after March 2014; and (iii) independent test on FDA experimental drugs. Experimental results show that DrugE-Rank outperforms competing methods significantly, especially achieving more than 30% improvement in Area under Prediction Recall curve for FDA approved new drugs and FDA experimental drugs. http://datamining-iip.fudan.edu.cn/service/DrugE-Rank zhusf@fudan.edu.cn Supplementary data are available at Bioinformatics online. © The Author 2016. Published by Oxford University Press.

Drug-related problems in hospitalized patients on polypharmacy: the influence of age and gender

PubMed Central

Koh, Yvonne; Kutty, Fatimah Bte Moideen; Li, Shu Chuen

2005-01-01

Background Drug-related problems (DRPs) have been shown to prevail in hospitalized patients, and polypharmacy and increasing age have been identified as two important risk factors. Objective We investigated the occurrence of DRPs and adverse drug reactions (ADRs) amongst hospitalized patients prescribed polypharmacy, and the association of advanced age and female gender. Method A retrospective cross-sectional study was performed in an acute-care hospital in Singapore. Only patients prescribed polypharmacy were included. Mann-Whitney test was used to test for significant difference between the age and gender of patients and their risk of acquiring DRPs. The relative risks of developing DRP and ADR for geriatric patients and female patients were estimated. Results Of 347 patients prescribed polypharmacy (43% female and 58.2% geriatrics), no statistical correlations were observed between age and gender with developing DRPs. An increased number of medications was associated with higher risk for patients with DRPs on admission (p = 0.001), but not for inpatients with DRPs (p = 0.119). Results from patients with ADRs showed that the relative risk (RR) of geriatrics prescribed polypharmacy and major polypharmacy (10 and more drugs) were 1.01 and 1.23, respectively. Female patients had a RR of 0.79 compared with male patients in developing ADRs. Conclusion Results showed that among patients with polypharmacy, age and gender may not be as important as number of drugs prescribed as predictors of experiencing a DRP. A similar trend was observed in the development of ADRs. PMID:18360542

Role of Molecular Dynamics and Related Methods in Drug Discovery.

PubMed

De Vivo, Marco; Masetti, Matteo; Bottegoni, Giovanni; Cavalli, Andrea

2016-05-12

Molecular dynamics (MD) and related methods are close to becoming routine computational tools for drug discovery. Their main advantage is in explicitly treating structural flexibility and entropic effects. This allows a more accurate estimate of the thermodynamics and kinetics associated with drug-target recognition and binding, as better algorithms and hardware architectures increase their use. Here, we review the theoretical background of MD and enhanced sampling methods, focusing on free-energy perturbation, metadynamics, steered MD, and other methods most consistently used to study drug-target binding. We discuss unbiased MD simulations that nowadays allow the observation of unsupervised ligand-target binding, assessing how these approaches help optimizing target affinity and drug residence time toward improved drug efficacy. Further issues discussed include allosteric modulation and the role of water molecules in ligand binding and optimization. We conclude by calling for more prospective studies to attest to these methods' utility in discovering novel drug candidates.

Problem solving styles among people who use alcohol and other drugs in South Africa.

PubMed

Sorsdahl, Katherine; Stein, Dan J; Carrara, Henri; Myers, Bronwyn

2014-01-01

The present study examines the relationship between problem-solving styles, socio-demographic variables and risk of alcohol and other drug (AOD)-related problems among a South African population. The Social Problem-Solving Inventory-Revised, Center for Epidemiologic Studies Depression Scale (CES-D) and the Alcohol, Smoking and Substance Involvement Screening Test (ASSIST) were administered to a convenience sample of 1000 respondents. According to the ASSIST, 32% and 49% of respondents met criteria for moderate to high risk of alcohol use and illicit drug use respectively. After adjusting for the effects of other variables in the model, respondents who were of "Coloured" ancestry (PR=1.20, 95% CI 1.0-1.4), male (PR=1.19, 95% CI 1.04-1.37), older (PR=1.01, 95% CI 1.00-1.02), who adopted an avoidance style of coping with problems (PR=1.03, 95% CI 1.01-1.05) and who met criteria for depression (PR=1.42, 95% CI 1.12-1.79) were more likely to be classified as having risky AOD use. This suggests that interventions to improve problem solving and provide people with cognitive strategies to cope better with their problems may hold promise for reducing risky AOD use. © 2013.

Meshless Local Petrov-Galerkin Method for Bending Problems

NASA Technical Reports Server (NTRS)

Phillips, Dawn R.; Raju, Ivatury S.

2002-01-01

Recent literature shows extensive research work on meshless or element-free methods as alternatives to the versatile Finite Element Method. One such meshless method is the Meshless Local Petrov-Galerkin (MLPG) method. In this report, the method is developed for bending of beams - C1 problems. A generalized moving least squares (GMLS) interpolation is used to construct the trial functions, and spline and power weight functions are used as the test functions. The method is applied to problems for which exact solutions are available to evaluate its effectiveness. The accuracy of the method is demonstrated for problems with load discontinuities and continuous beam problems. A Petrov-Galerkin implementation of the method is shown to greatly reduce computational time and effort and is thus preferable over the previously developed Galerkin approach. The MLPG method for beam problems yields very accurate deflections and slopes and continuous moment and shear forces without the need for elaborate post-processing techniques.

What are some signs and symptoms of someone with a drug use problem?

MedlinePlus

... Prevention Phone Numbers and Websites Search Share You are here Home » What is Addiction? » What ... of someone with a drug use problem? What are some signs and symptoms of someone with a ...

Path optimization method for the sign problem

NASA Astrophysics Data System (ADS)

Ohnishi, Akira; Mori, Yuto; Kashiwa, Kouji

2018-03-01

We propose a path optimization method (POM) to evade the sign problem in the Monte-Carlo calculations for complex actions. Among many approaches to the sign problem, the Lefschetz-thimble path-integral method and the complex Langevin method are promising and extensively discussed. In these methods, real field variables are complexified and the integration manifold is determined by the flow equations or stochastically sampled. When we have singular points of the action or multiple critical points near the original integral surface, however, we have a risk to encounter the residual and global sign problems or the singular drift term problem. One of the ways to avoid the singular points is to optimize the integration path which is designed not to hit the singular points of the Boltzmann weight. By specifying the one-dimensional integration-path as z = t +if(t)(f ɛ R) and by optimizing f(t) to enhance the average phase factor, we demonstrate that we can avoid the sign problem in a one-variable toy model for which the complex Langevin method is found to fail. In this proceedings, we propose POM and discuss how we can avoid the sign problem in a toy model. We also discuss the possibility to utilize the neural network to optimize the path.

Multigrid Methods for Aerodynamic Problems in Complex Geometries

NASA Technical Reports Server (NTRS)

Caughey, David A.

1995-01-01

Work has been directed at the development of efficient multigrid methods for the solution of aerodynamic problems involving complex geometries, including the development of computational methods for the solution of both inviscid and viscous transonic flow problems. The emphasis is on problems of complex, three-dimensional geometry. The methods developed are based upon finite-volume approximations to both the Euler and the Reynolds-Averaged Navier-Stokes equations. The methods are developed for use on multi-block grids using diagonalized implicit multigrid methods to achieve computational efficiency. The work is focused upon aerodynamic problems involving complex geometries, including advanced engine inlets.

Drug Abuse in Southeast Asia.

ERIC Educational Resources Information Center

Scorzelli, James F.

This report examines the incidence of drug abuse and the methods of treatment and prevention of drug abuse used in Southeast Asia. Countries studied include Malaysia, Singapore, Thailand, Indonesia, and the Philippines. Because of Malaysia's intensive effort to eliminate its drug abuse problem, emphasis is placed on this country's treatment and…

Multigrid Methods for EHL Problems

NASA Technical Reports Server (NTRS)

Nurgat, Elyas; Berzins, Martin

1996-01-01

In many bearings and contacts, forces are transmitted through thin continuous fluid films which separate two contacting elements. Objects in contact are normally subjected to friction and wear which can be reduced effectively by using lubricants. If the lubricant film is sufficiently thin to prevent the opposing solids from coming into contact and carries the entire load, then we have hydrodynamic lubrication, where the lubricant film is determined by the motion and geometry of the solids. However, for loaded contacts of low geometrical conformity, such as gears, rolling contact bearings and cams, this is not the case due to high pressures and this is referred to as Elasto-Hydrodynamic Lubrication (EHL) In EHL, elastic deformation of the contacting elements and the increase in fluid viscosity with pressure are very significant and cannot be ignored. Since the deformation results in changing the geometry of the lubricating film, which in turn determines the pressure distribution, an EHL mathematical model must simultaneously satisfy the complex elasticity (integral) and the Reynolds lubrication (differential) equations. The nonlinear and coupled nature of the two equations makes numerical calculations computationally intensive. This is especially true for highly loaded problems found in practice. One novel feature of these problems is that the solution may exhibit sharp pressure spikes in the outlet region. To this date both finite element and finite difference methods have been used to solve EHL problems with perhaps greater emphasis on the use of the finite difference approach. In both cases, a major computational difficulty is ensuring convergence of the nonlinear equations solver to a steady state solution. Two successful methods for achieving this are direct iteration and multigrid methods. Direct iteration methods (e.g Gauss Seidel) have long been used in conjunction with finite difference discretizations on regular meshes. Perhaps one of the best examples of

Problems in the regulatory policy of the drug market

PubMed Central

Miziara, Nathália Molleis; Coutinho, Diogo Rosenthal

2015-01-01

OBJECTIVE Analyze the implementation of drug price regulation policy by the Drug Market Regulation Chamber. METHODS This is an interview-based study, which was undertaken in 2012, using semi-structured questionnaires with social actors from the pharmaceutical market, the pharmaceuticals industry, consumers and the regulatory agency. In addition, drug prices were compiled based on surveys conducted in the state of Sao Paulo, at the point of sale, between February 2009 and May 2012. RESULTS The mean drug prices charged at the point of sale (pharmacies) were well below the maximum price to the consumer, compared with many drugs sold in Brazil. Between 2009 and 2012, 44 of the 129 prices, corresponding to 99 drugs listed in the database of compiled prices, showed a variation of more than 20.0% in the mean prices at the point of sale and the maximum price to the consumer. In addition, many laboratories have refused to apply the price adequacy coefficient in their sales to government agencies. CONCLUSIONS The regulation implemented by the pharmaceutical market regulator was unable to significantly control prices of marketed drugs, without succeeding to push them to levels lower than those determined by the pharmaceutical industry and failing, therefore, in its objective to promote pharmaceutical support for the public. It is necessary reconstruct the regulatory law to allow market prices to be reduced by the regulator as well as institutional strengthen this government body. PMID:26083945

The averaging method in applied problems

NASA Astrophysics Data System (ADS)

Grebenikov, E. A.

1986-04-01

The totality of methods, allowing to research complicated non-linear oscillating systems, named in the literature "averaging method" has been given. THe author is describing the constructive part of this method, or a concrete form and corresponding algorithms, on mathematical models, sufficiently general , but built on concrete problems. The style of the book is that the reader interested in the Technics and algorithms of the asymptotic theory of the ordinary differential equations, could solve individually such problems. For specialists in the area of applied mathematics and mechanics.

Risk pathways among traumatic stress, posttraumatic stress disorder symptoms, and alcohol and drug problems: a test of four hypotheses.

PubMed

Haller, Moira; Chassin, Laurie

2014-09-01

The present study utilized longitudinal data from a community sample (n = 377; 166 trauma-exposed; 54% males; 73% non-Hispanic Caucasian; 22% Hispanic; 5% other ethnicity) to test whether pretrauma substance use problems increase risk for trauma exposure (high-risk hypothesis) or posttraumatic stress disorder (PTSD) symptoms (susceptibility hypothesis), whether PTSD symptoms increase risk for later alcohol/drug problems (self-medication hypothesis), and whether the association between PTSD symptoms and alcohol/drug problems is attributable to shared risk factors (shared vulnerability hypothesis). Logistic and negative binomial regressions were performed in a path analysis framework. Results provided the strongest support for the self-medication hypothesis, such that PTSD symptoms predicted higher levels of later alcohol and drug problems, over and above the influences of pretrauma family risk factors, pretrauma substance use problems, trauma exposure, and demographic variables. Results partially supported the high-risk hypothesis, such that adolescent substance use problems increased risk for assaultive violence exposure but did not influence overall risk for trauma exposure. There was no support for the susceptibility hypothesis. Finally, there was little support for the shared vulnerability hypothesis. Neither trauma exposure nor preexisting family adversity accounted for the link between PTSD symptoms and later substance use problems. Rather, PTSD symptoms mediated the effect of pretrauma family adversity on later alcohol and drug problems, thereby supporting the self-medication hypothesis. These findings make important contributions to better understanding the directions of influence among traumatic stress, PTSD symptoms, and substance use problems.

Operational analysis for the drug detection problem

NASA Astrophysics Data System (ADS)

Hoopengardner, Roger L.; Smith, Michael C.

1994-10-01

New techniques and sensors to identify the molecular, chemical, or elemental structures unique to drugs are being developed under several national programs. However, the challenge faced by U.S. drug enforcement and Customs officials goes far beyond the simple technical capability to detect an illegal drug. Entry points into the U.S. include ports, border crossings, and airports where cargo ships, vehicles, and aircraft move huge volumes of freight. Current technology and personnel are able to physically inspect only a small fraction of the entering cargo containers. The complexities of how to best utilize new technology to aid the detection process and yet not adversely affect the processing of vehicles and time-sensitive cargo is the challenge faced by these officials. This paper describes an ARPA sponsored initiative to develop a simple, yet useful, method for examining the operational consequences of utilizing various procedures and technologies in combination to achieve an `acceptable' level of detection probability. Since Customs entry points into the U.S. vary from huge seaports to a one lane highway checkpoint between the U.S. and Canadian or Mexico border, no one system can possibly be right for all points. This approach can examine alternative concepts for using different techniques/systems for different types of entry points. Operational measures reported include the average time to process vehicles and containers, the average and maximum numbers in the system at any time, and the utilization of inspection teams. The method is implemented via a PC-based simulation written in GPSS-PC language. Input to the simulation model is (1) the individual detection probabilities and false positive rates for each detection technology or procedure, (2) the inspection time for each procedure, (3) the system configuration, and (4) the physical distance between inspection stations. The model offers on- line graphics to examine effects as the model runs.

[Achievements and problems of modern trials of antihypertensive drugs].

PubMed

Kobalava, Zh D; Kotovskaia, Iu V

2011-01-01

Most important value of lowering of substantially elevated arterial pressure (AP) for improvement of outcomes in patients with arterial hypertension (AH) was convincingly confirmed by large truly placebo controlled randomized clinical trials (RCT) with the use of mainly diuretics, and/or beta-adrenoblockers in the 60-80ths. Later comparative RCT confirmed equal antihypertensive efficacy of 5 main drug classes relative to AP level in brachial artery. In this review we discuss merit of auxiliary class-specific properties of antihypertensive agents potentially affecting prognosis besides AP lowering. We also discuss problems related to decline of significance of quantitative criteria of AH and consideration of AP level in general context of cardiovascular risk; problems of external validity of RCT; extrapolation of RCT results obtained in patients with complicated AH and very high cardiovascular risk on young patients with uncomplicated AH; significance of hard and surrogate end points.

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

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

Why Research Design and Methods Is So Crucial to Understanding Drug Use/Abuse: Introduction to the Special Issue.

PubMed

Scheier, Lawrence M

2018-06-01

The collection of articles in this special issue both raise the bar and inspire new thinking with regard to both design and methodology concerns that influence drug use/abuse research. Thematically speaking, the articles focus on issues related to missing data, response formats, strategies for data harmonization, propensity scoring methods as an alternative to randomized control trials, integrative data analysis, statistical corrections to reduce bias from attrition, challenges faced from conducting large-scale evaluations, and employing abductive theory of method as an alternative to the more traditional hypothetico-deductive reasoning. Collectively, these issues are of paramount importance as they provide specific means to improve our investigative tools and refine the logical framework we employ to examine the problem of drug use/abuse. Each of the authors addresses a specific challenge outlining how it affects our current research efforts and then outlines remedies that can advance the field. To their credit, they have included issues that affect both etiology and prevention, thus broadening our horizons as we learn more about developmental processes causally related to drug use/abuse and intervention strategies that can mitigate developmental vulnerability. This is the essential dialogue required to advance our intellectual tool kit and improve the research skills we bring to bear on the important questions facing the field of drug use/abuse. Ultimately, the goal is to increase our ability to identify the causes and consequences of drug use/abuse and find ways to ameliorate these problems as we engage the public health agenda.

49 CFR 40.201 - What problems always cause a drug test to be cancelled and may result in a requirement for...

Code of Federal Regulations, 2010 CFR

2010-10-01

... cancelled and may result in a requirement for another collection? 40.201 Section 40.201 Transportation... TESTING PROGRAMS Problems in Drug Tests § 40.201 What problems always cause a drug test to be cancelled and may result in a requirement for another collection? As the MRO, you must cancel a drug test when a...

Identifying drugs that cause acute thrombocytopenia: an analysis using 3 distinct methods

PubMed Central

Reese, Jessica A.; Li, Xiaoning; Hauben, Manfred; Aster, Richard H.; Bougie, Daniel W.; Curtis, Brian R.; George, James N.

2010-01-01

Drug-induced immune thrombocytopenia (DITP) is often suspected in patients with acute thrombocytopenia unexplained by other causes, but documenting that a drug is the cause of thrombocytopenia can be challenging. To provide a resource for diagnosis of DITP and for drug safety surveillance, we analyzed 3 distinct methods for identifying drugs that may cause thrombocytopenia. (1) Published case reports of DITP have described 253 drugs suspected of causing thrombocytopenia; using defined clinical criteria, 87 (34%) were identified with evidence that the drug caused thrombocytopenia. (2) Serum samples from patients with suspected DITP were tested for 202 drugs; drug-dependent, platelet-reactive antibodies were identified for 67 drugs (33%). (3) The Food and Drug Administration's Adverse Event Reporting System database was searched for drugs associated with thrombocytopenia by use of data mining algorithms; 1444 drugs had at least 1 report associated with thrombocytopenia, and 573 (40%) drugs demonstrated a statistically distinctive reporting association with thrombocytopenia. Among 1468 drugs suspected of causing thrombocytopenia, 102 were evaluated by all 3 methods, and 23 of these 102 drugs had evidence for an association with thrombocytopenia by all 3 methods. Multiple methods, each with a distinct perspective, can contribute to the identification of drugs that can cause thrombocytopenia. PMID:20530792

49 CFR 40.201 - What problems always cause a drug test to be cancelled and may result in a requirement for...

Code of Federal Regulations, 2013 CFR

2013-10-01

... 49 Transportation 1 2013-10-01 2013-10-01 false What problems always cause a drug test to be cancelled and may result in a requirement for another collection? 40.201 Section 40.201 Transportation Office of the Secretary of Transportation PROCEDURES FOR TRANSPORTATION WORKPLACE DRUG AND ALCOHOL TESTING PROGRAMS Problems in Drug Tests § 40.201 Wha...

Fenethylline (Captagon) Abuse - Local Problems from an Old Drug Become Universal.

PubMed

Katselou, Maria; Papoutsis, Ioannis; Nikolaou, Panagiota; Qammaz, Samir; Spiliopoulou, Chara; Athanaselis, Sotiris

2016-08-01

Fenethylline is a theophylline derivative of amphetamine having stimulant effects similar to those of other amphetamine-type derivatives. Fenethylline was used as medicament for hyperactivity disorders in children, narcolepsy and depression, but it has also been used as a drug of abuse under the common name of 'captagon'. Unlike other drugs of abuse, the clandestine synthesis of fenethylline is simple, using inexpensive laboratory instrumentation and raw materials legal to obtain. A review of all the existing knowledge of fenethylline is reported, concerning its chemistry, synthesis, pharmacology and toxicology, legislation, its prevalence and use as drug of abuse, as well as its analysis in biological or seized samples. Published or reported captagon-related cases and seizures are also presented. All the reviewed information was gathered through a detailed search of PubMed and the Internet. The primary drug market for fenethylline (as captagon) has traditionally been countries located on the Arabian Peninsula but also North Africa since 2013. In Arab countries, millions of captagon tablets are seized every year which represents one-third of global amphetamines seizures within a year. Furthermore, three of four patients treated for drug problems in Saudi Arabia are addicted to amphetamines, almost exclusively in the form of captagon. Significant information on fenethylline is provided for pharmacologists, toxicologists and forensic pathologists. Fenethylline, although old, has recently been introduced to the drug market, especially in Arab countries. Continuous community alertness is needed to tackle this current growing phenomenon. © 2016 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

Pattern of drug therapy problems and interventions in ambulatory patients receiving antiretroviral therapy in Nigeria

PubMed Central

Ojeh, Victor B.; Naima, Nasir; Abah, Isaac O.; Falang, Kakjing D.; Lucy, Ogwuche; London, Ibrahim; Dady, Christiana; Agaba, Patricia; Agbaji, Oche

2015-01-01

Objectives: We describe the frequency and types of drug therapy problems (DTPs), and interventions carried out to resolve them, among a cohort of HIV-infected patients on ART in Jos, Nigeria. Methods: A prospective pharmacists’ intervention study was conducted between January and August 2012 at the outpatient HIV clinic of the Jos University Teaching Hospital (JUTH). Pharmacists identified DTPs and made recommendations to resolve them. The main outcome measures were number of DTPs encountered, interventions proposed and acceptance rate of recommendations. Results: A total of 42,416 prescriptions were dispensed to 9339 patients during the eight months study. A total of 420 interventions (Intervention rate of 1 per 100 prescriptions) were made to resolve DTPs in 401 (4.3%) patients with a mean age of 41 (SD=10) years, and made up of 73% females. DTPs encountered were drug omission (n=89, 21.2%), unnecessary drug (n=55, 13.1%) and wrong drug indication (n=55, 13.1%). Recommendations offered included; Addition of another drug to the therapy (n=87, 20.7%), rectification of incomplete prescriptions (n=85, 20.2%), change of drug or dosage (n=67, 16.0%), and discontinuation of the offending drug (n=59, 14.0%). A total of 389 (93%) out of 420 of the recommendations were accepted. In all, 50.4% (212) of the problematic prescriptions were changed and dispensed, 22.2% (89) were clarified and dispensed, while wrong identities were corrected in 11.7% (49). However, 7.5% (30) prescriptions were dispensed as prescribed, 5.2% (21) were not dispensed, and 3% (12) were unresolved. Conclusion: Our findings suggest that pharmacists-initiated interventions can ameliorate DTPs in patients receiving ART given the high intervention acceptance rate recorded. The implication of this finding is that pharmacists with requisite training in HIV pharmacotherapy are an excellent resource in detecting and minimizing the effect of antiretroviral drug-related errors. PMID:26131046

Comparison of two DSC-based methods to predict drug-polymer solubility.

PubMed

Rask, Malte Bille; Knopp, Matthias Manne; Olesen, Niels Erik; Holm, René; Rades, Thomas

2018-04-05

The aim of the present study was to compare two DSC-based methods to predict drug-polymer solubility (melting point depression method and recrystallization method) and propose a guideline for selecting the most suitable method based on physicochemical properties of both the drug and the polymer. Using the two methods, the solubilities of celecoxib, indomethacin, carbamazepine, and ritonavir in polyvinylpyrrolidone, hydroxypropyl methylcellulose, and Soluplus® were determined at elevated temperatures and extrapolated to room temperature using the Flory-Huggins model. For the melting point depression method, it was observed that a well-defined drug melting point was required in order to predict drug-polymer solubility, since the method is based on the depression of the melting point as a function of polymer content. In contrast to previous findings, it was possible to measure melting point depression up to 20 °C below the glass transition temperature (T g ) of the polymer for some systems. Nevertheless, in general it was possible to obtain solubility measurements at lower temperatures using polymers with a low T g . Finally, for the recrystallization method it was found that the experimental composition dependence of the T g must be differentiable for compositions ranging from 50 to 90% drug (w/w) so that one T g corresponds to only one composition. Based on these findings, a guideline for selecting the most suitable thermal method to predict drug-polymer solubility based on the physicochemical properties of the drug and polymer is suggested in the form of a decision tree. Copyright © 2018 Elsevier B.V. All rights reserved.

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.

Spectral methods for time dependent problems

NASA Technical Reports Server (NTRS)

Tadmor, Eitan

1990-01-01

Spectral approximations are reviewed for time dependent problems. Some basic ingredients from the spectral Fourier and Chebyshev approximations theory are discussed. A brief survey was made of hyperbolic and parabolic time dependent problems which are dealt with by both the energy method and the related Fourier analysis. The ideas presented above are combined in the study of accuracy stability and convergence of the spectral Fourier approximation to time dependent problems.

SemaTyP: a knowledge graph based literature mining method for drug discovery.

PubMed

Sang, Shengtian; Yang, Zhihao; Wang, Lei; Liu, Xiaoxia; Lin, Hongfei; Wang, Jian

2018-05-30

Drug discovery is the process through which potential new medicines are identified. High-throughput screening and computer-aided drug discovery/design are the two main drug discovery methods for now, which have successfully discovered a series of drugs. However, development of new drugs is still an extremely time-consuming and expensive process. Biomedical literature contains important clues for the identification of potential treatments. It could support experts in biomedicine on their way towards new discoveries. Here, we propose a biomedical knowledge graph-based drug discovery method called SemaTyP, which discovers candidate drugs for diseases by mining published biomedical literature. We first construct a biomedical knowledge graph with the relations extracted from biomedical abstracts, then a logistic regression model is trained by learning the semantic types of paths of known drug therapies' existing in the biomedical knowledge graph, finally the learned model is used to discover drug therapies for new diseases. The experimental results show that our method could not only effectively discover new drug therapies for new diseases, but also could provide the potential mechanism of action of the candidate drugs. In this paper we propose a novel knowledge graph based literature mining method for drug discovery. It could be a supplementary method for current drug discovery methods.

Semismooth Newton method for gradient constrained minimization problem

NASA Astrophysics Data System (ADS)

Anyyeva, Serbiniyaz; Kunisch, Karl

2012-08-01

In this paper we treat a gradient constrained minimization problem, particular case of which is the elasto-plastic torsion problem. In order to get the numerical approximation to the solution we have developed an algorithm in an infinite dimensional space framework using the concept of the generalized (Newton) differentiation. Regularization was done in order to approximate the problem with the unconstrained minimization problem and to make the pointwise maximum function Newton differentiable. Using semismooth Newton method, continuation method was developed in function space. For the numerical implementation the variational equations at Newton steps are discretized using finite elements method.

Realizing drug repositioning by adapting a recommendation system to handle the process.

PubMed

Ozsoy, Makbule Guclin; Özyer, Tansel; Polat, Faruk; Alhajj, Reda

2018-04-12

Drug repositioning is the process of identifying new targets for known drugs. It can be used to overcome problems associated with traditional drug discovery by adapting existing drugs to treat new discovered diseases. Thus, it may reduce associated risk, cost and time required to identify and verify new drugs. Nowadays, drug repositioning has received more attention from industry and academia. To tackle this problem, researchers have applied many different computational methods and have used various features of drugs and diseases. In this study, we contribute to the ongoing research efforts by combining multiple features, namely chemical structures, protein interactions and side-effects to predict new indications of target drugs. To achieve our target, we realize drug repositioning as a recommendation process and this leads to a new perspective in tackling the problem. The utilized recommendation method is based on Pareto dominance and collaborative filtering. It can also integrate multiple data-sources and multiple features. For the computation part, we applied several settings and we compared their performance. Evaluation results show that the proposed method can achieve more concentrated predictions with high precision, where nearly half of the predictions are true. Compared to other state of the art methods described in the literature, the proposed method is better at making right predictions by having higher precision. The reported results demonstrate the applicability and effectiveness of recommendation methods for drug repositioning.

Fluorescence And Alternative Methods In Urine Drug Testing

NASA Astrophysics Data System (ADS)

Jain, Naresh C.

1988-04-01

Drug abuse has become-one of the most compelling realities _ ot contemporary society. It has penetrated every segment ot our population: trom schools to sports and trom organized crime to board rooms . Drugs in tie w9rkplace allegedly cost government agencies and business millions ot dollars each year in increased absenteeism,. poor work performance, thefts,accidents andwastedtime. The President's Commission on Organized Crime and the federal government are in tavor ot urine drug testing. In fact many employers are now resorting to urine drug testing on current and prospective employees. This presep.tation discusses different laboratory methods used in urine drug.testing, including immunoassays, fluorescence polarization, thin layer chromatography, high pressure liquid chromatography, gas chromatography and gas-chromatography-mass spectrometry.

Modified Finite Particle Methods for Stokes problems

NASA Astrophysics Data System (ADS)

Montanino, A.; Asprone, D.; Reali, A.; Auricchio, F.

2018-04-01

The Modified Finite Particle Method (MFPM) is a numerical method belonging to the class of meshless methods, nowadays widely investigated due to their characteristic of being capable to easily model large deformation and fluid-dynamic problems. Here we use the MFPM to approximate the Stokes problem. Since the classical formulation of the Stokes problem may lead to pressure spurious oscillations, we investigate alternative formulations and focus on how MFPM discretization behaves in those situations. Some of the investigated formulations, in fact, do not enforce strongly the incompressibility constraint, and therefore an important issue of the present work is to verify if the MFPM is able to correctly reproduce the incompressibility in those cases. The numerical results show that for the formulations in which the incompressibility constraint is properly satisfied from a numerical point of view, the expected second-order is achieved, both in static and in dynamic problems.

Changes in psychiatric symptoms among persons with methamphetamine dependence predicts changes in severity of drug problems but not frequency of use.

PubMed

Polcin, Douglas L; Korcha, Rachael; Bond, Jason; Galloway, Gantt; Nayak, Madhabika

2016-01-01

Few studies have examined how changes in psychiatric symptoms over time are associated with changes in drug use and severity of drug problems. No studies have examined these relationships among methamphetamine (MA)-dependent persons receiving motivational interviewing within the context of standard outpatient treatment. Two hundred seventeen individuals with MA dependence were randomly assigned to a standard single session of motivational interviewing (MI) or an intensive 9-session model of MI. Both groups received standard outpatient group treatment. The Addiction Severity Index (ASI) and timeline follow-back (TLFB) for MA use were administered at treatment entry and 2-, 4-, and 6-month follow-ups. Changes in ASI psychiatric severity between baseline and 2 months predicted changes in ASI drug severity during the same time period, but not changes on measures of MA use. Item analysis of the ASI drug scale showed that psychiatric severity predicted how troubled or bothered participants were by their drug us, how important they felt it was for them to get treatment, and the number of days they experienced drug problems. However, it did not predict the number days they used drugs in the past 30 days. These associations did not differ between study conditions, and they persisted when psychiatric severity and outcomes were compared across 4- and 6-month time periods. Results are among the first to track how changes in psychiatric severity over time are associated with changes in MA use and severity of drug problems. Treatment efforts targeting reduction of psychiatric symptoms among MA-dependent persons might be helpful in reducing the level of distress and problems associated with MA use but not how often it is used. There is a need for additional research describing the circumstances under which the experiences and perceptions of drug-related problems diverge from frequency of consumption.

Is There a Space-Based Technology Solution to Problems with Preclinical Drug Toxicity Testing?

PubMed

Hammond, Timothy; Allen, Patricia; Birdsall, Holly

2016-07-01

Even the finest state-of-the art preclinical drug testing, usually in primary hepatocytes, remains an imperfect science. Drugs continue to be withdrawn from the market due to unforeseen toxicity, side effects, and drug interactions. The space program may be able to provide a lifeline. Best known for rockets, space shuttles, astronauts and engineering, the space program has also delivered some serious medical science. Optimized suspension culture in NASA's specialized suspension culture devices, known as rotating wall vessels, uniquely maintains Phase I and Phase II drug metabolizing pathways in hepatocytes for weeks in cell culture. Previously prohibitively expensive, new materials and 3D printing techniques have the potential to make the NASA rotating wall vessel available inexpensively on an industrial scale. Here we address the tradeoffs inherent in the rotating wall vessel, limitations of alternative approaches for drug metabolism studies, and the market to be addressed. Better pre-clinical drug testing has the potential to significantly reduce the morbidity and mortality of one of the most common problems in modern medicine: adverse events related to pharmaceuticals.

Materials and methods for delivery of biological drugs

NASA Astrophysics Data System (ADS)

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

2016-11-01

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

Drug Abuse

MedlinePlus

... drugs, including opioids Drug abuse also plays a role in many major social problems, such as drugged driving, violence, stress, and child abuse. Drug abuse can lead to homelessness, crime, and missed work or problems with keeping a job. It harms ...

Poor Response Inhibition as a Predictor of Problem Drinking and Illicit Drug Use in Adolescents at Risk for Alcoholism and Other Substance Use Disorders

ERIC Educational Resources Information Center

Nigg, Joel T.; Wong, Maria M.; Martel, Michelle M.; Jester, Jennifer M.; Puttler, Leon I.; Glass, Jennifer M.; Adams, Kenneth M.; Fitzgerald, Hiram E.; Zucker, Robert A.

2006-01-01

Objective: To evaluate the predictive power of executive functions, in particular, response inhibition, in relation to alcohol-related problems and illicit drug use in adolescence. Method: A total of 498 children from 275 families from a longitudinal high-risk study completed executive function measures in early and late adolescence and lifetime…

Advances in industrial biopharmaceutical batch process monitoring: Machine-learning methods for small data problems.

PubMed

Tulsyan, Aditya; Garvin, Christopher; Ündey, Cenk

2018-04-06

Biopharmaceutical manufacturing comprises of multiple distinct processing steps that require effective and efficient monitoring of many variables simultaneously in real-time. The state-of-the-art real-time multivariate statistical batch process monitoring (BPM) platforms have been in use in recent years to ensure comprehensive monitoring is in place as a complementary tool for continued process verification to detect weak signals. This article addresses a longstanding, industry-wide problem in BPM, referred to as the "Low-N" problem, wherein a product has a limited production history. The current best industrial practice to address the Low-N problem is to switch from a multivariate to a univariate BPM, until sufficient product history is available to build and deploy a multivariate BPM platform. Every batch run without a robust multivariate BPM platform poses risk of not detecting potential weak signals developing in the process that might have an impact on process and product performance. In this article, we propose an approach to solve the Low-N problem by generating an arbitrarily large number of in silico batches through a combination of hardware exploitation and machine-learning methods. To the best of authors' knowledge, this is the first article to provide a solution to the Low-N problem in biopharmaceutical manufacturing using machine-learning methods. Several industrial case studies from bulk drug substance manufacturing are presented to demonstrate the efficacy of the proposed approach for BPM under various Low-N scenarios. © 2018 Wiley Periodicals, Inc.

Random Walk Method for Potential Problems

NASA Technical Reports Server (NTRS)

Krishnamurthy, T.; Raju, I. S.

2002-01-01

A local Random Walk Method (RWM) for potential problems governed by Lapalace's and Paragon's equations is developed for two- and three-dimensional problems. The RWM is implemented and demonstrated in a multiprocessor parallel environment on a Beowulf cluster of computers. A speed gain of 16 is achieved as the number of processors is increased from 1 to 23.

Establishment of an evaluation method to detect drug distribution in hair follicles.

PubMed

Abe, Akinari; Saito, Miyuki; Kadhum, Wesam R; Todo, Hiroaki; Sugibayashi, Kenji

2018-05-05

Development of an appropriate method to evaluate drug disposition or targeting ability in hair follicles (HFs) is urgently needed in order to develop useful pharmaceutical products with pharmacological effects in HFs. In the present study, a cyanoacrylate biopsy (CB) method was used to measure drug disposition in HFs using a model hydrophilic drug, caffeine (CAF), and a lipophilic drug, 4-butylresorcinol (BR), in excised porcine skin. As a result, the height of HF replicas and the recovery ratio decreased with an increase in the application times of the CB method. HF replicas with a length of approximately 175 µm were obtained using a single application of the CB method. Drug distribution in the HF was detected even 5 min after topical application regardless of the lipophilicity of the drugs, although no drug disposition was observed in the deeper layers of the stratum corneum at the same time (5 min). Furthermore, significantly higher amounts of BR were observed in the stratum corneum and HF, compared with those of CAF. These results suggested that the CB method could be useful to evaluate the safety and efficacy as well as the disposition of topically applied chemicals, especially for HF-targeting drugs. Copyright © 2018 Elsevier B.V. All rights reserved.

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

PubMed

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

2017-09-01

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

Predicting New Indications for Approved Drugs Using a Proteo-Chemometric Method

PubMed Central

Dakshanamurthy, Sivanesan; Issa, Naiem T; Assefnia, Shahin; Seshasayee, Ashwini; Peters, Oakland J; Madhavan, Subha; Uren, Aykut; Brown, Milton L; Byers, Stephen W

2012-01-01

The most effective way to move from target identification to the clinic is to identify already approved drugs with the potential for activating or inhibiting unintended targets (repurposing or repositioning). This is usually achieved by high throughput chemical screening, transcriptome matching or simple in silico ligand docking. We now describe a novel rapid computational proteo-chemometric method called “Train, Match, Fit, Streamline” (TMFS) to map new drug-target interaction space and predict new uses. The TMFS method combines shape, topology and chemical signatures, including docking score and functional contact points of the ligand, to predict potential drug-target interactions with remarkable accuracy. Using the TMFS method, we performed extensive molecular fit computations on 3,671 FDA approved drugs across 2,335 human protein crystal structures. The TMFS method predicts drug-target associations with 91% accuracy for the majority of drugs. Over 58% of the known best ligands for each target were correctly predicted as top ranked, followed by 66%, 76%, 84% and 91% for agents ranked in the top 10, 20, 30 and 40, respectively, out of all 3,671 drugs. Drugs ranked in the top 1–40, that have not been experimentally validated for a particular target now become candidates for repositioning. Furthermore, we used the TMFS method to discover that mebendazole, an anti-parasitic with recently discovered and unexpected anti-cancer properties, has the structural potential to inhibit VEGFR2. We confirmed experimentally that mebendazole inhibits VEGFR2 kinase activity as well as angiogenesis at doses comparable with its known effects on hookworm. TMFS also predicted, and was confirmed with surface plasmon resonance, that dimethyl celecoxib and the anti-inflammatory agent celecoxib can bind cadherin-11, an adhesion molecule important in rheumatoid arthritis and poor prognosis malignancies for which no targeted therapies exist. We anticipate that expanding our TMFS

Novel drug delivery systems in pain therapy.

PubMed

Al Malyan, M; Becchi, C; Boncinelli, S; Ashammakhi, N

2007-03-01

Pain is an unpleasant sensory experience resulting from damage to bodily tissues. It is considered a significant public health problem because it affects 1/5 of the world population and causes loss of great amounts of money. Pain reflects a mixture of pathological, psychological and genetic conditions that need deep understanding to be efficiently treated. If under-treated, pain results in serious immune and metabolic problems. Pain management faces many problems that limit its control. For instance, efficiency of pain killers is limited, pain killers give rise to serious side effects and inability of drug administration methods to help in pain control. Technology can overcome some of these problems and the introduction of implantable controlled drug delivery systems (CDDS), manufactured from biodegradable materials, offers a solution. Implantable CDDS provide good level of pain control, as they continuously provide drug, reduce side effects and improve patients' compliance. Biodegradable type of implantable CDDS are polymer based devices that are fabricated to locally deliver drugs in a pre-designed manner. They are currently a focus of research in the field of pain therapy in order to explore their chance to offer an alternative to the conventional methods for drug delivery. This paper aims to highlight the dimensions of pain issue and to overview the basics of drug release from polymers used for CDDS in pain management. In addition, it discusses the recent advances in the technologically designed drug delivery systems in the field of pain medicine and their clinical applications. Future perspectives are also presented.

A direct method for nonlinear ill-posed problems

NASA Astrophysics Data System (ADS)

Lakhal, A.

2018-02-01

We propose a direct method for solving nonlinear ill-posed problems in Banach-spaces. The method is based on a stable inversion formula we explicitly compute by applying techniques for analytic functions. Furthermore, we investigate the convergence and stability of the method and prove that the derived noniterative algorithm is a regularization. The inversion formula provides a systematic sensitivity analysis. The approach is applicable to a wide range of nonlinear ill-posed problems. We test the algorithm on a nonlinear problem of travel-time inversion in seismic tomography. Numerical results illustrate the robustness and efficiency of the algorithm.

Solid dispersions, part II: new strategies in manufacturing methods for dissolution rate enhancement of poorly water-soluble drugs.

PubMed

Bikiaris, Dimitrios N

2011-12-01

The absorption of poorly water-soluble drugs, when presented in the crystalline state to the gastrointestinal tract, is typically dissolution rate-limited, and according to BCS these drugs belong mainly to class II. Both dissolution kinetics and solubility are particle size dependent. Nowadays, various techniques are available to the pharmaceutical industry for dissolution rate enhancement of such drugs. Among such techniques, nanosuspensions and drug formulation in solid dispersions are those with the highest interest. This review discusses strategies undertaken over the last 10 years, which have been applied for the dissolution enhancement of poorly water-soluble drugs; such processes include melt mixing, electrospinning, microwave irradiation and the use of inorganic nanoparticles. Many problems in this field still need to be solved, mainly the use of toxic solvents, and for this reason the use of innovative new procedures and materials will increase over the coming years. Melt mixing remains extremely promising for the preparation of SDs and will probably become the most used method in the future for the preparation of solid drug dispersions.

Extension of modified power method to two-dimensional problems

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

Zhang, Peng; Ulsan National Institute of Science and Technology, 50 UNIST-gil, Ulsan 44919; Lee, Hyunsuk

2016-09-01

In this study, the generalized modified power method was extended to two-dimensional problems. A direct application of the method to two-dimensional problems was shown to be unstable when the number of requested eigenmodes is larger than a certain problem dependent number. The root cause of this instability has been identified as the degeneracy of the transfer matrix. In order to resolve this instability, the number of sub-regions for the transfer matrix was increased to be larger than the number of requested eigenmodes; and a new transfer matrix was introduced accordingly which can be calculated by the least square method. Themore » stability of the new method has been successfully demonstrated with a neutron diffusion eigenvalue problem and the 2D C5G7 benchmark problem. - Graphical abstract:.« less

On illicit drug policies; methods of evaluation and comments on recent practices.

PubMed

Trovato, Giovanni; Vezzani, Antonio

2013-06-01

This contribution provides an overview of different approaches used to analyse drug policies within and across countries. Besides the great number of cost of illness studies which have contributed to the assessment of health harms and risks associated to the drug use, most of the recent efforts have focused on the creation of synthetic indices to classify countries around the world or to evaluate particular law enforcement policies in some countries. This is probably due to a general lack of comparable data across countries. The wide variety of budgetary practices in the drugs field in Europe contributes to the problems that exist in estimating drug-related public expenditure. These heterogeneous accounting practices, together with the complexity of the drug phenomenon and the multiplicity of perspectives on the issue, strongly constrains the possibility of economically evaluate and compare drug laws across countries.

An active role for machine learning in drug development

PubMed Central

Murphy, Robert F.

2014-01-01

Due to the complexity of biological systems, cutting-edge machine-learning methods will be critical for future drug development. In particular, machine-vision methods to extract detailed information from imaging assays and active-learning methods to guide experimentation will be required to overcome the dimensionality problem in drug development. PMID:21587249

Problem-oriented drug information: physicians' expectations and impact on clinical practice.

PubMed

Hedegaard, U; Damkier, P

2009-05-01

Problem-oriented drug information (POD) is a service in which health professionals provide evidence-based answers to clinical questions posed by physicians. The objective of this study was to evaluate the user satisfaction and clinical impact of POD, to investigate predictors for use and to examine the kind of sources physicians search before applying for POD. To evaluate POD, a questionnaire was distributed with problem-oriented answers sent from a drug information centre to physicians during the period of April 2006 to March 2007. Of 197 questionnaires, 183 (93%) were returned. The information from the POD service was highly valued by the physicians, and 90% of the answers led to reported impact on clinical practice in the specific clinical situation. Furthermore, 74% of the answers were intended to be used in a wider context either for future patients (67%) or for dissemination to colleagues (51%). Secondary-care physicians more often than general practitioners (GPs) used the information for dissemination to colleagues (63 vs. 39%, P = 0.0008), while GPs more often used the answer to support patient information (88 vs. 70%, P = 0.0029). The most prominent motive for applying for POD was a request for evidence-based information (78%), and the service was used to overcome barriers to practicing evidence-based medicine such as lack of time (36%), skills for searching (26%), and appraising the literature (13%). Before inquiring, 74% of the physicians had tried other information sources; the most frequent sources used were a drug reference (68%) and consulting a colleague (24%). Secondary-care physicians reported fewer barriers than GPs when seeking information, and secondary-care physicians searched other sources more often than GPs before contacting the service (81 vs. 67%, P = 0.031). POD represents a useful source for acquiring evidence-based drug information by physicians. POD is highly valued by the users. It was reported to have an impact on clinical practice

Microparticles Produced by the Hydrogel Template Method for Sustained Drug Delivery

PubMed Central

Lu, Ying; Sturek, Michael; Park, Kinam

2014-01-01

Polymeric microparticles have been used widely for sustained drug delivery. Current methods of microparticle production can be improved by making homogeneous particles in size and shape, increasing the drug loading, and controlling the initial burst release. In the current study, the hydrogel template method was used to produce homogeneous poly(lactide-co-glycolide) (PLGA) microparticles and to examine formulation and process-related parameters. Poly(vinyl alcohol) (PVA) was used to make hydrogel templates. The parameters examined include PVA molecular weight, type of PLGA (as characterized by lactide content, inherent viscosity), polymer concentration, drug concentration and composition of solvent system. Three model compounds studied were risperidone, methylprednisolone acetate and paclitaxel. The ability of the hydrogel template method to produce microparticles with good conformity to template was dependent on molecular weight of PVA and viscosity of the PLGA solution. Drug loading and encapsulation efficiency were found to be influenced by PLGA lactide content, polymer concentration and composition of the solvent system. The drug loading and encapsulation efficiency were 28.7% and 82% for risperidone, 31.5% and 90% for methylprednisolone acetate, and 32.2 % and 92 % for paclitaxel, respectively. For all three drugs, release was sustained for weeks, and the in vitro release profile of risperidone was comparable to that of microparticles prepared using the conventional emulsion method. The hydrogel template method provides a new approach of manipulating microparticles. PMID:24333903

Direct SQP-methods for solving optimal control problems with delays

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

Goellmann, L.; Bueskens, C.; Maurer, H.

The maximum principle for optimal control problems with delays leads to a boundary value problem (BVP) which is retarded in the state and advanced in the costate function. Based on shooting techniques, solution methods for this type of BVP have been proposed. In recent years, direct optimization methods have been favored for solving control problems without delays. Direct methods approximate the control and the state over a fixed mesh and solve the resulting NLP-problem with SQP-methods. These methods dispense with the costate function and have shown to be robust and efficient. In this paper, we propose a direct SQP-method formore » retarded control problems. In contrast to conventional direct methods, only the control variable is approximated by e.g. spline-functions. The state is computed via a high order Runge-Kutta type algorithm and does not enter explicitly the NLP-problem through an equation. This approach reduces the number of optimization variables considerably and is implementable even on a PC. Our method is illustrated by the numerical solution of retarded control problems with constraints. In particular, we consider the control of a continuous stirred tank reactor which has been solved by dynamic programming. This example illustrates the robustness and efficiency of the proposed method. Open questions concerning sufficient conditions and convergence of discretized NLP-problems are discussed.« less

Inhalation Exposure Method for Illegal Drugs.

PubMed

Inomata, Akiko; Ogata, Akio; Tada, Yukie; Nagasawa, Akemichi; Yuzawa, Katsuhiro; Ando, Hiroshi; Kubo, Yoshikazu; Takahashi, Hiroshi; Kaihoko, Fujifumi; Tanaka, Kazuyoshi; Nakajima, Jun'ichi; Suzuki, Atsuko; Uemura, Nozomi; Moriyasu, Takako; Watanabe, Daisuke; Ishihara, Kei; Usami, Takashi; Kamei, Satoru; Kohno, Yasuaki

2017-01-01

We developed a new inhalation exposure method to evaluate effects of synthetic cannabimimetics that are being distributed as new, unregulated drugs in the Tokyo area. We selected the commercial product "SOUTOU" containing AB-CHMINACA and 5F-AMB as the test drug and dried marshmallow (Althaea officinalis) leaves as the negative control. A half cigarette packed with dried marshmallow leaves or SOUTOU was ignited, then mainstream smoke from each was delivered to five mice in an exposure box. After the cigarettes were fully consumed, neurobehavioral observations and a catalepsy test were performed at 15, 30 and 60 min after exposure. The effluent air from the exposure box was poured into impingers containing acetonitrile (first impinger) and dimethyl sulfoxide (second impinger). The resulting solutions were analyzed to assess decomposition of the synthetic cannabimimetics. Mice exposed to SOUTOU smoke showed many excitement behaviors and some suppressive behaviors at 15, 30 and 60 min. These clearly included cannabimimetic specific pharmacological actions. Negative control mice also showed some suppressive behaviors at 15 min but these were attenuated at later times, nearly disappearing at 60 min. In addition, the behavioral effects observed in controls were less pronounced than those in SOUTOU exposed mice. The inhalation exposure method developed in our study would be effective for determining cannabinoid specific pharmacological effects of illegal drugs, as well as for assessing the presence of active compound(s) by comparing the test substance with a negative control.

Environmental factors selectively impact co-occurrence of problem/pathological gambling with specific drug-use disorders in male twins.

PubMed

Xian, Hong; Giddens, Justine L; Scherrer, Jeffrey F; Eisen, Seth A; Potenza, Marc N

2014-04-01

Multiple forms of drug abuse/dependence frequently co-occur with problem/pathological gambling (PPG). The current study examines the extent to which genetic and environmental factors contribute to their co-occurrence. Bivariate models investigated the magnitude and correlation of genetic and environmental contributions to problem/pathological gambling and its co-occurrence with nicotine dependence, cannabis abuse/dependence and stimulant abuse/dependence. Computer-assisted telephone interviews in the community. Participants were 7869 male twins in the Vietnam Era Twin Registry, a USA-based national twin registry. Life-time DSM-III-R diagnoses for problem/pathological gambling, nicotine dependence, cannabis abuse/dependence and stimulant abuse/dependence were determined using the Diagnostic Interview Schedule. All drug-use disorders displayed additive genetic and non-shared environmental contributions, with cannabis abuse/dependence also displaying shared environmental contributions. Both genetic [genetic correlation rA  = 0.22; 95% confidence interval (CI) = 0.10-0.34] and non-shared environmental components (environmental correlation rE  = 0.24; 95% CI = 0.10-0.37) contributed to the co-occurrence of problem/pathological gambling and nicotine dependence. This pattern was shared by cannabis abuse/dependence (rA  = 0.32; 95% CI = 0.05-1.0; rE  = 0.36; 95% CI = 0.16-0.55) but not stimulant abuse/dependence (SAD), which showed only genetic contributions to the co-occurrence with problem/pathological gambling (rA  = 0.58; 95% CI = 0.45-0.73). Strong links between gambling and stimulant-use disorders may relate to the neurochemical properties of stimulants or the illicit nature of using 'hard' drugs such as cocaine. The greater contribution of environmental factors to the co-occurrence between problem/pathological gambling and 'softer' forms of drug abuse/dependence (cannabis, tobacco) suggest that environmental interventions

Hybrid Monte Carlo/deterministic methods for radiation shielding problems

NASA Astrophysics Data System (ADS)

Becker, Troy L.

For the past few decades, the most common type of deep-penetration (shielding) problem simulated using Monte Carlo methods has been the source-detector problem, in which a response is calculated at a single location in space. Traditionally, the nonanalog Monte Carlo methods used to solve these problems have required significant user input to generate and sufficiently optimize the biasing parameters necessary to obtain a statistically reliable solution. It has been demonstrated that this laborious task can be replaced by automated processes that rely on a deterministic adjoint solution to set the biasing parameters---the so-called hybrid methods. The increase in computational power over recent years has also led to interest in obtaining the solution in a region of space much larger than a point detector. In this thesis, we propose two methods for solving problems ranging from source-detector problems to more global calculations---weight windows and the Transform approach. These techniques employ sonic of the same biasing elements that have been used previously; however, the fundamental difference is that here the biasing techniques are used as elements of a comprehensive tool set to distribute Monte Carlo particles in a user-specified way. The weight window achieves the user-specified Monte Carlo particle distribution by imposing a particular weight window on the system, without altering the particle physics. The Transform approach introduces a transform into the neutron transport equation, which results in a complete modification of the particle physics to produce the user-specified Monte Carlo distribution. These methods are tested in a three-dimensional multigroup Monte Carlo code. For a basic shielding problem and a more realistic one, these methods adequately solved source-detector problems and more global calculations. Furthermore, they confirmed that theoretical Monte Carlo particle distributions correspond to the simulated ones, implying that these methods

Weaving a Formal Methods Education with Problem-Based Learning

NASA Astrophysics Data System (ADS)

Gibson, J. Paul

The idea of weaving formal methods through computing (or software engineering) degrees is not a new one. However, there has been little success in developing and implementing such a curriculum. Formal methods continue to be taught as stand-alone modules and students, in general, fail to see how fundamental these methods are to the engineering of software. A major problem is one of motivation — how can the students be expected to enthusiastically embrace a challenging subject when the learning benefits, beyond passing an exam and achieving curriculum credits, are not clear? Problem-based learning has gradually moved from being an innovative pedagogique technique, commonly used to better-motivate students, to being widely adopted in the teaching of many different disciplines, including computer science and software engineering. Our experience shows that a good problem can be re-used throughout a student's academic life. In fact, the best computing problems can be used with children (young and old), undergraduates and postgraduates. In this paper we present a process for weaving formal methods through a University curriculum that is founded on the application of problem-based learning and a library of good software engineering problems, where students learn about formal methods without sitting a traditional formal methods module. The process of constructing good problems and integrating them into the curriculum is shown to be analagous to the process of engineering software. This approach is not intended to replace more traditional formal methods modules: it will better prepare students for such specialised modules and ensure that all students have an understanding and appreciation for formal methods even if they do not go on to specialise in them.

Function in job seekers with mental illness and drug and alcohol problems who access community based disability employment services.

PubMed

Matthews, Lynda R; Harris, Lynne M; Jaworski, Alison; Alam, Ashraful; Bozdag, Gokcen

2013-03-01

This study identified functioning, health, and social needs in jobseekers with mental disorders independently assessed as having capacity to work and referred to disability employment services. Differences in function between jobseekers with mental illness alone and with additional drug and alcohol problems were examined with view to identifying interventions for vocational rehabilitation. A convenience sample of 116 jobseekers completed BASIS-32, CANSAS, AUDIT, DAST-10 and 6 items from the EXIT interview and were divided into two groups: mental illness only, and additional drug and alcohol issues (AUDIT total score >8 and/or DAST total score >3). Analysis of variance was used to determine group differences. Jobseekers reported low-moderate problems with function. Over 40% of the sample reported unresolved psychological distress, physical health needs, and social/daytime activity needs. Thirty-five jobseekers (30%) had additional drug and alcohol problems and reported significantly greater difficulty with impulsive/addictive behavior and poorer memory and executive function than the mental illness only group. No significant differences were identified in past work functioning. Screening all job seekers for psychological, physical, and social needs to identify suitable treatment and rehabilitation strategies and providing interventions that improve emotional regulation and executive function for job seekers with additional drug and alcohol problems may improve employability of job seekers accessing disability employment services.

Gender Differences among Israeli Adolescents in Residential Drug Treatment

ERIC Educational Resources Information Center

Isralowitz, Richard; Reznik, Alex

2007-01-01

Aims: The use of licit and illicit drugs is considered to be primarily a male problem. Numerous studies, however, question the extent of gender differences. This article reports on last 30 day drug use and related problem behaviour among male and female youth prior to residential treatment. Methods: Self-report data were collected from 95 male and…

A Qualitative Approach to a Better Understanding of the Problems Underlying Drug Shortages, as Viewed from Belgian, French and the European Union’s Perspectives

PubMed Central

Prokop, Anna; Pilc, Andrzej

2015-01-01

The problem of drug shortages has been reported worldwide, gaining prominence in multiple domains and several countries in recent years. The aim of the study was to analyze, characterise and assess this problem in Belgium and France, while also adopting a wider perspective from the European Union. A qualitative methodological approach was employed, including semi-structured interviews with the representatives of respective national health authorities, pharmaceutical companies and wholesalers, as well as hospital and community pharmacists. The research was conducted in early 2014. Four themes, which were identified through the interviews, were addressed in the paper, i.e. a) defining drug shortages, b) their dynamics and perception, c) their determinants, d) the role of the European and national institutions in coping with the problem. Three groups of determinants of drug shortages were identified throughout this study: manufacturing problems, distribution and supply problems, and problems related to economic aspects. Currently, the Member States of the European Union are striving to resolve the problem very much on their own, although a far more focused and dedicated collaboration may well prove instrumental in coping with drug shortages throughout Europe more effectively. To the best of the authors’ knowledge, this is the first qualitative study to investigate the characteristics, key determinants, and the problem drivers of drug shortages, focusing on this particular group of countries, while also adopting the European Union’s perspective. PMID:25942432

Rank-k modification methods for recursive least squares problems

NASA Astrophysics Data System (ADS)

Olszanskyj, Serge; Lebak, James; Bojanczyk, Adam

1994-09-01

In least squares problems, it is often desired to solve the same problem repeatedly but with several rows of the data either added, deleted, or both. Methods for quickly solving a problem after adding or deleting one row of data at a time are known. In this paper we introduce fundamental rank-k updating and downdating methods and show how extensions of rank-1 downdating methods based on LINPACK, Corrected Semi-Normal Equations (CSNE), and Gram-Schmidt factorizations, as well as new rank-k downdating methods, can all be derived from these fundamental results. We then analyze the cost of each new algorithm and make comparisons tok applications of the corresponding rank-1 algorithms. We provide experimental results comparing the numerical accuracy of the various algorithms, paying particular attention to the downdating methods, due to their potential numerical difficulties for ill-conditioned problems. We then discuss the computation involved for each downdating method, measured in terms of operation counts and BLAS calls. Finally, we provide serial execution timing results for these algorithms, noting preferable points for improvement and optimization. From our experiments we conclude that the Gram-Schmidt methods perform best in terms of numerical accuracy, but may be too costly for serial execution for large problems.

Problems and pitfalls in cardiac drug therapy.

PubMed

Stone, S M; Rai, N; Nei, J

2001-01-01

Medical errors in the care of patients may account for 44,000 to 98,000 deaths per year, and 7,000 deaths per year are attributed to medication errors alone. Increasing awareness among health care providers of potential errors is a critical step toward improving the safety of medical care. Because today's medications are increasingly complex, approved at an accelerated rate, and often have a narrow therapeutic window with only a small margin of safety, patient and provider education is critical in assuring optimal therapeutic outcomes. Providers can use electronic resources such as Web sites to keep informed on drug-drug, drug-food, and drug-nutritional supplements interactions.

Developments in Methods for Measuring the Intestinal Absorption of Nanoparticle-Bound Drugs

PubMed Central

Liu, Wei; Pan, Hao; Zhang, Caiyun; Zhao, Liling; Zhao, Ruixia; Zhu, Yongtao; Pan, Weisan

2016-01-01

With the rapid development of nanotechnology, novel drug delivery systems comprising orally administered nanoparticles (NPs) have been paid increasing attention in recent years. The bioavailability of orally administered drugs has significant influence on drug efficacy and therapeutic dosage, and it is therefore imperative that the intestinal absorption of oral NPs be investigated. This review examines the various literature on the oral absorption of polymeric NPs, and provides an overview of the intestinal absorption models that have been developed for the study of oral nanoparticles. Three major categories of models including a total of eight measurement methods are described in detail (in vitro: dialysis bag, rat gut sac, Ussing chamber, cell culture model; in situ: intestinal perfusion, intestinal loops, intestinal vascular cannulation; in vivo: the blood/urine drug concentration method), and the advantages and disadvantages of each method are contrasted and elucidated. In general, in vitro and in situ methods are relatively convenient but lack accuracy, while the in vivo method is troublesome but can provide a true reflection of drug absorption in vivo. This review summarizes the development of intestinal absorption experiments in recent years and provides a reference for the systematic study of the intestinal absorption of nanoparticle-bound drugs. PMID:27455239

Drug Use Normalization: A Systematic and Critical Mixed-Methods Review.

PubMed

Sznitman, Sharon R; Taubman, Danielle S

2016-09-01

Drug use normalization, which is a process whereby drug use becomes less stigmatized and more accepted as normative behavior, provides a conceptual framework for understanding contemporary drug issues and changes in drug use trends. Through a mixed-methods systematic review of the normalization literature, this article seeks to (a) critically examine how the normalization framework has been applied in empirical research and (b) make recommendations for future research in this area. Twenty quantitative, 26 qualitative, and 4 mixed-methods studies were identified through five electronic databases and reference lists of published studies. Studies were assessed for relevance, study characteristics, quality, and aspects of normalization examined. None of the studies applied the most rigorous research design (experiments) or examined all of the originally proposed normalization dimensions. The most commonly assessed dimension of drug use normalization was "experimentation." In addition to the original dimensions, the review identified the following new normalization dimensions in the literature: (a) breakdown of demographic boundaries and other risk factors in relation to drug use; (b) de-normalization; (c) drug use as a means to achieve normal goals; and (d) two broad forms of micro-politics associated with managing the stigma of illicit drug use: assimilative and transformational normalization. Further development in normalization theory and methodology promises to provide researchers with a novel framework for improving our understanding of drug use in contemporary society. Specifically, quasi-experimental designs that are currently being made feasible by swift changes in cannabis policy provide researchers with new and improved opportunities to examine normalization processes.

a Novel Discrete Optimal Transport Method for Bayesian Inverse Problems

NASA Astrophysics Data System (ADS)

Bui-Thanh, T.; Myers, A.; Wang, K.; Thiery, A.

2017-12-01

We present the Augmented Ensemble Transform (AET) method for generating approximate samples from a high-dimensional posterior distribution as a solution to Bayesian inverse problems. Solving large-scale inverse problems is critical for some of the most relevant and impactful scientific endeavors of our time. Therefore, constructing novel methods for solving the Bayesian inverse problem in more computationally efficient ways can have a profound impact on the science community. This research derives the novel AET method for exploring a posterior by solving a sequence of linear programming problems, resulting in a series of transport maps which map prior samples to posterior samples, allowing for the computation of moments of the posterior. We show both theoretical and numerical results, indicating this method can offer superior computational efficiency when compared to other SMC methods. Most of this efficiency is derived from matrix scaling methods to solve the linear programming problem and derivative-free optimization for particle movement. We use this method to determine inter-well connectivity in a reservoir and the associated uncertainty related to certain parameters. The attached file shows the difference between the true parameter and the AET parameter in an example 3D reservoir problem. The error is within the Morozov discrepancy allowance with lower computational cost than other particle methods.

Pre-treatment Drug Use Characteristics and Experiences among Patients in a Voluntary Substance Abuse Treatment Center in Malaysia: A Mixed Methods Approach

PubMed Central

Krishnan, Archana; Brown, Shan-Estelle; Ghani, Mansur; Khan, Farrah; Kamarulzaman, Adeeba; Altice, Frederick L.

2017-01-01

Background Drug use in Malaysia remains a significant public health and social problem despite implementation of harsh punitive drug policies such as forcibly placing suspected drug users into compulsory drug detention centers (CDDCs). Following criticism over human right violations in CDDCs, Malaysia has begun to transition towards voluntary drug treatment centers known as Cure & Care (C&C) Centers. To best serve the needs of regional C&Cs, data on drug use are essential among patients accessing treatment. Using a mixed methods approach, we examined pre-treatment drug use characteristics and experiences with addiction treatment among C&C patients in Kelantan – a religiously conservative state in Northeast Malaysia with high prevalence of drug use but where limited data are available on drug use patterns. Methods A mixed methods study utilizing surveys (N=96) and semi-structured interviews (N=20) was conducted among a convenience sample of inpatients and outpatients at the Pengkalan Chepa C&C Center in Kelantan. Results Survey results showed 89.6% of participants met screening criteria for moderate to severe addiction severity. Nearly 90% reported lifetime illicit amphetamine (syabu, meth, ice, and pil kuda) use followed by alcohol (60.4%) and opioids (52.1%). Qualitative results pointed to the powerful influence of peer networks in drug initiation and relapse, and the positive effect of the C&C on drug rehabilitation. Conclusions The drug use profile of the Kelantan C&C enrollees shows extensive pre-treatment amphetamine use, polysubstance use, and injection drug use including high-risk behaviors such as sharing needles, syringes and containers. Evidence points to the need for integration of social support-oriented practices and behavioral interventions into the rehabilitation of drug users in this region. PMID:26914230

[Moderation-integrated-balance presupposition of Chinese medicine compound and pharmacological problems in traditional Chinese drug research].

PubMed

Zhao, Jun-Ning

2017-03-01

The moderation-integrated-balance presupposition (MIBP) of Chinese medicine compound was first proposed in this paper based on the review of function characteristics and action principles of Chinese medicine compound. Furthermore, the pharmacological problems of traditional Chinese drug research were discussed in details. The results were of important value in accelerating the transformation of traditional Chinese medicine compound, and constructing the new drug innovation and review system for traditional Chinese medicine. Copyright© by the Chinese Pharmaceutical Association.

2D signature for detection and identification of drugs

NASA Astrophysics Data System (ADS)

Trofimov, Vyacheslav A.; Varentsova, Svetlana A.; Shen, Jingling; Zhang, Cunlin; Zhou, Qingli; Shi, Yulei

2011-06-01

The method of spectral dynamics analysis (SDA-method) is used for obtaining the2D THz signature of drugs. This signature is used for the detection and identification of drugs with similar Fourier spectra by transmitted THz signal. We discuss the efficiency of SDA method for the identification problem of pure methamphetamine (MA), methylenedioxyamphetamine (MDA), 3, 4-methylenedioxymethamphetamine (MDMA) and Ketamine.

A New Method for Delivering a Hydrophobic Drug for Photodynamic Therapy Using Pure Nanocrystal Form of the Drug

PubMed Central

Baba, Koichi; Pudavar, Haridas E.; Roy, Indrajit; Ohulchanskyy, Tymish Y.; Chen, Yihui; Pandey, Ravindra; Prasad, Paras N.

2008-01-01

A carrier free method for delivery of a hydrophobic drug in its pure form, using nanocrystals (nano sized crystals) is proposed. To demonstrate this technique, nanocrystals of a hydrophobic photosensitizing anticancer drug 2-devinyl-2-(1-hexyloxyethyl)pyropheophorbide (HPPH), have been synthesized using re-precipitation method. The resulting drug nanocrystals were monodispersed and stable in aqueous dispersion, without the necessity of an additional stabilizer (surfactant). As shown by confocal microscopy, these pure drug nanocrystals were taken-up by the cancer cells with high avidity. Though the fluorescence and photodynamic activity of the drug were substantially quenched in the form of nanocrystals in aqueous suspension, both these characteristics were recovered under in vitro and in vivo conditions. This recovery of drug activity and fluorescence is possibly due to the interaction of nanocrystals with serum albumin, resulting in conversion of the drug nanocrystals into the molecular form. This was confirmed by demonstrating similar recovery in presence of Fetal Bovine Serum (FBS) or Bovine Serum Albumin (BSA). Under similar treatment conditions, the HPPH in nanocrystal form or in 1% Tween 80/water formulation showed comparable in vitro and in vivo efficacy. PMID:17266331

Comparison of HPLC & spectrophotometric methods for estimation of antiretroviral drug content in pharmaceutical products.

PubMed

Hemanth Kumar, A K; Sudha, V; Swaminathan, Soumya; Ramachandran, Geetha

2010-10-01

Simple and reliable methods to estimate drugs in pharmaceutical products are needed. In most cases, antiretroviral drug estimations are performed using a HPLC method, requiring expensive equipment and trained technicians. A relatively simple and accurate method to estimate antiretroviral drugs in pharmaceutical preparations is by spectrophotometric method, which is cheap and simple to use as compared to HPLC. We undertook this study to standardise methods for estimation of nevirapine (NVP), lamivudine (3TC) and stavudine (d4T) in single tablets/capsules by HPLC and spectrophotometry and to compare the content of these drugs determined by both these methods. Twenty tablets/capsules of NVP, 3TC and d4T each were analysed for their drug content by HPLC and spectrophotometric methods. Suitably diluted drug solutions were run on HPLC fitted with a C18 column using UV detection at ambient temperature. The absorbance of the diluted drug solutions were read in a spectrophotometer at 300, 285 and 270 nm for NVP, 3TC and d4T respectively. Pure powders of the drugs were used to prepare calibration standards of known drug concentrations, which was set up with each assay. The inter-day variation (%) of standards for NVP, 3TC and d4T ranged from 2.5 to 6.7, 2.1 to 7.7 and 6.2 to 7.7, respectively by HPLC. The corresponding values by spectrophotometric method were 2.7 to 4.7, 4.2 to 7.2 and 3.8 to 6.0. The per cent variation between the HPLC and spectrophotometric methods ranged from 0.45 to 4.49 per cent, 0 to 4.98 per cent and 0.35 to 8.73 per cent for NVP, 3TC and d4T,respectively. The contents of NVP, 3TC and d4T in the tablets estimated by HPLC and spectrophotometric methods were similar, and the variation in the amount of these drugs estimated by HPLC and spectrophotometric methods was below 10 per cent. This suggests that the spectrophotometric method is as accurate as the HPLC method for estimation of NVP, 3TC and d4T in tablet/capsule. Hence laboratories that do not have

A Novel Numerical Method for Fuzzy Boundary Value Problems

NASA Astrophysics Data System (ADS)

Can, E.; Bayrak, M. A.; Hicdurmaz

2016-05-01

In the present paper, a new numerical method is proposed for solving fuzzy differential equations which are utilized for the modeling problems in science and engineering. Fuzzy approach is selected due to its important applications on processing uncertainty or subjective information for mathematical models of physical problems. A second-order fuzzy linear boundary value problem is considered in particular due to its important applications in physics. Moreover, numerical experiments are presented to show the effectiveness of the proposed numerical method on specific physical problems such as heat conduction in an infinite plate and a fin.

Probabilistic numerical methods for PDE-constrained Bayesian inverse problems

NASA Astrophysics Data System (ADS)

Cockayne, Jon; Oates, Chris; Sullivan, Tim; Girolami, Mark

2017-06-01

This paper develops meshless methods for probabilistically describing discretisation error in the numerical solution of partial differential equations. This construction enables the solution of Bayesian inverse problems while accounting for the impact of the discretisation of the forward problem. In particular, this drives statistical inferences to be more conservative in the presence of significant solver error. Theoretical results are presented describing rates of convergence for the posteriors in both the forward and inverse problems. This method is tested on a challenging inverse problem with a nonlinear forward model.

Fatty acid ethyl esters (FAEEs) as markers for alcohol in meconium: method validation and implementation of a screening program for prenatal drug exposure.

PubMed

Hastedt, Martin; Krumbiegel, Franziska; Gapert, René; Tsokos, Michael; Hartwig, Sven

2013-09-01

Alcohol consumption during pregnancy is a widespread problem and can cause severe fetal damage. As the diagnosis of fetal alcohol syndrome is difficult, the implementation of a reliable marker for alcohol consumption during pregnancy into meconium drug screening programs would be invaluable. A previously published gas chromatography mass spectrometry method for the detection of fatty acid ethyl esters (FAEEs) as alcohol markers in meconium was optimized and newly validated for a sample size of 50 mg. This method was applied to 122 cases from a drug-using population. The meconium samples were also tested for common drugs of abuse. In 73 % of the cases, one or more drugs were found. Twenty percent of the samples tested positive for FAEEs at levels indicating significant alcohol exposure. Consequently, alcohol was found to be the third most frequently abused substance within the study group. This re-validated method provides an increase in testing sensitivity, is reliable and easily applicable as part of a drug screening program. It can be used as a non-invasive tool to detect high alcohol consumption in the last trimester of pregnancy. The introduction of FAEEs testing in meconium screening was found to be of particular use in a drug-using population.

Numerical methods for the inverse problem of density functional theory

DOE PAGES

Jensen, Daniel S.; Wasserman, Adam

2017-07-17

Here, the inverse problem of Kohn–Sham density functional theory (DFT) is often solved in an effort to benchmark and design approximate exchange-correlation potentials. The forward and inverse problems of DFT rely on the same equations but the numerical methods for solving each problem are substantially different. We examine both problems in this tutorial with a special emphasis on the algorithms and error analysis needed for solving the inverse problem. Two inversion methods based on partial differential equation constrained optimization and constrained variational ideas are introduced. We compare and contrast several different inversion methods applied to one-dimensional finite and periodic modelmore » systems.« less

Numerical methods for the inverse problem of density functional theory

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

Jensen, Daniel S.; Wasserman, Adam

Here, the inverse problem of Kohn–Sham density functional theory (DFT) is often solved in an effort to benchmark and design approximate exchange-correlation potentials. The forward and inverse problems of DFT rely on the same equations but the numerical methods for solving each problem are substantially different. We examine both problems in this tutorial with a special emphasis on the algorithms and error analysis needed for solving the inverse problem. Two inversion methods based on partial differential equation constrained optimization and constrained variational ideas are introduced. We compare and contrast several different inversion methods applied to one-dimensional finite and periodic modelmore » systems.« less

Emerging Computational Methods for the Rational Discovery of Allosteric Drugs

PubMed Central

2016-01-01

Allosteric drug development holds promise for delivering medicines that are more selective and less toxic than those that target orthosteric sites. To date, the discovery of allosteric binding sites and lead compounds has been mostly serendipitous, achieved through high-throughput screening. Over the past decade, structural data has become more readily available for larger protein systems and more membrane protein classes (e.g., GPCRs and ion channels), which are common allosteric drug targets. In parallel, improved simulation methods now provide better atomistic understanding of the protein dynamics and cooperative motions that are critical to allosteric mechanisms. As a result of these advances, the field of predictive allosteric drug development is now on the cusp of a new era of rational structure-based computational methods. Here, we review algorithms that predict allosteric sites based on sequence data and molecular dynamics simulations, describe tools that assess the druggability of these pockets, and discuss how Markov state models and topology analyses provide insight into the relationship between protein dynamics and allosteric drug binding. In each section, we first provide an overview of the various method classes before describing relevant algorithms and software packages. PMID:27074285

Emerging Computational Methods for the Rational Discovery of Allosteric Drugs.

PubMed

Wagner, Jeffrey R; Lee, Christopher T; Durrant, Jacob D; Malmstrom, Robert D; Feher, Victoria A; Amaro, Rommie E

2016-06-08

Allosteric drug development holds promise for delivering medicines that are more selective and less toxic than those that target orthosteric sites. To date, the discovery of allosteric binding sites and lead compounds has been mostly serendipitous, achieved through high-throughput screening. Over the past decade, structural data has become more readily available for larger protein systems and more membrane protein classes (e.g., GPCRs and ion channels), which are common allosteric drug targets. In parallel, improved simulation methods now provide better atomistic understanding of the protein dynamics and cooperative motions that are critical to allosteric mechanisms. As a result of these advances, the field of predictive allosteric drug development is now on the cusp of a new era of rational structure-based computational methods. Here, we review algorithms that predict allosteric sites based on sequence data and molecular dynamics simulations, describe tools that assess the druggability of these pockets, and discuss how Markov state models and topology analyses provide insight into the relationship between protein dynamics and allosteric drug binding. In each section, we first provide an overview of the various method classes before describing relevant algorithms and software packages.

Pretreatment drug use characteristics and experiences among patients in a voluntary substance abuse treatment center in Malaysia: A mixed-methods approach.

PubMed

Krishnan, Archana; Brown, Shan-Estelle; Ghani, Mansur A; Khan, Farrah; Kamarulzaman, Adeeba; Altice, Frederick L

2016-01-01

Drug use in Malaysia remains a significant public health and social problem despite implementation of harsh punitive drug policies such as forcibly placing suspected drug users into compulsory drug detention centers (CDDCs). Following criticism over human right violations in CDDCs, Malaysia has begun to transition towards voluntary drug treatment centers known as Cure & Care (C&C) centers. To best serve the needs of regional C&C centers, data on drug use are essential among patients accessing treatment. Using a mixed-methods approach, the authors examined pretreatment drug use characteristics and experiences with addiction treatment among C&C patients in Kelantan-a religiously conservative state in northeast Malaysia with high prevalence of drug use but where limited data are available on drug use patterns. A mixed-methods study utilizing surveys (n = 96) and semistructured interviews (n = 20) was conducted among a convenience sample of inpatients and outpatients at the Pengkalan Chepa C&C Center in Kelantan. Survey results showed that 89.6% of participants met screening criteria for moderate to severe addiction severity. Nearly 90% reported lifetime illicit amphetamine (syabu, meth, ice, and pil kuda) use, followed by alcohol (60.4%) and opioids (52.1%). Qualitative results pointed to the powerful influence of peer networks in drug initiation and relapse, and the positive effect of the C&C center on drug rehabilitation. The drug use profile of the Kelantan C&C center enrollees shows extensive pretreatment amphetamine use, polysubstance use, and injection drug use, including high-risk behaviors such as sharing needles, syringes, and containers. Evidence points to the need for integration of social support-oriented practices and behavioral interventions into the rehabilitation of drug users in this region.

A review on proniosomal drug delivery system for targeted drug action.

PubMed

Radha, G V; Rani, T Sudha; Sarvani, B

2013-03-01

Proniosomes are dry formulation of water soluble carrier particles that are coated with surfactant. They are rehydrated to form niosomal dispersion immediately before use on agitation in hot aqueous media within minutes. Proniosomes are physically stable during the storage and transport. Drug encapsulated in the vesicular structure of proniosomes prolong the existence of drug in the systematic circulation and enhances the penetration into target tissue and reduce toxicity. From a technical point of view, niosomes are promising drug carriers as they possess greater chemical stability and lack of many disadvantages associated with liposomes, such as high- cost and variable purity problems of phospholipids. The present review emphasizes on overall methods of preparation characterization and applicability of proniosomes in targeted drug action.

Faculty Member's Handbook. Strategies for Preventing Alcohol and Other Drug Problems. The College Series.

ERIC Educational Resources Information Center

CSR, Inc., Washington, DC.

This handbook for higher education faculty is designed to inform them of the nature and extent of alcohol and other drug abuse on the nation's campuses and to enlist their involvement in responding to these problems. Based on the premise that each individual can make a difference, the faculty member is encouraged to help shape the campus…

Methodes entropiques appliquees au probleme inverse en magnetoencephalographie

NASA Astrophysics Data System (ADS)

Lapalme, Ervig

2005-07-01

This thesis is devoted to biomagnetic source localization using magnetoencephalography. This problem is known to have an infinite number of solutions. So methods are required to take into account anatomical and functional information on the solution. The work presented in this thesis uses the maximum entropy on the mean method to constrain the solution. This method originates from statistical mechanics and information theory. This thesis is divided into two main parts containing three chapters each. The first part reviews the magnetoencephalographic inverse problem: the theory needed to understand its context and the hypotheses for simplifying the problem. In the last chapter of this first part, the maximum entropy on the mean method is presented: its origins are explained and also how it is applied to our problem. The second part is the original work of this thesis presenting three articles; one of them already published and two others submitted for publication. In the first article, a biomagnetic source model is developed and applied in a theoretical con text but still demonstrating the efficiency of the method. In the second article, we go one step further towards a realistic modelization of the cerebral activation. The main priors are estimated using the magnetoencephalographic data. This method proved to be very efficient in realistic simulations. In the third article, the previous method is extended to deal with time signals thus exploiting the excellent time resolution offered by magnetoencephalography. Compared with our previous work, the temporal method is applied to real magnetoencephalographic data coming from a somatotopy experience and results agree with previous physiological knowledge about this kind of cognitive process.

Child Neglect and the Development of Externalizing Behavior Problems: Associations with Maternal Drug Dependence and Neighborhood Crime

PubMed Central

Manly, Jody Todd; Oshri, Assaf; Lynch, Michael; Herzog, Margaret; Wortel, Sanne

2013-01-01

Given the high prevalence of child neglect among maltreatment subtypes, and its association with exposure to additional environmental adversity, understanding the processes that potentiate child neglect and link neglect to subsequent child externalizing psychopathology may shed light on key targets for preventive intervention. Among 170 urban low-income children (ages four-nine years) and their mothers, this five-year prospective study examined the effects of early neglect severity and maternal substance abuse, as well as neighborhood crime, on children’s later externalizing behavior problems. Severity of child neglect (up to age six years) mediated the relation between maternal drug dependence diagnosis, determined at children’s age of four, and children’s externalizing behavior problems at age nine. Rates of neighborhood crime mediated the link between presence of child neglect and children’s externalizing behavior problems. The roles of maternal drug dependence diagnosis, child neglect, and community violence in the development of child psychopathology are discussed in terms of their implications for intervention. PMID:23136210

Decomposition method for zonal resource allocation problems in telecommunication networks

NASA Astrophysics Data System (ADS)

Konnov, I. V.; Kashuba, A. Yu

2016-11-01

We consider problems of optimal resource allocation in telecommunication networks. We first give an optimization formulation for the case where the network manager aims to distribute some homogeneous resource (bandwidth) among users of one region with quadratic charge and fee functions and present simple and efficient solution methods. Next, we consider a more general problem for a provider of a wireless communication network divided into zones (clusters) with common capacity constraints. We obtain a convex quadratic optimization problem involving capacity and balance constraints. By using the dual Lagrangian method with respect to the capacity constraint, we suggest to reduce the initial problem to a single-dimensional optimization problem, but calculation of the cost function value leads to independent solution of zonal problems, which coincide with the above single region problem. Some results of computational experiments confirm the applicability of the new methods.

Drugs of abuse detection in saliva based on actuated optical method

NASA Astrophysics Data System (ADS)

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

2014-12-01

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

Tools, information sources, and methods used in deciding on drug availability in HMOs.

PubMed

Barner, J C; Thomas, J

1998-01-01

The use and importance of specific decision-making tools, information sources, and drug-use management methods in determining drug availability and use in HMOs were studied. A questionnaire was sent to 303 randomly selected HMOs. Respondents were asked to rate their use of each of four formal decision-making tools and its relative importance, as well as the use and importance of eight information sources and 11 methods for managing drug availability and use, on a 5-point scale. The survey response rate was 28%. Approximately half of the respondents reported that their HMOs used decision analysis or multiattribute analysis in deciding on drug availability. If used, these tools were rated as very important. There were significant differences in levels of use by HMO type, membership size, and age. Journal articles and reference books were reported most often as information sources. Retrospective drug-use review was used very often and perceived to be very important in managing drug use. Other management methods were used only occasionally, but the importance placed on these tools when used ranged from moderately to very important. Older organizations used most of the management methods more often than did other HMOs. Decision analysis and multiattribute analysis were the most commonly used tools for deciding on which drugs to make available to HMO members, and reference books and journal articles were the most commonly used information sources. Retrospective and prospective drug-use reviews were the most commonly applied methods for managing HMO members' access to drugs.

Drug exposure in register-based research—An expert-opinion based evaluation of methods

PubMed Central

Taipale, Heidi; Koponen, Marjaana; Tolppanen, Anna-Maija; Hartikainen, Sirpa; Ahonen, Riitta; Tiihonen, Jari

2017-01-01

Background In register-based pharmacoepidemiological studies, construction of drug exposure periods from drug purchases is a major methodological challenge. Various methods have been applied but their validity is rarely evaluated. Our objective was to conduct an expert-opinion based evaluation of the correctness of drug use periods produced by different methods. Methods Drug use periods were calculated with three fixed methods: time windows, assumption of one Defined Daily Dose (DDD) per day and one tablet per day, and with PRE2DUP that is based on modelling of individual drug purchasing behavior. Expert-opinion based evaluation was conducted with 200 randomly selected purchase histories of warfarin, bisoprolol, simvastatin, risperidone and mirtazapine in the MEDALZ-2005 cohort (28,093 persons with Alzheimer’s disease). Two experts reviewed purchase histories and judged which methods had joined correct purchases and gave correct duration for each of 1000 drug exposure periods. Results The evaluated correctness of drug use periods was 70–94% for PRE2DUP, and depending on grace periods and time window lengths 0–73% for tablet methods, 0–41% for DDD methods and 0–11% for time window methods. The highest rate of evaluated correct solutions for each method class were observed for 1 tablet per day with 180 days grace period (TAB_1_180, 43–73%), and 1 DDD per day with 180 days grace period (1–41%). Time window methods produced at maximum only 11% correct solutions. The best performing fixed method TAB_1_180 reached highest correctness for simvastatin 73% (95% CI 65–81%) whereas 89% (95% CI 84–94%) of PRE2DUP periods were judged as correct. Conclusions This study shows inaccuracy of fixed methods and the urgent need for new data-driven methods. In the expert-opinion based evaluation, the lowest error rates were observed with data-driven method PRE2DUP. PMID:28886089

Multigrid methods for bifurcation problems: The self adjoint case

NASA Technical Reports Server (NTRS)

Taasan, Shlomo

1987-01-01

This paper deals with multigrid methods for computational problems that arise in the theory of bifurcation and is restricted to the self adjoint case. The basic problem is to solve for arcs of solutions, a task that is done successfully with an arc length continuation method. Other important issues are, for example, detecting and locating singular points as part of the continuation process, switching branches at bifurcation points, etc. Multigrid methods have been applied to continuation problems. These methods work well at regular points and at limit points, while they may encounter difficulties in the vicinity of bifurcation points. A new continuation method that is very efficient also near bifurcation points is presented here. The other issues mentioned above are also treated very efficiently with appropriate multigrid algorithms. For example, it is shown that limit points and bifurcation points can be solved for directly by a multigrid algorithm. Moreover, the algorithms presented here solve the corresponding problems in just a few work units (about 10 or less), where a work unit is the work involved in one local relaxation on the finest grid.

Application of supercritical antisolvent method in drug encapsulation: a review

PubMed Central

Kalani, Mahshid; Yunus, Robiah

2011-01-01

The review focuses on the application of supercritical fluids as antisolvents in the pharmaceutical field and demonstrates the supercritical antisolvent method in the use of drug encapsulation. The main factors for choosing the solvent and biodegradable polymer to produce fine particles to ensure effective drug delivery are emphasized and the effect of polymer structure on drug encapsulation is illustrated. The review also demonstrates the drug release mechanism and polymeric controlled release system, and discusses the effects of the various conditions in the process, such as pressure, temperature, concentration, chemical compositions (organic solvents, drug, and biodegradable polymer), nozzle geometry, CO2 flow rate, and the liquid phase flow rate on particle size and its distribution. PMID:21796245

Does trauma exposure predict prescription drug problems beyond the contribution of post-traumatic stress disorder and depression? An analysis of the Mind Your Heart cohort study.

PubMed

Kalapatapu, Raj K; Dannenbaum, Tatiana P; Harbison, John D; Cohen, Beth E

2017-01-01

It is not clear from prior studies whether trauma exposure predicts substance use problems independent of psychiatric comorbidities. Most prior studies were cross-sectional in nature, and none focused on prescription drug problems. To address this gap in the literature, the current article is a secondary analysis of veterans from the Mind Your Heart prospective cohort study. The primary research question is whether trauma exposure predicts prescription drug problems even after controlling for major psychiatric symptoms, such as post-traumatic stress disorder and depression. Multinomial logistic regression was used to assess whether the 10-item lifetime Brief Trauma Questionnaire (e.g., serious car accidents, war traumas, life-threatening illness, natural disasters, physical, or sexual abuse) predicts prescription drug problems as determined by a self-report categorical question (three answer choices) over a 4-year follow-up time period (n = 661 [100%] at year 1; 83.4% at year 2; 85.9% at year 3; and 78.2% at year 4). Trauma exposure was positively associated with prescription drug problems in unadjusted and age-, sex-, and race-adjusted analyses at follow-up. After accounting for post-traumatic stress disorder (PTSD Checklist-17 Civilian Version) and depression (Patient Health Questionnaire-9) symptoms, trauma exposure was no longer associated with prescription drug problems at all time points (relative risk ratios range 0.91-1.47). These results were robust to different missing data strategies. Trauma exposure was not associated with prescription drug problems over a 4-year follow-up in a prospective cohort study of veterans. Future directions include detailed measures of prescription drug problems and recruitment from community sites.

Finite element methods on supercomputers - The scatter-problem

NASA Technical Reports Server (NTRS)

Loehner, R.; Morgan, K.

1985-01-01

Certain problems arise in connection with the use of supercomputers for the implementation of finite-element methods. These problems are related to the desirability of utilizing the power of the supercomputer as fully as possible for the rapid execution of the required computations, taking into account the gain in speed possible with the aid of pipelining operations. For the finite-element method, the time-consuming operations may be divided into three categories. The first two present no problems, while the third type of operation can be a reason for the inefficient performance of finite-element programs. Two possibilities for overcoming certain difficulties are proposed, giving attention to a scatter-process.

Explicit methods in extended phase space for inseparable Hamiltonian problems

NASA Astrophysics Data System (ADS)

Pihajoki, Pauli

2015-03-01

We present a method for explicit leapfrog integration of inseparable Hamiltonian systems by means of an extended phase space. A suitably defined new Hamiltonian on the extended phase space leads to equations of motion that can be numerically integrated by standard symplectic leapfrog (splitting) methods. When the leapfrog is combined with coordinate mixing transformations, the resulting algorithm shows good long term stability and error behaviour. We extend the method to non-Hamiltonian problems as well, and investigate optimal methods of projecting the extended phase space back to original dimension. Finally, we apply the methods to a Hamiltonian problem of geodesics in a curved space, and a non-Hamiltonian problem of a forced non-linear oscillator. We compare the performance of the methods to a general purpose differential equation solver LSODE, and the implicit midpoint method, a symplectic one-step method. We find the extended phase space methods to compare favorably to both for the Hamiltonian problem, and to the implicit midpoint method in the case of the non-linear oscillator.

Overview of Krylov subspace methods with applications to control problems

NASA Technical Reports Server (NTRS)

Saad, Youcef

1989-01-01

An overview of projection methods based on Krylov subspaces are given with emphasis on their application to solving matrix equations that arise in control problems. The main idea of Krylov subspace methods is to generate a basis of the Krylov subspace Span and seek an approximate solution the the original problem from this subspace. Thus, the original matrix problem of size N is approximated by one of dimension m typically much smaller than N. Krylov subspace methods have been very successful in solving linear systems and eigenvalue problems and are now just becoming popular for solving nonlinear equations. It is shown how they can be used to solve partial pole placement problems, Sylvester's equation, and Lyapunov's equation.

DrugE-Rank: improving drug–target interaction prediction of new candidate drugs or targets by ensemble learning to rank

PubMed Central

Yuan, Qingjun; Gao, Junning; Wu, Dongliang; Zhang, Shihua; Mamitsuka, Hiroshi; Zhu, Shanfeng

2016-01-01

Motivation: Identifying drug–target interactions is an important task in drug discovery. To reduce heavy time and financial cost in experimental way, many computational approaches have been proposed. Although these approaches have used many different principles, their performance is far from satisfactory, especially in predicting drug–target interactions of new candidate drugs or targets. Methods: Approaches based on machine learning for this problem can be divided into two types: feature-based and similarity-based methods. Learning to rank is the most powerful technique in the feature-based methods. Similarity-based methods are well accepted, due to their idea of connecting the chemical and genomic spaces, represented by drug and target similarities, respectively. We propose a new method, DrugE-Rank, to improve the prediction performance by nicely combining the advantages of the two different types of methods. That is, DrugE-Rank uses LTR, for which multiple well-known similarity-based methods can be used as components of ensemble learning. Results: The performance of DrugE-Rank is thoroughly examined by three main experiments using data from DrugBank: (i) cross-validation on FDA (US Food and Drug Administration) approved drugs before March 2014; (ii) independent test on FDA approved drugs after March 2014; and (iii) independent test on FDA experimental drugs. Experimental results show that DrugE-Rank outperforms competing methods significantly, especially achieving more than 30% improvement in Area under Prediction Recall curve for FDA approved new drugs and FDA experimental drugs. Availability: http://datamining-iip.fudan.edu.cn/service/DrugE-Rank Contact: zhusf@fudan.edu.cn Supplementary information: Supplementary data are available at Bioinformatics online. PMID:27307615

Psychosocial interventions to reduce alcohol consumption in concurrent problem alcohol and illicit drug users.

PubMed

Klimas, Jan; Tobin, Helen; Field, Catherine-Anne; O'Gorman, Clodagh S M; Glynn, Liam G; Keenan, Eamon; Saunders, Jean; Bury, Gerard; Dunne, Colum; Cullen, Walter

2014-12-03

Problem alcohol use is common among illicit drug users and is associated with adverse health outcomes. It is also an important factor contributing to a poor prognosis among drug users with hepatitis C virus (HCV) as it impacts on progression to hepatic cirrhosis or opiate overdose in opioid users. To assess the effects of psychosocial interventions for problem alcohol use in illicit drug users (principally problem drug users of opiates and stimulants). We searched the Cochrane Drugs and Alcohol Group trials register (June 2014), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, Issue 11, June 2014), MEDLINE (1966 to June 2014); EMBASE (1974 to June 2014); CINAHL (1982 to June 2014); PsycINFO (1872 to June 2014) and the reference lists of eligible articles. We also searched: 1) conference proceedings (online archives only) of the Society for the Study of Addiction, International Harm Reduction Association, International Conference on Alcohol Harm Reduction and American Association for the Treatment of Opioid Dependence; 2) online registers of clinical trials: Current Controlled Trials, Clinical Trials.org, Center Watch and the World Health Organization International Clinical Trials Registry Platform. Randomised controlled trials comparing psychosocial interventions with another therapy (other psychosocial treatment, including non-pharmacological therapies, or placebo) in adult (over the age of 18 years) illicit drug users with concurrent problem alcohol use. We used the standard methodological procedures expected by The Cochrane Collaboration. Four studies, involving 594 participants, were included. Half of the trials were rated as having a high or unclear risk of bias. The studies considered six different psychosocial interventions grouped into four comparisons: (1) cognitive-behavioural coping skills training versus 12-step facilitation (one study; 41 participants), (2) brief intervention versus treatment as usual (one study; 110

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

PubMed

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

2014-04-01

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

Effects of lifetime tobacco, alcohol and drug use on psychological and behavioral problems among 10th grade students in Istanbul.

PubMed

Evren, Cuneyt; Evren, Bilge; Bozkurt, Muge; Ciftci-Demirci, Arzu

2015-11-01

The aim of this study was to determine the effects of life-time tobacco, alcohol, and substance use on psychological and behavioral variables among 10th grade students in Istanbul/Turkey. This study employed a cross-sectional online self-report survey conducted in 45 schools from the 15 districts in Istanbul. The questionnaire featured a section about use of substances, including tobacco, alcohol, and drugs. The depression, anxiety, anger, assertiveness, sensation seeking and impulsiveness subscales of the Psychological Screening Test for Adolescents (PSTA) were used. The analyses were conducted based on 4957 subjects. Logistic regression analyses were conducted with each school with the related and behavioral variables as the dependent variables. Gender, tobacco, alcohol, and drug use being the independent variables. All four independent variables predicted the dependent variables. Lifetime tobacco and drug use had significant effects on all the subscale score, whereas lifetime alcohol use had significant effects on all the subscale scores other than lack of assertiveness, and male gender was a significant covariant for all the subscale scores. Drug use showed the highest effect on dependent variables. Interaction was found between effects of tobacco and alcohol on anxiety, whereas interactions were found between effects of tobacco and drugs on lack of assertiveness and impulsiveness. The findings suggested that male students with lifetime tobacco, alcohol or drug use have particularly high risk of psychological and behavioral problems. The unique effects of substance clusters on these problems may be useful in developing secondary preventive practices for substance use and abuse problems in Istanbul.

The pre-image problem in kernel methods.

PubMed

Kwok, James Tin-yau; Tsang, Ivor Wai-hung

2004-11-01

In this paper, we address the problem of finding the pre-image of a feature vector in the feature space induced by a kernel. This is of central importance in some kernel applications, such as on using kernel principal component analysis (PCA) for image denoising. Unlike the traditional method which relies on nonlinear optimization, our proposed method directly finds the location of the pre-image based on distance constraints in the feature space. It is noniterative, involves only linear algebra and does not suffer from numerical instability or local minimum problems. Evaluations on performing kernel PCA and kernel clustering on the USPS data set show much improved performance.

Comparative Study of Different Methods for the Prediction of Drug-Polymer Solubility.

PubMed

Knopp, Matthias Manne; Tajber, Lidia; Tian, Yiwei; Olesen, Niels Erik; Jones, David S; Kozyra, Agnieszka; Löbmann, Korbinian; Paluch, Krzysztof; Brennan, Claire Marie; Holm, René; Healy, Anne Marie; Andrews, Gavin P; Rades, Thomas

2015-09-08

In this study, a comparison of different methods to predict drug-polymer solubility was carried out on binary systems consisting of five model drugs (paracetamol, chloramphenicol, celecoxib, indomethacin, and felodipine) and polyvinylpyrrolidone/vinyl acetate copolymers (PVP/VA) of different monomer weight ratios. The drug-polymer solubility at 25 °C was predicted using the Flory-Huggins model, from data obtained at elevated temperature using thermal analysis methods based on the recrystallization of a supersaturated amorphous solid dispersion and two variations of the melting point depression method. These predictions were compared with the solubility in the low molecular weight liquid analogues of the PVP/VA copolymer (N-vinylpyrrolidone and vinyl acetate). The predicted solubilities at 25 °C varied considerably depending on the method used. However, the three thermal analysis methods ranked the predicted solubilities in the same order, except for the felodipine-PVP system. Furthermore, the magnitude of the predicted solubilities from the recrystallization method and melting point depression method correlated well with the estimates based on the solubility in the liquid analogues, which suggests that this method can be used as an initial screening tool if a liquid analogue is available. The learnings of this important comparative study provided general guidance for the selection of the most suitable method(s) for the screening of drug-polymer solubility.

Simple and Accurate Method for Central Spin Problems

NASA Astrophysics Data System (ADS)

Lindoy, Lachlan P.; Manolopoulos, David E.

2018-06-01

We describe a simple quantum mechanical method that can be used to obtain accurate numerical results over long timescales for the spin correlation tensor of an electron spin that is hyperfine coupled to a large number of nuclear spins. This method does not suffer from the statistical errors that accompany a Monte Carlo sampling of the exact eigenstates of the central spin Hamiltonian obtained from the algebraic Bethe ansatz, or from the growth of the truncation error with time in the time-dependent density matrix renormalization group (TDMRG) approach. As a result, it can be applied to larger central spin problems than the algebraic Bethe ansatz, and for longer times than the TDMRG algorithm. It is therefore an ideal method to use to solve central spin problems, and we expect that it will also prove useful for a variety of related problems that arise in a number of different research fields.

Boundary-integral methods in elasticity and plasticity. [solutions of boundary value problems

NASA Technical Reports Server (NTRS)

Mendelson, A.

1973-01-01

Recently developed methods that use boundary-integral equations applied to elastic and elastoplastic boundary value problems are reviewed. Direct, indirect, and semidirect methods using potential functions, stress functions, and displacement functions are described. Examples of the use of these methods for torsion problems, plane problems, and three-dimensional problems are given. It is concluded that the boundary-integral methods represent a powerful tool for the solution of elastic and elastoplastic problems.

A Microfluidic Channel Method for Rapid Drug-Susceptibility Testing of Pseudomonas aeruginosa

PubMed Central

Matsumoto, Yoshimi; Grushnikov, Andrey; Kikuchi, Kazuma; Noji, Hiroyuki; Yamaguchi, Akihito; Yagi, Yasushi

2016-01-01

The recent global increase in the prevalence of antibiotic-resistant bacteria and lack of development of new therapeutic agents emphasize the importance of selecting appropriate antimicrobials for the treatment of infections. However, to date, the development of completely accelerated drug susceptibility testing methods has not been achieved despite the availability of a rapid identification method. We proposed an innovative rapid method for drug susceptibility testing for Pseudomonas aeruginosa that provides results within 3 h. The drug susceptibility testing microfluidic (DSTM) device was prepared using soft lithography. It consisted of five sets of four microfluidic channels sharing one inlet slot, and the four channels are gathered in a small area, permitting simultaneous microscopic observation. Antimicrobials were pre-introduced into each channel and dried before use. Bacterial suspensions in cation-adjusted Mueller–Hinton broth were introduced from the inlet slot and incubated for 3 h. Susceptibilities were microscopically evaluated on the basis of differences in cell numbers and shapes between drug-treated and control cells, using dedicated software. The results of 101 clinically isolated strains of P. aeruginosa obtained using the DSTM method strongly correlated with results obtained using the ordinary microbroth dilution method. Ciprofloxacin, meropenem, ceftazidime, and piperacillin caused elongation in susceptible cells, while meropenem also induced spheroplast and bulge formation. Morphological observation could alternatively be used to determine the susceptibility of P. aeruginosa to these drugs, although amikacin had little effect on cell shape. The rapid determination of bacterial drug susceptibility using the DSTM method could also be applicable to other pathogenic species, and it could easily be introduced into clinical laboratories without the need for expensive instrumentation. PMID:26872134

Solving Fluid Structure Interaction Problems with an Immersed Boundary Method

NASA Technical Reports Server (NTRS)

Barad, Michael F.; Brehm, Christoph; Kiris, Cetin C.

2016-01-01

An immersed boundary method for the compressible Navier-Stokes equations can be used for moving boundary problems as well as fully coupled fluid-structure interaction is presented. The underlying Cartesian immersed boundary method of the Launch Ascent and Vehicle Aerodynamics (LAVA) framework, based on the locally stabilized immersed boundary method previously presented by the authors, is extended to account for unsteady boundary motion and coupled to linear and geometrically nonlinear structural finite element solvers. The approach is validated for moving boundary problems with prescribed body motion and fully coupled fluid structure interaction problems. Keywords: Immersed Boundary Method, Higher-Order Finite Difference Method, Fluid Structure Interaction.

Applying the Problem Behavior Theory to Adolescent Drug Use Among a Cross-Sectional Sample of Boys Participating in a Community-Based Youth Organization.

PubMed

Alexander, Adam C; Obong'o, Christopher O; Chavan, Prachi; Vander Weg, Mark W; Ward, Kenneth D

2018-03-21

Drug use remains an important public health concern in the United States, and understanding drug use among young adolescents is vital towards improving the health of the population. This study applied the Problem Behavior Theory (PBT) to lifetime drug use among a cross-sectional sample of Boy Scouts (N = 770). The PBT provides a conceptual framework for identifying risk and protective factors for adolescent problem behaviors, including drug use. Scouts reported their drug use and socio-demographics, and were assessed on several risk and protective factors. For analyses, sociodemographic and risk and protective factors were selected according to the framework provided by PBT, and use of each drug was regressed logistically on these selected factors. Final logistic models were assessed for goodness of fit and discriminatory power. The PBT demonstrated discriminatory power for all drugs (Tjur's R 2 values ≥.29), but fell sharply for illicit drug use (Tjur's R 2 =.20). There were no consistent correlates of drug use. Conclusions/Importance: The PBT had less explanatory power for illicit drug use compared to tobacco, alcohol, and marijuana, which suggests different risk and protective factors were associated with illicit drug use.

The impact of calcium carbonate as pore forming agent and drug entrapment method towards drug dissolution mechanism of amoxicillin trihydrate encapsulated by chitosan-methyl cellulose semi-IPN hydrogel for floating drug delivery system

NASA Astrophysics Data System (ADS)

Dewantara, Fauzi; Budianto, Emil

2018-04-01

Chitosan-methyl cellulose semi-IPN hydrogel is used as floating drug delivery system, and calcium carbonate also added as pore forming agent. The hydrogel network arranged by not only using biopolymer chitosan and methyl cellulose, but also the crosslink agent that is glutaraldehyde. Amoxicillin trihydrate entrapped into the polymer network with two different method, in situ loading and post loading. Furthermore both method has been tested for drug entrapment efficiency along with drug dissolution test, and the result for drug entrapment efficiency is in situ loading method has highest value of 100%, compared to post loading method which has value only 71%. Moreover, at the final time of drug dissolution test shows in situ loading method has value of 96% for total accumulative of drug dissolution, meanwhile post loading method has 72%. The value of drug dissolution test from both method is used for analyzing drug dissolution mechanism of amoxicillin trihydrate from hydrogel network with four mathematical drug mechanism models as parameter. The polymer network encounter destructive degradation causes by acid solution which used as dissolution medium, and the level of degradation is observed with optical microscope. However the result shows that degradation of the polymer network doesn't affect drug dissolution mechanism directly. Although the pore forming agent causes the pore inside the hydrogel network create interconnection and it was quite influential to drug dissolution mechanism. Interconnected pore is observed with Scanning Electron Microscope (SEM) and shows that the amount and area of interconnected pore inside the hydrogel network is increasing as drug dissolution goes on.

Integrated Force Method Solution to Indeterminate Structural Mechanics Problems

NASA Technical Reports Server (NTRS)

Patnaik, Surya N.; Hopkins, Dale A.; Halford, Gary R.

2004-01-01

Strength of materials problems have been classified into determinate and indeterminate problems. Determinate analysis primarily based on the equilibrium concept is well understood. Solutions of indeterminate problems required additional compatibility conditions, and its comprehension was not exclusive. A solution to indeterminate problem is generated by manipulating the equilibrium concept, either by rewriting in the displacement variables or through the cutting and closing gap technique of the redundant force method. Compatibility improvisation has made analysis cumbersome. The authors have researched and understood the compatibility theory. Solutions can be generated with equal emphasis on the equilibrium and compatibility concepts. This technique is called the Integrated Force Method (IFM). Forces are the primary unknowns of IFM. Displacements are back-calculated from forces. IFM equations are manipulated to obtain the Dual Integrated Force Method (IFMD). Displacement is the primary variable of IFMD and force is back-calculated. The subject is introduced through response variables: force, deformation, displacement; and underlying concepts: equilibrium equation, force deformation relation, deformation displacement relation, and compatibility condition. Mechanical load, temperature variation, and support settling are equally emphasized. The basic theory is discussed. A set of examples illustrate the new concepts. IFM and IFMD based finite element methods are introduced for simple problems.

Non-Medical Prescription Drug Use among University Students

ERIC Educational Resources Information Center

Vidourek, Rebecca A.; King, Keith A.; Knopf, Ellen E.

2010-01-01

Background: Non-medical prescription drug use is an increasing problem among university students. Purpose: The present study investigated university students' involvement in non-medical prescription drug (NMPD) use and associations between use and other risky behaviors. Methods: A sample of 363 university students completed a four page survey…

Nano-sized crystalline drug production by milling technology.

PubMed

Moribe, Kunikazu; Ueda, Keisuke; Limwikrant, Waree; Higashi, Kenjirou; Yamamoto, Keiji

2013-01-01

Nano-formulation of poorly water-soluble drugs has been developed to enhance drug dissolution. In this review, we introduce nano-milling technology described in recently published papers. Factors affecting the size of drug crystals are compared based on the preparation methods and drug and excipient types. A top-down approach using the comminution process is a method conventionally used to prepare crystalline drug nanoparticles. Wet milling using media is well studied and several wet-milled drug formulations are now on the market. Several trials on drug nanosuspension preparation using different apparatuses, materials, and conditions have been reported. Wet milling using a high-pressure homogenizer is another alternative to preparing production-scale drug nanosuspensions. Dry milling is a simple method of preparing a solid-state drug nano-formulation. The effect of size on the dissolution of a drug from nanoparticles is an area of fundamental research, but it is sometimes incorrectly evaluated. Here, we discuss evaluation procedures and the associated problems. Lastly, the importance of quality control, process optimization, and physicochemical characterization are briefly discussed.

Modern Methods for Analysis of Antiepileptic Drugs in the Biological Fluids for Pharmacokinetics, Bioequivalence and Therapeutic Drug Monitoring

PubMed Central

Park, Yoo-Sin; Kim, Shin-Hee; Kim, Sang-Hyun; Jun, Min-Young

2011-01-01

Epilepsy is a chronic disease occurring in approximately 1.0% of the world's population. About 30% of the epileptic patients treated with availably antiepileptic drugs (AEDs) continue to have seizures and are considered therapy-resistant or refractory patients. The ultimate goal for the use of AEDs is complete cessation of seizures without side effects. Because of a narrow therapeutic index of AEDs, a complete understanding of its clinical pharmacokinetics is essential for understanding of the pharmacodynamics of these drugs. These drug concentrations in biological fluids serve as surrogate markers and can be used to guide or target drug dosing. Because early studies demonstrated clinical and/or electroencephalographic correlations with serum concentrations of several AEDs, It has been almost 50 years since clinicians started using plasma concentrations of AEDs to optimize pharmacotherapy in patients with epilepsy. Therefore, validated analytical method for concentrations of AEDs in biological fluids is a necessity in order to explore pharmacokinetics, bioequivalence and TDM in various clinical situations. There are hundreds of published articles on the analysis of specific AEDs by a wide variety of analytical methods in biological samples have appears over the past decade. This review intends to provide an updated, concise overview on the modern method development for monitoring AEDs for pharmacokinetic studies, bioequivalence and therapeutic drug monitoring. PMID:21660146

Proposal of Evolutionary Simplex Method for Global Optimization Problem

NASA Astrophysics Data System (ADS)

Shimizu, Yoshiaki

To make an agile decision in a rational manner, role of optimization engineering has been notified increasingly under diversified customer demand. With this point of view, in this paper, we have proposed a new evolutionary method serving as an optimization technique in the paradigm of optimization engineering. The developed method has prospects to solve globally various complicated problem appearing in real world applications. It is evolved from the conventional method known as Nelder and Mead’s Simplex method by virtue of idea borrowed from recent meta-heuristic method such as PSO. Mentioning an algorithm to handle linear inequality constraints effectively, we have validated effectiveness of the proposed method through comparison with other methods using several benchmark problems.

An investigation into drug-related problems identifiable by commercial medication review software.

PubMed

Curtain, Colin; Bindoff, Ivan; Westbury, Juanita; Peterson, Gregory

2013-01-01

Accredited pharmacists conduct home medicines reviews (HMRs) to detect and resolve potential drug-related problems (DRPs). A commercial expert system, Medscope Review Mentor (MRM), has been developed to assist pharmacists in the detection and resolution of potential DRPs. This study compares types of DRPs identified with the commercial system which uses multiple classification ripple down rules (MCRDR) with the findings of pharmacists. HMR data from 570 reviews collected from accredited pharmacists was entered into MRM and the DRPs were identified. A list of themes describing the main concept of each DRP identified by MRM was developed to allow comparison with pharmacists. Theme types, frequencies, similarity and dissimilarity were explored. The expert system was capable of detecting a wide range of potential DRPs: 2854 themes; compared to pharmacists: 1680 themes. The system identified the same problems as pharmacists in many patient cases. Ninety of 119 types of themes identifiable by pharmacists were also identifiable by software. MRM could identify the same problems in the same patients as pharmacists for 389 problems, resulting in a low overlap of similarity with an averaged Jaccard Index of 0.09. MRM found significantly more potential DRPs than pharmacists. MRM identified a wide scope of DRPs approaching the range of DRPs that were identified by pharmacists. Differences may be associated with system consistency and perhaps human oversight or human selective prioritisation. DRPs identified by the system were still considered relevant even though the system identified a larger number of problems.

Links between alcohol and other drug problems and maltreatment among adolescent girls: Perceived discrimination, ethnic identity, and ethnic orientation as moderators

PubMed Central

Gray, Calonie M. K.; Montgomery, Marilyn J.

2012-01-01

Objectives This study examined the links between maltreatment, posttraumatic stress symptoms, ethnicity-specific factors (i.e., perceived discrimination, ethnic identity, and ethnic orientation), and alcohol and/or other drug (AOD) problems among adolescent girls. Methods These relations were examined using archived data from a community sample of 168 Black and Hispanic adolescent girls who participated in a school-based substance use intervention. Results The results revealed that maltreatment was linked to AOD problems, but only through its relation with posttraumatic stress symptoms; maltreatment was positively related to posttraumatic stress symptoms, which were positively related to AOD problems. Both perceived discrimination and ethnic orientation were significant moderators. Specifically, greater perceived discrimination was associated with an increased effect of maltreatment on posttraumatic stress symptoms. Ethnic orientation demonstrated protective properties in the relation between maltreatment and AOD problem severity, such that the effect of maltreatment on AOD problem severity was less for girls with average to high ethnic orientation compared to girls with low ethnic orientation. Conclusions The findings of this study underscore the importance of developing interventions for Black and Hispanic girls that target maltreatment and AOD use concurrently and address ethnicity-specific factors. PMID:22608406

21 CFR 530.24 - Procedure for announcing analytical methods for drug residue quantification.

Code of Federal Regulations, 2011 CFR

2011-04-01

..., DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS EXTRALABEL DRUG USE IN ANIMALS Specific Provisions Relating to Extralabel Use of Animal and Human Drugs in Food-Producing Animals § 530.24 Procedure for announcing analytical methods for drug residue quantification. (a...

Human placental perfusion method in the assessment of transplacental passage of antiepileptic drugs

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

Myllynen, Paeivi; Pienimaeki, Paeivi; Vaehaekangas, Kirsi

2005-09-01

Epilepsy is one of the most common neurological diseases, affecting about 0.5 to 1% of pregnant women. It is commonly accepted that older antiepileptic drugs bear teratogenic potential. So far, no agreement has been reached about the safest antiepileptic drug during pregnancy. It is known that nearly all drugs cross the placenta at least to some extent. Nowadays, there is very little information available of the pharmacokinetics of drugs in the feto-placental unit. Detailed information about drug transport across the placenta would be valuable for the development of safe and effective treatments. For reasons of safety, human studies on placentalmore » transfer are restricted to a limited number of drugs. Interspecies differences limit the extrapolation of animal data to humans. Several in vitro methods for the study of placental transfer have been developed over the past decades. The placental perfusion method is the only experimental method that has been used to study human placental transfer of substances in organized placental tissue. The aim of this article is to review human placental perfusion data on antiepileptic drugs. According to perfusion data, it seems that most of the antiepileptic drugs are transferred across the placenta meaning significant fetal exposure.« less

The aggregated unfitted finite element method for elliptic problems

NASA Astrophysics Data System (ADS)

Badia, Santiago; Verdugo, Francesc; Martín, Alberto F.

2018-07-01

Unfitted finite element techniques are valuable tools in different applications where the generation of body-fitted meshes is difficult. However, these techniques are prone to severe ill conditioning problems that obstruct the efficient use of iterative Krylov methods and, in consequence, hinders the practical usage of unfitted methods for realistic large scale applications. In this work, we present a technique that addresses such conditioning problems by constructing enhanced finite element spaces based on a cell aggregation technique. The presented method, called aggregated unfitted finite element method, is easy to implement, and can be used, in contrast to previous works, in Galerkin approximations of coercive problems with conforming Lagrangian finite element spaces. The mathematical analysis of the new method states that the condition number of the resulting linear system matrix scales as in standard finite elements for body-fitted meshes, without being affected by small cut cells, and that the method leads to the optimal finite element convergence order. These theoretical results are confirmed with 2D and 3D numerical experiments.

Development and validation of a headspace gas chromatographic method for the determination of residual solvents in arterolane (RBx11160) maleate bulk drug

PubMed Central

Gupta, Abhishek; Singh, Yogendra; Srinivas, Kona S.; Jain, Garima; Sreekumar, V. B.; Semwal, Vinod Prasad

2010-01-01

Objective: Arterolane maleate is an antimalarial drug currently under Phase III clinical evaluation, and presents a simple, economical and scalable synthesis, and does not suffer from safety problems. Arterolane maleate is more active than artemisinin; and is cheap to produce. It has a longer lifetime in the plasma, so it stays active longer in the body. To provide quality control over the manufacture of any API, it is essential to develop highly selective analytical methods. In the current article we are reporting the development and validation of a rapid and specific Head space gas chromatographic (HSGC) method for the determination of organic volatile impurities (residual solvents) in Arterolane Maleate bulk drug. Materials and Methods: The method development and its validation were performed on Perkin Elmer's gas chromatographic system equipped with Flame Ionization detector and head space analyzer. The method involved a thermal gradient elution of ten residual solvents present in arterolane maleate salt in RTx-624, 30 m × 0.32 mm, 1.8 μ column using nitrogen gas as a carrier. The flow rate was 0.5 ml/min and flame ionization detector (FID) was used. Results: During method validation, parameters such as precision, linearity, accuracy, limit of quantification and detection and specificity were evaluated, which remained within acceptable limits. Conclusions: The method has been successfully applied for the quantification of the amount of residual solvents present in arterolane maleate bulk drug.The method presents a simple and reliable solution for the routine quantitative analysis of residual solvents in Arterolane maleate bulk drug. PMID:21814428

Data sources and methods for ascertaining human exposure to drugs.

PubMed

Jones, J K; Kennedy, D L

Estimates of population exposure based on drug use data are critical elements in the post marketing surveillance of drugs and provide a context for assessing the various risks and benefits associated with drug treatment. Such information is important in predicting morbidity and planning public health protection strategies, indepth studies, and regulatory actions. Knowledge that a population of one thousand instead of one million may potentially be exposed to a drug can help determine how a particular regulatory problem will be handled and would obviously be a major determinant in designing a case-control or cohort study. National estimates of drug use give an overview of the most commonly used drug therapies in current practice. They also furnish valuable comparison data for specific studies of drug use limited to one group of drugs, one geographic region, or one medical care setting. The FDA has access to several different national drug use data bases, each measuring a different point in the drug distribution channels. None covers the entire spectrum of drug exposures. The major "holes" in this patchwork of data bases are the inability to measure OTC drug use with any accuracy and the lack of qualitative information on drug use in hospitals. In addition, there is no patient linkage with the data. The data can only show trends in drug use. They impart no sense of the longitudinal use of drugs for individual patients. There is no direct connection between the different data bases, all of which have their own sampling frames and their own projection methodologies. The market research companies have complete control over these methodologies and they are subject to periodic changes, a situation not entirely satisfactory for epidemiologic research. Sometimes it is a struggle to keep up with these changes. Over the past two years, every one of these data bases has undergone some type of sampling or projection methodology change. One important limitation to the use of all

Fuzzy Hungarian Method for Solving Intuitionistic Fuzzy Travelling Salesman Problem

NASA Astrophysics Data System (ADS)

Prabakaran, K.; Ganesan, K.

2018-04-01

The travelling salesman problem is to identify the shortest route that the salesman journey all the places and return the starting place with minimum cost. We develop a fuzzy version of Hungarian algorithm for the solution of intuitionistic fuzzy travelling salesman problem using triangular intuitionistic fuzzy numbers without changing them to classical travelling salesman problem. The purposed method is easy to empathize and to implement for finding solution of intuitionistic travelling salesman problem happening in real life situations. To illustrate the proposed method numerical example are provided.

Time spent by Belgian hospital pharmacists on supply disruptions and drug shortages: An exploratory study

PubMed Central

De Weerdt, Elfi; De Rijdt, Thomas; Simoens, Steven; Casteels, Minne; Huys, Isabelle

2017-01-01

Introduction Supply problems of drugs are an increasing and worldwide problem, also in Belgium. Hospital pharmacists try to manage drug supply problems to minimize the impact on patient care. This study aims to quantify in a detailed manner how much time employees of 17 Belgian hospital pharmacies spend on drug supply problems. Methods During six months, employees of Belgian hospital pharmacies filled in the daily time spent on drug supply problems using a template containing all steps which can be executed to manage drug supply problems. Additionally, Belgian hospital pharmacists were asked to report the drugs which experienced drug supply problems together with the solution for this problem. Results Hospital pharmacists spent a median of 109 minutes a week on drug supply problems, with a minimum of 40 minutes per week and a maximum of 216 minutes per week. Fifty-nine percent of the total time spent on drug supply problems was executed by hospital pharmacists, 27% by pharmacy technicians; the rest was performed by logistic or administrative personnel. About one third of the total time spent was invested in gathering information on the supply problem. About two third of the supply disruptions caused drug shortages, meaning there was a need to switch to another (generic) therapeutic alternative. For most drug shortages, a Belgian generic medicine could be found. However in some cases, the alternative had to be ordered abroad or for some drug shortages, no alternative was available. Conclusion These exploratory results on time spent by hospital pharmacists on drug supply problems in Belgium highlight the economic impact of drug supply problems for hospital pharmacies. A fully reliable, daily updated list on the federal agencies websites would be a major help to hospital pharmacists. PMID:28350827

A Method for Overcoming the Problem of Concept-Scale Interaction in Semantic Differential Research

ERIC Educational Resources Information Center

Bynner, John; Romney, David

1972-01-01

Data collected in a study of hospital staff attitudes to drug addicts and other types of patients are used to illustrate the problem of concept-scale interaction in semantic differential research. (Authors)

Methods Development for Blood Borne Macrophage Carriage of Nanoformulated Antiretroviral Drugs

PubMed Central

Roy, Upal; Martinez-Skinner, Andrea; McMillan, JoEllyn; Gendelman, Howard E.

2010-01-01

Nanoformulated drugs can improve pharmacodynamics and bioavailability while serving also to reduce drug toxicities for antiretroviral (ART) medicines. To this end, our laboratory has applied the principles of nanomedicine to simplify ART regimens and as such reduce toxicities while improving compliance and drug pharmacokinetics. Simple and reliable methods for manufacturing nanoformulated ART (nanoART) are shown. Particles of pure drug are encapsulated by a thin layer of surfactant lipid coating and produced by fractionating larger drug crystals into smaller ones by either wet milling or high-pressure homogenization. In an alternative method free drug is suspended in a droplet of a polymer. Herein, drug is dissolved within a polymer then agitated by ultrasonication until individual nanosized droplets are formed. Dynamic light scattering and microscopic examination characterize the physical properties of the particles (particle size, charge and shape). Their biologic properties (cell uptake and retention, cytotoxicity and antiretroviral efficacy) are determined with human monocyte-derived macrophages (MDM). MDM are derived from human peripheral blood monocytes isolated from leukopacks using centrifugal elutriation for purification. Such blood-borne macrophages may be used as cellular transporters for nanoART distribution to human immunodeficiency virus (HIV) infected organs. We posit that the repackaging of clinically available antiretroviral medications into nanoparticles for HIV-1 treatments may improve compliance and positively affect disease outcomes. PMID:21178968

Detection of Drug-Resistant Mycobacterium tuberculosis.

PubMed

Engström, Anna; Juréen, Pontus

2015-01-01

Tuberculosis (TB) remains a global health problem. The increasing prevalence of drug-resistant Mycobacterium tuberculosis, the causative agent of TB, demands new measures to combat the situation. Rapid and accurate diagnosis of the pathogen and its drug susceptibility pattern is essential for timely initiation of optimal treatment, and, ultimately, control of the disease. We have developed a molecular method for detection of first- and second-line drug resistance in M. tuberculosis by Pyrosequencing(®). The method consists of seven Pyrosequencing assays for the detection of mutations in the genes or promoter regions, which are most commonly responsible for resistance to the drugs rifampicin, isoniazid, ethambutol, amikacin, kanamycin, capreomycin, and fluoroquinolones. The method was validated on clinical isolates and it was shown that the sensitivity and specificity of the method were comparable to those of Sanger sequencing. In the protocol in this chapter we describe the steps necessary for setting up and performing Pyrosequencing for M. tuberculosis. The first part of the protocol describes the assay development and the second part of the protocol describes utilization of the method.

Variational Methods For Sloshing Problems With Surface Tension

NASA Astrophysics Data System (ADS)

Tan, Chee Han; Carlson, Max; Hohenegger, Christel; Osting, Braxton

2016-11-01

We consider the sloshing problem for an incompressible, inviscid, irrotational fluid in a container, including effects due to surface tension on the free surface. We restrict ourselves to a constant contact angle and we seek time-harmonic solutions of the linearized problem, which describes the time-evolution of the fluid due to a small initial disturbance of the surface at rest. As opposed to the zero surface tension case, where the problem reduces to a partial differential equation for the velocity potential, we obtain a coupled system for the velocity potential and the free surface displacement. We derive a new variational formulation of the coupled problem and establish the existence of solutions using the direct method from the Calculus of Variations. In the limit of zero surface tension, we recover the variational formulation of the classical Steklov eigenvalue problem, as derived by B. A. Troesch. For the particular case of an axially symmetric container, we propose a finite element numerical method for computing the sloshing modes of the coupled system. The scheme is implemented in FEniCS and we obtain a qualitative description of the effect of surface tension on the sloshing modes.

Employee assistance program services for alcohol and other drug problems: implications for increased identification and engagement in treatment.

PubMed

Jacobson, Jodi M; Sacco, Paul

2012-01-01

Fourteen million U.S. workers meet the diagnostic criteria for substance dependence, costing millions in lost productivity. Prior research suggests that employees who follow through with their Employee Assistance Program's (EAP) recommendations are more likely to participate and remain engaged in alcohol and other drug (AOD) treatment programs. This study identified rates of lifetime EAP service use for AOD problems and compared adults who reported using EAP services for AOD problems with those who used services other than EAP. Researchers analyzed a subset of participants from the National Epidemiologic Survey of Alcohol and Related Conditions who reported having received help for an AOD problem (NESARC, 2001-2002). Statistical analyses tested for differences in sociodemographic variables, lifetime mental health and substance abuse disorders, and health disability between EAP services users and users of other types of services. Among adults who sought services for AOD problems (n= 2,272), 7.58% (n= 166) reported using EAP services for these problems at some point during their lives. Major depressive disorder (lifetime), a drug use disorder (lifetime), and Black race/ethnicity were associated with a greater likelihood that someone would seek EAP services for help with their AOD problem. Results provide a foundation for researchers to understand who uses EAP services for AOD problems. Health and mental health professionals should increase their knowledge of EAP services to improve continuity of care for employees with AOD problems. EAPs are in a unique position to reach out to vulnerable employees in the workplace and engage them in treatment. Copyright © American Academy of Addiction Psychiatry.

Pseudo-time methods for constrained optimization problems governed by PDE

NASA Technical Reports Server (NTRS)

Taasan, Shlomo

1995-01-01

In this paper we present a novel method for solving optimization problems governed by partial differential equations. Existing methods are gradient information in marching toward the minimum, where the constrained PDE is solved once (sometimes only approximately) per each optimization step. Such methods can be viewed as a marching techniques on the intersection of the state and costate hypersurfaces while improving the residuals of the design equations per each iteration. In contrast, the method presented here march on the design hypersurface and at each iteration improve the residuals of the state and costate equations. The new method is usually much less expensive per iteration step since, in most problems of practical interest, the design equation involves much less unknowns that that of either the state or costate equations. Convergence is shown using energy estimates for the evolution equations governing the iterative process. Numerical tests show that the new method allows the solution of the optimization problem in a cost of solving the analysis problems just a few times, independent of the number of design parameters. The method can be applied using single grid iterations as well as with multigrid solvers.

Collaborative Problem Solving Methods towards Critical Thinking

ERIC Educational Resources Information Center

Yin, Khoo Yin; Abdullah, Abdul Ghani Kanesan; Alazidiyeen, Naser Jamil

2011-01-01

This research attempts to examine the collaborative problem solving methods towards critical thinking based on economy (AE) and non economy (TE) in the SPM level among students in the lower sixth form. The quasi experiment method that uses the modal of 3X2 factorial is applied. 294 lower sixth form students from ten schools are distributed…

Recent advances in reduction methods for nonlinear problems. [in structural mechanics

NASA Technical Reports Server (NTRS)

Noor, A. K.

1981-01-01

Status and some recent developments in the application of reduction methods to nonlinear structural mechanics problems are summarized. The aspects of reduction methods discussed herein include: (1) selection of basis vectors in nonlinear static and dynamic problems, (2) application of reduction methods in nonlinear static analysis of structures subjected to prescribed edge displacements, and (3) use of reduction methods in conjunction with mixed finite element models. Numerical examples are presented to demonstrate the effectiveness of reduction methods in nonlinear problems. Also, a number of research areas which have high potential for application of reduction methods are identified.

Searching for Truth: Internet Search Patterns as a Method of Investigating Online Responses to a Russian Illicit Drug Policy Debate

PubMed Central

Gillespie, James A; Quinn, Casey

2012-01-01

Background This is a methodological study investigating the online responses to a national debate over an important health and social problem in Russia. Russia is the largest Internet market in Europe, exceeding Germany in the absolute number of users. However, Russia is unusual in that the main search provider is not Google, but Yandex. Objective This study had two main objectives. First, to validate Yandex search patterns against those provided by Google, and second, to test this method's adequacy for investigating online interest in a 2010 national debate over Russian illicit drug policy. We hoped to learn what search patterns and specific search terms could reveal about the relative importance and geographic distribution of interest in this debate. Methods A national drug debate, centering on the anti-drug campaigner Egor Bychkov, was one of the main Russian domestic news events of 2010. Public interest in this episode was accompanied by increased Internet search. First, we measured the search patterns for 13 search terms related to the Bychkov episode and concurrent domestic events by extracting data from Google Insights for Search (GIFS) and Yandex WordStat (YaW). We conducted Spearman Rank Correlation of GIFS and YaW search data series. Second, we coded all 420 primary posts from Bychkov's personal blog between March 2010 and March 2012 to identify the main themes. Third, we compared GIFS and Yandex policies concerning the public release of search volume data. Finally, we established the relationship between salient drug issues and the Bychkov episode. Results We found a consistent pattern of strong to moderate positive correlations between Google and Yandex for the terms "Egor Bychkov" (r s = 0.88, P < .001), “Bychkov” (r s = .78, P < .001) and “Khimki”(r s = 0.92, P < .001). Peak search volumes for the Bychkov episode were comparable to other prominent domestic political events during 2010. Monthly search counts were 146,689 for “Bychkov” and

Active Subspace Methods for Data-Intensive Inverse Problems

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

Wang, Qiqi

2017-04-27

The project has developed theory and computational tools to exploit active subspaces to reduce the dimension in statistical calibration problems. This dimension reduction enables MCMC methods to calibrate otherwise intractable models. The same theoretical and computational tools can also reduce the measurement dimension for calibration problems that use large stores of data.

Gas chromatography-mass spectrometry assay method for the therapeutic drug monitoring of the antiepileptic drug tiagabine.

PubMed

Chollet, D F; Castella, E; Goumaz, L; Anderegg, G

1999-11-01

A gas chromatography-mass spectrometry assay method suitable for the therapeutic drug monitoring of the antiepileptic drug tiagabine is described. Tiagabine and its desmethylated analogue used as internal standard were first extracted from serum by liquid-liquid extraction using an ethyl ether-isobutanol 98:2 mixture. Tiagabine and the internal standard were then methylated in the organic phase in presence of methanol by means of a safe and stable diazomethane derivative. After evaporation, the reconstituted extracts were chromatographed on a crosslinked phenyl methyl siloxane capillary column and detected by mass fragmentometry at m/z = 156. No other antiepileptic drug possibly administrated in polytherapy and no metabolite were found to interfere in the assay. The limit of quantification was 5 ng/ml. The precision and the accuracy were found to be suitable for the therapeutic drug monitoring of tiagabine.

A meta-heuristic method for solving scheduling problem: crow search algorithm

NASA Astrophysics Data System (ADS)

Adhi, Antono; Santosa, Budi; Siswanto, Nurhadi

2018-04-01

Scheduling is one of the most important processes in an industry both in manufacturingand services. The scheduling process is the process of selecting resources to perform an operation on tasks. Resources can be machines, peoples, tasks, jobs or operations.. The selection of optimum sequence of jobs from a permutation is an essential issue in every research in scheduling problem. Optimum sequence becomes optimum solution to resolve scheduling problem. Scheduling problem becomes NP-hard problem since the number of job in the sequence is more than normal number can be processed by exact algorithm. In order to obtain optimum results, it needs a method with capability to solve complex scheduling problems in an acceptable time. Meta-heuristic is a method usually used to solve scheduling problem. The recently published method called Crow Search Algorithm (CSA) is adopted in this research to solve scheduling problem. CSA is an evolutionary meta-heuristic method which is based on the behavior in flocks of crow. The calculation result of CSA for solving scheduling problem is compared with other algorithms. From the comparison, it is found that CSA has better performance in term of optimum solution and time calculation than other algorithms.

Reading the problem family: post-structuralism and the analysis of social problems.

PubMed

Reekie, G

1994-01-01

Post-structuralist theory questions the rational pursuit of an underlying 'truth' that often characterizes social scientific inquiry, proposing instead the simultaneous existence of multiple and often contradictory truths. The problem family can, from this perspective, only be known through the different discourses that produce it. This paper suggests some of the political advantages of developing methods of reading 'problems' related to drugs and alcohol. Without this critical attention to language, we risk perpetuating the ways in which problems are talked about and thought about. Drawing on examples from debates surrounding teenage pregnancy and youth drinking, the paper argues that post-structuralism allows us to analyse the specific ways in which professional discourses write social problems, and hence to own them and to re-write them.

Challenges for Detecting Valproic Acid in a Nontargeted Urine Drug Screening Method.

PubMed

Pope, Jeffrey D; Black, Marion J; Drummer, Olaf H; Schneider, Hans G

2017-08-01

Valproic acid (VPA) is a widely prescribed medicine, and acute toxicity is possible. As such, it should be included in any nontargeted urine drug screening method. In many published liquid chromatography-electrospray ionization-mass spectrometry (LC-ESI-MS/MS) methods, VPA is usually measured using a pseudo-multiple reaction monitoring (MRM) transition. We investigate a simple ultra-high-performance liquid chromatography-quadrupole time-of-flight (QTof) approach to detect the presence of VPA with more confidence. Three commercially sourced VPA metabolites were characterized and added to a nontargeted high-resolution MS urine drug screening method. All analyses were performed on a Waters Xevo G2-XS LC-QTof in negative electrospray ionization mode. The mass detector was operated in MS mode, and data were processed with UNIFI software. Sixty-eight patient urine samples, which were previously identified by a well-established gas chromatography-MS method as containing VPA, were analyzed on the Waters Xevo G2-XS LC-QTof, to validate this approach. VPA metabolite standards were characterized, and their detection data were added to the broad drug screening library. VPA metabolites were readily detectable in the urine of patients taking VPA. The inclusion of characterized VPA metabolites provides a simple and reliable method enabling the detection of VPA in nontargeted urine drug screening.

Problems in diagnosis and treatment of tuberculosis infection.

PubMed

Tsara, V; Serasli, E; Christaki, P

2009-01-01

Tuberculosis is still a major health problem in industrialized countries due to specific socioeconomic factors and there is the growing need of new rapid and accurate diagnostic methods, in order to achieve higher sensitivity and specificity compared to traditional methods of microscopic sputum examination and culture. Such methods, recently introduced, are nucleic acid amplification (NAA) tests, used directly on clinical specimens and blood tests (QuantiFERON-TB, T-SPOT.TB test), measuring the IFN-gamma released by stimulated T cells. Furthermore, new drugs for the disease need to be developed, aiming to better treatment results and to prevention of Multiple Drug Resistance (MDR) cases. Critical aspects in the management of drug resistance cases should be the careful choices of drugs combination, the close follow up of the patients alongside with the patients adherence to therapy. The role of national and international tuberculosis programs is invaluable in TB control and therapy, as well as the collaboration of all the health system departments. However, most of the clinical problems that may arise are addressed by the International Standards for Tuberculosis Care-ISTC and these guidelines should be taken into consideration, at least until future research provides more promising diagnostic and therapeutic modalities for control of the disease.

Two spectrophotometric methods for simultaneous determination of some antihyperlipidemic drugs

PubMed Central

Abdelwahab, Nada S.; El-Zeiny, Badr A.; Tohamy, Salwa I.

2012-01-01

Two simple, accurate, precise and economic spectrophotometric methods have been developed for simultaneous determination of Atorvastatin calcium (ATR) and Ezetimibe (EZ) in their bulk powder and pharmaceutical dosage form. Method (I) is based on dual wavelength analysis while method (II) is the mean centering of ratio spectra spectrophotometric (MCR) method. In method (I), two wavelengths were selected for each drug in such a way that the difference in absorbance was zero for the second drug. At wavelengths 226.6 and 244 nm EZ had equal absorbance values; therefore, these two wavelengths have been used to determine ATR; on a similar basis 228.6 and 262.8 nm were selected to determine EZ in their binary mixtures. In method II, the absorption spectra of both ATR and EZ with different concentrations were recorded over the range 200–350, divided by the spectrum of suitable divisor of both ATR and EZ and then the obtained ratio spectra were mean centered. The concentrations of active components were then determined from the calibration graphs obtained by measuring the amplitudes at 215–260 nm (peak to peak) for both ATR and EZ. Accuracy and precision of the developed methods have been tested; in addition recovery studies have been carried out in order to confirm their accuracy. On the other hand, selectivities of the methods were tested by application for determination of different synthetic mixtures containing different ratios of the studied drugs. The developed methods have been successfully used for determination of ATR and EZ in their combined dosage form and statistical comparison of the developed methods with the reported spectrophotometric one using F and Student's t-tests showed no significant difference regarding both accuracy and precision. PMID:29403754

Two spectrophotometric methods for simultaneous determination of some antihyperlipidemic drugs.

PubMed

Abdelwahab, Nada S; El-Zeiny, Badr A; Tohamy, Salwa I

2012-08-01

Two simple, accurate, precise and economic spectrophotometric methods have been developed for simultaneous determination of Atorvastatin calcium (ATR) and Ezetimibe (EZ) in their bulk powder and pharmaceutical dosage form. Method (I) is based on dual wavelength analysis while method (II) is the mean centering of ratio spectra spectrophotometric (MCR) method. In method (I), two wavelengths were selected for each drug in such a way that the difference in absorbance was zero for the second drug. At wavelengths 226.6 and 244 nm EZ had equal absorbance values; therefore, these two wavelengths have been used to determine ATR; on a similar basis 228.6 and 262.8 nm were selected to determine EZ in their binary mixtures. In method II, the absorption spectra of both ATR and EZ with different concentrations were recorded over the range 200-350, divided by the spectrum of suitable divisor of both ATR and EZ and then the obtained ratio spectra were mean centered. The concentrations of active components were then determined from the calibration graphs obtained by measuring the amplitudes at 215-260 nm (peak to peak) for both ATR and EZ. Accuracy and precision of the developed methods have been tested; in addition recovery studies have been carried out in order to confirm their accuracy. On the other hand, selectivities of the methods were tested by application for determination of different synthetic mixtures containing different ratios of the studied drugs. The developed methods have been successfully used for determination of ATR and EZ in their combined dosage form and statistical comparison of the developed methods with the reported spectrophotometric one using F and Student's t -tests showed no significant difference regarding both accuracy and precision.

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

PubMed

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

2016-12-22

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

Enhanced Molecular Dynamics Methods Applied to Drug Design Projects.

PubMed

Ziada, Sonia; Braka, Abdennour; Diharce, Julien; Aci-Sèche, Samia; Bonnet, Pascal

2018-01-01

Nobel Laureate Richard P. Feynman stated: "[…] everything that living things do can be understood in terms of jiggling and wiggling of atoms […]." The importance of computer simulations of macromolecules, which use classical mechanics principles to describe atom behavior, is widely acknowledged and nowadays, they are applied in many fields such as material sciences and drug discovery. With the increase of computing power, molecular dynamics simulations can be applied to understand biological mechanisms at realistic timescales. In this chapter, we share our computational experience providing a global view of two of the widely used enhanced molecular dynamics methods to study protein structure and dynamics through the description of their characteristics, limits and we provide some examples of their applications in drug design. We also discuss the appropriate choice of software and hardware. In a detailed practical procedure, we describe how to set up, run, and analyze two main molecular dynamics methods, the umbrella sampling (US) and the accelerated molecular dynamics (aMD) methods.

Degradation of components in drug formulations: a comparison between HPLC and DSC methods.

PubMed

Ceschel, G C; Badiello, R; Ronchi, C; Maffei, P

2003-08-08

Information about the stability of drug components and drug formulations is needed to predict the shelf-life of the final products. The studies on the interaction between the drug and the excipients may be carried out by means of accelerated stability tests followed by analytical determination of the active principle (HPLC and other methods) and by means of the differential scanning calorimetry (DSC). This research has been focused to the acetyl salicylic acid (ASA) physical-chemical characterisation by using DSC method in order to evaluate its compatibility with some of the most used excipients. It was possible to show, with the DSC method, the incompatibility of magnesium stearate with ASA; the HPLC data confirm the reduction of ASA concentration in the presence of magnesium stearate. With the other excipients the characteristic endotherms of the drug were always present and no or little degradation was observed with the accelerated stability tests. Therefore, the results with the DSC method are comparable and in good agreement with the results obtained with other methods.

The making of a public health problem: multi-drug resistant tuberculosis in India.

PubMed

Engel, Nora C

2013-07-01

This paper examines how actors construct the public problem of multi-drug resistant tuberculosis (MDR-TB) in India. MDR-TB has been framed by the World Health Organization as a pressing, global public health problem. The responses to MDR-TB are complicated as treatment takes longer and is more expensive than routine TB treatment. This is particularly problematic in countries, such as India, with high patient loads, a large and unregulated private sector, weak health systems and potentially high numbers of MDR-TB cases. This paper analyses how actors struggle for control over ownership, causal theories and political responsibility of the public problem of MDR-TB in India. It combines Gusfield's theory on the construction of public problems with insights from literature on the social construction of diseases and on medical social control. It highlights that there are flexible definitions of public problems, which are negotiated among actor groups and which shift over time. The Indian government has shifted its policy in recent years and acknowledged that MDR-TB needs to be dealt with within the TB programme. The study results reveal how the policy shift happened, why debates on the construction of MDR-TB as a public problem in India continue, and why actors with alternative theories than the government do not succeed in their lobbying efforts. Two main arguments are put forward. First, the construction of the public problem of MDR-TB in India is a social and political process. The need for representative data, international influence and politics define what is controllable. Second, the government seems to be anxious to control the definition of India's MDR-TB problem. This impedes an open, critical and transparent discussion on the definition of the public problem of MDR-TB, which is important in responding flexibly to emerging public health challenges.

A new method to assess Pavlovian conditioning of psychostimulant drug effects.

PubMed

Damianopoulos, E N; Carey, R J

1994-07-01

Experimental studies of psychoactive drugs by pavlovian drug-conditioning methods, which originally began with investigations of drug-induced responses mediated by the autonomic nervous system, have now been expanded to include drug-induced response effects expressed as modulations of spontaneous motoric behaviors. In the latter application, however, equivalent behavioral response outcomes in post-treatment tests for conditioning can occur following a psychostimulant drug treatment either through drug interference effects on habituation processes, drug-induced stress effects and/or by pavlovian conditioning of the drug-induced motoric activation effect. Current methodologies for the study of pavlovian conditioned drug effects and/or drug sensitization cannot distinguish among these possibilities. This methodological inadequacy was addressed by a modification of the conventional paired-unpaired treatment protocol. In the new protocol, the animal is sequentially placed into two test compartments with the drug treatment administered in conjunction with placement into the second test compartment. This design permits a differentiation of a pavlovian conditioned drug responses from non-conditioned drug effects through continuous measurement of the non-drug behavioral baseline in both the drug and non-drug control treatment groups combined with multiple response measurements and post-treatment tests for conditioning at variable post-conditioning intervals. The present study details the use of the new modified pavlovian protocol with repeated cocaine (10 mg/kg) treatment. A cocaine conditioned response at 1, 7, and 21 days post-conditioning was identified and distinguished from habituation and stress effects.

Discontinued drugs in 2012: cardiovascular drugs.

PubMed

Zhao, Hong-Ping; Jiang, Hong-Min; Xiang, Bing-Ren

2013-11-01

The continued high rate of cardiovascular morbidity and mortality has attracted wide concern and great attention of pharmaceutical industry. In order to reduce the attrition of cardiovascular drug R&D, it might be helpful recapitulating previous failures and identifying the potential factors to success. This perspective mainly analyses the 30 cardiovascular drugs dropped from clinical development in 2012. Reasons causing the termination of the cardiovascular drugs in the past 5 years are also tabulated and analysed. The analysis shows that the attrition is highest in Phase II trials and financial and strategic factors and lack of clinical efficacy are the principal reasons for these disappointments. To solve the four problems (The 'better than the Beatles' problem, the 'cautious regulator' problem, the 'throw money at it' tendency and the 'basic researchbrute force' bias) is recommended as the main measure to increase the number and quality of approvable products.

Searching for truth: internet search patterns as a method of investigating online responses to a Russian illicit drug policy debate.

PubMed

Zheluk, Andrey; Gillespie, James A; Quinn, Casey

2012-12-13

This is a methodological study investigating the online responses to a national debate over an important health and social problem in Russia. Russia is the largest Internet market in Europe, exceeding Germany in the absolute number of users. However, Russia is unusual in that the main search provider is not Google, but Yandex. This study had two main objectives. First, to validate Yandex search patterns against those provided by Google, and second, to test this method's adequacy for investigating online interest in a 2010 national debate over Russian illicit drug policy. We hoped to learn what search patterns and specific search terms could reveal about the relative importance and geographic distribution of interest in this debate. A national drug debate, centering on the anti-drug campaigner Egor Bychkov, was one of the main Russian domestic news events of 2010. Public interest in this episode was accompanied by increased Internet search. First, we measured the search patterns for 13 search terms related to the Bychkov episode and concurrent domestic events by extracting data from Google Insights for Search (GIFS) and Yandex WordStat (YaW). We conducted Spearman Rank Correlation of GIFS and YaW search data series. Second, we coded all 420 primary posts from Bychkov's personal blog between March 2010 and March 2012 to identify the main themes. Third, we compared GIFS and Yandex policies concerning the public release of search volume data. Finally, we established the relationship between salient drug issues and the Bychkov episode. We found a consistent pattern of strong to moderate positive correlations between Google and Yandex for the terms "Egor Bychkov" (r(s) = 0.88, P < .001), "Bychkov" (r(s) = .78, P < .001) and "Khimki"(r(s) = 0.92, P < .001). Peak search volumes for the Bychkov episode were comparable to other prominent domestic political events during 2010. Monthly search counts were 146,689 for "Bychkov" and 48,084 for "Egor Bychkov", compared to 53

A Cross-Lagged Evaluation of Eating Disorder Symptomatology and Substance-Use Problems*

PubMed Central

Dunn, Erin C.; Neighbors, Clayton; Fossos, Nicole; Larimer, Mary E.

2009-01-01

Objective: The purpose of this study was to conduct a temporal examination of the associations among disordered eating behaviors, substance use, and use-related negative consequences in female college students—a population at high risk for developing eating and substance-use disorders. Method: Participants completed assessments of disordered eating behaviors, alcohol and drug use, and use-related negative consequences. Results: Results support previous research suggesting that disordered eating behaviors are more strongly associated with alcohol- and substance-related problems rather than use per se. With respect to temporal precedence, results indicated that binge eating preceded alcohol-use problems, but a bidirectional relationship was found for vomiting. With regard to drug problems, laxatives use preceded drug problems, whereas drug problems preceded fasting. These associations were not better accounted for by pre-existing eating or substance-use problems or psychiatric distress (e.g., depression, anxiety). Conclusions: This study further supports the importance of assessing consequences, in addition to use patterns, when examining substance use in individuals demonstrating threshold and subthreshold eating-disordered behaviors. PMID:19118399

Guide to drug porphyrogenicity prediction and drug prescription in the acute porphyrias

PubMed Central

Thunell, Stig; Pomp, Erik; Brun, Atle

2007-01-01

What is already known about this subject Many drug safety lists for acute porphyrias, largely based on anecdotal evidence, are put forward, but no methods or rationale for the risk estimates are given. Many unexplained discrepancies between the lists exist. What this study adds A standardized method for assessment of the risk that a certain drug may activate these diseases has been developed. It also allows risk assessments for drugs lacking porphyria related clinical experience. About one thousand therapeutic drugs have been classified with regard to porphyrogenicity by the proposed method, which is most valuable for the care of porphyria patients. Aims This paper addresses two common problems in the care of carriers of acute porphyria: the choice of safe drugs for pharmacotherapy and the strategy to apply when potentially unsafe drugs cannot be avoided. Methods and results A technique is presented for prediction of risk that a certain drug may activate the disease in a gene carrier for acute porphyria. It is based on a model explaining the clinical manifestations as a result of the acute overloading of a deficient enzyme within the hepatic heme biosynthetic chain. The capacity of the drug for induction of the rate-limiting enzyme in heme biosynthesis, e.g. housekeeping 5-aminolevulinate synthase (ALAS1), is assessed by critical appraisal of reports of the outcomes of clinical use of the drug, and by theoretical criteria. The assessment occurs within the frame of a flow-scheme employing variables of increasing specificity, i.e. endocrine properties of the drug, structure and metabolism pointing to affinity to cytochrome P450, hepatic load in therapeutic use, recognized affinity to major CYP species, capacity for CYP-induction or irreversible inhibition, and capacity to activate or modulate the transduction mechanisms of nuclear receptors affecting ALAS1-gene transcription. It is proposed that in the absence of a safer alternative, an urgently needed drug not

A least-squares finite element method for incompressible Navier-Stokes problems

NASA Technical Reports Server (NTRS)

Jiang, Bo-Nan

1992-01-01

A least-squares finite element method, based on the velocity-pressure-vorticity formulation, is developed for solving steady incompressible Navier-Stokes problems. This method leads to a minimization problem rather than to a saddle-point problem by the classic mixed method and can thus accommodate equal-order interpolations. This method has no parameter to tune. The associated algebraic system is symmetric, and positive definite. Numerical results for the cavity flow at Reynolds number up to 10,000 and the backward-facing step flow at Reynolds number up to 900 are presented.

Invisibility problem in acoustics, electromagnetism and heat transfer. Inverse design method

NASA Astrophysics Data System (ADS)

Alekseev, G.; Tokhtina, A.; Soboleva, O.

2017-10-01

Two approaches (direct design and inverse design methods) for solving problems of designing devices providing invisibility of material bodies of detection using different physical fields - electromagnetic, acoustic and static are discussed. The second method is applied for solving problems of designing cloaking devices for the 3D stationary thermal scattering model. Based on this method the design problems under study are reduced to respective control problems. The material parameters (radial and tangential heat conductivities) of the inhomogeneous anisotropic medium filling the thermal cloak and the density of auxiliary heat sources play the role of controls. A unique solvability of direct thermal scattering problem in the Sobolev space is proved and the new estimates of solutions are established. Using these results, the solvability of control problem is proved and the optimality system is derived. Based on analysis of optimality system, the stability estimates of optimal solutions are established and numerical algorithms for solving particular thermal cloaking problem are proposed.

Prevalence and pathways of recovery from drug and alcohol problems in the United States population: Implications for practice, research, and policy.

PubMed

Kelly, John F; Bergman, Brandon; Hoeppner, Bettina B; Vilsaint, Corrie; White, William L

2017-12-01

Alcohol and other drug (AOD) problems confer a global, prodigious burden of disease, disability, and premature mortality. Even so, little is known regarding how, and by what means, individuals successfully resolve AOD problems. Greater knowledge would inform policy and guide service provision. Probability-based survey of US adult population estimating: 1) AOD problem resolution prevalence; 2) lifetime use of "assisted" (i.e., treatment/medication, recovery services/mutual help) vs. "unassisted" resolution pathways; 3) correlates of assisted pathway use. Participants (response=63.4% of 39,809) responding "yes" to, "Did you use to have a problem with alcohol or drugs but no longer do?" assessed on substance use, clinical histories, problem resolution. Weighted prevalence of problem resolution was 9.1%, with 46% self-identifying as "in recovery"; 53.9% reported "assisted" pathway use. Most utilized support was mutual-help (45.1%,SE=1.6), followed by treatment (27.6%,SE=1.4), and emerging recovery support services (21.8%,SE=1.4), including recovery community centers (6.2%,SE=0.9). Strongest correlates of "assisted" pathway use were lifetime AOD diagnosis (AOR=10.8[7.42-15.74], model R2=0.13), drug court involvement (AOR=8.1[5.2-12.6], model R2=0.10), and, inversely, absence of lifetime psychiatric diagnosis (AOR=0.3[0.2-0.3], model R2=0.10). Compared to those with primary alcohol problems, those with primary cannabis problems were less likely (AOR=0.7[0.5-0.9]) and those with opioid problems were more likely (AOR=2.2[1.4-3.4]) to use assisted pathways. Indices related to severity were related to assisted pathways (R2<0.03). Tens of millions of Americans have successfully resolved an AOD problem using a variety of traditional and non-traditional means. Findings suggest a need for a broadening of the menu of self-change and community-based options that can facilitate and support long-term AOD problem resolution. Copyright © 2017 Elsevier B.V. All rights reserved.

Structured product labeling improves detection of drug-intolerance issues.

PubMed

Schadow, Gunther

2009-01-01

This study sought to assess the value of the Health Level 7/U.S. Food and Drug Administration Structured Product Labeling (SPL) drug knowledge representation standard and its associated terminology sources for drug-intolerance (allergy) decision support in computerized provider order entry (CPOE) systems. The Regenstrief Institute CPOE drug-intolerance issue detection system and its knowledge base was compared with a method based on existing SPL label content enriched with knowledge sources used with SPL (NDF-RT/MeSH). Both methods were applied to a large set of drug-intolerance (allergy) records, drug orders, and medication dispensing records covering >50,000 patients over 30 years. The number of drug-intolerance issues detected by both methods was counted, as well as the number of patients with issues, number of distinct drugs, and number of distinct intolerances. The difference between drug-intolerance issues detected or missed by either method was qualitatively analyzed. Although <70% of terms were mapped to SPL, the new approach detected four times as many drug-intolerance issues on twice as many patients. The SPL-based approach is more sensitive and suggests that mapping local dictionaries to SPL, and enhancing the depth and breadth of coverage of SPL content are worth accelerating. The study also highlights specificity problems known to trouble drug-intolerance decision support and suggests how terminology and methods of recording drug intolerances could be improved.

Bioanalytical procedures for monitoring in utero drug exposure

PubMed Central

Gray, Teresa

2009-01-01

Drug use by pregnant women has been extensively associated with adverse mental, physical, and psychological outcomes in their exposed children. This manuscript reviews bioanalytical methods for in utero drug exposure monitoring for common drugs of abuse in urine, hair, oral fluid, blood, sweat, meconium, amniotic fluid, umbilical cord tissue, nails, and vernix caseosa; neonatal matrices are particularly emphasized. Advantages and limitations of testing different maternal and neonatal biological specimens including ease and invasiveness of collection, and detection time frames, sensitivities, and specificities are described, and specific references for available analytical methods included. Future research involves identifying metabolites unique to fetal drug metabolism to improve detection rates of in utero drug exposure and determining relationships between the amount, frequency, and timing of drug exposure and drug concentrations in infant biological fluids and tissues. Accurate bioanalytical procedures are vital to defining the scope of and resolving this important public health problem. PMID:17370066

Transport Test Problems for Hybrid Methods Development

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

Shaver, Mark W.; Miller, Erin A.; Wittman, Richard S.

2011-12-28

This report presents 9 test problems to guide testing and development of hybrid calculations for the ADVANTG code at ORNL. These test cases can be used for comparing different types of radiation transport calculations, as well as for guiding the development of variance reduction methods. Cases are drawn primarily from existing or previous calculations with a preference for cases which include experimental data, or otherwise have results with a high level of confidence, are non-sensitive, and represent problem sets of interest to NA-22.

The Effectiveness of Using the Model Method to Solve Word Problems

ERIC Educational Resources Information Center

Bao, Lei

2016-01-01

The aim of this study is to investigate whether the model method is effective to assist primary students to solve word problems. The model method not only provides students with an opportunity to interpret the problem by drawing the rectangular bar but also helps students to visually represent problem situations and relevant relationships on the…

Drug Solubility: Importance and Enhancement Techniques

PubMed Central

Savjani, Ketan T.; Gajjar, Anuradha K.; Savjani, Jignasa K.

2012-01-01

Solubility, the phenomenon of dissolution of solute in solvent to give a homogenous system, is one of the important parameters to achieve desired concentration of drug in systemic circulation for desired (anticipated) pharmacological response. Low aqueous solubility is the major problem encountered with formulation development of new chemical entities as well as for the generic development. More than 40% NCEs (new chemical entities) developed in pharmaceutical industry are practically insoluble in water. Solubility is a major challenge for formulation scientist. Any drug to be absorbed must be present in the form of solution at the site of absorption. Various techniques are used for the enhancement of the solubility of poorly soluble drugs which include physical and chemical modifications of drug and other methods like particle size reduction, crystal engineering, salt formation, solid dispersion, use of surfactant, complexation, and so forth. Selection of solubility improving method depends on drug property, site of absorption, and required dosage form characteristics. PMID:22830056

Microfabrication for Drug Delivery

PubMed Central

Koch, Brendan; Rubino, Ilaria; Quan, Fu-Shi; Yoo, Bongyoung; Choi, Hyo-Jick

2016-01-01

This review is devoted to discussing the application of microfabrication technologies to target challenges encountered in life processes by the development of drug delivery systems. Recently, microfabrication has been largely applied to solve health and pharmaceutical science issues. In particular, fabrication methods along with compatible materials have been successfully designed to produce multifunctional, highly effective drug delivery systems. Microfabrication offers unique tools that can tackle problems in this field, such as ease of mass production with high quality control and low cost, complexity of architecture design and a broad range of materials. Presented is an overview of silicon- and polymer-based fabrication methods that are key in the production of microfabricated drug delivery systems. Moreover, the efforts focused on studying the biocompatibility of materials used in microfabrication are analyzed. Finally, this review discusses representative ways microfabrication has been employed to develop systems delivering drugs through the transdermal and oral route, and to improve drug eluting implants. Additionally, microfabricated vaccine delivery systems are presented due to the great impact they can have in obtaining a cold chain-free vaccine, with long-term stability. Microfabrication will continue to offer new, alternative solutions for the development of smart, advanced drug delivery systems. PMID:28773770

Online and Mobile Interventions for Problem Gambling, Alcohol, and Drugs: A Systematic Review.

PubMed

Giroux, Isabelle; Goulet, Annie; Mercier, Jonathan; Jacques, Christian; Bouchard, Stéphane

2017-01-01

Online interventions for gambling, alcohol, and illegal drug related problems have been developing at a fast pace over the past decade. Yet, little is known about the content and efficacy of interventions provided entirely online for reducing drug/alcohol use and gambling, or about the characteristics of those who use these interventions. This systematic review aims to describe the characteristics of online interventions, their efficacy, and the profile of their clientele. Documentation was mainly obtained through four scientific databases in psychology, technology, and medical research (PsychINFO, MedLine, Francis, and INSPEC) using three keywords (substances or gambling, intervention, Internet). Of the 4,708 documents initially identified, 18 studies meeting admissibility criteria were retained and analyzed after exclusion of duplicates and non-relevant documents. No study in the review related to problem gambling. The majority of interventions were based upon motivational or cognitive-behavioral theoretical approaches and called upon well-established therapeutic components in the field of addictions. The participants in these studies were generally adults between 30 and 46 years old with a high school education and presenting a high risk or problematic use. More than three quarters of the studies showed a short-term decrease in use that was maintained 6 months later, but only two studies included a 12 months follow-up. Online interventions seem promising and appear to meet the needs of participants who are in the workforce and seeking help for the first time. Long-term efficacy studies should nonetheless be conducted.

Agreement between PRE2DUP register data modeling method and comprehensive drug use interview among older persons

PubMed Central

Taipale, Heidi; Tanskanen, Antti; Koponen, Marjaana; Tolppanen, Anna-Maija; Tiihonen, Jari; Hartikainen, Sirpa

2016-01-01

Background PRE2DUP is a modeling method that generates drug use periods (ie, when drug use started and ended) from drug purchases recorded in dispensing-based register data. It is based on the evaluation of personal drug purchasing patterns and considers hospital stays, possible stockpiling of drugs, and package information. Objective The objective of this study was to investigate person-level agreement between self-reported drug use in the interview and drug use modeled from dispensing data with PRE2DUP method for various drug classes used by older persons. Methods Self-reported drug use was assessed from the GeMS Study including a random sample of persons aged ≥75 years from the city of Kuopio, Finland, in 2006. Drug purchases recorded in the Prescription register data of these persons were modeled to determine drug use periods with PRE2DUP modeling method. Agreement between self-reported drug use on the interview date and drug use calculated from register-based data was compared in order to find the frequently used drugs and drug classes, which was evaluated by Cohen’s kappa. Kappa values 0.61–0.80 were considered to represent good and 0.81–1.00 as very good agreement. Results Among 569 participants with mean age of 82 years, the agreement between interview and register data was very good for 75% and very good or good for 93% of the studied drugs or drug classes. Good or very good agreement was observed for drugs that are typically used on regular bases, whereas “as needed” drugs represented poorer results. Conclusion PRE2DUP modeling method validly describes regular drug use among older persons. For most of drug classes investigated, PRE2DUP-modeled register data described drug use as well as interview-based data which are more time-consuming to collect. Further studies should be conducted by comparing it with other methods and in different drug user populations. PMID:27785101

Applications of Genetic Methods to NASA Design and Operations Problems

NASA Technical Reports Server (NTRS)

Laird, Philip D.

1996-01-01

We review four recent NASA-funded applications in which evolutionary/genetic methods are important. In the process we survey: the kinds of problems being solved today with these methods; techniques and tools used; problems encountered; and areas where research is needed. The presentation slides are annotated briefly at the top of each page.

The association between parent early adult drug use disorder and later observed parenting practices and child behavior problems: testing alternate models.

PubMed

Bailey, Jennifer A; Hill, Karl G; Guttmannova, Katarina; Oesterle, Sabrina; Hawkins, J David; Catalano, Richard F; McMahon, Robert J

2013-05-01

This study tested the association between parent illicit drug use disorder (DUD) in early adulthood and observed parenting practices at ages 27-28 and examined the following 3 theoretically derived models explaining this link: (a) a disrupted parent adult functioning model,(b) a preexisting parent personality factor model, and (c) a disrupted adolescent family process model. Associations between study variables and child externalizing problems also were examined. Longitudinal data linking 2 generations were drawn from the Seattle Social Development Project (SSDP) and The SSDP Intergenerational Project (TIP), and included 167 parents and their 2- to 8-year-old child. Path modeling revealed that parent DUD in early adulthood predicted later observed low-skilled parenting, which was related to child externalizing problems. The preexisting parent personality factor model was supported. Parent negative emotionality accounted for the association between parent early adult DUD and later parenting practices. Parent negative emotionality also was related directly to child externalizing behavior. Limited support for the disrupted transition to adulthood model was found. The disrupted adolescent family process model was not supported. Results suggest that problem drug use that occurs early in adulthood may affect later parenting skills, independent of subsequent parent drug use. Findings highlight the importance of parent negative emotionality in influencing his or her own problem behavior, interactions with his or her child, and his or her child's problem behavior. Prevention and treatment programs targeting young adult substance use, poor parenting practices, and child behavior problems should address parent personality factors that may contribute to these behaviors.

The Association between Parent Early Adult Drug Use Disorder and Later Observed Parenting Practices and Child Behavior Problems: Testing Alternate Models

PubMed Central

Bailey, Jennifer A.; Hill, Karl G.; Guttmannova, Katarina; Oesterle, Sabrina; Hawkins, J. David; Catalano, Richard F.; McMahon, Robert J.

2012-01-01

This study tested the association between parent illicit drug use disorder (DUD) in early adulthood and observed parenting practices at ages 27 – 28 and examined the following three, theoretically-derived models explaining this link: a) a disrupted parent adult functioning model, b) a pre-existing parent personality factor model, c) a disrupted adolescent family process model. Associations between study variables and child externalizing problems also were examined. Longitudinal data linking two generations were drawn from the Seattle Social Development Project (SSDP) and The SSDP Intergenerational Project (TIP), and included 167 parents and their 2- to 8-year-old child. Path modeling revealed that parent DUD in early adulthood predicted later observed low-skilled parenting, which was related to child externalizing problems. The pre-existing parent personality factor model was supported. Parent negative emotionality accounted for the association between parent early adult DUD and later parenting practices. Parent negative emotionality also was related directly to child externalizing behavior. Limited support for the disrupted transition to adulthood model was found. The disrupted adolescent family process model was not supported. Results suggest that problem drug use that occurs early in adulthood may affect later parenting skills, independent of subsequent parent drug use. Findings highlight the importance of parent negative emotionality in influencing their own problem behavior, their interactions with their child, and their child’s problem behavior. Prevention and treatment programs targeting young adult substance use, poor parenting practices, and child behavior problems should address parent personality factors that may contribute to these behaviors. PMID:22799581

Abuse of prescription drugs.

PubMed Central

Wilford, B B

1990-01-01

An estimated 3% of the United States population deliberately misuse or abuse psychoactive medications, with severe consequences. According to the National Institute on Drug Abuse, more than half of patients who sought treatment or died of drug-related medical problems in 1989 were abusing prescription drugs. Physicians who contribute to this problem have been described by the American Medical Association as dishonest--willfully misprescribing for purposes of abuse, usually for profit; disabled by personal problems with drugs or alcohol; dated in their knowledge of current pharmacology or therapeutics; or deceived by various patient-initiated fraudulent approaches. Even physicians who do not meet any of these descriptions must guard against contributing to prescription drug abuse through injudicious prescribing, inadequate safeguarding of prescription forms or drug supplies, or acquiescing to the demands or ruses used to obtain drugs for other than medical purposes. PMID:2349801

Sensitivity analysis and approximation methods for general eigenvalue problems

NASA Technical Reports Server (NTRS)

Murthy, D. V.; Haftka, R. T.

1986-01-01

Optimization of dynamic systems involving complex non-hermitian matrices is often computationally expensive. Major contributors to the computational expense are the sensitivity analysis and reanalysis of a modified design. The present work seeks to alleviate this computational burden by identifying efficient sensitivity analysis and approximate reanalysis methods. For the algebraic eigenvalue problem involving non-hermitian matrices, algorithms for sensitivity analysis and approximate reanalysis are classified, compared and evaluated for efficiency and accuracy. Proper eigenvector normalization is discussed. An improved method for calculating derivatives of eigenvectors is proposed based on a more rational normalization condition and taking advantage of matrix sparsity. Important numerical aspects of this method are also discussed. To alleviate the problem of reanalysis, various approximation methods for eigenvalues are proposed and evaluated. Linear and quadratic approximations are based directly on the Taylor series. Several approximation methods are developed based on the generalized Rayleigh quotient for the eigenvalue problem. Approximation methods based on trace theorem give high accuracy without needing any derivatives. Operation counts for the computation of the approximations are given. General recommendations are made for the selection of appropriate approximation technique as a function of the matrix size, number of design variables, number of eigenvalues of interest and the number of design points at which approximation is sought.

A side-effect free method for identifying cancer drug targets.

PubMed

Ashraf, Md Izhar; Ong, Seng-Kai; Mujawar, Shama; Pawar, Shrikant; More, Pallavi; Paul, Somnath; Lahiri, Chandrajit

2018-04-27

Identifying effective drug targets, with little or no side effects, remains an ever challenging task. A potential pitfall of failing to uncover the correct drug targets, due to side effect of pleiotropic genes, might lead the potential drugs to be illicit and withdrawn. Simplifying disease complexity, for the investigation of the mechanistic aspects and identification of effective drug targets, have been done through several approaches of protein interactome analysis. Of these, centrality measures have always gained importance in identifying candidate drug targets. Here, we put forward an integrated method of analysing a complex network of cancer and depict the importance of k-core, functional connectivity and centrality (KFC) for identifying effective drug targets. Essentially, we have extracted the proteins involved in the pathways leading to cancer from the pathway databases which enlist real experimental datasets. The interactions between these proteins were mapped to build an interactome. Integrative analyses of the interactome enabled us to unearth plausible reasons for drugs being rendered withdrawn, thereby giving future scope to pharmaceutical industries to potentially avoid them (e.g. ESR1, HDAC2, F2, PLG, PPARA, RXRA, etc). Based upon our KFC criteria, we have shortlisted ten proteins (GRB2, FYN, PIK3R1, CBL, JAK2, LCK, LYN, SYK, JAK1 and SOCS3) as effective candidates for drug development.

Study Drugs

MedlinePlus

... to quit, they may have withdrawal symptoms like depression, thoughts of suicide, intense drug cravings, sleep problems, and fatigue. The health risks aren't the only downside to study drugs. Students caught with illegal prescription drugs may get suspended ...

Machine learning plus optical flow: a simple and sensitive method to detect cardioactive drugs

NASA Astrophysics Data System (ADS)

Lee, Eugene K.; Kurokawa, Yosuke K.; Tu, Robin; George, Steven C.; Khine, Michelle

2015-07-01

Current preclinical screening methods do not adequately detect cardiotoxicity. Using human induced pluripotent stem cell-derived cardiomyocytes (iPS-CMs), more physiologically relevant preclinical or patient-specific screening to detect potential cardiotoxic effects of drug candidates may be possible. However, one of the persistent challenges for developing a high-throughput drug screening platform using iPS-CMs is the need to develop a simple and reliable method to measure key electrophysiological and contractile parameters. To address this need, we have developed a platform that combines machine learning paired with brightfield optical flow as a simple and robust tool that can automate the detection of cardiomyocyte drug effects. Using three cardioactive drugs of different mechanisms, including those with primarily electrophysiological effects, we demonstrate the general applicability of this screening method to detect subtle changes in cardiomyocyte contraction. Requiring only brightfield images of cardiomyocyte contractions, we detect changes in cardiomyocyte contraction comparable to - and even superior to - fluorescence readouts. This automated method serves as a widely applicable screening tool to characterize the effects of drugs on cardiomyocyte function.

Meshless method for solving fixed boundary problem of plasma equilibrium

NASA Astrophysics Data System (ADS)

Imazawa, Ryota; Kawano, Yasunori; Itami, Kiyoshi

2015-07-01

This study solves the Grad-Shafranov equation with a fixed plasma boundary by utilizing a meshless method for the first time. Previous studies have utilized a finite element method (FEM) to solve an equilibrium inside the fixed separatrix. In order to avoid difficulties of FEM (such as mesh problem, difficulty of coding, expensive calculation cost), this study focuses on the meshless methods, especially RBF-MFS and KANSA's method to solve the fixed boundary problem. The results showed that CPU time of the meshless methods was ten to one hundred times shorter than that of FEM to obtain the same accuracy.

Solid dispersions, part I: recent evolutions and future opportunities in manufacturing methods for dissolution rate enhancement of poorly water-soluble drugs.

PubMed

Bikiaris, Dimitrios N

2011-11-01

In recent years, the number of active pharmaceutical ingredients with high therapeutic impact, but very low water solubility, has increased significantly. Thus, a great challenge for pharmaceutical technology is to create new formulations and efficient drug-delivery systems to overcome these dissolution problems. Drug formulation in solid dispersions (SDs) is one of the most commonly used techniques for the dissolution rate enhancement of poorly water-soluble drugs. Generally, SDs can be defined as a dispersion of active ingredients in molecular, amorphous and/or microcrystalline forms into an inert carrier. This review covers literature which states that the dissolution enhancement of SDs is based on the fact that drugs in the nanoscale range, or in amorphous phase, dissolve faster and to a greater extent than micronized drug particles. This is in accordance to the Noyes-Whitney equation, while the wetting properties of the used polymer may also play an important role. The main factors why SD-based pharmaceutical products on the market are steadily increasing over the last few years are: the recent progress in various methods used for the preparation of SDs, the effect of evolved interactions in physical state of the drug and formulation stability during storage, the characterization of the physical state of the drug and the mechanism of dissolution rate enhancement.

Medicinal Chemistry Projects Requiring Imaginative Structure-Based Drug Design Methods.

PubMed

Moitessier, Nicolas; Pottel, Joshua; Therrien, Eric; Englebienne, Pablo; Liu, Zhaomin; Tomberg, Anna; Corbeil, Christopher R

2016-09-20

Computational methods for docking small molecules to proteins are prominent in drug discovery. There are hundreds, if not thousands, of documented examples-and several pertinent cases within our research program. Fifteen years ago, our first docking-guided drug design project yielded nanomolar metalloproteinase inhibitors and illustrated the potential of structure-based drug design. Subsequent applications of docking programs to the design of integrin antagonists, BACE-1 inhibitors, and aminoglycosides binding to bacterial RNA demonstrated that available docking programs needed significant improvement. At that time, docking programs primarily considered flexible ligands and rigid proteins. We demonstrated that accounting for protein flexibility, employing displaceable water molecules, and using ligand-based pharmacophores improved the docking accuracy of existing methods-enabling the design of bioactive molecules. The success prompted the development of our own program, Fitted, implementing all of these aspects. The primary motivation has always been to respond to the needs of drug design studies; the majority of the concepts behind the evolution of Fitted are rooted in medicinal chemistry projects and collaborations. Several examples follow: (1) Searching for HDAC inhibitors led us to develop methods considering drug-zinc coordination and its effect on the pKa of surrounding residues. (2) Targeting covalent prolyl oligopeptidase (POP) inhibitors prompted an update to Fitted to identify reactive groups and form bonds with a given residue (e.g., a catalytic residue) when the geometry allows it. Fitted-the first fully automated covalent docking program-was successfully applied to the discovery of four new classes of covalent POP inhibitors. As a result, efficient stereoselective syntheses of a few screening hits were prioritized rather than synthesizing large chemical libraries-yielding nanomolar inhibitors. (3) In order to study the metabolism of POP inhibitors by

Numerical methods on some structured matrix algebra problems

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

Jessup, E.R.

1996-06-01

This proposal concerned the design, analysis, and implementation of serial and parallel algorithms for certain structured matrix algebra problems. It emphasized large order problems and so focused on methods that can be implemented efficiently on distributed-memory MIMD multiprocessors. Such machines supply the computing power and extensive memory demanded by the large order problems. We proposed to examine three classes of matrix algebra problems: the symmetric and nonsymmetric eigenvalue problems (especially the tridiagonal cases) and the solution of linear systems with specially structured coefficient matrices. As all of these are of practical interest, a major goal of this work was tomore » translate our research in linear algebra into useful tools for use by the computational scientists interested in these and related applications. Thus, in addition to software specific to the linear algebra problems, we proposed to produce a programming paradigm and library to aid in the design and implementation of programs for distributed-memory MIMD computers. We now report on our progress on each of the problems and on the programming tools.« less

Problems of Mathematical Finance by Stochastic Control Methods

NASA Astrophysics Data System (ADS)

Stettner, Łukasz

The purpose of this paper is to present main ideas of mathematics of finance using the stochastic control methods. There is an interplay between stochastic control and mathematics of finance. On the one hand stochastic control is a powerful tool to study financial problems. On the other hand financial applications have stimulated development in several research subareas of stochastic control in the last two decades. We start with pricing of financial derivatives and modeling of asset prices, studying the conditions for the absence of arbitrage. Then we consider pricing of defaultable contingent claims. Investments in bonds lead us to the term structure modeling problems. Special attention is devoted to historical static portfolio analysis called Markowitz theory. We also briefly sketch dynamic portfolio problems using viscosity solutions to Hamilton-Jacobi-Bellman equation, martingale-convex analysis method or stochastic maximum principle together with backward stochastic differential equation. Finally, long time portfolio analysis for both risk neutral and risk sensitive functionals is introduced.

Predicting drug-target interaction for new drugs using enhanced similarity measures and super-target clustering.

PubMed

Shi, Jian-Yu; Yiu, Siu-Ming; Li, Yiming; Leung, Henry C M; Chin, Francis Y L

2015-07-15

Predicting drug-target interaction using computational approaches is an important step in drug discovery and repositioning. To predict whether there will be an interaction between a drug and a target, most existing methods identify similar drugs and targets in the database. The prediction is then made based on the known interactions of these drugs and targets. This idea is promising. However, there are two shortcomings that have not yet been addressed appropriately. Firstly, most of the methods only use 2D chemical structures and protein sequences to measure the similarity of drugs and targets respectively. However, this information may not fully capture the characteristics determining whether a drug will interact with a target. Secondly, there are very few known interactions, i.e. many interactions are "missing" in the database. Existing approaches are biased towards known interactions and have no good solutions to handle possibly missing interactions which affect the accuracy of the prediction. In this paper, we enhance the similarity measures to include non-structural (and non-sequence-based) information and introduce the concept of a "super-target" to handle the problem of possibly missing interactions. Based on evaluations on real data, we show that our similarity measure is better than the existing measures and our approach is able to achieve higher accuracy than the two best existing algorithms, WNN-GIP and KBMF2K. Our approach is available at http://web.hku.hk/∼liym1018/projects/drug/drug.html or http://www.bmlnwpu.org/us/tools/PredictingDTI_S2/METHODS.html. Copyright © 2015 Elsevier Inc. All rights reserved.

Solving multi-objective optimization problems in conservation with the reference point method

PubMed Central

Dujardin, Yann; Chadès, Iadine

2018-01-01

Managing the biodiversity extinction crisis requires wise decision-making processes able to account for the limited resources available. In most decision problems in conservation biology, several conflicting objectives have to be taken into account. Most methods used in conservation either provide suboptimal solutions or use strong assumptions about the decision-maker’s preferences. Our paper reviews some of the existing approaches to solve multi-objective decision problems and presents new multi-objective linear programming formulations of two multi-objective optimization problems in conservation, allowing the use of a reference point approach. Reference point approaches solve multi-objective optimization problems by interactively representing the preferences of the decision-maker with a point in the criteria (objectives) space, called the reference point. We modelled and solved the following two problems in conservation: a dynamic multi-species management problem under uncertainty and a spatial allocation resource management problem. Results show that the reference point method outperforms classic methods while illustrating the use of an interactive methodology for solving combinatorial problems with multiple objectives. The method is general and can be adapted to a wide range of ecological combinatorial problems. PMID:29293650

Factors associated with serum retinol, x-tocopherol, carotenoids, and selenium in Hispanics with problems of HIV, chornis hepatitis, chronic hepatitis C, and drug use

USDA-ARS?s Scientific Manuscript database

The effects of hepatitis and drug use on nutritional problems in HIV infection have rarely been examined despite the importance of drug use in the global HIV pandemic. We examined the effects of HIV, hepatitis C, and drug use on serum micronutrients in 300 US Hispanic adults. Chronic hepatitis C inf...

Design of Drug Delivery Methods for the Brain and Central Nervous System

NASA Astrophysics Data System (ADS)

Lueshen, Eric

-enhanced drug delivery (CED) is a technique used to bypass the BBB via direct intracranial injection using a catheter driven by a positive pressure gradient from an infusion pump. Although CED boasts the advantage of achieving larger drug distribution volumes compared to diffusion driven methods, difficulty in predicting drug spread and preventing backflow along the catheter shaft commonly occur. In this dissertation, a method for predicting drug distributions in the brain using diffusion tensor imaging (DTI) data is employed to show how small variations in catheter placement can lead to drastically different volumes of drug distribution in vivo. The impact that microfluid flow has on deformable brain phantom gel is studied in order to elucidate the causes of backflow, and the results are used to develop backflow-free catheters with safe volumetric flow rates up to 10 ?l/min. Through implementation of our backflow-free catheter designs, physicians will be able to target specific regions of the brain with improved accuracy, increased drug concentration, and larger drug distribution geometries. Intrathecal (IT) drug delivery involves direct drug infusion into the spinal canal and has become standard practice for treating many CNS diseases. Although IT drug delivery boasts the advantage of reduced systemic toxicity compared to oral and intravenous techniques, current IT delivery protocols lack a means of sufficient drug targeting at specific locations of interest within the CNS. In this dissertation, the method of intrathecal magnetic drug targeting (IT-MDT) is developed to overcome the limited targeting capabilities of standard IT drug delivery protocols. The basic idea behind IT-MDT is to guide intrathecally-injected, drug-functionalized magnetic nanoparticles (MNPs) using an external magnetic field to diseased regions within the spinal canal. Cerebrospinal fluid (CSF) transport phenomena are studied, and in vitro human spine surrogates are built. Experiments are run on the in

An Iterative Method for Problems with Multiscale Conductivity

PubMed Central

Kim, Hyea Hyun; Minhas, Atul S.; Woo, Eung Je

2012-01-01

A model with its conductivity varying highly across a very thin layer will be considered. It is related to a stable phantom model, which is invented to generate a certain apparent conductivity inside a region surrounded by a thin cylinder with holes. The thin cylinder is an insulator and both inside and outside the thin cylinderare filled with the same saline. The injected current can enter only through the holes adopted to the thin cylinder. The model has a high contrast of conductivity discontinuity across the thin cylinder and the thickness of the layer and the size of holes are very small compared to the domain of the model problem. Numerical methods for such a model require a very fine mesh near the thin layer to resolve the conductivity discontinuity. In this work, an efficient numerical method for such a model problem is proposed by employing a uniform mesh, which need not resolve the conductivity discontinuity. The discrete problem is then solved by an iterative method, where the solution is improved by solving a simple discrete problem with a uniform conductivity. At each iteration, the right-hand side is updated by integrating the previous iterate over the thin cylinder. This process results in a certain smoothing effect on microscopic structures and our discrete model can provide a more practical tool for simulating the apparent conductivity. The convergence of the iterative method is analyzed regarding the contrast in the conductivity and the relative thickness of the layer. In numerical experiments, solutions of our method are compared to reference solutions obtained from COMSOL, where very fine meshes are used to resolve the conductivity discontinuity in the model. Errors of the voltage in L2 norm follow O(h) asymptotically and the current density matches quitewell those from the reference solution for a sufficiently small mesh size h. The experimental results present a promising feature of our approach for simulating the apparent conductivity related

A computational method for drug repositioning using publicly available gene expression data.

PubMed

Shabana, K M; Abdul Nazeer, K A; Pradhan, Meeta; Palakal, Mathew

2015-01-01

The identification of new therapeutic uses of existing drugs, or drug repositioning, offers the possibility of faster drug development, reduced risk, lesser cost and shorter paths to approval. The advent of high throughput microarray technology has enabled comprehensive monitoring of transcriptional response associated with various disease states and drug treatments. This data can be used to characterize disease and drug effects and thereby give a measure of the association between a given drug and a disease. Several computational methods have been proposed in the literature that make use of publicly available transcriptional data to reposition drugs against diseases. In this work, we carry out a data mining process using publicly available gene expression data sets associated with a few diseases and drugs, to identify the existing drugs that can be used to treat genes causing lung cancer and breast cancer. Three strong candidates for repurposing have been identified- Letrozole and GDC-0941 against lung cancer, and Ribavirin against breast cancer. Letrozole and GDC-0941 are drugs currently used in breast cancer treatment and Ribavirin is used in the treatment of Hepatitis C.

Estimating Community Drug Abuse by Wastewater Analysis

PubMed Central

Zuccato, Ettore; Chiabrando, Chiara; Castiglioni, Sara; Bagnati, Renzo; Fanelli, Roberto

2008-01-01

Background The social and medical problems of drug abuse are a matter of increasing global concern. To tackle drug abuse in changing scenarios, international drug agencies need fresh methods to monitor trends and patterns of illicit drug consumption. Objective We tested a sewage epidemiology approach, using levels of excreted drug residues in wastewater, to monitor collective use of the major drugs of abuse in near real time. Methods Selected drug target residues derived from use of cocaine, opiates, cannabis, and amphetamines were measured by mass spectrometry in wastewater collected at major sewage treatment plants in Milan (Italy), Lugano (Switzerland), and London (United Kingdom). The amounts of drug residues conveyed to the treatment plants, reflecting the amounts collectively excreted with urine, were used to estimate consumption of the active parent drugs. Results Reproducible and characteristic profiles of illicit drug use were obtained in the three cities, thus for the first time quickly revealing changes in local consumption (e.g., cocaine consumption rose significantly on weekends in Milan). Profiles of local drug consumption based on waste-water measurements are in line with national annual prevalence estimates. Conclusions Patterns and trends of drug abuse in local communities can be promptly monitored by this tool, a convenient new complement to more complex, lengthy survey methods. In principle, searching the sewage for excreted compounds relevant to public health issues appears to have the potential to become a convenient source of real-time epidemiologic information. PMID:18709161

Alternating method applied to edge and surface crack problems

NASA Technical Reports Server (NTRS)

Hartranft, R. J.; Sih, G. C.

1972-01-01

The Schwarz-Neumann alternating method is employed to obtain stress intensity solutions to two crack problems of practical importance: a semi-infinite elastic plate containing an edge crack which is subjected to concentrated normal and tangential forces, and an elastic half space containing a semicircular surface crack which is subjected to uniform opening pressure. The solution to the semicircular surface crack is seen to be a significant improvement over existing approximate solutions. Application of the alternating method to other crack problems of current interest is briefly discussed.

Application of the boundary integral method to immiscible displacement problems

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

Masukawa, J.; Horne, R.N.

1988-08-01

This paper presents an application of the boundary integral method (BIM) to fluid displacement problems to demonstrate its usefulness in reservoir simulation. A method for solving two-dimensional (2D), piston-like displacement for incompressible fluids with good accuracy has been developed. Several typical example problems with repeated five-spot patterns were solved for various mobility ratios. The solutions were compared with the analytical solutions to demonstrate accuracy. Singularity programming was found to be a major advantage in handling flow in the vicinity of wells. The BIM was found to be an excellent way to solve immiscible displacement problems. Unlike analytic methods, it canmore » accommodate complex boundary shapes and does not suffer from numerical dispersion at the front.« less

Determine equilibrium dissociation constant of drug-membrane receptor affinity using the cell membrane chromatography relative standard method.

PubMed

Ma, Weina; Yang, Liu; Lv, Yanni; Fu, Jia; Zhang, Yanmin; He, Langchong

2017-06-23

The equilibrium dissociation constant (K D ) of drug-membrane receptor affinity is the basic parameter that reflects the strength of interaction. The cell membrane chromatography (CMC) method is an effective technique to study the characteristics of drug-membrane receptor affinity. In this study, the K D value of CMC relative standard method for the determination of drug-membrane receptor affinity was established to analyze the relative K D values of drugs binding to the membrane receptors (Epidermal growth factor receptor and angiotensin II receptor). The K D values obtained by the CMC relative standard method had a strong correlation with those obtained by the frontal analysis method. Additionally, the K D values obtained by CMC relative standard method correlated with pharmacological activity of the drug being evaluated. The CMC relative standard method is a convenient and effective method to evaluate drug-membrane receptor affinity. Copyright © 2017 Elsevier B.V. All rights reserved.

Structured Product Labeling Improves Detection of Drug-intolerance Issues

PubMed Central

Schadow, Gunther

2009-01-01

Objectives This study sought to assess the value of the Health Level 7/U.S. Food and Drug Administration Structured Product Labeling (SPL) drug knowledge representation standard and its associated terminology sources for drug-intolerance (allergy) decision support in computerized provider order entry (CPOE) systems. Design The Regenstrief Institute CPOE drug-intolerance issue detection system and its knowledge base was compared with a method based on existing SPL label content enriched with knowledge sources used with SPL (NDF-RT/MeSH). Both methods were applied to a large set of drug-intolerance (allergy) records, drug orders, and medication dispensing records covering >50,000 patients over 30 years. Measurements The number of drug-intolerance issues detected by both methods was counted, as well as the number of patients with issues, number of distinct drugs, and number of distinct intolerances. The difference between drug-intolerance issues detected or missed by either method was qualitatively analyzed. Results Although <70% of terms were mapped to SPL, the new approach detected four times as many drug-intolerance issues on twice as many patients. Conclusion The SPL-based approach is more sensitive and suggests that mapping local dictionaries to SPL, and enhancing the depth and breadth of coverage of SPL content are worth accelerating. The study also highlights specificity problems known to trouble drug-intolerance decision support and suggests how terminology and methods of recording drug intolerances could be improved. PMID:18952933

New drugs and methods of doping and manipulation.

PubMed

Thevis, Mario; Kohler, Maxie; Schänzer, Wilhelm

2008-01-01

The issue of doping in sport is multifaceted. New drugs not only with anabolic properties such as selective androgen receptor modulators, synthetic insulins, blood doping with erythropoietins or homologous and autologous blood transfusions but also with sample manipulation have necessitated sensitive, comprehensive and specific detection assays allowing for the identification of cheats. New methods based on mass spectrometry, flow cytometry and immunological techniques have been introduced and improved in the past years to support and enhance the antidoping fight. Although numerous approaches are successful and promising, these methods still have some shortcomings.

Online and Mobile Interventions for Problem Gambling, Alcohol, and Drugs: A Systematic Review

PubMed Central

Giroux, Isabelle; Goulet, Annie; Mercier, Jonathan; Jacques, Christian; Bouchard, Stéphane

2017-01-01

Online interventions for gambling, alcohol, and illegal drug related problems have been developing at a fast pace over the past decade. Yet, little is known about the content and efficacy of interventions provided entirely online for reducing drug/alcohol use and gambling, or about the characteristics of those who use these interventions. This systematic review aims to describe the characteristics of online interventions, their efficacy, and the profile of their clientele. Documentation was mainly obtained through four scientific databases in psychology, technology, and medical research (PsychINFO, MedLine, Francis, and INSPEC) using three keywords (substances or gambling, intervention, Internet). Of the 4,708 documents initially identified, 18 studies meeting admissibility criteria were retained and analyzed after exclusion of duplicates and non-relevant documents. No study in the review related to problem gambling. The majority of interventions were based upon motivational or cognitive-behavioral theoretical approaches and called upon well-established therapeutic components in the field of addictions. The participants in these studies were generally adults between 30 and 46 years old with a high school education and presenting a high risk or problematic use. More than three quarters of the studies showed a short-term decrease in use that was maintained 6 months later, but only two studies included a 12 months follow-up. Online interventions seem promising and appear to meet the needs of participants who are in the workforce and seeking help for the first time. Long-term efficacy studies should nonetheless be conducted. PMID:28649211

Computational inverse methods of heat source in fatigue damage problems

NASA Astrophysics Data System (ADS)

Chen, Aizhou; Li, Yuan; Yan, Bo

2018-04-01

Fatigue dissipation energy is the research focus in field of fatigue damage at present. It is a new idea to solve the problem of calculating fatigue dissipation energy by introducing inverse method of heat source into parameter identification of fatigue dissipation energy model. This paper introduces the research advances on computational inverse method of heat source and regularization technique to solve inverse problem, as well as the existing heat source solution method in fatigue process, prospects inverse method of heat source applying in fatigue damage field, lays the foundation for further improving the effectiveness of fatigue dissipation energy rapid prediction.

The dimension split element-free Galerkin method for three-dimensional potential problems

NASA Astrophysics Data System (ADS)

Meng, Z. J.; Cheng, H.; Ma, L. D.; Cheng, Y. M.

2018-06-01

This paper presents the dimension split element-free Galerkin (DSEFG) method for three-dimensional potential problems, and the corresponding formulae are obtained. The main idea of the DSEFG method is that a three-dimensional potential problem can be transformed into a series of two-dimensional problems. For these two-dimensional problems, the improved moving least-squares (IMLS) approximation is applied to construct the shape function, which uses an orthogonal function system with a weight function as the basis functions. The Galerkin weak form is applied to obtain a discretized system equation, and the penalty method is employed to impose the essential boundary condition. The finite difference method is selected in the splitting direction. For the purposes of demonstration, some selected numerical examples are solved using the DSEFG method. The convergence study and error analysis of the DSEFG method are presented. The numerical examples show that the DSEFG method has greater computational precision and computational efficiency than the IEFG method.

Detection of medication-related problems in hospital practice: a review

PubMed Central

Manias, Elizabeth

2013-01-01

This review examines the effectiveness of detection methods in terms of their ability to identify and accurately determine medication-related problems in hospitals. A search was conducted of databases from inception to June 2012. The following keywords were used in combination: medication error or adverse drug event or adverse drug reaction, comparison, detection, hospital and method. Seven detection methods were considered: chart review, claims data review, computer monitoring, direct care observation, interviews, prospective data collection and incident reporting. Forty relevant studies were located. Detection methods that were better able to identify medication-related problems compared with other methods tested in the same study included chart review, computer monitoring, direct care observation and prospective data collection. However, only small numbers of studies were involved in comparisons with direct care observation (n = 5) and prospective data collection (n = 6). There was little focus on detecting medication-related problems during various stages of the medication process, and comparisons associated with the seriousness of medication-related problems were examined in 19 studies. Only 17 studies involved appropriate comparisons with a gold standard, which provided details about sensitivities and specificities. In view of the relatively low identification of medication-related problems with incident reporting, use of this method in tracking trends over time should be met with some scepticism. Greater attention should be placed on combining methods, such as chart review and computer monitoring in examining trends. More research is needed on the use of claims data, direct care observation, interviews and prospective data collection as detection methods. PMID:23194349

Model reduction method using variable-separation for stochastic saddle point problems

NASA Astrophysics Data System (ADS)

Jiang, Lijian; Li, Qiuqi

2018-02-01

In this paper, we consider a variable-separation (VS) method to solve the stochastic saddle point (SSP) problems. The VS method is applied to obtain the solution in tensor product structure for stochastic partial differential equations (SPDEs) in a mixed formulation. The aim of such a technique is to construct a reduced basis approximation of the solution of the SSP problems. The VS method attempts to get a low rank separated representation of the solution for SSP in a systematic enrichment manner. No iteration is performed at each enrichment step. In order to satisfy the inf-sup condition in the mixed formulation, we enrich the separated terms for the primal system variable at each enrichment step. For the SSP problems by regularization or penalty, we propose a more efficient variable-separation (VS) method, i.e., the variable-separation by penalty method. This can avoid further enrichment of the separated terms in the original mixed formulation. The computation of the variable-separation method decomposes into offline phase and online phase. Sparse low rank tensor approximation method is used to significantly improve the online computation efficiency when the number of separated terms is large. For the applications of SSP problems, we present three numerical examples to illustrate the performance of the proposed methods.

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

PubMed

Wang, Nianyang; Xie, Xin

2018-02-22

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

Prevention des Toxicomanies Aupres des Filles avec des Problemes de Comportement: Effets a Court Terme (Prevention of Drug Addiction in Girls with Behavior Problems: Short-Term Effects).

ERIC Educational Resources Information Center

Vitaro, Frank; And Others

1992-01-01

This article, written in French, describes and evaluates the first phase of a program to prevent drug addiction among 110 fifth-grade girls with behavior problems in Montreal (Quebec, Canada). Evaluation of the instructional program showed positive results for student knowledge level, attitudes, and behaviors and supported program continuation…

Impact of drug reconciliation at discharge and communication between hospital and community pharmacists on drug-related problems: study protocol for a randomized controlled trial.

PubMed

Pourrat, Xavier; Roux, Clarisse; Bouzige, Brigitte; Garnier, Valérie; Develay, Armelle; Allenet, Benoit; Fraysse, Martial; Halimi, Jean-Michel; Grassin, Jacqueline; Giraudeau, Bruno

2014-06-30

Patients are at risk of drug-related problems (DRPs) at transition points during hospitalization. The community pharmacist (CP) is often the first healthcare professional patients visit after discharge. CPs lack sufficient information about the patient and so they may be unable to identify problems in medications, which may lead to dispensing the wrong drugs or dosage, and/or giving wrong information. We aim to assess the impact of a complex intervention comprising of medication reconciliation performed at discharge by a hospital pharmacist (HP) with communication between the HP and CP on DRPs during the seven days following discharge. The study is a cluster randomized crossover trial involving 46 care units (each unit corresponding to a cluster) in 22 French hospitals during two consecutive 14-day periods, randomly assigned as 'experimental' or 'control' (usual care) periods. We will recruit patients older than 18 years of age and visiting the same CP for at least three months. We will exclude patients with a hospital length of stay of more than 21 days, who do not return home or those in palliative care. During the experimental period, the HP will perform a medications reconciliation that will be communicated to the patient. The HP will inform the patient's CP about the patient's drug therapy (modification in home medication, acute drugs prescribed, nonprescription treatments, and/or lab results). The primary outcome will be a composite outcome of any kind of drug misuse during the seven days following discharge assessed at day seven (±2) post-discharge by a pharmacist in charge of the study who will contact both patients and CPs by phone. The secondary outcome will be unplanned hospitalizations assessed by phone contact at day 35 (±5) after discharge. We plan to recruit 1,176 patients. This study will assess the impact of a reconciliation of medications performed at patient discharge followed by communication between the HP and the patient's CP. It will allow

The Needs of Pregnant and Parenting American Indian Women at Risk for Problem Alcohol or Drug Use.

ERIC Educational Resources Information Center

Zahnd, Elaine; Klein, Dorie

1997-01-01

A survey of 171 American Indian women in California who were pregnant or parenting and were considered at risk for problem substance abuse covered demographic information; personal and family history; alcohol, tobacco, and drug use; HIV risk; and a needs assessment regarding health care, economic needs, and parenting and children's needs. (LP)

A Meshless Method Using Radial Basis Functions for Beam Bending Problems

NASA Technical Reports Server (NTRS)

Raju, I. S.; Phillips, D. R.; Krishnamurthy, T.

2004-01-01

A meshless local Petrov-Galerkin (MLPG) method that uses radial basis functions (RBFs) as trial functions in the study of Euler-Bernoulli beam problems is presented. RBFs, rather than generalized moving least squares (GMLS) interpolations, are used to develop the trial functions. This choice yields a computationally simpler method as fewer matrix inversions and multiplications are required than when GMLS interpolations are used. Test functions are chosen as simple weight functions as they are in the conventional MLPG method. Compactly and noncompactly supported RBFs are considered. Noncompactly supported cubic RBFs are found to be preferable. Patch tests, mixed boundary value problems, and problems with complex loading conditions are considered. Results obtained from the radial basis MLPG method are either of comparable or better accuracy than those obtained when using the conventional MLPG method.

Method for loading lipid like vesicles with drugs of other chemicals

DOEpatents

Mehlhorn, R.J.

1998-06-09

A method for accumulating drugs or other chemicals within synthetic, lipid-like vesicles by means of a pH gradient imposed on the vesicles just prior to use is described. The method is suited for accumulating molecules with basic or acid moieties which are permeable to the vesicles membranes in their uncharged form and for molecules that contain charge moieties that are hydrophobic ions and can therefore cross the vesicle membranes in their charged form. The method is advantageous over prior art methods for encapsulating biologically active materials within vesicles in that is achieves very high degrees of loading with simple procedures that are economical and require little technical expertise, furthermore kits which can be stored for prolonged periods prior to use without impairment of the capacity to achieve drug accumulation are described. A related application of the method consists of using this technology to detoxify animals that have been exposed to poisons with basic, weak acid or hydrophobic charge groups within their molecular structures. 2 figs.

Method for loading lipid like vesicles with drugs of other chemicals

DOEpatents

Mehlhorn, Rolf Joachim

1998-01-01

A method for accumulating drugs or other chemicals within synthetic, lipid-like vesicles by means of a pH gradient imposed on the vesicles just prior to use is described. The method is suited for accumulating molecules with basic or acid moieties which are permeable to the vesicles membranes in their uncharged form and for molecules that contain charge moieties that are hydrophobic ions and can therefore cross the vesicle membranes in their charged form. The method is advantageous over prior art methods for encapsulating biologically active materials within vesicles in that is achieves very high degrees of loading with simple procedures that are economical and require little technical expertise, furthermore kits which can be stored for prolonged periods prior to use without impairment of the capacity to achieve drug accumulation are described. A related application of the method consists of using this technology to detoxify animals that have been exposed to poisons with basic, weak acid or hydrophobic charge groups within their molecular structures.

Drug abuse first aid

MedlinePlus

... use of these drugs is a form of drug abuse. Medicines that are for treating a health problem ... about local resources. Alternative Names Overdose from drugs; Drug abuse first aid References Myck MB. Hallucinogens and drugs ...

Don't Flush! Why Your Drug Disposal Method Matters ...

EPA Pesticide Factsheets

April 30th is the U.S. Drug Enforcement Administration’s National Drug Take-Back Day. All over the country there will be facilities accepting any unwanted or expired medications from 10:00 AM – 2:00 PM – it is the perfect opportunity to clean out your medicine cabinet while simultaneously helping to protect aquatic animals and their environment from chemical exposure!Have you ever participated in a drug take-back program? If not, what do you typically do with leftover medications after you defeat a bacterial infection or find an old bottle of Tylenol? Many people may flush unwanted or expired pharmaceuticals down the toilet or throw them in the trash, but those methods can actually harm our environment.When flushed or thrown-out, these drugs end up in our coastal ecosystems; and all the chemicals in those little pills that were once working together to make us feel better, are now dissolving in our waterways where they can negatively impact aquatic animals.Scientists throughout EPA continue to evaluate the potential toxicity of different drugs in order to determine what specific effects they have on aquatic wildlife, and to develop new ways to detect if an organism has been exposed to those drugs.I recently spoke with Bushra Khan (NRC post-doc) and Theresa Johnson (ORISE fellow) of the EPA’s Atlantic Ecology Division to learn about some of the specific effects they have observed in their research. Bushra talked to me about the effects beta blockers, m

Simplified computational methods for elastic and elastic-plastic fracture problems

NASA Technical Reports Server (NTRS)

Atluri, Satya N.

1992-01-01

An overview is given of some of the recent (1984-1991) developments in computational/analytical methods in the mechanics of fractures. Topics covered include analytical solutions for elliptical or circular cracks embedded in isotropic or transversely isotropic solids, with crack faces being subjected to arbitrary tractions; finite element or boundary element alternating methods for two or three dimensional crack problems; a 'direct stiffness' method for stiffened panels with flexible fasteners and with multiple cracks; multiple site damage near a row of fastener holes; an analysis of cracks with bonded repair patches; methods for the generation of weight functions for two and three dimensional crack problems; and domain-integral methods for elastic-plastic or inelastic crack mechanics.

Reliable Multi Method Assessment of Metacognition Use in Chemistry Problem Solving

ERIC Educational Resources Information Center

Cooper, Melanie M.; Sandi-Urena, Santiago; Stevens, Ron

2008-01-01

Metacognition is fundamental in achieving understanding of chemistry and developing of problem solving skills. This paper describes an across-method-and-time instrument designed to assess the use of metacognition in chemistry problem solving. This multi method instrument combines a self report, namely the Metacognitive Activities Inventory…

Multigrid one shot methods for optimal control problems: Infinite dimensional control

NASA Technical Reports Server (NTRS)

Arian, Eyal; Taasan, Shlomo

1994-01-01

The multigrid one shot method for optimal control problems, governed by elliptic systems, is introduced for the infinite dimensional control space. ln this case, the control variable is a function whose discrete representation involves_an increasing number of variables with grid refinement. The minimization algorithm uses Lagrange multipliers to calculate sensitivity gradients. A preconditioned gradient descent algorithm is accelerated by a set of coarse grids. It optimizes for different scales in the representation of the control variable on different discretization levels. An analysis which reduces the problem to the boundary is introduced. It is used to approximate the two level asymptotic convergence rate, to determine the amplitude of the minimization steps, and the choice of a high pass filter to be used when necessary. The effectiveness of the method is demonstrated on a series of test problems. The new method enables the solutions of optimal control problems at the same cost of solving the corresponding analysis problems just a few times.

Boundary Approximation Methods for Sloving Elliptic Problems on Unbounded Domains

NASA Astrophysics Data System (ADS)

Li, Zi-Cai; Mathon, Rudolf

1990-08-01

Boundary approximation methods with partial solutions are presented for solving a complicated problem on an unbounded domain, with both a crack singularity and a corner singularity. Also an analysis of partial solutions near the singular points is provided. These methods are easy to apply, have good stability properties, and lead to highly accurate solutions. Hence, boundary approximation methods with partial solutions are recommended for the treatment of elliptic problems on unbounded domains provided that piecewise solution expansions, in particular, asymptotic solutions near the singularities and infinity, can be found.

Drug policy, intravenous drug use, and heroin addiction in the UK.

PubMed

Geraghty, Jemell

In order to fully understand and appreciate today's drug problem in the UK, the foundations of drug legislation and the history of drug evolution require exploration. This paper critically examines the history of drug policy and the growth of heroin addiction from the perspective of a novice researcher who works closely with intravenous drug users in relation to leg ulceration and wound care in the acute setting. Today's drug policy has come a long way in understanding the problems of heroin addiction and establishing services to meet intravenous drug users' needs and the needs of society. This paper highlights the early warning signs of drug addiction and growth within the UK from an early stage with key areas such as who the early users were and how addiction grew so rapidly between 1920 and 1960. Current policy and decision makers as well as clinicians and researchers in this field must understand the impacts of past policy and embed it within their decisions surrounding drug policy today.

An Optimization-Based Method for Feature Ranking in Nonlinear Regression Problems.

PubMed

Bravi, Luca; Piccialli, Veronica; Sciandrone, Marco

2017-04-01

In this paper, we consider the feature ranking problem, where, given a set of training instances, the task is to associate a score with the features in order to assess their relevance. Feature ranking is a very important tool for decision support systems, and may be used as an auxiliary step of feature selection to reduce the high dimensionality of real-world data. We focus on regression problems by assuming that the process underlying the generated data can be approximated by a continuous function (for instance, a feedforward neural network). We formally state the notion of relevance of a feature by introducing a minimum zero-norm inversion problem of a neural network, which is a nonsmooth, constrained optimization problem. We employ a concave approximation of the zero-norm function, and we define a smooth, global optimization problem to be solved in order to assess the relevance of the features. We present the new feature ranking method based on the solution of instances of the global optimization problem depending on the available training data. Computational experiments on both artificial and real data sets are performed, and point out that the proposed feature ranking method is a valid alternative to existing methods in terms of effectiveness. The obtained results also show that the method is costly in terms of CPU time, and this may be a limitation in the solution of large-dimensional problems.

Conceptual carpentry as problem handling: the case of drugs and coercive treatment in social democratic welfare regimes.

PubMed

Edman, Johan; Stenius, Kerstin

2014-03-01

The drug and alcohol fields are characterised by continuous contestations of key concepts and the competing uses of concepts by various actors, in different geographies and over time. This study investigates the political processes leading to legislation enabling coercive treatment of (non-psychotic) drug users in Finland and Sweden from the 1950s until the early 1980s. The drug treatment policies are analysed through conceptual changes and innovations. The article analyses conceptual discussions in public reports in Finland and Sweden, focusing on the work preceding the first legislations where both alcohol and drug treatment were included (in Finland 1961, in Sweden 1982). Theories from conceptual history are applied. The Finnish and Swedish discussions carry arguments from two periods of the Nordic welfare state: in an early development stage and a fragile situation in Finland, and in a more mature and affluent time in Sweden. The paternalistic arguments vary over time and between countries. Still, in both countries and time periods, the view of the drug problem as a youth issue, as particularly enslaving and on society's obligation to protect drug using individuals from damaging their future give enough motivation for coercive treatment. The conceptual work included avoidance of certain terms but in other cases, a broadening of their meaning, to adopt them to the political goals. Close analyses of conceptual history can reveal new features of drug policy struggles and show how central concepts in drugs and alcohol field are continuously contested. Copyright © 2013 Elsevier B.V. All rights reserved.

A choice-based screening method for compulsive drug users in rats.

PubMed

Lenoir, Magalie; Augier, Eric; Vouillac, Caroline; Ahmed, Serge H

2013-07-01

We describe a protocol for screening compulsive drug users among cocaine self-administering rats, the most frequently used animal model in addiction research. Rats are first trained on several alternating days to self-administer either cocaine (i.v.) or saccharin-sweetened water (by mouth)--a potent, albeit nonessential, nondrug reward. Then rats are allowed to choose between the two rewards over several days until the preference stabilizes. Most rats choose to stop using cocaine and pursue the alternative reward. Only a minority of Wistar strain rats (generally 15%) persist in taking the drug, regardless of the severity of past cocaine use and even when made hungry and offered the possibility to relieve their physiological need. Persistence of cocaine use in the face of a high-stakes choice is a core defining feature of compulsion. This choice-based screening method for compulsive drug users is easy to implement, has several important applications, and compares well with other methods in the field. 2013 by John Wiley & Sons, Inc.

Development and validation of a liquid chromatography-tandem mass spectrometry analytical method for the therapeutic drug monitoring of eight novel anticancer drugs.

PubMed

Herbrink, M; de Vries, N; Rosing, H; Huitema, A D R; Nuijen, B; Schellens, J H M; Beijnen, J H

2018-04-01

To support therapeutic drug monitoring of patients with cancer, a fast and accurate method for simultaneous quantification of the registered anticancer drugs afatinib, axitinib, ceritinib, crizotinib, dabrafenib, enzalutamide, regorafenib and trametinib in human plasma using liquid chromatography tandem mass spectrometry was developed and validated. Human plasma samples were collected from treated patients and stored at -20°C. Analytes and internal standards (stable isotopically labeled analytes) were extracted with acetonitrile. An equal amount of 10 mm NH 4 CO 3 was added to the supernatant to yield the final extract. A 2 μL aliquot of this extract was injected onto a C 18 -column, gradient elution was applied and triple-quadrupole mass spectrometry in positive-ion mode was used for detection. All results were within the acceptance criteria of the latest US Food and Drug Administration guidance and European Medicines Agency guidelines on method validation, except for the carry-over of ceritinib and crizotinib. These were corrected for by the injection order of samples. Additional stability tests were carried out for axitinib and dabrafenib in relation to their reported photostability. In conclusion, the described method to simultaneously quantify the eight selected anticancer drugs in human plasma was successfully validated and applied for therapeutic drug monitoring in cancer patients treated with these drugs. Copyright © 2017 John Wiley & Sons, Ltd.

In Silico Prediction of Chemical Toxicity for Drug Design Using Machine Learning Methods and Structural Alerts

PubMed Central

Yang, Hongbin; Sun, Lixia; Li, Weihua; Liu, Guixia; Tang, Yun

2018-01-01

During drug development, safety is always the most important issue, including a variety of toxicities and adverse drug effects, which should be evaluated in preclinical and clinical trial phases. This review article at first simply introduced the computational methods used in prediction of chemical toxicity for drug design, including machine learning methods and structural alerts. Machine learning methods have been widely applied in qualitative classification and quantitative regression studies, while structural alerts can be regarded as a complementary tool for lead optimization. The emphasis of this article was put on the recent progress of predictive models built for various toxicities. Available databases and web servers were also provided. Though the methods and models are very helpful for drug design, there are still some challenges and limitations to be improved for drug safety assessment in the future. PMID:29515993

In Silico Prediction of Chemical Toxicity for Drug Design Using Machine Learning Methods and Structural Alerts

NASA Astrophysics Data System (ADS)

Yang, Hongbin; Sun, Lixia; Li, Weihua; Liu, Guixia; Tang, Yun

2018-02-01

For a drug, safety is always the most important issue, including a variety of toxicities and adverse drug effects, which should be evaluated in preclinical and clinical trial phases. This review article at first simply introduced the computational methods used in prediction of chemical toxicity for drug design, including machine learning methods and structural alerts. Machine learning methods have been widely applied in qualitative classification and quantitative regression studies, while structural alerts can be regarded as a complementary tool for lead optimization. The emphasis of this article was put on the recent progress of predictive models built for various toxicities. Available databases and web servers were also provided. Though the methods and models are very helpful for drug design, there are still some challenges and limitations to be improved for drug safety assessment in the future.

Escuelas sin Drogas. Como Actuar. Edicion 1992. (Schools without Drugs. What Works. 1992 Edition).

ERIC Educational Resources Information Center

Department of Education, Washington, DC.

Across the United States, schools and communities have found ways to turn the tide in the battle against drugs. This guidebook describes the methods they have used and the actions they have taken. The first section, "Children and Drugs" outlines the nature and extent of the drug problem and summarizes the latest research on the effects of drugs on…

Nitsche’s Method For Helmholtz Problems with Embedded Interfaces

PubMed Central

Zou, Zilong; Aquino, Wilkins; Harari, Isaac

2016-01-01

SUMMARY In this work, we use Nitsche’s formulation to weakly enforce kinematic constraints at an embedded interface in Helmholtz problems. Allowing embedded interfaces in a mesh provides significant ease for discretization, especially when material interfaces have complex geometries. We provide analytical results that establish the well-posedness of Helmholtz variational problems and convergence of the corresponding finite element discretizations when Nitsche’s method is used to enforce kinematic constraints. As in the analysis of conventional Helmholtz problems, we show that the inf-sup constant remains positive provided that the Nitsche’s stabilization parameter is judiciously chosen. We then apply our formulation to several 2D plane-wave examples that confirm our analytical findings. Doing so, we demonstrate the asymptotic convergence of the proposed method and show that numerical results are in accordance with the theoretical analysis. PMID:28713177

New Method to Prepare Mitomycin C Loaded PLA-Nanoparticles with High Drug Entrapment Efficiency

NASA Astrophysics Data System (ADS)

Hou, Zhenqing; Wei, Heng; Wang, Qian; Sun, Qian; Zhou, Chunxiao; Zhan, Chuanming; Tang, Xiaolong; Zhang, Qiqing

2009-07-01

The classical utilized double emulsion solvent diffusion technique for encapsulating water soluble Mitomycin C (MMC) in PLA nanoparticles suffers from low encapsulation efficiency because of the drug rapid partitioning to the external aqueous phase. In this paper, MMC loaded PLA nanoparticles were prepared by a new single emulsion solvent evaporation method, in which soybean phosphatidylcholine (SPC) was employed to improve the liposolubility of MMC by formation of MMC-SPC complex. Four main influential factors based on the results of a single-factor test, namely, PLA molecular weight, ratio of PLA to SPC (wt/wt) and MMC to SPC (wt/wt), volume ratio of oil phase to water phase, were evaluated using an orthogonal design with respect to drug entrapment efficiency. The drug release study was performed in pH 7.2 PBS at 37 °C with drug analysis using UV/vis spectrometer at 365 nm. MMC-PLA particles prepared by classical method were used as comparison. The formulated MMC-SPC-PLA nanoparticles under optimized condition are found to be relatively uniform in size (594 nm) with up to 94.8% of drug entrapment efficiency compared to 6.44 μm of PLA-MMC microparticles with 34.5% of drug entrapment efficiency. The release of MMC shows biphasic with an initial burst effect, followed by a cumulated drug release over 30 days is 50.17% for PLA-MMC-SPC nanoparticles, and 74.1% for PLA-MMC particles. The IR analysis of MMC-SPC complex shows that their high liposolubility may be attributed to some weak physical interaction between MMC and SPC during the formation of the complex. It is concluded that the new method is advantageous in terms of smaller size, lower size distribution, higher encapsulation yield, and longer sustained drug release in comparison to classical method.

Engendering drug problems: Materialising gender in the DUDIT and other screening and diagnostic 'apparatuses'.

PubMed

Dwyer, Robyn; Fraser, Suzanne

2017-06-01

It is widely accepted that alcohol and other drug consumption is profoundly gendered. Just where this gendering is occurring, however, remains the subject of debate. We contend that one important and overlooked site where the gendering of substance consumption and addiction is taking place is through AOD research itself: in particular, through the addiction screening and diagnostic tools designed to measure and track substance consumption and problems within populations. These tools establish key criteria and set numerical threshold scores for the identification of problems. In many of these tools, separate threshold scores for women and men are established or recommended. Drawing on Karen Barad's concept of post-humanist performativity, in this article we examine the ways in which gender itself is being materialised by these apparatuses of measurement. We focus primarily on the Drug Use Disorders Identification Test (DUDIT) tool as an exemplar of gendering processes that operate across addiction tools more broadly. We consider gendering processes operating through tools questions themselves and we also examine the quantification and legitimation processes used in establishing gender difference and the implications these have for women. We find tools rely on and reproduce narrow and marginalising assumptions about women as essentially fragile and vulnerable and simultaneously reinforce normative expectations that women sacrifice pleasure. The seemingly objective and neutral quantification processes operating in tools naturalise gender as they enact it. Copyright © 2017 Elsevier B.V. All rights reserved.

Substructure method in high-speed monorail dynamic problems

NASA Astrophysics Data System (ADS)

Ivanchenko, I. I.

2008-12-01

The study of actions of high-speed moving loads on bridges and elevated tracks remains a topical problem for transport. In the present study, we propose a new method for moving load analysis of elevated tracks (monorail structures or bridges), which permits studying the interaction between two strained objects consisting of rod systems and rigid bodies with viscoelastic links; one of these objects is the moving load (monorail rolling stock), and the other is the carrying structure (monorail elevated track or bridge). The methods for moving load analysis of structures were developed in numerous papers [1-15]. At the first stage, when solving the problem about a beam under the action of the simplest moving load such as a moving weight, two fundamental methods can be used; the same methods are realized for other structures and loads. The first method is based on the use of a generalized coordinate in the expansion of the deflection in the natural shapes of the beam, and the problem is reduced to solving a system of ordinary differential equations with variable coefficients [1-3]. In the second method, after the "beam-weight" system is decomposed, just as in the problem with the weight impact on the beam [4], solving the problem is reduced to solving an integral equation for the dynamic weight reaction [6, 7]. In [1-3], an increase in the number of retained forms leads to an increase in the order of the system of equations; in [6, 7], difficulties arise when solving the integral equations related to the conditional stability of the step procedures. The method proposed in [9, 14] for beams and rod systems combines the above approaches and eliminates their drawbacks, because it permits retaining any necessary number of shapes in the deflection expansion and has a resolving system of equations with an unconditionally stable integration scheme and with a minimum number of unknowns, just as in the method of integral equations [6, 7]. This method is further developed for

A prediction model of drug-induced ototoxicity developed by an optimal support vector machine (SVM) method.

PubMed

Zhou, Shu; Li, Guo-Bo; Huang, Lu-Yi; Xie, Huan-Zhang; Zhao, Ying-Lan; Chen, Yu-Zong; Li, Lin-Li; Yang, Sheng-Yong

2014-08-01

Drug-induced ototoxicity, as a toxic side effect, is an important issue needed to be considered in drug discovery. Nevertheless, current experimental methods used to evaluate drug-induced ototoxicity are often time-consuming and expensive, indicating that they are not suitable for a large-scale evaluation of drug-induced ototoxicity in the early stage of drug discovery. We thus, in this investigation, established an effective computational prediction model of drug-induced ototoxicity using an optimal support vector machine (SVM) method, GA-CG-SVM. Three GA-CG-SVM models were developed based on three training sets containing agents bearing different risk levels of drug-induced ototoxicity. For comparison, models based on naïve Bayesian (NB) and recursive partitioning (RP) methods were also used on the same training sets. Among all the prediction models, the GA-CG-SVM model II showed the best performance, which offered prediction accuracies of 85.33% and 83.05% for two independent test sets, respectively. Overall, the good performance of the GA-CG-SVM model II indicates that it could be used for the prediction of drug-induced ototoxicity in the early stage of drug discovery. Copyright © 2014 Elsevier Ltd. All rights reserved.

Spectral methods and their implementation to solution of aerodynamic and fluid mechanic problems

NASA Technical Reports Server (NTRS)

Streett, C. L.

1987-01-01

Fundamental concepts underlying spectral collocation methods, especially pertaining to their use in the solution of partial differential equations, are outlined. Theoretical accuracy results are reviewed and compared with results from test problems. A number of practical aspects of the construction and use of spectral methods are detailed, along with several solution schemes which have found utility in applications of spectral methods to practical problems. Results from a few of the successful applications of spectral methods to problems of aerodynamic and fluid mechanic interest are then outlined, followed by a discussion of the problem areas in spectral methods and the current research under way to overcome these difficulties.

[Irrational use of drugs as a source of drug - induced diseases].

PubMed

Woroń, Jarosław; Porebski, Grzegorz; Kostka-Trabka, Elzbieta; Goszcz, Aleksandra

2007-01-01

The irrational use of medication, by which we understand the administration of drugs for indications where their effectiveness has not been confirmed, the disregard of restrictions and warnings against their use, and the use of drug combinations which do not increase the therapeutic effect but to the contrary increase the risk of adverse drug reactions, is a serious problem encountered in paediatric pharmacotherapy. Each year the centres for monitoring of adverse drug reactions receive many reports, the analysis of which show that the reasons of occurrence of adverse drug reactions after drug administration, are specifically due to irrational use of medications. In order to prevent in an active way the occurrence, of adverse drug reactions following drug administration it is worthwhile to bring to attention the reasons for their occurrence which not infrequently bring about pathological effects. Our work which is based on reports received by the Regional Centre for Adverse Drug Reactions Monitoring in Krakow concerning the occurrence of adverse drug reactions in an attempt to bring to attention in our view important problems in current pharmacotherapy.

In Vivo Methods for the Assessment of Topical Drug Bioavailability

PubMed Central

Herkenne, Christophe; Alberti, Ingo; Naik, Aarti; Kalia, Yogeshvar N.; Mathy, François-Xavier; Préat, Véronique

2007-01-01

This paper reviews some current methods for the in vivo assessment of local cutaneous bioavailability in humans after topical drug application. After an introduction discussing the importance of local drug bioavailability assessment and the limitations of model-based predictions, the focus turns to the relevance of experimental studies. The available techniques are then reviewed in detail, with particular emphasis on the tape stripping and microdialysis methodologies. Other less developed techniques, including the skin biopsy, suction blister, follicle removal and confocal Raman spectroscopy techniques are also described. PMID:17985216

A comparison of several methods of solving nonlinear regression groundwater flow problems

USGS Publications Warehouse

Cooley, Richard L.

1985-01-01

Computational efficiency and computer memory requirements for four methods of minimizing functions were compared for four test nonlinear-regression steady state groundwater flow problems. The fastest methods were the Marquardt and quasi-linearization methods, which required almost identical computer times and numbers of iterations; the next fastest was the quasi-Newton method, and last was the Fletcher-Reeves method, which did not converge in 100 iterations for two of the problems. The fastest method per iteration was the Fletcher-Reeves method, and this was followed closely by the quasi-Newton method. The Marquardt and quasi-linearization methods were slower. For all four methods the speed per iteration was directly related to the number of parameters in the model. However, this effect was much more pronounced for the Marquardt and quasi-linearization methods than for the other two. Hence the quasi-Newton (and perhaps Fletcher-Reeves) method might be more efficient than either the Marquardt or quasi-linearization methods if the number of parameters in a particular model were large, although this remains to be proven. The Marquardt method required somewhat less central memory than the quasi-linearization metilod for three of the four problems. For all four problems the quasi-Newton method required roughly two thirds to three quarters of the memory required by the Marquardt method, and the Fletcher-Reeves method required slightly less memory than the quasi-Newton method. Memory requirements were not excessive for any of the four methods.

In Vitro-In Vivo Extrapolation of Metabolism- and Transporter-Mediated Drug-Drug Interactions-Overview of Basic Prediction Methods.

PubMed

Yoshida, Kenta; Zhao, Ping; Zhang, Lei; Abernethy, Darrell R; Rekić, Dinko; Reynolds, Kellie S; Galetin, Aleksandra; Huang, Shiew-Mei

2017-09-01

Evaluation of drug-drug interaction (DDI) risk is vital to establish benefit-risk profiles of investigational new drugs during drug development. In vitro experiments are routinely conducted as an important first step to assess metabolism- and transporter-mediated DDI potential of investigational new drugs. Results from these experiments are interpreted, often with the aid of in vitro-in vivo extrapolation methods, to determine whether and how DDI should be evaluated clinically to provide the basis for proper DDI management strategies, including dosing recommendations, alternative therapies, or contraindications under various DDI scenarios and in different patient population. This article provides an overview of currently available in vitro experimental systems and basic in vitro-in vivo extrapolation methodologies for metabolism- and transporter-mediated DDIs. Published by Elsevier Inc.

Estimating time-varying drug adherence using electronic records: extending the proportion of days covered (PDC) method.

PubMed

Bijlsma, Maarten J; Janssen, Fanny; Hak, Eelko

2016-03-01

Accurate measurement of drug adherence is essential for valid risk-benefit assessments of pharmacologic interventions. To date, measures of drug adherence have almost exclusively been applied for a fixed-time interval and without considering changes over time. However, patients with irregular dosing behaviour commonly have a different prognosis than patients with stable dosing behaviour. We propose a method, based on the proportion of days covered (PDC) method, to measure time-varying drug adherence and drug dosage using electronic records. We compare a time-fixed PDC method with the time-varying PDC method through detailed examples and through summary statistics of 100 randomly selected patients on statin therapy. We demonstrate that time-varying PDC method better distinguishes an irregularly dosing patient from a stably dosing patient and demonstrate how the time-fixed method can result in a biassed estimate of drug adherence. Furthermore, the time-varying PDC method may be better used to reduce certain types of confounding and misclassification of exposure. The time-varying PDC method may improve longitudinal and time-to-event studies that associate adherence with a clinical outcome or (intervention) studies that seek to describe changes in adherence over time. Copyright © 2015 John Wiley & Sons, Ltd.

Examining Information Problem-Solving, Knowledge, and Application Gains within Two Instructional Methods: Problem-Based and Computer-Mediated Participatory Simulation

ERIC Educational Resources Information Center

Newell, Terrance S.

2008-01-01

This study compared the effectiveness of two instructional methods--problem-based instruction within a face-to-face context and computer-mediated participatory simulation--in increasing students' content knowledge and application gains in the area of information problem-solving. The instructional methods were implemented over a four-week period. A…

Similarities and Differences between Individuals Seeking Treatment for Gambling Problems vs. Alcohol and Substance Use Problems in Relation to the Progressive Model of Self-stigma

PubMed Central

Gavriel-Fried, Belle; Rabayov, Tal

2017-01-01

Aims: People with gambling as well as substance use problems who are exposed to public stigmatization may internalize and apply it to themselves through a mechanism known as self-stigma. This study implemented the Progressive Model for Self-Stigma which consists four sequential interrelated stages: awareness, agreement, application and harm on three groups of individuals with gambling, alcohol and other substance use problems. It explored whether the two guiding assumptions of this model (each stage is precondition for the following stage which are trickle-down in nature, and correlations between proximal stages should be larger than correlations between more distant stages) would differentiate people with gambling problems from those with alcohol and other substance use problems in terms of their patterns of self-stigma and in terms of the stages in the model. Method: 37 individuals with gambling problems, 60 with alcohol problems and 51 with drug problems who applied for treatment in rehabilitation centers in Israel in 2015–2016 were recruited. They completed the Self-stigma of Mental Illness Scale-Short Form which was adapted by changing the term “mental health” to gambling, alcohol or drugs, and the DSM-5-diagnostic criteria for gambling, alcohol or drug disorder. Results: The assumptions of the model were broadly confirmed: a repeated measures ANCOVA revealed that in all three groups there was a difference between first two stages (aware and agree) and the latter stages (apply and harm). In addition, the gambling group differed from the drug use and alcohol groups on the awareness stage: individuals with gambling problems were less likely to be aware of stigma than people with substance use or alcohol problems. Conclusion: The internalization of stigma among individuals with gambling problems tends to work in a similar way as for those with alcohol or drug problems. The differences between the gambling group and the alcohol and other substance groups at

Discontinuous Galerkin Finite Element Method for Parabolic Problems

NASA Technical Reports Server (NTRS)

Kaneko, Hideaki; Bey, Kim S.; Hou, Gene J. W.

2004-01-01

In this paper, we develop a time and its corresponding spatial discretization scheme, based upon the assumption of a certain weak singularity of parallel ut(t) parallel Lz(omega) = parallel ut parallel2, for the discontinuous Galerkin finite element method for one-dimensional parabolic problems. Optimal convergence rates in both time and spatial variables are obtained. A discussion of automatic time-step control method is also included.

Overview of Drug Delivery Methods in Exotics, Including Their Anatomic and Physiologic Considerations.

PubMed

Coutant, Thomas; Vergneau-Grosset, Claire; Langlois, Isabelle

2018-05-01

Drug delivery to exotic animals may be extrapolated from domestic animals, but some physiologic and anatomic differences complicate treatment administration. Knowing these differences enables one to choose optimal routes for drug delivery. This review provides practitioners with a detailed review of the currently reported methods used for drug delivery of various medications in the most common exotic animal species. Exotic animal peculiarities that are relevant for drug administration are discussed in the text and outlined in tables and boxes to help the reader easily find targeted information. Copyright © 2018 Elsevier Inc. All rights reserved.

An Automatic Orthonormalization Method for Solving Stiff Boundary-Value Problems

NASA Astrophysics Data System (ADS)