The Motivation,Skills, and Decision-Making Model of “Drug Abuse” Prevention

This article summarizes the theoretical basis for targeted prevention programs as they apply to different high-risk groups. We explain the advantages and disadvantages of different definitions of risk and discuss strategies for preventing drug use related problems in high-risk youth. Productive prevention programs for many at-risk groups share similar components, including those that address motivation, skills, and decision making. We present key aspects of these three components and link them to theories in clinical psychology, social psychology, sociology, and chemical dependence treatment. Among a total of 29 promising targeted prevention programs, we describe examples of empirically evaluated, intensive interventions that have made a positive impact on the attitudes and behavior of multiple problem youth. Incorporating the perspectives of multiple disciplines appears essential for progress in drug abuse and other problem behavior prevention.     

EXPANSION of diabetes education in a United States–Mexico border community (Expanding Services for Patients to Acquire New Skills,Set Goals,and Improve Overall Knowledge)

Objectives

To describe the process used by a pharmacy team at a community health center to coordinate and expand diabetes education services (English and Spanish) for a predominantly Hispanic, Spanish-speaking population.

Methadone Maintenance Patients’ Knowledge,Attitudes, Beliefs,and Experiences Concerning Treatment for Hepatitis C Virus Infection

Hepatitis C virus (HCV) knowledge, attitudes, beliefs, and experiences (KABE) of 64 HCV antibody positive methadone maintenance treatment (MMT) patients were assessed in conjunction with acceptability of an on-site semi-structured HCV education session, HCV RNA diagnostic testing, HCV treatment motivational assessment, and initiation of HCV treatment. The KABE interviews were conducted in 2006 and 2007 in an urban New York State MMT clinic in affiliation with a NIDA-funded HCV research project. The majority had basic knowledge of HCV disease, but poor understanding of HCV testing and treatment. While the majority of participants expressed fear of HCV treatment side effects, 88%% accepted HCV RNA testing and 78%% expressed willingness to start HCV treatment with the majority of chronically infected choosing to start HCV treatment medications. Study limitations and implications are discussed.     

Methylene blue and vasoplegia: who, when, and how?

Systemic inflammatory response can be associated with clinically significant and, at times, refractory hypotension. Despite the lack of uniform definitions, this condition is frequently called vasoplegia or vasoplegic syndrome (VS), and is thought to be due to dysregulation of endothelial homeostasis and subsequent endothelial dysfunction secondary to direct and indirect effects of multiple inflammatory mediators. Vasoplegia has been observed in all age groups and in various clinical settings, such as anaphylaxis (including protamine reaction), sepsis, hemorrhagic shock, hemodialysis, and cardiac surgery. Among mechanisms thought to be contributory to VS, the nitric oxide (NO)/cyclic guanosine monophosphate (cGMP) pathway appears to play a prominent role. In search of effective treatment for vasoplegia, methylene blue (MB), an inhibitor of nitric oxide synthase (NOS) and guanylate cyclase (GC), has been found to improve the refractory hypotension associated with endothelial dysfunction of VS. There is evidence that MB may indeed be effective in improving systemic hemodynamics in the setting of vasoplegia, with reportedly few side effects. This review describes the current state of clinical and experimental knowledge relating to MB use in the setting of VS, highlighting the potential risks and benefits of therapeutic MB administration in refractory hypotensive states.     

Outcomes,performance, and quality-What's the difference?

Calls for greater accountability within the addiction treatment field have led to a wide range of efforts designed to improve treatment performance, quality, and outcomes. However, efforts with conceptually and methodologically different approaches have used the same umbrella terms such as “quality,” “performance indicators,” and “outcome domains,” causing substantial confusion among providers and policymakers. This article provides operational definitions of the terms used in discussing quality, performance, and outcomes, as well as a discussion of ways to integrate efforts to measure treatment system performance and quality during treatment with patient outcomes during and following treatment. This article thus helps build a common understanding about how these efforts to bring greater accountability can be combined and integrated to improve the attractiveness and effectiveness of addiction treatments.     

NSAIDs, corticosteroids and atrial fibrillation?

Evidence that a number of drugs can cause atrial fibrillation has been accumulating since the 2000s. A case-control analysis of a UK general medicine database showed statistically significant increases in the risk of chronic atrial fibrillation in patients taking NSAIDs, after as little as one month of treatment. When NSAID treatment lasted more than 30 days, the incidence was 9.4%, versus 4.7% in the control group, corresponding to a relative risk (RR) of 1.57 (95% confidence interval (95% CI): 1.15 to 2.15). Similar results were found in patients with no history of heart failure. A Danish case-control study yielded similar results. In the UK case-control study, a statistically significant increase in the risk of chronic atrial fibrillation was found in patients taking corticosteroids (5% versus 1.4% in the control group, RR=2.5, 95% CI: 1.6 to 4). The risk increased with the dose. Another Danish case-control study showed that hospitalisation for atrial fibrillation or flutter was twice as frequent among patients exposed to corticosteroids. In contrast, trials in which corticosteroids were given shortly after cardiac surgery, a highly specific setting, showed a decreased risk of atrial fibrillation. In practice, the risk of atrial fibrillation should be taken into account before deciding whether or not to prescribe a corticosteroid or an NSAID, especially to a patient with known risk factors for atrial fibrillation. The heart rate of treated patients should be closely monitored.     

TAP and TAP-like — Brothers in arms?

The transporter associated with antigen processing like (TAPL, ABCB9) is a member of the ATP-binding cassette (ABC) transporter family. Moreover, TAPL belongs to the TAP family due to its high sequence homology to TAP1 and TAP2. TAPL forms a homodimer which is localized in lysosomes with a minor fraction in the ER. It functions as an ATP-dependent peptide transporter which shows a broad peptide specificity ranging from 6-mer up to 59-mer peptides. In contrast to TAP, TAPL transports peptides with low affinity but high efficiency. This review will briefly summarize current knowledge about the structural organization and possible physiological function of TAPL in antigen processing and presentation.     

Relationships between Inmates’ Past Drug Practices and Current Drug Knowledge and Attitudes

A questionnaire used in the measurement of past drug practices and current drug knowledge and attitudes was completed by 200 inmates. Data analysis provided an examination of relationships between the variables. Significant positive correlations were recorded between drug knowledge and drug practices, and between drug knowledge and drug attitude scores. However, a significant negative relationship was noted between drug practices and drug attitude scores. Additional findings are presented regarding inmates’ demographic characteristics and drug variable measures. Implications are discussed for the development of drug education programs in jails and prisons.     

Does the Life Skills Training program reduce use of marijuana?

The Life Skills Training (LST) program is one of the most widely disseminated drug prevention programs developed during the past 30 years. It is estimated that 50,000 teachers and 3 million students in the USA have participated in the program since 1995, and the program has been used in more than 30 other countries worldwide. This article reviews the evaluation studies that have assessed the effects of the LST program on the use of marijuana. Evaluations conducted by both the program developer and other research teams are reviewed. Most of the available evidence, especially coming from the analysis of data from full samples and not subgroup analysis, indicates that the program is unlikely to reduce use or abuse of marijuana among adolescents. The reason that the program has come to be considered so efficacious in preventing marijuana use is that those who promote the program pay little attention to the preponderance of evidence which supports the null hypothesis of no effect.     

DMSA,DMPS, and DMPA—as arsenic antidotes

meso-Dimercaptosuccinic acid (DMSA), 2,3-dimercapto-1-propanesulfonic acid, Na salt (DMPS), and N-(2,3-dimercaptopropyl)-phthalamidic acid (DMPA) are water soluble analogs of 2,3-dimercapto-1-propanol (BAL). The relative effectiveness or therapeutic index of these dimercapto compounds in protecting mice from the lethal effects of an LD99 of sodium arsenite is DMSA > DMPS > DMPA > BAL in the magnitude of 42:14:4:1, respectively. DMPS, DMPA, or DMSA will mobilize tissue arsenic. BAL, however, increases the arsenic content of the brain of rabbits injected with sodium arsenite. These results raise the question as to the appropriateness of BAL as the treatment for systemic arsenic poisoning. Either DMSA or DMPS, when given sc or po, will protect rabbits against the lethal systemic effects of subcutaneously administered Lewisite. DMPS and DMSA have promise as prophylactics for the prevention of the vesicant action of Lewisite. The sodium arsenite inhibition of the pyruvate dehydrogenase (PDH) complex can be prevented and reversed in vitro or in vivo by DMPS, DMSA, DMPA, or BAL. Of them all, DMPS is most potent and BAL appears to be the least potent. The usefulness of all these dimercapto compounds would be enhanced by a careful study of their metabolism and biotransformation. These dimercapto compounds are in a great many respects orphan drugs. At this stage of their development, it is very difficult for the clinician to obtain funds to study them clinically even though they appear to be useful for treatment of poisoning by any one of the heavy metals.     

Pricing, profits and pharmacoeconomics--for whose benefit?

In today's troubled healthcare climate, it is not uncommon to run across headlines like: 'Health insurance premiums increasing by 10 percent to 30 percent across the country.' This particular New York Times article went on to explain that this premium price hike, the third consecutive double digit increase in 3 years, is driven largely by escalating pharmaceutical costs. The pharmaceutical industry has largely been vilified in the media and in the recent presidential debates, for fueling healthcare inflation and setting what many perceive to be 'unfair' prices in light of the profit margins on their life-saving products. A report released by the Congressional Research Service found that after tax, profits for the pharmaceutical industry averaged 17% of sales, compared with 5% for all other industries. The White House has added its voice to the popular discontent with notices such as this one reported in the New York Times: 'There is a rising tide politically in this country of strong antagonism against the pharmaceutical industry on the dimension of prices. (Without expanded access to insurance) price controls are an inevitable outcome.' Although the prospect of price control remains dubious in America's entrenched laissez-faire economy, David Kessler, former head of the FDA and the Dean of the Yale School of Medicine, described the situation as a 'powder keg,' stating 'the current system is simply not sustainable'. Although there does not appear to be an immediate solution to this escalating crisis, this editorial will examine pharmaceutical pricing, industry profits and the role of pharmacoeconomic analyses amidst the chaos.     

Docking and scoring--theoretically easy, practically impossible?

Structure-based Drug Design (SBDD) is an essential part of the modern medicinal chemistry, and has led to the acceleration of many projects, and even to drugs on the market. Programs that perform docking and scoring of ligands to receptors are powerful tools in the drug designer's armoury that enhance the process of SBDD. They are even deployed on the desktop of many bench chemists. It is timely to review the state of the art, to understand how good our docking programs are, and what are the issues. In this review we would like to provide a guide around the reliable aspects of docking and scoring and the associated pitfalls aiming at an audience of medicinal chemists rather than modellers. For convenience, we will divide the review into two parts: docking and scoring. Docking concerns the preparation of the receptor and the ligand(s), the sampling of conformational space and stereochemistry (if appropriate). Scoring concerns the evaluation of all of the ligand-receptor poses generated by docking. The two processes are not truly independent, and this will be discussed here in detail. The preparation of the receptor and ligand(s) before docking requires great care. For the receptor, issues of protonation, tautomerisation and hydration are key, and we will discuss current approaches to these issues. Even more important is the degree of sampling: can the algorithms reproduce what is observed experimentally? If they can, are the scoring algorithms good enough to recognise this pose as the best? Do the scores correlate with observed binding affinity? How does local knowledge of the target (for example hinge-binding to a kinase) affect the accuracy of the predictions? We will review the key findings from several evaluation studies and present conclusions about when and how to interpret and trust the results of docking and scoring. Finally, we will present an outline of some of the latest developments in the area of scoring functions.