Developing Treatment for Tobacco Addicted Youth–Issues and Challenges

SUMMARY

It is now clear that adolescence is not only the primary time during which cigarette smoking is initiated; it is also the time during which the transition from experimentation to some level of dependence occurs. As discussed in this review, by age 18 approximately two-thirds of cigarette smokers regret having started smoking, one-half have already made a quit attempt, and nearly 40% have some interest in obtaining treatment for their dependence. Unfortunately, treatment in young people has not kept pace with the emerging need for treatment and many fundamental issues require study; in fact it is not clear the degree to which adult-validated treatments, such as nicotine replacement therapies, will be of comparable levels of benefit and risk in young people. The issues that require research include (1) a thorough consideration of adolescent nicotine dependence and potential pharmacologic adjuncts, (2) a consideration of social, health, risk perception, and intrapersonal factors that may facilitate or inhibit cessation attempts of maintenance among youth, and (3) advanced youth cessation trials research designs and measurement. We conclude that although the research challenges are many and diverse, all are surmountable by concerted efforts, and the opportunity to reduce the current projections of premature tobacco-caused mortality in one-third to one-half of cigarette smoking youth strongly argue for such efforts.     

Treatment options for refractory Wegener's granulomatosis: a role for rituximab?

Wegener's granulomatosis (WG) is a small-vessel vasculitis of unknown etiology, involving mainly the upper airways, lungs and kidneys. Organ inflammatory damage is mediated by anti-neutrophil cytoplasm antibodies, and their detection is a component of the diagnostic work-up as well as clinical signs and symptoms, and histopathological biopsy abnormalities. Conventional therapeutic regimens, such as cyclophosphamide and corticosteroids, can be used to induce and maintain disease remission. Alternatively, other cytotoxic agents (eg, methotrexate or mycophenolate mofetil), anti-TNFalpha agents (eg, infliximab or etanercept) or anti-lymphocyte antibodies (eg, rituximab) can be used. Rituximab, a mAb which targets CD20+ B-cells, is currently used in the treatment non-Hodgkin's lymphoma and rheumatoid arthritis, and is being investigated for refractory WG therapy and other autoimmune diseases.     

Transient lower oesophageal sphincter relaxations—a pharmacological target for gastro‐oesophageal reflux disease?

The oesophago-gastric junction functions as an anti-reflux barrier preventing increased exposure of the oesophageal mucosa to gastric contents. Failure of this anti-reflux barrier results in gastro-oesophageal reflux disease, and may lead to complications such as oesophagitis, Barrett's oesophagus and eventually oesophageal carcinoma. Recent studies have suggested that transient lower oesophageal sphincter relaxation is the main mechanism underlying gastro-oesophageal reflux. It involves a prolonged relaxation of the lower oesophageal sphincter, mediated by a vago-vagal neural pathway, synapsing in the brainstem. Several drugs, such as atropine, baclofen and loxiglumide, have been shown to reduce the rate of transient lower oesophageal sphincter relaxations and concomitantly the number of reflux episodes. These findings illustrate that transient lower oesophageal sphincter relaxations may represent a potential new target for the pharmacological treatment of gastro-oesophageal reflux disease. It is possible that the reduction in the number of transient lower oesophageal sphincter relaxations may also contribute to the beneficial effect of fundoplication and new endoscopic anti-reflux procedures. It should be emphasized, however, that other factors, such as low lower oesophageal sphincter pressure, the presence of a hiatal hernia and impaired oesophageal peristalsis, are also of great importance. Therefore, whether the targeting of transient lower oesophageal sphincter relaxations is the 'golden bullet' in anti-reflux therapy remains to be proven, as evidence of an effective control of gastro-oesophageal reflux in reflux patients is still lacking.     

Donepezil in a chronic drug user—a potential treatment?

The objective of the current study was to explore the potential cognitive benefits of an anticholinesterase inhibitor, donepezil, in a former chronic drug user. A neuropsychological test battery composed of the vocabulary and matrix reasoning subtests of the Wechsler adult intelligence scale-III, measures of everyday executive functioning (behavioural assessment of the dysexecutive syndrome [BADS]), and verbal learning and memory tasks (California verbal learning test-II; Rivermead behavioural memory test) was completed at baseline, at 3 months after introducing donepezil, and at 3 months after donepezil was discontinued. After donepezil treatment, substantial improvements were found on tasks of nonverbal fluid reasoning (i.e. matrix reasoning) and other executive functioning tests (i.e. BADS). At entry into the study, poor academic performance and subjective problems with memory and concentration were reported, particularly after amphetamine use (i.e. MDMA and crystal methamphetamine); after donepezil treatment, dramatic increases in memory, concentration and academic achievement were observed. The finding of improvements in tests of executive functioning and in academic performance in this case study, together with the minimal adverse side effects of donepezil, warrants the investigation of controlled studies of cholinergic enhancement in chronic amphetamine and other drug users.     

In Control?: Ukrainian Opiate Substitution Treatment Patients Strive for a Voice in Their Treatment

This article explores the burgeoning advocacy movement for methadone and buprenorphine treatment by patients, parents, and doctors in Ukraine, and their efforts to remake a system that infantilizes and controls patients into one where patients have a voice in their treatment. Through a review of gray literature and in-depth interviews with 28 patient-advocates and doctors in five Ukrainian cities between October 2009 and July 2010, this piece chronicles the emergence of opiate substitution treatment in Ukraine, describes successes toward patient-friendly treatment, and explores the institutionalized barriers that have pushed the patients to become advocates for their own treatment.     

Treatment of heparin-induced thrombocytopenia: is there a role for bivalirudin?

The recognition and management of heparin-induced thrombocytopenia (HIT) and heparin-induced thrombocytopenia with thrombosis syndrome (HITTS) has been evolving over the past several years. Although HIT is a relatively uncommon adverse event in patients receiving heparin therapy, it bears a significant risk of thrombotic events. If patients are left untreated, 50% can develop thrombosis. Several direct thrombin inhibitors have been studied as alternative anticoagulants in patients with HIT. Lepirudin and argatroban are both approved by the United States Food and Drug Administration (FDA) for the management of HIT. Lepirudin requires dosage adjustments in patients with renal insufficiency and has potential for antibody formation. Argatroban requires dosage adjustments in patients with hepatic insufficiency. Argatroban increases the international normalized ratio when coadministered with warfarin, leading to dosage difficulties when transitioning to warfarin therapy. Bivalirudin is the most recent direct thrombin inhibitor to be introduced to the market, but it is not currently FDA approved for HIT. Controversy still exists over which direct thrombin inhibitor to use, especially in acutely ill patients and in those requiring invasive or surgical procedures. Bivalirudin has a relatively short half-life and a predictable response, which makes it attractive as an anticoagulant in patients requiring invasive or surgical procedures, those who are acutely ill, or patients with both renal and hepatic insufficiency. It offers promise as an additional direct thrombin inhibitor for use in patients with HIT, but additional studies need to be performed to further define its use.     

The War on Drugs—a war on drug users?

The authors argue that since the 1980s UK drug policy has largely been ill considered, reactive and counter productive. Rather than reducing drug taking and drug related crime, such policies have exacerbated the problem and contributed towards an environment in which drug use and illegal drug activities are likely to flourish. One of the consequences of this 'war on drugs' is that it manifests itself as a 'war on drug users' with an emphasis not upon the development of appropriate rehabilitative models, but upon prevention, prohibition and punishment. Drawing on the authors' qualitative research on Merseyside, England involving 200 problem drug users, it will be argued that the war on drug users has subjected these people to a process of stigmatization, marginalization and social exclusion, and prevented many of them from recovery by hindering their reintegation into the wider social and economic community. Instead, growing numbers of problematic drug users remain locked into a cycle of chronic drug relapse.     

Drug Use–Chronic and Relapsing or a Treatable Condition?

It is argued that the term “chronic relapsing disorder,” which is used frequently to characterize drug use, does not capture the complexity of drug treatment evaluation findings and thereby limits an understanding and appreciation of the accomplishments of drug treatment. Specifically, it is noteworthy that a substantial minority (19%) of treated drug users have been found to maintain abstinence over a 6-year period posttreat-ment, and that the three major multisite treatment evaluations sponsored by NIDA have all found that overwhelming majorities of treated drug users do not revert to the levels of drug use (or criminal activity) shown pretreatment. Thus, the view of inevitable and continuing adoption of pretreatment behaviors, i.e., chronic relapse, gives undeserved comfort to those who deny the utility of drug treatment, and does so at a time when changes in the health care industry threaten the integrity of that treatment.