The poppy seed defense: a novel solution

A major toxicological challenge is distinguishing whether morphine in urine, in the absence of 6‐monoacetylmorphine (6‐MAM), originates from ‘street’ heroin use or poppy seed ingestion. Manufacturing byproducts from the synthesis of illicit heroin include those that originate from the reaction of acetic anhydride with the alkaloid impurity, thebaine, which undergoes skeletal rearrangement, resulting in compounds with a 2‐(N‐methylacetamido)ethyl side‐chain. The hypothesis that the tertiary amide in this side‐chain is resistant to endogenous hydrolysis was supported from in‐vitro experiments; a glucuronide metabolite (designated ‘ATM4G’) was identified that may be used as a marker of ‘street’ heroin administration. Liquid chromatography‐tandem mass spectrometry (LC‐MS/MS) analysis for this metabolite was then performed on selected urine specimens from 22 known heroin users, these being negative on routine testing for 6‐MAM by gas chromatography‐mass spectrometry (GC‐MS), using the generally applied reporting threshold of 10 ng/mL, but positive for the presence of morphine. Peaks corresponding to the retention time for the metabolite marker were clearly observed for 16 of the 22 samples, with variations of the ratios of its three dependent ions being within ± 30% of that produced in vitro. Conversely, 6‐MAM was detected in only 3 samples, but at concentrations <1 ng/mL. Such a high frequency for the presence of the metabolite marker in urine, in the absence of 6‐MAM, is noteworthy and suggests that detection of this metabolite may offer an important advance in forensic toxicology, allowing the development of a new and more definitive test for heroin abuse and thus a potential solution to the so‐called ‘poppy seed defense’. Copyright © 2013 John Wiley & Sons, Ltd.     

Drug-eluting stents: a multidisciplinary success story

Coronary stenting is the most common form of interventional treatment for symptomatic coronary artery disease. In-stent restenosis following bare metal stent (BMS) placement is the most common cause of procedural failure and occurs as a result of vessel wall trauma secondary to balloon angioplasty and stent deployment that results in an overly aggressive healing response (neointimal hyperplasia) that overgrows the stent lumen and causes vascular narrowing. Drug-eluting stents (DES) are specialized vascular stents capable of delivering drugs to the arterial wall in a controlled manner such that neointimal hyperplasia is reduced or prevented, luminal patency is preserved, coronary blood flow is maintained and the patient is spared a repeat procedure to re-open the vessel. The objectives of the review are to provide an overview of the major contributions that a broad range of disciplines have made to the design and development of drug-eluting stents and to summarize future directions of these fields of research. Engineers and biomaterials scientists have explored relationships between stent design and stent performance and work continues to optimize stent design and biocompatibility of stent biomaterials. Pharmaceutical scientists are continually expanding the range of candidate drugs for pharmacological intervention, and improving the technology using novel coatings to modulate drug release. Clinical scientists are investigating issues such as long-term safety and efficacy, new applications of drug-eluting stents and optimal deployment techniques.     

Horse chestnut:a multidisciplinary clinical review

Horse chestnut seed extract (HCSE) is widely used in Europe for the management of chronic venous insufficiency (CVI). Although traditionally recommended for a variety of medical conditions, CVI is the only indication for which there is strong supportive scientific evidence. Review of the literature reveals 14 randomized controlled trials, of which seven are methodologically of high quality, albeit limited by small sample sizes and short durations. These studies support the superiority of HCSE over placebo, and suggest equivalence to compression stockings and to oral oxerutins. In the future, a longer and adequately powered randomized trial is warranted to compare HCSE to standard of care, and to further assess safety and long-term efficacy. There are no data to suggest that horse chestnut flower, raw seed, branch bark, or leaf are effective for any indication, and it is recommended that these products not be used, as they are known to be toxic when ingested.     

Consulting the oracle: a Delphi Study to determine the content of a postgraduate distance learning course in therapeutics

Aims To determine the content of a distance learning course in therapeutics for general practitioners (GPs).
Methods This paper reports the results of a three-round Delphi study. The respondent group comprised 21 GPs who were expert in their field. In the first round, the experts were interviewed to determine the knowledge, skills, competencies and attitudes required by GPs to prescribe effectively; the justification for, and scope of a distance learning course; and the preferred learning methods, format and methods of assessment. The first round generated 251 statements, which were collapsed into 108 statements covering thirteen domains. In the second and third rounds, a questionnaire was posted to the GPs. 95% responded to the second round questionnaire and agreed upon 86 statements, which were then collated into four domains. In the third round, 19 GPs rated each of the 86 statements on a five point scale. Consensus was reached for 99% of statements: 40 on the aims, design, format, organization and assessment of the course; and 45 on the knowledge and skills to be acquired by GPs who complete the course.
Results The results revealed a consensus in favour of:
• modules at regular intervals
• some flexibility in meeting deadlines
• interaction among students for mutual support
• easy access to course tutors
• some face-to-face contact to complement distance learning material
• clear guidance on effective and safe prescribing
• emphasis on importance of 'people skills'
Conclusions The Delphi process can be used to determine the competencies required for continuing medical education in therapeutics.     

Introduction: the need for a multidimensional and multidisciplinary approach

This special issue combines contributions from several disciplines within the social sciences on how to understand long-term use or dependency on various kinds of psychotropics. It emphasizes the need for a multidisciplinary approach in order to understand the complexity of such long-term use. The papers in this issue will base their arguments on psychological, sociological, anthropological, clinical, and social pharmacy perspectives. Different disciplines focus specially on certain topics. For example, psychology can help us to understand what kind of mental processes that are involved in the development of long-term tranquillizer use. Sociology, anthropology and social pharmacy have a particular contribution to make in helping us, in different ways, to understand the social meanings of psychotropic drug use.     

Lung microcytoma: a multidisciplinary therapeutic approach.

This report is of 26 patients diagnosed with microcytoma of the lung in stages I, II, and IIIa. All patients received surgical treatment as well as postoperative chemoradiotherapy when indicated by stage. Mean survival rates were 16 months for stage 1, 10 months for stage II and 6 months for stage IIIa disease. For many years surgery was considered contraindicated in the treatment of pulmonary microcytoma. Now a multidisciplinary approach is being used in which surgery has a crucial role. Microcytoma of the lung has a poor prognosis due to its early metastasis and rapid growth. It is crucial to have early diagnosis and accurate, consistent staging as the basis for treatment. A review of literature shows that the use of surgery, chemotherapy and radiotherapy are all important in treatment of microcytoma. Chemotherapy is successfully utilized preoperatively to improve local control, decrease neoplastic mass, induce histological regression and as postoperative adjuvant therapy. Radiotherapy has been shown to be effective preoperatively to reduce local mass and prophylactically for cerebral metastasis. Surgery is crucial to irradicate the neoplastic mass, improve staging accuracy, decrease the possible selection of neoplastic clones resistant to postoperative therapy, decrease local recurrence and allow less aggressive chemoradiotherapy. We feel the most effective protocol for pulmonary microcytoma includes preoperative chemotherapy and radiotherapy when indicated followed by surgical intervention and finally successive adjuvant therapy. The limited number of our cases does not consent a statistically significative conclusion. Our data confirm the importance of the surgical procedure in stages I and II, where according also to other authors, the best results are obtained. Surgical indication in stage IIIa is still discussed due to precocius lymphnode dissemination that significantly affects long-term survival.     

The development of chronic pain: physiological CHANGE necessitates a multidisciplinary approach to treatment

Abstract

Chronic pain is currently under-diagnosed and under-treated, partly because doctors’ training in pain management is often inadequate. This situation looks certain to become worse with the rapidly increasing elderly population unless there is a wider adoption of best pain management practice. This paper reviews current knowledge of the development of chronic pain and the multidisciplinary team approach to pain therapy. The individual topics covered include nociceptive and neuropathic pain, peripheral sensitization, central sensitization, the definition and diagnosis of chronic pain, the biopsychosocial model of pain and the multidisciplinary approach to pain management. This last section includes an example of the implementation of a multidisciplinary approach in Belgium and describes the various benefits it offers; for example, the early multidimensional diagnosis of chronic pain and rapid initiation of evidence-based therapy based on an individual treatment plan. The patient also receives continuity of care, while pain relief is accompanied by improvements in physical functioning, quality of life and emotional stress. Other benefits include decreases in catastrophizing, self-reported patient disability, and depression. Improved training in pain management is clearly needed, starting with the undergraduate medical curriculum, and this review is intended to encourage further study by those who manage patients with chronic pain.     

Building a better aspirin: gaseous solutions to a century-old problem

The gastrointestinal adverse effects of nonsteroidal anti-inflammatory drugs (NSAIDs) have been recognized since shortly after the introduction of aspirin to the marketplace over a century ago. However, the underlying pathogenesis of NSAID-induced gastropathy remains incompletely understood. Advances in understanding some of the factors that contribute to the mucosal injury have provided clues for the development of safer NSAIDs. The inhibitory effects of nitric oxide (NO) on NSAID-induced leukocyte adherence were exploited in the development of NO-releasing NSAIDs. As well as eliciting less gastrointestinal damage than conventional NSAIDs, these drugs do not elevate blood pressure and show anti-inflammatory effects, additional to those of the parent drugs. Modification of other drugs in a similar manner (i.e., NO-releasing derivatives) has similarly resulted in more effective drugs. More recently, hydrogen sulphide-releasing derivatives of NSAIDs and of other drugs, have been developed, based on the observed ability of H(2)S to reduce inflammation and pain in experimental models. H(2)S-releasing NSAIDs produce negligible gastric damage and exhibit enhanced anti-inflammatory potency as compared to the parent drugs. The NO-NSAIDs and H(2)S-releasing NSAIDs represent examples of new anti-inflammatory drugs with greatly reduced toxicity and improved therapeutic activity, both created through the concept of exploiting the beneficial effects of endogenous gaseous mediators.     

Pharmaceutical impurity identification: a case study using a multidisciplinary approach

A multidisciplinary team approach to identify pharmaceutical impurities is presented in this article. It includes a representative example of the methodology. The first step is to analyze the sample by LC-MS. If the structure of the unknown impurity cannot be conclusively determined by LC-MS, LC-NMR is employed. If the sample is unsuitable for LC-NMR, the impurity needs to be isolated for conventional NMR characterization. Although the technique of choice for isolation is preparative HPLC, enrichment is often necessary to improve preparative efficiency. One such technique is solid-phase extraction. For complete verification, synthesis may be necessary to compare spectroscopic characteristics to those observed in the original sample. Although not widely practiced, an effective means of getting valuable structural information is to conduct a degradation study on the purified impurity itself. This systematic strategy was successfully applied to the identification of an impurity in the active pharmaceutical ingredient 1-(1,2,3,5,6,7-hexahydro-s-indacen-4-yl)-3-[4-(1-hydroxy-1-methyl-ethyl)-furan-2-sulphonylurea. Identification required the use of all of the previously mentioned techniques. The instability of the impurity under acidic chromatographic conditions presented an additional challenge to purification and identification. However, we turned this acidic instability to an advantage, conducting a degradation study of the impurity, which provided extensive and useful information about its structure. The following discussion describes how the information gained from each analytical technique was brought together in a complementary fashion to elucidate a final structure.     

Update in the treatment of locally advanced breast cancer: a multidisciplinary approach

Locally advanced breast cancer represents a wide variety of neoplasms and constitutes approximately 10%-20% of the newly diagnosed breast cancers. These cancers may have widely different clinical and biological characteristics. According to the American Joint Committee on Cancer (AJCC) staging system, all of stage III disease is considered locally advanced. The clinical treatment of locally advanced breast cancer is complex and should be tailored to the individual patient. In this paper we discuss the options of management of locally advanced breast cancer, focusing on a multidisciplinary approach through a combined-modality care involving surgery, radiotherapy and systemic therapy.     

The use of a decision analysis model in multidisciplinary decision making

This paper describes a conceptual decision analysis model for use in multidisciplinary decision making. Decision analysis was used to structure a decision process that ensured the best choice through consensus building among hospital decision makers. The four basic steps of the decision analysis model included: (1) identifying and establishing boundaries of the decision problem; (2) structuring the decision problem; (3) characterizing information needed to fill in the structure; and (4) choosing a preferred course of action. The selection of the best intermittent intravenous drug delivery system for Presbyterian Hospital illustrates the application of the conceptual model. This type of decision analysis model becomes a useful consensus building and communication device for the administrative pharmacist who is involved in multidisciplinary decision-making processes.     

Patient education: a multidisciplinary approach to influence patient compliance

The Department of Pharmacy and Nursing should collaborate on a consistent basis to proactively implement and evaluate the patient education program. Although many hospitals educate their patients, the systems can often be fragmented. Unanswered questions may include how and where the education takes place, the method of documentation, and who specifically educates the patient. Selection of the best media for educational materials requires that the broad array of printed (i.e., manuals, programmed texts, booklets) and nonprint material (i.e., videotape, motion pictures, etc.) be considered. A multidisciplinary patient education committee facilitates the program at MSKCC. Approximately 50 chemotherapy fact cards have been used at MSKCC for six years. This program has yielded positive perceptions from patients as well as from the pharmacy and nursing staff. Future trends will probably include widespread use of interactive patient education programs to provide indexing, order entry, and documentation of patient education materials.     

Impact of the pharmacist on a multidisciplinary team in an antimicrobial stewardship program: a quasi-experimental study

Background Antimicrobial stewardship programs (ASP) have been implemented to promote rational use of antimicrobial drugs. Multidisciplinary teams are needed to form effective committees. Objective Assess the impact of ASP, with and without the presence of a pharmacist, in a cardiology hospital in Brazil. Methods The program started with an infectious disease (ID) physician, and after 22?months, a pharmacist started to work in the ASP team. We present data related to: stage 1??before the program implementation; stage 2??with the ID physician; and stage 3 with the inclusion of a pharmacist. Analysis was made by segmented regression of time series. Results After the start of ASP there was a significant reduction of consumption of all antimicrobials. The pharmacist contributed to the significant reduction in consumption of fluoroquinolones, clindamycin and ampicillin/sulbactam and in increase in total cephalosporins use in stage 3. Adherence rate to the ASP team recommendations was 64.1%. There was a significant reduction of 69% in hospital antibiotics costs. Conclusion A non-expensive ASP in a limited resource country resulted in reductions in antimicrobial consumption and costs. The multidisciplinary team contributed to maximize the impact of interventions.