Mechanisms of Prescription Drug Diversion among Drug-Involved Club and Street-Based Populations

OBJECTIVE: Prescription drug diversion involves the unlawful channeling of regulated pharmaceuticals from legal sources to the illicit marketplace, and can occur along all points in the drug delivery process, from the original manufacturing site to the wholesale distributor, the physician\u27s office, the retail pharmacy, or the patient. However, empirical data on diversion are limited. METHOD: In an attempt to develop a better understanding of how specific drug-using populations are diverting prescription opioids and other medications, or obtaining controlled drugs that have already been diverted, qualitative interviews and focus group data were collected on four separate populations of prescription drug abusers in Miami, Florida--club drug users, street-based illicit drug users, methadone maintenance patients, and HIV positive individuals who abuse and/or divert drugs. RESULTS: Sources of abused prescription drugs cited by focus group participants were extremely diverse, including their physicians and pharmacists; parents and relatives; doctor shopping ; leftover supplies following an illness or injury; personal visits to Mexico, South America and the Caribbean; prescriptions intended for the treatment of mental illness; direct sales on the street and in nightclubs; pharmacy and hospital theft; through friends or acquaintances; under-the-door apartment flyers advertising telephone numbers to call; and stealing from grandma\u27s medicine cabinet. CONCLUSION: While doctor shoppers, physicians and the Internet receive much of the attention regarding diversion, the data reported in this paper suggest that there are numerous active street markets involving patients, Medicaid recipients and pharmacies as well. In addition, there are other data which suggest that the contributions of residential burglaries, pharmacy robberies and thefts, and sneak thefts to the diversion problem may be understated

Patterns of Prescription Opioid Abuse and Comorbidity in an Aging Treatment Population

Very little is known about the impact of age and gender on drug abuse treatment needs. To examine this, we recruited 2,573 opioid-dependent patients, aged from 18 to 75 years, entering treatment across the country from 2008 to 2010 to complete a self-administered survey examining drug use histories and the extent of comorbid psychiatric and physical disorders. Moderate to very severe pain and psychiatric disorders, including polysubstance abuse, were present in a significant fraction of 18- to 24-year-olds, but their severity grew exponentially as a function of age: 75% of those older than 45 years had debilitating pain and psychiatric problems. Women had more pain than men and much worse psychiatric issues in all age groups. Our results indicate that a one-size-fits-all approach to prevention, intervention, and treatment of opioid abuse that ignores the shifting needs of opioid-abusing men and women as they age is destined to fail

The Black Box of Prescription Drug Diversion

A variety of surveys and studies are examined in an effort to better understand the scope of prescription drug diversion and to determine whether there are consistent patterns of diversion among various populations of prescription drug abusers. Data are drawn from the RADARS System, the National Survey of Drug Use and Health, the Delaware School Survey, and a series of quantitative and qualitative studies conducted in Miami, Florida. The data suggest that the major sources of diversion include drug dealers, friends and relatives, smugglers, pain patients, and the elderly, but these vary by the population being targeted. In all of the studies examined, the use of the Internet as a source for prescription drugs is insignificant. Little is known about where drug dealers are obtaining their supplies, and as such, prescription drug diversion is a black box requiring concentrated, systematic study

Multiple Determinants of Specific Modes of Prescription Opioid Diversion

Numerous national surveys and surveillance programs have shown a substantial rise in the abuse of prescription opioids over the past 15 years. Accessibility of these drugs to non-patients is the result of their unlawful channeling from legal sources to the illicit marketplace (diversion). Empirical data on diversion remain absent from the literature. This paper examines abusers\u27 sources of diverted drugs from two large studies: 1) a national sample of opioid treatment clients (N=1983), and 2) a South Florida study targeting diverse populations of opioid abusers (N=782). The most common sources of diverted medications were dealers, sharing/trading, legitimate medical practice (e.g., unknowing medical providers), illegitimate medical practice (e.g., pill mills), and theft, in that order. Sources varied by users\u27 age, gender, ethnicity, risk-aversiveness, primary opioid of abuse, injection drug use, physical health, drug dependence, and either access to health insurance or relative financial wealth. Implications for prescription drug control policy are discussed

Relationship between therapeutic use and abuse of opioid analgesics in rural, suburban, and urban locations in the United States

SUMMARY Purpose The goal of these studies was to determine the relationship between prescribed use of opioid analgesics and their non-medically related use (abuse) at a regional level across the country. Methods To gather information about prescription drug abuse, we asked 233 drug abuse treatment specialists to provide us Quarterly reports on the number of cases of prescription opioid analgesic abusers who used opioid analgesics to get high in the past 30 days. Results and Conclusions We found that there was a very strong correlation between therapeutic exposure to opioid analgesics, as measured by prescriptions filled, and their abuse. There were, however, geographical loci that represented outliers in which abuse was disproportionately high relative to therapeutic use (>95th percentile), most of which were in very small urban, suburban, and rural areas. The rank order of abuse shows that buprenorphine products, extended release (ER) oxycodone and methadone are the most intensely abused prescription opioid analgesics, with hydrocodone the least abused, when the data are corrected for degree of exposure, i.e., cases/1000 persons filling a prescription. If, on the other hand, one uses the number of cases/100 000 population, hydrocodone ranked as high as ER oxycodone and all other drugs grouped together at very low levels of abuse. Since the latter conclusion ignores therapeutic exposure, we conclude that the rate of abuse of highly efficacious opioid analgesics is best expressed as cases of abuse/1000 persons filling a prescription, which yields the best possible estimate of the risk-benefit ratio of these drugs

The effect of chemical composition on the PCT durability of mixed waste glasses from wastewater treatment sludges

An experimental program has been designed to examine the chemical durability of glass compositions derived from the vitrification of simulated wastewater treatment sludges. These sludges represent the majority of low-level mixed wastes currently in need of treatment by the US DOE. The major oxides in these model glasses included SiO{sub 2}, Al{sub 2}O{sub 3}, B{sub 2}O{sub 3}, Na{sub 2}O, CaO and Fe{sub 2}O{sub 3}. In addition, three minor oxides, BaO, NiO, and PbO, were added as hazardous metals. The major oxides were each varied at two levels resulting in 32 experimental glasses. The chemical durability was measured by the 7-Day Product Consistency Test (PCT). The normalized sodium release rates (NRR{sub Na}) of these glasses ranged from 0.01 to 4.99 g/m{sup 2}. The molar ratio of the glass-former to glass-modifier (F/M) was found to have the greatest effect on PCT durability. Glass-formers included SiO{sub 2}, Al{sub 2}O{sub 3}, and B{sub 2}O{sub 3}, while Na{sub 2}O, CaO, BaO, NiO, and PbO were glass-modifiers. As this ratio increased from 0.75 to 2.0, NRR{sub Na} was found to decrease between one and two orders of magnitude. Another important effect on NRR{sub Na} was the Na{sub 2}O/CaO ratio. As this ratio increased from 0.5 to 2.0, NRR{sub Na} increased up to two orders of magnitude for the glasses with the low F/M ratio but almost no effect was observed for the glasses with the high F/M ratio. Increasing the iron oxide content from 2 to 18 mole% was found to decrease NRR{sub Na} one order of magnitude for the glasses with low F/M but iron had little effect on the glasses with the high F/M ratio. The durability also increased when 10 mole percent Al{sub 2}O{sub 3} was included in low iron oxide glasses but no effect was observed with the high iron glasses. The addition of B{sub 2}O{sub 3} had little effect on durability. The effects of other composition parameters on durability are discussed as well

Detection of urinary microRNA biomarkers using diazo sulfonamide-modified screen printed carbon electrodes

This paper describes a straightforward electrochemical method for rapid and robust urinary microRNA (miRNA) quantification using disposable biosensors that can discriminate between urine from diabetic kidney disease (DKD) patients and control subjects. Aberrant miRNA expression has been observed in several major human disorders, and we have identified a urinary miRNA signature for DKD. MiRNAs therefore have considerable promise as disease biomarkers, and techniques to quantify these transcripts from clinical samples have significant clinical and commercial potential. Current RT-qPCR-based methods require technical expertise, and more straightforward methods such as electrochemical detection offer attractive alternatives. We describe a method to detect urinary miRNAs using diazo sulfonamide-modified screen printed carbon electrode-based biosensors that is amenable to parallel analysis. These sensors showed a linear response to buffered miR-21, with a 17 fM limit of detection, and successfully discriminated between urine samples (n = 6) from DKD patients and unaffected control subjects (n = 6) by differential miR-192 detection. Our technique for quantitative miRNA detection in liquid biopsies has potential for development as a platform for non-invasive high-throughput screening and/or to complement existing diagnostic procedures in disorders such as DKD

Enhanced feedback interventions to promote evidence-based blood transfusion guidance and reduce unnecessary use of blood components:The AFFINITIE research programme including two cluster factorial RCTs

Background: Blood transfusion is a common but costly treatment. Repeated national audits in the UK suggest that up to one-fifth of transfusions are unnecessary when judged against recommendations for good clinical practice. Audit and feedback seeks to improve patient care and outcomes by comparing clinical care against explicit standards. It is widely used internationally in quality improvement. Audit and feedback generally has modest but variable effects on patient care. A considerable scope exists to improve the impact that audit and feedback has, particularly through head-to-head trials comparing different ways of delivering feedback. Objectives: The AFFINITIE (Development & Evaluation of Audit and Feedback INterventions to Increase evidence-based Transfusion practIcE) programme aimed to design and evaluate enhanced feedback interventions, within a national blood transfusion audit programme, to promote evidence-based guidance and reduce the unnecessary use of blood components. We developed, piloted and refined two feedback interventions, ‘enhanced content’ and ‘enhanced follow-on’ (workstream 1), evaluated the effectiveness and cost-effectiveness of the two feedback interventions compared with standard feedback practice (workstream 2), examined intervention fidelity and contextual influences (workstream 3) and developed general implementation recommendations and tools for other audit and feedback programmes (workstream 4). Design: Interviews, observations and documentary analysis in four purposively sampled hospitals explored contemporary practice and opportunities for strengthening feedback. We developed two interventions: ‘enhanced content’, to improve the clarity and utility of feedback reports, and ‘enhanced follow-on’, to help hospital staff with action-planning (workstream 1). We conducted two linked 2 × 2 factorial cross-sectional cluster-randomised trials within transfusion audits for major surgery and haematological oncology, respectively (workstream 2). We randomised hospital clusters (the organisational level at which hospital transfusion teams operate) to enhanced or standard content or enhanced or standard follow-on. Outcome assessment was masked to assignment. Decision-analytic modelling evaluated the costs, benefits and cost-effectiveness of the feedback interventions in both trials from the perspective of the NHS. A parallel process evaluation used semistructured interviews, documentary analyses and web analytics to assess the fidelity of delivery, receipt and enactment and to identify contextual influences (workstream 3). We explored ways of improving the impact of national audits with their representatives (workstream 4). Setting and participants: All NHS hospital trusts and health boards participating in the National Comparative Audit of Blood Transfusions were invited to take part. Among 189 hospital trusts and health boards screened, 152 hospital clusters participated in the surgical audit. Among 187 hospital trusts and health boards screened, 141 hospital clusters participated in the haematology audit. Interventions: ‘Enhanced content’ aimed to ensure that the content and format of feedback reports were consistent with behaviour change theory and evidence. ‘Enhanced follow-on’ comprised a web-based toolkit and telephone support to facilitate local dissemination, planning and response to feedback. Main outcome measures: Proportions of acceptable transfusions, based on existing evidence and guidance and algorithmically derived from national audit data. Data sources: Trial primary outcomes were derived from manually collected, patient-level audit data. Secondary outcomes included routinely collected data for blood transfusion. Results: With regard to the transfusions in the major surgery audit, 135 (89%) hospital clusters participated from 152 invited. We randomised 69 and 66 clusters to enhanced and standard content, respectively, and 68 and 67 clusters to enhanced and standard follow-on, respectively. We analysed a total of 2222 patient outcomes at 12 months in 54 and 58 (enhanced and standard content, respectively) and 54 and 58 (enhanced and standard follow-on, respectively) hospital clusters. With regard to the haematology audit, 134 hospital clusters (95%) participated from 141 invited. We randomised 66 and 68 clusters to enhanced and standard content, respectively, and 67 clusters to both enhanced and standard follow-on. We analysed a total of 3859 patient outcomes at 12 months in 61 and 61 (enhanced and standard content, respectively) and 63 and 59 (enhanced and standard follow-on) hospital clusters. We found no effect of either of the enhanced feedback interventions in either trial across all outcomes. Incremental enhanced intervention costs ranged from £18 to £248 per site. The enhanced feedback interventions were dominated by the standard intervention in cost-effectiveness analyses. The interventions were delivered as designed and intended, but subsequent local engagement was low. Although the enhancements were generally acceptable, doubts about the credibility of the blood transfusion audits undermined the case for change. Limitations: Limitations included the number of participating clusters; loss to follow-up of trial clusters, reducing statistical power and validity; incomplete audit and cost data contributing to outcome measures; participant self-selection; reporting; missing data related to additional staff activity generated in response to receiving feedback; and recall biases in the process evaluation interviews. Conclusions: The enhanced feedback interventions were acceptable to recipients but were more costly and no more effective than standard feedback in reducing unnecessary use of blood components, and, therefore, should not be recommended on economic grounds. Future work: We have demonstrated the feasibility of embedding ambitious large-scale rigorous research within national audit programmes. Further head-to-head comparisons of different feedback interventions are needed in these programmes to identify cost-effective ways of increasing the impact of the interventions

The rapid formation of functional monolayers on silicon under mild conditions

We report on an exceedingly mild chemical functionalization of hydrogen-terminated Si(100) with unactivated and unprotected bifunctional α,ω-dialkynes. Monolayer formation occurs rapidly in the dark, and at room temperature, from dilute solutions of an aromatic-conjugated acetylene. The method addresses the poor reactivity of p-type substrates under mild conditions. We suggest the importance of several factors, including an optimal orientation for electron transfer between the adsorbate and the Si surface, conjugation of the acetylenic function with a π-system, as well as the choice of a solvent system that favors electron transfer and screens Coulombic interactions between surface holes and electrons. The passivated Si(100) electrode is amenable to further functionalization and shown to be a viable model system for redox studies at non-oxide semiconductor electrodes in aqueous solutions