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CORK Bibliography: Prescription Drugs

116 citations. July 2008 to present

Prepared: June 2009

Akgur SA; Altintoprak AE; Yuncu Z; Coskunol H. The determination of non-alcoholic substance use in drivers: Why? How? Where? (Turkish). Clinical Psychopharmacology 18(3): 201-207, 2008. (36 refs.)

This article describes the background, legislations and new approaches in Turkey for control of drug use of drivers. In recent years, in parallel to the widespread use of illicit drugs, the number of drivers affected by drugs is also increasing. It is well established that alcohol impairs driving ability and increases the risk of accidents. New studies show the contribution of illicit drugs to fatal/nonfatal rood accidents. With the addition of social, economical and cultural factors, the traffic of drugs has resulted in an increased ratio of drugs of abuse and addiction in our country which is located in a crowded transition area (UNCLEAR). Drinking and driving have become less socially acceptable. Awareness has also grown about the impairment caused by other drugs. Driving under the influence of a legal (prescription drug) or an illegal drug as a controlled substance is controlled by low (Turkish Road Traffic Act 2918 and Related Legislation-Section/97 Prohibition for DUI of alcoholic beverages, narcotics and euphoric substances). In addition, using screening tests on the road (on-site tests) requirement for controlling DUID is compulsory in order to ensure security of our country's roads from materials including saliva, and sweat to determine the drivers who are under the influence of drugs, according to important developments in EU countries in recent years. Proof of drug consumption requires analysis of a body fluid to identify the drug. The various methods of drug analyses in alternative samples each have problems with respect to sample collection, handling, and transportation as well as toxicological assays used. Therefore the determination of illicit drug use in drivers and its influence on driving is very important. Many prescription drugs, especially sedative-hypnotic or strong analgesics, are classified as controlled substances. Also, it should be kept in mind that many addicted patients who constitute a considerable proportion of psychiatric patients may be drivers. Apprehension and punishment of people who chose to drive while impaired has become a higher priority. More stringent controls and onsite tests should be adopted. In this article, drug testing regulations on drivers were evaluated based on legal, social and toxicological principals and the requirements of international standards are discussed.

Albertin P; Iniguez L. Using drugs: The meaning of opiate substances and their consumption from the consumer perspective. Addiction Research & Theory 16(5): 434-452, 2008. (58 refs.)

This article reports on the ethnographical study carried out among an opiate consumer community in Barcelona (Spain) and analyses the meanings that those consumers build and handle around the substances that they consume. Our approach emphasises the point of view of the consumers in their understanding of drugs and the type of relationships that they maintain between themselves and with their social environment.

Aquina CT; Marques-Baptista A; Bridgeman P; Merlin MA. OxyContin (R) abuse and overdose. Postgraduate Medicine 121(2): 163-167, 2009. (31 refs.)

Background: OxyContin (R) (controlled-release oxycodone hydrochloride) (Purdue Pharma, Stamford, CT) was approved in 1995 by the US Food and Drug Administration (FDA) for moderate-to-severe chronic pain. Crushing and snorting the delayed-release tablets results in a rapid release of the drug, increased absorption, and high peak serum concentrations. The propensity for addiction to OxyContin (R) and the trend of increased prescription drug abuse have made it imperative for physicians and health care providers to recognize the clinical presentation of overdose and know how to manage associated complications. Objectives: In this review of OxyContin (R), we discuss current trends in its abuse and the clinical presentation of overdose. We review the specific effects of the drug on body systems and the recognition of symptomatology, differential diagnosis, and management. Discussion: Many of the clinical findings in acute opioid overdoses are nonspecific, making diagnosis difficult. OxyContin (R) overdose presents with a typical opiate toxidrome, including decreased respirations, miosis, hypothermia, bradycardia, hypotension, and altered mental status. The presence of coingestants can cloud the clinical picture. If OxyContin (R) overdose is suspected, early ventilation and oxygenation should be administered, which is generally sufficient to prevent death. Even in the absence of a confirmation, cautious administration of naloxone-the opiate receptor antagonist and antidote for opioid overdoses-may have both diagnostic and therapeutic effects. Summary: With increasing rates of prescription drug abuse, OxyContin (R) will continue to present challenges to physicians and health care providers. Physicians should be aware of potential patients who are seeking OxyContin (R) for recreational use.

Arbanas G; Arbanas D; Dujam K. Adverse effects of benzodiazepines in psychiatric outpatients. Psychiatria Danubina 21(1): 103-107, 2009. (18 refs.)

Background. Benzodiazepines are among the most frequently prescribed drugs. Of all their side. effects, hip fractures and possibility of developing dependence are usually studied. Objective: The aim of this study was to determine how often do psychiatric outpatients suffer from adverse effects of benzodiazepines, and which adverse effects do they notice. Subjects and method. 109 patients on two consecutive days were asked to fill in the questionnaire. Among them were 29 women and 80 men, Ten women (113) and 20 men (114) refused to participate in the study. Results: 68% of women and 93% of men used benzodiazepines at least once in a lifetime; 40% of women used benzodiazepines in the last seven days, and 93% of men (32% of women and 44% of men used benzodiazepines every day for the last seven days). Unfortunately, 8%. of men used more then one benzodiazepine daily. All of the women who used benzodiazepines had at least one adverse effect; and 91% of men had adverse effects. One third of women and one quarter of men stopped taking benzodiazepines due to adverse effects. The mean number of adverse effects was 4.8 both in men and women. Those who stopped taking benzodiazepines didn't have more adverse effects in comparison to those who continued to use them. More than half of the participants suffered from sleepiness, slowness and fatigue. One third of the participants said they noticed the change in sexual drive. More then 30% of women noticed dizziness and only 6% of men. None of the participants said to have jaundice after using benzodiazepines, The same adverse effects were present in those who stopped taking the drugs and in those who continued to use them. Conclusion: The prevalence of benzodiazepine use is very high in psychiatric patients. Many of them notice adverse effects, but mainly continue to use the drug.

Arkes J; Iguchi MY. How predictors of prescription drug abuse vary by age. Journal of Drug Issues 38(4): 1027-1043, 2008. (20 refs.)

Previous studies that have identified the predictors of prescription drug abuse have either focused on a specific age group or pooled all age groups together into one sample. This approach constrains the predictors to have the same effect across age groups. In this study, we use the 2001 to 2003 National Survey on Drug Use and Health to estimate separate models across five age groups for the past year nonmedical use of prescription drugs. The results indicate that several factors (e.g., gender, race/ethnicity, marital status, other substance use) have quite different correlations with prescription drug abuse across age groups. This suggests that more accurate profiles of prescription drug abusers can be obtained by estimating separate models for different age groups.

Arria AM; Caldeira KM; Vincent KB; O'Grady KE; Wish ED. Perceived harmfulness predicts nonmedical use of prescription drugs among college students: Interactions with sensation-seeking. Prevention Science 9(3): 191-201, 2008. (53 refs.)

This study describes the level of perceived harmfulness of nonmedical prescription stimulant and analgesic use in a sample of college students, and examines the prospective relationship between perceived harmfulness and subsequent nonmedical use. In addition, we explore whether the association between perceived harmfulness and nonmedical use varies by level of sensation-seeking. Personal interviews, including questions on sensation-seeking and drug use, were conducted with 1,253 first-year college students. Participants were then followed-up twice at 6-month intervals. Perceived harmfulness of nonmedical use of prescription drugs was assessed at 6 months via a web-based survey. At the 12-month follow-up interview, drug use was again assessed. Students who never had the opportunity to use prescription drugs nonmedically were excluded from all analyses. Results revealed that one in four students perceived a great risk of harm from occasional nonmedical use of prescription stimulants (25.2%) and analgesics (27.8%). As expected, low perceived harmfulness and high sensation-seeking were independently associated with increased risk of nonmedical use, holding constant demographic characteristics. The protective effect of high perceived harmfulness could be seen at all levels of sensation-seeking with one important exception: Among high sensation-seekers, perceived harmfulness was not related to nonmedical use of prescription analgesics. Perceived harmfulness appears to distinguish nonmedical users from non-users, given the opportunity to use. Increasing perceived harmfulness may be a viable prevention strategy for most students, but alternative approaches might need to be developed that are tailored to high sensation-seekers.

Bailey JE; Campagna E; Dart RC. The underrecognized toll of prescription opioid abuse on young children. Annals of Emergency Medicine 53(4): 419-424, 2009. (8 refs.)

Study objective: The impact of prescription opioid abuse on young children is underrecognized and poorly documented. We hypothesize that poisoning of young children from prescription opioids occurs regularly in the United States and is associated with serious health events, including death. Methods: Using data from poison centers participating in the Researched Abuse, Diversion and Addiction-Related Surveillance (RADARS) System, exposures in children younger than 6 years, involving buprenorphine, fentanyl, hydrocodone, hydromorphone, methadone, morphine, and oxycodone (January 2003 to June 2006), were quantified and described. Results: We identified 9,179 children exposed to a prescription opioid. The median age was 2.0 years (range newborn to 5.5 years), and 54% were boys. Nearly all exposures involved ingestion (99%) and occurred in the home (92%). Exposures to any opioid were associated with 8 deaths, 43 major effects, and 214 moderate effects. Of 51 patients who experienced a major effect or death, 35 were treated with naloxone: a beneficial response was documented in 34 patients. All 5 exposures to buprenorphine associated with a major effect were treated with naloxone, and a beneficial response was recorded in all 5. Nearly all exposures were to medications prescribed for adults in the household. The number of prescriptions filled for an opioid in an area correlated well with exposures in young children in the same area; children have access to household members' prescription drugs. Conclusion: Young children are exposed to prescription opioids, typically prescribed for other patients, resulting in major health effects and death.

Banta-Green CJ; Maynard C; Koepsell TD; Wells EA; Donovan DM. Retention in methadone maintenance drug treatment for prescription-type opioid primary users compared to heroin users. Addiction 104(5): 775-783, 2009. (28 refs.)

Aims: To assess retention in methadone maintenance treatment for prescription-type opioid primary (PTOP) users compared to heroin users. Design and participants A retrospective cohort study was carried out to examine the association between opiate types used on 12-month retention. The study population consisted of adults admitted to one of 11 not-for-profit methadone maintenance clinics in 2004 and 2005 throughout Washington State (n = 2308). Logistic regression analyses with fixed effects for treatment agencies were conducted. Measurements Opiate use type in past 30 days: any heroin use or primary prescription opioid without heroin use. Demographics, other drugs used, self-reported medical and psychiatric concerns, social, familial and legal issues, public assistance type and housing stability were documented at intake using a comprehensive biopsychosocial instrument, the Treatment and Assessment Reports Generation Tool. Findings The odds of being retained in treatment for PTOP compared to heroin users not adjusting for other factors was 1.33 (95% confidence interval [CI], 1.03, 1.71). In the final logistic regression model the odds of retention for PTOP compared to heroin users was 1.25 (95% CI, 0.93, 1.67), indicating that there was no statistically significant difference in treatment retention by opiate type after adjusting for demographics, treatment agencies, other drug use, public assistance type, medical, psychiatric, social, legal and familial factors. Conclusion: The findings of this study suggest that PTOP can be treated at methadone maintenance treatment facilities at least as effectively as heroin users in terms of treatment retention.

Becker WC; Fiellin DA; Gallagher RM; Barth KS; Ross JT; Oslin DW. The association between chronic pain and prescription drug abuse in veterans. Pain Medicine 10(3): 531-536, 2009. (27 refs.)

We sought to investigate the association between chronic pain and self-reported prescription drug abuse in a large cohort of patients referred from primary care for a behavioral health assessment. We performed a cross-sectional analysis of responses to a telephone assessment administered to patients referred for a behavioral health evaluation between April 25, 2005 and October 31, 2007. We conducted descriptive statistics and investigated multivariable associations. Multivariable analyses included age, gender, race, financial status, employment, current smoking, drinking problem, past-year illicit drug use, depression, and chronic pain. Veterans referred from primary care (N = 6,377). Mean age of the sample was 56.5 years with a range of 19-97. The majority of respondents was white, unmarried, and was unemployed. Nearly 5% of the sample reported past 6-month prescription drug abuse. On multivariable analysis, younger age, possible depression (odds ratio [OR] 1.9; 1.3-2.8), probable depression (OR 2.4; 1.6-3.4), smoking (OR 1.4; 1.1-1.8), illicit drug use (OR 2.8; 2.2-3.7), and chronic pain (OR 1.9; 1.4-2.5) were associated with prescription drug abuse. We have identified specific variables associated with self-reported prescription drug abuse in primary care patients. Chronic pain is associated both with an indication for prescribing opioids and with abuse of prescription medications. Clinicians are encouraged to follow treatment algorithms when managing patients with chronic pain as a method for reducing misuse.

Becker WC; Meghani SH; Barth KS; Wiedemer N; Gallagher RM. Characteristics and outcomes of patients discharged from the opioid renewal clinic at the Philadelphia VA Medical Center. American Journal on Addictions 18(2): 135-139, 2009. (13 refs.)

The Opioid Renewal Clinic (ORC) is a pharmacist-run program that assists primary care providers in the management of chronic pain patients with aberrant behavior or high risk of prescription opioid abuse. In this study, charts of all discharged patients over a 22-month span (n = 86) were reviewed for outcomes for two years after discharge. The most frequent reason for discharge from the program was recurrent positive urine drug screens for illicit substances (n = 40; 47%). Only 15 (17%) were seen for addiction treatment in the two-year follow-up period. Forty-one percent of patients (n = 35) were prescribed opioids within two years of discharge. There was a positive correlation between length of time in the ORC and receipt of opioids post discharge. These outcomes reveal areas of need in the management of this complex population.

Bjornsdottir I; Almarsdottir AB; Traulsen JM. The lay public's explicit and implicit definitions of drugs. Research in Social and Administrative Pharmacy 5(1): 40-50, 2009. (12 refs.)

Background: The research project: Public Beliefs about Medicine was initiated in 2001, aiming at exploring people's views, hopes, and fears with respect to drugs/medicines, now and in the future. Objectives: A part of the research project mapping Public beliefs about medicines aimed at getting the Public to discuss definitions of drugs/medicines to grasp their explicit and implicit definitions and understand their point of reference when using the term(s). Methods: Eight focus groups were conducted in urban and rural Iceland, with 42 participants of both genders and varying age, a fifty-fifty mix of lay and educated groups. The interviews were transcribed verbatim and excerpts translated into English. Results: The direct question about definition of drugs generally resulted in a consensus among the informants about drugs/medicines being used to combat diseases and/or symptoms. Some included only prescribed or physician-recommended drugs in their definitions, others also over-the-counter products. Inclusion/exclusion of vitamins, food supplements, herbal remedies, functional foods, and illicit drugs was discussed without consensus and defining drugs in chemical terms or as interfering with bodily functions also occurred. New nuances emerged spontaneously later in the discussions, like viewing drugs as profit-making products, preferably prudently marketed, wishing information about "new release" drugs for the informants' diseases, and being concerned about side effects, overuse, misuse, and abuse. Other implicit definitions included viewing drugs as a product-service package, or as a necessary evil and/or as products with increasing potency and associated future problems or considering drugs to exert unreliable minor influence. Conclusion: Professionals should be aware of the variety of lay people's drug definitions when discussing drugs/medicines with them to avoid misunderstandings caused by definition discrepancies.

Boyd CJ; McCabe SE. Coming to terms with the nonmedical use of prescription medications. (editorial). Substance Abuse Treatment, Prevention and Policy 3: e-article 22, 2008. (8 refs.)

In this commentary we highlight limitations with the way nonmedical use of prescription medications has been measured in U. S. national studies. We also offer an alternative way of conceptualizing the nonmedical use of prescription medications for future study.

Bruce RD; Govindasamy S; Sylla L; Kamarulzaman A; Altice FL. Lack of reduction in buprenorphine injection after introduction of co-formulated buprenorphine/naloxone to the Malaysian market. American Journal of Drug and Alcohol Abuse 35(2): 68-72, 2009. (26 refs.)

Background: Diversion of buprenorphine (BPN) has been described in settings where it is legally prescribed and has resulted in increasing concern. To address this concern, co-formulation of buprenorphine/naloxone (BPN/NLX) replaced buprenorphine alone in Malaysia in December 2006. Methods: To assess the significance of BPN/NLX introduction, 41 BPN/NLX injectors in Kuala Lumpur, Malaysia were recruited using a modified snowball recruitment technique. Results: In January 2007, all subjects had previously injected BPN alone. During the transition from injecting BPN alone to co-formulated BPN/NLX, the mean daily BPN injection dose increased from 1.88 mg (range 1.0-4.0 mg) to 2.49 mg/day (p .001). Overall, 18 (44%) subjects increased their daily amount of injection while 22 (54%) had no change in dose; only one subject reduced the amount of injection. Development of opioid withdrawal symptoms was the primary outcome, however the only symptom that was significantly associated with BPN/NLX dosage was the report of stomach pains (p = .01). In logistic regression analysis, the development of opioid withdrawal symptoms was associated with increased benzodiazepine injection and increased syringe sharing. Conclusion and Scientific Significance: These data suggests that the introduction of BPN/NLX did not reduce injection related risk behaviors such as syringe sharing and was associated with increased benzodiazepine use. Evidence-based approaches to treat BPN injection are urgently needed.

Brulotte J; Vohra S. Epidemiology of natural health products-drug interactions: Identification and evaluation. (review). Current Drug Metabolism 9(10): 1049-1054, 2008. (96 refs.)

Increasing numbers of adults and children around the world are using natural health products (NHPs) to promote wellbeing or alleviate illness. Although often considered safe due to their natural origin, NHPs are potentially pharmacologically active and, therefore may cause harm. Limited data suggest that NHPs can interact with other NHPs as well as with prescription medication and foods. Although some common NHP-drug interactions have been identified and studied, in general, the epidemiology of NHP-drug interactions is not well-understood, in part because these harms are often underreported. Users rarely disclose NHP use to their physicians, and physicians rarely enquire about such use. Even if physicians become aware of a potential NHP-drug interaction, passive surveillance systems mean that it is left to the physician's discretion whether or not to report it to the proper authority. It is likely that active surveillance of NHP-drug interactions would result in increased reporting of NHP-related harms as well as better quality reports. Subsequent lab investigation would determine if adulteration, contamination, species misidentification, or misuse was responsible for the harm, or if a pharmacokinetic or pharmacodynamic NHP-drug interaction occurred. This kind of thorough detection and investigation of potential NHP-drug interactions is necessary to ensure the safe use of NHPs.

Butler SF; Budman SH; Licari A; Cassidy TA; Lioy K; Dickinson J et al. National addictions vigilance intervention and prevention program (NAVIPPRO (TM)): a real-time, product-specific, public health surveillance system for monitoring prescription drug abuse. Pharmacoepidemiology and Drug Safety 17(12): 1142-1154, 2008. (31 refs.)

Purpose: The National Addictions Vigilance Intervention and Prevention Program (NAVIPPRO (TM)) is a scientific, comprehensive risk management program for scheduled therapeutics. NAVIPPRO (TM) provides post-marketing surveillance, signal detection, signal verification and prevention and intervention programs. Here we focus on one component of NAVIPPRO (TM) surveillance, the Addiction Severity Index-Multi media Version (R) (ASI-MV (R)) Connect, a continuous, real-time, national data stream that assesses pharmaceutical abuse by patients entering substance abuse treatment by collecting product-specific, geographically-detailed information. Methods We evaluate population characteristics for data collected through the ASI-MV (R) Connect in 2007 and 2008 and assess the representativeness, geographic coverage, and timeliness of report of the data. Analyses based on 41923 admissions to 265 treatment centers in 29 states were conducted on product-specific opioid abuse rates, source of drug, and route of administration. Results ASI-MV (R) Connect data revealed that 11.5% of patients reported abuse of at least one opioid analgesic product in the 30 days prior to entering substance abuse treatment; differences were observed among sub-populations of prescription opioid abusers, among products, and also within various geographic locations. Conclusions: The ASI-MV (R) Connect component of NAVIPPRO (TM) represents a potentially valuable data stream for post-marketing surveillance of prescription drugs. Analyses conducted with data obtained from the ASI-MV (R) Connect allow for the characterization of product-specific and geospatial differences for drug abuse and can serve as a tool to monitor responses of the abuse population to newly developed "abuse deterrent" drug formulations. Additional data, evaluation, and comparison to other systems are important next steps in establishing NAVIPPRO (TM) as a comprehensive, post-marketing surveillance system for prescription drugs.

Cicero TJ; Lynskey M; Todorov A; Inciardi JA; Surratt HL. Co-morbid pain and psychopathology in males and females admitted to treatment for opioid analgesic abuse. Pain 139(1): 127-135, 2008. (27 refs.)

The purpose of this study was to identify co-morbidity in a national sample (N = 1408) of males and females entering treatment for opioid abuse. Our sample was primarily white, lived in small urban, suburban or rural locations (80%,), and was well-educated. Chronic pain was a symptomatic feature in over 60% of all subjects. Furthermore, 79% of male and 85% of female prescription opioid abusers indicated that their first exposure to an opioid was a legitimate prescription for pain which subsequently led 60-70% to misuse to get high. Our data also indicate that the use of prescription opioids to get high represents the end stage on a continuum of substance abuse, beginning at a very early age. The age of first alcohol use, getting drunk, smoking, use of marijuana, stimulants and other non-opioid prescription or illicit drugs occurred very early (13-19) in prescription opioid misusers/abusers, whose first use of opioids did not occur, on average, until age 22. Finally, most of the sample had sought treatment 3 or more times for substance abuse prior to the treatment admission in which the survey was completed. Physical and mental health were very poor in both male and female prescription opioid abusers, but females were more ill and dysfunctional than males in all physical and particularly emotional domains. Our results suggest that a small number of "at risk" opioid naive pain patients, who might abuse their therapeutically appropriate opioid analgesics, can be identified by assessing pre- and co-morbid substance abuse and significant psychopathology.

Clements RM. Reducing psychotropic medications in elderly rehabilitation inpatients with a fall-related admission: How often is it happening? Geriatrics & Gerontology International 8(3): 139-142, 2008. (13 refs.)

Aim: To assess the frequency of psychotropic medication withdrawal in an inpatient geriatric rehabilitation population with a fall-related admission diagnosis. Methods: A retrospective medical record audit. The medical records department randomly selected 100 patients admitted between October 2006 and April 2007 to the geriatric rehabilitation ward of Casey Hospital with a fall-related admission diagnosis. Results: The population was predominantly female (71%) and elderly (average age, 80 years) with the vast majority of patients living at home (88%) prior to admission. Twenty-six of 49 (53%) of patients admitted on psychotropic medication were on a reduced regime by discharge (reduced dose or number of psychotropic medications). Just 7 of 100 patients had an increased psychotropic medication regime by discharge. Benzodiazepines were far more likely to be reduced (20/24, 83%) than other psychotropic medications. Conclusion: This audit does suggest an acceptable awareness in this geriatric rehabilitation setting of the fall risk posed by psychotropic medication. It needs to be further explored why benzodiazepines are so much more likely to be reduced in this population than other psychotropic medications, despite those other types also posing a significant fall risk.

Croissant B; Grosshans M; Diehl A; Mann K. Oxcarbazepine in rapid benzodiazepine detoxification. American Journal of Drug and Alcohol Abuse 34(5): 534-540, 2008. (21 refs.)

Objective: This study aims at evaluating the tolerability and efficacy of the antiepileptic drug oxcarbazepine in benzodiazepine detoxification in ten patients. Methods: In this case study of an inpatient withdrawal program, each of the ten patients was detoxified using oxcarbazepine and completed withdrawal successfully without the occurrence of withdrawal symptoms. The detoxification program followed an outlined dosage scheme with oxcarbazepine increase and benzodiazepine tapering. Results: The rapidity of benzodiazepine detoxification using oxcarbazepine was remarkable, benzodiazepine withdrawal being completed in as little as 11 days. Conclusions: The results support the assumption that oxcarbazepine is a valuable drug for inpatient benzodiazepine withdrawal programs.

Culberson JW Ziska M. Prescription drug misuse/abuse in the elderly. Geriatrics 63(9): 22+, 2008. (25 refs.)

One quarter of the prescription drugs sold in the United States are used by the elderly, often for problems such as chronic pain, insomnia, and anxiety. The prevalence of abuse may be as high as 11% with female gender, social Isolation, depression, and history of substance abuse Increasing risk. Screening instruments for prescription drug abuse have not been validated in the geriatric population. Benzodiazepines, opiate analgesics, and some skeletal muscle relaxants may result in physical dependence; however, tolerance, withdrawal syndrome, and dose escalation may be less common in the older patient. Lower doses may decrease the risk of abuse and dependence; however, fear of abuse often results in a failure to adequately treat symptoms such as anxiety, pain, and insomnia.

Daughton CG; Ruhoy IS. The afterlife of drugs and the role of pharmecovigilance. Drug Safety 31(12): 1069-1082, 2008. (62 refs.)

The prescribing and usage of medications (for both humans and domestic animals) have ramifications extending far beyond the traditional objectives of conventional medical care. The healthcare industry has an environmental footprint that includes the active pharmaceutical ingredients (APIs) from medications, residues of which can establish themselves as environmental pollutants. This occurs by a variety of routes, but primarily from excretion, bathing and disposal. Many parallels exist between healthcare and the protection and remediation of the environment, spanning the stages from symptomology and diagnosis to treatment. The critical role played by pharmacovigilance in healthcare has a counterpart with the ecological environment. The term ecopharmacovigilance has been used with respect to the unforeseen consequences APIs can have once they enter the environment. We propose that conventional phannacovigilance could be expanded to encompass environmental concerns - a concept we term pharmEcovigilance - as a way to unify the parallel but interconnected needs for protecting both human and ecological health. To convey the scope of a pharmEcovigilance programme, we provide an overview of the occurrence of APIs as environmental pollutants, their ramifications for human health and the environment and some of the ways in which their impact could be reduced or minimized. The major areas discussed include: (i) the routes by which APIs become contaminants in the environment; (ii) the hazards of leftover drugs as a result of stockpiling and from disposal to sewage, which can also eventually contribute to the contamination of drinking water; (iii) why drugs accumulate unused; and (iv) the benefits for humans and the environment that could accrue from reducing the accumulation of leftover drugs and the subsequent introduction of APIs into the environment. A broad spectrum of actions could be taken by prescribers (including veterinarians) and the healthcare industry at large (including manufacturers and insurers) to reduce the release or introduction of APIs to the environment. Most significantly, however, a major reason to consider implementing a pharmEcovigilance programme - beyond reducing the environmental footprint of healthcare - is the previously unforeseen collateral benefit in making further progress in optimizing the delivery, effectiveness, outcomes and cost of healthcare, as well as improving safety for humans, pets and wildlife. For this reason, the relationships that healthcare professionals and patients have with medications might also include consideration of pharmEcovigilance. Like any profession that deals with chemicals, perhaps a major challenge to be faced is how to ensure the sustainability (and minimize the life cycle exposure hazards) of a chemical-based, chemical-centric society in the most cost-effective and safest manner. Given that the medical community is a major source of numerous 'exotic' chemical pollutants in the environment (with thousands of chemically distinct APIs in current use), albeit at very low levels, an imperative could be created for designing and implementing approaches for reducing and controlling this source of pollution. With reduced wastage of medications, in part driven by appropriate or rational prescribing and dispensing, the ecological footprint of medicine could be greatly reduced, with concomitant improvements in many aspects of healthcare.

Demyttenaere K; Bonnewyn A; Bruffaerts R; De Girolamo G; Gasquet I; Kovess V; Haro JM; Alonso J. Clinical factors influencing the prescription of antidepressants and benzodiazepines: Results from the European Study of the Epidemiology of Mental Disorders (ESEMeD). Journal of Affective Disorders 110(1/2): 84-93, 2008. (25 refs.)

Objective: To examine factors associated with the use of antidepressants (AD) and benzodiazepines (BZD) in 6 European countries. Methods: A cross-sectional, population-based study was conducted in: Belgium, France, Germany, Italy, the Netherlands and Spain. 21,425 non-institutionalized individuals aged 18 years and over were interviewed using the third version of the Composite International Interview (C[D]-3.0). Respondents were asked about AD and BZD use, and whether they consulted formal health services for emotional problems in the previous year. Sociodemographic variables, presence of mood/anxiety disorders and of painful physical symptoms were collected. Results: 34.38% and 9.17% of the sample reported the use of AD and BZD respectively in the previous 12 months. Only 29.95% of subjects with a 12-month prevalence of major depressive episode (MDE) had been taking antidepressants. After controlling for several clinical and non-clinical factors, help seeking for emotional problems was the most important independent predictor for the use of AD or BZD (OR: 13.58 and 5.17, respectively). Higher age was the second important predictor (OR: 6.52 and 4.86, respectively). A 12-month or lifetime prevalence of MDE or an anxiety disorder were also predictors for AD or BZD use (OR for MDE: 5.00 and 2.82, OR for anxiety disorders: 2.13 and 1.85). Finally, the presence of painful physical symptoms also predicted the use of AD and BZD, while female gender, lower education and higher age predicted only the use of BZD. Conclusion: Less than one third of subjects with a 12-month prevalence of MDE had been taking antidepressants. But seeking help for emotional problems was a more important predictor of the use of ADs or BZDs than a formal (DSM-IV) psychiatric diagnosis, suggesting that usage of ADs is not always according to the licensed DSM-IV indication.

Denisco RA; Chandler RK; Compton WM. Addressing the intersecting problems of opioid misuse and chronic pain treatment. Experimental and Clinical Psychopharmacology 16(5): 417-428, 2008. (86 refs.)

Misuse of prescription opioid medications has continued as a major public health problem in the United States. Review of major epidemiologic databases shows that the prevalence of opioid misuse rose markedly through the 1990s and the early part of the current decade. In this same period of time, the number of prescriptions for chronic noncancer pain increased markedly, and the intersection of these two public health problems remains a concern. Further, despite some leveling off of the overall rate of prescription opioid misuse in the past several years, surveillance data show high and increasing mortality associated with these drugs. Analysis of the 2006 National Survey of Drug Use and Health indicates the increasing prevalence of prescription opioid misuse is associated more with an increase in the general availability of these medications than misuse of the medications by those who were directly prescribed them. National Institute on Drug Abuse initiatives to address the prescription opioid problem include programs to stimulate research in the basic and clinical sciences, and to educate physicians and other health personnel.

Dersh J; Mayer TG; Gatchel RJ; Polatin PB; Theodore BR; Mayer EAK. Prescription opioid dependence is associated with poorer outcomes in disabling spinal disorders. Spine 33(20): 2219-2227, 2008. (90 refs.)

Study Design. Prospective outcomes study involving patients with chronic disabling occupational spinal disorders (CDOSD) diagnosed with (n = 199) or without (n = 1124) postinjury opioid-dependence disorder (ODD), based on the Diagnostic and Statistical Manual of Mental Disorders-fourth edition cirteria. Objective. To determine whether prescription opioid dependence, assessed at the beginning of rehabilitation treatment, is associated with poorer treatment outcomes in patients with CDOSDs attending an interdisciplinary rehabilitation program. Summary of Background Data. Controversy exists regarding the risk of iatrogenic ODD and treatment outcomes when long-term opioid therapy is used in the treatment of chronic nonmalignant pain conditions. Methods. A consecutive sample of patients with CDOSDs [n = 1323; mean (SD) length of disability = 18.8 (20.7) months] attending a tertiary referral center received intensive physical reactivation and pain/disability management interventions, based on a functional restoration model, including detoxification from opioids. One-year outcomes included return to work, work retention, healthcare utilization, new surgeries, recurrent injuries, and disability claim settlement. Results. Prevalence of ODD in this CDOSD population on entering the rehabilitation program was 15%. Even after adjusting for relevant demographic factors and comorbid psychiatric disorders, opioid-dependent patients were 1.7 times [95% confidence interval (CI): 1.0, 2.7] less likely to return to work, 2 times (95% CI: 1.3, 3.0) less likely to retain work at the 1-year interview, and 1.7 times (95% CI: 1.2, 2.5) more likely to engage in healthcare utilization from new providers, compared with nonopioid-dependent patients. Conclusions. Iatrogenic prescription opioid dependence may be a risk factor for less successful long-term work and health outcomes, even after detoxification from opioids as part of an interdisciplinary functional rehabilitation program. Chronic prescription opioid dependence in this patient population is also associated with a significantly higher prevalence of comorbid psychiatric conditions, both axis I and II.

DeSantis AD; Webb EM; Noar SM. Illicit use of prescription ADHD medications on a college campus: A multimethodological approach. Journal of American College Health 56(3): 315-323, 2008. (24 refs.)

Objective: The authors used quantitative and qualitative methodologies to investigate college students' perceptions and use of illegal Attention Deficit Hyperactivity Disorder (ADHD) Stimulants during spring and summer 2006. Participants: From fall 2005 through fall 2006, the authors studied 1,811 undergraduates at a large, public, Southeastern research university in the United States. Methods: The authors administered Surveys to these students and conducted 175 in-depth interviews. Results: Of the study participants, 34% reported the illegal use of ADHD stimulants. Most illegal users reported using ADHD stimulants primarily in periods of high academic stress and found them to reduce fatigue while increasing reading comprehension, interest, cognition, and memory. Furthermore, most had little information about the drug and found procurement to be both easy and stigma-free. Conclusions: This study supplies a rich understanding of the growing national trend of illegal ADHD stimulant use. The authors discuss strategies for stemming the tide of ADHD stimulant use.

Dubois S; Bedard M; Weaver B. The impact of benzodiazepines on safe driving. Traffic Injury Prevention 9(5): 404-413, 2008. (48 refs.)

Objective. Benzodiazepines are prescribed to relieve anxiety and aid sleep. Studies demonstrate that benzodiazepines increase odds of crash involvement, but little evidence exists regarding their impact on crash responsibility. We examined the impact of benzodiazepines on crash responsibility by drug half-life and driver age, using a case-control design with drivers aged 20 and over involved in fatal crashes in the United States from 1993-2006. Methods. Drivers (all with BAC = 0) were classified as having no benzodiazepines detected versus short, intermediate, or long half-life benzodiazepines. Cases were drivers with at least one potentially unsafe driving action (UDA) in relation to the crash (e.g., speeding), a proxy measure for crash responsibility; controls had no UDAs recorded. Odds ratios (ORs) of any UDA by benzodiazepines half-life exposure were calculated, with adjustment for age, sex, other medication usage, and prior driving record. Results. Compared with drivers not using benzodiazepines, drivers taking intermediate or long half-life benzodiazepines demonstrated increased odds of an UDA from ages 25 (intermediate OR: 1.59; 95% CI = 1.08, 2.33; long OR: 1.68; 95% CI = 1.34, 2.12) to 55 (intermediate OR: 1.50; 95% CI = 1.09, 2.06; long OR: 1.33; 95% CI = 1.12, 1.57). Drivers taking short half-life benzodiazepines did not demonstrate increased odds compared to drivers not using benzodiazepines. Conclusions. Given the potential impact of benzodiazepines on driver safety, further experimental research is needed to better understand the effect of benzodiazepines on crash responsibility.

Dunn KE; Sigmon SC; Mcgee MR; Heil SH; Higgins ST. Evaluation of ongoing oxycodone abuse among methadone-maintained patients. Journal of Substance Abuse Treatment 35(4): 451-456, 2008. (29 refs.)

Prevalence of prescription opioid abuse has increased dramatically in recent years in the United States generally, and a similar pattern of increasing prescription opioid use has also been noted among patients seeking treatment for opioid dependence. This study presents results from an internal quality assurance project conducted by an outpatient methadone maintenance (MM) treatment clinic which sought to examine the extent of ongoing, oxycodone abuse among patients that might be going undetected with current urinalysis-testing methods. One hundred five MM patients provided 437 urine samples over a 6-week period. Samples were analyzed using the clinic's usual enzyme multiplied immunoassay test (EMIT) opiate assay (1300 ng/ml opiate cutpoint) and a supplemental oxycodone test strip (100 ng/ml oxycodone cutpoint). The EMIT assay identified only 6% (20/437) of samples as positive for oxycodone, whereas the oxycodone test strip indicated that 19% (83/437) tested positive for recent oxycodone use. Inspection of patient characteristics revealed that oxycodone users were more likely to report a prescription opioid as their primary drug at intake, be in MM treatment for a significantly shorter duration, and provide significantly more opioid- and cocaine-positive urine samples. Overall, these data illustrate the potential importance of monitoring for ongoing oxycodone use in MM clinics. Although future efforts should examine this question using more rigorous experimental methods, findings from this initial project have implications for clinical issues such as evaluating patient stability in treatment, making medication-dosing, decisions. and determining patient eligibility for methadone take-home privileges.

Elger BS. Prisoners' insomnia: To treat or not to treat? Medical decision-making in places of detention. Medicine, Science and the Law 48(4): 307-316, 2008. (43 refs.)

Insomnia is a frequent reason for medical and psychiatric consultation in prisons. Medical decision-making in correctional health care should be based on the same principles as outside correctional institutions. In places of detention, principles should be balanced according to the same criteria as outside correctional institutions, while taking into account the unique harm-benefit ratios related to the specific context. The aim of this paper was to examine the existing attitudes and ethical issues related to decision-making about insomnia evaluation and treatment in places of detention. An analysis of the ethical issues and an evidence-based review of the consequences of different attitudes and treatments with regard to prison medicine were carried out. Insomnia is a public health problem and requires adequate evaluation and treatment to avoid more serious health consequences both within and outside correctional institutions. Insomnia treatment in places of detention is an ethical dilemma, but there is no evidence-based reason to avoid benzodiazepines in prison completely and to use only neuroleptics and antidepressants, which might represent more dangerous and less efficient treatment. In prison medicine, should we even treat insomnia? Widely accepted ethical strategies of decision-making indicate that we should. Institutional guidelines on insomnia should be based on ethically sound decision-making that takes into account the available evidence.

Esimone CO; Okoye FBC; Nworu CS; Agubata CO. In vitro interaction between caffeine and some penicillin antibiotics against Staphylococcus aureus. Tropical Journal of Pharmaceutical Research 7(2): 969-974, 2008. (29 refs.)

Purpose: The aim of this study is to evaluate the in vitro interaction of some penicillins (amoxicillin, ampicillin and benzylpenicillin) and caffeine against Staphylococcus aureus. Method: The interaction between the penicillins and caffeine was studied using the Overlay Inoculum Susceptibility Disc (OLISD) method. Minimum inhibitory concentrations (MIC) of the drugs were determined separately and in combination with caffeine (5 and 10 mg/ml). Result: At 5 and 10 mg/ml, caffeine decreased the MIC of amoxicillin by 22 and 25 times respectively, while that of ampicillin was decreased by 6 and 8 times. The MIC of benzylpenicillin against Staphylococcus aureus was, however, increased by 59 and 40 times at caffeine concentrations of 5 and 10 mg/ml respectively. The inhibition zone diameter increment above 19 % (index of synergism in OLISD method) was recorded only for amoxicillin at amoxicillin concentrations of 7.81, 15.3, 31.25 and 62.5 mg/ml. Conclusion: The results of this study revealed that the concomitant use of caffeine and the studied antibiotics may potentiate the antibacterial effect of amoxicillin against Staphylococcus aureus, decrease that of benzylpenicillin and has virtually no effect on that of ampicillin. This implies that the intake of caffeine in form of analgesic combination or as tea, coffee, beverages or from other food sources may affect the effectiveness of a co - administered amoxicillin and bezylpenicillin.

Firestone M; Fischer B. A qualitative exploration of prescription opioid injection among street-based drug users in Toronto: Behaviours, preferences and drug availability. Harm Reduction Journal 5(1): e-article 130, 2008. (56 refs.)

Background: There is evidence of a high prevalence of prescription opioid (PO) and crack use among street drug users in Toronto. The purpose of this qualitative study was to describe drug use behaviours and preferences as well as the social and environmental context surrounding the use of these drugs among young and old street-based drug injection drug users (IDUs). Methods: In-depth interviews were conducted with 25 PO injectors. Topics covered included drug use history, types of drugs used, how drugs were purchased and transitions to PO use. Interviews were taped and transcribed. Content analysis was conducted to identify themes. Results: Five prominent themes emerged from the interviews: 1) Combination of crack and prescription opioids, 2) First injection experience and transition to prescription opioids, 3) Drug preferences and availability, 4) Housing and income and 5) Obtaining drugs. There was consensus that OxyContin and crack were the most commonly available drugs on the streets of Toronto. Drug use preferences and behaviours were influenced by the availability of drugs, the desired effect, ease of administration and expectations around the purity of the drugs. Distinct experiences were observed among younger users as compared to older users. In particular, the initiation of injection drug use and experimentation with POs among younger users was influenced by their experiences on the street, their peers and general curiosity. Conclusions: Given the current profile of street-based drug market in Toronto and the emergence of crack and POs as two predominant illicit drug groups, understanding drug use patterns and socio-economic factors among younger and older users in this population has important implications for preventive and therapeutic interventions.

Fischer B; Patra J; Cruz MF; Gittins J; Rehm J. Comparing heroin users and prescription opioid users in a Canadian multi-site population of illicit opioid users. Drug and Alcohol Review 27(6): 625-632, 2008. (55 refs.)

Introduction and Aims. Recent data suggest increasing prescription opioid and decreasing heroin use among street drug users, yet little is known on possible differential use characteristics and outcomes associated with these drugs. [While we recognise that, correctly, these populations would need to be labelled as opioid 'abusers' or 'non-medical users', we rely on the simpler terms 'use' and 'users' for the population under study within the wider context of them being engaged overall in illicit opioid use activities.] This study compared drug use, health, and socio-economic characteristics between heroin-only, prescription opioid-only and mixed heroin and prescription users in a Canadian multi-site cohort of illicit opioid and other drug users (OPICAN). Design and Methods. Data from the most recent (2005) multi-component assessment of the heroin-only (n=94), prescription opioid-only (n=304) and prescription opioid and heroin (n=86) cohort sub-samples were analysed. Based on bivariate analyses of variables of interest, a multinomial logistic regression analysis (MLRA) model was computed, comparing prescription opioid-only and prescription opioid and heroin groups to the heroin-only reference group, respectively. Results. Heroin-only users were found in two of the seven study sites. Based on the MLRA, prescription opioid-only and prescription opioid and heroin users, compared to heroin-only users, were more likely to: be older, use benzodiazepines and cocaine, use drop-in shelters and less likely to use walk-in clinics. Prescription opioid-only users were also more likely to: be white; receive legal income; use drugs by non-injection; have physical health problems; and use private physician services. Discussion and Conclusions. Our study underscores the increasing prevalence of prescription opioid compared to heroin use in the study population. Differences between prescription opioid-only and heroin-only users were more pronounced than differences between prescription opioid-only and prescription opioid and heroin users. Prescription opioid-only use may be associated with lowered health risks and social burdens, yet concerns regarding polysubstance use and drug sourcing arise. Challenges for targeted interventions are discussed.

Fischer B; Patra J; Cruz MF; Gittins J; Rehm J. Comparing heroin users and prescription opioid users in a Canadian multi-site population of illicit opioid users. Drug and Alcohol Review 190(1): 7-11, 2009. (20 refs.)

Introduction and Aims. Recent data suggest increasing prescription opioid and decreasing heroin use among street drug users, yet little is known on possible differential use characteristics and outcomes associated with these drugs. [While we recognise that, correctly, these populations would need to be labelled as opioid 'abusers' or 'non-medical users', we rely on the simpler terms 'use' and 'users' for the population under study within the wider context of them being engaged overall in illicit opioid use activities.] This study compared drug use, health, and socio-economic characteristics between heroin (H)-only, prescription opioid (PO)-only and mixed heroin and prescription (POH) users in a Canadian multi-site cohort of illicit opioid and other drug users (OPICAN). Design and Methods. Data from the most recent (2005) multi-component assessment of the H-only (n=94), PO-only (n=304) and POH (n=86) cohort sub-samples were analysed. Based on bivariate analyses of variables of interest, a multinomial logistic regression analysis (MLRA) model was computed, comparing PO-only and POH groups to the H-only reference group, respectively. Results. H-only users were found in two of the seven study sites. Based on the MLRA, PO-only and POH users, compared to H-only users, were more likely to: be older, use benzodiazepines and cocaine, use drop-in shelters and less likely to use walk-in clinics. PO-only users were also more likely to: be white; receive legal income; use drugs by non-injection; have physical health problems; and use private physician services. Discussion and Conclusions. Our study underscores the increasing prevalence of PO compared to heroin use in the study population. Differences between PO-only and H-only users were more pronounced than differences between PO-only and POH users. PO-only use may be associated with lowered health risks and social burdens, yet concerns regarding polysubstance use and drug sourcing arise. Challenges for targeted interventions are discussed.

Fleming MF; Davis J; Passik SD. Reported lifetime aberrant drug-taking behaviors are predictive of current substance use and mental health problems in primary care patients. Pain Medicine 9(8): 1098-1106, 2008. (32 refs.)

The aim of this report is to determine the frequency of aberrant drug behaviors and their relationship to substance abuse disorders in a large primary sample of patients receiving opioids for chronic pain. The data utilized for this report was obtained from 904 chronic pain patients receiving opioid therapy from their primary care physician. A questionnaire was developed based on 12 aberrant drug behaviors reported in the clinical literature. The diagnosis of a current substance use disorder was determined using Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition(DSM-IV) criteria. The average duration of chronic pain in the sample was 16 years and for opioid therapy, 6.4 years. Of the patients, 80.5% reported one or more lifetime aberrant drug behaviors. The most frequent behaviors reported included early refills (41.7%), increase dose without physician consent (35.7%), and felt intoxicated from opioids (32.2%). Only 1.1% of subjects with 1-3 aberrant behaviors (N = 464, 51.2%) met DSM-IV criteria for current opioid dependence compared with 9.9% of patients with four or more behaviors (N = 264, 29.3%). Persons with positive urine toxicology tests for cocaine were 14 times more likely to report four or more behaviors than no behaviors (14.1% vs1.1%). A logistic model found that subjects who reported four or more aberrant behaviors were more likely to have a current substance use disorder (odds ratio [OR] 10.14; 3.72, 27.64), a positive test for cocaine (odds ratio [OR] 3.01; 1.74, 15.4), an Addiction Severity Index (ASI) psychiatric composite score > 0.5 (OR 2.38; 1.65, 3.44), male gender (OR 2.08: 1.48, 2.92), and older age (OR 0.69; 0.59, 0.81) compared with subjects with three or fewer behaviors. Pain levels, employment status, and morphine equivalent dose do not enter the model. Patients who report four or more aberrant drug behaviors are associated with a current substance use disorder and illicit drug use, whereas subjects with up to three aberrant behaviors have a very low probability of a current substance abuse disorder. Four behaviors -- oversedated oneself, felt intoxicated, early refills, increase dose on own -- appear useful as screening questions to predict patients at greatest risk for a current substance use disorders.

Focazio MJ; Kolpin DW; Barnes KK; Furlong ET; Meyer MT; Zaugg SD et al. A national reconnaissance for pharmaceuticals and other organic wastewater contaminants in the United States - II) Untreated drinking water sources. Science of the Total Environment 402(2-3): 201-216, 2008. (57 refs.)

Numerous studies have shown that a variety of manufactured and natural organic compounds such as pharmaceuticals, steroids, surfactants, flame retardants, fragrances, plasticizers and other chemicals often associated with wastewaters have been detected in the vicinity of municipal wastewater discharges and livestock agricultural facilities. To provide new data and insights about the environmental presence of some of these chemicals in untreated sources of drinking water in the United States targeted sites were sampled and analyzed for 100 analytes with sub-parts per billion detection capabilities. The sites included 25 ground- and 49 surface-water sources of drinking water serving populations ranging from one family to over 8 million people. Sixty-three of the 100 targeted chemicals were detected in at least one water sample. Interestingly, in spite of the low detection levels 60% of the 36 pharmaceuticals (including prescription drugs and antibiotics) analyzed were not detected in any water sample. The five most frequently detected chemicals targeted in surface water were: cholesterol (59%, natural sterol), metolachlor (53%, herbicide), cotinine (51%, nicotine metabolite), beta-sitosterol (37%, natural plant sterol), and 1,7-dimethylxanthine (27%, caffeine metabolite); and in groundwater: tetrachloroethylene (24%, solvent), carbamazepine (20%, pharmaceutical), bisphenol-A (20%, plasticizer), 1,7-dimethylxanthine (16%, caffeine metabolite), and tri (2-chloroethyl) phosphate (12%, fire retardant). A median of 4 compounds were detected per site indicating that the targeted chemicals generally occur in mixtures (commonly near detection levels) in the environment and likely originate from a variety of animal and human uses and waste sources. These data will help prioritize and determine the need, if any, for future occurrence, fate and transport, and health-effects research for subsets of these chemicals and their degradates most likely to be found in water resources used for drinking water in the United States.

Fonad E; Emami A; Wahlin TBR; Winblad B; Sandmark H. Falls in somatic and dementia wards at community care units. Scandinavian Journal of Caring Sciences 23(1): 2-10, 2009. (57 refs.)

Falls and fall injuries are common problems for patients at nursing homes in Sweden. Impaired cognitive function, a poor sense of orientation and a high intake of medicine, can lead to an increase in falls among older people. The objective of this study was to investigate the associations between falls and: fall risks, fractures, the use of physical restraints and the use of certain medications in somatic and dementia wards, respectively. The study design is ecological, and aggregated data regarding falls, fall risk assessments, fractures, the use of physical restraints and medication were collected between 2000 and 2003. The Pearson correlation analysis and regression analyses were used to investigate associations between fall risks, medication, fractures, wheelchair-bound situations, bed rails and falls. The total number of reported fall incidents was 2651; of these, 737 incidents were registered in dementia wards and 1914 in somatic wards. Dementia wards and somatic wards differed regarding falls and fractures, as it was only in dementia wards that falls were associated with fractures. There was also a significant correlation between falls and assessed risk of falling, the use of certain medication, and physical restraints such as wheelchairs and bed rails in dementia wards. Falls at somatic wards were associated with the use of sleeping pills with benzodiazepines. For dementia wards there were associations between falls and fractures, physical restraints and the use of certain medications. Fractures were associated with the use of neuroleptics, sleeping pills and sleeping pills with benzodiazepines. At somatic wards, falls correlated with the use of sleeping pills with benzodiazepines, and with the use of wheelchairs and bed rails.

Ford J; Schroeder R. Academic strain and non-medical use of prescription stimulants among college students. (review). Deviant Behavior 30(1): 26-53, 2009. (89 refs.)

Recent research indicates that the prevalence of non-medical prescription drug use is now greater than the prevalence of other illicit drug use, with the exception of marijuana. Existing research focuses on demographic characteristics of users, risk factors and motivations for use, and sources of diversion. A significant gap in the extant literature is an examination of theoretical predictors of use. Using data from the Harvard School of Public Health's College Alcohol Study, the current research addressed this limitation by applying Agnew's general strain theory to the study of non-medical prescription drug use. Specifically, we examine whether academic strain is associated with the non-medical use of prescription stimulants. Findings are supportive of general strain theory, as students who experience academic strain report higher levels of depression, our measure of negative affect, and students who report higher levels of depression are more likely to report the non-medical use of prescription stimulants.

Ford JA. Nonmedical prescription drug use among adolescents: The influence of bonds to family and school. Youth & Society 40(3): 336-352, 2009. (81 refs.)

There has been a tremendous increase in the prevalence of nonmedical prescription drug use among adolescents in recent years. Research now indicates that the prevalence of nonmedical prescription drug use is greater than the prevalence of other illicit drug use, excluding marijuana. Despite these recent trends, there is a dearth of research in the social sciences on this issue. Furthermore, existing research on this topic is largely atheoretical. Using the 2005 National Survey on Drug Use and Health, a nationally representative survey of persons age 12 and older, the current study examines the impact of social bonds to family and school on nonmedical prescription drug use among adolescents. The findings provide support for social control theory. Adolescents with strong bonds to family and school are less likely to report nonmedical prescription drug use. Important implications and future research needs are discussed.

Ford JA; Rivera FI. Nonmedical prescription drug use among Hispanics. Journal of Drug Issues 38(1): 285-310, 2008. (77 refs.)

Past research shows distinct racial/ethnic differences in substance use. Given the changing racial/ethnic composition of the United States, continued research in this area is important This is especially true for Hispanics, the fastest growing and largest minority group in the United States. One area of particular importance is nonmedical prescription drug use. The rate of nonmedical prescription drug use has increased substantially in recent years, and current research shows that the prevalence of nonmedical prescription drug use is now greater than the prevalence of the use of illicit drugs other than marijuana. With an emphasis on Hispanics, the current study examines racial/ethnic variation in nonmedical prescription drug use using a large, national sample of adolescents and young adults. Findings indicate that Hispanics are less likely to report nonmedical prescription drug use than Whites, but more likely to report use than Blacks and Asians. Additional analyses, conducted using Hispanic respondents only, indicate that acculturation is significantly associated with nonmedical prescription drug use.

Formiga F; Navarro M; Duaso E; Chivite D; Ruiz D; Perez-Castejon JM et al. Factors associated with hip fracture-related falls among patients with a history of recurrent falling. Bone 43(5): 941-944, 2008. (29 refs.)

Background: People who have Suffered falls are at greater risk of falling again. We Study the characteristics of falls leading to hip fracture in people with a history of recurrent falls, comparing them with those of people with a history of sporadic falling. Materials and methods: Analysis of the characteristics of a sample of 1225 patients consecutively admitted to six hospitals because of a hip fracture secondary to a fall (index fall) - index fall characteristics (location, time and the possible cause of the fall: intrinsic, extrinsic or combined risk factors) were also determined. Patients with a history of three or more falls (recurrent fallers) in the year prior to the index fall were identified as high-risk fillers: those with less than three falls were considered to be sporadic fallers. Results: The mean number of fills in the year prior to the index fall was 1.7 +/- 6.5; 227 patients (22%) had experienced three or more falls within that period. Most index falls (880, 71.8%) took place at the patient's home, 232 (18.95%) in the street and 113 (9.2%) elsewhere; most (892, 72.9%) took place during daytime. Multiple stepwise logistic regression analysis showed that recurrent fallers were characterized by poorer baseline independence for activities of the daily living, a prior diagnosis of dementia, greater use of prescription drugs and a greater use of neuroleptics. For frequent fallers, the index fall was more often associated with an intrinsic factor than for sporadic fallers. Conclusions: A significant percentage of patients experiencing a fall followed by hip fracture have a history of recurrent failing in the year prior to a fall-related hip fracture. Poorer functional and cognitive status, polypharmacy and the use of neuroleptics are more prevalent in this subgroup of patients, and intrinsic factors as a cause of the fall are more common in this group. Whether these circumstances associated with recurrent falling are responsible for this higher prevalence of intrinsic, non-accidental falls should be addressed prospectively in order to implement preventive strategies.

Gallagher R. Methadone: An effective, safe drug of first choice for pain management in frail older adults. Pain Medicine 10(2): 319-326, 2009. (44 refs.)

Frail older adults have a high prevalence of chronic pain with major effects on function and quality of life. Many analgesics, including opioids, have adverse effects on older adults with multiple co-morbidities. Methadone has been increasingly used for analgesia in the last 10 years. However, a number of adverse events such as sleep-disordered breathing, methadone-induced torsades de pointes arrhythmias, as well as the "addiction stigma," have made people reluctant to use this medication. This article uses examples of five cases of pain in frail older adults living in a skilled nursing facility. Safe and effective use of methadone is illustrated with these cases. The pharmacology of methadone in frail elders is reviewed to demonstrate the specific benefits of the drug in older adults and how adverse events can be minimized. Methadone is an excellent choice for pain in frail older adults.

Gascon DJ; Spiller HA. Relationship of unemployment rate and rate of opiate exposure in Kentucky. Journal of Psychoactive Drugs 41(1): 99-102, 2009. (13 refs.)

There are conflicting reports regarding the relationship of labor supply and substance abuse. Opioid analgesic abuse, particularly with Oxycontin and hydrocodone, has increased in the past years. Kentucky is one of the states with the highest abuse rate for these substances. The purpose of this trend study is to determine if there is a relationship between unemployment rate and rate of opiate exposure in Kentucky. The time period analyzed was year 2000 to year 2005. Data were obtained from the United States Census Bureau, United States Department of Labor and the Kentucky Regional Poison Center. Three of the six years (2000, 2002, 2003) showed a significant positive correlation between higher unemployment rate and higher rate of opiate exposure. The largest negative correlation was noted in 2004, which was also the period wherein the unemployment rate decreased statewide. Correlations for the remaining two years (2001 and 2005) approached statistical significance.

Ghitza UE; Epstein DH; Preston KL. Self-report of illicit benzodiazepine use on the Addiction Severity Index predicts treatment outcome. Drug and Alcohol Dependence 97(1-2): 150-157, 2008. (56 refs.)

The relationship between pre-treatment illicit benzodiazepine use (days of use in the last 30) assessed on the Addiction Severity Index (ASI) and treatment outcome was investigated by retrospective analysis of data from two controlled clinical trials in 361 methadone maintained cocaine/opiate users randomly assigned to 12-week voucher- or prize-based contingency management (CM) or control interventions. Based on screening ASI, participants were identified as non-users (BZD-N; 0 days of use) or users (BZD-U; >0 days of use). Outcome measures were: urine drug screens (thrice weekly): quality of life and self-reported HIV-risk behaviors (every 2 weeks): and current DSM-IV diagnosis of cocaine and heroin dependence (study exit). In the CM group, BZD-U had significantly worse outcomes on in-treatment cocaine use, quality-of-life scores, needle-sharing behaviors, and current heroin dependence diagnoses at study exit compared to BZD-N. In the control group. BZD-U had significantly higher in-treatment cocaine use but did not differ from BZD-N on psychosocial measures. Thus, in a sample of non-dependent BZD users, self-reported illicit BZD use on the ASI, even at low levels, predicted worse outcome on cocaine use and blunted response to CM.

Gibson JE; Hubbard RB; Smith CJP; Tata LJ; Britton JR; Fogarty AW. Use of self-controlled analytical techniques to assess the association between use of prescription medications and the risk of motor vehicle crashes. American Journal of Epidemiology 169(6): 761-768, 2009. (22 refs.)

Case-crossover and case-series analyses are 2 epidemiologic approaches that can be used to evaluate the association of exposures with acute events. Using a primary care database from the United Kingdom and these 2 statistical approaches, the authors investigated the impact of using benzodiazepines, nonbenzodiazepine hypnotics, beta-blockers, selective serotonin reuptake inhibitors, tricyclic antidepressants, opioids, and antihistamines on the risk of motor vehicle crashes in 1986-2004. For 49,821 individuals aged 18-74 years, involvement in a motor vehicle crash was documented. The outcome of the case-crossover analyses varied according to the choice of control period, so the case-series approach was preferred. The first 4 weeks of treatment with a combined acetaminophen and opioid preparation was associated with an increased risk of motor vehicle crash (incidence rate ratio = 2.06, 99% confidence interval: 1.84, 2.32), as was use of an opioid alone (incidence rate ratio = 1.70, 99% confidence interval: 1.39, 2.08) and benzodiazepines (incidence rate ratio = 1.94, 99% confidence interval: 1.62, 2.32). Use of selective serotonin reuptake inhibitors, nonbenzodiazepine hypnotics, and antihistamines for more than 4 weeks was associated with motor vehicle crash, but shorter term use was not. The results obtained are broadly consistent with those from well-designed case-control studies and demonstrate how case-only techniques optimize the use of routinely collected data for epidemiologic studies.

Gjerde H; Normann PT; Pettersen BS; Assum T; Aldrin M Johansen U et al. Prevalence of alcohol and drugs among Norwegian motor vehicle drivers: A roadside survey. Accident Analysis and Prevention 40(5): 1765-1772, 2008. (31 refs.)

The objective of the study was to determine the prevalence of alcohol, psychoactive medicinal drugs and illegal drugs among drivers in Norwegian road traffic. Drivers of motor vehicles were selected from April 2005 to April 2006 in the south-eastern part of Norway, surrounding, but not including the capital, Oslo. A stratified two-stage cluster sampling procedure was used. In the first stage, random road sites and time intervals were selected, and in the second stage, drivers were stopped by random at those sites and time intervals. Altogether about 12,000 drivers were asked to provide a sample of oral fluid (saliva) and answer a few questions. Samples of oral fluid were obtained from 88% of the drivers, of whom 30% were females and 70% males. The prevalence of each drug was estimated by a weighted average using weights adjusted for under- or over-sampling compared to traffic statistics. Alcohol or drugs were found in oral fluid samples of 4.5% of the drivers; alcohol in 0.4%, psychoactive medicinal drugs in 3.4%, and illegal drugs in 1.0%. Illegal drugs were found more frequently in samples from younger drivers, while psychoactive medicinal drugs were more frequently found in samples from older drivers. Psychoactive medicinal drugs were more prevalent among females than males, among drivers stopped on working days rather than weekends, and among those who reported annual driving distances less than 16,000 km. The drugs found most frequently were zopiclone (1.4%), benzodiazepines (1.4%), codeine (0.8%), tetrahydrocannabinol (0.6%) and amphetamines (0.3%). Two or more drugs were found in 0.6% of the samples, corresponding to 15% of the drug-positive drivers.

Goel RK. Cigarette prices and illicit drug use: is there a connection? Applied Economics 41(9): 1071-1076, 2009. (14 refs.)

Using cross-sectional data from the United States, this study examines the effects of cigarette prices on the use of marijuana and illicit drugs (including marijuana, cocaine, heroin, inhalants, hallucinogens or any prescription drugs for nonmedical use). Five primary contributions of this work are: First, it provides evidence on the cross-relation between cigarettes and marijuana and illicit drugs. Second, besides the 'standard' control variables used in demand studies (namely, price, education and income), we also control for the influence of employment status and health insurance coverage. Third, this research provides new evidence on the price elasticity of cigarette demand for a recent time period. Fourth, the data used in this study are the latest available. Five, based on our results, implications for drug use policy are provided. Several key points may be noted from our results: (i) Cigarette demand seems to have become elastic in recent years. This is in contrast to findings in earlier years; (ii) Consumers seem to view cigarettes and marijuana as substitutes and cigarettes and illicit drugs as substitutes. (iii) Greater consumer income increases illegal drug use, but does not seem to have a significant impact on smoking and marijuana use; (iv) The unemployment rate and health insurance converge do not seem to significantly affect smoking or drug use; and (v) Policymakers should pay attention to the cross effects among drugs in framing drug use policies.

Gompel CHPAV; Wensing M; De Smet PAGM. Implementation of a discontinuation letter to reduce long-term benzodiazepine use: A cluster randomized trial. Drug and Alcohol Dependence 99(1-3): 105-114, 2009. (42 refs.)

Rationale: Although it is recommended to restrict long-term use of benzodiazepines, and considerable attention has been paid to this, long-term use continues to be a problem. An informative discontinuation letter for patients has been shown to reduce long-term benzodiazepine use in general practice. However, little is known about its wide scale implementation in primary care. Objective: To determine the effectiveness of an intensive Support programme for community pharmacies to send discontinuation letters to patients in cooperation with GPs. Methods: In a Cluster randomized trial, 43 control pharmacies received a written manual and 47 experimental pharmacies received an intensive Support programme. Primary outcome measures were the percentage of GPs who reviewed and returned lists of eligible patients and the percentage of long-term users who were sent it discontinuation letter within 4 months. Results: The outcomes did not differ for the experimental versus control groups: 38% and 31% of the GPs, respectively, returned the patient lists; 14% and 10% of all long-term users in the two groups, respectively, received the discontinuation letter within 4 months. Substantially more pharmacies in the experimental group than in the control group finally managed to send discontinuation letters (70% vs. 40%). Conclusion: About one third of the pharmacies in the control group and two thirds of the pharmacies in the intervention group finally implemented the discontinuation letter. However, this difference was not apparent in the primary outcome measures. It seems crucial to involve GPs more effectively ill implementation of the discontinuation letter.

Goodfellow A. Pharmaceutical intimact: Sex, death, and methamphetamine. Home Cultures 5(3, Special Issues): 271-300, 2008. (51 refs.)

In this article, I draw from ethnographic work conducted among residents of an "in-house" drug and alcohol treatment center in Baltimore, Maryland, to discuss the relationships born of pharmaceutical (ab)use. By looking in close detail at the autobiographical accounts of one man in treatment for addiction to methamphetamine, I attempt to chart the way life and death are at times brought into close proximity, and at others wedged firmly apart, by such things as love and avoidance. My concern is with the ethics of care that emerge through the so-called "small events" in everyday relations; that so often define a life or a relationship as falling under the category "normal" or "pathological". I ask how such things as the known demands placed on the body by the need to maintain or avoid relations, whether pharmaceutically mediated or not, come to bear on the decision to "let die" or the resurgence of moral worlds. I end by discussing the different aspects of relatedness revealed by the dependencies and alliances formed by the kinship between pharmaceuticals and humans. In compliance with current ethical research standards, the names of all informants have been changed to assure their anonymity.

Goodman K. Prosecution of physicians as drug traffickers: The United States' failed protection of legitimate opioid prescription under the Controlled Substances Act and South Australia's alternative regulatory approach. Columbia Journal of Transnational Law 47(1): 210-244, 2008. (26 refs.)

The Controlled Substances Act (CSA), the principal federal legislation criminalizing drug trafficking, was traditionally employed to combat the illegal drug trade, but prescription narcotics also fall within the law's purview. The CSA permits physicians to prescribe narcotics when acting in their professional capacity, but neither the statute nor its accompanying regulations explicitly defines these parameters. In contrast, the foreign jurisdiction of South Australia possesses textually equivalent drug trafficking legislation, yet its distinct regulatory paradigm-to codify unambiguously the boundaries of legitimate opioid prescription-effectively delineates the "safe zone " of physician prescribing practice. Unlike their South Australian counterparts, pain management physicians in the United States have therefore endured considerable governmental scrutiny. When criminal charges result, as in the recent high-profile case of U.S. v. Hurvitz, courts' current interpretation of the CSA imperils legitimate pain management practice, criminalizing what should remain lawful physician conduct. Specifically, federal circuits inappropriately conflate the CSA's "legitimate medical purpose " and "usual course of [] professional practice" requirements, as well as nullify any meaningful good-faith defense for practitioners. Ultimately, the current standard improperly lowers the CSA's mens rea requirement, permitting a finding of little more than medical negligence sufficient for criminal drug trafficking conviction in the United States.

Gwinnell E; Adamec C. The Encyclopedia of Drug Abuse. New York: Facts on File, 2008

With approximately 200 entries, this encyclopedia covers the range of illegal and legal drugs and how they impact society. Taking a global perspective, it incorporates information the worldwide drug trade and the effects of drug abuse in countries and cultures around the world, as well as in the United States. This comprehensive reference examines various types of drugs and how they function, risks, causes and consequences of abuse, social issues, psychiatric issues, means of prevention, law enforcement efforts, and drugs in special social groups. Appendixes provide statistics, directories of helpful groups and organizations, and resources for further research. Topics include: accidental overdose deaths; barbiturates; club drugs; drug dependence; gangs and drugs; narcotics; opiates; pregnancy and substance abuse; prescription drug abuse; treatment; and, violence.

Haider SI; Johnell K; Weitoft GR; Thorslund M; Fastbom J. The Influence of educational level on polypharmacy and inappropriate drug use: A register-based study of more than 600,000 older people. Journal of the American Geriatrics Society 57(1): 62-69, 2009. (41 refs.)

To investigate whether low educational attainment is associated with polypharmacy and potential inappropriate drug use (IDU) in older people. Cross-sectional register-based study. Sweden. Older people aged 75 to 89 who, filled at least one drug prescription between August and October 2005 and, consequently, were listed in the Swedish Prescribed Drug Register (SPDR) (N=626,258). Data were obtained from the SPDR, the inpatient register, and the education register. The main outcome measures were polypharmacy (concurrent use of >= 5 drugs), excessive polypharmacy (concurrent use of >= 10 drugs), and potential IDU. Four quality indicators developed by the Swedish National Board of Health and Welfare were used for the assessment of potential IDU: concurrent use of three or more psychotropic drugs, prescription of long-acting benzodiazepines, prescription of anticholinergics, and at least one clinically relevant potential drug-drug interaction (DDI). Comorbidity was measured using the Charlson Comorbidity Index. Subjects with low education had a higher probability of polypharmacy (odds ratio (OR)=1.11, 95% confidence interval (CI)=1.10-1.12), excessive polypharmacy (OR=1.15, 95% CI=1.13-1.17), and potential IDU (OR=1.09, 95% CI=1.07-1.17), after adjustment for age, sex, comorbidity, and type of residential area (urban or rural). Decreasing educational attainment was associated with a higher probability of using three or more psychotropic drugs and potential DDIs, whereas the opposite association was observed for anticholinergic drugs. Long-acting benzodiazepines showed no association. Elderly women with low education were slightly more likely to have polypharmacy, excessive polypharmacy, and potential IDU than men with low education. Overall, the ORs were modest and statistically significant because of the large sample size. Low educational attainment was associated with a greater likelihood of poypharmacy, excessive polypharmacy, and potential IDU in elderly Swedish persons, even after controlling for age, sex, place of residence, and comorbidity. Women with low education had slightly higher likelihood of receiving polypharmacy and potential IDU than men with low education. The recently established SPDR may be useful for continuous monitoring and for designing interventions to improve drug quality in low-educated elderly people.

Hakkarainen P; Metso L. Joint use of drugs and alcohol. European Addiction Research 15(2): 113-120, 2009. (39 refs.)

Aims: To determine the relationships between the different patterns of drinking and drug use in the general population. Design: The data from three nationwide surveys conducted in Finland in 1998, 2002 and 2004 were pooled into one dataset (n = 7,227). Participants: Population aged 15-69. Measurements: Use of illicit drugs was analyzed in relation to annual alcohol consumption, heavy episodic drinking, frequenting of pubs and restaurants, and the misuse of prescribed drugs. Respondents were divided into five different groups according to their involvement in drug cultures, i.e. 'no contact with drug cultures', 'some contact with drug cultures', 'drug experimenters and ex-users', 'cannabis users' and 'multidrug users'. Findings: The prevalence of drug use increased along with the annual alcohol consumption, and polysubstance use was most prevalent among heavy drinkers. Heavy episodic drinking and frequenting of pubs and restaurants increased in parallel with involvement in drug cultures. Misuse of prescribed drugs was most prevalent among multidrug users. Conclusions: Polysubstance use patterns reveal an interlacing of alcohol and drug cultures. However, standard measures employed in alcohol and drug research are insufficient to capture the phenomenon in detail, and more research and the development of new approaches are needed.

Hall AJ; Logan JE; Toblin RL; Kaplan JA; Kraner JC; Bixler D et al. Patterns of abuse among unintentional pharmaceutical overdose fatalities. Journal of the American Medical Association 300(22): 2613-2620, 2008. (29 refs.)

Context: Use and abuse of prescription narcotic analgesics have increased dramatically in the United States since 1990. The effect of this pharmacoepidemic has been most pronounced in rural states, including West Virginia, which experienced the nation's largest increase in drug overdose mortality rates during 1999- 2004. Objective To evaluate the risk characteristics of persons dying of unintentional pharmaceutical overdose in West Virginia, the types of drugs involved, and the role of drug abuse in the deaths. Design, Setting, and Participants Population- based, observational study using data from medical examiner, prescription drug monitoring program, and opiate treatment program records. The study population was all state residents who died of unintentional pharmaceutical overdoses in West Virginia in 2006. Main Outcome Measures: Rates and rate ratios for selected demographic variables. Prevalence of specific drugs among decedents and proportion that had been prescribed to decedents. Associations between demographics and substance abuse indicators and evidence of pharmaceutical diversion, defined as a death involving a prescription drug without a documented prescription and having received prescriptions for controlled substances from 5 or more clinicians during the year prior to death ( ie, doctor shopping). Results Of 295 decedents, 198 ( 67.1%) were men and 271 ( 91.9%) were aged 18 through 54 years. Pharmaceutical diversion was associated with 186 ( 63.1%) deaths, while 63 ( 21.4%) were accompanied by evidence of doctor shopping. Prevalence of diversion was greatest among decedents aged 18 through 24 years and decreased across each successive age group. Having prescriptions for a controlled substance from 5 or more clinicians in the year prior to death was more common among women (30 [ 30.9%]) and decedents aged 35 through 44 years ( 23 [ 30.7%]) compared with men ( 33 [ 16.7%]) and other age groups ( 40 [ 18.2%]). Substance abuse indicators were identified in 279 decedents ( 94.6%), with nonmedical routes of exposure and illicit contributory drugs particularly prevalent among drug diverters. Multiple contributory substances were implicated in 234 deaths ( 79.3%). Opioid analgesics were taken by 275 decedents (93.2%), of whom only 122 ( 44.4%) had ever been prescribed these drugs. Conclusion: The majority of overdose deaths in West Virginia in 2006 were associated with nonmedical use and diversion of pharmaceuticals, primarily opioid analgesics.

Hanlon JG; Hayter MA; Bould MD; Joo HS; Naik VN. Perceived sleepiness in Canadian anesthesia residents: A national survey. Canadian Journal of Anaesthesia 56(1): 27-34, 2009. (47 refs.)

Purpose: To compare the self-perceived sleepiness of Canadian anesthesia residents providing modified on-call ditties (12-16 h) vs. traditional on-call ditties (24 h). Methods: A 25-item online survey was distributed to all Canadian anesthesia residents who, at that time, were on, anesthesia rotations. The survey assessed resident demographics, perceived work patterns, and sleepiness, as well as their opinions on resident work hour reform. Self-perceived sleepiness was quantified using the validated Epworth sleepiness scale (ESS). Results: Three hundred eight of 400 (77%) eligible Canadian anesthesia residents completed the survey. Fort),three percent of residents who worked traditional on-call (duration 24.1 +/- 0.5 h) shifts and 48% of residents who worked modified on-call (duration 15.5 +/- 1.8 h) shifts met ESS criteria for excessive daytime sleepiness. Overall mean ESS scores did not differ significant); between. the traditional (9.1 +/- 4.9) and the modified call groups (9.5 +/- 4.8). Residents with an on-call frequency of >= 1:4 days or those who slept <= 2 It while on call perceived themselves as significantly more sleepy (P = 0.045 and P = 0.008, respectively). Six percent of residents admitted to taking "something other than caffeine" to stay awake on call. Conclusion: Many anesthesia residents do exhibit excessive daytime sleepiness, with a similar incidence for those working within either modified or traditional call systems. Our study suggests that sleepiness may be reduced by scheduling on-call duties no more frequently than one in every five nights and by ensuring that residents sleep more than 2 h while on call.

Havens JR; Stoops WW; Leukefeld CG; Garrity T; Carlson RG; Falck R et al. Prescription opiate misuse among rural stimulant users in a multistate community-based study. American Journal of Drug and Alcohol Abuse 35(1): 18-23, 2009. (26 refs.)

Objectives: The purpose of the current analysis was to examine the factors associated with prescription opiate misuse among stimulant users from rural counties in Arkansas, Kentucky, and Ohio (N = 714). Methods: Multiple logistic regression was utilized to determine the independent correlates of recent (prior 6 months) prescription opiate misuse. Results: More than half of participants (53.2%) reported prescription opiate misuse in the previous 6 months. Other drug use (heroin, cocaine, methamphetamine, and marijuana) and anxiety (Adjusted Odds Ratio: 2.04, 95% Confidence Interval: 1.60, 2.59) were independently associated with prescription opiate misuse. Chronic pain and other health indicators were not associated with prescription opiate misuse after adjustment for covariates. Conclusions: Results indicate that illicit drug involvement and psychiatric symptoms may be driving the high rates of prescription opiate misuse among rural stimulant users. These findings have implications for the provision of treatment in resource-deprived rural areas.

Hay JL; White JM; Bochner F; Somogyi AA. Antinociceptive effects of high dose remifentanil in male methadone-maintained patients. European Journal of Pain 12(7): 926-933, 2008. (38 refs.)

The treatment of acute pain in patients maintained on methadone is difficult due to increased pain sensitivity (hyperalgesia) and cross-tolerance to other opioids. This study aimed to investigate whether remifentanil elicits antinociception in methadone-maintained subjects in a dose-dependent manner. Eight chronic methadone-maintained subjects attended the testing session approxiamately 20 h after their normal methadone dose (range 50-110 mg day(-1)). Following a 20 min saline infusion, Subjects were administered intravenous remifentanil in seven increasing doses ranging from 0.5 to 3.5 mu g kg(-1) min(-1), each for 20 min. Testing was performed in the last 10 min of each infusion. The testing measures included nociception, as measured by the cold pressor test, withdrawal using the subjective opiate withdrawal scale (SOWS), and subjective opioid effects using the morphine-berizedrine group scale (MBG). Results showed dose-dependent increase in cold pressor tolerance time from baseline of 15.6 +/- 3.5 (mean +/- SEM) s up to 77.3 +/- 24.7 s during this closing protocol. During the infusion typical mu-opioid receptor agonist side effects were observed, but with no withdrawal. Methadone-maintained patients demonstrate significant tolerance to remifentanil and may require opioid doses 20-30 higher than required for the treatment of acute pain in opioid-naive patients.

Heyerdahl F; Bjornaas MA; Dahl R; Hovda KE; Nore AK; Ekeberg O et al. Repetition of acute poisoning in Oslo: 1-year prospective study. British Journal of Psychiatry 194(1): 73-79, 2009. (32 refs.)

Background: The repetition of acute poisoning occurs frequently. The intention may change between episodes and many poisonings are treated outside the hospital setting. Few studies have taken this into account. Aims: To quantify the repetition frequency regardless of the level of health care or the intention behind the poisoning, and to identify possible risk factors for repetition. Method: A prospective multicentre study of all acute poisonings in Oslo treated in hospital, at an out-patient clinic or by the ambulance service. Repetition was estimated using Kaplan-Meier calculations, and predictive factors were identified using Cox regression analysis. Results: The estimated 1-year repetition rate was 30% (95% CI 24-35). Independent predictors of repetition were middle age (30-49 years), poisoning with opiates or sedatives, unemployment or living on social welfare, a previous suicide attempt, and a history of psychiatric treatment. intention was not a significant predictor. Conclusions: Repetition of acute poisoning is high, irrespective of the level of healthcare and the intention behind the poisoning.

Inciardi JA; Surratt HL; Cicero TJ; Beard RA. Prescription opioid abuse and diversion in an urban community: The results of an ultrarapid assessment. Pain Medicine 10(3): 537-548, 2009. (54 refs.)

Prescription-drug diversion is a topic about which comparatively little is known, and systematic information garnered from prescription-drug abusers and dealers on the specific mechanisms of diversion is extremely limited. A pilot ultrarapid assessment was carried out in Wilmington, Delaware, during December 2006 to better understand the scope and dynamics of prescription-drug abuse and diversion. This involved focus groups with prescription-drug abusers and key informant interviews with police, regulatory officials, prescription-drug dealers, and pill brokers. The research team recruited focus group participants from the two residential substance abuse treatment programs in Wilmington reporting the highest proportions of prescription drug abusing clients. A total of six focus groups were conducted with 32 patients in these two programs. Dealers were recruited from the same treatment facilities, and three in-depth interviews were completed. In-depth interviews were also conducted with two prescription pill brokers recruited through the authors' existing contacts in the drug abusing community. Six in-depth interviews were conducted with representatives from a number of Delaware agencies-the Attorney General's Office, the Department of Professional Regulation, the State Police; the Wilmington Police Department, and the Newark Police Department. In-depth interview and focus group guides were developed for each of the target populations. The in-depth interviews with police and regulatory officials focused on the extent of prescription drug abuse and diversion in the community, the types of drugs most commonly diverted, and mechanisms being used to channel the drugs to the illicit market. The focus group areas of inquiry with prescription drug abusers included general perceptions of the prescription drug problem in Delaware, sources and mechanisms of access to prescription drugs, popularity and prices of prescription medications on the street, as well as the initiation and progression of prescription and illicit drug abuse. The primary sources of prescription drugs on the street were the elderly, patients with pain, and doctor shoppers, as well as pill brokers and dealers who work with all of the former. The popularity of prescription drugs in the street market was rooted in the abusers' perceptions of these drugs as 1) less stigmatizing; 2) less dangerous; and, 3) less subject to legal consequences than illicit drugs. For many, the abuse of prescription opioids also appeared to serve as a gateway to heroin use. The diversion of prescription opioids might be reduced through physician education focusing on 1) recognizing that a patient is misusing and/or diverting prescribed medications; 2) considering a patient's risk for opioid misuse before initiating opioid therapy; and 3) understanding the variation in the abuse potential of different opioid medications currently on the market. Patient education also appears appropriate in the areas of safeguarding medications, disposal of unused medications, and understanding the consequences of manipulating physicians and selling their medications.

Jasinski DR; Faries DE; Moore RJ; Schuh LM; Allen AJ. Abuse liability assessment of atomoxetine in a drug-abusing population. Drug and Alcohol Dependence 95(1/2): 140-146, 2008. (34 refs.)

Background: Atomoxetine is a non-amphetamine medication approved to treat ADHD in children, adolescents, and adults. Previous studies demonstrated low abuse potential for atomoxetine in recreational drug users. This study assessed the abuse potential of atomoxetine in stimulant-preferring drug abusers compared to methylphenidate and phentermine as positive controls and desipramine and placebo as negative controls. Methods: Forty male and female, 32-53 years old stimulant-preferring drug abusers completed this balanced Latin-square designed study. Subjects received acute, double-blind doses of placebo, desipramine (100 and 200mg), methylphenidate (90mg), phentermine (60mg), and atornoxetine (45, 90, and 180 mg). Subjective and physiological effects were collected for 24 It following each drug treatment. Results: Methylphenidate and phentermine were liked significantly more than placebo, atomoxetine, or desipramine. No atomoxetine dose was liked significantly more than placebo and liking scores for atomoxetine were similar to, or significantly lower than, desipramine, as assessed by the Drug Rating Questionnaire-Subject. While atomoxetine 45 and 180 mg did not significantly change any Addiction Research Center Inventory (ARCI) scores, atomoxetine 90 mg significantly increased A and BG stimulant scores of the ARCI and both methylphenidate and phentermine produced greater A and BG increases than any atomoxetine dose and also increased MBG (euphoria) scores relative to placebo. Conclusions: Atomoxetine has significantly less abuse liability than methylphenidate or phentermine and no greater abuse liability than desiprarnme.

Killgore WDS; Kahn-Greene ET; Grugle NL; Killgore DB; Balkin TJ. Sustaining executive functions during sleep deprivation: A comparison of caffeine, dextroamphetamine, and modafinil. Sleep 32(2): 205-216, 2009. (70 refs.)

Objectives: Stimulant medications appear effective at restoring simple alertness and psychomotor vigilance in sleep deprived individuals, but it is not clear whether these medications are effective at restoring higher order complex cognitive capacities such as planning, sequencing, and decision making. Design: After 44 hours awake, participants received a double-blind dose of one of 3 stimulant medications or placebo. After 45-50 hours awake, participants were tested on computerized versions of the 5-Ring Tower of Hanoi (TOH), the Tower of London (TOL), and the Wisconsin Card Sorting Test (WCST). Setting: In-residence sleep-laboratory facility at the Walter Reed Army Institute of Research. Participants: Fifty-four healthy adults (29 men, 25 women), ranging in age from 18 to 36 years. Interventions: Participants were randomly assigned to 1 of 3 stimulant medication groups, including caffeine, 600 mg (n = 12), modafinil, 400 mg (n = 12), dextroamphetamine, 20 mg (n = 16), or placebo (n = 14). Measurements and Results: At the doses tested, modafinil and dextroamphetamine groups completed the TOL task in significantly fewer moves than the placebo group, and the modafinil group demonstrated greater deliberation before making moves. In contrast, subjects receiving caffeine completed the TOH in fewer moves than all 3 of the other groups, although speed of completion was not influenced by the stimulants. Finally, the modafinil group outperformed all other groups on indices of perseverative responding and perseverative errors from the WCST Conclusions: Although comparisons across tasks cannot be made due to the different times of administration, within-task comparisons suggest that, at the doses tested here, each stimulant may produce differential advantages depending on the cognitive demands of the task.

Knisely JS; Wunsch MJ; Cropsey KL; Campbell ED. Prescription Opioid Misuse Index: A brief questionnaire to assess misuse. Journal of Substance Abuse Treatment 35(4): 380-386, 2008. (21 refs.)

The Prescription Opioid Misuse Index (POMI) was developed and used in a larger study designed to assess correlates of OxyContin abuse in pain patients prescribed OxyContin, patients treated for OxyContin addiction, and individuals incarcerated for OxyContin-related charges. The POMI was administered to 40 subjects with addiction problems and 34 pain patients who had received OxyContin for pain. Receiver operating characteristic curve analysis indicated that endorsing two or more of six items reliably classified a person as at risk for misuse of their medication. When comparing drug abuse/dependence in subjects classified as misusers or users, significantly more misusers received a diagnosis for alcohol (p < .01), illicit drugs (p < .05), and other prescription medications (p < .05) and reported greater lifetime use of alcohol (p < .002) and illicit drugs (p < .01). No between-group differences were found regarding psychiatric problems. The POMI appears to be a sensitive and specific instrument for identifying patients who misuse opioid medications.

Kokkevi A; Fotiou A; Arapaki A; Richardson C. Prevalence, patterns, and correlates of tranquilizer and sedative use among European adolescents. Journal of Adolescent Health 43(6): 584-592, 2008. (40 refs.)

Purpose: To examine the prevalence. patterns, and correlates of nonmedical use of tranquilizers or sedatives in 85,000 adolescent students from 31 European countries participating in the European School Survey on Alcohol and Other Drugs (ESPAD) in 2003. Methods: Surveys in each country followed a standardized protocol. Logistic regression analysis was performed to identify sociodemographic and risk behavior correlates of medical and nonmedical tranquilizer or sedative use. Results: Lifetime nonmedical tranquilizer or sedative use was reported by 5.6% overall. Medical tranquilizer or sedative use multiplies the odds of nonmedical use by 10.7 (95% confidence interval 9.1-12.5) for boys and 7.2 (6.3-8.3) for girls. Nonmedical tranquilizer or sedative use is also associated with the use of tobacco (odds ratio 1.3, 1.1-1.5). alcohol (1.3. 1.2-1.5). and illicit drugs (3.5, 3.1-3.9). Further correlates are truancy (1.4. 1.2-1.6). tranquilizer or sedative use by friends (6.0 5.5-6.7) and siblings (2.7, 2.2-3.4). and dissatisfaction with relationships with parents. Medical tranquilizer or sedative use shares to a large extent the same correlates. Conclusions: Findings indicate similarities in adolescent tranquilizer or sedative use between Europe and United States. The implications of the results for prevention policies are discussed.

Lader M. Coming off tranquillizers: A Sisyphean toil. (commentary). Addiction 104(1): 25-26, 2009. (10 refs.)

Launiainen T; Vuori E; Ojanpera I. Prevalence of adverse drug combinations in a large post-mortem toxicology database. International Journal of Legal Medicine 123(2): 109-115, 2009. (40 refs.)

The prevalence of important adverse drug combinations was studied among the 37,367 cases included in the Finnish post-mortem toxicology database during 2000-2006. The new SFINX interaction database (Swedish, Finnish, INteraction X-referencing) was utilised to identify adverse drug combinations. Consequently, the 24 drugs chosen for the study generated 96 two-compound combinations possessing potentially severe interactions. The total number of hits for the combinations found in the post-mortem database was 267, which accounts for approximately 0.71% of all cases. The potential role of adverse drug interaction (ADI) in these cases was evaluated from the background information and death certificate. The possible ADI cases comprised 23% of all hits and 0.17% of all cases analysed. In cases with a pharmacodynamic mechanism, the most prominent combinations were medicines causing serotonin syndrome or a beta(1)-blocker with verapamil or diltiazem. In cases with a pharmacokinetic mechanism, half of the cases involved digoxin in combination with verapamil. In one third of the possible ADI cases, a forensic pathologist had noted the studied compounds as an underlying or contributing cause of death, although the agents' specific role in ADIs was rarely recognised.

Levine SB; Coupey SM. Nonmedical use of prescription medications: An emerging risk behavior among rural adolescents. Journal of Adolescent Health 44(4): 407-409, 2009. (10 refs.)

Little is known about prescription medication abuse by rural youth. We surveyed 849 rural high school students and found that 34% reported lifetime nonmedical use of prescription medication higher than the 12% reported nationally. Boys and marijuana users had higher odds of nonmedical use of prescription medication than did girls or marijuana nonusers (odds ratio 1.9 and 3.8, respectively).

Loganathan B; Phillips M; Mowery H; Jones-Lepp TL. Contamination profiles and mass loadings of macrolide antibiotics and illicit drugs from a small urban wastewater treatment plant. Chemosphere 75(1): 70-77, 2009. (37 refs.)

Information is limited regarding sources, distribution, environmental behavior, and fate of prescribed and illicit drugs. Wastewater treatment plant (WWTP) effluents can be one of the sources of pharmaceutical and personal care products (PPCP) into streams, rivers and lakes. The objective of this study was to determine the contamination profiles and mass loadings of urobilin (a chemical marker of human waste), macrolide antibiotics (azithromycin, clarithromycin, roxithromycin), and two drugs of abuse (methamphetamine and ecstasy), from a small (<19 mega liters day(-1), equivalent to <5 million gallons per day) wastewater treatment plant in southwestern Kentucky. The concentrations of azithromycin, clarithromycin, methamphetamine and ecstasy in wastewater samples varied widely, ranging from non-detects to 300 ng L-1. Among the macrolide antibiotics analyzed, azithromycin was consistently detected in influent and effluent samples. in general, influent samples contained relatively higher concentrations of the analytes than the effluents. Based on the daily flow rates and an average concentration of 17.5 ng L-1 in the effluent, the estimated discharge of azithromycin was 200 mg day(-1) (range 63-400 mg day(-1)). Removal efficiency of the detected analytes from this WWTP were in the following order: Urobilin > amethamphetamine > azithromycin with percentages of removal of 99.9%, 54.5% and 47%, respectively, indicating that the azithromycin and methamphetamine are relatively more recalcitrant than others and have potential for entering receiving waters.

Mackesy-Amiti ME; Fendrich M; Johnson TP. Substance-related problems and treatment among men who have sex with men in comparison to other men in Chicago. Journal of Substance Abuse Treatment 36(2): 227-233, 2009. (32 refs.)

This study compares a sample of urban men who have sex with men (MSM) with a general population sample of men in the same city on self-reported problems with substance use indicative of dependence and history of substance use treatment. Both samples were randomly selected using multistage probability methods. All participants completed audio computer-assisted self-interviews, including questions on substance use, problems related to substance use experienced in the past 12 months, and substance treatment. Problem use of alcohol, marijuana, and cocaine did not differ between samples. Compared to men in the general population sample, MSM were significantly more likely to experience problems related to the use of sedatives, tranquilizers, or prescription pain relievers. Among MSM, history of substance treatment was associated with a positive HIV test, and treatment usually preceded HIV diagnosis. Research is needed on effective methods for integrating HIV prevention for MSM into substance treatment settings, including physician-administered buprenorphine treatment for opiate addiction.

Magura S. What more do we need to know about medication-assisted treatment for prescription opioid abusers? (editorial). Addiction 104(5): 784-785, 2009. (56 refs.)

Majumder MMA; Basher A; Faiz MA; Kuch U; Pogoda W; Kauert GF et al. Criminal poisoning of commuters in Bangladesh: Prospective and retrospective study. Forensic Science International 180(1): 10-16, 2008. (36 refs.)

Travel-related poisoning is an emerging social and public health emergency in Bangladesh but its cause and significance have not been determined. To investigate this syndrome we performed a prospective clinical study and retrospective analysis of hospital records in a general medicine unit of a public tertiary care teaching hospital in Dhaka, Bangladesh, using toxicological analysis by fluorescence polarization immunoassay (FPIA) and liquid chromatography coupled to time-of-flight mass spectrometry (LC-TOF MS). The participants of the prospective study were 130 consecutive patients aged 16-80 years who were admitted with central nervous system depression (Glasgow Coma Score 3-14) after using public transportation, in the absence of other abnormalities, from January through June 2004, and a convenience sample of 15 such patients admitted during 3 days in May 2006. In 2004-2006, travel-related poisoning increased from 6.1 to 9.5% of all admissions (210-309 of 3266-3843 per year), representing 46.6-55.7% of all admitted poisoning cases. Incidents were associated with bus (76%), taxi, train, and air travel, or local markets: 98% of patients remembered buying or accepting food or drinks before losing consciousness. Direct financial damage (missing property) was diverse and frequently existential. Among 94 Urine samples analyzed by FPIA, 74% tested positive for benzodiazepines. Among 15 urine samples analyzed by LC-TOF MS, lorazepam was detected in all: five also contained diazepam or metabolites: nitrazepam was present in three. FPIA results obtained for these 15 samples were below the recommended cut-off in eight (53%; lorazepam only). Our findings show that the massive medicosocial emergency of travel-related poisoning in Bangladesh is the result of drug-facilitated organized crime and that benzodiazepine drugs are used to commit these crimes, suggesting modifications to the local emergency management of the victims of this type of poisoning. They also highlight the need for more research in the neglected field of acute poisoning in Bangladesh, and for Criminal investigations of the use of benzodiazepine drugs in this country.

Mark TL; Kassed CA; Vandivort-Warren R; Levit KR; Kranzler HR. Alcohol and opioid dependence medications: Prescription trends, overall and by physician specialty. Drug and Alcohol Dependence 99(1-3): 345-349, 2009. (18 refs.)

Over the past decade, advances in addiction neurobiology have led to the approval of new medications to treat alcohol and opioid dependence. This study examined data from the IMS National Prescription Audit (NPA) Plus (TM) database of retail pharmacy transactions to evaluate trends in U.S. retail sales and prescriptions of FDA-approved medications to treat substance use disorders. Data reveal that prescriptions for alcoholism medications grew from 393,000 in 2003 ($30 million in sales) to an estimated 720,000 ($78 million in sales) in 2007. The growth was largely driven by the introduction of acamprosate in 2005, which soon became the market leader ($35 million in sales). Prescriptions for the two buprenorphine formulations increased from 48,000 prescriptions ($5 million in sales) in the year of their introduction (2003) to 1.9 million prescriptions ($327 million in sales) in 2007. While acamprosate and buprenorphine grew rapidly after market entry, overall substance abuse retail medication sales remain small relative to the size of the population that could benefit from treatment and relative to sales for other medications, such as antidepressants. The extent to which substance dependence medications will be adopted by physicians and patients, and marketed by industry, remains uncertain.

Martins SS; Storr CL; Zhu H; Chilcoat HD. Correlates of extramedical use of OxyContin (R) versus other analgesic opioids among the US general population. Drug and Alcohol Dependence 99(1-3): 58-67, 2009. (43 refs.)

Background: There has been substantial public and media attention regarding extramedical use of OxyContin (R), but few studies focus on the characteristics of extramedical OxyContin (R) users and whether they differ from extramedical other opioid users. Methods: We used data from 8218 respondents who were past-year extramedical opioid analgesic users in the 2005 and 2006 National Survey of Drug Use and Health (NSDUH). We investigated differences in socio-demgraphic and psychiatric characteristics associated with past-year extramedical OxyContin (R) use (n = 1144) versus extramedical other opioid analgesics use (n = 7074). Data on opioid sources was compared among past-month users. We also compared extramedical opioid users (it = 8218) versus other drug users (it = 16,214), and individuals with an analgesic disorder who had past-year extramedical OxyContin (R) use (it = 339) versus those with other opioid use (it = 820). Results: Past-year opioid users were more likely than users of other illegal drugs to be more educated and have a past-year major depressive episode. Past-year OxyContin (R) users were more likely than other opioid users to be 18-25 years old (aOR = 1.9[ 1.1,3.2]), and have mental health and deviant behavior problems. Those with past-year analgesic disorder who used OxyContin (R) were more likely to be younger, sell illegal drugs (aOR = 2.5[1.5,4.2]), and use illegal drugs than those who used other opioids. Past-month OxyContin (R) users were more likely than past-month other opioid users to buy analgesics from drug dealers/other strangers and obtain opioid analgesics from Multiple Sources. Conclusion: Our findings point out differences between OxyContin (R) and other opioid users that might help prevention specialists and assist efforts to curb opioid analgesics diversion.

McCabe SE; Cranford JA; West BT. Trends in prescription drug abuse and dependence, co-occurrence with other substance use disorders, and treatment utilization: Results from two national surveys. Addictive Behaviors 33(10): 1297-1305, 2008. (33 refs.)

Objectives: This study examined trends in prescription drug abuse and dependence (sedatives, tranquilizers, opioids, and stimulants), co-occurrence with other substance use disorders and substance abuse treatment utilization among those with diagnoses of prescription drug abuse and dependence in two large, nationally representative, independent samples of adults in the United States in 1991-1992 and 2001-2002. Methods: Two nationally representative cross-sectional samples of civilian non-institutionalized adults 18 years or older in the United States, of which 52% were women. Data were collected from structured diagnostic interviews using the NIAAA Alcohol Use Disorder and Associated Disabilities interview Schedule: Diagnostic and Statistical Manual version IV (DSM-IV). National prevalence estimates were derived from the 1991-1992 National Longitudinal Alcohol Epidemiologic Survey (n = 42,862) and the 2001-2002 National Epidemiologic Survey on Alcohol and Related Conditions (n = 43.093). Results: The past-year prevalence of prescription sedative abuse, sedative dependence, opioid abuse, and opioid dependence increased from 1991-1992 to 2001-2002. The majority of individuals with past-year sedative (56.8%), tranquilizer (89.0%), stimulant (67.9%) and opioid (74.2%) use disorders also met DSM-IV criteria for an additional past-year substance use disorder. The co-occurrence of several forms of prescription drug use disorders and other substance use disorders increased from 1991-1992 to 2001-2002. A minority of individuals with past-year prescription drug abuse and approximately one-half of those with past-year prescription drug dependence utilized substance abuse treatment Conclusions: The findings reinforce the importance of continued national monitoring based on the increases in prescription drug abuse and dependence, high co-occurrence with other substance use disorders, and underutilization of substance abuse treatment services.

Mendelson J; Flower K; Pletcher MJ; Galloway GP. Addiction to prescription opioids: Characteristics of the emerging epidemic and treatment with buprenorphine. Experimental and Clinical Psychopharmacology 16(5): 435-441, 2008. (49 refs.)

Dependence on and abuse of prescription opioid drugs is now a major health problem, with initiation of prescription opioid abuse exceeding cocaine in young people. Coincident with the emergence of abuse and dependence on prescription opioids, there has been an increased emphasis on the treatment of pain. Pain is now the "5th vital sign" and physicians face disciplinary action for failure to adequately relieve pain. Thus, physicians are whipsawed between the imperative to treat pain with opioids and the fear of producing addiction in some patients. In this article, the authors characterize the emerging epidemic of prescription opioid abuse, discuss the utility of buprenorphine in the treatment of addiction to prescription opioids, and present illustrative case histories of successful treatment with buprenorphine.

Miller P; Degenhardt L. The global diversion of pharmaceutical drugs series. (editorial). Addiction 104(3): 333-334, 2009. (10 refs.)

Motamed M; Marsch LA; Solhkhah R; Bickel WK; Badger GJ. Differences in treatment outcomes between prescription opioid-dependent and heroin-dependent adolescents. Journal of Addiction Medicine 2(3): 158-164, 2008. (24 refs.)

Objective: This Study was designed to examine the extent to which heroin-dependent and prescription opioid-dependent adolescents experienced differential outcomes during a clinical trial designed to evaluate combined behavioral-pharmacological treatment. Methods: Participants were a volunteer sample of 36 adolescents who met DSM-IV criteria for opioid-dependence (ages 13-18 years eligible) 53% of which were heroin-dependent and 47% of which were dependent on prescription opioids used for nonmedical put-poses. Participants received a 28-day, outpatient, medication-assisted withdrawal with the partial opioid agonist, buprenorphine, or the centrally active A-adrenergic blocker, clonidine, along with behavioral counseling and incentives contingent on opioid abstinence. Heroin-dependent and prescription opioid-dependent participants were compared on baseline characteristics and treatment Outcomes, which included retention, opioid abstinence, HIV risk behavior, opioid withdrawal, and medication effects. Results: Heroin-dependent and prescription opioid-dependent youth had similar characteristics at intake. Heroin-dependent youth had higher baseline rates of drug-related HIV risk, behavior and greater opioid withdrawal before receiving medication during treatment; however, this same group showed markedly greater improvements on these domains during treatment relative to prescription opioid-dependent youth. Both participant groups showed comparable outcomes based on clinically meaningful measures of treatment retention and opioid abstinence. Both heroin-dependent and prescription opioid-dependent youth who received buprenorphine experienced markedly better treatment outcomes relative to those who received clonidine. Conclusions: These results demonstrate that combined behavioral and buprenorphine treatment seems safe and efficacious in the treatment of both heroin-dependent and prescription opioid-dependent adolescents and provide novel information relating to treatment outcomes for these subgroups of opioid-dependent youth.

Mounteney J; Haugland S. Earlier warning: A multi-indicator approach to monitoring trends in the illicit use of medicines. International Journal of Drug Policy 20(2): 161-169, 2009. (43 refs.)

Background: The availability of medicines on the illicit drug market is currently high on the international policy agenda, linked to adverse health consequences including addiction, drug related overdoses and injection related problems. Continuous surveillance of illicit use of medicines allows for earlier identification and reporting of emerging trends and increased possibilities for earlier intervention to prevent spread of use and drug related harm. This paper aims to identify data sources capable of monitoring the illicit use of medicines; present trend findings for Rohypnol and Subutex using a multi-indicator monitoring approach; and consider the relevance of such models for policy makers. Methods: Data collection and analysis were undertaken in Bergen, Norway, using the Bergen Earlier Warning System (BEWS), a multi-indicator drug monitoring system. Data were gathered at six monthly intervals from April 2002 to September 2006. Drug indicator data from seizures, treatment, pharmacy sales, helplines, key informants and media monitoring were triangulated and an aggregated differential was used to plot trends. Results: Results: for the 4-year period showed a decline in the illicit use of Rohypnol and an increase in the illicit use of Subutex. Conclusion: Multi-indicator Surveillance models can play a strategic role in the earlier identification and reporting of emerging trends in illicit use of medicines.

Nielsen S; Barratt MJ. Prescription drug misuse: Is technology friend or foe? Drug and Alcohol Review 28(1): 81-86, 2009. (54 refs.)

Introduction and Aims. Prescription drug misuse and related harms have been increasing considerably over the past decade. At the same time, there has also been rapid growth in the use of online and Internet technologies. Thus, it is important that we understand the role online and Internet technologies play in prescription drug misuse. Design and Methods. Published work addressing the role of technology in prescription drug misuse is explored. Topics include: Internet supply, online monitoring of prescription drug use trends and electronic prescription monitoring. Results. Little is known about the prevalence of acquiring prescription drugs from online pharmacies. Prescription drugs are easily accessible through vendor websites, and 'rogue' no-prescription websites have proven difficult to control. There has so far been limited application of real-time monitoring to prevent overuse of prescription medications. Online monitoring of drug use trends may also prove to be a useful and timely source of information about new methods of 'off-label' prescription drug use. Discussion and Conclusions. Technology has the potential to play a more prominent role in facilitating drug acquisition, while also enhancing the monitoring and prevention of prescription drug misuse. As technology becomes more ubiquitous in everyday life, the continued investigation of its relationship with prescription drug misuse becomes even more important.

Novak SP; Herman-Stahl M; Flannery B; Zimmerman M. Physical pain, common psychiatric and substance use disorders, and the non-medical use of prescription analgesics in the United States. Drug and Alcohol Dependence 100(1-2): 63-70, 2009. (45 refs.)

This study investigated the link between physical pain and non-medical prescription analgesic use (NMPAU), as well as the degree to which this association may vary by the presence of psychiatric and substance use disorders. Data were from the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC), a nationally representative, in-person probability sample of adults (n = 43,093) aged 18 or older in the United States (2001-2002). Face-to-face interviews were used to gather information on past-year levels of physical pain (i.e., low, medium, high), in addition to DSM-IV classifications for mood, anxiety, substance use problems (i.e., abuse and/or dependence), and personality disorders. Within the analytic sample of those with valid data (n = 42,734), the past-year rate of NMPAU was 1.8%, of which 20% met the DSM-IV criteria for abuse/dependence. Among past-year NMPAUs, 53% was incidental (e.g., less than monthly), but daily use was substantial (13% of NMPAUs). Accounting for our target confounding factors, pain was positively associated (p < 0.05) with an increased probability of non-disordered (i.e., no abuse and/or dependence) and disordered (i.e., abuse and/or dependence) NMPAU in the past year. Within each level of pain, the odds of past-year non-disordered and disordered NMPAU were significantly higher (p < 0.05) for those with disordered alcohol use compared with non-disordered users. This pattern was similar for illicit drugs, although marginally significant (p = 0.060) and specific to disordered NMPAU. In contrast, psychiatric disorders increased the probability of both types of NMPAU, but these associations did not differ by levels of pain. These findings suggest that pain is an independent risk factor for non-disordered and disordered NMPAU, yet its effects are substantially modified by patterns of substance use.

Office of Applied Studies, Substance Abuse and Mental Health Services Administration. The NSDUH Report. Trends in Substance Use, Dependence or Abuse, and Treatment among Adolescents: 2002 to 2007. (December 4, 2008). Rockville MD: Substance Abuse and Mental Health Services Administration, 2008. (1 refs.)

Trends in past month substance use show that while there was little change in past month use of cigarettes, alcohol, and illicit drugs among adolescents between 2006 and 2007, the rates generally declined between 2002 and 2007 (cigarettes from 13.0 to 9.8 percent, alcohol from 17.6 to 15.9 percent, and illicit drugs from 11.6 to 9.5 percent). The decline in past month illicit drug use can be attributed primarily to a decline in marijuana use, with 8.2 percent of adolescents using marijuana in 2002 compared with 6.7 percent in 2007. The two other most commonly used illicit drugs among adolescents are inhalants and the nonmedical use of prescription-type drugs. Use of inhalants remained stable, while nonmedical use of prescription-type drugs declined from 4.0 to 3.3 percent over the 6-year period covered in this report. Past year dependence on or abuse of alcohol remained relatively stable among adolescents between 2002 and 2007, but dependence on or abuse of illicit drugs declined from 5.6 to 4.3 percent. What Are the Trends in Substance Use Treatment? Among adolescents who needed treatment for alcohol use in the past year, the percentage who received treatment at a specialty facility fluctuated between 5.9 and 8.1 percent from 2002 through 2007. The percentages for treatment for illicit drug use fluctuated between 8.5 and 11.3 percent. There were no statistically significant changes between 2002 and 2007 for either of these treatment indicators. Comments: The findings in this report present mixed results. On the positive side, past month use of cigarettes, alcohol, and illicit drugs declined among adolescents between 2002 and 2007, as did dependence on or abuse of illicit drugs. On the other hand, the rates of alcohol dependence or abuse remained fairly steady. In addition, given that the rate of adolescents receiving specialty treatment remained unchanged between 2002 and 2007, it is necessary to look at strategies to expand the continuum of care to engage adolescent problem users who cannot or will not go to specialty substance use treatment programs.

Public Domain

Ompad DC; Fuller CM; Chan CA; Frye V; Vlahov D; Galea S. Correlates of illicit methadone use in New York City: A cross-sectional study. BMC Public Health 8(e-article 375), 2008. (35 refs.)

Background: Despite growing concern about illicit methadone use in the US and other countries, there is little data about the prevalence and correlates of methadone use in large urban areas. We assessed the prevalence and examined correlates of lifetime and recent illicit methadone use in New York City (NYC). Methods: 1,415 heroin, crack, and cocaine users aged 15-40 years were recruited in NYC between 2000 and 2004 to complete interviewer-administered questionnaires. Results: In multivariable logistic regression, non-injection drug users who used illicit methadone were more likely to be heroin dependent, less than daily methamphetamine users and to have a heroin using sex partner in the last two months. Injection drug users who used illicit methadone were more likely to use heroin daily, share injection paraphernalia and less likely to have been in a detoxification program and to have not used marijuana in the last six months. Conclusion: The results overall suggest that illicit (or street) methadone use is likely not a primary drug of choice, but is instead more common in concert with other illicit drug use.

Parr JM; Kavanagh DJ; Cahill L; Mitchell G; Young RM. Effectiveness of current treatment approaches for benzodiazepine discontinuation: A meta-analysis. Addiction 104(1): 13-24, 2009. (61 refs.)

Aims: To assess the effectiveness of current treatment approaches to assist benzodiazepine discontinuation. Methods: A systematic review of approaches to benzodiazepine discontinuation in general practice and out-patient settings was undertaken. Routine care was compared with three treatment approaches: brief interventions, gradual dose reduction (GDR) and psychological interventions. GDR was compared with GDR plus psychological interventions or substitutive pharmacotherapies. Results: Inclusion criteria were met by 24 studies, and a further eight were identified by future search. GDR [odds ratio (OR) = 5.96, confidence interval (CI) = 2.08-17.11] and brief interventions (OR = 4.37, CI = 2.28-8.40) provided superior cessation rates at post-treatment to routine care. Psychological treatment plus GDR were superior to both routine care (OR = 3.38, CI = 1.86-6.12) and GDR alone (OR = 1.82, CI = 1.25-2.67). However, substitutive pharmacotherapies did not add to the impact of GDR (OR = 1.30, CI = 0.97-1.73), and abrupt substitution of benzodiazepines by other pharmacotherapy was less effective than GDR alone (OR = 0.30, CI = 0.14-0.64). Few studies on any technique had significantly greater benzodiazepine discontinuation than controls at follow-up. Conclusions: Providing an intervention is more effective than routine care. Psychological interventions may improve discontinuation above GDR alone. While some substitutive pharmacotherapies may have promise, current evidence is insufficient to support their use.

Passik SD; Kirsh KL. The interface between pain and drug abuse and the evolution of strategies to optimize pain management while minimizing drug abuse. Experimental and Clinical Psychopharmacology 16(5): 400-404, 2008. (25 refs.)

Pain management is facing continued undertreatment of pain despite a growing problem with prescription opioid abuse. This has created a tension among prescribers and feelings of helplessness with regards to what constitutes appropriate practice. This article provides a review of pain management efforts and focuses on two key areas of potential interest. First, the emergence of prescreening tools for identifying appropriate candidates for opioid therapy are introduced and discussed, including the Opioid Risk Tool (ORT), the Screener and Opioid Assessment for Patients with Pain (SOAPP), and the Pain Assessment and Documentation Tool (PADT). In addition to these screening efforts, a novel concept of "in and out of the box" prescribing is presented. focusing on five areas of concern for judging whether one's prescribing patterns are matching peer prescribing patterns. While more work needs to be done. the discussion of these areas should offer some questions for self analysis by physicians regarding their prescribing patterns. Overall. the authors must embrace the concept of rational pain management and assess patients for risk both before writing the first opioid prescription for them and thereafter. In addition, we must remember that good pain management should lead to some decreases in pain perception for the patient combined with a corresponding increase in ability to function. By reviewing these tools and proposed novel guidelines for in/out of the box prescribing and adopting them into practice its appropriate, the physician will take a significant step in providing effective pain management while minimizing risk of opioid misuse.

Patra J; Fischer B; Maksimowska S; Rehm J. Profiling poly-substance use typologies in a multi-site cohort of illicit opioid and other drug users in Canada: A latent class analysis. Addiction Research & Theory 17(2): 168-185, 2009. (85 refs.)

'Poly-substance use' is increasingly prevalent among street drug user populations. The objective was to employ latent class analysis (LCA) to empirically categorize and extract potential typologies of poly-substance users within a multi-site cohort of illicit opioid and other drug users (OPICAN) in Canada, and examine potential associations with social and health indicators. Drug use patterns of 582 participants from the most recent follow-up (2005) of the cohort study-focusing on drug use prevalence indicators in the past 30 days-were empirically analyzed via LCA. These classes were further examined for associations with social and health variables using chi-square, ANOVA. Binomial logistic regression models were used to predict class membership. LCA analysis resulted in eight distinct user typologies, characterized both by the distinct relative prevalence of different substances (e.g., including: heroin, prescription opioids, benzodiazepines, cocaine, crack, alcohol, cannabis, and others) used and administration routes (e.g., injection or noninjection), the majority of which were described by the predominant use of two or more distinct substance groups (e.g., opioids and stimulants). At least two of the active poly-substance user classes were described by predominant noninjection as the primary route of administration. 'Poor or fair' health status was reported at the highest prevalence level by the class of intensive poly-substance injectors, while HCV-positive status was disproportionately low in the classes of current noninjectors. Analytical examination of poly-substance use patterns is a distinct challenge for meaningful drug use monitoring, also providing important evidence for targeted prevention and treatment interventions.

Paulozzi LJ; Xi YL. Recent changes in drug poisoning mortality in the United States by urban-rural status and by drug type. Pharmacoepidemiology and Drug Safety 17(10): 997-1005, 2008. (40 refs.)

Purpose: This study was conducted to determine how the recently reported increase in drug poisoning mortality rates in the United States varied by degree of urbanization. Although drug poisoning is traditionally seen as an urban problem, evidence suggested that at least one component of the recent increase, deaths involving opioid analgesics, was increasing more rapidly in rural areas. Methods: The study compared age-adjusted unintentional and undetermined drug poisoning mortality rates between 1999 and 2004 from the National Vital Statistics System (NVSS) in each of six urban-rural categories. Results: Unintentional and undetermined drug poisoning mortality rates rose 62% from 1999 to 2004. Metropolitan county rates rose 51 %, an increase of 2.66/100 000, while nonmetropolitan county rates rose 159%, an increase of 4.81/100 000. By 2004, metropolitan and nonmetropolitan drug poisoning rates had roughly equalized. In the narcotic drug category, which included heroin, cocaine, and opioid analgesics, the most urban ("large central metro") counties increased only 16% while the most rural ("noncore, nonmetropolitan") counties increased 248%. Heroin rates did not increase significantly for any urban-rural category. Cocaine rate increases were largest in nonmetropolitan counties. Opioid analgesic rate increases ranged from a low of 52% in large central metro counties to an increase of 371% in nonmetropolitan, noncore counties. Conclusions: Prescription drugs have replaced heroin and cocaine as the leading drugs involved in fatal drug overdoses in all urban-rural categories. Fatal drug overdoses are no longer a predominantly urban phenomenon. National prevention efforts will have to shift to address nontraditional populations using nontraditional drugs.

Popova S; Patra J; Mohapatra S; Fischer B; Rehm J. How many people in Canada use prescription opioids non-medically in general and street drug using populations? Canadian Journal of Public Health 100(2): 104-108, 2009. (29 refs.)

Objective: Medical prescriptions for opioids as well as their non-medical use have increased in Canada in recent years. This study aimed to estimate the number of non-medical prescription opioid (PO) users in the general and street drug using populations in Canada. Methods: The number of non-medical PO users among the general population and the number of non-medical PO users, heroin users, or both among the street drug using population was estimated for Canada and for the most populous Canadian provinces. Different estimation methods were used: 1) the number of non-medical PO users in the Canadian general population was estimated based on Canadian availability data, and the ratio of US availability to non-medical PO use from US survey data; 2) numbers within the street drug using population were indirectly estimated based on overdose death data, and a key informants survey. Distribution and trends by usage of opioids were determined by using the multi-site Canadian OPICAN cohort data. Results: Between 321,000 to 914,000 non-medical PO users were estimated to exist among the general population in Canada in 2003. The estimated number of non-medical PO users, heroin users, or both among the street drug using population was about 72,000, with more individuals using non-medical PO than heroin in 2003. Based on data from the OPICAN survey, in 2005 the majority of the street drug using population in main Canadian cities was non-medical PO users, with the exception of Vancouver and Montreal. A relative increase of 24% was observed from 2002 to 2005 in the proportion of the street drug using population who used non-medical POs only. Discussion: There is an urgent need to further assess the extent and patterns of non-medical prescription opioid use, related problems and drug distribution channels in Canada.

Prudent M; Drame M; Jolly D; Trenque T; Parjoie R; Mahmoudi R et al. Potentially inappropriate use of psychotropic medications in hospitalized elderly patients in France cross-sectional analysis of the prospective, multicentre SAFEs cohort. Drugs & Aging 25(11): 933-946, 2008. (60 refs.)

Background: In France, there is evidence to suggest that 50% of elderly individuals are prescribed psychotropic medications. However, it is known that use of these agents increases the risk of falls, fractures and delirium in older people. Objective: To study the consumption of 'potentially inappropriate medication' (PIM) among patients aged >= 75 years, paying particular attention to psychotropic drugs and the factors influencing the use of 'potentially inappropriate psychotropics' (PIPs). Method: This was a cross-sectional analysis of a prospective multicentre cohort of 1306 hospitalized French patients aged >= 75 years (the SAFEs [Sujet Age Fragile: Evaluation et suivi (Frail Elderly Subjects: Evaluation and follow-up)] cohort). The present analysis involved the 1176 patients for whom there was information on the usual treatments being taken in the 2 weeks before hospitalization. The drugs were coded according to the Anatomical Therapeutic Chemical classification; the Beers list as updated in 2003 defined which medications were considered PIPs. Standardized geriatric assessment variables were recorded on inclusion in the study. Logistic regression analysis was performed to identify factors linked to use of psychotropics and PIPs. Results: The mean number of drugs taken was 5.7 +/- 2.9 per patient. Twenty-eight percent of patients took at least one PIM. The number of patients who had taken at least one psychotropic drug in the 2 weeks before hospitalization (mean 1.6 +/- 0.9 psychotropics per patient) was 589 (50.1%). More than half of both the 510 patients with a depressive syndrome and the 543 patients affected by dementia were treated with psychotropics. Multivariate analysis showed that prescription of psychotropics was linked to the presence of a dementia syndrome (odds ratio [OR] = 1.4; 95% CI 1.1, 1.9; p = 0.03), the presence of a depressive syndrome (OR = 1.7; 95% CI 1.3, 2.1; p < 0.001), living in an institution (OR = 2.2; 95% CI 1.5, 3.4; p < 0.001), use of more than five drugs (OR = 3.2; 95% CI 2.5, 4.2; p < 0.001) and Charlson's co-morbidity score >1 (OR = 0.6; 95% Cl 0.5, 0.8; p = 0.001). Nineteen percent of all psychotropics prescribed were PIPs. Of these PIPs, 66.5% were anxiolytics, 28.4% were antidepressants and 5.1% were antipsychotics. Use of PIPs in the multivariate analysis was associated only with consumption of more than five drugs (OR = 1.7; 95% CI 1.1, 2.5; p = 0.01). Conclusion: PIM use is common among hospitalized older adults in France. The most important determinant of risk of receiving a psychotropic medication or a PIP was the number of drugs being taken. The elderly, who have multiple co-morbidities, complex chronic conditions and are usually receiving polypharmacy, are at increased risk for adverse drug events. These adverse events are often linked to problems that could be preventable such as delirium, depression and falls. Regular review of prescriptions would help optimize prescription of psychotropics in the elderly. The Beers list is a good tool for evaluating PIMs but is too restrictive with respect to psychotropics; in the latter respect, the list could usefully be widened.

Rasmussen N. On Speed. The Many Lives of Amphetamine. New York: New York University Press, 2008

The book presents the history of the amphetamine class of drugs that were first created in the early part of the 20th century. Paralleling the discussion of the drug's use and resulting problems for individuals due to its abuse potention, is the story of the pharmaceutical industry's efforts to retain the drug in the pharmacopia and its efforts to find problems for which it can be prescribed. Amphetamine, as a class of drugs, was first discovered by Gordon Alles in 1929 while he was doing research on adrenaline substitutes. Although not the first to actually identify the molecule, he was the first to precipitate the salt form and identify it as a potential drug. Eventually he sold the rights to the drug to the Smith Kline French. The story sets forth the efforts to find a use for the new compound and the efforts by the company to get doctors to experiment with "creative" uses, which have included during WW II use by the military to maintain alertness, medically use for weight loss, most recently, attention deficit disorders. The author notes the major property was seemingly to make people feel happy and empowered, and it's emergence as a recreational drug is recounted.

Ray LA; MacKillop J; Tidey JW; Gwaltney C; Miranda R; McGeary J et al. A preliminary pharmacogenetic investigation of adverse events from topiramate in heavy drinkers. Experimental and Clinical Psychopharmacology 17(2): 122-129, 2009. (38 refs.)

Topiramate, an anticonvulsant medication, is an efficacious treatment for alcohol dependence. To date, little is known about genetic moderators of side effects from topiramate. The objective of this study was to examine 3 single nucleotide polymorphisms (SNPs) of the glutamate receptor GluR5 gene (GRIK1) as predictors of topiramate-induced side effects in the context of a laboratory study of topiramate. Heavy drinkers (n = 51, 19 women and 32 men), 75% of whom met criteria for an alcohol use disorder, completed a 5-week dose escalation schedule to a target dose of either 200 or 300 mg or matched placebo. The combined medication groups were compared with placebo-treated individuals for side effects at target dose. Analyses revealed that an SNP in intron 9 of the GRIK1 gene (rs2832407) was associated with the severity of topiramate-induced side effects and with serum levels of topiramate. Genes underlying glutamatergic neurotransmission, such as the GRIK1 gene, may help predict heterogeneity in topiramate-induced side effects. Future studies in larger samples are needed to more fully establish these preliminary findings.

Rosen P. No opiates for headache. (editorial). Journal of Emergency Medicine 36(3): 302-304, 2009. (0 refs.)

Rosenblum A; Marsch LA; Joseph H; Portenoy RK. Opioids and the treatment of chronic pain: Controversies, current status, and future directions. (review). Experimental and Clinical Psychopharmacology 16(5): 405-416, 2008. (147 refs.)

Opioids have been regarded for millennia as among the most effective drugs for the treatment of pain. Their use in the management of acute severe pain and chronic pain related to advanced medical illness is considered the standard of care in most of the world. In contrast, the long-term administration of an opioid for the treatment of chronic noncancer pain continues to be controversial. Concerns related to effectiveness, safety, and abuse liability have evolved over decades, sometimes driving a more restrictive perspective and sometimes leading to a greater willingness to endorse this treatment. The past several decades in the United States have been characterized by attitudes that have shifted repeatedly in response to clinical and epidemiological observations, and events in the legal and regulatory communities. The interface between the legitimate medical use of opioids to provide analgesia and the phenomena associated with abuse and addiction continues to challenge the clinical community, leading to uncertainly about the appropriate role of these drugs in the treatment of pain. This narrative review briefly describes the neurobiology of opioids and then focuses on the complex issues at this interface between analgesia and abuse, including terminology, clinical challenges, and the potential for new agents, such as buprenorphine, to influence practice.

Ruhoy IS; Daughton CG. Beyond the medicine cabinet: An analysis of where and why medications accumulate. Environment International 34(8): 1157-1169, 2008. (57 refs.)

Active pharmaceutical ingredients (APIs) from medications can enter the environment as trace contaminants, at individual concentrations generally below a part per billion (mu g/L). APIs enter the environment primarily via the discharge of raw and treated sewage. Residues of unmetabolized APIs from parenteral and enteral drugs are excreted in feces and urine, and topically applied medications are washed from skin during bathing. These trace residues may pose risks for aquatic life and cause concern with regard to subsequent human exposure. APIs also enter the environment from the disposal of unwanted medications directly to sewers and trash. The relative significance of this route compared with excretion and bathing is poorly understood and has been subject to much speculation. Two major aspects of uncertainty exist: the percentage of any particular API in the environment originating from disposal is unknown, and disposal undoubtedly occurs from a variety of dispersed sources. Sources of disposal, along with the types and quantities of APIs resulting from each source, are important to understand so that effective pollution prevention approaches can be designed and implemented. Accumulation of leftover, unwanted drugs poses three major concerns: (i) APIs disposed to sewage or trash compose a diverse source of potential chemical stressors in the environment. (ii) Accumulated drugs represent increased potential for drug diversion, with its attendant risks of unintentional poisonings and abuse. (iii) Leftover drugs represent wasted healthcare resources and lost opportunities for medical treatment. This paper has four major purposes: (1) Define the processes, actions, and behaviors that control and drive the consumption, accumulation, and need for disposal of pharmaceuticals. (2) Provide an overview of the diverse locations where drugs are used and accumulate. (3) Present a summary of the first cataloging of APIs disposed by a defined subpopulation. (4) Identify opportunities for pollution prevention and source reduction.

Schmidt C; Bischof G; Harting M; Rumpf HJ. Motivation to change and readiness for counseling in prescription-drug-dependent patients in a general hospital population. Addiction Research & Theory 17(2): 186-190, 2009. (18 refs.)

At the present time, only a small minority of prescription-drug-dependent patients is provided with adequate treatment. The purpose of this article is to investigate the motivation to change and the readiness to accept consultation in prescription-drug-dependent patients. Among 952 general hospital patients, aged 18 to 64 years, 45 individuals dependent on prescription drugs were identified, using a screening questionnaire and a structured psychiatric interview as diagnostic instruments. The stage of change was examined following the stage concept of the Transtheoretical Model (TTM). According to the TTM 55.5% (n = 25) of the study population were in the precontemplation stage, 37.8% (n = 17) were on the contemplation stage and 6.7% (n = 3) had reached the level of preparation. For analyzing variables that might influence motivation to change, contemplators and preparators were merged into one group. The self-efficacy to change current drug consumption was significantly higher in patients with elevated motivation to change (p = 0.001). Overall, receiving counseling was rated positive by the sample. The majority of the prescription-drug-dependent patients were in a low stage of motivation to give up their drug consumption, but highly motivated to receive counseling making the general hospital a suitable setting to start early interventions.

Schneider NK; Ling PM. How tobacco protects you against the flu. (editorial). Tobacco Control 17(3): 215-216, 2008. (4 refs.)

This editorial highlights a recent advertising campaign conducted in Germany, conducted in the wake of limitations on tobacco advertising within the European Union.

Smith AJ; Sketris I; Cooke C; Gardner D; Kisely S; Tett SE. A comparison of benzodiazepine and related drug use in Nova Scotia and Australia. Canadian Journal of Psychiatry 53(8): 545-552, 2008. (47 refs.)

Objective: Benzodiazepines can be a problem if used for long periods, or in at-risk populations, such as the elderly. We compared the use of benzodiazepine and related prescription medicines in Nova Scotia and Australia. Methods: The Nova Scotia Pharmacare Program and the Pharmaceutical Benefits Scheme in Australia were used to obtain dispensing data in comparable populations for all publicly subsidized benzodiazepines and related compounds. Usage was compared from 2000 to 2003, using the World Health Organization anatomical therapeutic chemical and defined daily dosage (DDD) system. We also determined differences in the types of benzodiazepines prescribed. Results: The use of benzodiazepines increased at a steady but comparable rate in both areas. However, the use of benzodiazepines in Nova Scotia was more than double that of Australia in 2000 (123 and 48 DDD/1000 beneficiaries per day, respectively) through 2003 (138 and 57 DDD/1000 beneficiaries per day, respectively). Eight different benzodiazepines made up 90% of the drug use in Nova Scotia by contrast to only 4 different benzodiazepines in Australia. Conclusions: Large differences exist between the type and rate of benzodiazepine prescribing in Nova Scotia and Australia, with Nova Scotia reporting more than twice as much use. Benzodiazepine use in both jurisdictions is increasing. The Canadian findings are especially concerning as benzodiazepine use in the Atlantic provinces has been reported to be less than other provinces. The variations between the 2 jurisdictions may be due to factors such as fewer benzodiazepines available in Australia, differences in prescriber, patient attitudes and behaviours, or different initiatives to influence benzodiazepine use.

Smith AJ; Tett SE. How do different age groups use benzodiazepines and antidepressants? Analysis of an Australian administrative database, 2003-6. Drugs & Aging 26(2): 113-122, 2009. (40 refs.)

Background: The use of antidepressants and benzodiazepines is increasing in Australia and worldwide, and it is thought that some of the prescribing of these classes of drugs may be inappropriate. However, the demographic characteristics of the subgroups of the population responsible for this increase remain unexplored. Objective: The aim of this study was to examine changes in the utilization of antidepressants and benzodiazepines between different age groups within Australia from 2003 to 2006. Methods: The Australian Pharmaceutical Benefits Scheme administrative database was used to obtain dispensing data for all antidepressants and Publicly subsidized benzodiazepines. Changes in utilization (amounts and patterns of use of different compounds) were compared between different age groups from 2003 to 2006. The WHO Anatomic Therapeutic Chemical/Defined Daily Dose system was used. Results: Use of antidepressants increased from 2003 to 2006, and in each year increased with age, with those >= 65 years having the greatest use. Differences were seen in the antidepressant most utilized, with the elderly using more tricyclic antidepressants than those who are younger. The utilization of benzodiazepines decreased from 2003 to 2006 in elderly individuals and those receiving social welfare benefits. Individuals aged >= 85 years had the highest use of benzodiazepines and used more long-acting benzodiazepines compared with those aged 35-44 years. Conclusion: The elderly still account for most use per capita of benzodiazepines. Some of this use may be inappropriate (e.g. use of long-acting benzodiazepines) and, hence, may represent a useful target for future educational intervention. The elderly also still account for the largest per capita use of antidepressants.

Spiller H; Lorenz DJ; Bailey EJ; Dart RC. Epidemiological trends in abuse and misuse of prescription opioids. Journal of Addictive Diseases 28(2): 130-136, 2009. (16 refs.)

The authors evaluated trends between social, geographic, and demographic factors and cases of select scheduled drugs (buprenorphine, fentanyl, hydrocodone, hydromorphone, morphine, methadone, and oxycodone) using the Researched Abuse, Diversion and Addiction-Related Surveillance System poison center data and census data. Spontaneous calls from the public and healthcare professionals are recorded by poison centers using a standardized, electronic data collection system. We compared the annual incidence of total prescription opioid drug cases to annual data from the U.S. Department of Labor and U.S. Census Bureau by year and by state for unemployment rate, poverty rate, population density, high school graduation rate, and bachelor's degree proportion using the best least square fit in an evaluation for trends for 2003 to 2006. Two strong positive trends were found between poverty rate, unemployment rate, and prescription opioid drug rates, with prescription opioid drug rates increasing as poverty rate and unemployment rate increased. This trend was consistent over the 4 years of study and strongly influenced by the hydrocodone and methadone rates, with less influence from oxycodone rates. The high school graduation rate trend was consistent over the 4 years and was strongly influenced by the hydrocodone and methadone rate. No consistent trend was identified with population density and prescription opioid drug rates. Understanding trends may help guide distribution of scarce resources and prevention efforts to where they may have their greatest impact.

Stein K; Ramil M; Fink G; Sander M; Ternes TA. Analysis and sorption of psychoactive drugs onto sediment. Environmental Science & Technology 42(17): 6415-6423, 2008. (44 refs.)

An analytical method was developed to analyze eight psychoactive pharmaceuticals -- including the antiepileptic carbamazepine, the opiates morphine, codeine, dihydrocodeine, the opiode tramadol, and the tranquilizers diazepam, oxazepam, temazepam -- and the antibiotic sulfa methoxazole as well as three metabolites (10,11-dihydrocarbamazepine (DHC), 10,11-dihydroxy-10, 11-dihydrocarbamazepine, and N-4-acetylsulfamethoxazole) in river sediments. Relative recoveries of all analytes exceeded 97% using either deuterated or (CN)-C-13-N-15-labeled surrogate standards. Sorption isotherms of all analytes were constructed at pH 6.5-6.6 on two natural river sediments (Burgen and Dausenau) that differed in organic carbon contents and particle size distributions. Affinities of all analytes were up to an order of magnitude higher for the Dausenau sediment in comparison to the Burgen sediment. Isotherms were well described by the Freundlich model. Sorption of all analytes was linear on the Burgen sediment except for structurally similar carbamazepine (n = 0.90) and DHC (n = 0.88). Conversely, most analytes showed pronounced nonlinear sorption to the Dausenau sediment (n = 0.77-0.92) except for positively charged codeine, dihydrocodeine, and tramadol. Linear sorption of the latter was taken to arise from concentration-independent electrostatic interactions of the organocations with negatively charged surfaces on clay minerals or in the sediment organic matter. Desorption gave rise to hysteresis in 13 out of 16 investigated analyte-sorbent systems. Hysteresis was likely due to slow desorption kinetics beyond 24 h used in the experiment.

Sterke CS; Verhagen AP; Van Beeck EF; van der Cammen TJM. The influence of drug use on fall incidents among nursing home residents: A systematic review. (review). International Psychogeriatrics 20(5): 890-910, 2008. (39 refs.)

Background: Falls are a major health problem among the elderly, particularly in nursing homes. Abnormalities of balance and gait, psychoactive drug use, and dementia have been shown to contribute to fall risk. Methods: We conducted a systematic review of the literature to investigate which psychoactive drugs increase fall risk and what is known about the influence of these drugs on gait in nursing home residents with dementia. We included studies with a prospective cohort design on psychoactive drug use in nursing homes with dementia residents and with falls as an outcome measure. Results: Seventeen studies were included in the review. Pooled risk estimates were not calculated because there was no homogeneity across studies. We assessed the strength of evidence for psychoactive drugs as a prognostic factor for falls by defining four levels of evidence: strong, moderate, limited or inconclusive. Strong evidence was defined as consistent findings (>= 80%) in at least two high quality cohorts. We found strong evidence that the use of multiple drugs (3/3 cohorts, effect sizes 1.30-10.30), antidepressants (10/12 cohorts, effect sizes 1.10-7.60), and anti-anxiety drugs (2/2 cohorts, effect sizes 1.22-1.32) is associated with increased fall risk. The evidence for the association of other psychoactive drug classes with fall risk was limited or inconclusive. Conclusions: Research on the contribution of psychoactive drugs to fall risk in nursing home residents with dementia is limited. The scarce evidence shows, however, that multiple drugs, antidepressants and anti-anxiety drugs increase fall risk in nursing home populations with residents with dementia.

Stowell KR; Chang CCH; Bilt J; Stoehr GP; Ganguli M. Sustained benzodiazepine use in a community sample of older adults. Journal of the American Geriatrics Association 56(12): 2285-2291, 2008. (29 refs.)

To identify factors associated with sustained benzodiazepine use in older adults. Twelve-year cohort study. Community-based epidemiological survey. One thousand three hundred forty-two individuals aged 65 and older. Demographics, medication use, depressive symptoms, sleep complaints, alcohol use, and smoking assessed at 2-year intervals; descriptive analysis to characterize benzodiazepine users and identify factors associated with sustained benzodiazepine use (use at two consecutive waves); and longitudinal lag-time analysis to determine characteristics that predicted sustained use. Initially, 5.5% of men and 9.8% of women were using benzodiazepines. Users were significantly more likely than nonusers to be female and less educated, report more depressive and anxiety symptoms, use more prescription medications, have lower self-rated health, have difficulty maintaining sleep, and be less likely to consume alcohol. Approximately 50%, 44%, and 25% of these users aged 65 to 74, 75 to 84, and 85 and older, respectively, were sustained users at follow-up. Being female, using two or more nonbenzodiazepine prescription medications, and smoking were independently associated with subsequent sustained benzodiazepine use. At the population level, women, smokers, and users of at least two prescription drugs have higher probabilities of sustaining benzodiazepine use once started. This information can facilitate risk assessment and counseling of older adults before prescribing benzodiazepines.

Takougang I; Ngogang J; Sihom F; Ntep M; Kamgno J; Eyamba A et al. Does alcohol consumption increase the risk of severe adverse events to ivermectin treatment? African Journal of Pharmacy and Pharmacology 2(4): 77-82, 2008. (22 refs.)

The present investigation is a case-control study designed to assess the level of association between alcohol consumption and the occurrence of severe adverse reaction (SAE) following ivermectin consumption. [Note: Ivermectin is a medication to deal with worms that cause river blindness] Thirty-six (36) cases of SAE occurred in the health districts of Bankim, Nanga Eboko, Obala, Okola and Sa'a. Case and control (43) individuals were submitted to a questionnaire related to their alcohol consumption 24 before and 24 to 48 h following ivermectin intake. An in-depth interview of siblings and local health worker was conducted to assess alcohol consumption around Mectizan intake. The degree of alcohol use was assessed using the level of serum transaminases and the alcohol use disorder identification test (AUDIT). The alcoholic beverages of the study communities were conventional such as beer, whisky, or locally made. Locally produced beverages included "arki" ("Odontol", "Hah", ...) and palm wine. The bark, sap or fruit of plants adjuvant are known to contain alkaloids and tannins which are potent neurotropic substances. The likelihood of developing SAE among cases and controls did not differ significantly with history of consumption of alcoholic beverages. Nor did it differ for other indicators of chronic alcohol consumption.

Tavafian SS; Zadeh FR. Cigarette smoking, illicit medicine, substance and alcohol abuse among pregnant women: A cross sectional study from Iran. International Journal of Fertility & Sterility 2(1): 35-38, 2008. (20 refs.)

Background: The aim of this study was to investigate the prevalence of illicit medicine abuse among. pregnant women who referred to the general teaching hospital in Tehran. Materials and Methods: A non-randomized sample of 2189 eligible pregnant women, which were at 2nd and 3rd trimester, were visited for 2nd prenatal care or subsequent consultation and being confident regarding the time of taking illicit medicine, were enrolled from 15 teaching obstetric clinics, located in Tehran, during August and September 2004. A self administered questionnaire that was consisted of questions regarding demographic characteristics, obstetric history, illicit medicine taking, substance and alcohol abuse by pregnant women and their family members'/friends' during current pregnancy, was used to collect data. Data were analyzed by SPSS, version 13. Results: 2189 pregnant women with the mean age of 26 +/- 5.5 years studied in this study. Of all, 967(44.9%) were prime gravid and 464(21.2%) carrying unwanted pregnancy, 116 ones (5.29%) had taken medicine at first trimester, among them 114 participants (98.3) used unsafe medicine. In all, 16 individuals (0.7%) smoked cigarette, 3 participants (0.2%) abused substance. The rate of alcohol abuse was 0.2% among studied participants, 11% among participants' husbands and 15.7% among participants' family member. Of all, 641 participants' husband (29.3%) were smoker. Conclusion: Although this study showed insignificant rate of substance abuse among studied women, the high percent of these women exposed to non prescribed illicit medicines and passive smoking during their first trimester of their pregnancy that should be considered strongly.

Tcheremissine OV. Is quetiapine a drug of abuse? Reexamining the issue of addiction. (review). Expert Opinion on Drug Safety 7(6): 739-748, 2008. (92 refs.)

Background: The abuse and diversion of pharmacological agents with CNS mechanisms of action is an important concern from governmental, regulatory, public health and safety perspectives. In recent years, there have been an increased number of reports concerning the abuse and diversion of quetiapine in forensic population and in individuals with histories of substance abuse. Objective: To better understand this surging pattern the available body of evidence was critically examined. Methods: A literature search from January 1991 to July 2008 restricting papers to English and using PUBMED and PsychInfo was performed. Results: Nine papers were identified. The content of these papers is discussed in light of recent research on drug abuse.

Tonje L; Elisabeth S; Lars W. Handling of drug-related emergencies: an evaluation of emergency medical dispatch. European Journal of Emergency Medicine 16(1): 37-42, 2009. (27 refs.)

Aims: Documenting the quality of emergency dispatch centres handling of emergency calls regarding intoxicated unconscious patients. Methods: Interview with eight emergency dispatch centre directors and a nationwide survey among 313 dispatchers in Norway were performed. In addition, a customized scoring system was used to evaluate dispatcher log recordings of real cases. The recordings were compared with information from corresponding ambulance records. Results: Ninety-nine percent of the dispatchers stated that they used the Norwegian protocol for medical emergencies and 89% of them found it useful. The interviews, the survey, and the recordings, however, documented frequent deviation from the protocol. This instructs ambulance dispatch for any unconscious patient, but 21% stated that they would not dispatch any resource for an unconscious patient without further survey in alcohol-related cases. This was significantly more often (P < 0.05) than for the narcotic, combination and prescription -drug-related cases with 4, 10 and 7%, respectively. The recordings revealed deviation from the protocol with dispatchers only determining the patients' level of consciousness and respiratory status in 64 and 70% of the cases, respectively. For 16% of the cases, the dispatcher did not ask the caller about consciousness at all, even though these patients later were found with reduced consciousness. Conclusion: On the basis of the interviews and the survey, cases were handled according to guidelines. The log recordings, however, disclosed deviation from the protocol. Alcohol intoxication was associated with higher rate of deviation from the protocol compared with other intoxications.

Trip AM; Visser ST; Kalverdijk LJ; de Jong-van den Berg LTW. Large increase of the use of psycho-stimulants among youth in the Netherlands between 1996 and 2006. British Journal of Clinical Pharmacology 67(4): 466-468, 2009. (5 refs.)

What is already known about this subject? In the USA psycho-stimulant use has increased rapidly in the 1990s and stabilized around 2000. This study describes the prevalence of psycho-stimulant use between1996 and 2006 in the Netherlands. What this study adds. The prevalence of psycho-stimulant use among youth in the Netherlands has increased more than eightfold in the period 1996-2006, but in 2006 it is still below the prevalence in the. To describe the use of psycho-stimulants in the Netherlands between 1996 and 2006 in children and adolescents, and in relation to age and sex. With the pharmacy prescription database the IADB.nl, yearly prevalences of psycho-stimulants per 1000 children were calculated, as was the length of psycho-stimulant use with Kaplan-Meier method in SPSS 12.0. Psycho-stimulant use increased in boys (0-19) from 4.5 parts per thousand in 1996 to 31.1 parts per thousand in 2006 and for girls from 0.7 to 8.1 parts per thousand, respectively. The largest increase was among boys aged 10-19 years. There is a trend towards prescribing the sustained release preparation of methylphenidate (Concerta). In the Netherlands a large increase in psycho-stimulants use is observed. However, in the Netherlands the prevalence ratio male/female declined from 6.4 in 1996 to 3.8 in 2006.

Tutka P. Nicotinic receptor partial agonists as novel compounds for the treatment of smoking cessation. (review). Expert Opinion on Investigational Drugs 17(10): 1473-1485, 2008. (94 refs.)

Nicotine addiction and the neurobiological mechanisms explaining nicotine reinforcement, withdrawal, and relapse involve alpha 4 beta 2 nicotinic acetylcholine receptors (nAChRs). This review updates readers on the preclinical and clinical pharmacology, as well as the therapeutic efficacy and safety of cytisine and varenicline, the two partial agonists of nAChRs for smoking cessation. Cytisine has been used for several decades; yet despite its surprising popularity in some parts of the world, it has been absent from almost all existing reviews of smoking cessation drugs. If safe and sufficiently efficacious, an obvious advantage would be its low cost, which could make cytisine an attractive treatment available to millions of smokers. Varenicline was recently introduced to the drug market and has been found to be more efficacious than existing treatments. Very encouraging results of early human trials and strong theoretical background for their use make the nAChRs partial agonists a promising alternative for currently available antismoking treatments.

Uchida H; Suzuki T; Mamo DC; Mulsant BH; Kikuchi T; Takeuchi H et al. Benzodiazepine and antidepressant use in elderly patients with anxiety disorders: A survey of 796 outpatients in Japan. Journal of Anxiety Disorders 23(4): 477-481, 2009. (37 refs.)

Since the literature on benzodiazepine use in elderly patients with anxiety disorders is limited, a large cross-sectional review of psychotropic prescriptions in 796 patients with neurotic disorders (ICID-10) (age range = 11-91 years) was conducted across 30 sites in Japan. Use of benzodiazepine-derivative anxiolytics was approximately 70% in all decades without a group difference. The proportion of subjects who received prescriptions for benzodiazepine-derivative anxiolytics in the absence of antidepressants was higher in older age groups (e.g., 27.7% and 43.2% in the third and sixth decades, respectively). On the other hand, antidepressants were less frequently prescribed in older age groups (e.g., 59.8% and 41.5% in the third and sixth decades, respectively). The very high use of anxiolytics in the elderly, especially in the absence of concomitant antidepressant use, is a cause for concern since they are not a preferred long-term treatment strategy given their adverse effects in the elderly.

Vrublevska K; Rukmane J; Burmistrs R; Sipols J; Muceniece R. Dispensing of psychotropic drugs to adults in community pharmacies in Latvia. Pharmacy World & Science 30(6): 934-939, 2008. (26 refs.)

Objective: To estimate outpatient utilization of psychotropic drugs before and after pharmaceutical reform in Latvia. Setting Data concerning prescribing and dispensing of psychotropic drugs were collected in six community pharmacies in the region of Latgale of Latvia. Method: An exploratory analysis of prescription data provided by six community pharmacies from 2004 to 2007. Drugs included in the study were classified according to an Anatomical-Therapeutic-Chemical (ATC) drug classification system, and ATC data were used to calculate defined daily doses (DDD) per 1,000 inhabitants. The National SSK-10 classification was used for analysis of codes of disease diagnosis. Main outcome measures Identification of the most often prescribed psychotropic drug and prescribing physician, patient characterization by age and gender, and analysis of codes of diseases. Results Benzodiazepines and benzodiazepine-related drugs were mainly prescribed in outpatient practice. Diazepam was the most frequently prescribed benzodiazepine-12 DDD/1,000/day. The drugs were prescribed mainly by family physicians (in 66% of cases). Female residents bought more psychotropic drugs than males. In addition, residents of cities bought little more drugs than those living outside urban areas. Accordingly to the recorded disease codes, the codes for neurotic and behavioral disorders dominated. Conclusion: The introduction of new norms neither increased nor decreased the number of psychotropic drug prescriptions filled. The most often prescribed psychotropic drugs over 4-year period were benzodiazepines and their derivates. Disease codes on the prescriptions fully justified a reason for psychotropic drug use.

Walsh SL; Nuzzo PA; Lofwall MR; Holtman JR. The relative abuse liability of oral oxycodone, hydrocodone and hydromorphone assessed in prescription opioid abusers. Drug and Alcohol Dependence 98(3): 191-202, 2008. (38 refs.)

Abuse of prescription opioids has risen precipitously in the United States. Few controlled comparisons of the abuse liability of the most commonly abused opioids have been conducted. This outpatient study employed a double-blind, randomized, within-subject, placebo-controlled design to examine the relative abuse potential and potency of oral oxycodone (10, 20 and 40mg), hydrocodone (15, 30 and 45 mg), hydromorphone (10, 17.5 and 25 mg) and placebo. Healthy adult volunteers (n = 9) with sporadic prescription opioid abuse participated in I I experimental sessions (6.5 h in duration) conducted in a hospital setting. All three opioids produced a typical mu opioid agonist profile of subjective (increased ratings of liking, good effects, high and opiate symptoms), observer-rated, and physiological effects (miosis, modest respiratory depression, exophoria and decrements in visual threshold discrimination) that were generally dose-related. Valid relative potency assays revealed that oxycodone was roughly equipotent to or slightly more potent than hydrocodone. Hydromorphone was only modestly more potent (less than two-fold) than either hydrocodone or oxycodone, which is inconsistent with prior estimates arising from analgesic studies. These data suggest that the abuse liability profile and relative potency of these three commonly used opioids do not differ substantially from one another and suggest that analgesic potencies may not accurately reflect relative differences in abuse liability of prescription opioids.

Wasan AD; Butler SF; Budman SH; Fernandez K; Weiss RD; Greenfield SF et al. Does report of craving opioid medication predict aberrant drug behavior among chronic pain patients? Clinical Journal of Pain 25(3): 193-198, 2009. (35 refs.)

Objective: To examine the relationship between the self-report of craving prescription medication and subsequent opioid misuse among chronic pain patients prescribed opioids for pain. Methods: Six hundred thirteen patients taking opioid medication for chronic noncancer pain were asked how often they have felt a craving for their medication on a scale from 0 - never to 4- very often. All participants completed a Series Of baseline questionnaires. After 0 months the participants were administered it structured prescription drug use interview (Prescription Drug Use Questionnaire), and submitted a urine sample for toxicology assessment. Their treating physicians also completed a substance misuse behavior checklist (Prescription Opioid Therapy Questionnaire). Results: Three hundred thirty-seven participants (55.0%) reported that they never felt a craving for their medication, whereas 276 (45.0%) reported sonic degree of craving their medication (seldom to very often). Those who reported craving their medication were significantly more often male (P < 0.01), unmarried (P < 0.05), had lower scores on social desirability (P<0.001) and had been prescribed opioids for a longer time (P < 0.05) than those who did not report craving medication. At 6-month follow-up, those who reported craving their medication showed higher scores on the Prescription Drug Use Questionnaire (P < 0.001), had a higher incidence of physician-rated aberrant drug behavior on the Prescription Opioid Therapy Questionnaire (P < 0.05), showed a higher frequency of abnormal urine toxicology screens (P < 0.001), and more often had a positive Aberrant Drug Behavior Index (P < 0.001). Dicussion: These result, Suggest that self-reported craving is a potential marker for identifiation of those at risk for opioid medication misuse.

Wilsey BL; Fishman SM; Tsodikov A; Ogden C; Symreng I; Ernst A. Psychological comorbidities predicting prescription opioid abuse among patients in chronic pain presenting to the emergency department. Pain Medicine 9(8): 1107-1117, 2008. (57 refs.)

We attempted to identify psychological comorbidities that are associated with the propensity for prescription opioid abuse. Patients presenting to an emergency department seeking opioid refills for chronic pain were evaluated with five validated self-report instruments and structured clinical interviews. The potential for prescription opioid abuse was modeled with multiple regression analysis using depression, anxiety disorders, personality disorder, and addiction as independent variables. Of the 113 patients studied, 91 (81%) showed a propensity for prescription opioid abuse as determined by scores on the Screener and Opioid Assessment for Patients with Pain instrument. Depression, anxiety, and a history of substance were common and panic attacks, posttraumatic stress disorder, and personality disorders were also found, albeit less frequently. Panic attacks, trait anxiety, and the presence of a personality disorder accounted for 38% of the variance in the potential for prescription opioid abuse. Patients in chronic pain should be assessed for psychological and addiction disorders because they are at increased risk for abusing opioids. They should also be referred for psychosocial treatment as part of their care, where appropriate.

Wright RM; Roumani YF; Boudreau R; Newman AB; Ruby CM; Studenski SA et al. Effect of central nervous system medication use on decline in cognition in community-dwelling older adults: Findings from the Health, Aging and Body Composition Study. Journal of the American Geriatrics Society 57(2): 243-250, 2009. (53 refs.)

To evaluate whether combined use of multiple central nervous system (CNS) medications over time is associated with cognitive change. Longitudinal cohort study. Pittsburgh, Pennsylvania, and Memphis, Tennessee. Two thousand seven hundred thirty-seven healthy adults (aged >= 65) enrolled in the Health, Aging and Body Composition study without baseline cognitive impairment (modified Mini-Mental State Examination (3MS) score >= 80). CNS medication (benzodiazepine- and opioid-receptor agonists, antipsychotics, antidepressants) use, duration, and dose were determined at baseline (Year 1) and Years 3 and 5. Cognitive function was measured using the 3MS at baseline and Years 3 and 5. The outcome variables were incident cognitive impairment (3MS score < 80) and cognitive decline (>= 5-point decline on 3MS). Multivariable interval-censored survival analyses were conducted. By Year 5, 7.7% of subjects had incident cognitive impairment; 25.2% demonstrated cognitive decline. CNS medication use increased from 13.9% at baseline to 15.3% and 17.1% at Years 3 and 5, respectively. It was not associated with incident cognitive impairment (adjusted hazard ratio (adj HR)=1.11, 95% confidence interval (CI)=0.73-1.69) but was associated with cognitive decline (adj HR 1.37, 95% CI=1.11-1.70). Longer duration (adj HR=1.39, CI=1.08-1.79) and higher doses (> 3 standardized daily doses) (adj HR=1.87, 95% CI=1.25-2.79) of CNS medications suggested greater risk of cognitive decline than with nonuse. Combined use of CNS medications, especially at higher doses, appears to be associated with cognitive decline in older adults. Future studies must explore the effect of combined CNS medication use on vulnerable older adults.

Wright C; Schnoll S; Bernstein D. Risk evaluation and mitigation strategies for drugs with abuse liability public interest, special interest, conflicts of interest, and the industry perspective. Annals of the New York Academy of Sciences 1141(Addiction Reviews 2008): 284-303, 2008. (48 refs.)

Risk evaluation and mitigation strategies (REMS) formerly known as Risk Minimization Action Plans (RiskMAPs) are a regulatory technique for dealing with anticipated risks of new medications and are especially important for new drugs with abuse potential. This paper describes the origin and history of risk-management plans for drugs that might be abused, the proper use of these plans in minimizing the risk to the public, and the special difficulties inherent in managing risks for drugs with abuse potential. Drugs with abuse liability are distinctive since the risks inherent in manufacture and distribution include not only risks to patients prescribed the medications, but also risks to the general public including subgroups in the population not intended to get the drug and who receive no medical benefit from the medication. The crafting of risk-management plans intended to protect nonpatient populations is unique for these products. The content, extent, and level of intensity of these plans affect areas of medical ethics, civil liability, and criminal prosecution. The need for risk-management plans for drugs with abuse liability can potentially act as a deterrent to investment and is a factor in decisions concerning the development of new medications for the treatments of pain, ADHD, anxiety disorders, and addictions. This paper provides a framework for moving the process of REMS development forward and criteria for evaluating the probity and adequacy of such programs.

Wu LT; Ringwalt CL; Mannelli P; Patkar AA. Prescription pain reliever abuse and dependence among adolescents: A nationally representative study. Journal of the American Academy of Child and Adolescent Psychiatry 47(9): 1020-1029, 2008. (35 refs.)

Objective: We examined the prevalence, patterns, and correlates of adolescents' abuse, subthreshold dependence ("diagnostic orphans"), and dependence on prescription pain relievers (PPRs) such as opioids in a representative national sample (N = 36,992). Method: Data were from the 2005-2006 National Surveys of Drug Use and Health. DSM-IV criteria for abuse and dependence were examined. Results: Of all adolescents ages 12 to 17, 7% (n = 2,675) reported nonprescribed PPR use in the past year, and 1% (n = 400) met criteria for past-year PPR abuse or dependence. Among the 2,675 adolescents who reported nonprescribed PPR use, more than one in three reported symptoms of abuse or dependence: 7% abuse, 20% subthreshold dependence, and 9% dependence. Regular PPR use, major depressive episodes, and alcohol use disorders were associated with each diagnostic category. Compared with asymptomatic nonprescribed PPR users, increased odds of abuse were noted among nonstudents (adjusted odds ratio [AOR] 2.6), users of mental health services (AOR 1.8), and those reporting poor or fair health (AOR 2.4); and increased odds of dependence were observed among females (AOR 1.6), those who were involved in selling illicit drugs (AOR 1.7), and users of multiple drugs (AOR 2.9). Subthreshold dependent users resembled dependent users in major depressive episodes (AOR 1.5), alcohol use disorders (AOR 1.8), and use of multiple drugs (AOR 1.7). Conclusions: Dependence on PPRs can occur without abuse, and subthreshold dependence deserves to be investigated further for consideration in major diagnostic classification systems.

Wunsch M; Nakamoto K; Behonick G; Massello W. Opioid deaths in rural Virginia: A description of the high prevalence of accidental fatalities involving prescribed medications. American Journal on Addictions 18(1): 5-14, 2009. (30 refs.)

In rural Virginia, drug overdose deaths increased 300% from 1997 to 2003. Polydrug deaths predominate (57.9%) in this review of 893 medical examiner cases. Prescription opioids (74.0%), antidepressants (49.0%), and benzodiazepines (39.3%) were more prevalent than illicit drugs. Two-thirds of decedents were 35-54 years old; 37% were female. When compared to western Virginia metropolitan cases, polydrug abuse was more common, specific medication combinations were found, the death rate per population was higher, and fewer illicit drugs were detected. These rural prescription overdose deaths differ from urban illicit drug deaths, suggesting the need for different strategies in prevention, treatment, and intervention by clinicians and policymakers.

Yang SSY; Lee K. Unusual complication of intravenous Subutex abuse: Two cases of septic sacroiliitis. Singapore Medical Journal 49(12): E343-E346, 2008. (13 refs.)

We report two unusual cases of septic sacroiliitis resulting from intravenous Subutex abuse that initially masqueraded as low back pain. Both patients, a 48-year-old Malay man and a 30-year-old Malay woman, presented with chills, rigor and progressive lower back pain, and eventually experienced difficulty in ambulating. The Malay woman also developed severe pain in her left elbow, with swelling and restriction of movement. Blood investigations and cultures revealed an infective process. Imaging of the pelvis and lower back confirmed the diagnosis of septic arthritis of the sacroiliac joints. The first patient underwent computed tomography-guided drainage of the abscess and was administered intravenous antibiotics via a peripherally-inserted central catheter (PICC) line. The second patient underwent an arthrotomy for her elbow and her left sacroiliac joint was managed conservatively with intravenous antibiotics, also via a PICC line. The diagnostic difficulty and the need for a high index of suspicion are discussed.

Zacny JR; Gutierrez S. Within-subject comparison of the psychopharmacological profiles of oral hydrocodone and oxycodone combination products in non-drug-abusing volunteers. Drug and Alcohol Dependence 101(1/2): 107-114, 2009. (49 refs.)

Background: Non-medical use and abuse of prescription opioids is a significant problem in the United States. Little attention has been paid to assessing the relative psychopharmacological profile (including abuse liability-related effects) of specific prescription opioids. The purpose of this study was to directly compare the psychopharmacological profile of two widely prescribed and abused oral opioid combination products within the same subject. Methods: Twenty non-drug-abusing volunteers participated in a crossover, randomized, double blind Study in which they received, all p.o.: placebo; 975mg acetaminophen (ACET); 10 mg oxycodone (OXY)/487mg ACET; 20mg OXY/975mg ACET; 15 mg hydrocodone (HYD)/487mg ACFT; and 30 mg HYD/975 mg ACET. OXY and HYD doses were chosen to equate the drugs on an objective measure of opiate effects: miosis. Dependent measures were subjective, psychomotor/cognitive, reinforcing, and physiological effects, and relative potency estimates. Results: In general, the two opioid combination products at equi-miotic doses produced similar prototypic opiate-like effects and psychomotor impairment, and of similar magnitude. The higher dose of OXY/ACET produced slightly more abuse liability-related subjective effects than the higher dose of HYD/OXY, but also produced slightly more negative effects. Neither drug at either dose functioned as a reinforcer, as measured by the Multiple Choice Procedure. Relative potency ratios indicated that OXY/ACET was approximately 1.5 times more potent than HYD/ACET. Conclusions: Consistent with a recent study published in this journal using identical doses of HYD and OXY (without ACET) in prescription opioid abusers (Walsh, S.L., Nuzzo, RA., Lofwall, M.R., Holtman.J.R., 2008. The relative abuse liability of oral oxycodone, hydrocodone and hydromorphone assessed in prescription drug abusers. Drug Alcohol Depend. 198, 191-202), we found little difference in the pharmacodynamic effects of HYD/ACET and OXY/ACET in non-drug-abusing volunteers.

Zahradnik A; Otto C; Crackau B; L'hrmann I; Bischof G; John U et al. Randomized controlled trial of a brief intervention for problematic prescription drug use in non-treatment-seeking patients. Addiction 104(1): 109-117, 2009. (45 refs.)

Aims: Dependence on or problematic use of prescription drugs (PD) is estimated to be between 1 and 2% in the general population. In contrast, the proportion of substance-specific treatment in PD use disorders at 0.5% is comparatively low. With an estimated prevalence of 4.7%, PD-specific disorders are widespread in general hospitals compared to the general population. Brief intervention delivered in general hospitals might be useful to promote discontinuation or reduction of problematic prescription drug use. Design: A randomized, controlled clinical trial. Setting: Internal, surgical and gynaecological wards of a general and a university hospital. Participants: One hundred and twenty-six patients fulfilling criteria for either regular use of PD (more than 60 days within the last 3 months) or dependence on or abuse of PD, respectively, were allocated randomly to two conditions. Intervention: Subjects received two counselling sessions based on Motivational Interviewing plus an individualized written feedback (intervention group, IG) or a booklet on health behaviour (control group, CG). Measurements: The outcome was measured as reduction (>25%) and discontinuation of PD intake in terms of defined daily dosages (DDD). Findings: After 3 months, more participants in the IG reduced their DDD compared to the participants in the CG (51.8% versus 30%; _2 = 6.17; P = 0.017). In the IG 17.9%, in the CG 8.6% discontinued use of PD (_2 = 2.42; P = 0.17). Conclusions: Brief intervention based on motivational interviewing is effective in reducing PD intake in non-treatment-seeking patients.

Zee AV. The promotion and marketing of OxyContin: Commercial triumph, public health tragedy. (editorial). American Journal of Public Health 99(2): 221-227, 2009. (70 refs.)

I focus on issues surrounding the promotion and marketing of controlled drugs and their regulatory oversight. Compared with noncontrolled drugs, controlled drugs, with their potential for abuse and diversion, pose different public health risks when they are overpromoted and highly prescribed. An in-depth analysis of the promotion and marketing of OxyContin illustrates some of the associated issues. Modifications of the promotion and marketing of controlled drugs by the pharmaceutical industry and an enhanced capacity of the Food and Drug Administration to regulate and monitor such promotion can have a positive impact on the public health.