Noni A. Graham

Methadone- and heroin-related deaths in Florida.

Methadone is a potent synthetic opioid used for treatment of opioid dependence and chronic pain. Florida Department of Law Enforcement data were analyzed to examine trends in deaths related to or caused by methadone and/or heroin between 2001–2006. Results demonstrated that mortalities associated with methadone use increased steadily as mortalities associated with heroin decreased steadily. Though useful in the treatment of opioid dependence and chronic pain, methadone possesses high abuse potential and documented mortality risks. Treatment with methadone, for both pain and opioid dependence, should be preceded by an abuse liability evaluation. Attempts to minimize diversion should be implemented.

Tobacco and Psychiatric Dual Disorders

Abstract Smoking is a leading cause of morbidity and premature mortality in the United States. The relationship between tobacco smoking and several forms of cancer, heart disease, stroke, chronic lung disease, and other medical diseases is well recognized and accepted. Recent epidemiological studies are now focusing on the link between tobacco use and psychiatric diseases. Experts now suggest that in the differential diagnosis of “smoker,” depression, alcohol dependence, and schizophrenia are highest on the list. Studies are also focusing on the role of secondhand tobacco exposure, either in utero or during childhood, in the risk of dual disorders. Prenatal exposure may alter gene expression and change the risk for a variety of life-long psychiatric diseases, e.g., ADD/ADHD, antisocial personality disorders, substance use disorders, and major depression. Considerable time and effort have been devoted to studying the link between smoking and depression and also schizophrenia. We will focus on less well-studied areas in tobacco use and psychiatric dual disorders (including eating disorders), prenatal and early childhood secondhand smoke (SHS) exposure, and the relationship to the genesis of these dual disorders.

Second-Hand and Third-Hand Drug Exposures in the Operating Room: A Factor in Anesthesiologists’ Dependency on Fentanyl

Fentanyl is frequently identified as a drug of choice in opioid-dependent anesthesiologists. We commend Law et al. for their efforts to document secondhand exposure to fentanyl in their operating room.1 We have reviewed physician and health provider drug abuse and dependence elsewhere.2 Our experience with fentanyl, detection has been different. We recognize that fentanyl detection in the operating room likely depends on a variety of factors, including the size of the operating room, the air handling system, the dose of fentanyl administered in surgery, and method of analysis. Our nanotechnology group has measured fentanyl and propofol by a variety of methods, including propofol by gas chromatography-mass spectrometry (GC/MS) and fentanyl by liquid chromatography-mass spectrometry (LC/MS). We observed the presence of fentanyl in exhaled breath, patient expiratory circuits, over sharps boxes, on the skin of operating room personnel, and on various surfaces within the operating room.3 Currently, our nanotechnology group uses an API4000 LC-MS-MS, which has significantly enhanced sensitivity to detect low levels of fentanyl than a GC-MS. We have also observed propofol abuse and the presence of propofol in exhaled breath. Gong et al.,4 Perl et al.,5 and Grossherr et al.6 have also confirmed the presence of propofol in human breath. Furthermore, researchers have reported on operating room pollution due to the presence of “waste anesthetic gases,” such as nitrous oxide and inhaled anesthetics, despite best efforts to minimize exposure.7 Although low-level exposure may be the most relevant to addicts and recent post-addict health providers, we maintain that the integrity of operating room air and decreasing third-hand exposure through contaminated surfaces is of utmost importance for the health and safety of anyone entering this area. Our hypothesis on recovering anesthesiologists’ re-exposure to fentanyl or propofol in operating rooms has allowed our group to test several strategies to prevent harm, which we presented at the 2010 ASAM meeting in San Francisco.8 Our group and others have reported the presence of fentanyl in exhaled breath. When humans exhale, the breath containing the fentanyl (with the vast majority presumably in the form of airborne aerosol droplets) is expired into the operating room. As a consequence, by definition, one should see fentanyl in the room, but the breath concentration of fentanyl will be markedly diluted in the room and air turnover/handling in the room will be factors in determining the room air fentanyl concentration. In our opinion, the issue of detection of fentanyl in operating room air is a matter of sensitivity. Health care workers’ exposure to fentanyl is not only a matter of airborne fentanyl in rooms, but also the presence of this drug on multiple surfaces, which when touched by the health care worker will cause fentanyl to be readily absorbed through the skin and into the blood. In view of these findings, we continue to believe that exposure to fentanyl, propofol, or other drugs in the operating room may be factors in anesthesiologists’ relapses and the frequency of dependency on opioids such as fentanyl.

Prescription Opioids and Overdose Deaths

1. Kibbe AH. Handbook of Pharmaceutical Excipients. 3rd ed. Washington, DC: American Pharmaceutical Association; 2000. 2. Baxter AJ, Krenzelok EP. Pediatric fatality secondary to EDTA chelation. Clin Toxicol (Phila). 2008;46(10):1083-1084. 3. Why does Fisher’s exact test disagree with the confidence interval for the odds ratio? Stata Web site. http://www.stata.com/support/faqs/stat/disagree.html. Accessed February 23, 2009. 4. Agresti A. Categorical Data Analysis. 2nd ed. New York, NY: John Wiley & Sons Ltd; 2002. 5. Macassey EA, Baguley C, Dawes P, Gray A. 15-year audit of post-tonsillectomy haemorrhage at Dunedin Hospital. ANZ J Surg. 2007;77(7):579-582.

A marked increase in cocaine-related deaths in the State of Florida: precursor to an epidemic?

Abstract The history of cocaine misuse includes a destructive epidemic during the 1980s. While recent surveys suggest cocaine use is stable or decreasing, we have observed increasing trends of cocaine-related death through analysis of medical examiner data collected by the Florida Department of Law Enforcement (FDLE). Floridas per capita cocaine-related death rates nearly doubled from 2001 to 2005. Electronic collection of data such as that collected by the FDLE nationally and in real-time would greatly advance understanding of drug-use patterns and consequences. For example, results from Florida suggest that high school and college students, and members of higher socioeconomic status, appear to be at increased risk of cocaine abuse. Public health interventions are necessary to prevent another full-fledged epidemic.

Educational intervention to improve secondhand smoke awareness, competency, and screening among health professions students

Alcohol use and tobacco smoke exposure are frequently correlated, with many individuals smoking and/or experiencing secondhand smoke (SHS) exposure while drinking (e.g., in bars, bowling alleys, or clubs). Unfortunately, most medical school curricula do not adequately address the topic of screening and brief intervention (SBI) for tobacco use, SHS exposure, and/or problematic drinking. The aim of this study was to assess the effectiveness of a three-part educational intervention for health-professions schools to address the consequences of SHS exposure and develop SBI skills in medical students. Because information regarding the effects of smoking and SHS can be effectively communicated via self-directed online lectures, we developed an online training module including a videotaped lecture series with accompanying PowerPoint slides. To help students develop diagnostic skills related to SHS and other substance exposure, 10 standardized patient cases were included for instruction and testing. Finally, a clinical-instruction DVD provided examples of how practitioners can implement motivational-interviewing strategies in behavior change counseling related to tobacco use, with or without co-occurring alcohol use. Participants in the educational intervention, compared with controls (no intervention), scored significantly higher on the SHS Competency Exam. In addition, 100% of students who received the intervention reported plans to screen for SHS exposure. This educational intervention may be a valuable addition to medical and health professional school curricula while requiring minimal faculty time and effort.

Women Tipping the Scale During Pregnancy: A Special Population for Obesity Interventions, Treatments and Clinical Trials

New treatments for obesity are often focused on reducing appetite in otherwise healthy adults. Similarly, health guidelines and promotion programs are focused on healthy adults. We have become alarmed by the increasing prevalence of overweight and obesity in women of reproductive age. This issue has been equally overlooked in policy debates and clinical trials. The proportion of overweight or obese young women has overwhelmed the proportion of underweight and normal weight women. In order to prevent obesity in women and their offspring, clinical interventions and trials need to be developed for women before and in between pregnancies.

Drug-induced compulsive behaviors: exceptions to the rule.

To the Editor: We are intrigued by the recent article by Bostwick et al1 on the emergence of impulse control behaviors after treatment with dopamine agonists. It is amazing how these gambling and hypersexuality adverse effects occur and then seem to immediately abate simply by discontinuing the Parkinson disease medication without need for any additional addiction-related treatment. Ropinirole was recently investigated in a phase 4 clinical trial as a treatment for sexual dysfunction secondary to antidepressant pharmacotherapy,2 which speaks to its possible effects on sexual behavior. Dopamine agonists may affect the mesolimbic pathway, as do drugs like cocaine and methamphetamine, whose behavioral properties are attributed to this dopaminergic activity; sexual compulsivity is a well-established adverse effect of these medications.3 Furthermore, dopamine dysregulation syndrome, an addictive use pattern of dopamine agonists, causes the same behaviors observed in cocaine-dependent patients, such as punding, a stereotypical motor behavior characterized by an intense fascination with the repetitive handling and examination of objects, particularly mechanical ones. Examples of punding include picking at oneself, taking apart watches and radios, or sorting and arranging common objects (eg, lining up pebbles, rocks, or other small objects). People engaging in punding find immersion in such activities comforting, even when they serve no purpose, and generally feel frustrated when diverted from them. Punding is thought to be related to dopamine use and has been observed in (meth)amphetamine and cocaine users, as well as in some patients with Parkinson disease, gambling addictions, and hypersexuality.4 We have questioned whether drugs like cocaine precipitate these psychiatric issues or whether they preexist the drug use. Robinson and Berridge5 suggest that prior use of certain drugs sensitizes the mesolimbic reward pathways, producing neuroplastic effects on the brain and increasing the likelihood of future abuse/dependence. Because impulse control disorders such as pathologic gambling and sexual compulsivity are associated with dysfunction in the same neural circuitry, we propose that use of these substances may directly activate these pathways (precipitating acute symptoms of compulsive gambling and/or hypersexuality) and over time may produce neuroplastic changes in these pathways (leading to chronic impulse control behaviors). With cocaine and other dopaminergic-stimulating medications, there may be a temporal use interval necessary to produce adaptive synaptic changes in the mesolimbic system of patients using these substances, and future studies should focus on the timeline of drug use. In addition, we have treated hundreds of cocaine abusers with comorbid gambling addiction and/or hypersexuality for whom behavioral remission was not automatic once they stopped using cocaine. In fact, most of our patients need long-term treatment in addition to discontinuation of the substance. It would be useful to study the differences in cocaine-induced gambling and/or hypersexuality and dopamine agonist-induced behaviors. A long-term follow-up of the patients in the study by Bostwick et al1 would also be useful to determine whether true behavioral remission was achieved.