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      Pain management, prescription opioid mortality, and the CDC: is the devil in the data?

      1 , 2 , 3

      Journal of Pain Research

      Dove Medical Press

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          Abstract

          Introduction Transparency, freedom from bias, and accountability are, in principle, hallmarks of taxpayer-funded institutions. Unfortunately, it seems that at least one institution, the Centers for Disease Control and Prevention (CDC), continues to struggle with all three. What began with a prescribing guideline created in secrecy has now evolved to the use of statistical data and public statements that fail to capture not only the complexity of the problem but also the distinction between licit and illicit opioids and their relationship to the alarming increase in unintentional overdose. This is unfortunately consistent with Mark Twain’s assertion that “There are lies, there are damn lies, and then there are statistics.”1 For instance, when the CDC was in the process of drafting guidelines for the use of long-term prescription opioids to treat chronic pain, the identities of the project’s Core Expert Group members remained a secret until they were leaked.2,3 When its members were eventually identified, many were concerned that the group’s composition was not balanced and had an inherent bias against the use of prescription opioids to treat pain.4 Then, when the time came for public input on the draft of the prescribing guideline, the CDC’s invitation for meaningful comment can be best described as somewhere between a charade and a comedy of errors. For example, the only way the public could view the draft was during a one-time internet webinar. The actual guideline itself was not publicly available and was not posted on the CDC website, and admission to the webinar was limited. Those fortunate enough to gain entry were sometimes able to see the actual recommendation as it flashed on the screen, and while attendees were permitted to ask questions, the CDC stated that they would not provide any answers. At the end of the webinar, attendees could then email their comments to the CDC, but they only had 25 hours to do so.5 Due to the many technical problems associated with the first webinar (which was reminiscent of Get Smart’s Cone of Silence),6 the CDC decided to repeat the webinar on the following day and allow an additional 24-hour comment period. 4 But the controversy did not end there. Following the webinar, allegations of unlawful behavior by the CDC in the creation of the guideline were made, specifically that the CDC had violated the Federal Advisory Committee Act.7 The United States Congress eventually stepped in, and the CDC caved under pressure and permitted a 30-day open comment period8 during the Christmas holidays. Although the new open comment period yielded several thousand comments in the Federal Register, there was little change between the draft guideline and the final guideline. And while the CDC had asserted that they would be open to revising the guideline, and one of their own consultants had notified them that the guideline may be negatively impacting prescribing and pain treatment, there is no evidence that the CDC intends to do so.9 Remarkably, the actions of the CDC in the creation and publication of the prescribing guideline appears to violate every single standard that the Institute of Medicine recommended whenever clinical practice guidelines are created.10 Consequently, the authors of this commentary fear that the CDC’s earlier lack of transparency, freedom from bias, and accountability in the creation of a prescribing guideline has now infected the way they characterize statistical data to the public regarding the relationship between opioids (licit and illicit) and unintentional overdose. Simplicity and data conflation is making the problem worse The United States is in the midst of an opioid crisis and prescribers and policymakers continue to struggle with how to effectively reduce the incidence of harm from prescription drugs while at the same time ensuring appropriate access. While accurate measurement of the degree by which various actors or variables have contributed to the initiation and prolongation of the current crisis remains challenging, it is fair to say that prescribers, policymakers, patients, non-patients, the pharmaceutical industry, the insurance industry, regulators, illicit opioids, prescription opioids, dosage,11 and the addiction community have all played a role, whether in isolation or in combination with the above. While we do not believe that all actors or variables contributed equally to the present crisis, nor do we believe that the unintended negative outcomes flowing from their actions were intended, there is understandably one universal contributor to the increase in unintentional overdose that continues to be singled out by policymakers and the CDC: opioids. But the more important question becomes: about what opioids are they speaking? All opioids in general, some opioids in particular, illicit opioids such as heroin and illicitly manufactured fentanyl, or prescription opioids? These distinctions matter. According to the CDC, the “majority of drug overdose deaths (more than six out of ten) involve an opioid,”12 and “as many as 1 in 4 people who receive prescription opioids long term for noncancer pain in primary care settings struggles with addiction.”13 Absent accompanying qualification of the statistics associated with these alarming statements, are they facially accurate or do they reflect a particular agenda – a campaign that fails to recognize the complexity of the issues, the factors, sources, and problems that once identified could help forge effective solutions? We believe it is the latter. The following commentary examines some of the recent statistical claims asserted by the CDC and argues that not only are these statements inaccurate, but they also impede the ability of the public and policymakers to understand the complexity of the problem and create solutions that are balanced and effective. In brief, while prescription opioids continue to play a part in the crisis, illicit opioids such as heroin and illicitly manufactured fentanyl, not prescription opioids and overprescribing, are currently the driving forces behind the increase in unintentional overdose deaths in the United States. This critical distinction is often ignored or underappreciated by the press and policymakers, and is a distinction that needs to be emphasized by the CDC. The failure to do so has far-reaching consequences in terms of policy, pain treatment, substance abuse prevention, and reduction of unintentional overdose. Prescribing: is the problem under-or over-prescribing? The Institute of Medicine has estimated that over 100 million Americans suffer from chronic, long-term pain.14 Pain is individualized, and so should be its treatment. Opioids can be effective in treating pain, and while there may be a variety of alternatives to opioids, some may not be as effective or covered by insurance reimbursement. Yet despite the millions of people who suffer from chronic pain in the United States, there is scant evidence that the CDC considers chronic pain a serious public health problem. For instance, the CDC maintains an A–Z index on their public website, an index of “topics with relevance to a broad cross-section of CDC.gov’s audiences” that “are representative of popular topics […] or have critical importance to CDC’s public health mission.”15 A search using the A–Z index under the letter “C” found references to chronic conditions, but chronic pain was not one of them; a search using the letter “P” found only two topics containing the word “pain”: Pain Killer OD, and Pain Killer Overdose.16 While undertreated pain does not seem to be of critical importance to the CDC, that has not prevented them from creating a prescribing guideline to treat pain, recommending against the use of prescription opioids, and asserting that nonpharmacologic therapy is preferred.17 But whether pain is treated with or without prescription opioids, one thing seems clear: it has been undertreated for decades. Although myriad reasons for undertreatment exist, decades ago many well-intentioned health care providers responded to this public health crisis by increasing their prescribing of opioids. While more prescription drugs were made available to treat pain, it undoubtedly increased the likelihood of leftover medication which in turn increased the potential for misuse, abuse, and diversion. In fact, studies continue to provide evidence that a small percentage of individuals who started using heroin began by misusing prescription drugs (whether they were the drugs they were originally prescribed or someone else’s), so regardless of how one characterizes over- and underprescribing, there should always be efforts aimed at reducing the amount of leftover medication since the common source of diverted pharmaceuticals is a friend or relative. 18 So, what amount of prescribing is appropriate? This represents a difficult question since one size does not fit all. A particular type or dose of one medication may be appropriate for one patient and condition and wholly inappropriate for someone else. Yet despite the medical necessity of tailoring treatments to the individual, the tendency today is for an across-the-board reduction in prescription opioid availability. We can certainly understand the calls for reduction in the surgical context if one considers emerging evidence that a substantial portion of prescription pain medication goes unused by patients in the perioperative care setting.19 But is prescription pain medication the driving force in today’s overdose epidemic, and if not, does an across-the-board reduction in opioid availability and prescribing make sense? We recognize that an excessive supply of prescription opioids can create serious public health problems, much like the overprescribing of antibiotics can have micro and macro health concerns. But are prescribers prescribing more, or less than they used to? According to the CDC and several states’ Departments of Health, less opioids are being prescribed, which in turn indicates that there may be something other than just prescription opioids that are contributing to the escalation in unintentional overdose. Data from the CDC indicate that between 2010 and 2015, the amount of opioids prescribed in the United States actually decreased by more than 18%, with a 13.1% decrease reported between 2012 and 2015 alone.20 Survey data also suggest that more than half of physicians in the United States have reduced their opioid prescribing, with nearly 10% having stopped prescribing opioids altogether.21 Although more recent federal data on the decrease in opioid prescribing are not available, state data are helpful. For example, in Tennessee between 2015 and 2016, the total amount of opioids prescribed decreased by another 9.2%.22 In New Mexico, the Department of Health reported that the amount of opioids prescribed decreased by 5% from the first quarter of 2016 to the first quarter of 2017.23 In terms of prescriptions filled, Michigan reported a 9.7% decrease between 2015 and 2016, Maine reported an 11.9% decrease, Massachusetts reported a 12.7% decrease, West Virginia reported a 15.6% decrease, and so on.24 In fact, perusal of the data from the study24 indicated that every state (with the exception of Florida) and the District of Columbia reported a decrease in the number of opioid prescriptions written between 2015 and 2016. Consequently, there is little doubt that the amount of opioids being prescribed is decreasing dramatically, so it would be disingenuous to suggest otherwise. While the rate of prescribing continues to decline, what about the trends in prescription opioid mortality? Are they declining as well? This question is a more complex one, and thus needs to be considered carefully. Measuring and reporting prescription opioid mortality What constitutes “a prescription opioid death?” It appears that there is some disagreement and controversy regarding this issue,25,26 a disagreement that may be agenda-driven or subject to bias. In 2009, to its credit, the CDC reported that the tremendous variation between states’ rates of prescription opioid overdose deaths “should be interpreted with caution as there is some variation in the reporting of substances on death records.”27 This is an understatement. Determining therapeutic levels and causes of unintentional overdose can be challenging, and postmortem drug redistribution has been described as a toxicological nightmare.28 Although there is a need for more consistency between coroners and medical examiner offices across the United States when opioid-related deaths are involved,29,30 many states utilize death certificate data, which often do not include the source of a drug, the purpose for which the drug was used, the level of opioid tolerance in the decedent, and even the specific type or the name of the drug(s) that were involved.31 A recent study32 looked at “fentanyl deaths” in southeastern Massachusetts, with the authors of that study determining that 82% of the fentanyl deaths over a 6-month period from 2014 to 2015 were likely due to illicitly manufactured fentanyl, with only 4% attributed to legal, pharmaceutical fentanyl. It is important to note that carfentanil, a common contaminate, has 100× the potency of fentanyl. Extrapolating from the reported figures, only a mere 5% of all “fentanyl” overdose deaths were due to a legal, pharmaceutical product, with the remaining 14% due to “an unknown source of fentanyl.” It is important to note, however, that Rudd et al33 warned in a 2016 article that “illicitly manufactured fentanyl cannot be distinguished from prescription fentanyl in death certificate data,” suggesting that this problem is widespread. In other words, if only 5% of all “fentanyl overdose deaths” are due to pharmaceutical fentanyl, and fentanyl (defined broadly) is now responsible for approximately 79% of all “prescription opioid overdose” and “fentanyl” deaths (extrapolating from 2016 Maryland data),34 could the number of actual prescription opioid deaths be only a small percentage of the overall opioid overdose statistics? This is not only a measurement problem; this becomes a policy and solution problem if the public and policymakers continue to fixate on prescription opioids as the problem and the primary factor involved in unintentional overdose. In order to more accurately assess the actual number of prescription opioid analgesic deaths, it was necessary for the first author (MES) to go to individual states’ Departments of Health (DOH). Looking at the data from Illinois, what were listed as deaths due to “Opioid Analgesics” reportedly increased from 589 to 1233 between 2015 and 2016.35 This 107% increase appeared extremely curious given the aforementioned decrease in opioid prescribing. In speaking to one of DOH’s statisticians, he confirmed our suspicion: This dramatic increase was almost completely driven by illicit fentanyl and its potent analogs, not by legitimate pharmaceutical opioids used to treat pain. Furthermore, he noted that irrespective of the number of dangerous substances that are found in toxicology reports, the state’s death certificate data categorize any death in which even an iota of a prescription opioid (or a nonpharmaceutical fentanyl product) is found as a “prescription opioid death” (J Tharp, personal communication, September 22, 2017). A number of other states (eg, Maryland, New Hampshire) have recently taken the initiative to delineate between fentanyl (generally illicit) and other prescription opioid deaths. So, for example, New Hampshire’s Department of Health data characterizes opioid deaths as attributable to specific legitimate prescription opioids, prescription opioids in combination with other licit and illicit drugs (including benzodiazepines, cocaine, methamphetamine and alcohol; methadone, oxycodone, hydrocodone, morphine, tramadol, and oxymorphone) (S Watkins, personal communication, September 22, 2017). A total of 59 deaths involving a legitimate prescription opioid were recorded, with 32 involving oxycodone. However, 72% of the deaths involving oxycodone included alcohol, a benzodiazepine (or both alcohol and a benzodiazepine), kratom, methamphetamine, or another prescription opioid (which may or may not have been prescribed concurrently). These data strongly suggest not a “prescription opioid crisis” but rather a “polypharmacy crisis.” The role of polypharmacy in “prescription opioid over-dose deaths” was recently elucidated empirically.36 The investigators determined that more than half of decedents with an opioid-positive toxicology had alcohol in their systems, and the average number of drugs identified in the toxicologies was six. The second most commonly used drug associated with mortality in New Hampshire was methadone, which was involved in 18 deaths – more than half of which involved other substances as well. The relatively high number of methadone-associated deaths is not surprising, certainly given the literature supporting the high level of potential lethality of this drug and its questionable suitability for use in treating chronic noncancer pain, especially for the inexperienced clinician that continues or initiates methadone, most particularly due to complex pharmacokinetics and unanticipated drug interactions.37 In fact, many in the pain community continued to express concern over the placement of methadone on Washington State’s formulary list to treat pain. Washington State officials defended the placement of methadone on the preferred drug list to treat pain, but it was not until the Seattle Times examined the escalation in overdose and its ties to methadone that the state revisited the matter.38 Consequently, a deeper analysis of the existing data helps reveal the complexity of the issue and what is really behind the current opioid crisis. Yet another cause of the unfortunate overestimation of opioid mortality in the United States (and its link to prescription pain medication) relates to difficulties in distinguishing between heroin and morphine in postmortem samples. Heroin is twice as potent as morphine, has a half-life of only 6–25 minutes prior to its metabolism to morphine in the liver,39 resulting in studies suggesting that heroin deaths are also underestimated while morphine deaths are overestimated in their prevalence.40,41 Given that the prescription opioid epidemic of the past is progressively being replaced by a surge in heroin use,42 the negative implications for inaccurate reporting that misidentifies a commonly prescribed opioid that has analgesic efficacy when used appropriately are clear. Compounding the problem is that heroin is frequently laced with illicit, nonpharmaceutical fentanyl products,43 resulting in coroners’ reports now often yielding inaccurate data suggesting that addicts are succumbing to the effects of not just one prescription opioid but two. Nevertheless, despite the data and their shortcomings, the CDC continues to claim that we are in the midst of a prescription opioid crisis. As their most recent published data suggest that “In 2015, more than 15,000 people died from overdoses involving prescription opioids,”44 one of the authors [MES] submitted a formal request for more recent data. The CDC responded by stating that it would be “addressed in a timely manner.” As of the time of writing of the present commentary, this still has not occurred. The concern is this: for the CDC to suggest that more than 15,000 died in that year from “prescription opioids” when a closer examination of the data indicates that illicit opioids and/or polypharmacy were involved is not only inaccurate and disingenuous, it can negatively impact patients who are well-managed on long-term opioid therapies and have no effective safe alternatives that are covered by insurance, negatively impact health care providers who seek to relieve suffering, and negatively impact people who are suffering from substance use disorders. The necessity of balance In medicine, as in life, there are risks and benefits. Prescription opioids can bring enormous benefits to those who are suffering from acute or chronic long-term pain. Prescribed appropriately, prescription pain medication has provided relief to millions of Americans; it has increased their quality of life, improved their function, provided an option to those for which other analgesics are contraindicated due to certain medical conditions, and reduced their suffering. At the same time, however, prescription opioids by their chemical nature are susceptible to abuse, misuse, and physical harm, particularly among certain subgroups of the population. Yet in today’s environment, the narrative is not about how to balance the need to ensure access while preventing abuse, nor is it about the people suffering from acute or chronic pain requiring long-term opioids. Rather, it is about opioids, their misuse and abuse, and the increase in unintentional overdose. The proposed solution by policymakers to this complex problem has often been simple: just say no to drugs, and those who are struggling with addiction simply need to be enrolled in a substance abuse program so that they can become clean again. But things are not so easy. Despite decreases in the prescribing of prescription opioids, we continue to see an increase in the rates of unintentional overdose. While there is clear evidence that this increase is driven by the use of illicit opioids such as heroin or illicitly manufactured fentanyl derivatives, this particular fact continues to get lost in the shuffle and results in knee-jerk reactions calling for the reduction of both the supply and use of prescription opioids. People who are not adequately treated for their pain will seek out alternatives, often harmful alternatives that can lead to addiction, unintentional overdose, or even suicide. Conclusion It is easy to demonize and point fingers at industry, prescribers, or anyone who calls into question the newest battle in the never-ending war on drugs. While we would agree that anyone involved in the distribution of illicit drugs such as heroin and illicitly manufactured fentanyl derivatives should be stopped from harming others, and the misuse and abuse of prescription opioids have played a role in the problems we see today, in the right hands prescription opioids can help eliminate human suffering. Prescription opioids are not the panacea, but they have medicinal benefits, unlike tobacco. For instance, according to the CDC, “cigarette smoking is responsible for more than 480,000 deaths per year in the United States, including more than 41,000 deaths resulting from secondhand smoke exposure.”45 In contrast to appropriately prescribed and administered opioids, we are unaware of any legitimate medical treatments involving the use of cigarettes, a product that continues to be available to anyone over 18 years without a prescription. Is there anything that can be done to help solve the opioid crisis? We believe so. First, we would suggest that the CDC refrain from making alarmist statements that cite statistics that are not supported by the evidence without qualification. As noted earlier, a recent web-based publication by the CDC cited an alarming statistic in support of its campaign to reduce addiction and unintentional overdose: “As many as 1 in 4 people who receive prescription opioids long term for noncancer pain in primary care settings struggles with addiction.”46 While the study cited by the CDC (appearing as Footnote number 7 in the CDC publication) was an important contribution to the field, the authors of the study, unlike the CDC publication, correctly noted the study’s limitations and the difficulty in generalizing the results: Study limitations include that our diagnostic data were based on patient self-report; that our survey completion rate was less than optimal, thus study estimates may be biased; and, as patients were drawn from a predominately Caucasian population in one US region, it may not be possible to generalize these findings.47 Second, the CDC should recognize that chronic pain impacts millions of people in the United States and should, at a minimum, create an entry for pain on their website’s A–Z index. We are concerned that the absence of information about the millions of Americans who suffer from chronic pain sends the message that pain does not “have critical importance to CDC’s public health mission.” Creating the link and providing information on this serious health problem will go a long way to bringing about balance. Finally, we need to find ways to work together, instead of against each other, emphasizing civil discourse instead of finger pointing. We are concerned that some people who are intent on blaming prescribers, patients, and the pharmaceutical industry for the problem without offering solutions (other than perhaps eliminating prescription opioids) are making it more about them than the people they are actually trying to help. We have many problems, but there are also many solutions. And while we are also concerned that the message about the opioid crisis is not accurately depicted in the media, we close with an interesting observation from a journalist that may be helpful to all of us. Malcolm Gladwell, a Canadian journalist, recently commented that the “one thing that continues to baffle me about American society is how Americans love to accentuate how they are different from each other. Whereas in Canada, all we do is celebrate what we have in common.”48 Maybe we should give that a try and find that common ground that unites all of us in achieving better outcomes not only in reducing abuse and harm but also in treating pain.

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          Most cited references 43

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          Risk factors for drug dependence among out-patients on opioid therapy in a large US health-care system.

          Our study sought to assess the prevalence of and risk factors for opioid drug dependence among out-patients on long-term opioid therapy in a large health-care system. Using electronic health records, we identified out-patients receiving 4+ physician orders for opioid therapy in the past 12 months for non-cancer pain within a large US health-care system. We completed diagnostic interviews with 705 of these patients to identify opioid use disorders and assess risk factors. Preliminary analyses suggested that current opioid dependence might be as high as 26% [95% confidence interval (CI) = 22.0-29.9] among the patients studied. Logistic regressions indicated that current dependence was associated with variables often in the medical record, including age <65 [odds ratio (OR) = 2.33, P = 0.001], opioid abuse history (OR = 3.81, P < 0.001), high dependence severity (OR = 1.85, P = 0.001), major depression (OR = 1.29, P = 0.022) and psychotropic medication use (OR = 1.73, P = 0.006). Four variables combined (age, depression, psychotropic medications and pain impairment) predicted increased risk for current dependence, compared to those without these factors (OR = 8.01, P < 0.001). Knowing that the patient also had a history of severe dependence and opioid abuse increased this risk substantially (OR = 56.36, P < 0.001). Opioid misuse and dependence among prescription opioid patients in the United States may be higher than expected. A small number of factors, many documented in the medical record, predicted opioid dependence among the out-patients studied. These preliminary findings should be useful in future research efforts. © 2010 The Authors, Addiction © 2010 Society for the Study of Addiction.
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            • Record: found
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            An analysis of the root causes for opioid-related overdose deaths in the United States.

            A panel of experts in pain medicine and public policy convened to examine root causes and risk factors for opioid-related poisoning deaths and to propose recommendations to reduce death rates. Panelists reviewed results from a search of PubMed and state and federal government sources to assess frequency, demographics, and risk factors for opioid-related overdose deaths over the past decade. They also reviewed results from a Utah Department of Health study and a summary of malpractice lawsuits involving opioid-related deaths. National data demonstrate a pattern of increasing opioid-related overdose deaths beginning in the early 2000s. A high proportion of methadone-related deaths was noted. Although methadone represented less than 5% of opioid prescriptions dispensed, one third of opioid-related deaths nationwide implicated methadone. Root causes identified by the panel were physician error due to knowledge deficits, patient non-adherence to the prescribed medication regimen, unanticipated medical and mental health comorbidities, including substance use disorders, and payer policies that mandate methadone as first-line therapy. Other likely contributors to all opioid-related deaths were the presence of additional central nervous system-depressant drugs (e.g., alcohol, benzodiazepines, and antidepressants) and sleep-disordered breathing. Causes of opioid-related deaths are multifactorial, so solutions must address prescriber behaviors, patient contributory factors, nonmedical use patterns, and systemic failures. Clinical strategies to reduce opioid-related mortality should be empirically tested, should not reduce access to needed therapies, should address risk from methadone as well as other opioids, and should be incorporated into any risk evaluation and mitigation strategies enacted by regulators. Wiley Periodicals, Inc.
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              Characteristics of Fentanyl Overdose — Massachusetts, 2014–2016

              Opioid overdose deaths in Massachusetts increased 150% from 2012 to 2015 ( 1 ). The proportion of opioid overdose deaths in the state involving fentanyl, a synthetic, short-acting opioid with 50–100 times the potency of morphine, increased from 32% during 2013–2014 to 74% in the first half of 2016 ( 1 – 3 ). In April 2015, the Drug Enforcement Agency (DEA) and CDC reported an increase in law enforcement fentanyl seizures in Massachusetts, much of which was believed to be illicitly manufactured fentanyl (IMF) ( 4 ). To guide overdose prevention and response activities, in April 2016, the Massachusetts Department of Public Health and the Office of the Chief Medical Examiner collaborated with CDC to investigate the characteristics of fentanyl overdose in three Massachusetts counties with high opioid overdose death rates. In these counties, medical examiner charts of opioid overdose decedents who died during October 1, 2014–March 31, 2015 were reviewed, and during April 2016, interviews were conducted with persons who used illicit opioids and witnessed or experienced an opioid overdose. Approximately two thirds of opioid overdose decedents tested positive for fentanyl on postmortem toxicology. Evidence for rapid progression of fentanyl overdose was common among both fatal and nonfatal overdoses. A majority of interview respondents reported successfully using multiple doses of naloxone, the antidote to opioid overdose, to reverse suspected fentanyl overdoses. Expanding and enhancing existing opioid overdose education and prevention programs to include fentanyl-specific messaging and practices could help public health authorities mitigate adverse effects associated with overdoses, especially in communities affected by IMF. Barnstable, Bristol, and Plymouth counties in Massachusetts were investigated because of high opioid overdose death rates (estimated 29.8–34.5 per 100,000 population in 2015), and feasibility of interviewee recruitment through existing harm reduction programs in these counties ( 5 ).* To rapidly obtain a cross section of persons misusing opioids for semistructured, in-person interviews, a nonrandom sample of approximately 20 knowledgeable respondents per county was recruited with the help of harm reduction programs. Eligible persons were aged ≥18 years, lived in Massachusetts, had used illicit opioids during the previous 12 months, and had witnessed or experienced an opioid overdose during the previous 6 months. Equal numbers of men and women were recruited. Trained interviewers asked respondents about their experiences, knowledge, attitudes, and beliefs regarding opioid overdose. Interviews were audio recorded, transcribed, and thematically coded by multiple investigators. Opioid overdose death data were abstracted from medical examiner charts, which included autopsy and toxicology reports, death scene reports, and emergency medical service logs. Abstracted charts met the following criteria: the death occurred during October 1, 2014–March 31, 2015; the decedent overdosed or resided in Barnstable, Bristol, or Plymouth counties; and opioids were listed as a contributing cause of death. Postmortem toxicology tests were used to categorize deaths as involving fentanyl (regardless of presence of other drugs), heroin or morphine (i.e., no fentanyl), † or other opioids (e.g., prescription opioids). Fentanyl deaths were further categorized using death scene evidence as suspected IMF, suspected prescription fentanyl, or unknown source of fentanyl. Rapidity of overdose death was determined from available evidence, including needles inserted in decedents’ bodies, syringes found in hand, tourniquets still in place, and bystander reports of rapid unconsciousness after drug use. Demographic and overdose characteristic frequencies were examined by drug type. Among 64 interview respondents, 52% were women, 61% were aged 25–44 years, and 81% were non-Hispanic white. Ninety-one percent reported that they were trained by a Massachusetts Department of Public Health-supported overdose education and naloxone distribution program in the use of naloxone for reversing an opioid overdose; trainees are taught that opioid overdose is defined by unresponsiveness and decreased respirations ( 6 ). During the 6 months before the interview, 95% of respondents witnessed an overdose and 42% overdosed themselves. Eighty-eight percent of respondents attributed the increase in opioid overdose deaths to suspected fentanyl, and 69% reported that suspected fentanyl was now available for purchase in powdered form (consistent with IMF preparation), and not as diverted prescription medications, (e.g., Duragesic transdermal fentanyl patch) (Box). Respondents reported that suspected fentanyl could be obtained alone or mixed with heroin, and persons using heroin often did not know whether fentanyl was mixed into the heroin they purchased. Respondents’ reactions to the addition of fentanyl to the illicit drug market varied. Although some persons sought out fentanyl and others attempted to avoid it, a majority of respondents reported that opioid-seeking behaviors were not altered in response to the emergence of fentanyl. A majority of respondents who witnessed a suspected fentanyl overdose (75%) described symptoms as occurring rapidly, within seconds to minutes. Twenty-five percent reported witnessing or experiencing an overdose when fentanyl was insufflated (snorted), and the remainder reported the overdose always involved injecting fentanyl. Atypical overdose characteristics described by respondents during suspected fentanyl overdose included immediate blue discoloration of the lips (20%), gurgling sounds with breathing (16%), stiffening of the body or seizure-like activity (13%), foaming at the mouth (6%), and confusion or strange affect before unresponsiveness (6%). Seventy-five percent of respondents reported witnessing naloxone administration, administering naloxone themselves, or receiving naloxone to successfully reverse an opioid or fentanyl overdose. Among these events, 83% of respondents reported that ≥2 naloxone doses (typical nasally administered dose in Massachusetts is 2 mg/2 mL § ) per suspected fentanyl overdose were used before the person responded. Thirty percent of respondents reported using heroin or fentanyl with others present to help protect themselves from a fatal overdose. BOX Sample quotations from persons who reported using opioids and who had witnessed or experienced an opioid overdose — Barnstable, Bristol, and Plymouth counties, Massachusetts, April 2016* Illicitly manufactured fentanyl (IMF) responsible for opioid overdose deaths “So, now what they [people selling illicit drugs] are doing is they’re cutting the heroin with the fentanyl to make it stronger. And the dope [heroin] is so strong with the fentanyl in it, that you get the whole dose of the fentanyl at once rather than being time-released [like the patch]. And that’s why people are dying—plain and simple. You know, they [people using illicit drugs] are doing the whole bag [of heroin mixed with fentanyl] and they don’t realize that they can’t handle it; their body can't handle it.” Overdoses involving IMF are acute and rapid “A person overdosing on regular dope [heroin] leans back and drops and then suddenly stops talking in a middle of a conversation and you look over and realize that they’re overdosing. Not like with fentanyl. I would say you notice it [a fentanyl overdose] as soon as they are done [injecting the fentanyl]. They don’t even have time to pull the needle out [of their body] and they’re on the ground.” Naloxone reverses overdoses involving IMF; multiple doses often required “So he put half [one dose] up one nose [nostril] and half [one dose] up the other nose, like they trained us to do, and she didn’t come to. So he put water on her face and kind of slapped her, which doesn’t really make you come to [regain consciousness]. It doesn’t. So he pulled out another thing of Narcan [brand of naloxone] and he put half of it [another dose] up one nose and then she came to…She just didn’t remember anything. She said, ‘What happened? I remember washing my hands and, like, what happened?’ We said, ‘You just overdosed in this room!’ So yeah, it was wicked scary.” Self-protective measures often employed “Like I will do a very, very, very little bit of fentanyl…and if I don’t feel it, I will do that little bit plus half. I’m just not going to throw the whole thing in the cooker and then do it, no way. I just know better.” Co-use of opioids and benzodiazepines “My daughter’s mother had benzos. And when she did one bag of heroin she already had done four or five Klonopin [brand of clonazepam] and she just died. That was it. She went into a coma for the night and she was dead in the morning.” * Categories are not mutually exclusive; all respondents reported using opioids in the past 12 months and had witnessed or experienced an overdose, or both. Among 196 opioid overdose decedents whose records were reviewed, 73% were men, 50% were aged 15–34 years, and 91% were non-Hispanic white. Demographics of fentanyl overdose decedents were similar to those of the overall opioid overdose decedents (Table). Among all opioid overdose decedents 64% tested positive for fentanyl on postmortem toxicology; this proportion increased from 44% in October 2014 to 76% in March 2015 (Figure). Eighty-two percent of fentanyl deaths were suspected to involve IMF, 4% were suspected to involve prescription fentanyl, and 14% involved an unknown source of fentanyl. Thirty-six percent of fentanyl deaths had evidence of an overdose occurring within seconds to minutes after drug use, and 90% of fentanyl overdose decedents were pulseless upon emergency medical services arrival (Table). Ninety-one percent of fatal fentanyl overdoses occurred in a hotel, motel, or private residence. Only 6% of fentanyl overdose deaths had evidence of lay bystander-administered naloxone, which is available from pharmacies and harm reduction programs in Massachusetts. In addition to the limited use of naloxone by laypersons, rapid bystander response to fentanyl overdose was inhibited by lack of bystanders (18%), spatial separation of decedents from bystanders (e.g., person was in another room of the house [58%]), lack of awareness of decedent’s drug use by bystanders (24%), intoxication of bystanders who were present (12%), failure of bystanders to recognize overdose symptoms (11%), or bystander assumption that the decedent had gone to sleep (15%). Clear evidence that a bystander was unimpaired, witnessed the drug consumption, and was present during an overdose (i.e., able to respond immediately) was reported in 1% of the fentanyl overdose decedent charts. TABLE Demographic characteristics and overdose precipitating circumstances of fentanyl overdose decedents (N = 125) — Barnstable, Bristol, and Plymouth counties, Massachusetts, October 1, 2014–March 31, 2015 Characteristic No. (%) Sex Male 100 (80) Female 25 (20) Age group (yrs) 15–24 15 (12) 25–34 52 (42) 35–44 24 (19) ≥45 34 (27) Race/Ethnicity White, non-Hispanic 111 (89) Other 14 (11) Location of overdose Decedent's home 85 (68) Other private residence 22 (18) Hotel or motel 7 (6) Other 11 (9) Overdose onset, pulselessness, and bystander naloxone administration Evidence of rapid onset of overdose symptoms 45 (36) Pulseless upon emergency medical services arrival 112 (90) Evidence of bystander naloxone administration 7 (6) Barriers to bystander response No bystander present 23 (18) Decedent spatially separated from any bystander* 73 (58) Bystander unaware of decedent’s drug use 30 (24) Bystander also using drugs or alcohol 15 (12) Bystander reported symptoms of intoxication or overdose (snoring, falling asleep, or nodding), but did not realize decedent was overdosing 14 (11) Decedent was thought to have gone to sleep 19 (15) Route of drug administration† Evidence of injection 83 (66) Evidence of insufflation (snorting) 11 (9) No evidence of route of administration 26 (21) * Spatial separation defined as having a bystander nearby, either during or shortly preceding the overdose, who potentially had an opportunity to intervene and respond to the overdose, but who was not in the same room or physical space as the decedent. † Categories were not defined as mutually exclusive, but all records with evidence of injection had no evidence of insufflation, and all records with evidence of insufflation had no evidence of injection. Any evidence of route of administration was coded but not linked to specific drugs. FIGURE Percentage of opioid overdose deaths involving fentanyl, heroin/morphine (without fentanyl), and other opioids (without fentanyl, heroin/morphine) — Barnstable, Bristol, and Plymouth counties, Massachusetts, October 2014–March 2015 Alternate Text: The figure above is a bar chart showing the percentage of opioid overdose deaths involving fentanyl, heroin/morphine (without fentanyl), and other opioids (without fentanyl, heroin/morphine) in Barnstable, Bristol, and Plymouth counties, Massachusetts, October 2014–March 2015 Discussion Introduction of fentanyl into the illicit drug market has been a major contributing factor to the rapid increase in opioid overdoses in southeastern Massachusetts and reflects a growing national public health issue ( 7 ). Previous DEA reports ( 4 ) and the findings of this investigation indicate that IMF is widely available through illicit drug markets in southeastern Massachusetts, and that the majority of fentanyl linked to fatal overdoses is suspected IMF rather than diverted prescription fentanyl. Taken together, these data highlight the need to integrate fentanyl testing into standard substance use toxicology tests employed by the medical, criminal justice, and treatment communities in Massachusetts areas with high levels of fentanyl use and overdose. Evidence from over one third of medical examiner charts and reports from 75% of interview respondents demonstrated that fentanyl overdose can begin suddenly, progress to death rapidly, and manifest atypical physical symptoms. Timely administration of a sufficient naloxone dose by a trained layperson or emergency medical services responder can reverse fentanyl overdose. Although bystanders were frequently present in the general location of overdose death, timely bystander naloxone administration did not occur because bystanders did not have naloxone, were spatially separated or impaired by substance use, or failed to recognize overdose symptoms. Findings indicate that persons using fentanyl have an increased chance of surviving an overdose if directly observed by someone trained and equipped with sufficient doses of naloxone. In some countries, including Canada and Australia, overdose morbidity and mortality rates have decreased in areas near supervised injection facilities where personnel are available to observe overdose onset, if it occurs, and administer naloxone as needed ( 8 ). Because multiple doses might be required to reverse a fentanyl overdose, emergency medical services and community naloxone distribution programs might need to ensure that appropriate numbers of doses are distributed. The findings in this report are subject to at least three limitations. First, toxicology reports in medical examiner charts cannot distinguish between prescription fentanyl and IMF; therefore, categorization was completed using death scene evidence, which varied and sometimes was inconclusive. In addition, samples were not tested for emerging fentanyl analogs, such as carfentanil. Overdose deaths were also categorized broadly as involving fentanyl, heroin or morphine, or other opioids, although in many cases other drugs also contributed to the death. Atypical symptoms reported during fentanyl overdose may be attributable to other drugs or drug combinations and not fentanyl. Second, circumstances or events preceding death (e.g., rapid onset of overdose symptoms) can be inferred from death scene evidence, but absence of evidence cannot be interpreted as evidence of absence; numbers presented therefore likely underestimate the actual prevalence of circumstances. Finally, interview respondents were recruited with the help of community-based harm reduction programs in which overdose prevention education and naloxone rescue kits were offered. Thus, this sample population was potentially more informed about and experienced with fentanyl, naloxone, overdose prevention and treatment, and rescue efforts than are all persons who use illicit opioids. In addition, interview comparability is limited because not all respondents were asked uniform questions. Adaptation of harm reduction practices designed to reduce health-related consequences of unsafe drug use, including the addition of warnings about fentanyl’s characteristics and toxicity, could mitigate the fentanyl-related impact of the U.S. opioid epidemic in communities affected by fentanyl. Population-based strategies to prevent and reduce opioid use and opioid use disorders, such as expansion of access to evidence-based treatment, are likely to be effective in preventing fentanyl overdose and death. The high percentage of fatal overdoses occurring at home with no naloxone present, coupled with the rapid onset of overdose symptoms after using fentanyl through injection or insufflation, underscores the urgent need to expand initiatives to link persons at high risk for overdose (such as persons using heroin, persons with past overdoses, or persons recently released from incarceration) to harm reduction services and evidence-based treatment ( 2 , 8 ). Summary What is already known about this topic? Fentanyl has a growing presence in the illicit drug market and is involved in an increasing proportion of opioid overdose deaths. What is added by this report? Approximately two thirds of investigated opioid overdose deaths in southeastern Massachusetts during October 1, 2014–March 31, 2015 involved fentanyl, a majority of which was suspected illicitly manufactured fentanyl (IMF), reported to be widely available in the illicit drug market. Fentanyl overdose can progress rapidly, and a majority of decedents were physically separated from bystanders. Naloxone can reverse fentanyl overdose if administered in sufficient dosage immediately upon recognition of overdose symptoms. What are the implications for public health practice? A comprehensive public health response is needed to address overdoses related to IMF. First, fentanyl should be included on standard toxicology screens to facilitate early identification. Second, existing harm reduction strategies to identify likely fentanyl exposure should be adapted, such as training for bystanders that includes direct observation of anyone injecting or insufflating illicit opioids, ensuring that trained bystanders are equipped with sufficient doses of naloxone, expanding layperson training, and providing access to naloxone. Third, access and linkages to medication for opioid use disorders need to be enhanced in fentanyl-affected areas.
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                Author and article information

                Journal
                J Pain Res
                J Pain Res
                Journal of Pain Research
                Journal of Pain Research
                Dove Medical Press
                1178-7090
                2017
                20 October 2017
                : 10
                : 2489-2495
                Affiliations
                [1 ]Research and Network Development, Boston Pain Care, Waltham, MA
                [2 ]Public Health and Community Medicine, Tufts University School of Medicine, Boston, MA
                [3 ]Department of Public Policy, Purdue University, Fort Wayne, IN, USA
                Author notes
                Correspondence: Michael E Schatman, Public Health and Community Medicine, Tufts University School of Medicine, Boston, MA, USA, Email michael.schatman@ 123456tufts.edu
                Article
                jpr-10-2489
                10.2147/JPR.S153322
                5659223
                © 2017 Schatman and Ziegler. This work is published and licensed by Dove Medical Press Limited

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                Editorial

                Anesthesiology & Pain management

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