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The Opioid Epidemic in the United States
Emergency Medicine Clinics of North America, In Press, Corrected Proof, Available online 17 February 2016, Available online 17 February 2016
There is an epidemic of opioid abuse. This article discusses the history of opioid use. Abusers of opioids are at great risk of harm. There have been increasing legislative efforts to curb this abuse and we present a review of the current state of these laws. Naloxone has made a profound impact in the care of these patients if they present for medical care early enough. This paper discusses naloxone pharmacodynamics, its use in the medical setting, and how its use is now being expanded to include nontraditional providers with take home naloxone programs.
Keywords: Opioids, Opioid epidemic, Heroin, Prescription drugs, Overdose, Legal liability.
Key points
- There is an epidemic of opioid abuse in the United States.
- The risk of heroin abuse has been appreciated for more than a century with it now being considered to have no justifiable medical use.
- Opioids commonly prescribed to treat painful conditions have had a dramatic increase in the rate of abuse, addiction, overdose, and death.
- The increase in complications corresponds with a dramatic increase in the rate of opioid prescriptions that resulted from pressures placed on practitioners to avoid undertreatment of pain.
- Naloxone is a competitive opioid antagonist that is used to reverse the adverse effects of opioid intoxication. It is increasingly being prescribed for emergent outpatient administration.
Pain is a more terrible lord of mankind than even death itself. —Dr Albert Schweitzer, 1931.
The United States is currently experiencing an epidemic of opioid abuse. This article discusses the history of opioid use for pain management and how epidemiologic data demonstrate a convincing degree of association between the increasing rate of opioid prescriptions and the increasing rate of adverse effects, aberrant use, and unintentional death from opioids. There is a clear but not complete overlap between prescription opioid abuse and heroin use. Regardless of drug of choice, abusers of opioids are at great risk of harm. There have been increasing legislative efforts to curb this abuse and we present a review of the current state of these laws. Naloxone, an opioid antagonist, has made a profound impact in the care of opioid overdose patients who present for medical care early enough. This paper discusses naloxone pharmacodynamics, its use in the medical setting and how its use is now being expanded to include nontraditional providers with take home naloxone (THN) programs.
Opioid is the term used to describe a substance that is able to bind the opioid receptors. The more specific term, opiate, refers to a class of agents that are directly derived from naturally occurring opium. The opiate class includes morphine and codeine. The term narcotic is less informative, has a negative connotation, and tends to be reserved for law enforcement and the lay public when referring to an opioid that is used illicitly.
The use of opiates dates back to the Sumerians of Mesopotamia who first cultivated the opium poppy around 3400 bc. The plant was known as Hul gil or "joy plant."1 Opium use, both recreationally and for the treatment of various medical ailments, spread along routes of trade and conquest. Its use was abandoned in most of Europe during the Medieval Inquisition. Philippus von Hohenheim (1493–1541), known as Paracelsus and sometimes called the "father" of toxicology, is credited with the reintroduction and promotion of laudanum, a tincture of opium, for medical treatment in Europe.2 Thomas Sydenham (1624–1689) further popularized the medical use of laudanum and related products. Friedrich Sertürner (1783–1855) first isolated morphine in 1804.3 In an effort to find a nonaddictive alternative to morphine, Charles R. A. Wright first synthesized diacetylmorphine, or heroin, in 1874. Bayer Pharmaceutical Products later marketed heroin as an analgesic and cough suppressant.4 It was also touted a medication to help those addicted to morphine.5
In modern times, there have been multiple swings in prevailing attitudes regarding the use of opioids for analgesia. For example, the first edition of the classic text, Cope's Early Diagnosis of the Acute Abdomen, in 1921 directed the provider to withhold opioid analgesics until a diagnosis was certain in patients with undifferentiated abdominal pain. This practice persisted to some degree until recent times, despite numerous studies that demonstrated that the use of opioid analgesics does not interfere with the diagnostic process in these patients.6, 7, 8, and 9 The use of opioids for acute traumatic injuries or other acute painful conditions is less controversial.
Opioid use for patients with chronic pain owing to cancer has long been a mainstay of therapy. The goal of this therapy is to maintain pain relief to tolerable levels to allow for improved quality of life. The risk of addiction or overdose is ethically justified through application of the principle of double effect. This principle dates back to St. Thomas Aquinas (1225–1274) and states that it is moral to perform an action in the pursuit of a good outcome with the knowledge that a foreseeable harm may occur. The action must fulfill the following conditions: the action cannot of itself be morally wrong, the good outcome cannot be directly caused by the harm, the potential harm cannot be the intention of the action, and the harm cannot be disproportionate to the good outcome.10 and 11
Chronic pain has been estimated by the World Health Organization to be present in up to 22% of patients attending primary care clinics.12 Through most of the 20th century, physicians avoided the use of opioids in treating chronic noncancer pain. This practice was owing to fear of addiction, overdose, and lack of effectiveness. The concern over addiction started to wane in 1980 with the publication of a 1-paragraph letter in which the authors stated there were only 4 instances of addiction in review of more than 11,000 cases of patients receiving at least one opioid prescription.13 In 1986, Portenoy and Foley14 published a retrospective review showing addiction in only 2 of 38 patients treated with chronic opioid therapy. Both patients had a history of prior drug abuse. After this, there was a campaign of editorials proclaiming the safety of chronic opioid therapy for noncancer pain.15 and 16
The drumbeat to eradicate pain continued despite no quality efforts to research the effects of opioid use in chronic pain. The term "oligoanalgesia" was coined in 1989 and worked to shift the blame onto the provider if the patient experienced pain.17 James Campbell18 introduced the concept of pain as the fifth vital sign in his 1995 Presidential Address to the American Pain Society. Numerous medical societies and organizations adopted policies of pain control that championed the use of opioids.19 and 20 The Veterans Health Administration adopted "Pain: the 5th vital sign" as the name of its 1999 pain management initiative that mandated evaluation and treatment of pain at all clinical encounters.21 The Joint Commission on Accreditation of Healthcare Organizations (now known as The Joint Commission) began assessing pain management as a requirement for accreditation in 2000.22 The balance shifted toward treatment of pain with less regard given for contributing to development of abuse and risk of opioid overdose.
Despite the increase in opioid addiction and deaths that contemporaneously occurred with the dramatic increase in prescriptions for opioid pain medications, there has been a very slow response in the medical community. Numeric pain scores remain a part of the vital signs collected at clinical encounters, regardless of the reason for the encounter and often without consideration of the score given in a broader context. Within the past few years there has been some increased momentum to control the opioid epidemic.23 and 24 This paper looks at some of the responses to the epidemic including the implementation of prescription drug monitoring programs (PDMPs) and the use of THN. To effectively manage this problem, there will need to be increased research into pain, pain management, and opioid abuse.
Opioid Prescription Epidemic
The first decade of the new millennium saw a significant increase in the availability, use, and abuse of prescription opioid medications and the development of an unprecedented drug overdose epidemic. This situation slowly garnered the attention of medical organizations, news media and individual practitioners. As described previously, this phenomenon is complex and multifactorial in etiology, owing in part to increased emphasis on treating pain, a push toward the philosophy that opioid pain medications are "safe," insufficient or ineffective oversight, and a marked growth in nationwide consumption and demand in the United States. As general medical use became more commonplace, so too did nonmedical use. This parallel relationship led to an estimated 25 million Americans engaging in the nonmedical use of prescription opioids from 2002 to 2011.25 The general epidemic seems to have peaked around 2010, the eleventh consecutive year that saw an increase in the number of prescription opioid-related deaths with 16,651 fatalities.26 Put into perspective, in that year, opioid analgesics contributed to more than twice as many deaths as heroin and cocaine combined.27 In 2009, deaths attributed to drug overdose surpassed mortality from motor vehicle collisions for the very first time.25 More than three-quarters of these drug overdose deaths are unintentional.26 Although medication overdoses frequently involve multiple classes of drugs, 4903 of 16,651 opioid deaths (29.4%) in 2010 involved solely the ingestion of opioids, a proportion nearly 3 times higher than fatal single-class ingestions of any other psychotropic or central nervous system medicine.28
Morbidity and Economic Burden
Prescription opioid-associated deaths notwithstanding, there are other considerable health consequences associated with these medications, and the morbidity associated with prescription drug overuse has also increased in recent years. Prescription opioids are associated with chronic constipation and narcotic bowel syndrome,29 falls and orthopedic injuries in the elderly,30 neonatal abstinence syndrome, and transition to intravenous (IV) drug use with further associated health risks such as infectious complications and human immunodeficiency virus and hepatitis C virus exposure.
The resource costs associated with opioid abuse are considerable. Over the past decade, there has been a general increase in the number of emergency department visits and inpatient hospitalizations related to prescription drug use.31 and 32 From 2004 to 2011, the number of emergency department visits related to opioid abuse or misuse increased by 183%. In 2011, there were 420,040 emergency department visits for prescription opioid abuse.31 The increase in patient volume alone is yet another affliction on an already overtaxed health care system, but the financial cost is substantial as well. It is estimated that the abuse and misuse of prescription opioids are responsible for somewhere between $53 to $72 billion in cumulative costs annually.33 and 34 These figures account for insurance payments and fraud, lost productivity, criminal justice costs, drug abuse treatment, and general medical complications.
Demographics: Who Is at Risk?
Chronic nonmedical use of opioids is almost twice as high in men, although women have higher rates of being prescribed types drugs that are prone to abuse. Men also have a higher rate of death related to opioids compared with women. Use of emergency departments for abuse or misuse of opioids seems to be similar across the sexes.35 About 13% of high school seniors report having used prescription opioids for nonmedical purposes at some time in their life.36 For adults, the rate of nonmedical use of opioids is highest among 18 to 25 year olds and decreases with increasing age.37 Despite that trend, death rates from opioid overdoses are highest in 45 to 54 year olds.35 Overdose death rates of non-Hispanic whites and Native Americans have been 3 times as high as Hispanic whites and African Americans.32
Certain socioeconomic and clinical factors have also seemed to play a role in differential opioid prescribing, misuse, and poor outcomes. Patients who have lower educational attainment, are eligible to receive Medicaid, or have history of previous substance abuse and/or psychiatric disease all tend to be prescribed more opioids and at higher doses.38 Perhaps predictably, the rate of opioid overdose death is higher in Medicaid-eligible populations, and also in those with previous substance abuse or psychiatric histories.39 and 40 It has been shown previously that patients with psychiatric conditions are at risk for opioid overuse and abuse.41
Which Prescription Opioids Are Most Common?
Hydrocodone has been the most frequently reported drug exposure for cases called into United States poison centers.42 According to data analyzed from 2009 involving 13 states in the Drug Abuse Warning Network Medical Examiner System, oxycodone, closely followed by methadone, were the 2 most frequently implicated drugs in fatal overdoses. Methadone has been associated in the most single-drug deaths, twice as many as any other opioid.43 From 1999 to 2009, the rate of overdose death from methadone increased by 5-fold. Methadone is not a medicine prescribed frequently from the emergency department, but patients may be taking it as a replacement therapy or for chronic pain management, so exceptional caution should be exercised with patients on chronic therapy, or those who admit to recreational use.
Providers should also take caution with patients who are taking other types of prescription medications, especially psychiatric or central nervous systems agents, when considering prescribing an opioid. Opioid analgesics are by far the most commonly involved medications for pharmaceutical overdose deaths, followed distantly by benzodiazepines and antidepressants. However, overdose deaths are frequently owing to coingestions, and opioids are often implicated in many deaths from other medications. For instance, opioids have been identified in the majority of overdose deaths involving benzodiazepines (77.2%), antiepileptics/anti-Parkinsonian medication (65.5%), antipsychotic and neuroleptic drugs (58.0%), antidepressants (57.6%), other analgesics, antipyretics, and antirheumatics (56.5%), and other psychotropic drugs (54.2%).28
Limitations of Data
One shortcoming of the data used for reporting the amount of prescription opioid abuse is that the true incidence is likely underreported. Much of the research is culled from numerous sources, encompassing a patchwork-like pattern that involves self-reporting, criminal databases, poison control center data, autopsy or death certificate results, pharmacy data, and hospital billing coding. All of these sources have limitations.
As with any other illegal activity, self-reporting is likely limited to the degree to which any individual may be forthcoming. Overdoses of prescription opioid medications are coingested frequently with other medications, street drugs, and alcohol.28 Furthermore, deaths can be multifactorial, and unless there is a known ingestion or autopsy performed, suspected cause of death by the certifying physician may be incorrect. Another problem underlying the reliance on data from death certificates is that a specific drug is not reported in almost a quarter of all reports.44 Fluctuating criminal justice priorities and state/regional variance in reporting, rates of abuse, or prescribing of opioids affect the generalizability of information available from those sources. A majority of the opioid prescribing and abuse has been dominant in the Southeast and Western United States,45 and although no area of the country has been immune, research studies that focus exclusively on particular regions may not capture the full picture. Complete representative data from the entire country are lacking.
Recent trends
According to data from the Researched Abuse, Diversion, and Addiction-Related Surveillance system, prescriptions for opioid analgesics increased substantially from 2002 through 2010 in the United States, but then decreased slightly from 2011 through 2013. Similarly, the diversion and abuse of prescription opioid medications also increased between 2002 and 2010 and plateaued or decreased between 2011 and 2013.46 Furthermore, data analyzed by the Centers for Disease Control and Prevention from 28 states indicated that the death rate from prescription opioids in their study population decreased from 6.0 per 100,000 in 2010 to 5.6 per 100,000 in 2012.47 Comparable patterns were seen in the Researched Abuse, Diversion, and Addiction-Related Surveillance data.
Although the longevity of these changes is yet to be determined, it is nevertheless encouraging and may be representative of a general trend toward recognition of the problem and improvement of care on a nationwide scale. Multiple factors likely contribute. Most states now have active and functional PDMPs48 and local, state and federal efforts aimed at reducing questionable practices such as doctor shopping and so-called pill mills have likely had an impact. Introduction of abuse-deterrent formulations of opioids, such as the transition of oxycodone in 2010, have been shown to decrease the popularity of their misuse.49 Unfortunately, these recent downtrends have also been accompanied by a marked increase of heroin use, and therefore, for some, one drug may have been supplanted or supplemented with another.
Heroin epidemic
Unlike the slight decrease that has recently been seen with prescription opioid–related deaths, there has been a noticeable growth in the abuse of heroin and the number of heroin-related deaths since 2010. From 1999 to 2010, deaths from prescription opioids essentially quadrupled whereas deaths from heroin increased by less than 50%. However, in the span of the next 3 years, the heroin overdose death rate nearly tripled from 1.0 per 100,000 in 2010 to 2.7 per 100,000 (8257 total deaths) in 2013. Heroin overdose death rates increased in both genders, all age groups, all geographic regions, and all ethnicities except Native Americans.47, 50, and 51
Demographics: Who Is at Risk?
In 2013, there were an estimated 517,000 people who were dependent on or abusers of heroin, which included 169,000 new users.52 A well-identified trend is that the overall demographic of heroin users has changed over time. Primarily affecting urban minorities in the 1980s and 1990s, heroin abuse has become more prevalent in suburban and rural areas.53 New heroin users over the past decade are also now predominantly Caucasian (90.3%), and although heroin use was previously much more common in men, it is now similar between the sexes. Heroin overdose deaths remain nearly 4 times more frequent in men.54 People with annual household income less than $20,000, the uninsured and Medicaid recipients are also at increased risk for dependence and overdose.55
Heroin use has become more commonly accepted among individuals who engage in nonmedical prescription opioid use. The odds of heroin use in prescription opioid abusers from 2008 to 2011 were double what they were in 2002 to 2005. Prescription opioids also seem to have served as a "gateway" for this new breed of heroin user. Among new heroin initiates from 2009 to 2011, 86.1% reported abusing prescription opioids before their first use of heroin.56 A major factor that has been attributed to the recent increase in overall heroin use is the introduction of a higher volume and lower cost product into the drug marketplace.57 Research on this transition is limited, but evidence suggests that many users adopt heroin because it is cheaper and easier to obtain than similarly potent or injectable prescription opioids.54 As mentioned, this overall trend seems to have coincided with reformulation of common medications previously associated with abuse, such as the introduction of abuse-deterrent extended-release oxycodone hydrochloride,46 and an uptick in the regulation and monitoring of prescription drugs.
It would seem to make intuitive sense then that the recent decline in opioid-related deaths is simply the result of a shift to heroin use. However, in 1 study across multiple states from 2010 to 2012, decrease in opioid pain reliever deaths were not found to be associated with increased heroin death rates. In other words, independent of whether a state had an increase, decrease or no change in opioid deaths, all of the included states had an increase in heroin deaths during that time.47 This illustrates that although populations that utilize either type of drug are known to overlap to a certain extent, usage, demographic patterns, and factors contributing to these deaths remain partially independent. Overall, there seems to be a rapidly worsening problem with heroin, superimposed on a continued problem with nonmedical use of prescription opioids.
Limitations of Data
Data for heroin abuse are fraught with the same limitations as prescription opioids; however, some heroin overdose deaths may also be underreported owing to death certificate reporting. Because heroin is metabolized to morphine, listing of that metabolite on an autopsy report or death certificate may lead to misclassification of an opioid pain medication death rather than from heroin itself. This has been demonstrated in several states.44
Furthermore, there have been 2 major reported outbreaks of overdoses related to fentanyl being sold as heroin or being mixed with heroin in 2005 to 2007 and 2013 to 2014. This caused a number of overdose deaths, even among veteran heroin users, because of the relative potency of fentanyl or its analogs and its surreptitious introduction into the marketplace. Between the 2 spikes there were more than 1700 fatalities, although this number is likely underestimated. Fentanyl may not be tested for by medical examiners at autopsy. Adulteration of heroin with fentanyl was initially most prevalent in the Northeast and Midwest, but became much more widespread during the more recent outbreak.58
Opioid antagonist agents
Naloxone hydrochloride (Narcan) is a competitive opioid antagonist that is frequently administered to reverse the adverse effects of opioid intoxication (ie, opioid-induced central nervous system and ventilatory depression). It has a high affinity for the mu (μ)-opioid receptor and effectively reverses the effects of both exogenous and endogenous opioids.59, 60, and 61 Unlike opioid antagonists that were used before its availability (eg, nalorphin and levallorphan), naloxone is a pure antagonist that is devoid of any opioid receptor agonism.62 Naloxone has no pharmacologic or adverse effects regardless of dose when administered in the absence of opioid agonist.59 and 63 However, in the opioid-dependent population, excessive dosing of naloxone may precipitate acute opioid withdrawal syndrome (OWS). Abstinence-related OWS typically has limited clinical consequence (eg, piloerection, vomiting, diarrhea, dysphoria).64 In contrast, clinical effects of pharmaceutically precipitated OWS can result in significant morbidity including acute agitation, delirium, seizure, acute respiratory distress syndrome, and cardiac dysrhythmias.64, 65, and 66
A patient's history of opioid use is often not available when caring for patients in the emergency department with signs and symptoms of acute opioid intoxication. Several case reports have shown that the standard recommended initial dose of naloxone (0.4 mg) can precipitate acute OWS in opioid-dependent patients.65 and 67 To minimize the risk of precipitating acute OWS, several resources advocate for the use of low-dose naloxone (0.04 mg IV with titration every 2–3 minutes).64, 68, 69, and 70 Two commonly used emergency medicine textbooks adopted similar dose recommendation.71 and 72 Outside of the standard dose of 0.4 mg, which was established from anesthesiology research from the 1960s, there is limited clinical evidence to support the use of low-dose naloxone.62, 73, and 74 A recent small case series (n = 15) demonstrated that low-dose naloxone with titration reversed methadone-induced ventilatory depression with a median total dose administration of 0.08 mg IV.68 There is insufficient evidence to advocate the use of low-dose naloxone as the standard of care. However, the use of low-dose naloxone may be a prudent approach to minimize potential harm to patients in the emergency department while reversing opioid-induced ventilatory depression.
Hypoxic end-organ injury owing to ventilatory depression, irrespective of the type or dose of opioid, is responsible for opioid overdose deaths. Opioid-induced central nervous system depression alone is usually of limited clinical consequence. Therefore, the indication for naloxone administration should be to reverse the opioid-induced ventilatory depression. Diagnostic use of naloxone to determine acute opioid intoxication in patients in the emergency department with central nervous system depression alone provides limited clinical benefit and should be avoided. In apneic patients, assisted manual ventilation (via bag–valve–mask) should be initiated until naloxone is available. It has been demonstrated in animal studies that an increase in partial pressure of CO2 (Pco2) potentiated the catecholaminergic response to naloxone-assisted reversal of opioid intoxication, which may increase the risk of OWS.75 and 76 Therefore, normalizing Pco2 via assisted manual ventilation may decrease the risk of precipitating OWS.64
Naloxone can be administered by several different routes: IV, intraosseous, intramuscular, subcutaneous, intranasal, inhalational (nebulized), and, less commonly, via intralingual injection. The onset of action of naloxone can range widely, from 30 seconds (intralingual) to 6 minutes (intramuscular), depending on the route of administration. The duration of action of naloxone is approximately 20 to 90 minutes.64 and 69 The duration depends on the type and dose of the opioid agonist, as well as the dose and route of naloxone administration.64 The short duration of action of naloxone compared with many opioid agonists (eg, methadone) can lead to recrudescence of opioid intoxication, requiring repeat administration of naloxone or a continuous infusion (two-thirds of the response dose per hour).77 Patients in the emergency department who received naloxone for the opioid-induced ventilatory depression should be observed in the emergency department for possible recurrence of intoxication. The observation period of 2 hours may be adequate for the majority of acute opioid intoxication as the opioid receptor antagonism effect of naloxone is short lived.78 Based on several case reports of delayed recurrence of opioid intoxication in a setting of long-acting opioid exposure, a longer observation of 4 hours has been suggested.64, 79, 80, and 81
The reversal of buprenorphine-induced ventilatory depression, unlike other opioids, has been shown to be delayed and to require large doses of naloxone (>2 mg IV).82 and 83 This has been attributed to the slow association and dissociation rate between buprenorphine and opioid receptors, which limits the competitive antagonism of naloxone by reducing its ability to displace buprenorphine from opioid receptors.64, 82, and 83 Administration of naloxone doses of greater than 4 mg have resulted in an inverse dose–response relationship with a decrease in the reversal of ventilatory depression.82 and 83 Caution should be exercised when caring for patients in the emergency department with suspected buprenorphine-induced ventilatory depression because their response to naloxone may be inconsistent and/or delayed compared with other opioid overdoses.
Take Home Naloxone
Distribution of naloxone to opiate users at high risk for overdose is gaining momentum in the United States. The first THN programs in the United States started in Chicago in the mid 1990s as an extension of harm reduction practices for IV drug users.84 Robust programs are now in place in many other cities and states.85, 86, 87, and 88 The World Health Organization placed naloxone on its Model List of Essential Medicines in 2012 and released a manual titled "Community Management of Opioid Overdose" in 2014.89 From 2010 to 2014, there was an increase in the number of local sites that dispense naloxone from 188 to 644. Despite this increase, in 2013 there were 20 states that had no local dispensing sites.90
Detractors of THN programs cite multiple reasons why they should not exist. There is concern that providing this rescue medication encourages the use of opioids. This view is based in drug control rather than public health policy. Similar arguments have been made regarding provision of condoms and needle exchange programs. The practice of "flat lining" was purported to be the practice of 1 person using a high dose of opioid with another person standing by with naloxone in case of overdose. There was also concern that naloxone may be used as a weapon against other opioid abusers.91 A survey of opioid addicts enrolled in a methadone program revealed that 6% of the respondents felt that having naloxone available might lead to them increasing their heroin dosages.92 Despite these concerns, these issues do not seem to be present in the many successful THN programs that exist today.
Another argument is that laypersons do not have the medical knowledge to administer this medication appropriately. The use of lifesaving medications and devices by laypersons is not a novel concept. Epinephrine autoinjectors have been given to patients with anaphylaxis for more than 30 years. Patients with hereditary angioedema are now being given icatibant for self-administration at the onset of life-threatening symptoms.93 Training for both of these medications often involves caregivers or family, and they may sometimes be administered by a third party in a life-threatening situation. Automated external defibrillator availability is widespread and their use by people with no or minimal training is encouraged.
Other concerns regarding layperson administration of naloxone include the short duration of action of this antidote. People who are treated successfully may be given the false sense that they are no longer at risk from the current overdose. The risk is greatest when the overdose was with long-acting opioids, especially methadone. THN programs stress the importance that administration of naloxone by a layperson should be followed by prompt medical attention. Often patients who are given naloxone by medical providers leave once they experience the unpleasant symptoms of withdrawal that this may precipitate. In a review of 552 refusals of care after prehospital administration of naloxone, no patient was found to have died within 48 hours.94
The assertion that THN programs saves lives is less clear. The data are mostly anecdotal.85 and 95 One analysis of the Massachusetts's Overdose Education and Nasal Naloxone Distribution program showed an association of fewer opioid overdose fatalities in communities where Overdose Education and Nasal Naloxone Distribution was implemented.87 The N-ALIVE trial is an ongoing study assessing the impact of distribution of naloxone to a high-risk population.96 The population being studied is prisoners at the time of release. There is an increased rate of opioid overdose in the weeks after release owing to reduced tolerance after a period of prolonged abstinence. This study plans to randomize 56,000 participants to either receiving a supply of naloxone or standard care (no naloxone).
THN programs have used multiple delivery systems for the administration of naloxone to overdose patients. Currently, naloxone is approved by the US Food and Drug Administration for IV, intramuscular, and subcutaneous administration. The recommended route is IV, but this recommendation is for medical providers and not laypersons. Naloxone kits that come as a syringe with a separate ampule of medication require the person administering the medication to successfully draw up and then inject the medication. Owing to concern over needle stick injuries, some Emergency Medical Services (EMS) systems have moved to intranasal delivery despite its lack of US Food and Drug Administration approval. Using an approved medical device called the mucosal atomization device (MAD Nasal, Wolfe Tory Medical, Inc), naloxone can be administered without risk of needle stick to the provider. Some THN programs have also adopted intranasal delivery devices. Recently, the only manufacturer of naloxone that makes it in a dose appropriate for intranasal delivery doubled the price of the medication to $40.97
In 2014, the US Food and Drug Administration approved a handheld naloxone autoinjector (EVZIO; kaléo, Inc, Richmond, VA, USA) that uses technology that was first successfully used for an epinephrine autoinjector made by the same company. One benefit of the autoinjector is that it eliminates the need for assembly of parts to administer the medication. Cost of this product may limit its widespread adoption. In a recent interview, it was announced that the wholesale cost of the kit, which includes a trainer device and 2 naloxone autoinjectors, is $575.98 Third-party payers who are able to negotiate bulk discounts may easily absorb this cost. Community and small municipal programs may be unable to afford this when compared with alternative delivery mechanisms.
When naloxone from a THN program is administered, it is often done so by a person other than the overdose victim.99 and 100 This is owing to the nature of the overdose and the fact that most overdoses occur in the presence of other people, who are often opioid users themselves. Training family members and other people likely to witness an overdose in the administration of naloxone may be beneficial.101 There may also be additional benefit in training these groups in cardiopulmonary resuscitation.102 Overall, there is a growing body of evidence that naloxone can be safely and effectively administered to victims of opioid overdose.
Opioid antagonists and public health laws: barriers and solutions
Legislative responses to increasing opioid use in the United States initially focused on taxing the commercial trade of the product. Later, the Harrison Narcotics Tax Act passed by the US Congress of 1915 not only regulated the taxation and trade of opioids, but also regulated their medical use. The Controlled Substances Act of 1970 is the current federal legislative basis for most opioid regulation. Under this act, drugs are classified based on their abuse potential and medical use into 5 schedules. Schedule 1 drugs have a high abuse potential and no accepted medical use. Schedule 5 drugs have the least abuse potential.103
In light of the current epidemic of opioid abuse, state legislatures have implemented a patchwork of laws in an effort to overcome barriers to the dispensing and use of naloxone for narcotic overdoses.104 and 105 Generally, there are 2 main varieties of laws that have been promulgated to combat the current epidemic: laws that increase access and use of naloxone and laws that promote reporting of overdoses.
First, there are laws that provide greater access and use of naloxone. They do this by allowing physicians to engage in third-party prescribing (prescriptions for patients not examined), prescribing by standing order and broadening the personnel who can prescribe antagonists (eg, pharmacists).104, 105, 106, 107, and 108 Other laws have been created to encourage distribution and use of opioid antagonists by limiting the civil and criminal liability of prescribing physicians and laypersons administering the reversal agents.104 and 105
The second type of laws addresses the reluctance of overdose witnesses to call EMS for fear of criminal prosecution.64, 109, 110, and 111 This is owing to the fact that witnesses to overdoses are often themselves engaging in the criminal use of controlled substances, are in possession of such substances, or are afraid of arrest for other reasons (eg, possession of illegal drugs or outstanding warrants).109, 110, and 112 To combat this, many states have enacted Good Samaritan laws that provide limited criminal immunity to bystanders who report an overdose.
Laws Encouraging Access to Naloxone by Limiting Liability
In 2001, New Mexico became the first jurisdiction to create a law to specifically provide liability protection for providers who dispensed and lay rescuers who administered naloxone.113 Currently, New Mexico and several other states have an Opioid Antagonist Administration Training Program that provides naloxone to certified lay rescuers.105
As of July 2015, 40 states and the District of Columbia of have made changes to their laws to allow the prescribing of naloxone with varying limits to civil and criminal liability (Table 1).104 Some of these laws provide for both civil and criminal liability protections to varying degrees for both prescribers and lay rescuers, whereas others only protect either providers or rescuers but not both. Some states have enacted laws that protect providers from disciplinary action by the state medical board. Interestingly, despite a flurry of legislation that would seem to indicate prosecution of prescriber and layperson rescuers was a major issue, but in reality prosecution is extremely rare.105
|Civil Liability or Disciplinary Protection for Prescribers
|Criminal Liability Protection for Prescribers
|Civil Liability Protection for Lay Rescuers
|Criminal Liability Protection for Lay Rescuers
|Third-party Prescription Allowed
Laws to Promote Prescribing of Opioid Antagonists
To increase the distribution of opioid antagonists, many states have enacted laws to facilitate the prescription of this medication. Usually a provider cannot prescribe medication to a patient unless the provider has examined that patient personally.105 and 106 Strategies to circumvent this issue have included third-party prescriptions, standing orders, and collaborative practice agreements.105, 106, 107, and 108 Third-party prescriptions allow physicians to prescribe medication for patients they have neither seen nor examined. For example, under the Massachusetts law, an "opioid antagonist may lawfully be prescribed and dispensed to a person at risk of experiencing an opiate-related overdose or a family member, friend or other person in a position to assist a person at risk of experiencing an opiate-related overdose."114 Similar strategies have been adopted to combat sexually transmitted diseases using Expedited Partner Therapy.
Many jurisdictions have created similar legislation specifically for opioid antagonists third-party prescriptions (see Table 1).106 In other jurisdictions, standing orders signed by a physician allow other providers to dispense opioid antagonists through established protocols.106 and 108 Another way of facilitating dispensing of naloxone is through the use of collaborative practice agreements that allow for pharmacists to prescribe opioid antagonists on behalf of and in conjunction with licensed physicians.106 and 107 New Mexico, a state that has led the way in legislative solutions for the opioid epidemic, recently was the first state to give pharmacists the authority to dispense opioid antagonists independently.106
These legislative efforts demonstrate attempts to increase opioid antagonist availability through standing orders, pharmacist prescribing, and third-party prescriptions. An even better way to distribute antagonists to the public might be to simply provide the medication as an over-the-counter drug. However, for naloxone to be approved by the US Food and Drug Administration for over-the-counter use, some entity would have to fund clinical trials and then the application process. This process would take years and would likely be cost prohibitive.105 and 106
Good Samaritan Laws: Providing Immunity to Bystanders Who Report Overdose
Opioid overdose is commonly witnessed by individuals who also use opioids.85, 90, and 112 In 1 survey study of 329 drug users, 34% stated that they had experienced an unintentional overdose and 64% stated that they had witnessed an overdose.90 and 115 Another study surveyed 1184 drug abusers, of which 797 (67.3%) had witnessed a nonfatal or fatal overdose.90 Of these, 278 (23.5%) had seen an overdose within the previous 6 months.110
Despite bystanders' familiarity with potentially deadly overdoses, they often do not call EMS. Survey data estimate that only 10% to 60% of bystander witnesses actually call EMS when drug overdoses occur.85, 109, 110, and 112 The primary reason that bystanders do not call is fear of arrest and criminal prosecution.109 and 110 In a survey of 301 bystanders who delayed or did not call for help during an overdose, 152 (52%) stated that they feared police response and potential arrest.64, 109, and 110 Although prior surveys of police officers indicate that they are unlikely to arrest an overdose victim or bystander, the fear of legal action remains a significant barrier to calling for assistance.110 and 111 Although uncommon, the legal risk to the bystander is not completely absent.105, 112, 116, and 117
To address this fear of arrest and to encourage bystanders to call for EMS, many states have passed laws that create limited criminal immunity for bystanders who report an overdose.64, 104, 105, and 109 As of July 15, 2015, 31 states and the District of Columbia have passed Good Samaritan laws (Table 2).104 Most of these laws provide protection from criminal charges regarding possessing a controlled substance, whereas others also provide protection from possession of drug paraphernalia.
|No Charge for Controlled Substance Possession
|No Charge for Drug Paraphernalia
|Protection from Other Crimes
|Reporting Overdose Can Mitigate Prosecution of a Crime
Safe opioid prescribing practice in the emergency department
As many as 42% of all emergency department visits are owing to pain-related conditions.118 Between 2001 and 2010, there has been a 49% increase in the percentage of total emergency department visits where an opioid was prescribed for pain.119 In 2010 alone, enough morphine milligram equivalents were prescribed by all specialties nationwide to provide every adult American with enough to take 5 mg every 4 hours for a month.32 Although primary care providers and dentists prescribe the majority of opioids in the United States, emergency medicine ranks among the top 5 specialties (for ages 0–39 years) for opioid prescribing in the ambulatory setting.120 Some data suggest that there is an increased rate of diversion and abuse of opioids that are prescribed from emergency departments, especially by young people.36 The primary challenge for emergency department providers in the current opioid abuse epidemic is how to balance the need to provide adequate pain control for patients in the emergency department while minimizing the availability of opioids for abuse or diversion. Recently, the American College of Emergency Physicians, American Academy of Emergency Medicine, 14 states (AK, AZ, CA, CT, DE, HI, MA, MD, ME, OH, OK, OR, PA, and WA), and New York City have established opioid prescribing guidelines specifically for emergency medicine providers.121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, and 133 In addition, numerous other states have adapted opioid prescribing and pain treatment guidelines for all health care providers.121 Emergency department–specific guidelines generally recommend prescribing small quantities (eg, a 3-day supply) of short-acting opioids for acute pain. They also discourage replacing lost, stolen, or destroyed prescriptions.24, 124, 132, and 133 These guidelines also advocate for the use of PDMP to review prescription history and to identify potential at-risk patterns for "doctor shopping."24, 123, and 134 Some health care providers have expressed concerns that these guidelines may result in undertreatment of pain, especially for those patients who use emergency department as their source of primary care. Others argue that prescribing guidelines can interfere with their professional independence and judgment.135
PDMPs have been advocated as a promising tool to decrease inappropriate opioid prescribing and to identify patients with at-risk pattern for misuse. To date, 49 states (except Missouri) have operational PDMPs.136 and 137 However, the state-based PDMPs are not standardized and vary in their complexity and completeness.24 The use of PDMPs has been shown to decrease "doctor shopping"; however, there is inconsistent evidence as to how PDMPs affect health care provider's opioid prescribing behavior.138, 139, 140, 141, and 142 The possibility that PDMPs have little effect on prescribers' behavior has been attributed to the difficulty of obtaining PDMP access, lack of use, and incomplete data within PDMPs.24, 138, and 140 To improve provider use, 22 of the 49 states with PDMPs mandated all prescribers of controlled substances to query the PDMP for at-risk pattern for misuse and/or diversion.138 The mandated query of PDMPs, based on the experience from Kentucky, New York, and Tennessee, did decrease the overall number of opioid prescriptions by 7% to 9%.143 However, these mandates face opposition from health care providers to owing to limitations of PDMPs and their intrusion into clinical practice.138
The impact of the emergency department opioid guidelines on opioid prescribing practice is unknown. One recent study showed that the introduction of an emergency department opioid guideline in 2 academic affiliated EDs decreased the number of discharged patients with opioid prescriptions from 52.7% to 33.8%.144 Its impact on outpatient pain management was not assessed and further investigation is needed. The use of opioid prescribing guidelines is voluntary and not a mandated practice. Each emergency department provider must use his or her clinical intuition and judgment to adequately address and treat the pain experienced by each patients in the emergency department. Although emergency department providers are not the leading prescribers of opioids, appropriate prescribing practice is essential to help decrease the availability of opioids for abuse or diversion.
Opioid pain medication abuse is one of the leading public health problems in the United States. Health care providers have contributed to the current opioid abuse epidemic through our prescribing practices. In 2012, 4.2 billion prescriptions were written in the United States; 289 million (6.8%) were for opioids, an increase of 11.7% from 2007.145 There has been a concerted effort among government, state, and professional organizations, and members of medical specialties to address the increasing incidence of opioid abuse and overdose-related deaths. Nationally, numerous medical specialties have made conscientious effort to decrease inappropriate opioid prescribing. Between 2007 and 2012, large decreases in opioid prescriptions were noted in emergency medicine (–8.9%), followed by dentistry (–5.7%) and surgery (–3.9%).145 Numerous states have developed emergency department opioid prescribing guidelines, and implemented PDMPs and health care provider education programs. Patient-directed interventions also need to be developed with a focus on remediating the deficiencies in patients' understanding of the risk of opioid use and the expected outcome of "adequate" pain management.146 and 147
There is an epidemic of opioid abuse in the United States. The risk of heroin abuse has been appreciated for more than a century with it now being considered to have no justifiable medical use. Opioids that are prescribed commonly to treat painful conditions have had a dramatic increase in the rate of abuse, addiction, overdose, and death. The increase in complications corresponds with a dramatic increase in the rate of opioid prescriptions that resulted from pressures placed on practitioners to avoid undertreatment of pain.
Naloxone is an opioid receptor antagonist that is used to treat opioid overdoses. Its use as a rescue medication by laypersons is becoming increasingly accepted. Other efforts to combat the opioid epidemic include the use of PDMPs and implementation of safe opioid prescribing guidelines. The laws that govern these efforts vary from state to state resulting in a wide range of effectiveness. The efforts to reign in the abuse of opioids will require further research and a reexamination of the balance between the need to treat pain and the recognition that opioid medications are not without risk.
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- 113 N.M. Stat. Ann. § 24-23-2 (2001).
- 114 Mass. Gen. Laws ch. 94c § 19 (d) (2012).
- 115 T. Lagu, B.J. Anderson, M. Stein. Overdoses among friends: drug users are willing to administer naloxone to others. J Subst Abuse Treat. 2006;30(2):129-133 Crossref
- 116 Spears v. State, 929 So. 2d 477 (Ala. Civ. App. 2005).
- 117 People v. Besz, 802 N.E.2d 841 (Ill. App. Ct. 2003).
- 118 M.J. Pletcher, S.G. Kertesz, M.A. Kohn, et al. Trends in opioid prescribing by race/ethnicity for patients seeking care in US emergency departments. JAMA. 2008;299(1):70-78
- 119 M. Mazer-Amirshahi, P.M. Mullins, I. Rasooly, et al. Rising opioid prescribing in adult US emergency department visits: 2001–2010. Acad Emerg Med. 2014;21(3):236-243 Crossref
- 120 N.D. Volkow, T.A. McLellan, J.H. Cotto, et al. Characteristics of opioid prescriptions in 2009. JAMA. 2011;305(13):1299-1301 Crossref
- 121 American Academy of Physical Medicine and Rehabilitation. Pain Management and opioid prescribing policies by state. 2014. Available at: http://www.aapmr.org/advocacy/outreach/AAPMR%20Documents/Pain-Management-and-Opioid-Prescribing-Policies-By-State.pdf. Accessed August 30, 2015.
- 122 Arkansas Department of Health. Arkansas emergency department opioid prescribing guidelines. Available at: http://www.aapmr.org/advocacy/outreach/AAPMR%20Documents/Pain-Management-and-Opioid-Prescribing-Policies-By-State.pdf. Accessed August 30, 2015.
- 123 California American College of Emergency Physicians. Safe pain medicine prescribing. Available at: http://californiaacep.org/wp-content/uploads/CAL-ACEP_ED-Handout_8-5x11_ENG_v8.pdf. Accessed August 31, 2015.
- 124 Connecticut State Medical Society. Connecticut emergency department opioid prescribing guidelines. 2015. Available at: http://documents.cthosp.org/9/Opioid Guidelines FINAL 1_20_2015.pdf. Accessed August 31, 2015.
- 125 H.S. Martins, R.V. Silva, D. Bugano, et al. Should naloxone be prescribed in the ED management of patients with cardiac arrest? A case report and review of literature. Am J Emerg Med. 2008;26(1):113.e5-113.e8 Crossref
- 126 Hawaii American College of Emergency Physicians. Hawaii emergency department opioid guidelines. 2014. Available at: http://www.hawaiiacep.org/uploadedFiles/Hawaii/Best Practices.pdf. Accessed August 30, 2015.
- 127 Maine American College of Emergency Physicians. Emergency department opioid prescribing guidelines. 2014. Available at: http://www.maineacep.org/Resources/. Accessed August 30, 2015.
- 128 Opioid prescribing guidelines for Oklahoma workgroup. Oklahoma emergency department (ED) and urgent care clinic (UCC) opioid prescribing guidelines. 2015. Available at: http://www.ok.gov/health2/documents/UP_Oklahoma_ED-UCC_Guidelines.pdf. Accessed August 30, 2015.
- 129 Oregon College of Emergency Physicians. Oregon emergency department (ED) opioid prescribing guidelines. 2012. Available at: http://www.ocep.org/images/pdf/ed_opioid_abuse_guidelines.pdf. Accessed August 30, 2015.
- 130 Pennsylvania College of Emergency Physicians. Pennsylvania guidelines: Emergency department (ED) pain treatment guidelines. 2014. Available at: http://www.pamedsoc.org/DocumentVault/VaultPDFs/PatientcarePDFs/ER-opioid-guidelines-PDF.pdf. Accessed August 30, 2015.
- 131 Maryland American College of Emergency Physicians. Maryland emergency department and acute care facility guidelines for prescribing opioids. 2014. Available at: http://www.mdacep.org/MD ACEP Pamphlet FINAL_April 2014.pdf. Accessed August 30, 2015.
- 132 Cheng D, Majlesi N, Heller M, et al. Clinical practice statement: Emergency department opioid prescribing guidelines for the treatment of non-cancer related pain. 2013. Available at: http://www.aaem.org/UserFiles/file/Emergency-Department-Opoid-Prescribing-Guidelines.pdf. Accessed August 31, 2015.
- 133 Emergency Department Opioid Abuse Workgroup. Washington Emergency Department Opioid Prescribing Guidelines. 2011. Available at: http://washingtonacep.org/Postings/edopioidabuseguidelinesfinal.pdf. Accessed December 15, 2012.
- 134 New York City Department of Health and Mental Hygiene. New York City emergency department discharge opioid prescribing guidelines. 2013. Available at: http://www.nyc.gov/html/doh/downloads/pdf/basas/opioid-prescribing-guidelines.pdf. Accessed August 31, 2015.
- 135 D.N. Juurlink, I.A. Dhalla, L.S. Nelson. Improving opioid prescribing: the New York City recommendations. JAMA. 2013;309(9):879-880 Crossref
- 136 National Association of State Controlled Substances Authorities. Prescription monitoring programs. 2014. Available at: http://www.nascsa.org/nascsaPMP/NationalPDMPmap1.26.14.pdf. Accessed August 29, 2015.
- 137 Missouri prescription drug monitoring program NOW coalition. Get the facts. 2015. Available at: http://mopdmpnow.com/get-the-facts/. Accessed August 29, 2015.
- 138 R.L. Haffajee, A.B. Jena, S.G. Weiner. Mandatory use of prescription drug monitoring programs. JAMA. 2015;313(9):891-892 Crossref
- 139 D.F. Baehren, C.A. Marco, D.E. Droz, et al. A statewide prescription monitoring program affects emergency department prescribing behaviors. Ann Emerg Med. 2010;56(1):19-23.e1-e3
- 140 C.A. Griggs, S.G. Weiner, J.A. Feldman. Prescription drug monitoring programs: examining limitations and future approaches. West J Emerg Med. 2015;16(1):67 Crossref
- 141 T.M. Haegerich, L.J. Paulozzi, B.J. Manns, et al. What we know, and don't know, about the impact of state policy and systems-level interventions on prescription drug overdose. Drug Alcohol Depend. 2014;145:34-47 Crossref
- 142 J.E. Brady, H. Wunsch, C. DiMaggio, et al. Prescription drug monitoring and dispensing of prescription opioids. Public Health Rep. 2014;129(2):139-147
- 143 Prescription Drug Monitoring Program Center of Excellence at Brandeis. COE Briefing. Mandating PDMP participation by medical providers: current status and experience in selected states. 2014. Available at: http://www.pdmpexcellence.org/sites/all/pdfs/COE%20briefing%20on%20mandates%20revised_a.pdf. Accessed August 30, 2015.
- 144 D.A. Del Portal, M.E. Healy, W.A. Satz, et al. Impact of an opioid prescribing guideline in the acute care setting. J Emerg Med. 2015; [Epub ahead of print]
- 145 B. Levy, L. Paulozzi, K.A. Mack, et al. Trends in opioid analgesic–prescribing rates by specialty, US, 2007–2012. Am J Prev Med. 2015;49(3):409-413
- 146 M. Conrardy, P. Lank, K.A. Cameron, et al. Emergency department patient perspectives on the risk of addiction to prescription opioids. Pain Med. 2015; [Epub ahead of print]
- 147 R.J. Smith, K. Rhodes, B. Paciotti, et al. Patient perspectives of acute pain management in the era of the opioid epidemic. Ann Emerg Med. 2015;66(3):246-252.e1
Department of Emergency Medicine, University of Maryland School of Medicine, 110 South Paca Street, 6th Floor, Suite 200, Baltimore, MD 21201, USA
∗ Corresponding author.
Disclosures: None.
Article information
DOI: 10.1016/j.emc.2015.11.002
© 2015 Elsevier Inc., All rights reserved.


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Some excerpts from the book I've been working on (on and off) for the past few years:
Raw Book Excerpt (December 4, 2015): My grandmothers had a huge influence on my life. This is something I didn't realize until they were on their deathbed or already gone. My grandfathers were gone long ago so I don't know much about them All I know is through stories. They were gentle, kind, and passive men overtaken by the powerful women in their lives. They died, not naturally, but one from a stroke and the other from a heart attack.
My mother was close with her father just as I am with mine. At the time of his death, she was new to the United States and living in Chicago. She had her first born and was unable to visit him or go to his funeral. This is what I can't imagine. The sacrifices our parents made for us as immigrants. The lives they constructed to ensure their future generations never suffered. We have and always will, I've realized, remain at the epicenter of their dreams. We remain at the center of theirs so they can remain on the outskirts of ours.
Book Launch (September 8, 2015): I have not told many people of my plans to write a book about my parents' lives, being a first generation Indian-American, and how all of this ties together to the rise of a new generation. Right now, I believe we are in an incredible period where two cultures, well two worlds are merging into one incredibly complicated, but enriching period. Many immigrants, similar to my parents immigrated in the 1980s, struggled to set a stable foundation for their future children, and are now at period where they are watching their children grow older. Their children are making their own decisions to carry this other world their parents have come from into the world that has grown to be their own 'home'. This is the story I would like to tell plus more about how this old world has brought many positive social and economic changes to this "new" world (the rise of Silicon Valley, tech, start-ups, social impact, etc.).
Since there are many facets of this story such as my family history in India, my parents' journey to the United States, other immigrant stories, stories of being a first-generation, and more, I've struggled to map out how to best tell this story. However, over the past 5 years, I've believed that there's an incredible story here, especially of my parent's lives, and it needs to be told. I know it's a story, although in various narratives, that has been told and probably will be told over again over the next few generations.
I've learned through mistakes and lessons that it's good to start small, so when I started gathering snippets of interviews with my parents, with villagers from my parents childhoods, and my own personal experiences and thoughts as a first-generation Indian- American, I was hopeful that it would grow to be something substantial enough to put into one piece.
Now these stories, interviews, and snippets are slowly coming together (although they are still very raw). I've refused to let anyone read them until now, and now you guys will have the opportunity to read little excerpts that I hope will one day become one book. By no means do I have chapters and chapters written. I am still gathering the content I will need to make this into the story I want to tell. I still have a long time to go and as it has over the past few years, life will get in the way and progress might be a little slow.
Now that I'm entering a new chapter of my life and learning more about how these stories have shaped the person I'm becoming, I feel as though I owe the world this. This is my contribution to the world- to tell the stories of people that the world has never and may never get the opportunity to experience and understand.
Finally, I'm open to any suggestions/recommendations you might have. This is a story that will be told through numerous lenses, so your perspective will bring more color to me as I continue to write this book.
Special thank you to my amazing and close friend Jennifer Everett (Follow her amazing life as an entrepreneur and traveler here: http://jenniferleverett.com/) who has given me so much helpful advice, including this one to formally announce my book launch.

subset: commoncrawl


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An excellent interview with Richard Ford on the BBC World Service World Book Club, Ford's succinct description on the potency of dialogue in fiction was worth noting:
Dialogues are doing a lot of very complex things at the same time. They are trying to seem true to the person who is saying them. They are load bearing, they're carrying lots of information, they are at the same time utterly unpredictable from one phrase to the next which is pretty much the way most of our dialogue is in life (pretty unpredictable and seem spontaneous), and they also have, as far as I'm concerned, to be funny ... I guess that little menu of things that they have to perform means that I work at them pretty hard ... I almost never write a dialogue or a couple of pages full of dialogue without going over it and over it and over it and over it, trying to be sure that it is satisfying all those ends at once.


text:
Defining true audio
|Design principle
|bass reflex
|Nominal/music power (W)
|Frequency response (Hz)
|35...65.000 Hz
|Crossover frequency (Hz)
|500/3000 Hz
|Efficiency (dB/1W/1m)
|88 dB
|Impedance (Ohm)
|135 mm Ø Titanium-PP
|135 mm Ø Titanium-PP
|Size (w x h x d) in cm
|941x166x232 (Dimensions without base plate) mm
|Socket Ø (cm)
|30 cm
|Weight in kg
|12,2 kg
av-magazin.de, 03/2013
"The Chromium Style home cinema set from Quadral gives you first-class tone quality coupled with an elegant, modern and timeless design. The generous technical configuration enables the Chromium Style set to produce a powerful, gripping sound, which guarantees impressive music and film sound reproduction."
+ good spatiality
+ powerful bass reproduction
+ impressive reproduction capabilities
Assessment: Excellent sound Excellent fittings
areadvd.de, 01/2013
CHROMIUM STYLE range, 5.1 box set, consisting of: STYLE 52, STYLE 12 BASE and QUBE 10
The Quadral Chromium Style set including QUBE 10 active is, same as the first Chromium Style ensemble that we tested, a hit in every regard! Excellent workmanship gives it both a truly noble appearance and polished acoustics. The expensive and complex ribbon tweeter ensures that the Style 52 and Style 12 Base give the optimum values for this price class, especially with regard to homogeneity and an extensive high tone range. The coupling of the ribbons to the mid-tone ranges, which is quite a problem on its own, has been completed brilliantly by Quadral, as the sound appears to come from a single source. The precise voice reproduction and authentic spatiality make the mid-tone ranges extremely satisfying to listen to. The new QUBE 10 has worked wonders for the bass ranges. The new active subwoofer is powerful, precise and has tremendous depth."
5.1 speaker system in the upper mid-range class
+ First-class high frequency range – pleasant and rich in detail
+ Excellent voice reproduction
+ Superb spatiality
+ QUBE 10 has a rich bass and high precision reproduction
+ Very homogenous acoustic field with four upright speakers
+ Superior workmanship
+ Superb appearance
- Only in two high gloss finishes
- No Bi-amping/Bi-wiring
(translated by quadral)


text:
A Colorful, Fall Engagement Session in Marks, MS | Carter & Madison
I took a little trip down to Marks, MS to photograph Madison and Carter and to explore a beautiful patch of land full of trails, changing leaves, deer, and untouched beauty. Carter knows every inch of the 800 acre property that we spent adventuring through, and gave me the full tour. I literally can't even wrap my mind around how beautiful nature is and all the colors that it creates just with the change of a season.
I loved getting to photograph these two on their property and document their engagement this way, because this land means something to them. This is a special place that they will always have in their hearts; they can re-walk these trails, roam the woods, watch the leaves change every year here, visit these same special spots and together and maybe even eventually walk with their children and grandchildren here.
Thank you guys for inviting me down to Marks and for taking the time to show me around and let me pet your sweet pup <3 SO ready for your wedding next October!
"When I met Carter it was during the fall and during hunting season, so anytime we wanted to hang out we just met at the ranch, it was closer to me (I was living in Cleveland) and he was always down there hunting. I always loved going because it was beautiful, quiet, and this is really where it d of all started.
One weekend I went down there after we first started dating and he took me hunting. It was probably 36 degrees outside. He gave me all of his hunting clothes to wear and a buddy heater, all he had on was blue jeans and a flannel. We sat out there for 3 hours. He said he knew he loved me then because I was so loud and he was freezing. We saw 0 deer or any sign of life at all might I add. I knew I loved him because I am not a huge fan of hunting or freezing or my phone dying but I would tolerate it just for him."


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Most brands now engage in organic and paid search to a greater or lesser degree, but most do so with little understanding of the interaction between the two mediums, and therefore fail to acknowledge that search is one medium and not two and should be managed as such for maximum return.
The key differences between organic and paid listings are more about the mechanics that power them than how searchers actually engage with them. For the consumer they are simply using Google, Yahoo, or Bing, and not algorithmic listings or sponsored ads.
We have found that managing the medium as one can increase budget efficiency by 30% on average. Ultimately, search is two channels within a single medium with huge gains to be had if this fact is reflected in their management.
The benefits of operating a 'One Search' vision
The ultimate benefit is a 30% improvement in the efficiency of your search campaigns. That's 30% less costs or 30% more sales, or indeed somewhere in between. How does an integrated approach achieve this? Essentially through efficiencies, economies and improvements in the following areas
Unified reporting
The management of all search data, its retrieval, analysis, and presentation, should happen once, not twice. Your consumption of that data again should be based on one material output, not two. It facilitates better and faster decision making, ROI clarity, and both saves you and makes you money as a result.
Problem identification
A disparity in performance between a paid search ad and an organic search listing can identify problems or issues with particular pages and messaging in one channel over another, and your identification, investigation and response can then be and should be, rapid.
Brand bidding
Should you bid against your brand terms? The answer is yes, but all the time? Regardless of what's happening in your natural search space? Looking holistically you can experiment with your levels of brand bidding, including day-parting strategies or even the need to saturate your organic search space with your own web assets if necessary.
Risk mitigation
The search engines operate in a heightened competitive universe, fuelled by rapid innovation and significant R&D budgets. This means that they develop and change quickly and this is true for both organic search (algorithmic changes, for instance) and paid search (trademark policies, one-box implementations, etc) and as such, your revenue stream from each can be open to significant fluctuation. Operating organic and paid search efficiently implies that you know if, when, and why to move budget to the other, across which keywords, at what time and for what length of time to mitigate your risk and maintain total revenue and CPA levels as forecasted.
Ad copy effectiveness
Testing paid search ad copy effectiveness is the mainstay of all good paid search campaigns, but these insights are hardly ever ported over to your natural search listings. When research suggests that natural search achieves between 2.5x and 4x more traffic than paid, this is unforgivable.
Keyword cannibalisation
There are various instances where your organic and paid listings will cannibalise the clicks of the other and understanding when this is happening is important and acknowledging that not all cannibalization is bad, given that you may have CPA or volume targets that this cannibalisation actually helps you achieve. Being able to manipulate this cannibalization is key.
A limited degree of paid and natural search technological convergence has occurred over recent years, largely limited to Google looking to on-page relevancy for both organic and paid search. Within paid search, on-page relevancy affects what you pay per click as part of how your Quality Score is calculated. This means that optimizing your pages for the keywords you are buying against will, all things being equal, reduce what you pay per click. Given that SEO as a discipline is the principle authority on on-page relevancy, there are clear benefits of using SEO expertise to produce landing pages for both natural and paid search.
Businesses will often have targets and objectives that they formulate forecasts to achieve. A forecast, to be anywhere near accurate for organic and paid search, must reflect the effects of each of those activities over the other. Planning which keywords should be primary, secondary, or discarded keywords for natural search and paid search can deliver incredible improvements to your ROI very quickly.
Alignment of method to goal
What are you using search to achieve? And how does each medium better reach different goals? Paid search is great at aggressively pushing a new promotion that may need to be pulled at a moment's notice. It is also great at carpeting an entire keyword set, even if you don't have the pages to perfectly reflect the keywords you're targeting. It also has a great branding role to play. Organic search in contrast delivers traffic and sales at typically a cheaper rate and is utilized more and indeed trusted more, for informational searches, which means it has a reputational (PR) and social media role too. Organic search is also often the first click, with paid often the last click, and so they have goals in relation to each other's goals too that should be understood and optimised against.
The multiplier effect
Perhaps most important of all, research points to a clear statistical advantage in securing the click from a searcher if you are holding more real estate on a search engine results page (SERP) than just one solitary organic or paid listing. This means that occupying more of Page 1 of any given results page not only increases your paid search click through rate (CTR) and therefore increases your number of visitors and decreases your per click costs (due to quality score improvements) but also reduces your click costs further by ensuring that organic search is doing its part in facilitating a blended cost per click (CPC) from the medium which might not have been possible with PPC alone. On that basis it's important to understand how your paid and organic visibility overlaps and when and where to create this multiplier effect.
However, it's easier said than done…
Most agencies, brands and search professionals will place an emphasis on either organic or paid search and as a result fail to optimise the medium in its entirety, ignoring that organic and paid search power each other, have their specific benefits and drawbacks, and also represent an opportunity to optimise spend and ROI for the total benefit of the advertiser. More specifically, the holistic optimisation of search is a rare activity due to the following reasons:
Paid Search is often treated like TV advertising
Much of this lack of strategic integration stems from a hugely flawed outlook on paid search, propagated by the more traditional agencies who view paid search as something you simply allocate spend to, as a trivial bolt on to a TV, radio and print budget, where the media planning objective of negotiating the lowest rates reigns supreme. But paid search is not TV – it can achieve some of the same objectives – but TV cannot be optimized to the same extent as paid search and so it cannot be managed in the same way.
To put this into perspective, and I appreciate controversially perhaps, the optimization of a TV campaign has only a handful of variables that can be manipulated – which TV channel, at what time of the day, before/after/between which programming. A paid search campaign will often have hundreds of thousands of keywords being targeted, with every single one being a variable that needs to be optimized against the same variables as TV and a few more too. Paid Search is not TV; it is an optimisational discipline, just as SEO is.
Furthermore, paid and organic search not only need to be optimized in their own right, but also optimized against each others' performance as they are targeting the same user, on the same SERPs, at the same time. If you're not talking about paid search as an optimisational discipline you're losing money right now and the benefits of strategic integration far beyond your grasp.
An imbalance in capabilities and competencies
Most people, brands and agencies only have genuine competency and experience in either natural search or paid search, very rarely both, in many cases neither. For instance, only 20% of the top 30 search agencies in the UK are in a position where at least 30% of their revenue comes from natural and 30% from paid search. A third of all search agencies focus exclusively on just SEO or PPC.
It's worse for the full service media agencies where they treat paid search as a media buy and employ a handful of really capable SEO and PPC practitioners at best; limited resources in a vacuum of genuine leadership isn't the best recipe for cutting edge search.
It's all very confusing
Does a natural search ranking affect my paid search click through or conversion rate if the user sees both listings and clicks on one or the other? Are there instances where you shouldn't use paid or natural search? Are there ever grounds to not bid against a keyword? Most marketers and agencies acknowledge that these are important questions, but the answers are specific to your brand, your spend, your website, your sector, and cannot be found in a manual. The only way of integrating your search strategy is to dare to collect, disseminate, analyse and test your own data and build your own models. Not an easy task and one that most will simply not dare tackle because, well, its just very confusing and time consuming.
Lack of analytics & mathematical modelling
It is only quite recently that most brands have robust enough analytics in place to be able to measure the contribution of natural search and paid search, and indeed the relationship between them with click path analysis. Click path analysis is key to running a holistic search existence, as you will only know how the two channels behave in isolation and in various combinations of the other once you've gathered and analysed the data. Current analytics provision only provides the raw data however, it still needs to be analysed and modelled to have any bearing on how an integrated search system should operate.
Based on the above obstacles, gaining competitive advantage from running a real, integrated search methodology necessitates that five requirements are satisfied:
- The treatment of paid search as an optimisational discipline.
- Genuine capabilities under one roof in both SEO and PPC, either in-house or in your agency of record.
- Real time interpreted data and the ability and agility to manoeuvre based on that data. This implies consistent action-inspiring mathematical rigour, i.e. technology making millions of calculations each and every minute analysing scenarios and trading off metrics against each other.
- Inter-disciplinary experts, data-driven, with PHD-level mathematical modelling capabilities.
- Brands and agencies ready and willing to go on the One Search journey and invest ahead of bearing the fruits of it.
These five requirements are undoubtedly tough obstacles – it's not as easy as just sharing the odd piece of data between agencies or moving desks around so your organic people are sitting near your paid search people.
Bearing the fruits of 'one search' entails a much more ambitious approach to analytics, reporting, expertise, messaging, mathematics, and user engagement, pulling all these things together to produce intelligent, actionable information.
Zero excuses
Just because something is difficult doesn't mean it should be ignored. Many agencies, brands and professionals have for years spoken about the benefits of SEO and PPC 'integration', but have done little to make it a useful reality.
The benefits however are very clear and may perhaps represent the last major area available to marketers to create some real competitive advantage in their search channel. Moreover, this doesn't even begin to touch on other beneficial integrations, such as search with social media. On that basis, there really is no excuse, so start now.