“Alarming” Death Rate in Primary care for Opiate Abusers

Patients with opioid use disorder (OUD) who are seen in the general healthcare setting are more than 10 times more likely to die than their counterparts without OUD, new research shows.
An analysis of electronic health records (EHRs) for more than 2500 patients with OUD who were treated at a major university hospital system showed a crude mortality rate of 48.6 deaths per 1000 person-years — a rate that was more than 10 times higher than the expected death rate in the general population for individuals of the same age and sex. The data covered an 8-year period.
“My original thinking was that the mortality rate could not be very high in the general healthcare setting because general healthcare centers are supposed to have more comprehensive health services, and most people are insured. But when I saw such a high mortality rate, I was shocked,” lead investigator Yih-Ing Hser, PhD, professor of psychiatry and behavioral sciences, David Geffen School of Medicine at the University of California, Los Angeles, told Medscape Medical News.
The study was published online April 20 in the Journal of Addiction Medicine.

Too Little, Too Late

Treatment of OUD has traditionally been delivered in specialty addiction centers, such as methadone treatment programs, “isolated from the primary care system or general medical systems,” the authors note.
Recent healthcare reforms through the Federal Mental Health Parity and Addiction Equity Act and the Affordable Care Act have led to an expansion of services for substance use disorders (SUDs) in primary care. Although most clinicians in the general healthcare system are aware of the risk for elevated mortality among OUD patients in publicly funded SUD treatment settings, they “do not fully appreciate the mortality risks to their patients,” the authors note.
To investigate the mortality rates of OUD in the general healthcare environment, the researchers studied the EHRs from a large university health system from 2006 to 2014. They identified 2576 patients, who ranged in age from 18 to 64 years at their first OUD diagnosis.
They also obtained mortality data from the National Death Index of the US Centers for Disease Control and Prevention. The duration of follow-up was from either the time of first OUD diagnosis to death or to December 31, 2014, for those still alive.
During the follow-up period (a mean of 3.7 person-years), there were 465 (18.5%) confirmed deaths, yielding an all-cause crude mortality rate of 48.6 per 1000 person-years.
Individuals who died were older at the time of first OUD diagnosis (48.4 vs 39.8 years) and were more likely to be male (41.7% vs 31.6%), black (11.2% vs 6.8%), and uninsured (87.1% vs 51.3%). The mean age of patients at death was 51.0 years (SD = 11.0).
Deceased patients were more likely to have been diagnosed with other co-occurring SUDs (particularly SUDs involving tobacco, alcohol, cannabis, and cocaine). Drug-related problems represented the most common cause of death (19.8%). These included accidental poisoning or drug overdose, intentional poisoning, and alcohol use disorder or drug use disorder.
Physical health problems associated with death included heart disease, respiratory disorders, hepatitis C virus (HCV) infection, liver disease, cancer, and diabetes.
Cardiovascular disease and cancer were the most common physical causes of death (17.4% and 16.8%, respectively), followed by infectious diseases (13.5%, with 12.0% HCV and 0.8% HIV), diseases of the digestive system (12.2%, with 4.9% alcohol-related liver disease), and external causes (6.7%).
HCV (hazard ratio [HR], 1.99; 95% confidence interval [CI], 1.62 – 2.46) and alcohol use disorder (HR, 1.27; 95% CI, 1.05 – 1.55) were the two statistically significant and clinically important indicators of overall mortality risk.

Lack of Screening

The overall indirect standardized mortality rate of 10.3 (95% CI, 9.4 – 11.3) represented a mortality risk that was more than 10-fold higher than that of the general population, after adjustment for sex and age.
The researchers call these findings “alarming,” suggesting that they “may reflect several past and current issues with current healthcare delivery systems in identifying and addressing OUD problems.”
“The general healthcare system has not been well studied with regard to substance abuse,” Dr Hser noted.
“Patients in this setting are much older at diagnosis than in publicly funded settings, and they have much higher morbidity and morbid conditions,” she said. “But general healthcare providers are not sufficiently screening for addictions, so it comes very late in the process for the person to receive appropriate interventions.
“Even when patients with OUD are identified, these clinicians may not have the resources to treat them, because general systems usually do not have addiction specialists on board,” she added.
The responsibility does not lie solely with individual practitioners.
“The timing is perfect, because the 21st Century Cures Act that former President Obama signed is now dispersed throughout the states to improve access to medication-assisted treatment. Policy makers and healthcare systems in each state need to start talking with each other and come up with a better plan to improve the infrastructure, train the physicians, and provide support when they need it,” she said.

More Training Needed

Commenting on the study for Medscape Medical News, Daniel G. Tobin MD, assistant professor of medicine, Yale University School of Medicine, and medical director of adult primary care, the Saint Rafael Campus, Yale–New Haven Hospital, described the study as “meaningful” but recommended caution when interpreting the findings.
“The study analyzed data from electronic medical records and identified people with opioid use disorder based on coding, which is a study limitation, because the coding had to be done correctly,” said Dr Tobin, who was not involved with the study.
“If clinicians did not include the diagnosis in the chart or did not code correctly, the number of opioid users might be underrepresented in the data,” he said, “leading to an overestimation of mortality rates in OUD in the general healthcare setting,” he explained.
Nevertheless, he said, “the study does show that having this diagnosis is associated with a high risk of mortality, and that the mortality is not necessarily due to overdose, which is the general conception of mortality from OUD.
“Since the patients in the study were identified roughly 5 years later than in addiction centers, these 5 additional years can lead to many health problems. I agree with the authors’ conclusion that the later the diagnosis is made, the more damage is done, so one interesting take-away is that we have to diagnose and treat OUD as soon as possible,” he said.
He agreed that more money, training, and infrastructure are necessary. “Not only do individual doctors need to take ownership, but there also has to be some infrastructure support so it becomes a routine part of primary care.”
Dr Hser added that clinicians in primary care settings can be an important force in shaping the nation’s effort to effectively address the opioid epidemic, but they need a lot of help. “They should get adequate training and get connected with an appropriate network that can help overcome many barriers that we are facing in treating addiction.”

Cheap and Available: The Growing Threat of Synthetic Cannabinoids

Synthetic Cannabinoids
Synthetic cannabinoids (sometimes referred to as “synthetic marijuana,” “spice,” or “K2”) are a family of man-made, psychoactive chemicals that are sprayed onto plant material, which is often smoked or ingested to achieve a “high.” Use of these products carries the potential for acute adverse health effects.

Historically, synthetic cannabinoid compounds were developed to study cannabinoid receptors, but in recent years these compounds have emerged as drugs of abuse. In 2005, synthetic cannabinoid products emerged in European countries before appearing in the United States in 2009.

Today, synthetic cannabinoid products are distributed worldwide under countless trade names and packaged in colorful wrappers designed to appeal to teens, young adults, and first-time drug users. These products are sold under a variety of names and are sometimes sold in convenience stores and other retail outlets as incense or natural herbal products. The lack of oversight over the manufacture and labeling of synthetic cannabinoid products means that users do not actually know the kind of synthetic cannabinoids in the product and the amount to which they are being exposed.[1]

Although these products are often labeled as “not for human consumption” and marketed as “incense,” health professionals and legal authorities are keenly aware that people use these products for their psychoactive effects. Despite federal and state regulations to prohibit synthetic cannabinoid sale and distribution, reports of harmful effects are increasing. All states now have at least one law on the books, but these laws vary widely. This is not only a problem in the United States but around the world.

Signs and Symptoms of Synthetic Cannabinoid Exposure
In April 2015, the CDC’s Health Studies Branch worked with the Mississippi Department of Health during an outbreak of 724 cases of illness and death associated with synthetic cannabinoid use in the state.[2] We used clinician-suspected or patient-reported synthetic cannabinoid use, plus the presence of symptoms, as our case criteria, so it is possible that 724 cases are an underrepresentation. Synthetic cannabinoids are metabolized quickly, so not detecting them (even if testing is available) does not rule out exposure. Of course, this method may also have included people whom providers suspected of having used synthetic cannabinoids but who did not actually use the drug.

As part of that investigation, CDC analyzed the medical records of 119 patients who presented to the University of Mississippi Medical Center (UMMC) for illness related to synthetic cannabinoid use. Like other instances of synthetic cannabinoid intoxication, these patients had nonspecific symptoms, but the most frequently reported signs and symptoms were:



Aggressive or violent behavior;


Alternating agitation and aggression; and

Depressed mental status (such as somnolence or unresponsiveness).

As seen in previous outbreaks of adverse events linked to synthetic cannabinoid use, most users were young men, with a median age of 29 years. Statewide, from April 2 to May 3, 2015, nine deaths associated with synthetic cannabinoid use were reported to the state’s poison center, although the number of people who died could be higher due to underreporting. At the UMMC, patients who were older and had a history of psychiatric illness or substance abuse were more likely to die or be admitted to the intensive care unit. The median age of those who died was 32 years.

Synthetic cannabinoids are not detected on routine urine or serum drug screens, and most hospital laboratories do not have the capability to test for synthetic cannabinoids. Testing at referral laboratories is available; however, clinicians should be aware that test panels are limited in scope and will not detect all of the synthetic cannabinoids currently being used. In the Mississippi investigation, patient samples were sent to a research laboratory that specializes in detecting novel synthetic cannabinoids. The lab detected MAB-CHMINACA, a chemical compound that had recently entered the market.

An Emerging Public Health Threat
The use of synthetic cannabinoids may indicate an emerging public health threat due to:

Apparent rapid increase in use;

Variable and unpredictable toxicity of new compounds on the market; and

Difficulty in enforcing legal bans due to fast-changing types and mixtures of drug contents.

Here are some key points to keep in mind about synthetic cannabinoid use:

Synthetic cannabinoids are not marijuana and are not safe.

They are dangerous and can cause severe illness and even death.

Easy access and a misperception that these products are legal and relatively safe are contributing to their popularity.

Although the legality of these products may vary by state, many specific synthetic cannabinoids have been banned at the federal level. Consider synthetic cannabinoid use in patients with symptoms of drug intoxication with negative drug screens. Symptoms are generally short-lived, and most patients recover rapidly.

If you suspect that a severely ill patient may have used synthetic cannabinoids, check for rhabdomyolysis and kidney injury, and monitor for seizures and cardiac arrhythmias. Care is symptomatic and supportive. Low-dose benzodiazepines have been used successfully to treat agitation.

And finally, if you see severe illness or clusters of illness following patients’ use of these products, notify your local poison center or health department.

Medical Community Needs Better Understanding of Power of AA

The medical-community-needs-better-understanding-of-power-of-alcoholics-anonymous.Many doctors, even those who specialize in addiction treatment, do not have a good understanding of Alcoholics Anonymous (AA) and its benefits for people struggling to give up drinking, says Marc Galanter, M.D., Founding Director of the Division of Alcoholism and Drug Abuse at NYU Langone Medical Center.

“Doctors don’t necessarily know about the 12 Steps and how going to AA can be useful to patients,” says Dr. Galanter, a former president of the American Society of Addiction Medicine and the American Academy of Addiction Psychiatry. “They need to know how valuable it can be for people to go to meetings and meet people who have achieved abstinence, and learn how the program helped them.”

Of the more than 3,400 addiction treatment programs in the United States, many use the AA model, but half don’t have any relationship with a physician, Dr. Galanter notes. “It’s essential to bridge the gap between the medical and rehab communities,” he says.

Although it began in the 1930s, AA still has an important place in addiction treatment today, in an era when people tend to look to medications as the answer to solving everything, Dr. Galanter says.

“I can tell them as their doctor that they need to stop drinking, but if they go to AA meetings and meet other people with the same problem, it can mean more to them in terms of recovery,” says Dr. Galanter, author of What is Alcoholics Anonymous? A Path from Addiction to Recovery (Oxford).

Last year, Dr. Galanter published a study that looked at the effect of prayer on the brains of 20 long-term AA members, as measured by MRI. The twelfth step in AA involves “spiritual awakening,” an important part of the AA experience that can be interpreted in different ways. For many people spiritual awakening is related to prayer and meditation, which helps them stay sober, Dr. Galanter explains. “We wanted to see if there is a physiologic basis for prayer and meditation having a role in keeping people sober,” he said.

The participants were placed in an MRI scanner and then shown either pictures of alcoholic drinks or people drinking. The pictures were presented twice: first after asking the participant to read neutral material from a newspaper, and again after the participant recited an AA prayer promoting abstinence from alcohol.

Dr. Galanter found members who recited an AA prayer after viewing drinking-related images reported less craving for alcohol after praying than after reading a newspaper. The reduced cravings in people who prayed corresponded to increased activity in brain regions responsible for attention and emotion.

He said the findings suggest that AA has a physiologic effect on the brain, and doesn’t just lead to a general change in attitude about drinking. “A lot of people don’t appreciate that AA isn’t just a sort of club. It actually changes how people think and how their brains work,” Dr. Galanter said.

Alcohol Dependence Linked to Insufficient Enzyme ?

Alcoholism, or alcohol dependence, whichever you prefer, is a condition characterized by a physical and/or mental addiction to alcohol. Persons with this addiction continue to drink frequently, despite the negative effects associated with their behavior, health, and life outcomes.

Expert insight has pointed to impaired function in alcoholics in the the brain’s frontal lobes. This impairment is thought to lead to a decrease in impulse control when it comes to drinking. However, the exact molecular mechanism has remained somewhat of a mystery.

Recently,however, a study reviewed in the Molecular Psychiatry journal revealed that a specific enzyme is lacking in the brain of alcohol-dependent rats. The study was led by professor Markus Heilig of Linkoping University (Sweden). The enzyme in question is PRDM2, a member of the histone/protein methyltransferase family.

Past studies on the enzyme have mostly focused on its relationship to cancer. However, in this study researchers found additional functions in the brain. PRDM2 regulates the expression of genes necessary to transmit data between neurons.

Heilig’s team of researchers took a close look at alcohol-dependent rats and discovered that a history of alcoholism consistently affected the producton of PRDM2. This decrease ultimately disrupts impulse control.

In additional experiments, the researchers intentionally suppressed PRDM2 expression in non-alcohol-dependent rats, and discovered that their impulse control was disrupted as well, thus resulted in a signficant uptick in alcohol consumption.


“PRDM2 controls the expression of several genes that are necessary for effective signalling between nerve cells. When too little enzyme is produced, no effective signals are sent from the cells that are supposed to stop the impulse.”

He continues to add:

“We see how a single molecular manipulation gives rise to important characteristics of an addictive illness. Now that we’re beginning to understand what’s happening, we hope we’ll also be able to intervene. Over the long term, we want to contribute to developing effective medicines, but over the short term the important thing, perhaps, is to do away with the stigma of alcoholism.”

This new finding is exciting in the field of addiction medicine, and reveals a promising new approach to treating alcohol dependence.

Increases in Drug and Opioid Overdose Deaths — United States, 2000–2014

The United States is experiencing an epidemic of drug overdose (poisoning) deaths. Since 2000, the rate of deaths from drug overdoses has increased 137%, including a 200% increase in the rate of overdose deaths involving opioids (opioid pain relievers and heroin). CDC analyzed recent multiple cause-of-death mortality data to examine current trends and characteristics of drug overdose deaths, including the types of opioids associated with drug overdose deaths. During 2014, a total of 47,055 drug overdose deaths occurred in the United States, representing a 1-year increase of 6.5%, from 13.8 per 100,000 persons in 2013 to 14.7 per 100,000 persons in 2014. The rate of drug overdose deaths increased significantly for both sexes, persons aged 25–44 years and ≥55 years, non-Hispanic whites and non-Hispanic blacks, and in the Northeastern, Midwestern, and Southern regions of the United States. Rates of opioid overdose deaths also increased significantly, from 7.9 per 100,000 in 2013 to 9.0 per 100,000 in 2014, a 14% increase. Historically, CDC has programmatically characterized all opioid pain reliever deaths (natural and semisynthetic opioids, methadone, and other synthetic opioids) as “prescription” opioid overdoses (1). Between 2013 and 2014, the age-adjusted rate of death involving methadone remained unchanged; however, the age-adjusted rate of death involving natural and semisynthetic opioid pain relievers, heroin, and synthetic opioids, other than methadone (e.g., fentanyl) increased 9%, 26%, and 80%, respectively. The sharp increase in deaths involving synthetic opioids, other than methadone, in 2014 coincided with law enforcement reports of increased availability of illicitly manufactured fentanyl, a synthetic opioid; however, illicitly manufactured fentanyl cannot be distinguished from prescription fentanyl in death certificate data. These findings indicate that the opioid overdose epidemic is worsening. There is a need for continued action to prevent opioid abuse, dependence, and death, improve treatment capacity for opioid use disorders, and reduce the supply of illicit opioids, particularly heroin and illicit fentanyl.

During 2014, 47,055 drug overdose deaths occurred in the United States. Since 2000, the age-adjusted drug overdose death rate has more than doubled, from 6.2 per 100,000 persons in 2000 to 14.7 per 100,000 in 2014 (Figure 1). The overall number and rate of drug overdose deaths increased significantly from 2013 to 2014, with an additional 3,073 deaths occurring in 2014 (Table), resulting in a 6.5% increase in the age-adjusted rate. From 2013 to 2014, statistically significant increases in drug overdose death rates were seen for both males and females, persons aged 25–34 years, 35–44 years, 55–64 years, and ≥65 years; non-Hispanic whites and non-Hispanic blacks; and residents in the Northeast, Midwest and South Census Regions (Table). In 2014, the five states with the highest rates of drug overdose deaths were West Virginia (35.5 deaths per 100,000), New Mexico (27.3), New Hampshire (26.2), Kentucky (24.7) and Ohio (24.6).† States with statistically significant increases in the rate of drug overdose deaths from 2013 to 2014 included Alabama, Georgia, Illinois, Indiana, Maine, Maryland, Massachusetts, Michigan, New Hampshire, New Mexico, North Dakota, Ohio, Pennsylvania, and Virginia.

In 2014, 61% (28,647, data not shown) of drug overdose deaths involved some type of opioid, including heroin. The age-adjusted rate of drug overdose deaths involving opioids increased significantly from 2000 to 2014, increasing 14% from 2013 (7.9 per 100,000) to 2014 (9.0) (Figure 1). From 2013 to 2014, the largest increase in the rate of drug overdose deaths involved synthetic opioids, other than methadone (e.g., fentanyl and tramadol), which nearly doubled from 1.0 per 100,000 to 1.8 per 100,000 (Figure 2). Heroin overdose death rates increased by 26% from 2013 to 2014 and have more than tripled since 2010, from 1.0 per 100,000 in 2010 to 3.4 per 100,000 in 2014 (Figure 2). In 2014, the rate of drug overdose deaths involving natural and semisynthetic opioids (e.g., morphine, oxycodone, and hydrocodone), 3.8 per 100,000, was the highest among opioid overdose deaths, and increased 9% from 3.5 per 100,000 in 2013. The rate of drug overdose deaths involving methadone, a synthetic opioid classified separately from other synthetic opioids, was similar in 2013 and 2014.

More persons died from drug overdoses in the United States in 2014 than during any previous year on record. From 2000 to 2014 nearly half a million persons in the United States have died from drug overdoses. In 2014, there were approximately one and a half times more drug overdose deaths in the United States than deaths from motor vehicle crashes Opioids, primarily prescription pain relievers and heroin, are the main drugs associated with overdose deaths. In 2014, opioids were involved in 28,647 deaths, or 61% of all drug overdose deaths; the rate of opioid overdoses has tripled since 2000. The 2014 data demonstrate that the United States’ opioid overdose epidemic includes two distinct but interrelated trends: a 15-year increase in overdose deaths involving prescription opioid pain relievers and a recent surge in illicit opioid overdose deaths, driven largely by heroin.

Drug overdose deaths involving heroin continued to climb sharply, with heroin overdoses more than tripling in 4 years. This increase mirrors large increases in heroin use across the country and has been shown to be closely tied to opioid pain reliever misuse and dependence. Past misuse of prescription opioids is the strongest risk factor for heroin initiation and use, specifically among persons who report past-year dependence or abuse. The increased availability of heroin, combined with its relatively low price (compared with diverted prescription opioids) and high purity appear to be major drivers of the upward trend in heroin use and overdose.