Sherry McKee, PhD, DADR Associate Editor

“Keyes, Katherine M., Caroline Rutherford, Ava Hamilton, Joshua A. Barocas, Kitty H. Gelberg, Peter P. Mueller, Daniel J. Feaster, Nabila El-Bassel, and Magdalena Cerdá. “What Is the Prevalence of and Trend in Opioid Use Disorder in the United States from 2010 to 2019? Using Multiplier Approaches to Estimate Prevalence for an Unknown Population Size.” Drug and Alcohol Dependence Reports 3 (June 1, 2022): 100052.”

Author Summary: The true prevalence of opioid use disorder (OUD) in the United States (US) is unknown. Survey and administrative data sources provide some estimates, but their generalizability is limited and biases abound. We used classical epidemiological techniques to provide new estimates of the number of people with OUD in the United States. First, we estimated OUD in the National Survey on Drug Use and Health (NSDUH), and based on existing capture-recapture studies, multiplied prevalence by 4.5x. Second, we estimated the probability of drug poisoning death among people with OUD (meta-analysis indicates 0.52/100,000), and divided the number of drug poisoning deaths in the US by this probability. Estimates were weighted to account for increase in drug-related mortality in recent years due to fentanyl. We estimate that approximately 6.7 to 7.6 million adults in the US are currently living with OUD. These estimates underscore the unmet need for capacity building around services for individuals with OUD that are urgently needed.

Editor justification: Rates of opiate use disorder and risk of overdose continue to be a significant public health concern, particularly as the US drug supply has become increasingly dangerous with the proliferation of fentanyl. The paper by Dr. Katherine Keyes and colleagues provides critical information regarding the current prevalence for opioid use disorder, necessary to inform national policy.

Teri Franklin, PhD, DADR EiC

“Carter, Amir, Cristina Bares, Lisha Lin, Beth Glover Reed, Marjorie Bowden, Robert A. Zucker, Wei Zhao, Jennifer A. Smith, and Jill B. Becker. “Sex-Specific and Generational Effects of Alcohol and Tobacco Use on Epigenetic Age Acceleration in the Michigan Longitudinal Study.” Drug and Alcohol Dependence Reports 4 (September 1, 2022): 100077.”

Study Summary: Excessive alcohol and tobacco use are risk factors for poor health in both men and women, but use patterns and relationships with diseases and mortality differ between sexes. One possible index of the effects of substance use on overall health is epigenetic aging as assessed by DNA methylation profiles. This study assessed the sex-specific effects of individuals’ alcohol and tobacco use, as well as paternal alcohol and paternal/maternal tobacco use, on their children’s cellular aging as measured by four different measures of epigenetic age acceleration. We found that current or former tobacco smoking were associated with epigenetic age acceleration with sex-specific effects. Additionally for females drinking alcohol was associated with epigenetic age acceleration. When looking at the long-term effects of alcohol use on offspring, paternal heavy alcohol use when children were 12 or younger was associated with epigenetic age acceleration when the children were adults. Thus, there are sex-specific effects of alcohol and tobacco use, as well as paternal heavy alcohol use, on epigenetic age acceleration.

Editor justification: This study brings to light important knowledge regarding the effects of alcohol and tobacco use on epigenetic age acceleration, and makes me hungry for more.  In particular, as shown by the authors, paternal heavy alcohol use was associated with a 4 and ½ year increased epigenetic age acceleration among offspring (as adults) while heavy alcohol use in and of itself, does not directly influence the epigenome of the offspring.  The authors point out that future studies are warranted to understand mediation factors (i.e., psychosocial stressors).

Teresa Franklin, PhD, DADR EiC

 “Reed, Megan K., Nicholas S. Imperato, Jeanette M. Bowles, Venise J. Salcedo, Amanda Guth, and Kristin L. Rising. “Perspectives of People in Philadelphia Who Use Fentanyl/Heroin Adulterated with the Animal Tranquilizer Xylazine; Making a Case for Xylazine Test Strips.” Drug and Alcohol Dependence Reports 4 (September 1, 2022): 100074.”

Article Summary: Xylazine, a veterinary tranquilizer, is often present in heroin/fentanyl in Philadelphia and is increasingly found elsewhere. To explore how people who use heroin/fentanyl in Philadelphia feel about xylazine adulteration, we analyzed interviews with people who use drugs during interviews about their fentanyl test strip practices. The topic of xylazine arose in 13 out of 29 interviews. Among these 13, participants believed they were frequently exposed to xylazine when intending to use solely heroin/fentanyl and unanimously voiced disliking the presence of xylazine in their drugs. In addition to disliking the feeling of the xylazine and heroin/fentanyl combination, they described long periods of sedation accompanied with memory loss. Several voiced safety concerns related to heavy sedation after use and noted complications with treating withdrawal from xylazine and an opioid. Participants indicated a desire to obtain and use xylazine test strips, the technology for which did not exist at the time of interviews. Many indicated they would prefer those test strips over fentanyl test strips to avoid xylazine exposure. A xylazine test strip may have the potential to positively impact drug use in a similar manner to fentanyl test strips, especially if accompanied with risk reduction communication.

Editor justification: It always piques my interest when findings oppose what we generally consider to be truth. This is an eye-opener and important information as the problem of xylazine-adulterated heroin is sweeping our nation.

Walter Roberts, PhD, Social Media Editor

“Rudolph, Kara E., Matthew Russell, Sean X. Luo, John Rotrosen, and Edward V. Nunes. “Under-Representation of Key Demographic Groups in Opioid Use Disorder Trials.” Drug and Alcohol Dependence Reports 4 (September 1, 2022): 100084.”

Study Summary: We identified interpretable, multidimensional subgroups who were prescribed medication for opioid use disorder (MOUD) in substance use treatment programs in the US (using TEDS-A data, N=740,015) but who were not represented or were under-represented by clinical trial participants (using 3 harmonized comparative effectiveness trials for MOUD that are part of the NIDA CTN, N=2,199).  Excluding pregnancy as a subgroup-defining characteristic, 8.3% of those treated with MOUD in TEDS-A were not represented at all in any of the clinical trials, and 44% were underrepresented. Under-represented subgroups were dominated by non-Hispanic Black individuals who were older, never married, with lower-levels of education, and who reported no past-30-day use of amphetamines, benzodiazepines, nor cannabis. In general, older age was a common feature of non-represented and under-represented subgroups despite age not being a reason for exclusion in any of the trials. This is an increasingly relevant subpopulation, as the number of older adults entering MOUD treatment tripled 2007-2017, and the number of older adults with opioid-related emergency department visits quadrupled over the same period. By characterizing subgroups who initiate MOUD treatment but who are under-represented in trials, we hope to support better accountability for representation and inform targeting for future trial recruitment.

Editor’s Rationale: I thought the authors of this study did a nice job of quantifying a potential source of health outcome inequality in addiction treatment. It is important that participants in clinical trials reflect the characteristics of patients who will ultimately receive the treatment. In the era of personalized medicine, it is becoming increasingly clear that these types of demographic characteristics can impact how well a treatment works. This paper shows that a course adjustment is needed to improve consilience between participants in clinical trials for addiction treatments and people who will actually receive those treatments in the clinic. I also appreciated the authors’ clever use of multiple preexisting data sources to draw these comparisons.