Objectives. To examine trends in overdose deaths by intent and drug category to better understand the recent decrease in overdose suicides amid the overdose epidemic. Methods. We examined trends in rates of overdose deaths by intent (unintentional, suicide, or undetermined) across 9 drug categories from 1999 to 2022 using US National Vital Statistics System mortality data. Results. Unintentional overdoses involving synthetic opioids, polydrug toxicity involving synthetic opioids, psychostimulants, and cocaine increased exponentially with annual percentage changes ranging from 15.0% to 104.9% during 2010 to 2022. The death rates also increased for suicides involving these drugs, especially for psychostimulants (annual percentage change = 12.9% for 2010-2022; P < .001). However, these drugs accounted for relatively small percentages of overdose suicides. The leading drug categories among suicides were antidepressants, prescription opioids, and benzodiazepines, though these deaths have decreased or leveled off in recent years. Conclusions. Different drugs commonly involved in suicides and unintentional overdoses may contribute to their divergent trends. Public Health Implications. Amid the overdose epidemic, safe storage of medications remains a crucial strategy to prevent overdose suicides. The large increases in suicides involving psychostimulants warrant monitoring. (Am J Public Health. Published online ahead of print August 8, 2024:e1-e5. https://doi.org/10.2105/AJPH.2024.307745).

Preliminary reports indicate that more than 109,000 drug overdose deaths occurred in the United States in 2022; nearly 70% of these involved synthetic opioids other than methadone, primarily illegally manufactured fentanyl and fentanyl analogs (IMFs). Data from the western United States suggested a transition from injecting heroin to smoking IMFs. CDC analyzed data from the State Unintentional Drug Overdose Reporting System to describe trends in routes of drug use in 27 states and the District of Columbia among overdose deaths that occurred during January 2020-December 2022, overall and by region and drugs detected. From January-June 2020 to July-December 2022, the percentage of overdose deaths with evidence of injection decreased 29.1%, from 22.7% to 16.1%, whereas the percentage with evidence of smoking increased 73.7%, from 13.3% to 23.1%. The number of deaths with evidence of smoking increased 109.1%, from 2,794 to 5,843, and by 2022, smoking was the most commonly documented route of use in overdose deaths. Trends were similar in all U.S. regions. Among deaths with only IMFs detected, the percentage with evidence of injection decreased 41.6%, from 20.9% during January-June 2020 to 12.2% during July-December 2022, whereas the percentage with evidence of smoking increased 78.9%, from 10.9% to 19.5%. Similar trends were observed among deaths with both IMFs and stimulants detected. Strengthening public health and harm reduction services to address overdose risk related to diverse routes of drug use, including smoking and other noninjection routes, might reduce drug overdose deaths.

Using data from CDC's State Unintentional Drug Overdose Reporting System, this report describes trends in overdose deaths with evidence of counterfeit pill use during July 2019-December 2021 in 29 states and the District of Columbia (DC) and characteristics of deaths with and without evidence of counterfeit pill use during 2021 in 34 states and DC. The quarterly percentage of deaths with evidence of counterfeit pill use more than doubled from 2.0% during July-September 2019 to 4.7% during October-December 2021, and more than tripled in western jurisdictions (from 4.7% to 14.7%). Illicitly manufactured fentanyls were the only drugs involved (i.e., caused death) in 41.4% of deaths with evidence of counterfeit pill use and 19.5% of deaths without evidence. Decedents with evidence of counterfeit pill use, compared with those without evidence, were younger (57.1% versus 28.1% were aged <35 years), more often Hispanic or Latino (18.7% versus 9.4%), and more frequently had a history of prescription drug misuse (27.0% versus 9.4%). Smoking was the most common noningestion drug use route among deaths with evidence of counterfeit pill use (39.5%). Overdose prevention messaging that highlights the dangers of pills obtained illicitly or without a prescription (because they might be counterfeit), encourages drug product testing by persons using drugs, and is tailored to persons most at risk (e.g., younger persons) could help prevent overdose deaths.

A non-immune library of human single chain fragment variable (scFv) antibodies displayed on Saccharomyces cerevisiae was screened for binding to the Clostridium botulinum neurotoxin serotype A binding domain [BoNT/A (H(c) )] with the goal of identifying scFv to novel epitopes. To do this, an antibody-mediated labeling strategy was used in which antigen-binding yeast clones were selected after labeling with previously characterized monoclonal antibodies (MAbs) specific to the H(c) . Twenty unique scFv clones were isolated that bound H(c) . Of these, 3 also bound to full-length BoNT/A toxin complex with affinities ranging from 5 to 48 nM. Epitope binning showed that the three unique clones recognized at least two epitopes distinct from one another as well as from the detection MAbs. After production in E. coli, scFv were coupled to magnetic particles and tested for their ability to capture BoNT/A holotoxin using an Endopep-MS assay. In this assay, toxin captured by scFv coated magnetic particles was detected by incubation of the complex with a peptide containing a BoNT/A-specific cleavage sequence. Mass spectrometry was used to detect the ratio of intact peptide to cleavage products as evidence for toxin capture. When tested individually, each of the scFv showed a weak positive Endopep-MS result. However, when the particles were coated with all three scFv simultaneously, they exhibited significantly higher Endopep-MS activity, consistent with synergistic binding. These results demonstrate novel approaches toward the isolation and characterization of scFv antibodies specific to unlabeled antigens. They also provide evidence that distinct scFv antibodies can work synergistically to increase the efficiency of antigen capture onto a solid support. Biotechnol. Bioeng. (c) 2011 Wiley Periodicals, Inc.