LSU chemists unlock the key to improving biofuel and biomaterial production

Peer-Reviewed Publication

LOUISIANA STATE UNIVERSITY

 

IMAGE: PLANT BIOMASS CONSTRUCTED BY CARBOHYDRATE AND AROMATIC COMPONENTS. view more 

CREDIT: LSU

As the world searches for and demands more sustainable sources of energy and materials, plant biomass may provide the solution by serving as a renewable resource for biomaterials and biofuel production. However, until now, the complex physical and chemical interactions in plant biomass have been a challenge in post-harvest processing. 

In a new study published today in Nature Communications, LSU Department of Chemistry Associate Professor Tuo Wang and his research team reveal how carbohydrates interact with the aromatic polymer, lignin, to form plant biomass. This new information can help advance the development of better technology to use biomass for energy and materials.  

The Wang research team examined the nanoscale assembly of lignocellulosic components in multiple plant species, including grasses and hardwood and softwood species. The grasses contain many food crops, such as maize, and are the primary feedstock for biofuel production in the U.S. Woody plants, often used for building construction materials, have become promising candidates for the next generation of biofuel to reduce the dependence on food crops. 

The team used their expertise in solid-state nuclear magnetic resonance spectroscopy to compare the nanoscale organization of the lignin-carbohydrate interfaces across the three plant species and reveal how the structures of biopolymers affect their association with other cell wall components.  

“We discovered that the hemicellulose xylan uses its flat structure to bind cellulose microfibrils and primarily relies on its non-flat structure to associate with lignin nanodomains,” Wang said. “However, in the tightly packed woody materials, cellulose is also forced to serve as a secondary interactor with lignin.” 

The newly discovered, high-resolution information on the organization of the lignin-carbohydrate interfaces has revised the research of plant biomaterials. Through the spectroscopy method, samples being studied were kept in their native status, without chemical perturbation. Results unveiled structural differences underlying the cell wall construction among the different plants. 

The research was conducted by a team comprised of LSU graduate students Alex Kirui and Wancheng Zhao as well as postdoctoral researchers Fabien Deligey and Xue Kang from the Wang research group; Frederic Mentink-Vigier, an expert in Dynamic Nuclear Polarization technique at the National High Magnetic Field Laboratory (Tallahassee, Fla.) who collaborated on the project; and Hui Yang at the Pennsylvania State University, who offered extensive modeling expertise.

This methodology enables future opportunities for looking at complex biomolecules in different plants and engineered mutants, which will assist the development of better technology for the production of biorenewable energy and biomaterials. 

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JOURNAL

Nature Communications

DOI

10.1038/s41467-022-28165-3 

METHOD OF RESEARCH

Imaging analysis

SUBJECT OF RESEARCH

Cells

ARTICLE TITLE

Carbohydrate-Aromatic Interface and Molecular Architecture of Lignocellulose

ARTICLE PUBLICATION DATE

27-Jan-2022

Leafy greens first dished up 3,500 years ago

Archaeologists and archaeobotanists from Goethe University reconstruct the roots of West African cuisine.

Peer-Reviewed Publication

GOETHE UNIVERSITY FRANKFURT

 

IMAGE: EXCAVATION OF A NOK VESSEL AT THE IFANA 3 SITE. view more 

CREDIT: PETER BREUNIG

FRANKFURT. Over 450 prehistoric pots were examined, 66 of them contained traces of lipids, that is, substances insoluble in water. On behalf of the Nok research team at Goethe University, chemists from the University of Bristol extracted lipid profiles, with the aim of revealing which plants had been used. The results have now been published in “Archaeological and Anthropological Sciences”: over a third of the 66 lipid profiles displayed very distinctive and complex distributions – indicating that different plant species and parts had been processed.

Today, leafy vegetables, for example the cooked leaves of trees such as the baobab (Adansonia digitata) or of the shrubby – nomen est omen – bitter leaf (Vernonia amygdalina), accompany many West African dishes. These leafy sauces are enhanced with spices and vegetables as well as fish or meat, and complement the starchy staples of the main dish, such as pounded yam in the southern part of West Africa or thick porridge made from pearl millet in the drier savannahs in the north. By combining their expertise, archaeology and archaeobotany researchers at Goethe University and chemical scientists from the University of Bristol have corroborated that the origins of such West African dishes date back 3,500 years.

The studies are part of a project funded by the German Research Foundation, which was headed by Professor Peter Breunig and Professor Katharina Neumann and ended in December 2021. For over twelve years, archaeologists and archaeobotanists from Goethe University studied the Nok culture of Central Nigeria, which is known for its large terracotta figures and early iron production in West Africa in the first millennium BC – although the roots of the Nok culture in fact stretch back to the middle of the second millennium. Research focused above all on the social context in which the sculptures were created, that is, including eating habits and economy. Using carbonised plant remains from Central Nigeria, it was possible to prove that the Nok people grew pearl millet. But whether they also used starchy plants, such as yam, and which dishes they prepared from the pearl millet had so far been a mystery.

“Carbonised plant remains such as seeds and nutshells preserved in archaeological sediments reflect only part of what people ate back then,” explains Professor Katharina Neumann. They hoped, she says, that the chemical analyses would deliver additional insights into food preparation. And indeed, with the help of lipid biomarkers and analyses of stable isotopes, the researchers from Bristol were able to show, by examining over 450 prehistoric pots, that the Nok people included different plant species in their diet.

Dr Julie Dunne from the University of Bristol’s Organic Geochemistry Unit says: “These unusual and highly complex plant lipid profiles are the most varied seen (globally) in archaeological pottery to date.” There appear to be at least seven different lipid profiles in the vessels, which clearly indicates the processing of various plant species and plant organs in these vessels, possibly including underground storage organs (tubers) such as yam.

Since the beginning of the project, the archaeobotanists have sought evidence for the early use of yam. After all, the Nok region is situated in the “yam belt” of West Africa, that is, the area of the continent in which yam is nowadays grown. Carbonised remains are of no further help here because the soft flesh of the tubers is often poorly preserved and mostly non-specific as well. The chemical analyses indicate that – apart from leaves and other as yet unidentified vegetables – the Nok people also cooked plant tissue containing suberin. This substance is found in the periderm of both overground and underground plant organs – possibly a first indication that yam was used, if not the unequivocal proof hoped for.

Through the archaeobotanical study of carbonised remains, pearl millet (Cenchrus americanus) and cowpea (Vigna unguiculata), the oily fruits of the African elemi (Canarium schweinfurthii) and a fruit known as African peach (Nauclea latifolia), which due to its high number of seeds is reminiscent of a large fig, were already known. Molecular analysis now rounds off the picture of food preparation at the sites of the Nok culture. Archaeobotanist Dr Alexa Höhn from Goethe University explains: “The visible and invisible remains of food preparation in the archaeological sediment and the pottery give us a much more complete picture of past eating habits. This new evidence suggests a significant time depth in West African cuisine.”  

Publication: Julie Dunne, Alexa Höhn, Katharina Neumann, Gabriele Franke, Peter Breunig, Louis Champion, Toby Gillard, Caitlin Walton‑Doyle, Richard P. Evershed Making the invisible visible: tracing the origins of plants in West African cuisine through archaeobotanical and organic residue analysis. Archaeological and Anthropological Sciences https://doi.org/10.1007/s12520-021-01476-0

Picture download: https://www.uni-frankfurt.de/111577824

Caption: Excavation of a Nok vessel at the Ifana 3 site. (Photo: Peter Breunig)

Further information
Dr Alexa Höhn

African Archaeology and Archaeobotany
Telephone +49 (0)69-798-32089

Email a.hoehn@em.uni-frankfurt.de 

 

 

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JOURNAL

Archaeological and Anthropological Sciences

DOI

10.1007/s12520-021-01476-0 

METHOD OF RESEARCH

Imaging analysis

SUBJECT OF RESEARCH

Not applicable

ARTICLE TITLE

Making the invisible visible: tracing the origins of plants in West African cuisine through archaeobotanical and organic residue analysis.

ARTICLE PUBLICATION DATE

14-Jan-2022

Caribou and muskoxen buffer climate impacts for rare plants

Large herbivores help rare species persist in a warming arctic

Peer-Reviewed Publication

UNIVERSITY OF CALIFORNIA - DAVIS

 

IMAGE: ARCTIC WINTERGREEN, A VERY RARE SPECIES, GROWS AMONG BIRCH AND WILLOW SHRUBS NEAR KANGERLUSSUAQ, GREENLAND. view more 

CREDIT: ERIC POST,UC DAVIS

Being common is rather unusual. It’s far more common for a species to be rare, spending its existence in small densities throughout its range. How such rare species persist, particularly in an environment undergoing rapid climate change, inspired a 15-year study in arctic Greenland from the University of California, Davis.

The study, published in the journal Scientific Reports, found that caribou and muskoxen helped mitigate the effects of climate change on rare arctic plants, lichens and mushrooms at the study site.

The authors suggest that by constraining the abundance of the two most common plant species — dwarf birch and gray willow — large herbivores may allow other, less common species to persist rather than be shaded or outcompeted for nutrients by the woody shrub’s canopy, or suppressed by leaf litter and cooler soils. 

“This is more evidence that conserving large herbivores is really important to maintaining the compositional integrity of species-poor systems like the arctic tundra,” said lead author Eric Post, director of the UC Davis Polar Forum and a professor in the UC Davis Department of Wildlife, Fish and Conservation Biology.

A rare find

Recent studies have shown that when rare species risk extinction due to climate change, it is often due to effects on local habitat. Greater numbers of rare species persist in regions with a stable climate than in regions with a changing climate. This study shows that species interactions can also be important in maintaining rare species under climate change. 

For this study, the scientists investigated the effects of warming and the presence or exclusion of large herbivores — caribou and muskoxen — on 14 species of tundra plants, lichens and mushrooms, three of which were common and 11 of which were rare in the study site, looking for trends in commonness or rarity.

They found no predictable pattern related to warming. It made some plants more common and others rarer.

But the presence or absence of caribou and muskoxen made a clear difference. Excluding large herbivores from study plots made seven species —  five of them rare — less common, and two species more common, and led to common species dominating study plots.

A herd of caribou in arctic Greenland. Caribou at this study site have been declining over the past several years, while muskoxen have been increasing. Such herbivores help rare plant species persist in a rapidly changing climate.

CREDIT

Eric Post, UC Davis

Herbivores’ critical role in sustaining biodiversity

Caribou at the study site near Kangerlussuaq, Greenland, dropped from several hundred animals in the early 2000s, at the beginning of this study, to a little over 100 by the study’s end. Muskoxen increased from about 20 to 50 over the same period, according to a March 2021 study Post co-authored. Meanwhile, the arctic tundra is warming two to three times as fast as the rest of the planet. 

“The conservation of large herbivores will serve a critical role in preserving arctic tundra as it warms,” Post said. “If caribou or muskoxen eventually go locally extinct from parts of the Arctic, or even fall to severely low abundance, what we’ll likely see in response to warming is a tundra increasingly dominated by a few common species, like shrubs.”

Post said that rare species contribute vitally to biodiversity, ecosystem function and resilience, largely because there are so many of them compared to common species.

“Creative solutions to sustaining tundra biodiversity, such as maintaining intact populations of large herbivores, will help buffer this sensitive biome against climate change,” Post said.

This study’s co-authors include Christian Pedersen of the Norwegian Institute of Bioeconomy Research, and David A. Watts of Alaska Department of Health and Social Services.

The study was funded by the National Science Foundation, National Geographic Committee for Research and Exploration, and Penn State University.

A muskox stands amid Greenland's arctic tundra. Large herbivores have been found to play a critical role in maintaining tundra biodiversity.

CREDIT

Eric Post, UC Davis

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JOURNAL

Scientific Reports

DOI

10.1038/s41598-022-05388-4 

METHOD OF RESEARCH

Experimental study

SUBJECT OF RESEARCH

Not applicable

ARTICLE TITLE

Large herbivores facilitate the persistence of rare taxa under tundra warming

ARTICLE PUBLICATION DATE

25-Jan-2022

Arctic harebell, a rare wildflower species, grows at a long-term study site near Kangerlussuaq, Greenland.

CREDIT

Eric Post, UC Davis

 Tackling PPE waste: Engineers propose sustainable recycling method

Peer-Reviewed Publication

CORNELL UNIVERSIT

ITHACA, N.Y. – Under the intensity of a prolonged pandemic, the world finds an ever-growing and seemingly never-ending waste stream of used surgical masks, plastic face shields, and medical gloves and gowns. Cornell University engineers now offer a solution to sustainably reroute the discarded material.

A medium-temperature reaction called pyrolysis can reduce the plasticized medical-protection garb back into an original form – such as chemicals and petroleum – and then recycle it, perhaps into fuels, according to a new study.

The method involves no incineration or landfill use.

Xiang Zhao, a doctoral student, working with his advisor Fengqi You, professor in energy systems engineering, published the proposed technology framework in the journal Renewable and Sustainable Energy Reviews.

Their framework – first focusing on New York state – proposes collecting waste PPE from hospitals and medical centers, and then sending it to pre-processing and decontamination facilities in New York or Suffolk counties. There, it would be shredded, sterilized and dehydrated to become small particles, and then brought to an integrated pyrolysis plant, like one contemplated for Rockland County, north of New York City.

In the case of You and Zhao’s model, the medium-temperature pyrolysis (about 1,200 degrees Fahrenheit) can deconstruct the plasticized gowns and gloves, which are derived from petroleum, into chemicals such as ethylene, butane, gasoline, bauxite, propene, propane, diesel, light naphtha and sulfur.

“For an analogy, pyrolysis is similar to baking in an oven,” said You, a senior faculty fellow at the Cornell Atkinson Center for Sustainability. “If you set the oven temperature very high, your meat becomes a chunk and charcoal. But if you use a lower oven temperature, the meat is going to be juicy. In pyrolysis, the temperature is the trick.”

Health care facilities around the world are creating about 7.5 pounds per person of PPE waste daily through COVID-19-associated services, according to the United Nations Environment Programme.

To get a sense of the enormity of the disposal dilemma, one hospital with 300 medical personnel could generate more than a ton of medical garb waste daily. That translates to more than 400 tons of annual medical PPE waste in a single COVID-handling facility, You said.

In the paper’s energy analysis and environmental lifecycle assessment, the proposed optimal PPE processing system avoids 41.52% of total landfilling and 47.64% of the incineration processes. This method shows an environmental advantage by reducing total greenhouse gas emissions by 35.42% emissions from conventional incineration and energy saving by 43.5% from landfilling, the researchers said.

“This is a viable strategy for disposing and processing waste PPE,” You said. “It is a treatment method with low greenhouse gas emissions, it alleviates fossil fuel emission depletion and it saves a lot of polluting material from landfills.”

Funding for this research was provided by Cornell’s David M. Einhorn Center for Community Engagement and Cornell Atkinson.

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JOURNAL

Renewable and Sustainable Energy Reviews

DOI

10.1016/j.rser.2021.111786 

ARTICLE TITLE

Energy and environmental sustainability of waste personal protective equipment (PPE) treatment under COVID-19

Population Council awarded NIH Center Grant to develop first non-hormonal vaginal ring for pregnancy and STI prevention

Grant and Award Announcement

POPULATION COUNCIL

The Population Council’s Center for Biomedical Research has been awarded an $11 million P50 Clinical Research Center Grant from the Eunice Kennedy Shriver National Institute for Child Health and Development (NICHD) of the National Institute of Health (NIH). Queen’s University Belfast and Weill Cornell Medical College will partner with the Council on this grant over the next five years.

The grant will spur research and development of a novel non-hormonal contraceptive multi-purpose technology (MPT) vaginal ring that will combat the overlapping burdens of unintended pregnancy and sexually transmitted infections, including HIV. The product will fill a critical gap in reproductive healthcare, responding to women’s evolving preferences and reproductive needs.

“This single product has potential to address a wide range of sexual and reproductive needs including protection against sexually transmitted infections, contraception, and support of vaginal health,” said Lisa Haddad, MD, MPH, Council Medical Director and the Principal Investigator on the grant. “Women need more options to manage their changing sexual and reproductive health needs. The non-hormonal MPT ring offers hope of an important new contraceptive option that could provide women with protection from the growing risk of STIs.”

NON-HORMONAL OPTION

Many women want to avoid hormonal methods and the associated side effects. A non-hormonal method would allow women to maintain a regular menses cycle without loss of menstruation (amenorrhea) or unscheduled and irregular bleeding. Currently, non-hormonal options available are limited to gels or long-acting methods that require a physician to insert, such as the copper IUD.

PROTECTION AGAINST STIS AND HIV

Sexually transmitted infections are on the rise worldwide, with more than 1 million new cases every day. In 2019, approximately 1.7 million people became newly infected with HIV globally. Increasing antibiotic resistance makes it more difficult for healthcare providers to treat STIs, which currently costs more than $2 billion annually. Despite national efforts to reduce STI transmission, the US experienced steep, sustained increases for five years—reporting more than 1.7 million cases of chlamydia and 555,000 cases of gonorrhea in 2018.

STIs pose broad-reaching risks for women and their children, including the increased risk of HIV acquisition and transmission, chronic pelvic pain, infertility, and preterm delivery—the leading cause of infant morbidity and mortality.

Recent data indicate that women overwhelmingly prefer, and are more likely to use, contraception that prevents both pregnancy and STIs/HIV. To build further understanding of women’s preferences, the grant will also fund behavioral and acceptability studies alongside biomedical research on formulation and testing.

“The goal is to have the product ready for clinical trials at the end of the five-year grant. Along the way, we will generate new data about vaginal ring acceptability and the factors that increase acceptability and adherence to vaginal rings,” said Dr. Haddad.

Learn more about the novel non-hormonal contraceptive MPT vaginal ring.

NYU Tandon cybersecurity expert wins NSF CAREER Award for improving software vulnerability testing & education

Brendan Dolan-Gavitt is laying the groundwork for more efficient, less costly vulnerability testing.

Grant and Award Announcement

NYU TANDON SCHOOL OF ENGINEERING

 

IMAGE: BRENDAN DOLAN-GAVITT, ASSISTANT PROFESSOR IN THE DEPARTMENT OF COMPUTER SCIENCE AND ENGINEERING view more 

CREDIT: NYU TANDON

BROOKLYN, New York, Thursday, January 27 2022 —The National Science Foundation (NSF) has selected an NYU Tandon School of Engineering researcher who is developing better ways to assess vulnerability discovery tools – thus allowing cybersecurity professionals to better understand what techniques are most effective and ultimately leading to safer software – to receive its most prestigious award for promising young academics.

Brendan Dolan-Gavitt, an assistant professor in the Department of Computer Science and Engineering and a faculty member of NYU’s Center for Cybersecurity, received a 2022 NSF Faculty Early Career Development Award, more widely known as a CAREER Award, which supports early-career faculty who have the potential to serve as academic role models in research and education.

A five-year, $500,000 grant will support a project that aims to create techniques for automatically generating benchmark corpora of software vulnerabilities that can be used to rigorously assess newly developed and existing tools used to root out dangerous programming bugs.

Software vulnerabilities pose a major threat to the safety and security of computer systems, and while there is a large body of research on how to find vulnerabilities in programs, the large, empirically tested corpora of vulnerabilities required to rigorously test that research are difficult and expensive to assemble. 

Although researchers have discovered ways to automatically generate vulnerabilities and inject them into software, the vulnerabilities created in that way are unrealistic (containing artifacts that made them easier to discover than real vulnerabilities inadvertently created by human programmers) and not varied enough.

Dolan-Gavitt intends to address those shortcomings by employing large language models trained on code to synthesize vulnerabilities that are both realistic and diverse, placing vulnerabilities in hard-to-discover paths, allowing new vulnerability classes to be added quickly with a customized domain-specific language, and automatically generating exploits for each vulnerability. The end result will be a limitless supply of highly realistic vulnerability corpora that can be generated cheaply, at scale, and on-demand, giving researchers valuable benchmarks in measuring the efficacy of their cybersecurity tools.  

In addition to his work’s benefit to cybersecurity researchers and industry professionals, it is also expected to be a boon to educators. Since joining NYU Tandon in 2015, Dolan-Gavitt has been involved in CSAW, the most comprehensive student-run cybersecurity event in the world, and among the most popular offerings at the annual event is a “capture the flag” competition that challenges students to find vulnerabilities in a software program. “These types of competitions are an extremely popular and effective means of teaching a variety of cybersecurity skills, but they require large amounts of time, money, and expertise to create and manage,” he explains. “If the creation of the challenges can be partially or wholly automated, it could bring new educational opportunities within reach of a broader and more diverse population of students by dramatically lowering costs and reducing the time and effort needed.” 

“Brendan Dolan-Gavitt is helping place the field of vulnerability finding on solid scientific footing, allowing for repeatable and reproducible experiments and facilitating comparative evaluations of the cyber tools meant to protect us,” said NYU Tandon Dean Jelena Kovačević. “His work has the potential to make a major impact on cybersecurity education, broadening access and helping to build the next generation of security researchers. We’re proud that his techniques will be employed right here in our own cybersecurity courses and at CSAW and pleased that the NSF has chosen him to receive this much-deserved CAREER Award.”

Dolan-Gavitt joins the over 50% of NYU Tandon’s engineering junior faculty members who hold CAREER Awards or similar young-investigator honors, including 10 since 2019 alone.

His award reflects the NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

Factors Associated With Opioid Overdose After an Initial Opioid Prescription

Scott G. Weiner, MD, MPH¹; Sanae El Ibrahimi, PhD^2,3; Michelle A. Hendricks, PhD²; et alSara E. Hallvik, MPH²; Christi Hildebran, LMSW²; Michael A. Fischer, MD⁴; Roger D. Weiss, MD^5,6; Edward W. Boyer, MD, PhD¹; Peter W. Kreiner, PhD⁷; Dagan A. Wright, PhD, MSPH⁸; Diana P. Flores, BS²; Grant A. Ritter, PhD⁷

Author Affiliations Article Information

JAMA Netw Open. 2022;5(1):e2145691. doi:10.1001/jamanetworkopen.2021.45691

Original Investigation 

Substance Use and Addiction

January 28, 2022

Key Points

Question  What factors are associated with an increased risk for opioid overdose after the initial opioid prescription to a previously opioid-naive individual?

Findings  In this cohort study of 236 921 individuals who received a first opioid prescription, 667 experienced an incident opioid overdose. Patient risk factors included being aged 75 years or older, being male, receiving Medicaid or Medicare Advantage coverage, having a comorbid substance use disorder or depression, and having medical comorbidities. Prescription-related risk factors included an initial prescription of oxycodone or tramadol, concurrent use of benzodiazepines, and filling opioid prescriptions from 3 or more pharmacies.

Meaning  Findings from this study suggest that several patient- and prescription-related risk factors are associated with opioid overdose; prescribers, researchers, policy makers, and insurers can apply this information to guide opioid counseling and monitoring, develop clinical decision-making tools, and provide additional opioid prevention and treatment resources to individuals who are at greatest risk for opioid overdose.

Abstract

Importance  The opioid epidemic continues to be a public health crisis in the US.

Objective  To assess the patient factors and early time-varying prescription-related factors associated with opioid-related fatal or nonfatal overdose.

Design, Setting, and Participants  This cohort study evaluated opioid-naive adult patients in Oregon using data from the Oregon Comprehensive Opioid Risk Registry, which links all payer claims data to other health data sets in the state of Oregon. The observational, population-based sample filled a first (index) opioid prescription in 2015 and was followed up until December 31, 2018. Data analyses were performed from March 1, 2020, to June 15, 2021.

Exposures  Overdose after the index opioid prescription.

Main Outcomes and Measures  The outcome was an overdose event. The sample was followed up to identify fatal or nonfatal opioid overdoses. Patient and prescription characteristics were identified. Prescription characteristics in the first 6 months after the index prescription were modeled as cumulative, time-dependent measures that were updated monthly through the sixth month of follow-up. A time-dependent Cox proportional hazards regression model was used to assess patient and prescription characteristics that were associated with an increased risk for overdose events.

Results  The cohort comprised 236 921 patients (133 839 women [56.5%]), of whom 667 (0.3%) experienced opioid overdose. Risk of overdose was highest among individuals 75 years or older (adjusted hazard ratio [aHR], 3.22; 95% CI, 1.94-5.36) compared with those aged 35 to 44 years; men (aHR, 1.29; 95% CI, 1.10-1.51); those who were dually eligible for Medicaid and Medicare Advantage (aHR, 4.37; 95% CI, 3.09-6.18), had Medicaid (aHR, 3.77; 95% CI, 2.97-4.80), or had Medicare Advantage (aHR, 2.18; 95% CI, 1.44-3.31) compared with those with commercial insurance; those with comorbid substance use disorder (aHR, 2.74; 95% CI, 2.15-3.50), with depression (aHR, 1.26; 95% CI, 1.03-1.55), or with 1 to 2 comorbidities (aHR, 1.32; 95% CI, 1.08-1.62) or 3 or more comorbidities (aHR, 1.90; 95% CI, 1.42-2.53) compared with none. Patients were at an increased overdose risk if they filled oxycodone (aHR, 1.70; 95% CI, 1.04-2.77) or tramadol (aHR, 2.80; 95% CI, 1.34-5.84) compared with codeine; used benzodiazepines (aHR, 1.06; 95% CI, 1.01-1.11); used concurrent opioids and benzodiazepines (aHR, 2.11; 95% CI, 1.70-2.62); or filled opioids from 3 or more pharmacies over 6 months (aHR, 1.38; 95% CI, 1.09-1.75).

Conclusions and Relevance  This cohort study used a comprehensive data set to identify patient and prescription-related risk factors that were associated with opioid overdose. These findings may guide opioid counseling and monitoring, the development of clinical decision-making tools, and opioid prevention and treatment resources for individuals who are at greatest risk for opioid overdose.

Introduction

Opioid medications remain a mainstay of treatment of severe pain. In the setting of the modern opioid overdose and death epidemic, use of such medications has decreased, but there were still 168.9 million opioid prescriptions in the US in 2018.¹ Each prescription of an opioid to a previously opioid-naive patient creates the potential for the development of chronic opioid use and opioid use disorder.² For this reason, multiple entities and states have produced opioid prescribing guidelines, such as the Centers for Disease Control and Prevention Guideline for Prescribing Opioids for Chronic Pain in 2016 and the Oregon Acute Opioid Prescribing Guidelines in 2018.^3,4 The surgical literature has declared opioid dependence to be a never-event (along with use disorder and overdose)⁵ and as the most common surgical complication,⁶ affecting approximately 5% to 7% of patients who started a new episode of opioid use.⁷

An association exists between the characteristics of a patient’s first opioid prescription and long-term use. Shah et al⁸ discovered that the number of days’ supply of the initial prescription was directly associated with the development of long-term use. Deyo et al⁹ found that greater morphine milligram equivalents (MMEs) of the initial prescription were associated with increased likelihood of developing long-term use. Previous work with the Ohio prescription drug monitoring program (PDMP) database found that different prescriber specialties had different rates of long-term use by patients¹⁰ likely because the indications of opioid use and underlying patient factors create different risks for long-term use.

Although chronic opioid use is an undesirable outcome, the most substantial harms from a new episode of prescription opioid use are overdose and death. Unfortunately, the ability to link prescribing decisions to specific outcomes has been hampered by data source limitations. Prescription drug monitoring programs describe the prescription filling patterns of patients with long-term use but do not contain data about drug indications, comorbid conditions, the patient’s environment, or intervening outcomes, such as opioid use disorder or overdose. Administrative claim files are useful because they capture prescriptions that are covered by insurance but may be incomplete if the prescriptions are paid in cash or if patients change insurers. In addition, the most serious outcome of interest, opioid-related death, is often found not in PDMP or insurance data but in vital records.

To address data source limitations and provide a more comprehensive analysis of risk factors after the initiation of opioid therapy, we combined claims data with several public health data sets (including All Payer All Claims Data [APCD], vital records, PDMP, and hospital discharge data) to create the Oregon Comprehensive Opioid Risk Registry.¹¹ Using the Comprehensive Opioid Risk Registry, we constructed a retrospective cohort of opioid-naive patients who received an initial opioid prescription to assess the patient factors and early time-varying prescription-related factors associated with opioid-related fatal or nonfatal overdose. We hypothesized that some patient factors (eg, insurance type and high disease burden) and prescription factors in the first 6 months after opioid initiation (eg, high doses, and opioid and benzodiazepine overlap) are associated with increased risk of opioid overdose.

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Factors Associated With Opioid Overdose After an Initial Opioid Prescription | Addiction Medicine | JAMA Network Open | JAMA Network