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1: Comparing rapid micro-induction and standard induction of buprenorphine/naloxone for treatment of opioid use disorder: Protocol for an open-label, parallel-group, superiority, randomized controlled trial
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Posted 26 May 2020

Comparing rapid micro-induction and standard induction of buprenorphine/naloxone for treatment of opioid use disorder: Protocol for an open-label, parallel-group, superiority, randomized controlled trial
2,143 downloads medRxiv addiction medicine

James S.H. Wong, Mohammadali Nikoo, Jean N. Westenberg, Janet G. Suen, Jennifer Wong, Reinhard M. Krausz, Christian G. Schutz, Marc Vogel, Jesse A. Sidhu, Jessica Moe, Shane Arishenkoff, Donald Griesdale, Nickie Mathew, Pouya Azar

Background: Buprenorphine/naloxone (Suboxone) is a current first-line treatment for opioid use disorder (OUD). The standard induction method of buprenorphine/naloxone requires patients to be abstinent from opioids and therefore experience withdrawal symptoms prior to induction, which can be a barrier in starting treatment. Rapid micro-induction (micro-dosing) involves the administration of small, frequent does of buprenorphine/naloxone and removes the need for a period of withdrawal prior to the start of treatment. This study aims to compare the effectiveness and safety of rapid micro-induction versus standard induction of buprenorphine/naloxone in patients with OUD. Methods: This is a randomized, open-label, two-arm, superiority, controlled trial comparing the safety and effectiveness of rapid micro-induction versus standard induction of buprenorphine/naloxone for the treatment of OUD. A total of 50 participants with OUD will be randomized at one Canadian hospital. The primary outcome is successful induction of buprenorphine/naloxone with low levels of withdrawal. Secondary outcomes are treatment retention, illicit drug use, self-reported drug use behaviour, craving, pain, physical health, safety, and client satisfaction. Discussion: This is the first randomized controlled trial to compare the effectiveness and safety of rapid micro-induction versus standard induction of buprenorphine/naloxone. This study will thereby generate evidence for a novel induction method which eliminates substantial barriers to the use of buprenorphine/naloxone in the midst of the ongoing opioid crisis.

2: A global survey on changes in the supply, price and use of illicit drugs and alcohol, and related complications during the 2020 COVID-19 pandemic
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Posted 21 Jul 2020

A global survey on changes in the supply, price and use of illicit drugs and alcohol, and related complications during the 2020 COVID-19 pandemic
1,101 downloads medRxiv addiction medicine

Ali Farhoudian, Seyed Ramin Radfar, Hossein Mohaddes Ardabili, Parnian Rafei, Mohsen Ebrahimi, Arash Khojasteh Zonoozi, Cornelis A J De Jong, Mehrnoosh Vahidi, Masud Yunesian, Christos Kouimtsidis, Shalini Arunogiri, Helena Hansen, Kathleen T Brady, Marc Potenza, ISAM-PPIG Global Survey Consortium, Alexander Mario Baldacchino, Hamed Ekhtiari

Background and aims: COVID-19 has infected more than 13 million people worldwide and impacted the lives of many more, with a particularly devastating impact on vulnerable populations, including people with substance use disorders (SUDs). Quarantines, travel bans, regulatory changes, social distancing and 'lockdown' measures have affected drug and alcohol supply chains and subsequently their availability, price and use patterns, with possible downstream effects on presentations of SUDs and demand for treatment. Given the lack of multicentric epidemiologic studies, we conducted a rapid global survey within the International Society of Addiction Medicine (ISAM) network in order to understand the status of substance-use patterns during the current pandemic. Design: Cross-sectional survey. Setting: Worldwide. Participants: Starting on April 4th, 2020 during a 5-week period, the survey received 185 responses from 77 countries. Measurements: To assess addiction medicine professionals' perceived changes in drug and alcohol supply, price, use pattern and related complications during the COVID-19 pandemic. Findings: Participants reported (among who answered ''decreased'' or ''increased'', percentage of those who were in majority is reported in the parenthesis) a decrease in drug supply (69.0%), and at the same time an increase in price (95.3%) globally. With respect to changes in use patterns, an increase in alcohol (71.7%), cannabis (63.0%), prescription opioids (70.9%), and sedative/hypnotics (84.6%) use was reported while the use of amphetamines (59.7%), cocaine (67.5%), and opiates (58.2%) was reported to decrease overall. Conclusions: The global report on changes in the availability, use patterns and complications of alcohol and drugs during the COVID-19 pandemic should be considered in making new policies and in developing mitigating measures and guidelines during the current pandemic (and probable future ones) in order to minimize risks to SUDs. Key words: COVID-19, pandemic, alcohol, drug, substance use disorder, supply, price.

3: A Randomized Controlled Trial of a Digital Therapeutic Intervention for Smoking Cessation.
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Posted 26 Jun 2020

A Randomized Controlled Trial of a Digital Therapeutic Intervention for Smoking Cessation.
853 downloads medRxiv addiction medicine

Jamie Webb, Sarrah Peerbux, Peter Smittenaar, Sarim Siddiqui, Yusuf Sherwani, Maroof Ahmed, Hannah MacRae, Hannah Puri, Sangita Bhalla, Azeem Majeed

Background and Aims: Tobacco smoking remains the leading cause of preventable death and disease worldwide. Digital interventions delivered through smartphones offer a promising alternative to traditional methods, but little is known about their effectiveness. Our aim was to determine the effectiveness of Quit Genius, a novel digital therapeutic intervention for smoking cessation. Design: Two-arm, single-blinded, parallel-group randomized controlled trial Setting: Referrals from primary care practices Participants: 556 Adult smokers (aged [&ge;]18 years), smoking at least five cigarettes a day for the past year. 530 were included for the final analysis. Intervention and comparator: Digital therapeutic intervention for smoking cessation consisting of a smartphone application delivering cognitive behavioral therapy content, one-to-one coaching, craving tools and tracking capabilities. The control intervention was Very Brief Advice along the Ask, Advise, Act model. All participants were offered nicotine replacement therapy for three months. A random half of each arm was assigned a carbon monoxide (CO) device for biochemical verification. Measurements: The primary outcome was self-reported seven-day point prevalence abstinence at four-weeks post quit date. Findings: 556 participants were randomized (treatment n=277, control n=279). The intention-to-treat analysis included 530 participants (n=265 in each arm; 11 excluded for randomization before trial registration, and 15 for protocol violations at baseline visit). At four weeks post-quit date, 45% of participants in the treatment arm had not smoked in the preceding seven days, compared to 29% in control (risk ratio 1.55 [1.23, 1.96], p = 0.0002; intention-to-treat, n=530). Self-reported seven-day abstinence agreed with CO measurement (CO <10 ppm) in 96% of cases (80/83) where CO readings were available. No harmful effects of the intervention were observed. Conclusions: The Quit Genius digital therapeutic intervention is a superior treatment in achieving smoking cessation four weeks post quit date compared to very brief advice.

4: Problem drinking before and during the COVID-19 crisis in US and UK adults: Evidence from two population-based longitudinal studies
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Posted 28 Jun 2020

Problem drinking before and during the COVID-19 crisis in US and UK adults: Evidence from two population-based longitudinal studies
848 downloads medRxiv addiction medicine

Michael Daly, Eric Robinson

Background The impact of the COVID-19 crisis on potentially harmful alcohol consumption is unclear. Aims To test whether the prevalence of problem drinking has changed from before to during the COVID-19 crisis in the US and UK. Design/Setting We examined nationally representative longitudinal data on how problem drinking has changed from pre-pandemic levels among adults in the US (N=7,327; Understanding America Study) and UK (N=12,594; UK Household Longitudinal Study). Methods In the US, we examined rates of consuming alcohol [&ge;] 4 times in the past week at baseline (March, 2020) and across four waves of follow-up (April-May, 2020). In the UK we assessed the prevalence of consuming alcohol [&ge;] 4 times per week and weekly heavy episodic drinking using the AUDIT-C at baseline (2017-2019) and during the COVID-19 lockdown (April, 2020). We also tested whether there were specific groups at greater risk of increased problem drinking during the pandemic. Results Among US adults, there was a statistically significant increase in the percentage of participants reporting drinking alcohol [&ge;] 4 times a week which rose significantly from 11.7% to 17.9% (53% increase, p < .001) as the COVID-19 crisis developed in the US. Among UK adults, the percentage of participants reporting drinking [&ge;] 4 times a week increased significantly from 14.2% to 23% (62% increase, p < .001) and heavy episodic drinking at least weekly increased significantly from 9.7% to 16.6% (71% increase, p < .001) when compared to pre-COVID-19 lockdown levels. Trends were similar across population demographics, although those aged under 50 years and higher income groups displayed the largest increases. Conclusions The COVID-19 crisis has been associated with substantial increases in problematic drinking in both US and UK adults.

5: Take-Home Dosing Experiences among Persons Receiving Methadone Maintenance Treatment During COVID-19
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Posted 02 Sep 2020

Take-Home Dosing Experiences among Persons Receiving Methadone Maintenance Treatment During COVID-19
643 downloads medRxiv addiction medicine

Mary C. Figgatt, Zach Salazar, Elizabeth Day, Louise Vincent, Nabarun Dasgupta

PurposeMethadone maintenance treatment is a life-saving treatment for people with opioid use disorders (OUD). The coronavirus pandemic (COVID-19) introduces many concerns surrounding access to opioid treatment. In March 2020, the Substance Abuse and Mental Health Services Administration (SAMHSA) issued guidance allowing the expansion of take-home methadone doses. We sought to describe changes to treatment experiences from the perspective of persons receiving methadone at outpatient treatment facilities for OUD. MethodsWe conducted an in-person survey among 104 persons receiving methadone from three clinics in central North Carolina in June and July 2020. Surveys collected information on demographic characteristics, methadone treatment history, and experiences with take-home methadone doses in the context of COVID-19 (i.e., before and since March 2020). ResultsBefore COVID-19, the clinic-level percent of participants receiving any amount of days supply of take-home doses at each clinic ranged from 56% to 82%, while it ranged from 78% to 100% since COVID-19. The clinic-level percent of participants receiving a take-homes days supply of a week or longer (i.e., [&ge;]6 days) since COVID-19 ranged from 11% to 56%. Among 87 participants who received take-homes since COVID-19, only four reported selling their take-home doses. ConclusionsOur study found variation in experiences of take-home dosing by clinic and little diversion of take-home doses. While SAMSHA guidance should allow expanded access to take-home doses, adoption of these guidelines may vary at the clinic level. The adoption of these policies should be explored further, particularly in the context of benefits to patients seeking OUD treatment. HighlightsO_LIMethadone take-home dosing of survey participants varied by clinic. C_LIO_LIDiversion of take-home doses was rare. C_LIO_LIImplementation of COVID-19 opioid treatment guidelines should be examined further. C_LI

6: Genetic Data Can Lead to Medical Discrimination: Opioid Use Disorder as a Cautionary Tale
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Posted 14 Sep 2020

Genetic Data Can Lead to Medical Discrimination: Opioid Use Disorder as a Cautionary Tale
621 downloads medRxiv addiction medicine

Alexander S. Hatoum, Frank R. Wendt, Marco Galimberti, Renato Polimanti, Benjamin Neale, Henry R. Kranzler, Joel Gelernter, Howard J. Edenberg, Arpana Agrawal

Using genetics to predict the likelihood of future psychiatric disorders such as Opioid Use Disorder (OUD) poses scientific and ethical challenges. This report illustrates flaws in current machine learning (ML) approaches to such predictions using, as an example, a proposed genetic test for OUD derived from 16 candidate gene variants. In an independent sample of OUD cases and controls of European and African descent, results from five ML algorithms trained with purported "reward-system" candidate variants demonstrate that ML methods predict genomic ancestry rather than OUD. Further, sets of variants matched to the candidate SNPs by allele frequency produced similarly flawed predictions, questioning the plausibility of the selected candidate variants. We conclude that the genetic prediction of OUD (and by extension other highly polygenic psychiatric diseases) by ML has high potential to increase the likelihood of medical discrimination against population subgroups, with no benefit of accurate prediction for early intervention.

7: Optimal Control Strategy Applied to Dynamic Model of Drug Abuse Incident for Reducing Its Adverse Effects
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Posted 06 May 2020

Optimal Control Strategy Applied to Dynamic Model of Drug Abuse Incident for Reducing Its Adverse Effects
559 downloads medRxiv addiction medicine

Md. Haider Ali Biswas, Md. Azmir Ibne Islam

The present world is facing a devastating reality as drug abuse prevails in every corner of a society. The progress of a country is obstructed due to the excessive practice of taking drugs by the young generation. Like other countries, Bangladesh is also facing this dreadful situation. The multiple use of drug substances leads an individual to a sorrowful destination and for this reason, the natural behavior of human mind is disrupted. An addicted individual may regain his normal life by proper monitoring and treatment. The objective of this study is to analyze a mathematical model on the dynamics of drug abuse in the perspective of Bangladesh and reduce the harmful consequences with effective control policies using the idea of optimal control theory. The model has been solved analytically introducing a specific optimal goal. Numerical simulations have also been performed to review the behaviors of analytical findings. The analytical results have been verified with the numerical simulations. The analysis of this paper shows that it is possible to control drug addiction if there is less interaction among general people with the addicted individuals. Family based care, proper medical treatment, awareness and educational programs can be the most effective ways to reduce the adverse effects of drug addiction in a shortest possible time.

8: Clinical and functional connectivity outcomes of 5-Hz repeated transcranial magnetic stimulation as an add-on treatment in cocaine use disorder: a double-blind randomized controlled trial.
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Posted 19 Jul 2020

Clinical and functional connectivity outcomes of 5-Hz repeated transcranial magnetic stimulation as an add-on treatment in cocaine use disorder: a double-blind randomized controlled trial.
552 downloads medRxiv addiction medicine

Eduardo A. Garza-Villareal, Ruth Alcala-Lozano, Sofia Fernandez-Lozano, Erik Morelos-Santana, Alan Dávalos, Viviana Villicaña, Sarael Alcauter, F. Xavier Castellanos, Jorge J. Gonzalez-Olvera

BACKGROUND: Cocaine use disorder (CUD) is a global condition lacking effective treatment. Repeated magnetic transcranial stimulation (rTMS) may reduce craving and frequency of cocaine use, but little is known about its efficacy and neural effects. METHODS: Using a double-blind placebo-controlled randomized clinical trial (RCT) [NCT02986438], we sought to elucidate short- and long-term clinical benefits of 5-Hz rTMS as an add-on to standard treatment in CUD patients and discern underlying functional connectivity effects using magnetic resonance imaging. Forty-four randomly assigned CUD patients completed the 2-week double-blind acute phase [Sham (n=20, 2f/18m) and Active (n=24, 4f/20m)], in which they received 2 daily sessions of rTMS (5,000 pulses) on the left dorsolateral prefrontal cortex. Subsequently, n=20 CUD patients continued to open-label maintenance (2 weekly sessions for up to 6 months). Measures were acquired at baseline, 2 weeks, 3 months and 6 months. RESULTS: Overall, 5-Hz rTMS plus standard treatment for 2 weeks significantly reduced craving and impulsivity in the Active group; decreased impulsivity correlated with improvements in functional connectivity in executive control and default mode networks. Clinical and functional connectivity effects were maintained for 3 months but they dissipated by 6 months. We did not observe reduction of positive cocaine urine tests, however, self-reported frequency and grams consumed for 6 months were reduced. CONCLUSIONS: With this RCT we show that 5-Hz rTMS has potential promise as an adjunctive treatment for CUD and merits further research.

9: Reorganization of Substance Use Treatment and Harm Reduction Services during the COVID-19 Pandemic: A Global Survey
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Posted 22 Sep 2020

Reorganization of Substance Use Treatment and Harm Reduction Services during the COVID-19 Pandemic: A Global Survey
546 downloads medRxiv addiction medicine

Seyed Ramin Radfar, Cornelis A J De Jong, Ali Farhoudian, Mohsen Ebrahimi, Parnian Rafei, Mehrnoosh Vahidi, Masud Yunesian, Christos Kouimtsidis, Shalini Arunogiri, Omid Massah, Abbas Deylamizadeh, Kathleen T Brady, Anja Busse, ISAM-PPIG Global Survey Consortium, Marc Potenza, Hamed Ekhtiari, Alexander Mario Baldacchino

Background: The COVID-19 pandemic has impacted people with substance use disorders (SUDs) worldwide, and healthcare systems have reorganized their services in response to the pandemic. Methods: One week after the announcement of the COVID-19 as a pandemic, in a global survey, 177 addiction medicine professionals described COVID-19-related health responses in their own 77 countries in terms of SUD treatment and harm reduction services. The health response is categorized around (1) managerial measures and systems, (2) logistics, (3) service providers, and (4) vulnerable groups. Results: Respondents from over 88% of countries reported that core medical and psychiatric care for SUDs had continued; however, only 56% of countries reported having had any business continuity plan, and 37.5% of countries reported shortages of methadone or buprenorphine supplies. Participants of 41% of countries reported partial discontinuation of harm-reduction services such as needle and syringe programs and condom distribution. 57% of overdose prevention interventions and 81% of outreach services also having been negatively impacted. Conclusions: Participants reported that SUD treatment and harm reduction services had been significantly impacted globally early during the COVID-19 pandemic. Based on our findings, we provide a series of recommendations to support countries to be prepared more efficiently for future waves or similar pandemics to 1) help policymakers generate business continuity plans, 2) maintain the use of evidence-based interventions for people with SUDs, 3) be prepared for adequate medication supplies, 4) integrate harm reduction programs with other treatment modalities and 5) have specific considerations for vulnerable groups such as immigrants and refugees.

10: Predicting Alcohol Dependence from Multi-Site Brain Structural Measures
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Posted 23 Jan 2020

Predicting Alcohol Dependence from Multi-Site Brain Structural Measures
527 downloads medRxiv addiction medicine

Sage Hahn, Scott Mackey, Janna Cousijn, John J. Foxe, Robert Hester, Kent Hutchinson, Ozlem Korucuoglu, Edythe London, Valentina Lorenzetti, Maartje Luijten, Reza Momenan, Catherine Orr, Martin Paulus, Lianne Schmaal, Rajita Sinha, Zsuzsika Sjoerds, Dan Stein, Elliot Stein, Ruth J. van Holst, Dick Veltman, Reinout W Wiers, Murat Yucel, Paul M. Thompson, Patricia Conrod, Nicholas Allgaier, Hugh Garavan

BackgroundThe search for neuroimaging biomarkers of alcohol use disorder (AUD) has primarily been restricted to significance testing in small datasets of low diversity. To identify neurobiological markers beyond individual differences, it may be useful to develop classification models for AUD. The ever-increasing quantity of neuroimaging data demands methods that are robust to the complexities of multi-site designs and are generalizable to data from new scanners. MethodsThis study represents a mega-analysis of previously published datasets from 2,034 AUD and comparison participants spanning 27 sites, coordinated by the ENIGMA Addiction Working Group. Data were grouped into a training set including 1,652 participants (692 AUD, 24 sites), and test set with 382 participants (146 AUD, 3 sites). A battery of machine learning classifiers was evaluated using repeated random cross-validation (CV) and leave-site-out CV. Area under the receiver operating characteristic curve (AUC) was our base metric of performance. ResultsMulti-objective evolutionary search was conducted to identify sparse, generalizable, and high performing subsets of brain measurements. Cortical thickness in the left superior frontal gyrus and right lateral orbitofrontal cortex, cortical surface area in the right transverse temporal gyrus, and left putamen volume, appeared most frequently across searches. Restricting a regularized logistic regression model to these four features yielded a test-set AUC of .768. ConclusionsDeveloping classification models on multi-site data with varied underlying class distributions poses unique challenges. Supplementing datasets with controls from new sites and performing feature selection increases generalizability. Four features identified by evolutionary search may serve as specific biomarkers for individuals with current AUD.

11: Polygenic Risk Scores for Alcohol Involvement Relate to Brain Structure in Substance-Naive Children: Results from the ABCD Study
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Posted 28 Jul 2020

Polygenic Risk Scores for Alcohol Involvement Relate to Brain Structure in Substance-Naive Children: Results from the ABCD Study
510 downloads medRxiv addiction medicine

Alexander S. Hatoum, Emma C. Johnson, David AA Baranger, Sarah E. Paul, Arpana Agrawal, Ryan Bogdan

In substance naive children (n=3,013), polygenic risk score (PRS) for problematic alcohol use was associated with lower volume of the frontal pole and greater cortical thickness of the supramarginal gyrus. Several other areas showed nominal significance. These associations suggest that genetic liability to alcohol involvement may manifest as variability in brain structure prior to consumption of the first alcoholic drink and alter brain morphometry during the start of adolescence.

12: Convergent cross-sectional and longitudinal evidence for gaming-cue specific posterior parietal dysregulations in early stages of Internet Gaming Disorder
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Posted 24 Jan 2020

Convergent cross-sectional and longitudinal evidence for gaming-cue specific posterior parietal dysregulations in early stages of Internet Gaming Disorder
504 downloads medRxiv addiction medicine

Fangwen Yu, Rayna Sariyska, Bernd Lachmann, Qianqian Wang, Martin Reuter, Bernd Weber, Peter Trautner, Shuxia Yao, Christian Montag, B Becker

Exaggerated reactivity to drug-cues and emotional dysregulations represent key symptoms of early stages of substance use disorders. The diagnostic criteria for (Internet) Gaming Disorder strongly resemble symptoms for substance-related addictions. However, previous cross-sections studies revealed inconsistent results with respect to neural cue reactivity and emotional dysregulations in these populations. To this end the present fMRI study applied a combined cross-sectional and prospective longitudinal design in excessive online gamers (n=37) and gaming-naive controls (n=67). To separate gaming-associated changes from predisposing factors, gaming-naive subjects were randomly assigned to 6 weeks of daily Internet gaming or a non-gaming condition. At baseline and after the training subjects underwent an fMRI paradigm presenting gaming-related cues and non-gaming related emotional stimuli. Cross-sectional comparisons revealed gaming-cue specific enhanced valence attribution and neural reactivity in a parietal network, including the posterior cingulate/precuneus in excessive gamers as compared to gaming naive-controls. Prospective analysis revealed that six weeks of gaming elevated valence ratings as well as neural cue-reactivity in a similar parietal network, specifically the posterior cingulate/precuneus in previously gaming-naive controls. Together, the prospective longitudinal design did not reveal supporting evidence for altered emotional processing of non-gaming associated stimuli in excessive gamers while convergent evidence for increased emotional and neural reactivity to gaming-associated stimuli was observed. Findings suggest that exaggerated neural reactivity in posterior parietal regions engaged in self-referential processing already occur during early stages of regular gaming probably promoting continued engagement in gaming behavior.

13: Increasing Heroin, Cocaine, and Buprenorphine Arrests Reported to the Maine Diversion Alert Program
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Posted 09 Aug 2019

Increasing Heroin, Cocaine, and Buprenorphine Arrests Reported to the Maine Diversion Alert Program
504 downloads medRxiv addiction medicine

Kevin J Simpson, Matthew T Moran, Kenneth L McCall, John Herbert, Michelle Foster, Olapeju M Simoyan, Dipam T Shah, Clare Desrosiers, Stephanie D. Nichols, Brian J. Piper

BackgroundThe opioid overdose crisis is especially pronounced in Maine. The Diversion Alert Program (DAP) was developed to combat illicit drug use and prescription drug diversion by facilitating communication between law enforcement and healthcare providers with the goal of limiting drug-related harms and criminal behaviors. Our objectives in this report were to analyze 2014-2017 DAP for: 1) trends in drug arrests and, 2) differences in arrests by offense, demographics (sex and age) and by region. MethodsDrug charges (N = 8,193, 31.3% female, age = 33.1 {+/-} 9.9) reported to the DAP were examined by year, demographics, and location. ResultsThe most common substances of the 10,064 unique arrests reported were heroin (N = 2,203, 21.9%), crack/cocaine (N = 945, 16.8%), buprenorphine (N = 812, 8.1%), and oxycodone (N = 747, 7.4%). While the overall number of arrests reported to the DAP declined in 2017, the proportion of arrests involving opioids (heroin, buprenorphine, or fentanyl) and stimulants (cocaine/crack cocaine, or methamphetamine), increased (p < .05). Women had significantly increased involvement in arrests involving sedatives and miscellaneous pharmaceuticals (e.g. gabapentin) while men had an elevation in stimulant arrests. Heroin accounted for a lower percentage of arrests among individuals age > 60 (6.6%) relative to young-adults (18-29, 22.3%, p < .0001). Older-adults had significantly more arrests than younger-adults for oxycodone, hydrocodone, and marijuana. ConclusionHeroin had the most arrests from 2014-2017. Buprenorphine, fentanyl and crack/cocaine arrests increased appreciably suggesting that improved treatment is needed to prevent further nonmedical use and overdoses. The Diversion Alert Program provided a unique data source for research, a harm-reduction tool for health care providers, and an informational resource for law enforcement.

14: Rise and Regional Disparities in Buprenorphine Utilization in the United States
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Posted 09 Sep 2019

Rise and Regional Disparities in Buprenorphine Utilization in the United States
494 downloads medRxiv addiction medicine

Amir Azar R. Pashmineh, Alexandra Cruz-Mullane, Jaclyn C. Podd, Warren S. Lam, Suhail H. Kaleem, Laura B. Lockard, Mark R. Mandel, Daniel Y. Chung, Corey S. Davis, Stephanie D. Nichols, Kenneth L McCall, Brian J. Piper

AimsBuprenorphine is an opioid partial-agonist used to treat Opioid Use Disorders (OUD). While several state and federal policy changes have attempted to increase buprenorphine availability, access remains well below optimal levels. This study characterized how buprenorphine utilization in the United States has changed over time and whether there are regional disparities in distribution. MeasurementsBuprenorphine weights distributed from 2007 to 2017 were obtained from the Drug Enforcement Administration. Data was expressed as the percent change and as the mg per person in each state. Separately, the formulations for prescriptions covered by Medicaid (2008 to 2018) were examined. FindingsBuprenorphine distributed to pharmacies increased about seven-fold (476.8 to 3,179.9 kg) while the quantities distributed to hospitals grew five-fold (18.6 to 97.6 kg) nationally from 2007 to 2017. Buprenorphine distribution per person was almost 20-fold higher in Vermont (40.4 mg/person) relative to South Dakota (2.1 mg/person). There was a strong association between the number of waivered physicians per 100K population and distribution per state (r(49) = +0.76, p < .0005). The buprenorphine/naloxone sublingual film (Suboxone) was the predominant formulation (92.6% of 0.31 million Medicaid prescriptions) in 2008 but this accounted for less than three-fifths (57.3% of 6.56 million prescriptions) in 2018. ConclusionsAlthough buprenorphine availability has substantially increased over the last decade, distribution was very non-homogenous across the US.

15: Machine Learning Applied to Clinical Laboratory Data Predicts Patient-Specific, Near-Term Relapse in Patients in Medication for Opioid Use Disorder Treatment
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Posted 14 Aug 2020

Machine Learning Applied to Clinical Laboratory Data Predicts Patient-Specific, Near-Term Relapse in Patients in Medication for Opioid Use Disorder Treatment
483 downloads medRxiv addiction medicine

Paul Pyzowski, Barbara Herbert, Wasim Q. Malik

We have developed a data-driven, algorithmic method for identifying patients in an outpatient buprenorphine program at high risk for relapse in the following seven days. This method uses data already available in clinical laboratory data, can be made available in a timely matter, and is easily understandable and actionable by clinicians. Use of this method could significantly reduce the rate of relapse in addiction treatment programs by targeting interventions at those patients most at risk for near term relapse.

16: Peripheral Biomarkers of Tobacco-Use Disorder: A Systematic Review
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Posted 14 Aug 2019

Peripheral Biomarkers of Tobacco-Use Disorder: A Systematic Review
471 downloads medRxiv addiction medicine

Dwight F. Newton

IntroductionTobacco use disorder (TUD) is a major worldwide healthcare burden resulting in 7 million deaths annually. TUD has few approved cessation aids, all of which are associated a high rate of relapse within one year. Biomarkers of TUD severity, treatment response, and risk of relapse have high potential clinical utility to identify ideal responders and guide additional treatment resources. MethodsA MEDLINE search was performed using the terms biomarkers, dihydroxyacetone phosphate, bilirubin, inositol, cotinine, adrenocorticotropic hormone, cortisol, pituitary-adrenal system, homovanillic acid, dopamine, pro-opiomelanocortin, lipids, lipid metabolism all cross-referenced with tobacco-use disorder. ResultsThe search yielded 424 results, of which 57 met inclusion criteria. The most commonly studied biomarkers were those related to nicotine metabolism, the hypothalamic-pituitary-adrenal (HPA) axis, and cardiovascular (CVD) risk. Nicotine metabolism was most associated with severity of dependence and treatment response, where as HPA axis and CVD markers showed less robust associations with dependence and relapse risk. ConclusionsNicotine-metabolite ratio, cortisol, and atherogenicity markers appear to be the most promising lead biomarkers for further investigation, though the body of literature is still preliminary. Longitudinal, repeated-measures studies are required to determine the directionality of the observed associations and determine true predictive power of these biomarkers. Future studies should also endeavour to study populations with comorbid psychiatric disorders to determine differences in utility of certain biomarkers.

17: The Concurrent Initiation of Medications Is Associated with Discontinuation of Buprenorphine Treatment for Opioid Use Disorder
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Posted 18 Jan 2020

The Concurrent Initiation of Medications Is Associated with Discontinuation of Buprenorphine Treatment for Opioid Use Disorder
463 downloads medRxiv addiction medicine

Pengyue Zhang, Chien-Wei Chiang, Sara Quinney, Macarius Donneyong, Bo Lu, Lei Frank Huang, Feixiong Cheng

IntroductionRetention in buprenorphine treatment for opioid use disorder (OUD) yields better opioid abstinence and reduces all-cause mortality for patients with OUD. Despite significant efforts have been made to expand the availability and use of buprenorphine in the United States, its retention rates remain on a low level. The current study examines discontinuation of buprenorphine with respect to concurrent initiation of other medications using real-world evidence. MethodsCase-crossover study was conducted to examine discontinuation of buprenorphine using a large-scale longitudinal health dataset including 148,306 commercially-insured individuals initiated on medications for opioid use disorder (MOUD). Odds ratios and Bonferroni adjusted p-values were calculated for medications and therapeutic classes of medications. ResultsClonidine was associated with increased discontinuation risk of buprenorphine both using the buprenorphine dataset alone (OR = 1.583 and adjusted p-value = 1.22 x 10-6) and using naltrexone as a comparison drug (OR = 2.706 and adjusted p-value = 4.11 x 10-5). Opioid medications (oxycodone, morphine and fentanyl) and methocarbamol were associated with increased discontinuation risk of buprenorphine using the buprenorphine dataset alone (adjusted p-value < 0.05), but not significant using naltrexone as a comparison drug. 6 drug therapeutic classes were associated with increased discontinuation risk of buprenorphine both using the buprenorphine dataset alone and using naltrexone as a comparison drug (adjusted p-value < 0.05). ConclusionConcurrent initiation of medications is associated with increased discontinuation risk of buprenorphine. Opioid medications are prescribed among patients on MOUD and associated with increased discontinuation risk of buprenorphine. Analgesics is associated with increased discontinuation risk of buprenorphine for patients without previous exposure of pain medications.

18: Inconsistent Addiction Treatment for Patients Undergoing Cardiac Surgery for Injection Drug Use-Associated Infective Endocarditis
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Posted 10 Oct 2019

Inconsistent Addiction Treatment for Patients Undergoing Cardiac Surgery for Injection Drug Use-Associated Infective Endocarditis
454 downloads medRxiv addiction medicine

Max Jordan Nguemeni Tiako, Seong Hong, Syed Usman Bin Mahmood, Makoto Mori, Abeel Mangi, James Yun, Manisha Juthani-Mehta, Arnar Geirsson

IntroductionCases of injection drug use-related infective endocarditis (IDU-IE) requiring surgery are rising in the setting of the current U.S. opioid epidemic. We thus aimed to determine the nature of addiction interventions in the perioperative period. MethodsThis is a retrospective review of surgical IDU-IE from 2011 to 2016 at a tertiary care center in New Haven, Connecticut. The data collected included substances consumed recreationally, consultations by social work (SW), psychiatry, pharmacotherapy for addiction, and evidence of enrollment in a drug rehabilitation program upon discharge. Among patients with active drug use (ADU), we compared the 24-month survival of those who received at least one form of addiction intervention to that of those who did not. ResultsForty-two patients (75%) had active drug use. Among them, 22 used heroin. Forty-one patients (73.2%) saw SW, 17 (30.4%) saw psychiatry; 14 (25%) saw neither SW nor psychiatry. Twenty-one patients (37.5%) received methadone, 6 (10.7%) received buprenorphine, 1 (0.02%) received naltrexone; 26 (46.4%) did not receive any pharmacotherapy. Fifteen patients (26.8%) attended a drug rehabilitation program, 13 (86.7%) of whom had seen SW and 8 (53%) psychiatry. Among patients with ADU, there was no statistically significant difference in survival between those who received at least one intervention and those who did not (p=0.1 by log rank). ConclusionAddiction interventions are deployed inconsistently for patients with surgical IDU-IE. Untreated substance use disorder and recurrent endocarditis are the leading cause of death in this population. Studying best-practices for perioperative interventions in IDU-IE and establishing protocols are of the upmost importance.

19: A Critical Interpretive Synthesis to Develop Quality Assessment Tools for E-Cigarette Systematic Reviews: Scope and Protocol
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Posted 29 May 2020

A Critical Interpretive Synthesis to Develop Quality Assessment Tools for E-Cigarette Systematic Reviews: Scope and Protocol
439 downloads medRxiv addiction medicine

R. O’Leary, Federica Costanzo

One component of a systematic review is the quality assessment of studies to determine their inclusion or exclusion. Studies on e-cigarettes are conducted in the contentious atmosphere surrounding tobacco harm reduction, which has resulted at times in research bias. Therefore, the quality assessment of studies on e-cigarettes requires more scrutiny than what is provided by generic tools on study design. This topic-specific quality assessment must examine the tests, measurements, and analysis methods used for their adherence to research standards. Furthermore, the studies need to be carefully screened for bias. Because standard quality assessment tools do not provide this topic-specific guidance, we propose to develop quality assessment tools specifically for reviews on e-cigarettes, and for our living systematic reviews on e-cigarettes for tobacco harm reduction.

20: Medication Improves Age Disparities in Six-Month Treatment Retention for Opioid Use Disorder
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Posted 23 Feb 2020

Medication Improves Age Disparities in Six-Month Treatment Retention for Opioid Use Disorder
430 downloads medRxiv addiction medicine

Carrie M. Mintz, Ned J. Presnall, John M. Sahrmann, Jacob T. Borodovsky, Paul E.A. Glaser, Laura J. Bierut, Richard A. Grucza

Background and AimsAdolescents with opioid use disorder (OUD) are an understudied and vulnerable population. We examined the association between age and six-month treatment retention, and whether any such association was moderated by medication treatment. MethodsIn this retrospective cohort study, we used an insurance database with OUD treatment claims from 2006-2016. We examined 261,356 OUD treatment episodes in three age groups: adolescents (ages 12-17), young adults (18-25) and older adults (26-64). We used logistic regression to estimate prevalence of six-month retention before and after stratification by treatment type (buprenorphine, naltrexone, or psychosocial services only). Insurance differences (commercial vs Medicaid) in medication treatment prevalence were also assessed. ResultsAdolescents were far less likely to be retained compared to adults (17.6%; 95% CI 16.5-18.7% for adolescents; 25.1%; 95% CI 24.7-25.4% for young adults; 33.3%; 95% CI 33.0-33.5% for older adults). This disparity was markedly reduced after adjusting for treatment type. For all ages, buprenorphine was more strongly associated with retention than naltrexone or psychosocial services. Adolescents who received buprenorphine were more than four times as likely to be retained in treatment (44.5%, 95% CI 40.6-49.0) compared to those who received psychosocial services (9.7%, 95% CI 8.8-10.8). Persons with commercial insurance were more likely to receive medication than those with Medicaid (73.3% vs 36.4%, {chi}2 =57,870.6, (p<.001). ConclusionsAge disparities in six-month treatment retention are strongly related to age disparities in medication treatment. Results point to need for improved implementation of medication treatment for persons with OUD, regardless of age or insurance status.

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