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2. The Phase-I Trigger Readout Electronics Upgrade of the ATLAS Liquid Argon Calorimeters

Author

Aad, G., Akimov, A. V., Khoury, K. Al, Aleksa, M., Andeen, T., Anelli, C., Aranzabal, N., Armijo, C., Bagulia, A., Ban, J., Barillari, T., Bellachia, F., Benoit, M., Bernon, F., Berthold, A., Bervas, H., Besin, D., Betti, A., Bianga, Y., Biaut, M., Boline, D., Boudreau, J., Bouedo, T., Braam, N., Bret, M. Cano, Brooijmans, G., Cai, H., Camincher, C., Camplani, A., Cap, S., Carbone, A., Carter, J. W. S., Chekulaev, S. V., Chen, H., Chen, K., Chevillot, N., Citterio, M., Cleland, B., Constable, M., de Jong, S., Deiana, A. M., Delmastro, M., Deng, B., Deschamps, H., Diaconu, C., Dik, A., Dinkespiler, B., Dayot, N. Dumont, Emerman, A., Enari, Y., Falke, P. J., Farrell, J., Fielitz, W., Fortin, E., Fragnaud, J., Franchino, S., Gantel, L., Gigliotti, K., Gong, D., Grabas, A., Grohs, P., Guettouche, N., Guillemin, T., Guo, D., Guo, J., Hasley, L., Hayes, C., Hentges, R., Hervas, L., Hils, M., Hobbs, J., Hoffman, A., Hoffmann, D., Horn, P., Hryn'ova, T., Iconomidou-Fayard, L., Iguchi, R., James, T., Johns, K., Junkermann, T., Kahra, C., Kay, E. F., Keeler, R., Haghighat, S. Ketabchi, Kinget, P., Knoops, E., Kolbasin, A., Krieger, P., Kuppambatti, J., Kurchaninov, L. L., Ladygin, E., Lafrasse, S., Landon, M. P. J., Lanni, F., Latorre, S., Laugier, D., Lazzaroni, M., Le, X., Bourlout, P. Le, Lee, C. A., Lefebvre, M., Leite, M. A. L., Leroy, C., Li, X., Li, Z., Liang, F., Liu, H., Liu, C., Liu, T., Ma, H., Ma, L. L., Mahon, D. J., Mallik, U., Mansoulie, B., Maslennikov, A. L., Matsuzawa, N., McPherson, R. A., Menke, S., Milic, A., Minami, Y., Molina, E., Monnier, E., Morange, N., Morvaj, L., Mueller, J., Mwewa, C., Narayan, R., Nikiforou, N., Ochoa, I., Oishi, R., Damazio, D. Oliveira, Owen, R. E., Pancake, C., Panchal, D. K., Perrot, G., Pleier, M. -A., Poffenberger, P., Porter, R., Quan, S., Rabel, J., Roy, A., Rutherfoord, J. P., Sabatini, F., Salomon, F., Sauvan, E., Schaffer, A. C., Schamberger, R. D., Schwemling, Ph., Secord, C., Selem, L., Sexton, K., Shafto, E., Oliveira, M. V. Silva, Simion, S., Singh, S., Sippach, W., Snesarev, A. A., Snyder, S., Spalla, M., Stärz, S., Straessner, A., Strizenec, P., Stroynowski, R., Sulin, V. V., Tanaka, J., Tang, S., Tapprogge, S., Tartarelli, G. F., Tateno, G., Terashi, K., Tisserant, S., Tompkins, D., Unal, G., Unal, M., Uno, K., Vallier, A., de Souza, S. Vieira, Walker, R., Wang, Q., Wang, C., Wang, R., Wessels, M., Wingerter-Seez, I., Wolniewicz, K., Wu, W., Xiandong, Z., Xu, R., Xu, H., Yamamoto, S., Yang, Y., Ye, J., Zaghia, H., Zang, J., Zhang, T., Zhu, H. L., Zhulanov, V., Zonca, E., and Zuk, G.

Subjects
Physics - Instrumentation and Detectors, High Energy Physics - Experiment
Abstract

The Phase-I trigger readout electronics upgrade of the ATLAS Liquid Argon calorimeters enhances the physics reach of the experiment during the upcoming operation at increasing Large Hadron Collider luminosities. The new system, installed during the second Large Hadron Collider Long Shutdown, increases the trigger readout granularity by up to a factor of ten as well as its precision and range. Consequently, the background rejection at trigger level is improved through enhanced filtering algorithms utilizing the additional information for topological discrimination of electromagnetic and hadronic shower shapes. This paper presents the final designs of the new electronic elements, their custom electronic devices, the procedures used to validate their proper functioning, and the performance achieved during the commissioning of this system., Comment: 56 pages, 41 figures, 6 tables

Published
2022
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3. Substance Use in the Performing Artist with Chronic Pain.

Author

Hay, Kaitlyn R, Jardot, Jasmyne, Huhn, Andrew S, and Tompkins, D Andrew

Subjects
Allied Health and Rehabilitation Science, Health Sciences, Sports Science and Exercise, Substance Misuse, Neurosciences, Prescription Drug Abuse, Clinical Research, Pain Research, Brain Disorders, Chronic Pain, Drug Abuse (NIDA only), Good Health and Well Being, Analgesics, Opioid, Cross-Sectional Studies, Humans, Opioid-Related Disorders, Pain Measurement, Clinical Sciences, Performing Arts and Creative Writing, Orthopedics, Allied health and rehabilitation science, Sports science and exercise
Abstract

ObjectivesTo evaluate how performing artists (PAs) with chronic pain may differ on measures of substance use compared to non-PA controls.Methods157 participants reporting chronic pain (89 PAs, 68 non-PA controls) completed an online cross-sectional survey. Participants were assessed for self-reported current pain severity using the Brief Pain Inventory Short-Form, opioid misuse risk using the Screener and Opioid Assessment for Patients with Pain-Revised, opioid withdrawal using the Subjective Opiate Withdrawal Scale, and symptoms of opioid use disorder (OUD) using a modified version of the DSM-V checklist.ResultsPAs had lower pain severity (p

Published
2022

4. “I got a bunch of weed to help me through the withdrawals”: Naturalistic cannabis use reported in online opioid and opioid recovery community discussion forums

Author

Meacham, Meredith C, Nobles, Alicia L, Tompkins, D Andrew, and Thrul, Johannes

Subjects
Pharmacology and Pharmaceutical Sciences, Biomedical and Clinical Sciences, Substance Misuse, Drug Abuse (NIDA only), Mental health, Good Health and Well Being, Analgesics, Opioid, Cannabinoid Receptor Agonists, Cannabinoids, Cannabis, Humans, Marijuana Abuse, Marijuana Smoking, Medical Marijuana, Narcotics, Opioid-Related Disorders, Social Media, Social Support, Substance Withdrawal Syndrome, General Science & Technology
Abstract

A growing body of research has reported on the potential opioid-sparing effects of cannabis and cannabinoids, but less is known about specific mechanisms. The present research examines cannabis-related posts in two large online communities on the Reddit platform ("subreddits") to compare mentions of naturalistic cannabis use by persons self-identifying as actively using opioids versus persons in recovery. We extracted all posts mentioning cannabis-related keywords (e.g., "weed", "cannabis", "marijuana") from December 2015 through August 2019 from an opioid use subreddit and an opioid recovery subreddit. To investigate how cannabis is discussed at-scale, we identified and compared the most frequent phrases in cannabis-related posts in each subreddit using term-frequency-inverse document frequency (TF-IDF) weighting. To contextualize these findings, we also conducted a qualitative content analysis of 200 random posts (100 from each subreddit). Cannabis-related posts were about twice as prevalent in the recovery subreddit (n = 908; 5.4% of 16,791 posts) than in the active opioid use subreddit (n = 4,224; 2.6% of 159,994 posts, p < .001). The most frequent phrases from the recovery subreddit referred to time without using opioids and the possibility of using cannabis as a "treatment." The most frequent phrases from the opioid subreddit referred to concurrent use of cannabis and opioids. The most common motivations for using cannabis were to manage opioid withdrawal symptoms in the recovery subreddit, often in conjunction with anti-anxiety and GI-distress "comfort meds," and to enhance the "high" when used in combination with opioids in the opioid subreddit. Despite limitations in generalizability from pseudonymous online posts, this examination of reports of naturalistic cannabis use in relation to opioid use identified withdrawal symptom management as a common motivation. Future research is warranted with more structured assessments that examines the role of cannabis and cannabinoids in addressing both somatic and affective symptoms of opioid withdrawal.

Published
2022

6. Methadone maintenance patients lack analgesic response to a cumulative intravenous dose of 32 mg of hydromorphone

Author

Agin-Liebes, Gabrielle, Huhn, Andrew S, Strain, Eric C, Bigelow, George E, Smith, Michael T, Edwards, Robert R, Gruber, Valerie A, and Tompkins, D Andrew

Subjects
Pharmacology and Pharmaceutical Sciences, Biomedical and Clinical Sciences, Clinical Sciences, Neurosciences, Opioids, Drug Abuse (NIDA only), Chronic Pain, Clinical Trials and Supportive Activities, Opioid Misuse and Addiction, Substance Misuse, Pain Research, Clinical Research, 6.1 Pharmaceuticals, Good Health and Well Being, Analgesics, Opioid, Drug Tolerance, Humans, Hydromorphone, Methadone, Opioid-Related Disorders, Methadone maintenance, Analgesia, Pain, Quantitative sensory testing, Medical and Health Sciences, Psychology and Cognitive Sciences, Substance Abuse, Biochemistry and cell biology, Pharmacology and pharmaceutical sciences, Epidemiology
Abstract

ObjectivesAcute pain management in patients with opioid use disorder who are maintained on methadone presents unique challenges due to high levels of opioid tolerance in this population. This randomized controlled study assessed the analgesic and abuse liability effects of escalating doses of acute intravenous (IV) hydromorphone versus placebo utilizing a validated experimental pain paradigm, quantitative sensory testing (QST).MethodsIndividuals (N = 8) without chronic pain were maintained on 80-100 mg/day of oral methadone. Participants received four IV, escalating/incremental doses of hydromorphone over 270 min (32 mg total) or four placebo doses within a session test day. Test sessions were scheduled at least one week apart. QST and abuse liability measures were administered at baseline and after each injection.ResultsNo significant differences between the hydromorphone and placebo control conditions on analgesic indices for any QST outcomes were detected. Similarly, no differences on safety or abuse liability indices were detected despite the high doses of hydromorphone utilized. Few adverse events were detected, and those reported were mild in severity.ConclusionsThe findings demonstrate that methadone-maintained individuals are highly insensitive to the analgesic effects of high-dose IV hydromorphone and may require very high doses of opioids, more efficacious opioids, or combined non-opioid analgesic strategies to achieve adequate analgesia.

Published
2021

8. Individuals with Chronic Pain Who Misuse Prescription Opioids Report Sex-Based Differences in Pain and Opioid Withdrawal.

Author

Huhn, Andrew S, Tompkins, D Andrew, Campbell, Claudia M, and Dunn, Kelly E

Subjects
Pharmacology and Pharmaceutical Sciences, Biomedical and Clinical Sciences, Clinical Sciences, Psychology, Substance Misuse, Drug Abuse (NIDA only), Clinical Research, Prescription Drug Abuse, Pain Research, Chronic Pain, Adult, Analgesics, Opioid, Catastrophization, Ethnicity, Female, Humans, Male, Middle Aged, Opioid-Related Disorders, Pain Measurement, Prescription Drug Misuse, Sex Characteristics, Socioeconomic Factors, Substance Withdrawal Syndrome, Surveys and Questionnaires, Young Adult, Opioids, Opioid Misuse, Sex Differences, Opioid Withdrawal, Public Health and Health Services, Anesthesiology, Clinical sciences, Health services and systems, Clinical and health psychology
Abstract

Objective Individuals with chronic pain who misuse prescription opioids are at high risk for developing opioid use disorder and/or succumbing to opioid overdose. The current study conducted a survey to evaluate sex-based differences in pain catastrophizing, opioid withdrawal, and current pain in persons with co-occurring chronic pain and opioid misuse. We hypothesized that women with chronic pain who misused prescription opioids would self-report higher pain ratings compared with men and that the relationship between pain catastrophizing and self-reported current pain would be moderated by symptoms of opioid withdrawal in women only. Design Survey assessment of the relationship between pain and opioid misuse. Setting Online via Amazon Mechanical Turk. Participants Persons with ongoing chronic pain who also misused prescription opioids on one or more days in the last 30 days were eligible (N = 181). Methods Participants completed demographic and standardized assessments including the Brief Pain Inventory (BPI), Pain Catastrophizing Scale (PCS), and Subjective Opiate Withdrawal Scale (SOWS). Results Women reported higher levels of current (P

Published
2019

9. The relationship between pupil diameter and other measures of opioid withdrawal during naloxone precipitated withdrawal

Author

Bergeria, Cecilia L, Huhn, Andrew S, Tompkins, D Andrew, Bigelow, George E, Strain, Eric C, and Dunn, Kelly E

Subjects
Pharmacology and Pharmaceutical Sciences, Biomedical and Clinical Sciences, Neurosciences, Substance Misuse, Drug Abuse (NIDA only), Clinical Research, Adult, Analgesics, Opioid, Female, Humans, Male, Morphine, Naloxone, Narcotic Antagonists, Opiate Substitution Treatment, Opioid-Related Disorders, Pupil, Substance Withdrawal Syndrome, Opioid use disorder, Opioid withdrawal, Medical and Health Sciences, Psychology and Cognitive Sciences, Substance Abuse, Biochemistry and cell biology, Pharmacology and pharmaceutical sciences, Epidemiology
Abstract

BackgroundUnderstanding mechanisms of physiological opioid withdrawal symptoms can inform treatment strategies. This secondary analysis evaluated the association between mydriasis (dilated pupils), a commonly-assessed opioid withdrawal metric, with self- and observer-rated opioid withdrawal severity.MethodNinety-five participants with opioid physical dependence were stabilized with morphine before receiving an injection of the opioid antagonist naloxone to precipitate withdrawal. Pupil diameter, the Subjective Opiate Withdrawal Scale (SOWS), and the Clinical Opiate Withdrawal Scale (COWS) were collected at baseline and in 15-minute intervals for 120 min following naloxone administration. Pearson product-moment correlations and linear regressions characterized the relationships between pupil measurements (baseline and peak naloxone-induced) and self- and observer-rated measures of withdrawal. Repeated-measures ANOVAs tested whether self and observer-rated withdrawal severity corresponded to unique patterns in pupil changes.ResultsBaseline pupil diameter significantly correlated with SOWS and COWS peak scores. Peak naloxone-induced pupil diameter significantly correlated with SOWS scores only. Peak changes in pupil from baseline did not correspond to peak changes in self- and observer-rated withdrawal scales.ConclusionsThis study suggests that pupil diameter measurements were more closely associated with acute opioid withdrawal severity than changes in pupil diameter. Prospective research examining the mechanisms underlying the relationship between pupil diameter and opioid withdrawal severity are warranted.

Published
2019

10. Prefrontal cortex response to drug cues, craving, and current depressive symptoms are associated with treatment outcomes in methadone-maintained patients

Author

Huhn, Andrew S, Sweeney, Mary M, Brooner, Robert K, Kidorf, Michael S, Tompkins, D Andrew, Ayaz, Hasan, and Dunn, Kelly E

Subjects
Biological Psychology, Pharmacology and Pharmaceutical Sciences, Biomedical and Clinical Sciences, Psychology, Depression, Brain Disorders, Clinical Research, Mental Health, Behavioral and Social Science, Substance Misuse, Neurosciences, Evaluation of treatments and therapeutic interventions, 6.1 Pharmaceuticals, Mental health, Good Health and Well Being, Adolescent, Adult, Analgesics, Opioid, Craving, Cues, Female, Humans, Male, Methadone, Opiate Substitution Treatment, Opioid-Related Disorders, Prefrontal Cortex, Spectroscopy, Near-Infrared, Substance Abuse Detection, Treatment Outcome, Young Adult, Medical and Health Sciences, Psychology and Cognitive Sciences, Psychiatry, Biological psychology
Abstract

Methadone maintenance is an effective treatment for opioid use disorder, yet many methadone-maintained patients (MMPs) continue to struggle with chronic relapse. The current study evaluated whether functional near-infrared spectroscopy (fNIRS) could identify prefrontal cortex (PFC) markers of ongoing opioid use in MMPs, and whether clinical measures of depression and self-report measures of craving would also be associated with opioid use. MMPs (n = 29) underwent a drug cue reactivity paradigm during fNIRS measurements of PFC reactivity. Self-reported opioid craving (measured by a visual analog scale; 0-100) was collected before and after drug cue reactivity, and depressive symptoms were assessed via the 17-item Hamilton Depression Rating Scale (HAM-D). Hierarchical regression and partial correlations were used to evaluate associations between weekly urine drug screens over a 90-day follow-up period and fNIRS, craving, and HAM-D assessments. Neural response to drug cues in the left lateral PFC, controlling for age, sex, and days in treatment was significantly associated with percent opioid-negative urine screens during follow-up (∆F1, 24 = 13.19, p = 0.001, ∆R2 = 0.30), and correctly classified 86% of MMPs as either using opioids, or abstaining from opioids (χ2(4) = 16.28, p = 0.003). Baseline craving (p

Published
2019

11. Sex differences in measures of central sensitization and pain sensitivity to experimental sleep disruption: implications for sex differences in chronic pain

Author

Smith, Michael T, Remeniuk, Bethany, Finan, Patrick H, Speed, Traci J, Tompkins, D Andrew, Robinson, Mercedes, Gonzalez, Kaylin, Bjurstrom, Martin F, and Irwin, Michael R

Subjects
Prevention, Chronic Pain, Pain Research, Neurosciences, Clinical Research, Sleep Research, Adult, Antipruritics, Attention, Capsaicin, Central Nervous System Sensitization, Female, Hot Temperature, Humans, Hyperalgesia, Male, Pain Measurement, Pain Threshold, Polysomnography, Sex Characteristics, Sleep, Sleep Deprivation, sleep disruption, pain sensitivity, central sensitization, sex differences, temporal summation, secondary hyperalgesia, capsaicin, chronic pain, sex effects, Biological Sciences, Medical and Health Sciences, Psychology and Cognitive Sciences, Neurology & Neurosurgery
Abstract

Females demonstrate heightened central sensitization (CS), a risk factor for chronic pain characterized by enhanced responsivity of central nervous system nociceptors to normal or subthreshold input. Sleep disruption increases pain sensitivity, but sex has rarely been evaluated as a moderator and few experiments have measured CS. We evaluated whether two nights of sleep disruption alter CS measures of secondary hyperalgesia and mechanical temporal summation in a sex-dependent manner. We also evaluated differences in measures of pain sensitivity. Seventy-nine healthy adults (female n = 46) participated in a randomized crossover experiment comparing two consecutive nights of eight pseudorandomly distributed forced awakenings (FA [-200 min sleep time]) against two nights of undisturbed sleep (US). We conducted sensory testing the mornings following Night 2; the heat-capsaicin pain model was used to induce secondary hyperalgesia. FA reduced total sleep time (REM and NREM Stage 3) more profoundly in males. We observed divergent, sex-dependent effects of FA on secondary hyperalgesia and temporal summation. FA significantly increased secondary hyperalgesia in males and significantly increased temporal summation in females. Sex differences were not attributable to differential sleep loss in males. FA also significantly reduced heat-pain threshold and cold pressor pain tolerance, independently of sex. Sleep disruption enhances different pain facilitatory measures of CS in males and females suggesting that sleep disturbance may increase risk for chronic pain in males and females via distinct pathways. Findings have implications for understanding sex differences in chronic pain and investigating sleep in chronic pain prevention efforts.

Published
2019

12. Analgesic Effects of Hydromorphone versus Buprenorphine in Buprenorphine-maintained Individuals.

Author

Huhn, Andrew S, Strain, Eric C, Bigelow, George E, Smith, Michael T, Edwards, Robert R, and Tompkins, D Andrew

Subjects
Chronic Pain, Drug Abuse (NIDA only), Clinical Trials and Supportive Activities, Neurosciences, Substance Misuse, Pain Research, Clinical Research, Evaluation of treatments and therapeutic interventions, 6.1 Pharmaceuticals, Adult, Analgesia, Analgesics, Opioid, Buprenorphine, Double-Blind Method, Female, Humans, Hydromorphone, Male, Opioid-Related Disorders, Pain, Treatment Outcome, Clinical Sciences, Anesthesiology
Abstract

BackgroundManaging acute pain in buprenorphine-maintained individuals in emergency or perioperative settings is a significant challenge. This study compared analgesic and abuse liability effects of adjunct hydromorphone and buprenorphine using quantitative sensory testing, a model of acute clinical pain, in persons maintained on 12 to 16 mg sublingual buprenorphine/naloxone.MethodsParticipants (N = 13) were enrolled in a randomized within-subject, double-blind, placebo-controlled three-session experiment. Each session used a cumulative dosing design with four IV injections (4, 4, 8, and 16 mg of hydromorphone or 4, 4, 8, and 16 mg of buprenorphine); quantitative sensory testing and abuse liability assessments were measured at baseline and after each injection. The primary analgesia outcome was change from baseline cold pressor testing; secondary outcomes included thermal and pressure pain testing, as well as subjective drug effects and adverse events.ResultsA significant two-way interaction between study drug condition and dose was exhibited in cold pressor threshold (F10,110 = 2.14, P = 0.027) and tolerance (F10,110 = 2.69, P = 0.006). Compared to after placebo, participants displayed increased cold pressor threshold from baseline after cumulative doses of 32 mg of IV hydromorphone (means ± SD) (10 ± 14 s, P = 0.035) and 32 mg of buprenorphine (3 ± 5 s, P = 0.0.39) and in cold pressor tolerance after cumulative doses of 16 mg (18 ± 24 s, P = 0.018) and 32 mg (48 ± 73 s, P = 0.041) IV hydromorphone; cold pressor tolerance scores were not significant for 16 mg (1 ± 15 s, P = 0.619) or 32 mg (7 ± 16 s, P = 0.066) buprenorphine. Hydromorphone and buprenorphine compared with placebo showed greater ratings on subjective measures of high, any drug effects, good effects, and drug liking. Adverse events were more frequent during the hydromorphone compared with buprenorphine and placebo conditions for nausea, pruritus, sedation, and vomiting.ConclusionsIn this acute clinical pain model, high doses of IV hydromorphone (16 to 32 mg) were most effective in achieving analgesia but also displayed higher abuse liability and more frequent adverse events. Cold pressor testing was the most consistent measure of opioid-related analgesia.

Published
2019

13. A hidden aspect of the U.S. opioid crisis: Rise in first-time treatment admissions for older adults with opioid use disorder

Author

Huhn, Andrew S, Strain, Eric C, Tompkins, D Andrew, and Dunn, Kelly E

Subjects
Pharmacology and Pharmaceutical Sciences, Biomedical and Clinical Sciences, Aging, Drug Abuse (NIDA only), Brain Disorders, Substance Misuse, Clinical Research, Evaluation of treatments and therapeutic interventions, 6.1 Pharmaceuticals, Good Health and Well Being, Age Factors, Aged, Cross-Sectional Studies, Female, Heroin, Hospitalization, Humans, Male, Middle Aged, Opioid-Related Disorders, Sex Factors, Older adults, Opioid use disorder, Treatment, Trend analysis, Prescription opioids, Medical and Health Sciences, Psychology and Cognitive Sciences, Substance Abuse, Biochemistry and cell biology, Pharmacology and pharmaceutical sciences, Epidemiology
Abstract

BackgroundOlder adults with opioid use disorder (OUD) are a medically complex population. The current study evaluated trends in older adults seeking treatment for OUD, with a focus on primary heroin versus prescription opioid use. This study also compared older adults with OUD to the younger OUD population on demographics and drug use behaviors.MethodsPublicly available data from state-certified addiction treatment centers were collected via the Treatment Episode Data Set - Admissions (TEDS-A) between 2004-2015. This study utilized Joinpoint Regression to conduct a cross-sectional, longitudinal analysis of trends in first-time treatment admissions for OUD in adults 55 and older (older adults; n = 400,421) versus adults under the age of 55 (n = 7,795,839). Given the rapid increase in older adults seeking treatment for OUD between 2013-2015, secondary outcomes include changes in demographics and drug use between 2012 (as a baseline year) and 2015.ResultsThe proportion of older adults seeking treatment for OUD rose steadily between 2004-2013 (41.2% increase; p-trend = 0.046), then rapidly between 2013-2015 (53.5% increase; p-trend = 0.009). The proportion of older adults with primary heroin use more than doubled between 2012-2015 (p

Published
2018

14. Induction to Methadone 80 mg in the First Week of Treatment of PatientsWho Use Fentanyl: A Case Series From an Outpatient Opioid Treatment Program.

Author

Steiger, Scott, McCuistian, Caravella, Suen, Leslie W., Shapiro, Brad, Tompkins, D. Andrew, and Bazazi, Alexander R.

Abstract

Objectives: Current guidelines for methadone titration may unnecessarily delay reaching effective doses for patients using fentanyl, resulting in an increased risk of ongoing fentanyl use, dissatisfaction with treatment, and early dropout. Development and evaluation of rapid methadone induction protocols may improve treatment for patients using fentanyl. Methods: Retrospective chart review was conducted for patients admitted in 2022 to a single licensed opioid treatment program (OTP) where a rapid induction protocol provides methadone 40 mg on day 1, 60 mg on day 2, and 80 mg on day 3 to patients using fentanyl <65 years old without significant medical comorbidities. The primary feasibility outcome was completion of the protocol, defined by receipt of methadone dose 80 mg or more on treatment day 7. The primary safety outcomes were oversedation, nonfatal overdose, and death. A secondary outcome was retention in treatment at 30 days. Results: Rapid induction was ordered for 93 patients and completed by 65 (70%). Average dose on day 7 for patients who completed was 89 mg (SD 9.5 mg) versus 49 mg (SD 14.0 mg) for those who did not. No episodes of oversedation, nonfatal overdose, or death were observed. At 30 days, 85% of the patients who had the rapid protocol ordered (79/93) were retained, with 88% (57/65) who completed the protocol retained versus 79% (22/28) who did not complete (OR 1.9, 95% CI 0.6--6.2). Conclusions: Rapid induction to methadone 80 mg by day 7 was feasible for outpatients using fentanyl in this study at a single OTP. No significant safety events were identified. [ABSTRACT FROM AUTHOR]

Published
2024
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15. Extended‐release injectable naltrexone for opioid use disorder: a systematic review

Author

Jarvis, Brantley P, Holtyn, August F, Subramaniam, Shrinidhi, Tompkins, D Andrew, Oga, Emmanuel A, Bigelow, George E, and Silverman, Kenneth

Subjects
Clinical and Health Psychology, Public Health, Health Sciences, Psychology, Clinical Research, Clinical Trials and Supportive Activities, Prevention, Brain Disorders, Neurosciences, Evaluation of treatments and therapeutic interventions, 6.1 Pharmaceuticals, Analgesics, Opioid, Delayed-Action Preparations, Drug Overdose, Humans, Injections, Intramuscular, Medication Adherence, Naltrexone, Narcotic Antagonists, Opioid-Related Disorders, Treatment Outcome, Extended-release, heroin, injectable, medication-assisted treatment, naltrexone, opioid use disorder, prescription opioids, Medical and Health Sciences, Psychology and Cognitive Sciences, Substance Abuse, Public health, Clinical and health psychology
Abstract

AIMS:To review systematically the published literature on extended-release naltrexone (XR-NTX, Vivitrol® ), marketed as a once-per-month injection product to treat opioid use disorder. We addressed the following questions: (1) how successful is induction on XR-NTX; (2) what are adherence rates to XR-NTX; and (3) does XR-NTX decrease opioid use? Factors associated with these outcomes as well as overdose rates were examined. METHODS:We searched PubMed and used Google Scholar for forward citation searches of peer-reviewed papers from January 2006 to June 2017. Studies that included individuals seeking treatment for opioid use disorder who were offered XR-NTX were included. RESULTS:We identified and included 34 studies. Pooled estimates showed that XR-NTX induction success was lower in studies that included individuals that required opioid detoxification [62.6%, 95% confidence interval (CI) = 54.5-70.0%] compared with studies that included individuals already detoxified from opioids (85.0%, 95% CI = 78.0-90.1%); 44.2% (95% CI = 33.1-55.9%) of individuals took all scheduled injections of XR-NTX, which were usually six or fewer. Adherence was higher in prospective investigational studies (i.e. studies conducted in a research context according to a study protocol) compared to retrospective studies of medical records taken from routine care (6-month rates: 46.7%, 95% CI = 34.5-59.2% versus 10.5%, 95% CI = 4.6-22.4%, respectively). Compared with referral to treatment, XR-NTX reduced opioid use in adults under criminal justice supervision and when administered to inmates before release. XR-NTX reduced opioid use compared with placebo in Russian adults, but this effect was confounded by differential retention between study groups. XR-NTX showed similar efficacy to buprenorphine when randomization occurred after detoxification, but was inferior to buprenorphine when randomization occurred prior to detoxification. CONCLUSIONS:Many individuals intending to start extended-release naltrexone (XR-NTX) do not and most who do start XR-NTX discontinue treatment prematurely, two factors that limit its clinical utility significantly. XR-NTX appears to decrease opioid use but there are few experimental demonstrations of this effect.

Published
2018

16. Frequency and correlates of sleep disturbance in methadone and buprenorphine-maintained patients

Author

Dunn, Kelly E, Finan, Patrick H, Tompkins, D Andrew, and Strain, Eric C

Subjects
Biological Psychology, Clinical and Health Psychology, Psychology, Behavioral and Social Science, Neurosciences, Brain Disorders, Clinical Research, Clinical Trials and Supportive Activities, Sleep Research, Mental health, Good Health and Well Being, Adult, Buprenorphine, Comorbidity, Female, Humans, Male, Methadone, Middle Aged, Opiate Substitution Treatment, Opioid-Related Disorders, Sleep Wake Disorders, Treatment Outcome, United States, Opioid use disorder, Sleep, Opioid maintenance treatment, Public Health and Health Services, Substance Abuse, Public health, Biological psychology, Clinical and health psychology
Abstract

BackgroundOpioid use disorder (OUD) is a significant public health problem, and opioid maintenance treatment (OMT) on methadone or buprenorphine is a common approach. This study characterized sleep impairment in patients maintained on methadone or buprenorphine, and evaluated its association with psychiatric and medical comorbidities.MethodsParticipants (N=185) maintained on methadone (N=125) or buprenorphine (N=60) for OUD completed the Medical Outcomes Study Sleep Scale (MOS) to provide a point-prevalence assessment of sleep impairment. Measures of lifetime problems and current functioning were also examined and compared as both a function of OMT and level of sleep impairment.ResultsParticipants reported high levels of sleep impairment on the MOS, including not getting the amount of sleep they needed (42.9%), not sleeping enough to feel rested (39.6%) and trouble falling asleep (23.3%) or falling back asleep after waking (25.8%). Few differences were observed between OMT groups, and psychiatric dysfunction emerged as the most robust predictor of sleep impairment ratings. Patients with sleep impairment, independent of OMT medications, also reported current opioid withdrawal, psychiatric impairment, negative affect, and pain.ConclusionsResults demonstrate substantial and clinically-significant impairments in sleep that are associated with a variety of current problems that could impact OMT outcomes and decrease quality of life. Outcomes support the development of methods to improve sleep in OMT patients, and to examine the degree to which sleep improvements may be associated with improvements in mood and other health-related measures.

Published
2018

17. To take or not to take: the association between perceived addiction risk, expected analgesic response and likelihood of trying novel pain relievers in self‐identified chronic pain patients

Author

Tompkins, D Andrew, Huhn, Andrew S, Johnson, Patrick S, Smith, Michael T, Strain, Eric C, Edwards, Robert R, and Johnson, Matthew W

Subjects
Clinical and Health Psychology, Public Health, Health Sciences, Psychology, Brain Disorders, Clinical Research, Chronic Pain, Substance Misuse, Basic Behavioral and Social Science, Behavioral and Social Science, Prevention, Pain Research, Neurosciences, Prescription Drug Abuse, Drug Abuse (NIDA only), Mental health, Good Health and Well Being, Adult, Analgesics, Analgesics, Opioid, Attitude to Health, Cross-Sectional Studies, Decision Making, Female, Humans, Male, Middle Aged, Perception, Risk, Risk Assessment, Substance-Related Disorders, Surveys and Questionnaires, Addiction, analgesic medications, BARQ, chronic pain, decision-making, probability discounting, SOAPP-R, Medical and Health Sciences, Psychology and Cognitive Sciences, Substance Abuse, Public health, Clinical and health psychology
Abstract

Background and aimsProbability discounting refers to the effect of outcome uncertainty on decision making. Using probability discounting, we examined the degree to which self-identified chronic pain patients (CPP) were likely to try a novel analgesic medication given increasing addiction risk. We postulated that propensity for opioid misuse, trait impulsivity and previous opioid experience would be associated positively with likelihood of risky medication use.DesignThis cross-sectional on-line study determined state/trait associations with addiction-related medication decisions in CPP.SettingUS-based CPP participated via Amazon Mechanical Turk; data were collected and analyzed in Baltimore, Maryland.ParticipantsA total of 263 CPP (70.6% female) participated in the study from 12-13 December 2014.MeasurementsCPP responded to the Benefit versus Addiction Risk Questionnaire (BARQ) assessing likelihood of taking a hypothetical once-daily oral analgesic medication as a function of two factors: risk of addiction (0-50%) and duration of expected complete pain relief (3, 30 or 365 days). The primary outcome was the BARQ, quantified as area under the curve (AUC). Grouping of CPP at high or low risk for opioid misuse was based on the Screener and Opioid Assessment for Patients with Pain-Revised (SOAPP-R). Predictors included previous experience with opioids, as well as various measures of chronic pain and mental health.FindingsAcross hypothetical addiction risk assessed in the BARQ, the likelihood of taking a novel analgesic medication was elevated significantly in patients with high (≥18; n = 137) versus low (

Published
2018

19. The relationship between treatment accessibility and preference amongst out-of-treatment individuals who engage in non-medical prescription opioid use

Author

Huhn, Andrew S, Tompkins, D Andrew, and Dunn, Kelly E

Subjects
Pharmacology and Pharmaceutical Sciences, Biomedical and Clinical Sciences, Behavioral and Social Science, Prescription Drug Abuse, Drug Abuse (NIDA only), Clinical Research, Substance Misuse, Brain Disorders, Health Services, 8.1 Organisation and delivery of services, Health and social care services research, Generic health relevance, Mental health, Good Health and Well Being, Adult, Analgesics, Opioid, Humans, Insurance, Health, Opioid-Related Disorders, Physicians, Primary Care, Prescriptions, Self Report, Surveys and Questionnaires, Opioid use disorder, Medication-assisted treatment, Prescription opioid, Treatment accessibility, Insurance, Medical and Health Sciences, Psychology and Cognitive Sciences, Substance Abuse, Biochemistry and cell biology, Pharmacology and pharmaceutical sciences, Epidemiology
Abstract

BackgroundRelatively little is known regarding the perception of medication-assisted treatments (MATs) and other treatment options amongst individuals that engage in non-medical prescription opioid use. This study surveyed out-of-treatment individuals that misuse opioids to better understand how perceived access to treatment shapes treatment preference.MethodsParticipants (n=357) were out-of-treatment adults registered as workers on the Amazon Mechanical Turk platform who reported current non-medical prescription opioid use. Participants were surveyed regarding demographics, insurance status, attitudes toward opioid use disorder (OUD) treatments, and self-reported symptoms of OUD.ResultsParticipants who were male, did not have health insurance, and knew that counseling-type services were locally available were most likely to first attempt counseling/detox treatments (χ2(6)=30.19, p

Published
2017

20. Providing chronic pain management in the “Fifth Vital Sign” Era: Historical and treatment perspectives on a modern-day medical dilemma

Author

Tompkins, D Andrew, Hobelmann, J Greg, and Compton, Peggy

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Health Sciences, Neurosciences, Pharmacology and Pharmaceutical Sciences, Drug Abuse (NIDA only), Brain Disorders, Clinical Research, Substance Misuse, Pain Research, Chronic Pain, Health Services, Health and social care services research, 8.1 Organisation and delivery of services, Generic health relevance, Good Health and Well Being, Adult, Aged, Analgesics, Opioid, Comparative Effectiveness Research, History, 17th Century, History, 18th Century, History, 19th Century, History, 20th Century, History, 21st Century, Humans, Interdisciplinary Communication, Intersectoral Collaboration, Middle Aged, Pain Management, Research, United States, Vital Signs, Opioids, Chronic pain, Chronic pain management, Multidisciplinary pain treatment, John J. Bonica, Medical and Health Sciences, Psychology and Cognitive Sciences, Substance Abuse, Biochemistry and cell biology, Pharmacology and pharmaceutical sciences, Epidemiology
Abstract

BackgroundOver 100 million Americans are living with chronic pain, and pain is the most common reason that patients seek medical attention. Despite the prevalence of pain, the practice of pain management and the scientific discipline of pain research are relatively new fields compared to the rest of medicine - contributing to a twenty-first century dilemma for health care providers asked to relieve suffering in the "Fifth Vital Sign" era.MethodsThis manuscript provides a narrative review of the basic mechanisms of chronic pain and history of chronic pain management in the United States - including the various regulatory, health system and provider factors that contributed to the decline of multidisciplinary pain treatment in favor of the predominant opioid treatment strategy seen today. Multiple non-opioid pain treatment strategies are then outlined. The manuscript concludes with three key questions to help guide future research at the intersection of pain and addiction.ConclusionsThe assessment and treatment of chronic pain will continue to be one of the most common functions of a health care provider. To move beyond an over reliance on opioid medications, the addiction and pain research communities must unite with chronic pain patients to increase the evidence base supporting non-opioid analgesic strategies.

Published
2017

21. Temporal preference in individuals reporting chronic pain

Author

Tompkins, D Andrew, Johnson, Patrick S, Smith, Michael T, Strain, Eric C, Edwards, Robert R, and Johnson, Matthew W

Subjects
Pharmacology and Pharmaceutical Sciences, Biomedical and Clinical Sciences, Clinical Sciences, Brain Disorders, Pain Research, Substance Misuse, Drug Abuse (NIDA only), Neurosciences, Clinical Research, Chronic Pain, Adult, Aged, Analgesics, Opioid, Behavior, Addictive, Choice Behavior, Delay Discounting, Female, Humans, Male, Middle Aged, Neuropsychological Tests, Opioid-Related Disorders, Reward, Delay discounting, Chronic pain, Addiction, Opioid misuse, Amazon Mechanical Turk, Medical and Health Sciences, Psychology and Cognitive Sciences, Anesthesiology, Biomedical and clinical sciences, Health sciences, Psychology
Abstract

Opioid therapy for pain is associated with an increased risk for substance use disorders. This study's purpose was to determine the association between opioid misuse propensity (Screener and Opioid Assessment for Patients in Pain-Revised) and delay discounting (DD), a behavioral process linked to substance use disorders, which quantifies the extent to which outcomes are devalued because of their delay. Participants reporting chronic pain (N = 249) answered pain and opioid use questions and then completed 4 DD tasks. Each of these tasks assessed either money or pain consequences, framed as either rewards or punishments. Each task involved hypothetical choices between immediate smaller vs delayed larger consequences. The extant Monetary Choice Questionnaire assessed DD of money rewards, and a modified version assessed discounting of money losses (immediate smaller loss vs larger delayed loss). Based on the Monetary Choice Questionnaire, the novel Pain Relief Choice Questionnaire assessed choices between an immediate short duration of pain relief vs a longer duration of pain relief. Similarly, the novel Additional Pain Choice Questionnaire assessed choices between an immediate short duration of additional pain vs a longer duration of additional pain. Discounting of both additional pain and money losses were significantly associated with high Screener and Opioid Assessment for Patients in Pain-Revised scores-indicating participants at greatest risk for opioid misuse discount future punishments rather than future rewards compared with those at low risk. Measures of DD may have promise in more accurately identifying individuals at highest risk for opioid misuse during chronic opioid therapy.

Published
2016

22. The Growing Regulation of Conversion Therapy.

Author

Drescher, Jack, Schwartz, Alan, Casoy, Flávio, McIntosh, Christopher A, Hurley, Brian, Ashley, Kenneth, Barber, Mary, Goldenberg, David, Herbert, Sarah E, Lothwell, Lorraine E, Mattson, Marlin R, McAfee, Scot G, Pula, Jack, Rosario, Vernon, and Tompkins, D Andrew

Subjects
Human Society, Commerce, Management, Tourism and Services, Strategy, Management and Organisational Behaviour, Good Health and Well Being, LGBT, conversion therapy, ethics, gay, homosexuality, legislative bans, lesbian, licensing, psychiatry, psychotherapy, reparative therapy, sexual orientation, sexual orientation change efforts, state policies
Abstract

Conversion therapies are any treatments, including individual talk therapy, behavioral (e.g. aversive stimuli), group therapy or milieu (e.g. "retreats or inpatient treatments" relying on all of the above methods) treatments, which attempt to change an individual's sexual orientation from homosexual to heterosexual. However these practices have been repudiated by major mental health organizations because of increasing evidence that they are ineffective and may cause harm to patients and their families who fail to change. At present, California, New Jersey, Oregon, Illinois, Washington, DC, and the Canadian Province of Ontario have passed legislation banning conversion therapy for minors and an increasing number of US States are considering similar bans. In April 2015, the Obama administration also called for a ban on conversion therapies for minors. The growing trend toward banning conversion therapies creates challenges for licensing boards and ethics committees, most of which are unfamiliar with the issues raised by complaints against conversion therapists. This paper reviews the history of conversion therapy practices as well as clinical, ethical and research issues they raise. With this information, state licensing boards, ethics committees and other regulatory bodies will be better able to adjudicate complaints from members of the public who have been exposed to conversion therapies.

Published
2016

23. Recruitment Techniques for Alcohol Pharmacotherapy Clinical Trials

Author

Tompkins, D Andrew, Sides, Jessica A, Harrison, Joseph A, and Strain, Eric C

Subjects
Clinical and Health Psychology, Psychology, Alcoholism, Alcohol Use and Health, Clinical Research, Brain Disorders, Comparative Effectiveness Research, Clinical Trials and Supportive Activities, Substance Misuse, Prevention, Good Health and Well Being, alcohol-use disorders, clinical trials, recruitment, advertisement methods, alcohol use disorders, Pharmacology and Pharmaceutical Sciences, Substance Abuse, Clinical and health psychology
Abstract

ObjectivesAlcohol use disorders (AUDs) represent a large public health burden with relatively few efficacious pharmacotherapies. Randomized controlled trials (RCTs) for new AUD therapies can be hampered by ineffective recruitment, leading to increased trial costs. The current analyses examined the effectiveness of recruitment efforts during two consecutive outpatient RCTs of novel AUD pharmacotherapies conducted between 2009 and 2012.MethodsDuring an initial phone screen, participants identified an ad source for learning about the study. Qualified persons were then scheduled for in-person screens. The present analyses examined demographic differences amongst the eight ad sources utilized. Recruitment effectiveness was determined by dividing the number of persons meeting criteria for an in-person screen by the total number of callers from each ad source. Cost-effectiveness was determined by dividing total ad source cost by number of screens, participants randomized, and completers.Results1,813 calls resulted in 1,005 completed phone screens. The most common ad source was TV (34%), followed by print (29%), word-of-mouth (11%), flyer (8%), internet (5%), radio (5%), bus ad (2%), and billboard (1%). Participants reporting bus ads (46%), billboard (44%), or print ads (34%) were significantly more likely than the other sources to meet criteria to be scheduled for in-person screens. The most cost-effective ad source was print ($2,506 per completer), while bus ad was the least cost-effective ($13,376 per completer).ConclusionsRecruitment in AUD RCTs can be successful using diverse advertising methods. The present analyses favored use of print ads as most cost-effective.

Published
2015

24. Characterizing pain and associated coping strategies in methadone and buprenorphine-maintained patients

Author

Dunn, Kelly E, Finan, Patrick H, Tompkins, D Andrew, Fingerhood, Michael, and Strain, Eric C

Subjects
Pharmacology and Pharmaceutical Sciences, Biomedical and Clinical Sciences, Clinical Sciences, Neurosciences, Clinical Research, Pain Research, Substance Misuse, Drug Abuse (NIDA only), Chronic Pain, Brain Disorders, 7.1 Individual care needs, Management of diseases and conditions, Adaptation, Psychological, Adult, Analgesics, Opioid, Buprenorphine, Female, Humans, Maintenance Chemotherapy, Male, Methadone, Middle Aged, Opioid-Related Disorders, Pain Management, Pain Threshold, Prevalence, Chronic pain, Coping, Opioid, Medical and Health Sciences, Psychology and Cognitive Sciences, Substance Abuse, Biochemistry and cell biology, Pharmacology and pharmaceutical sciences, Epidemiology
Abstract

BackgroundChronic pain is common among patients receiving opioid maintenance treatment (OMT) for opioid use disorder. To aid development of treatment recommendations for coexisting pain and opioid use disorder, it is necessary to characterize pain treatment needs and assess whether needs differ as a function of OMT medication.MethodsA point-prevalence survey assessing pain and engagement in coping strategies was administered to 179 methadone and buprenorphine-maintained patients.ResultsForty-two percent of participants were categorized as having chronic pain. Methadone patients had greater severity of pain relative to buprenorphine patients, though both groups reported high levels of interference with daily activities, and participants with pain attended the emergency room more frequently relative to participants without pain. Only 2 coping strategies were being utilized by more than 50% of participants (over-the-counter medication, prayer).ConclusionsResults indicate that pain among OMT patients is common, severe, and of significant impairment. Methadone patients reported greater severity pain, particularly worse pain in the past 24h, though interference from pain in daily activities did not vary as a function of OMT. Most participants with pain were utilizing few evidenced-based pain coping strategies. Increasing OMT patient access to additional pain treatment strategies is an opportunity for immediate intervention, and similarities across OMT type suggest interventions do not need to be customized to methadone vs. buprenorphine patients.

Published
2015

27. Is diabetes mellitus associated with increased incidence and disease-specific mortality in endometrial cancer? A systematic review and meta-analysis of cohort studies

Author

Liao, Caiyun, Zhang, Dongyu, Mungo, Chemtai, Tompkins, D Andrew, and Zeidan, Amer M

Subjects
Reproductive Medicine, Biomedical and Clinical Sciences, Cancer, Diabetes, Clinical Research, Prevention, Good Health and Well Being, Cause of Death, Cohort Studies, Diabetes Complications, Endometrial Neoplasms, Female, Humans, Incidence, Diabetes mellitus, Endometrial cancer, Disease-specific mortality, Systematic review, Meta-analysis, Oncology and Carcinogenesis, Paediatrics and Reproductive Medicine, Oncology & Carcinogenesis, Clinical sciences, Oncology and carcinogenesis, Reproductive medicine
Abstract

ObjectiveTo assess the association between diabetes mellitus (DM) and the incidence and disease-specific mortality of endometrial cancer (EC).MethodsMEDLINE, EMBASE and conference abstracts of the 2011-2013 Annual Meetings of Society of Gynecological Oncology were searched for reports of original cohort studies that enrolled diabetic and non-diabetic women who were free of EC at baseline to compare the incidence and disease-specific mortality of EC by DM status. The included reports were examined for demographic characteristics of study populations, study design, effect measures and risk of bias. Statistical heterogeneity was evaluated with Chi-square test of the Cochrane Q statistics at the 0.05 significance level and I(2) statistic. Publication bias was assessed by visual examination of a funnel plot and the Egger's test for small-study effects.ResultsTwenty-nine cohort studies (17 prospective, 12 retrospective) were eligible for this review, 23 of which reported EC incidence, five reported disease-specific mortality and one reported both. For incidence of EC among women with versus without DM, the summary relative risk (RR) was 1.89 (95%CI, 1.46-2.45; p

Published
2014

28. Topiramate for cocaine dependence during methadone maintenance treatment: A randomized controlled trial

Author

Umbricht, Annie, DeFulio, Anthony, Winstanley, Erin L, Tompkins, D Andrew, Peirce, Jessica, Mintzer, Miriam Z, Strain, Eric C, and Bigelow, George E

Subjects
Pharmacology and Pharmaceutical Sciences, Biomedical and Clinical Sciences, Comparative Effectiveness Research, Clinical Trials and Supportive Activities, Brain Disorders, Clinical Research, Drug Abuse (NIDA only), Neurosciences, Substance Misuse, Behavioral and Social Science, 6.1 Pharmaceuticals, Evaluation of treatments and therapeutic interventions, Mental health, Good Health and Well Being, Adolescent, Adult, Cocaine-Related Disorders, Double-Blind Method, Female, Fructose, Humans, Male, Methadone, Middle Aged, Narcotics, Neuroprotective Agents, Opiate Substitution Treatment, Patient Compliance, Substance Abuse Detection, Topiramate, Treatment Outcome, Young Adult, Cocaine dependence, Antiepileptic, Glutamate, GABA, Contingency Management, Medical and Health Sciences, Psychology and Cognitive Sciences, Substance Abuse, Biochemistry and cell biology, Pharmacology and pharmaceutical sciences, Epidemiology
Abstract

BackgroundDual dependence on opiate and cocaine occurs in about 60% of patients admitted to methadone maintenance and negatively impacts prognosis (Kosten et al. 2003. Drug Alcohol Depend. 70, 315). Topiramate (TOP) is an antiepileptic drug that may have utility in the treatment of cocaine dependence because it enhances the GABAergic system, antagonizes the glutamatergic system, and has been identified by NIDA as one of only a few medications providing a "positive signal" warranting further clinical investigation. (Vocci and Ling, 2005. Pharmacol. Ther. 108, 94).MethodIn this double-blind controlled clinical trial, cocaine dependent methadone maintenance patients (N=171) were randomly assigned to one of four groups. Under a factorial design, participants received either TOP or placebo, and monetary voucher incentives that were either contingent (CM) or non-contingent (Non-CM) on drug abstinence. TOP participants were inducted onto TOP over 7 weeks, stabilized for 8 weeks at 300 mg daily then tapered over 3 weeks. Voucher incentives were supplied for 12 weeks, starting during the fourth week of TOP induction. Primary outcome measures were cocaine abstinence (Y/N) as measured by thrice weekly urinalysis and analyzed using Generalized Estimating Equations (GEE) and treatment retention. All analyses were intent to treat and included the 12-week evaluation phase of combined TOP/P treatment and voucher intervention period.ResultsThere was no significant difference in cocaine abstinence between the TOP vs. P conditions nor between the CM vs. Non-CM conditions. There was no significant TOP/CM interaction. Retention was not significantly different between the groups.ConclusionTopiramate is not efficacious for increasing cocaine abstinence in methadone patients.

Published
2014

29. Vaccine for cocaine dependence: A randomized double-blind placebo-controlled efficacy trial

Author

Kosten, Thomas R, Domingo, Coreen B, Shorter, Daryl, Orson, Frank, Green, Charles, Somoza, Eugene, Sekerka, Rachelle, Levin, Frances R, Mariani, John J, Stitzer, Maxine, Tompkins, D Andrew, Rotrosen, John, Thakkar, Vatsal, Smoak, Benjamin, and Kampman, Kyle

Subjects
Pharmacology and Pharmaceutical Sciences, Biomedical and Clinical Sciences, Prevention, Drug Abuse (NIDA only), Clinical Trials and Supportive Activities, Vaccine Related, Clinical Research, Immunization, Substance Misuse, Evaluation of treatments and therapeutic interventions, 6.1 Pharmaceuticals, Infection, Good Health and Well Being, Adolescent, Adult, Antibodies, Cocaine, Cocaine-Related Disorders, Double-Blind Method, Ethnicity, Female, Humans, Immunotherapy, Male, Middle Aged, Safety, Treatment Outcome, Vaccination, Vaccines, Young Adult, Vaccine, Clinical trial, Ethnic Groups, Medical and Health Sciences, Psychology and Cognitive Sciences, Substance Abuse, Biochemistry and cell biology, Pharmacology and pharmaceutical sciences, Epidemiology
Abstract

AimsWe evaluated the immunogenicity, efficacy, and safety of succinylnorcocaine conjugated to cholera toxin B protein as a vaccine for cocaine dependence.MethodsThis 6-site, 24 week Phase III randomized double-blind placebo-controlled trial assessed efficacy during weeks 8 to 16. We measured urine cocaine metabolites thrice weekly as the main outcome.ResultsThe 300 subjects (76% male, 72% African-American, mean age 46 years) had smoked cocaine on average for 13 days monthly at baseline. We hypothesized that retention might be better and positive urines lower for subjects with anti-cocaine IgG levels of ≥42 μg/mL (high IgG), which was attained by 67% of the 130 vaccine subjects receiving five vaccinations. Almost 3-times fewer high than low IgG subjects dropped out (7% vs 20%). Although for the full 16 weeks cocaine positive urine rates showed no significant difference between the three groups (placebo, high, low IgG), after week 8, more vaccinated than placebo subjects attained abstinence for at least two weeks of the trial (24% vs 18%), and the high IgG group had the most cocaine-free urines for the last 2 weeks of treatment (OR=3.02), but neither were significant. Injection site reactions of induration and tenderness differed between placebo and active vaccine, and the 29 serious adverse events did not lead to treatment related withdrawals, or deaths.ConclusionsThe vaccine was safe, but it only partially replicated the efficacy found in the previous study based on retention and attaining abstinence.

Published
2014

30. A Double Blind, within Subject Comparison of Spontaneous Opioid Withdrawal from Buprenorphine versus Morphine

Author

Tompkins, D Andrew, Smith, Michael T, Mintzer, Miriam Z, Campbell, Claudia M, and Strain, Eric C

Subjects
Pharmacology and Pharmaceutical Sciences, Biomedical and Clinical Sciences, Clinical Research, Drug Abuse (NIDA only), Prescription Drug Abuse, Clinical Trials and Supportive Activities, Substance Misuse, Pain Research, Neurosciences, Evaluation of treatments and therapeutic interventions, 6.1 Pharmaceuticals, Good Health and Well Being, Adult, Analgesics, Opioid, Buprenorphine, Diagnostic and Statistical Manual of Mental Disorders, Double-Blind Method, Humans, Injections, Intramuscular, Male, Middle Aged, Morphine, Narcotic Antagonists, Opiate Substitution Treatment, Opioid-Related Disorders, Patient Dropouts, Psychiatric Status Rating Scales, Receptors, Opioid, mu, Remission, Spontaneous, Residential Treatment, Severity of Illness Index, Time Factors, Pharmacology & Pharmacy, Pharmacology and pharmaceutical sciences
Abstract

Preliminary evidence suggests that there is minimal withdrawal after the cessation of chronically administered buprenorphine and that opioid withdrawal symptoms are delayed compared with those of other opioids. The present study compared the time course and magnitude of buprenorphine withdrawal with a prototypical μ-opioid agonist, morphine. Healthy, out-of-treatment opioid-dependent residential volunteers (N = 7) were stabilized on either buprenorphine (32 mg/day i.m.) or morphine (120 mg/day i.m.) administered in four divided doses for 9 days. They then underwent an 18-day period of spontaneous withdrawal, during which four double-blind i.m. placebo injections were administered daily. Stabilization and spontaneous withdrawal were assessed for the second opioid using the same time course. Opioid withdrawal measures were collected eight times daily. Morphine withdrawal symptoms were significantly (P < 0.05) greater than those of buprenorphine withdrawal as measured by mean peak ratings of Clinical Opiate Withdrawal Scale (COWS), Subjective Opiate Withdrawal Scale (SOWS), all subscales of the Profile of Mood States (POMS), sick and pain (0-100) Visual Analog Scales, systolic and diastolic blood pressure, heart rate, respiratory rate, and pupil dilation. Peak ratings on COWS and SOWS occurred on day 2 of morphine withdrawal and were significantly greater than on day 2 of buprenorphine withdrawal. Subjective reports of morphine withdrawal resolved on average by day 7. There was minimal evidence of buprenorphine withdrawal on any measure. In conclusion, spontaneous withdrawal from high-dose buprenorphine appears subjectively and objectively milder compared with that of morphine for at least 18 days after drug cessation.

Published
2014

31. Expected Performance of the ATLAS Experiment - Detector, Trigger and Physics

Author

The ATLAS Collaboration, Aad, G., Abat, E., Abbott, B., Abdallah, J., Abdelalim, A. A., Abdesselam, A., Abdinov, O., Abi, B., Abolins, M., Abramowicz, H., Acharya, B. S., Adams, D. L., Addy, T. N., Adorisio, C., Adragna, P., Adye, T., Aguilar-Saavedra, J. A., Aharrouche, M., Ahlen, S. P., Ahles, F., Ahmad, A., Ahmed, H., Aielli, G., Akdogan, T., Akesson, T. P. A., Akimoto, G., Alam, M. S., Alam, M. A., Albert, J., Albrand, S., Aleksa, M., Aleksandrov, I. N., Alessandria, F., Alexa, C., Alexander, G., Alexandre, G., Alexopoulos, T., Alhroob, M., Alimonti, G., Alison, J., Aliyev, M., Allport, P. P., Allwood-Spiers, S. E., Aloisio, A., Alon, R., Alonso, A., Alonso, J., Alviggi, M. G., Amako, K., Amaral, P., Amelung, C., Ammosov, V. V., Amorim, A., Amoros, G., Amram, N., Anastopoulos, C., Anders, C. F., Anderson, K. J., Andreazza, A., Andrei, V., Andrieux, M-L., Anduaga, X. S., Anghinolfi, F., Antonaki, A., Antonelli, M., Antonelli, S., Antunovic, B., Anulli, F. A., Arabidze, G., Aracena, I., Arai, Y., Arce, A. T. H., Archambault, J. P., Arfaoui, S., Arguin, J-F., Argyropoulos, T., Arik, E., Arik, M., Armbruster, A. J., Arnaez, O., Arnault, C., Artamonov, A., Arutinov, D., Asai, M., Asai, S., Ask, S., Asman, B., Asner, D., Asquith, L., Assamagan, K., Astbury, A., Astvatsatourov, A., Atkinson, T., Atoian, G., Auerbach, B., Auge, E., Augsten, K., Aurousseau, M. A., Austin, N., Avolio, G., Avramidou, R., Axen, A., Ay, C., Azuelos, G., Azuma, Y., Baak, M. A., Baccaglioni, G., Bacci, C., Bachacou, H., Bachas, K., Backes, M., Badescu, E., Bagnaia, P., Bai, Y., Bailey, D. C., Baines, J. T., Baker, O. K., Pedrosa, F. Baltasar Dos Santos, Banas, E., Banerjee, S., Banfi, D., Bangert, A., Bansal, V., Baranov, S. P., Baranov, S., Barashkou, A., Barber, T. B., Barberio, E. L., Barberis, D., Barbero, M. B., Bardin, D. Y., Barillari, T., Barisonzi, M., Barklow, T., Barlow, N. B., Barnett, B. M., Barnett, R. M., Baron, S., Baroncelli, A., Barr, A. J., Barreiro, F., da Costa, J. Barreiro Guimaraes, Barrillon, P., Bartoldus, R., Bartsch, D., Bastos, J., Bates, R. L., Batley, J. R., Battaglia, A., Battistin, M., Bauer, F., Bazalova, M., Beare, B., Beauchemin, P. H., Beccherle, R. B., Becerici, N., Bechtle, P., Beck, G. A., Beck, H. P., Beckingham, M., Becks, K. H., Bedajanek, I., Beddall, A. J., Beddall, A., Bednar, P., Bednyakov, V. A., Bee, C., Harpaz, S. Behar, Behera, P. K., Beimforde, M., Belanger-Champagne, C., Bell, P. J., Bell, W. H., Bella, G., Bellagamba, L., Bellina, F., Bellomo, M., Belloni, A., Belotskiy, K., Beltramello, O., Ami, S. Ben, Benary, O., Benchekroun, D., Bendel, M., Benedict, B. H., Benekos, N., Benhammou, Y., Benincasa, G. P., Benjamin, D. P., Benoit, M., Bensinger, J. R., Benslama, K., Bentvelsen, S., Beretta, M., Berge, D., Kuutmann, E. Bergeaas, Berger, N., Berghaus, F., Berglund, E., Beringer, J., Bernardet, K., Bernat, P., Bernhard, R., Bernius, C., Berry, T., Bertin, A., Besson, N., Bethke, S., Bianchi, R. M., Bianco, M., Biebel, O., Biesiada, J., Biglietti, M., Bilokon, H., Binet, S., Bingul, A., Bini, C., Biscarat, C., Bischofberger, M., Bitenc, U., Black, K. M., Blair, R. E., Blanchot, G., Blocker, C., Blocki, J., Blondel, A., Blum, W., Blumenschein, U., Boaretto, C., Bobbink, G. J., Bocci, A., Bodine, B., Boek, J., Boelaert, N., Boeser, S., Bogaerts, J. A., Bogouch, A., Bohm, C., Bohm, J., Boisvert, V., Bold, T., Boldea, V., Bondarenko, V. G., Bondioli, M., Boonekamp, M., Booth, C. N., Booth, P. S. L., Booth, J. R. A., Borisov, A., Borissov, G., Borjanovic, I., Borroni, S., Bos, K., Boscherini, D., Bosman, M., Bosteels, M., Boterenbrood, H., Bouchami, J., Boudreau, J., Bouhova-Thacker, E. V., Boulahouache, C., Bourdarios, C., Boyd, J., Boyko, I. R., Braem, A., Branchini, P., Brandenburg, G. W., Brandt, A., Brandt, O., Bratzler, U., Brau, J. E., Braun, H. M., Brelier, B., Bremer, J., Brenner, R., Bressler, S., Breton, D., Brett, N. D., Britton, D., Brochu, F. M., Brock, I., Brock, R., Brodet, E., Broggi, F., Brooijmans, G., Brooks, W. K., Brubaker, E., de Renstrom, P. A. Bruckman, Bruncko, D., Bruneliere, R., Brunet, S., Bruni, A., Bruni, G., Bruschi, M., Buanes, T., Bucci, F. B., Buchholz, P., Buckley, A. G., Budagov, I. A., Buescher, V., Bugge, L., Bujor, F., Bulekov, O., Bunse, M., Buran, T., Burckhart, H., Burdin, S., Burke, S., Busato, E., Buszello, C. P., Butin, F., Butler, B., Butler, J. M., Buttar, C. M., Butterworth, J. M., Byatt, T., Urban, S. Cabrera, Caforio, D., Cakir, O., Calafiura, P., Calderini, G., Calkins, R., Caloba, L. P., Caloi, R., Calvet, D., Camarri, P., Cambiaghi, M., Cameron, D., Segura, F. Campabadal, Campana, S., Campanelli, M., Canale, V., Cantero, J., Garrido, M. D. M. 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Subjects
High Energy Physics - Experiment
Abstract

A detailed study is presented of the expected performance of the ATLAS detector. The reconstruction of tracks, leptons, photons, missing energy and jets is investigated, together with the performance of b-tagging and the trigger. The physics potential for a variety of interesting physics processes, within the Standard Model and beyond, is examined. The study comprises a series of notes based on simulations of the detector and physics processes, with particular emphasis given to the data expected from the first years of operation of the LHC at CERN.

Published
2008

37. Opioid abusers’ ability to differentiate an opioid from placebo in laboratory challenge testing

Author

Antoine, Denis G, Strain, Eric C, Tompkins, D Andrew, and Bigelow, George E

Subjects
Pharmacology and Pharmaceutical Sciences, Biomedical and Clinical Sciences, Clinical Research, Clinical Trials and Supportive Activities, Prescription Drug Abuse, Drug Abuse (NIDA only), Substance Misuse, 6.1 Pharmaceuticals, Evaluation of treatments and therapeutic interventions, Adolescent, Adult, Aged, Analgesics, Opioid, Cross-Over Studies, Discrimination, Psychological, Dose-Response Relationship, Drug, Double-Blind Method, Euphoria, Female, Humans, Male, Middle Aged, Narcotics, Opioid-Related Disorders, Oxycodone, Placebos, Pupil, Young Adult, Abuse liability, Qualification, Opioids, Placebo, Discrimination, Medical and Health Sciences, Psychology and Cognitive Sciences, Substance Abuse, Biochemistry and cell biology, Pharmacology and pharmaceutical sciences, Epidemiology
Abstract

BackgroundAbuse liability assessments influence drug development, federal regulation, and clinical care. One suggested procedure to reduce variability of assessments is a qualification phase, which assesses whether study applicants adequately distinguish active drug from placebo; applicants failing to make this distinction are disqualified. The present analyses assessed differences between qualification phase qualifiers and non-qualifiers.MethodsData were collected from 23 completers of the qualification phase of an abuse liability study. Opioid abusing participants received 30 mg oxycodone and placebo orally on separate days, and were characterized as qualifiers (vs. non-qualifiers) if their peak visual analog scale liking rating for oxycodone was at least 20 points higher than placebo's peak rating. Groups were compared on demographic characteristics, drug history, and physiologic, subject and observer ratings.Results61% of participants were qualifiers and 39% were non-qualifiers. Groups had similar demographic characteristics, drug use histories, and pupillary constriction responses. However, unlike qualifiers, non-qualifiers had an exaggerated placebo response for the liking score (p=0.03) and an attenuated oxycodone response for the liking score (p

Published
2013

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