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Resurgence refers to the relapse of a target behavior following the worsening of a source of alternative reinforcement that was made available during response elimination. Most laboratory analyses of resurgence have used a combination of extinction and alternative reinforcement to reduce target behavior. In contingency-management treatments for alcohol use disorder, however, alcohol use is not placed on extinction. Instead, participants voluntarily abstain from alcohol use to access nondrug alternative reinforcers. Inasmuch, additional laboratory research on resurgence following voluntary abstinence is warranted. The present experiment evaluated resurgence of rats' ethanol seeking following voluntary abstinence produced by differential reinforcement of other behavior (DRO). Lever pressing produced ethanol reinforcers during baseline phases. During DRO phases, lever pressing continued to produce ethanol and food reinforcers were delivered according to resetting DRO schedules. Ethanol and food reinforcers were suspended during resurgence test phases to evaluate resurgence following voluntary abstinence. Lever pressing was elevated during baseline phases and occurred at near-zero rates during DRO phases. During the resurgence test phases, lever pressing increased, despite that it no longer produced ethanol. The procedure introduced here may help researchers better understand the variables that affect voluntary abstinence from ethanol seeking and resurgence following voluntary abstinence., (© 2024 Society for the Experimental Analysis of Behavior.)

Opioid use disorder has become an epidemic in the United States, fuelled by the widespread availability of fentanyl, which produces rapid and intense euphoria followed by severe withdrawal and emotional distress. We developed a new preclinical model of fentanyl seeking in outbred male and female rats using volitional oral self-administration (SA) that can be readily applied in labs without intravascular access. Using a traditional two-lever operant procedure, rats learned to take oral fentanyl vigorously, escalated intake across sessions, and readily reinstated responding to conditioned cues after extinction. Oral SA also revealed individual and sex differences that are essential to studying substance use risk propensity. During a behavioural economics task, rats displayed inelastic demand curves and maintained stable intake across a wide range of fentanyl concentrations. Oral SA was also neatly patterned, with distinct 'loading' and 'maintenance' phases of responding within each session. Using our software DeepSqueak, we analysed ultrasonic vocalizations (USVs), which are innate expressions of current emotional state in rats. Rats produced 50 kHz USVs during loading then shifted quickly to 22 kHz calls despite ongoing maintenance of oral fentanyl taking, reflecting a transition to negative reinforcement. Using fibre photometry, we found that the lateral habenula differentially processed drug cues and drug consumption depending on affective state, with potentiated modulation by drug cues and consumption during the negative affective maintenance phase. Together, these results indicate a rapid progression from positive to negative reinforcement occurs even within an active drug taking session, revealing a within-session opponent process., (© 2023 The Authors. Addiction Biology published by John Wiley & Sons Ltd on behalf of Society for the Study of Addiction.)

Introduction: Patients admitted for allogeneic hematopoietic stem cell transplantation (allo-HSCT) are discharged with multiple new medications. At our institution, a new patient Self Medication Program (SMP) was implemented on the allo-HSCT units. An SMP allows patients to practice self-administration of medications in a controlled environment before discharge. We assessed the impact of the SMP on patient medication knowledge, self-efficacy, adherence, and safety. Patient and staff satisfaction with the SMP was also explored., Methods: Participants in the SMP group received medication counseling by a pharmacist and self-managed their medications with nursing supervision until discharge. Participants in the pre-SMP group received medication counseling by a pharmacist at discharge. All participants completed a Medication Knowledge and Self-Efficacy Questionnaire before discharge and at follow-up. Safety endpoints were assessed for SMP participants., Results: Twenty-six patients in the pre-SMP group and 25 patients in the SMP group completed both questionnaires. Median knowledge scores in the pre-SMP group versus the SMP group were 8.5/10 versus 10/10 at discharge ( p  = 0.0023) and 9/10 versus 10/10 at follow-up ( p  = 0.047). Median self-efficacy scores were 38/39 in the pre-SMP group versus 39/39 in the SMP group at both discharge and follow-up ( p discharge  = 0.11, p follow-up  = 0.10). The SMP was associated with at least 1 medication event in 7 participants, but no medication incidents. Patient and staff surveys showed a positive perceived value of the SMP., Conclusion: Our results demonstrate that the SMP is associated with durable, improved medication knowledge, a trend towards improved self-efficacy, and largely positive perceptions among both staff and patient participants.

Literature data suggest that activation and blockade of the GABAB receptor may produce similar effects on several reward-related behaviours. Accordingly, the present study was designed to investigate whether treatment with the GABAB receptor antagonist, SCH 50911, reproduced the suppressing effect of the GABAB receptor agonist, baclofen, and several positive allosteric modulators of the GABAB receptor on operant oral alcohol self-administration in rats. To this end, Sardinian alcohol-preferring (sP) rats were trained to lever-respond for alcohol (15% v/v) under the fixed ratio (FR) 4 (FR4) schedule of reinforcement. Once lever-responding had stabilized, rats were exposed to test sessions preceded by treatment with SCH 50911 (0, 25, 50, and 100 mg/kg; i.p.). Two independent experiments were conducted, differing solely in the set of rats used. Selectivity of SCH 50911 effect on alcohol self-administration was assessed by evaluating the effect of SCH 50911 (0, 25, 50, and 100 mg/kg; i.p.) on self-administration of a sucrose solution (0.7% w/v) in sP rats exposed to the FR4 schedule. In both 'alcohol' experiments, treatment with SCH 50911 reduced lever-responding for alcohol and amount of self-administered alcohol. SCH 50911 effect was characterized by large interindividual variability, with several instances of dose-unrelated reductions, and frequent occurrence of complete suppression of lever-responding for alcohol. Similar data were collected in the 'sucrose' experiment. These results extend to alcohol self-administration with the notion that activation and blockade of GABAB receptor may produce unidirectional effects on reward-related behaviours; these similarities are discussed in terms of differential contribution of pre- and postsynaptic GABAB receptors., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Alcohol use disorder (AUD) constitutes a major burden to global health. Recently, the translational success of animal models of AUD has come under increased scrutiny. Efforts to refine models to gain a more precise understanding of the neurobiology of addiction are warranted. Appetitive responding for ethanol (seeking) and its consumption (taking) are governed by distinct neurobiological mechanisms. However, consumption is often inferred from appetitive responding in operant ethanol self-administration paradigms, preventing identification of distinct experimental effects on seeking and taking. In the present study, male Long-Evans, Wistar, and Sprague-Dawley rats were trained to lever press for ethanol using a lickometer-equipped system that precisely measures both appetitive and consummatory behavior. Three distinct operant phenotypes emerged during training: 1) Drinkers, who lever press and consume ethanol; 2) Responders, who lever press but consume little to no ethanol; and 3) Non-responders, who do not lever press. While the prevalence of each phenotype differed across strains, appetitive and consummatory behavior was similar across strains within each phenotype. Appetitive and consummatory behaviors were significantly correlated in Drinkers, but not Responders. Analysis of drinking microstructure showed that greater consumption in Drinkers relative to Responders is due to increased incentive for ethanol rather than increased palatability. Importantly, withdrawal from chronic ethanol exposure resulted in a significant increase in appetitive responding in both Drinkers and Responders, but only Drinkers exhibited a concomitant increase in ethanol consumption. Together, these data reveal important strain differences in appetitive and consummatory responding for ethanol and uncover the presence of distinct operant phenotypes., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

A randomised controlled trial was conducted. The primary objective was to evaluate the efficacy of a pillbox for increasing iron supplement compliance by comparing the proportion of pregnant women who had no remaining iron tablets between pregnant women attending ANC who were given a pillbox to use and women with no pillbox in four-week period between ANC visits. The secondary objective was to evaluate the reasons for poor compliance and possible factors associated with the non-compliance. One hundred and ninety pregnant women were enrolled, 95 participants were randomised into each of the groups. The proportion of pregnant women who had no remaining iron tablets at the end was statistically significantly lower in the pillbox group than in the control group [53.3% and 23.1%, respectively, p  < .001, RR2.308 (95% CI 1.515 - 3.517)]. The most common reason given for having of iron tablets remaining was forgetfulness. The visual analog scale (VAS) scores indicated that patient's responsibility feeling, duration of sleep each day and presence of a handicapped or small child in care significantly influenced the proportion of pregnant women who had remaining iron tablets at the end in both groups. We concluded that a pillbox was found to be an effective tool for improving pregnant women's compliance with taking their iron supplements.IMPACT STATEMENT What is already known about this subject? Antenatal care (ANC) influences maternal and neonatal outcomes. The incidence of anaemia in pregnant women is reported to be around 42% and approximately 50% result from iron deficiency. Maternal anaemia increases the risk of foetal low birth weight, preterm birth, perinatal mortality, stillbirth and maternal mortality. What do the results of this study add? The 28-compartment pillbox is effective for improving iron supplement compliance in healthy pregnant women. Forgetfulness is the most common reason given for having remaining iron tablets. The lower score on the visual analog scale of patient's feeling of responsibility, long duration of sleep a day and the presence of a handicapped or small child in their care were significantly associated with having remaining iron tablets. What are the implications are of these finding for clinical practice and/or further research? The 28-compartment pillbox can be implied to routine antenatal care for improving iron supplement compliance in healthy pregnant women. Health care providers should be reminded to encourage compliance with iron supplement prescription in pregnant women who are at risk of poor compliance as indicated by low VAS of the patient's feeling of responsibility, long duration of sleep in a day and pregnant women who have responsibility to take care of handicapped or small children.

A subset of rats that self-administer 3,4-methylenedioxypyrovalerone (MDPV) develop unusually high levels of drug taking. A history of responding maintained by cocaine, but not food, prevents the development of this high-responder phenotype; however, it is unclear how histories of noncontingent cocaine exposure or self-administering drugs from other pharmacological classes would affect its development. In the current studies, 5 groups of male Sprague-Dawley rats were used to determine whether histories of responding maintained by drugs from different pharmacological classes (e.g., MDPV, cocaine, fentanyl, nicotine, or ketamine) would differentially impact the development of the high-responder phenotype when MDPV was available for self-administration. Two additional groups were used to determine whether noncontingent exposure to cocaine would prevent the development of the high-responder phenotype when MDPV was available for self-administration, and whether noncontingent exposure to MDPV would facilitate the development of the high-responder phenotype when cocaine was available for self-administration. Consistent with previous reports, a history of response-contingent cocaine, and to a lesser extent noncontingent cocaine, prevented the MDPV high-responder phenotype; however, when responding was initially maintained by fentanyl, nicotine, or ketamine, the MDPV high-responder phenotype developed in ∼45% of rats. By manipulating behavioral and pharmacological histories prior to evaluating MDPV self-administration, the current studies provide additional evidence that a history of response-contingent (or noncontingent) cocaine can prevent the transition from well regulated to aberrant drug-taking when responding is maintained by MDPV. Although the mechanism(s) that underlies this novel high-responder phenotype are unknown, elucidation may provide insight into individual differences relating to substance use disorder. SIGNIFICANCE STATEMENT: A subset of outbred Sprague-Dawley rats self-administer high levels of the synthetic cathinone 3,4-methylenedioxypyrovalerone (MDPV). Understanding the behavioral and/or pharmacological factors that can prevent the development of dysregulated MDPV self-administration may provide insight into individual differences in vulnerability to develop a substance use disorder., (Copyright © 2021 by The American Society for Pharmacology and Experimental Therapeutics.)

Objective: To explore the experiences of women in Scotland who accessed medical abortion at home up to 12 weeks' gestation, delivered via a telemedicine abortion service implemented in response to the coronavirus (COVID-19) pandemic, to identify areas for improvement and inform service provision., Design: Qualitative interview study., Setting: Abortion service in one National Health Service health board in Scotland., Population or Sample: Twenty women who accessed telemedicine abortion services and self-administered mifepristone and misoprostol at home up to 12 weeks' gestation., Methods: Thematic analysis of semi-structured qualitative interviews, informed by the Framework analytic approach., Main Outcome Measures: Women's experiences of accessing telemedicine for medical abortion at home, specifically: acceptability of the telephone consultation and remote support; views on no pre-abortion ultrasound scan; and self-administration of abortion medications at home., Results: Novel study findings were three-fold: (1) participants valued the option of accessing abortion care via telemedicine and emphasised the benefits of providing a choice of telephone and in-person consultation to suit those with different life circumstances; (2) the quality of abortion care was enhanced by the telemedicine service in relation to access, comfort and flexibility, and ongoing telephone support; (3) participants described being comfortable with, and in some cases a preference for, not having an ultrasound scan., Conclusions: This research demonstrates support for the continuation of telemedicine abortion services beyond the temporary arrangements in place during COVID-19, and lends weight to the argument that offering the option of telemedicine abortion care can enable women to access this essential health service. TWEETABLE ABSTRACT: #Telemedicine provision of medical #abortion at home up to 12 weeks' gestation is acceptable and highly valued by #women #Research #SRHR @nbw80 @doctorjjrw @jeniharden @cameronsharon @mrc&#95;crh @edinuniusher., (© 2021 The Authors. BJOG: An International Journal of Obstetrics and Gynaecology published by John Wiley & Sons Ltd.)

Purpose: To examine how patients self-administer ear drops, ascertain their perceived difficulty in performing the task and determine if they are able to deliver the correct dosage., Materials and Methods: This is a prospective cohort study performed in an otology outpatient clinic with twenty-one subjects with a condition requiring ototopical antibiotics. The number of ear drops applied as well as skills performed during ear drop application was measured. Patient reported difficulty and confidence in application of ear drops data was also obtained., Results: The mean number of drops applied was 2.91 ± 2.1 (target = 3 drops) with a large variance in drop application, range of 0.6 to 9.2 drops. If "correct dosage" is considered 85-115% of the intended dose, then almost half of patients, 47.6%, underdosed with 23.8% that over dosed. Patients reported that the average difficulty in applying drops to themselves was 3.6 (1 being easy and 10 being difficult). Patients reported a high confidence level in applying the correct dose of ear drops of 6.7 (1 being not confident and 10 being very confident)., Conclusions: In our study of 21 patients self-administering ear drops, only 28.6% of patients were able to correctly apply the appropriate treatment dose, with almost half of patients underdosing. Questionnaire data indicated that most patients were unaware they were administering an incorrect dose. Inaccurate administration of ear drops could be problematic and lead to longer durations of symptoms, false treatment failures, and increased costs., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Why do so many people struggle with their medicines despite decades of research on medicines taking? Research into how people experience medicines in their everyday life remains scarce with the majority of research in this area of focusing on whether or not people take their medicines as prescribed. Hence, this study used a phenomenological hermeneutical qualitative design to gain a deeper understanding of individuals' perspectives on the lived experience of medicine-taking. Findings from this study highlight five main themes where participants experience medicines as: 1) life-saving and indispensable, 2) normal and a daily routine, 3) confusing and concerning, 4) unsuitable without adjustment, and 5) intrusive and unwelcome. These results can be the basis for mutually agreed prescribing through a co-creative approach that aims at enhancing open and honest dialogues between patients and healthcare professionals in partnership about medicines., Competing Interests: The authors declare that there is no conflict of interest.

Rationale: Tobacco products are very addictive, partly because they contain nicotine which is reinforcing, but also because they include appealing aromas and tastes. Flavor additives are such sensory stimuli which enhance attractiveness, as well as use and abuse of tobacco and vaping products. Yet, the interaction between these flavor additives and nicotine remains poorly understood., Objectives: We want to understand how flavors may reduce nicotine' aversive taste and how it may enhance its voluntary oral self-administration in mice., Methods: We first studied the effect of flavor additives on nicotine solution palatability in a free bottle choice paradigm. Second, we investigated the effect of vanilla flavoring on the different stages of nicotine (40 μg/ml) oral self-administration in mice., Results: We show that adding flavors increase nicotine palatability and facilitate acquisition and maintenance of oral self-administration when compared to nicotine-alone group. Mice adapt their operant behavior depending on changes in nicotine concentration. All mice reinstate nicotine seeking upon presentation of associated cues. Nevertheless, vanilla-flavored nicotine was not more reinforcing than vanilla-flavored water which was reinforcing enough to drive similar operant response rates., Conclusions: Flavor additives increase nicotine oral consumption and help maintaining operant behavior in mice. Moreover, flavors can be very attractive and can have high reinforcing value by themselves. Thus, it is crucial that the investigation on how taste signals play an important role in modulating oral nicotine intake in rodent models remains explored., (© 2021. This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.)

Rationale: Reducing nicotine content of inhaled tobacco products may prevent nicotine addiction, but the threshold for nicotine reinforcement has not been systematically evaluated in controlled human laboratory studies., Objectives: The current study uses a novel double-blind placebo-controlled intravenous (IV) nicotine self-administration (NSA) model to determine threshold for subjective effects of nicotine and nicotine reinforcement using a forced choice self-administration procedure., Methods: Young adults (n = 34) had 5 laboratory sessions after overnight nicotine abstinence. In each session, participants sampled and rated the subjective effects of an IV dose of nicotine (0.0125, 0.025, 0.05, 0.1, or 0.2 mg nicotine/70 kg bodyweight) versus saline (placebo), then were given a total of 10 opportunities to self-administer either the IV dose of nicotine or placebo., Results: Mixed effect models revealed a significant effect of nicotine dose for positive (i.e., "stimulatory" and "pleasurable"; p < .0001) effects, but not "aversive" effects during sampling period. Post hoc comparisons showed that higher doses (i.e., 0.1 and 0.2 mg) were associated with greater stimulatory, pleasurable, and physiological effects than placebo and lower doses. Mixed effect models revealed that only the highest dose (i.e., 0.2 mg) was consistently preferred over placebo. Sex differences were generally weak (p = .03-.05)., Conclusions: Using our IV nicotine NSA model, the threshold for detecting positive effects of nicotine in young adult smokers is about 0.1 mg, but a higher dose of nicotine, 0.2 mg, is required to produce a consistent nicotine reinforcement. Regarding the regulatory impact, our findings further support the value of nicotine reinforcement threshold as a tobacco regulatory target., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Rationale: Escalation of drug intake and craving are two DSM-5 hallmark symptoms of opioid use disorder (OUD)., Objectives: This study determined if escalation of intake as modeled by long access (LgA) self-administration (SA) and craving measured by reinstatement are related., Methods: Adult male and female Sprague-Dawley rats were trained to self-administer fentanyl across 7 daily 1-h short access (ShA) sessions, followed by 21 SA sessions of either 1- or 6-h duration (ShA or LgA). Following 14 1-h extinction sessions, Experiment 1 assessed reinstatement induced by either fentanyl (10 or 30 µg/kg) or yohimbine (1 or 2 mg/kg), and Experiment 2 assessed reinstatement induced by a drug-associated cue light., Results: Females acquired fentanyl SA faster than males. When shifted to LgA sessions, LgA rats escalated fentanyl intake, but ShA rats did not; no reliable sex difference in the rate of escalation was observed. In extinction, compared to ShA rats, LgA rats initially responded less and showed less decay of responding across sessions. A priming injection of fentanyl induced reinstatement, with LgA rats reinstating more than ShA rats at the 30 µg/kg dose. Yohimbine (1 mg/kg) also induced reinstatement, but there was no effect of access group or sex. With cue-induced reinstatement, LgA females reinstated less than LgA males and ShA females., Conclusion: Among the different reinstatement tests assessed, escalation of fentanyl SA increased only drug-primed reinstatement, suggesting a limited relationship between escalation of drug intake and craving (reinstatement) for OUD., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Patients with opioid use disorder experience high rates of relapse during recovery, despite successful completion of rehabilitation programs. A key factor contributing to this problem is the long-lasting nature of drug-seeking behavior associated with opioid use. We modeled this behavior in a rat drug self-administration paradigm in which drug-seeking is higher after extended abstinence than during the acute abstinence phase. The goal of this study was to determine the contribution of discrete or discriminative drug cues and drug dosage to time-dependent increases in drug-seeking. We examined heroin-seeking after 2 or 21 days of abstinence from two different self-administration cue-context environments using high or low doses of heroin and matched animals for their drug intake history. When lower dosages of heroin are used in discriminative or discrete cue protocols, drug intake history contributed to drug-seeking after abstinence, regardless of abstinence length. Incubation of opioid craving at higher dosages paired with discrete drug cues was not dependent on drug intake. Thus, interactions between drug cues and drug dosage uniquely determined conditions permissible for incubation of heroin craving. Understanding factors that contribute to long-lasting opioid-seeking can provide essential insight into environmental stimuli and drug-taking patterns that promote relapse after periods of successful abstinence., (© 2021. The Author(s).)

The mu opioid receptor antagonist/kappa opioid receptor (KOR) partial agonist nalmefene (NMF), a close structural analog of naltrexone (NTX), has been shown to reduce cocaine reward in preclinical models. Given the greater KOR potency and improved bioavailability compared to NTX, NMF may be a promising pharmacotherapeutic for cocaine use disorder (CUD). Here we examine the effects of NMF pretreatment on chronic daily extended access (4h) cocaine intravenous self-administration (IVSA) in adult male C57Bl/6J mice., Methods: separate groups of mice had daily 4h cocaine IVSA sessions (0.25 or 0.5 mg/kg/inf, FR1) for 14 days. Starting on day 8, mice were pretreated with NMF (0, 1, or 10 mg/kg) 30m before each session. A separate group of mice acquired cocaine IVSA [seven days FR1 then four FR3 of 4h daily sessions (0.5 mg/kg/inf)] prior to a single progressive ratio 3 session to examine the effect of 1 mg/kg NMF on cocaine motivation., Results: No significant effect of NMF pretreatment on cocaine intake was observed. Acute pretreatment of 1 mg/kg NMF significantly potentiated cocaine motivation as measured by progressive ratio breakpoint., Conclusions: NMF did not significantly attenuate cocaine intake and increased motivation for cocaine suggesting that NMF may not be suitable for non-abstinent CUD patients. Further research is needed with KOR selective partial or full agonists to determine their effect on cocaine reinforcement., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Intravenous drug self-administration remains the 'gold standard' for assessing abuse liability. Failure of a drug to maintain self-administration might indicate the absence of positive reinforcing effects but might also indicate the presence of aversive effects. Sensitivity to aversive and punishing effects of drugs (as well as nondrug stimuli) might collectively determine the likelihood of use, abuse and relapse. Using a choice procedure, this study compared the effects of remifentanil (mu opioid receptor agonist; 0.001-0.01 mg/kg/infusion) and histamine (H1-4 receptor agonist; 0.32-3.2 mg/kg/infusion), alone and in mixtures, to test the hypothesis that remifentanil/histamine mixtures are less reinforcing compared with remifentanil alone and less punishing compared with histamine alone. Male Sprague-Dawley rats (n = 10) chose between an intravenous infusion + a pellet and a pellet alone. Rats were indifferent to saline, chose remifentanil + a pellet over a pellet alone, and chose a pellet alone over histamine + a pellet. The effects of remifentanil/histamine mixtures generally were different from the constituent doses of histamine alone but not from remifentanil alone. A mixture containing 3.2 mg/kg/infusion histamine and either 0.001 or 0.0032 mg/kg/infusion remifentanil was not different from saline but was different from the effects of the constituent dose, insofar as choice increased compared with 3.2 mg/kg/infusion histamine alone and decreased compared with 0.001 or 0.0032 mg/kg/infusion remifentanil alone. Reinforcing doses of remifentanil combined with punishing doses of histamine can yield mixtures that are neither preferred nor avoided, offering 'proof-of-principle' for using drug mixtures to avoid adverse effects of opioid receptor agonists., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Opioid use disorder imposes great societal harm in the United States and in countries worldwide. Animal models that accurately capture motivational changes that occur in opioid dependence are critical to studying this disorder. The present study used a model of opioid vapor self-administration combined with a behavioral economics approach to determine whether rats would be more motivated to "work" to defend their baseline intake of fentanyl (i.e., more inelastic demand) following sufficiently frequent, intense, and chronic exposure to self-administered vaporized fentanyl. Male rats were allowed to respond for deliveries of 1.5-s of vaporized 10 mg/ml fentanyl solution. Following 15 sessions of short access (ShA; 1 h) vs. long access (LgA; 12 h) to self-administration, we conducted a between-sessions demand curve procedure, and observed significantly more inelastic demand for fentanyl (Essential Value; EV), and increased maximal response output (O max ) in LgA compared with ShA rats. In a subsequent phase, the unit-dose was doubled to 3 s of fentanyl vaporization. After seven ShA vs. LgA sessions, we assessed demand again and found that LgA rats, contrasted to ShA rats, demonstrated significantly higher baseline intake or "hedonic setpoint" (Q 0 ), in addition to significantly increased EV and O max . These results demonstrate that extended access to self-administration of a vaporized opioid causes changes in behavioral economic metrics consistent with development of an addiction-like state in rats. The combination of the vapor model with a translationally relevant behavioral economics framework opens new avenues to study dysregulated motivational processes in substance use disorders., (Published by Elsevier Ltd.)

The US geriatric population is growing and using more opioids than ever before. The purpose of this study was to determine whether aging influenced the reinforcing efficacy of morphine in male and female rats using a rodent intravenous self-administration paradigm. Male and female aged (20-24 months) and young (2-4 months) Wistar rats were tested at 2 doses of morphine (0.75 mg/kg/infusion and 0.25 mg/kg/infusion). During 10 days of self-administration, aged rats took significantly less morphine than their younger counterparts at the 0.25 mg/kg/infusion dose. Aged males also earned significantly fewer infusions on a progressive ration reinforcement schedule at this dose, suggesting that the reinforcing efficacy of morphine is decreased for this group at this dose. These effects dissipated when a separate group of animals had access to the 0.75 mg/kg/infusion dose for both sexes. Our results indicate that morphine is less reinforcing at lower doses in aged male, but not female rats. This research has potential clinical implications for the chronic treatments involving opioids in aged individuals., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Introduction: To gain a better understanding of gynecologic oncology patient adherence to oral anticancer agents through both a cross-sectional survey of adherence and qualitative interviews with patients and clinicians regarding their experience with these medications., Methods: Eligible participants completed a survey for this cross-sectional study that included an assessment of adherence, distress, quality of life, and health literacy. Any woman taking an oral anticancer agent for a gynecologic malignancy at a tertiary academic medical center for 30 days or more was eligible. Semi-structured qualitative interviews (n=14) were then conducted to explore experiences with oral anticancer agents. We also conducted a qualitative group interview with physicians and nurse practitioners., Results: One hundred women taking oral anticancer agents were enrolled. Fifty-four percent reported perfect adherence to their medication, 21% reported equivocal adherence (demonstrating at least one nonadherent behavior in the previous 7 days), and 25% reported nonadherence (demonstrating more than one nonadherent behavior in the previous 7 days). Qualitative analysis identified five major themes: ease of use compared with traditional therapy; the mental burden of self-administrated medication; perceived importance of the medication; management of side effects; and the desire for consistent physician communication. Common misperceptions expressed in the health care professional interviews included high adherence to oral medications and a belief that cost was the biggest barrier to adherence., Conclusion: Almost half of the patients surveyed reported equivocal or nonadherence to their oral anticancer agent. The qualitative interviews identified several important themes, many of which were not recognized by physicians and nurse practitioners. These findings highlight the need for patient and health care professional interventions to improve patient adherence.

Background: Patient-reported outcome (PRO) instruments provide robust and effective means of evaluating patients' treatment experience; however, none adequately cover experience using self-injection devices with enhanced features, such as an electromechanical autoinjector (e-Device). The aim of this study was to develop a PRO instrument that accurately assesses patient experience of using an e-Device and to evaluate its psychometric properties., Methods: A mixed-methods approach was taken; two parallel, targeted literature reviews were conducted to identify relevant concepts and existing self-injection PRO instruments that could be adapted. Patient feedback obtained from two focus groups was used to inform initial instrument development. The pilot instrument was then administered in a multicenter, open-label, phase 3 clinical study in which patients self-injected certolizumab pegol using an e-Device, to gather evidence of its psychometric qualities. Exit interviews were conducted with a sub-sample of patients enrolled in the study to confirm the appropriateness and clarity of the items included and cognitively debrief the instrument. Confirmatory factor analysis (CFA) was conducted on all items, and each domain's internal consistency was measured using Cronbach's ɑ., Results: The literature searches identified several e-Device-specific concepts related to device features, device function, side effects/reactions/pain, confidence, and interference/convenience in daily life. Seven existing PRO instruments were identified. The Self-Injection Assessment Questionnaire (SIAQ), containing pre- and post-injection questionnaire modules, was selected as most suitable and adapted using feedback from 19 patients in the two focus groups to form the pilot Assessment of Self-Injection (ASI) questionnaire. CFA resulted in some changes to the grouping of items in the post-injection module domains following psychometric evaluation of the ASI. Internal consistency was satisfactory for all pre- and post-injection domains (ɑ > 0.8). Cognitive debriefing results from 12 patient exit interviews confirmed the ASI's appropriateness and clarity., Conclusions: The ASI was developed iteratively with patient input and was evaluated in its intended clinical context of use. Psychometric analyses indicated promising cross-sectional results; the ASI was well understood and considered relevant by patients self-injecting using the e-Device, suggesting that it could be used in real-world settings to aid with clinical decision making., Trial Registration: NCT03357471.

Aim: The purpose of this brief narrative review is to address the complexities and benefits of extending animal alcohol addiction research to the human domain, emphasizing Allostasis and Incentive Sensitization, two models that inform many pre-clinical and clinical studies., Methods: The work reviewed includes a range of approaches, including: a) animal and human studies that target the biology of craving and compulsive consumption; b) human investigations that utilize alcohol self-administration and alcohol challenge paradigms, in some cases across 10 years; c) questionnaires that document changes in the positive and negative reinforcing effects of alcohol with increasing severity of addiction; and d) genomic structural equation modeling based on data from animal and human studies., Results: Several general themes emerge from specific study findings. First, positive reinforcement is characteristic of early stage addiction and sometimes diminishes with increasing severity, consistent with both Allostasis and Incentive Sensitization. Second, evidence is less consistent for the predominance of negative reinforcement in later stages of addiction, a key tenant of Allostasis. Finally, there are important individual differences in motivation to drink at a given point in time as well as person-specific change patterns across time., Conclusions: Key constructs of addiction, like stage and reinforcement, are by necessity operationalized differently in animal and human studies. Similarly, testing the validity of addiction models requires different strategies by the two research domains. Although such differences are challenging, they are not insurmountable, and there is much to be gained in understanding and treating addiction by combining pre-clinical and clinical approaches., (© The Author(s) 2020. Medical Council on Alcohol and Oxford University Press. All rights reserved.)

Objectives: The aim of this study was to investigate any association between self-rated health (SRH) and general perception about medicines using the Beliefs About Medicine Questionnaire-General (BMQ-G) in Hong Kong hospital outpatients. Moreover, the study aims to demonstrate any association between social desirability bias or response (SDR) and BMQ-G, SRH reporting in this population., Methods: Seven hundred and sixty-nine outpatients, who satisfied the selection criteria, were cordially invited to participate in this study by completing a combined questionnaire of demographic information, BMQ-G, SRH and SDR Set-5 in person, while waiting to collect their medications outside a Hong Kong hospital pharmacy. Results were analysed statistically., Key Findings: The number of valid questionnaires returned for statistical analysis was 698. Logistic regressions indicated age groups, gender and SRH were significant predictors for BMQ-G reporting. Patients aged over 62, male or those with high SRH were less likely to present high BMQ-G scores, compared to patients aged under 45, female or those with low SRH, respectively (OR 0.43, 0.73 and 0.66, respectively, all CIs 95%). Logistic regressions also demonstrated overall BMQ-G, and SRH reporting was unlikely to be associated with SDR (all P > 0.05) although age was a significant predictor for SDR reporting (OR = 1.10; CI 95%)., Conclusions: This study illustrated age groups, gender and self-rated health significantly associated with general medicine beliefs reporting. The possible association between socially desirable bias and general medicine beliefs or self-rated health reporting was insignificant., (© 2020 Royal Pharmaceutical Society.)

Rationale: Virtually all cocaine self-administration studies have used a "unit dose" as a reinforcing stimulus; the subject is a passive recipient of an experimenter-selected dose., Objectives: The present experiments examined the consequence of requiring the subject to actively determine the dose and speed of each injection., Methods: A two-lever procedure was used in which responding on a progressive ratio (PR) schedule provided access to cocaine on a hold down (HD) schedule. With HD, the pump is turned on for the duration that the lever is held down, thus the dose and speed of injection is determined by the behavior of the subject. The procedure allows for the evaluation of both drug taking and drug seeking responses., Results: The results were qualitatively different from PR self-administration studies using unit dose. The self-administered HD dose varied across the session; the self-administered dose was found to inversely correlate with drug levels at the time of access. Importantly, the 2 L-PR-HD procedure identified a subpopulation of subjects that showed extremes in both drug seeking and drug taking. Subjects at the top end of the distribution displayed unprecedented final ratios (> 900) and rapidly self-administered very large doses (> 1.4 mg; ~ 4.2 mg/kg). Manipulation of drug-taking variables (HD access duration and concentration of drug in the pump) showed that the immediacy of a cocaine bolus, not the duration of access, is the major determinant of drug seeking., Conclusions: Incorporating a consummatory response into a PR procedure provides a unique perspective on the interactions of drug-seeking and drug-taking.

Rationale: Although both psilocybin and dextromethorphan (DXM) produce psychedelic-like subjective effects, rates of non-medical use of psilocybin are consistently greater than DXM., Objective: New data are presented from a study of psilocybin and DXM relevant to understanding the features of psilocybin subjective effects that may account for its higher rates of non-medical use., Methods: Single, acute oral doses of psilocybin (10, 20, 30 mg/70 kg), DXM (400 mg/70 kg), and placebo were administered under double-blind conditions to 20 healthy participants with histories of hallucinogen use., Results: High doses of both drugs produced similar time courses and increases in participant ratings of peak overall drug effect strength. Nine subjective effect domains are proposed to be related to the reinforcing effects of psilocybin: liking, visual effects, positive mood, insight, positive social effects, increased awareness of beauty (both visual and music), awe/amazement, meaningfulness, and mystical experience. For most ratings, (1) psilocybin and DXM both produced effects significantly greater than placebo; (2) psilocybin showed dose-related increases; 3, DXM was never significantly higher than psilocybin; (4) the two highest psilocybin doses were significantly greater than DXM. These differences were consistent with two measures of desire to take the drug condition again., Conclusions: This analysis provides new information about domains of psilocybin subjective effects proposed to be related to its reinforcing effects (alternatively described as the "motivation" to use). Observed differences on these domains between psilocybin and DXM are consistent with the relative rates of non-medical use of psilocybin and DXM.

Rationale: Abuse of the psychostimulant methamphetamine (METH) can cause long-lasting damage to brain monoaminergic systems and is associated with profound mental health problems for users, including lasting cognitive impairments. Animal models of METH exposure have been useful in dissecting the molecular effects of the drug on cognition, but many studies use acute, non-contingent "binge" administrations of METH which do not adequately approximate human METH use. Long-term METH exposure via long-access (LgA) self-administration paradigms has been proposed to more closely reflect human use and induce cognitive impairments., Objective: To better understand the role of contingency and patterns of exposure in METH-induced cognitive impairments, we analyzed behavioral and neurochemical outcomes in adult male rats, comparing non-contingent "binge" METH administration with contingent (LgA) METH self-administration and non-contingent yoked partners., Results: Binge METH (40 mg/kg, i.p., over 1 day) dramatically altered striatal and hippocampal dopamine, DOPAC, 5-HT, 5-HIAA, BDNF, and TrkB 75 days after drug exposure. In contrast, 6-h LgA METH self-administration (cumulative 24.8-48.9 mg METH, i.v., over 16 days) altered hippocampal BDNF in both contingent and yoked animals but reduced striatal 5-HIAA in only contingent animals. Neurochemical alterations following binge METH administration were not accompanied by cognitive deficits in Morris water maze, novel object recognition, or Y-maze tests. However, contingent LgA METH self-administration resulted in impaired spatial memory in the water maze., Conclusions: Overall, substantial differences in neurochemical markers between METH exposure and self-administration paradigms did not consistently translate to deficits in cognitive tasks, highlighting the complexity of correlating METH-induced neurochemical changes with cognitive outcomes.

Background: Clinical observations suggest an association between methamphetamine (METH) use and cardiovascular disease, but preclinical studies are lacking. The purpose of the current study was to explore changes in left ventricular function as a potential precursor to cardiovascular disease in a rodent model of METH use., Methods: Male rats were allowed to self-administer either METH or saline for 9 d. On the day following the 4th and 9th self-administration sessions, an echocardiogram was performed to assess left-ventricular parameters under basal conditions and following a low-dose of METH (1 mg/kg)., Results: A low challenge dose of METH resulted in subtle but statistically significant changes in cardiac function during the echocardiogram in both the METH and saline self-administering groups. Further, differences in left-ventricular parameters such as stroke volume and heart rate were observed between METH and saline groups following the 9th self-administration session. Finally, supervised machine learning correctly predicted the self-administration group assignment (saline or METH) using cardiac parameters following the 9th self-administration session., Conclusions: The findings of the current study suggest the heart, specifically the left ventricle, is sensitive to METH. Overall, these findings and emerging clinical observations highlight the need for research to investigate the effects of METH use on the heart., Competing Interests: Declaration of Competing Interest Methamphetamine was generously supplied by the National Institute on Drug Abuse, National Institute of Health, Bethesda, MD. The authors have no further declarations of interest to disclose., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Along with sexual partners of other high-risk groups, men who purchase sex (MWPS) represented 18% of new HIV diagnoses worldwide in 2018. They are therefore an important population for HIV prevention globally. Despite very low HIV testing coverage among MWPS in many countries, the role of HIV self-testing to increase testing coverage has not been explored. We, therefore, conducted a pilot intervention study to evaluate the uptake and acceptability of assisted and unassisted HIV self-testing among MWPS in Indonesia., Methods: MWPS attending seven brothels in Bali between December 2017 and January 2018 were recruited by lay health providers to participate in a brief health survey, and then invited to have a HIV self-test (assisted or unassisted) with an OraQuick® ADVANCE Rapid HIV-1/2 Antibody Test and complete a post-test acceptability survey., Results: A total of 292 men completed the health survey (response rate: 70%) and 188 (64.6%) accepted HIV self-testing. Of these men, 13.3% had ever tested for HIV and 58.9% reported condom use at their last sexual encounter with a brothel-based female sex worker. Nearly all men (98.9%) who accepted a HIV self-test preferred assisted HIV self-testing - of whom 83.9% preferred to be fully assisted and 16.1% opted to be partially assisted and read their results privately. Of the men who accepted the test and showed the result to the lay health providers, 4 (2.1%) received reactive results. Linkage following HIV self-test is a concern, as none of the four men with a reactive result attended HIV testing at the recommended referral HIV testing clinic over a two-month follow-up period., Conclusions: This study is the first to investigate the acceptance of HIV self-testing when offered to MWPS in brothels by lay health providers. The high uptake of HIV self-testing suggests that this testing model is acceptable and could increase the very low HIV testing coverage among MWPS. The strong preference for fully assisted HIV self-testing highlights the importance of involving lay health providers in future testing programs. When scaling up HIV self-testing programmatically, strategies to improve linkage-to-care should be considered and evaluated.

Rationale: The role of negative affect as a motivational factor in animal models of drug addiction has been underexplored in the context of cocaine self-administration., Objectives: The present investigation studied the relationship between magnitude of affective response and quantity of cocaine consumed in order to clarify the affective components that drive drug use in a preclinical model., Methods: Rats self-administered (SA) cocaine 6 h/day for 14 consecutive days while their ultrasonic vocalizations (USVs) were recorded., Results: Animals displayed an increase in 50-kHz call rates (indicating positive affect) when their drug levels were rapidly rising and an increase in 22-kHz call rates (indicating negative affect) when forced to abstain. The rate of 50-kHz calls predicted drug consumption during the 1st week of SA, but not week two. Contrarily, there was a strongly predictive positive association between rate of 22-kHz calls and amount of drug consumed during the 2nd week of SA., Conclusions: Experimental results indicate that after chronic cocaine self-administration, negative affect emerges when animals are deprived of expected drug during withdrawal. Moreover, the increase in USVs indicating negative affect when deprived of drug was directly related to drug intake, concurrent with a decay in the direct relationship between USVs indicating positive affect and drug intake. The present preclinical support for the widely hypothesized shift from positive to negative affect as a salient motivational factor in human drug abuse adds to growing evidence of the unique value of rat USVs for understanding the role of emotion in drug addiction.

Under paradigms of combined intravenous cocaine and ethanol self-administration, the effects on behavior have been poorly explored. Numerous studies have found sex differences in amino acids profile and behavioral responses to each drug, yet few have focused on the interactions between cocaine and ethanol. The main objective of this work was to explore the acquisition and maintenance of intravenous self-administration behavior with a combination of cocaine and ethanol in male and female young adult rats. Likewise, the amino acids profile in blood plasma was quantified 48 hours after the last self-administration session. Male and female 52 days old Wistar rats were randomly assigned to one of 3 groups: i) saline control, ii) cocaine (1 mg/kg bodyweight/injection) and iii) cocaine and ethanol (1 mg + 133 mg/kg bodyweight/ injection). After 24 self-administration sessions carried out on a fixed-ratio-1 schedule, with a limit of 15 doses per session, 14 plasma amino acids were quantified by mean Capillary Electrophoresis technique. The curve of cocaine and ethanol combined self-administration was similar to that associated with cocaine administration alone, with females acquiring self-administration criterion before males. The self-administration of cocaine and ethanol altered the plasma concentration and relative ratios of the amino acid L-Tyrosine. In our intravenous self-administration model, females appeared more vulnerable to acquire abusive consumption of the cocaine and ethanol combination, which altered plasma L-Tyrosine levels., Competing Interests: The authors have declared that no competing interests exist.

Background: Lorcaserin, a high-affinity 5-HT 2C receptor agonist approved for treating obesity, decreased self-administration of oxycodone and cue-induced reinstatement of drug-seeking behavior in preclinical studies. The current investigation is the first clinical trial to evaluate the ability of lorcaserin to alter the reinforcing and subjective effects of oxycodone., Methods: In this 7-week inpatient trial, 12 non-treatment-seeking volunteers (11 males) with moderate-to-severe opioid use disorder were detoxified from opioids. In a randomized cross-over fashion, participants were first stabilized on lorcaserin (10 mg BID) or placebo (0 mg BID). Participants underwent a two-week testing period during which the reinforcing and subjective effects of intranasal oxycodone were examined in verbal choice, cue-exposure, and progressive-ratio choice sessions. The two testing weeks were identical with the exception that during the first week, active oxycodone (10 mg) was available during verbal choice (self-administration) sessions, and during the second week placebo oxycodone was available. Subsequently, participants were stabilized on the other medication condition (placebo or lorcaserin) and underwent the same testing procedures again., Results: Lorcaserin did not alter oxycodone self-administration. However, lorcaserin had a trend to increase "wanting heroin" when oxycodone was available, and to accentuate oxycodone-induced miosis., Conclusion: Under the current experimental conditions, lorcaserin at a dose of 10 mg BID did not reliably decrease the abuse liability of oxycodone, even though the study was sufficiently powered (≥80 %) to detect clinically meaningful differences in the main outcome variables between the placebo and active lorcaserin condition. Future research could explore a wider dose range of lorcaserin and oxycodone., Competing Interests: Declaration of competing interest All authors declare there are no competing financial interests or potential conflicts of interest in relation to the research described., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Medication for idiopathic Parkinson's disease (PD) is for symptomatic relief, and typically, patients are advised to take their medication at agreed regular times. Here, we present a lady with moderate PD and superimposed anxiety for whom this management strategy did not work well as it increased her anxiety significantly around dosing times. She was switched to an PRN regime and although taking the same total dose of levodopa with similar symptom control was overall much happier. Although there are sound reasons behind regular dosing of levodopa (its short duration of action and relationship of clinical response to plasma concentration), a holistic co-created management plan against classical advice but taking into account the psychological burden of disease and medication may in many cases be more appropriate., (© The Author(s) 2020. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: In inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), nonadherence to biologic therapy increases risk of disease flare. The aim of this study was to identify risk factors for nonadherence., Methods: This was a single-center retrospective study evaluating patients with IBD treated at a tertiary care center and prescribed self-injectable biologic therapy using the center's specialty pharmacy. Adherence was defined using medication possession ratio (MPR). Nonadherence was defined as MPR <0.86., Results: Four hundred sixty patients (n = 393 with CD and n = 67 with UC) were evaluated with mean MPR (interquartile range) equaling 0.89 (0.48-1). Overall, 69% of patients were adherent (defined as MPR ≥0.86), 66% of patients with CD and 87% of patients with UC. In univariate analysis, several factors increased risk of nonadherence: CD diagnosis, insurance type, psychiatric history, smoking, prior biologic use, and narcotic use (P < 0.05). In multivariable analysis, Medicaid insurance (odds ratio [OR], 5.5; 95% confidence interval [CI], 1.85-15.6) and CD diagnosis (OR, 2.8; 95% CI, 1.3-6.0) increased risk of nonadherence. In CD, as the number of risk factors increased (narcotic use, psychiatric history, prior biologic use, and smoking), the probability of nonadherence increased. Adherence was 72% in patients with 0-1 risk factors, decreasing to 62%, 61%, and 42% in patients with 2, 3, and 4 risk factors, respectively (P < 0.05)., Conclusions: This study identified risk factors for nonadherence to biologic therapy. In patients with CD, the probability of nonadherence increased as the number of risk factors increased., (Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation 2019.)

Background: There is limited information regarding the impact of patients' perception of injection pain on adherence to treatments, specifically in inflammatory bowel disease (IBD) patients. Therefore, we aimed to determine the impact of the pain associated with the subcutaneous administration of adalimumab in patients with IBD treated with the old formulation and the new low-volume/citrate-free formulation., Methods: A specifically-designed questionnaire was completed by 76 patients with IBD, who started treatment with adalimumab before the availability of the low-volume/citrate-free formulation and were switched to this new formulation. Intensity of pain was measured by using visual analog scales (VAS)., Results: A total of 62 patients (82%) experienced injection-related pain with the initial formulation. The perception of pain was associated with a decreased adherence to the treatment (37%), an increase in pre-administration anxiety (25%) or, as a consequence, the patient required someone else to carry out the injection (21%). Younger age was the only factor associated with pain perception. After switching to the new formulation, perception of pain persisted only in 2 patients (3%). Among those who felt pain with the initial formulation, pre-administration anxiety disappeared in 44%; 32% and 42% stated that the new formulation eased adherence and self-administration., Conclusions: The perception of pain related to the subcutaneous administration of therapy negatively impacts on treatment adherence in IBD patients. Improved formulations for subcutaneous administration of drugs can positively impact patients' convenience and adherence., (Copyright © 2019 Elsevier España, S.L.U. All rights reserved.)

Neuronal defense against oxidative damage is mediated primarily by the glutathione redox system. Traditionally considered a mechanism to protect proteins from irreversible oxidation, mounting evidence supports a role for protein S-glutathionylation in cell signaling in response to changes in intracellular redox status. Here we determined the specific sites on the actin binding protein cofilin that undergo S-glutathionylation. In addition, we show that S-glutathionylation of cofilin reduces its capacity to depolymerize F-actin. We further describe an assay to determine the S-glutathionylation of target proteins in brain tissue from behaving rodents. Using this technique, we show that cofilin in the rat nucleus accumbens undergoes S-glutathionylation during 15-minutes of cued cocaine seeking in the absence of cocaine. Our findings demonstrate that cofilin S-glutathionylation is increased in response to cocaine-associated cues and that increased cofilin S-glutathionylation reduces cofilin-dependent depolymerization of F-actin. Thus, S-glutathionylation of cofilin may serve to regulate actin cycling in response to drug-conditioned cues., Competing Interests: The authors have declared that no competing interests exist.

Objectives: To examine the effect of burden of treatment and multimorbidity on the relationship between baseline characteristics and oral oncolytic agent (OOA) temporary stoppages., Sample & Setting: 272 patients newly prescribed OOAs at six National Cancer Institute-designated comprehensive cancer centers., Methods & Variables: Patients were randomly assigned to an adherence and symptom management group or a usual care/control group. Temporary OOA stoppages, symptom interference, OOA regimen complexity, and multimorbidities were explored. Data were collected at four-week intervals for 12 weeks., Results: Burden of treatment variables and multimorbidity had no significant effect on OOA temporary stoppages. Women and those prescribed kinase inhibitors were significantly more likely to experience a temporary stoppage., Implications for Nursing: Oncology nurses are in a crucial position to educate patients on self-management of OOAs and symptoms. Nurses should be aware of patients who may be more susceptible to severe symptoms, including those with multimorbidities. Future research is needed to better understand OOA stoppages and factors associated with preventing stoppages.

In the United States, black patients are less likely than white patients to receive biologic treatment for their psoriasis. We conducted a qualitative free-listing study to identify patient-generated factors that may explain this apparent racial disparity in psoriasis treatment by comparing the perceptions of biologics and other psoriasis therapies between white and black adults with psoriasis. Participants included 68 white and black adults with moderate to severe psoriasis who had and had not received biologic treatment. Each participant was asked to list words in response to verbal probes querying five psoriasis treatments: self-injectable biologics, infliximab, methotrexate, apremilast, and phototherapy. Salience scores indicating the relative importance of each word were calculated, and salient words were compared across each race/treatment group. Participants who had experience with biologics generally associated positive words with self-injectable biologics. Among biologic-naïve participants, "apprehension," "side effects," and "immune suppression" were most salient. "Unfamiliar" and "dislike needles" were salient only among black participants who were biologic naïve. Participants were generally unfamiliar with the other psoriasis therapies except phototherapy. Unfamiliarity with biologics, particularly among black, biologic-naïve patients, may partly explain the existing racial disparity in biologic treatment for psoriasis and might stem from lack of exposure to or poor understanding of biologics., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Suggestibility, defined as an individual's inclination to accept and internalize messages, has not been studied in relation to alcohol use. Peer conformity, a component of suggestibility, may be related to alcohol use, as peer groups show similarities in patterns of alcohol use. Few studies have assessed how suggestibility and peer conformity relate to alcohol self-administration or to reinforcing effects of alcohol., Aims: This study assessed whether suggestibility and peer conformity were associated with drinking behavior, alcohol self-administration, subjective response to alcohol, and drinking motives and expectancies., Methods: Study 1 participants were alcohol drinkers ( n =20), who completed a laboratory study of free-access intravenous alcohol self-administration. Study 2 participants were adolescents and young adults, age 14-25 ( n =150), with lifetime alcohol use. Participants completed surveys of suggestibility and drinking patterns (Study 1 and 2), subjective alcohol effects (Study 1 only), and alcohol motives and expectancies (Study 2 only)., Results/outcomes: In Study 1, participants with higher levels of suggestiblity self-administered more alcohol, and reported greater subjective alcohol effects. Peer conformity, though correlated with suggestibility, was not related to these measures. In Study 2, participants with higher suggestiblity reported more alcohol consumption, higher drinking motives and alcohol expectancies. Peer conformity was not related to alcohol consumption, but was related to coping and enhancement drinking motives, and all expectancies measures., Conclusions/interpretation: Results indicate that suggestibility, beyond peer conformity, may be a critical factor to study when examining alcohol consumption behavior, and may provide insight into the development of alcohol use disorder.

The purpose of the current study was to examine the feasibility and acceptability of a SystemCHANGE™ intervention in improving medication adherence in older adults with heart failure (HF). Adults age ≥50 years with HF who self-administered diuretics were screened for 2 months using electronic monitoring to determine baseline adherence scores. Participants were randomized into the SystemCHANGE™ or attention-control group if adherence scores were <88%. The SystemCHANGE™ intervention focuses on changing the individual's environment by including medication taking into existing routines, receiving support from individuals who impact routines, and using small experiments with feedback. Challenges were noted by participants in using the electronic medication monitor technology during the screening phase. Lessons learned from this study emphasize the need to revise recruitment procedures and include multiple sites. Education and counseling should be adapted to the cognitive level of the participant and address technology challenges. [Journal of Gerontological Nursing, 45(4), 15-19.]., (Copyright 2019, SLACK Incorporated.)

Background Automated multidose drug dispensing is used to support patients with their medication management. Though multidose drug dispensing systems are frequently used, little is known about patients' experiences with multidose drug dispensing systems. Objective To explore patients' experiences with the initiation and use of multidose drug dispensing systems. Setting A survey was carried out with patients using multidose drug dispensing systems through three community pharmacies. Method A semi-structured interview protocol was designed based on existing literature and a pilot study. Main outcome measures The main outcome measures were (1) patients' experiences with initiating multidose drug dispensing systems and (2) patients' experienced advantages and disadvantages of multidose drug dispensing systems. Results The start of multidose drug dispensing was discussed with 76% of the patients (n = 62). Ninety percent of patients expressed the opinion that the multidose drug dispensing system supported them with their medication management. Sixty patients reported 110 advantages, which can be organized into the following categories: improved medication adherence and medication safety (59%); patient's convenience (40%); and other (1%). Sixty-nine percent of patients reported no disadvantages, 24% had problems opening the bags or outer packaging and 13% had problems with the legibility of the printed text on the bag. Conclusion In concordance with the Dutch guideline, patients are generally involved in the decision to initiate an multidose drug dispensing system. Patients are very satisfied using the system and report multiple advantages. Multidose drug dispensing systems may be further improved by simplifying the manual opening of the bags and improving the legibility of the text on the bags.

Results from clinical studies suggest that drug relapse and craving are often provoked by exposure to drug-associated contexts. Since 2002, this phenomenon has been modeled in laboratory animals using the ABA renewal model. In the classical version of this model, rats with a history of drug self-administration in one context (A) undergo extinction in a different context (B) and reinstate (or relapse to) drug seeking after exposure to the original drug-associated context (A). In a more recent version of the model introduced in 2013, the experimental conditions in context A are identical to those used in the classical model, but drug-reinforced responding in context B is suppressed by probabilistic punishment. The punishment-based ABA renewal model is proposed to resemble abstinence in humans, which is often initiated by the desire to avoid the negative consequences of drug use. The goal of our review is to discuss similarities and differences in mechanisms that play a role in suppression of drug seeking in context B and context-induced relapse to drug seeking in context A in the two models. We first describe psychological mechanisms that mediate extinction and punishment of drug-reinforced responding in context B. We then summarize recent findings on brain mechanisms of context-induced relapse of drug seeking after extinction, or punishment-imposed abstinence. These findings demonstrate both similarities and differences in brain mechanisms underlying relapse in the two variations of the ABA renewal model. We conclude by briefly discussing clinical implications of the preclinical studies.

Objective: To describe women's experiences with subcutaneous depot medroxyprogesterone acetate (DMPA-SC) to inform scale-up of self-administered DMPA-SC., Study Design: We conducted a 12-month randomized controlled trial in Malawi to measure DMPA-SC continuation rates. A total of 731 women presenting at six Ministry of Health clinics or to community health workers (CHWs) in rural communities were randomized to receive DMPA-SC administered by a provider or be trained to self-inject DMPA-SC. Data collectors contacted women after the reinjection window at 3, 6 and 9 months to collect data on satisfaction and use; self-injectors were also queried about storage and disposal of DMPA-SC. We compared frequencies of injection experiences and satisfaction by study group and over time., Results: Ninety-two percent of women who self-injected felt it was easy to do the first time. Women in the self-administered group primarily gave themselves the injection versus having someone else inject them; stored DMPA-SC mostly in bags, often in ways to keep the product away from others; and properly disposed of DMPA-SC in pit latrines. Women in both groups used printed calendars to remember when to get/be given their next injection. Both groups reported high satisfaction with DMPA-SC., Conclusions: Women in low-resource settings can be successfully trained by public sector CHWs and clinic-based providers to self-inject and to appropriately store and dispose of DMPA-SC. DMPA-SC and self-injection are acceptable and feasible in a low-resource setting., Implications: Self-administered and provider-administrated DMPA-SC should be scaled up, and the lessons learned during our trial should be applied to future scale-up efforts., (Published by Elsevier Inc.)

Objective: While there are various medication self-efficacy scales that exist, none assess self-efficacy for appropriate antibiotic use. The Appropriate Antibiotic Use Self-Efficacy Scale (AAUSES) was developed, pilot tested, and its psychometric properties were examined., Methods: Following pilot testing of the scale, a 28-item questionnaire was examined using a sample (n = 289) recruited through the Amazon Mechanical Turk platform. Participants also completed other scales and items, which were used in assessing discriminant, convergent, and criterion-related validity. Test-retest reliability was also examined., Results: After examining the scale and removing items that did not assess appropriate antibiotic use, an exploratory factor analysis was conducted on 13 items from the original scale. Three factors were retained that explained 65.51% of the variance. The scale and its subscales had adequate internal consistency. The scale had excellent test-retest reliability, as well as demonstrated convergent, discriminant, and criterion-related validity., Conclusions: The AAUSES is a valid and reliable scale that assesses three domains of appropriate antibiotic use self-efficacy., Practice Implications: The AAUSES may have utility in clinical and research settings in understanding individuals' beliefs about appropriate antibiotic use and related behavioral correlates. Future research is needed to examine the scale's utility in these settings., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Post-traumatic stress disorder (PTSD) is a debilitating psychological disorder typified by diagnostic symptom clusters including hyperarousal, avoidance, negative cognitions and mood, and intrusive re-experiencing of the traumatic event. Patients with PTSD have been reported to self-medicate with alcohol to ameliorate hyperarousal symptoms associated with the disorder. Research utilizing rodent models of PTSD to emulate this behavioral phenomenon has thus far yielded inconsistent results. In the present study, we examined the effects of a predator-based psychosocial stress model of PTSD on voluntary ethanol consumption. In the first of two experiments, following exposure to a 31-day stress or control paradigm, rats were singly housed during the dark cycle with free access to 1% sucrose solution or 10% ethanol, which was also sweetened with 1% sucrose. Over the course of a 20-day period of ethanol access, stressed rats consumed significantly less ethanol than non-stressed rats. These counterintuitive results prompted the completion of a second experiment which was identical to the first, except rats were also exposed to the two-bottle paradigm for 20 days before the stress or control paradigm. In the second experiment, after the stress manipulation, stressed rats exhibited significantly greater ethanol preference than non-stressed rats. These findings suggest that prior exposure to ethanol influences the subsequent effect of stress on ethanol intake. They also validate the use of the present model of PTSD to examine potential mechanisms underlying stress-related changes in ethanol-seeking behavior., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: In oral agent clinical trials, patients may not be adherent to self-administration of study medication; this nonadherence can affect validity and reliability. Many factors contribute to nonadherence to protocol requirements, and managing patients with fidelity issues is the responsibility of the research team., Objectives: The aim is to identify which group (patients, physicians/principal investigators, nurses, or other personnel) research nurses report as most responsible for protocol nonadherence and to characterize the most observed causes and contributors to nonadherence within each group., Methods: Sixty-seven protocol nurses completed a nine-question survey developed from pilot data. Descriptive statistics and ordinal regressions addressed the objectives of the study., Findings: More than half of the nurses observed clinical trial nonadherence in their practices. Nurses identified challenges regarding physician, patient, and nurse factors. The most frequently identified causes included patients' forgetfulness, refusal to undergo study procedures, inadequate family or caregiver support to complete study activities, ineffective communication, and collaboration within the research team.

Objective: This study assessed training time with the dulaglutide single-use pen (SUP) and the insulin degludec disposable prefilled pen (FlexTouch ® ) in self-injection-naïve patients with type 2 diabetes mellitus (T2DM) in Japan., Methods: This multi-center, open-label, comparative, crossover study measured training time with the dulaglutide SUP vs FlexTouch ® . Participants learned how to use both devices in a randomly assigned order. Healthcare providers (HCP) conducted the training. The primary end-point was the time required to train self-injection-naïve T2DM participants to self-inject correctly using each device. Secondary end-points included performance measures, such as success and error rates, patient perceptions related to ease-of-use, and factors associated with training time and performance., Results: Overall, 48 participants were randomized and completed the study. The mean training time to achieve correct administration was significantly shorter with the dulaglutide SUP vs FlexTouch ® (7.4 min vs 19.7 min, p < .001). The proportions of participants who successfully completed the mock injection without error were similar for both devices. Ninety-two percent (44/48) of participants reported that the dulaglutide SUP was easier to use than FlexTouch ® ., Conclusions: In this study, participants required a shorter training time to achieve correct administration with the dulaglutide SUP, and had a higher preference for the dulaglutide SUP, when compared to FlexTouch ® . These data suggest that the dulaglutide SUP is easy-to-use, which may decrease the burden on HCPs to train diabetic patients how to administer injection therapy and reduce patient injection hurdles, such as needle fear.

Rationale: Adolescence is a period of considerable development of brain and behavior and is the time during which most drug use is initiated., Objective: Age-dependent differences in motivated behaviors may be one of the factors that contribute to heightened vulnerability to developing substance use disorders, so we sought to compare age differences in methamphetamine (METH) and saccharin seeking., Methods: Beginning during adolescence or adulthood, male and female Sprague-Dawley rats were trained to self-administer 0.1% saccharin (via liquid dipper cup) or intravenous METH at one of three doses (0.02, 0.05, 0.08 mg/kg/inf) under increasing fixed ratio schedules of reinforcement. Subsequently, responding for METH (0.02, 0.05, 0.08, or 0.1 mg/kg/inf) under progressive ratio response requirements was assessed in rats that acquired METH self-administration at the highest dose (0.08 mg/kg/inf)., Results: We found that adult-onset rats acquired METH self-administration more readily and exhibited higher motivation compared to adolescent-onset rats, although there were no differences in METH intake during acquisition. Adult rats also acquired saccharin self-administration more readily, but in contrast to METH, there were age and sex differences in saccharin intake driven by high levels of responding in adult females., Conclusions: These findings challenge the prevailing notion that adolescents are hypersensitive to reward and instead raise questions about the potential role of methodological factors on which rodent studies often differ.

Aim: To describe the knowledge as well as current and potential use of self-sampling kits among men who have sex with men (MSM) and to analyse their preferred biological sample and result communication method., Methods: We analyse data of MSM of HIV negative or unknown serostatus from an online survey conducted in eight countries (Belgium, Denmark, Germany, Greece, Portugal, Romania, Slovenia and Spain) between April and December 2016. It was advertised mainly in gay dating websites. We conduct a descriptive analysis of the main characteristics of the participants, and present data on indicators of knowledge, use and potential use of HIV self-sampling as well as their preferences regarding blood or saliva sample and face or non-face-to-face result communication by country of residence., Results: A total of 8.226 participants of HIV negative or unknown serostatus were included in the analysis. Overall, 25.5% of participants knew about self-sampling (range: 18.8-47.2%) and 1.1% had used it in the past (range: 0.3-8.9%). Potential use was high, with 66.6% of all participants reporting that they would have already used it if available in the past (range: 62.1-82.1%). Most (78.6%) reported that they would prefer using a blood-based kit, and receiving the result of the test through a non-face-to-face-method (70.8%), even in the case of receiving a reactive result., Conclusion: The high potential use reported by MSM recruited in eight different European countries suggests that self-sampling kits are a highly acceptable testing methodology that could contribute to the promotion of HIV testing in this population., (© 2018 British HIV Association.)

We assessed predictors of choosing self-administered oral HIV testing in the clinic with supervision versus the standard provider-administered blood test when offered the choice among 149 Kenyan truck drivers, described the types of guidance participants needed during self-testing and predictors of needing guidance. Overall, 56.38% of participants chose the self-test, 23.49% the provider-administered test, and 20.13% refused testing. In the adjusted regression models, each additional unit on the fatalism and self-efficacy scales was associated with 0.97 (p = 0.003) and 0.83 (p = 0.008) times lower odds of choosing the self-test, respectively. Overall, 52.38% of self-testers did so correctly without questions, 47.61% asked questions, and 13.10% required unsolicited correction from the provider. Each additional unit on the fatalism scale was associated with 1.07 times higher odds of asking for guidance when self-testing (p < 0.001). Self-administered oral HIV testing seems to be acceptable and feasible among Kenyan truck drivers, especially if given the opportunity to ask questions.

Aims and Objectives: To explore healthcare providers' and patients' perspectives on self-management of medication during the patients' hospital stay., Background: Self-administration of medications relates to the process in which hospitalised patients-instead of healthcare professionals-prepare and consume medications by themselves. Literature suggests possible advantages of medication self-management such as increased patient satisfaction, adherence to pharmacotherapy and self-care competence., Design: A qualitative descriptive study design was adopted, using semistructured interviews and qualitative content analysis to examine data., Methods: Six physicians, 11 nurses, six hospital pharmacists and seven patients were recruited from one regional hospital and two university hospitals, situated in Belgium. Interviews were conducted between October 2014-January 2015., Results: Strengths of medication self-management were described by participants, relating to benefits of self-management for patients, time-saving benefits for nurses and benefits for better collaboration between patients and healthcare providers. Weaknesses were also apparent for patients as well as for nurses and physicians. Opportunities for self-management of medication were described, relating to the organisation, the patient and the process for implementing self-management. Threats for self-management of medication included obstacles related to implementation of self-managed medications and the actual process of providing medication self-management. A structured overview of conditions that should be fulfilled before allowing self-management of medication concerned patient-related conditions, the self-managed medication and the organisation of self-management of medication., Conclusions: This study provides new insights on the strengths, weaknesses, opportunities and threats from the perspectives of key stakeholders. Interpretation of these findings resulted in an overview of adaptations in the medication management process to facilitate implementation of self-management of medication., Relevance to Clinical Practice: A medication management process for self-management of medication was proposed. Further interventional studies are needed to test and refine this process before implementing it in daily practice., (© 2017 John Wiley & Sons Ltd.)