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Abstract Objective To evaluate measurement and associations between pain severity and opioid craving in individuals with chronic pain on long-term opioid therapy and/or with opioid use disorder. Study Design . Systematic review of randomized controlled trials and observational studies. Methods . The PubMed, EMBASE, and PsycINFO databases were searched in October 2018. Eligible studies evaluated pain severity and opioid craving in individuals with chronic pain on long-term opioid therapy and/or with opioid use disorder. Two reviewers independently screened eligible studies, assessed risk of bias, and extracted data. Results Of 625 studies, 16 fulfilled the inclusion/exclusion criteria of this review and were grouped by diagnostic focus (i.e., chronic pain on long-term opioid therapy, opioid use disorder, or both). Methods of assessment varied considerably across studies, especially with respect to opioid craving in chronic pain populations. Mean levels of pain were at what is considered moderate to severe in individuals with chronic pain and/or opioid use disorder. There was a modest positive relationship between pain and opioid craving that was more pronounced in studies of individuals with opioid use disorder compared with those with chronic pain on long-term opioid therapy. Conclusions Pain severity and opioid craving are likely related, but inconsistencies in measurement limit confidence. The overall quality of evidence is moderate, and careful consideration of how pain and craving are assessed in both chronic pain and opioid use disorder patients is warranted.

The multitude of treatments available for tens of millions of US adults with moderate/severe chronic pain have limited efficacy. Long-term opioid therapy (LTOT) is a widely available option for controlling pain among patients with chronic pain refractory to other treatments. The recent recognition of LTOT inefficacy and complications has led to more frequent opioid tapering, which in turn has revealed its own set of complications. The occurrence of the same set of symptoms—worsening pain, declining function, and clinical instability—in contrasting contexts of LTOT ineffectiveness and opioid tapering has led to increasing recognition of the utility of complex persistent opioid dependence (CPOD), a clinically distinct but biologically similar state compared with opioid use disorder as an explanatory diagnosis/heuristic. Recent guidelines for LTOT tapering have incorporated buprenorphine treatment based on CPOD concepts as a recommended treatment for problems due to opioid tapering with limited supportive evidence. The increasing utilization of buprenorphine for both LTOT ineffectiveness and opioid tapering problems raises the urgent need for a review of the clinical definition, mechanisms, and treatment of CPOD and pertinent policies. In this manuscript, we discuss various issues related to CPOD that requires further clarification through research and policy development.

RationaleMinocycline, a tetracycline antibiotic, inhibits activation of microglia. In preclinical studies, minocycline prevented development of opioid tolerance and opioid-induced hyperalgesia (OIH). The goal of this study was to determine if minocycline changes pain threshold and tolerance in individuals with opioid use disorder who are maintained on agonist treatment.MethodsIn this double-blind, randomized human laboratory study, 20 participants were randomized to either minocycline (200 mg/day) or placebo treatment for 15 days. The study had three test sessions (days 1, 8, and 15 of treatment) and one follow-up visit 1 week after the end of treatment. In each test session, participants were assessed on several subjective and cognitive measures, followed by assessment of pain sensitivity using the Cold Pressor Test (CPT). Daily surveys and cognitive measures using Ecological Momentary Assessment (EMA) were also collected four times a day on days 8 through 14 of treatment, and proinflammatory serum cytokines were assessed before and on the last day of treatment.ResultsMinocycline treatment did not change pain threshold or tolerance on the CPT. Similarly, minocycline did not change severity of pain, opioid craving, withdrawal, or serum cytokines. Minocycline treatment increased accuracy on a Go/No-Go task.ConclusionsWhile these findings do not support minocycline’s effects on OIH, minocycline may have a potential use as a cognitive enhancer for individuals with opioid use disorder, a finding that warrants further systematic studies.

Background Given the current prevalence of both cigarette use and obesity in the United States, identification of dietary patterns that reduce mortality risk are important public health priorities. The objective of the present study was to evaluate the correlation between cigarette use and dietary energy density, a marker for diet quality, in a population of current smokers, former smokers, and never smokers. Methods Data from a nationally representative sample of 5293 adults who participated in the 2013–2014 National Health and Nutrition Examination Surveys (NHANES) were analyzed. Specific survey procedures were used in the analysis to account for sample weights, unequal selection probability, and clustered design when evaluating the association between dietary energy density (ED, energy per weight of food, kcal/g) and current smoking status. Never smokers reported < 100 lifetime cigarettes. Smokers were identified as individuals reporting > 100 lifetime cigarettes and current smoking status was recorded as daily, some days (nondaily), or not at all (former). Results A strong linear relationship was observed between smoking pattern and dietary ED in current smokers. Compared to never smokers, daily smokers and nondaily smokers have significantly higher dietary ED (1.79 vs. 2.02 and 1.88, respectively; both p  < 0.05); demonstrating that any amount of current cigarette consumption is associated with poor diet. Though former smokers had a higher dietary ED than never smokers, this difference still significantly lower than that of current smokers ( p  = 0.002). Conclusion These findings suggest that smoking status is associated with poor diet quality. Former smokers had a slightly lower ED value (1.84) than current non-daily smokers (1.89) but a higher value than never smokers (1.79).

Cocaine use disorder (CUD) is a devastating disorder, impacting both individuals and society. Individuals with CUD face many barriers in accessing treatment for CUD, and most individuals with CUD never receive treatment. In this review, we provide an overview of CUD, including risk factors for CUD, common co-occurring disorders, acute and chronic effects of cocaine use, and currently available pharmacological and behavioral treatments. There are no FDA-approved pharmacological treatments for CUD. Future studies with larger sample sizes and testing treatment combinations are warranted. However, individuals with CUD and co- occurring disorders (eg, a mood or anxiety disorder) may benefit from medication treatments. There are behavioral interventions that have demonstrated efficacy in treating CUD--contingency management (CM) and cognitive-behavioral therapy for substance use disorders (CBT-SUD) in particular--however many barriers remain in delivering these treatments to patients. Following the discussion of current treatments, we highlight some promising emerging treatments, as well as offer a framework that can be used in building a treatment plan for individuals with CUD. Keywords: cocaine, cocaine use disorder, treatment, pharmacotherapy, behavioral interventions

Background Cognitive behavioral therapy for chronic pain (CBT-CP) has a strong evidence base, but little is known about when treatment benefits are achieved. The present study is a secondary analysis of individuals with chronic back pain recruited for a noninferiority trial comparing interactive voice response (IVR) CBT-CP with in-person CBT-CP. Methods On the basis of data from daily IVR surveys, a clinically meaningful change was defined as a 30% reduction in pain intensity (n = 108) or a 45% increase in daily steps (n = 104) compared with the baseline week. We identified individuals who achieved a meaningful change at any point during treatment, and then we compared those who maintained a meaningful change in their final treatment week (i.e., responders) with those who did not or who achieved a meaningful change but lapsed (i.e., nonresponders). Results During treatment, 46% of participants achieved a clinically meaningful decrease in pain intensity, and 66% achieved a clinically significant increase in number of steps per day. A total of 54% of patients were classified as responders in terms of decreases in pain intensity, and 70% were responders in terms of increases in step count. Survival analyses found that 50% of responders first achieved a clinically meaningful change by week 4 for pain intensity and week 2 for daily steps. Dropout and demographic variables were unrelated to responder status, and there was low agreement between the two measures of treatment response. Conclusions Collectively, results suggest that most responders improve within 4 weeks. Evaluating treatment response is highly specific to the outcome measure, with little correlation across outcomes.

RationaleReducing 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.ObjectivesThe 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.MethodsYoung 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.ResultsMixed 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).ConclusionsUsing 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.

The Balloon Analogue Risk Task (BART) is a behavioral measure that is commonly used to assess risk taking propensity. The primary goal of the present study was to introduce a mobile version of the BART (mBART) that can be included within ambulatory assessment protocols to assess risk taking in daily life. Study 1 compared common BART indices (i.e., total money earned, adjusted average pumps, balloon explosions, and coefficient of variability [CV]) on a single administration of the laboratory BART on a computer and the mBART on a smartphone (n = 78). Results revealed generally consistent relationships between indices of risk taking propensity in both the laboratory BART and mBART. Study 2 administered the mBART as part of a 7-day ecological momentary assessment (EMA) protocol in a population of nondaily smokers (n = 51). Using multi-level models, results suggest that males have greater adjusted average pumps (p = .03), and that a participant’s average CV is negatively related to trait sensation seeking (p = .03) and positively associated with trait positive urgency (p = .04). There were within-person effects of study day (p = .05) and environment (p = .02) with respect to adjusted average pumps such that individuals took greater risks as the study progressed and were riskier when alone compared to with others. Inclusion of the mBART in EMA did not appear to significantly increase participant burden and demonstrated acceptable levels of compliance. These results offer initial evidence supporting the feasibility and utility of the mBART for ambulatory research designs.

Abstract Background Given access barriers to cognitive behavioral therapy for chronic pain (CBT-CP), this pragmatic superiority trial will determine whether a remotely delivered CBT-CP intervention that addresses these barriers outperforms in-person and other synchronous forms of CBT-CP for veterans with musculoskeletal pain. Design This pragmatic trial compares an asynchronous form of CBT-CP that uses interactive voice response (IVR) to allow patients to participate from their home (IVR CBT-CP) with synchronous CBT-CP delivered by a Department of Veterans Affairs (VA) clinician. Veterans (n=764; 50% male) with chronic musculoskeletal pain throughout nine VA medical centers will participate. The primary outcome is pain interference after treatment (4 months). Secondary outcomes, including pain intensity, depression symptom severity, sleep, self-efficacy, and global impression of change, are also measured after treatment. Where possible, outcomes are collected via electronic health record extraction, with remaining measures collected via IVR calls to maintain blinding. Quantitative and qualitative process evaluation metrics will be collected to evaluate factors related to implementation. A budget impact analysis will be performed. Summary This pragmatic trial compares the outcomes, cost, and implementation of two forms of CBT-CP as delivered in the real-world setting. Findings from the trial can be used to guide future policy and implementation efforts related to these interventions and their use in the health system. If one of the interventions emerges as superior, resources can be directed to this modality. If both treatments are effective, patient preferences and health care system factors will take precedence when making referrals. Implications of COVID-19 on treatment provision and trial outcomes are discussed.