Sociodemographic and patient reported outcomes by racial and ethnicity status among participants in a randomized controlled trial for methamphetamine use disorder.

Background: There has been a significant increase in methamphetamine use and methamphetamine use disorder (Meth UD) in the United States, with evolving racial and ethnic differences. Objectives: This secondary analysis explored racial and ethnic differences in baseline sociodemographic and clinical characteristics as well as treatment effects on a measure of substance use recovery, depression symptoms, and methamphetamine craving among participants in a pharmacotherapy trial for Meth UD. Methods: The ADAPT-2 trial (ClinicalTrials.gov number, NCT03078075; N=403; 69% male) was a multisite, 12-week randomized, double-blind, trial that employed a two-stage sequential parallel design to evaluate the efficacy of combination naltrexone (NTX) and oral bupropion (BUP) vs. placebo for Meth UD. Treatment effect was calculated as the weighted mean change in outcomes in the NTX-BUP minus placebo group across the two stages of treatment. Results: Of the 403 participants in the ADAPT-2 trial, the majority (65%) reported non-Hispanic White, while 14%, 11% and 10% reported Hispanic, non-Hispanic Black, and non-Hispanic other racial and ethnic categories respectively. At baseline non-Hispanic Black participants reported less severe indicators of methamphetamine use than non-Hispanic White. Treatment effects for recovery, depression symptoms and methamphetamine cravings did not significantly differ by race and ethnicity. Conclusions: Although we found racial and ethnic differences at baseline, our findings did not show racial and ethnic differences in treatment effects of NTX-BUP on recovery, depression symptoms and methamphetamine cravings. However, our findings also highlight the need to expand representation of racial and ethnic minority groups in future trials.

Pediatric influenza vaccination in the perioperative setting: A quality improvement project.

INTRODUCTION/BACKGROUND: Unmet need for seasonal influenza vaccination administration to pediatric patients exists at national and local levels. Vaccination during the perioperative period remains controversial, though opportunity exists to meet vaccination need through perioperative programs. The initial SMART Aim of this quality improvement initiative was to establish and increase seasonal influenza vaccination rate in eligible patients during in person preoperative clinic visits in a pediatric perioperative surgical home (PSH) to 10%. Informed by each prior season's experience, we increased our SMART Aim target for vaccinations in seasons two and three to 15 and 18%, respectively. METHODS: Following the Model for Improvement methodology, the PSH team developed and implemented a perioperative pediatric influenza vaccination program. Across three influenza seasons, key interventions included updates to organizational perioperative vaccination policy, obtaining material influenza vaccination supplies, development of EHR tools, PSH staff education, and communication with patient-families. Rate of eligible patients receiving influenza vaccination at their PSH clinic appointment was tracked over time. Influenza vaccination rates were reported monthly during Season 1, then weekly during seasons two and three. The balancing measure was same day surgery case cancellations related to influenza vaccination given at PSH clinic appointment. Statistical analysis methods utilized include Shewart's control chart and statistical process control (SPC) standards. Special cause variation was determined by eight or more consecutive data points above or below the centerline. RESULTS: The influenza vaccination rates in each of the three influenza seasons exceeded vaccination rate goals of 10, 15, and 18%, respectively. A total of 695 vaccines have been administered since program inception. No same day surgical case cancellations were observed as balancing measure. CONCLUSIONS: Over three consecutive influenza vaccination seasons, we safely established and met vaccination rate goals of 10, 15, and 18% to eligible patients during preoperative clinic visits within a pediatric PSH system. Through iterative PDSA cycles, we continue to identify opportunities for future improvement. This suggests that the perioperative period presents opportunity for seasonal influenza vaccination with potential program expansion to include routine vaccines of childhood.

Stigma towards opioid use disorder in primary care remain a barrier to integrating software-based measurement based care.

BACKGROUND: Opioid use disorder (OUD) is a deadly illness that remains undertreated, despite effective pharmacological treatments. Barriers, such as stigma, treatment affordability, and a lack of training and prescribing within medical practices result in low access to treatment. Software-delivered measurement-based care (MBC) is one way to increase treatment access. MBC uses systematic patient symptom assessments to inform an algorithm to support clinicians at critical decision points. METHOD: Focus groups of faculty clinicians (N = 33) from 3 clinics were conducted to understand perceptions of OUD diagnosis and treatment and whether a computerized MBC model might assist with diagnosis and treatment. Themes from the transcribed focus groups were identified in two phases: (1) content analysis focused on uncovering general themes; and (2) systematic coding and interpretation of the data. RESULTS: Analysis revealed six major themes utilized to develop the coding terms: "distinguishing between chronic pain and OUD," "current practices with patients using prescribed or illicit opioids or other drugs," "attitudes and mindsets about providing screening or treatment for OUD in your practice," "perceived resources needed for treating OUD," "primary care physician role in patient care not specific to OUD," and "reactions to implementation of proposed clinical decision support tool." CONCLUSION: Results revealed that systemic and attitudinal barriers to screening, diagnosing, and treating OUD continue to persist. Providers tended to view the software-based MBC program favorably, indicating that it may be a solution to increasing accessibility to OUD treatment; however, further interventions to combat stigma would likely be needed prior to implementation of these programs. TRIAL REGISTRATION: ClinicalTrials.gov; NCT04059016; 16 August 2019; retrospectively registered; https://clinicaltrials.gov/ct2/show/NCT04059016 .

Social Support and the Rehabilitation of Alcohol-Impaired Drivers: Drinking Motives as Moderators.

Alcohol-impaired driving is a common and costly public health problem associated with alcohol misuse. This investigation aims to understand the role of social support and drinking motives in motivating alcohol-impaired drivers to reduce alcohol use. One hundred nineteen participants with a history of driving-while-intoxicated arrest were recruited from either a correctional treatment facility (n = 59) or the community (n = 60) and asked about their motivation to change alcohol use. Motivation to change was tested in relationships with two types of social support (i.e. Abstinence-Specific Social Support and General Social Support) and drinking motives (Coping, Enhancement, and Social Motives). The results showed: (1) only Abstinence-Specific Social Support was positively associated with motivation to change; (2) Coping and Social Motives had a negative association with motivation to change; (3) the impact of Abstinence-Specific Social Support on motivation to change was greater among those with a stronger Enhancement Motives. In other words, those who drink primarily for pleasure showed a greater increase in motivation to change when more Abstinence-Specific Social Support is available, compared to those with lower Enhancement Motives. The findings of this investigation contribute to our knowledge of the roles of communication in the rehabilitation of alcohol-impaired drivers.

The Development of Impulsivity and Sensation Seeking: Associations with Substance Use among At-Risk Adolescents.

We investigated if the dual systems model could explain the increased rates of substance use among at-risk youth. This study sampled 365 adolescents, 289 of which had a family history of substance use disorder, assessed biannually between the ages 13-16 years old. Growth curve analyses revealed that higher levels of impulsivity were related to higher levels of sensation seeking and a slower rate of decline in impulsivity was related to a faster rate of increase in sensation seeking. Only family history status and sensation seeking were directly associated with substance use (marijuana, alcohol) at age 16, though family history status was also indirectly related to substance use through higher levels of impulsivity to higher levels of sensation seeking.

Estimating resource utilization demands in implementing statewide screening, brief intervention, and referral to treatment for alcohol-impaired drivers.

OBJECTIVES: The Alcohol Use Disorders Identification Test (AUDIT) is used to assess the level of alcohol use/misuse and to inform the intensity of intervention delivered within screening, brief intervention, and referral to treatment (SBIRT) programs. Policy initiatives are recommending delivery of SBIRT within health care settings to reduce alcohol misuse and prevent alcohol-impaired driving. Recent reports are considering extending delivery of SBIRT to criminal justice settings. One consideration in implementing SBIRT delivery is the question of resource utilization; the amount of effort required in delivering the 4 different intensities of intervention in SBIRT: Alcohol education, simple advice, brief counseling and continued monitoring, and brief counseling and referral to specialist (from least to most intense in terms of delivery time, the skill level of the provider, and personnel resources). METHODS: In order to inform expectations about intervention intensity, this article describes the AUDIT scores from 982 adults recently arrested for alcohol-impaired driving. The distribution of scores is extrapolated to state rates for individuals arrested for alcohol-impaired driving by intervention level. RESULTS: Though alcohol education was the most common intervention category, about one quarter of the sample scored in a range corresponding with the more intensive interventions using the brief counseling, continued monitoring for ongoing alcohol use, and/or referral to specialist for diagnostic evaluation and treatment. CONCLUSIONS: This article provides local distribution of AUDIT scores and state estimates for the number of individuals scoring in each level of risk (AUDIT risk zone) and corresponding intervention type. Routine criminal justice practice is well positioned to deliver alcohol screening, education, simple advice, and continued alcohol monitoring, making delivery of SBIRT feasible for the majority of alcohol-impaired drivers. Challenges to implementing the full range of SBIRT services include resource demands of brief counseling, identifying the appropriate providers within a criminal justice context, and availability of community providers for referral to diagnostic and specialty care. Solutions may vary by state due to differences in population density and incidence rates of alcohol-impaired driving.

Mitigating the Effect of Pain Severity on Activity and Disability in Patients with Chronic Pain: The Crucial Context of Acceptance.

OBJECTIVE: The purpose of this study was to examine the effect of pain severity on activity levels and physical disability in the context of high pain acceptance. We hypothesized that pain acceptance moderates the effect of pain severity on general activity and physical disability, such that at higher levels of acceptance, the deleterious effect of pain is mitigated. METHODS: Two hundred seven patients with chronic pain were recruited from three clinics in a large southwestern military treatment facility. Participants completed an anonymous self-report battery of standardized measures, including the Chronic Pain Acceptance Questionnaire, modified Oswestry Disability Index, and Pain Severity and General Activity subscales of the West Haven-Yale Multidimensional Pain Inventory. RESULTS: Chronic pain acceptance was found to significantly moderate relations between pain severity and general activity (b = 0.0061, t(198) = 2.75, P = 0.007, 95% confidence interval [CI] = 0.002 to 0.011) and pain severity and disability (b = 0.036, t(193) = -2.564, P = 0.011, 95% CI = -0.063 to -0.008). In the context of higher acceptance, the negative effect of pain on activity and disability appeared reduced. Conversely, in the context of low acceptance, the effect of pain on disability appeared accentuated at all levels of pain severity. CONCLUSIONS: Higher acceptance mitigated both activity level and disability in a military-affiliated clinical sample of patients with chronic pain. Results further establish the role of acceptance in relation to functioning in a unique sample of people with chronic pain. These findings have implications for understanding and enhancing functioning in chronic pain populations.

The Role of Social Support in Motivating Reductions in Alcohol Use: A Test of Three Models of Social Support in Alcohol-Impaired Drivers.

BACKGROUND: Social support has been linked to many therapeutic benefits (e.g., treatment retention, reduced posttreatment relapse) for individuals with alcohol use disorder. However, the positive impacts of social support have not been well understood in the context of alcohol-impaired driving. This article examines the role of social support in motivating those with histories of driving while intoxicated (DWI) arrest to reduce alcohol use by testing 3 major models of social support: the Main-Effects model, the Buffering model, and the Optimal Matching model. METHODS: One hundred and nineteen participants with histories of DWI arrest were recruited from a correctional treatment facility (n = 59) and the local community (n = 60). Participants completed interviews to assess alcohol consumption, psychiatric/physical conditions, and psychosocial factors associated with drinking behavior (e.g., social support, alcohol-related problems, and motivation to change). Hierarchical regression analyses were conducted to test the 3 models. Additionally, the relative magnitude of the effects of general and recovery-specific social support was compared based on the approach of statistical inference of confidence intervals. RESULTS: Overall social support was positively associated with some motivation to change (i.e., importance of change, confidence in change) among alcohol-impaired drivers, supporting the Main-Effects model. However, the impact of overall social support on motivation to change was not moderated by alcohol-related problems of individuals arrested for DWI, which did not confirm the Buffering model. Last, recovery-specific social support, rather than general social support, contributed to increasing motivation to reduce alcohol use, which supported the Optimal Matching model. CONCLUSIONS: These findings highlight the benefits of social support (i.e., increased motivation to change alcohol use) for alcohol-impaired drivers. Regardless of the severity of alcohol-related problems of alcohol-impaired drivers, social support had direct positive impacts on motivation to change. In particular, the results underscore that social support can be more effective when it is matched to the recovery effort of individuals, which is consistent with the Optimal Matching model.

Processing transdermal alcohol concentration (TAC) data to detect low-level drinking.

BACKGROUND: Several studies have objectively quantified drinking through the use of Alcohol Monitoring System's (AMS) transdermal alcohol concentration (TAC) device known as SCRAM CAM. Criteria that AMS uses to detect drinking are known to be conservative and only reliably detect heavy drinking equivalent to 5 or more standard drinks. Our group has developed Research Rules used to process TAC data in a manner that will detect low-level and moderate drinking even though it is below the AMS criteria for detection. METHODS: Sixteen male and 14 female paid research volunteers wore TAC monitors for 28 days in their natural environments and responded daily to text message prompts to self-report the previous day's drinking. Current analyses describe the Research Rules that we developed and how use of those rules impacts the detection of self-reported drinking treated as the standard in sensitivity/specificity analysis. RESULTS: We observed 606 occurrences of positive TAC events over a total of 867 days and processed the TAC data to retain 345 as possible drinking events, even though AMS criteria confirmed drinking for only 163 of these events. The kinds of TAC events removed or retained by our rules are illustrated as cases of low and moderate drinking days that were detected by our rules but not by the conservative AMS criteria. AMS-confirmed TAC events have a high specificity (99.8%) to detect primarily heavy drinking, but have a poor sensitivity to detect lower-level drinking and a poor specificity as an indicator of alcohol abstinence. In contrast, our Research Rules detected 100% of TAC events detected by AMS but also detected 31% of the lower-level drinking events not detected by AMS, with 91% specificity. CONCLUSIONS: Reliance upon the AMS criteria for alcohol detection affords a high specificity for detection of heavy drinking but is a poor indicator of abstinence rates. In contrast, use of our Research Rules provides more sensitive means to quantify either any drinking or low-moderate levels of drinking while still maintaining good specificity.

Pharmacokinetics of Phosphatidylethanol 16:0/20:4 in Human Blood After Alcohol Intake.

BACKGROUND: The purpose of this study was to characterize the pharmacokinetics of the phosphatidylethanol (PEth) 16:0/20:4 homolog in uncoagulated human blood samples taken from 18 participants in a clinical laboratory setting after consumption of 2 standard doses of ethanol (EtOH). METHODS: Male and female participants received either 0.4 or 0.8 g/kg oral doses of EtOH during a 15-minute period. Blood samples were collected before and throughout 6 hours immediately after alcohol administration and then again at days 2, 4, 7, 11, and 14 of the follow-up period. PEth 16:0/20:4 levels were quantified by high-performance liquid chromatography with tandem mass spectrometry detection. RESULTS: (i) The increase in PEth 16:0/20:4 from baseline to maximum concentration was less than that of PEth 16:0/18:1 or PEth 16:0/18:2 homologs during the 6-hour period after EtOH administration; (ii) the mean half-life of PEth 16:0/20:4 was 2.1 ± 3 (SD) days, which was shorter than the mean half-life of either PEth 16:0/18:1 or PEth 16:0/18:2, 7.6 ± 3 (SD) or 6.8 ± 4 (SD) days, respectively. CONCLUSIONS: The pharmacokinetics of PEth 16:0/20:4 in whole blood samples is detectable after alcohol consumption and differs in amount synthesized and rate of elimination versus PEth 16:0/18:1 and 16:0/18:2. Measuring the concentrations of these 3 homologs has the potential to provide more information about the amount and time frame of alcohol consumption than any one alone.

The correspondence between transdermal alcohol monitoring and daily self-reported alcohol consumption.

Alcohol consumption is typically assessed via self-report methods, though there are concerns over the accuracy of this information. Transdermal alcohol monitoring can passively and continuously measure alcohol consumption with minimal interference in daily life. The current study examines the correspondence between daily self-reported alcohol consumption and transdermal alcohol monitors. Thirty-two healthy men (n = 16) and women (n = 16) wore a transdermal alcohol monitor for 28 days. Participants were instructed to drink as they usually do and prompted daily with a survey link to report yesterday's drinking. Data analyses focused on the following comparisons: (1) the overall correspondence between self-reported drinking and TAC readings; (2) the sensitivity of various TAC criteria thresholds to detect self-reported drinking (TAC thresholds of none, low, moderate, and heavy); and (3) the risks of false positive TAC findings using self-reported drinking as the Gold Standard. Participants self-reported drinking a total of 324 days, of which, TAC events were detected on 212 days (65.4%). When participants self-reported not drinking (399 days), zero TAC was also found on 366 days (92%). The correspondence between self-reported drinking and transdermal concentrations tended to be good: overall, when self-reported drinking was reported, TAC also detected drinking 65.4% of the time.

Differences in the Synthesis and Elimination of Phosphatidylethanol 16:0/18:1 and 16:0/18:2 After Acute Doses of Alcohol.

BACKGROUND: The purpose of this study was to examine the synthesis and elimination of phosphatidylethanol (PEth) 16:0/18:1 and 16:0/18:2 following the consumption of alcohol among 56 light and heavy drinkers. METHODS: A transdermal alcohol monitor was used to promote alcohol absence 7 days prior, and 14 days after, alcohol consumption in the laboratory. Participants consumed a 0.4 or 0.8 g/kg dose of alcohol in 15 minutes. Blood and breath samples were collected before, at various times up to 360 minutes postconsumption, and 2, 4, 7, 11, and 14 days after alcohol consumption. Initial rates of PEth synthesis, 360 minutes area under the PEth pharmacokinetic curves (AUCs), and elimination half-lives were determined. RESULTS: (i) Nonzero PEth levels were observed before alcohol dosing for most participants, despite 7 days of alcohol use monitoring; (ii) 0.4 and 0.8 g/kg doses of alcohol produced proportional increases in PEth levels in all but 1 participant; (iii) the initial rate of synthesis of both PEth homologues did not differ between the 2 doses, but was greater for PEth 16:0/18:2 than PEth 16:0/18:1 at both doses; (iv) the mean AUC of both PEth homologues was higher at 0.8 g/kg than at 0.4 g/kg; (v) the mean AUC of 16:0/18:2 was greater than that of PEth 16:0/18:1 at both alcohol doses; (vi) the mean half-life of PEth 16:0/18:1 was longer than that of PEth 16:0/18:2 (7.8 ± 3.3 [SD] days and 6.4 ± 5.0 [SD] days, respectively); and (vii) there were no sex differences in PEth 16:0/18:1 or 16:0/18:2 pharmacokinetics. CONCLUSIONS: The results of this study support the use of PEth 16:0/18:1 and 16:0/18:2 as biomarkers for alcohol consumption. Because of consistent pharmacokinetic differences, the levels of these 2 PEth homologues may provide more information regarding the quantity and recentness of alcohol consumption than either alone.

Translating transdermal alcohol monitoring procedures for contingency management among adults recently arrested for DWI.

Recent developments in alcohol monitoring devices have made it more feasible to use contingency management (CM) procedures to reduce alcohol use. A growing body of literature is demonstrating the effectiveness of CM to reduce alcohol use among community recruited adults wearing transdermal alcohol concentration (TAC) monitoring devices. This article describes the quality improvement process aimed at adapting TAC-informed CM aimed at minimizing alcohol use and maximizing treatment completion. This extends literature to a high-risk population; adults arrested and awaiting trial (pretrial) for criminal charge of driving while intoxicated (DWI). Participants were enrolled during their orientation to pretrial supervision conditions of DWI bond release. At enrollment, participants completed a screening, brief intervention, and referral to treatment; those with high risk alcohol histories were enrolled in an 8-week CM procedure to avoid TAC readings. Four Plan-Do-Study-Act (PDSA) quality improvement cycles were conducted where the TAC cutoff for determining alcohol use, the quantity of reinforcer, and handling of tampers on the transdermal alcohol monitor were manipulated. Across four PDSA cycles, the retention for the full 8-weeks of treatment was increased. The proportion of weeks with alcohol use was not decreased across cycles, the peak TAC values observed during drinking weeks were significantly lower in Cycles 1 and 4 than 3. CM may be developed as a tool for pretrial supervision to be used to increase bond compliance of those arrested for DWI and for others as a method to identify the need for additional judicial services.

Time Delays in Transdermal Alcohol Concentrations Relative to Breath Alcohol Concentrations.

AIMS: Monitors of transdermal alcohol concentration (TAC) provide an objective measurement of alcohol consumption that is less invasive than measurements in blood, breath or urine; however, there is a substantial time delay in the onset of TAC compared to blood or breath alcohol concentrations (BrACs). The current study examined the characteristics of the delay between peak TAC and peak BrAC. METHODS: Data was aggregated from three experimental laboratory studies (N = 61; 32 men, 29 women) in which participants wore a TAC monitor and BrAC was monitored while drinking one, two, three, four and five beers in the laboratory. Analyses examined the sex- and dose-related differences in peak BrAC and TAC, the time-to-peak BrAC and TAC, and time lag between the peak BrAC and TAC values. RESULTS: The times-to-peak were an increasing function of the number of beers consumed. At each level of beer consumption the peak TAC averaged lower than peak BrAC and times-to-peak TAC were longer than for BrAC. The time-to-peak BrAC and TAC was longer for women than men. The congruence between peak TAC and BrAC increased as a function of the beers consumed. No sex difference in the time lag between peak BrAC and TAC was detected. CONCLUSIONS: The congruence between TAC and BrAC and time lags between TAC and BrAC are related to the number of beers consumed. Peak values of TAC and BrAC became more congruent with higher doses but the time lag increased as a function of the amount of alcohol consumed. SHORT SUMMARY: The time delay (or lag) and congruence between transdermal vs. BrACs increases as the number of beers increases. Though sex differences are evident in peak transdermal and BrACs, no sex differences were evident in the time lag and the congruence between transdermal and breath alcohol concentrations.

Characterization of the Pharmacokinetics of Phosphatidylethanol 16:0/18:1 and 16:0/18:2 in Human Whole Blood After Alcohol Consumption in a Clinical Laboratory Study.

BACKGROUND: The purpose of this study was to characterize the pharmacokinetics of 2 homologues of phosphatidylethanol (PEth) and their combined total in uncoagulated, whole blood samples taken from participants in a human clinical laboratory study after consumption of low doses of ethanol (EtOH). METHODS: As part of a larger study, 14 male and 13 female participants received either 0.25 or 0.50 g/kg oral doses of EtOH during a 15-minute period. Blood samples were collected before and throughout 6 hours after each EtOH dose on the day of consumption and then every 3 days during the next 14 days. PEth 16:0/18:1 and PEth 16:0/18:2 levels were quantified in blood samples by HPLC/MS/MS and reported separately or as their combined total (combined PEth). Breath alcohol concentrations (BrACs) were measured concurrently with each blood collection. Transdermal alcohol concentrations were measured every 30 minutes during the entire 22-day study to confirm the absence of drinking during a 7-day period before and the 14-day period after EtOH consumption. RESULTS: (i) Single doses of 0.25 and 0.50 g EtOH/kg produced proportional increases in BrAC and combined PEth levels of all participants; (ii) the areas under the curve (AUCs) for each participant's BrAC levels during the 6-hour period after EtOH administration were correlated with AUCs of cPEth (calculated as the AUC of the increase above baseline for combined PEth); (iii) the mean half-life of combined PEth, determined during the 14-day period after EtOH consumption, was 4.6 ± 3.5 (SD) days (range: 1.0 to 13.1 days). CONCLUSIONS: Combined PEth is a sensitive biomarker for the identification of relatively low levels of EtOH consumption. The measurement of these 2 homologues may provide additional sensitivity to identify low levels of drinking.

A cross-sectional study of the prevalence and associations of iron deficiency in a cohort of patients with chronic obstructive pulmonary disease.

OBJECTIVES: Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality. Iron deficiency, with or without anaemia, is associated with other chronic conditions, such as congestive heart failure, where it predicts a worse outcome. However, the prevalence of iron deficiency in COPD is unknown. This observational study aimed to determine the prevalence of iron deficiency in COPD and associations with differences in clinical phenotype. SETTING: University hospital outpatient clinic. PARTICIPANTS: 113 adult patients (65% male) with COPD diagnosed according to GOLD criteria (forced expiratory volume in 1 s (FEV1): forced vital capacity (FVC) ratio <0·70 and FEV1 <80% predicted); with age-matched and sex-matched control group consisting of 57 healthy individuals. MAIN OUTCOME MEASURES: Prevalence of iron deficiency, defined as: any one or more of (1) soluble transferrin receptor >28.1 nmol/L; (2) transferrin saturation <16% and (3) ferritin <12 µg/L. Severity of hypoxaemia, including resting peripheral arterial oxygen saturation (SpO2) and nocturnal oximetry; C reactive protein (CRP); FEV1; self-reported exacerbation rate and Shuttle Walk Test performance. RESULTS: Iron deficiency was more common in patients with COPD (18%) compared with controls (5%). In the COPD cohort, CRP was higher in patients with iron deficiency (median 10.5 vs 4.0 mg/L, p<0.001), who were also more hypoxaemic than their iron-replete counterparts (median resting SpO2 92% vs 95%, p<0.001), but haemoglobin concentration did not differ. Patients with iron deficiency had more self-reported exacerbations and a trend towards worse exercise tolerance. CONCLUSIONS: Non-anaemic iron deficiency is common in COPD and appears to be driven by inflammation. Iron deficiency associates with hypoxaemia, an excess of exacerbations and, possibly, worse exercise tolerance, all markers of poor prognosis. Given that it has been shown to be beneficial in other chronic diseases, intravenous iron therapy should be explored as a novel therapeutic option in COPD.

Chronic alcohol alters rewarded behaviors and striatal plasticity.

Chronic intermittent ethanol (CIE) alters neural functions and behaviors mediated by the dorsolateral striatum (DLS) and prefrontal cortex. Here, we examined the effects of prolonged (16-bout) CIE on DLS plasticity and DLS-mediated behaviors. Ex vivo electrophysiological recordings revealed loss in efficacy of DLS synaptically induced activation and absent long-term depression after CIE. CIE increased two-bottle choice drinking and impaired Pavlovian-to-instrumental transfer but not discriminated approach. These data suggest prolonged CIE impaired DLS plasticity, to produce associated changes in drinking and cue-controlled reward-seeking. Given recent evidence that less-prolonged CIE can promote certain dorsal striatal-mediated behaviors, CIE may drive chronicity-dependent adaptations in corticostriatal systems regulating behavior.

GluN2B in corticostriatal circuits governs choice learning and choice shifting.

A choice that reliably produces a preferred outcome can be automated to liberate cognitive resources for other tasks. Should an outcome become less desirable, behavior must adapt in parallel or it becomes perseverative. Corticostriatal systems are known to mediate choice learning and flexibility, but the molecular mechanisms of these processes are not well understood. We integrated mouse behavioral, immunocytochemical, in vivo electrophysiological, genetic and pharmacological approaches to study choice. We found that the dorsal striatum (DS) was increasingly activated with choice learning, whereas reversal of learned choice engaged prefrontal regions. In vivo, DS neurons showed activity associated with reward anticipation and receipt that emerged with learning and relearning. Corticostriatal or striatal deletion of Grin2b (encoding the NMDA-type glutamate receptor subunit GluN2B) or DS-restricted GluN2B antagonism impaired choice learning, whereas cortical Grin2b deletion or OFC GluN2B antagonism impaired shifting. Our convergent data demonstrate how corticostriatal GluN2B circuits govern the ability to learn and shift choice behavior.

Do GluA1 knockout mice exhibit behavioral abnormalities relevant to the negative or cognitive symptoms of schizophrenia and schizoaffective disorder?

The glutamate system has been strongly implicated in the pathophysiology of psychotic illnesses, including schizophrenia and schizoaffective disorder. We recently found that knockout (KO) mice lacking the AMPA GluA1 subunit displayed behavioral abnormalities relevant to some of the positive symptoms of these disorders. Here we phenotyped GluA1 KO mice for behavioral phenotypes pertinent to negative and cognitive/executive symptoms. GluA1 KO mice were tested for conspecific social interactions, the acquisition and extinction of an operant response for food-reward, operant-based pairwise visual discrimination and reversal learning, and impulsive choice in a delay-based cost/benefit decision-making T-maze task. Results showed that GluA1 KO mice engaged in less social interaction than wildtype (WT) controls when tested in a non-habituated, novel environment, but, conversely, displayed more social interaction in a well habituated, familiar environment. GluA1 KO mice were faster to acquire an operant stimulus-response for food reward than WT and were subsequently slower to extinguish the response. Genotypes showed similar pairwise discrimination learning and reversal, although GluA1 KO mice made fewer errors during early reversal. GluA1 KO mice also displayed increased impulsive choice, being less inclined to choose a delayed, larger reward when given a choice between this and a smaller, immediate reward, compared to WT mice. Finally, sucrose preference did not differ between genotypes. Collectively, these data add to the growing evidence that GluA1 KO mice display at least some phenotypic abnormalities mimicking those found in schizophrenia/schizoaffective disorder. Although these mice, like any other single mutant line, are unlikely to model the entire disease, they may nevertheless provide a useful tool for studying the role of GluA1 in certain aspects of the pathophysiology of major psychotic illness.