Sequencing Analysis at 8p23 Identifies Multiple Rare Variants in DLC1 Associated with Sleep-Related Oxyhemoglobin Saturation Level.

Average arterial oxyhemoglobin saturation during sleep (AvSpO2S) is a clinically relevant measure of physiological stress associated with sleep-disordered breathing, and this measure predicts incident cardiovascular disease and mortality. Using high-depth whole-genome sequencing data from the National Heart, Lung, and Blood Institute (NHLBI) Trans-Omics for Precision Medicine (TOPMed) project and focusing on genes with linkage evidence on chromosome 8p23,1,2 we observed that six coding and 51 noncoding variants in a gene that encodes the GTPase-activating protein (DLC1) are significantly associated with AvSpO2S and replicated in independent subjects. The combined DLC1 association evidence of discovery and replication cohorts reaches genome-wide significance in European Americans (p = 7.9 × 10-7). A risk score for these variants, built on an independent dataset, explains 0.97% of the AvSpO2S variation and contributes to the linkage evidence. The 51 noncoding variants are enriched in regulatory features in a human lung fibroblast cell line and contribute to DLC1 expression variation. Mendelian randomization analysis using these variants indicates a significant causal effect of DLC1 expression in fibroblasts on AvSpO2S. Multiple sources of information, including genetic variants, gene expression, and methylation, consistently suggest that DLC1 is a gene associated with AvSpO2S.

Variability of Competition-Based Caloric Expenditure and Relative Heart Rates in National Collegiate Athletic Association Division I Women's Basketball.

ABSTRACT: Sanders, GJ, Boos, B, Rhodes, J, Peacock, CA, Kollock, RO, and Scheadler, CM. Variability of competition-based caloric expenditure and relative heart rates in National Collegiate Athletic Association Division I women's basketball. J Strength Cond Res 36(1): 162-166, 2022-Basketball athletes frequently engage in high intensities (≥85% HRpeak) throughout competition, and it is unknown how high-intensity play coincides with caloric expenditure and average and peak relative heart rates. The purpose of the study was to assess caloric expenditure throughout 31 games (4- to 10-minute quarters) in National Collegiate Athletic Association Division I women's basketball. A total of 11 female athletes were tested for peak heart rate (HRpeak) and peak oxygen uptake (V̇o2peak) before the season, then monitored in-season with heart rate-based wearable devices. Estimated caloric expenditure, average (% HRavg) and peak (% HRpeak) relative heart rates, time played at intensities ≥85% HRpeak, and live time (i.e., game minutes not including stoppages in play) were recorded each game. Data were assessed as a team and compared across 4 quarters, and then, interathlete comparisons were made based on full game data. There were significant main effects of 10-minute quarters on calories (p < 0.001) and % HRavg (p = 0.015) but not playing intensity ≥85% HRpeak (p = 0.125) and % HRpeak (p = 0.629). Caloric expenditure was the only variable to increase from the first to the fourth quarter. There were main effects of individual athletes on calories, % HRavg, % HRpeak, live time, and playing intensity ≥85% HRpeak (p < 0.001 for all). Assessing individual athletes, relative to a team assessment across quarters, can provide practitioners with more accurate caloric expenditure, heart rate, and playing intensity data per athlete to improve training and fueling protocols.

Priorities and expectations of patients attending a multidisciplinary interstitial lung disease clinic.

BACKGROUND AND OBJECTIVE: The significant and progressive morbidity associated with ILD mean that patients often struggle with the impact of this disease on their QOL and independence. To date, no studies have investigated the importance of multidisciplinary care on patient experience in ILD. We aimed to determine the expectations and priorities of patients attending a tertiary referral centre multidisciplinary ILD clinic. In particular, we sought to learn how important the multidisciplinary element of the clinic was to patients and which aspects of the clinic were most valued. METHODS: An 18-item patient questionnaire was developed in conjunction with expert physicians and specialist nurses involved in the ILD clinic and sent to all patients on the centre's ILD registry at the time of the study (n = 240). Patients rated the importance of different aspects of their experience of attending the clinic. Data collected were analysed using descriptive statistics. Comparisons across disease severity were made using two-sided Z-tests for independent proportions. RESULTS: A total of 100 respondents comprised the study group. Almost all respondents valued the multidisciplinary aspect of the clinic. Obtaining an accurate diagnosis and improving their disease understanding was most important to respondents. The importance of the ILD specialist nurse for both education and support increased with worsening disease severity. CONCLUSION: Our results suggest that a multidisciplinary approach to the management of ILD with additional focus on patient education, as well as tailoring care to disease severity, is a plausible pathway to improving the patient experience with ILD.

Competition-Based Heart Rate, Training Load, and Time Played Above 85% Peak Heart Rate in NCAA Division I Women's Basketball.

ABSTRACT: Sanders, GJ, Boos, B, Rhodes, J, Kollock, RO, and Peacock, CA. Competition-based heart rate, training load, and time played above 85% peak heart rate in NCAA division I women's basketball. J Strength Cond Res 35(4): 1095-1102, 2021-Basketball athletes frequently engage in intensities ≥85% HRpeak throughout competition. Knowing the time spent competing at intensities ≥85% HRpeak can improve training protocols. The purpose of the study was to assess heart rate responses across 4-quarter games (N = 31) in an NCAA Division I women's basketball season. Ten female athletes were tested and monitored with heart rate-based wearable microsensor devices. Before the season, HRpeak was recorded through a peak metabolic test (V̇o2peak). Average (HRavg) and HRpeak were recorded for each game, and time spent in 5 heart rate zones (HRZones) were recorded: HRZone1 = 50-60% HRpeak, HRZone2 = 60-70% HRpeak, HRZone3 = 70-76% HRpeak, HRZone4 = 77-84% HRpeak, and HRZone5 = 85-100% HRpeak. Training load was calculated with the summated-heart-rate-zone model (SHRZmod). There was a main effect of position (p ≤ 0.019) and quarter (p ≤ 0.005) on SHRZmod and on time spent in HRZone1-5. Athletes accumulated the most time in HRZone4 and HRZone5 and in the fourth quarter, and SHRZmod was the greatest in the fourth quarter. There was no main effect for HRavg and HRpeak (p ≥ 0.110). Athletes averaged 34.5 minutes per game competing in HRZone5 or ≥85% HRpeak with nearly one-third of those minutes accumulated in the fourth quarter. Although there were no differences in HRavg and HRpeak from quarter to quarter, SHRZmod increased from the first to fourth quarter. Utilizing time spent in heart rate zones and training load with SHRZmod can provide valuable information to practitioners regarding the intensity and physiological demands of competitive basketball games.

Australasian interstitial lung disease registry (AILDR): objectives, design and rationale of a bi-national prospective database.

BACKGROUND: Interstitial Lung Disease (ILD) is a group of respiratory conditions affecting the lung interstitium often associated with progressive respiratory failure. There is increasing recognition of the need for improved epidemiological data to help determine best practice and improve standardisation of care. The Australasian ILD Registry (AILDR) is a bi-national registry of patients with all ILD subtypes designed to establish a clinically meaningful database reflecting real world practice in Australasia with an objective to improve diagnostic and treatment pathways through research and collaboration. METHODS: AILDR is a prospective observational registry recruiting patients attending ILD clinics at centres around Australia and New Zealand. Core and non-core data are stored on a secure server. The pilot phase was launched in 2016 consisting of four sites in Australia. Currently in its second phase a further 16 sites have been recruited, including three in New Zealand. RESULTS: A total of 1061 participants were consented during the pilot phase. Baseline data demonstrated a mean age 68.3 ± 12.5 (SD) years, mean FVC (%predicted) 79.1 ± 20.4 (SD), mean DLCO (%predicted) 58.5 ± 17.9 (SD) and nadir exertional SpO2 (%) 91 ± 6.9 (SD). Idiopathic pulmonary fibrosis (31%) and connective-tissue disease related ILD (21.7%) were the two most common subtypes. Baseline demographics and physiology were not significantly different across the four centres. CONCLUSION: AILDR is an important clinical and research tool providing a platform for epidemiological data that will prove essential in promoting understanding of a rare cohort of lung disease and provide foundations for our aspiration to standardise investigation and treatment pathways of ILD across Australasia.

Factors associated with minimal changes in countermovement jump performance throughout a competitive division I collegiate basketball season.

The purpose of the study was to assess factors that contribute to countermovement jump (CMJ) performance in women's basketball athletes. Thirteen female athletes participated and were tested for maximal oxygen uptake (VO2max) and heart rate (HRmax). Athletes were monitored, daily for a total of 21 weeks with heart rate-based wearable devices and CMJ performance and body weight were tested weekly after one day of recovery. 3-jump average height (CMJavg), maximum height jump (CMJmax), and CMJ power (Watts) were calculated and recorded. Playing intensities >85% HRmax, HRavg, HRmax and training load were averaged for three consecutive days prior to the recovery day. After the season, data was grouped as changes in CMJ power from week one: Large (≤ -4.39% change), Moderate (-4.4% to -0.62% change), and Minimal (≥ -0.61% change) changes. Fixed-effects models revealed a main effect of group (p ≤ 0.05) for CMJavg, CMJmax, VO2max, weekly percent changes in body weight and for 3-day training load, HRavg, and playing time at >85% HRmax. When athletes experienced minimal changes in CMJ performance, relative to large changes, they produced greater power, jumped higher, avoided negative changes in weekly body weight, had a greater preseason VO2max and 3-day average workloads appeared to have an impact on CMJ performance.

Does Extended Pre Quit Bupropion Aid in Extinguishing Smoking Behavior?

INTRODUCTION: Understanding the mechanisms by which bupropion promotes smoking cessation may lead to more effective treatment. To the extent that reduced smoking reinforcement is one such mechanism, a longer duration of pre quit bupropion treatment should promote extinction of smoking behavior. We evaluated whether 4 weeks of pre quit bupropion (extended run-in) results in greater pre quit reductions in smoking rate and cotinine and, secondarily, greater short-term abstinence, than standard 1 week of pre quit bupropion (standard run-in). METHODS: Adult smokers (n = 95; 48 females) were randomized to a standard run-in group (n = 48; 3-week placebo, then 1-week bupropion pre quit) or an extended run-in group (4-week pre quit bupropion; n = 47). Both groups received group behavioral counseling and 7 weeks of post quit bupropion. Smoking rate (and craving, withdrawal, and subjective effects) was collected daily during the pre quit period; biochemical data (cotinine and carbon monoxide) were collected at study visits. RESULTS: During the pre quit period, the extended run-in group exhibited a greater decrease in smoking rate, compared to the standard run-in group, interaction p = .03. Cigarette craving and salivary cotinine followed a similar pattern, though the latter was evident only among women. Biochemically verified 4-week continuous abstinence rates were higher in the extended run-in group (53%) than the standard run-in group (31%), p = .033. CONCLUSIONS: The extended use of bupropion prior to a quit attempt reduces smoking behavior during the pre quit period and improved short-term abstinence rates. The data are consistent with an extinction-of-reinforcement model and support further investigation of extended run-in bupropion therapy for smoking cessation.

The interaction between self-regulation and motivation prospectively predicting problem behavior in adolescence.

A large literature suggests associations between self-regulation and motivation and adolescent problem behavior; however, this research has mostly pitted these constructs against one another or tested them in isolation. Following recent neural-systems based theories (e.g., Ernst & Fudge, 2009 ), the present study investigated the interactions between self-regulation and approach and avoidance motivation prospectively predicting delinquency and depressive symptoms in early adolescence. The community sample included 387 adolescents aged 11 to 13 years old (55% female; 17% minority). Laboratory tasks were used to assess self-regulation and approach and avoidance motivation, and adolescent self-reports were used to measure depressive symptoms and delinquency. Analyses suggested that low levels of approach motivation were associated with high levels of depressive symptoms, but only at high levels of self-regulation (p = .01). High levels of approach were associated with high levels of rule breaking, but only at low levels of self-regulation (p < .05). These findings support contemporary neural-based systems theories that posit integration of motivational and self-regulatory individual differences via moderational models to understand adolescent problem behavior.

An Examination of the Role of Sluggish Cognitive Tempo as a Moderator of the Relationship Between ADHD and Nicotine Use.

OBJECTIVE: ADHD is a neurodevelopmental disorder characterized by executive dysfunction and functional impairments including nicotine consumption. Sluggish cognitive tempo (SCT) has been associated with ADHD and posited as an independent construct. The present study hypothesized that SCT would moderate the relationships between ADHD and nicotine-related behaviors. METHOD: Participants (n = 309) were recruited using Mechanical Turk and completed measures of ADHD symptoms, SCT, and smoking history. RESULTS: ADHD was associated with age of initiation of smoking and more severe withdrawal symptoms for both combustible and electronic cigarettes. SCT significantly moderated the relationship between ADHD and withdrawal symptom severity (both electronic and combustible cigarettes). CONCLUSION: The results of the present study suggest that SCT plays an important role in the complex relationship between ADHD and smoking withdrawal. Future research should further explore the construct of SCT to better understand its role in psychopathology and intervention strategies.

Changes in Head and Pelvic Movement Symmetry after Diagnostic Anaesthesia: Interactions between Subjective Judgement Categories and Commonly Applied Blocks.

Limited evidence is available relating gait changes to diagnostic anaesthesia. We investigated associations between specific movement patterns and diagnostic anaesthesia of different anatomical structures in a retrospective analysis. Referral-level lameness cases were included with the following criteria: presence of diagnostic anaesthesia of a forelimb and/or hind limb; subjective efficacy classified as "negative", "partially positive", or "positive"; quantitative gait data available from inertial measurement units. Gait changes were calculated for three forelimb (palmar digital, abaxial sesamoid, low 4-point nerve block) and five hind limb diagnostic blocks (tarso-metatarsal, metatarsophalangeal joint block, deep branch of lateral plantar, low 6-point, abaxial sesamoid nerve block). Mixed models (random factor "case", fixed factors "diagnostic anaesthesia type" and "efficacy", two-way interaction) assessed the head and pelvic movement (p < 0.05, Bonferroni correction). Four parameters were significantly affected by forelimb anaesthesia (N = 265) (all p ≤ 0.031) and six by hind limb anaesthesia (N = 342) efficacy (all p ≤ 0.001). All head movement parameters and pelvic push-off asymmetry were significantly affected by the two-way interaction after forelimb anaesthesia (all p ≤ 0.023) and two pelvic movement symmetry parameters by the two-way interaction after hind limb anaesthesia (all p ≤ 0.020). There are interactions between block efficacy and type resulting in changes in weight-bearing and push-off-associated head and pelvic movement symmetry after diagnostic anaesthesia.

Smoking-Specific Risk Factors in Early Adulthood That Mediate Risk of Daily Smoking by Age 29 for Children with ADHD.

OBJECTIVE: To test whether smoking-specific risk factors in early adulthood mediate prediction to daily smoking from childhood ADHD. METHODS: Participants were 237 with and 164 without childhood ADHD. A smoking risk profile score comprising smoking-specific factors measured between ages 18 to 25 (e.g., craving severity) and age of initiation was tested as mediator of the association between childhood ADHD and age 29 daily smoking. RESULTS: Childhood ADHD predicted age 29 smoking (ß = -.15, p = .019), 35% of ADHD versus 17% of nonADHD, and the profile score (ß = -.07, p = .004), which in turn mediated prediction to age 29 daily smoking (ß = -.03; p = .007). When tested individually, three profile variables (# cigarettes/day, difficulty concentrating during abstinence, and nicotine dependence) were significant mediators (ps = 0.005-0.038), above and beyond early adult smoking, ADHD persistence, and delinquency. CONCLUSIONS: These behavioral smoking characteristics help explain later daily cigarette smoking for adults with ADHD histories and may need to be targeted in intervention.

Gallbladder fossa volume decreased in livers without gallbladders: A cadaveric study.

The gallbladder normally lies within a fossa on the visceral surface of the liver. The primary purpose of this study was to determine whether the volume of this fossa was reduced after cholecystectomy. Livers were obtained from embalmed cadavers of 19 females and 15 males with a mean age of 84.1 ± 10.8 yrs. The presence of a gallbladder was assessed, the volume of the irregularly-shaped gallbladder fossa determined from a mold of the fossa, and the dimensions of each fossa were estimated. The mean volume of gallbladder fossae from livers with gallbladders (n = 26; 13 females and 13 males) was 31.01 ± 17.82 ml, which was significantly greater than fossae in livers without gallbladders (n = 8, 6 females, 2 males) which was 8.75 ± 4.72 ml (P<0.0001). This difference still was significant after correcting fossa volume for overall liver weight and length of the femur. Livers with gallbladders had significantly larger dimensions (depth, length, and width) of their fossae molds than did livers without gallbladders (P<0.05). The largest percentage difference between the two groups in these dimensions was in the fossae depth, and there was a significant, positive correlation between all three of these dimensions and the overall volume of the fossae. Even looking only at female livers which tend to be smaller, gallbladder fossa volume was reduced in livers without a gallbladder. Thus, the present study demonstrated that the mean gallbladder fossa volume was significantly decreased in livers lacking gallbladders, even after correcting for the liver weight and size of the individual. While the mechanisms behind these changes in fossa volume currently are unknown, alterations in mechanical pressure relayed to adjacent liver cells after gallbladder removal may play a role in these fossa volume differences.

Diagnostic accuracy of transbronchial lung cryobiopsy for interstitial lung disease diagnosis (COLDICE): a prospective, comparative study.

BACKGROUND: Transbronchial lung cryobiopsy (TBLC) is a novel technique for sampling lung tissue for interstitial lung disease diagnosis. The aim of this study was to establish the diagnostic accuracy of TBLC compared with surgical lung biopsy (SLB), in the context of increasing use of TBLC in clinical practice as a less invasive biopsy technique. METHODS: COLDICE was a prospective, multicentre, diagnostic accuracy study investigating diagnostic agreement between TBLC and SLB, across nine Australian tertiary hospitals. Patients with interstitial lung disease aged between 18 and 80 years were eligible for inclusion if they required histopathological evaluation to aid diagnosis, after detailed baseline evaluation. After screening at a centralised multidisciplinary discussion (MDD), patients with interstitial lung disease referred for lung biopsy underwent sequential TBLC and SLB under one anaesthetic. Each tissue sample was assigned a number between 1 and 130, allocated in a computer-generated random sequence. Encoded biopsy samples were then analysed by masked pathologists. At subsequent MDD, de-identified cases were discussed twice with either TBLC or SLB along with clinical and radiological data, in random non-consecutive order. Co-primary endpoints were agreement of histopathological features in TBLC and SLB for patterns of definite or probable usual interstitial pneumonia, indeterminate for usual interstitial pneumonia, and alternative diagnosis; and for agreement of consensus clinical diagnosis using TBLC and SLB at MDD. Concordance and κ values were calculated for each primary endpoint. This study is registered with the Australian New Zealand Clinical Trials Registry, ACTRN12615000718549. FINDINGS: Between March 15, 2016, and April 15, 2019, we enrolled 65 patients (31 [48%] men, 34 [52%] women; mean age 66·1 years [SD 9·3]; forced vital capacity 83·7% [SD 14·2]; diffusing capacity for carbon monoxide 63·4% [SD 12·8]). TBLC (7·1 mm, SD 1·9) and SLB (46·5 mm, 14·9) samples were each taken from two separate ipsilateral lobes. Histopathological agreement between TBLC and SLB was 70·8% (weighted κ 0·70, 95% CI 0·55-0·86); diagnostic agreement at MDD was 76·9% (κ 0·62, 0·47-0·78). For TBLC with high or definite diagnostic confidence at MDD (39 [60%] of 65 cases), 37 (95%) were concordant with SLB diagnoses. In the 26 (40%) of 65 cases with low-confidence or unclassifiable TBLC diagnoses, SLB reclassified six (23%) to alternative high-confidence or definite MDD diagnoses. Mild-moderate airway bleeding occurred in 14 (22%) patients due to TBLC. The 90-day mortality was 2% (one of 65 patients), following acute exacerbation of idiopathic pulmonary fibrosis. INTERPRETATION: High levels of agreement between TBLC and SLB for both histopathological interpretation and MDD diagnoses were shown. The TBLC MDD diagnoses made with high confidence were particularly reliable, showing excellent concordance with SLB MDD diagnoses. These data support the clinical utility of TBLC in interstitial lung disease diagnostic algorithms. Further studies investigating the safety profile of TBLC are needed. FUNDING: University of Sydney, Hunter Medical Research Institute, Erbe Elektromedizin, Medtronic, Cook Medical, Rymed, Karl-Storz, Zeiss, and Olympus.

Association of DAT1 genetic variants with habitual sleep duration in the UK Biobank.

Short sleep duration has been linked to negative health effects, but is a complex phenotype with many contributing factors, including genetic. We evaluated 27 common single nucleotide polymorphisms (SNPs) in candidate genes previously reported to be associated with other sleep variables for association with self-reported habitual sleep duration in the UK Biobank in 111 975 individuals of European ancestry. Genetic variation in DAT1 (rs464049) was significantly associated with sleep duration after correction for multiple testing (p = 4.00 × 10-5), whereas SNPs correlated to a previously studied variable number tandem repeat (VNTR) in DAT1 were not significant in this population. We also replicated a previously reported association in DRD2. Independent replication of these associations and a second signal in DRD2 (rs11214607) was observed in an additional 261 870 participants of European ancestry from the UK Biobank. Meta-analysis confirmed genome-wide significant association of DAT1 rs464049 (G, beta [standard error, SE] = -0.96 [0.18] minutes/allele, p = 5.71 × 10-10) and study-wide significant association of DRD2 (rs17601612, C, beta [SE] = -0.66 [0.18] minutes/allele, p = 1.77 × 10-5; rs11214607, C, beta [SE] = 1.08 (0.24) minutes/allele, p = 1.39 × 10-6). Overall, SNPs in two dopamine-related genes were significantly associated with sleep duration, highlighting the important link of the dopamine system with adult sleep duration in humans.

Genome-wide association study identifies genetic loci for self-reported habitual sleep duration supported by accelerometer-derived estimates.

Sleep is an essential state of decreased activity and alertness but molecular factors regulating sleep duration remain unknown. Through genome-wide association analysis in 446,118 adults of European ancestry from the UK Biobank, we identify 78 loci for self-reported habitual sleep duration (p < 5 × 10-8; 43 loci at p < 6 × 10-9). Replication is observed for PAX8, VRK2, and FBXL12/UBL5/PIN1 loci in the CHARGE study (n = 47,180; p < 6.3 × 10-4), and 55 signals show sign-concordant effects. The 78 loci further associate with accelerometer-derived sleep duration, daytime inactivity, sleep efficiency and number of sleep bouts in secondary analysis (n = 85,499). Loci are enriched for pathways including striatum and subpallium development, mechanosensory response, dopamine binding, synaptic neurotransmission and plasticity, among others. Genetic correlation indicates shared links with anthropometric, cognitive, metabolic, and psychiatric traits and two-sample Mendelian randomization highlights a bidirectional causal link with schizophrenia. This work provides insights into the genetic basis for inter-individual variation in sleep duration implicating multiple biological pathways.

Smoke and mirrors: The overnight abstinence paradigm as an index of disrupted cognitive function.

RATIONALE: Smoking abstinence is known to cause decrements in cognition, but the effects are small and variable. One way to reduce variance may be to aggregate measures or visits. Although trait-like individual differences in smoking abstinence effects on cognition are theorized to predict relapse, the test-retest reliability (TRR) assumed in trait models has not been evaluated. OBJECTIVES: The objectives of this study were to assess the value of aggregating measures to determine effect sizes (ESs) of smoking versus abstinence on measures of cognition and to assess the short-term TRR of abstinence effects on cognition. METHODS: Thirty adult smokers completed the typical overnight abstinence paradigm twice; each visit pair consisted of one smoking visit and one abstinent visit. Measures of attention, working memory, and inhibitory control were obtained in each visit. RESULTS: There were small to medium ESs for smoking abstinence on individual cognitive measures during the first abstinence experience ("visit pair"). Aggregating the measures within the visit pair and across visit pairs additively increased the ES of smoking versus abstinence. Although TRRs were acceptable between smoking visits and between abstinent visits, TRRs for abstinence effects (smoking vs. abstinent visit differences) on cognition were consistently weak. DISCUSSION: The ability of the typical overnight abstinence paradigm to reflect disrupted cognition at the group level can be substantially improved by aggregating across cognitive outcomes and/or multiple study visits. However, the patterns of poor TRR of smoking-abstinence differences in cognition caution against their use as trait-like markers in studies of relapse or treatment response.

Cigarette smoking and ADHD: An examination of prognostically relevant smoking behaviors among adolescents and young adults.

Attention-deficit/hyperactivity disorder (ADHD) is associated with health risks in adolescence which includes the potential for smoking cigarettes, early smoking initiation, and rapid progression to daily smoking. Much less is known, however, about prognostically relevant smoking behaviors among individuals with childhood ADHD. Further research in this area is important for identifying individuals at pronounced risk for nicotine addiction, and for developing effective interventions for this population. This study examined initiation of cigarette smoking, progression to regular smoking, quantity of use, indicators of tobacco dependence, and quit rates among adolescents and young adults with (n = 364) and without (n = 240) childhood ADHD. Individuals with, versus without, ADHD histories were significantly more likely to become daily smokers independent of conduct disorder (CD). They were also more likely to initiate smoking at younger ages and to progress to regular smoking more quickly. There were no significant group differences in cigarettes smoked per day, Fagerström Test of Nicotine Dependence (FTND), or Nicotine Dependence Syndrome Scale (NDSS) scores or in smoking within 30 min of waking. However, smokers with ADHD reported more intense withdrawal and craving during periods of abstinence than non-ADHD smokers. There were no significant group differences in number of quit attempts. Lastly, there were no significant differences among symptom persisters and desisters in daily smoking and amount. Individuals with ADHD histories are at high risk for persistent smoking given their early onset, rapid course, and abstinence characteristics. Smoking cessation programs may need to be adapted or otherwise intensified for those with ADHD. (PsycINFO Database Record

Selection criteria limit generalizability of smoking pharmacotherapy studies differentially across clinical trials and laboratory studies: A systematic review on varenicline.

BACKGROUND: The selection criteria used in clinical trials for smoking cessation and in laboratory studies that seek to understand mechanisms responsible for treatment outcomes may limit their generalizability to one another and to the general population. METHODS: We reviewed studies on varenicline versus placebo and compared eligibility criteria and participant characteristics of clinical trials (N=23) and laboratory studies (N=22) across study type and to nationally representative survey data on adult, daily USA smokers (2014 National Health Interview Survey; 2014 National Survey on Drug Use and Health). RESULTS: Relative to laboratory studies, clinical trials more commonly reported excluding smokers who were unmotivated to quit and for specific medical conditions (e.g., cardiovascular disease, COPD), although both study types frequently reported excluding for general medical or psychiatric reasons. Laboratory versus clinical samples smoked less, had lower nicotine dependence, were younger, and more homogeneous with respect to smoking level and nicotine dependence. Application of common eligibility criteria to national survey data resulted in considerable elimination of the daily-smoking population for both clinical trials (≥47%) and laboratory studies (≥39%). Relative to the target population, studies in this review recruited participants who smoked considerably more and had a later smoking onset age, and were under-representative of Caucasians. CONCLUSIONS: Results suggest that selection criteria of varenicline studies limit generalizability in meaningful ways, and differences in criteria across study type may undermine efforts at translational research. Recommendations for improvements in participant selection and reporting standards are discussed.

The effects of varenicline on attention and inhibitory control among treatment-seeking smokers.

RATIONALE: Varenicline represents a new class of smoking cessation aids that has different mechanisms of action that are unique from bupropion or nicotine replacement therapies. An improved understanding of these mechanisms may lead to greater treatment success in quitting smoking. OBJECTIVES: We examined the effects of steady-state varenicline on attention and inhibitory control among adult treatment-seeking smokers. METHODS: Adult smokers enrolled in a randomized clinical trial received either 4 weeks of pre-quit varenicline (n = 31) or 3 weeks of placebo (n = 26) followed by 1 week of standard varenicline treatment. Participants in the present work completed cognitive assessments at a baseline session (prior to treatment) and again 3 weeks later (during active treatment). At both sessions, participants completed the stop signal task to assess both lapses in attention and inhibitory control. RESULTS: Analyses indicated that varenicline improved lapses in attention compared to placebo. There were no significant differences observed between groups at either session for inhibitory control. CONCLUSIONS: The present study demonstrated that varenicline improves lapses in attention among treatment-seeking smokers preparing to make a quit attempt. These findings suggest that the domain of attention may be a good candidate for larger studies of the role of improved cognition in understanding the mechanisms of varenicline treatment for smoking cessation.

Methylphenidate enhances prepulse inhibition during processing of task-relevant stimuli in attention-deficit/hyperactivity disorder.

ADHD is characterized by inattention, hyperactivity, and disinhibition, including the inability to screen out distracting stimuli. Prepulse inhibition (PPI) of startle indexes a related gating process and is enhanced during attended compared to ignored stimuli. We predicted that PPI during attended stimuli would be enhanced by the stimulant methylphenidate (MPH) and that this effect would be moderated by baseline PPI. Children with ADHD (n=36) completed a baseline day and a randomized, double-blind medication trial (placebo vs. sustained release MPH). Bilateral startle eyeblink EMG was measured during a tone discrimination task. MPH enhanced PPI during attended, but not during ignored stimuli. Extending findings that pretreatment functioning moderates stimulant effects on PPI, this effect tended to be inversely related to baseline PPI. These data fit with the clinical literature on ADHD and the hypothesis that MPH enhances interference control for important environmental stimuli.