Sleep Duration and Quality in Relation to Fruit and Vegetable Intake of US Young Adults: a Secondary Analysis.

BACKGROUND: Sleep is gaining recognition as a determinant of diet, yet this relationship remains understudied among young adults. We sought to examine how sleep duration and quality were related to fruit and vegetable (FV) intake within a diverse sample of young adults. METHODS: Participants (n = 1444) ages 21-30 (69% women, 15% African American, 35% full or part time in college) consuming < 5 servings/day of FV (eligibility criteria) completed a baseline survey to enroll in a randomized online FV intervention. Sleep questions included duration, perceived sleep quality, time to fall asleep, and insomnia symptoms. Overall and gender-stratified linear regression models compared average daily FV intake and sleep characteristics, adjusting for confounders. RESULTS: One-third (32%) of the participants reported < 7 h of sleep per night, and 36% noted insomnia symptoms ≥ 3 times per week. Women, a BMI > 30, African American race/ethnicity, less education, unemployment, higher depression, and stress were related to suboptimal sleep. Bivariate analyses showed that better sleep was associated with higher FV intake. After accounting for confounders, men with better sleep quality and shorter time to fall asleep had higher intakes of FV (1.12 serving/day difference in highest versus lowest quality [95% CI 0.48, 1.75] and a 0.52 serving/day higher intake difference for shortest versus longest fall asleep time [95% CI 0.90, 0.15], respectively). CONCLUSION: Sleep was highly prevalent in a diverse sample of community-based young adults and may contribute to lower FV intake among men. These associations highlight young adulthood as an important period for promoting healthy sleep habits.

Opioid stewardship training during the transition to residency to prepare medical students to recognize and treat opioid use disorder.

Background: With a drastic shortage of addiction medicine specialists-and an ever-growing number of patients with opioid use disorder (OUD)-there is a dire need for more clinicians to feel confident in prevention and management of OUD and obtain a DEA-X waiver to prescribe medications to treat OUD. Here we determine if it is feasible to certify 4th year medical students with DEA-X waiver training as a component of the PROUD (Prevent and Reduce Opioid Use Disorder) curriculum, and if PROUD enhanced preparedness for medical students to manage OUD as interns. Methods: We implemented a sequential mixed-methods IRB approved study to assess feasibility (completing all required components of DEA-X waiver training) and impact of PROUD (measured by knowledge growth, enhancement for residency, and utilization of training during internship). Students completed 11 hours of required OUD training. Quantitative data included pre-/post- knowledge and curriculum satisfaction assessments as well as long-term impact with follow up survey as interns. Qualitative data was collected by survey and semi-structured focus groups. Results: All 120 graduating medical students completed the required components of the curriculum. Knowledge improved on the Provider Clinical Support Services (12.9-17.3, p < 0.0001) and Brief Opioid Overdose Knowledge assessments (10.15-10.81, p < 0.0001). Course satisfaction was high: 90% recommended online modules; 85% recommended training overall. Six qualitative themes emerged: (1) curriculum content was practical, (2) online modules allowed flexibility, (3) in-person seminars ensured authenticity, (4) timing at the transition to residency was optimal, (5) curriculum enhanced awareness and confidence, and (6) training was applicable to future careers. At 3 months, 60% reported using their training during internship; 64% felt more prepared to treat OUD than peers. Conclusions: PROUD trained 4th year medical students in opioid stewardship. As interns, students felt ready to serve as change agents to prevent, diagnose, and treat OUD.

Treatment of adolescent obesity comparing self-guided and group lifestyle modification programs: a potential model for primary care.

Lifestyle modification programs (LMP) for weight loss in adolescents with obesity are effective but not available. Primary care may be a setting for reaching more adolescents. Two models of LMP for use in primary care were examined. Adolescents and caregivers enrolled in a 1-year randomized trial comparing Group LMP with Self-Guided LMP. All participants (N = 169) received the same treatment recommendations and met with a health coach six times in clinic. Group LMP participants had an additional 17 group sessions; those in Self-Guided LMP followed the remainder of the program at home with parental support. The primary outcome was percentage change in initial body mass index. The mean (SE) 1.31% (0.95%) reduction in Group LMP did not differ significantly from the 1.17% (0.99%) decrease in the Self-Guided LMP (p = 0.92). Both treatments were significantly effective in reducing body mass index. Given its brevity, the Self-Guided LMP offers an innovative approach for primary care.

Changes in fruit and vegetable consumption in relation to changes in sleep characteristics over a 3-month period among young adults.

OBJECTIVE: To evaluate whether increases in fruit and vegetable (FV) consumption were associated with concomitant changes in insomnia symptoms, sleep duration, and quality. DESIGN: Secondary longitudinal analysis of a randomized trial, baseline to 3 months. SETTING: Integrated health care systems in Detroit, Michigan and Danville, Pennsylvania. PARTICIPANTS: About 1165 young adults who were low consumers of FV (<3 servings/day) at baseline. INTERVENTION: Online 3-arm program designed to increase FV consumption. MEASUREMENTS: We categorized FV changes into 4 categories: no change or decrease, 1 serving increase, 2 serving increase, and 3 or more serving increase. We then compared the changes in chronic insomnia classification (yes or no), sleep duration, quality, and time to fall asleep (all self-reported) across the FV change categories. Analyses were both overall and stratified by gender, adjusting for potential confounders (depression, physical activity, education, children, and study site). RESULTS: Average age ± SD was 26 ± 2.8 years (71% women). At 3-month follow-up, participants on average increased FV intake by 1.2 ± 1.4 servings. Women who increased FV intake by 3+ servings showed improvements in insomnia symptoms (2-fold higher odds of improvement; 95% CI 1.1 to 3.6), sleep quality (0.2-point higher sleep quality score; 95% CI -0.01, 0.3), and time to fall asleep (4.2 minutes; 95% CI -8, 0) compared to women who did not change or decreased their FV intake. Associations were not as apparent among men. CONCLUSION: Young women with low consumption of FV may experience improvements in insomnia-related sleep difficulties by increasing their consumption of FV.

Nicotinic acetylcholine receptor genes on chromosome 15q25.1 are associated with nicotine and opioid dependence severity.

A locus on chromosome 15q25.1 previously implicated in nicotine, alcohol, and cocaine dependence, smoking, and lung cancer encodes subunits of the nicotinic acetylcholine receptor (nAChR) expressed in the mesolimbic system and thought to mediate substance dependence. Opioid dependence severity (ODS), nicotine dependence severity (NDS), smoking status and quantity, and the number of attempts to quit were assessed using questionnaire instruments in 505 subjects who were prescribed opioid medications for chronic pain in outpatient practice sites. Multivariate regression was used to test for genetic association of these phenotypes with 5 SNPs in the nAChR gene cluster on chromosome 15q25.1, adjusting for background variables. A coding variant in CHRNA5 (rs16969968[A]) was significantly associated with 1.4-unit higher ODS (p < 0.00017). A variant in the 3' untranslated region of CHRNA3 (rs660652[G]) was significantly associated with 1.7-fold higher odds of lifetime smoking (p < 0.0092), 1.1-unit higher NDS (p < 0.0007), 0.7 more pack-years of cigarette smoking (p < 0.0038), and 0.8 more lifetime attempts to quit (p < 0.0084). Our data suggest an association of DNA variants in the nAChR gene cluster on chromosome 15q25.1 with ODS, as well as NDS and related smoking phenotypes. While the association of this locus with NDS and smoking phenotypes is well known, the association with ODS, a dimension of opioid substance dependence, is novel and requires verification in independent studies.

Body mass index measurement and obesity prevalence in ten U.S. health plans.

OBJECTIVE: The objective of this study was to examine the frequency of body mass index (BMI) measurement before the implementation of two new Healthcare Effectiveness Data and Information Set (HEDIS) performance measures for obesity that require U.S. health plans to annually report the frequency of BMI and BMI percentile measurement among all adults and children who had at least one outpatient visit during the past two years. DESIGN: Cross-sectional study. SETTING: A consortium of ten U.S. health plans and care delivery systems from the Health Maintenance Organization Research Network, which together provide care to more than 6.5 million adults and children. PARTICIPANTS: Children and adults, age 2 years and older, who were continuously enrolled in one of ten U.S. health plans for at least one full year from 2005 to 2006. METHODS: We extracted available anthropometric data for 3.7 million adults and 1.2 million children with at least one visit captured from ten electronic medical record databases from 2005 to 2006. RESULTS: We found that the availability of BMI measurements for adults ranged widely across health plans from 28% to 88%, and availability of BMI percentiles for children ranged from 21% to 81%. Among adults and children with BMI measures in these ten health plans, the overall prevalence of overweight and obesity were very similar to those reported in the 2005 to 2006 U.S. national surveys that used measured heights and weights. CONCLUSION: The newly approved HEDIS performance measures likely represent an important step in addressing the quality of obesity care in the United States. The current study demonstrates that these HEDIS measures are achievable, especially among health plans that have implemented electronic medical records. Future research should assess the relationship between BMI assessment, provider counseling and treatment practices, and long-term changes in obesity rates among different population groups.

Opioid Stewardship in Urology: Quality Improvement Summit 2018.

INTRODUCTION: We summarize the 2018 AUA (American Urological Association) Quality Improvement Summit, Opioid Stewardship in Urology, highlighting appropriate urological opioid use as well as reviewing programs that have been successful in reducing opioid prescribing. The AUA brought together nearly 100 attendees from across the United States, including clinicians who specialize in urology and other specialties, as well as researchers, government officials and others. METHODS: The 2018 AUA Quality Improvement Summit was a 1-day meeting held at AUA headquarters in Linthicum, Maryland. Talks and panels highlighted opioid stewardship programs and emphasized research on the nature and management of postoperative pain. RESULTS: The impact of the opioid epidemic is profound and the contribution of postoperative prescribing is noteworthy (eg 6% of opioid naïve patients demonstrate new persistent use habits after surgery and up to 70% of opioid pills prescribed after surgery go unused). Speakers raised awareness of these facts and detailed opportunities to improve, including prudent prescribing, opioid reclamation, use of nonopioid alternatives, and outreach and education. CONCLUSIONS: The 2018 AUA Quality Improvement Summit provided a platform for urologists to discuss the opioid epidemic and to learn strategies for combatting this issue from multidisciplinary experts. Physician led opioid stewardship and research, facilitated by this Summit, may enhance the quality and safety of medical care and improve the lives of patients, their families and their communities.

5-2-1-0 Lifestyle risk factors predict obesity in Millennials.

The Making Effective Nutritional Choices Generation Y (MENU GenY) study is a web-based intervention trial aimed at improving food choices in those aged 21-30 years. We report baseline levels of the 5-2-1-0 healthy lifestyle patterns to predict a body mass index (BMI) ≥30 vs <30 kg m-2 . Overall, 1674 young adults (69% female) from two large health systems enroled and completed an online survey asking questions about lifestyle habits. A multivariable binary logistic regression model was utilized to predict a BMI ≥30 while controlling for known predictors of obesity. Consuming >3 daily servings of fruits/vegetables (odds ratio, OR = 0.90, 95% confidence interval, CI = 0.81, 0.99), and reporting >2.5 hours/week of vigorous physical activity (OR = 0.93, 95% CI = 0.89-0.96, P < 0.001) was associated with a BMI <30. Conversely, time sitting (OR = 1.07, 95% CI = 1.04, 1.11) and consuming sugar-sweetened beverages (OR = 1.08, 95% CI = 1.00, 1.15) were related to a BMI ≥30. In this cohort of 20-30-year-olds, we observed a consistent relationship between obesity and the 5-2-1-0 healthy lifestyle patterns previously reported among children and adolescents.

Cost-effectiveness of pharmacogenetic testing to tailor smoking-cessation treatment.

We evaluated the cost-effectiveness of a range of smoking cessation drug treatments, including varenicline, transdermal nicotine (TN), bupropion and the use of a genetic test to choose between TN and bupropion. We performed Monte Carlo simulation with sensitivity analysis, informing analyses with published estimates of model parameters and current prices for genetic testing and smoking-cessation therapy. The primary outcomes were discounted life-years (LY) and lifetime tobacco-cessation treatment costs. In the base case, varenicline treatment was optimal with an ICER, compared to bupropion, of $2985/LY saved. In sensitivity analyses, varenicline was in all cases (and bupropion in most cases) admissible; only under favorable assumptions was the genetically tailored approach competitive. Our data suggest that an untailored approach of treatment with either bupropion or varenicline is a cost-effective form of tobacco dependence treatment, but a tailored approach for selecting between TN and bupropion can be cost-effective under plausible assumptions.

Motivations of Young Adults for Improving Dietary Choices: Focus Group Findings Prior to the MENU GenY Dietary Change Trial.

BACKGROUND: Young adulthood is often associated with poor dietary habits that may increase risk of obesity and chronic diseases. As independence grows, little is known about strategies to help balance social, work, and education commitments that may override desires to incorporate healthful food choices. OBJECTIVE: In advance of a randomized trial to test an online intervention targeting young adults, we sought to identify views and experiences with healthy eating, and specifically, eating more fruits and vegetables. METHODS: We conducted 13 focus groups with 68 young adults in metropolitan Detroit (Henry Ford Health System) and rural Pennsylvania (Geisinger Health System). Randomly selected adults aged 21 to 30 years, using health system automated data, were sent recruitment letters. Questions were grounded in social cognitive theory and self-determination theory. Audiotapes were transcribed, content themes identified, coded, verified for reliability, and analyzed qualitatively. RESULTS: Young adults' efforts to eat healthfully included three major themes of (1) motivations to create a healthy lifestyle, teach by example, feel better, and manage weight and future health problems; (2) learning to eat well from childhood, independent living, and peers; and (3) strategies to eat better through planning, tracking, and commitment. DISCUSSION: We uncovered theory-based factors that facilitate healthy dietary behavior change among young adults, including managing their behavior through self-monitoring, goal-setting, small steps, meaningful reinforcements, and social opportunities. CONCLUSIONS: Targeted interventions encouraging reflection on personal values related to meaningful contemporary health benefits are likely to resonate with young adults, as will opportunities to receive and share new information.

Translating basic science to improve pharmacotherapy for nicotine dependence.

Nicotine dependence has a complex multifactorial etiology, underscoring the value of applying a transdisciplinary research model. The important goal of treating nicotine dependence can be realized by transdisciplinary research that translates discoveries in basic neuroscience, pharmacology, genetics, and behavioral science to develop new treatment models that can be translated readily into the clinic and community. As part of this special issue highlighting work at the Transdisciplinary Tobacco Use Research Centers (TTURCs), we describe transdisciplinary research at the University of Pennsylvania TTURC aimed at elucidating the neurobiological and genetic basis of nicotine dependence, the development of novel medications, and the translation of this research to practice.

Role of functional genetic variation in the dopamine D2 receptor (DRD2) in response to bupropion and nicotine replacement therapy for tobacco dependence: results of two randomized clinical trials.

Although bupropion and nicotine replacement therapy (NRT) are efficacious tobacco dependence treatments, there is substantial interindividual variability in therapeutic response and most smokers relapse. Pharmacogenetics research may improve treatment outcomes by identifying genetic variants predictive of therapeutic response. We investigated the roles of two functional genetic variants in the dopamine D2 receptor (DRD2) gene in response to pharmacotherapy for tobacco dependence among participants in two randomized clinical trials with a 6-month follow-up period: a double-blind placebo-controlled trial of bupropion (n=414) and an open label trial of transdermal nicotine vs nicotine nasal spray (n=368). At the end of the treatment phase, a statistically significant (p=0.01) interaction between the DRD2 - 141C Ins/Del genotype and treatment indicated a more favorable response to bupropion among smokers homozygous for the Ins C allele compared to those carrying a Del C allele. By contrast, smokers carrying the Del C allele had statistically significantly (p=0.006) higher quit rates on NRT compared to those homozygous for the Ins C allele, independent of NRT type. The C957T variant was also associated (p=0.03) with abstinence following NRT. These results suggest that bupropion may be the preferred pharmacologic treatment for smokers homozygous for the DRD2 - 141 Ins C allele, while NRT may be more beneficial for those who carry the Del C allele. Study findings require confirmation in additional larger samples before they are applied in practice.

Smoking cessation treatment by primary care physicians: An update and call for training.

BACKGROUND: Public health and government organizations have invested considerably to increase physician adherence to smoking-cessation practice guidelines. METHODS: A random sample of 2000 U.S. primary care physicians was ascertained from the American Medical Association (AMA) in 2002. Respondents (n = 1120, 62.3%) provided self-reported data about individual and practice characteristics and smoking-cessation practices. Data were analyzed in 2005. RESULTS: Most primary care physicians (75%) advised cessation, 64% recommended nicotine patches, 67% recommended bupropion, 32% recommended nicotine gum, 10% referred to cessation experts, and 26% referred to cessation programs "often or always." Advising cessation was related to being older, having a faculty appointment, having trained staff for smoking counseling, and having confidence to counsel patients about smoking. Physicians who were internists, younger, and those with greater confidence to counsel patients about smoking recommended nicotine replacement more often. Prescribing bupropion was less common among older physicians, in the Northeast, with trained staff available for counseling, and with a greater proportion of minority or Medicaid patients. Prescribing bupropion was more common among AMA-member physicians and physicians with greater confidence to counsel patients about smoking. Providing a referral to an outside expert or program was more common among female physicians, and physicians in the Northeast or West, with larger clinical practices, and with trained staff for cessation counseling. CONCLUSIONS: Current physician self-reported practices for smoking cessation suggest opportunity for improvement. Targeted efforts to educate and support subsets of primary care physicians may improve physician adherence and smoking outcomes.

Antipsychotic medications and extreme weight gain in two health systems.

OBJECTIVE: We conducted this study to investigate the rate of clinically important, extreme weight gain (EWG; ≥7% body weight gain) among all second generation antipsychotic (SGA) users in two large health care systems in the United States. STUDY DESIGN: Retrospective observational cohort study. METHODS: We used electronic medical record databases of two health systems to identify adults aged 18-79 years who from 1 January 2004 to 31 December 2011 had initiated a SGA medication. All patients had to have a minimum of two weight measures in the medical record: (1) one or more weights in the 180-day pre-treatment (baseline) period; and (2) one or more weights in the first year after initiating SGA treatment. RESULTS: We found that EWG occurred in 7.7-17.0% of SGA users. At one year, the average weight gain was nearly 10kg among SGA users who experienced EWG. Olanzapine was the SGA most commonly associated with EWG with a rate of 17.0 per 100 users [95% confidence interval (CI): 14.2-20.5], while ziprasidone was least commonly associated with EWG (7.7 per 100 users; 95% CI: 4.6-13.0). CONCLUSIONS: We found that clinically-important weight gain was common after the initiation of SGA treatment, and the EWG phenotype was easily identifiable within electronic medical records. There was significant heterogeneity in the rate of EWG across SGA medications. Weight gains of this magnitude are likely to have adverse health consequences and there is a significant unmet opportunity for physicians to identify these events and mitigate the harms of SGA use.

Naltrexone reduces the relative reinforcing value of nicotine in a cigarette smoking choice paradigm.

RATIONALE: Human behavioral pharmacology studies can examine how medications that target different neurotransmitter systems influence different aspects of smoking. Naltrexone and bupropion have been shown to alter ad lib smoking behavior; however, medication effects on nicotine reward in a cigarette choice paradigm have yet to be investigated. OBJECTIVE: This study explored the effects of an acute dose of naltrexone, bupropion, or placebo on the relative reinforcing value of nicotine from cigarette smoking using new nicotine and de-nicotinized (Quest, 0.6 and 0.05 mg = "denicotinized") cigarettes. METHODS: In a double-blind, within-subjects design, 26 dependent smokers participated in three experimental cigarette smoking sessions following pretreatment with either naltrexone (50 mg), bupropion (300 mg), or placebo. After medication administration and 2 h of monitored deprivation from cigarettes and food, participants rated their responses to the initial exposure to the cigarettes and then participated in four choice sessions over a 2-h period during which they could take four puffs from either cigarette. RESULTS: The relative reinforcing value of nicotine, as measured by the number of nicotine puffs chosen out of 16, was significantly lower following naltrexone compared to placebo. There were no effects of an acute dose of bupropion on nicotine choices. CONCLUSIONS: These results suggest that naltrexone may reduce the relative reinforcing effects of nicotine via cigarette smoking and support ongoing investigation of opioid antagonists as potential smoking cessation pharmacotherapies.

Atomoxetine and nicotine enhance prepulse inhibition of acoustic startle in C57BL/6 mice.

Deficits in sensory-gating, often measured as deficits in prepulse inhibition of acoustic startle (PPI), are associated multiple with disorders including schizophrenia, attention deficit and hyperactivity disorder (ADHD), and withdrawal from nicotine. Drugs that can reverse deficits in PPI may serve as therapeutic agents for nicotine withdrawal, ADHD, and/or schizophrenia. The present study investigated the effects of acute atomoxetine, a norepinephrine reuptake inhibitor, nicotine, and mecamylamine, a nicotinic acetylcholinergic antagonist, on PPI and acoustic startle in C57BL/6 mice. Three doses of atomoxetine (0.2, 2.0, and 20 mg/kg) were administered prior to testing PPI and startle. The 0.2 and 2.0 mg/kg doses enhanced PPI and the 20 mg/kg dose enhanced startle. A second experiment investigated the effects of 2.0 mg/kg atomoxetine and 1.0mg/kg mecamylamine administered alone or together on PPI and startle. As before, atomoxetine enhanced PPI. Mecamylamine did not alter PPI and did not block the enhancement of PPI by atomoxetine. Neither drug altered startle. A third experiment investigated the effects of 2.0 mg/kg atomoxetine and 0.125 mg/kg nicotine administered alone or together on PPI and startle. Both drugs enhanced PPI when administered alone. However, when co-administered, no enhancement of PPI was seen. Neither nicotine nor atomoxetine altered startle. The present results demonstrate that acute doses of nicotine and atomoxetine enhance PPI independent of effects on startle and that the enhancement of PPI by atomoxetine occurs independent of the nicotinic acetylcholinergic system. Thus, the newly available medication for ADHD, atomoxetine, could be a potential therapeutic agent for disorders associated with disrupted PPI such as withdrawal from nicotine.

Informal mentoring between faculty and medical students.

Mentoring skills are valuable assets for academic medicine faculty, who help shape the professionalism of the next generation of physicians. Mentors are role models who also act as guides for students' personal and professional development over time. Mentors can be instrumental in conveying explicit academic knowledge required to master curriculum content. Importantly, they can enhance implicit knowledge about the "hidden curriculum" of professionalism, ethics, values and the art of medicine not learned from texts. In many cases, mentors also provide emotional support and encouragement. The relationship benefits mentors as well, through greater productivity, career satisfaction, and personal gratification. Maximizing the satisfaction and productivity of such relationships entails self-awareness, focus, mutual respect, and explicit communication about the relationship. In this article, the authors describe the development of optimal mentoring relationships, emphasizing the importance of experience and flexibility in working with beginning to advanced students of different learning styles, genders, and races. Concrete advice for mentor "do's and don'ts"is offered, with case examples illustrating key concepts.

Increases in hyperactive-impulsive symptoms predict relapse among smokers in nicotine replacement therapy.

Inattention and hyperactive-impulsive symptoms have been associated with nicotine dependence. In an open-label randomized trial (N = 454) of transdermal nicotine versus nicotine nasal spray, we examined whether increases in inattention and hyperactive-impulsive symptoms measured by self-report in the first quit week predicted relapse at the end of 8 weeks of treatment (EOT). During the first quit week, 166 (37%) participants reported an increase whereas 288 (63%) reported no change/decrease in total symptoms; changes were not influenced by treatment type. In a logistic regression model of abstinence, an increase in total symptoms in the first quit week significantly reduced odds of abstinence at EOT (continuous change score: OR = 0.94, 95% CI = 0.91-0.98, p = .002; dichotomized change score: OR = 0.57, 95% CI = 0.37-0.87, p = .009). Early increases in inattention and hyperactive-impulsive symptoms following quit date during nicotine replacement therapy predicted relapse to smoking, suggesting that treatments targeting these symptoms in the first quit week may facilitate abstinence.

Effects of different nicotine replacement therapies on postcessation psychological responses.

Transdermal nicotine patch (TN) and nicotine nasal spray (NS) are both efficacious forms of smoking cessation treatment, but have different pharmacokinetic properties and modes of action. To understand better psychological responses to treatment, we investigated the effects of TN versus NS on positive affect, negative affect, and withdrawal symptoms during treatment. Participants were randomly assigned to receive TN (n=172) or NS (n=163) plus seven sessions of behavioral counseling, and completed self-report questionnaires at pretreatment and during treatment. TN participants, but not NS participants, reported significant increases in positive affect during treatment. Increases in negative affect and withdrawal were observed, independent of treatment. Only changes in negative affect predicted relapse by the end of the treatment phase. These findings indicate that, although TN may enhance positive affect for smokers in treatment compared with NS, only changes in negative affect predict treatment outcome.