The Impact of Aerobic Training on Cardiovascular Reactivity to and Recovery From Psychological and Orthostatic Challenge.

OBJECTIVE: Elevated cardiovascular reactivity to, and reduced recovery from, challenging events may increase the risk of cardiovascular disease, and exercise training may reduce this reactivity. However, in a randomized controlled trial of aerobic versus strength training in sedentary, healthy young adults, we found no training group differences in reactivity or recovery. Because strength training also may have a reactivity-reducing effect, we conducted a secondary analysis of data from another trial, this time with a wait-list control condition. METHODS: One hundred nineteen healthy, young, sedentary adults were randomized to a 12-week aerobic training program or wait-list control. Before (T1) and after (T2) training and after 4 weeks of sedentary deconditioning (T3), we measured heart rate (HR), heart rate variability, and blood pressure at rest and in response to and recovery from psychological and orthostatic challenge. Data were analyzed using a group (aerobic versus wait-list) by session (T1, T2, and deconditioning) and by period (baseline, psychological challenge, recovery, standing) three-way analysis of variance with prespecified contrasts. RESULTS: Aerobic capacity significantly increased at T2 and decreased at T3 only in the aerobic training group. The groups did not differ on HR, heart rate variability, or blood pressure reactivity to or recovery from challenge. Without baseline adjustment, there were no significant treatment differences in response to challenges. With baseline adjustment, there were significant treatment by session effects for HR (Cohen d = 0.54, p = .002), systolic blood pressure (d = 0.44, p = .014), diastolic blood pressure (d = 0.74, p = .002), and root mean squared successive difference (d = 0.48, p = .006) reactivity from T1 to T2 only for orthostatic challenge: at T2, reactivity in the aerobic group was nonsignificantly reduced, compared with T1. In the wait-list group, reactivity significantly increased after T1. CONCLUSIONS: This study raises further doubt about attenuation of cardiovascular reactivity or enhancement of recovery as a cardioprotective mechanism of aerobic exercise training.Clinical Trial Registration:ClinicalTrials.gov Unique identifier: NCT01335737.

Exploring longitudinal course and treatment-baseline severity interactions in secondary outcomes of smoking cessation treatment in individuals with attention-deficit hyperactivity disorder.

BACKGROUND: A double blind, placebo-controlled randomized trial (NCT00253747) evaluating osmotic-release oral system methylphenidate (OROS-MPH) for smoking-cessation revealed a significant interaction effect in which participants with higher baseline ADHD severity had better abstinence outcomes with OROS-MPH while participants with lower baseline ADHD severity had worse outcomes. OBJECTIVES: This current report examines secondary outcomes that might bear on the mechanism for this differential treatment effect. METHODS: Longitudinal analyses were conducted to evaluate the effect of OROS-MPH on three secondary outcomes (ADHD symptom severity, nicotine craving, and withdrawal) in the total sample (N = 255, 56% Male), and in the high (N = 134) and low (N = 121) baseline ADHD severity groups. RESULTS: OROS-MPH significantly improved ADHD symptoms and nicotine withdrawal symptoms in the total sample, and exploratory analyses showed that in both higher and lower baseline severity groups, OROS-MPH statistically significantly improved these two outcomes. No effect on craving overall was detected, though exploratory analyses showed statistically significantly decreased craving in the high ADHD severity participants on OROS-MPH. No treatment by ADHD baseline severity interaction was detected for the outcomes. CONCLUSIONS: Methylphenidate improved secondary outcomes during smoking cessation independent of baseline ADHD severity, with no evident treatment-baseline severity interaction. Our results suggest divergent responses to smoking cessation treatment in the higher and lower severity groups cannot be explained by concordant divergence in craving, withdrawal and ADHD symptom severity, and alternative hypotheses may need to be identified.

Prediction Tool for Individual Outcome Trajectories Across the Next Year in First-Episode Psychosis in Coordinated Specialty Care.

Importance: In coordinated specialty care (CSC) settings for people with a first episode of psychosis, the development of reliable, validated individual-level prediction tools for key outcomes may be informative for shared clinician and client decision-making. Objective: To develop an individual-level prediction tool using machine-learning methods that predicts a trajectory of education/work status or psychiatric hospitalization outcomes over a client's next year of quarterly follow-up assessments. Additionally, to visualize these predictions in a way that is informative to clinicians and clients. Design, Setting, and Participants: Individual-level data were collected for all patients enrolled in the OnTrackNY program at enrollment and at quarterly follow-ups using standardized forms. The OnTrackNY program, a network of CSC sites in New York State, provides person-centered, recovery-oriented, and evidence-based psychosocial and pharmaceutical interventions to individuals aged 16 to 30 years with recent-onset (<2 years) nonaffective psychosis. Although data collection is ongoing, data for this study were collected from October 2013 to December 2018, and the time frame for analysis was July 2020 to May 2021. Data were separated into a training/cross-validation set to perform internally validated model development and a separate holdout test set (~20% of the sample) for external validation. Random probability forest models were developed to predict individual-level trajectories of outcomes. Exposures: Forty-three individual-level demographic and clinical features collected at enrollment in OnTrackNY, 25 of which were time-varying and updated at quarterly follow-up assessments, and 13 site-level demographic and economic census variables. Main Outcomes and Measures: Individual-level education and/or employment status and psychiatric hospitalization trajectories at quarterly follow-up periods across the first 2 years of CSC. Results: The total study sample consists of 1298 individuals aged 16 to 30 years and included 341 women (26.3%), 949 men (73.1%), and 8 (<1%) with another gender. Prediction models performed well for 1-year trajectories of education/work across all validation sets, with areas under the receiver operating characteristic curve (AUCs) ranging from 0.68 (95% CI, 0.63-0.74) to 0.88 (95% CI, 0.81-0.96). Predictive accuracy for psychiatric hospitalization 3 months ahead reached AUC above 0.70; moreover, predictions of future psychiatric hospitalizations at 6 months and beyond were consistently poor, with AUCs below 0.60. Given the good externally validated performance for predicting education/work, a prototype interactive visualization tool displaying individual-level education/work trajectories and related features was developed. Conclusions and Relevance: This study suggests that accurate prediction tools can be developed for outcomes in people with first-episode psychosis, which may help inform shared clinician/client decision-making. Future work should study the effectiveness of its deployment, including proper communication to inform shared clinician/client decision-making in the context of a learning health care system. At present, more work is needed to develop better performing prediction models for future psychiatric hospitalizations before any tool is recommended for this outcome.

An Intersectional Approach to Ethnoracial Disparities in Pathways to Care Among Individuals With Psychosis in Coordinated Specialty Care.

Importance: Intersecting factors of social position including ethnoracial background may provide meaningful ways to understand disparities in pathways to care for people with a first episode of psychosis. Objective: To examine differences in pathways to care by ethnoracial groups and by empirically derived clusters combining multiple factors of social and clinical context in an ethnoracially diverse multisite early-intervention service program for first-episode psychosis. Design, Setting, and Participants: This cohort study used data collected on individuals with recent-onset psychosis (<2 years) by clinicians with standardized forms from October 2013 to January 2020 from a network of 21 coordinated specialty care (CSC) programs in New York State providing recovery-oriented, evidence-based psychosocial interventions and medications to young people experiencing early psychosis. Exposures: Ethnoracial group and other factors of social position (eg, insurance status, living situation, English fluency, geographic region) intersecting with first-contact experiences (ie, type of first service, referral source, and symptoms at referral). Main Outcomes and Measures: Outcome measures were time from onset to first contact, first contact to CSC, and onset to CSC. Results: The total study sample consists of 1726 individuals aged 16 to 30 years and included 452 women (26%), 1263 men (73%), and 11 (<1%) with another gender enrolled in the network of CSC programs. The total sample consisted of 153 Asian (9%), 599 Black (35%), 454 Latinx (26%), and 417 White individuals (24%). White individuals had a significantly shorter time from onset to first contact (median [IQR], 17 [0-80] days) than Asian (median [IQR], 34 [7-94] days) and Black (median [IQR], 30 [1-108] days) individuals but had the longest period from first contact to CSC (median [IQR], 102.5 [45-258] days). Five distinct clusters of individuals emerged that cut across ethnoracial groups. The more disadvantaged clusters in terms of both social position and first-contact experiences had the longest time from onset to first contact, which were longer than for any single ethnoracial group. Conclusions and Relevance: In this cohort study of individuals with recent-onset psychosis, time-to-treatment outcomes differed by ethnoracial group and by empirically derived clusters combining multiple factors of social and clinical context. The examination of disparities in durations to treatment through an intersectional, ethnoracial lens may improve understanding of the inequities resulting from the various intersecting factors that may compound delays in treatment initiation.

Sublingual Buprenorphine-Naloxone Compared With Injection Naltrexone for Opioid Use Disorder: Potential Utility of Patient Characteristics in Guiding Choice of Treatment.

OBJECTIVE: Sublingual buprenorphine-naloxone and extended-release injection naltrexone are effective treatments, with distinct mechanisms, for opioid use disorder. The authors examined whether patients' demographic and clinical characteristics were associated with better response to one medication or the other. METHODS: In a multisite 24-week randomized comparative-effectiveness trial of assignment to buprenorphine-naloxone (N=287) compared with extended-release naltrexone (N=283) comprising inpatients planning to initiate medication treatment for opioid use disorder, 50 demographic and clinical characteristics were examined as moderators of the effect of medication assignment on relapse to regular opioid use and failure to initiate medication. Moderator-by-medication interactions were estimated using logistic regression with correction for multiple testing. RESULTS: In the intent-to-treat sample, patients who reported being homeless had a lower relapse rate if they were assigned to receive extended-release naltrexone (51.6%) compared with buprenorphine-naloxone (70.4%) (odds ratio=0.45, 95% CI=0.22, 0.90); patients who were not homeless had a higher relapse rate if they were assigned to extended-release naltrexone (70.9%) compared with buprenorphine-naloxone (53.1%) (odds ratio=2.15, 95% CI=1.44, 3.21). In the subsample of patients who initiated medication, the interaction was not significant, with a similar pattern of lower relapse with extended-release naltrexone (41.4%) compared with buprenorphine (68.6%) among homeless patients (odds ratio=0.32, 95% CI=0.15, 0.68) but less difference among those not homeless (extended-release naltrexone, 57.2%; buprenorphine, 52.0%; odds ratio=1.24, 95% CI=0.80, 1.90). For failure to initiate medication, moderators were stated preference for medication (failure was less likely if the patient was assigned to the medication preferred), parole and probation status (fewer failures with extended-release naltrexone for those on parole or probation), and presence of pain and timing of randomization (more failure with extended-release naltrexone for patients endorsing moderate to severe pain and randomized early while still undergoing medically managed withdrawal). CONCLUSIONS: Among patients with opioid use disorder admitted to inpatient treatment, homelessness, parole and probation status, medication preference, and factors likely to influence tolerability of medication initiation may be important in matching patients to buprenorphine or extended-release naltrexone.

The effects of aerobic training on subclinical negative affect: A randomized controlled trial.

OBJECTIVE: The antidepressant and anxiolytic effects of aerobic exercise are well known, but less is known about its effects on subclinical levels of trait negative affect in healthy but sedentary adults. In the present study, we test the effects of a 3-month randomized controlled trial of aerobic exercise training in young to midlife adults on trait measures of depression, anxiety, hostility, and anger. METHOD: One-hundred and 19 men (n = 56) and women (n = 63) aged 20-45 were randomized to 1 of 2 conditions: (a) 12 weeks of aerobic exercise after which they were asked to halt exercising and decondition for 4 weeks, or (b) a 16-week waitlist control group. Assessments of depression, anxiety, hostility and anger were completed at study entry, Week 12 and Week 16. RESULTS: At study entry, participants scored low on measures of depression, anxiety, hostility and anger. Analyses among the intent-to-treat and per protocol samples found significant treatment effects of aerobic training for hostility and depression, but not for anxiety and anger. Within-group analyses demonstrated that depression and hostility scores decreased in the exercise group over the course of the intervention, while remaining stable in the control group. These effects persisted for the exercise group at nonsignificant levels after 4 weeks of deconditioning. CONCLUSIONS: Aerobic exercise training has significant psychological effects even in sedentary yet euthymic adults, adding experimental data on the known benefits of exercise in this population. (PsycINFO Database Record (c) 2020 APA, all rights reserved).

Anger-reduction treatment reduces negative affect reactivity to daily stressors.

OBJECTIVE: Negative affect (NA) reactivity to daily stressors may confer health risks over and above stress exposure, especially in chronically angry adults. This randomized controlled trial tests the hypothesis that a 12-week cognitive-behavioral therapy (CBT) anger-reduction treatment would decrease NA reactivity to daily stressors assessed via ambulatory diary for those in treatment, but not on a wait-list for treatment. METHOD: Healthy adults (N = 158, aged 20-45 years, 53.20% women) scoring high on Spielberger's (1988) Trait Anger, a scale from the State-Trait Anger Expression Inventory, were randomly assigned to a CBT treatment or wait-list control group, and completed 24 hr of prerandomization and postintervention ecological momentary assessment (EMA) of NA intensity and stress events every 20 ± 5 min. A longitudinal model using a generalized estimating equation examined whether stressor exposure and NA reactions to momentary stressors changed from pre- to posttreatment in the CBT group. RESULTS: There was a significant 3-way interaction (t28 = 2.29, p = .03) between stressor, treatment group, and EMA day, indicating that NA reactivity decreased for the treatment group 1.60 points more than for the wait-list group (a 379.38% greater change in NA reactivity). NA during stressors was 1.18 points lower (a 28.42% decrease) for the treatment group at EMA Day 2 (p = .04), whereas wait-list NA during stressors nonsignificantly increased. CONCLUSION: CBT to decrease chronic anger is associated with lower NA reactivity to daily stressors in this sample and could be a promising treatment to mitigate the health impact of stress in this clinical population. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Aerobic Exercise Training and Inducible Inflammation: Results of a Randomized Controlled Trial in Healthy, Young Adults.

Background Consensus panels regularly recommend aerobic exercise for its health-promoting properties, due in part to presumed anti-inflammatory effects, but many studies show no such effect, possibly related to study differences in participants, interventions, inflammatory markers, and statistical approaches. This variability makes an unequivocal determination of the anti-inflammatory effects of aerobic training elusive. Methods and Results We conducted a randomized controlled trial of 12 weeks of aerobic exercise training or a wait list control condition followed by 4 weeks of sedentary deconditioning on lipopolysaccharide (0, 0.1, and 1.0 ng/mL)-inducible tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), and on toll-like receptor 4 in 119 healthy, sedentary young adults. Aerobic capacity by cardiopulmonary exercise testing was measured at study entry (T1) and after training (T2) and deconditioning (T3). Despite a 15% increase in maximal oxygen consumption, there were no changes in inflammatory markers. Additional analyses revealed a differential longitudinal aerobic exercise training effect by lipopolysaccharide level in inducible TNF -α ( P=0.08) and IL-6 ( P=0.011), showing T1 to T2 increases rather than decreases in inducible (lipopolysaccharide 0.1, 1.0 versus 0.0 ng/mL) TNF- α (51% increase, P=0.041) and IL-6 (42% increase, P=0.11), and significant T2 to T3 decreases in inducible TNF- α (54% decrease, P=0.007) and IL-6 (55% decrease, P<0.001). There were no significant changes in either group at the 0.0 ng/mL lipopolysaccharide level for TNF- α or IL-6. Conclusions The failure to support the primary hypotheses and the unexpected post hoc findings of an exercise-training-induced proinflammatory response raise questions about whether and under what conditions exercise training has anti-inflammatory effects. Clinical Trial Registration URL : http://www.clinicaltrials.gov . Unique identifier: NCT 01335737.

Change in Odor Identification Impairment is Associated with Improvement with Cholinesterase Inhibitor Treatment in Mild Cognitive Impairment.

BACKGROUND: Anticholinergic challenge can induce odor identification impairment that indicates Alzheimer's disease pathology. OBJECTIVE: To determine if decline in odor identification ability with anticholinergic challenge can predict improvement with donepezil, a cholinesterase inhibitor (ChEI), in patients with mild cognitive impairment (MCI). METHODS: At baseline, the University of Pennsylvania Smell identification Test (UPSIT) was administered before and after an anticholinergic atropine nasal spray challenge. Donepezil was started at 5 mg daily, increased to 10 mg daily if tolerated, and then the dose was kept constant for 52 weeks. Main outcomes were change in Selective Reminding Test (SRT) total immediate recall and ADAS-Cog total score from baseline to 26 and 52 weeks. RESULTS: In 37 participants, mean age 70.4 (SD 9.8) y, greater atropine-induced decrease in UPSIT score at baseline was associated with greater improvement in SRT total recall score from baseline to 26 and 52 weeks (p < 0.03). This effect remained after adjusting for time, age, education, gender, APOE ɛ4 status, and baseline cognitive score (p < 0.05). Decrease in UPSIT score was associated with global improvement (CIBIC-plus) over 52 weeks (p < 0.02). After excluding patients with congential anosmia, increase in UPSIT score from 0 to 8 weeks showed a trend-level association with improvement on the ADAS-Cog (p = 0.07). CONCLUSIONS: Anticholinergic challenge-induced odor identification decline was associated with cognitive improvement, and short-term improvement in odor identification tended to predict longer term cognitive improvement. These simple inexpensive strategies have the potential to improve selection of patients with MCI for ChEI treatment.