Interannual changes in atmospheric oxidation over forests determined from space.

The hydroxyl radical (OH) is the central oxidant in Earth's troposphere, but its temporal variability is poorly understood. We combine 2012-2020 satellite-based isoprene and formaldehyde measurements to identify coherent OH changes over temperate and tropical forests with attribution to emission trends, biotic stressors, and climate. We identify a multiyear OH decrease over the Southeast United States and show that with increasingly hot/dry summers the regional chemistry could become even less oxidizing depending on competing temperature/drought impacts on isoprene. Furthermore, while global mean OH decreases during El Niño, we show that near-field effects over tropical rainforests can alternate between high/low OH anomalies due to opposing fire and biogenic emission impacts. Results provide insights into how atmospheric oxidation will evolve with changing emissions and climate.

Impact of Real-World Outpatient Cancer Rehabilitation Services on Health-Related Quality of Life of Cancer Survivors across 12 Diagnosis Types in the United States.

Compared to adults without cancer, cancer survivors report poorer health-related quality of life (HRQOL), which is associated with negative treatment outcomes and increased healthcare use. Cancer-specialized physical and occupational therapy (PT/OT) could optimize HRQOL; however, the impact among survivors with non-breast malignancies is unknown. This retrospective (2020-2022), observational, study of medical record data of 12 cancer types, examined pre/post-HRQOL among cancer survivors who completed PT/OT. PROMIS® HRQOL measures: Global Health (physical [GPH] and mental [GMH]), Physical Function (PF), and Ability to Participate in Social Roles and Activities (SRA) were evaluated using linear mixed effect models by cancer type, then compared to the minimal important change (MIC, 2 points). Survivors were 65.44 ± 12.84 years old (range: 19-91), male (54%), with a median of 12 visits. Improvements in GPH were significant (p < 0.05) for all cancer types and all achieved MIC. Improvements in GMH were significant for 11/12 cancer types and 8/12 achieved MIC. Improvements in PF were significant for all cancer types and all achieved the MIC. Improvements in SRA were significant for all cancer types and all groups achieved the MIC. We observed statistically and clinically significant improvements in HRQOL domains for each of the 12 cancer types evaluated.

Geriatric assessment-identified impairments and frailty in adults with cancer younger than 65: An opportunity to optimize oncology care.

INTRODUCTION: Frailty, a state of increased vulnerability to stressors due to aging or treatment-related accelerated aging, is associated with declines in physical, cognitive and/or social functioning, and quality of life for cancer survivors. For survivors aged <65 years, little is known about frailty status and associated impairments to inform intervention. We aimed to evaluate the prevalence of frailty and contributing geriatric assessment (GA)-identified impairments in adults aged <65 versus ≥65 years with cancer. MATERIALS AND METHODS: This study is a secondary analysis of clinical trial data (NCT04852575). Participants were starting a new line of systemic therapy at a community-based oncology private practice. Before starting treatment, participants completed an online patient-reported GA and the Physical Activity (PA) Vital Sign questionnaire. Frailty score and category were derived from GA using a validated deficit accumulation model: frail (>0.35), pre-frail (0.2-0.35), or robust (0-0.2). PA mins/week were calculated, and participants were coded as either meeting/not-meeting guidelines (≥90 min/week). We used Spearman (ρ) correlation to examine the association between age and frailty score and chi-squared/Fisher's-exact or ANOVA/Kruskal-Wallis statistic to compare frailty and PA outcomes between age groups. RESULTS: Participants (n = 96) were predominantly female (62%), Caucasian (68%), beginning first-line systemic therapy (69%), and 1.75 months post-diagnosis (median). Most had stage III to IV disease (66%). Common cancer types included breast (34%), gastrointestinal (23%), and hematologic (15%). Among participants <65, 46.8% were frail or pre-frail compared to 38.7% of those ≥65. There was no association between age and frailty score (ρ = 0.01, p = 0.91). Between age groups, there was no significant difference in frailty score (p = 0.95), the prevalence of frailty (p = 0.68), number of GA impairments (p = 0.33), or the proportion meeting PA guidelines (p = 0.72). However, older adults had more comorbid conditions (p = 0.03) and younger adults had non-significant but clinically relevant differences in functional ability, falls, and PA level. DISCUSSION: In our cohort, the prevalence of frailty was similar among adults with cancer <65 when compared to those older than 65, however, types of GA impairments differed. These results suggest GA and the associated frailty index could be useful to identify needs for intervention and inform clinical decisions during cancer treatment regardless of age. Additional research is needed to confirm our findings.

Obstetric imaging practice characteristics associated with prenatal detection of critical congenital heart disease in a rural US region over 20 years.

OBJECTIVE: To identify clinical practice characteristics associated with the frequency of prenatal critical congenital heart disease (CCHD) detection (i.e., the number of liveborn infants with postnatally confirmed CCHD identified on prenatal sonography) over 20 years in a rural setting comprised of 11 primarily low-volume obstetric hospitals and the single tertiary academic hospital to which they refer. METHODS: This was a retrospective cohort study of all patients in the referral region with an initial prenatal and/or postnatal diagnosis of CCHD from 01/01/2002 to 12/31/2021. The frequency of prenatal CCHD detection at the time of an obstetric ultrasound was reported, as was the change in detection over time. Critical congenital heart disease detection was assessed as a function of cardiac lesion type, practice setting, and practice characteristics. RESULTS: There were 271 cases with a confirmed postnatal CCHD diagnosis, of which 49% were identified prenatally. The majority of community practices each averaged <10 CCHD cases in total over the study period. Prenatal detection at the tertiary academic hospital's obstetric ultrasound unit was 64%, compared to 22% at the combined referring community practices (p < 0.001), though CCHD detection improved over time in both settings. Professional accreditation by the American Institute of Ultrasound in Medicine, image interpretation by radiology or Maternal Fetal Medicine, and use of video clips of ventricular outflow tracts were associated with improved prenatal CCHD detection. CONCLUSIONS: Our data demonstrate the infrequency of CCHD cases at small-volume, rural hospitals and the substantial variation in prenatal CCHD detection across practice settings. Our methods allowed for the identification of practice characteristics associated with prenatal CCHD detection.

California Case Study of Wildfires and Prescribed Burns: PM2.5 Emissions, Concentrations, and Implications for Human Health.

Wildfires are a significant threat to human health, in part through degraded air quality. Prescribed burning can reduce wildfire severity but can also lead to an increase in air pollution. The complexities of fires and atmospheric processes lead to uncertainties when predicting the air quality impacts of fire and make it difficult to fully assess the costs and benefits of an expansion of prescribed fire. By modeling differences in emissions, surface conditions, and meteorology between wildfire and prescribed burns, we present a novel comparison of the air quality impacts of these fire types under specific scenarios. One wildfire and two prescribed burn scenarios were considered, with one prescribed burn scenario optimized for potential smoke exposure. We found that PM2.5 emissions were reduced by 52%, from 0.27 to 0.14 Tg, when fires burned under prescribed burn conditions, considerably reducing PM2.5 concentrations. Excess short-term mortality from PM2.5 exposure was 40 deaths for fires under wildfire conditions and 39 and 15 deaths for fires under the default and optimized prescribed burn scenarios, respectively. Our findings suggest prescribed burns, particularly when planned during conditions that minimize smoke exposure, could be a net benefit for the impacts of wildfires on air quality and health.

Preclinical translational platform of neuroinflammatory disease biology relevant to neurodegenerative disease.

Neuroinflammation is a key driver of neurodegenerative disease, however the tools available to model this disease biology at the systems level are lacking. We describe a translational drug discovery platform based on organotypic culture of murine cortical brain slices that recapitulate disease-relevant neuroinflammatory biology. After an acute injury response, the brain slices assume a chronic neuroinflammatory state marked by transcriptomic profiles indicative of activation of microglia and astrocytes and loss of neuronal function. Microglia are necessary for manifestation of this neuroinflammation, as depletion of microglia prior to isolation of the brain slices prevents both activation of astrocytes and robust loss of synaptic function genes. The transcriptomic pattern of neuroinflammation in the mouse platform is present in published datasets derived from patients with amyotrophic lateral sclerosis, Huntington's disease, and frontotemporal dementia. Pharmacological utility of the platform was validated by demonstrating reversal of microglial activation and the overall transcriptomic signature with transforming growth factor-ß. Additional anti-inflammatory targets were screened and inhibitors of glucocorticoid receptors, COX-2, dihydrofolate reductase, and NLRP3 inflammasome all failed to reverse the neuroinflammatory signature. Bioinformatics analysis of the neuroinflammatory signature identified protein tyrosine phosphatase non-receptor type 11 (PTPN11/SHP2) as a potential target. Three structurally distinct inhibitors of PTPN11 (RMC-4550, TN0155, IACS-13909) reversed the neuroinflammatory disease signature. Collectively, these results highlight the utility of this novel neuroinflammatory platform for facilitating identification and validation of targets for neuroinflammatory neurodegenerative disease drug discovery.

Large Community Outbreak of Legionnaires Disease Potentially Associated with a Cooling Tower - Napa County, California, 2022.

Legionnaires disease is a serious infection acquired by inhalation of water droplets from human-made building water systems that contain Legionella bacteria. On July 11 and 12, 2022, Napa County Public Health (NCPH) in California received reports of three positive urinary antigen tests for Legionella pneumophila serogroup 1 in the town of Napa. By July 21, six Legionnaires disease cases had been confirmed among Napa County residents, compared with a baseline of one or two cases per year. NCPH requested assistance from the California Department of Public Health (CDPH) and CDC to aid in the investigations. Close temporal and geospatial clustering permitted a focused environmental sampling strategy of high-risk facilities which, coupled with whole genome sequencing results from samples and investigation of water system maintenance, facilitated potential linking of the outbreak with an environmental source. NCPH, with technical support from CDC and CDPH, instructed and monitored remediation practices for all environmental locations that tested positive for Legionella. The investigation response to this community outbreak illustrates the importance of interdisciplinary collaboration by public health agencies, laboratory support, timely communication with the public, and cooperation of managers of potentially implicated water systems. Timely identification of possible sources, sampling, and remediation of any facility testing positive for Legionella is crucial to interrupting further transmission.

In-Clinic versus Hybrid Cancer Rehabilitation Service Delivery during the COVID-19 Pandemic: An Outcome Comparison Study.

Diminished health-related quality of life (HRQOL) is common among cancer survivors but often amendable to rehabilitation. However, few access real-world rehabilitation services. Hybrid delivery modes (using a combination of in-clinic and synchronous telehealth visits) became popular during the COVID-19 pandemic and offer a promising solution to improve access beyond the pandemic. However, it is unclear if hybrid delivery has the same impact on patient-reported outcomes and experiences as standard, in-clinic-only delivery. To fill this gap, we performed a retrospective, observational, comparative outcomes study of real-world electronic medical record (EMR) data collected by a national outpatient rehabilitation provider in 2020-2021. Of the cases meeting the inclusion criteria (N = 2611), 60 were seen to via hybrid delivery. The outcomes evaluated pre and post-rehabilitation included PROMIS® global physical health (GPH), global mental health (GMH), physical function (PF), and the ability to participate in social roles and activities (SRA). The patient experience outcomes included the Net Promoter Survey (NPS®) and the Select Medical Patient-Reported Experience Measure (SM-PREM). A linear and logistic regression was used to examine the between-group differences in the PROMIS and SM-PREM scores while controlling for covariates. The hybrid and in-clinic-only cases improved similarly in all PROMIS outcomes (all p < 0.05). The association between the delivery mode and the likelihood of achieving the minimal important change in the PROMIS outcomes was non-significant (all p > 0.05). No between-group differences were observed in the NPS or SM-PREM scores (all p > 0.05). Although more research is needed, this real-world evidence suggests that hybrid rehabilitation care may be equally beneficial for and acceptable to cancer survivors and supports calls to expand access to and reimbursement for telerehabilitation.

The complexities of investigating mitochondria dynamics in multiple sclerosis and mouse models of MS.

Multiple sclerosis (MS) is a demyelinating, degenerating disorder of the central nervous system (CNS) that is accompanied by mitochondria energy production failure. A loss of myelin paired with a deficit in energy production can contribute to further neurodegeneration and disability in patients in MS. Mitochondria are essential organelles that produce adenosine triphosphate (ATP) via oxidative phosphorylation in all cells in the CNS, including neurons, oligodendrocytes, astrocytes, and immune cells. In the context of demyelinating diseases, mitochondria have been shown to alter their morphology and undergo an initial increase in metabolic demand. This is followed by mitochondrial respiratory chain deficiency and abnormalities in mitochondrial transport that contribute to progressive neurodegeneration and irreversible disability. The current methodologies to study mitochondria are limiting and are capable of providing only a partial snapshot of the true mitochondria activity at a particular timepoint during disease. Mitochondrial functional studies are mostly performed in cell culture or whole brain tissue, which prevents understanding of mitochondrial pathology in distinct cell types in vivo. A true understanding of cell-specific mitochondrial pathophysiology of MS in mouse models is required. Cell-specific mitochondria morphology, mitochondria motility, and ATP production studies in animal models of MS will help us understand the role of mitochondria in the normal and diseased CNS. In this review, we present currently used methods to investigate mitochondria function in MS mouse models and discuss the current advantages and caveats with using each technique. In addition, we present recently developed mitochondria transgenic mouse lines expressing Cre under the control of CNS specific promoters to relate mitochondria to disease in vivo.

Single-Dose Psilocybin Treatment for Major Depressive Disorder: A Randomized Clinical Trial.

Importance: Psilocybin shows promise as a treatment for major depressive disorder (MDD). Objective: To evaluate the magnitude, timing, and durability of antidepressant effects and safety of a single dose of psilocybin in patients with MDD. Design, Setting, and Participants: In this phase 2 trial conducted between December 2019 and June 2022 at 11 research sites in the US, participants were randomized in a 1:1 ratio to receive a single dose of psilocybin vs niacin placebo administered with psychological support. Participants were adults aged 21 to 65 years with a Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition diagnosis of MDD of at least 60 days' duration and moderate or greater symptom severity. Exclusion criteria included history of psychosis or mania, active substance use disorder, and active suicidal ideation with intent. Participants taking psychotropic agents who otherwise met inclusion/exclusion criteria were eligible following medication taper. Primary and secondary outcomes and adverse events (AEs) were assessed at baseline (conducted within 7 days before dosing) and at 2, 8, 15, 29, and 43 days after dosing. Interventions: Interventions were a 25-mg dose of synthetic psilocybin or a 100-mg dose of niacin in identical-appearing capsules, each administered with psychological support. Main Outcomes and Measures: The primary outcome was change in central rater-assessed Montgomery-Asberg Depression Rating Scale (MADRS) score (range, 0-60; higher scores indicate more severe depression) from baseline to day 43. The key secondary outcome measure was change in MADRS score from baseline to day 8. Other secondary outcomes were change in Sheehan Disability Scale score from baseline to day 43 and MADRS-defined sustained response and remission. Participants, study site personnel, study sponsor, outcome assessors (raters), and statisticians were blinded to treatment assignment. Results: A total of 104 participants (mean [SD] age, 41.1 [11.3] years; 52 [50%] women) were randomized (51 to the psilocybin group and 53 to the niacin group). Psilocybin treatment was associated with significantly reduced MADRS scores compared with niacin from baseline to day 43 (mean difference,-12.3 [95% CI, -17.5 to -7.2]; P <.001) and from baseline to day 8 (mean difference, -12.0 [95% CI, -16.6 to -7.4]; P < .001). Psilocybin treatment was also associated with significantly reduced Sheehan Disability Scale scores compared with niacin (mean difference, -2.31 [95% CI, 3.50-1.11]; P < .001) from baseline to day 43. More participants receiving psilocybin had sustained response (but not remission) than those receiving niacin. There were no serious treatment-emergent AEs; however, psilocybin treatment was associated with a higher rate of overall AEs and a higher rate of severe AEs. Conclusions and Relevance: Psilocybin treatment was associated with a clinically significant sustained reduction in depressive symptoms and functional disability, without serious adverse events. These findings add to increasing evidence that psilocybin-when administered with psychological support-may hold promise as a novel intervention for MDD. Trial Registration: ClinicalTrials.gov Identifier: NCT03866174.

A Systematic Approach to Standardizing Drinking Outcomes From Timeline Followback Data.

Objective: The timeline followback (TLFB) interview is the gold standard for the quantitative assessment of alcohol use. However, self-reported "drinks" can vary in alcohol content. If this variability is not accounted for, it can compromise the reliability and validity of TLFB data. To improve the precision of the TLFB data, we developed a detailed standard operating procedure (SOP) to calculate standard drinks more accurately from participant reports. Method: For the new SOP, the volume and alcohol content by volume (ABV) of distinct types of alcoholic beverages were determined based on product websites and other reliable sources. Recipes for specific cocktails were constructed based on recipes from bartending education websites. One standard drink was defined as 0.6 oz (14 g) of absolute alcohol. Standard drink totals were contrasted for the new SOP approach and the standard procedure, which generally assumed that one self-reported drink was equivalent to one standard drink. Results: Relative to the standard TLFB procedure, higher numbers of standard drinks were reported after implementing the TLFB SOP. Conclusions: Variability in procedures for conversion of self-reported alcohol consumption to standard drinks can confound the interpretation of TLFB data. The use and reporting of a detailed SOP can significantly reduce the potential for such inconsistencies. Detailed and consistent procedures for calculation of standard drinks can enhance the quality of TLFB drinking data.

Rapid determination of SARS-CoV-2 antibody neutralization titer using Bio-Rad Bio-Plex correlates strongly with pseudovirus-determined neutralization titer.

Accurate and rapid evaluation of SARS-CoV-2 half-maximal neutralizing antibody (nAb) titer (NT50) is an important research tool for measuring nAb responses after prophylaxis or therapeutics for COVID-19 prevention and management. Compared with ACE2-competitive enzyme immunoassays for nAb detection, pseudovirus assays remain low-throughput and labor intensive. A novel application of the Bio-Rad Bio-Plex Pro Human SARS-CoV-2 D614G S1 Variant nAb Assay was used to determine NT50 from COVID-19-vaccinated individuals and showed strong correlation to a laboratory-developed SARS-CoV-2 pseudovirus nAb assay. The Bio-Plex nAb assay could provide a rapid, high-throughput, culture-free method for NT50 determination in sera.

Understanding Patient Experience with Outpatient Cancer Rehabilitation Care.

BACKGROUND: Understanding patient experience is key to optimize access and quality of outpatient cancer rehabilitation (physical or occupational therapy, PT/OT) services. METHODS: We performed a retrospective mixed-method analysis of rehabilitation medical record data to better understand patient experience and aspects of care that influenced experience. From the medical record, we extracted case characteristics, patient experience data (Net Promoter Survey®, NPS) and patient-reported outcome (PRO) data. We categorized cases as 'promoters' (i.e., highly likely to recommend rehabilitation) or 'detractors', then calculated NPS score (-100 [worst] to 100 [best]). We identified key themes from NPS free-text comments using inductive content analysis, then used Pearson [r] or Spearman [ρ] correlation to explore relationships between NPS, characteristics, and PRO improvement. RESULTS: Patients (n = 383) were 60.51 ± 12.02 years old, predominantly women with breast cancer (69.2%), and attended 14.23 ± 12.37 visits. Most were 'promoters' (92%); NPS score was 91.4. Patients described two experiences (themes) that influenced their likelihood to recommend rehabilitation: (1) feeling comfortable with the process and (2) observable improvement in health/functioning, and described attributes of clinic staff, environment and clinical care that influenced themes. Likelihood to recommend rehabilitation was associated with achieving the minimal clinical important difference on a PRO (ρ = 0.21, p < 0.001) and cancer type (ρ = 0.10, p < 0.001). CONCLUSION: Patients who received specialized cancer PT/OT were highly likely to recommend rehabilitation. Feeling comfortable with the rehabilitation process and making observable improvements in health and/or functioning influenced likelihood to recommend. Rehabilitation providers should leverage the findings of this study optimize access to and quality of cancer rehab services.

Evaluation of Dilution Susceptibility Testing Methods for Aztreonam in Combination with Avibactam against Enterobacterales.

As multidrug and pan-resistance among Enterobacterales continue to increase, there is an urgent need for more therapeutic options to treat these infections. New ß-lactam and ß-lactam inhibitor (BLI) combinations have a broad spectrum of activity, but those currently approved do not provide coverage against isolates harboring metallo-ß-lactamases (MBL). Aztreonam (ATM) and avibactam (AVI) in combination (ATM/AVI; AVI at 4 µg/mL fixed concentration) provides a similarly broad range of activity while maintaining activity against MBL-producing isolates. The in vitro susceptibility testing of ATM/AVI by standard methods was evaluated during development. This study investigated the impact of nonstandard testing conditions on the activity of ATM/AVI as observed during broth microdilution testing as well as the equivalency between agar dilution and broth microdilution MIC values when testing a diverse panel of Enterobacterales (N = 201). Nonstandard test conditions evaluated included inoculum density, atmosphere of incubation, media pH, varied medium cation concentrations, incubation time, varied serum concentrations, testing in pooled urine instead of media, addition of blood to the media, and the presence of surfactant. Generally, apart from low pH and high inoculum density, nonstandard testing parameters did not affect ATM/AVI broth microdilution MIC values. Correlation of MIC values obtained by agar dilution and broth microdilution resulted in an essential agreement of 97.0% for all tested Enterobacterales. Variation of standard testing conditions had little impact on broth microdilution MIC values for ATM/AVI. The correlation between broth microdilution and agar dilution MICs suggests both methods are reliable for determination of ATM/AVI MIC values. IMPORTANCE Increasing antibiotic resistance and emergence of pan-resistant isolates threaten the ability to control infections and to provide many other medical interventions such as surgery and chemotherapy, among others. New therapies are required to control emerging resistance mechanisms, including the increase in metallo-ß-lactamases. Some new antibiotic combinations provide coverage against highly resistant isolates but are unable to target organisms that produce metallo-ß-lactamases. Aztreonam in combination with avibactam provides a broad spectrum of activity against highly resistant isolates that also targets metallo-ß-lactamase-producing organisms. An important part of drug development is the ability for clinical labs to determine the susceptibility of isolates to the antimicrobial. This manuscript investigates the in vitro susceptibility testing of aztreonam/avibactam with nonstandard testing conditions and a correlation study between broth microdilution and agar dilution against clinical isolates encoding a variety of resistance mechanisms. Overall, aztreonam/avibactam was generally unaffected by changes in testing conditions and showed strong agar/broth correlation.

Psilocybin for alcohol use disorder: Rationale and design considerations for a randomized controlled trial.

Several lines of evidence suggest that classic psychedelics (5-HT2A receptor agonists or partial agonists) such as psilocybin might facilitate behavior change in individuals with substance use disorders. We conducted a multi-site, double-blind, randomized controlled trial (RCT) to assess the effects of psilocybin-assisted psychotherapy in alcohol-dependent volunteers. In addition to a structured 12-week psychotherapy platform, participants (n = 96) were randomly assigned (1:1) to receive either oral psilocybin or an active placebo (oral diphenhydramine) in each of two dosing sessions (at weeks 4 and 8). Initial doses were 25 mg/70 kg psilocybin or 50 mg diphenhydramine, which could be increased in the second session depending on initial response. The psychotherapy platform combined evidence-based, manualized therapy for alcohol dependence with a supportive context for the dosing sessions. All participants were followed in the RCT through week 36. At the end of the RCT, participants who still met safety criteria were offered an open-label psilocybin session. Data collected at screening, baseline and throughout the study included: demographics, measures of alcohol use, subjective response to psilocybin and diphenhydramine, and safety measures. The primary outcome was the proportion of heavy drinking days during the 32 weeks after the first dosing session (i.e., between week 4 and week 36). Secondary outcomes included safety, additional measures of drinking (e.g., abstinence, drinking days, etc.), craving, self-efficacy, and acute effects. We will also explore moderators and mediators of the primary outcome. The primary outcomes will be published elsewhere. In this paper, we describe the protocol and rationale for our design decisions.

The Role of Exercise Self-Efficacy in Exercise Participation Among Women With Persistent Fatigue After Breast Cancer: A Mixed-Methods Study.

OBJECTIVE: Survivors of breast cancer with persistent cancer-related fatigue (CRF) report less exercise participation compared with survivors of breast cancer without CRF. Although CRF predicts other domains of self-efficacy among survivors, the effect of CRF on exercise self-efficacy (ESE)-an important predictor of exercise participation-has not been quantified. This study examined the relationship between CRF, ESE, and exercise participation and explored the lived experience of engaging in exercise among survivors of breast cancer with persistent CRF. METHODS: Fifty-eight survivors of breast cancer (3.7 [SD = 2.4] years after primary treatment) self-reported CRF, ESE, and exercise participation (hours of moderate-intensity exercise per week). Regression and mediation analyses were conducted. Survivors who reported clinically significant CRF and weekly exercise were purposively sampled for 1-on-1 interviews (N = 11). Thematic analysis was performed across participants and within higher versus lower ESE subsets. RESULTS: Greater CRF predicted lower ESE (ß = -0.32) and less exercise participation (ß = -0.08). ESE mediated the relationship between CRF and exercise participation (ß = -0.05, 95% CI = -0.09 to -0.02). Qualitative data showed that survivors of breast cancer with higher ESE perceived exercise as a strategy to manage fatigue, described self-motivation and commitment to exercise, and had multiple sources of support. In contrast, survivors with lower ESE described less initiative to manage fatigue through exercise, greater difficulty staying committed to exercise, and less support. CONCLUSIONS: Survivors of breast cancer with persistent CRF may experience decreased ESE, which negatively influences exercise participation. Clinicians should screen for or discuss confidence as it relates to exercise and consider tailoring standardized exercise recommendations for this population to optimize ESE. This may facilitate more sustainable exercise participation and improve outcomes. IMPACT: This study highlights the behavioral underpinnings of CRF as a barrier to exercise. Individualized exercise tailored to optimize ESE may facilitate sustainable exercise participation among survivors of breast cancer with CRF. Strategies for clinicians to address ESE are described and future research is suggested. LAY SUMMARY: Women with fatigue after breast cancer treatment may have lower confidence about their ability to engage in exercise. Individually tailoring exercise to build confidence as it relates to exercise may result in more consistent exercise and better health-related outcomes.