Purpose Examine mediators of fatigue response to an exercise intervention for breast cancer survivors (BCS) in a pilot randomized controlled trial. Methods Postmenopausal BCS (n=46; ≤ Stage II), off primary treatment, and reporting fatigue and/or sleep dysfunction were randomized to a 3-month exercise intervention (160 minutes/week of moderate intensity aerobic walking, twice weekly resistance training with resistance bands) or control group. Six discussion group sessions provided behavioral support to improve adherence. Fatigue, serum cytokines, accelerometer physical activity, cardiorespiratory fitness, sleep dysfunction, and psychosocial factors were assessed at baseline and 3 months. Results Exercise intervention effect sizes for fatigue were: fatigue intensity d=0.30 (p=.34), interference d=−0.38 (p=.22), and general fatigue d=−0.49 (p=.13). Using Freedman-Schatzkin difference-in-coefficients tests, increase in fatigue intensity was significantly mediated by interleukin (IL)-6 (82%), IL-10 (94%), IL-6:IL-10 (49%), and tumor necrosis factor (TNF)-alpha:IL-10 (78%) with reduced sleep dysfunction increasing the relationship between intervention and fatigue intensity rather than mediating intervention effects (−88%). Decrease in fatigue interference was mediated by sleep dysfunction (35%) while IL-10 and pro:anti-inflammatory cytokine ratios increased the relationship between intervention and interference (−25% to −40%). The reduction in general fatigue was significantly mediated by minutes of physical activity (76%), sleep dysfunction (45%), and physical activity enjoyment (40%) with IL-10 (−40%) and IL-6:IL-10 (−11%) increasing the intervention-fatigue relationship. In the intervention group, higher baseline fatigue, anxiety, depression, and perceived exercise barriers interference predicted a greater decline in fatigue interference and/or general fatigue during the intervention. Conclusions Biobehavioral factors mediated and enhanced intervention effects on fatigue while psychosocial factors predicted fatigue response. Further study is warranted to confirm our results and improve understanding of relationships that mediate and strengthen the intervention-fatigue association.

Objective To improve mechanistic understanding, this pilot randomized controlled trial examined mediators of an exercise intervention effects on sleep in breast cancer survivors (BCS). Methods Forty-six postmenopausal BCS (≤ Stage II, off primary treatment) were randomized to a 3-month exercise intervention or control group. Intervention included 160 minutes/week of moderate intensity aerobic walking, twice weekly resistance training (resistance bands), and six discussion groups (to improve adherence). Blinded assessments at baseline and post-intervention included sleep disturbance (PSQI and PROMIS®), objective sleep quality (accelerometer), serum cytokines, accelerometer physical activity, cardiorespiratory fitness, body composition, fatigue, and psychosocial factors. Mediation was tested using Freedman-Schatzkin difference-in-coefficients tests. Results When compared with control, the intervention group demonstrated a significant increase in PSQI sleep duration (i.e., fewer hours of sleep/night) (d=0.73, p=.03). Medium to large but non-significant standardized effect sizes were noted for PSQI daytime somnolence (d=-0.63, p=.05) and accelerometer latency (d=-0.49, p=.14). No statistically significant mediators were detected for PSQI sleep duration score or accelerometer latency. Daytime somnolence was mediated by tumor necrosis factor (TNF)-alpha (mediated 23% of intervention effect, p<.05), interleukin (IL)-6: IL-10 (16%, p<.01), IL-8:IL-10 (26%, p<.01), and fatigue (38%, p<.05). Mediating or enhancing relationships for several of the sleep outcomes were noted for accelerometer physical activity, PROMIS® fatigue, exercise social support, and/or physical activity enjoyment. Conclusions Inflammation and psychosocial factors may mediate or enhance sleep response to our exercise intervention. Further study is warranted to confirm our results and translate our findings into more effective interventions aimed at improving sleep quality in BCS.

Objectives: With decreasing mortality in PICUs, a growing number of survivors experience long-lasting physical impairments. Early physical rehabilitation and mobilization during critical illness are safe and feasible, but little is known about the prevalence in PICUs. We aimed to evaluate the prevalence of rehabilitation for critically ill children and associated barriers. Design: National 2-day point prevalence study. Setting: Eighty-two PICUs in 65 hospitals across the United States. Patients: All patients admitted to a participating PICU for greater than or equal to 72 hours on each point prevalence day. Interventions: None. Measurements and Main Results: The primary outcome was prevalence of physical therapy– or occupational therapy–provided mobility on the study days. PICUs also prospectively collected timing of initial rehabilitation team consultation, clinical and patient mobility data, potential mobility–associated safety events, and barriers to mobility. The point prevalence of physical therapy– or occupational therapy–provided mobility during 1,769 patient-days was 35% and associated with older age (adjusted odds ratio for 13–17 vs < 3 yr, 2.1; 95% CI, 1.5–3.1) and male gender (adjusted odds ratio for females, 0.76; 95% CI, 0.61–0.95). Patients with higher baseline function (Pediatric Cerebral Performance Category, ≤ 2 vs > 2) less often had rehabilitation consultation within the first 72 hours (27% vs 38%; p < 0.001). Patients were completely immobile on 19% of patient-days. A potential safety event occurred in only 4% of 4,700 mobility sessions, most commonly a transient change in vital signs. Out-of-bed mobility was negatively associated with the presence of an endotracheal tube (adjusted odds ratio, 0.13; 95% CI, 0.1–0.2) and urinary catheter (adjusted odds ratio, 0.28; 95% CI, 0.1–0.6). Positive associations included family presence in children less than 3 years old (adjusted odds ratio, 4.55; 95% CI, 3.1–6.6). Conclusions: Younger children, females, and patients with higher baseline function less commonly receive rehabilitation in U.S. PICUs, and early rehabilitation consultation is infrequent. These findings highlight the need for systematic design of rehabilitation interventions for all critically ill children at risk of functional impairments.

Systemic antibiotics, as part of acute SSTI management, impact S. aureus colonization, contributing to a decreased incidence of recurrent SSTI. The mechanism by which clindamycin differentially affects colonization and recurrent SSTI compared to TMP-SMX warrants further study.