PurposeAthletes involved in team sports may be subject to varying degrees of sleep
deprivation either before or after training and competition. Despite the
belief among athletes and coaches of the importance of adequate sleep for
ensuing performance, the effect of sleep loss on team-sport anaerobic
performance remains unclear. There is conflicting evidence in the scientific
literature as to the impact of acute sleep deprivation and caffeine
supplementation on anaerobic performance indices. The purpose of this study
is to investigate the effect of 24 hours of acute sleep deprivation on
anaerobic performance and the effect of caffeine supplementation on
anaerobic performance in the sleep deprived state.Methods11 club level games players (n=11, 25±4 yr, 178±7.5 cm,
80.2±10.4 kg, 15.1±5.6% body fat) participated in a repeated
measures double-blinded placebo control trial. Following familiarisation,
each participant returned for testing on three separate occasions. One of
the testing sessions took place following a night of normal sleep and the
other two sessions took place following 24 hours of sleep deprivation with
supplementation of either placebo or 6 mg.kg- 1 of caffeine. During each
testing session participants performed the vertical jump height, 20-m
straight sprint, Illinois speed agility test and 5-m shuttle run.ResultsNo significant differences were detected comparing non sleep deprived and
sleep deprived interventions in any of the assessed outcome measures. There
were also no significant differences observed in any of the outcome measures
when comparing caffeine and placebo data in the sleep deprived state.ConclusionIn this cohort of athletes, a 24-h period of acute sleep deprivation did not
have any significant impact on anaerobic performance. Caffeine also did not
have any effect of on anaerobic performance in the sleep-deprived state.
Background
Ustekinumab (UST), a human monoclonal antibody that binds the p40 subunit of interleukin 12 (IL-12) and IL-23, is licensed for induction and maintenance therapy of moderate to severe inflammatory bowel disease (IBD). To date, there is limited data published on any potential association between ustekinumab serum trough levels and mucosal healing in order to guide treatment strategies and appropriate dosing.
Aim
This study aims to identify a relationship between maintenance ustekinumab serum trough levels and mucosal healing and/or response in patients with Crohn’s disease in an observational cohort study.
Methods
Ustekinumab serum trough levels and antibody titres were analyzed in patients on maintenance drug using an ELISA drug-tolerant assay. Mucosal response (MR) was defined as ≥50% reduction in fecal calprotectin level (FC) and/or ≥50% reduction in the Simple Endoscopic Score for Crohn’s Disease (SES-CD score). Mucosal healing (MH) was defined as FC ≤150 µg/mL and/or global SES-CD score ≤5. Median trough levels were analyzed using the Kruskal-Wallis test, and logistic regression was used to determine sensitivity and specificity of levels predicting mucosal response.
Results
Forty-seven patients on maintenance ustekinumab for Crohn’s disease were included in this study. The majority were female (66%), with a median age of 40 years (21-78 years). The majority of patients were biologic-experienced (89.4%, n = 42). Patients with histologically confirmed Crohn’s disease represented 100% (n = 47) of the cohort. Over one-third of patients (n = 18, 38.3%) were on higher than standard dosing of 90 mg every 8 weeks. Patients with mucosal healing (n = 30) had significantly higher mean serum ustekinumab levels (5.7 µg/mL, SD 6.4) compared with those with no response (1.1 µg/mL, SD 0.52; n = 7, P < .0001). A serum ustekinumab trough level greater than 2.3 µg/mL was associated with MH, with a sensitivity of 100% and specificity of 90.6% (likelihood ratio 10.7). Similarly, for patients with MR (n = 40), we observed a higher mean serum ustekinumab trough level (5.1 µg/mL, SD 6.1) compared with those with no response (1.1 µg/mL, SD 0.52; n = 7, P < .0001). Furthermore, a serum ustekinumab trough level greater than 2.3 µg/mL was associated with a 10-fold increased likelihood of mucosal response vs mucosal nonresponse (sensitivity 100%, specificity 90.5%, likelihood ratio 10.5).
Conclusion
This study demonstrates that higher ustekinumab serum trough levels are associated with a greater likelihood of achieving mucosal healing and mucosal response in patients with Crohn’s disease regardless of prior biologic exposure. Further prospective studies are required to correlate target maintenance trough levels and the optimal time to dose-escalate in order to improve patient outcomes.
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