Exercise Parameters for Postconcussion Symptom Rehabilitation: A Systematic Review.

CONTEXT: Exercise rehabilitation for postconcussion symptoms (PCS) has shown some benefits in adolescent athletes; but a synthesis of evidence on exercise per se has been lacking. OBJECTIVE: This systematic review aimed to determine if unimodal exercise interventions are useful to treat PCS and if so, to identify a set of clearly defined and effective exercise parameters for further research. EVIDENCE ACQUISITION: Relevant health databases and clinical trial registries were searched from inception to June 2022. The searches used a combination of subject headings and keywords related to mild traumatic brain injury (mTBI), PCSs, and exercise. Two independent reviewers screened and appraised the literature. The Cochrane Collaboration's Risk of Bias-2 tool for randomized controlled trials was used to assess methodological quality of studies. EVIDENCE SYNTHESIS: Seven studies were included in the review. Four studies were assessed to have a low overall risk of bias, 2 with low risk and 1 with some concerns. Participants in the studies comprised mostly adolescents with sports-related concussion. The review found exercise to be more beneficial than control conditions in 2 studies investigating acute PCS and 2 studies investigating persistent PCS. Within-group differences showing symptom improvement over time were observed in all 7 studies. In general, the review found support for programmatic exercise that commences after an initial period of rest for 24 to 48 hours. Recommendations for exercise parameters that can be explored in subsequent research include progressive aerobic exercise starting from 10 to 15 minutes at least 4 times a week, at a starting intensity of 50% HR of the subsymptom threshold, with length of program depending on recovery. CONCLUSION: The evidence in support of exercise rehabilitation for PCSs is moderate based on the small pool of eligible studies. Further research can be guided by the exercise parameters identified in this review.

Can the flow of medicines be improved? Fundamental pharmacokinetic and pharmacological principles toward improving Phase II survival.

In an effort to uncover systematic learnings that can be applied to improve compound survival, an analysis was performed on data from Phase II decisions for 44 programs at Pfizer. It was found that not only were the majority of failures caused by lack of efficacy but also that, in a large number of cases (43%), it was not possible to conclude whether the mechanism had been tested adequately. A key finding was that an integrated understanding of the fundamental pharmacokinetic/pharmacodynamic principles of exposure at the site of action, target binding and expression of functional pharmacological activity (termed together as the 'three Pillars of survival') all determine the likelihood of candidate survival in Phase II trials and improve the chance of progression to Phase III.