Potential confounding factors include age, sex, concussion history, years of education, medication, and alcohol use, as well as comorbidities and premorbidities (eg, migraine, depression or other mental health disorders, attention-deficit/hyperactivity disorder, learning disabilities, and sleep disorders).1 and 49 Experience, level of competition (ie, amateur vs professional), and type of sport should also be taken into account in future studies. The use of appropriate comparison Alectinib order groups is also recommended.49

A comparison group of uninjured athletes drawn from the same source population would help to deal with issues related to repeat test administration (ie, practice effects and motivation/response bias).36 and 50 Additionally, Pexidartinib price comparison groups consisting of participants with musculoskeletal or orthopedic injuries are recommended.

This would help address whether postconcussion sequelae are actually due to MTBI, and not to other factors common to other injuries such as pain, stress, and removal from play.51 Considerable research is also needed to improve the reliability, validity, and accuracy of serial assessments of athletes in the domains of subjectively experienced and reported symptoms, and measured cognitive abilities.48 Lastly, consensus guidelines have been developed and are widely implemented,1 and 52 but they need to be scientifically tested, preferably with randomized controlled trials. While our review has several strengths, such as the use of a comprehensive and sensitive search strategy, and a best-evidence synthesis based on studies of higher methodological quality, important limitations also exist. The strength of our findings is limited by the lack of high-quality and confirmatory (phase III) studies available in the literature. Comper et al49 also concluded that Janus kinase (JAK) the methodological quality of neuropsychological sport concussion studies

is highly variable, with many lacking proper scientific rigor. Many of the same biases and issues of confounding found in the previous WHO review8 still exist in the studies we reviewed for our best-evidence synthesis. Examples of selection bias include small sample sizes, unknown response rates, poorly described sample selection, the use of voluntary or convenience samples, insufficient description of nonparticipants, nonreporting of reasons for attrition, and the inappropriate selection of controls (eg, from different sports than cases).53 Information bias was also problematic. Different studies used varying definitions of concussion, or concussion was not always well defined. The exposures (concussions) were not consistently ascertained. For example, with respect to concussion history, in many cases, either the information was not collected or it was given via athlete self-report. Thus, the potential for recall bias also exists.