Intensive care unit-acquired weakness (ICUAW) occurs in critically ill patients stemming from the critical illness itself, and results in sustained disability long after the ICU stay. Weakness can be attributed to muscle wasting, impaired contractility, neuropathy, and major pathways associated with muscle protein degradation such as the ubiquitin proteasome system and dysregulated autophagy. Furthermore, it is characterized by the preferential loss of myosin, a distinct feature of the condition. While many risk factors for ICUAW have been identified, effective interventions to offset these changes remain elusive. In addition, our understanding of the mechanisms underlying the long-term, sustained weakness observed in a subset of patients after discharge is minimal. Herein, we discuss the various proposed pathways involved in the pathophysiology of ICUAW, with a focus on the mechanisms underpinning skeletal muscle wasting and impaired contractility, and the animal models used to study them. Furthermore, we will explore the contributions of inflammation, steroid use, and paralysis to the development of ICUAW and how it pertains to those with the corona virus disease of 2019 (COVID-19). We then elaborate on interventions tested as a means to offset these decrements in muscle function that occur as a result of critical illness, and we propose new strategies to explore the molecular mechanisms of ICUAW, including serum-related biomarkers and 3D human skeletal muscle culture models.

Objective: Reactive balance training is an emerging approach to reduce falls risk in people with balance impairments. The purpose of this study was to determine the effect of reactive balance training on falls in daily life among individuals at increased risk of falls, and to document associated adverse events. Data sources: Databases searched were Ovid MEDLINE (1946-November 2020), Embase Classic and Embase (1947-November 2020), Cochrane Central Register of Controlled Trials (2014-November 2020), Physiotherapy Evidence Database (PEDro; searched on 9 November 2020). Study selection: Randomized controlled trials of reactive balance training were included. The literature search was limited to English language. Records were screened by two investigators separately. Data extraction: Outcome measures were number of participants who reported falls after training, number of falls reported after training, and the nature, frequency, and severity of adverse events. Authors of included studies were contacted to obtain additional information. Data synthesis: Twenty-five trials were included, of which 14 reported falls and 19 monitored adverse events. Participants assigned to reactive balance training groups were less likely to fall compared to control groups (fall risk ratio: 0.75, 95% confidence interval=[0.60, 0.92]; p=0.006, I2=37%) and reported fewer falls than control groups (rate ratio: 0.60, 95% confidence interval=[0.42, 0.86]; p=0.005, I2=83%). Prevalence of adverse events was higher in reactive balance training (29%) compared to control groups (19%; p=0.018). Conclusion: RBT reduces the likelihood of falls in daily life for older adults and people with balance impairments. More adverse events were reported for reactive balance training than control groups. Impact: Balance training that evokes balance reactions can reduce falls among people at increased risk of falls.