114 CHAPTER 7 from protein and exercise interventions. The focus of this review was on studies with the aim to prevent the decline in muscle health, reduce the incidence of PICS, and improve long-term recovery, including QoL using PROMs in specific subgroups of ICU-survivors. 7.2 MATERIALS & METHODS 7.2.1 Protocol and registration This systematic review was described and conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement (Appendix 1)35 and the Cochrane Handbook for Systematic Reviews of Interventions.34-36 The protocol was registered on the International Prospective Register of Systematic Reviews (PROSPERO) (CRD42021229216) and can be accessed at https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=229216. 7.2.2 Eligibility criteria Studies were included if they met de following inclusion criteria: (I) randomised controlled trials (all designs including pilot/feasibility trials) and non-randomised studies on intervention effects,34 (II) enrolment of critically ill adults (≥18 years) admitted to the ICU for ≥48 hours, (III) use of PP as intervention delivered at any time point between ICU-admission and within one year after ICU-discharge (including all types of protein or amino acids and feeding routes) or the use of CPE (with exercise comprised of mobilisation, endurance, interval, strength or mobility training, with or without neuromuscular electrical stimulation (NMES)37 and regardless of intensity, frequency or duration), (IV) use of a placebo, standard care and/or a significant different protein target in the comparator group, (V) reporting at least one of the following outcomes: muscle health (lean body mass, cellular muscle health; using anthropometry measurements, bio electrical impedance, ultrasound or computed tomography techniques), mortality, and nutritional delivery (protein and energy) measured at any time point, physical functioning (activity limitations: i.e. muscle strength and mobility measures; participation restriction: i.e. activities of daily living and subjective physical measures), and quality of life (QoL), measured between ICU-discharge and one year after ICU-discharge. For mortality outcomes, we choose to include only NRSI, since a preliminary search revealed two meta-analysis reporting non statistical significant results from RCTs for the effect of protein provision on mortality.25,26
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