Background Physical therapy can prevent functional impairments and improve the quality of life of patients after hospital discharge. However, the effect of early mobilization on patients with a critical illness remains unclear. This study was performed to assess the evidence available regarding the effect of early mobilization on critically ill patients in the intensive care unit (ICU). Methods Electronic databases were searched from their inception to March 21, 2019. Randomized controlled trials (RCTs) comprising critically ill patients who received early mobilization were included. The methodological quality and risk of bias of each eligible trial were assessed using the Cochrane Collaboration tool. Data were extracted using a standard collection form each included study, and processed using the Mantel-Haenszel (M-H) or inverse-variance (I-V) test in the STATA v12.0 statistical software. Results A total of 1,898 records were screened. Twenty-three RCTs comprising 2,308 critically ill patients were ultimately included. Early mobilization decreased the incidence of ICU-acquired weakness (ICU-AW) at hospital discharge (three studies, 190 patients, relative risk (RR): 0.60, 95% confidence interval (CI) [0.40, 0.90]; p = 0.013, I2 = 0.0%), increased the number of patients who were able to stand (one study, 50 patients, 90% vs. 62%, p = 0.02), increased the number of ventilator-free days (six studies, 745 patients, standardized mean difference (SMD): 0.17, 95% CI [0.02, 0.31]; p = 0.023, I2 = 35.5%) during hospitalization, increased the distance the patient was able to walk unassisted (one study, 104 patients, 33.4 (0-91.4) meters vs. 0 (0-30.4) meters, p = 0.004) at hospital discharge, and increased the discharged-to-home rate (seven studies, 793 patients, RR: 1.16, 95% CI [1.00, 1.34]; p = 0.046). The mortality (28-day, ICU and hospital) and adverse event rates were moderately increased by early mobilization, but the differences were statistically non-significant. However, due to the substantial heterogeneity among the included studies, and the low quality of the evidence, the results of this study should be interpreted with caution. Publication bias was not identified. Conclusions Early mobilization appears to decrease the incidence of ICU-AW, improve the functional capacity, and increase the number of ventilator-free days and the discharged-to-home rate for patients with a critical illness in the ICU setting.

/pdf/early-mobilization-of-critically-ill-patients-in-the-38pq96zcwo.pdf

Early mobilization of critically ill patients in the intensive care unit: A systematic review and meta-analysis.

BACKGROUND The aim of this meta-analysis was to assess if early mobilization and rehabilitation in the intensive care unit (ICU) could reduce ICU-acquired weakness (ICU-AW), improve functional recovery, improve muscle strength, shorten the length of ICU and hospital stays, and reduce the mortality rate. METHODS A comprehensive literature search in PubMed, Embase, Web of Science, SinoMed (Chinese BioMedical Literature Service System, China), and National Knowledge Infrastructure, China (CNKI) was performed. Results were expressed as a risk ratio (RR) with 95% confidence intervals (95% CIs) or weight mean difference (WMD) with 95% CIs. Pooled estimates were calculated using a fixed-effects or random-effects model according to the heterogeneity among studies. RESULTS Fifteen randomized controlled trials involving a total of 1941 patients were included in this meta-analysis. Pooled estimates suggested that early mobilization significantly reduced the incidence of ICU-AW (RR = 0.49, 95% CI: 0.26, 0.91; P = .025), shortened the length of ICU (WMD = -1.82 days, 95% CI: -2.88, -0.76; P = .001) and hospital (WMD = -3.90 days, 95% CI: -5.94, -1.85; P < .001) stays, and improved the Medical Research Council score (WMD = 4.47, 95% CI: 1.43, 7.52; P = .004) and Barthel Index score at hospital discharge (WMD = 21.44, 95% CI: 10.97, 31.91; P < .001). Moreover, early mobilization also decreased complications such as deep vein thrombosis (RR = 0.16, 95% CI: 0.04, 0.59; P = .006), ventilator-associated pneumonia (RR = 0.26, 95% CI: 0.11, 0.63; P = .003), and pressure sores (RR = 0.14, 95% CI: 0.04, 0.44; P = .001). However, early mobilization did not reduce the ICU mortality rate (RR = 1.31, 95% CI: 0.97, 1.76; P = .074), improve the handgrip strength (WMD = 4.03 kg, 95% CI: -0.68, 8.74; P = .094), and shorten the duration of mechanical ventilation (WMD = 0.20 days, 95% CI: -0.10, 0.50; P = .194). CONCLUSION This study indicated that early mobilization was effective in preventing the occurrence of ICU-AW, shortening the length of ICU and hospital stay, and improving the functional mobility. However, it had no effect on the ICU mortality rate and ventilator-free days. RELEVANCE TO CLINICAL PRACTICE ICU-AW is a common neuromuscular complication of critical illness, and it is predictive of adverse outcomes. Early mobilization of critically ill patients is a candidate intervention to reduce the incidence and severity of ICU-AW. Some clinical studies have demonstrated this, whereas others found opposite results. The aim of our study is to assess if early mobilization and rehabilitation in the ICU could reduce the ICU-AW, improve functional recovery, improve muscle strength, shorten length of ICU and hospital stay, and reduce the mortality rate.

The effect of early mobilization in critically ill patients: A meta-analysis.

Background Muscular weakness and/or muscle wasting is recognized as a key medical problem in critically ill patients on intensive care units (ICUs) worldwide. Methods and results Intensive care unit-acquired weakness (ICUAW) results from various diseases leading to critical illness and is observed in about 40% [1080/2686 patients, 95% confidence interval (CI): 38-42%] of mixed (medical-surgical) ICU patients. Muscle strength at ICU discharge is directly associated with mortality 5 years after discharge [hazard ratio 0.946, 95% CI: 0.928-0.968 per point increase in Medical Research Council (MRC) scores, P = 0.001]. ICUAW serves as umbrella term for the subgroups ‘critical illness myopathy’, ‘critical illness polyneuropathy’, and ‘critical illness polyneuromyopathy’, the latter distinguished using electrophysiology and/or biopsy studies. Diagnosing, studying, and developing treatments for ICUAW among the critically ill seems challenging due to the acuity and severity of the underlying heterogeneous diseases. Ventilator-induced diaphragmatic dysfunction occurs in up to 80% (n = 32/40) of ICUAW patients after mechanical ventilation and mostly results from distinct muscular pathologies, disuse, underlying critical illness, and/or effects imposed directly by mechanical ventilation. Swallowing disorders/dysphagia likely represent an additional (local) neuromuscular dysfunction/ICUAW sequelae and presents in 10.3% (n = 96/933) of mixed medical-surgical ICU survivors, with 60.4% (n = 58/96) of patients remaining dysphagia positive until hospital discharge. Key independent risk factors for dysphagia following mechanical ventilation are baseline neurological disease [odds ratio (OR) 4.45, 95% CI: 2.74-7.24, P Conclusions Neuromuscular weakness and muscle wasting is observed in many survivors of critical illness. ICUAW, ventilator-induced diaphragmatic dysfunction, and dysphagia are associated with complicated and prolonged ICU stay, impaired weaning from mechanical ventilation, impeded rehabilitative measures, and a considerable impact on morbidity and mortality is noted. Future research strategies should further explore underlying pathomechanisms and lead to development of causal treatment strategies.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/jcsm.12620

Muscular weakness and muscle wasting in the critically ill.

OBJECTIVES To assess the impact of rehabilitation in ICU on clinical outcomes. DATA SOURCES Secondary data analysis of randomized controlled trials published between 1998 and October 2019 was performed in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. STUDY SELECTION We have selected trials investigating neuromuscular electrical stimulation or cycling exercises or protocolized physical rehabilitation as compared to standard of care in critically ill adults. DATA EXTRACTION Mortality, length of stay in ICU and at hospital, days on mechanical ventilator, and adverse events. DATA SYNTHESIS We found 43 randomized controlled trials (nine on cycling, 14 on neuromuscular electrical stimulation alone and 20 on protocolized physical rehabilitation) into which 3,548 patients were randomized and none of whom experienced an intervention-related serious adverse event. The exercise interventions had no influence on mortality (odds ratio 0.94 [0.79-1.12], n = 38 randomized controlled trials) but reduced duration of mechanical ventilation (mean difference, -1.7 d [-2.5 to -0.8 d], n = 32, length of stay in ICU (-1.2 d [-2.5 to 0.0 d], n = 32) but not at hospital (-1.6 [-4.3 to 1.2 d], n = 23). The effects on the length of mechanical ventilation and ICU stay were only significant for the protocolized physical rehabilitation subgroup and enhanced in patients with longer ICU stay and lower Acute Physiology and Chronic Health Evaluation II scores. There was no benefit of early start of the intervention. It is likely that the dose of rehabilitation delivered was much lower than dictated by the protocol in many randomized controlled trials and negative results may reflect the failure to implement the intervention. CONCLUSIONS Rehabilitation interventions in critically ill patients do not influence mortality and are safe. Protocolized physical rehabilitation significantly shortens time spent on mechanical ventilation and in ICU, but this does not consistently translate into long-term functional benefit. Stable patients with lower Acute Physiology and Chronic Health Evaluation II at admission (<20) and prone to protracted ICU stay may benefit most from rehabilitation interventions.

Effects of Rehabilitation Interventions on Clinical Outcomes in Critically Ill Patients: Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Introduction Neuromuscular weakness resulting in severe functional impairment is common in critical care survivors. This study aimed to evaluate effects of an early progressive rehabilitation intervention in mechanically ventilated adults at risk. Methods This was a parallel, two-arm, assessor-blinded, randomised controlled trial with 6-months follow-up that was conducted in a mixed ICU of an academic centre in Switzerland. Previously independent, mechanically ventilated, critically ill adults with expected critical care stay ≥72 hours (n = 115) were randomised to a control group receiving standard physiotherapy including early mobilisation or to an experimental group with early endurance and resistance training combined with mobilisation. Primary endpoints were functional capacity (6-Minute Walk Distance) and functional independence (Functional Independence Measure) at hospital discharge. Secondary endpoints including muscle strength were assessed at critical care discharge. Safety was monitored closely by standard monitoring and predefined adverse events. Results Physiotherapy started within 48 hours of critical care admission while 97% of participants were still ventilated and 68% on inotropes. Compared to the control group (n = 57), the experimental group (n = 58) received significantly more physiotherapy (sessions: 407 vs 377, p<0.001; time/session: 25min vs 18min, p<0.001) and had less days with sedation (p<0.001). Adverse events were rare (0.6%) and without consequences. There were no significant between-group differences in 6-Minute Walk Distance (experimental 123m (IQR 25–280) vs control 100m (IQR 0–300); p = 0.542) or functional independence (98 (IQR 66–119) vs 98 (IQR 18–115); p = 0.308). Likewise, no differences were found for the secondary outcomes, except a trend towards improved mental health in the experimental group after 6 months (84 (IQR 68–88) vs 70 (IQR 64–76); p = 0.023). Conclusions Early endurance and resistance training in mechanically ventilated, intensive care patients does not improve functional capacity or independence at hospital discharge compared to early standard physiotherapy but may improve mental health 6-months after critical care discharge. Trial registration German Clinical Trials Register (DRKS): DRKS00004347, registered on 10 September 2012.

/pdf/effects-of-early-combined-endurance-and-resistance-training-2tjj4itrjj.pdf

Effects of early, combined endurance and resistance training in mechanically ventilated, critically ill patients: A randomised controlled trial.

Importance Early in-bed cycling and electrical muscle stimulation may improve the benefits of rehabilitation in patients in the intensive care unit (ICU). Objective To investigate whether early in-bed leg cycling plus electrical stimulation of the quadriceps muscles added to standardized early rehabilitation would result in greater muscle strength at discharge from the ICU. Design, setting, and participants Single-center, randomized clinical trial enrolling critically ill adult patients at 1 ICU within an 1100-bed hospital in France. Enrollment lasted from July 2014 to June 2016 and there was a 6-month follow-up, which ended on November 24, 2016. Interventions Patients were randomized to early in-bed leg cycling plus electrical stimulation of the quadriceps muscles added to standardized early rehabilitation (n = 159) or standardized early rehabilitation alone (usual care) (n = 155). Main outcomes and measures The primary outcome was muscle strength at discharge from the ICU assessed by physiotherapists blinded to treatment group using the Medical Research Council grading system (score range, 0-60 points; a higher score reflects better muscle strength; minimal clinically important difference of 4 points). Secondary outcomes at ICU discharge included the number of ventilator-free days and ICU Mobility Scale score (range, 0-10; a higher score reflects better walking capability). Functional autonomy and health-related quality of life were assessed at 6 months. Results Among 314 randomized patients, 312 (mean age, 66 years; women, 36%; receiving mechanical ventilation at study inclusion, 78%) completed the study and were included in the analysis. The median global Medical Research Council score at ICU discharge was 48 (interquartile range [IQR], 29 to 58) in the intervention group and 51 (IQR, 37 to 58) in the usual care group (median difference, -3.0 [95% CI, -7.0 to 2.8]; P = .28). The ICU Mobility Scale score at ICU discharge was 6 (IQR, 3 to 9) in both groups (median difference, 0 [95% CI, -1 to 2]; P = .52). The median number of ventilator-free days at day 28 was 21 (IQR, 6 to 25) in the intervention group and 22 (IQR, 10 to 25) in the usual care group (median difference, 1 [95% CI, -2 to 3]; P = .24). Clinically significant events occurred during mobilization sessions in 7 patients (4.4%) in the intervention group and in 9 patients (5.8%) in the usual care group. There were no significant between-group differences in the outcomes assessed at 6 months. Conclusions and relevance In this single-center randomized clinical trial involving patients admitted to the ICU, adding early in-bed leg cycling exercises and electrical stimulation of the quadriceps muscles to a standardized early rehabilitation program did not improve global muscle strength at discharge from the ICU. Trial registration ClinicalTrials.gov Identifier: NCT02185989.

/pdf/effect-of-in-bed-leg-cycling-and-electrical-stimulation-of-4jnhmncbp2.pdf

Effect of In-Bed Leg Cycling and Electrical Stimulation of the Quadriceps on Global Muscle Strength in Critically Ill Adults: A Randomized Clinical Trial

Fabrication of more and more complex multichip assemblies with quantum devices and quantum bits is driving efforts toward superconducting interconnect developments. In this context, we investigate the damascene integration of Nb-based vias with a focus on the chemical mechanical polishing of Nb. Various slurries typically used for common metal or oxide polishing are evaluated using the following criteria: the removal rate of Nb, the selectivity on SiO2 dielectrics, the polishing within wafer non uniformity and the resulting Nb roughnesses. Damascene integration of the Nb-based vias is then presented using the selected slurries.

Chemical Mechanical Polishing of Superconducting Metals for Quantum Device Interconnections

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Effect of In-Bed Leg Cycling and Electrical Stimulation of the Quadriceps on Global Muscle Strength in Critically Ill Adults: A Randomized Clinical Trial

Chemical Mechanical Polishing of Superconducting Metals for Quantum Device Interconnections