To assess the relative effects of different types of exercise and other non-pharmaceutical interventions on cancer-related fatigue (CRF) in patients during and after cancer treatment.
Systematic ...review and indirect-comparisons meta-analysis.
Articles were searched in PubMed, Cochrane CENTRAL and published meta-analyses.
Randomised studies published up to January 2017 evaluating different types of exercise or other non-pharmaceutical interventions to reduce CRF in any cancer type during or after treatment.
Risk of bias assessment with PEDro criteria and random effects Bayesian network meta-analysis.
We included 245 studies. Comparing the treatments with usual care during cancer treatment, relaxation exercise was the highest ranked intervention with a standardisedmean difference (SMD) of -0.77 (95% Credible Interval (CrI) -1.22 to -0.31), while massage (-0.78; -1.55 to -0.01), cognitive-behavioural therapy combined with physical activity (combined CBT, -0.72; -1.34 to -0.09), combined aerobic and resistance training (-0.67; -1.01 to -0.34), resistance training (-0.53; -1.02 to -0.03), aerobic (-0.53; -0.80 to -0.26) and yoga (-0.51; -1.01 to 0.00) all had moderate-to-large SMDs. After cancer treatment, yoga showed the highest effect (-0.68; -0.93 to -0.43). Combined aerobic and resistance training (-0.50; -0.66 to -0.34), combined CBT (-0.45; -0.70 to -0.21), Tai-Chi (-0.45; -0.84 to -0.06), CBT (-0.42; -0.58 to -0.25), resistance training (-0.35; -0.62 to -0.08) and aerobic (-0.33; -0.51 to -0.16) showed all small-to-moderate SMDs.
Patients can choose among different effective types of exercise and non-pharmaceutical interventions to reduce CRF.
Intensive care unit acquired weakness (ICUAW) may contribute to functional disability in ICU survivors, yet performance-based data for general ICU patients are lacking. This study explored functional ...outcomes of (1) and risk factors for (2) weakness at ICU discharge.
Data from a randomised controlled trial that investigated two early exercise regimes in previously independent, ventilated adults (n = 115) without any significant outcome-differences were used for the present analysis. ICUAW was clinically diagnosed in cooperative participants (n = 83) at ICU discharge with the Medical Research Council sum-score (MRC-SS) using a cut-off <48 for moderate or <36 for severe weakness. Primary outcomes were the 6-Minute Walk Test and Functional Independence Measure at hospital discharge. Secondary outcomes included health-related quality of life after six months. Risk factors during the ICU stay were explored for their effect on MRC-SS with linear regression.
Functional outcomes and length of hospital stay significantly differed in patients with severe, moderate to no weakness (6-Minute Walk test: p = 0.013; 110m IQR 75-240, 196m 90-324.25, 222.5m 129-378.75, Functional Independence Measure: p = 0.001; 91IQR 68-101, 113102.5-118.5, 11297-123, length of stay after ICU discharge: p = 0.008; 20.9d IQR 15.83-30.73, 16.86d 13.07-27.10, 11.16d 7.35-19.74). However, after six months participants had similar values for quality of life regardless of their strength at ICU discharge (Short-Form 36 sum-scores physical health: p = 0.874, mental health: p = 0.908). In-bed immobilisation was the most significant factor associated with weakness at ICU discharge in the regression models (MRC-SS: -24.57(95%CI -37.03 to -12.11); p<0.001).
In this general, critically ill cohort, weakness at ICU discharge was associated with short-term functional disability and prolonged hospital length of stay, but not with quality of life, which was equivalent to the values for patients without ICUAW within six months. Immobilisation may be a modifiable risk factor to prevent ICUAW. Prospective trials are needed to validate these results.
German Clinical Trials Register (DRKS) identification number: DRKS00004347, registered on September 10, 2012.
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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.
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.
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).
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.
German Clinical Trials Register (DRKS): DRKS00004347, registered on 10 September 2012.
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Virtual reality-based training has found increasing use in neurorehabilitation to improve upper limb training and facilitate motor recovery.
The aim of this study was to directly compare virtual ...reality-based training with conventional therapy.
In a multi-center, parallel-group randomized controlled trial, patients at least 6 months after stroke onset were allocated either to an experimental group (virtual reality-based training) or a control group receiving conventional therapy (16x45 minutes within 4 weeks). The virtual reality-based training system replicated patients´ upper limb movements in real-time to manipulate virtual objects. Blinded assessors tested patients twice before, once during, and twice after the intervention up to 2-month follow-up for dexterity (primary outcome: Box and Block Test), bimanual upper limb function (Chedoke-McMaster Arm and Hand Activity Inventory), and subjective perceived changes (Stroke Impact Scale).
54 eligible patients (70 screened) participated (15 females, mean age 61.3 years, range 20-81 years, time since stroke 3.0±SD 3 years). 22 patients were allocated to the experimental group and 32 to the control group (3 drop-outs). Patients in the experimental and control group improved: Box and Block Test mean 21.5±SD 16 baseline to mean 24.1±SD 17 follow-up; Chedoke-McMaster Arm and Hand Activity Inventory mean 66.0±SD 21 baseline to mean 70.2±SD 19 follow-up. An intention-to-treat analysis found no between-group differences.
Patients in the experimental and control group showed similar effects, with most improvements occurring in the first two weeks and persisting until the end of the two-month follow-up period. The study population had moderate to severely impaired motor function at entry (Box and Block Test mean 21.5±SD 16). Patients, who were less impaired (Box and Block Test range 18 to 72) showed higher improvements in favor of the experimental group. This result could suggest that virtual reality-based training might be more applicable for such patients than for more severely impaired patients.
ClinicalTrials.gov NCT01774669.
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Early rehabilitation is indicated in critically ill adults to counter functional complications. However, the physiological response to rehabilitation is poorly understood. This study aimed to ...determine the cardiorespiratory response to rehabilitation and to investigate the effect of explanatory variables on physiological changes during rehabilitation and recovery.
In a prospectively planned, secondary analysis of a randomised controlled trial conducted in a tertiary, mixed intensive care unit (ICU), we analysed the 716 physiotherapy-led, pragmatic rehabilitation sessions (including exercise, cycling and mobilisation). Participants were previously functionally independent, mechanically ventilated, critically ill adults (n = 108). Physiological data (2-minute medians) were collected with standard ICU monitoring and indirect calorimetry, and their medians calculated for baseline (30min before), training (during physiotherapy) and recovery (15min after). We visualised physiological trajectories and investigated explanatory variables on their estimated effect with mixed-effects models.
This study found a large range of variation within and across participants' sessions with clinically relevant variations (>10%) occurring in more than 1 out of 4 sessions in mean arterial pressure, minute ventilation (MV) and oxygen consumption (VO2), although early rehabilitation did not generally affect physiological values from baseline to training or recovery. Active patient participation increased MV (mean difference 0.7l/min 0.4-1.0, p<0.001) and VO2 (23ml/min 95%CI: 13-34, p<0.001) during training when compared to passive participation. Similarly, session type 'mobilisation' increased heart rate (6.6bpm 2.1-11.2, p = 0.006) during recovery when compared to 'exercise'. Other modifiable explanatory variables included session duration, mobilisation level and daily medication, while non-modifiable variables were age, gender, body mass index and the daily Sequential Organ Failure Assessment.
A large range of variation during rehabilitation and recovery mirrors the heterogenous interventions and patient reactions. This warrants close monitoring and individual tailoring, whereby the best option to stimulate a cardiorespiratory response seems to be active patient participation, shorter session durations and mobilisation.
German Clinical Trials Register (DRKS) identification number: DRKS00004347, registered on 10 September 2012.
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High-energy particle accelerators have been crucial in providing a deeper understanding of fundamental particles and the forces that govern their interactions. To increase the energy of the particles ...or to reduce the size of the accelerator, new acceleration schemes need to be developed. Plasma wakefield acceleration
, in which the electrons in a plasma are excited, leading to strong electric fields (so called 'wakefields'), is one such promising acceleration technique. Experiments have shown that an intense laser pulse
or electron bunch
traversing a plasma can drive electric fields of tens of gigavolts per metre and above-well beyond those achieved in conventional radio-frequency accelerators (about 0.1 gigavolt per metre). However, the low stored energy of laser pulses and electron bunches means that multiple acceleration stages are needed to reach very high particle energies
. The use of proton bunches is compelling because they have the potential to drive wakefields and to accelerate electrons to high energy in a single acceleration stage
. Long, thin proton bunches can be used because they undergo a process called self-modulation
, a particle-plasma interaction that splits the bunch longitudinally into a series of high-density microbunches, which then act resonantly to create large wakefields. The Advanced Wakefield (AWAKE) experiment at CERN
uses high-intensity proton bunches-in which each proton has an energy of 400 gigaelectronvolts, resulting in a total bunch energy of 19 kilojoules-to drive a wakefield in a ten-metre-long plasma. Electron bunches are then injected into this wakefield. Here we present measurements of electrons accelerated up to two gigaelectronvolts at the AWAKE experiment, in a demonstration of proton-driven plasma wakefield acceleration. Measurements were conducted under various plasma conditions and the acceleration was found to be consistent and reliable. The potential for this scheme to produce very high-energy electron bunches in a single accelerating stage
means that our results are an important step towards the development of future high-energy particle accelerators
.
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The aim of this study was to capture and understand the immediate recovery journey of patients following lumbar spinal fusion surgery and explore the interacting constructs that shape their journey. ...A qualitative study using Interpretive Phenomenological Analysis (IPA) approach. A purposive sample of 43 adult patients (≥16 years) undergoing ≤4 level instrumented fusion for back and/or leg pain of degenerative cause, were recruited pre-surgery from 4 UK spinal surgery centres. Patients completed a weekly diary expressed in their own words for the first 4 weeks following surgery to capture their life as lived. Diary content was based on previous research findings and recorded progress, recovery, motivation, symptoms, medications, healthcare appointments, rehabilitation, positive/negative thoughts, and significant moments; comparing to the previous week. To maximise completion and data quality, diaries could be completed in paper form, word document, as online survey or as audio recording. Strategies to enhance diary adherence included a weekly prompt. A framework analysis for individual diaries and then across participants (deductive and inductive components) captured emergent themes. Trustworthiness was enhanced by strategies including reflexivity, attention to negative cases and use of critical co-investigators. Twenty-eight participants (15 female; n = 18 (64.3%) aged 45-64) contributed weekly diaries (12 withdrew post-surgery, 3 did not follow through with surgery). Adherence with diaries was 89.8%. Participants provided diverse and vivid descriptions of recovery experiences. Three distinct recovery trajectories were identified: meaningful recovery (engagement in physical and functional activities to return to functionality/mobility); progressive recovery (small but meaningful improvement in physical ability with increasing confidence); and disruptive recovery (limited purpose for meaningful recovery). Important interacting constructs shaped participants' recovery including their pain experience and self-efficacy. This is the first account of immediate recovery trajectories from patients' perspectives. Recognition of a patient's trajectory may inform patient-centred recovery, follow-up and rehabilitation to improve patient outcomes.
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We describe an external electron injection scheme for the AWAKE experiment. We use scattering in two foils, that are necessary as vacuum window and laser beam dump, to decrease the betatron function ...of the incoming electron beam for injection and matching into plasma wakefields driven by a self-modulated proton bunch. We show that, for a total aluminum foil thickness of ~ 280 μm, multiple Coulomb scattering increases the beam emittance by a factor of ~ 10 and decreases the betatron function by a factor of ~ 3. The plasma in the accelerator is created by a ionizing laser pulse, counter-propagating with respect to the electron beam. This allows for the electron bunch to enter the plasma through an "infinitely" sharp vapor-plasma boundary, away from the foils.
We measure the effects of transverse wakefields driven by a relativistic proton bunch in plasma with densities of 2.1×10^{14} and 7.7×10^{14} electrons/cm^{3}. We show that these wakefields ...periodically defocus the proton bunch itself, consistently with the development of the seeded self-modulation process. We show that the defocusing increases both along the bunch and along the plasma by using time resolved and time-integrated measurements of the proton bunch transverse distribution. We evaluate the transverse wakefield amplitudes and show that they exceed their seed value (<15 MV/m) and reach over 300 MV/m. All these results confirm the development of the seeded self-modulation process, a necessary condition for external injection of low energy and acceleration of electrons to multi-GeV energy levels.
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The space-charge field of a relativistic charged bunch propagating in plasma is screened due to the presence of mobile charge carriers. We experimentally investigate such screening by measuring the ...effect of dielectric wakefields driven by the bunch in a uncoated dielectric capillary where the plasma is confined. We show that the plasma screens the space-charge field and therefore suppresses the dielectric wakefields when the distance between the bunch and the dielectric surface is much larger than the plasma skin depth. Before full screening is reached, the effects of dielectric and plasma wakefields are present simultaneously.The space-charge field of a relativistic charged bunch propagating in plasma is screened due to the presence of mobile charge carriers. We experimentally investigate such screening by measuring the effect of dielectric wakefields driven by the bunch in a uncoated dielectric capillary where the plasma is confined. We show that the plasma screens the space-charge field and therefore suppresses the dielectric wakefields when the distance between the bunch and the dielectric surface is much larger than the plasma skin depth. Before full screening is reached, the effects of dielectric and plasma wakefields are present simultaneously.
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