Association between changes in disease severity and physical function after surviving a critical illness: A multicentre retrospective observational study.

BACKGROUND: Whilst disease severity can significantly impact functional outcomes, the ability to predict the scale of this impact has not been consistent. AIM: We aimed to investigate whether changes in disease severity within the first 48 h of ICU admission are more strongly associated with physical dysfunction than a single-time assessment of disease severity at ICU admission. METHODS: A multicentre retrospective study in seven tertiary ICUs in Japan, including all consecutive adult ICU patients (>48 h ICU stay) between September 2019 and February 2020. The primary outcome was physical function defined as the Barthel Index, which is an ordinal scale (0-100: larger indicates better function) to measure physical independence and performance. The association between Barthel Index score at hospital discharge and the Sequential Organ Failure Assessment (SOFA) scores, measured at ICU admission, the highest recorded score within 48 h of ICU admission, and the level of change between these two timepoints were investigated in multivariable analysis. RESULTS: A total of 199 patients were included. Median SOFA score at ICU admission and the highest recorded score within the first 48 h were 6 (interquartile range: 5-10) and 8 (interquartile range: 6-11), respectively. A quarter of patients had a Barthel Index score of 60 or less at hospital discharge. The highest SOFA score within 48 h of ICU admission and the level of change in SOFA scores between ICU admission and the highest recorded score within 48 h were significantly associated with lower Barthel Index scores at hospital discharge. No significant association was identified with regard to Barthel Index scores and SOFA score at ICU admission. An increase in SOFA score of 1 or more within the first 48 h of ICU admission was the threshold to predict a Barthel Index score of 60 or less at hospital discharge. Larger changes in SOFA scores over the first 48 h of ICU admission were also significantly associated with smaller changes in Barthel Index scores from ICU discharge to hospital discharge. CONCLUSIONS: The level of change in SOFA score between ICU admission and the highest recorded score within the first 48 h of ICU stay can more accurately predict the presence of physical dysfunction at hospital discharge than a single-time assessment of disease severity at ICU admission. The larger worsening in SOFA potentially indicates lower recovery after a critical illness.

Mobilization in the evening to prevent delirium: A pilot randomized trial.

BACKGROUND: Delirium is a common complication in patients in Intensive Care Units (ICU). Interventions such as mobilization are effective in the prevention and treatment of delirium, although this is usually completed during the daytime. AIM: The aim of this study was to assess the feasibility of mobilization in the evening to prevent and treat ICU patients from delirium by an additional mobility team over 2 weeks. METHODS: The design was a pilot, multi-centre, randomized, controlled trial in four mixed ICUs over a period of 2 weeks. The mobility team consisted of trained nurses and physiotherapists. Patients in the intervention group were mobilized onto the edge of the bed or more between 21.00 and 23.00. Patients in the control group received usual care. The primary outcome parameter was the feasibility of the study, measured as recruitment rate, delivery rate, and safety. Secondary outcomes were duration and incidence of delirium, mortality, duration of mechanical ventilation (MV), and hospital length of stay for 28 days follow-up, and power calculation for a full trial. RESULTS: Out of 185 patients present in the ICUs, 28.6% (n = 53) were eligible and could be recruited, of which 24.9% (n = 46, Intervention = 26, Control = 20) were included in the final analysis. In the intervention group, mobilization could be delivered in 75% (n = 54) of 72 possible occasions; mobilization-related safety events appeared in 16.7% (n = 9) without serious consequences. Secondary parameters were similar, with less delirium in the intervention group albeit not significant. With an association of Cramer's V = 0.237, a complete study reaching statistical significance would require at least 140 patients, last 6 weeks, and cost >30 000 €. CONCLUSIONS: In a mixed ICU population, mobilization in the evening was feasible in one-quarter of patients with a low rate of safety events. Future trials seem to be feasible and worth conducting.

Physical Therapy and Rehabilitation in Chronic Obstructive Pulmonary Disease Patients Admitted to the Intensive Care Unit.

Chronic obstructive pulmonary disease (COPD) is a progressive lung condition that affects a person's ability to exercise and undertake normal physical function due to breathlessness, poor physical fitness, and muscle fatigue. Patients with COPD often experience exacerbations due to pulmonary infections, which result in worsening of their symptoms, more loss of function, and often require hospital treatment or in severe cases admission to intensive care units. Recovery from such exacerbations is often slow, and some patients never fully return to their previous level of activity. This can lead to permanent disability and premature death.Physical therapists play a key role in the respiratory management and rehabilitation of patients admitted to intensive care following acute exacerbation of COPD. This article discusses the key considerations for respiratory management of patients requiring invasive mechanical ventilation, providing an evidence-based summary of commonly used interventions. It will also explore the evidence to support the introduction of early and structured programs of rehabilitation to support recovery in both the short and the long term, as well as active mobilization, which includes strategies to minimize or prevent physical loss through early retraining of both peripheral and respiratory muscles.

Analysis of Whole Exome Sequencing with Cardiometabolic Traits Using Family-Based Linkage and Association in the IRAS Family Study.

Family-based methods are a potentially powerful tool to identify trait-defining genetic variants in extended families, particularly when used to complement conventional association analysis. We utilized two-point linkage analysis and single variant association analysis to evaluate whole exome sequencing (WES) data from 1205 Hispanic Americans (78 families) from the Insulin Resistance Atherosclerosis Family Study. WES identified 211,612 variants above the minor allele frequency threshold of ≥0.005. These variants were tested for linkage and/or association with 50 cardiometabolic traits after quality control checks. Two-point linkage analysis yielded 10,580,600 logarithm of the odds (LOD) scores with 1148 LOD scores ≥3, 183 LOD scores ≥4, and 29 LOD scores ≥5. The maximal novel LOD score was 5.50 for rs2289043:T>C, in UNC5C with subcutaneous adipose tissue volume. Association analysis identified 13 variants attaining genome-wide significance (P < 5 × 10-08 ), with the strongest association between rs651821:C>T in APOA5 and triglyceride levels (P = 3.67 × 10-10 ). Overall, there was a 5.2-fold increase in the number of informative variants detected by WES compared to exome chip analysis in this population, nearly 30% of which were novel variants relative to the Database of Single Nucleotide Polymorphisms (dbSNP) build 138. Thus, integration of results from two-point linkage and single-variant association analysis from WES data enabled identification of novel signals potentially contributing to cardiometabolic traits.

The Sara Combilizer® as an early mobilisation aid for critically ill patients: A prospective before and after study.

BACKGROUND: Early mobility within the ICU is associated with a number of positive outcomes including reductions in ICU and hospital length of stay and better functional recovery. The exact definition of 'early' mobility is still not defined, with the actual ability to mobilise limited by a number of perceived factors. The Sara Combilizer® is a combined tilt table and stretcher chair, which allows passive transfer of patients out of bed. This study aimed to assess whether the introduction of the Sara Combilizer® reduced time taken to first mobilise for patients mechanically ventilated for at least five days and at risk of ICU acquired weakness. METHODS: Patients admitted to a large UK critical care unit during the trial period and ventilated for ≥5days were included in the study. Baseline data was collected prospectively for a period of four months. The Sara Combilizer® was then introduced for a one month training and familiarisation period, followed by a further four months prospective data collection. The primary outcome was time to first mobilisation, defined as a Manchester Mobility Score ≥2. RESULTS: Following the introduction of the Sara Combilizer®, time taken to mobilise reduced significantly from 13.6 to 10.6days (p=0.028). SOFA scores were significantly higher at the point of first mobilisation in the Combilizer group (mean: 2.9±0.5 vs. 5.1±2.4; p=0.005). There was no statistical difference in therapy time between the groups, or ICU or hospital length of stay. CONCLUSIONS: The introduction of the Sara Combilizer® was associated with a significant reduction in time to mobilise patients ventilated for ≥5days, and patients were mobilised with a higher degree of organ failure. This was achieved without any increase in therapy time. The Sara Combilizer® may be a useful adjunct to an early mobility protocol within the ICU.

Mapping adipose and muscle tissue expression quantitative trait loci in African Americans to identify genes for type 2 diabetes and obesity.

Relative to European Americans, type 2 diabetes (T2D) is more prevalent in African Americans (AAs). Genetic variation may modulate transcript abundance in insulin-responsive tissues and contribute to risk; yet, published studies identifying expression quantitative trait loci (eQTLs) in African ancestry populations are restricted to blood cells. This study aims to develop a map of genetically regulated transcripts expressed in tissues important for glucose homeostasis in AAs, critical for identifying the genetic etiology of T2D and related traits. Quantitative measures of adipose and muscle gene expression, and genotypic data were integrated in 260 non-diabetic AAs to identify expression regulatory variants. Their roles in genetic susceptibility to T2D, and related metabolic phenotypes, were evaluated by mining GWAS datasets. eQTL analysis identified 1971 and 2078 cis-eGenes in adipose and muscle, respectively. Cis-eQTLs for 885 transcripts including top cis-eGenes CHURC1, USMG5, and ERAP2 were identified in both tissues. 62.1 % of top cis-eSNPs were within ±50 kb of transcription start sites and cis-eGenes were enriched for mitochondrial transcripts. Mining GWAS databases revealed association of cis-eSNPs for more than 50 genes with T2D (e.g. PIK3C2A, RBMS1, UFSP1), gluco-metabolic phenotypes (e.g. INPP5E, SNX17, ERAP2, FN3KRP), and obesity (e.g. POMC, CPEB4). Integration of GWAS meta-analysis data from AA cohorts revealed the most significant association for cis-eSNPs of ATP5SL and MCCC1 genes, with T2D and BMI, respectively. This study developed the first comprehensive map of adipose and muscle tissue eQTLs in AAs (publically accessible at https://mdsetaa.phs.wakehealth.edu ) and identified genetically regulated transcripts for delineating genetic causes of T2D, and related metabolic phenotypes.

Rare Coding Variation and Risk of Intracerebral Hemorrhage.

BACKGROUND AND PURPOSE: Intracerebral hemorrhage has a substantial genetic component. We performed a preliminary search for rare coding variants associated with intracerebral hemorrhage. METHODS: A total of 757 cases and 795 controls were genotyped using the Illumina HumanExome Beadchip (Illumina, Inc, San Diego, CA). Meta-analyses of single-variant and gene-based association were computed. RESULTS: No rare coding variants were associated with intracerebral hemorrhage. Three common variants on chromosome 19q13 at an established susceptibility locus, encompassing TOMM40, APOE, and APOC1, met genome-wide significance (P<5e-08). After adjusting for the APOE epsilon alleles, this locus was no longer convincingly associated with intracerebral hemorrhage. No gene reached genome-wide significance level in gene-based association testing. CONCLUSIONS: Although no coding variants of large effect were detected, this study further underscores a major challenge for the study of genetic susceptibility loci; large sample sizes are required for sufficient power except for loci with large effects.

An Environmental Scan for Early Mobilization Practices in U.S. ICUs.

OBJECTIVE: Early mobilization improves patient outcomes. However, diffusion of this intervention into standard ICU practice is unknown. Dissemination and implementation efforts may be guided by an environmental scan to detail readiness for early mobilization, current practice, and barriers to early mobilization. DESIGN: A telephone survey. SETTING: U.S. ICUs. SUBJECTS: Five hundred randomly selected U.S. ICUs stratified by regional hospital density and hospital size. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We surveyed 687 ICUs for a 73% response rate (500 ICUs); 99% of respondents were nursing leadership. Fifty-one percent of hospitals reported an academic affiliation. Surveyed ICUs were most often mixed medical/surgical (58%) or medical (22%) with a median of 16 beds (12-24). Thirty-four percent reported presence of a dedicated physical and/or occupational therapy team for the ICU. Overall, 45% of ICUs reported early mobilization practice; two thirds of ICUs with early mobilization practice reported using a written early mobilization protocol. In ICUs with early mobilization practice, 52% began the intervention at admission and 74% enacted early mobilization for both ventilated and nonventilated patients. Early mobilization was provided a median of 6 days per week, twice daily. Factors independently associated with early mobilization protocols include dedicated physical/occupational therapy (odds ratio, 3.34; 95% CI, 2.13-5.22; p<0.01), American Hospital Association region 2 (odds ratio, 3.33; 95% CI, 1.04-10.64; p=0.04), written sedation protocol (odds ratio, 2.36; 95% CI, 1.25-4.45; p<0.01), daily multidisciplinary rounds (odds ratio, 2.31; 95% CI, 1.29-4.15; p<0.01), and written daily goals for patients (odds ratio, 2.17; 95% CI, 1.02-4.64; p=0.04). Commonly cited barriers included equipment, staffing, patient and caregiver safety, and competing priorities. In ICUs without early mobilization adoption, 78% have considered implementation but cite barriers including competing priorities and need for further planning. CONCLUSIONS: Diffusion regarding benefits of early mobilization has occurred, but adoption into practice is lagging. Mandates for multidisciplinary rounds and formal sedation protocols may be necessary strategies to increase the likelihood of successful early mobilization implementation. Methods to accurately assess and compare institutional performance via practice audit are needed.

Differential transit peptide recognition during preprotein binding and translocation into flowering plant plastids.

Despite the availability of thousands of transit peptide (TP) primary sequences, the structural and/or physicochemical properties that determine TP recognition by components of the chloroplast translocon are not well understood. By combining a series of in vitro and in vivo experiments, we reveal that TP recognition is determined by sequence-independent interactions and vectorial-specific recognition domains. Using both native and reversed TPs for two well-studied precursors, small subunit of ribulose-1,5-bis-phosphate carboxylase/oxygenase, and ferredoxin, we exposed these two modes of recognition. Toc34 receptor (34-kD subunit of the translocon of the outer envelope) recognition in vitro, preprotein binding in organellar, precursor binding in vivo, and the recognition of TPs by the major stromal molecular motor Hsp70 are specific for the physicochemical properties of the TP. However, translocation in organellar and in vivo demonstrates strong specificity to recognition domain organization. This organization specificity correlates with the N-terminal placement of a strong Hsp70 recognition element. These results are discussed in light of how individual translocon components sequentially interact with the precursor during binding and translocation and helps explain the apparent lack of sequence conservation in chloroplast TPs.

Re-Sequencing of the APOL1-APOL4 and MYH9 Gene Regions in African Americans Does Not Identify Additional Risks for CKD Progression.

BACKGROUND: In African Americans (AAs), APOL1 G1 and G2 nephropathy risk variants are associated with non-diabetic end-stage kidney disease (ESKD) in an autosomal recessive pattern. Additional risk and protective genetic variants may be present near the APOL1 loci, since earlier age ESKD is observed in some AAs with one APOL1 renal-risk variant, and because the adjacent gene MYH9 is associated with nephropathy in populations lacking G1 and G2 variants. METHODS: Re-sequencing was performed across a ∼275 kb region encompassing the APOL1-APOL4 and MYH9 genes in 154 AA cases with non-diabetic ESKD and 38 controls without nephropathy who were heterozygous for a single APOL1 G1 or G2 risk variant. RESULTS: Sequencing identified 3,246 non-coding single nucleotide polymorphisms (SNPs), 55 coding SNPs, and 246 insertion/deletions. No new coding variations were identified. Eleven variants, including a rare APOL3 Gln58Ter null variant (rs11089781), were genotyped in a replication panel of 1,571 AA ESKD cases and 1,334 controls. After adjusting for APOL1 G1 and G2 risk effects, these variations were not significantly associated with ESKD. In subjects with <2 APOL1 G1 and/or G2 alleles (849 cases; 1,139 controls), the APOL3 null variant was nominally associated with ESKD (recessive model, OR 1.81; p = 0.026); however, analysis in 807 AA cases and 634 controls from the Family Investigation of Nephropathy and Diabetes did not replicate this association. CONCLUSION: Additional common variants in the APOL1-APOL4-MYH9 region do not contribute significantly to ESKD risk beyond the APOL1 G1 and G2 alleles.

Clinical effectiveness of an online supervised group physical and mental health rehabilitation programme for adults with post-covid-19 condition (REGAIN study): multicentre randomised controlled trial.

OBJECTIVE: To evaluate whether a structured online supervised group physical and mental health rehabilitation programme can improve health related quality of life compared with usual care in adults with post-covid-19 condition (long covid). DESIGN: Pragmatic, multicentre, parallel group, superiority randomised controlled trial. SETTING: England and Wales, with home based interventions delivered remotely online from a single trial hub. PARTICIPANTS: 585 adults (26-86 years) discharged from NHS hospitals at least three months previously after covid-19 and with ongoing physical and/or mental health sequelae (post-covid-19 condition), randomised (1:1.03) to receive the Rehabilitation Exercise and psycholoGical support After covid-19 InfectioN (REGAIN) intervention (n=298) or usual care (n=287). INTERVENTIONS: Best practice usual care was a single online session of advice and support with a trained practitioner. The REGAIN intervention was delivered online over eight weeks and consisted of weekly home based, live, supervised, group exercise and psychological support sessions. MAIN OUTCOME MEASURES: The primary outcome was health related quality of life using the patient reported outcomes measurement information system (PROMIS) preference (PROPr) score at three months. Secondary outcomes, measured at three, six, and 12 months, included PROMIS subscores (depression, fatigue, sleep disturbance, pain interference, physical function, social roles/activities, and cognitive function), severity of post-traumatic stress disorder, general health, and adverse events. RESULTS: Between January 2021 and July 2022, 39 697 people were invited to take part in the study and 725 were contacted and eligible. 585 participants were randomised. Mean age was 56 (standard deviation (SD) 12) years, 52% were female participants, mean health related quality of life PROMIS-PROPr score was 0.20 (SD 0.17), and mean time from hospital discharge was 323 (SD 144) days. Compared with usual care, the REGAIN intervention led to improvements in health related quality of life (adjusted mean difference in PROPr score 0.03 (95% confidence interval 0.01 to 0.05), P=0.02) at three months, driven predominantly by greater improvements in the PROMIS subscores for depression (1.39 (0.06 to 2.71), P=0.04), fatigue (2.50 (1.19 to 3.81), P<0.001), and pain interference (1.80 (0.50 to 3.11), P=0.01). Effects were sustained at 12 months (0.03 (0.01 to 0.06), P=0.02). Of 21 serious adverse events, only one was possibly related to the REGAIN intervention. In the intervention group, 141 (47%) participants fully adhered to the programme, 117 (39%) partially adhered, and 40 (13%) did not receive the intervention. CONCLUSIONS: In adults with post-covid-19 condition, an online, home based, supervised, group physical and mental health rehabilitation programme was clinically effective at improving health related quality of life at three and 12 months compared with usual care. TRIAL REGISTRATION: ISRCTN registry ISRCTN11466448.

Comparing rehabilitation outcomes for patients admitted to the intensive care unit with COVID-19 requiring mechanical ventilation during the first two waves of the pandemic: A service evaluation.

OBJECTIVES: To compare rehabilitation outcomes of patients admitted to the intensive care unit with COVID-19 and mechanically ventilated during wave 1 and 2, receiving two different models of physiotherapy delivery. METHODS: Adults admitted to the intensive care unit between October-March 2021 (wave 2) with a confirmed diagnosis of COVID-19 and mechanically ventilated for >24 hours were included. During wave 2, rehabilitation was provided by physiotherapists over five days, with only emergency respiratory physiotherapy delivered at weekends. Rehabilitation status was measured daily using the Manchester Mobility Score to identify time taken to first mobilise and highest level of mobility achieved at ICU discharge. Outcomes were compared to data previously published from the same ICU during 'wave 1' (March-April 2020) when a seven-day rehabilitation physiotherapy service was provided. RESULTS: A total of n = 291 patients were included in analysis; 110 from wave 1, and 181 from wave 2. Patient characteristics and medical management were similar between waves. Mean ± SD time to first mobilise was slower in wave 2 (15 ± 11 days vs 14 ± 7 days), with overall mobility scores lower at both ICU (MMS 5 (Step transferring) vs MMS 4 (standing practice) (4), p < 0.05) and hospital (MMS 7 (Mobile > 30 m MMS) vs MMS 6 (Mobile < 30 m MMS), p < 0.0001) discharge. Significantly more patients in wave 2 required ongoing rehabilitation either at home or as an inpatient compared to wave 1 (81 % vs 49 %, p = 0.003). CONCLUSION: The change in physiotherapy staff provision from a seven-day rehabilitation service during wave 1 to a five day rehabilitation service with emergency respiratory physio only at weekends in wave 2 was associated with delayed time to first mobilise, lower levels of mobility at both intensive care unit and hospital discharge and higher requirement for ongoing rehabilitation at the point of hospital discharge.

Early mobilisation for prevention and treatment of delirium in critically ill patients: Systematic review and meta-analysis.

OBJECTIVE: Does early mobilisation as standalone or part of a bundle intervention, compared to usual care, prevent and/or shorten delirium in adult patients in Intensive Care Units? BACKGROUND: Early mobilisation is recommended for the prevention and treatment of delirium in critically ill patients, but the evidence remains inconclusive. METHOD: Systematic literature search in Pubmed, CINAHL, PEDRo, Cochrane from inception to March 2022, and hand search in previous meta-analysis. Included were randomized trials or quality-improvement projects. meta-analysis was performed for Odds Ratios or mean differences including 95% Confidence Intervals for presence/duration of delirium. Risk of bias was assessed by using Joanna Briggs Quality criteria. meta-regression was performed to analyse heterogeneity. RESULTS: The search led to 13 studies of low-moderate risk of bias including 2,164 patients. Early mobilisation reduced the risk of delirium by 47 % (13 studies, 2,164 patients, low to moderate risk of bias: Odds Ratio 0.53 (95 % Confidence Interval 0.34 till 0.83, p = 0.01), with significant heterogeneity (I2 = 78 %, p < 0.001). Early mobilisation also reduced the duration of delirium by 1.8 days (3 studies, 296 patients, low-moderate risk of bias: Mean difference -1.78 days (95 % Confidence Interval -2.73 till -0.83 days, p < 0.001), heterogeneity 0 % (p = 0.41). Other analyses such as low risk of bias studies, randomised trials, studies published ≥ 2017, high intensity, and mobilisation as stand-alone intervention showed no significant results, with conflicting certainty of evidence and high heterogeneity. meta-regression could not explain heterogeneity. CONCLUSION: There is an uncertain effect of mobilisation on delirium. Provision of early mobilisation to critical ill patients might prevent delirium. There is a possible effect of early mobilisation to shorten the duration of delirium. Due to the heterogeneity in the findings, further research to define the best method and dosage of early rehabilitation is required.

Mobilisation in the EveNing to TreAt deLirium (MENTAL): protocol for a mixed-methods feasibility randomised controlled trial.

INTRODUCTION: Delirium is common in critically ill patients and is associated with longer hospital stays, increased mortality and higher healthcare costs. A number of risk factors have been identified for the development of delirium in intensive care, two of which are sleep disturbance and immobilisation. Non-pharmacological interventions for the management of intensive care unit (ICU) delirium have been advocated, including sleep protocols and early mobilisation. However, there is a little published evidence evaluating the feasibility and acceptability of evening mobilisation. METHODS AND ANALYSIS: Mobilisation in the EveNing to TreAt deLirium (MENTAL) is a two-centre, mixed-methods feasibility randomised controlled trial (RCT). Sixty patients will be recruited from ICUs at two acute NHS trusts and randomised on a 1:1 basis to receive additional evening mobilisation, delivered between 19:00 and 21:00, or standard care. The underpinning hypothesis is that the physical exertion associated with evening mobilisation will promote better sleep, subsequently having the potential to reduce delirium incidence. The primary objective is to assess the feasibility and acceptability of a future, multicentre RCT. The primary outcome measures, which will determine feasibility, are recruitment and retention rates, and intervention fidelity. Acceptability of the intervention will be evaluated through semi-structured interviews of participants and staff. Secondary outcome measures include collecting baseline, clinical and outcome data to inform the power calculations of a future definitive trial. ETHICS AND DISSEMINATION: Ethical approval has been obtained through the Wales Research and Ethics Committee 6 (22/WA/0106). Participants are required to provide written informed consent. We aim to disseminate the findings through international conferences, international peer-reviewed journals and social media. TRIAL REGISTRATION NUMBER: NCT05401461.

Mobilisation in the EveNing to prevent and TreAt deLirium (MENTAL): a mixed-methods, randomised controlled feasibility trial.

Background: Delirium is common in critically ill patients and associated with longer hospital stays, increased morbidity and higher healthcare costs. Non-pharmacological interventions have been advocated for delirium management, however there is little evidence evaluating feasibility and acceptability of physical interventions administered in the evening. The aim of this study was to conduct a feasibility trial of evening mobilisation to prevent and treat delirium in patients admitted to intensive care. Methods: In this mixed-methods, randomised controlled feasibility trial we recruited participants from intensive care units at two university hospitals in the United Kingdom. Eligible participants who were able to respond to verbal stimulus (Richmond agitation and sedation scale ≥3) and expected to stay in intensive care for at least 24 h were randomly assigned (1:1) to receive usual care or usual care plus evening mobilisation. The evening mobilisation was delivered between 19:00 and 21:00, for up to seven consecutive evenings or ICU discharge, whichever was sooner. All outcome assessments were completed by a team member blinded to randomisation and group allocation. Primary objective was to assess feasibility and acceptability of evening mobilisation. Primary feasibility outcomes were recruitment, consent and retention rates, and intervention fidelity. Intervention acceptability was evaluated through semi-structured interviews of participants and staff. Secondary outcomes included prevalence in incidence and duration of delirium, measured using the Confusion Assessment Method for ICU. This trial is registered at ClinicalTrials.gov, NCT05401461. Findings: Between July 16th, 2022, and October 31st, 2022, 58 eligible patients (29 usual care; 29 usual care plus evening mobilisation) were enrolled. We demonstrated the feasibility and acceptability of both the trial design and evening mobilisation intervention. Consent and retention rates over three months were 88% (58/66) and 90% (52/58) respectively, with qualitative analysis demonstrating good acceptability reported by both participants and staff. Secondary outcomes for the evening intervention group compared with the control group were: delirium incidence 5/26 (19%; 95% CI: 6-39%) vs 8/28 (29%; 95% CI: 13-49%) and mean delirium duration 2 days (SD 0.7) vs 4.25 days (SD 2.0). Interpretation: Results of this trial will inform the development of a definitive full-scale randomised controlled trial investigating the effects of evening mobilisation to treat delirium and improve health-related outcomes. Funding: None.

Development of an online intervention for the Rehabilitation Exercise and psycholoGical support After covid-19 InfectioN (REGAIN) trial.

Background: Up to half of people hospitalised with COVID-19 report diverse and persistent symptoms affecting quality of life for months and sometimes years after discharge (long-COVID). We describe the development of an online group exercise and behavioural support intervention for people who continue to experience such physical and/or emotional health problems more than three months after hospital discharge. Methods: Intervention development was informed by the Medical Research Council framework for complex interventions. Our multidisciplinary team of academics, clinicians, and people with long-COVID, had collective expertise in the development and testing of complex interventions. We integrated a bio-psycho-social model of care drawing on rehabilitation literature for long-term health conditions and experiences from our pre-pilot study. Multiple stakeholder meetings were held to refine the intervention which was designed to be deliverable within the UK National Health Service. We adhere to TIDieR guidance for transparent and explicit reporting of telehealth interventions. Results: The final REGAIN online exercise and behavioural support intervention consisted of an initial 1:1 consultation with a trained practitioner, followed by eight online group exercise, and six group support, sessions delivered over eight weeks. Participants could also access an online library of on-demand exercise and support videos. Conclusions: The final REGAIN intervention, combining exercise and behavioural support, is fully manualised with clear pathways to delivery and implementation. It is currently being tested in a randomised controlled trial. The intervention, developed with extensive patient and stakeholder engagement, could be incorporated into existing NHS rehabilitation programmes, should it prove to be clinically and cost-effective for people with long-COVID. Trial registration: International Standard Randomised Controlled Trial Number (ISRCTN) 11466448: Rehabilitation exercise and psychological support after COVID-19 infection: REGAIN.

Long-COVID has many debilitating symptoms, such as breathlessness, muscle weakness and fatigue, which significantly affect peoples' physical and mental health and quality of life. Rehabilitation programmes can help people improve their quality of life in other medical conditions with similar symptoms. We developed a programme of physical and mental health rehabilitation, delivered online, specifically to support people with ongoing long-COVID symptoms more than three months after hospital discharge. The programme was developed by people with long-COVID along with clinicians and researchers. The programme described in this article is now being tested in a large research trial to see if it can help people with long-COVID.

Virtual Post-Intensive-Care Rehabilitation for Survivors of COVID-19: A Service Evaluation.

AIM: The objective of this study is to evaluate the safety, utilisation, and effectiveness of a novel, virtual rehabilitation programme for survivors of SARS­CoV­2 infection (COVID-19) and intensive care admission. METHODS: A service evaluation was performed. Adults admitted to a United Kingdom intensive care unit with COVID-19-induced respiratory failure and surviving hospital discharge were invited to an eight-week rehabilitation programme. The programme consisted of virtually delivered exercise classes and support groups led by critical care physiotherapists and follow-up nurses. RESULTS: Thirty-eight of 76 eligible patients (50%) agreed to participate, of which 28 (74%) completed the rehabilitation programme. On completion of the rehabilitation programme, there were significant improvements in exercise capacity (one-minute sit-to-stand test; 20 stands vs. 25 stands, p < 0.001), perceived breathlessness (Medical Research Council dyspnoea scale; 3 vs. 2 p < 0.001), shoulder disability (Quick Dash; 43 vs. 19 p = 0.001), anxiety (Hospital Anxiety Depression Scale; 4 vs. 3 p = 0.021), depression (Hospital Anxiety Depression Scale; 4 vs. 2.5 p = 0.010), and psychological distress (Intensive Care Psychological Assessment Tool; 3 vs. 2 p = 0.002). No adverse events or injuries were recorded during the programme. CONCLUSION: It is feasible to recruit and retain survivors of COVID-19-induced respiratory failure for virtual post-intensive-care rehabilitation. It appears that the virtual rehabilitation programme is safe and improves physical and psychological morbidity.

Self-directed versus peer-supported digital self-management programmes for mental and sexual wellbeing after acquired brain injury (HOPE4ABI): protocol for a feasibility randomised controlled trial.

BACKGROUND: Acquired brain injury (ABI) can lead to biopsychosocial changes such as depression, low self-esteem and fatigue. These changes can cause, and be caused by, sexual issues affecting relationships and wellbeing. Given the relationship between sexual wellbeing and mental health, it is feasible that supporting sexual wellbeing will benefit psychological wellbeing. However, neurorehabilitation is inconsistent and often fragmented across the UK, and psychological, sexual and social support are lacking. Research shows that self-management and peer-support programmes can improve quality of life, self-efficacy and psychological wellbeing after brain injury. This protocol describes a feasibility randomised controlled trial (RCT) of a digital self-management programme to support mental and sexual wellbeing (known as HOPE4ABI), co-designed with and for people with ABI. METHODS: This mixed-methods feasibility RCT has two parallel trial arms of the 8-week digital HOPE4ABI self-management programme. Eligibility criteria include age > 18 years, diagnosed or suspected ABI > 3 months prior to trial entry, access to an Internet-enabled device and ability to engage with the intervention. Referrals to the study website will be made via the National Health Service (NHS), social media and partnering organisations. Sixty eligible participants will be randomised at a ratio of 1:1 to peer-supported (n = 30) or self-directed (n = 30) HOPE4ABI programmes. Primary feasibility outcomes include recruitment and retention rates, engagement, adherence and usage. Secondary outcomes related to standardised measures of quality of life, sexual wellbeing and mental wellbeing. Participants and peer facilitators will be interviewed after the course to assess acceptability across both trial arms. DISCUSSION: This feasibility trial data is not sufficiently powered for inferential statistical analyses but will provide evidence of the feasibility of a full RCT. Quantitative trial data will be analysed descriptively, and participant screening data representing age, ethnicity and gender will be presented as proportions at the group level. These data may indicate trends in reach to particular demographic groups that can inform future recruitment strategies to widen participation. Progression to a definitive trial will be justified if predetermined criteria are met, relating to recruitment, retention, engagement and acceptability. TRIAL REGISTRATION: ISRCTN46988394 registered on March 1, 2023.

Rehabilitation Levels in Patients with COVID-19 Admitted to Intensive Care Requiring Invasive Ventilation. An Observational Study.

Rationale: Patients with severe coronavirus disease (COVID-19) have complex organ support needs that necessitate prolonged stays in the intensive care unit (ICU), likely to result in a high incidence of neuromuscular weakness and loss of well-being. Early and structured rehabilitation has been associated with improved outcomes for patients requiring prolonged periods of mechanical ventilation, but at present no data are available to describe similar interventions or outcomes in COVID-19 populations.Objectives: To describe the demographics, clinical status, level of rehabilitation, and mobility status at ICU discharge of patients with COVID-19.Methods: Adults admitted to the ICU with a confirmed diagnosis of COVID-19 and mechanically ventilated for >24 hours were included. Rehabilitation status was measured daily using the Manchester Mobility Score to identify the time taken to first mobilize (defined as sitting on the edge of the bed or higher) and highest level of mobility achieved at ICU discharge.Results: A total of n = 177 patients were identified, of whom n = 110 survived to ICU discharge and were included in the subsequent analysis. While on ICU, patients required prolonged periods of mechanical ventilation (mean 19 ± 10 d), most received neuromuscular blockade (90%) and 67% were placed in the prone position on at least one occasion. The mean ± standard deviation time to first mobilize was 14 ± 7 days, with a median Manchester Mobility Score at ICU discharge of 5 (interquartile range: 4-6), which represents participants able to stand and step around to a chair with or without assistance. Time to mobilize was significantly longer in those with higher body mass index (P < 0.001), and older patients (P = 0.012) and those with more comorbidities (P = 0.017) were more likely to require further rehabilitation after discharge.Conclusions: The early experience of the COVID-19 pandemic in the United Kingdom resembles the experience in other countries, with high acuity of illness and prolonged period of mechanical ventilation required for those patients admitted to the ICU. Although the time to commence rehabilitation was delayed owing to this severity of illness, rehabilitation was possible within the ICU and led to increased levels of mobility from waking before ICU discharge.Clinical trial registered with ClinicalTrials.gov (NCT04396197).