Julia Boyd

Increased Hospital-Based Physical Rehabilitation and Information Provision After Intensive Care Unit Discharge: The RECOVER Randomized Clinical Trial

IMPORTANCE Critical illness results in disability and reduced health-related quality of life (HRQOL), but the optimum timing and components of rehabilitation are uncertain. OBJECTIVE To evaluate the effect of increasing physical and nutritional rehabilitation plus information delivered during the post-intensive care unit (ICU) acute hospital stay by dedicated rehabilitation assistants on subsequent mobility, HRQOL, and prevalent disabilities. DESIGN, SETTING, AND PARTICIPANTS A parallel group, randomized clinical trial with blinded outcome assessment at 2 hospitals in Edinburgh, Scotland, of 240 patients discharged from the ICU between December 1, 2010, and January 31, 2013, who required at least 48 hours of mechanical ventilation. Analysis for the primary outcome and other 3-month outcomes was performed between June and August 2013; for the 6- and 12-month outcomes and the health economic evaluation, between March and April 2014. INTERVENTIONS During the post-ICU hospital stay, both groups received physiotherapy and dietetic, occupational, and speech/language therapy, but patients in the intervention group received rehabilitation that typically increased the frequency of mobility and exercise therapies 2- to 3-fold, increased dietetic assessment and treatment, used individualized goal setting, and provided greater illness-specific information. Intervention group therapy was coordinated and delivered by a dedicated rehabilitation practitioner. MAIN OUTCOMES AND MEASURES The Rivermead Mobility Index (RMI) (range 0-15) at 3 months; higher scores indicate greater mobility. Secondary outcomes included HRQOL, psychological outcomes, self-reported symptoms, patient experience, and cost-effectiveness during a 12-month follow-up (completed in February 2014). RESULTS Median RMI at randomization was 3 (interquartile range [IQR], 1-6) and at 3 months was 13 (IQR, 10-14) for the intervention and usual care groups (mean difference, -0.2 [95% CI, -1.3 to 0.9; P = .71]). The HRQOL scores were unchanged by the intervention (mean difference in the Physical Component Summary score, -0.1 [95% CI, -3.3 to 3.1; P = .96]; and in the Mental Component Summary score, 0.2 [95% CI, -3.4 to 3.8; P = .91]). No differences were found for self-reported symptoms of fatigue, pain, appetite, joint stiffness, or breathlessness. Levels of anxiety, depression, and posttraumatic stress were similar, as were hand grip strength and the timed Up & Go test. No differences were found at the 6- or 12-month follow-up for any outcome measures. However, patients in the intervention group reported greater satisfaction with physiotherapy, nutritional support, coordination of care, and information provision. CONCLUSIONS AND RELEVANCE Post-ICU hospital-based rehabilitation, including increased physical and nutritional therapy plus information provision, did not improve physical recovery or HRQOL, but improved patient satisfaction with many aspects of recovery. TRIAL REGISTRATION isrctn.com Identifier: ISRCTN09412438.

Restrictive versus liberal transfusion strategies for older mechanically ventilated critically ill patients: a randomized pilot trial.

Objectives:To compare hemoglobin concentration (Hb), RBC use, and patient outcomes when restrictive or liberal blood transfusion strategies are used to treat anemic (Hb ⩽ 90 g/L) critically ill patients of age ≥ 55 years requiring ≥ 4 days of mechanical ventilation in ICU. Design:Parallel-group randomized multicenter pilot trial. Setting:Six ICUs in the United Kingdom participated between August 2009 and December 2010. Patients:One hundred patients (51 restrictive and 49 liberal groups). Interventions:Patients were randomized to a restrictive (Hb trigger, 70 g/L; target, 71–90 g/L) or liberal (90 g/L; target, 91–110 g/L) transfusion strategy for 14 days or the remainder of ICU stay, whichever was longest. Measurements and Main Results:Baseline comorbidity rates and illness severity were high, notably for ischemic heart disease (32%). The Hb difference among groups was 13.8 g/L (95% CI, 11.5–16.0 g/L); p < 0.0001); mean Hb during intervention was 81.9 (SD, 5.1) versus 95.7 (6.3) g/L; 21.6% fewer patients in the restrictive group were transfused postrandomization (p < 0.001) and received a median 1 (95% CI, 1–2; p = 0.002) fewer RBC units. Protocol compliance was high. No major differences in organ dysfunction, duration of ventilation, infections, or cardiovascular complications were observed during intensive care and hospital follow-up. Mortality at 180 days postrandomization trended toward higher rates in the liberal group (55%) than in the restrictive group (37%); relative risk was 0.68 (95% CI, 0.44–1.05; p = 0.073). This trend remained in a survival model adjusted for age, gender, ischemic heart disease, Acute Physiology and Chronic Health Evaluation II score, and total non-neurologic Sequential Organ Failure Assessment score at baseline (hazard ratio, 0.54 [95% CI, 0.28–1.03]; p = 0.061). Conclusions:A large trial of transfusion strategies in older mechanically ventilated patients is feasible. This pilot trial found a nonsignificant trend toward lower mortality with restrictive transfusion practice.

A randomised controlled trial evaluating a rehabilitation complex intervention for patients following intensive care discharge: the RECOVER study

Introduction Patients who survive an intensive care unit admission frequently suffer physical and psychological morbidity for many months after discharge. Current rehabilitation pathways are often fragmented and little is known about the optimum method of promoting recovery. Many patients suffer reduced quality of life. Methods and analysis The authors plan a multicentre randomised parallel group complex intervention trial with concealment of group allocation from outcome assessors. Patients who required more than 48 h of mechanical ventilation and are deemed fit for intensive care unit discharge will be eligible. Patients with primary neurological diagnoses will be excluded. Participants will be randomised into one of the two groups: the intervention group will receive standard ward-based care delivered by the NHS service with additional treatment by a specifically trained generic rehabilitation assistant during ward stay and via telephone contact after hospital discharge and the control group will receive standard ward-based care delivered by the current NHS service. The intervention group will also receive additional information about their critical illness and access to a critical care physician. The total duration of the intervention will be from randomisation to 3 months postrandomisation. The total duration of follow-up will be 12 months from randomisation for both groups. The primary outcome will be the Rivermead Mobility Index at 3 months. Secondary outcomes will include measures of physical and psychological morbidity and function, quality of life and survival over a 12-month period. A health economic evaluation will also be undertaken. Groups will be compared in relation to primary and secondary outcomes; quantitative analyses will be supplemented by focus groups with patients, carers and healthcare workers. Ethics and dissemination Consent will be obtained from patients and relatives according to patient capacity. Data will be analysed according to a predefined analysis plan. Trial registration The trial is registered as ISRCTN09412438 and funded by the Chief Scientist Office, Scotland.

Underestimation of Staphylococcus aureus (MRSA and MSSA) carriage associated with standard culturing techniques: One third of carriers missed

Objectives Nasal carriers of Staphylococcus (S.) aureus (MRSA and MSSA) have an increased risk for healthcare-associated infections. There are currently limited national screening policies for the detection of S. aureus despite the World Health Organization’s recommendations. This study aimed to evaluate the diagnostic performance of molecular and culture techniques in S. aureus screening, determine the cause of any discrepancy between the diagnostic techniques, and model the potential effect of different diagnostic techniques on S. aureus detection in orthopaedic patients. Methods Paired nasal swabs for polymerase chain reaction (PCR) assay and culture of S. aureus were collected from a study population of 273 orthopaedic outpatients due to undergo joint arthroplasty surgery. Results The prevalence of MSSA nasal colonization was found to be between 22.4% to 35.6%. The current standard direct culturing methods for detecting S. aureus significantly underestimated the prevalence (p = 0.005), failing to identify its presence in approximately one-third of patients undergoing joint arthroplasty surgery. Conclusion Modelling these results to national surveillance data, it was estimated that approximately 5000 to 8000 S. aureus surgical site infections could be prevented, and approximately

Protocol for validation of the 4AT, a rapid screening tool for delirium: a multicentre prospective diagnostic test accuracy study

140 million to

The Age of BLood Evaluation (ABLE) randomised controlled trial: description of the UK-funded arm of the international trial, the UK cost-utility analysis and secondary analyses exploring factors associated with health-related quality of life and health-care costs during the 12-month follow-up.

950 million (approximately £110 million to £760 million) saved in treatment costs annually in the United States and United Kingdom combined, by using alternative diagnostic methods to direct culture in preoperative S. aureus screening and eradication programmes. Cite this article: S. T. J. Tsang, M. P. McHugh, D. Guerendiain, P. J. Gwynne, J. Boyd, A. H. R. W. Simpson, T. S. Walsh, I. F. Laurenson, K. E. Templeton. Underestimation of Staphylococcus aureus (MRSA and MSSA) carriage associated with standard culturing techniques: One third of carriers missed. Bone Joint Res 2018;7:79–84. DOI: 10.1302/2046-3758.71.BJR-2017-0175.R1.

Evaluation of Staphylococcus aureus eradication therapy in orthopaedic surgery

Introduction Delirium is a severe neuropsychiatric syndrome of rapid onset, commonly precipitated by acute illness. It is common in older people in the emergency department (ED) and acute hospital, but greatly under-recognised in these and other settings. Delirium and other forms of cognitive impairment, particularly dementia, commonly coexist. There is a need for a rapid delirium screening tool that can be administered by a range of professional-level healthcare staff to patients with sensory or functional impairments in a busy clinical environment, which also incorporates general cognitive assessment. We developed the 4 ’A’s Test (4AT) for this purpose. This study’s primary objective is to validate the 4AT against a reference standard. Secondary objectives include (1) comparing the 4AT with another widely used test (the Confusion Assessment Method (CAM)); (2) determining if the 4AT is sensitive to general cognitive impairment; (3) assessing if 4AT scores predict outcomes, including (4) a health economic analysis. Methods and analysis 900 patients aged 70 or over in EDs or acute general medical wards will be recruited in three sites (Edinburgh, Bradford and Sheffield) over 18 months. Each patient will undergo a reference standard delirium assessment and will be randomised to assessment with either the 4AT or the CAM. At 12 weeks, outcomes (length of stay, institutionalisation and mortality) and resource utilisation will be collected by a questionnaire and via the electronic patient record. Ethics and dissemination Ethical approval was granted in Scotland and England. The study involves administering tests commonly used in clinical practice. The main ethical issues are the essential recruitment of people without capacity. Dissemination is planned via publication in high impact journals, presentation at conferences, social media and the website www.the4AT.com. Trial registration number ISRCTN53388093; Pre-results.

A randomized controlled trial comparing the outcome of critically ill adults who received fresher vs. older red cells units

BACKGROUND At present, red blood cells (RBCs) are stored for up to 42 days prior to transfusion. The relative effectiveness and safety of different RBC storage times prior to transfusion is uncertain. OBJECTIVE To assess the clinical effectiveness and cost-effectiveness of transfusing fresher RBCs (stored for ≤ 7 days) compared with current standard-aged RBCs in critically ill patients requiring blood transfusions. DESIGN The international Age of BLood Evaluation (ABLE) trial was a multicentre, randomised, blinded trial undertaken in Canada, the UK, the Netherlands and France. The UK trial was funded to contribute patients to the international trial and undertake a UK-specific health economic evaluation. SETTING Twenty intensive care units (ICUs) in the UK, as part of 64 international centres. PARTICIPANTS Critically ill patients aged ≥ 18 years (≥ 16 years in Scotland) expected to require mechanical ventilation for ≥ 48 hours and requiring a first RBC transfusion during the first 7 days in the ICU. INTERVENTIONS All decisions to transfuse RBCs were made by clinicians. One patient group received exclusively fresh RBCs stored for ≤ 7 days whenever transfusion was required from randomisation until hospital discharge. The other group received standard-issue RBCs throughout their hospital stay. MAIN OUTCOME MEASURES The primary outcome was 90-day mortality. Secondary outcomes included development of organ dysfunction, new thrombosis, infections and transfusion reactions. The primary economic evaluation was a cost-utility analysis. RESULTS The international trial took place between March 2009 and October 2014 (UK recruitment took place between January 2012 and October 2014). In total, 1211 patients were assigned to receive fresh blood and 1219 patients to receive standard-aged blood. RBCs were stored for a mean of 6.1 days [standard deviation (SD) ± 4.9 days] in the group allocated to receive fresh blood and 22.0 days (SD ± 8.4 days) in the group allocated to receive standard-aged blood. Patients received a mean of 4.3 RBC units (SD ± 5.2 RBC units) and 4.3 RBC units (SD ± 5.5 RBC units) in the groups receiving fresh blood and standard-aged blood, respectively. At 90 days, 37.0% of patients in the group allocated to receive fresh blood and 35.3% of patients in the group allocated to receive standard-aged blood had died {absolute risk difference 1.7% [95% confidence interval (CI) -2.1% to 5.5%]}. There were no between-group differences in any secondary outcomes. The UK cohort comprised 359 patients randomised and followed up for 12 months for the cost-utility analysis. UK patients had similar characteristics and outcomes to the international cohort. Mean total costs per patient were £32,346 (95% CI £29,306 to £35,385) in the group allocated to receive fresh blood and £33,353 (95% CI £29,729 to £36,978) in the group allocated to receive standard-aged blood. Approximately 85% of the total costs were incurred during the index hospital admission. There were no significant cost differences between the two groups [mean incremental costs for those receiving fresh vs. standard-aged blood: -£231 (95% CI -£4876 to £4415)], nor were there significant differences in outcomes (mean difference in quality-adjusted life-years -0.010, 95% CI -0.078 to 0.057). LIMITATIONS Adverse effects from the exclusive use of older RBCs compared with standard or fresh RBCs cannot be excluded. CONCLUSIONS The use of RBCs aged ≤ 7 days confers no clinical or economic benefit in critically ill patients compared with standard-aged RBCs. FUTURE WORK Future studies should address the safety of RBCs near the end of the current permitted storage age. TRIAL REGISTRATION Current Controlled Trials ISRCTN44878718. FUNDING This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 21, No. 62. See the NIHR Journals Library website for further project information. The international ABLE trial was also supported by peer-reviewed grants from the Canadian Institutes of Health Research (177453), Fonds de Recherche du Québec - Santé (24460), the French Ministry of Health Programme Hospitalier de Recherche Clinique (12.07, 2011) and by funding from Établissement Français du Sang and Sanquin Blood Supply.

Underestimation of Staphylococcus aureus carriage associated with standard culturing techniques

Purpose. Despite WHO recommendations, there is currently no national screening and eradication policy for the detection of methicillin‐sensitive Staphylococcus aureus (MSSA) in the UK prior to elective orthopaedic surgery. This study aimed to evaluate the effectiveness of current standard methicillin‐resistant S. aureus (MRSA) eradication therapies in the context of S. aureus (both MRSA and MSSA) decolonization in an elective orthopaedic population. Methodology. A total of 100 patients awaiting joint replacement surgery who were positive for S. aureus on PCR nasal screening underwent the current standard MRSA pre‐operative decolonization regimen for 5 days. Prior to commencement of the eradication therapy, swabs of the anterior nares, throat and perineum were taken for culture. Further culture swabs were taken at 48–96 h following treatment, at hospital admission for surgery and at hospital discharge. Following the completion of treatment, patients were asked to provide feedback on their experience using Likert rating scales. The primary outcome of this study was S. aureus clearance 48–96 h following eradication treatment. Results/Key Findings. Clearance of S. aureus 48–96 h following treatment was 94 % anterior nares, 66 % throat and 88 % groin. Mean completion with nasal mupirocin was 98 %. There was no statistically significant recolonization effect between the end of the eradication treatment period and the day of surgery (P>0.05) at a median time of 10 days. Conclusion. Current MRSA decolonisation regimens are well tolerated and effective for MSSA decolonization for the anterior nares and groin. The decolonization effect is preserved for at least 10 days following treatment.

Increased Hospital-Based Physical Rehabilitation and Information Provision After Intensive Care Unit Discharge

Red blood cell (RBC) units are stored up to 42 days postcollection. The standard policy is to deliver the oldest units in order to limit blood wastage. The hypothesis of the ‘Age of Blood Evaluation’ (ABLE) study was that the outcomes of adults transfused in intensive care units (ICU) with RBC units stored ≤7 days will be better than controls who received the oldest RBC units.