Ashley Cohen

Comparison of standard and accelerated initiation of renal replacement therapy in acute kidney injury.

In patients with severe acute kidney injury (AKI) but no urgent indication for renal replacement therapy (RRT), the optimal time to initiate RRT remains controversial. While starting RRT preemptively may have benefits, this may expose patients to unnecessary RRT. To study this, we conducted a 12-center open-label pilot trial of critically ill adults with volume replete severe AKI. Patients were randomized to accelerated (12 h or less from eligibility) or standard RRT initiation. Outcomes were adherence to protocol-defined time windows for RRT initiation (primary), proportion of eligible patients enrolled, follow-up to 90 days, and safety in 101 fully eligible patients (57 with sepsis) with a mean age of 63 years. Median serum creatinine and urine output at enrollment were 268 micromoles/l and 356 ml per 24 h, respectively. In the accelerated arm, all patients commenced RRT and 45/48 did so within 12 h from eligibility (median 7.4 h). In the standard arm, 33 patients started RRT at a median of 31.6 h from eligibility, of which 19 did not receive RRT (6 died and 13 recovered kidney function). Clinical outcomes were available for all patients at 90 days following enrollment, with mortality 38% in the accelerated and 37% in the standard arm. Two surviving patients, both randomized to standard RRT initiation, were still RRT dependent at day 90. No safety signal was evident in either arm. Our findings can inform the design of a large-scale effectiveness randomized control trial.

Restrictive or Liberal Red-Cell Transfusion for Cardiac Surgery

BACKGROUND The effect of a restrictive versus liberal red‐cell transfusion strategy on clinical outcomes in patients undergoing cardiac surgery remains unclear. METHODS In this multicenter, open‐label, noninferiority trial, we randomly assigned 5243 adults undergoing cardiac surgery who had a European System for Cardiac Operative Risk Evaluation (EuroSCORE) I of 6 or more (on a scale from 0 to 47, with higher scores indicating a higher risk of death after cardiac surgery) to a restrictive red‐cell transfusion threshold (transfuse if hemoglobin level was <7.5 g per deciliter, starting from induction of anesthesia) or a liberal red‐cell transfusion threshold (transfuse if hemoglobin level was <9.5 g per deciliter in the operating room or intensive care unit [ICU] or was <8.5 g per deciliter in the non‐ICU ward). The primary composite outcome was death from any cause, myocardial infarction, stroke, or new‐onset renal failure with dialysis by hospital discharge or by day 28, whichever came first. Secondary outcomes included red‐cell transfusion and other clinical outcomes. RESULTS The primary outcome occurred in 11.4% of the patients in the restrictive‐threshold group, as compared with 12.5% of those in the liberal‐threshold group (absolute risk difference, ‐1.11 percentage points; 95% confidence interval [CI], ‐2.93 to 0.72; odds ratio, 0.90; 95% CI, 0.76 to 1.07; P<0.001 for noninferiority). Mortality was 3.0% in the restrictive‐threshold group and 3.6% in the liberal‐threshold group (odds ratio, 0.85; 95% CI, 0.62 to 1.16). Red‐cell transfusion occurred in 52.3% of the patients in the restrictive‐threshold group, as compared with 72.6% of those in the liberal‐threshold group (odds ratio, 0.41; 95% CI, 0.37 to 0.47). There were no significant between‐group differences with regard to the other secondary outcomes. CONCLUSIONS In patients undergoing cardiac surgery who were at moderate‐to‐high risk for death, a restrictive strategy regarding red‐cell transfusion was noninferior to a liberal strategy with respect to the composite outcome of death from any cause, myocardial infarction, stroke, or new‐onset renal failure with dialysis, with less blood transfused. (Funded by the Canadian Institutes of Health Research and others; TRICS III ClinicalTrials.gov number, NCT02042898.)

Efficacy and safety of non-immersive virtual reality exercising in stroke rehabilitation (EVREST): a randomised, multicentre, single-blind, controlled trial

BACKGROUND Non-immersive virtual reality is an emerging strategy to enhance motor performance for stroke rehabilitation. There has been rapid adoption of non-immersive virtual reality as a rehabilitation strategy despite the limited evidence about its safety and effectiveness. Our aim was to compare the safety and efficacy of virtual reality with recreational therapy on motor recovery in patients after an acute ischaemic stroke. METHODS In this randomised, controlled, single-blind, parallel-group trial we enrolled adults (aged 18-85 years) who had a first-ever ischaemic stroke and a motor deficit of the upper extremity score of 3 or more (measured with the Chedoke-McMaster scale) within 3 months of randomisation from 14 in-patient stroke rehabilitation units from four countries (Canada [11], Argentina [1], Peru [1], and Thailand [1]). Participants were randomly allocated (1:1) by a computer-generated assignment at enrolment to receive a programme of structured, task-oriented, upper extremity sessions (ten sessions, 60 min each) of either non-immersive virtual reality using the Nintendo Wii gaming system (VRWii) or simple recreational activities (playing cards, bingo, Jenga, or ball game) as add-on therapies to conventional rehabilitation over a 2 week period. All investigators assessing outcomes were masked to treatment assignment. The primary outcome was upper extremity motor performance measured by total time to complete the Wolf Motor Function Test (WMFT) at the end of the 2 week intervention period, analysed in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NTC01406912. FINDINGS The study was done between May 12, 2012, and Oct 1, 2015. We randomly assigned 141 patients: 71 received VRWii therapy and 70 received recreational activity. 121 (86%) patients (59 in the VRWii group and 62 in the recreational activity group) completed the final assessment and were included in the primary analysis. Each group improved WMFT performance time relative to baseline (decrease in median time from 43·7 s [IQR 26·1-68·0] to 29·7 s [21·4-45·2], 32·0% reduction for VRWii vs 38·0 s [IQR 28·0-64·1] to 27·1 s [21·2-45·5], 28·7% reduction for recreational activity). Mean time of conventional rehabilitation during the trial was similar between groups (VRWii, 373 min [SD 322] vs recreational activity, 397 min [345]; p=0·70) as was the total duration of study intervention (VRWii, 528 min [SD 155] vs recreational activity, 541 min [142]; p=0·60). Multivariable analysis adjusted for baseline WMFT score, age, sex, baseline Chedoke-McMaster, and stroke severity revealed no significant difference between groups in the primary outcome (adjusted mean estimate of difference in WMFT: 4·1 s, 95% CI -14·4 to 22·6). There were three serious adverse events during the trial, all deemed to be unrelated to the interventions (seizure after discharge and intracerebral haemorrhage in the recreational activity group and heart attack in the VRWii group). Overall incidences of adverse events and serious adverse events were similar between treatment groups. INTERPRETATION In patients who had a stroke within the 3 months before enrolment and had mild-to-moderate upper extremity motor impairment, non-immersive virtual reality as an add-on therapy to conventional rehabilitation was not superior to a recreational activity intervention in improving motor function, as measured by WMFT. Our study suggests that the type of task used in motor rehabilitation post-stroke might be less relevant, as long as it is intensive enough and task-specific. Simple, low-cost, and widely available recreational activities might be as effective as innovative non-immersive virtual reality technologies. FUNDING Heart and Stroke Foundation of Canada and Ontario Ministry of Health.

Interactive media as a tool for reducing waiting anxiety at paediatric rehabilitation hospitals: a randomized controlled trial

To investigate the efficacy of waiting room media for reducing anxiety and increasing satisfaction at a paediatric rehabilitation hospital.

The effect of brief case management on emergency department use of frequent users in mental health: Findings of a randomized controlled trial

Frequent users of hospital emergency departments (EDs) are a medically and socially vulnerable population. The Coordinated Access to Care from Hospital EDs (CATCH-ED) study examined the effectiveness of a brief case management intervention in reducing ED use and improving health outcomes among frequent ED users with mental health or addiction challenges in a large urban centre. Adults (≥18 years of age) who had five or more ED visits in the past 12-months, with at least one visit for mental health or addictions problems were randomized to either brief case management (N = 83) or usual care (N = 83) and followed for 12 months. The primary outcome of effectiveness was the frequency of ED visits during 12 months after study enrolment. Secondary outcomes included days in hospital, mental health and addiction symptom severity and health-related quality of life, measured by the SF-12. Compared to usual care, CATCH-ED participants saw a 14% reduction in frequency of ED visits during the 12-month post-randomization period [rate ratio (RR) = 0.86, 95% CI 0.64–1.15)], however, this finding did not reach statistical significance. There were also no statistically significant differences between the groups at 12 months in the number of days spent in hospital (RR = 1.16, 95% CI 0.59–2.29), physical (1.50, 95% CI -2.15–5.15) or mental (-3.97, 95% CI -8.13–0.19) component scores of the SF-12, severity of psychiatric symptoms (-0.41, 95% CI -2.30–1.49), alcohol (0.053 95% -0.017–0.12) or drug (-0.0027, 95% CI -0.0028–0.023) use. Compared to usual care, a brief case management intervention did not result in significantly reduced ED use or improved health outcomes among frequent ED users with mental health or addictions challenges in a large urban centre in Canada. Future studies need to evaluate the availability and accessibility of community-based resources for individuals with frequent ED use.

The “DOC” screen: Feasible and valid screening for depression, Obstructive Sleep Apnea (OSA) and cognitive impairment in stroke prevention clinics

Background Post-stroke Depression, Obstructive sleep apnea (OSA) and Cognitive impairment (“DOC”) are associated with greater mortality, worse recovery and poorer quality of life. Best practice recommendations endorse routine screening for each condition; yet, all are under-assessed, diagnosed and treated. We seek to determine the feasibility and validity of an integrated tool (“DOC” screen) to identify stroke clinic patients at high-risk of depression, OSA, and cognitive impairment. Methods All consecutive new referrals to a regional Stroke Prevention Clinic who were English-speaking and non-aphasic were eligible to be screened. Time for screen completion was logged. DOC screen results were compared to the neuropsychological battery and polysomnogram assessments using a modified receiver operator characteristic and area under the curve analysis. Data is reported to conform to STARD guidelines. Findings 1503 people were screened over 2 years. 89% of eligible patients completed the screen in 5 minutes or less (mean 4.2 minutes), less than half the time it takes to complete the Montreal Cognitive Assessment (MoCA). 437 people consented to detailed testing. Of those, 421 completed the Structured Clinical Interview for Depression within 3 months of screening, 387 completed detailed neuropsychological testing within 3 months, and 88 had overnight polysomnograms. Screening scores combined with demographic variables (age, sex, education, body mass index), had excellent validity compared to gold standard diagnoses: DOC-Mood AUC 0.90; DOC-Apnea AUC 0.80; DOC-Cog AUC 0.81. DOC screen scores can reliably categorize patients in to low-, intermediate- or high-risk groups for further action and can do so with comparable accuracy to more time-consuming screens. Conclusions Systematic screening of depression, obstructive sleep apnea, and cognitive impairment in 5 minutes or less is feasible and valid in a high volume stroke clinic using the DOC screen. The DOC screen may facilitate improved identification and treatment of these comorbidities to improve function in patients after stroke and in those with other neurological diseases that share these comorbid conditions (e.g. Alzheimer’s disease/mild cognitive impairment, Parkinson’s disease, Traumatic Brain Injury, multiple sclerosis).

A Randomized Control Trial Using a Validated Prediction Model for Diagnosing Acute Heart Failure in Undifferentiated Dyspneic Emergency Department Patients-Results of the GASP4Ar Study.

BACKGROUND Diagnosing acute heart failure (AHF) in undifferentiated dyspneic emergency department (ED) patients can be challenging. We prospectively studied a validated diagnostic prediction model for AHF that uses patient age, clinician pretest probability for AHF, and N-terminal pro-B-type natriuretic peptide (NT-proBNP) as a continuous value to determine its utility and performance. METHODS AND RESULTS This was a multicenter randomized controlled trial of undifferentiated dyspneic patients with an indeterminate pretest probability of AHF as assessed by the treating emergency physician (EP). After recording its components, the calculated model results with validated treatment threshold guidelines were provided to EPs for patients randomized to the intervention arm. Final diagnoses with the use of 60-day follow-up information were adjudicated by 2 independent cardiologists. The primary outcomes were accuracy of the model and of physician diagnosis comparing intervention and standard care arms. A total of 197 patients were randomized and had outcome data recorded; 41% were determined to have had heart failure. Final EP diagnostic accuracy was 76% (sensitivity 68.2%, specificity 83.9%) with no significant difference between exposed versus blinded arms (accuracy 77% vs 74%; P = .77). Area under the model receiver operating characteristic curve was 0.93. Using the model treatment thresholds would have redirected 48% of patients with 95% accuracy. CONCLUSIONS This study prospectively validated the diagnostic accuracy of our AHF model in a significant proportion of indeterminate dyspneic ED patients, but provision of this information did not improveEP diagnostic accuracy. Future studies should determine how such a clinical prediction tool could be effectively integrated into routine practice and improve early management of suspected AHF patients in the ED.

Validating a Pragmatic Approach to Cognitive Screening in Stroke Prevention Clinics Using the Montreal Cognitive Assessment

Background and Purpose— The Montreal Cognitive Assessment (MoCA) is used commonly to identify cognitive impairment (CI), but there are multiple published cut points for normal and abnormal. We seek to validate a pragmatic approach to screening for moderate–severe CI, by classifying patients into high-, intermediate-, and low-risk categories. Methods— A total of 390 participants attending an academic Stroke Prevention Clinic completed the MoCA and more detailed neuropsychological testing. Between April 23, 2012 and April 30, 2014, all consecutive new referrals to the regional Stroke Prevention Clinic who were English-speaking, not severely aphasic, and could see and write well enough to complete neuropsychological testing were assessed for inclusion, and consenting patients were enrolled. CI was defined as ≥2 SDs below normal for age and education on at least 2 cognitive subtests. A single cut point for CI was compared with 2 cut points (high sensitivity and high specificity) generated using receiver operator characteristic and area under the curve analyses. The intermediate-risk group contained those scoring between the 2 cut points. Results— Thirty-four percent of participants had a symptomatic or silent stroke, 34% were seen for possible or probable transient ischemic attack, and 32% were diagnosed with other vascular or nonvascular conditions. Using a single cut point, sensitivity and specificity were optimal with MoCA ⩽22, (sensitivity=60.4%, specificity=89.9%, area under the curve=0.801, positive predictive value=48.5%, negative predictive value=93.5%, positive likelihood ratio=6, and negative likelihood ratio=0.4). Using 2 cut points, sensitivity was optimal with MoCA ≥28 (sensitivity=96.2%, negative predictive value =97.6%, and negative likelihood ratio=1.27), and specificity was optimal with MoCA ⩽22 (specificity=89.9%, positive predictive value=48.5%, and positive likelihood ratio=6). Conclusions— Stratifying participants into 3 categories facilitates the identification of a homogenous group at low risk for CI, as well as 2 other groups with intermediate and higher risk. This approach could facilitate clinical care pathways and patient selection for research.