The SOS Pilot Study: a RCT of routine oxygen supplementation early after acute stroke—effect on recovery of neurological function at one week

Mild hypoxia is common after stroke and associated with poor long-term outcome. Oxygen supplementation could prevent hypoxia and improve recovery. A previous study of routine oxygen supplementation showed no significant benefit at 7 and 12 months. This pilot study reports the effects of routine oxygen supplementation for 72 hours on oxygen saturation and neurological outcomes at 1 week after a stroke

The stroke oxygen pilot study: a randomized control trial of the effects of routine oxygen supplementation early after acute stroke--effect on key outcomes at six months

Introduction: Post-stroke hypoxia is common, and may adversely affect outcome. We have recently shown that oxygen supplementation may improve early neurological recovery. Here, we report the six-month outcomes of this pilot study. Methods: Patients with a clinical diagnosis of acute stroke were randomized within 24 h of admission to oxygen supplementation at 2 or 3 L/min for 72 h or to control treatment (room air). Outcomes (see below) were assessed by postal questionnaire at 6 months. Analysis was by intention-to-treat, and statistical significance was set at p#0.05. Results: Out of 301 patients randomized two refused/withdrew consent and 289 (148 in the oxygen and 141 in the control group) were included in the analysis: males 44%, 51%; mean (SD) age 73 (12), 71 (12); median (IQR) National Institutes of Health Stroke Scale score 6 (3, 10), 5 (3, 10) for the two groups respectively. At six months 22 (15%) patients in the oxygen group and 20 (14%) in the control group had died; mean survival in both groups was 162 days (p= 0.99). Median (IQR) scores for the primary outcome, the modified Rankin Scale, were 3 (1, 5) and 3 (1, 4) for the oxygen and control groups respectively. The covariate-adjusted odds ratio was 1.04 (95% CI 0.67, 1.60), indicating that the odds of a lower (i.e. better) score were non-significantly higher in the oxygen group (p= 0.86). The mean differences in the ability to perform basic (Barthel Index) and extended activities of daily living (NEADL), and quality of life (EuroQol) were also non-significant. Conclusions: None of the key outcomes differed at 6 months between the groups. Although not statistically significant and generally of small magnitude, the effects were predominantly in favour of the oxygen group; a larger trial, powered to show differences in longer-term functional outcomes, is now on-going. Trial Registration: Controlled-Trials.com ISRCTN12362720; Eudract.ema.europa.eu 2004-001866-4

Statistical analysis plan for the Stroke Oxygen Study (SO₂S): a multi-center randomized controlled trial to assess whether routine oxygen supplementation in the first 72 hours after a stroke improves long-term outcome.

BACKGROUND: The Stroke Oxygen Study (SO₂S) is a multi-center randomized controlled trial of oxygen supplementation in patients with acute stroke. The main hypothesis for the trial is that fixed-dose oxygen treatment during the first 3 days after an acute stroke improves outcome. The secondary hypothesis is that restricting oxygen supplementation to night time only is more effective than continuous supplementation. This paper describes the statistical analysis plan for the study. METHODS AND DESIGN: Patients (n = 8000) are randomized to three groups: (1) continuous oxygen supplementation for 72 hours; (2) nocturnal oxygen supplementation for three nights; and (3) no routine oxygen supplementation. Outcomes are recorded at 7 days, 90 days, 6 months, and 12 months. The primary outcome measure is the modified Rankin scale at 90 days. Data will be analyzed according to the intention-to-treat principle. Methods of statistical analysis are described, including the handling of missing data, the covariates used in adjusted analyses, planned subgroups analyses, and planned sensitivity analyses. TRIAL REGISTRATION: This trial is registered with the ISRCTN register, number ISRCTN52416964 (30 September 2005)

Continuous or intermittent? Which regiment of enteral nutrition is better for acute stroke patients? A systematic review and meta-analysis

Background and purpose: Enteral nutrition via nasogastric tube in acute stroke patients with dysphagia is an important determinant of patient outcomes. It is unclear whether intermittent or continuous feeding is more efficacious. The aim of this review is to examine the current evidence comparing the effectiveness of intermittent versus continuous feeding in stroke patients in terms of nutritional status, gastrointestinal intolerance and other complications. Methods: A systematic review of randomized controlled studies comparing intermittent with continuous nasogastric feeding in acute stroke patients was conducted in accordance with PRISMA (Preferred Reporting Items for Systematic Reviews and Metaanalyses) guidance using predefined search terms. The search was conducted in MEDLINE and EMBASE up to 1st March 2019. Two independent reviewers assessed study quality using the Joanna Briggs Institute Critical Appraisal Tool. Meta-analyses were conducted, where appropriate, using a random-effects model to pool risk ratio with corresponding 95% CI. Results: Three studies including a total of 184 patients were identified. All three were medium to low quality. The definition of intermittent enteral nutrition within each study varied considerably in terms of volume, rate and mode of delivery. Achievement of nutritional targets was the same for both feeding patterns in the one study it was reported. Only aspiration pneumonia and diarrhea were measured by all three studies. There was no significant difference in the incidence of aspiration pneumonia (RR 0.91, 95% CI 0.53-1.57, p=0.74, I2=50%) and diarrhea (RR 1.74, 95% CI 0.70-4.30, p=0.23, I2=42%) between the two patterns of feeding. Other outcomes including, vomiting, gastric retention, mortality, pre-albumin and nasogastric tube complications showed no significant differences. Conclusion: There is very little and low-quality evidence to inform patterns of enteral feeding after stroke. The available evidence shows no significant difference in nutritional achievement and complications between intermittent and continuous nasogastric tube feeding in acute stroke patients

The trans influence in unsymmetrical pincer palladacycles: an experimental and computational study

A library of unsymmetrical SCN pincer palladacycles, [ClPd{2-pyr-6-(RSCH2)C6H3}], R = Et, Pr, Ph, p-MePh, and p-MeOPh, pyr = pyridine, has been synthesized via C–H bond activation, and used, along with PCN and N’CN unsymmetrical pincer palladacycles previously synthesized by the authors, to determine the extent to which the trans influence is exhibited in unsymmetrical pincer palladacycles. The trans influence is quantified by analysis of structural changes in the X-ray crystal and density functional theory (DFT) optimized structures and a topological analysis of the electron density using quantum theory of atoms in molecules (QTAIM) to determine the strength of the Pd-donor atom interaction. It is found that the trans influence is controlled by the nature of the donor atom and although the substituents on the donor-ligand affect the Pd-donor atom interaction through the varied electronic and steric constraints, they do not influence the bonding of the ligand trans to it. The data indicate that the strength of the trans influence is P > S > N. Furthermore, the synthetic route to the family of SCN pincer palladacycles presented demonstrates the potential of late stage derivitization for the effective synthesis of ligands towards unsymmetrical pincer palladacycles

Single-shot error correction of three-dimensional homological product codes

Single-shot error correction corrects data noise using only a single round of noisy measurements on the data qubits, removing the need for intensive measurement repetition. We introduce a general concept of confinement for quantum codes, which roughly stipulates qubit errors cannot grow without triggering more measurement syndromes. We prove confinement is sufficient for single-shot decoding of adversarial errors and linear confinement is sufficient for single-shot decoding of local stochastic errors. Further to this, we prove that all three-dimensional homological product codes exhibit confinement in their X components and are therefore single shot for adversarial phase-flip noise. For local stochastic phase-flip noise, we numerically explore these codes and again find evidence of single-shot protection. Our Monte Carlo simulations indicate sustainable thresholds of 3.08(4)% and 2.90(2)% for three-dimensional (3D) surface and toric codes, respectively, the highest observed single-shot thresholds to date. To demonstrate single-shot error correction beyond the class of topological codes, we also run simulations on a randomly constructed family of 3D homological product codes

Single-shot error correction of three-dimensional homological product codes

Single-shot error correction corrects data noise using only a single round of noisy measurements on the data qubits, removing the need for intensive measurement repetition. We introduce a general concept of confinement for quantum codes, which roughly stipulates qubit errors cannot grow without triggering more measurement syndromes. We prove confinement is sufficient for single-shot decoding of adversarial errors and linear confinement is sufficient for single-shot decoding of local stochastic errors. Further to this, we prove that all three-dimensional homological product codes exhibit confinement in their X components and are therefore single shot for adversarial phase-flip noise. For local stochastic phase-flip noise, we numerically explore these codes and again find evidence of single-shot protection. Our Monte Carlo simulations indicate sustainable thresholds of 3.08(4)% and 2.90(2)% for three-dimensional (3D) surface and toric codes, respectively, the highest observed single-shot thresholds to date. To demonstrate single-shot error correction beyond the class of topological codes, we also run simulations on a randomly constructed family of 3D homological product codes

Routine low-dose continuous or nocturnal oxygen for people with acute stroke: three-arm Stroke Oxygen Supplementation RCT.

BACKGROUND: Stroke is a major cause of death and disability worldwide. Hypoxia is common after stroke and is associated with worse outcomes. Oxygen supplementation could prevent hypoxia and secondary brain damage. OBJECTIVES: (1) To assess whether or not routine low-dose oxygen supplementation in patients with acute stroke improves outcome compared with no oxygen; and (2) to assess whether or not oxygen given at night only, when oxygen saturation is most likely to be low, is more effective than continuous supplementation. DESIGN: Multicentre, prospective, randomised, open, blinded-end point trial. SETTING: Secondary care hospitals with acute stroke wards. PARTICIPANTS: Adult stroke patients within 24 hours of hospital admission and 48 hours of stroke onset, without definite indications for or contraindications to oxygen or a life-threatening condition other than stroke. INTERVENTIONS: Allocated by web-based minimised randomisation to: (1) continuous oxygen: oxygen via nasal cannula continuously (day and night) for 72 hours after randomisation at a flow rate of 3 l/minute if baseline oxygen saturation was ≤ 93% or 2 l/minute if > 93%; (2) nocturnal oxygen: oxygen via nasal cannula overnight (21:00-07:00) for three consecutive nights. The flow rate was the same as the continuous oxygen group; and (3) control: no routine oxygen supplementation unless required for reasons other than stroke. MAIN OUTCOME MEASURES: Primary outcome: disability assessed by the modified Rankin Scale (mRS) at 3 months by postal questionnaire (participant aware, assessor blinded). Secondary outcomes at 7 days: neurological improvement, National Institutes of Health Stroke Scale (NIHSS), mortality, and the highest and lowest oxygen saturations within the first 72 hours. Secondary outcomes at 3, 6, and 12 months: mortality, independence, current living arrangements, Barthel Index, quality of life (European Quality of Life-5 Dimensions, three levels) and Nottingham Extended Activities of Daily Living scale by postal questionnaire. RESULTS: In total, 8003 patients were recruited between 24 April 2008 and 17 June 2013 from 136 hospitals in the UK [continuous,n = 2668; nocturnal,n = 2667; control,n = 2668; mean age 72 years (standard deviation 13 years); 4398 (55%) males]. All prognostic factors and baseline characteristics were well matched across the groups. Eighty-two per cent had ischaemic strokes. At baseline the median Glasgow Coma Scale score was 15 (interquartile range 15-15) and the mean and median NIHSS scores were 7 and 5 (range 0-34), respectively. The mean oxygen saturation at randomisation was 96.6% in the continuous and nocturnal oxygen groups and 96.7% in the control group. Primary outcome: oxygen supplementation did not reduce disability in either the continuous or the nocturnal oxygen groups. The unadjusted odds ratio for a better outcome (lower mRS) was 0.97 [95% confidence interval (CI) 0.89 to 1.05;p = 0.5] for the combined oxygen groups (both continuous and nocturnal together) (n = 5152) versus the control (n = 2567) and 1.03 (95% CI 0.93 to 1.13;p = 0.6) for continuous versus nocturnal oxygen. Secondary outcomes: oxygen supplementation significantly increased oxygen saturation, but did not affect any of the other secondary outcomes. LIMITATIONS: Severely hypoxic patients were not included. CONCLUSIONS: Routine low-dose oxygen supplementation in stroke patients who are not severely hypoxic is safe, but does not improve outcome after stroke. FUTURE WORK: To investigate the causes of hypoxia and develop methods of prevention. TRIAL REGISTRATION: Current Controlled Trials ISRCTN52416964 and European Union Drug Regulating Authorities Clinical Trials (EudraCT) number 2006-003479-11. FUNDING DETAILS: This project was funded by the National Institute for Health Research (NIHR) Research for Patient Benefit and Health Technology Assessment programmes and will be published in full inHealth Technology Assessment; Vol. 22, No. 14. See the NIHR Journals Library website for further project information