Associations Between 30-Day Mortality, Specialist Nursing, and Daily Physician Ward Rounds in a National Stroke Registry.

Background and Purpose- Well-organized stroke care is associated with better patient outcomes, but the most important organizational factors are unknown. Methods- Data were extracted from the Sentinel Stroke National Audit Programme of adults with acute stroke treated in stroke hospitals in England and Wales between April 2013 and March 2015. Multilevel models with random intercepts for hospitals were used to estimate the association of each variable with 30-day mortality to estimate the impact of admission to differently organized hospitals. Results- Of the 143 578 patients with acute stroke admitted to 154 hospitals, 14.4% died within 30 days of admission. In adjusted analyses, admission to hospitals with higher ratios of nurses trained in swallow screening was associated with reduced odds of death ( P=0.004), and admission to hospitals with daily physician ward rounds was associated with 10% lower odds of mortality compared with less-frequent ward rounds (95% CI, 0.82-0.98; P=0.013). Number of stroke admissions and overall ratio of registered nurses on duty at weekends were not found to be independently associated with mortality after adjustment for other factors. Conclusions- If these associations are causal, an extra 1332 deaths annually in England and Wales could be saved by hospitals providing care associated with a ratio of nurses trained in swallow screening of at least 3 per 10 beds and daily stroke physician ward rounds.

20 years of researching stroke through audit.

Over the last 20 years, England, Wales and Northern Ireland have developed an audit programme that now encompasses nearly all patients admitted to hospital with a stroke. This article records and reviews some questions that have been answered using data from the audit: Is the rate of institutional care after rehabilitation a possible measure of outcome? Does stroke unit care in routine practice give the benefits shown in randomized controlled trials? How is the quality of stroke care affected by a patient's age and the time of their stroke? Do patient-reported measures match those obtained from the professionals recording of processes of care? How do the processes of care after stroke affect mortality? Is thrombolysis safe to use in patients over the age of 80? Do staffing levels matter? Does assessing the safety of swallowing really make a difference? Do clinicians make rational decisions about end-of-life care in patients with haemorrhage? Does socioeconomic status influence the risk of stroke, outcome after stroke and the quality of stroke care? How much does stroke really cost in England, Wales and Northern Ireland? The article concludes that this national audit has improved stroke care across the United Kingdom, has given answers to important questions that could not be answered in any other way and has shown that benefits found in research do generalize into real clinical benefits in day-to-day practice.

Why do stroke survivors not receive recommended amounts of active therapy? Findings from the ReAcT study, a mixed-methods case-study evaluation in eight stroke units.

OBJECTIVE: To identify why the National Clinical Guideline recommendation of 45 minutes of each appropriate therapy daily is not met in many English stroke units. DESIGN: Mixed-methods case-study evaluation, including modified process mapping, non-participant observations of service organisation and therapy delivery, documentary analysis and semi-structured interviews. SETTING: Eight stroke units in four English regions. SUBJECTS: Seventy-seven patients with stroke, 53 carers and 197 stroke unit staff were observed; 49 patients, 50 carers and 131 staff participants were interviewed. RESULTS: Over 1000 hours of non-participant observations and 433 patient-specific therapy observations were undertaken. The most significant factor influencing amount and frequency of therapy provided was the time therapists routinely spent, individually and collectively, in information exchange. Patient factors, including fatigue and tolerance influenced therapists' decisions about frequency and intensity, typically resulting in adaptation of therapy rather than no provision. Limited use of individual patient therapy timetables was evident. Therapist staffing levels were associated with differences in therapy provision but were not the main determinant of intensity and frequency. Few therapists demonstrated understanding of the evidence underpinning recommendations for increased therapy frequency and intensity. Units delivering more therapy had undertaken patient-focused reorganisation of therapists' working practices, enabling them to provide therapy consistent with guideline recommendations. CONCLUSION: Time spent in information exchange impacted on therapy provision in stroke units. Reorganisation of therapists' work improved alignment with guidelines.

Effects of Centralizing Acute Stroke Services on Stroke Care Provision in Two Large Metropolitan Areas in England.

BACKGROUND AND PURPOSE: In 2010, Greater Manchester and London centralized acute stroke care into hyperacute units (Greater Manchester=3, London=8), with additional units providing ongoing specialist stroke care nearer patients' homes. Greater Manchester patients presenting within 4 hours of symptom onset were eligible for hyperacute unit admission; all London patients were eligible. Research indicates that postcentralization, only London's stroke mortality fell significantly more than elsewhere in England. This article attempts to explain this difference by analyzing how centralization affects provision of evidence-based clinical interventions. METHODS: Controlled before and after analysis was conducted, using national audit data covering Greater Manchester, London, and a noncentralized urban comparator (38 623 adult stroke patients, April 2008 to December 2012). Likelihood of receiving all interventions measured reliably in pre- and postcentralization audits (brain scan; stroke unit admission; receiving antiplatelet; physiotherapist, nutrition, and swallow assessments) was calculated, adjusting for age, sex, stroke-type, consciousness, and whether stroke occurred in-hospital. RESULTS: Postcentralization, likelihood of receiving interventions increased in all areas. London patients were overall significantly more likely to receive interventions, for example, brain scan within 3 hours: Greater Manchester=65.2% (95% confidence interval=64.3-66.2); London=72.1% (71.4-72.8); comparator=55.5% (54.8-56.3). Hyperacute units were significantly more likely to provide interventions, but fewer Greater Manchester patients were admitted to these (Greater Manchester=39%; London=93%). Differences resulted from contrasting hyperacute unit referral criteria and how reliably they were followed. CONCLUSIONS: Centralized systems admitting all stroke patients to hyperacute units, as in London, are significantly more likely to provide evidence-based clinical interventions. This may help explain previous research showing better outcomes associated with fully centralized models.

Derivation and external validation of a case mix model for the standardized reporting of 30-day stroke mortality rates.

BACKGROUND AND PURPOSE: Case mix adjustment is required to allow valid comparison of outcomes across care providers. However, there is a lack of externally validated models suitable for use in unselected stroke admissions. We therefore aimed to develop and externally validate prediction models to enable comparison of 30-day post-stroke mortality outcomes using routine clinical data. METHODS: Models were derived (n=9000 patients) and internally validated (n=18 169 patients) using data from the Sentinel Stroke National Audit Program, the national register of acute stroke in England and Wales. External validation (n=1470 patients) was performed in the South London Stroke Register, a population-based longitudinal study. Models were fitted using general estimating equations. Discrimination and calibration were assessed using receiver operating characteristic curve analysis and correlation plots. RESULTS: Two final models were derived. Model A included age (<60, 60-69, 70-79, 80-89, and ≥90 years), National Institutes of Health Stroke Severity Score (NIHSS) on admission, presence of atrial fibrillation on admission, and stroke type (ischemic versus primary intracerebral hemorrhage). Model B was similar but included only the consciousness component of the NIHSS in place of the full NIHSS. Both models showed excellent discrimination and calibration in internal and external validation. The c-statistics in external validation were 0.87 (95% confidence interval, 0.84-0.89) and 0.86 (95% confidence interval, 0.83-0.89) for models A and B, respectively. CONCLUSIONS: We have derived and externally validated 2 models to predict mortality in unselected patients with acute stroke using commonly collected clinical variables. In settings where the ability to record the full NIHSS on admission is limited, the level of consciousness component of the NIHSS provides a good approximation of the full NIHSS for mortality prediction.

Associations between stroke mortality and weekend working by stroke specialist physicians and registered nurses: prospective multicentre cohort study.

BACKGROUND: Observational studies have reported higher mortality for patients admitted on weekends. It is not known whether this "weekend effect" is modified by clinical staffing levels on weekends. We aimed to test the hypotheses that rounds by stroke specialist physicians 7 d per week and the ratio of registered nurses to beds on weekends are associated with mortality after stroke. METHODS AND FINDINGS: We conducted a prospective cohort study of 103 stroke units (SUs) in England. Data of 56,666 patients with stroke admitted between 1 June 2011 and 1 December 2012 were extracted from a national register of stroke care in England. SU characteristics and staffing levels were derived from cross-sectional survey. Cox proportional hazards models were used to estimate hazard ratios (HRs) of 30-d post-admission mortality, adjusting for case mix, organisational, staffing, and care quality variables. After adjusting for confounders, there was no significant difference in mortality risk for patients admitted to a stroke service with stroke specialist physician rounds fewer than 7 d per week (adjusted HR [aHR] 1.04, 95% CI 0.91-1.18) compared to patients admitted to a service with rounds 7 d per week. There was a dose-response relationship between weekend nurse/bed ratios and mortality risk, with the highest risk of death observed in stroke services with the lowest nurse/bed ratios. In multivariable analysis, patients admitted on a weekend to a SU with 1.5 nurses/ten beds had an estimated adjusted 30-d mortality risk of 15.2% (aHR 1.18, 95% CI 1.07-1.29) compared to 11.2% for patients admitted to a unit with 3.0 nurses/ten beds (aHR 0.85, 95% CI 0.77-0.93), equivalent to one excess death per 25 admissions. The main limitation is the risk of confounding from unmeasured characteristics of stroke services. CONCLUSIONS: Mortality outcomes after stroke are associated with the intensity of weekend staffing by registered nurses but not 7-d/wk ward rounds by stroke specialist physicians. The findings have implications for quality improvement and resource allocation in stroke care. Please see later in the article for the Editors' Summary.

Intra- and interlaboratory reliability of a cryopreserved trout hepatocyte assay for the prediction of chemical bioaccumulation potential.

Measured rates of intrinsic clearance determined using cryopreserved trout hepatocytes can be extrapolated to the whole animal as a means of improving modeled bioaccumulation predictions for fish. To date, however, the intra- and interlaboratory reliability of this procedure has not been determined. In the present study, three laboratories determined in vitro intrinsic clearance of six reference compounds (benzo[a]pyrene, 4-nonylphenol, di-tert-butyl phenol, fenthion, methoxychlor and o-terphenyl) by conducting substrate depletion experiments with cryopreserved trout hepatocytes from a single source. O-terphenyl was excluded from the final analysis due to nonfirst-order depletion kinetics and significant loss from denatured controls. For the other five compounds, intralaboratory variability (% CV) in measured in vitro intrinsic clearance values ranged from 4.1 to 30%, while interlaboratory variability ranged from 27 to 61%. Predicted bioconcentration factors based on in vitro clearance values exhibited a reduced level of interlaboratory variability (5.3-38% CV). The results of this study demonstrate that cryopreserved trout hepatocytes can be used to reliably obtain in vitro intrinsic clearance of xenobiotics, which provides support for the application of this in vitro method in a weight-of-evidence approach to chemical bioaccumulation assessment.

Optimizing the use of rainbow trout hepatocytes for bioaccumulation assessments with fish.

Biotransformation rates measured using cryopreserved trout hepatocytes can be extrapolated to the whole animal to predict metabolism impacts on chemical bioaccumulation. Future use of these methods within a regulatory context requires, however, that they be optimized and standardized. Specifically, questions exist concerning gender differences in metabolism, cryopreservability of cells, and the accuracy of in vitro-in vivo scaling factors. 2. In this study, we evaluated hepatocytes from juvenile male and female trout. No gender differences in cell size, protein abundance, cytochrome P450 content, ethoxyresorufin-O-deethylase activity, uridine diphosphate glucuronosyltransferase activity or intrinsic clearance of pyrene were observed for freshly isolated hepatocytes. There was a small difference in measured glutathione-S-transferase activity (<25%; males > females). 3. Cells were cryopreserved by two methods: direct placement into liquid N2 vapor and controlled, slow-rate freezing. Comparable live recovery and enzymatic activity were observed regardless of freezing method or gender. Cells cryopreserved in liquid N2 vapor exhibited activity levels similar to those of freshly isolated cells, although there were small but significant differences in pyrene clearance and glutathione-S-transferase activity (frozen < fresh). Hepatocellularity values did not differ by sex. 4. These results suggest that hepatocytes from male and female juvenile trout may be used interchangeably for in vitro-in vivo metabolism extrapolations.

Modeling Population Growth under Climate Stressors Using Age-structured Matrix Models.

Climate resilience, a focus of many recent studies, has been examined from ecological, physiological, and evolutionary perspectives. However, sampling biases towards adults, males, and certain species have made establishing the link between environmental change and population-level change problematic. Here we used data from four laboratory studies, in which we administered pre- and post-natal stressors, such as suboptimal incubation temperature, heat stress, and food restriction, to zebra finches and quantified hatching success, post-hatch survival, and reproductive success, to parameterize age-structured population dynamics models with the goal of estimating the effect of the stressors on relative population growth rates. Using the same model structure, we tested the hypothesis that early life stages influence population growth rate more than later life stages. Our models suggested that stressful events during embryonic development, such as suboptimal incubation temperatures and reduced gas exchange for the embryos, have a greater total impact on population growth than post-hatch stressors, such as heat stress and food restriction. However, among life history traits, differences in hatching success and sex ratio of offspring in response to stressors changed population growth rates more than differences in any other demographic rate estimates. These results suggest that when predicting population resilience against climate change, it is critical to account for effects of climate change on all life stages, including early stages of life, and to incorporate individuals' physiology and stress tolerance that likely influence future stress responses, reproduction, and survival.

Bigger, faster? Associations between hospital thrombolysis volume and speed of thrombolysis administration in acute ischemic stroke.

BACKGROUND AND PURPOSE: There is evidence that high-volume hospitals may produce better patient outcomes. We aimed to identify whether there were any associations between hospital thrombolysis volume and speed of thrombolysis (tissue-type plasminogen activator [tPA]) administration in patients with ischemic stroke. METHODS: Data were drawn from 2 national clinical audits in England: the Stroke Improvement National Audit Program and the 2012 Sentinel Stroke Audit. Hospitals were categorized into 3 groups based on the annualized volume of thrombolysis: 0 to 24, 25 to 49, and ≥50 cases per annum. Arrival-brain scan, onset-tPA, and arrival-tPA times were compared across groups and stratified by onset-arrival time. Multilevel logistic models were used to estimate the odds of receiving tPA within 60 minutes of arrival. RESULTS: Of the 42 024 patients with acute ischemic stroke admitted to 80 hospitals, 4347 received tPA (10.3%). Patients admitted to hospitals with an annual thrombolysis volume of ≥50 cases per annum had median arrival-tPA times that were 28 and 22 minutes shorter than patients admitted to hospitals with volumes of 0 to 24 and 25 to 49, respectively. Onset-tPA times were shorter by 24 to 32 minutes across strata of onset-arrival times. In multivariable analysis, patients admitted to hospitals with a volume of ≥50 cases per annum had 4.33 (2.21-8.50; P<0.0001) the odds of receiving tPA within 60 minutes of arrival. No differences in safety outcomes were observed, with similar 30-day mortality and complication rates across the groups. CONCLUSIONS: Hospitals with higher volumes of thrombolysis activity achieve statistically and clinically significant shorter delays in administering tPA to patients after arrival in hospital.

Stroke thrombolysis in England: an age stratified analysis of practice and outcome.

INTRODUCTION: until very recently, only small numbers of older patients with stroke had been recruited into randomised controlled trials of thrombolysis with recombinant tissue plasminogen activator (rt-PA) and patients aged >80 are excluded in the European licence for this therapy. We aimed to estimate the use and outcome of stroke thrombolysis in England across age groups, including the oldest-old. METHODS: data were collected as part of the Stroke Improvement National Audit Programme. All adults receiving thrombolysis for acute ischaemic stroke as part of routine care between April 2010 and November 2011 were included. Multilevel multivariable logistic regression was used to analyse the associations between age, process of care and 30-day mortality. RESULTS: of 37,151 adults admitted with acute ischaemic stroke, 3,374 (9.1%) received rt-PA. Patients aged >80 accounted for 21% of the thrombolysis recipients and 4.8% of patients in this age group received rt-PA. Treatment times were similar across all age groups, but older thrombolysis recipients were more likely to have Total anterior circulation infarct strokes and less likely to be functionally independent prior to stroke. Similar rates of post-thrombolysis complications were observed between patients aged >80 and younger patients. Mortality was high among older patients whether they were treated with rt-PA or not. Among patients treated with rt-PA, those aged 81-90 and >90 had, respectively, 34 and 270% higher odds of 30-day mortality than patients aged 70-80. CONCLUSION: treatment with rt-PA is now carried out frequently for older stroke patients in England. Their care is as timely as younger patients with no higher risk of major complication but mortality rates in older patients with stroke remain high.

National sentinel stroke audit 1998-2011.

Stroke is a common and devastating disease and, until very recently, was largely unrecognised as a -preventable or treatable condition. Between 1998 and 2010, the National Sentinel Stroke Audit (NSSA) achieved 100% voluntary participation, collecting data on more than 60,000 patients from stroke services within England, Wales and Northern Ireland and becoming a benchmark for hospital stroke services. In this way it has informed stroke improvement at the local, regional and national levels and has overseen a radical change in stroke care within the NHS. This article describes the achievements of the NSSA and the -lessons learned.

In Vitro-In Vivo Extrapolation of Hepatic Biotransformation Data for Fish. III. An In-depth Case Study with Pyrene.

Computational models that predict chemical bioaccumulation in fish generally account for biotransformation using an apparent first-order whole-body rate constant (kB ; d-1 ). The use of such models requires, therefore, that methods exist for estimating kB , ideally without the need to expose live animals. One promising approach for estimating kB involves the extrapolation of measured in vitro intrinsic clearance (CLIN VITRO,INT ) to the whole animal (in vitro-in vivo extrapolation, [IVIVE]). To date, however, the accuracy of such predictions has been difficult to assess due to uncertainties associated with one or more extrapolation factors and/or a mismatch between fish used to generate in vitro data and those used to conduct in vivo exposures. In the present study we employed a combined in vitro and in vivo experimental approach to evaluate the IVIVE procedure using pyrene (PYR) as a model chemical. To the extent possible, measured rates of CLIN VITRO,INT were extrapolated to estimates of kB using extrapolation factors based on measured values. In vitro material (liver S9 fraction) was obtained from fish exposed to PYR in a controlled bioconcentration study protocol. Fish from the same study were then used to estimate in vivo kB values from an analysis of chemical depuration data. Averaged across four study groups, kB values estimated by IVIVE underestimated those determined from in vivo data by 2.6-fold. This difference corresponds to a 4.1-fold underestimation of true in vivo intrinsic clearance, assuming the liver is the only site of biotransformation. These findings are consistent with previous work performed using mammals and have important implications for use of measured CLIN VITRO,INT values in bioaccumulation assessments with fish. Environ Toxicol Chem 2023;42:1501-1515. Published 2023. This article is a U.S. Government work and is in the public domain in the USA.

Addition of Phenylmethylsulfonyl Fluoride Increases the Working Lifetime of the Trout Liver S9 Substrate Depletion Assay, Resulting in Improved Detection of Low Intrinsic Clearance Rates.

The activity of a trout liver S9 substrate depletion assay has been shown to decline over time, presumably due to proteolytic degradation of biotransformation enzymes. To address this problem, assay performance was evaluated following the addition of phenylmethylsulfonyl fluoride (PMSF) or a general-purpose protease inhibitor cocktail to liver homogenization buffers and/or S9 reaction mixtures. Addition of PMSF to liver homogenization buffers and/or S9 reaction mixtures had little or no effect on clearance of phenanthrene, a model cytochrome P450 substrate, in short-term (25 or 30 min) depletion experiments but resulted in significant improvements in retention of this initial activity over time. The protease inhibitor cocktail strongly inhibited initial activity when added to homogenization buffers or reaction mixtures. Taking into consideration potential effects on liver carboxylesterases, the treatment approach determined to be optimal was addition of 10 µM PMSF to the S9 reaction mixture. Addition of 10 µM PMSF to the mixture resulted in significantly higher rates of phenanthrene clearance in 2-h incubations relative to those obtained in the absence of PMSF and a 6-fold increase in the working lifetime of the preparation. The results of a statistical power analysis suggest that by increasing the working lifetime of the assay, addition of PMSF to the reaction mixture could result in substantially improved detection of low in vitro clearance rates when compared to current practice. These findings demonstrate the value of adding PMSF to the trout S9 preparation and may have broad implications for use of this assay to support chemical bioaccumulation assessments for fish. Environ Toxicol Chem 2021;40:148-161. © 2020 SETAC. This article has been contributed to by US Government employees and their work is in the public domain in the USA.

Effect of stroke early supported discharge on length of hospital stay: analysis from a national stroke registry.

OBJECTIVE: The first observational study to investigate the impact of early supported discharge (ESD) on length of hospital stay in real-world conditions. DESIGN: Using historical prospective Sentinel Stroke National Audit Programme (SSNAP) data (1 January 2013-31 December 2016) and multilevel modelling, cross-sectional (2015-2016; 30 791 patients nested within 55 hospitals) and repeated cross-sectional (2013-2014 vs 2015-2016; 49 266 patients nested within 41 hospitals) analyses were undertaken. SETTING: Hospitals were sampled across a large geographical area of England covering the West and East Midlands, the East of England and the North of England. PARTICIPANTS: Stroke patients whose data were entered into the SSNAP database by hospital teams. INTERVENTIONS: Receiving ESD along the patient care pathway. PRIMARY AND SECONDARY OUTCOME MEASURES: Length of hospital stay. RESULTS: When adjusted for important case-mix variables, patients who received ESD on their stroke care pathway spent longer in hospital, compared with those who did not receive ESD. The percentage increase was 15.8% (95% CI 12.3% to 19.4%) for the 2015-2016 cross-sectional analysis and 18.8% (95% CI 13.9% to 24.0%) for the 2013-2014 versus 2015-2016 repeated cross-sectional analysis. On average, the increased length of hospital stay was approximately 1 day. CONCLUSIONS: This study has shown that by comparing ESD and non-ESD patient groups matched for important patient characteristics, receiving ESD resulted in a 1-day increase in length of hospital stay. The large reduction in length of hospital stay overall, since original trials were conducted, may explain why a reduction was not observed. The longer term benefits of accessing ESD need to be investigated further. TRIAL REGISTRATION NUMBER: http://www.isrctn.com/ISRCTN15568163.

Dietary Bioaccumulation and Biotransformation of Hydrophobic Organic Sunscreen Agents in Rainbow Trout.

The present study investigated the dietary bioaccumulation and biotransformation of hydrophobic organic sunscreen agents, 2-ethylhexyl-4-methoxycinnamate (EHMC) and octocrylene (OCT), in rainbow trout using a modified Organisation for Economic Co-operation and Development 305 dietary bioaccumulation test that incorporated nonbiotransformed reference chemicals. Trout were exposed to 3 dietary concentrations of each chemical to investigate the relationship between dietary exposure concentration and observed accumulation and depuration. Both EHMC and OCT were significantly biotransformed, resulting in mean in vivo whole-body biotransformation rate constants (kMET ) of 0.54 ± 0.06 and 0.09 ± 0.01 d-1 , respectively. The kMET values generated for both chemicals did not differ between dietary exposure concentrations, indicating that chemical concentrations in the fish were not high enough to saturate biotransformation enzymes. Both somatic and luminal biotransformation substantially reduce EHMC and OCT bioaccumulation potential in trout. Biomagnification factors (BMFs) and bioconcentration factors (BCFs) of EHMC averaged 0.0035 kg lipid kg lipid-1 and 396 L kg-1 , respectively, whereas those of OCT averaged 0.0084 kg lipid kg lipid-1 and 1267 L kg-1 . These values are 1 to 2 orders of magnitude lower than the BMFs and BCFs generated for reference chemicals of similar log KOW . In addition, for both chemicals, derived BMFs and BCFs fell below established bioaccumulation criteria (1.0 kg lipid kg lipid-1 and 2000 L kg-1 , respectively), suggesting that EHMC ad OCT are unlikely to bioaccumulate to a high degree in aquatic biota. Environ Toxicol Chem 2020;39:574-586. © 2019 SETAC.

Effectiveness of Stroke Early Supported Discharge: Analysis From a National Stroke Registry.

BACKGROUND: Implementation of stroke early supported discharge (ESD) services has been recommended in many countries' clinical guidelines, based on clinical trial evidence. This is the first observational study to investigate the effectiveness of ESD service models operating in real-world conditions, at scale. METHODS AND RESULTS: Using historical prospective data from the United Kingdom Sentinel Stroke National Audit Programme (January 1, 2016-December 31, 2016), measures of ESD effectiveness were "days to ESD" (number of days from hospital discharge to first ESD contact; n=6222), "rehabilitation intensity" (total number of treatment days/total days with ESD; n=5891), and stroke survivor outcome (modified Rankin scale at ESD discharge; n=6222). ESD service models (derived from Sentinel Stroke National Audit Programme postacute organizational audit data) were categorized with a 17-item score, reflecting adoption of ESD consensus core components (evidence-based criteria). Multilevel modeling analysis was undertaken as patients were clustered within ESD teams across the Midlands, East, and North of England (n=31). A variety of ESD service models had been adopted, as reflected by variability in the ESD consensus score. Controlling for patient characteristics and Sentinel Stroke National Audit Programme hospital score, a 1-unit increase in ESD consensus score was significantly associated with a more responsive ESD service (reduced odds of patient being seen after ≥1 day of 29% [95% CI, 1%-49%] and increased treatment intensity by 2% [95% CI, 0.3%-4%]). There was no association with stroke survivor outcome measured by the modified Rankin Scale. CONCLUSIONS: This study has shown that adopting defined core components of ESD is associated with providing a more responsive and intensive ESD service. This shows that adherence to evidence-based criteria is likely to result in a more effective ESD service as defined by process measures. Registration: URL: http://www.isrctn.com/; Unique identifier: ISRCTN15568163.

Staffing levels and patient dependence in English stroke units.

Little research has been performed to determine how a stroke unit should be staffed and what the links are between patient dependency and staffing. For this study, 140 stroke units were randomly selected--35 from each of the four quartiles of performance in the National Sentinel Audit of Stroke. A questionnaire was sent to each of the units to collect data on patient numbers and dependency, staffing numbers and therapy, and nursing contact times on a single weekday. The response rate was 66% (92 sites) and information on 1,398 patients was provided. The median number of beds was 18 (interquartile range 12-24). Staffing levels per 10 beds were a median of 10.9 nurses, 1.7 physiotherapists, 1.3 occupational therapists and 0.4 speech and language therapists. Of the patients, 74% received physiotherapy, 46% occupational therapy and 25% speech and language therapy during the day with median contact times being 170 minutes for nursing, 40 minutes for physiotherapy, 45 minutes for occupational therapy and 30 minutes for speech therapy. There was a weak correlation between patient dependency and contact time with nurses and therapists. Stroke patients in England receive relatively little rehabilitation from therapists and there is a wide variation in the amount of nursing time each patient receives.

Physiotherapy provision to hospitalised stroke patients: Analysis from the UK Sentinel Stroke National Audit Programme.

INTRODUCTION: The purpose of this study is to investigate which factors are associated with physiotherapy provision to hospitalised stroke patients. METHODS: Data were analysed for stroke patients admitted to hospital in England and Wales between April 2013 and March 2017 recorded on the Sentinel Stroke National Audit Programme (SSNAP) national stroke register. Associations between different patient factors, and applicability for and intensity of physiotherapy were measured using multi-level logistic and regression models.Findings: Data from 306,078 patients were included on the SSNAP register. Median age was 77 years (IQR 67-85) and 84.7% of patients with completed stroke severity data had a mild-moderate stroke. In all, 85.2% of patients recorded on SSNAP were deemed applicable for physiotherapy. Applicability for physiotherapy was 47% higher among thrombolysed patients (aOR 1.47, 95% CI 1.40-1.54), 36% lower in those with severe pre-morbid disability (aOR 0.64, 95% CI 0.58-0.71) and more than 2.5-fold higher among patients admitted to hospitals with greater availability of early supported discharge (aOR 2.62, 95% CI 1.28-5.37). Patients who were younger, male, had less pre-morbid disability, lower stroke severity, sustained an infarction, received thrombolysis, and had fewer medical complications were more likely to receive more intensive physiotherapy post-stroke. CONCLUSION: Several patient and service organisational factors are associated with physiotherapy provision to stroke patients, some of which may not be justifiable. Physiotherapists should be aware of these factors when planning and delivering physiotherapy as well as any possible biases associated with physiotherapy provision to patients post-stroke.

Biotransformation of Polycyclic Aromatic Hydrocarbons by Trout Liver S9 Fractions: Evaluation of Competitive Inhibition Using a Substrate Depletion Approach.

Environmental contaminants frequently occur as part of a chemical mixture, potentially resulting in competitive inhibition among multiple substrates metabolized by the same enzyme. Trout liver S9 fractions were used to evaluate the biotransformation of 3 polycyclic aromatic hydrocarbons (PAHs): phenanthrene, pyrene, and benzo[a]pyrene, tested as binary mixtures. Initial rates of biotransformation were determined using a substrate-depletion approach. The resulting data were then fitted by simultaneous nonlinear regression to a competitive inhibition model. In each case, the PAH possessing the lower Michaelis-Menten affinity constant (KM ) competitively inhibited biotransformation of the other compound. Inhibition constants determined for the lower-KM compound were generally close to previously determined KM values, consistent with the suggestion that phase I biotransformation of PAHs is largely catalyzed by one or a small number of cytochrome P450 enzymes. The use of a substrate-depletion approach to perform enzyme-inhibition studies imposes practical limitations on experimental design and complicates the interpretation of derived kinetic constants. Nevertheless, the resulting information may have utility for chemical hazard assessments as well as the design and interpretation of controlled laboratory studies. Depletion experiments informed by measured chemical concentrations in tissues may also provide a means of determining whether enzyme inhibition occurs under relevant environmental conditions. Environ Toxicol Chem 2019;38:2729-2739. Published 2019 Wiley Periodicals, Inc. on behalf of SETAC. This article is a US government work, and as such, is in the public domain in the United States of America.