Quality of Life After Intravenous Thrombolysis for Acute Ischemic Stroke: Results From the AcT Randomized Controlled Trial.

BACKGROUND: Recent evidence from thrombolysis trials indicates the noninferiority of intravenous tenecteplase to intravenous alteplase with respect to good functional outcomes in patients with acute stroke. We examined whether the health-related quality of life (HRQOL) of patients with acute stroke differs by the type of thrombolysis treatment received. In addition, we examined the association between the modified Rankin Scale score 0 to 1 and HRQOL and patient-reported return to prebaseline stroke functioning at 90 days. METHODS: Data were from all patients included in the AcT trial (Alteplase Compared to Tenecteplase), a pragmatic, registry-linked randomized trial comparing tenecteplase with alteplase. HRQOL at 90-day post-randomization was assessed using the 5-item EuroQOL questionnaire (EQ5D), which consists of 5 items and a visual analog scale (VAS). EQ5D index values were estimated from the EQ5D items using the time tradeoff approach based on Canadian norms. Tobit regression and quantile regression models were used to evaluate the adjusted effect of tenecteplase versus alteplase treatment on the EQ5D index values and VAS score, respectively. The association between return to prebaseline stroke functioning and the modified Rankin Scale score 0 to 1 and HRQOL was quantified using correlation coefficient (r) with 95% CI. RESULTS: Of 1577 included in the intention-to-treat analysis patients, 1503 (95.3%) had complete data on the EQ5D. Of this, 769 (51.2%) were administered tenecteplase and 717 (47.7%) were female. The mean EQ5D VAS score and EQ5D index values were not significantly higher for those who received intravenous tenecteplase compared with those who received intravenous alteplase (P=0.10). Older age (P<0.01), more severe stroke assessed using the National Institutes of Health Stroke Scale (P<0.01), and longer stroke onset-to-needle time (P=0.004) were associated with lower EQ5D index and VAS scores. There was a strong association (r, 0.85 [95% CI, 0.81-0.89]) between patient-reported return to prebaseline functioning and modified Rankin Scale score 0 to 1 Similarly, there was a moderate association between return to prebaseline functioning and EQ5D index (r, 0.45 [95% CI, 0.40-0.49]) and EQ5D VAS scores (r, 0.42 [95% CI, 0.37-0.46]). CONCLUSIONS: Although there is no differential effect of thrombolysis type on patient-reported global HRQOL and EQ 5D-5L index values in patients with acute stroke, sex- and age-related differences in HRQOL were noted in this study. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03889249.

Sex-Based Analysis of Workflow and Outcomes in Acute Ischemic Stroke Patients Treated With Alteplase Versus Tenecteplase.

BACKGROUND: Understanding sex differences in stroke care is important in reducing potential disparities. Our objective was to explore sex differences in workflow efficiency, treatment efficacy, and safety in the AcT trial (Alteplase Compared to Tenecteplase). METHODS: AcT was a multicenter, registry-linked randomized noninferiority trial comparing tenecteplase (0.25 mg/kg) with alteplase (0.9 mg/kg) in acute ischemic stroke within 4.5 hours of onset. In this post hoc analysis, baseline characteristics, workflow times, successful reperfusion (extended Thrombolysis in Cerebral Infarction score ≥2b), symptomatic intracerebral hemorrhage, 90-day functional independence (modified Rankin Scale score, 0-1), and 90-day mortality were compared by sex. Mixed-effects regression analysis was used adjusting for age, stroke severity, and occlusion site for outcomes. RESULTS: Of 1577 patients treated with intravenous thrombolysis (2019-2022), 755 (47.9%) were women. Women were older (median, 77 [68-86] years in women versus 70 [59-79] years in men) and had a higher proportion of severe strokes (National Institutes of Health Stroke Scale score >15; 32.4% versus 24.9%) and large vessel occlusions (28.7% versus 21.5%) compared with men. All workflow times were comparable between sexes. Women were less likely to achieve functional independence (31.7% versus 39.8%; unadjusted relative risk, 0.80 [95% CI, 0.70-0.91]) and had higher mortality (17.7% versus 13.3%; unadjusted relative risk, 1.33 [95% CI, 1.06-1.69]). Adjusted analysis showed no difference in outcomes between sexes. CONCLUSIONS: Differences in prognostic factors of age, stroke severity, and occlusion site largely accounted for higher functional dependence and mortality in women. No sex disparities were apparent in workflow quality indicators. Given the integration of the AcT trial into clinical practice, these results provide reassurance that no major sex biases are apparent in acute stroke management throughout participating Canadian centers. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03889249.

Safety and efficacy of tenecteplase versus alteplase in stroke patients with carotid tandem lesions: Results from the AcT trial.

BACKGROUND: Carotid tandem lesions ((TL) ⩾70% stenosis or occlusion) account for 15-20% of acute stroke with large vessel occlusion. AIMS: We investigated the safety and efficacy of intravenous tenecteplase (0.25 mg/kg) versus intravenous alteplase (0.9 mg/kg) in patients with carotid TL. METHODS: This is a substudy of the alteplase compared with the tenecteplase trial. Patients with ⩾70% stenosis of the extracranial internal carotid artery (ICA) and concomitant occlusion of the intracranial ICA, M1 or M2 segments of the middle cerebral artery on baseline computed tomography angiography (CTA) were included. Primary outcome was 90-day-modified Rankin Scale (mRS) 0-1. Secondary outcomes were mRS 0-2, mortality, and symptomatic ICH (sICH). Angiographic outcomes were successful recanalization (revised Arterial Occlusive Lesion (rAOL) 2b-3) on first and successful reperfusion (eTICI 2b-3) on final angiographic acquisitions. Multivariable mixed-effects logistic regression was performed. RESULTS: Among 1577 alteplase versus tenecteplase randomized controlled trial (AcT) patients, 128 (18.8%) had carotid TL. Of these, 93 (72.7%) underwent intravenous thrombolysis plus endovascular thrombectomy (IVT + EVT), while 35 (27.3%) were treated with IVT alone. In the IVT + EVT group, tenecteplase was associated with higher odds of 90-day-mRS 0-1 (46.0% vs. 32.6%, adjusted OR (aOR) 3.21; 95% CI = 1.06-9.71) compared with alteplase. No statistically significant differences in rates of mRS 0-2 (aOR 1.53; 95% CI = 0.51-4.55), initial rAOL 2b-3 (16.3% vs. 28.6%), final eTICI 2b-3 (83.7% vs. 85.7%), and mortality (18.0% vs. 16.3%) were found. SICH only occurred in one patient. There were no differences in outcomes between thrombolytic agents in the IVT-only group. CONCLUSION: In patients with carotid TL treated with EVT, intravenous tenecteplase may be associated with similar or better clinical outcomes, similar angiographic reperfusion rates, and safety outcomes as compared with alteplase.

Safety and Efficacy of Tenecteplase Compared With Alteplase in Patients With Large Vessel Occlusion Stroke: A Prespecified Secondary Analysis of the ACT Randomized Clinical Trial.

Importance: It is unknown whether intravenous thrombolysis using tenecteplase is noninferior or preferable compared with alteplase for patients with acute ischemic stroke. Objective: To examine the safety and efficacy of tenecteplase compared to alteplase among patients with large vessel occlusion (LVO) stroke. Design, Setting, and Participants: This was a prespecified analysis of the Intravenous Tenecteplase Compared With Alteplase for Acute Ischaemic Stroke in Canada (ACT) randomized clinical trial that enrolled patients from 22 primary and comprehensive stroke centers across Canada between December 10, 2019, and January 25, 2022. Patients 18 years and older with a disabling ischemic stroke within 4.5 hours of symptom onset were randomly assigned (1:1) to either intravenous tenecteplase or alteplase and were monitored for up to 120 days. Patients with baseline intracranial internal carotid artery (ICA), M1-middle cerebral artery (MCA), M2-MCA, and basilar occlusions were included in this analysis. A total of 1600 patients were enrolled, and 23 withdrew consent. Exposures: Intravenous tenecteplase (0.25 mg/kg) vs intravenous alteplase (0.9 mg/kg). Main Outcomes and Measures: The primary outcome was the proportion of modified Rankin scale (mRS) score 0-1 at 90 days. Secondary outcomes were an mRS score from 0 to 2, mortality, and symptomatic intracerebral hemorrhage. Angiographic outcomes were successful reperfusion (extended Thrombolysis in Cerebral Infarction scale score 2b-3) on first and final angiographic acquisitions. Multivariable analyses (adjusting for age, sex, National Institute of Health Stroke Scale score, onset-to-needle time, and occlusion location) were carried out. Results: Among 1577 patients, 520 (33.0%) had LVO (median [IQR] age, 74 [64-83] years; 283 [54.4%] women): 135 (26.0%) with ICA occlusion, 237 (45.6%) with M1-MCA, 117 (22.5%) with M2-MCA, and 31 (6.0%) with basilar occlusions. The primary outcome (mRS score 0-1) was achieved in 86 participants (32.7%) in the tenecteplase group vs 76 (29.6%) in the alteplase group. Rates of mRS 0-2 (129 [49.0%] vs 131 [51.0%]), symptomatic intracerebral hemorrhage (16 [6.1%] vs 11 [4.3%]), and mortality (19.9% vs 18.1%) were similar in the tenecteplase and alteplase groups, respectively. No difference was noted in successful reperfusion rates in the first (19 [9.2%] vs 21 [10.5%]) and final angiogram (174 [84.5%] vs 177 [88.9%]) among 405 patients who underwent thrombectomy. Conclusions and Relevance: The findings in this study indicate that intravenous tenecteplase conferred similar reperfusion, safety, and functional outcomes compared to alteplase among patients with LVO.

Enhanced Vulnerability of Asylum Seekers in Times of Crisis.

This article examines the impact of law and policy changes enacted in times of crisis on asylum seekers, and considers the extent to which considerations of vulnerability have played a part in the various approaches of governments. What emerges is a shift towards further exclusion, and a widening divide between how states approach citizens versus others. The result is enhanced vulnerability, and an environment in which the utility of the vulnerability concept to provide the necessary levels of support and protection is tested. By looking at how vulnerability is used by states, and contrasting this use with how the concept is often used by other community actors, the article asks what role the concept of vulnerability might play in the effects of crises on vulnerable groups and the priorities and actions of states.

Mortality After Total Anterior Circulation Stroke: A 25-Year Observational Study.

BACKGROUND: Mortality remains a substantial problem after acute ischemic stroke, despite advances in acute stroke treatment over the past three decades. Mortality is particularly high among patients with Total Anterior Circulation Stroke (TACS), generally representing patients with middle cerebral artery occlusions. Notably however, these patients also stand to benefit most from new therapies including endovascular thrombectomy (EVT). In this study, we aimed to examine temporal trends in, and factors associated with, 30-day in-hospital mortality after TACS. METHODS: Information on all patients with community-onset TACS from 1994 through 2019 was extracted from a prospective acute stroke registry. Multivariate analysis was performed on the primary outcome of 30-day in-hospital mortality, as well as secondary functional outcomes. RESULTS: We studied 1106 patients hospitalized for community-onset TACS, 456 (41%) of whom experienced 30-day in-hospital mortality. Over the 25 years of observation, 30-day in-hospital mortality rose and then fell. Increased odds of mortality was associated with age and stroke severity. Decreased odds of mortality was associated with alteplase therapy and EVT, as well as presentation to hospital more than 12 hours after stroke onset. Treatment with alteplase, EVT, or both was associated with higher odds of functional independence and discharge home, and shorter lengths of stay in acute care. CONCLUSIONS: Patients receiving alteplase, EVT, or both had lower 30-day in-hospital mortality and better functional outcomes than those who were untreated. These observational data demonstrate the benefits of recanalization therapy in routine clinical practice.

Selective Laser Trabeculoplasty and Outcomes of Subsequent Phacoemulsification Combined with Kahook Dual Blade Goniotomy.

INTRODUCTION: To investigate the relationship between intraocular pressure (IOP)-lowering success of selective laser trabeculoplasty (SLT) and combined phacoemulsification/Kahook Dual Blade (phaco/KDB) goniotomy in eyes with mild to severe open angle glaucoma (OAG). METHODS: Eyes undergoing combined phaco/KDB goniotomy and that had previously undergone SLT were analyzed. Data collected included demographics, glaucoma type and severity, IOP, and topical IOP-lowering medications before and after both procedures. Eyes were divided into two groups based on success of SLT, defined as IOP reduction of at least 20% maintained on at least two consecutive follow-up visits without any subsequent medication additions or interventions. Phaco/KDB goniotomy success was defined as IOP reduction of at least 20% and/or reduction in the number of IOP-lowering medications of at least one up to 12 months of follow-up. RESULTS: Overall, SLT was successful in 20 of 43 eyes (46.5%), of which 63.6% (7/11) had successful phaco/KDB goniotomy at 12 months follow-up. Among eyes with unsuccessful SLT, 60.0% (9/15) had successful phaco/KDB at 12 months follow-up. Phaco/KDB success rate was similar in patients regardless of their previous response to SLT at all postoperative time points up to 12 months follow-up (p = 0.87). CONCLUSIONS: The presence or lack of IOP-lowering response to SLT did not influence the success rate of subsequent phaco/KDB goniotomy in eyes with mild to severe OAG. Patients who did not respond to SLT still benefited from phaco/KDB goniotomy at a later date.

Intravenous tenecteplase compared with alteplase for acute ischaemic stroke in Canada (AcT): a pragmatic, multicentre, open-label, registry-linked, randomised, controlled, non-inferiority trial.

BACKGROUND: Intravenous thrombolysis with alteplase bolus followed by infusion is a global standard of care for patients with acute ischaemic stroke. We aimed to determine whether tenecteplase given as a single bolus might increase reperfusion compared with this standard of care. METHODS: In this multicentre, open-label, parallel-group, registry-linked, randomised, controlled trial (AcT), patients were enrolled from 22 primary and comprehensive stroke centres across Canada. Patients were eligible for inclusion if they were aged 18 years or older, with a diagnosis of ischaemic stroke causing disabling neurological deficit, presenting within 4·5 h of symptom onset, and eligible for thrombolysis per Canadian guidelines. Eligible patients were randomly assigned (1:1), using a previously validated minimal sufficient balance algorithm to balance allocation by site and a secure real-time web-based server, to either intravenous tenecteplase (0·25 mg/kg to a maximum of 25 mg) or alteplase (0·9 mg/kg to a maximum of 90mg; 0·09 mg/kg as a bolus and then a 60 min infusion of the remaining 0·81 mg/kg). The primary outcome was the proportion of patients who had a modified Rankin Scale (mRS) score of 0-1 at 90-120 days after treatment, assessed via blinded review in the intention-to-treat (ITT) population (ie, all patients randomly assigned to treatment who did not withdraw consent). Non-inferiority was met if the lower 95% CI of the difference in the proportion of patients who met the primary outcome between the tenecteplase and alteplase groups was more than -5%. Safety was assessed in all patients who received any of either thrombolytic agent and who were reported as treated. The trial is registered with ClinicalTrials.gov, NCT03889249, and is closed to accrual. FINDINGS: Between Dec 10, 2019, and Jan 25, 2022, 1600 patients were enrolled and randomly assigned to tenecteplase (n=816) or alteplase (n=784), of whom 1577 were included in the ITT population (n=806 tenecteplase; n=771 alteplase). The median age was 74 years (IQR 63-83), 755 (47·9%) of 1577 patients were female and 822 (52·1%) were male. As of data cutoff (Jan 21, 2022), 296 (36·9%) of 802 patients in the tenecteplase group and 266 (34·8%) of 765 in the alteplase group had an mRS score of 0-1 at 90-120 days (unadjusted risk difference 2·1% [95% CI - 2·6 to 6·9], meeting the prespecified non-inferiority threshold). In safety analyses, 27 (3·4%) of 800 patients in the tenecteplase group and 24 (3·2%) of 763 in the alteplase group had 24 h symptomatic intracerebral haemorrhage and 122 (15·3%) of 796 and 117 (15·4%) of 763 died within 90 days of starting treatment INTERPRETATION: Intravenous tenecteplase (0·25 mg/kg) is a reasonable alternative to alteplase for all patients presenting with acute ischaemic stroke who meet standard criteria for thrombolysis. FUNDING: Canadian Institutes of Health Research, Alberta Strategy for Patient Oriented Research Support Unit.

Evaluation of the Accuracy of a New Geometric Approach to Implant Guidance.

PURPOSE: Implant surgical guides are often fabricated using CBCT technology. In this study, an alternative technique is proposed. The aim of this in vitro study was to compare the accuracy of the guide sleeve corrections of a geometric approach to guided surgery to the accuracy of in vitro studies of stereolithographic guides. MATERIALS AND METHODS: Four arch forms were milled from acrylic blocks each with 12 root form sites. Root form inserts were made. Holes were milled in the inserts at arbitrary angles. Guide posts were placed in these sites. Guide sleeves were placed on the posts and connected with light-cured resin to form verification jigs. The goal was to correct the angles of the guide sleeves to a vertical position 90 degrees from the base of the arch forms. The initial angles from the vertical and horizontal positions of the center of each guide sleeve were determined radiographically and geometrically. Horizontal and angle corrections were made using two-piece guide posts. Guide sleeves placed over the corrected guide posts were connected with light-cured resin, forming new verification jigs. The accuracy of the angle correction and the coronal horizontal and apical horizontal deviations of the 3-mm guide sleeves were determined. The experimental sites were divided into two groups to determine if the size of the initial angles of the guide sleeves had any effect on the accuracy of the corrections. RESULTS: The initial angles of the guide sleeves before corrections revealed the mean difference between the two methods of measurements in groups 1 and 2 as 0.36 degrees (P = .14) and 0.69 degrees (P = .07), respectively. A comparison of the angle error measurements from 90 degrees after corrections between the two groups in the mesiodistal and buccolingual planes was not significant. The coronal and apical horizontal deviations after corrections revealed a significant difference between the two groups at the coronal level (P = .005) but not at the apical level (P = .14). In comparison of the methods of the two measurements of the angle error from vertical after corrections, the mean difference was 1.23 degrees (P = .01) and 0.69 degrees (P = .02). CONCLUSION: The in vitro accuracy of the guide sleeve corrections made with the geometric approach for implant guidance was compared to the results of the meta-analyses of in vitro studies of implant placement with stereolithographic guides. The mean errors were smaller and within the recommendations of the EAO Consensus Conference of 2012.

Effect of continuing versus stopping pre-stroke antihypertensive agents within 12 h on outcome after stroke: A subgroup analysis of the efficacy of nitric oxide in stroke (ENOS) trial.

BACKGROUND: It is not known whether to continue or temporarily stop existing antihypertensive drugs in patients with acute stroke. METHODS: We performed a prospective subgroup analysis of patients enrolled into the Efficacy of Nitric Oxide in Stroke (ENOS) trial who were randomised to continue vs stop prior antihypertensive therapy within 12 h of stroke onset. The primary outcome was functional outcome, assessed with the modified Rankin Scale at 90 days by observers blinded to treatment assignment, and analysed with ordinal logistic regression. FINDINGS: Of 4011 patients recruited into ENOS from 2001 to 2014, 2097 patients were randomised to continue vs stop prior antihypertensive treatment, and 384 (18.3%, continue 185, stop 199) were enrolled within 12 h of ictus: mean (SD) age 71.8 (11.8) years, female 193 (50.3%), ischaemic stroke 342 (89.1%) and total anterior circulation syndrome 114 (29.7%). As compared with stopping, continuing treatment within 12 h of onset lowered blood pressure by 15.5/9.6 mmHg (p<0.001/<0.001) by 7 days, shifted the modified Rankin Scale to a worse outcome by day 90, adjusted common odds ratio (OR) 1.46 (95% CI 1.01-2.11), and was associated with an increased death rate by day 90 (hazard ratio 2.17, 95% CI 1.24-3.79). Other outcomes (disability - Barthel Index, quality of life - EQ-visual analogue scale, cognition - telephone mini-mental state examination, and mood - Zung depression scale) were also worse with continuing treatment. INTERPRETATION: In this pre-specified subgroup analysis of the large ENOS trial, continuing prior antihypertensive therapy within 12 h of stroke onset in a predominantly ischaemic stroke population was unsafe with worse functional outcome, disability, cognition, mood, quality of life and increased death. Future studies assessing continuing or stopping prior antihypertensives in the context of thrombectomy are awaited.

Program of Rehabilitative Exercise and Education to Avert Vascular Events After Non-Disabling Stroke or Transient Ischemic Attack (PREVENT Trial): A Randomized Controlled Trial.

BACKGROUND: Non-disabling stroke (NDS) and transient ischemic attack (TIA) herald the possibility of future, more debilitating vascular events. Evidence is conflicting about potency of exercise and education in reducing risk factors for second stroke. METHODS: Three-site, single-blinded, randomized controlled trial with 184 participants <3 months of NDS or TIA (mean age, 65 years; 66% male) randomized to usual care (UC) or UC + 12-week program of exercise and education (PREVENT). Primary (resting systolic blood pressure) and secondary outcomes (diastolic blood pressure [DBPrest], high-density lipoprotein cholesterol [HDL-C], low-density lipoprotein cholesterol [LDL-C], total cholesterol [TC], TC/HDL, triglycerides, fasting glucose, and body mass index) were assessed at baseline, post-intervention, and 6- and 12-month follow-up. Peak oxygen consumption (VO2peak) was measured at baseline, post-intervention, 12-month assessments. RESULTS: Significant between-group differences at post-intervention favored PREVENT group over UC: DBPrest (mean difference [MD]: -3.2 mmHg, 95% confidence interval [CI]: -6.3, -.2, P = .04) and LDL-C (MD: -.31 mmol/L, 95% CI: -.42, -.20, P = .02). Trends of improvement in PREVENT group were noted in several variables between baseline and 6-month follow-up but not sustained at 12-month follow-up. Of note, VO2 peak did not change over time in either group. CONCLUSION: Impact of PREVENT on vascular risk factor reduction was more modest than anticipated, possibly because several outcome variables approximated normative values at baseline and training intensity may have been sub-optimal. Further investigation is warranted to determine when exercise and education programs are viable adjuncts to pharmaceutical management for reduction of risk factors for second stroke.Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifier: #NCT00885456.

Improving stroke care in Nova Scotia, Canada: a population-based project spanning 14 years.

Stroke is a complex disorder that challenges healthcare systems. An audit of in-hospital stroke care in the province of Nova Scotia, Canada, in 2004-2005 indicated that many aspects of care delivery fell short of national best practice recommendations. Stroke care in Nova Scotia was reorganised using a combination of interventions to facilitate systems change and quality improvement. The focus was mainly on implementing evidence-based stroke unit care, augmenting thrombolytic therapy and enhancing dysphagia assessment. Key were the development of a provincial network to facilitate ongoing collaboration and structured information exchange, the creation of the stroke coordinator and stroke physician champion roles, and the implementation of a registry to capture information about adults hospitalised because of stroke or transient ischaemic attack. To evaluate the interventions, a longitudinal analysis compared the audit results with registry data for 2012, 2015 and 2019. The proportion of patients receiving multidisciplinary stroke unit care rose from 22.4% in 2005 to 74.0% in 2019. The proportion of patients who received alteplase increased steadily from 3.2% to 18.5%, and the median delay between hospital arrival and alteplase administration decreased from 102 min to 56 min, without an increase in intracranial haemorrhage. Dysphagia screening increased from 41.4% to 77.4%. More patients were transferred from acute care to a dedicated in-patient rehabilitation unit, and fewer were discharged to residential or long-term care. These enhancements did not prolong length-of-stay in acute care. The network was a critical success factor; competing priorities in the healthcare system were the main challenge to implementing change. A multidimensional, multiyear, improvement intervention yielded substantial and sustained improvements in the process and structure of stroke care in Nova Scotia.

Routine postoperative blood tests in all patients undergoing Total Hip Arthroplasty as part of an enhanced recovery pathway: Are they necessary?

INTRODUCTION: The increasing demand for Total Hip replacement (THR)/Total Hip Arthroplasty (THA) continues to place significant financial pressure on the National Health Service (NHS). Many institutions undertake post-operative blood tests routinely in this group of patients. The aim of this study was to identify if such routine blood tests (Full Blood Count (FBC) and Urea and Electrolytes(U&Es)) are required in all THR patients post-operatively. METHODS: Single institute, Multi-surgeon, retrospective observational study of consecutive patients who underwent primary elective THR done from Jan 2014 to Dec 2018.Post-operative blood tests and medical records were reviewed to identify derangement in haemoglobin (Hb) level and renal function requiring clinical intervention. RESULTS: Over the period of 4 years, 353 patients underwent elective THR with mean age of 70 years (range: 42-90). There were 203 Males and 150 Females. Mean pre-operative Hb was 134.7 g/l. Mean post-operative drop in Hb was 22.3 g/l. None of the patients in ASA grade 1 and 2 with age ≤70 years required blood transfusion post operatively.6.4% of patients (n = 18/280) with an ASA of 1-2 had postoperative blood results requiring intervention of which only four (1.2%) were ≤70 years of age compared to 17.8% of patients (n = 14/73) with ASA 3-4.Overall none of the patients in ASA grade 1 and 2 with age ≤70 years required blood transfusion post operatively nor had electrolyte disturbance. 1.2% had deranged renal function that needed minor clinical intervention. CONCLUSION: Routine post-operative blood analyses may not required for all patients undergoing THA. Young and healthier patients seldom have significant abnormalities on routine post-operative blood analyses which requires clinical intervention.

A multifactorial approach to specify comfortable rail seats.

BACKGROUND: A robust rail seat comfort assessment can inform the GB rail industry when procuring new seats and identify areas for comfort improvement in the refurbishment of existing seats, improving the customer experience. OBJECTIVE: To take a multifactorial approach to measuring comfort and to create a robust seat comfort assessment method for the GB rail industry. METHODS: Seat comfort assessment scores were developed by identifying seat dimensions (e.g. Seat height, seat width, seat depth), seat pad thickness and hardness requirements, seat accessories and seat attractiveness components. Scores for each seat feature were verified by conducting a fitting trial and asking 7 participants to rank dimensions through a range of adjustment. The combined scoring of features was verified by asking 14 participants to rank seats in three configurations (minimum comfort). The seat comfort dimensions scores were then validated by ranking seven existing rail seats using the assessment method and comparing the ranks with subjective comfort ranks of 12 participants. RESULTS: The validation testing resulted in a moderate positive correlation, indicating an alignment between the seat comfort assessment method and subjective comfort scores. CONCLUSIONS: A multifactorial seat comfort assessment has been shown to be a good indicator of passenger seat comfort.

Neck of femur fracture: who gets a total hip replacement? A review of 230 eligible patients.

PURPOSE: To investigate patient-specific factors that predict Total Hip Replacement (THR) in patients with fracture neck of femur (NOF), fulfilling the National Institute of Health and Care Excellence (NICE) criteria. METHODS: Hip fracture database from a district general hospital and university hospital was retrospectively reviewed to identify patients fulfilling NICE criteria for THR after fracture NOF. Patient demographics, Nottingham Hip Fracture score (NHFS), complications, re-operations, revision, 30 days and one-year mortality was obtained from patient-records. Independent predictors correlating with the outcome of surgery were identified. A logistic regression analysis was used to predict the type of surgery in these patients. RESULTS: A total of 230 (114 WMH and 116 MH) were identified; 133 (57.8 per-cent) received hip hemiarthroplasty (HA), and 97 (42.2 per-cent) received THR. Patients receiving THR (mean 73.5 years, 95% CI 72-74.8) were significantly younger in comparison to patients receiving HA (mean 81.7 years, 95% CI 80.5-82.8). A negative correlation is noted between NHFS and type of surgery (Pearson's correlation - 0.537, p < 0.01), implying higher NHFS decreased the likelihood of receiving THR. Regression analysis showed NHFS (p-0.001) and walking ability (p-0.001) as significant predictors for the type of surgery (Nagelkerke R2-0.472). A log-rank test showed higher estimated survival time in patients with THR in comparison to HA (p-value 0.002). CONCLUSIONS: NHFS and walking ability can be used as an adjunct to the NICE criteria for selecting patients for THR after fracture NOF. Carefully selected patients treated with THR survive longer and have a better outcome in comparison to HA.

Relationship between nitrate headache and outcome in patients with acute stroke: results from the efficacy of nitric oxide in stroke (ENOS) trial.

INTRODUCTION: Nitrate-induced headache is common and may signify responsive cerebral vasculature. We assessed the relationship between nitrate headache and outcome in patients with acute stroke. MATERIALS AND METHODS: Patients were those randomised to glyceryl trinitrate (GTN) versus no GTN in the efficacy of nitric oxide in stroke trial. Development of headache by end of treatment (day 7), and functional outcome (modified Rankin Scale, primary outcome) at day 90, were assessed. Analyses are adjusted for baseline prognostic factors and give OR and mean difference (MD) with 95% CI. RESULTS: In 4011 patients, headache was more common in GTN than control (360, 18.0% vs 170, 8.5%; p<0.001). Nitrate-related headache was associated with: younger age, female sex, higher diastolic blood pressure, non-total anterior circulation syndrome, milder stroke and absence of dysphasia (p<0.05). Nitrate headache was not associated with improved functional outcome (OR 0.90, 95% CI 0.73 to 1.10, p=0.30) or death (day 90) (HR 0.64, 95% CI 0.40 to 1.02, p=0.062), but reduced death or deterioration (day 7) (OR 0.45, 95% CI 0.25 to 0.82), death in hospital (OR 0.44, 95% CI 0.22 to 0.88) and improved activities of daily living (Barthel index, MD 3.7, 95% CI 0.3 to 7.1) and cognition (telephone interview cognitive screen, MD 2.0, 95% CI 0.7 to 3.3) (day 90). Non-nitrate headache was not associated with death, disability or cognition. DISCUSSION AND CONCLUSION: Development of a nitrate headache by day 7 after stroke may be associated with improved activities of daily living and cognitive impairment at day 90, which was not seen with non-nitrate headache.

Behavioral Assessment of Visual Function via Optomotor Response and Cognitive Function via Y-Maze in Diabetic Rats.

The optomotor response and the Y-maze are behavioral tests useful for assessing visual and cognitive function, respectively. The optomotor response is a valuable tool to track changes in spatial frequency (SF) and contrast sensitivity (CS) thresholds over time in a number of retinal disease models, including diabetic retinopathy. Similarly, the Y-maze can be used to monitor spatial cognition (as measured by spontaneous alternation) and exploratory behavior (as measured by a number of entries) in a number of disease models that affect the central nervous system. Advantages of the optomotor response and the Y-maze include sensitivity, speed of testing, the use of innate responses (training is not needed), and the ability to be performed on awake (non-anesthetized) animals. Here, protocols are described for both the optomotor response and the Y-maze and examples of their use shown in models of Type I and Type II diabetes. Methods include preparation of rodents and equipment, performance of the optomotor response and the Y-maze, and post-test data analysis.

Improving Clinical Detection of Acute Lacunar Stroke: Analysis From the IST-3.

Background and Purpose- We aim to identify factors associated with imaging-confirmed lacunar strokes and improve their rapid clinical identification early after symptom onset using data from the IST-3 (Third International Stroke Trial). Methods- We selected patients likely to have lacunar infarcts as those presenting with: Oxfordshire Community Stroke Project lacunar syndrome; a random sample with National Institutes of Health Stroke Scale (NIHSS) score <7; and recent lacunar infarct identified on imaging by IST-3 central blinded expert panel. An independent reviewer rated brain scans of this sample and classified visible infarcts according to type, size, and location. We investigated factors associated with presence of lacunar infarct on a 24 to 48 hour follow-up scan using multivariable logistic regression and calculated sensitivity and specificity of Oxfordshire Community Stroke Project alone and in combination with NIHSS score <7. Results- We included 568 patients (330 lacunar syndrome; 147 with NIHSS score <7; 91 with lacunar infarct on baseline imaging, numbers exclude overlaps between groups), mean (±SD) age, 73.2 (±13.6) years, 316 (56%) males, and median NIHSS score 5 (IQR, 4-8). On 24 to 48 hour scan, 138 (24%) patients had lacunar infarcts, 176 (31%) other infarct subtypes, 254 (45%) no visible infarct. Higher baseline systolic blood pressure (odds ratio, 1.01 [95% CI, 1.01-1.02]) and preexisting lacunes (odds ratio, 2.29 [95% CI, 1.47-3.57) were associated with recent lacunar infarcts. Sensitivity and specificity of lacunar syndrome was modest (58% and 45%, respectively), but adding NIHSS score <7 increased specificity (99%), positive and negative predictive values (97% and 87%, respectively). Conclusions- In patients presenting within 6 hours of stroke onset, adding NIHSS score <7 to Oxfordshire Community Stroke Project lacunar syndrome classification may increase specificity for identifying lacunar stroke early after stroke onset. Our findings may help selection of patients for clinical trials of lacunar stroke and should be validated externally. Registration- URL: http://www.controlled-trials.com/; Unique identifier: ISRCTN25765518.

BAP1 Immunoreactivity Correlates with Gene Expression Class in Uveal Melanoma.

BACKGROUND: Uveal melanoma (UM) is the most common intraocular tumour in adults. Currently there are different tests available to determine the risk of UM for metastasis, among which include BRCA1-associated protein-1 (BAP1) immunohistochemistry (IHC) and gene expression profiling (GEP). BAP1 is a deubiquitylating enzyme (DUB) that has tumour suppressor activity, the loss of which therefore is associated with higher risk for tumour growth and metastasis. OBJECTIVES: To compare and correlate the prognostic significance of BAP1-IHC staining patterns and GEP in the prediction of UM's risk for metastasis. METHODS: This is a retrospective chart review with prospective follow-up of patients with primary UM who underwent enucleation from the year 2008 to 2018. Clinical history, histopathologic findings, GEP classification, BAP1-IHC of the formalin-fixed paraffin-embedded tissues, and follow-up data for metastasis were collected and statistically analysed. RESULTS: A total of 30 enucleated eyes with UM were included in the study. All class 1a tumours had high nuclear BAP1 expression and all class 2 had low nuclear BAP1 expression. Fifty percent of the class 1b tumours had low nuclear BAP1 expression. Among the tumours with low nuclear BAP1 expression, 68% developed metastasis, while 9% developed metastasis among high nuclear expression. Fifty-five percent developed metastasis in tumours with high cytoplasmic expression and 42% for low cytoplasmic expression. Predictive values for metastasis (positive predictive value, negative predictive value) are as follows: (1) nuclear BAP1-IHC (68%, 91%), (2) cytoplasmic BAP1-IHC (55%, 58%), and (3) GEP (73%, 80%). Nuclear BAP1-IHC and GEP had the same accuracy rate of 77% and cytoplasmic BAP1-IHC had an accuracy of 57%. CONCLUSION: Low nuclear BAP1-IHC strongly correlates with GEP class 2 and was equally accurate in the prediction of metastasis.