Baseline perihematomal edema, C-reactive protein, and 30-day mortality are not associated in intracerebral hemorrhage.

Background: The relationship between baseline perihematomal edema (PHE) and inflammation, and their impact on survival after intracerebral hemorrhage (ICH) are not well understood. Objective: Assess the association between baseline PHE, baseline C-reactive protein (CRP), and early death after ICH. Methods: Analysis of pooled data from multicenter ICH registries. We included patients presenting within 24 h of symptom onset, using multifactorial linear regression model to assess the association between CRP and edema extension distance (EED), and a multifactorial Cox regression model to assess the association between CRP, PHE volume and 30-day mortality. Results: We included 1,034 patients. Median age was 69 (interquartile range [IQR] 59-79), median baseline ICH volume 11.5 (IQR 4.3-28.9) mL, and median baseline CRP 2.5 (IQR 1.5-7.0) mg/L. In the multifactorial analysis [adjusting for cohort, age, sex, log-ICH volume, ICH location, intraventricular hemorrhage (IVH), statin use, glucose, and systolic blood pressure], baseline log-CRP was not associated with baseline EED: for a 50% increase in CRP the difference in expected mean EED was 0.004 cm (95%CI 0.000-0.008, p = 0.055). In a further multifactorial analysis, after adjusting for key predictors of mortality, neither a 50% increase in PHE volume nor CRP were associated with higher 30-day mortality (HR 0.97; 95%CI 0.90-1.05, p = 0.51 and HR 0.98; 95%CI 0.93-1.03, p = 0.41, respectively). Conclusion: Higher baseline CRP is not associated with higher baseline edema, which is also not associated with mortality. Edema at baseline might be driven by different pathophysiological processes with different effects on outcome.

Tranexamic acid versus placebo in individuals with intracerebral haemorrhage treated within 2 h of symptom onset (STOP-MSU): an international, double-blind, randomised, phase 2 trial.

BACKGROUND: Tranexamic acid, an antifibrinolytic agent, might attenuate haematoma growth after an intracerebral haemorrhage. We aimed to determine whether treatment with intravenous tranexamic acid within 2 h of an intracerebral haemorrhage would reduce haematoma growth compared with placebo. METHODS: STOP-MSU was an investigator-led, double-blind, randomised, phase 2 trial conducted at 24 hospitals and one mobile stroke unit in Australia, Finland, New Zealand, Taiwan, and Viet Nam. Eligible participants had acute spontaneous intracerebral haemorrhage confirmed on non-contrast CT, were aged 18 years or older, and could be treated with the investigational product within 2 h of stroke onset. Using randomly permuted blocks (block size of 4) and a concealed pre-randomised assignment procedure, participants were randomly assigned (1:1) to receive intravenous tranexamic acid (1 g over 10 min followed by 1 g over 8 h) or placebo (saline; matched dosing regimen) commencing within 2 h of symptom onset. Participants, investigators, and treating teams were masked to group assignment. The primary outcome was haematoma growth, defined as either at least 33% relative growth or at least 6 mL absolute growth on CT at 24 h (target range 18-30 h) from the baseline CT. The analysis was conducted within the estimand framework with primary analyses adhering to the intention-to-treat principle. The primary endpoint and secondary safety endpoints (mortality at days 7 and 90 and major thromboembolic events at day 90) were assessed in all participants randomly assigned to treatment groups who did not withdraw consent to use any data. This study was registered with ClinicalTrials.gov, NCT03385928, and the trial is now complete. FINDINGS: Between March 19, 2018, and Feb 27, 2023, 202 participants were recruited, of whom one withdrew consent for any data use. The remaining 201 participants were randomly assigned to either placebo (n=98) or tranexamic acid (n=103; intention-to-treat population). Median age was 66 years (IQR 55-77), and 82 (41%) were female and 119 (59%) were male; no data on race or ethnicity were collected. CT scans at baseline or follow-up were missing or of inadequate quality in three participants (one in the placebo group and two in the tranexamic acid group), and were considered missing at random. Haematoma growth occurred in 37 (38%) of 97 assessable participants in the placebo group and 43 (43%) of 101 assessable participants in the tranexamic acid group (adjusted odds ratio [aOR] 1·31 [95% CI 0·72 to 2·40], p=0·37). Major thromboembolic events occurred in one (1%) of 98 participants in the placebo group and three (3%) of 103 in the tranexamic acid group (risk difference 0·02 [95% CI -0·02 to 0·06]). By 7 days, eight (8%) participants in the placebo group and eight (8%) in the tranexamic acid group had died (aOR 1·08 [95% CI 0·35 to 3·35]) and by 90 days, 15 (15%) participants in the placebo group and 19 (18%) in the tranexamic acid group had died (aOR 1·61 [95% CI 0·65 to 3·98]). INTERPRETATION: Intravenous tranexamic acid did not reduce haematoma growth when administered within 2 h of intracerebral haemorrhage symptom onset. There were no observed effects on other imaging endpoints, functional outcome, or safety. Based on our results, tranexamic acid should not be used routinely in primary intracerebral haemorrhage, although results of ongoing phase 3 trials will add further context to these findings. FUNDING: Australian Government Medical Research Future Fund.

A scoping review of applications of artificial intelligence in kinematics and kinetics of ankle sprains - current state-of-the-art and future prospects.

BACKGROUND: Despite the existence of evidence-based rehabilitation strategies that address biomechanical deficits, the persistence of recurrent ankle problems in 70% of patients with acute ankle sprains highlights the unresolved nature of this issue. Artificial intelligence (AI) emerges as a promising tool to identify definitive predictors for ankle sprains. This paper aims to summarize the use of AI in investigating the ankle biomechanics of healthy and subjects with ankle sprains. METHODS: Articles published between 2010 and 2023 were searched from five electronic databases. 59 papers were included for analysis with regards to: i). types of motion tested (functional vs. purposeful ankle movement); ii) types of biomechanical parameters measured (kinetic vs kinematic); iii) types of sensor systems used (lab-based vs field-based); and, iv) AI techniques used. FINDINGS: Most studies (83.1%) examined biomechanics during functional motion. Single kinematic parameter, specifically ankle range of motion, could obtain accuracy up to 100% in identifying injury status. Wearable sensor exhibited high reliability for use in both laboratory and on-field/clinical settings. AI algorithms primarily utilized electromyography and joint angle information as input data. Support vector machine was the most used supervised learning algorithm (18.64%), while artificial neural network demonstrated the highest accuracy in eight studies. INTERPRETATIONS: The potential for remote patient monitoring is evident with the adoption of field-based devices. Nevertheless, AI-based sensors are underutilized in detecting ankle motions at risk of sprain. We identify three key challenges: sensor designs, the controllability of AI models, and the integration of AI-sensor models, providing valuable insights for future research.

Can umbilical cord testing add to maternal urine drug screen for evaluation of infants at risk of neonatal opioid withdrawal syndrome?

OBJECTIVE: This study evaluated maternal urine drug screen (UDS) at delivery and umbilical cord drug testing and its association with neonatal opioid withdrawal syndrome (NOWS) diagnosis and severity following opioid exposed pregnancy. METHODS: A retrospective chart review of 770 mother-infant dyads at five birthing hospitals in the United States Appalachian region for a five-year period was performed. Variables of interest included dyad demographics, results of maternal UDS at delivery and umbilical cord drug testing, and three neonatal outcomes: NOWS diagnosis, pharmacologic treatment administered for NOWS, and length of hospital stay (LOS) of the newborn. RESULTS: Opioid-positivity was between 8.5% and 66.3% based on maternal UDS at delivery or umbilical cord testing. Odds of NOWS diagnosis and increased infant LOS was best associated with opioid detection in maternal UDS alone (OR = 5.62, 95% CI [3.06, 10.33] and OR = 8.33, 95% CI [3.67, 18.89], respectively). However, odds of pharmacologic treatment for NOWS was best associated with opioid detection in both maternal UDS and umbilical cord testing on the same dyad (OR = 3.22, 95% CI [1.14, 9.09]). CONCLUSION: Maternal UDS is a better option compared to umbilical cord testing for evaluation of opioid-exposed infants and risk of NOWS diagnosis and increased infant LOS.

Safety and Efficacy of Tenecteplase and Alteplase in Patients With Tandem Lesion Stroke: A Post Hoc Analysis of the EXTEND-IA TNK Trials.

BACKGROUND AND OBJECTIVES: The safety and efficacy of tenecteplase (TNK) in patients with tandem lesion (TL) stroke is unknown. We performed a comparative analysis of TNK and alteplase in patients with TLs. METHODS: We first compared the treatment effect of TNK and alteplase in patients with TLs using individual patient data from the EXTEND-IA TNK trials. We evaluated intracranial reperfusion at initial angiographic assessment and 90-day modified Rankin scale (mRS) with ordinal logistic and Firth regression models. Because 2 key outcomes, mortality and symptomatic intracranial hemorrhage (sICH), were few in number among those who received alteplase in the EXTEND-IA TNK trials, we generated pooled estimates for these outcomes by supplementing trial data with estimates of incidence obtained through a meta-analysis of studies identified in a systematic review. We then calculated unadjusted risk differences to compare the pooled estimates for those receiving alteplase with the incidence observed in the trial among those receiving TNK. RESULTS: Seventy-one of 483 patients (15%) in the EXTEND-IA TNK trials possessed a TL. In patients with TLs, intracranial reperfusion was observed in 11/56 (20%) of TNK-treated patients vs 1/15 (7%) alteplase-treated patients (adjusted odds ratio 2.19; 95% CI 0.28-17.29). No significant difference in 90-day mRS was observed (adjusted common odds ratio 1.48; 95% CI 0.44-5.00). A pooled study-level proportion of alteplase-associated mortality and sICH was 0.14 (95% CI 0.08-0.21) and 0.09 (95% CI 0.04-0.16), respectively. Compared with a mortality rate of 0.09 (95% CI 0.03-0.20) and an sICH rate of 0.07 (95% CI 0.02-0.17) in TNK-treated patients, no significant difference was observed. DISCUSSION: Functional outcomes, mortality, and sICH did not significantly differ between patients with TLs treated with TNK and those treated with alteplase. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that TNK is associated with similar rates of intracranial reperfusion, functional outcome, mortality, and sICH compared with alteplase in patients with acute stroke due to TLs. However, the CIs do not rule out clinically important differences. TRIAL REGISTRATION INFORMATION: clinicaltrials.gov/ct2/show/NCT02388061; clinicaltrials.gov/ct2/show/NCT03340493.

Addition of clobazam successfully treating drug resistant seizures in Heidenhain variant Creutzfeldt Jakob disease: A case report.

Creutzfeldt Jakob Disease (CJD) is a rapidly progressive and fatal neurodegenerative disease that is uncommonly accompanied with seizures. In this case report, we describe a 63-year-old male patient who presented with a 3-week history of visual disturbances and clonic movement of his left arm. Additionally, the patient was reported to have developed erratic behaviors along with insomnia during this period. An EEG showed 4 electrographic seizures of bilateral temporo-occipital onset characterized by 1.5 Hz periodic discharges, lasting 2-13 min. Levetiracetam was started and titrated to the maximal dose however seizures continued so lacosamide and clonazepam were initiated. Despite these aggressive treatments, seizures continued, and oral clobazam 5 mg BID replaced clonazepam. Continued electrographic seizures warranted an increase in clobazam to 10 mg BID after which the seizures stopped; of note, lateralized periodic discharges (LPDs) remained. The patient's symptoms were consistent with the Heidenhain variant, along with probable CJD due to positive RT-QuIC assay, positive 14-3-3 protein, MRI FLAIR hyperintensities, and EEG findings. Although the patient passed away 3 weeks following admission as a result of CJD, we propose that there may be clinical benefit in the use of clobazam in suspected CJD patients presenting with seizures, and its use merits further investigation.

Impact of increasing total knee replacement constraint within a single implant line on coronal stability: an ex vivo investigation.

INTRODUCTION: Despite the existence of diverse total knee implant designs, few data is available on the relationship between the level of implant constraint and the postoperative joint stability in the frontal plane and strain in the collateral ligaments. The current study aimed to document this relation in an ex vivo setting. MATERIALS AND METHODS: Six fresh-frozen lower limbs underwent imaging for preparation of specimen-specific surgical guides. Specimens were dissected and assessed for joint laxity using the varus-valgus stress tests at fixed knee flexion angles. A handheld dynamometer applied tensile loads at the ankle, thereby resulting in a knee abduction-adduction moment of 10 Nm. Tibiofemoral kinematics were calculated using an optical motion capture system, while extensometers attached to medial collateral (MCL) and lateral collateral ligament (LCL) measured strain. Native joint testing was followed by four TKA designs from a single implant line-cruciate retaining, posterior stabilised, varus-valgus constrained and hinged knee (HK)-and subsequent testing after each implantation. Repeated measures linear mixed-models (p < 0.05) were used to compare preoperative vs. postoperative data on frontal plane laxity and collateral ligament strain. RESULTS: Increasing implant constraint reduced frontal plane laxity across knee flexion, especially in deep flexion (r2 > 0.76), and MCL strain in extension; however, LCL strain reduction was not consistent. Frontal plane laxity increased with knee flexion angle, but similar trends were inconclusive for ligament strain. HK reduced joint laxity and ligament strain as compared to the native condition consistently across knee flexion angle, with significant reductions in flexion (p < 0.024) and extension (p < 0.001), respectively, thereby elucidating the implant design-induced joint stability. Ligament strain exhibited a strong positive correlation with varus-valgus alignment (r2 = 0.96), notwithstanding knee flexion angle or TKA implant design. CONCLUSION: The study demonstrated that increasing the constraint of a TKA resulted in lower frontal plane laxity of the knee. With implant features impacting laxity in the coronal plane, consequentially affecting strain in collateral ligaments, surgeons must consider these factors when deciding a TKA implant, especially for primary TKA. LEVEL OF EVIDENCE: V.

Mediation of Successful Reperfusion Effect through Infarct Growth and Cerebral Edema: A Pooled, Patient-Level Analysis of EXTEND-IA Trials and SELECT Prospective Cohort.

OBJECTIVE: Reperfusion therapy is highly beneficial for ischemic stroke. Reduction in both infarct growth and edema are plausible mediators of clinical benefit with reperfusion. We aimed to quantify these mediators and their interrelationship. METHODS: In a pooled, patient-level analysis of the EXTEND-IA trials and SELECT study, we used a mediation analysis framework to quantify infarct growth and cerebral edema (midline shift) mediation effect on successful reperfusion (modified Treatment in Cerebral Ischemia ≥ 2b) association with functional outcome (modified Rankin Scale distribution). Furthermore, we evaluated an additional pathway to the original hypothesis, where infarct growth mediated successful reperfusion effect on midline shift. RESULTS: A total 542 of 665 (81.5%) eligible patients achieved successful reperfusion. Baseline clinical and imaging characteristics were largely similar between those achieving successful versus unsuccessful reperfusion. Median infarct growth was 12.3ml (interquartile range [IQR] = 1.8-48.4), and median midline shift was 0mm (IQR = 0-2.2). Of 249 (37%) demonstrating a midline shift of ≥1mm, median shift was 2.75mm (IQR = 1.89-4.21). Successful reperfusion was associated with reductions in both predefined mediators, infarct growth (ß = -1.19, 95% confidence interval [CI] = -1.51 to -0.88, p < 0.001) and midline shift (adjusted odds ratio = 0.36, 95% CI = 0.23-0.57, p < 0.001). Successful reperfusion association with improved functional outcome (adjusted common odds ratio [acOR] = 2.68, 95% CI = 1.86-3.88, p < 0.001) became insignificant (acOR = 1.39, 95% CI = 0.95-2.04, p = 0.094) when infarct growth and midline shift were added to the regression model. Infarct growth and midline shift explained 45% and 34% of successful reperfusion effect, respectively. Analysis considering an alternative hypothesis demonstrated consistent results. INTERPRETATION: In this mediation analysis from a pooled, patient-level cohort, a significant proportion (~80%) of successful reperfusion effect on functional outcome was mediated through reduction in infarct growth and cerebral edema. Further studies are required to confirm our findings, detect additional mediators to explain successful reperfusion residual effect, and identify novel therapeutic targets to further enhance reperfusion benefits. ANN NEUROL 2023;93:793-804.

Tenecteplase Improves Reperfusion across Time in Large Vessel Stroke.

OBJECTIVE: Tenecteplase improves reperfusion compared to alteplase in patients with large vessel occlusions. To determine whether this improvement varies across the spectrum of thrombolytic agent to reperfusion assessment times, we performed a comparative analysis of tenecteplase and alteplase reperfusion rates. METHODS: Patients with large vessel occlusion and treatment with thrombolysis were pooled from the Melbourne Stroke Registry, and the EXTEND-IA and EXTEND-IA TNK trials. The primary outcome, thrombolytic-induced reperfusion, was defined as the absence of retrievable thrombus or >50% reperfusion at imaging reassessment. We compared the treatment effect of tenecteplase and alteplase, accounting for thrombolytic to assessment exposure times, via Poisson modeling. We compared 90-day outcomes of patients who achieved reperfusion with a thrombolytic to patients who achieved reperfusion via endovascular therapy using ordinal logistic regression. RESULTS: Among 893 patients included in the primary analysis, thrombolytic-induced reperfusion was observed in 184 (21%) patients. Tenecteplase was associated with higher rates of reperfusion (adjusted incidence rate ratio [aIRR] = 1.50, 95% confidence interval [CI] = 1.09-2.07, p = 0.01). Findings were consistent in patient subgroups with first segment (aIRR = 1.41, 95% CI = 0.93-2.14) and second segment (aIRR = 2.07, 95% CI = 0.98-4.37) middle cerebral artery occlusions. Increased thrombolytic to reperfusion assessment times were associated with reperfusion (tenecteplase: adjusted risk ratio [aRR] = 1.08 per 15 minutes, 95% CI = 1.04-1.13 vs alteplase: aRR = 1.06 per 15 minutes, 95% CI = 1.00-1.13). No significant treatment-by-time interaction was observed (p = 0.87). Reperfusion via thrombolysis was associated with improved 90-day modified Rankin Scale scores (adjusted common odds ratio = 2.15, 95% CI = 1.54-3.01) compared to patients who achieved reperfusion following endovascular therapy. INTERPRETATION: Tenecteplase, compared to alteplase, increases prethrombectomy reperfusion, regardless of the time from administration to reperfusion assessment. Prethrombectomy reperfusion is associated with better clinical outcomes. ANN NEUROL 2023;93:489-499.

Thrombectomy Outcomes With General vs Nongeneral Anesthesia: A Pooled Patient-Level Analysis From the EXTEND-IA Trials and SELECT Study.

BACKGROUND AND OBJECTIVES: The effect of anesthesia choice on endovascular thrombectomy (EVT) outcomes is unclear. Collateral status on perfusion imaging may help identify the optimal anesthesia choice. METHODS: In a pooled patient-level analysis of EXTEND-IA, EXTEND-IA TNK, EXTEND-IA TNK part II, and SELECT, EVT functional outcomes (modified Rankin Scale score distribution) were compared between general anesthesia (GA) vs non-GA in a propensity-matched sample. Furthermore, we evaluated the association of collateral flow on perfusion imaging, assessed by hypoperfusion intensity ratio (HIR) - Tmax > 10 seconds/Tmax > 6 seconds (good collaterals - HIR < 0.4, poor collaterals - HIR ≥ 0.4) on the association between anesthesia type and EVT outcomes. RESULTS: Of 725 treated with EVT, 299 (41%) received GA and 426 (59%) non-GA. The baseline characteristics differed in presentation National Institutes of Health Stroke Scale score (median [interquartile range] GA: 18 [13-22], non-GA: 16 [11-20], p < 0.001) and ischemic core volume (GA: 15.0 mL [3.2-38.0] vs non-GA: 9.0 mL [0.0-31.0], p < 0.001). In addition, GA was associated with longer last known well to arterial access (203 minutes [157-267] vs 186 minutes [138-252], p = 0.002), but similar procedural time (35.5 minutes [23-59] vs 34 minutes [22-54], p = 0.51). Of 182 matched pairs using propensity scores, baseline characteristics were similar. In the propensity score-matched pairs, GA was independently associated with worse functional outcomes (adjusted common odds ratio [adj. cOR]: 0.64, 95% CI: 0.44-0.93, p = 0.021) and higher neurologic worsening (GA: 14.9% vs non-GA: 8.9%, aOR: 2.10, 95% CI: 1.02-4.33, p = 0.045). Patients with poor collaterals had worse functional outcomes with GA (adj. cOR: 0.47, 95% CI: 0.29-0.76, p = 0.002), whereas no difference was observed in those with good collaterals (adj. cOR: 0.93, 95% CI: 0.50-1.74, p = 0.82), p interaction: 0.07. No difference was observed in infarct growth overall and in patients with good collaterals, whereas patients with poor collaterals demonstrated larger infarct growth with GA with a significant interaction between collaterals and anesthesia type on infarct growth rate (p interaction: 0.020). DISCUSSION: GA was associated with worse functional outcomes after EVT, particularly in patients with poor collaterals in a propensity score-matched analysis from a pooled patient-level cohort from 3 randomized trials and 1 prospective cohort study. The confounding by indication may persist despite the doubly robust nature of the analysis. These findings have implications for randomized trials of GA vs non-GA and may be of utility for clinicians when making anesthesia type choice. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that use of GA is associated with worse functional outcome in patients undergoing EVT. TRIAL REGISTRATION INFORMATION: EXTEND-IA: ClinicalTrials.gov (NCT01492725); EXTEND-IA TNK: ClinicalTrials.gov (NCT02388061); EXTEND-IA TNK part II: ClinicalTrials.gov (NCT03340493); and SELECT: ClinicalTrials.gov (NCT02446587).

The use of augmented reality for patient and significant other stroke education: a feasibility study.

BACKGROUND: Stroke education is a key factor in minimising secondary stroke risk, yet worldwide stroke education rates are low. Technology has the potential to increase stroke education accessibility. One technology that could be beneficial is augmented reality (AR). We developed and trialled a stroke education lesson using an AR application with stroke patients and significant others. METHODS: A feasibility study design was used. Following development of the AR stroke education lesson, 19 people with stroke and three significant others trialled the lesson then completed a customised mixed method questionnaire. The lesson involved narrated audio while participants interacted with a model brain via a tablet. Information about participant recruitment and retention, usage, and perceptions were collected. RESULTS: Fifty-eight percent (n = 22) of eligible individuals consented to participate. Once recruited, 100% of participants (n = 22) were retained. Ninety percent of participants used the lesson once. Most participants used the application independently (81.82%, n = 18), had positive views about the lesson (over 80% across items including enjoyment, usefulness and perception of the application as a good learning tool) and reported improved confidence in stroke knowledge (72.73%, n = 16). Confidence in stroke knowledge post-lesson was associated with comfort using the application (p = 0.046, Fisher's exact test) and perception of the application as a good learning tool (p = 0.009, Fisher's exact test). CONCLUSIONS: Technology-enhanced instruction in the form of AR is feasible for educating patients and significant others about stroke. Further research following refinement of the lesson is required.

Prospective Observational Cohort Study of Tenecteplase Versus Alteplase in Routine Clinical Practice.

BACKGROUND: A 10-hospital regional network transitioned to tenecteplase as the standard of care stroke thrombolytic in September 2019 because of potential workflow advantages and reported noninferior clinical outcomes relative to alteplase in meta-analyses of randomized trials. We assessed whether tenecteplase use in routine clinical practice reduced thrombolytic workflow times with noninferior clinical outcomes. METHODS: We designed a prospective registry-based observational, sequential cohort comparison of tenecteplase- (n=234) to alteplase-treated (n=354) stroke patients. We hypothesized: (1) an increase in the proportion of patients meeting target times for target door-to-needle time and transfer door-in-door-out time, and (2) noninferior favorable (discharge to home with independent ambulation) and unfavorable (symptomatic intracranial hemorrhage, in-hospital mortality or discharge to hospice) in the tenecteplase group. Total hospital cost associated with each treatment was also compared. RESULTS: Target door-to-needle time within 45 minutes for all patients was superior for tenecteplase, 41% versus 29%; adjusted odds ratio, 1.85 (95% CI, 1.27-2.71); P=0.001; 58% versus 41% by Get With The Guidelines criteria. Target door-in-door-out time within 90 minutes was superior for tenecteplase 37% (15/43) versus 14% (9/65); adjusted odds ratio, 3.62 (95% CI, 1.30-10.74); P=0.02. Favorable outcome for tenecteplase fell within the 6.5% noninferiority margin; adjusted odds ratio, 1.26 (95% CI, 0.89-1.80). Unfavorable outcome was less for tenecteplase, 7.3% versus 11.9%, adjusted odds ratio, 0.77 (95% CI, 0.42-1.37) but did not fall within the prespecified 1% noninferior boundary. Net benefit (%favorable-%unfavorable) was greater for the tenecteplase sample: 37% versus 27%. P=0.02. Median cost per hospital encounter was less for tenecteplase cases ($13 382 versus $15 841; P<0.001). CONCLUSIONS: Switching to tenecteplase in routine clinical practice in a 10-hospital network was associated with shorter door-to-needle time and door-in-door-out times, noninferior favorable clinical outcomes at discharge, and reduced hospital costs. Evaluation in larger, multicenter cohorts is recommended to determine if these observations generalize.

Impact of COVID-19 on ready-mix concrete (RMC) industry in Ahmedabad - A case study.

India witnessed its first case of coronavirus infection (COVID-19) on January 27, 2020, in Kerala, India. Since then, the infection has spread rapidly across the country and the pandemic outbreak has affected all industries severely including the construction sector. This study aims to understand the effect of the COVID-19 pandemic on the construction sector, particularly the ready-mix concrete (RMC) industry. An attempt was made to investigate the liabilities and the losses incurred by the RMC industry in terms of income and change in the production of concrete during the coronavirus outbreak. A preliminary survey was carried out to create a database of the RMC plants located nearby the study area i.e., Ahmedabad City in the state of Gujarat, and to prepare a questionnaire using google forms. The RMC plants were visited and from the inputs of RMC officials, statistical insights were drawn. The study reveals that during the COVID-19 lockdown period there was almost a 40% loss in concrete production & 60% loss in the income generated by the ready-mix concrete industry. In addition to this, it was also found that the industry had to pay off liabilities like land rent, electricity bills, staff salaries, etc. during the time of the pandemic. This study provides the opportunity for RMC plants to identify the vital elements involved in the operation of the plant which can be affected due to such pandemic and provides guidelines to reduce the effect of any such pandemic on the plant's production & sales by ensuring the stability of all assets involved in its supply chain.

What do stroke survivors want in stroke education and information provision in Australia?

Despite evidence that stroke education is important and effective, low rates of stroke education are reported worldwide. Many stroke survivors and carers report that current stroke information does not meet their needs. The aim of the current study was to explore the perceptions of stroke survivors and carers towards stroke education in an Australian health context. A qualitative descriptive approach using focus groups was used to explore education received and preferred content, format and timing of education. Data were analysed inductively using qualitative content analysis to identify key categories, sub-categories and an overarching theme. Fifteen stroke survivors and four carers participated. Four categories emerged: the timing of stroke education, the content of stroke education, the format of stroke education, and reactions to stroke education. Each category contained a number of sub-categories. One overarching theme was woven through the transcripts: everyone is different and has different needs. Overall, participants generally expressed positive attitudes towards stroke education. Participants reported that education should occur at multiple timepoints and in a mixed format. All participants reported receiving stroke education in hospital, but not in the community. Stroke survivors preferred group education, while carers did not share this preference. Both stroke survivors and carers desired information about post-stroke physical changes and computer use; however, stroke survivors desired additional information spanning a variety of areas such as motivation and driving. Tailoring of stroke education for each individual is critical to ensure that education meets the needs of stroke survivors and carers from the hospital to the community.

Biomechanics and Outcomes of Modern Tibial Polyethylene Inserts.

PURPOSE OF REVIEW: There have been many attempts to use variations in tibial polyethylene design to better recreate normal knee kinematics in the total knee arthroplasty. The goal of this review is to provide an overview of the various types of tibial inserts that exist and review the theoretical mechanics versus what was demonstrated in vivo. RECENT FINDINGS: Many polyethylene inserts have been attempted to re-create normal knee kinematics, but none have been able to successfully do so. Previously the only two types of inserts were posterior stabilized (PS) and cruciate retaining (CR) polyethylene inserts. Both of these have shown excellent long-term survival but neither has demonstrated native kinematics. Initially, it was thought that retention of the posterior cruciate ligament (PCL) would allow for more native kinematics, but fluoroscopic evidence has shown that the PCL alone cannot accomplish this. Newer inserts try to restore femoral roll back and the screw home mechanism. The bicruciate retaining total knee inserts are having the most "normal" kinematics, suggesting the importance of both the ACL and PCL in knee biomechanics. Modern polyethylene inserts show favorable short-term data with bicruciate retaining inserts having the best kinematics; however, long-term studies are still needed to determine if survivorship and patient outcomes remain favorable.

Stress Radiograph Confirmation of Translational Instability After Cruciate-Retaining Total Knee Arthroplasty.

INTRODUCTION: Late rupture of the posterior cruciate ligament (PCL) in cruciate-retaining total knee arthroplasty (TKA) can lead to increased AP instability. This results in increased stress on the medial hamstrings resulting in hamstring-based pain. We looked to identify patients with late PCL failure using a lateral stress radiograph. METHODS: A prospective cohort analysis was completed at a single institution. Eligible patients were divided into two groups based on the amount of anterior knee pain. Pain was defined as a visual analog scale of greater than or equal to 3. Each group completed a visual analog scale, Knee Injury and Osteoarthritis Outcome Score Junior, Patient-Reported Outcome Measurement Information System score and underwent a lateral posterior stress/nonstress radiograph. Amount of posterior translation and posterior tibial slope was measured. RESULTS: Patients who had painful TKAs at the follow-up had lower Knee Injury and Osteoarthritis Outcome Score Junior (45.86 ± 13.52 versus 78.00 ± 13.26 P < 0.001). Those patients were also found to have significantly higher posterior tibial translation with stress radiograph (6.89 ± 1.874 versus 3.91 ± 2.15 mm P < 0.001) and significantly increased tibial slope (6.51 ± 2.37° versus 3.98 ± 1.79°, P = 0.004). Seven of the 14 patients in the pain group underwent revision surgery, with 6 patients found to have incompetent PCLs. DISCUSSION: Patients with increased AP translation and increased posterior tibial slope after cruciate-retaining TKA are likely to have worse pain and outcome measures.

Endovascular Thrombectomy Versus Medical Management in Isolated M2 Occlusions: Pooled Patient-Level Analysis from the EXTEND-IA Trials, INSPIRE, and SELECT Studies.

OBJECTIVE: The objective of this study was to evaluate functional and safety outcomes of endovascular thrombectomy (EVT) versus medical management (MM) in patients with M2 occlusion and examine their association with perfusion imaging mismatch and stroke severity. METHODS: In a pooled, patient-level analysis of 3 randomized controlled trials (EXTEND-IA, EXTEND-and IA-TNK parts 1 and 2) and 2 prospective nonrandomized studies (INSPIRE and SELECT), we evaluated EVT association with 90-day functional independence (modified Rankin Scale [mRS] = 0-2) in isolated M2 occlusions as compared to medical management overall and in subgroups by mismatch profile status and stroke severity. RESULTS: We included 517 patients (EVT = 195 and MM = 322), baseline median (interquartile range [IQR]) National Institutes of Health Stroke Scale (NIHSS) was 13 (8-19) in EVT versus 10 (6-15) in MM, p < 0.001. Pretreatment ischemic core did not differ (EVT = 10 [0-24] ml vs MM = 9 [3-21] ml, p = 0.59). Compared to MM, EVT was more frequently associated with functional independence (68.3 vs 61.6%, adjusted odds ratio [aOR] = 2.42, 95% confidence interval [CI] = 1.25-4.67, p = 0.008, inverse probability of treatment weights [IPTW]-OR = 1.75, 95% CI = 1.00-3.75, p = 0.05) with a shift toward better mRS outcomes (adjusted cOR = 2.02, 95% CI:1.23-3.29, p = 0.005), and lower mortality (5 vs 10%, aOR = 0.32, 95% CI = 0.12-0.87, p = 0.025). EVT was associated with higher functional independence in patients with a perfusion mismatch profile (EVT = 70.7% vs MM = 61.3%, aOR = 2.29, 95% CI = 1.09-4.79, p = 0.029, IPTW-OR = 2.02, 1.08-3.78, p = 0.029), whereas no difference was found in those without mismatch (EVT = 43.8% vs MM = 62.7%, p = 0.17, IPTW-OR: 0.71, 95% CI = 0.18-2.78, p = 0.62). Functional independence was more frequent with EVT in patients with moderate or severe strokes, as defined by baseline NIHSS above any thresholds from 6 to 10, whereas there was no difference between groups with milder strokes below these thresholds. INTERPRETATION: In patients with M2 occlusion, EVT was associated with improved clinical outcomes when compared to MM. This association was primarily observed in patients with a mismatch profile and those with higher stroke severity. ANN NEUROL 2022;91:629-639.

Impact of in utero opioid exposure on newborn outcomes: beyond neonatal opioid withdrawal syndrome.

BACKGROUND AND OBJECTIVES: Research on in utero opioid exposure impacts has focused on Neonatal Opioid Withdrawal Syndrome (NOWS). However, possible impacts on fetal growth and newborn wellbeing have emerged, with inconsistencies likely driven by methodological issues. Our goal was to compare birth outcomes between newborns with prenatal opioid exposure and a matched control group. METHODS: Participants were identified via manual review of electronic medical records of all deliveries over five years within a regional health system (6 delivery hospitals across 2 states). From over 18,000 births, 300 with prenatal opioid exposure and 300 control newborns matched on exposure, medical, and background factors were included. Additional factors were statistically controlled. Outcomes included pregnancy/delivery complications, newborn size, and newborn health complications. RESULTS: Compared to biochemically verified controls, exposed newborns had higher rates of fetal growth restriction, weighed less, had decreased length and head circumference, and had higher rates of respiratory distress, sepsis, and jaundice. No significant differences in gestational length, Apgar scores, or neonatal hypoglycemia were found. Adjusted regression analyses revealed that compared to controls, those exposed had an average 150 g decrease in birth weight, a two-fold increased risk for IUGR (OR = 2.09), a nearly three-fold (OR = 2.80) increased risk for jaundice, a more than seven-fold (OR = 7.40) increased risk for respiratory distress, and a thirty-fold (OR = 30.47) increased risk for sepsis. CONCLUSIONS: Results suggest significant pregnancy and newborn outcomes beyond NOWS following pregnancy opioid use, informing clinical screening and treatment decisions to enhance health and wellbeing in pregnancy, during the neonatal period, and beyond.

Effect of the Coronavirus Disease 2019 Pandemic on the Quality of Stroke Care in Stroke Units and Alternative Wards: A National Comparative Analysis.

BACKGROUND AND PURPOSE: Changes to hospital systems were implemented from March 2020 in Australia in response to the coronavirus disease 2019 pandemic, including decreased resources allocated to stroke units. We investigate changes in the quality of acute care for patients with stroke or transient ischemic attack during the pandemic according to patients' treatment setting (stroke unit or alternate ward). METHODS: We conducted a retrospective cohort study of patients admitted with stroke or transient ischemic attack between January 2019 and June 2020 in the Australian Stroke Clinical Registry (AuSCR). The AuSCR monitors patients' treatment setting, provision of allied health and nursing interventions, prescription of secondary prevention medications, and discharge destination. Weekly trends in the quality of care before and during the pandemic period were assessed using interrupted time series analyses. RESULTS: In total, 18,662 patients in 2019 and 8,850 patients in 2020 were included. Overall, 75% were treated in stroke units. Before the pandemic, treatment in a stroke unit was superior to alternate wards for the provision of all evidence-based therapies assessed. During the pandemic period, the proportion of patients receiving a swallow screen or assessment, being discharged to rehabilitation, and being prescribed secondary prevention medications decreased by 0.58% to 1.08% per week in patients treated in other ward settings relative to patients treated in stroke units. This change represented a 9% to 17% increase in the care gap between these treatment settings during the period of the pandemic that was evaluated (16 weeks). CONCLUSIONS: During the first 6 months of the pandemic, widening care disparities between stroke units and alternate wards have occurred.

Reduced Severity of Tissue Injury Within the Infarct May Partially Mediate the Benefit of Reperfusion in Ischemic Stroke.

BACKGROUND: Emerging data suggest tissue within the infarct lesion is not homogenously damaged following ischemic stroke but has a gradient of injury. Using blood-brain-barrier (BBB) disruption as a marker of tissue injury, we tested whether therapeutic reperfusion improves clinical outcome by reducing the severity of tissue injury within the infarct in patients with ischemic stroke. METHODS: In a pooled analysis of patients treated for anterior circulation large vessel occlusion in the EXTEND-IA TNK (Tenecteplase Versus Alteplase Before Endovascular Therapy for Ischemic Stroke) and EXTEND-IA part-2 (Determining the Optimal Dose of Tenecteplase Before Endovascular Therapy for Ischaemic Stroke) trials, post-treatment BBB permeability at 24 hours was calculated based on the extent of T1-brightening by extravascular gadolinium on T2* perfusion-weighted imaging and measured within the diffusion-weighted-imaging lesion. First, to determine the clinical significance of BBB disruption as a marker of severity of tissue injury, we examined the association between post-treatment BBB permeability and functional outcome. Second, we performed an exploratory (reperfusion, BBB permeability, functional outcome) mediation analysis to estimate the proportion of the reperfusion-outcome relationship that is mediated by change in BBB permeability. RESULTS: In the 238 patients analyzed, an increased BBB permeability measured within the infarct at 24 hours was associated with a reduced likelihood of favorable outcome (90-day modified Rankin Scale score of ≤2) after adjusting for age, baseline National Institutes of Health Stroke Scale, premorbid modified Rankin Scale, infarct topography, laterality, thrombolytic agent, sex, parenchymal hematoma, and follow-up infarct volume (adjusted odds ratio, 0.86 [95% CI, 0.75-0.98]; P=0.023). Mediation analysis suggested reducing the severity of tissue injury (as estimated by BBB permeability) accounts for 18.2% of the association between reperfusion and favorable outcome, as indicated by a reduction in the regression coefficient of reperfusion after addition of BBB permeability as a covariate. CONCLUSIONS: In patients with ischemic stroke, reduced severity of tissue injury within the infarct, as determined by assessing the integrity of the BBB, is independently associated with improved functional outcome. In addition to reducing diffusion-weighted imaging-defined infarct volume, reperfusion may also improve clinical outcome by reducing tissue injury severity within the infarct.