Combining Early Ischemic Change and Collateral Extent for Functional Outcomes After Endovascular Therapy: An Analysis From AcT Trial.

BACKGROUND: Early ischemic change and collateral extent are colinear with ischemic core volume (ICV). We investigated the relationship between a combined score using the Alberta Stroke Program Early Computed Tomography Score and multiphase computed tomography angiography (mCTA) collateral extent, named mCTA-ACE score, on functional outcomes in endovascular therapy-treated patients. METHODS: We performed a post hoc analysis of a subset of endovascular therapy-treated patients from the Alteplase Compared to Tenecteplase trial which was conducted between December 2019 and January 2022 at 22 centers across Canada. Ten-point mCTA collateral corresponding to M2 to M6 regions of the Alberta Stroke Program Early Computed Tomography Score grid was evaluated as 0 (poor), 1 (moderate), or 2 (normal) and additively combined with the 10-point Alberta Stroke Program Early Computed Tomography Score to produce a 20-point mCTA-ACE score. We investigated the association of mCTA-ACE score with modified Rankin Scale score ≤2 and return to prestroke level of function at 90 to 120 days using mixed-effects logistic regression. In the subset of patients who underwent baseline computed tomography perfusion imaging, we compared the mCTA-ACE score and ICV for outcome prediction. RESULTS: Among 1577 intention-to-treat population in the trial, 368 (23%; 179 men; median age, 73 years) were included, with Alberta Stroke Program Early Computed Tomography Score, mCTA collateral, and combination of both (mCTA-ACE score: median [interquartile range], 8 [7-10], 9 [8-10], and 17 [16-19], respectively). The probability of modified Rankin Scale score ≤2 and return to prestroke level of function increased for each 1-point increase in mCTA-ACE score (odds ratio, 1.16 [95% CI, 1.06-1.28] and 1.22 [95% CI, 1.06-1.40], respectively). Among 173 patients in whom computed tomography perfusion data was assessable, the mCTA-ACE score was inversely correlated with ICV (ρ=-0.46; P<0.01). The mCTA-ACE score was comparable to ICV to predict a modified Rankin Scale score ≤2 and return to prestroke level of function (C statistics 0.71 versus 0.69 and 0.68 versus 0.64, respectively). CONCLUSIONS: The mCTA-ACE score had a significant positive association with functional outcomes after endovascular therapy and had a similar predictive performance as ICV.

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.

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.

Unsupervised item response theory models for assessing sample heterogeneity in patient-reported outcomes measures.

PURPOSE: Unsupervised item-response theory (IRT) models such as polytomous IRT based on recursive partitioning (IRTrees) and mixture IRT (MixIRT) models can be used to assess differential item functioning (DIF) in patient-reported outcome measures (PROMs) when the covariates associated with DIF are unknown a priori. This study examines the consistency of results for IRTrees and MixIRT models. METHODS: Data were from 4478 individuals in the Alberta Provincial Project on Outcome Assessment in Coronary Heart Disease registry who received cardiac angiography in Alberta, Canada, and completed the Hospital Anxiety and Depression Scale (HADS) depression subscale items. The partial credit model (PCM) based on recursive partitioning (PCTree) and mixture PCM (MixPCM) were used to identify covariates associated with differential response patterns to HADS depression subscale items. Model covariates included demographic and clinical characteristics. RESULTS: The median (interquartile range) age was 64.5(15.7) years, and 3522(78.5%) patients were male. The PCTree identified 4 terminal nodes (subgroups) defined by smoking status, age, and body mass index. A 3-class PCM fits the data well. The MixPCM latent classes were defined by age, disease indication, smoking status, comorbid diabetes, congestive heart failure, and chronic obstructive pulmonary disease. CONCLUSION: PCTree and MixPCM were not consistent in detecting covariates associated with differential interpretations of PROM items. Future research will use computer simulations to assess these models' Type I error and statistical power for identifying covariates associated with DIF.

Response shift in coronary artery disease.

PURPOSE: Patients with coronary artery disease (CAD) experience significant angina symptoms and lifestyle changes. Revascularization procedures can result in better patient-reported outcomes (PROs) than optimal medical therapy (OMT) alone. This study evaluates the impact of response shift (RS) on changes in PROs of patients with CAD across treatment strategies. METHODS: Data were from patients with CAD in the Alberta Provincial Project on Outcome Assessment in Coronary Heart Disease (APPROACH) registry who completed the 16-item Canadian version of the Seattle Angina Questionnaire at 2 weeks and 1 year following a coronary angiogram. Multi-group confirmatory factor analysis (MG-CFA) was used to assess measurement invariance across treatment groups at week 2. Longitudinal MG-CFA was used to test for RS according to receipt of coronary artery bypass grafting (CABG), percutaneous coronary intervention (PCI), or optimal medical therapy (OMT) alone. RESULTS: Of the 3116 patients included in the analysis, 443 (14.2%) received CABG, 2049(65.8%) PCI, and the remainder OMT alone. The MG-CFA revealed a partial-strong invariance across the treatment groups at 2 weeks (CFI = 0.98, RMSEA [90% CI] = 0.05 [0.03, 0.06]). Recalibration RS was detected on the Angina Symptoms and Burden subscale and its magnitude in the OMT, PCI, and CABG groups were 0.32, 0.28, and 0.53, respectively. After adjusting for RS effects, the estimated target changes were largest in the CABG group and negligible in the OMT group. CONCLUSION: Adjusting for RS is recommended in studies that use SAQ-CAN to assess changes in patients with CAD who have received revascularization versus OMT alone.

Workflow and Outcome of Thrombectomy in Late Time Window: A Pooled Multicenter Analysis.

BACKGROUND: We investigated the impact of workflow times on the outcomes of patients treated with endovascular thrombectomy (EVT) in the late time window. METHODS: Individual patients' data who underwent EVT in the late time window (onset to imaging >6 hours) were pooled from seven registries and randomized clinical trials. Multiple time intervals were analyzed. Mixed-effects logistic regression was used to estimate the likelihood of functional independence at 90 days (modified Rankin Scale 0-2). Mixed-effects negative binomial regression was used to evaluate the relationship between patient characteristics and workflow time intervals. RESULTS: 608 patients were included. The median age was 70 years (IQR: 58-71), 307 (50.5%) were female, and 310 (53.2%) had wake-up strokes. Successful reperfusion was achieved in 493 (81.2%) patients, and 262 (44.9%) achieved 90-day mRS 0-2. The estimated odds of functional independence decreased by 13% for every 30 minute delay from emergency department (ED) arrival to imaging time and by 7% from ED arrival to the end of EVT in the entire cohort. Also, the estimated odds of functional independence decreased by 33% for every 30 minute delay in the interval from arterial puncture to end of EVT, 16% in the interval from arrival in ED to end of EVT and 6% in the interval from stroke onset to end of EVT among patients who had a wake-up stroke. CONCLUSION: Faster workflow from ED arrival to end of EVT is associated with improved functional independence among stroke patients treated in the late window.

Validating the Ontario Child Health Study Emotional Behavioural Scales-Brief Version (OCHS-EBS-B) in children with chronic physical illness.

BACKGROUND: A substantial proportion of children have a physical illness; these children commonly experience physical-mental comorbidity. To assess child mental health, brief scales that can be used in clinical and research settings are needed. This study assessed the validity and reliability of parent-reported Ontario Child Health Study Emotional Behavioural Scale-Brief Version (OCHS-EBS-B) scores. METHODS: Data come from a longitudinal study of children aged 2-16 years with a physical illness recruited from outpatient clinics at a pediatric hospital. Confirmatory factor analysis and McDonald's coefficient assessed the factor structure and internal consistency reliability of the OCHS-EBS-B, respectively. Point biserial correlations assessed agreement between the OCHS-EBS-B and Mini International Neuropsychiatric Interview for Children and Adolescents (MINI-KID), a structured diagnostic interview. The Wilcoxon rank sum test compared OCHS-EBS-B scores between children with versus without physical-mental comorbidity (known-group validity). RESULTS: The three-factor structure of the OCHS-EBS-B was replicated in this sample of children with physical illness (χ2 = 196.23(272), p < 0.001; CFI = 0.98; TLI = 0.98; SRMR = 0.06; RMSEA [90% CI] = 0.034 [0.027, 0.044]). It had excellent internal consistency reliability (ω = 0.86-0.92) and was moderately correlated with the MINI-KID (baseline: rpb = 0.43-0.51; 6 months: rpb = 0.55-0.65). OCHS-EBS-B scores were significantly higher among children with versus without physical-mental comorbidity. CONCLUSIONS: Findings confirm psychometric evidence that the OCHS-EBS-B is a valid and reliable measure of mental health in children with chronic physical illness. Its brevity and robust psychometric properties make the OCHS-EBS-B a strong candidate for routine use in integrated pediatric physical and mental health services.

Poor postoperative pain control is associated with poor long-term patient-reported outcomes after elective spine surgery: an observational cohort study.

BACKGROUND CONTEXT: A significant proportion of patients experience poorly controlled surgical pain and fail to achieve satisfactory clinical improvement after spine surgery. However, a direct association between these variables has not been previously demonstrated. PURPOSE: To investigate the association between poor postoperative pain control and patient-reported outcomes after spine surgery. STUDY DESIGN: Ambispective cohort study. PATIENT SAMPLE: Consecutive adult patients (≥18-years old) undergoing inpatient elective cervical or thoracolumbar spine surgery. OUTCOME MEASURE: Poor surgical outcome was defined as failure to achieve a minimal clinically important difference (MCID) of 30% improvement on the Oswestry Disability Index or Neck Disability Index at follow-up (3-months, 1-year, and 2-years). METHODS: Poor pain control was defined as a mean numeric rating scale score of >4 during the first 24-hours after surgery. Multivariable mixed-effects regression was used to investigate the relationship between poor pain control and changes in surgical outcomes while adjusting for known confounders. Secondarily, the Calgary Postoperative Pain After Spine Surgery (CAPPS) Score was investigated for its ability to predict poor surgical outcome. RESULTS: Of 1294 patients, 47.8%, 37.3%, and 39.8% failed to achieve the MCID at 3-months, 1-year, and 2-years, respectively. The incidence of poor pain control was 56.9%. Multivariable analyses showed poor pain control after spine surgery was independently associated with failure to achieve the MCID (OR 2.35 [95% CI=1.59-3.46], p<.001) after adjusting for age (p=.18), female sex (p=.57), any nicotine products (p=.041), ASA physical status >2 (p<.001), ≥3 motion segment surgery (p=.008), revision surgery (p=.001), follow-up time (p<.001), and thoracolumbar surgery compared to cervical surgery (p=.004). The CAPPS score was also found to be independently predictive of poor surgical outcome. CONCLUSION: Poor pain control in the first 24-hours after elective spine surgery was an independent risk factor for poor surgical outcome. Perioperative treatment strategies to improve postoperative pain control may lead to improved patient-reported surgical outcomes.