Risk of stroke within 3, 7, 14, 21 and 30 days after influenza vaccination in Alberta, Canada: A population-based study.

BACKGROUND AND PURPOSE: Influenza vaccination is associated with a longer-term protective effect against stroke; however, it has a short-term inflammatory response which may increase short-term risk of stroke. The aim was to investigate the association between influenza vaccination and short-term risk of stroke in adults. METHODS: Administrative data were obtained from the Alberta Health Care Insurance Plan for all adults in Alberta, Canada, from September 2009 to December 2018. The hazard of any stroke (acute ischaemic stroke, intracerebral haemorrhage, subarachnoid haemorrhage and transient ischaemic attack) within 3, 7, 14, 21 and 30 days of influenza vaccination compared to unexposed time was analysed using Andersen-Gill Cox models, with adjustment for age, sex, anticoagulant use, atrial fibrillation, chronic obstructive pulmonary disease, diabetes, hypertension, income quintile, and rural or urban home location. RESULTS: In the entire cohort consisting of 4,141,209 adults (29,687,899 person-years), 1,769,565 (42.7%) individuals received at least one vaccination. In total 38,126 stroke events were recorded with 1309 occurring within 30 days of a vaccination event. Influenza vaccination was associated with a significantly reduced hazard of stroke within 3 days (hazard ratio [HR] 0.83, 95% confidence interval [CI] 0.73-0.93), 7 days (HR 0.87, 95% CI 0.80-0.95), 14 days (HR 0.87, 95% CI 0.81-0.93), 21 days (HR 0.85, 95% CI 0.80-0.91) and 30 days (HR 0.66, 95% CI 0.65-0.68). CONCLUSIONS: An increased early risk associated with vaccination was not observed. The risk of stroke was reduced at all time points within 30 days after influenza vaccination.

Adverse Events and Serological Responses After SARS-CoV-2 Vaccination in Individuals With Inflammatory Bowel Disease.

INTRODUCTION: We determined adverse events after 4 doses of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) vaccine in those with inflammatory bowel disease (IBD), associations between antibodies and injection site reactions (ISR), and risk of IBD flare. METHODS: Individuals with IBD were interviewed for adverse events to SARS-CoV-2 vaccine. Multivariable linear regression assessed the association between antibody titers and ISR. RESULTS: Severe adverse events occurred in 0.03%. ISR were significantly associated with antibody levels after the fourth dose (geometric mean ratio = 2.56; 95% confidence interval 1.18-5.57). No cases of IBD flare occurred. DISCUSSION: SARS-CoV-2 vaccines are safe for those with IBD. ISR after the fourth dose may indicate increased antibodies.

Estimating the Number of Hospital or Emergency Department Presentations for Stroke in Canada.

BACKGROUND: Although age-standardized stroke occurrence has been decreasing, the absolute number of stroke events globally, and in Canada, is increasing. Stroke surveillance is necessary for health services planning, informing research design, and public health messaging. We used administrative data to estimate the number of stroke events resulting in hospital or emergency department presentation across Canada in the 2017-18 fiscal year. METHODS: Hospitalization data were obtained from the Canadian Institute for Health Information (CIHI) Discharge Abstract Database and the Ministry of Health and Social Services in Quebec. Emergency department data were obtained from the CIHI National Ambulatory Care Reporting System (Alberta and Ontario). Stroke events were identified using ICD-10 coding. Data were linked into episodes of care to account for readmissions and interfacility transfers. Projections for emergency department visits for provinces/territories outside of Alberta and Ontario were generated based upon age and sex-standardized estimates from Alberta and Ontario. RESULTS: In the 2017-18 fiscal year, there were 108,707 stroke events resulting in hospital or emergency department presentation across the country. This was made up of 54,357 events resulting in hospital admission and 54,350 events resulting in only emergency department presentation. The events resulting in only emergency department presentation consisted of 25,941 events observed in Alberta and Ontario and a projection of 28,409 events across the rest of the country. CONCLUSIONS: We estimate a stroke event resulting in hospital or emergency department presentation occurs every 5 minutes in Canada.

Sex Differences of Hospital and Emergency Department Presentations of Stroke in Canada.

We provide an updated estimate of adult stroke event rates by age group, sex, and stroke type using Canadian administrative data. In the 2017-2018 fiscal year, there were an estimated 81,781 hospital or emergency department visits for stroke events in Canada, excluding Quebec. Our findings show that overall, the event rate of stroke is similar between women and men. There were slight differences in stroke event rate at various ages by sex and stroke type and emerging patterns warrant attention in future studies. Our findings emphasize the importance of continuous surveillance to monitor the epidemiology of stroke in Canada.

Quantifying Improved Outcomes, Cost Savings, and Hospital Volume Changes From Optimized Emergency Stroke Transport.

BACKGROUND: A previously published conditional probability model optimizes prehospital emergency transport protocols for patients with suspected large-vessel occlusion by recommending the transport strategy, drip-and-ship or mothership, that results in a higher probability of an excellent outcome. In this study, we create generalized models to quantify the change in annual hospital patient volume, the expected annual increase in the number of patients with an excellent outcome, and the annual cost savings to a single-payer healthcare system resulting from these optimized transport protocols. METHODS: We calculated the expected number of patients with suspected large-vessel occlusion transported by ambulance over a 1-year period in a region of interest, using the annual stroke incidence rate and a large-vessel occlusion screening tool. Assuming transport to the closest hospital is the baseline transport policy across the region (drip-and-ship), we determined the change in annual hospital patient volume from implementing optimized transport protocols. We also calculated the resulting annual increase in the number of patients with an excellent outcome (modified Rankin Score of 0-1 at 90 days) and associated cost savings to a single-payer healthcare system. We then performed a case study applying these generalized models to the stroke system serving the Greater Vancouver and Fraser Valley Area, BC, Canada. RESULTS: In the Greater Vancouver and Fraser Valley Area, there was an annual increase of 36 patients with an excellent outcome, translating to an annual cost savings of CA$2 182 824 to the British Columbia healthcare system. We also studied how these results change depending on our assumptions of treatment times at the regional stroke centers. CONCLUSIONS: Our framework quantifies the impact of optimized emergency stroke transport protocols on hospital volume, outcomes, and cost savings to a single-payer healthcare system. When applied to a specific region of interest, these models can help inform health policies concerning emergency transport of patients with suspected large-vessel occlusion.

Changes in ischemic stroke presentations, management and outcomes during the first year of the COVID-19 pandemic in Alberta: a population study.

BACKGROUND: Pandemics may promote hospital avoidance, and added precautions may exacerbate treatment delays for medical emergencies such as stroke. We sought to evaluate ischemic stroke presentations, management and outcomes during the first year of the COVID-19 pandemic. METHODS: We conducted a population-based study, using linked administrative and stroke registry data from Alberta to identify all patients presenting with stroke before the pandemic (Jan. 1, 2016 to Feb. 27, 2020) and in 5 periods over the first pandemic year (Feb. 28, 2020 to Mar. 31, 2021), reflecting changes in case numbers and restrictions. We evaluated changes in hospital admissions, emergency department presentations, thrombolysis, endovascular therapy, workflow times and outcomes. RESULTS: The study included 19 531 patients in the prepandemic period and 4900 patients across the 5 pandemic periods. Presentations for ischemic stroke dropped in the first pandemic wave (weekly adjusted incidence rate ratio [IRR] 0.54, 95% confidence interval [CI] 0.50 to 0.59). Population-level incidence of thrombolysis (adjusted IRR 0.50, 95% CI 0.41 to 0.62) and endovascular therapy (adjusted IRR 0.63, 95% CI 0.47 to 0.84) also decreased during the first wave, but proportions of patients presenting with stroke who received acute therapies did not decline. Rates of patients presenting with stroke did not return to prepandemic levels, even during a lull in COVID-19 cases between the first 2 waves of the pandemic, and fell further in subsequent waves. In-hospital delays in thrombolysis or endovascular therapy occurred in several pandemic periods. The likelihood of in-hospital death increased in Wave 2 (adjusted odds ratio [OR] 1.48, 95% CI 1.25 to 1.74) and Wave 3 (adjusted OR 1.46, 95% CI 1.07 to 2.00). Out-of-hospital deaths, as a proportion of stroke-related deaths, rose during 4 of 5 pandemic periods. INTERPRETATION: The first year of the COVID-19 pandemic saw persistently reduced rates of patients presenting with ischemic stroke, recurrent treatment delays and higher risk of in-hospital death in later waves. These findings support public health messaging that encourages care-seeking for medical emergencies during pandemic periods, and stroke systems should re-evaluate protocols to mitigate inefficiencies.

Determinants of Leptomeningeal Collateral Status Variability in Ischemic Stroke Patients.

BACKGROUND: Collateral status is an indicator of a favorable outcome in stroke. Leptomeningeal collaterals provide alternative routes for brain perfusion following an arterial occlusion or flow-limiting stenosis. Using a large cohort of ischemic stroke patients, we examined the relative contribution of various demographic, laboratory, and clinical variables in explaining variability in collateral status. METHODS: Patients with acute ischemic stroke in the anterior circulation were enrolled in a multi-center hospital-based observational study. Intracranial occlusions and collateral status were identified and graded using multiphase computed tomography angiography. Based on the percentage of affected territory filled by collateral supply, collaterals were graded as either poor (0-49%), good (50-99%), or optimal (100%). Between-group differences in demographic, laboratory, and clinical factors were explored using ordinal regression models. Further, we explored the contribution of measured variables in explaining variance in collateral status. RESULTS: 386 patients with collateral status classified as poor (n = 64), good (n = 125), and optimal (n = 197) were included. Median time from symptom onset to CT was 120 (IQR: 78-246) minutes. In final multivariable model, male sex (OR 1.9, 95% CIs [1.2, 2.9], p = 0.005) and leukocytosis (OR 1.1, 95% CIs [1.1, 1.2], p = 0.001) were associated with poor collaterals. Measured variables only explained 44.8-53.0% of the observed between-patient variance in collaterals. CONCLUSION: Male sex and leukocytosis are associated with poorer collaterals. Nearly half of the variance in collateral flow remains unexplained and could be in part due to genetic differences.

Comparing regression modeling strategies for predicting hometime.

BACKGROUND: Hometime, the total number of days a person is living in the community (not in a healthcare institution) in a defined period of time after a hospitalization, is a patient-centred outcome metric increasingly used in healthcare research. Hometime exhibits several properties which make its statistical analysis difficult: it has a highly non-normal distribution, excess zeros, and is bounded by both a lower and upper limit. The optimal methodology for the analysis of hometime is currently unknown. METHODS: Using administrative data we identified adult patients diagnosed with stroke between April 1, 2010 and December 31, 2017 in Ontario, Canada. 90-day hometime and clinically relevant covariates were determined through administrative data linkage. Fifteen different statistical and machine learning models were fit to the data using a derivation sample. The models' predictive accuracy and bias were assessed using an independent validation sample. RESULTS: Seventy-five thousand four hundred seventy-five patients were identified (divided into a derivation set of 49,402 and a test set of 26,073). In general, the machine learning models had lower root mean square error and mean absolute error than the statistical models. However, some statistical models resulted in lower (or equal) bias than the machine learning models. Most of the machine learning models constrained predicted values between the minimum and maximum observable hometime values but this was not the case for the statistical models. The machine learning models also allowed for the display of complex non-linear interactions between covariates and hometime. No model captured the non-normal bucket shaped hometime distribution. CONCLUSIONS: Overall, no model clearly outperformed the others. However, it was evident that machine learning methods performed better than traditional statistical methods. Among the machine learning methods, generalized boosting machines using the Poisson distribution as well as random forests regression were the best performing. No model was able to capture the bucket shaped hometime distribution and future research on factors which are associated with extreme values of hometime that are not available in administrative data is warranted.

Using random forests to model 90-day hometime in people with stroke.

BACKGROUND: Ninety-day hometime, the number of days a patient is living in the community in the first 90 after stroke, exhibits a non-normal bucket-shaped distribution, with lower and upper constraints making its analysis difficult. In this proof-of-concept study we evaluated the performance of random forests regression in the analysis of hometime. METHODS: Using administrative data we identified stroke hospitalizations between 2010 and 2017 in Ontario, Canada. We used random forests regression to predict 90-day hometime using 15 covariates. Model accuracy was determined using the r-squared statistic. Variable importance in prediction and the marginal effects of each covariate were explored. RESULTS: We identified 75,745 eligible patients. Median 90-day hometime was 59 days (Q1: 2, Q3: 83). Random forests predicted hometime with reasonable accuracy (adjusted r-squared 0.3462); no implausible values were predicted but extreme values were predicted with low accuracy. Frailty, stroke severity, and age exhibited inverse non-linear relationships with hometime and patients arriving by ambulance had less hometime than those who did not. CONCLUSIONS: Random forests may be a useful method for analyzing 90-day hometime and capturing the complex non-linear relationships which exist between predictors and hometime. Future work should compare random forests to other models and focus on improving the accuracy of predictions of extreme values of hometime.

Modeling the Optimal Transportation for Acute Stroke Treatment: The Impact of the Drip-and-Drive Paradigm.

Background and Purpose- Health systems are faced with the challenge of ensuring fast access to appropriate therapy for patients with acute stroke. The paradigms primarily discussed are mothership and drip and ship. Less attention has been focused on the drip-and-drive (DD) paradigm. Our aim was to analyze whether and under what conditions DD would predict the greatest probability of good outcome for patients with suspected ischemic stroke in Northwestern Germany. Methods- Conditional probability models based on the decay curves for endovascular therapy and intravenous thrombolysis were created to determine the best transport paradigm, and results were displayed using map visualizations. Our study area consisted of the federal states of Lower Saxony, Hamburg, and Schleswig-Holstein in Northwestern Germany covering an area of 64 065 km2 with a population of 12 703 561 in 2017 (198 persons per km2). In several scenarios, the catchment area, that is, the region that would result in the greatest probability of good outcomes, was calculated for each of the mothership, drip-and-ship, and the DD paradigms. Several different treatment time parameters were varied including onset-to-first-medical-response time, ambulance-on-scene time, door-to-needle time at primary stroke center, needle-to-door time, door-to-needle time at comprehensive stroke center, door-to-groin-puncture time, needle-to-interventionalist-leave time, and interventionalist-arrival-to-groin-puncture time. Results- The mothership paradigm had the largest catchment area; however, the DD catchment area was larger than the drip-and-ship catchment area so long as the needle-to-interventionalist-leave time and the interventionalist-arrival-to-groin-puncture time remain <40 minutes each. A slowed workflow in the DD paradigm resulted in a decrease of the DD catchment area to 1221 km2 (2%). Conclusions- Our study suggests the largest catchment area for the mothership paradigm and a larger catchment area of DD paradigm compared with the drip-and-ship paradigm in Northwestern Germany in most scenarios. The existence of different paradigms allows the spread of capacities, shares the cost and hospital income, and gives primary stroke centers the possibility to provide endovascular therapy services 24/7.

In What Scenarios Does a Mobile Stroke Unit Predict Better Patient Outcomes?: A Modeling Study.

Background and Purpose- The mobile stroke unit (MSU) brings imaging and thrombolysis to patients in the field. The MSU has the potential to decrease time from onset to thrombolysis; however, this depends on the location of the patient, the MSU, and the hospital. The MSU will only be able to treat a small subset of patients it is dispatched to. Using conditional probability modeling, we evaluate in which scenarios the MSU exhibits clear benefit over the direct-to-mothership method. Methods- Previously published conditional probability models for drip-and-ship versus mothership transport were modified to reflect MSU workflow. It was assumed that the MSU was dispatched from the endovascular therapy center. Eight scenarios were generated, varying treatment efficiency on the MSU and at the endovascular therapy center and the threshold for dispatching the MSU (low threshold: low treatment rate but few missed patients; high threshold: higher treatment rate, potential for missed treatment opportunities). Results- The relative difference in outcomes between the MSU and mothership was small. Geographic areas where the MSU is superior to mothership increase in size as treatment time on the MSU decreases. When a high-threshold dispatch system is used, the area where the MSU is superior decreases, but the relative difference in predicted outcomes between the MSU and mothership increases. The largest relative difference favoring the MSU was found in areas where the patient would forgo access to alteplase, based upon a 4.5-hour treatment threshold, using mothership transport. Conclusions- There are few scenarios where MSU transport predicts substantially superior outcomes to the mothership method when the MSU is dispatched from the endovascular therapy center. Outcomes using the MSU are maximized when dispatch criteria that maximize patients eligible for thrombolysis treatment are used and treatment times on the MSU are short relative to those of the endovascular therapy center.

Drip 'n Ship Versus Mothership for Endovascular Treatment: Modeling the Best Transportation Options for Optimal Outcomes.

BACKGROUND AND PURPOSE: There is uncertainty regarding the best way for patients outside of endovascular-capable or Comprehensive Stroke Centers (CSC) to access endovascular treatment for acute ischemic stroke. The role of the nonendovascular-capable Primary Stroke Centers (PSC) that can offer thrombolysis with alteplase but not endovascular treatment is unclear. A key question is whether average benefit is greater with early thrombolysis at the closest PSC before transportation to the CSC (Drip 'n Ship) or with PSC bypass and direct transport to the CSC (Mothership). Ideal transportation options were mapped based on the location of their endovascular-capable CSCs and nonendovascular-capable PSCs. METHODS: Probability models for endovascular treatment were developed from the ESCAPE trial's (Endovascular Treatment for Small Core and Anterior Circulation Proximal Occlusion With Emphasis on Minimizing CT to Recanalization Times) decay curves and for alteplase treatment were extracted from the Get With The Guidelines decay curve. The time on-scene, needle-to-door-out time at the PSC, door-to-needle time at the CSC, and door-to-reperfusion time were assumed constant at 25, 20, 30, and 115 minutes, respectively. Emergency medical services transportation times were calculated using Google's Distance Matrix Application Programming Interface interfaced with MATLAB's Mapping Toolbox to create map visualizations. RESULTS: Maps were generated for multiple onset-to-first medical response times and door-to-needle times at the PSCs of 30, 60, and 90. These figures demonstrate the transportation option that yields the better modeled outcome in specific regions. The probability of good outcome is shown. CONCLUSIONS: Drip 'n Ship demonstrates that a PSC that is in close proximity to a CSC remains significant only when the PSC is able to achieve a door-to-needle time of ≤30 minutes when the CSC is also efficient.

History, Evolution, and Importance of Emergency Endovascular Treatment of Acute Ischemic Stroke.

More than 800,000 people in North America suffer a stroke each year, with ischemic stroke making up the majority of these cases. The outcomes of ischemic stroke range from complete functional and cognitive recovery to severe disability and death; outcome is strongly associated with timely reperfusion treatment. Historically, ischemic stroke has been treated with intravenous thrombolytic agents with moderate success. However, five recently published positive trials have established the efficacy of endovascular treatment in acute ischemic stroke. In this review, we will discuss the history of stroke treatments moving from various intravenous thrombolytic drugs to intra-arterial thrombolysis, early mechanical thrombectomy devices, and finally modern endovascular devices. Early endovascular therapy failures, recent successes, and implications for current ischemic stroke management and future research directions are discussed.

Active Negative Pressure Peritoneal Therapy After Abbreviated Laparotomy: The Intraperitoneal Vacuum Randomized Controlled Trial.

OBJECTIVE: To determine whether active negative pressure peritoneal therapy with the ABThera temporary abdominal closure device reduces systemic inflammation after abbreviated laparotomy. BACKGROUND: Excessive systemic inflammation after abdominal injury or intra-abdominal sepsis is associated with poor outcomes. METHODS: We conducted a single-center, randomized controlled trial. Forty-five adults with abdominal injury (46.7%) or intra-abdominal sepsis (52.3%) were randomly allocated to the ABThera (n = 23) or Barker's vacuum pack (n = 22). On study days 1, 2, 3, 7, and 28, blood and peritoneal fluid were collected. The primary endpoint was the difference in the plasma concentration of interleukin-6 (IL-6) 24 and 48 hours after temporary abdominal closure application. RESULTS: There was a significantly lower peritoneal fluid drainage from the ABThera at 48 hours after randomization. Despite this, there was no difference in plasma concentration of IL-6 at baseline versus 24 (P = 0.52) or 48 hours (P = 0.82) between the groups. There was also no significant intergroup difference in the plasma concentrations of IL-1ß, -8, -10, or -12 p70 or tumor necrosis factor α between these time points. The cumulative incidence of primary fascial closure at 90 days was similar between groups (hazard ratio, 1.6; 95% confidence interval, 0.82-3.0; P = 0.17). However, 90-day mortality was improved in the ABThera group (hazard ratio, 0.32; 95% confidence interval, 0.11-0.93; P = 0.04). CONCLUSIONS: This trial observed a survival difference between patients randomized to the ABThera versus Barker's vacuum pack that did not seem to be mediated by an improvement in peritoneal fluid drainage, fascial closure rates, or markers of systemic inflammation. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT01355094.

Towards understanding the de-adoption of low-value clinical practices: a scoping review.

BACKGROUND: Low-value clinical practices are common in healthcare, yet the optimal approach to de-adopting these practices is unknown. The objective of this study was to systematically review the literature on de-adoption, document current terminology and frameworks, map the literature to a proposed framework, identify gaps in our understanding of de-adoption, and identify opportunities for additional research. METHODS: MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, the Cochrane Database of Systematic Reviews, the Cochrane Database of Abstracts and Reviews of Effects, and CINAHL Plus were searched from 1 January 1990 to 5 March 2014. Additional citations were identified from bibliographies of included citations, relevant websites, the PubMed 'related articles' function, and contacting experts in implementation science. English-language citations that referred to de-adoption of clinical practices in adults with medical, surgical, or psychiatric illnesses were included. Citation selection and data extraction were performed independently and in duplicate. RESULTS: From 26,608 citations, 109 were included in the final review. Most citations (65%) were original research with the majority (59%) published since 2010. There were 43 unique terms referring to the process of de-adoption-the most frequently cited was "disinvest" (39% of citations). The focus of most citations was evaluating the outcomes of de-adoption (50%), followed by identifying low-value practices (47%), and/or facilitating de-adoption (40%). The prevalence of low-value practices ranged from 16% to 46%, with two studies each identifying more than 100 low-value practices. Most articles cited randomized clinical trials (41%) that demonstrate harm (73%) and/or lack of efficacy (63%) as the reason to de-adopt an existing clinical practice. Eleven citations described 13 frameworks to guide the de-adoption process, from which we developed a model for facilitating de-adoption. Active change interventions were associated with the greatest likelihood of de-adoption. CONCLUSIONS: This review identified a large body of literature that describes current approaches and challenges to de-adoption of low-value clinical practices. Additional research is needed to determine an ideal strategy for identifying low-value practices, and facilitating and sustaining de-adoption. In the meantime, this study proposes a model that providers and decision-makers can use to guide efforts to de-adopt ineffective and harmful practices.

Pharmacokinetics and Pharmacodynamics of Tissue Plasminogen Activator Administered Through an External Ventricular Drain.

BACKGROUND: Intraventricular hemorrhage (IVH) frequently complicates spontaneous intracerebral or subarachnoid hemorrhage (SAH). Administration of intraventricular tissue plasminogen activator (TPA) accelerates blood clearance, but optimal dosing has not been clarified. Using a standardized TPA dose, we assessed peak cerebrospinal fluid (CSF) TPA concentrations, the rate at which TPA clears, and the relationship between TPA concentration and biological activity. METHODS: Twelve patients with aneurysmal SAH and IVH, treated with endovascular coiling and ventricular drainage, were randomized to receive either 2 mg intraventricular TPA or placebo every 12 h (five doses). CT scans were performed 12, 48, and 72 h after initial administration, and blood was quantified using the SAH Sum and IVH Scores. CSF TPA and fibrin degradation product (D-dimer) concentrations were measured at baseline and 1, 6, and 12 h after the first dose using ELISA assays. RESULTS: Median CSF TPA concentrations in seven TPA-treated patients were 525 (IQR 352-2129), 323 (233-413), and 47 (29-283) ng/ml, respectively, at 1, 6, and 12 h after drug administration. Peak concentrations varied markedly (401-8398 ng/ml). Two patients still had slightly elevated levels (283-285 ng/ml) when the second dose was due after 12 h. There was no significant correlation between the magnitude of CSF TPA elevation and the rate of blood clearance or degree of D-dimer elevation. D-dimer peaked at 6 h, had declined by 12 h, and correlated strongly with radiographic IVH clearance (r = 0.82, p = 0.02). CONCLUSIONS: The pharmacokinetics of intraventricular TPA administration varies between individual patients. TPA dose does not need to exceed 2 mg. The optimal administration interval is every 8-12 h.