Defining the Need for Causal Inference to Understand the Impact of Social Determinants of Health: A Primer on Behalf of the Consortium for the Holistic Assessment of Risk in Transplantation (CHART).

Objective: This study aims to introduce key concepts and methods that inform the design of studies that seek to quantify the causal effect of social determinants of health (SDOH) on access to and outcomes following organ transplant. Background: The causal pathways between SDOH and transplant outcomes are poorly understood. This is partially due to the unstandardized and incomplete capture of the complex interactions between patients, their neighborhood environments, the tertiary care system, and structural factors that impact access and outcomes. Designing studies to quantify the causal impact of these factors on transplant access and outcomes requires an understanding of the fundamental concepts of causal inference. Methods: We present an overview of fundamental concepts in causal inference, including the potential outcomes framework and direct acyclic graphs. We discuss how to conceptualize SDOH in a causal framework and provide applied examples to illustrate how bias is introduced. Results: There is a need for direct measures of SDOH, increased measurement of latent and mediating variables, and multi-level frameworks for research that examine health inequities across multiple health systems to generalize results. We illustrate that biases can arise due to socioeconomic status, race/ethnicity, and incongruencies in language between the patient and clinician. Conclusions: Progress towards an equitable transplant system requires establishing causal pathways between psychosocial risk factors, access, and outcomes. This is predicated on accurate and precise quantification of social risk, best facilitated by improved organization of health system data and multicenter efforts to collect and learn from it in ways relevant to specialties and service lines.

Association of Recent Use of Non-Vitamin K Antagonist Oral Anticoagulants With Intracranial Hemorrhage Among Patients With Acute Ischemic Stroke Treated With Alteplase.

Importance: Current guidelines recommend against use of intravenous alteplase in patients with acute ischemic stroke who are taking non-vitamin K antagonist oral anticoagulants (NOACs). Objective: To evaluate the safety and functional outcomes of intravenous alteplase among patients who were taking NOACs prior to stroke and compare outcomes with patients who were not taking long-term anticoagulants. Design, Setting, and Participants: A retrospective cohort study of 163 038 patients with acute ischemic stroke either taking NOACs or not taking anticoagulants prior to stroke and treated with intravenous alteplase within 4.5 hours of symptom onset at 1752 US hospitals participating in the Get With The Guidelines-Stroke program between April 2015 and March 2020, with complementary data from the Addressing Real-world Anticoagulant Management Issues in Stroke registry. Exposures: Prestroke treatment with NOACs within 7 days prior to alteplase treatment. Main Outcomes and Measures: The primary outcome was symptomatic intracranial hemorrhage occurring within 36 hours after intravenous alteplase administration. There were 4 secondary safety outcomes, including inpatient mortality, and 7 secondary functional outcomes assessed at hospital discharge, including the proportion of patients discharged home. Results: Of 163 038 patients treated with intravenous alteplase (median age, 70 [IQR, 59 to 81] years; 49.1% women), 2207 (1.4%) were taking NOACs and 160 831 (98.6%) were not taking anticoagulants prior to their stroke. Patients taking NOACs were older (median age, 75 [IQR, 64 to 82] years vs 70 [IQR, 58 to 81] years for those not taking anticoagulants), had a higher prevalence of cardiovascular comorbidities, and experienced more severe strokes (median National Institutes of Health Stroke Scale score, 10 [IQR, 5 to 17] vs 7 [IQR, 4 to 14]) (all standardized differences >10). The unadjusted rate of symptomatic intracranial hemorrhage was 3.7% (95% CI, 2.9% to 4.5%) for patients taking NOACs vs 3.2% (95% CI, 3.1% to 3.3%) for patients not taking anticoagulants. After adjusting for baseline clinical factors, the risk of symptomatic intracranial hemorrhage was not significantly different between groups (adjusted odds ratio [OR], 0.88 [95% CI, 0.70 to 1.10]; adjusted risk difference [RD], -0.51% [95% CI, -1.36% to 0.34%]). There were no significant differences in the secondary safety outcomes, including inpatient mortality (6.3% for patients taking NOACs vs 4.9% for patients not taking anticoagulants; adjusted OR, 0.84 [95% CI, 0.69 to 1.01]; adjusted RD, -1.20% [95% CI, -2.39% to -0%]). Of the secondary functional outcomes, 4 of 7 showed significant differences in favor of the NOAC group after adjustment, including the proportion of patients discharged home (45.9% vs 53.6% for patients not taking anticoagulants; adjusted OR, 1.17 [95% CI, 1.06 to 1.29]; adjusted RD, 3.84% [95% CI, 1.46% to 6.22%]). Conclusions and Relevance: Among patients with acute ischemic stroke treated with intravenous alteplase, use of NOACs within the preceding 7 days, compared with no use of anticoagulants, was not associated with a significantly increased risk of intracranial hemorrhage.

Hospital Factors Associated With Interhospital Transfer Destination for Stroke in the Northeast United States.

Background We aimed to determine if there is an association between hospital quality and the likelihood of a given hospital being a preferred transfer destination for stroke patients. Methods and Results Data from Medicare claims identified acute ischemic stroke transferred between 394 northeast US hospitals from 2007 to 2011. Hospitals were categorized as transferring (n=136), retaining (n=241), or receiving (n=17) hospitals based on the proportion of acute ischemic stroke encounters transferred or received. We identified all 6409 potential dyads of sending and receiving hospitals, and categorized dyads as connected if ≥5 patients were transferred between the hospitals annually (n=82). We used logistic regression to identify hospital characteristics associated with establishing a connected dyad, exploring the effect of adjusting for different quality measures and outcomes. We also adjusted for driving distance between hospitals, receiving hospital stroke volume, and the number of hospitals in the receiving hospital referral region. The odds of establishing a transfer connection increased when rate of alteplase administration increased at the receiving hospital or decreased at the sending hospital, however this finding did not hold after applying a potential strategy to adjust for clustering. Receiving hospital performance on 90-day home time was not associated with likelihood of transfer connection. Conclusions Among northeast US hospitals, we found that differences in hospital quality, specifically higher levels of alteplase administration, may be associated with increased likelihood of being a transfer destination. Further research is needed to better understand acute ischemic stroke transfer patterns to optimize stroke transfer systems.

Ischemic Stroke Transfer Patterns in the Northeast United States.

BACKGROUND: Little is known about how hospitals are connected in the transfer of ischemic stroke (IS) patients. We aimed to describe differences in characteristics of transferred versus nontransferred patients and between transferring and receiving hospitals in the Northeastern United States, and to describe changes over time. METHODS: We used Medicare claims data, and a subset linked with the Get with the Guidelines-Stroke registry from 2007 to 2011. Receiving hospitals were those with annual IS volume greater than or equal to 120 and greater than or equal to 15% received as transfers, and transferring hospitals were nonaccepting hospitals that transferred greater than or equal to 15% of their total (ED plus inpatient) IS patient discharges. A transferring-to-receiving hospital connection was identified if greater than or equal to 5 patients per year were shared. ArcGIS 10.3.1 was used for network visualization. RESULTS: Among 177,270 admissions to 402 Northeast hospitals, 6906 (3.9%) patients were transferred. Transferred patients were younger with more severe strokes (78 versus 81 years, P < .001; National Institutes of Health Stroke Severity 7 versus 5, P < .001), and were as likely to receive tissue plasminogen activator as nontransferred (P = .29). From 2007 to 2011, there were more patients transferred (960 [3%] to 1777 [6%], P < .001), and more transferring hospitals (46 [12%] to 91 [24%], P < .001), and receiving hospitals (6 [2%] to 16 [4%], P < .001). Most transferring hospitals were exclusively connected to a single receiving hospital. CONCLUSIONS: From 2007 to 2011, hospitals in the United States Northeast became more connected in the care of IS patients, with increasing patient transfers and hospital connections. Yet most hospitals remained unconnected. Further characterization of this transfer network will be important for understanding and improving regional stroke systems of care.