Utilizing implementation science to bridge cerebrovascular health disparities: a local to global perspective

Abstract

Purpose of review:

Stroke is a prime example of a medical disorder whose incidence, prevalence, and outcomes are strongly characterized by health disparities across the globe. This scoping literature review seeks to depict how implementation science could be utilized to advance health equity in the prevention, acute treatment and post-acute management of stroke in the underserved regions of high-income countries as well as in all low-income countries.

Recent findings:

A major reason for the persisting and widening cerebrovascular disease disparities is that evidence-based stroke prevention and treatment interventions have been differentially translated (if at all) to various populations and settings. The field of implementation science is endowed with frameworks, theories, methodological approaches, and outcome measures, including equity indices, which could be harnessed to facilitate the translation of evidence-based interventions into clinical practice for underserved and vulnerable communities.

Summary:

Encouragingly, there are several novel frameworks, which eminently merge implementation science constructs with health equity determinants, thereby opening up key opportunities to bridge burgeoning worldwide gaps in cerebrovascular health equity.

Introduction:

Stroke is a prime example of a cerebrovascular disorder whose incidence, prevalence, and outcomes are strongly characterized by inequities across the globe. The World Health Organization defines health equity as the “absence of unfair and avoidable or remediable differences in health among population groups defined socially, economically, demographically, geographically or by other means of stratification”.¹ It is worth clarifying from the outset an important semantic difference between health inequality and health inequity. The generic term health inequality refers to any measurable aspect of health that varies across individuals or according to socially relevant groupings without any moral judgment on whether the observed differences are fair or just.² A health inequity, in contrast, is a specific type of health inequality whereby health differences are preventable and unnecessary and allowing them to persist is unjust.^3,4 Existence of health inequities and disparities has severely thwarted the mandated goal of universal health coverage (UHC) with approximately 50% of the world population not receiving needed health services.⁵

Cerebrovascular disease disparities have long been recognized to exist along racial, ethnic and socioeconomic lines, and is observed in both low-and high-income countries, and across geographical regions. These disparities contribute to significant mortality and morbidity from cerebrovascular disorders among vulnerable populations.⁶ A major reason for the persisting and widening cerebrovascular health inequities is that effective evidence-based interventions for addressing stroke prevention and treatment at both individual and population levels have not been translated equally to specific contexts and communities.^7,8 As shown in Figure 1, health inequity may contribute to decrements in translation of viable interventions to the most vulnerable populations. The field of implementation science holds considerable potential to close the disparity gap in stroke clinical care and prevention in communities.⁹ Implementation science is defined as the scientific study of methods to promote the systematic uptake of research findings and other evidence-based practices into routine practice, thereby improving the quality and effectiveness of health services.¹⁰ The field of implementation science is endowed with frameworks, theories, methodological approaches, study designs and outcome measures including equity indices, which could be harnessed to better promote translation of evidence-based interventions to high risk communities.¹⁰ This scoping literature review seeks to depict how implementation science could be utilized to advance cerebrovascular health equity. We first review the burden of stroke disparities in the US and sub-Saharan Africa to typify inequities due to racial and regional disparities. We then discuss implementation frameworks, strategies and outcome measures that will address inequities in stroke prevention, acute treatment, and post-acute management of stroke in the underserved regions of high-income countries as well as in all low-income countries.

Figure 1.

Continuum of Clinical and Translational Research

The Scope of Stroke Disparities in the US:

Stroke has the largest racial disparity of any chronic disease,¹³ with a striking disparity in the burden of stroke among African Americans (AA) vs. other race-ethnicities in the United States (US).^14–17 While there has been a recent downward trajectory in stroke incidence, prevalence and mortality rates in the US, the disparity in stroke outcomes has unfortunately increased for AA compared with Non-Hispanic Whites.¹⁸ The impact of this burgeoning disparity translates to huge economic costs for the US.^19,20 Adding to the sense of urgency is a projected substantial future widening of stroke prevalence in the US for AA compared to non-Hispanic Whites.¹⁹ Having a better understanding of the cause(s) for this disparity would be an effective way to reduce it.^21,22 African Americans and Hispanics in addition to having a higher burden of stroke are less likely to have access to acute and chronic neurological care compared to non-Hispanic whites.^22–24 Moreover, AAs and Hispanics have >2 fold higher incidence of stroke, disproportionately higher stroke mortality among younger working age populations, and increased rates of recurrent stroke (from reduced uptake of secondary prevention therapies) vs. non-Hispanic whites.

Below, we summarize cerebrovascular health inequities (Figure 2) under four broad domains with a view to proposing cross-cutting implementation science approaches to addressing these inequities in subsequent sections:

Figure 2:

Major domains of Cerebrovascular Health Inequities

(a). Disparities in burden of vascular risk factors for stroke:

It has become evident from recent epidemiological studies that the black-white disparities in stroke incidence and mortality across a wide age spectrum in the US may be partially explained by a higher prevalence of vascular risk factors in blacks, notably hypertension and diabetes mellitus, as well as socioeconomic indicators such as educational status.²¹ In addition, AAs are more susceptible to higher blood pressure, with the increase in stroke risk being 3-times greater in AAs than whites per millimeter of systolic blood pressure.²⁵ The REasons for Geographic and Racial Differences in Stroke (REGARDS) study is an ongoing, longitudinal, population-based cohort study of 30,239 black and white adults aged 45+ (at enrollment 2003-2007) designed to identify factors associated with higher stroke mortality and incidence among blacks and residents of the stroke belt region of the US.^17,26 So far, it has emerged clearly from REGARDS that blacks in the US remain at a higher risk for stroke even after adjusting for traditional risk factors such as age, sex, systolic blood pressure, use of antihypertensive medications, current smoking status, history of heart disease, diabetes mellitus, left ventricular hypertrophy, atrial fibrillation and socioeconomic status, defined by education and annual household income.²⁷ Importantly, the traditional risk factor and socioeconomic status (SES) adjustments accounted for only one-half of the disparity in the REGARDS cohort.²⁷ Thus the other half of the excess stroke incidence among blacks must be attributable to other factors that have not yet been discovered.²² It is plausible that biological factors, for instance, genetically determined perturbations in renin-aldosterone physiology may predispose African Americans to more resistant forms of hypertension and attendant target organ damage. ^28,29 Aside African Americans, other studies have also found a greater prevalence of hypertension, diabetes mellitus, hypercholesterolemia, heavy alcohol use and cigarette smoking among Hispanics compared with Caucasians.^30,31 These differences in risk factor load among ethnic minorities could be specifically targeted using culturally attuned implementation strategies for primordial and primary prevention addressing social determinants of health, risk factor awareness, detection, and control. Such an approach may yield significant dividends if appropriately structured to overcome the multilayered barriers which exist at the individual, interpersonal, clinical, organizational, local, state and national level on the social ecological model.³²

(b). Disparities in awareness of stroke symptoms and signs:

An awareness of symptoms and signs of stroke, and an understanding that timely treatment could improve outcomes is likely to prompt an individual or immediate family to initiate emergent health seeking behavior. However, there is a general inadequacy of knowledge about stroke presentation and treatment in the US which is more common among minorities.^33–35 This knowledge inequity is observed even among those with a prior history of stroke with a preponderance among Hispanics.³⁶ Notably Spanish-speaking Hispanics are significantly less likely to know all stroke symptoms (18%), compared with English-speaking Hispanics (31%), African Americans (41%) and Caucasians (50%).³⁷ Consequently, ambulance use is less common overall among minorities.³⁸ Further compounding this knowledge inequity are perceptions of discrimination in and mistrust of the healthcare system in the US, where many African Americans and Hispanics prefer same-race physician.³⁹

(c). Disparities in quality of acute stroke care:

There is evidence to suggest that even after presentation to the hospital for acute stroke care, disparities exist in the nature and quality of care provided with potential impact on care outcomes. First, racial differences exist in emergency department waiting times (EDWT) among a nationally representative sample of stroke patients with AAs having a 67% higher probability of prolonged EDWT than non-Hispanic whites.⁴⁰ Second, although there is an ≈4 times higher likelihood of being treated with tPA by an attending neurologist compared with an internist, only 10.6% of AAs vs. 20.3% of non-Hispanic whites with an acute stroke had a neurologist as an attending physician.⁴¹ Third, US data amply show disparities in tPA use by race with AAs less likely than non-Hispanic whites to receive tPA for an acute ischemic stroke even after presenting within 3 hours of symptom onset, not refusing tPA and not having contraindications to tPA (odds ratio of 0.24; 95%CI of 0.06 – 0.93).⁴² Fourth, tPA refusal rates appear to be higher among AAs vs. non-Hispanic whites, potentially stemming from mistrust engendered by historical antecedence of discrimination.⁴³ Finally, widespread implementation of time-efficient endovascular stroke care delivery using mechanical thrombectomy (MT) remains a challenge in rural areas,^44,45 utilization of MT for black/Hispanic patients is lower compared to non-Hispanic whites (7.0% vs. 9.8%; P<0.001), and Black/Hispanic patients are also less likely to be admitted to the endovascular center after transfer from a different hospital (20.0% vs. 30.1%; P<0.001).^46,47

(d). Disparities in post-stroke care and morbidity:

Post-stroke recovery care can be expensive and is administered at rehabilitation centers for many patients. This stroke treatment phase is particularly challenging as several co-morbidities including post-stroke depression, cognitive impairment, vascular risk factor management and lifestyle modification therapies, such as smoking cessation interventions, requiring care coordination by a broad spectrum of healthcare providers must be implemented. As a result, this phase of stroke care is susceptible to disparities by race, ethnicity and particularly by socioeconomic status. Thus, beside the higher rates of stroke recurrence among racial/ethnic minorities, other cerebrovascular health outcomes such as vascular cognitive impairment after stroke is commoner among AAs vs. non-Hispanic whites with other likely contributors being socio-cultural risks, epigenetic factors and vascular risk factor load.⁴⁸

The Scope of Stroke Disparities in the LIMICs:

Stroke also exacts a substantial toll in low-to middle-income countries (LMIC), especially in sub-Saharan Africa (SSA), where age-standardized stroke incidence & prevalence rates are up to 316 per 100,000 & 1.4 per 1,000 populations respectively, in-patient case fatality of 30-40% and a 3-year mortality rate of 84%.^49–52 Recurrent stroke rates,⁵³ post-stroke depression rates,⁵⁴ & post-stroke cognitive impairment rates in SSA are also high.⁵⁵ Congruent to observations among AAs in the US, stroke in SSA disproportionately affects a relatively young age group.^56–60 By comparing IA with AA, we may be able to dissect the impact of geographical location (ecology) on the expression of racial risk of stroke among blacks. Furthermore, learnings from implementation successes and failures in low-and-middle income countries could serve as models for translation (reverse diffusion of knowledge) in racial minority populations in the US and other developed countries.

Implementation Science Frameworks, study designs and outcomes metrics for bridging the Cerebrovascular Disease Disparities:

Implementation science has been posited as having the potential to bridge health equity and disparity gaps for multiple medical disorders. Our aspiration for mitigating the cerebrovascular disease disparities listed above would entail (a) a systematic analysis to elucidate the multilayered equity and disparity gaps in stroke prevention, acute therapy and post-acute care; (b) identify viable implementation strategies to promote equity in cerebrovascular health for all and (c) generate metrics for quantifying, and monitoring disparities to assess progress made.^61,62

Health equity/disparity & implementation science frameworks:

In order to advance the linkages between equity/disparity research and implementation science, novel frameworks should be adopted and adapted from those existing in both fields or derived de novo to target specific inequities/disparities in cerebrovascular health/disorders. Health equity frameworks include the Social Ecological Model⁶³, The National Institute on Minority Health and Health Disparities Research framework⁶⁴, Healthy People 2020⁶⁵ and the WHO’s Commission on the SDOH Conceptual Framework⁶⁶ could be utilized to dissect the transcendental levels at which cerebrovascular health inequities exist. An example of synthesis of potential health equity barriers of relevance to cerebrovascular health using the Social Ecological Model (SEM) from the individual patient level to National health policy environment is shown in Table 1.

Table 1.

Factors influencing Cerebrovascular inequities/disparities by levels of social ecological model

SEM Levels	Potential barriers	Impact on cerebrovascular disease care service provision
Patient	1. Household income	• Household income could limit access to healthcare services for vascular risk factor control
	2. Health literacy	• Low health literacy is associated with limited knowledge of CVD risk factors, CVD medications, increased likelihood of hospitalization with stroke and re-hospitalizations, increased risk of mortality.67
	3. Insurance cover	• Lack of insurance is associated with less likelihood of receiving evidence-based therapies, poorer care quality, less invasive procedures, less aggressive care, associated with increased mortality.68
	4. Language barriers	• Language barriers between patients and their healthcare providers may lead to poor quality care including misdiagnosis, delay in care, misuse of diagnostic testing, decreased patient engagement and empowerment.69,70
	5. Discrimination/societal stigma	• Societal stigma including prejudice, stereotyping, unfair treatment, discrimination are associated with stress and poor blood pressure control, heart rate variability and overall poor CVD health indicators.71
	6. Adherence of medications and lifestyle therapies	• Racial and sex for instance are strongly associated use of statins, non-adherence to statins and uptake of lifestyle therapies for modifiable risk factors such as diet, physical activity and smoking.72,73
	7. Functional limitations after stroke	• Cognitive and motor impairments after stroke may impair adherence to secondary prevention strategies leading to risk of stroke recurrence and further cognitive decline.74
Interpersonal	Family and social support    • Family dynamics    • Family history    • Financial strain    • Social networks/peer support	• Family-level factors such as marital status, living arrangements, family dynamics, social support for care, and financial strain could impact primary or secondary control of stroke vascular risk factors (hypertension, dyslipidemia, diabetes mellitus) through access and adherence to medications.75    • Family and social networks are instrumental to post-stroke rehabilitation.
Provider/clinical team	• Communication skills    • Cultural responsiveness	• Racial minorities may encounter barriers to stroke risk factor control, acute stroke care and post-stroke rehabilitation plus secondary risk reduction at the health system, provider and organizational team levels including (a) lower quality care, (b) poorer provider-patient communications such as verbal dominance by physicians and less engagement in participatory decision making and (c) lower levels of trust in health professionals.76–78
Organizational and/or practice setting	• Decision support    • Care coordination    • Patient education	• Organization structure and resources for hyperacute, acute, subacute and long-term stroke care; clinical decision support for algorithm driven stroke care protocols; availability of electronic medical records and patient education support and care coordination using a team-based approach that is sensitive to all phases of care along the stroke care continuum.
Local Community environment	• Income inequality    • Poverty levels    • Racial segregation    • Interpersonal racism    • Crime rates    • Food availability	• Pay-for-performance models of health care delivery may worsen cerebrovascular health inequity placing hospitals that serve large minority populations at financial risk. 79,80
State health policy environment	• Health care exchanges    • Hospital performance data policies    • State plans and programs
National Health Policy Environment	• Reimbursement    • Healthcare reform    • National Initiative

[adapted from Mueller et al⁸¹]

Furthermore, frameworks that are foundational to implementation science such the Consolidated Framework for Implementation Research (CFIR)⁸²; Reach Effectiveness Adoption Implementation Maintenance (RE-AIM)⁸³; Quality Implementation Framework and Promoting Action on Research Implementation in Health Services (PARiHS)⁸⁴ could be deployed to define and quantify the scope of cerebrovascular inequities, understand why marginalized populations for instance refuse or have limited access to evidence-based therapies for acute stroke and guide the selection of targeted strategies and approaches to addressing the gaps. The CFIR for instance is a comprehensive framework for assessment of baseline, process and final implementation includes five major domains (intervention characteristics, outer setting, inner setting, characteristics of individuals and process) with 39 underlying constructs and sub-constructs that can potentially influence efforts to change the practice. The constructs can be used as implementation and evaluation criteria in three different ways: they may (1) raise awareness about potentially influential factors, (2) facilitate analysis of pivotal processes and outcomes and (3) help organize all findings of an implementation process to explain the outcomes (i.e., to understand what worked where and why).

Novel frameworks that have merged constructs from health equity and implementation science include the (i) Health Equity Implementation Framework (HEIF) proposed by Woodward and colleagues⁶¹ and (ii) equity-based framework for implementation research by Eslava-Schmalbach et al.⁸⁵ HEIF for instance, coalesces the well-established PARiHS implementation framework⁸⁴ with the Health Care Disparities framework to devise an innovative approach to addressing a health inequity issue such as blood pressure control or other vascular risk factor control of relevance to cerebrovascular health. The HEIF model proposes to deliver an intervention such as hypertension control among stroke survivors via a team-based approach in primary care settings during a clinical encounter. The clinical encounter considers the local and organizational contexts to be addressed; the societal influences such as the economic, socio-political forces and physical structures which are likely to influence uptake and outcomes of intervention. In a primary care setting, facilitation strategies such as practice facilitation by specialist internists or neurologist to build capacity for evidence-based care of stroke survivors may be used to supplement this intervention for implementation success and potentially improve health equity.

Study designs:

An important consideration in designing interventions to reduce cerebrovascular disease disparities is that single component interventions are inherently weak in addressing multi-layered problems, hence bundled and coherent approaches are favored. Furthermore, pragmatic research designs such as hybrid effectiveness-implementation research approaches and mixed methods when deployed can enhance the external generalizability of an intervention in the real-world context and settings.⁸⁶ Hence clinical trial designs such as user-centered, factorial, stepped wedge or adaptive trial designs allows a tailored approach to gathering high quality clinical efficacy data⁸⁷ while simultaneously evaluating implementation outcomes such as adoption or uptake of intervention by ethnic minorities or low socioeconomic status can address health equity outcomes upfront. In planning implementation and dissemination research to address cerebrovascular disease disparities, it is important to perform formative qualitative community engagements including needs assessments of vulnerable or marginalized populations and communities before conducting clinical research. This will help bolster rapport and trust and inclusivity among those most prone to cerebrovascular disease disparities. Upon completion of the trial, post-intervention evaluation of lived experiences of patients, family members, healthcare providers, hospital administrators and policy makers are important to understand implementation successes and failures to foster multiple stakeholder engagements to promote uptake among marginalized sub-groups.^88,89

Implementation strategies & outcome measures for addressing cerebrovascular disease disparities:

Implementation strategies are methods or techniques used to enhance the adoption, implementation and sustainability of a clinical program or practice.⁹⁰ An accurate description of implementation strategies, which describe the ‘how to’ component of changing healthcare practice is of essence in implementation science. However, this aspect of the field of implementation science is challenged because implementation strategies are often inconsistently labelled and poorly described in the literature. To this end Proctor et al in 2013, made recommendations and proposed guidelines for naming, defining and operationalizing implementation strategies in seven (7) dimensions: actor, the action, action targets, temporality, dose, implementation outcomes addressed and theoretical justification.⁹¹ There is a broad array of implementation strategies which are often deployed in a combinatory manner to address practice changes. For instance, the Expert Recommendations for Implementing Change (ERIC) project⁹² identified and compiled 73 implementation strategies which is valuable reference resource for implementation researchers in cerebrovascular health equity.

Furthermore, thoughtful consideration should be given to how implementation outcomes measure health equity/disparity indices to determine whether implementation strategies are effective in reducing cerebrovascular health inequities. Examples of implementation outcomes include (i) acceptability (satisfaction with content, complexity, comfort, delivery and credibility of the intervention); (ii) adoption (uptake, utilization, intention to try, refusal rates); (iii) appropriateness (perceived fit, relevance, compatibility, usefulness); (iv) feasibility (suitability for everyday use, practicability); (v) fidelity (use checklist to assess whether the intervention was delivered as intended, quality of program delivery); (vi) Implementation cost (marginal costs of the intervention & delivery strategy). Finally, Dover and Belon have composed a comprehensive model to measure social inequities called the Health Equity Measurement Framework (HEMF).⁹³ The HEMF is a unified framework which builds on social determinants of health and health system utilization framework with a focus on identification and measurement of the interrelationships between socioeconomic, cultural, and political context, health policy context, social stratification, social location, material and social circumstances, environment, biological factors, health-related behaviors and beliefs, stress, quality of care, healthcare utilization and health outcomes.⁹³

An example of implementation research in Africa to address cerebrovascular disease disparities in a low-income setting:

The Sub-Saharan African (SSA) region now has the highest estimated effect size of hypertension for stroke causation worldwide. Several factors militate against favorable outcomes for stroke survivors in LMICs including (i) perennial lack of expertise to coordinate and implement evidence-based interventions for secondary prevention. It is estimated that the neurologist-to-population ratio is 0.3/1,000,000 in Africa and these few neurologists are found in major cities and (ii) limited access to post-stroke care due to geographical and financial barriers in a setting where a significant proportion reside in remote village dwellings. Thus an urgent priority for countries in sub-Saharan Africa is to develop and test self-management interventions to control hypertension among those at highest risk of adverse outcomes in particular stroke survivors. To address the health challenge in Africa, we developed a theoretical-model-based, mHealth technology-centered, nurse-led, multi-level integrated approach to improve longer term blood pressure (BP) control among stroke survivors. A feasibility study showed signal of effect over 9 months in a single center^94,95 and mixed methods approaches were utilized to obtain feedback from the pilot study to refine the intervention.⁹⁶ The refined intervention now comprises of (i) home BP monitoring at least once weekly with nurse navigation for high domiciliary BP readings; (2) medication reminders using mobile phone alerts and (3) education on hypertension and stroke delivered once weekly via audio messages in preferred local dialects. The Phone-based Intervention under Nurse Guidance after Stroke II study (PINGS-2) which has hybrid study design seeks to assess the efficacy of the multilevel intervention among 500 recent stroke survivors to be enrolled across 10 Ghanaian hospitals including primary, district and tertiary medical facilities.⁹⁷ Using a computer-generated sequence, patients will be randomly assigned 1:1 into the intervention or usual care arms. The intervention will last for 12 months. The control group will receive usual care as determined by local guidelines. The primary outcome is the proportion of patients with systolic BP <140 mm Hg at 12 months. Secondary outcomes will include medication adherence, self-management of hypertension, major adverse cardiovascular events, health related quality of life and implementation outcomes including adoption of PINGS across levels of hospital practices and implementation cost. Furthermore, multiple stakeholder engagements with stroke survivors, their family caregivers, doctors and nurses, hospital administrators and policy makers are planned to before, during and after the trial to enhance sustainment and uptake of the intervention into routine practice.

An example of implementation science approach to address cerebrovascular disparities in acute stroke care-Restructuring of Stroke Care in London:

This initiative was spearheaded by the London’s Regional Health Authority to create an acute stroke care model which was designed and managed by clinicians. The key components included

1. The creation of eight stroke hubs distributed within London’s 5 sectors called Hyper Acute Stroke Units (HASUs) equipped with competent staff and equipment to quickly evaluate, diagnose, treat and managed patients with suspected stroke during the first 48 to 72 hours of symptom onset.

2. A major public education campaign on recognition of common stroke signs and symptoms [“FAST” campaign] and stressing on the importance of prompt action by calling emergency services.

3. Training and capacity building of the London Ambulance Services on stroke assessment with the goal of directing any patient with stroke symptoms and signs to the nearest HASU. This strategy helped in improving access to high quality stroke care offered at the nearest HASU usually no more than 30 minutes away.

4. The HASU teams were led by either a neurologist or vascular neurologist who directed decisions on thrombolysis eligibility and other emergent clinical management decisions with other team members comprised stoke-trained nurses, physiotherapists, speech therapists, occupational therapists, psychologists, and dieticians.

5. After acute management at HASUs, stroke patients were triaged to one of 24 Acute Stroke Units (ASUs) for further inpatient stroke management, community rehabilitation services, or home.

6. Short-term outcome measures included a reduction of 30-day stroke mortality in London from 15% in 2008 to 7.6% in 2011; increase in thrombolysis rates from 3.5% in 2009 to 14% in 2011 and cost savings of 5.2 million pounds per year at 90 days [811 pounds per patient].⁹⁸

The key learning here is that standardizing acute care for stroke in a cosmopolitan city like London potentially enhance health equality through health systems strengthening. However, to address health disparities, additional support may be required to improve reach to marginalized populations who at substantially higher stroke risk and face greater challenges such as language barriers and financial constraints.

Conclusion:

As highlighted in this scoping review, cerebrovascular disease disparities abound in both resource replete and resource constrained settings around the globe. Implementation science offers a promising range of frameworks, constructs, study designs and evaluation metrics to bridge this profound contributor to health inequities and disparities worldwide.