Leveraging artificial intelligence to advance implementation science: potential opportunities and cautions.

BACKGROUND: The field of implementation science was developed to address the significant time delay between establishing an evidence-based practice and its widespread use. Although implementation science has contributed much toward bridging this gap, the evidence-to-practice chasm remains a challenge. There are some key aspects of implementation science in which advances are needed, including speed and assessing causality and mechanisms. The increasing availability of artificial intelligence applications offers opportunities to help address specific issues faced by the field of implementation science and expand its methods. MAIN TEXT: This paper discusses the many ways artificial intelligence can address key challenges in applying implementation science methods while also considering potential pitfalls to the use of artificial intelligence. We answer the questions of "why" the field of implementation science should consider artificial intelligence, for "what" (the purpose and methods), and the "what" (consequences and challenges). We describe specific ways artificial intelligence can address implementation science challenges related to (1) speed, (2) sustainability, (3) equity, (4) generalizability, (5) assessing context and context-outcome relationships, and (6) assessing causality and mechanisms. Examples are provided from global health systems, public health, and precision health that illustrate both potential advantages and hazards of integrating artificial intelligence applications into implementation science methods. We conclude by providing recommendations and resources for implementation researchers and practitioners to leverage artificial intelligence in their work responsibly. CONCLUSIONS: Artificial intelligence holds promise to advance implementation science methods ("why") and accelerate its goals of closing the evidence-to-practice gap ("purpose"). However, evaluation of artificial intelligence's potential unintended consequences must be considered and proactively monitored. Given the technical nature of artificial intelligence applications as well as their potential impact on the field, transdisciplinary collaboration is needed and may suggest the need for a subset of implementation scientists cross-trained in both fields to ensure artificial intelligence is used optimally and ethically.

A Novel Heterozygous De Novo MORC2 Missense Variant Causes an Early Onset and Severe Neurodevelopmental Disorder.

Microrchidia CW-type zinc finger protein 2 (MORC2) is an ATPase-containing nuclear protein which regulates transcription through chromatin remodelling and epigenetic silencing. MORC2 may have a role in the development of neurones, and dominant variants in this gene have recently been linked with disorders including Charcot-Marie-Tooth type 2Z disease, spinal muscular atrophy and, more recently, a neurodevelopmental syndrome consisting of developmental delay, impaired growth, dysmorphic facies, and axonal neuropathy (DIGFAN), presenting with hypotonia, microcephaly, brain atrophy, intellectual disability, hearing loss, faltering growth, and craniofacial dysmorphism. Notably, variants in MORC2 have shown clinical features overlapping with those of Cockayne and Leigh syndromes. Here, we report a case of MORC2-related DIGFAN syndrome in a female infant caused by a novel heterozygous de novo variant. The condition was early onset and severe, further expanding the range of genotypes associated with this disorder. Clinical features included unilateral hearing loss, developmental delay and regression within the first year of life, microcephaly, severe feeding difficulties, and faltering growth, resulting in death at 13 months of age.

Studying Trends of Auto-Regulation in Severe Head Injury in Paediatrics (STARSHIP): protocol to study cerebral autoregulation in a prospective multicentre observational research database study.

INTRODUCTION: Studying cerebral autoregulation, particularly PRx (Pressure Reactivity Index), is commonly employed in adult traumatic brain injury (TBI) and gives real-time information about intracranial pathophysiology, which can help in patient management. Experience in paediatric TBI (PTBI) is limited to single-centre studies despite disproportionately higher incidence of morbidity and mortality in PTBI than in adult TBI. PROJECT: We describe the protocol to study cerebral autoregulation using PRx in PTBI. The project called Studying Trends of Auto-Regulation in Severe Head Injury in Paediatrics is a multicentre prospective ethics approved research database study from 10 centres across the UK. Recruitment started in July 2018 with financial support from local/national charities (Action Medical Research for Children, UK). METHODS AND ANALYSIS: The first phase of the project is powered to detect optimal thresholds of PRx associated with favourable outcome in PTBI by recruiting 135 patients (initial target of 3 years which has changed to 5 years due to delays related to COVID-19 pandemic) from 10 centres in the UK with outcome follow-up to 1-year postictus. The secondary objectives are to characterise patterns of optimal cerebral perfusion pressure in PTBI and compare the fluctuations in these measured parameters with outcome. The goal is to create a comprehensive research database of a basic set of high-resolution (full waveforms resolution) neuromonitoring data in PTBI for scientific use. ETHICS AND DISSEMINATION: Favourable ethical approval has been provided by Health Research Authority, Southwest-Central Bristol Research Ethics Committee (Ref: 18/SW/0053). Results will be disseminated via publications in peer-reviewed medical journals and presentations at national and international conferences. TRIAL REGISTRATION NUMBER: NCT05688462.

Brain monoamine vesicular transport disease caused by homozygous SLC18A2 variants: A study in 42 affected individuals.

PURPOSE: Brain monoamine vesicular transport disease is an infantile-onset movement disorder that mimics cerebral palsy. In 2013, the homozygous SLC18A2 variant, p.Pro387Leu, was first reported as a cause of this rare disorder, and dopamine agonists were efficient for treating affected individuals from a single large family. To date, only 6 variants have been reported. In this study, we evaluated genotype-phenotype correlations in individuals with biallelic SLC18A2 variants. METHODS: A total of 42 affected individuals with homozygous SLC18A2 variant alleles were identified. We evaluated genotype-phenotype correlations and the missense variants in the affected individuals based on the structural modeling of rat VMAT2 encoded by Slc18a2, with cytoplasm- and lumen-facing conformations. A Caenorhabditis elegans model was created for functional studies. RESULTS: A total of 19 homozygous SLC18A2 variants, including 3 recurrent variants, were identified using exome sequencing. The affected individuals typically showed global developmental delay, hypotonia, dystonia, oculogyric crisis, and autonomic nervous system involvement (temperature dysregulation/sweating, hypersalivation, and gastrointestinal dysmotility). Among the 58 affected individuals described to date, 16 (28%) died before the age of 13 years. Of the 17 patients with p.Pro237His, 9 died, whereas all 14 patients with p.Pro387Leu survived. Although a dopamine agonist mildly improved the disease symptoms in 18 of 21 patients (86%), some affected individuals with p.Ile43Phe and p.Pro387Leu showed milder phenotypes and presented prolonged survival even without treatment. The C. elegans model showed behavioral abnormalities. CONCLUSION: These data expand the phenotypic and genotypic spectra of SLC18A2-related disorders.

Stakeholder perspectives on current determinants of ultrasound-guided thoracentesis in resource limited settings: a qualitative study.

OBJECTIVE: Preprocedure pleural fluid localization using bedside ultrasound has been shown to reduce complications related to thoracentesis and is now considered the standard of care. However, ultrasound-guided thoracentesis (USGT) has not been broadly adopted in many low-resource settings. With increasing affordability and portability of ultrasound equipment, barriers to USGT are changing. The aim of this multisite qualitative study is to understand the current barriers to USGT in two resource-limited settings. SETTING: We studied two geographically diverse settings, Harare, Zimbabwe, and Kathmandu, Nepal. PARTICIPANTS: 19 multilevel stakeholders including clinical trainees, attendings, clinical educators and hospital administrators were interviewed. There were no exclusion criteria. PRIMARY OUTCOME: To understand the current determinants of USGT adoption in these settings. RESULTS: Three main themes emerged from these interviews: (1) stakeholders perceived multiple advantages of USGT, (2) access to equipment and training were perceived as limited and (3) while an online training approach is feasible, stakeholders expressed scepticism that this was an appropriate modality for procedural training. CONCLUSION: Our data suggests that USGT implementation is desired by local stakeholders and that the development of an educational intervention, cocreated with local stakeholders, should be explored to ensure optimal contextual fit.

Biallelic CACNA1A variants: Review of literature and report of a child with drug-resistant epilepsy and developmental delay.

Biallelic variants in CACNA1A have previously been reported in nine individuals (four families) presenting with epilepsy and cognitive impairments of variable severity and age-of-onset. Here, we describe a child who presented at 6 months of age with drug-resistant epilepsy and developmental delay. At 10 years of age, she has profound impairments in motor function and communication. MRI was initially unremarkable, but progressed to severe cerebellar atrophy by age 3 years. Next Generation Sequencing and panel analysis identified a maternally inherited truncating variant c.2042_2043delAG, p.(Gln681ArgfsTer100) and paternally inherited missense variant c.1693G>A, p.(Glu565Lys). In contrast to previously reported biallelic cases, parents carrying these monoallelic variants did not display clear signs of a CACNA1A-associated syndrome. In conclusion, we provide further evidence that biallelic CACNA1A variants can cause a severe epileptic and developmental encephalopathy with progressive cerebellar atrophy, and highlight complexities of genetic counseling in such situations.

Using Iterative RE-AIM to enhance hospitalist adoption of lung ultrasound in the management of patients with COVID-19: an implementation pilot study.

BACKGROUND: Lung ultrasound (LUS) is a clinician-performed evidence-based imaging modality that has multiple advantages in the evaluation of dyspnea caused by multiple disease processes, including COVID-19. Despite these advantages, few hospitalists have been trained to perform LUS. The aim of this study was to increase adoption and implementation of LUS during the 2020 COVID-19 pandemic by using recurrent assessments of RE-AIM outcomes to iteratively revise our implementation strategies. METHODS: In an academic hospital, we implemented guidelines for the use of LUS in patients with COVID-19 in July 2020. Using a novel "RE-AIM dashboard," we used an iterative process of evaluating the high-priority outcomes of Reach, Adoption, and Implementation at twice monthly intervals to inform revisions of our implementation strategies for LUS delivery (i.e., Iterative RE-AIM process). Using a convergent mixed methods design, we integrated quantitative RE-AIM outcomes with qualitative hospitalist interview data to understand the dynamic determinants of LUS Reach, Adoption, and Implementation. RESULTS: Over the 1-year study period, 453 LUSs were performed in 298 of 12,567 eligible inpatients with COVID-19 (Reach = 2%). These 453 LUS were ordered by 43 out of 86 eligible hospitalists (LUS order adoption = 50%). However, the LUSs were performed/supervised by only 8 of these 86 hospitalists, 4 of whom were required to complete LUS credentialing as members of the hospitalist procedure service (proceduralist adoption 75% vs 1.2% non-procedural hospitalists adoption). Qualitative and quantitative data obtained to evaluate this Iterative RE-AIM process led to the deployment of six sequential implementation strategies and 3 key findings including (1) there were COVID-19-specific barriers to LUS adoption, (2) hospitalists were more willing to learn to make clinical decisions using LUS images than obtain the images themselves, and (3) mandating the credentialing of a strategically selected sub-group may be a successful strategy for improving Reach. CONCLUSIONS: Mandating use of a strategically selected subset of clinicians may be an effective strategy for improving Reach of LUS. Additionally, use of Iterative RE-AIM allowed for timely adjustments to implementation strategies, facilitating higher levels of LUS Adoption and Reach. Future studies should explore the replicability of these preliminary findings.

Comparison of four handheld point-of-care ultrasound devices by expert users.

BACKGROUND: Point-of-care ultrasound (POCUS) is rapidly becoming ubiquitous across healthcare specialties. This is due to several factors including its portability, immediacy of results to guide clinical decision-making, and lack of radiation exposure to patients. The recent growth of handheld ultrasound devices has improved access to ultrasound for many clinicians. Few studies have directly compared different handheld ultrasound devices among themselves or to cart-based ultrasound machines. We conducted a prospective observational study comparing four common handheld ultrasound devices for ease of use, image quality, and overall satisfaction. Twenty-four POCUS experts utilized four handheld devices (Butterfly iQ+™ by Butterfly Network Inc., Kosmos™ by EchoNous, Vscan Air™ by General Electric, and Lumify™ by Philips Healthcare) to obtain three ultrasound views on the same standardized patients using high- and low-frequency probes. RESULTS: Data were collected from 24 POCUS experts using all 4 handheld devices. No single ultrasound device was superior in all categories. For overall ease of use, the Vscan Air™ was rated highest, followed by the Lumify™. For overall image quality, Lumify™ was rated highest, followed by Kosmos™. The Lumify™ device was rated highest for overall satisfaction, while the Vscan Air™ was rated as the most likely to be purchased personally and carried in one's coat pocket. The top 5 characteristics of handheld ultrasound devices rated as being "very important" were image quality, ease of use, portability, total costs, and availability of different probes. CONCLUSIONS: In a comparison of four common handheld ultrasound devices in the United States, no single handheld ultrasound device was perceived to have all desired characteristics. POCUS experts rated the Lumify™ highest for image quality and Vscan Air™ highest for ease of use. Overall satisfaction was highest with the Lumify™ device, while the most likely to be purchased as a pocket device was the Vscan Air™. Image quality was felt to be the most important characteristic in evaluating handheld ultrasound devices.

Use of the reach, effectiveness, adoption, implementation, and maintenance (RE-AIM) framework to guide iterative adaptations: Applications, lessons learned, and future directions.

Introduction: Implementation science frameworks have been used widely for planning and evaluation, but seldom to guide adaptations during program implementation. There is great potential for these frameworks to be used to inform conceptual and data-driven decisions about adaptations. Methods: We summarize recent applications using Iterative RE-AIM to capture and guide adaptations. Iterative RE-AIM can be repeated at multiple time points customized to each project and involves the following activities: identification of key implementation partners; rating importance of and progress on each RE-AIM dimension (reach, effectiveness, adoption, implementation, and maintenance); use of summary data on ratings to identify one or two RE-AIM dimensions for adaptations and implementation strategies; and evaluation of progress and impact of adaptations. We summarize recent and ongoing Iterative RE-AIM applications across multiple care coordination and pain management projects within the Veterans Health Administration, a hypertension control trial in Guatemala, a hospital-based lung ultrasound implementation pilot, and a colorectal cancer screening program in underserved communities. Results: Iterative RE-AIM appears feasible, helpful, and broadly applicable across diverse health care issues, interventions, contexts, and populations. In general, the RE-AIM dimension showing the largest gap between importance and progress has been Reach. The dimensions most frequently selected for improvement have been Reach and Implementation. We discuss commonalities, differences and lessons learned across these various applications of Iterative RE-AIM. Challenges include having objective real time data on which to make decisions, having key implementation staff available for all assessments, and rapidly scoring and providing actionable feedback. We discuss print and online resources and materials to support Iterative RE-AIM. Conclusions: The use of Iterative RE-AIM to guide and support understanding of adaptations has proven feasible across diverse projects and in multiple case studies, but there are still questions about its strengths, limitations, essential components, efficiency, comparative effectiveness, and delivery details. Future directions include investigating the optimal frequency and timing for iterative applications; adding contextual assessments; developing more continuous and rapid data on which to make adaptation decisions; identifying opportunities to enhance health equity; and determining the level of facilitation that is most cost-effective.

Hospitalist Perceptions of Barriers to Lung Ultrasound Adoption in Diverse Hospital Environments.

Despite the many advantages of lung ultrasound (LUS) in the diagnosis and management of patients with dyspnea, its adoption among hospitalists has been slow. We performed semi-structured interviews of hospitals from four diverse health systems in the United States to understand determinants of adoption within a range of clinical settings. We used the diffusion of innovation theory to guide a framework analysis of the data. Of the 27 hospitalists invited, we performed 22 interviews from four hospitals of diverse types. Median years post-residency of interviewees was 10.5 [IQR:5-15]. Four main themes emerged: (1) There are important clinical advantages to LUS despite operator dependence, (2) LUS enhances patient and clinician experience, (3) Investment of clinician time to learn and perform LUS is a barrier to adoption but yields improved efficiency for the health system and (4) Mandated training and use may be necessary to achieve broad adoption as monetary incentives are less effective. Despite the perceived benefits of LUS for patients, clinicians and health systems, a significant barrier to broad LUS adoption is the experience of time scarcity by hospitalists. Future implementation strategies should focus on changes to the clinical environment that address clinician barriers to learning and adoption of new skills.

Multi-Level Stakeholder Perspectives on Determinants of Point of Care Ultrasound Implementation in a US Academic Medical Center.

There is growing interest from multiple specialties, including internal medicine, to incorporate diagnostic point of care ultrasound (POCUS) into standard clinical care. However, few internists currently use POCUS. The objective of this study was to understand the current determinants of POCUS adoption at both the health system and clinician level at a U.S. academic medical center from the perspective of multi-level stakeholders. We performed semi-structured interviews of multi-level stakeholders including hospitalists, subspecialists, and hospital leaders at an academic medical center in the U.S. Questions regarding the determinants of POCUS adoption were asked of study participants. Using the framework method, team-based analysis of interview transcripts were guided by the contextual domains of the Practical Robust Implementation and Sustainability Model (PRISM). Thirty-one stakeholders with diverse roles in POCUS adoption were interviewed. Analysis of interviews revealed three overarching themes that stakeholders considered important to adoption by clinicians and health systems: clinical impact, efficiency and cost. Subthemes included two that were deemed essential to high-fidelity implementation: the development of credentialing policies and robust quality assurance processes. These findings identify potential determinants of system and clinician level adoption that may be leveraged to achieve high-fidelity implementation of POCUS applications that result in improved patient outcomes.

Discharge-ready volume status in acute decompensated heart failure: a survey of hospitalists.

Acute decompensated heart failure is the leading cause of hospitalization in older adults. Clinical practice guidelines recommend patients should be euvolemic at hospital discharge - yet accurate assessment of volume status is recognized to be exceptionally challenging. This conundrum led us to investigate how hospitalists are assessing volume status and discharge- readiness of patients hospitalized with heart failure. We collected audience response data during a didactic heart failure presentation at the 2019 Society of Hospital Medicine annual meeting. Respondents (n = 216), 76% of whom were practicing physician hospitalists caring for more than 20 acute heart failure patients per year, were presented six questions. Eighteen percent of respondents reported not being able to determine the completeness of decongestion on discharge and 32% reported that complete decongestion was not a treatment target. These findings suggest important differences between guideline recommendations and how hospitalists treat heart failure in current clinical practice.

Hospitalist Perspectives of Available Tests to Monitor Volume Status in Patients With Heart Failure: A Qualitative Study.

Acute decompensated heart failure is the leading admitting diagnosis in patients 65 years and older with more than 1 million hospitalizations per year in the US alone. Traditional tools to evaluate for and monitor volume status in patients with heart failure, including symptoms and physical exam findings, are known to have limited accuracy. In contrast, point of care lung ultrasound is a practical and evidenced-based tool for monitoring of volume status in patients with heart failure. However, few inpatient clinicians currently use this tool to monitor diuresis. We performed semi-structured interviews of 23 hospitalists practicing in five geographically diverse academic institutions in the US to better understand how hospitalists currently assess and monitor volume status in patients hospitalized with heart failure. We also explored their perceptions and attitudes toward adoption of lung ultrasound. Hospitalist participants reported poor reliability and confidence in the accuracy of traditional tools to monitor diuresis and expressed interest in learning or were already using lung ultrasound for this purpose. The time required for training and access to equipment that does not impede workflow were considered important barriers to its adoption by interviewees.

Ultra-Sensitive Ultrasound.

Lung ultrasound (LUS) is a dynamic, real-time, non-invasive bedside tool that offers increased sensitivity over standard imaging modalities in identifying pulmonary edema. This case highlights acute post-operative hypoxia secondary to pulmonary edema that was initially missed by chest radiography (CXR) and chest computed tomography (CT). The edema was diagnosed first on same day by bedside LUS, later seen on next day follow-up CXR and resolved with diuresis. LUS has demonstrated superior accuracy compared to CXR, but scant evidence compares it to CT. This case presentation serves to increase awareness of LUS as a highly sensitive and easy-to-use diagnostic tool for hospital providers in the evaluation of acute hypoxia.

Implications of Guideline Updates for the Management of Apparent Treatment Resistant Hypertension in the United States (A NCDR Research to Practice [R2P] Project).

The 2018 resistant hypertension scientific statement offers new treatment recommendations. To determine the implications of these changes, we sought to ascertain the prevalence of apparent treatment resistant hypertension (aTRH) and the therapies used to treat it in an US national ambulatory cardiovascular registry before these recent developments. Using the PINNACLE Registry from 2013 to 2014, we identified all patients receiving treatment for hypertension and then determined the proportion with aTRH as those who met the following criteria over ≥2 consecutive visits: (1) 3 blood pressure medication classes including a diuretic and blood pressure >140/90, OR (2) ≥4 blood pressure medications. Among those with aTRH, we examined past use of therapies now recommended in guidelines including: (1) first-line therapy with an angiotensin-converting enzyme inhibitor or angiotensin-II receptor blocker, calcium channel blocker and a thiazide diuretic, (2) use of chlorthalidone, and (3) use of a mineralocorticoid receptor antagonist (MRA) for those requiring a 4th medication. Of 84,624 patients on treatment for hypertension, 11,147 (13.1%) met criteria for prevalent aTRH. Among these patients: (1) Of those on 3 antihypertensive agents (n = 1,255), 315 (25%) were on the first-line regimen now recommended in guidelines, (2) 520 (6.7%) of the 7,930 patients on thiazides were using chlorthalidone, and (3) 3061 (27%) were using a MRA; another 4,523 (40.6%) were eligible for its addition. In conclusion, our findings of low historic use of therapies now recommended in guidelines suggest opportunities to improve care among patients with aTRH.

Stakeholder Perceptions of Point-of-Care Ultrasound Implementation in Resource-Limited Settings.

BACKGROUND: Nearly half of the world lacks access to diagnostic imaging. Point of care ultrasound (POCUS) is a versatile and relatively affordable imaging modality that offers promise as a means of bridging the radiology gap and improving care in low resource settings. METHODS: We performed semi-structured interviews of key stakeholders at two diverse hospitals where POCUS implementation programs had recently been conducted: one in a rural private hospital in Haiti and the other in a public referral hospital in Malawi. Questions regarding the clinical utility of POCUS, as well as barriers and facilitators of its implementation, were asked of study participants. Using the Framework Method, analysis of interview transcripts was guided by the WHO ASSURED criteria for point of care diagnostics. RESULTS: Fifteen stakeholders with diverse roles in POCUS implementation were interviewed. Interviewees from both sites considered POCUS a valuable diagnostic tool that improved clinical decisions. They perceived barriers to adequate training as one of the most important remaining barriers to POCUS implementation. CONCLUSIONS: In spite of the increasing affordability and portability of ultrasounds devices, there are still important barriers to the implementation of POCUS in resource-limited settings.