Citations

AbstractObjectivesTo report lessons from integrating the methods and perspectives of clinical informatics (CI) and implementation science (IS) in the context of Improving the Management of symPtoms during and following Cancer Treatment (IMPACT) Consortium pragmatic trials.Materials and MethodsIMPACT informaticists, trialists, and implementation scientists met to identify challenges and solutions by examining robust case examples from 3 Research Centers that are deploying systematic symptom assessment and management interventions via electronic health records (EHRs). Investigators discussed data collection and CI challenges, implementation strategies, and lessons learned.ResultsCI implementation strategies and EHRs systems were utilized to collect and act upon symptoms and impairments in functioning via electronic patient-reported outcomes (ePRO) captured in ambulatory oncology settings. Limited EHR functionality and data collection capabilities constrained the ability to address IS questions. Collecting ePRO data required significant planning and organizational champions adept at navigating ambiguity.DiscussionBringing together CI and IS perspectives offers critical opportunities for monitoring and managing cancer symptoms via ePROs. Discussions between CI and IS researchers identified and addressed gaps between applied informatics implementation and theory-based IS trial and evaluation methods. The use of common terminology may foster shared mental models between CI and IS communities to enhance EHR design to more effectively facilitate ePRO implementation and clinical responses.ConclusionImplementation of ePROs in ambulatory oncology clinics benefits from common understanding of the concepts, lexicon, and incentives between CI implementers and IS researchers to facilitate and measure the results of implementation efforts.

Abstract Objective Limb girdle muscular dystrophies (LGMDs) are a group of genetically heterogeneous autosomal conditions with some degree of phenotypic homogeneity. LGMD is defined as having onset >2 years of age with progressive proximal weakness, elevated serum creatine kinase levels and dystrophic features on muscle biopsy. Advances in massively parallel sequencing have led to a surge in genes linked to LGMD. Methods The ClinGen Muscular Dystrophies and Myopathies gene curation expert panel (MDM GCEP, formerly Limb Girdle Muscular Dystrophy GCEP) convened to evaluate the strength of evidence supporting gene–disease relationships (GDR) using the ClinGen gene–disease clinical validity framework to evaluate 31 genes implicated in LGMD. Results The GDR was exclusively LGMD for 17 genes, whereas an additional 14 genes were related to a broader phenotype encompassing congenital weakness. Four genes ( CAPN3 , COL6A1 , COL6A2 , and COL6A3 ) were split into two separate disease entities, based on each displaying both dominant and recessive inheritance patterns, resulting in curation of 35 GDRs. Of these, 30 (86%) were classified as definitive, 4 (11%) as moderate, and 1 (3%) as limited. Two genes, POMGNT1 and DAG1 , though definitively related to myopathy, currently have insufficient evidence to support a relationship specifically with LGMD. Interpretation The expert‐reviewed assertions on the clinical validity of genes implicated in LGMDs form an invaluable resource for clinicians and molecular geneticists. We encourage the global neuromuscular community to publish case‐level data that help clarify disputed or novel LGMD associations.

ABSTRACT Over the last 13 years, the use of immune checkpoint inhibitor (ICI) therapy has grown remarkably, owing to their unprecedented anti-tumor efficacy in certain tumor groups. With increased use of ICIs, we are seeing immune-related adverse events (irAEs) more frequently. Renal irAEs, such as ICI-associated acute kidney injury (ICI-AKI), are reported in 2%–5% of patients treated with ICIs, with acute tubulointerstitial nephritis (ATIN) as the most common histopathologic lesion, though various forms of glomerulonephritis have also been reported. Modifiable risk factors for ICI-AKI include concurrent use of ATIN-associated drugs, like proton pump inhibitors, non-steroidal anti-inflammatory drugs and antibiotics, and dual ICI therapy with both Cytotoxic T-lymphocyte Associated Protein 4 (CTLA-4) and Programmed Cell Death Protein 1 and its ligand (PD1/PDL-1) blockade. Kidney biopsies remain the diagnostic modality of choice, though several promising non-invasive biomarkers, which have not yet been broadly clinically validated have emerged. The treatment of ICI-AKI involves holding ICIs, discontinuation of ATIN-associated drugs and initiation of immunosuppression with corticosteroids as first-line therapy. With prompt treatment initiation, most patients achieve full or partial renal recovery, allowing for re-challenge with ICI. However, a subset of patients will require additional steroid-sparing therapies for corticosteroid-dependent or refractory ICI-AKI. Here we review developments in our understanding of the pathophysiology of ICI-AKI, the approach to diagnosis (with a focus on the emergence of novel diagnostic tools), prognostic factors and the current evidence for establishing treatment standards for ICI-AKI. As the evidence base remains largely retrospective, we identify questions that would benefit from future prospective studies in the diagnosis, management and prognostication of ICI-AKI.

Abstract Coccidioidomycosis is a common cause of community-acquired pneumonia in endemic regions. Approximately 20 000 cases of coccidioidomycosis occur annually; however, this statistic is limited by a widespread lack of testing. Here, we analyze emergency medicine provider attitudes toward coccidioidal testing and assess the effect of an intervention to improve testing rates.

The COVID-19 pandemic challenged healthcare organisations in safely providing healthcare to patients while protecting employees and reducing the spread of the virus. This paper shows how the Mayo Clinic responded by implementing innovations, including screening, testing and tracing patients for COVID-19; expanding telehealth services; adjusting surgical and procedural operations and reallocating staffing and supplies. These changes were operationalised rapidly through the coordinated response from its leadership, partnership of experts across the organisation, prompt decision-making driven by data, redistribution of resources and expedited training. These innovations and methods of rapid implementation enabled Mayo Clinic to safely continue its mission of providing healing and hope to its patients worldwide, and quickly return to financial sustainability.

The COVID-19 pandemic has created unique logistical challenges for vaccine transportation, inventory management, allocation and distribution at multiple levels — the federal government, states and healthcare institutions. Unpredictable weekly vaccine allocation from state health departments, changing population priorities, stringent vaccine requirements for ultracold storage, transportation, reconstitution and 2-dose administration intervals have presented challenges never seen before in the history of mass vaccination programmes, including those at Mayo Clinic. To meet the challenges, an efficient system of allocation and administration for COVID-19 vaccines was developed through collaboration with process engineering. To understand the challenges, ten health systems engineers from the Department of Management Engineering & Consulting at Mayo Clinic facilitated the institution-wide COVID-19 vaccine project, collaborating closely with diverse multidisciplinary teams that included physicians, nurses, pharmacists, administrative services, information technology, human resources, scheduling operations and public affairs. The internal consultants designed tools and solutions based on systems and process engineering methodologies to solve a myriad of complex problems, including identifying priority populations, using resources efficiently and minimising vaccine waste. Tools designed included a vaccine resource playbook; dynamic staffing models based on vaccine allocation, storage, inventory and distribution processes using a hub-andspoke model; workflows and staffing models for face-to-face and drive-through vaccine administration sites; and end-of-day workflows to reduce vaccine waste. Through the collaboration, modelling and engineering, multiple sites across Mayo Clinic have implemented successful COVID-19 vaccination programmes that are efficient in resource utilisation and have minimal waste. In this paper, we share what we have learned to help other healthcare organisations prepare for future mass vaccination scenarios.

The demand for telehealth services in the United States saw an unprecedented increase following the 2020 COVID-19 pandemic. Prior to the pandemic, intake and virtual rooming functions for scheduled, synchronous video appointments at Mayo Clinic were supported by a small centralised team of virtual agents within its Center for Connected Care (Connected Care). In response to the pandemic-generated demand, Connected Care leveraged its existing model and the support of temporary staff to rapidly scale support for the increased video visit demand across the enterprise. Once demand stabilised in the summer of 2020, Mayo Clinic’s destination medical centres in Minnesota, Florida and Arizona, and Mayo Clinic Health System’s sites in the Midwest, launched pilots to evaluate alternative telehealth delivery models. The goal of these pilots was to test the flexibility of alternative intake models for supporting long-term scalability and growth. Through these pilots, each site developed unique workflows and staffing plans with the overall intake function remaining standardised across all locations. The workflows delineated responsibilities between clinical departments and virtual agents, leveraged current infrastructure and maximised best practices from the original model. This paper outlines the models implemented, and presents lessons learned and best practices garnered from each implementation.

Abstract INTRODUCTION Tau‐positron emission tomography (PET) outcome data of patients with Alzheimer's disease (AD) cannot currently be meaningfully compared or combined when different tracers are used due to differences in tracer properties, instrumentation, and methods of analysis. METHODS Using head‐to‐head data from five cohorts with tau PET radiotracers designed to target tau deposition in AD, we tested a joint propagation model (JPM) to harmonize quantification (units termed “CenTauR” [CTR]). JPM is a statistical model that simultaneously models the relationships between head‐to‐head and anchor point data. JPM was compared to a linear regression approach analogous to the one used in the amyloid PET Centiloid scale. RESULTS A strong linear relationship was observed between CTR values across brain regions. Using the JPM approach, CTR estimates were similar to, but more accurate than, those derived using the linear regression approach. DISCUSSION Preliminary findings using the JPM support the development and adoption of a universal scale for tau‐PET quantification. Highlights Tested a novel joint propagation model (JPM) to harmonize quantification of tau PET. Units of common scale are termed “CenTauRs”. Tested a Centiloid‐like linear regression approach. Using five cohorts with head‐to‐head tau PET, JPM outperformed linearregressionbased approach. Strong linear relationship was observed between CenTauRs values across brain regions.

Background: Women with stress urinary incontinence (SUI) may have altered running mechanics and reduced hip muscle strength compared with women without SUI. Little research has examined running metrics and functional lower extremity strength of parous runners. Objective: To determine whether SUI severity correlates with running metrics and lower extremity muscle strength among parous women. Study Design: This was a cross-sectional observational study of 22 parous participants (mean age 39.8 years, with a mean of 3.4 pregnancies and 8.1-year interval since last delivery). Methods: Participants completed the International Consultation on Incontinence Questionnaire–Urinary Incontinence Short Form (ICIQ-UI), Urinary Distress Inventory-6 (UDI-6), Colorectal-Anal Distress (CRAD) Inventory-8, and Pelvic Organ Prolapse Distress Inventory-6 (POPDI-6), and Questionnaire for Urinary Incontinence Diagnosis (QUID) and provided demographic, relevant running, and obstetric/gynecologic history information. After a brief warm-up, participants completed 30-second single-leg sit-to-stand tests bilaterally and a standardized 10-minute treadmill run with pod cadence assessment. Pearson-product moment correlation coefficients were calculated (α = .05). Results: Prolonged ground contact times were associated with higher ICIQ-UI SF (r= 0.523, P= .015), POPDI-6 (r= 0.694, P< .001), and UDI-6 scores (r= 0.577, P= .006), while lower cadences were associated with higher POPDI-6 (r=−0.550, P= .010) and UDI-6 scores (r=−0.444, P= .044). Conclusions: Parous female runners with more severe SUI and prolapse symptoms demonstrate altered running mechanics characterized by prolonged ground contact times and slower cadences.