Automated reporting of cervical biopsies using artificial intelligence.

When detected at an early stage, the 5-year survival rate for people with invasive cervical cancer is 92%. Being aware of signs and symptoms of cervical cancer and early detection greatly improve the chances of successful treatment. We have developed an Artificial Intelligence (AI) algorithm, trained and evaluated on cervical biopsies for automated reporting of digital diagnostics. The aim is to increase overall efficiency of pathological diagnosis and to have the performance tuned to high sensitivity for malignant cases. Having a tool for triage/identifying cancer and high grade lesions may potentially reduce reporting time by identifying areas of interest in a slide for the pathologist and therefore improving efficiency. We trained and validated our algorithm on 1738 cervical WSIs with one WSI per patient. On the independent test set of 811 WSIs, we achieved 93.4% malignant sensitivity for classifying slides. Recognising a WSI, with our algorithm, takes approximately 1.5 minutes on the NVIDIA Tesla V100 GPU. Whole slide images of different formats (TIFF, iSyntax, and CZI) can be processed using this code, and it is easily extendable to other formats.

Loss of the puromycin-sensitive aminopeptidase, PAM-1, triggers the spindle assembly checkpoint during the first mitotic division in Caenorhabditis elegans.

Puromycin-sensitive aminopeptidases have long been implicated in cell-cycle regulation, but the mechanism remains unknown. Here we show that mutations in the gene encoding the C. elegans puromycin-sensitive aminopeptidase, PAM-1 , cause chromosome segregation defects and an elongated mitosis in the one-cell embryo. Depleting a known regulator of the spindle assembly checkpoint (SAC), MDF-2 (MAD2 in humans), restores normal mitotic timing to pam-1 mutants but exacerbates the chromosome segregation defects. Thus, PAM-1 is required for proper attachment of chromosomes to the mitotic spindle and its absence triggers the SAC.

Perinatal Posttraumatic Stress Disorder Diagnoses Among Commercially Insured People Increased, 2008-20.

Posttraumatic stress disorder (PTSD) is a burdensome disorder, affecting 3-4 percent of delivering people in the US, with higher rates seen among Black and Hispanic people. The extent of clinical diagnosis remains unknown. We describe the temporal and racial and ethnic trends in perinatal PTSD diagnoses among commercially insured people with live-birth deliveries during the period 2008-20, using administrative claims from Optum's Clinformatics Data Mart Database. Predicted probabilities from our logistic regression analysis showed a 394 percent increase in perinatal PTSD diagnoses, from 37.7 per 10,000 deliveries in 2008 to 186.3 per 10,000 deliveries in 2020. White people had the highest diagnosis rate at all time points (208.0 per 10,000 deliveries in 2020), followed by Black people, people with unknown race, Hispanic people, and Asian people (188.7, 171.9, 146.9, and 79.8 per 10,000 deliveries in 2020, respectively). The significant growth in perinatal PTSD diagnosis rates may reflect increased awareness, diagnosis, or prevalence of the disorder. However, these rates fall well below the estimated prevalence of PTSD in the perinatal population.

"To prescribe or not to prescribe, that is the question": Perspectives on opioid prescribing for chronic, cancer-related pain from clinicians who treat pain in survivorship.

BACKGROUND: Opioid pain management in cancer survivorship is a complex and understudied topic. METHODS: The authors conducted in-depth, qualitative interviews to understand clinician approaches to opioid pain management in chronic cancer pain and to generate ideas for improvement. They used a rigorous, inductive, qualitative, descriptive approach to examine clinician (n = 20) perspectives about opioid pain management in survivorship, including oncologists (n = 5), palliative care clinicians (n = 8), primary care clinicians (n = 5), and pain management specialists (n = 2). RESULTS: The findings indicated that no consistent medical home exists for chronic pain management in cancer survivors and that there are fundamental differences in how each subspecialty approaches chronic pain management in survivorship (e.g., "Do we think of this as noncancer pain or cancer pain?… This is in this limbo zone-this gray zone-because it's cancer-related pain, right?"). Simultaneously, clinicians are influenced by their peers' perceptions of their opioid prescribing decisions, sparking intraprofessional tension when disagreement occurs. In these instances, clinicians described overthinking and doubting their clinical decision-making as well as a sense of judgment, pressure, and/or shame. Finally, clinicians acknowledged a fear of consequences for opioid prescribing decisions. Specifically, participants cited conflict with patients, sometimes escalating to aggression and threats of violence, as well as potential disciplinary actions and/or legal consequences. CONCLUSIONS: Participants suggested that opportunities to improve chronic cancer pain care include developing clear, systematic guidance for chronic cancer pain management, facilitating clinician communication and consultation, creating tailored survivorship care plans in partnership with patients, and developing accessible, evidence-based, complementary pain treatments.

Associations of Health Care Utilization and Therapeutic Alliance in Patients with Advanced Cancer.

Introduction: Therapeutic alliance (TA), or the extent to which patients feel a sense of caring and trust with their physician, may have an impact on health care utilization. We sought to determine if TA is associated with: (1) emergency department (ED) visits within 30 days of death and (2) hospice enrollment. Methods and Materials: This is a secondary analysis of data from a randomized clinical trial. We used restricted cubic splines to assess the relationship between TA scores and health care utilization. Results: Six hundred seventy-two patients were enrolled in the study, with 331 (49.3%) dying within 12 months. Patients with higher TA were less likely to have an ED visit in the last 30 days of life, but there was no evidence of a relationship between TA and enrollment in hospice. Conclusions: Higher TA was associated with decreased ED visits within 30 days of death. There was no association between TA and rates of hospice enrollment. Clinical Registration Number: NCT02712229.

Assaults and Microaggressions Against Psychiatric Residents: Findings from a US Survey.

OBJECTIVES: Psychiatric physicians may experience higher rates of assault than those in other fields. For many reasons, residents may be especially vulnerable. This study updates rates of assaults among US psychiatry residents as well as the reporting rates and emotional effects of these incidents. Little data exists to examine rates of microaggressions against psychiatry residents. METHODS: A cross-sectional online survey was distributed through a national residency database via a snowball-sampling approach between June and September of 2021. The questionnaire asked about experiences of verbal, physical, and sexual assaults, as well as microaggressions and their impact. Descriptive analyses of the obtained data were conducted. RESULTS: The survey was completed by 275 psychiatry residents from 29 states (63.6% women). At least one form of assault was experienced by 78.9% of participants with 74.5% experiencing verbal, 22.2% experiencing physical, and 6.2% experiencing sexual assault. At least one type of microaggression was experienced by 86.9% of trainees. Elevations in PTSD scores were seen in residents who identified as women and non-White and those physically injured or sexually assaulted. While 92.7% of residents stated their program provided training about assault, 25% of residents indicated they had no training on recognizing and responding to microaggressions. CONCLUSIONS: Psychiatric residents experience widespread assault and microaggressions in the clinical setting but often do not report them. Due to the ubiquitous nature of these events, programs should provide training about early recognition and de-escalation techniques for agitation, responding effectively to microaggressions, and the importance of reporting events.

Providers' Stigmas and the Effects on Patients with Opioid Use Disorder: A Scoping Review.

Introduction: One of the most prevalent, dangerous stigmas in health care is the complex bias toward patients with opioid use disorder (OUD). This stigma damages the vital patient-provider relationship, further perpetuating the opioid epidemic. Purpose: Unfortunately, research on the relationship between OUD and provider stigma is greatly lacking. To fill this gap, the present in-depth study undertakes a scoping review of research on providers' stigma toward OUD in order to determine how enacted stigma affects treatment plans. Methods: Four databases were used to identify articles published from 1999 to 2021. A comprehensive search strategy was developed through a collaborative process between the researchers and a medical librarian. The researchers used the methodological framework developed by Arksey and O'Malley (2005) and expanded upon by Levac et al.(2010) to chart study characteristics and themes. Results: A total of 196 search items were retrieved. After de-duplication (n=31), remaining articles were screened based on the inclusion and exclusion criteria detailed in the protocol. After both a title/abstract review and full-text review, an additional 158 articles were removed. This yielded a total of seven articles. Three main themes were identified in the literature: (1) rural-urban differences in bias; (2) provider concern regarding legal implications and regulatory concerns; and (3) the belief that OUD is a moral failing rather than a medical diagnosis. Implications: Additional research should further analyze prescribed treatment plans for patients with OUD and utilize this information to create future considerations aimed at reducing opioid-related stigma in healthcare in Appalachia.

Prophylactic anticoagulation after minimally invasive hysterectomy for endometrial cancer: a cost-effectiveness analysis.

OBJECTIVE: To determine our institutional rate of venous thromboembolism (VTE) following minimally invasive surgery for endometrial cancer and to perform a cost-effectiveness analysis of extended prophylactic anticoagulation after minimally invasive staging surgery for endometrial cancer. METHODS: All patients with newly diagnosed endometrial cancer who underwent minimally invasive staging surgery from January 1, 2017 to December 31, 2020 were identified retrospectively, and clinicopathologic and outcome data were obtained through chart review. Event probabilities and utility decrements were obtained through published clinical data and literature review. A decision model was created to compare 28 days of no post-operative pharmacologic prophylaxis, prophylactic enoxaparin, and prophylactic apixaban. Outcomes included no complications, deep vein thrombosis (DVT), pulmonary embolism, clinically relevant non-major bleeding, and major bleeding. We assumed a willingness-to-pay threshold of $100 000 per quality-adjusted life year (QALY) gained. RESULTS: Three of 844 patients (0.36%) had a VTE following minimally invasive staging surgery for endometrial cancer. In this model, no pharmacologic prophylaxis was less costly and more effective than prophylactic apixaban and prophylactic enoxaparin over all parameters examined. When all patients were assigned prophylaxis, prophylactic apixaban was both less costly and more effective than prophylactic enoxaparin. If the risk of DVT was ≥4.8%, prophylactic apixaban was favored over no pharmacologic prophylaxis. On Monte Carlo probabilistic sensitivity analysis for the base case scenario, no pharmacologic prophylaxis was favored in 41.1% of iterations at a willingness-to-pay threshold of $100 000 per QALY. CONCLUSIONS: In this cost-effectiveness model, no extended pharmacologic anticoagulation was superior to extended prophylactic enoxaparin and apixaban in clinically early-stage endometrial cancer patients undergoing minimally invasive surgery. This model supports use of prophylactic apixaban for 7 days post-operatively in select patients when the risk of DVT is 4.8% or higher.

Describing Self-Advocacy in Underrepresented Women With Advanced Cancer.

PURPOSE: To describe the self-advocacy experiences of women from underrepresented groups who have advanced breast or gynecologic cancer. PARTICIPANTS & SETTING: To be eligible for the study, participants had to self-identify as vulnerable, which was defined as a member of a group considered at risk for poor cancer outcomes and underrepresented in clinical research. METHODOLOGIC APPROACH: This descriptive, longitudinal, qualitative study consisted of one-on-one interviews of women within three months of an advanced breast or gynecologic cancer diagnosis. FINDINGS: 10 participants completed 25 interviews. The average age of participants was 60.2 years (range = 38-75 years). Three major themes emerged: (a) speaking up and speaking out, (b) interacting with the healthcare team, and (c) relying on support from others. IMPLICATIONS FOR NURSING: Women with advanced cancer who are from underrepresented groups self-advocated in unique ways, learning over time the importance of how to communicate their needs and manage their healthcare team. Future research should incorporate these findings into tailored self-advocacy interventions.

Association of the Mental Health Parity and Addiction Equity Act and the Affordable Care Act on severe maternal morbidity.

OBJECTIVE: This study aimed to characterize the association between Mental Health Parity and the Affordable Care Act and rates of severe maternal morbidity among a population of commercially insured individuals, including individuals with and without perinatal mood and anxiety disorders. METHODS: We conducted a serial, cross-sectional analysis of individuals with an inpatient delivery in Optum's Clinformatics® Data Mart Database from 2008 to 2021. We applied an interrupted time series model with autoregressive integrated moving average to evaluate changes in quarterly severe maternal morbidity rates. RESULTS: Adjusted severe maternal morbidity rates declined from 167.2 (95%CI: [152.6, 181.9]) per 10,000 deliveries in the first quarter of 2008 to 98.2 (95%CI: [83.5, 112.8]) per 10,000 deliveries in the last quarter of 2021. Severe maternal morbidity rates remained higher, but declined to a greater degree, among those with perinatal mood and anxiety disorders (435.6, 95%CI: [379.9, 491.3], to 165.0, 95%CI: [109.3, 220.8] per 10,000 deliveries) compared to those without (153.0, 95%CI: [140.7, 165.3] to 81.8, 95%CI: [69.6, 94.1] per 10,000 deliveries). CONCLUSION: The observed association suggests implementation of Mental Health Parity and Affordable Care Act may have played a role in lowering rates of severe maternal morbidity, particularly among individuals with perinatal mood and anxiety disorders.

What is known about what works in community-involved decision-making relating to urban green and blue spaces? A realist review protocol.

BACKGROUND: There is now a relatively well-established evidence base suggesting that greener living environments and time spent in urban green and blue spaces (UGBS) can be beneficial for human health and wellbeing. However, benefits are not universal and there remain widespread social inequalities in access to such resources and experiences, particularly along axes of class, race, ethnicity, age and disability, and in relation to efforts to increase the availability and accessibility of such spaces. These injustices often relate to distributive, procedural and recognition-based processes. There is growing interest in how to ensure that efforts to increase access to or use of UGBS (whether through infrastructural or social programmes) result in equitable outcomes whilst minimising potential for exacerbating existing inequalities and injustices. Community engagement is considered an important step towards more inclusive UGBS decision-making, from planning and design to management and maintenance processes. It is thought to contribute to better and more widely trusted decisions, enhanced democracy, community satisfaction, civic interest and feelings of green space ownership, and greater longevity of UGBS projects. However, uneven representation and barriers to participation can create imbalances and undermine these benefits. METHODS: An iterative, multi-stage realist-inspired review will be conducted to ask what works, in what context and in what ways relating to the meaningful involvement of communities in UGBS decision-making, focusing on the skills, capacities and capabilities of different stakeholders and the role of contexts and processes. 'Effectiveness' (or what works) will be understood as a multifaceted outcome, encompassing both the processes and results of community engagement efforts. Following a scoping stage to identify initial programme theory, inclusion/exclusion criteria and derive search terms, relevant databases and grey literature will be searched to identify interdisciplinary literature in two phases. The first phase will be used to further develop programme theories, which will be articulated as 'if then' statements. The second phase searches will be used to identify sources to further explore and evidence the programme and formal theory. We will assess all includable evidence for conceptual richness, prioritising more conceptually rich sources if needed. DISCUSSION: The realist synthesis will explore the key context, mechanism and outcome configurations that appear to explain if and how different approaches to community-involved UGBS decision-making are or are not effective. We will consider factors such as different conceptualisations of community, and if and how they have been involved in UGBS decision-making; the types of tools and approaches used; and the socio-cultural and political or governance structures within which decision-making takes place.

Development and Implementation of an Acute Kidney Injury Remote Patient Monitoring Program: Research Letter.

Acute kidney injury (AKI) survivors have a dynamic posthospital course which warrants close monitoring. Remote patient monitoring (RPM) could be used to improve quality and efficiency of AKI survivor care. Objective: The objective of this report was to describe the development and preliminary feasibility of an AKI RPM program launched in October 2021. Setting: Academic medical center. Patients: Patients enrolled in the AKI RPM program were those who experienced AKI during a hospitalization and underwent nephrology consultation. Measurements/Methods: At enrollment, patients were provided with home monitoring technology and underwent weekly laboratory assessments. Nurses evaluated the data daily and adhered to prespecified protocols for management and escalation of care if needed. Results: Twenty patients were enrolled in AKI RPM in the first 5 months. Median duration of program participation was 36 (31, 40) days. Eight patients (40%) experienced an unplanned readmission, or an emergency department visit, half (N = 4) of which were attributed to AKI and related circumstances. Of the 9 postgraduation survey respondents, all were satisfied with the RPM program and 89% would recommend RPM to other patients with similar health conditions. Limitations: Acute kidney injury RPM was made possible by the existing infrastructure in our integrated health system and the robust resources available in the Mayo Clinic Center for Digital Health. Such infrastructure may not be universally available which could limit scale and generalizability of such a program. Conclusions: Remote patient monitoring can offer a unique opportunity to bridge the care transition from hospital to home and increase access to quality care for the AKI survivors.

Les survivants d'un épisode d'insuffisance rénale aiguë (IRA) ont un parcours post-hospitalier dynamique qui justifie une surveillance étroite. La télésurveillance des patients (TSP) pourrait être employée pour améliorer la qualité et l'efficacité des soins pour les survivants de l'IRA. Objectif: L'objectif de ce rapport était de décrire le développement et la faisabilité préliminaire d'un programme de TSP-IRA (télésurveillance des patients atteints d'IRA) en octobre 2021. Cadre: Centre médical universitaire. Sujets: Les patients inscrits au programme de TSP-IRA étaient des patients qui avaient vécu un épisode d'IRA lors d'une hospitalisation et obtenu une consultation en néphrologie. Mesures et méthodologie: Au moment de l'inclusion, les patients ont reçu un dispositif de surveillance à domicile et se sont soumis à des évaluations de laboratoire hebdomadaires. Les infirmières ont évalué les données quotidiennement et ont respecté des protocoles prédéfinis pour la gestion et l'escalade des soins si nécessaire. Résultats: Vingt patients ont été inclus dans le programme de TSP-IRA au cours des cinq premiers mois. La durée médiane de participation au programme était de 36 (31, 40) jours. Huit patients (40%) ont dû être réadmis de façon non planifiée ou ont dû faire une visite aux urgences; pour la moitié d'entre eux (N = 4) en raison de l'IRA et de circonstances connexes. Parmi les neuf répondants qui ont répondu au sondage à la complétion du programme, tous se sont dits satisfaits du programme de TSP et 89% le recommanderaient à d'autres patients ayant des problèmes de santé similaires. Limites: Le programme de TSP-IRA a été rendu possible grâce à l'infrastructure existante dans notre système de santé intégré et aux ressources robustes disponibles au Mayo Clinic Center for Digital Health. Une telle infrastructure n'est peut-être pas universellement disponible, ce qui pourrait limiter l'ampleur et la généralisabilité d'un tel programme. Conclusion: La TSP peut offrir une occasion unique de faciliter la transition des soins entre l'hôpital et le domicile et d'accroître l'accès à des soins de qualité pour les survivants d'un épisode d'IRA.

The Impact of Downstream Procedures on Lung Cancer Screening Adherence.

OBJECTIVE: (1) Evaluate downstream procedures after lung cancer screening (LCS), including imaging and invasive procedures, in screened individuals without screen-detected lung cancer. (2) Determine the association between repeat LCS and downstream procedures and patient characteristics. METHODS: Individuals receiving LCS between January 1, 2015, and November 30, 2020, from Optum's deidentified Clinformatics Data Mart Database were included. Individuals with lung cancer after LCS were excluded. We determined frequency and costs of downstream procedures after LCS, including diagnostic imaging (chest CT, PET, or CT using fluorine-18-2-fluoro-2-deoxy-D-glucose imaging) and invasive procedures (bronchoscopy, needle biopsy, thoracic surgery). A generalized estimating equation was used to model repeat LCS as a function of downstream procedures and patient characteristics. The primary outcome was repeat screening within 1 year of index LCS, and a secondary analysis evaluated the outcome of repeat screening with 2 years of index LCS. RESULTS: In all, 23,640 individuals receiving 30,521 LCS examinations were included in the primary analysis; 17.7% of LCS examinations (5,414 of 30,521) prompted downstream testing, with chest CT within 4 months being most common (9.1%, 2,769 of 30,521). At multivariable analysis adjusted for patient characteristics, the occurrence of a downstream diagnostic imaging test or invasive procedure was associated with a decreased likelihood of repeat annual LCS (adjusted odds ratio, 95% confidence interval: 0.38, 0.34-0.44; adjusted odds ratio, 95% confidence interval: 0.75, 0.63-0.90, respectively). DISCUSSION: Downstream imaging and invasive procedures after LCS are potential barriers to LCS adherence. Efforts to reduce false-positives at LCS and reduce patient costs from downstream procedures are likely necessary to ensure that downstream workup after LCS does not discourage screening adherence.

Evaluation of safety and care outcomes after the introduction of a virtual registered nurse model.

OBJECTIVE: To evaluate the impact of a virtual registered nurse (ViRN) model on safety and care outcomes. ViRN is a telemedicine intervention that enables an experienced virtual nurse to assist the in-person care team in providing care to patients. DATA SOURCES AND STUDY SETTING: Electronic health records data were utilized from the Mayo Clinic during the intervention (December 2020-November 2021) and historical periods (December 2018-November 2019). ViRN was implemented on general medical units at the Mayo Clinic Rochester. We used general medical units at the Mayo Clinic Arizona as the comparison group. STUDY DESIGN: This study used a difference-in-differences design to evaluate the impact of ViRN compared to usual care on transfer to the intensive care unit (ICU), inpatient mortality, and length of stay (LOS). We used logistic regression for transfer to the ICU and inpatient mortality and negative binomial regression for LOS. We controlled for demographics, patient interaction with the health system, clinical characteristics, and admission characteristics. We clustered standard errors to account for patients who have multiple admissions during the study period. PRINCIPAL FINDINGS: There were no significant differences for transfer to the ICU (average marginal effect (AME) -0.08 percentage point [95% confidence interval (CI): -1.34, 1.18]), inpatient mortality (AME 0.43 percentage point [95% CI: -0.33, 1.18]), or LOS (AME -0.20 days [95% CI: -0.57, 0.17]). The findings were mostly consistent across the sensitivity analyses. CONCLUSIONS: Our results suggest that ViRN led to similar outcomes as usual care in general medical units. These findings support the potential to develop more advanced models of ViRN at the Mayo Clinic and the dissemination of the ViRN model to other systems. In the context of staffing shortages and other disruptions to the delivery of nursing care, it is critical to understand whether new models like ViRN provide nurse staffing alternatives without negatively affecting outcomes.

Patient Satisfaction With a Multisite, Multiregional Remote Patient Monitoring Program for Acute and Chronic Condition Management: Survey-Based Analysis.

BACKGROUND: Remote patient monitoring (RPM) is an option for continuously managing the care of patients in the comfort of their homes or locations outside hospitals and clinics. Patient engagement with RPM programs is essential for achieving successful outcomes and high quality of care. When relying on technology to facilitate monitoring and shifting disease management to the home environment, it is important to understand the patients' experiences to enable quality improvement. OBJECTIVE: This study aimed to describe patients' experiences and overall satisfaction with an RPM program for acute and chronic conditions in a multisite, multiregional health care system. METHODS: Between January 1, 2021, and August 31, 2022, a patient experience survey was delivered via email to all patients enrolled in the RPM program. The survey encompassed 19 questions across 4 categories regarding comfort, equipment, communication, and overall experience, as well as 2 open-ended questions. Descriptive analysis of the survey response data was performed using frequency distribution and percentages. RESULTS: Surveys were sent to 8535 patients. The survey response rate was 37.16% (3172/8535) and the completion rate was 95.23% (3172/3331). Survey results indicated that 88.97% (2783/3128) of participants agreed or strongly agreed that the program helped them feel comfortable managing their health from home. Furthermore, 93.58% (2873/3070) were satisfied with the RPM program and ready to graduate when meeting the program goals. In addition, patient confidence in this model of care was confirmed by 92.76% (2846/3068) of the participants who would recommend RPM to people with similar conditions. There were no differences in ease of technology use according to age. Those with high school or less education were more likely to agree that the equipment and educational materials helped them feel more informed about their care plans than those with higher education levels. CONCLUSIONS: This multisite, multiregional RPM program has become a reliable health care delivery model for the management of acute and chronic conditions outside hospitals and clinics. Program participants reported an excellent overall experience and a high level of satisfaction in managing their health from the comfort of their home environment.

GWAS using low-pass whole genome sequence reveals a novel locus in canine congenital idiopathic megaesophagus.

Congenital idiopathic megaesophagus (CIM) is a gastrointestinal disorder of dogs wherein the esophagus is dilated and swallowing activity is reduced, causing regurgitation of ingesta. Affected individuals experience weight loss and malnourishment and are at risk for aspiration pneumonia, intussusception, and euthanasia. Great Danes have among the highest incidences of CIM across dog breeds, suggesting a genetic predisposition. We generated low-pass sequencing data for 83 Great Danes and used variant calls to impute missing whole genome single-nucleotide variants (SNVs) for each individual based on haplotypes phased from 624 high-coverage dog genomes, including 21 Great Danes. We validated the utility of our imputed data set for genome-wide association studies (GWASs) by mapping loci known to underlie coat phenotypes with simple and complex inheritance patterns. We conducted a GWAS for CIM with 2,010,300 SNVs, identifying a novel locus on canine chromosome 1 (P-val = 2.76 × 10-10). Associated SNVs are intergenic or intronic and are found in two clusters across a 1.7-Mb region. Inspection of coding regions in high-coverage genomes from affected Great Danes did not reveal candidate causal variants, suggesting that regulatory variants underlie CIM. Further studies are necessary to assess the role of these non-coding variants.