Best Practices for Point of Care Ultrasound: An Interdisciplinary Expert Consensus.

Despite the growing use of point of care ultrasound (POCUS) in contemporary medical practice and the existence of clinical guidelines addressing its specific applications, there remains a lack of standardization and agreement on optimal practices for several areas of POCUS use. The Society of Point of Care Ultrasound (SPOCUS) formed a working group in 2022 to establish a set of recommended best practices for POCUS, applicable to clinicians regardless of their training, specialty, resource setting, or scope of practice. Using a three-round modified Delphi process, a multi-disciplinary panel of 22 POCUS experts based in the United States reached consensus on 57 statements in domains including: (1) The definition and clinical role of POCUS; (2) Training pathways; (3) Credentialing; (4) Cleaning and maintenance of POCUS devices; (5) Consent and education; (6) Security, storage, and sharing of POCUS studies; (7) Uploading, archiving, and reviewing POCUS studies; and (8) Documenting POCUS studies. The consensus statements are provided here. While not intended to establish a standard of care or supersede more targeted guidelines, this document may serve as a useful baseline to guide clinicians, leaders, and systems considering initiation or enhancement of POCUS programs.

Diagnostic Accuracy of Cardiac Point-of-Care Ultrasound in a Tertiary Medical Intensive Care Unit.

Objective: Critical care echocardiography (CCE) is a useful tool for managing critically ill patients in intensive care. However, concerns exist regarding the accuracy of CCE examinations because of operator dependence. We sought to evaluate the accuracy of CCE examinations compared with cardiology-performed transthoracic echocardiogram (TTE). Design Setting and Subjects: We retrospectively reviewed charts of patients in a medical ICU in a large academic medical center in the United States. We compared CCE examinations performed by a fellow and reviewed by a staff physician between May 5, 2020, and December 31, 2021, to TTE obtained within 24 hours of the CCE examination. Intervention Measurements and Main Results: We developed a standardized process for documentation of all CCE examinations performed in the medical ICU. We assessed agreement (kappa statistic), sensitivity and specificity of CCE examination compared with TTE. Features included left ventricle (LV) systolic function, right ventricle (RV) size, RV systolic function, pericardial effusion, mitral insufficiency, tricuspid insufficiency, and aortic insufficiency. The study analyzed 504 pairs of CCE and TTE examinations. Kappa statistics for detecting LV and RV systolic dysfunction, pericardial effusion, and RV size ranged from 0.60 to 0.74. CCE showed high sensitivity and specificity for detecting LV and RV systolic dysfunction and pericardial effusion, with values ranging from 0.85 to 0.99. The kappa statistic for detecting RV dilation was 0.59, with a sensitivity of 0.71 and a specificity of 0.85. In contrast, CCE examinations were nondiagnostic for mitral, tricuspid, or aortic insufficiency in 60-70% of cases, whereas TTE examinations were nondiagnostic in 20-30% of cases. Kappa statistics for mitral, tricuspid, and aortic insufficiency ranged from 0.32 to 0.42. Conclusions: CCE is a reliable tool for assessing LV and RV systolic function, pericardial effusion, and RV size. However, CCE may be limited in its ability to detect mitral, tricuspid, or aortic insufficiency.

Research design and baseline participant characteristics of the Resilient, Empowered, Active Living with Diabetes - Telehealth (REAL-T) Study: A randomized controlled trial for young adults with type 1 diabetes.

BACKGROUND: Type 1 diabetes (T1D) is a chronic condition affecting nearly 1.9 million people in the United States. Young adults (YAs) with T1D face unique challenges in managing their condition, experiencing poorer health and well-being than other age groups. The current study is evaluating the Resilient, Empowered, Active Living (REAL) intervention, previously shown to improve glucose levels and quality of life among YAs with diabetes, using telehealth delivery (REAL-T) to expand reach and accessibility. This paper reports on the methodology and baseline participant characteristics of the REAL-T study. METHODS: REAL-T is a two-arm randomized controlled trial that recruited 18-30 year olds with T1D via clinics and social media advertising. Data collection, which was adapted to be fully remote due to COVID-19, occurs every three months for one year. Participants receive either usual care or a 6-month telehealth occupational therapy intervention. The primary outcome is glycated hemoglobin (A1c); secondary outcomes include diabetes distress, quality of life, and continuous glucose monitor-derived measures. RESULTS: The study enrolled a diverse sample of 209 YAs with T1D. Analysis of baseline data indicates equivalence between the intervention and control groups. Study participants have notably higher diabetes distress and poorer mental well-being than similar populations. CONCLUSION: The REAL-T study successfully adapted to remote implementation during the COVID-19 pandemic. By examining long-term outcomes, mediating pathways, and cost-effectiveness, the study will contribute knowledge of the impact of tailored interventions for YAs with T1D, designed to reduce disparities and improve health and well-being in this population.

Early Serial Echocardiographic and Ultrasonographic Findings in Critically Ill Patients With COVID-19.

Background: Cardiac function of critically ill patients with COVID-19 generally has been reported from clinically obtained data. Echocardiographic deformation imaging can identify ventricular dysfunction missed by traditional echocardiographic assessment. Research Question: What is the prevalence of ventricular dysfunction and what are its implications for the natural history of critical COVID-19? Study Design and Methods: This is a multicenter prospective cohort of critically ill patients with COVID-19. We performed serial echocardiography and lower extremity vascular ultrasound on hospitalization days 1, 3, and 8. We defined left ventricular (LV) dysfunction as the absolute value of longitudinal strain of < 17% or left ventricle ejection fraction (LVEF) of < 50%. Primary clinical outcome was inpatient survival. Results: We enrolled 110 patients. Thirty-nine (35.5%) died before hospital discharge. LV dysfunction was present at admission in 38 patients (34.5%) and in 21 patients (36.2%) on day 8 (P = .59). Median baseline LVEF was 62% (interquartile range [IQR], 52%-69%), whereas median absolute value of baseline LV strain was 16% (IQR, 14%-19%). Survivors and nonsurvivors did not differ statistically significantly with respect to day 1 LV strain (17.9% vs 14.4%; P = .12) or day 1 LVEF (60.5% vs 65%; P = .06). Nonsurvivors showed worse day 1 right ventricle (RV) strain than survivors (16.3% vs 21.2%; P = .04). Interpretation: Among patients with critical COVID-19, LV and RV dysfunction is common, frequently identified only through deformation imaging, and early (day 1) RV dysfunction may be associated with clinical outcome.

Using a Low-Flow Extracorporeal Carbon Dioxide Removal (ECCO2R) System in the Management of Refractory Status Asthmaticus: A Case Series.

Rescue treatments for status asthmaticus remain limited. Current literature has mainly focused on using extracorporeal membrane oxygenation (ECMO) as a primary modality of care for these patients. Low-flow extracorporeal CO2 removal (ECCO2R) systems are an attractive option to improve refractory hypercapnic respiratory acidosis because of status asthmaticus. This is a retrospective case series that describes the feasibility and efficacy of the use of a low-flow ECCO2R device, the Hemolung Respiratory Assist System, in patients with refractory hypercapnic respiratory failure because of status asthmaticus. Eight patients were treated with the Hemolung Respiratory Assist System in eight separate locations globally. Seven (88%) of the patients survived to discharge in this case series. Both CO2 and pH resolution were seen in 6 hours. None of the ECCO2R runs were stopped because of mechanical- or device-related complications. One patient necessitated transition to ECMO. Low-flow ECCO2R systems is an effective option for resolution of refractory hypercapnia in status asthmaticus. Use of these systems are also associated with a survival rate of close to 90% in patients with status asthmaticus.

Design of SERENA-6, a phase III switching trial of camizestrant in ESR1-mutant breast cancer during first-line treatment.

ESR1 mutation (ESR1m) is a frequent cause of acquired resistance to aromatase inhibitor (AI) plus cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6i), which is a first-line therapy for hormone-receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer (ABC). Camizestrant is a next-generation oral selective estrogen receptor degrader (SERD) that in a phase II study significantly improved progression-free survival (PFS) over fulvestrant (also a SERD) in ER+/HER2- ABC. SERENA-6 (NCT04964934) is a randomized, double-blind, phase III study evaluating the efficacy and safety of switching from an AI to camizestrant, while maintaining the same CDK4/6i, upon detection of ESR1m in circulating tumor DNA before clinical disease progression on first-line therapy for HR+/HER2- ABC. The aim is to treat ESR1m clones and extend the duration of control of ER-driven tumor growth, delaying the need for chemotherapy. The primary end point is PFS; secondary end points include chemotherapy-free survival, time to second progression event (PFS2), overall survival, patient-reported outcomes and safety.

Why will we perform this study? Patients with advanced breast cancer in which the cancer cells have the receptor for the hormone estrogen and/or progesterone are typically treated with an aromatase inhibitor, a hormone therapy that decreases estrogen being made in the body, together with an inhibitor of cyclin-dependent kinases 4 and 6 (CDK4/6), a drug that blocks the growth of cancer cells. Although cancers usually respond to treatment initially, the cancer cells eventually change, so the drug combination no longer works. For example, mutation of the estrogen receptor (referred to as ESR1m) can stop aromatase inhibitors from working. Camizestrant is an investigational drug that blocks estrogen receptors, including mutated receptors, reducing the growth and spread of cancer. Here we describe the SERENA-6 clinical trial, which is testing camizestrant as a treatment for patients with breast cancer with ESR1m. How will we perform this research? The phase III SERENA-6 trial will use blood tests to monitor if patients with breast cancer develop ESR1m while being treated with an aromatase inhibitor and a CDK4/6 inhibitor. If ESR1m is detected, yet the disease is stable, participants will be randomly assigned to either continue with the same aromatase inhibitor or switch to camizestrant while continuing with the same CDK4/6 inhibitor. The study will assess whether switching to camizestrant prolongs the time before the cancer grows, spreads or worsens. It will also assess the length of time that participants live for versus those who continue with an aromatase inhibitor. Clinical Trial Registration: NCT04964934 (ClinicalTrials.gov).

Lung Ultrasonographic Signs in Pulmonary Disease - A Video Review.

Lung ultrasound (US) is a well-established imaging tool in the inpatient and critical care setting. It has proven its worth in the rapid bedside diagnosis of a variety of conditions pertaining to the lungs and the thorax. Lung US was initially introduced as a bedside imaging tool to evaluate the size and characteristics of pleural effusion. Over the years, the field of lung ultrasonography has rapidly expanded introducing nuances in image interpretation. Numerous primary and secondary signs have been described in the literature to identify both normal and abnormal findings. The primary signs can help narrow the list of differential diagnoses, whereas the addition of secondary signs help create an imaging pattern facilitating the confirmation of diagnosis or recognition of the underlying disease process. These wide variety of signs and patterns can present a challenge to the learning of lung ultrasonography, particularly to a novice user. We sought to compile a comprehensive list of these findings to serve as a useful resource to aid effortless adoption of lung ultrasonography in clinical practice. In this review, we narrate the evolution of lung US, describe common protocols applied in performance of the lung US, and illustrate a comprehensive list of common lung US signs and patterns along with their differential diagnosis and clinical utility.

On the horizon: Extracorporeal carbon dioxide removal.

Extracorporeal carbon dioxide removal (ECCO2R) uses mechanical systems to treat hypercapnic respiratory failure. Its utility has been investigated in acute respiratory distress syndrome (ARDS), acute exacerbations of chronic obstructive pulmonary disease (COPD), and status asthmaticus, and as a bridge to lung transplant. In this review, we discuss how it works, why it should help, and current evidence supporting its use.

A confounding bronchopulmonary situs abnormality after bilateral lung transplantation.

A 36-year-old female with a past medical history of primary ciliary dyskinesia and bilateral lung transplantation was noted to have a rare and confounding postsurgical anatomy acquired as a result of transplantation. Bronchoscopy and computed tomography showed isomeric main bronchi with a tri-lobed right lung, a bi-lobed left lung and dextrocardia. This rare phenomenon can be observed in lung transplant recipients with situs ambiguous morphology of their native lungs, who receive donor lungs with normal situs solitus morphology. To the best of our knowledge, ours is the first reported case of such a composite bronchopulmonary situs abnormality. Careful review of bronchial anatomy should be done with the help of CT imaging prior to undertaking any bronchial interventions in these subset of patients with bronchial isomerism and bilateral lung transplantation.

Secondary Prevention Using Cholesterol-Lowering Medications in Patients with Prior Atherosclerotic Cardiovascular Disease Events: A Retrospective Cohort Analysis.

Background: Secondary prevention with lipid-lowering medications in patients with atherosclerotic cardiovascular disease (ASCVD) is known to reduce the risk of clinical events and death. Current guidelines codify recommendations for implementing secondary prevention in appropriate patients. However, in real-world practice, secondary prevention is frequently initiated only after the patient experiences a cardiovascular-related hospitalization. The impact of these delays is not well known. Objectives: To estimate the effects of delaying treatment on the risk of cardiovascular-related hospitalization and on costs for patients who meet the criteria for secondary prevention as specified in the 2013 American College of Cardiology/American Heart Association (ACC/AHA) Guidelines for Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults. Methods: This is a retrospective cohort analysis using Humana data. Eligible patients were categorized by treatment group: (1) patients who initiated treatment before an ASCVD-related hospitalization and (2) patients who either did not initiate treatment until after an ASCVD hospitalization or never initiated treatment. The associations between the timely initiation of cholesterol-lowering medications for secondary prevention and (1) the risk for an ASCVD hospitalization and (2) health-care costs over one year, were estimated using multivariate regressions. Results: A total of 272 899 secondary prevention patients were identified who met study selection criteria. Early treatment was associated with significant reductions in the risk of an ASCVD hospitalization at any time following the identification of the patient's eligibility for secondary prevention (by 33% compared to those treated late or never, P<.0001), but was significantly associated with higher total cost over the first post-index year (by US $509, P<.001). Patients whose low-density lipoprotein cholesterol (LDL-C) levels were >130 mg/dL experienced higher ASCVD hospitalization risks, and also larger risk reductions if treated before an ASCVD hospitalization compared to patients with lower LDL-C levels who were treated late or never treated. Conclusions: More widespread implementation of the treatment policies specified in the 2013 ACC/AHA Guidelines for secondary prevention should significantly reduce cardiovascular disease hospitalizations and reduce costs.

Polycythemia Vera: Rapid Evidence Review.

Polycythemia vera is one of three stem-cell-derived myeloid malignancies commonly known as myeloproliferative neoplasms. It is characterized by erythrocytosis, often with associated leukocytosis and thrombocytosis. It has a significant negative impact on overall mortality and morbidity in the form of arterial and venous clots, symptoms of fatigue and pruritus, and conversion to leukemia and myelofibrosis. The World Health Organization's major diagnostic criteria include an elevated hemoglobin or hematocrit level, abnormal results on bone marrow biopsy, and presence of the Janus kinase 2 genetic mutation, which is present in approximately 98% of cases. The only minor criterion is a subnormal erythropoietin level, which helps differentiate polycythemia vera from common causes of secondary erythrocytosis such as smoking, sleep apnea, and testosterone use. First-line treatments, such as low-dose aspirin and goal-directed phlebotomy to a hematocrit level of less than 45% to reduce thrombotic events, improve quality of life and prolong survival. When indicated, cytoreductive therapy, primarily with hydroxyurea, can be added with consideration of second-line agents such as pegylated interferon-alfa, busulfan, and ruxolitinib, depending on the clinical scenario. Smoking cessation and cardiometabolic disease are modifiable risk factors that should be addressed to reduce the risk of thrombosis. Currently, no medications have been shown to cure the disease or to reduce the risk of conversion to leukemia and myelofibrosis.

Point-of-care ultrasonography for the hospitalist.

Point-of-care ultrasonography (POCUS) has emerged as a vital tool in medicine. Initially used for procedural guidance, POCUS is now used for diagnostics and monitoring of the lung, heart, abdomen, and deep vein thrombosis. This wide applicability makes it an essential tool for hospitalists in daily clinical practice. This article provides an overview of the clinical integration of POCUS and basic image interpretation.

Hypoglycemia and Glycemic Control in Older Adults With Type 1 Diabetes: Baseline Results From the WISDM Study.

BACKGROUND: Knowledge regarding the burden and predictors of hypoglycemia among older adults with type 1 diabetes (T1D) is limited. METHODS: We analyzed baseline data from the Wireless Innovations for Seniors with Diabetes Mellitus (WISDM) study, which enrolled participants at 22 sites in the United States. Eligibility included clinical diagnosis of T1D, age ≥60 years, no real-time continuous glucose monitoring (CGM) use in prior three months, and HbA1c <10.0%. Blinded CGM data from 203 participants with at least 240 hours were included in the analyses. RESULTS: Median age of the cohort was 68 years (52% female, 93% non-Hispanic white, and 53% used insulin pumps). Mean HbA1c was 7.5%. Median time spent in the glucose range <70 mg/dL was 5.0% (72 min/day) and <54 mg/dL was 1.6% (24 min/day). Among all factors analyzed, only reduced hypoglycemia awareness was associated with greater time spent <54 mg/dL (median time of 2.7% vs 1.3% [39 vs 19 minutes per day] for reduced awareness vs aware/uncertain, respectively, P = .03). Participants spent a mean 56% of total time in target glucose range of 70-180 mg/dL and 37% of time above 180 mg/dL. CONCLUSIONS: Over half of older T1D participants spent at least an hour a day with glucose levels <70 mg/dL. Those with reduced hypoglycemia awareness spent over twice as much time than those without in a serious hypoglycemia range (glucose levels <54 mg/dL). Interventions to reduce exposure to clinically significant hypoglycemia and increase time in range are urgently needed in this age group.

Evaluation and management of shock in patients with COVID-19.

Shock is common in critically ill patients with COVID-19, developing in up to 67% of patients in intensive care (5% to 10% overall) and is associated with high mortality. Optimal management requires prompt recognition with precise evaluation and differentiation. Correcting hypoperfusion and treating the underlying process are fundamental aspects of treatment. Undifferentiated shock may be treated initially with norepinephrine to optimize perfusion while additional evaluation is performed to categorize the shock pathophysiology. Physical examination, bedside echocardiography, hemodynamic monitoring, lactate and venous oxygen saturation are important components of the patient evaluation.

Point-of-care ultrasound and COVID-19.

Point-of-care ultrasound has an important role in the management of patients with COVID-19 infection. Because the utility of each application varies by setting, individual institutions should consider how they can best use ultrasound within their specific environments. In general, procedural guidance and focused echocardiography are high yield. Lung ultrasound has the potential to aid the diagnosis and management of patients with COVID-19 infection. Lower extremity point-of-care ultrasound for deep vein thrombosis may help guide decision making regarding anticoagulation or undifferentiated shock. It is of the utmost priority that ultrasound not spread infection, so point-of-care ultrasound must be used only when clinically indicated. Institutions should have protocols for machine disinfection.

A Deep Learning Approach for Automated Sleep-Wake Scoring in Pre-Clinical Animal Models.

BACKGROUND: Experimental investigation of sleep-wake dynamics in animals is an important part of pharmaceutical development. Typically, it involves recording of electroencephalogram, electromyogram, locomotor activity, and electrooculogram. Visual identification, or scoring, of the sleep-wake states from these recordings is time-consuming. We sought to develop software for automated sleep-wake scoring capable of processing large databases of multi-channel signal recordings in a range of species. NEW METHOD: We used a large historical database of signal recordings and scores in non-human primates, dogs, mice, and rats, to develop a deep Convolutional Neural Network (CNN) classification algorithm for automatically scoring sleep-wake states. We compared the performance of the CNN algorithm with that of a widely used Machine Learning algorithm, Random Forest (RF). RESULTS: CNN accuracy in sleep-wake scoring of data in non-human primates and dogs was significantly higher than RF accuracy (0.75 vs. 0.66 for non-human primates and 0.73 vs. 0.64 for dogs). In rodents, the difference between CNN and RF was smaller: 0.83 vs. 0.81 for mice and 0.78 vs. 0.77 for rats. The variability of CNN accuracy was lower than that of RF for non-human primates, dogs and mice but similar for rats. COMPARISON WITH EXISTING METHODS: Deep Learning algorithms have not been previously evaluated across a range of species for animal sleep-wake scoring. CONCLUSIONS: We recommend use of CNN for sleep-wake scoring in non-human primates and dogs, and RF for sleep-wake scoring in rodents.

Developing and Evaluating a Remote Quality Assurance System for Point-of-Care Ultrasound for an Internal Medicine Residency Global Health Track.

Background: A quality assurance system is vital when using point-of-care ultrasound (POCUS) to ensure safe and effective ultrasound use. There are many barriers to implementing a quality assurance system including need for costly software, faculty time, and extra work to log images. Methods: With minimal funding or protected faculty time, we successfully developed an effective remote quality assurance system between residents rotating internationally and faculty in the US. Results: 270 total exams were logged using this system (41 per resident over a 7 week period). Over the course of the implementation period, a significant increase was seen in average image quality (p = 0.030) and percent agreement with reviewer (p = 0.021). No significant increase was seen for percent images with quality rating 5/5 (p = 0.068) or for studies per resident per week (p = 0.30). Discussion/Conclusions: A quality assurance system for remote review and feedback of POCUS exams was successfully developed with limited available funding, using consumer-level software and an educational collaboration. Residents used the system regularly and demonstrated improvement in reviewer-rated image acquisition and interpretation skills. A similar system can be applied for physicians in any geographic area looking to learn POCUS, in partnership with local or international POCUS mentors. We detail a step-by-step approach, challenges encountered, and lessons learned, to help guide others seeking to implement similar programs.

Place cell firing cannot support navigation without intact septal circuits.

Though it has been known for over half a century that interference with the normal activity of septohippocampal neurons can abolish hippocampal theta rhythmicity, a definitive answer to the question of its function has remained elusive. To clarify the role of septal circuits and theta in location-specific activity of place cells and spatial behavior, three drugs were delivered to the medial septum of rats: Tetracaine, a local anesthetic; muscimol, a GABA-A agonist; and gabazine, a GABA-A antagonist. All three drugs disrupted normal oscillatory activity in the hippocampus. However, tetracaine and muscimol both reduced spatial firing and interfered with the rat's ability to navigate to a hidden goal. After gabazine, location-specific firing was preserved in the absence of theta, but rats were unable to accurately locate the hidden goal. These results indicate that theta is unnecessary for location-specific firing of hippocampal cells, and that place cell activity cannot support accurate navigation when septal circuits are disrupted.