Differential cardiopulmonary haemodynamic phenotypes in PASC-related exercise intolerance.

Background: Post-acute sequelae of COVID-19 (PASC) affect a significant proportion of patients who have previously contracted SARS-CoV-2, with exertional intolerance being a prominent symptom. This study aimed to characterise the invasive haemodynamic abnormalities of PASC-related exertional intolerance using invasive cardiopulmonary exercise testing (iCPET). Study design and intervention: 55 patients were recruited from the Yale Post-COVID-19 Recovery Program, with most experiencing mild acute illness. Supine right heart catheterisation and iCPET were performed on all participants. Main results: The majority (75%) of PASC patients exhibited impaired peak systemic oxygen extraction (pEO2) during iCPET in conjunction with supranormal cardiac output (CO) (i.e., PASC alone group). On average, the PASC alone group exhibited a "normal" peak exercise capacity, V'O2 (89±18% predicted). ∼25% of patients had evidence of central cardiopulmonary pathology (i.e., 12 with resting and exercise heart failure with preserved ejection fraction (HFpEF) and two with exercise pulmonary hypertension (PH)). PASC patients with HFpEF (i.e., PASC HFpEF group) exhibited similarly impaired pEO2 with well compensated PH (i.e., peak V'O2 and CO >80% respectively) despite aberrant central cardiopulmonary exercise haemodynamics. PASC patients with HFpEF also exhibited increased body mass index of 39±7 kg·m-2. To examine the relative contribution of obesity to exertional impairment in PASC HFpEF, a control group comprising obese non-PASC group (n=61) derived from a historical iCPET cohort was used. The non-PASC obese patients with preserved peak V'O2 (>80% predicted) exhibited a normal peak pulmonary artery wedge pressure (17±14 versus 25±6 mmHg; p=0.03) with similar maximal voluntary ventilation (90±12 versus 86±10% predicted; p=0.53) compared to PASC HFpEF patients. Impaired pEO2 was not significantly different between PASC patients who underwent supervised rehabilitation and those who did not (p=0.19). Conclusions: This study highlights the importance of considering impaired pEO2 in PASC patients with persistent exertional intolerance unexplained by conventional investigative testing. Results of the current study also highlight the prevalence of a distinct high output HFpEF phenotype in PASC with a primary peripheral limitation to exercise.

Accessibility of Pulmonary Rehabilitation in the US.

This cross-sectional study examines nationwide travel time to pulmonary rehabilitation (PR) programs and PR access in the US.

Acute and subacute neurovascular impact of cryptogenic air emboli.

Background: Cerebral air embolism is a rare cause of acute ischemic stroke that is becoming increasingly well-described in the literature. However, the mechanism and severity of this type of injury can vary, with ischemia typically emerging early in the course of care. To the best of our knowledge, delayed ischemia in this setting has not yet been described. Case Description: A stroke code was called for an unresponsive, hospitalized, 75-year-old man. A computerized tomography (CT) scan of the head revealed air within the right greater than left hemispheric cortical veins with loss of sulcation, concerning for developing ischemia, and CT angiography revealed absent opacification of the distal cortical vessels in the right anterior cerebral artery and middle cerebral artery territories. Magnetic resonance imaging (MRI) of the brain was obtained 5.75 h after the patient's last known well-showed small areas of subtle cortical diffusion restriction. Follow-up CT head within 24 h showed near-complete resolution of the air emboli after treatment with 100% fraction of inspired oxygen on mechanical ventilation. Subsequent MRI, performed 4 days after the initial event, showed extensive cortical diffusion restriction and cerebral edema crossing vascular territories. Conclusion: This case highlights that cerebral air emboli can cause delayed ischemia that may not be appreciated on initial imaging. As such, affected patients may require intensive neurocritical care management, close neurologic monitoring, and repeat imaging irrespective of initial radiographic findings.

Availability and Accessibility of Live Nonreplicating Smallpox/Mpox Vaccine.

This cross-sectional study compares the availability and accessibility of mpox vaccine sites with the number of reported cases and allocated vaccines.

Travel Times to Facilities Offering Oral Medication Therapy for COVID-19.

This quality improvement study evaluates access to oral COVID-19 therapeutics within communities in the 48 contiguous states and the District of Columbia.

Impact of a Medical Clinic Relocation on Travel Time: A Tale of 2 Modes of Transportation.

The aim of this study was to quantify access disparities by examining the impact of a medical clinic relocation on travel time differences for patients using private cars versus public transit. Longitude and latitude of patient home addresses were extracted from electronic medical records for the 4 years before the clinic move. Using offline, open-source, and HIPAA-compliant routing software, roundtrip travel times were computed from each home address to the old and new clinic locations via car and bus. Mean roundtrip travel time by a car changed from 41.3 (IQR 16.1-80.7) to 45.4 (IQR 25.9-78.1) minutes, a 9.9% increase. Mean roundtrip travel time by public transit changed from 67.5 (IQR 51.5-100.2) to 120.8 (100.3-156.1) minutes, a 78.9% increase. Even clinic relocations that minimally impact car travel times can nevertheless yield substantial changes to those traveling by public transit. Clinics and health systems that wish to reduce barriers to accessing health care, especially among those already facing structural inequities, would benefit from utilizing the analytic approach described here.

Relation of Cigarette Smoking and Heart Failure in Adults ≥65 Years of Age (From the Cardiovascular Health Study).

Cigarette smoking is associated with adverse cardiac outcomes, including incident heart failure (HF). However, key components of potential pathways from smoking to HF have not been evaluated in older adults. In a community-based study, we studied cross-sectional associations of smoking with blood and imaging biomarkers reflecting mechanisms of cardiac disease. Serial nested, multivariable Cox models were used to determine associations of smoking with HF, and to assess the influence of biochemical and functional (cardiac strain) phenotypes on these associations. Compared with never smokers, smokers had higher levels of inflammation (C-reactive protein and interleukin-6), cardiomyocyte injury (cardiac troponin T [hscTnT]), myocardial "stress"/fibrosis (soluble suppression of tumorigenicity 2 [sST2], galectin 3), and worse left ventricle systolic and diastolic function. In models adjusting for age, gender, and race (DEMO) and for clinical factors potentially in the causal pathway (CLIN), smoking exposures were associated with C-reactive protein and interleukin-6, sST2, hscTnT, and with N-terminal pro-brain natriuretic protein (in Whites). In DEMO adjusted models, the cumulative burden of smoking was associated with worse left ventricle systolic strain. Current smoking and former smoking were associated with HF in DEMO models (hazard ratio 1.41, 95% confidence interval 1.22 to 1.64 and hazard ratio 1.14, 95% confidence interval 1.03 to 1.25, respectively), and with current smoking after CLIN adjustment. Adjustment for time-varying myocardial infarction, inflammation, cardiac strain, hscTnT, sST2, and galectin 3 did not materially alter the associations. Smoking was associated with HF with preserved and decreased ejection fraction. In conclusion, in older adults, smoking is associated with multiple blood and imaging biomarker measures of pathophysiology previously linked to HF, and to incident HF even after adjustment for clinical intermediates.

Intercountry Differences in Guideline-Directed Medical Therapy and Outcomes Among Patients With Heart Failure.

OBJECTIVES: The aim of this study was to examine patterns of care and clinical outcomes among patients with heart failure with reduced ejection fraction (HFrEF) in the United States and Canada. BACKGROUND: In the GUIDE-IT (Guiding Evidence Based Therapy Using Biomarker Intensified Treatment) trial, the use of N-terminal pro-B-type natriuretic peptide-guided titration of guideline-directed medical therapy (GDMT) was compared with usual care alone for patients with HFrEF in the United States and Canada. It remains unknown whether the country of enrollment had an impact on outcomes or GDMT use. METHODS: A total of 894 patients at 45 sites across the United States and Canada with HFrEF (ejection fraction ≤40%) were enrolled in the trial. Kaplan-Meier survival estimates stratified by country of enrollment were developed for the trial outcomes, and log-rank testing was compared between the groups. GDMT use and titration were also compared. RESULTS: U.S. patients were more likely to be younger, to be Black, to have higher body mass index, and to have histories of defibrillator placement or sleep apnea. Use of ß-blockers was significantly higher in Canada at baseline (99.3% vs. 94.0%; p = 0.01) and 6 months (99.0% vs. 94.1%; p = 0.04), and use of mineralocorticoid receptor antagonists was higher in Canada at 6 months (68.3% vs. 55.1%; p = 0.01). Canadian patients were less likely to experience the primary study endpoint (hazard ratio [HR]: 0.65; 95% confidence interval [CI]: 0.45 to 0.93; p = 0.01) due to decreased rates of HF hospitalization (HR: 0.57; 95% CI: 0.38 to 0.86; p = 0.003). The differences in outcomes were driven by increased heart failure hospitalization among U.S. Black patients. CONCLUSIONS: In GUIDE-IT, patients with HFrEF in Canada were significantly less likely to be hospitalized for heart failure. Differences in GDMT use, along with differences in sociodemographics and care delivery structures, may contribute to these differences, highlighting the importance of increasing diversity in clinical trials. (Guiding Evidence Based Therapy Using Biomarker Intensified Treatment [GUIDE-IT]; NCT01685840).

Glucagon use by U.S. adults with type 1 and type 2 diabetes.

The American Diabetes Association recommends that all patients at risk for hypoglycemia be prescribed glucagon. Despite this recommendation, there is evidence that prescription rates are lower than expected for patients with type 1 and type 2 diabetes. This study investigated prescription patterns for glucagon among de-identified administrative claims from OptumLabs® Data Warehouse for prescriptions between January 1, 2014 and December 31, 2014 among pharmacologically treated type 1 and 2 diabetes patients. We find that glucagon was rarely filled by patients with type 1 and type 2 diabetes, including fewer than 5% of patients with prior hypoglycemia requiring emergency healthcare utilization. Among patients with type 1 diabetes, glucagon fills were unpredictable and not targeted to highest risk patients.

Accuracy of Height Measurement in the Inpatient Setting.

Accurate height measurement is critical for accurate dosing of medications, mechanical ventilation, and nutritional calculations. Prior research has identified inaccuracies with self-reported height, and height is notably important to measure accurately in critically ill patients. In this study, conducted in a large tertiary academic medical center, medical records rarely indicated the method of height measurement, and there were statistically significant variations in measured height across admissions.

Medical Student Patient Outreach to Ensure Continuity of Care During the COVID-19 Pandemic.

Background: In response to the COVID-19 pandemic, the Yale New Haven Health System began rescheduling nonurgent outpatient appointments as virtual visits in March 2020. While Yale New Haven Health expanded its telemedicine infrastructure to accommodate this shift, many appointments were delayed and patients faced considerable uncertainty. Objective: Medical students created the Medical Student Task Force (MSTF) to help ensure continuity of care by calling patients whose appointments were delayed during this transition to telemedicine. Methods: Eighty-five student volunteers called 3765 internal medicine patients with canceled appointments, completing screening for 2197 patients. Volunteers screened for health care needs, assessed preferences for future appointments, and offered emotional support and information about COVID-19. Urgent or emergent patient concerns were triaged and escalated to providers. In this analysis, we used a mixed-methods approach: call information and provider responses were analyzed quantitatively, and patient feedback was analyzed qualitatively via thematic analysis. Results: Ninety-one percent of patients screened found the MSTF calls helpful. Twenty-one percent of patients reported health concerns, with 1% reporting urgent concerns escalated to and addressed by providers. Themes of patient comments included gratitude for outreach and social contact, utility of calls, and well-wishes for health care workers. Conclusions: By calling patients whose appointments had been canceled during a rapid transition to telemedicine, the MSTF helped bridge a potential gap in care by offering patients communication with their care teams, information, and support. We propose that this model could be used in other care systems urgently transitioning to outpatient telemedicine, whether during ongoing outbreaks of COVID-19 or other public health emergencies.

Time-resolved cryo-EM using Spotiton.

We present an approach for preparing cryo-electron microscopy (cryo-EM) grids to study short-lived molecular states. Using piezoelectric dispensing, two independent streams of ~50-pl droplets of sample are deposited within 10 ms of each other onto the surface of a nanowire EM grid, and the mixing reaction stops when the grid is vitrified in liquid ethane ~100 ms later. We demonstrate this approach for four biological systems where short-lived states are of high interest.