Johns Hopkins Medicine

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help optimize medical and surgical decision-making for posterior cervical spinal fusion patients on GLP-1 agonists.

Contrast-enhanced echocardiography (CE-echo) is commonly used in adult patients to optimize endocardial border delineation (EBD) but there is limited experience in children. A prospective, open-label, non-randomized, multicenter study was performed to evaluate the efficacy of intravenous Optison for CE-echo in pediatric patients and determine the optimal dose of Optison. Subjects ≥ 9 and < 18years with suboptimal echocardiograms (defined as ≥ 2 contiguous segments that could not be adequately visualized) were enrolled. After a baseline non-contrast echocardiogram (NC-echo), CE-echo was performed with 2 dose levels of Optison based on patient weight. The primary endpoint was visualization of the LV wall segments (LVWS) in apical 2- and 4-chamber views. An EBD score was calculated by assigning a value from 0 (no visualization) to 3 (optimal visualization) for 12 LVWS. 37 subjects across 8 sites completed the study. 30 had complete echocardiograms at both dose levels. 2 patients had usable images at dose 2 only. Mean age was 13.4years (± 2.6) with 23 males (62%). Mean weight was 73.9kg (± 36.8) with wide distribution of weight (interquartile range of 42-102kg). There were 8 patients under 40kg. Most subjects had a prior medical/surgical history (n = 33, 89%). Both dose levels of Optison CE-echo improved the number of LVWS visualized from 3.7 ± 1.1 on NC-echo to 10.0 ± 0.1 with dose 1 (p < 0.001) and 10.5 ± 0.1 with dose 2 (p < 0.001). EBD score also improved at both dose levels from 11.9 ± 2.5 for NC-echo to 28.5 ± 1.7 for dose 1 (p < 0.001) and 30.2 ± 8.4 for dose 2 (p < 0.001). The number of suboptimal echocardiograms improved from 92.3% ± 10.7 in NC-echo to 26.2% ± 9 with dose 1 (p < 0.001) and 30.8% ± 4.5 with dose 2 (p < 0.001). CE-echo with intravenous Optison in pediatric patients improved the number of LVWS visualized, improved EBD score, and reduced the number of suboptimal echocardiograms at both dosages used in this study. Intravenous Optison can improve LV visualization in pediatric patients with suboptimal echocardiograms.

Airway mucus clearance from the lungs occurs by 2 widely recognized mechanisms: cilia-mediated clearance and high-velocity airflow-mediated cough clearance. However, a potentially important third mechanism of mucus clearance, referred to as cilia-independent gas–liquid transport (GLT), was proposed based on in vitro model systems to occur during normal tidal breathing but has largely been overlooked. We conducted in vitro and in vivo studies to investigate the role of tidal breathing airflow rates in mucus clearance. An in vitro airway culture bead-tracking model demonstrated airflow-dependent mucus transport at tidal breathing flow rates. As with other modes of mucus clearance, GLT was critically dependent on mucus concentration. In vivo studies in cilial beat-deficient mice demonstrated that GLT-mediated mucus clearance occurs during tidal breathing in the absence of cough, and the rate of GLT mucus clearance was dependent on breathing frequency and body orientation. These studies demonstrated that GLT is a third mechanism of mucus clearance and likely represents a significant mode of clearance in persons with cilial dysfunction. These findings indicate that increasing breathing rates through exercise, using mucus rehydrating agents or mucolytics, or combining these approaches may restore clinically and physiologically meaningful airway clearance in these patients.

BackgroundBrepocitinib is a first-in-class, oral, selective TYK2–JAK1 inhibitor that blocks cytokine signaling, which has been implicated in dermatomyositis.MethodsIn this phase 3, double-blind, randomized, placebo-controlled trial, adults with dermatomyositis were assigned in a 1:1:1 ratio to receive once-daily oral brepocitinib at a dose of 30 mg, brepocitinib at a dose of 15 mg, or placebo for 52 weeks. Standard therapies were continued, and glucocorticoids were tapered. The primary end point was the Total Improvement Score, a validated composite myositis index (with scores ranging from 0 to 100 and higher scores indicating greater improvement) at week 52. Key secondary end points, including skin disease activity, glucocorticoid tapering, and physical function, were tested in a multiplicity-controlled sequence.ResultsA total of 241 patients underwent randomization: 81 to receive brepocitinib 30 mg, 81 to receive brepocitinib 15 mg, and 79 to receive placebo. At week 52, the mean Total Improvement Score was 46.5, 37.5, and 31.2, respectively (difference with brepocitinib 30 mg vs. placebo, 15.3; 95% confidence interval [CI], 6.7 to 24.0; P<0.001; difference with brepocitinib 15 mg vs. placebo, 6.3; 95% CI, −2.4 to 14.9). Brepocitinib 30 mg was superior to placebo across all nine key secondary end points, including skin disease activity, systemic glucocorticoid tapering, and functional disability, with improvements observed as early as week 4. Serious infections were more frequent in the brepocitinib 30-mg group than in the placebo group (10% vs. 1%). No deaths occurred during the trial.ConclusionsIn adults with dermatomyositis that was resistant to previous therapy, the use of brepocitinib at a dose of 30 mg (but not at a dose of 15 mg) resulted in significant benefits with respect to a composite myositis index, skin disease severity, glucocorticoid tapering, and functional disability. (Funded by Priovant Therapeutics; ClinicalTrials.gov number, NCT05437263.)

BackgroundAmerican Indian and Alaska Native communities experience disproportionately high suicide rates. While machine learning (ML) models leveraging electronic health records have emerged as promising tools for suicide risk identification, the optimal integration of these models with existing screening practices remains unclear.ObjectiveThe objective of this study was to compare parallel and serial testing strategies that combine an ML suicide risk model and the Ask Suicide-Screening Questions (ASQ) against using the ASQ alone. To achieve this, we conducted a retrospective secondary analysis of electronic health record data. The cohort consisted of adult emergency department visits at an Indian Health Service facility between October 1, 2019, and October 2, 2021.MethodsSensitivity, specificity, predictive values, and 95% CIs were averaged across 10 cross-validated patient-level folds. The final sample included 7897 American Indian patients with 26,896 visits, 824 (3.1%) of which had a positive ASQ result and 102 (0.4%) of which had the outcome of suicide attempt or death within 90 days of the visit. The logistic regression ML model previously developed using Indian Health Service–specific data was operationalized at the 95th and 75th percentiles to evaluate high-risk and medium-risk thresholds, respectively. A sensitivity analysis was performed to evaluate identification approaches across all emergency department visits during this period.ResultsThe ML medium-risk threshold alone identified the most true positives (sensitivity: 0.782, 95% CI 0.648-0.915; specificity: 0.751, 95% CI 0.725-0.777; positive predictive value [PPV]: 0.012, 95% CI 0.009-0.014; negative predictive value [NPV]: 0.999, 95% CI 0.998-0.999) in comparison to the ML high-risk threshold alone (sensitivity: 0.429, 95% CI 0.287-0.572; specificity: 0.955, 95% CI 0.948-0.961; PPV: 0.035, 95% CI 0.022-0.048; NPV: 0.998, 95% CI 0.997-0.999) or the ASQ alone (sensitivity: 0.178, 95% CI 0.073-0.282; specificity: 0.970, 95% CI 0.968-0.971; PPV: 0.022, 95% CI 0.010-0.034; NPV: 0.997, 95% CI 0.996-0.998). Combining the ML high-risk threshold with the ASQ in series yielded the greatest positive predictive ability (PPV: 0.050, 95% CI 0.014-0.086) at the cost of reduced sensitivity (0.129, 95% CI 0.036-0.221). Finally, the parallel testing approach using the ML medium-risk threshold yielded the greatest sensitivity (0.795, 95% CI 0.671-0.920; specificity: 0.742, 95% CI 0.716-0.767; PPV: 0.012, 95% CI 0.009-0.014; NPV: 0.999, 95% CI 0.998-0.999) without missing any cases identified through screening.ConclusionsUnlike existing studies that evaluate ML and screening tools in isolation, this study innovates by assessing combined parallel and serial testing strategies in a real-world setting. We demonstrated that, while serial testing maximizes predictive accuracy, it is often infeasible. Instead, parallel testing brings value as a clinical “safety net” to catch at-risk patients missed by standard practices. Ultimately, integrating ML in suicide prevention requires balancing statistical accuracy with setting-specific, real-world workflows.

Although clinical guidelines endorse enoxaparin for the prevention of venous thromboembolism in patients with orthopaedic trauma, recent evidence from a large clinical trial has demonstrated that aspirin provides comparable protection against death and pulmonary embolism. This study evaluated the cost-effectiveness of thromboprophylaxis with enoxaparin compared with that with aspirin in patients with orthopaedic trauma from the perspective of the U.S. health-care system. The study modeled a hypothetical cohort of adult patients with an operatively treated extremity, pelvic, or acetabular fracture based on data from a recent clinical trial and national databases. We used a decision analysis model to compare 30 mg of enoxaparin with 81 mg of aspirin, administered twice daily in-hospital and prescribed for 21 days after discharge. Health-care costs and quality-adjusted life-years (QALYs) within 1 year after the injury derived from published research and publicly available cost data were based on potential disease states, including death or a combination of pulmonary embolism, proximal deep vein thrombosis, distal deep vein thrombosis, or a bleeding complication. We assessed cost-effectiveness compared with a willingness-to-pay threshold of $150,000 per QALY. Our model estimated that the 1-year health-care costs among patients prescribed enoxaparin were $35,301, producing 0.6705 QALYs. Aspirin was associated with $35,067 in 1-year health-care costs and 0.6701 QALYs. The overall health-care costs were $234 higher with enoxaparin but yielded only a 0.0004 improvement in QALYs, for an incremental cost-effectiveness ratio for enoxaparin of $635,340 per QALY, indicating that enoxaparin is not cost-effective compared with aspirin. In a sensitivity analysis, the probability of enoxaparin thromboprophylaxis being cost-effective compared with aspirin was 9.8% in 10,000 iterations. The findings suggest that enoxaparin is not cost-effective relative to aspirin for thromboprophylaxis in patients with orthopaedic trauma. The results support consideration of aspirin as a preferred agent in future guidelines, especially given the consistent patient preference for its oral administration. Economic and Decision Analysis Level I . See Instructions for Authors for a complete description of levels of evidence.