Citations

Migraine is one of the most disabling diseases worldwide, especially when it transforms into chronic migraine, which is often associated with medication overuse and can become resistant or even refractory to treatments. Molecular, neuroimaging and neurophysiological changes have been described in chronic migraine, some of which might not be fully reversible with preventive treatment. For these reasons, we should aim to prevent this transition, and initiate preventive treatment before disease becomes refractory and burden increases. Preventive migraine treatments are often delayed because of access to care, stigma leading to undertreatment and patients’ reluctance as a result of fear of side effects and, in some cases, fear of being labeled as chronically ill. With the availability of effective and well-tolerated preventive treatments, we must shift our mindset and take advantage of new opportunities to initiate preventive treatment earlier. In this International Headache Society position statement, we propose a migraine preventive strategy under the idea of shifting from reactive treatment once disability is established (prevention of attacks), to proactive, individualized prevention initiated early with safe, effective and tolerable therapies (prevention of disease progression). This approach is based on 1) promoting the early initiation of effective and tolerable preventive therapies, starting from two to four monthly migraine days in line with the majority of current guidelines and recommendations and 2) fostering longitudinal studies to gather more evidence on the potential benefit of early prevention, with the final goal of improving patient outcomes, promoting excellent migraine care, enhancing individual and social well-being, and, ultimately, preventing migraine progression and preserving brain health.

Objective To explore current approaches to evaluation and treatment decision-making for velopharyngeal insufficiency (VPI) following cleft palate repair. Design Cross-sectional, qualitative study. Setting/participants Participants included 28 surgeons and 17 speech-language pathologists (SLPs) from 12 cleft teams in the United States and Canada. Interventions Semi-structured, qualitative interviews were conducted exploring participants’ current approaches to VPI evaluation and treatment decision-making. Data were analyzed using thematic analysis. Results Participants viewed VPI evaluation as a joint effort of surgeons and SLPs. SLPs were entrusted to conduct formal speech evaluations. All teams completed a perceptual evaluation of speech resonance that included spontaneous speech and phrase repetition. Teams varied in their use of patient questionnaires and nasometry. Most teams performed nasoendoscopy as part of their evaluation, although providers noted limited cooperation in younger children and those with developmental delay. Treatment decision-making occurred either as a joint effort between the evaluating surgeon and SLP or exclusively by the surgeon. Most surgeons employed a personalized approach to treatment decision-making, with 19 distinct approaches described. Elements frequently considered in surgical procedure selection included velopharyngeal gap size and closure pattern as seen on nasoendoscopy. Providers were satisfied with their current approach, although most identified opportunities for improvement. Conclusions Cleft teams have individualized approaches to VPI evaluation and treatment decision-making, with the only common element being completion of a perceptual speech evaluation by an SLP. These findings suggest that efforts to implement new approaches will need to be customized to each team's current process.

Data from the current study support the hypothesis that the pressure-generating capacity of the diaphragm at high lung volume is compromised primarily due to a mechanism that involves a combined mechanical effect of hyperinflation and substantial muscle contraction rather than a significant loss of its muscle fiber curvature.

Purpose: To compare stone clearance, stone-free status, and complications between patients undergoing ureteroscopy for renal stones using either Flexible and Navigable Ureteral Access Sheath (FANS) or the CVAC 2.0 system. Materials and Methods: A prospective study was completed on patients undergoing flexible ureteroscopy for renal stones at a single institution from March 2024 to December 2024. Subject demographics, intra-op data, volumetric and single-dimension stone clearance on non-contrast CT, and complications were compared. Stone-free rates (SFRs) using standardized cutoffs were compared. Pearson correlation analysis was performed to assess the relationship between preoperative stone volume and postoperative stone burden. Subanalysis was performed for patients with preoperative stone burden >1.5 cm. Results: A total of 123 cases (CVAC 2.0-36, FANS-87) were included, with 64 eligible for volumetric analysis. Preoperative stone volume was larger in the CVAC group vs FANS (1075 mm 3 vs 397 mm 3 ; p < 0.001). Absolute stone clearance was greater in the CVAC group (1016 mm 3 vs 392 mm 3 ; p < 0.001), whereas residual stone volume (4.1 mm 3 vs 15.0 mm 3 ; p = 0.55) and SFRs (90% vs 81%; p = 0.48) were similar. In individuals with >1.5 cm preoperative stone burden, relative stone clearance was greater with CVAC 2.0 (98.9% vs 95.1%; p = 0.026). Pearson correlation analysis revealed positive linear relationship between preoperative stone volume and residual stone volume for FANS, but not for CVAC 2.0. Conclusions: In this comparative study of FANS and CVAC 2.0, over 95% stone clearance was observed in both groups despite large initial stone burdens. In contrast to FANS, residual stone volumes with CVAC 2.0 did not increase significantly with increasing preoperative stone volumes.

Introduction: Family medicine contributes less scholarship and receives much less grant money than other specialties. Understanding when and how this disparity begins is a key step in addressing the gap in family medicine scholarship. Methods: We analyzed data from the National Resident Matching Program’s (NRMP’s) Charting Outcomes in the Match (2016–2024) to compare family medicine applicants with applicants to other specialties (ie, internal medicine, pediatrics, and all specialties combined). We examined the mean number of research experiences and the number of presentations and publications applicants had completed prior to starting residency. Additionally, we analyzed NRMP surveys to evaluate the weight applicants placed on institutional research support when choosing a residency program and the weight program directors placed on applicants’ research experience. Results: Family medicine applicants consistently reported fewer research experiences and presentations/publications than applicants to internal medicine, pediatrics, and all specialties combined. Osteopathic applicants showed the lowest research participation across all specialties we compared. Among other specialties, family medicine applicants placed less importance on programs’ research support, and family medicine residency program directors were less likely to consider research involvement when selecting applicants. Conclusions: Our results suggest that family medicine’s underrepresentation in research begins during the residency application process or sooner. Increased involvement in family medicine research among medical students should be a key component of strategies for bridging the research gap.

Importance Prostate-specific membrane antigen positron emission tomography (PSMA-PET), a form of molecular imaging, increases detection of advanced and metastatic prostate cancer, but its potential to increase treatment costs due to increased detection is poorly defined. Objective To estimate lifetime health and cost outcomes and evaluate the cost-effectiveness associated with implementing PSMA-PET in the clinical evaluation of a patient with a biochemical recurrence (BCR) of prostate cancer, with evaluation of sources of uncertainty in the underlying evidence and assessment of the need and focus of additional data collection. Design, Setting, and Participants This economic evaluation developed a decision-analytic model consisting of a decision tree and a Markov model informed by published literature and a study of patients with BCR prostate cancer undergoing PSMA-PET after definitive surgery or radiation therapy at 2 high-volume US academic centers. The analysis was performed between August 1, 2024, and May 1, 2025. Interventions Patients underwent (1) PSMA-PET, (2) PSMA-PET imaging as a reflex test if computed tomography plus bone scan (CTBS) was negative or equivocal (CTBS + PSMA-PET), and (3) CTBS alone. Main Outcomes and Measures Lifetime quality-adjusted life-years (QALYs) and costs, incremental cost-effectiveness ratio (ICER), and value of information estimates were assessed, with 95% uncertainty intervals (UIs). We assumed a willingness-to-pay threshold of $150 000 per QALY. Results The model simulated 1000 patients with BCR (median age, 66 years) and estimated that up-front PSMA-PET is expected to have the highest mean QALYs (7.12 QALYs [95% UI, 6.71-7.51 QALYs]) compared with 6.55 QALYs (95% UI, 6.08-7.03 QALYs) for CTBS; it was also estimated to have higher mean costs ($451 000 [95% UI, $336 000-$577 000]) compared with $351 000 (95% UI, $263 000-$455 000]) for CTBS; consequently, PSMA-PET had mean increments of $99 000 (95% UI, $55 000-153,000) in costs and 0.58 QALYs (95% UI, 0.35-0.82 QALYs) compared with CTBS, leading to an ICER of $172 000 per QALY, which exceeded the assumed $150 000/QALY willingness-to-pay threshold. In patients with lower prostate-specific antigen levels (&amp;lt;2 ng/mL), PSMA had mean increments of $61 000 (95% UI, $21 000-$104 000) in costs and 0.54 QALYs (95% UI, 0.34-0.77 QALYs) compared with CTBS, leading to an ICER of $113 000/QALY, suggesting it had the potential to be cost-effective. Because of high decisional uncertainty, additional information regarding outcomes and diagnostic characteristics may be associated with reduced uncertainty and a gain of 15 747 QALYs. Conclusions and Relevance This study found that PSMA-PET may be associated with improved disease detection but may not be cost-effective due to high treatment costs offsetting moderate improvements in QALYs. Further research is needed to identify patient subsets and clinical scenarios in which molecular imaging provides the greatest value.

Abstract Background Carbon ion radiotherapy (CIRT), characterized by its Bragg peak and a reduced lateral scattering compared to proton radiotherapy (PT), offers excellent dose conformity in radiation treatment. Meanwhile, compared to PT, CIRT causes more complex and severe DNA damage in tumor cells, which results in a higher relative biological effectiveness (RBE), making it particularly advantageous in treating radioresistant and hypoxia tissues than conventional radiotherapy. However, CIRT's high RBE and the nuclear fragmentation dose tail outside the target presents challenges in sparing organ at risk (OARs). Combining PT and CIRT offers a potential hybrid modality that leverages the biological effectiveness of carbon ions while minimizing normal tissue toxicity with high biological damage. Purpose Despite the potential of combining PT and CIRT, balancing their respective advantages while mitigating disadvantages remains a significant challenge. This study aims to develop an optimized treatment approach that automatically adjusts the relative contributions of protons and carbon ions, improving target dose conformity while minimizing biological impact on OARs. Methods We propose a biological optimization framework for multi‐modality combining PT and CIRT (CCIPRT). The biological dose is modeled as the product of the physical dose and RBE. Through iterative Jacobian‐based linearization, the biological dose of carbon ion is expressed in a linear model, enabling the formulation of a linear least‐square objective. The biological dose of proton is formulated as a linear model using the physical dose and dose‐averaged linear energy transfer (LET). The joint optimization problem is then solved using iterative convex relaxation and the alternating direction method of multipliers. For comparison, single‐modality PT and CIRT were also implemented. Results When the target dose of CCIPRT is prescribed in terms of the physical dose, compared to PT, CCIPRT increased the mean biological dose in the target by 37.7%, 29.6%, and 31.1% for brain, lung, and abdomen, respectively; compared to CIRT, CCIPRT reduced the biological dose in CTV1cm (ring surrounding CTV with 1 cm width) by 47.2%, 32.3%, and 40.4% for brain, lung, and abdomen, respectively. When the target dose of CCIPRT is prescribed in terms of the biological dose, compared to PT, CCIPRT achieved higher conformity index (CCIPRT: 0.96 and 0.97; PT: 0.93 and 0.96 for brain and liver cases, respectively) and reduced the dose in CTV1cm by 9.5% and 7.0% for brain and liver cases, respectively; compared to CIRT, CCIPRT enhanced healthy tissue sparing, reducing the dose to the body by 7.5% and 9.2% for brain and liver cases, respectively. Conclusions A novel multi‐modality CCIPRT treatment planning is developed with demonstrated superior performance over single‐modality PT or CIRT, with enhanced biological effectiveness and dose conformity compared to PT and reduced OAR dose compared to CIRT.

INTRODUCTION: Esophageal adenocarcinoma (EAC) is an aggressive cancer with poor prognosis. Barrett's esophagus (BE) is a critical precursor of EAC. Patients with BE undergo endoscopic surveillance to monitor disease progression although only a small fraction develop EAC. These procedures are invasive and have limited accuracy in predicting BE progression. We evaluated the utility of an 8-protein mass spectrometry panel in predicting progression in patients with BE. METHODS: Eighty untreated controls and 20 cases were selected from our institutional tissue registry. Quantitative mass-spectrometry was performed on microdissected tissue sections. Data were split into 80% training and 20% test sets. We used Least Absolute Shrinkage and Selection Operator-regularized regression to train a logistic classifier on training data. Classifier performance was evaluated in test data. RESULTS: Ninety-two samples had sufficient tissue for mass spectrometry analysis (18 progressors, 74 nonprogressors). The multivariable regression model produced a sensitivity of 100% and a specificity of 39% in the overall cohort, with AUCs of 0.75 and 0.89 in the overall and test cohorts, respectively. Cox proportional hazards time-to-progression (TTP) showed a hazard ratio of 66.1 (95% CI 7.79–561, P = 0.00012) for the model prediction. DISCUSSION: The promising performance of the model generated here suggests that the test may aid in selecting patients most likely to benefit from active BE surveillance. Moreover, the association of this model's prediction with time-to-progression may offer decision support for management of patients likely to progress quickly. These results support continued development of this proteomic panel as a risk stratification tool for patients with BE.

Objective To determine the proportion of cases of lower extremity symptoms attributable to underlying musculoskeletal ( MSK ) rather than thrombotic etiologies in emergency versus non‐emergency settings. Methods We retrospectively reviewed all lower extremity Venous Doppler ultrasounds performed on emergency department ( ED ) and non‐ ED patients over a 1‐year period at a single institution. Using radiology report data mining software, keywords including tear, tendon, hematoma, and muscle were used to identify cases of MSK pathology of the lower leg. All reports were also reviewed for findings of venous thrombosis. Statistical significance between ED and non‐ ED patients for both incidental MSK pathology and venous thrombosis was assessed using chi‐squared tests. Results A total of 5714 lower extremity Doppler ultrasounds were performed at a single institution during the 1‐year period, 1829 in the ED and 3885 in non‐ ED settings. Sixty‐nine of 1829 (3.8%) ED patients had incidental MSK pathology of the lower extremity compared to 53/3885 (1.4%) in the non‐ ED setting ( p < .001). Two hundred sixty‐seven of 1829 (14.5%) ED patients had evidence of venous thrombosis and/or chronic post‐thrombotic change. When combined with thrombotic pathology as positive cases, incidental MSK injury accounted for 69/336 (20.5%) of ED cases with positive sonographic findings. Conclusions MSK pathology of the lower leg is significantly more likely to contribute to lower extremity symptoms in the ED compared to a non‐ ED setting. Therefore, a brief sonographic evaluation of the MSK apparatus may be beneficial in a subset of ED patients, particularly those with focal pain but no identifiable thrombotic etiology.