Carle Foundation Hospital

Recent court decisions have treated statements in drug labels as evidence of patent infringement by generic-drug manufacturers. The Supreme Court has an opportunity to address this trend.

Meningiomas, benign central nervous system tumors, express progesterone and estrogen receptors. Their proliferation has been associated with hormonal and demographic factors, including female sex, obesity, and race. Prior studies on oral contraceptive pill (OCP) use and meningioma risk have been limited in their analysis of the modifying effects of race, obesity, and polycystic ovary syndrome (PCOS). To assess the association between combined OCP use and meningioma development, and to assess how race, obesity, and PCOS influence this relationship. Retrospective cohort study using aggregated electronic health record data in Epic Cosmos. Women aged 13-50 from 2005 to 2023 with and without combined OCP use were identified. Patients with history of radiation, neurofibromatosis 2, progestin-only contraceptive use, and hormone replacement therapy were excluded. The cohort was then stratified by PCOS status, obesity, and race. Combined OCP users saw a 40% lower risk of meningioma compared to non-users. PCOS was associated with a bidirectional effect on meningioma risk, modified by obesity. Among patients with obesity, those with PCOS had a 30% lower risk of developing meningioma compared to those without PCOS. Among non-obese patients, those with PCOS had a 108% greater risk of developing meningioma compared to those without PCOS. After adjusting for both PCOS and obesity, women with a history of combined OCP usage had 42% reduced odds of developing meningioma. When stratified by race, combined OCP use was associated with 47% decreased risk in White patients, 34% lower risk in Black patients, and 28% lower risk in Asian patients. Controlling for race overall, combined OCP use remained significantly protective, with 43% reduced odds of meningioma development. Findings suggest a potential protective association between combined OCP use and meningioma that remained significant after controlling for obesity, PCOS status, and race. Additionally, this study found that meningioma risk in patients with PCOS differed based on obesity status.

Introduction: Midline Shift (MLS) quantifies mass effect and herniation risk in acute neurological emergencies. Manual MLS measurements are time-consuming and variable, delaying critical intervention. This study evaluated the performance of Rapid MLS (iSchemaView, Inc.), automated software that quantifies MLS and visualizes displacement on non-contrast CT scans. Methods: In this retrospective multicenter-study, patients with intracranial pathology causing MLS were identified from NCCT databases. Automated MLS measurements from Rapid MLS were compared to those by three expert neuroradiologists. The primary outcome assessed non-inferiority of Rapid MLS to the average mean absolute error (MAE) of experts across pairwise comparisons (one-sided α=0.025). Secondary analyses included Passing-Bablok regression and a Bland-Altman plot. Results: Of 157 initial cases, 153 (mean age 68.7 ± 16.3 years; 59 M, 89 F, 5 unknown) were analyzed after four exclusions due to non-axial images, excessive streak artifact, mass at septum pellucidum, and hemicraniectomy. The cases covered a range of pathologies and expected MLS values outlined in Table 1 and Figure 1 respectively. The primary endpoint analysis demonstrated the MAE of Rapid (0.8mm; 95% CI: 0.7-1.0 mm) was non-inferior to the average pairwise MAE of experts (0.9mm; 95% CI: 0.8-1.0mm) (p<0.0001). Passing-Bablok regression analysis showed high agreement (intercept=0.29; slope=0.90) with minimal bias (difference of 0.2; p=0.0516)(Figure 2). We note that Rapid MLS progressively underestimates values above 10mm where clinical concern is already high. Further investigation of the bias with a Bland-Altman analysis determined a small mean difference of 0.2mm (95% CI: 0.0-0.4mm) between Rapid MLS and expert measurements. Conclusion: Rapid MLS provides fast, reproducible MLS measurements on NCCT, with accuracy comparable to expert neuroradiologists. This tool may enhance triage and decision-making in stroke, traumatic brain injury, and other emergencies by reducing time to diagnosis and intervention.

Spinal cord stimulation (SCS) provides significant relief for patients with chronic pain; however, many approaches have limitations in programming complexity, personalization, and long-term efficacy. Traditional open-loop systems require manual programming and fail to adapt to patient-specific anatomical or physiological changes over time. In response, closed-loop SCS systems have emerged, offering real-time modulation based on biomarkers such as position and evoked compound action potentials (ECAPs). However, these systems still largely fail to integrate subjective aspects of pain alongside objective neural biomarkers. The purpose of this scoping review is to evaluate the control signals and algorithms used by closed-loop SCS devices and identify directions for improving their efficacy. Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses for Scoping Reviews guidelines, the PubMed, SCOPUS, and Web of Science data bases were queried on December 14, 2024. Peer-reviewed studies written in English related to closed-loop SCS were included. The inclusion criteria were 1) SCS therapy for chronic pain, and 2) real-time modulation of stimulation parameters. The exclusion criteria included review studies, book chapters, conference proceedings, small animal studies, or works unrelated to chronic pain. Initially, 688 unique articles were identified. After screening by two independent reviewers, 28 articles met all the established criteria, encompassing 19 unique studies. Three studies investigated subjective states, such as rating of pain, mood, and paresthesias; seven used objective features, including position and movement, and nine studies incorporated ECAP characteristics as a control signal. To our knowledge, no existing model has fully integrated both subjective and biophysical markers to inform closed-loop stimulation parameters. A closed-loop SCS algorithm that incorporates subjective and objective features may hold potential to improve quality of life in patients with chronic pain. Combining these approaches in a temporally resolved manner, for example, integrating patient reports with continuous electrophysiologic information using a state space mathematical model, could allow more optimized and patient-specific SCS programming.

Over 1 million sport-related concussions (SRCs) occur among US children annually. Enhancing sport safety requires a detailed understanding of SRC mechanisms. However, limited data characterize the specific actions causing SRCs in high-school athletes. The objective was to classify SRC mechanisms using a standardized hierarchical scheme and evaluate associations between mechanism categories and symptom profiles, overall and by sport and sex. This retrospective study analyzed Sport Concussion Assessment Tool (SCAT), evaluations and athletic-trainer documentation from high-school athletes (age 14-19 years) across 19 schools (2009-2023). SRCs were coded as hit-to-head and tackle/collision (present/absent) and, when applicable, by hit-to-head subtype, head contact location, and contact context (opponent/teammate; practice vs competition). Analyses included descriptive statistics, χ2/Fisher tests, and odds ratios (95% CIs) with Bonferroni adjustment. Symptom burden and individual symptom endorsement were compared by sex and mechanism (hit-to-head vs no hit-to-head). Logistic regressions with cluster-robust SEs, adjusted for sex and sport, assessed associations between mechanisms (and subtypes) and symptoms. A total of 455 SRCs (401 athletes) were analyzed; 111 (24.4%) occurred in females. Overall, 73.6% involved a hit-to-head and 65.9% a tackle/collision, with co-occurrence in 56.0%. SRCs most frequently occurred in football (53.8%), soccer (21.1%), and basketball (8.4%). Mechanisms were sport-specific: tackling in football (38.9%), heading in soccer (54.2%), rebounding or loose-ball play in basketball (41.7%), takedowns in wrestling (83.3%), spiking in volleyball (66.7%), and stunting in cheerleading (90.5%). After adjustment for sex, sport, and tackle/collision, headache and "don't feel right" remained significantly associated with a hit-to-head mechanism. Tackle/collision was independently associated with greater odds of dizziness (adjusted odds ratios 2.07), feeling slowed (1.92), and headache (2.82). High-school SRCs most often result from head-to-ground impacts, player collisions, or sport-specific actions such as tackling or heading. Characterizing these mechanisms can guide targeted, sport-specific prevention strategies.

BackgroundThe COVID-19 pandemic challenged families, youth, and frontline workers, including childcare providers. Studying lived experiences before, during, and near the pandemic’s end from multiple perspectives provides a more holistic and deeper understanding of its effects and impacts.ObjectiveThis study investigated how parental, childcare provider, and youth stress, mental health, and role overload relate to individual coping and family functioning, as well as vaccine attitudes and uptake patterns among youth, parents, and childcare providers. Information learned from this investigation will inform policy and messaging for future public health crises.MethodsThis study is an explanatory sequential mixed methods study designed to capture the voices of parents of children younger than 18 years of age, childcare providers, and youth aged 12-17 years through surveys and interviews. This retrospective cross-sectional study began with a web-based survey that included demographic questions and validated scales to assess personal well-being, household and family dynamics, behavioral problems, and vaccination-related perceptions, attitudes, and behaviors. Open-ended responses about pandemic experiences for themselves and their families were included. A subsample of parents, youth, and childcare providers was selected for in-depth interviews about their pandemic-related experiences. Descriptive statistics were used to summarize demographic characteristics, and internal consistency was assessed for all survey measures using Cronbach α. Future studies will use inferential statistical techniques to analyze survey measures, thematic analysis for open-ended survey responses and interview data, and mixed methods data integration to synthesize quantitative and qualitative findings.ResultsData collection for the study began in August 2022 and finished in August 2023. Data analysis is currently in progress to address research questions, and study preparation and dissemination efforts are underway. A total of 506 adults and 93 youths answered a study survey, and 45 adults and 21 youths completed in-depth interviews. Among the 506 adults, 166 were childcare providers. The adult sample had a mean age of 42.8 (SD 9.15) years and was predominantly female (467/506, 92.3%), with 9.7% (49/506) identifying as Black, 4.7% (24/506) as Hispanic, and 81.2% (411/506) being parents of children aged 17 years or younger. The youth sample had a mean age of 14.5 (SD 1.63) years, and 55.9% (52/93) were female, 6.4% (6/93) were Black, and 17.2% (16/93) were Hispanic. Several dyads and triads participated. The sample included 42 parent-child dyads, 3 parent-parent dyads, 2 parent-parent-child triads, and 21 parent-child-child triads.ConclusionsThese data will be used to understand the diverse experiences of families, youth, and childcare providers during and after the COVID-19 pandemic. This includes successful and unsuccessful adaptations, responses to policies and mandates, and the unmet needs for health messaging, programs, policies, and services. This research aims to guide the development of effective policies and public health communication, fostering scalable and sustainable messaging resources.International Registered Report Identifier (IRRID)DERR1-10.2196/77521

Background: Postpartum hypertensive disorders are a major cause of maternal mortality and hospital readmission. If untreated, elevated blood pressure can lead to complications such as eclampsia, stroke, and pulmonary edema. Labetalol, a combined α- and β-blocker, and nifedipine, a calcium channel blocker, are widely used oral agents for managing postpartum hypertension. Hypothesis: To compare the efficacy and safety of nifedipine versus labetalol in managing postpartum hypertension. Methods: A systematic review of PubMed, Google Scholar, and the Cochrane Library identified eight studies involving 31,436 patients (12,479 treated with nifedipine; 18,957 treated with labetalol). All randomized controlled trials and observational studies comparing nifedipine and labetalol in postpartum women were included. The primary outcome was hospital readmission. Secondary outcomes included time to blood pressure control, discharge on initial dose, and adverse effects, which included constipation, flushing, and headache. Dichotomous data were analyzed using risk ratios (RRs), and continuous data were assessed using mean differences (MDs) with their respective 95% confidence intervals (95% CIs). Statistical analysis was performed using Review Manager (RevMan) version 5.4.1. A p-value of less than 0.05 was considered statistically significant. Results: Nifedipine significantly reduced the risk of readmission compared to labetalol (RR = 0.40, 95% CI [0.31, 0.52]; P < 0.00001). No significant differences were found in time to blood pressure control (MD = –0.68, 95% CI [–2.20, 0.84]; P = 0.38), discharge on initial medication (RR = 0.78, 95% CI [0.45, 1.34]; P = 0.37), or incidence of adverse effects. Conclusion: Nifedipine was associated with lower readmission risk than labetalol, with comparable efficacy and safety in postpartum hypertension management. Keywords: Nifedipine, Labetalol, Postpartum hypertension, Oral antihypertensive

ABSTRACTThe internal arrangement of a muscle's fibers with respect to its mechanical line of action (muscle architecture) is a major determinant of muscle function. Muscle architecture can be quantified using diffusion tensor magnetic resonance imaging‐based tractography, which propagates streamlines from a set of seed points by integrating vectors that represent the direction of greatest water diffusion (and by inference, the local fiber orientation). Previous work in skeletal muscle has demonstrated that tractography outcomes are sensitive to the method for defining seed points, but this sensitivity has not been fully examined. To do so, we developed a realistic simulated muscle architecture and implemented three methods for tract seeding: seeding along the muscle‐aponeurosis boundary with an updated procedure for rounding seed points prior to lookup in the muscle boundary mask and diffusion tensor matrices (APO); voxel‐based seeding throughout the muscle volume at a uniform spatial frequency (VXL); and seeding near external and internal muscle boundaries (EDGE). We then implemented these methods in example human datasets. The updated aponeurosis seeding procedures allow more accurate and robust tract propagation from seed points. The voxel‐based seeding methods had quantification outcomes that closely matched the updated aponeurosis seeding method. Further, the voxel‐based methods can accelerate the overall workflow and may be beneficial in high throughput analysis of multi‐muscle datasets. Continued evaluation of these methods in a wider range of muscle architectures is warranted.