Role of insole material in treatment of plantar fasciitis: A randomized clinical trial.

BACKGROUND: In this randomized clinical trial, we compared the early effects of polyethylene (PE), polyurethane (PU), and Carbon Fiber insoles in the treatment of PF using a set of patient-reported outcomes. METHODS: Patients were randomly allocated one of the three prefabricated insoles - Carbon Fiber (n = 14), PU (n = 14), or PE (n = 17) for regular use. Their response was recorded using PROMIS 3a (for pain intensity), PROMIS 4a (for pain interference), FAOS (Foot and Ankle Outcome Score), and VAS for pain at baseline, two, six, and twelve weeks. RESULTS: The PROMIS pain intensity scores improved in both the Carbon Fiber and the PE groups starting at the 6th week (p = 0.04) and 2nd week (p = 0.002), respectively. PROMIS pain interference scores also showed positive trends in these two groups (p = 0.02, p = 0.004, respectively). CONCLUSION: Prefabricated Carbon Fiber and PE insoles showed significant pain-reducing effects in patients with PF. LEVELS OF EVIDENCE: Level I, Randomized controlled trial.

State-of-the-art for contrast-enhanced mammography.

Contrast-enhanced mammography (CEM) is an emerging breast imaging technology with promise for breast cancer screening, diagnosis, and procedural guidance. However, best uses of CEM in comparison with other breast imaging modalities such as tomosynthesis, ultrasound, and MRI remain inconclusive in many clinical settings. This review article summarizes recent peer-reviewed literature, emphasizing retrospective reviews, prospective clinical trials, and meta-analyses published from 2020 to 2023. The intent of this article is to supplement prior comprehensive reviews and summarize the current state-of-the-art of CEM.

A Combined Assessment Tool of Teamwork, Communication, and Workload in Hospital Procedural Units.

Teamwork, communication, and workload issues continue to contribute to patient safety events. The authors developed a diagnostic mixed methods toolkit combining a behavior observation tool, semistructured interview guide, and surveys to proactively identify relevant gaps. Applied across 14 units at three hospitals, this toolkit yielded 344 findings with 156 associated recommendations and took, on average, four days of observation. On a scale from 1 (not at all helpful) to 6 (substantially helpful), leaders indicated that the assessment and its recommendations were very helpful (median 5, interquartile range 5-6, 34 survey respondents, 47.9% individual-level response rate, 85.7% unit-level response rate). Integrating this tool into a broader safety strategy can help inform organizational improvement efforts.

Connecting pathogen transmission and healthcare worker cognition: a cognitive task analysis of infection prevention and control practices during simulated patient care.

BACKGROUND: Relatively little is known about the cognitive processes of healthcare workers that mediate between performance-shaping factors (eg, workload, time pressure) and adherence to infection prevention and control (IPC) practices. We taxonomised the cognitive work involved in IPC practices and assessed its role in how pathogens spread. METHODS: Forty-two registered nurses performed patient care tasks in a standardised high-fidelity simulation. Afterwards, participants watched a video of their simulation and described what they were thinking, which we analysed to obtain frequencies of macrocognitive functions (MCFs) in the context of different IPC practices. Performance in the simulation was the frequency at which participants spread harmless surrogates for pathogens (bacteriophages). Using a tertiary split, participants were categorised into a performance group: high, medium or low. To identify associations between the three variables-performance groups, MCFs and IPC practices-we used multiblock discriminant correspondence analysis (MUDICA). RESULTS: MUDICA extracted two factors discriminating between performance groups. Factor 1 captured differences between high and medium performers. High performers monitored the situation for contamination events and mitigated risks by applying formal and informal rules or managing their uncertainty, particularly for sterile technique and cleaning. Medium performers engaged more in future-oriented cognition, anticipating contamination events and planning their workflow, across many IPC practices. Factor 2 distinguished the low performers from the medium and high performers who mitigated risks with informal rules and sacrificed IPC practices when managing tradeoffs, all in the context of minimising cross-contamination from physical touch. CONCLUSIONS: To reduce pathogen transmission, new approaches to training IPC (eg, cognitive skills training) and system design are needed. Interventions should help nurses apply their knowledge of IPC fluidly during patient care, prioritising and monitoring situations for risks and deciding how to mitigate risks. Planning IPC into one's workflow is beneficial but may not account for the unpredictability of patient care.

Factors That Affect Drivers' Perception of Closing and an Immediate Hazard.

OBJECTIVE: To measure the looming threshold for when drivers perceive closing and an immediate hazard and determine what factors affect these thresholds. BACKGROUND: Rear-end collisions are a common type of crash. One key issue is determining when drivers first perceive they need to react. The looming threshold for closing and an immediate hazard are critical perceptual thresholds that reflect when drivers perceive they need to react. METHOD: Two driving simulator experiments examined whether engaging in a cell phone conversation and whether the complexity of the roadway environment affect these thresholds for the perception of closing and immediate hazard. Half of the participants engaged in a cognitive task, the last letter task, to emulate a cell phone conversation, and all participants experienced both simple and complex roadway environments. RESULTS: Drivers perceived an immediate hazard later when engaged in a cell phone conversation than when not engaged in a conversation but only when the driving task was relatively less demanding (e.g., simple roadway, slow closing velocity). Compared to simple scenes, drivers perceived closing and an immediate hazard later for complex scenes but only when closing velocity was 30 mph (48.28 km/h) or greater. CONCLUSION: Cell phone conversation can affect when drivers perceive an immediate hazard when the roadway is less demanding. Roadway complexity can affect when drivers perceive closing and an immediate hazard when closing velocity is high. APPLICATION: Results can aid accident analysis cases and the design of driving automation systems by suggesting when a typical driver would respond.

High-grade glioma imaging volumes and survival: a single-institution analysis of 101 patients after resection using intraoperative MRI.

PURPOSE: Intraoperative magnetic resonance imaging (iMRI) has been efficacious in maximizing resection of high-grade gliomas (HGGs). In this single-institution study of patients with HGGs who underwent resection using iMRI, the authors present a volumetric-based survival analysis to evaluate progression-free survival (PFS) and overall survival (OS), as well as the impact of additional resection on survival. METHODS: This retrospective analysis included patients with HGGs who underwent resection using iMRI from 2011 to 2021. Volumetric analyses of T1-weighted contrast-enhancing (T1W-CE), T2-weighted (T2W), and T2W fluid-attenuated inversion recovery (FLAIR) MRI sequences were assessed at preoperative, intraoperative, immediate postoperative, and three-month postoperative timepoints. Statistical analyses were carried out using log-rank and multivariable Cox proportional hazard regression analyses. RESULTS: A total of 101 patients (median age 57.0 years) were treated. In keeping with prior studies, statistically significant associations between greater EOR and longer PFS and OS were seen (p = 0.012 and p = 0.006, respectively). The results demonstrated significant associations of lower preoperative T2W, 3-month postoperative T2W, and 3-month postoperative FLAIR volumes with longer PFS and OS (p = 0.045 and p = 0.026, p = 0.031 and p = 0.006, p = 0.018 and p = 0.004, respectively), as well as associations between lower immediate postoperative T2W and immediate postoperative FLAIR volumes with longer OS (p = 0.002 and p = 0.02). There was no observed association in either PFS or OS for patients undergoing additional resection after initial iMRI scan (p = 0.387 and p = 0.592). CONCLUSION: This study of 101 patients with new or recurrent HGGs shows three-month postoperative T2W and FLAIR imaging volumes were significant prognosticators with respect to PFS and OS.

A Systematic Review and Meta-Analysis of Takeover Performance During Conditionally Automated Driving.

OBJECTIVE: The aim of this paper was to synthesize the experimental research on factors that affect takeover performance during conditionally automated driving. BACKGROUND: For conditionally automated driving, the automated driving system (ADS) can handle the entire dynamic driving task but only for limited domains. When the system reaches a limit, the driver is responsible for taking over vehicle control, which may be affected by how much time they are provided to take over, what they were doing prior to the takeover, or the type of information provided to them during the takeover. METHOD: Out of 8446 articles identified by a systematic literature search, 48 articles containing 51 experiments were included in the meta-analysis. Coded independent variables were time budget, non-driving related task engagement and resource demands, and information support during the takeover. Coded dependent variables were takeover timing and quality measures. RESULTS: Engaging in non-driving related tasks results in degraded takeover performance, particularly if it has overlapping resource demands with the driving task. Weak evidence suggests takeover performance is impaired with shorter time budgets. Current implementations of information support did not affect takeover performance. CONCLUSION: Future research and implementation should focus on providing the driver more time to take over while automation is active and should further explore information support. APPLICATION: The results of the current paper indicate the need for the development and deployment of vehicle-to-everything (V2X) services and driver monitoring.

p53 convergently activates Dux/DUX4 in embryonic stem cells and in facioscapulohumeral muscular dystrophy cell models.

In mammalian embryos, proper zygotic genome activation (ZGA) underlies totipotent development. Double homeobox (DUX)-family factors participate in ZGA, and mouse Dux is required for forming cultured two-cell (2C)-like cells. Remarkably, in mouse embryonic stem cells, Dux is activated by the tumor suppressor p53, and Dux expression promotes differentiation into expanded-fate cell types. Long-read sequencing and assembly of the mouse Dux locus reveals its complex chromatin regulation including putative positive and negative feedback loops. We show that the p53-DUX/DUX4 regulatory axis is conserved in humans. Furthermore, we demonstrate that cells derived from patients with facioscapulohumeral muscular dystrophy (FSHD) activate human DUX4 during p53 signaling via a p53-binding site in a primate-specific subtelomeric long terminal repeat (LTR)10C element. In summary, our work shows that p53 activation convergently evolved to couple p53 to Dux/DUX4 activation in embryonic stem cells, embryos and cells from patients with FSHD, potentially uniting the developmental and disease regulation of DUX-family factors and identifying evidence-based therapeutic opportunities for FSHD.

Early Seizures Are Predictive of Worse Health-Related Quality of Life at Follow-Up After Intracerebral Hemorrhage.

OBJECTIVES: Early seizures are a common complication of intracerebral hemorrhage, occurring in ~10% of patients. However, the independent effect of early seizures on patient outcomes, particularly health-related quality of life, is unclear. Without a potential benefit to patient outcomes, the widespread use (~40%) of prophylactic seizure medications has no reasonable chance of improving patient outcomes. We tested the hypothesis that health-related quality of life at follow-up is different between patients with and without early seizures (and secondarily, with nonconvulsive status epilepticus) after intracerebral hemorrhage. DESIGN: Patients with intracerebral hemorrhage were enrolled in an observational cohort study that prospectively collected clinical data and health-related quality of life at follow-up. SETTING: Academic medical center. PATIENTS: One-hundred thirty-three patients whose health-related quality of life was assessed 3 months after intracerebral hemorrhage onset. MEASUREMENTS AND MAIN RESULTS: Health-related quality of life was obtained at 3 months after intracerebral hemorrhage onset. T Scores of health-related quality of life were modeled with multivariable linear models accounting for severity with the intracerebral hemorrhage Score and hematoma location. Health-related quality of life was measured with National Institutes of Health Patient Reported Outcomes Measurement Information System/Neuroquality of life, expressed in T Scores (U.S. normal 50 ± 10). The modified Rankin Scale (a global measure) was a secondary outcome. There were 12 patients (9%) with early seizures. T Scores of health-related quality of life at follow-up were lower (worse) in patients with early seizure compared with patients without an early seizure (44 [32.75-51.85] vs 30.25 [18.9-39.15]; p = 0.04); results for other domains of health-related quality of life were similar. The association persisted in multivariable models. There was no association between early seizures and prophylactic seizure medications (p = 0.4). Results for patients with nonconvulsive status epilepticus were similar. There was no association between early seizures and the modified Rankin Scale at 3 months. CONCLUSIONS: Early seizures and nonconvulsive status epilepticus were associated with lower health-related quality of life at follow-up in survivors of intracerebral hemorrhage.

Identifying Modifiable Predictors of Patient Outcomes After Intracerebral Hemorrhage with Machine Learning.

BACKGROUND/OBJECTIVE: Demonstrating a benefit of acute treatment to patients with intracerebral hemorrhage (ICH) requires identifying which patients have a potentially modifiable outcome, where treatment could favorably shift a patient's expected outcome. A decision rule for which patients have a modifiable outcome could improve the targeting of treatments. We sought to determine which patients with ICH have a modifiable outcome. METHODS: Patients with ICH were prospectively identified at two institutions. Data on hematoma volumes, medication histories, and other variables of interest were collected. ICH outcomes were evaluated using the modified Rankin Scale (mRS), assessed at 14 days and 3 months after ICH, with "good outcome" defined as 0-3 (independence or better) and "poor outcome" defined as 4-6 (dependence or worse). Supervised machine learning models identified the best predictors of good versus poor outcomes at Institution 1. Models were validated using repeated fivefold cross-validation as well as testing on the entirely independent sample at Institution 2. Model fit was assessed with area under the ROC curve (AUC). RESULTS: Model performance at Institution 1 was strong for both 14-day (AUC of 0.79 [0.77, 0.81] for decision tree, 0.85 [0.84, 0.87] for random forest) and 3 month (AUC of 0.75 [0.73, 0.77] for decision tree, 0.82 [0.80, 0.84] for random forest) outcomes. Independent predictors of functional outcome selected by the algorithms as important included hematoma volume at hospital admission, hematoma expansion, intraventricular hemorrhage, overall ICH Score, and Glasgow Coma Scale. Hematoma expansion was the only potentially modifiable independent predictor of outcome and was compatible with "good" or "poor" outcome in a subset of patients with low hematoma volumes, good Glasgow Coma scale and premorbid modified Rankin Scale scores. Models trained on harmonized data also predicted patient outcomes well at Institution 2 using decision tree (AUC 0.69 [0.63, 0.75]) and random forests (AUC 0.78 [0.72, 0.84]). CONCLUSIONS: Patient outcomes are predictable to a high level in patients with ICH, and hematoma expansion is the sole-modifiable predictor of these outcomes across two outcome types and modeling approaches. According to decision tree analyses predicting outcome at 3 months, patients with a high Glasgow Coma Scale score, less than 44.5 mL hematoma volume at admission, and relatively low premorbid modified Rankin Score in particular have a modifiable outcome and appear to be candidates for future interventions to improve outcomes after ICH.

Concurrent Radiosurgery and Systemic Therapies for Melanoma Brain Metastases: A Systematic Review.

Intracranial metastatic melanoma is a major challenge for neuro-oncological teams. Historically, treatment has focused on surgical or radiosurgical treatment of appropriate lesions, mostly for palliative purposes. Immunotherapies and other targeted therapies (BRAF/mitogen-activated protein kinase kinase inhibitors (BRAFi/MEKi)) are mainstays of advanced melanoma therapy, yet the optimal timing and synergistic properties of concurrent combinations of these systemic therapies and stereotactic radiosurgery (SRS) are poorly understood. We performed a systematic review of the MEDLINE and Scopus databases focused on outcomes after therapy using SRS and either immunotherapies or targeted therapies in an effort to define the optimal timing. We defined concurrent therapy as SRS within three months of treatment with any systemic therapy. End points included local control, distant control, overall survival, and toxicities. We identified five retrospective cohort studies from the literature. These studies found that concurrent SRS plus immunotherapy or BRAFi/MEKi is well tolerated by most patients and generally improved local control, distant control, and overall survival. Importantly, no significant increases in toxicities were noted with concurrent therapy. Combining concurrent SRS with immunotherapy or BRAFi/MEKi may offer important advances for patients with intracranial metastatic melanoma. To address interstudy heterogeneity, we propose reporting two major time intervals defining "concurrent treatment": concurrent-SRS (≤4 weeks) and peri-SRS (≤3 months). Future large-scale, prospective trials considering truly concurrent SRS therapies with systemic therapies are desperately needed.

Conserved roles of mouse DUX and human DUX4 in activating cleavage-stage genes and MERVL/HERVL retrotransposons.

To better understand transcriptional regulation during human oogenesis and preimplantation development, we defined stage-specific transcription, which highlighted the cleavage stage as being highly distinctive. Here, we present multiple lines of evidence that a eutherian-specific multicopy retrogene, DUX4, encodes a transcription factor that activates hundreds of endogenous genes (for example, ZSCAN4, KDM4E and PRAMEF-family genes) and retroviral elements (MERVL/HERVL family) that define the cleavage-specific transcriptional programs in humans and mice. Remarkably, mouse Dux expression is both necessary and sufficient to convert mouse embryonic stem cells (mESCs) into 2-cell-embryo-like ('2C-like') cells, measured here by the reactivation of '2C' genes and repeat elements, the loss of POU5F1 (also known as OCT4) protein and chromocenters, and the conversion of the chromatin landscape (as assessed by transposase-accessible chromatin using sequencing (ATAC-seq)) to a state strongly resembling that of mouse 2C embryos. Thus, we propose mouse DUX and human DUX4 as major drivers of the cleavage or 2C state.

Complex I polymorphisms, bigenomic heterogeneity, and family history in Virginians with Parkinson's disease.

The electron transport chain enzyme complex I may play a role in Parkinson's disease (PD) pathogenesis. Association studies considering whether or not complex I-relevant gene polymorphisms contribute to PD risk are discordant. We evaluated four complex I-relevant gene polymorphisms alternatively reported to associate and not associate with PD (tRNA(Gln) T4336C, ND1 T4216C, ND2 G5460A, and the NDUFV2 exon 2 C182T transition). Our study included 111 PD subjects and 106 controls in central Virginia. Individuals with at least one copy of the NDUFV2 182T allele were more likely to report a PD family history than non-carriers, but aside from this no positive associations were found. Indeed, the tRNA(Gln) 4336C variant occurred more frequently in controls. We also observed that individuals in both groups often carried more than one of the assayed polymorphisms, and for the first time show bigenomic polymorphic variation (between nuclear and mtDNA complex I subunit genes) commonly occurs within individuals. In an exploratory sub-analysis, more control than case women had an ND1 4216C, NDUFV2 homozygous 182C compound genotype. Complex I compound genotype variation commonly occurs and may explain why particular complex I gene polymorphisms associate with PD in some populations but not others.