Timely Hip Surgery Access in Children With Cerebral Palsy: Unaffected by Social Disadvantage at a Large Urban Safety Net Hospital.

BACKGROUND: Socioeconomic disadvantage has been shown to limit timely access to pediatric orthopaedic care and can result in poor surgical outcomes. Insurance coverage has often served as a proxy for socioeconomic status; however, area deprivation index (ADI) and child opportunity index (COI) are more comprehensive measures of social determinants of health (SDOH). The treatment of hip displacement in children with cerebral palsy (CP) requires early radiographic identification and continuous surveillance, which may be impacted by SDOH. This study seeks to evaluate the influence of insurance, ADI, and COI on preoperative Reimer migration percentage and need for pelvic osteotomy during varus derotation osteotomy (VDRO) in children with CP. METHODS: This retrospective cohort study examined 219 patients with CP who underwent VDRO surgery for hip subluxation or dislocation at a tertiary referral center (135 male, mean age 7.9 y, SD: 2.9, range: 2.4 to 17.2; 17 GMFCS II, 21 GMFCS III, 89 GMFCS IV, 92 GMFCS V) from 2004 to 2022. Imaging and clinical documentation for patients with CP and hip displacement, age <18 years with ≥1 year of follow-up, treated with VDRO were reviewed. GMFCS level, preoperative Reimer migration percentages (MP), surgical details, and demographic and socioeconomic data were collected, and addresses were used to determine ADI (2018 version) and COI (2.0 database). The relationship of ADI, COI, and insurance type to preoperative Reimer MP of the more displaced hip and the need for pelvic osteotomy were analyzed with linear regressions and logistic regressions. RESULTS: The mean preoperative Reimer MP was 64.4% (SD: 25.0, range: 0 to 100). As expected, patients functioning at higher GMFCS levels presented with greater Reimer MPs. The average Reimer MP was 34.0 for GMFCS II, 44.2 for GMFCS III, 64.6 for GMFCS IV, and 74.5 for GMFCS V (P<0.01). The mean ADI state decile (1 to 10 scale) and COI (1 to 100 scale) for the cohort were 5.6 (SD: 2.2, range: 1 to 10) and 37.2 (SD: 28.1, range: 4 to 100), respectively. ADI (P=0.77), COI (P=0.30), and insurance type (P=0.78) were not related to preoperative Reimer MP. However, patients with lower ADIs (OR 0.83, 95% CI [0.70, 0.99], P=0.04) and higher COIs (OR 1.01, 95% CI [1.00, 1.03], P=0.03) underwent pelvic osteotomies at a higher rate. CONCLUSIONS: ADI, COI, and insurance type were not related to preoperative Reimer MP. Interestingly, greater social disadvantage was associated with a lower frequency of pelvic osteotomy at the time of VDRO. Our data demonstrate that at our institution, greater social disadvantage does not result in limited access to timely orthopaedic care for children with CP. This is likely due to adequate governmental insurance coverage for children with neuromuscular disorders in this state and the active involvement of pediatric orthopaedic surgeons in government-sponsored clinics, including ongoing hip screening programs for children with CP. These results provide hope that healthcare disparities can potentially be mitigated.

Design of a multicenter randomized controlled trial of a post-discharge suicide prevention intervention for high-risk psychiatric inpatients: The Veterans Coordinated Community Care Study.

BACKGROUND: The period after psychiatric hospital discharge is one of elevated risk for suicide-related behaviors (SRBs). Post-discharge clinical outreach, although potentially effective in preventing SRBs, would be more cost-effective if targeted at high-risk patients. To this end, a machine learning model was developed to predict post-discharge suicides among Veterans Health Administration (VHA) psychiatric inpatients and target a high-risk preventive intervention. METHODS: The Veterans Coordinated Community Care (3C) Study is a multicenter randomized controlled trial using this model to identify high-risk VHA psychiatric inpatients (n = 850) randomized with equal allocation to either the Coping Long Term with Active Suicide Program (CLASP) post-discharge clinical outreach intervention or treatment-as-usual (TAU). The primary outcome is SRBs over a 6-month follow-up. We will estimate average treatment effects adjusted for loss to follow-up and investigate the possibility of heterogeneity of treatment effects. RESULTS: Recruitment is underway and will end September 2024. Six-month follow-up will end and analysis will begin in Summer 2025. CONCLUSION: Results will provide information about the effectiveness of CLASP versus TAU in reducing post-discharge SRBs and provide guidance to VHA clinicians and policymakers about the implications of targeted use of CLASP among high-risk psychiatric inpatients in the months after hospital discharge. CLINICAL TRIALS REGISTRATION: ClinicalTrials.Gov identifier: NCT05272176 (https://www. CLINICALTRIALS: gov/ct2/show/NCT05272176).

Digital Cognitive Behavioral Therapy vs Education for Pain in Adults with Sickle Cell Disease.

Despite the significant burden of chronic pain in sickle cell disease (SCD), non-pharmacological approaches to manage pain in SCD are lacking. Behavioral interventions incorporating digital cognitive-behavioral therapy CBT) for pain should be compared to available education efforts. To compare a CBT intervention tailored for adults with SCD to a digital pain/SCD education intervention (Education) on improving pain and associated symptoms. Multisite randomized comparative effectiveness trial. Seven comprehensive SCD centers and virtual recruitment through community organizations in the United States. Adults (age 18+) with SCD-related chronic pain and/or daily opioid use randomized to CBT or Education. Over 12 weeks, the CBT arm received an app-based intervention for pain management; the Education arm received digital pain/SCD education. Both groups received interactive chatbot lessons plus personalized health coach support. Changes in pain interference scale (primary); and other patient-reported outcomes (secondary), including pain intensity, depression, anxiety, quality of life, and self-efficacy over 6 months. 453 participants completed screening, 359 (79%) were randomized to CBT (n=181) or Education (n=178), 332 (92%) were Black African American, 238 (66.3%) female. At 6 months, 250 (70%) participants (n=125 per arm) completed follow-up assessments, 93 (26%) missed their follow-up window, 16 (4%) withdrew. Engagement with the chatbot content was variable (76% connected, 48% completed ≥1 lesson). However, 80% of participants completed ≥1 session with a health coach via phone, video, or text. The 6 month change in pain interference for CBT (-2.13; 95% CI, -3.42 to -0.84) and Education (-2.66; 95%CI, -3.97 to -1.36) was not significantly different (mean difference: 0.54; 95%CI, -1.30 to 2.37; *P=*0.57). Daily pain intensity ratings did not change for either group. There were no between-arm differences in depression, anxiety, and quality of life. CBT and Education did not differ in their effect on pain and mental health in SCD when combined with health coaching. Variable engagement with digital components and high engagement with health coaching may explain the lack of between-group differences, but these findings also provide insights into delivering digital interventions in racial minority and hard-to-reach populations. Trial Registration: ClinicalTrials.gov NCT04419168.

Missed Adjuvant Therapy in Human Papillomavirus Positive Oropharyngeal Squamous Cell Carcinoma.

OBJECTIVE: Investigate missed adjuvant therapy and associated disparities in overall survival (OS) for human papillomavirus-associated (HPV+) oropharyngeal squamous cell carcinoma (OPSCC). METHODS: The 2010-2017 National Cancer Database was queried for patients with surgically resected HPV+ OPSCC. Indications for adjuvant radiotherapy (aRT) included pT3-4 classification, pN2-3 classification, lymphovascular invasion, pathologic extranodal extension (pENE), and/or positive surgical margins (PSM). Indication(s) for adjuvant chemoradiotherapy (aCRT) included pENE and/or PSM. Multivariable logistic and Cox regression models were implemented. RESULTS: Of 5297 patients satisfying inclusion criteria, 4288 had indication(s) for aRT; 775 did not receive any adjuvant therapy and were considered as missing aRT. A total of 2234 patients had indication(s) for aCRT. Of these, 1383 (61.9%) received aCRT, 555 (24.8%) patients received aRT alone and were considered as having missed aCRT, and 296 (13.2%) did not receive any adjuvant therapy. Missed aRT and missed aCRT were each associated with age, treatment facility type, pN classification, and surgical margin status (p < 0.015). Among patients with indication(s) for aRT alone, OS of those receiving no adjuvant therapy, aRT alone, and aCRT was 90.0%, 94.8%, and 93.4%, respectively (p = 0.080). Among patients with indication(s) for aCRT, those receiving aRT alone and aCRT had similar OS (89.0% vs. 86.6%, p = 0.357) which was superior to receiving no adjuvant therapy (74.9%, p < 0.001). These patterns in OS persisted on multivariable Cox regression. CONCLUSION: Among patients with HPV+ OPSCC and indication(s) for aRT, missed aRT was not associated with worse OS. For patients with indication(s) for aCRT, aRT alone was associated with similar OS as aCRT. LEVEL OF EVIDENCE: 3 Laryngoscope, 2024.

Free tools for crystallographic symmetry handling and visualization.

Online courses and innovative teaching methods have triggered a trend in education, where the integration of multimedia, online resources and interactive tools is reshaping the view of both virtual and traditional classrooms. The use of interactive tools extends beyond the boundaries of the physical classroom, offering students the flexibility to access materials at their own speed and convenience and enhancing their learning experience. In the field of crystallography, there are a wide variety of free online resources such as web pages, interactive applets, databases and programs that can be implemented in fundamental crystallography courses for different academic levels and curricula. This paper discusses a variety of resources that can be helpful for crystallographic symmetry handling and visualization, discussing four specific resources in detail: the Bilbao Crystallographic Server, the Cambridge Structural Database, VESTA and Jmol. The utility of these resources is explained and shown by several illustrative examples.

Reward neurocircuitry predicts longitudinal changes in alcohol use following trauma exposure.

BACKGROUND: Trauma is a risk factor for developing maladaptive alcohol use. Preclinical research has shown that stress alters the processing of midbrain and striatal reward and incentive signals. However, little research has been conducted on alterations in reward-related neurocircuitry post-trauma in humans. Neuroimaging markers may be particularly useful as they can provide insight into the mechanisms that may make an individual vulnerable to developing trauma-related psychopathologies. This study aimed to identify reward-related neural correlates associated with changes in alcohol use after trauma exposure. METHODS: Participants were recruited from U.S. emergency departments for the AURORA study (N=286, 178 female). Trauma-related change in alcohol use at 8 weeks post-trauma relative to pre-trauma was quantified as a change in 30-day total drinking per the PhenX Toolkit Alcohol 30-Day Quantity and Frequency Measure. Reward-related neurocircuitry activation and functional connectivity (FC) were assessed 2 weeks post-trauma using fMRI during a monetary reward task using region of interest and whole-brain voxelwise analyses. RESULTS: Greater increase in alcohol use from pre-trauma to 8 weeks post-trauma was predicted by (1) greater ventral tegmental area (VTA) and (2) greater cerebellum activation during Gain>Loss trials measured 2 weeks post-trauma and (3) greater seed-based FC between the VTA and lateral occipital cortex and precuneus. CONCLUSIONS: Altered VTA activation and FC early post-trauma may be associated with reward-seeking and processing, contributing to greater alcohol use post-trauma. These data provide novel evidence of neural correlates that underlie increased alcohol use early post-trauma that may be targeted via early interventions to prevent the development of maladaptive alcohol use.

Phenotyping Men With Lower Urinary Tract Symptoms: Results From the Symptoms of Lower Urinary Tract Dysfunction Research Network.

AIMS: Men with lower urinary tract symptoms (LUTS) represent a heterogeneous group, and treatment decisions are often based on severity of symptoms and physical examination findings. Identification of clinically meaningful subtypes could allow for more personalized care. This study advances phenotyping efforts from the Symptoms of Lower Urinary Tract Dysfunction Research Network (LURN) by adding data domains to previous phenotyping using urologic symptoms alone. METHODS: Two-hundred-seventeen LUTS, demographics, medical history, and physical examination datapoints from the LURN Observational Cohort study were assessed among 519 men with at least one bothersome LUTS, using weighted Tanimoto indices, semi-supervised learning, and resampling-based consensus clustering to identify distinct clusters of participants. Differentially abundant serum proteins of 220 men were compared across identified clusters. RESULTS: Five refined male clusters (RM1-RM5) were identified. Two clusters reported mild LUTS (RM1: n = 66; RM2: n = 84). RM1 was older than RM2 (70.3 vs. 56.1 years), had more comorbidities (functional comorbidity index 2.4 vs. 1.5) and erectile dysfunction. Two benign prostatic hyperplasia-like symptom clusters were identified (RM3: n = 64; RM4: n = 188). RM3 has the largest postvoid residual volume (275 mL); RM4 reported more urinary frequency, urgency, urinary incontinence, pain, and psychosocial symptoms. RM5 (n = 119) was characterized by urgency urinary incontinence, frequency, and significant comorbidities and psychosocial symptoms. Fifteen (RM2) to 87 (RM1) differentially abundant proteins were identified within each cluster. Minimal overlap was observed between affected proteins and pathways across clusters. CONCLUSIONS: Protein signatures across newly discovered subgroups suggest identified subtypes are biochemically distinct. Findings should be validated, but may represent populations with separate pathophysiology and therapeutic needs. CLINICAL TRIAL REGISTRATION: The LURN ClinicalTrials.gov Identifier is NCT02485808.

Combined temperature and salinity effects on the passive sampling of PAHs with an assessment of impacts to petroleum toxicity.

In equilibrium-based passive sampling applications, the accuracy of estimating freely dissolved concentration (Cfree) of hydrophobic organic compounds (HOCs) relies on the passive sampler-water partition coefficient (KPS-W) values applied. The vast majority of KPS-W are generated under standard conditions: 20 °C in deionized or freshwater. Few empirically derived values are available for non-standard conditions. In this study, polyethylene (PE)-water partitioning coefficients (KPE-W) were experimentally determined for 15 polycyclic aromatic hydrocarbons (PAHs, comprising 9 parent and 6 alkylated compounds) under three different temperature (10, 20, 30 °C) and salinity (0, 18 and 36‰) regimes, the KPE-W values were found to correlate strongly with a variety of molecular parameters (e.g., octanol-water partition coefficients (KOW), molecular weight (MW) and molecular volume (MVOL)). The effects of temperature and salinity on the magnitude of KPE-W were found to be substantial. For temperature, the values range between -0.005 and -0.023 log units per °C; these values indicate that every 10 °C rise in temperature would potentially decrease the KPE-W by a factor of between 0.4 to 1.6. For salinity, the values range from 0.0028 to 0.0057 log units per unit ‰, indicating that an 18‰ increase in salinity would likely increase the KPE-W by a factor of between 0.28 and 0.82. Moreover, temperature and salinity were shown to be independent of each other and non-interacting. Temperature effects were chemical-specific and moderately dependent on hydrophobicity (expressed as the KOW), whereas salinity effects were independent of hydrophobicity. We also assessed the combined impact of temperature and salinity, which showed increasing effects with the hydrophobicity of the PAHs studied. Based on the results, KPE-W values adjusted for site-specific temperature and salinity can be calculated. The impact of applying such site-specific values was demonstrated using a PE-based field monitoring dataset for PAHs from coastal waters of Grand Isle (LA, USA) collected during the 2010 Deepwater Horizon oil spill. When KPE-W values were adjusted to 10 °C and 30 °C, the final freely dissolved concentrations (Cfree) decreased or increased depending on the adjustment. Use of the results of this investigation allow for adjusting existing PE-based datasets to site-specific conditions resulting in more accurate Cfree values for estimating exposure and adverse ecological effects.

The Impact of Spliceosome Inhibition in SF3B1-Mutated Uveal Melanoma.

Purpose: Unfortunately, treatment of patients with uveal melanoma (UM) with metastatic disease is limited. Twenty percent of patients with UM harbor a mutation in the splicing factor gene SF3B1, suggesting that aberrant spliceosome function plays a vital role in tumorigenesis. Splicing inhibitors exploit the preferential sensitivity of spliceosome-compromised leukemic cells to these compounds. Methods: We studied the effect of the splicing inhibitor E7107 using two UM cell lines and ex vivo cultured SF3B1- and BAP1-mutated primary UM tumor slices. These UM cell lines and ex vivo tumor slices were exposed for 24 hours to different concentrations of E7107. Tumor slices were stained with hematoxylin and eosin (H&E) and incubated with BAP1, MelanA, MIB-1, and caspase-3 antisera. Results: The E7107-exposed UM cell lines exhibited decreased cell viability and increased apoptosis, with the greatest effect on SF3B1-mutated UM cells. A similar effect on UM tumor slices was observed upon exposure to E7107. Additionally, RNA was isolated for differential isoform expression analysis. No significant difference in isoform usage was found genome-wide. However, specific genes were differentially expressed after E7107 treatment in the SF3B1-mutated samples. Moreover, E7107 had the greatest effect on intron retention. Conclusions: This study indicates/suggests that mutated SF3B1 UM cells are more sensitive to the splicing inhibitor E7107 than wild-type SF3B1 UM cells.

Deep learning with photonic neural cellular automata.

Rapid advancements in deep learning over the past decade have fueled an insatiable demand for efficient and scalable hardware. Photonics offers a promising solution by leveraging the unique properties of light. However, conventional neural network architectures, which typically require dense programmable connections, pose several practical challenges for photonic realizations. To overcome these limitations, we propose and experimentally demonstrate Photonic Neural Cellular Automata (PNCA) for photonic deep learning with sparse connectivity. PNCA harnesses the speed and interconnectivity of photonics, as well as the self-organizing nature of cellular automata through local interactions to achieve robust, reliable, and efficient processing. We utilize linear light interference and parametric nonlinear optics for all-optical computations in a time-multiplexed photonic network to experimentally perform self-organized image classification. We demonstrate binary (two-class) classification of images using as few as 3 programmable photonic parameters, achieving high experimental accuracy with the ability to also recognize out-of-distribution data. The proposed PNCA approach can be adapted to a wide range of existing photonic hardware and provides a compelling alternative to conventional photonic neural networks by maximizing the advantages of light-based computing whilst mitigating their practical challenges. Our results showcase the potential of PNCA in advancing photonic deep learning and highlights a path for next-generation photonic computers.

Hyperpolarized 129Xe MRI and spectroscopy of gas exchange abnormalities in chronic hypersensitivity pneumonitis.

PURPOSE: To evaluate 3D gas-exchange functional imaging characteristics using 129Xe MRI in a group of study participants with chronic hypersensitivity pneumonitis (CHP) as compared with healthy control participants. METHODS: In this prospective study, 11 participants with clinical and CT findings of CHP (4M 7F, mean age 67 ± 6.1 years) as well as 41 healthy subjects (25M 16F, mean age 44 ± 18 years) were enrolled between 2017 and 2022 and underwent 129Xe MRI. Three-dimensional images of ventilation, interstitial membrane uptake, and RBC transfer were rendered into quantitative 3D maps relative to a healthy reference cohort. In addition, 129Xe spectroscopy was used to assess the RBC:membrane ratio (RBC:M), the oxygen-dependent RBC chemical shift, and cardiogenically-driven RBC oscillation amplitude. Differences between the CHP participants and healthy subjects were assessed using the two-sample t-test or Wilcoxon rank-sum test as appropriate. RESULTS: CHP participants demonstrated significant differences in 6 parameters (p < 0.001) including regions of reduced ventilation, increased membrane uptake, and reduced RBC transfer as compared to healthy subjects. Gas exchange abnormalities measured on spectroscopy included a reduced RBC:M, reduced RBC chemical shift, and increased RBC oscillation amplitude. CONCLUSION: In participants with CHP, 129Xe MRI demonstrated gas exchange abnormalities common to other fibrotic lung diseases including increased membrane uptake, deficits in RBC transfer, and reduced RBC:M. However, CHP participants also exhibited prominent ventilation abnormalities, which may be reflective of the airway-centric nature of the disease. Further, the high variability observed in the membrane uptake could suggest varying degrees of disease progression or activity.

Revitalizing grand rounds in the time of COVID.

COVID presented an opportunity to revolutionize the traditional format of Medical Grand Rounds (MGR). In this Commentary, we explore the educational ramifications of shifting MGR virtually with a focus on COVID-related content and its long-term sustainability. This transformation offers an inclusive interdisciplinary approach to sustain learner interest and improve education.

Utilising primary care electronic health records to deliver the ALABAMA randomised controlled trial of penicillin allergy assessment.

BACKGROUND: Use of electronic health records (EHR) to provide real-world data for research is established, but using EHR to deliver randomised controlled trials (RCTs) more efficiently is less developed. The Allergy AntiBiotics And Microbial resistAnce (ALABAMA) RCT evaluated a penicillin allergy assessment pathway versus usual clinical care in a UK primary care setting. The aim of this paper is to describe how EHRs were used to facilitate efficient delivery of a large-scale randomised trial of a complex intervention embracing efficient participant identification, supporting minimising GP workload, providing accurate post-intervention EHR updates of allergy status, and facilitating participant follow up and outcome data collection. The generalisability of the EHR approach and health economic implications of EHR in clinical trials will be reported in the main ALABAMA trial cost-effectiveness analysis. METHODS: A descriptive account of the adaptation of functionality within SystmOne used to deliver/facilitate multiple trial processes from participant identification to outcome data collection. RESULTS: An ALABAMA organisation group within SystmOne was established which allowed sharing of trial functions/materials developed centrally by the research team. The 'ALABAMA unit' within SystmOne was also created and provided a secure efficient environment to access participants' EHR data. Processes of referring consented participants, allocating them to a trial arm, and assigning specific functions to the intervention arm were developed by adapting tools such as templates, reports, and protocols which were already available in SystmOne as well as pathways to facilitate allergy de-labelling processes and data retrieval for trial outcome analysis. CONCLUSIONS: ALABAMA is one of the first RCTs to utilise SystmOne EHR functionality and data across the RCT delivery, demonstrating feasibility and applicability to other primary care RCTs. TRIAL REGISTRATION: ClinicalTrials.gov: NCT04108637, registered 05/03/2019. ISRCTN: ISRCTN20579216.

Comparing stand-alone endovascular embolization versus stereotactic radiosurgery in the treatment of arteriovenous malformations with Spetzler-Martin grades I-III: a propensity score matched study.

BACKGROUND: Arteriovenous malformations (AVMs) are uncommon cerebral lesions that can cause significant neurological complications. Surgical resection is the gold standard for treatment, but endovascular embolization and stereotactic radiosurgery (SRS) are viable alternatives. OBJECTIVE: To compare the outcomes of endovascular embolization versus SRS in the treatment of AVMs with Spetzler-Martin grades I-III. METHODS: This study combined retrospective data from 10 academic institutions in North America and Europe. Patients aged 1 to 90 years who underwent endovascular embolization or SRS for AVMs with Spetzler-Martin grades I-III between January 2010 and December 2023 were included. RESULTS: The study included 244 patients, including 84 who had endovascular embolization and 160 who had SRS. Before propensity score matching (PSM), complete obliteration at the last follow-up was achieved in 74.5% of the SRS group compared with 57.8% of the embolization group (OR=0.47; 95% CI 0.26 to 0.48; P=0.01). After propensity score matching, SRS still achieved significantly higher occlusion rates at last follow-up (78.9% vs 55.3%; OR=0.32; 95% CI 0.12 to 0.90; P=0.03).Hemorrhagic complications were higher in the embolization group than in the SRS group, although this difference did not reach statistical significance after PSM (13.2% vs 2.6%; OR=5.6; 95% CI 0.62 to 50.47; P=0.12). Similarly, re-treatment rate was higher in the embolization group (10.5% vs 5.3%; OR=2.11; 95% CI 0.36 to 12.31; P=0.40) compared with the SRS group. CONCLUSION: Our findings indicate that SRS has a significantly higher obliteration rate at last follow-up compared with endovascular embolization. Also, SRS has a higher tendency for fewer hemorrhagic complications and lower re-treatment rate. Further prospective studies are needed.

The pace of life for forest trees.

Tree growth and longevity trade-offs fundamentally shape the terrestrial carbon balance. Yet, we lack a unified understanding of how such trade-offs vary across the world's forests. By mapping life history traits for a wide range of species across the Americas, we reveal considerable variation in life expectancies from 10 centimeters in diameter (ranging from 1.3 to 3195 years) and show that the pace of life for trees can be accurately classified into four demographic functional types. We found emergent patterns in the strength of trade-offs between growth and longevity across a temperature gradient. Furthermore, we show that the diversity of life history traits varies predictably across forest biomes, giving rise to a positive relationship between trait diversity and productivity. Our pan-latitudinal assessment provides new insights into the demographic mechanisms that govern the carbon turnover rate across forest biomes.