Development and validation of the HMS-Sepsis mortality model.

BACKGROUND: When comparing outcomes after sepsis, it is essential to account for patient case mix to make fair comparisons. We developed a model to assess risk-adjusted 30-day mortality in the Michigan Hospital Medicine Safety's sepsis initiative (HMS-Sepsis). QUESTION: Can HMS-Sepsis registry data adequately predict risk of 30-day mortality? Do performance assessments using adjusted vs unadjusted data differ? STUDY DESIGN AND METHODS: Retrospective cohort of community-onset sepsis hospitalizations in HMS-Sepsis registry (4/2022-9/2023), with split derivation (70%) and validation (30%) cohorts. We fit a risk-adjustment model (HMS-Sepsis mortality model) incorporating acute physiology, demographic, and baseline health data and assessed model performance using c-statistics, Brier's scores, and comparisons of predicted vs observed mortality by deciles of risk. We compared hospital performance (1st quintile, middle quintiles, 5th quintile) using observed versus adjusted mortality to understand the extent to which risk-adjustment impacted hospital performance assessment. RESULTS: Among 17,514 hospitalizations from 66 hospitals during the study period, 12,260 (70%) were used for model derivation and 5,254 (30%) for model validation. 30-day mortality for the total cohort was 19.4%. The final model included 13 physiologic variables, two physiologic interactions, and 16 demographic and chronic health variables. The most significant variables were age, metastatic solid tumor, temperature, altered mental status, and platelet count. The model c-statistic was 0.82 for the derivation cohort, 0.81 for the validation cohort, and ≥0.78 for all subgroups assessed. Overall calibration error was 0.0% and mean calibration error across deciles of risk was 1.5%. Standardized mortality ratios yielded different assessments than observed mortality for 33.9% of hospitals. CONCLUSIONS: The HMS-Sepsis mortality model had strong discrimination, adequate calibration, and reclassified one-third of hospitals to a different performance category from unadjusted mortality. Based on its strong performance, the HMS-Sepsis mortality model can aid in fair hospital benchmarking, assessment of temporal changes, and observational causal inference analysis.

A massively parallel in vivo assay of TdT mutants yields variants with altered nucleotide insertion biases.

Terminal deoxynucleotidyl transferase (TdT) is a unique DNA polymerase capable of template-independent extension of DNA with random nucleotides. TdT's de novo DNA synthesis ability has found utility in DNA recording, DNA data storage, oligonucleotide synthesis, and nucleic acid labeling, but TdT's intrinsic nucleotide biases limit its versatility in such applications. Here, we describe a multiplexed assay for profiling and engineering the bias and overall activity of TdT variants in high throughput. In our assay, a library of TdTs is encoded next to a CRISPR-Cas9 target site in HEK293T cells. Upon transfection of Cas9 and sgRNA, the target site is cut, allowing TdT to intercept the double strand break and add nucleotides. Each resulting insertion is sequenced alongside the identity of the TdT variant that generated it. Using this assay, 25,623 unique TdT variants, constructed by site-saturation mutagenesis at strategic positions, were profiled. This resulted in the isolation of several altered-bias TdTs that expanded the capabilities of our TdT-based DNA recording system, Cell History Recording by Ordered Insertion (CHYRON), by increasing the information density of recording through an unbiased TdT and achieving dual-channel recording of two distinct inducers (hypoxia and Wnt) through two differently biased TdTs. Select TdT variants were also tested in vitro , revealing concordance between each variant's in vitro bias and the in vivo bias determined from the multiplexed high throughput assay. Overall, our work, and the multiplex assay it features, should support the continued development of TdT-based DNA recorders, in vitro applications of TdT, and further study of the biology of TdT.

Comparison of selected cytomorphological features of canine pemphigus foliaceus and superficial pyoderma.

BACKGROUND: Cytological detection of acantholytic keratinocytes (acantholytic cells [AC]) helps to identify canine pemphigus foliaceus (cPF) yet AC also occurs in superficial pyoderma (SP), the main differential diagnosis. HYPOTHESIS/OBJECTIVES: To compare selected cytomorphological features of cPF and SP and to establish cytological diagnostic criteria that could differentiate cPF from SP. ANIMALS: 40 and 51 client-owned dogs with PF and SP, respectively. MATERIALS AND METHODS: Impression smears from cPF (64), impetigo (40) and exfoliative superficial pyoderma (ESP) (17) samples were stained with Romanowsky stain, randomised, blinded and evaluated by two investigators independently. The entire sample was screened (×500 or ×1000 magnification) for round (AC1), boat (AC2) and raft AC, eosinophils and bacteria. Interobserver agreements were calculated. RESULTS: The average number of the 10 highest ×500 fields for AC1 and AC2 was significantly higher in PF than SP (p < 0.0001; Kruskal-Wallis test). Rafts and eosinophils were more common in PF than SP (p < 0.0001; chi-square test), while bacteria were rare in PF (5%; p < 0.0001; chi-square test). Observations between the experienced and novice investigators were highly correlated. An ROC analysis identified five AC1/×500-magnification field as a suitable cut-off value for predicting PF diagnosis. This cut-off value was tested by two additional investigators, who identified sensitivity of 84%-100%, specificity of 95%-97% and accuracy of 95%-96% for the diagnosis of cPF. CONCLUSIONS AND CLINICAL RELEVANCE: Criterion-based impression smear cytological evaluation can provide strong evidence to support the clinical diagnosis. Acantholytic cell morphology varies in cPF and SP, and experience can improve accuracy in cytological differentiation.

Residential proximity to toxic metal-emitting industrial sites and toenail metal concentrations in a United States-wide prospective cohort.

BACKGROUND: Industrial facilities across the United States (US) release millions of pounds of toxic chemicals, including metals. Exposure to toxic metals has been associated with adverse health outcomes, but there is limited evidence on the association between living near metal-releasing facilities and the body burden of emitted compounds. OBJECTIVE: To investigate the association between residential proximity to toxic metal-emitting industrial facilities and toenail metal concentrations and to evaluate whether associations differed by race. METHODS: In a sample of 1556 non-Hispanic Black (32.5%) and non-Hispanic White (67.5%) women from the Sister Study, we used the US Environmental Protection Agency Toxics Release Inventory to identify metal-emitting facilities within 3, 5, and 10 km of participants' baseline residences. We measured toenail concentrations (µg/g) of arsenic, cadmium, cobalt, chromium, and lead. Using multivariable linear regression, we examined associations between residential proximity to and emissions from metal-emitting facilities and toenail metal concentrations, stratifying by race. We explored modification of race-stratified associations by neighborhood deprivation, using the Area Deprivation Index (ADI). RESULTS: Black participants were more likely to reside within 3 km of chromium-releasing facilities and 5 and 10 km of all observed metal-emitting sites. Living near metal-releasing facilities was not associated with higher toenail metal concentrations overall. Among Black women, higher chromium emissions exposure was associated with higher toenail chromium levels (ßTertile3vs.non-exposed = 2.36 µg/g, 95% CI = 0.63, 4.10). An association with lead was observed among Black women residing in the most deprived areas (≥75th ADI percentile: ß = 3.08 µg/g, 95% CI = 1.46, 4.71). No associations were observed for White participants. CONCLUSIONS: Despite low exposure prevalence, our findings suggest that living near chromium- and lead-releasing facilities, especially at shorter distances, may be associated with higher corresponding toenail metal levels among Black women, particularly those residing in the most disadvantaged areas.

Mucosal emphysematous head and neck infections: Scoping review and a case of emphysematous tonsillitis.

Objective: This scoping review seeks to understand the existing research in otolaryngological mucosal emphysematous infections and to elucidate gaps in knowledge in the field. We also present a case of bilateral necrotizing tonsillitis in an immunocompromised patient with the first reported imaging findings of emphysematous abscess of the tonsils. Data Sources: PubMed, Embase, Web of Science. Review Methods: We conducted our review according to the Preferred Reporting Items for Systematic Reviews extension for Scoping Reviews. Patient presentation, management, and outcomes were summarized. We also describe the case of a patient with aplastic anemia found to have emphysematous tonsillitis, managed with intubation, broad spectrum intravenous antibiotics and bilateral tonsillectomy. Results: We identified seven case reports or series, involving nine total patients, who presented with emphysematous epiglottitis, supraglottitis, or tonsillitis. The hallmark imaging characteristic was submucosal "gas bubble" on computed tomography. Presenting symptoms included dysphagia, odynophagia, dysphonia, cough, and fever. Both immunocompetent and immunocompromised patients were affected. All patients were treated with broad spectrum antibiotics, and most with steroids. Patients at risk of airway compromise also underwent intubation and surgical drainage or debridement of the emphysematous infection. Conclusion: Emphysematous pharyngeal infections are rare but potentially life-threatening infections that can progress rapidly, resulting in airway compromise and sepsis in both immunocompetent and immunocompromised individuals. We highlight the importance of swift intervention, with intubation and surgical intervention often required for severe cases. More research is needed on common pathogens and patient risk factors to guide future medical and surgical management.

Ablating Myocardium Using Nanosecond Pulsed Electric Fields: Preclinical Assessment of Feasibility, Safety, and Durability.

BACKGROUND: Unlike conventional microsecond pulsed electrical fields that primarily target the cell membranes, nanosecond pulses are thought to primarily electroporate intracellular organelles. We conducted a comprehensive preclinical assessment of catheter-based endocardial nanosecond pulsed field ablation in swine. METHODS: A novel endocardial nanosecond pulsed field ablation system was evaluated in a total of 25 swine. Using either a low-dose (5-second duration) or high-dose (15-second duration) strategy, thoracic veins and discrete atrial and ventricular sites were ablated. Swine survived for <1 (n=1), ≈2 (n=7), ≈7 (n=6), 14 (n=2), or ≈28 (n=9) days, and venous isolation was assessed before euthanize. Safety assessments included evaluation of esophageal effects, phrenic nerve function, and changes in venous caliber. All tissues were subject to careful gross pathological and histopathologic examination. RESULTS: All (100%) veins (13 low-dose, 34 high-dose) were acutely isolated, and all reassessed veins (6 low-dose, 15 high-dose) were durably isolated. All examined vein lesions (10 low-dose, 22 high-dose) were transmural. Vein diameters (n=15) were not significantly changed. Of the animals assessed for phrenic palsy (n=9), 3 (33%) demonstrated only transient palsy. There were no differences between dosing strategies. Thirteen mitral isthmus lesions were analyzed, and all 13 (100%) were transmural (depth, 6.4±0.4 mm). Ventricular lesions were 14.7±4.5 mm wide and 7.1±1.3 mm deep, with high-dose lesions deeper than low-dose (7.9±1.2 versus 6.2±0.8 mm; P=0.007). The esophagus revealed nontransmural adventitial surface lesions in 5 of 5 (100%) animals euthanized early (2 days) post-ablation. In the 10 animals euthanized later (14-28 days), all animals demonstrated significant esophageal healing-8 with complete resolution, and 2 with only trace fibrosis. CONCLUSIONS: A novel, endocardial nanosecond pulsed field ablation system provides acute and durable venous isolation and linear lesions. Transient phrenic injury and nontransmural esophageal lesions can occur with worst-case assessments suggesting limits to pulsed field ablation tissue selectivity and the need for dedicated assessments during clinical studies.

Using Power Analysis to Choose the Unit of Randomization, Outcome, and Approach for Subgroup Analysis for a Multilevel Randomized Controlled Clinical Trial to Reduce Disparities in Cardiovascular Health.

We give examples of three features in the design of randomized controlled clinical trials which can increase power and thus decrease sample size and costs. We consider an example multilevel trial with several levels of clustering. For a fixed number of independent sampling units, we show that power can vary widely with the choice of the level of randomization. We demonstrate that power and interpretability can improve by testing a multivariate outcome rather than an unweighted composite outcome. Finally, we show that using a pooled analytic approach, which analyzes data for all subgroups in a single model, improves power for testing the intervention effect compared to a stratified analysis, which analyzes data for each subgroup in a separate model. The power results are computed for a proposed prevention research study. The trial plans to randomize adults to either telehealth (intervention) or in-person treatment (control) to reduce cardiovascular risk factors. The trial outcomes will be measures of the Essential Eight, a set of scores for cardiovascular health developed by the American Heart Association which can be combined into a single composite score. The proposed trial is a multilevel study, with outcomes measured on participants, participants treated by the same provider, providers nested within clinics, and clinics nested within hospitals. Investigators suspect that the intervention effect will be greater in rural participants, who live farther from clinics than urban participants. The results use published, exact analytic methods for power calculations with continuous outcomes. We provide example code for power analyses using validated software.

Hemocompatibility Evaluation of a Novel Ambulatory Pulmonary Assist System Using a Lightweight Axial-Flow Pump.

The Pulmonary Assist System (PAS) is currently under development as a wearable respiratory assist system. In this study, the hemocompatibility of the PAS's axial-flow mechanical pump (AFP) was compared to other contemporary mechanical pumps in an acute ovine model. The PAS was attached to a normal sheep in a venovenous configuration using one of three pumps: 1) AFP, 2) ReliantHeart HeartAssist 5 (control), or 3) Abbott Pedimag (control) (n = 5 each). Each sheep was supported on the PAS for 12 hours with two L/minute of blood flow and four L/minute of sweep gas. Hemolysis, coagulation, inflammation, and platelet activation and loss were compared among the groups. In this study, the plasma-free hemoglobin (pfHb) was less than 10 mg/dl in all groups. The pfHb was significantly lower in the AFP group compared to other groups. There was no significant clot formation in the pumps and oxygenators in all groups. Furthermore, no significant differences in coagulation (oxygenator resistance, fibrinopeptide A), inflammation (white blood cell counts, IL-8), and platelet activation and loss (p-selectin, platelet counts) were observed among the groups (all, p > 0.05). This study demonstrates equivalent hemocompatibility of the PAS's AFP to other contemporary mechanical pumps with a reduced level of hemolysis on startup.

Post-translation digital data encoding into the genomes of mammalian cell populations.

High resolution cellular signal encoding is critical for better understanding of complex biological phenomena. DNA-based biosignal encoders alter genomic or plasmid DNA in a signal dependent manner. Current approaches involve the signal of interest affecting a DNA edit by interacting with a signal specific promoter which then results in expression of the effector molecule (DNA altering enzyme). Here, we present the proof of concept of a biosignal encoding system where the enzyme terminal deoxynucleotidyl transferase (TdT) acts as the effector molecule upon directly interacting with the signal of interest. A template independent DNA polymerase (DNAp), TdT incorporates nucleotides at the 3' OH ends of DNA substrate in a signal dependent manner. By employing CRISPR-Cas9 to create double stranded breaks in genomic DNA, we make 3'OH ends available to act as substrate for TdT. We show that this system can successfully resolve and encode different concentrations of various biosignals into the genomic DNA of HEK-293T cells. Finally, we develop a simple encoding scheme associated with the tested biosignals and encode the message "HELLO WORLD" into the genomic DNA of HEK-293T cells at a population level with 91% accuracy. This work demonstrates a simple and engineerable system that can reliably store local biosignal information into the genomes of mammalian cell populations.

National Beef Quality Audit-2022: Transportation, mobility, live cattle, and hide assessments to determine producer-related defects that affect animal welfare and the value of market cows and bulls at processing facilities.

The National Beef Quality Audit (NBQA)-2022 serves as a benchmark of the current market cow and bull sectors of the U.S. beef industry and allows comparison to previous audits as a method of monitoring industry progress. From September 2021 through May 2022, livestock trailers (n = 125), live animals (n = 5,430), and post-slaughter hide-on animals (n = 6,674) were surveyed at 20 commercial beef processing facilities across the U.S. Cattle were transported in a variety of trailer types for an average distance of 490.6 km and a mean transport time of 6.3 h. During transit, cattle averaged 2.3 m2 of trailer space per animal indicating sufficient space was provided according to industry guidelines. Of all trailers surveyed, 55.3% transported cattle from an auction barn to a processing facility. When surveyed, 63.6% of all truck drivers reported to be Beef Quality Assurance certified. The majority (77.0%) of cattle were sound when evaluated for mobility. Mean body condition scores (9-point scale) for beef cows and bulls were 3.8 and 4.4, respectively, whereas mean body condition scores (5-point scale) for dairy cows and bulls were 2.3 and 2.6, respectively. Of the cattle surveyed, 45.1% had no visible live animal defects, and 37.9% had only a single defect. Of defects present in cows, 64.6% were attributed to an udder problem. Full udders were observed in 47.5% of all cows. Nearly all cattle were free of visible abscesses and knots (97.9% and 98.2%, respectively). No horns were observed in 89.4% of all cattle surveyed. Beef cattle were predominantly black-hided (68.9% and 67.4% of cows and bulls, respectively). Holstein was the predominant dairy animal observed and accounted for 85.7% of the cows and 98.0% of the bulls. Only 3.1% of all animals had no form of identification. Findings from the NBQA-2022 show improvements within the industry and identify areas that require continued education and research to improve market cow and bull welfare and beef quality.

Evaluating Colonoscopy Quality by Performing Provider Type.

BACKGROUND: Colorectal Cancer (CRC) is the third most diagnosed cancer and the second leading cause of cancer death in the United States. Colonoscopy is an essential tool for screening, used both as a primary approach and follow-up to an abnormal stool-based CRC screening result. Colonoscopy quality is often measured with four key indicators: bowel preparation, cecal intubation, mean withdrawal time, and adenoma detection. Colonoscopies are most often performed by gastroenterologists (GI), however, in rural and medically underserved areas non-GI providers often perform colonoscopies. This study aims to evaluate the quality and safety of screening colonoscopies performed by non-GI providers, comparing their outcomes to those of GI providers. METHODS: Descriptive statistics were used to characterize the study population. Results for quality indicators were stratified by provider type and compared. Statistical significance was determined using p < 0.05 as the threshold for all comparisons; all p-values were two-sided. RESULTS: No statistical difference was found when comparing performance by provider type. Median performance for gastroenterologists, general surgeons, and family medicine providers ranged form 98-100% for cecal intubation; 97.4-100% for bowel preparation; 57.4-88.9% for male adenoma detection rate; 47.7-62.13% for female adenoma detection rate; and 0:12:10-0:20:16 for mean withdrawal time. All provider types met and exceeded the goal metric for each of the quality indicators (p < 0.001). In this analysis, non-GI providers can be expected to perform colonoscopies with similar quality to GI providers based on performance outcomes for the key quality metrics.

Toward a Psychology of Ideas Rather Than Demographics: Commentary on Hommel (2024).

The public will rightly not value a science that is more concerned with demographic population matching than with ideas. Taking further steps in the direction of identity politics will reduce public confidence in psychology's conclusions and reduce trust and respect. If psychology embraces demographic quotas, there will be self-selection out of the discipline, and that self-selection will harm our science.

Ultrasonic Shears Decrease Postoperative Hematomas in Head and Neck Microvascular Reconstruction.

OBJECTIVE: To evaluate postoperative hematoma and takeback rates in a large series of microvascular reconstructions. We sought to determine whether the use of ultrasonic shears reduced these rates. STUDY DESIGN: Retrospective cohort study. SETTING: Tertiary referral hospital. METHODS: A total of 2288 patients undergoing free flap reconstruction for head and neck defects between 1995 and 2022 were reviewed. Patients undergoing dissection with and without ultrasonic shears were compared to determine postoperative hematoma and takeback rates. RESULTS: The overall hematoma rate was 1.3% (29/2288) for the entire cohort. The postoperative hematoma rates with and without ultrasonic shears were 0.63% (9/1418) and 2.3% (20/870), relative risk = 0.28, P = .0015. Of 870 patients undergoing surgery without ultrasonic shears, 14 (1.61%) were taken back to the operating room for control of bleeding compared to 8 of 1418 (0.56%) in the ultrasonic shears cohort. CONCLUSION: Our large series of patients undergoing microvascular reconstruction shows a decrease in postoperative hematoma rate and takeback for bleeding with the adoption of ultrasonic shears. Ultrasonic shears are an effective tool that can help decrease perioperative morbidity secondary to hematoma after head and neck tumor resection and microvascular reconstruction.

National Beef Quality Audit-2022 Phase 1: face-to-face and digital interviews.

The National Beef Quality Audit (NBQA) has been conducted regularly since 1991 to assess and benchmark quality in the U.S. beef industry, with the most recent iteration conducted in 2022. The goal of NBQA Phase I is to evaluate what needs to be managed to improve beef quality and demand. Interviews (n = 130) of industry personnel were conducted with the aid of routing software. In total, packers (n = 24), retailers (n = 20), further processors (n = 26), foodservice (n = 18), and allied government agencies and trade organizations (n = 42) were interviewed. Interviews were routed in software based on interviewee involvement in either the fed steer and heifer market cow and bull sectors, or both. Interviews were structured to elicit random responses in the order of determining "must-have" criteria (quality factors that are required to make a purchase), best/worst ranking (of quality factors based on importance), how interviewees defined quality terms, a strength, weakness, opportunities, threats (SWOT) analysis, general beef industry questions, and sustainability goals (the latter four being open-ended). Quality factors were 1) visual characteristics, 2) cattle genetics, 3) food safety, 4) eating satisfaction, 5) animal well-being, 6) weight and size, and 7) lean, fat, and bone. Best/worst analysis revealed that "food safety" was the most (P < 0.05) important factor in beef purchasing decisions for all market sectors and frequently was described as "everything" and "a way of business." Culture surrounding food safety changed compared to previous NBQAs with interviewees no longer considering food safety as a purchasing criterion, but rather as a market expectation. The SWOT analysis indicated that "eating quality of U.S. beef" was the greatest strength, and cited that educating both consumers and producers on beef production would benefit the industry. Irrespective of whether companies' products were fed or market cow/bull beef, respondents said that they believed "environmental concerns" were among the major threats to the industry. Perceived image of the beef industry in the market sectors has improved since NBQA-2016 for both fed cattle and market cow/bull beef.

Geriatric Emergency Medication Safety Recommendations (GEMS-Rx): Modified Delphi Development of a High-Risk Prescription List for Older Emergency Department Patients.

STUDY OBJECTIVE: Half of emergency department (ED) patients aged 65 years and older are discharged with new prescriptions. Potentially inappropriate prescriptions contribute to adverse drug events. Our objective was to develop an evidence- and consensus-based list of high-risk prescriptions to avoid among older ED patients. METHODS: We performed a modified, 3-round Delphi process that included 10 ED physician experts in geriatrics or quality measurement and 1 pharmacist. Consensus members reviewed all 35 medication categories from the 2019 American Geriatrics Society Beers Criteria and ranked each on a 5-point Likert scale (5=highest) for overall priority for avoidance (Round 1), risk of short-term adverse events and avoidability (Round 2), and reasonable medical indications for high-risk medication use (Round 3). RESULTS: For each round, questionnaire response rates were 91%, 82%, and 64%, respectively. After Round 1, benzodiazepines (mean, 4.60 [SD, 0.70]), skeletal muscle relaxants (4.60 [0.70]), barbiturates (4.30 [1.06]), first-generation antipsychotics (4.20 [0.63]) and first-generation antihistamines (3.70 [1.49]) were prioritized for avoidance. In Rounds 2 and 3, hypnotic "Z" drugs (4.29 [1.11]), metoclopramide (3.89 [0.93]), and sulfonylureas (4.14 [1.07]) were prioritized for avoidability, despite lower concern for short-term adverse events. All 8 medication classes were included in the final list. Reasonable indications for prescribing high-risk medications included seizure disorders, benzodiazepine/ethanol withdrawal, end of life, severe generalized anxiety, allergic reactions, gastroparesis, and prescription refill. CONCLUSION: We present the first expert consensus-based list of high-risk prescriptions for older ED patients (GEMS-Rx) to improve safety among older ED patients.

The emergency department trigger tool: Multicenter trigger query validation.

OBJECTIVES: We previously described derivation and validation of the emergency department trigger tool (EDTT) for adverse event (AE) detection. As the first step in our multicenter study of the tool, we validated our computerized screen for triggers against manual review, establishing our use of this automated process for selecting records to review for AEs. METHODS: This is a retrospective observational study of visits to three urban, academic EDs over 18 months by patients ≥ 18 years old. We reviewed 912 records: 852 with at least one of 34 triggers found by the query and 60 records with none. Two first-level reviewers per site each manually screened for triggers. After completion, computerized query results were revealed, and reviewers could revise their findings. Second-level reviewers arbitrated discrepancies. We compare automated versus manual screening by positive and negative predictive values (PPVs, NPVs), present population trigger frequencies, proportions of records triggered, and how often manual ratings were changed to conform with the query. RESULTS: Trigger frequencies ranged from common (>25%) to rare (1/1000) were comparable at U.S. sites and slightly lower at the Canadian site. Proportions of triggered records ranged from 31% to 49.4%. Overall query PPV was 95.4%; NPV was 99.2%. PPVs for individual trigger queries exceeded 90% for 28-31 triggers/site and NPVs were >90% for all but three triggers at one site. Inter-rater reliability was excellent, with disagreement on manual screening results less than 5% of the time. Overall, reviewers amended their findings 1.5% of the time when discordant with query findings, more often when the query was positive than when negative (47% vs. 23%). CONCLUSIONS: The EDTT trigger query performed very well compared to manual review. With some expected variability, trigger frequencies were similar across sites and proportions of triggered records ranged 31%-49%. This demonstrates the feasibility and generalizability of implementing the EDTT query, providing a solid foundation for testing the triggers' utility in detecting AEs.

Learning competing risks across multiple hospitals: one-shot distributed algorithms.

OBJECTIVES: To characterize the complex interplay between multiple clinical conditions in a time-to-event analysis framework using data from multiple hospitals, we developed two novel one-shot distributed algorithms for competing risk models (ODACoR). By applying our algorithms to the EHR data from eight national children's hospitals, we quantified the impacts of a wide range of risk factors on the risk of post-acute sequelae of SARS-COV-2 (PASC) among children and adolescents. MATERIALS AND METHODS: Our ODACoR algorithms are effectively executed due to their devised simplicity and communication efficiency. We evaluated our algorithms via extensive simulation studies as applications to quantification of the impacts of risk factors for PASC among children and adolescents using data from eight children's hospitals including the Children's Hospital of Philadelphia, Cincinnati Children's Hospital Medical Center, Children's Hospital of Colorado covering over 6.5 million pediatric patients. The accuracy of the estimation was assessed by comparing the results from our ODACoR algorithms with the estimators derived from the meta-analysis and the pooled data. RESULTS: The meta-analysis estimator showed a high relative bias (∼40%) when the clinical condition is relatively rare (∼0.5%), whereas ODACoR algorithms exhibited a substantially lower relative bias (∼0.2%). The estimated effects from our ODACoR algorithms were identical on par with the estimates from the pooled data, suggesting the high reliability of our federated learning algorithms. In contrast, the meta-analysis estimate failed to identify risk factors such as age, gender, chronic conditions history, and obesity, compared to the pooled data. DISCUSSION: Our proposed ODACoR algorithms are communication-efficient, highly accurate, and suitable to characterize the complex interplay between multiple clinical conditions. CONCLUSION: Our study demonstrates that our ODACoR algorithms are communication-efficient and can be widely applicable for analyzing multiple clinical conditions in a time-to-event analysis framework.

Improving ecosystem health in highly altered river basins: a generalized framework and its application to the Mississippi-Atchafalaya River Basin.

Continued large-scale public investment in declining ecosystems depends on demonstrations of "success". While the public conception of "success" often focuses on restoration to a pre-disturbance condition, the scientific community is more likely to measure success in terms of improved ecosystem health. Using a combination of literature review, workshops and expert solicitation we propose a generalized framework to improve ecosystem health in highly altered river basins by reducing ecosystem stressors, enhancing ecosystem processes and increasing ecosystem resilience. We illustrate the use of this framework in the Mississippi-Atchafalaya River Basin (MARB) of the central United States (U.S.), by (i) identifying key stressors related to human activities, and (ii) creating a conceptual ecosystem model relating those stressors to effects on ecosystem structure and processes. As a result of our analysis, we identify a set of landscape-level indicators of ecosystem health, emphasizing leading indicators of stressor removal (e.g., reduced anthropogenic nutrient inputs), increased ecosystem function (e.g., increased water storage in the landscape) and increased resilience (e.g., changes in the percentage of perennial vegetative cover). We suggest that by including these indicators, along with lagging indicators such as direct measurements of water quality, stakeholders will be better able to assess the effectiveness of management actions. For example, if both leading and lagging indicators show improvement over time, then management actions are on track to attain desired ecosystem condition. If, however, leading indicators are not improving or even declining, then fundamental challenges to ecosystem health remain to be addressed and failure to address these will ultimately lead to declines in lagging indicators such as water quality. Although our model and indicators are specific to the MARB, we believe that the generalized framework and the process of model and indicator development will be valuable in an array of altered river basins.

Children with bilateral cerebral palsy use their hip joint to complete a step-up task.

Performance in stair-climbing is largely associated with disruptions to mobility and community participation in children with cerebral palsy (CP). It is important to understand the nature of motor impairments responsible for making stairs a challenge in children with bilateral CP to clarify underlying causes of impaired mobility. In pediatric clinical populations, sensitive measurements of movement quality can be captured during the initial step of stair ascent. Thus, the purpose of this study was to quantify the lower limb joint moments of children with bilateral CP during the stance phases of a step-up task. Participants performed multiple stepping trials in a university gait laboratory. Outcome measures included extensor support moments (the sum of hip, knee, and ankle sagittal plane moments), hip abduction moments, and their timing. We recruited seven participants per group. We found that peak support and hip abduction moments were similar in the bilateral CP group compared to the typical development (TD) group. We also found that children with bilateral CP timed their peak moments closer together and increasingly depended on the hip joint to complete the task, especially in their more affected (MA) lower limb. Our investigation highlights some underlying causes that may make stair climbing a challenge for the CP population, including a loss of selective voluntary motor control (SVMC), and provides a possible treatment approach to strengthen lower limb muscles.