Geospatial Disparities in Youth Sexually Transmitted Infections During COVID-19.

INTRODUCTION: Early in the COVID-19 pandemic, routine sexually transmitted infection (STI) screenings decreased, and test positivity rates increased due to limited screening appointments, national-level STI testing supply shortages, and social distancing mandates. It is unclear if adolescent preventive STI screening has returned to pre-pandemic levels and if pre-existing disparities worsened in late-pandemic. METHODS: This cross-sectional study examined 22,974 primary care visits by 13-19-year-olds in the Philadelphia metropolitan area undergoing screening for gonorrhea and chlamydia in a 31-clinic pediatric primary care network during 2018-2022. Using interrupted-time-series analysis and logistic regression, pandemic-related changes in the asymptomatic STI screening rate and test positivity were tracked across patient demographics. Neighborhood moderation was investigated by census-tract-level Child Opportunity Index in 2023. RESULTS: The asymptomatic STI screening rate dropped by 27.8 percentage points (pp) and 13.5pp when the pandemic and national STI test supply shortage began, respectively, but returned to pre-pandemic levels after supply availability was restored in early 2021. Non-Hispanic-Black adolescents had a significant pandemic drop in STI screening rate, and it did not return to prep-andemic levels (-3.6 pp in the late-pandemic period, p<0.01). This decrease was more pronounced in socioeconomically and educationally disadvantaged neighborhoods (7.5 pp and 9.9 pp lower, respectively) than in advantaged neighborhoods (both p<0.001), controlling for sex, age, insurance type and clinic characteristics. CONCLUSIONS: Neighborhood socioeconomic and educational disadvantage amplified racial-ethnic disparities in STI screening during the pandemic. Future interventions should focus on improving primary care utilization of non-Hispanic-Black adolescents to increase routine STI screening and preventive care utilization.

Surgical neonates: A retrospective review of procedures and postoperative outcomes at a quaternary children's hospital.

INTRODUCTION: Neonates have a high incidence of respiratory and cardiac perioperative events. Disease severity and indications for surgical intervention often dovetail with an overall complex clinical course and predispose these infants to adverse long-term neurodevelopmental outcomes and increased length of stay. Our aims were to describe severe and nonsevere early postoperative complications to establish a baseline of care outcomes and to identify subgroups of surgical neonates and procedures for future prospective studies. METHODS: Electronic health record data were examined retrospectively for a cohort of patients who had general anesthesia from January 26, 2015 to August 31, 2018. Inclusion criteria were full-term infants with postmenstrual age less than 44 weeks or premature infants less than 60 weeks postmenstrual age undergoing nonimaging, noncardiac surgery. Severe postoperative complications were defined as mortality, reintubation, positive blood culture, and surgical site infection. Nonsevere early postoperative outcomes were defined as hypoglycemia, hyperglycemia, hypothermia, hyperthermia, and readmission within 30 days. RESULTS: About 2569 procedures were performed in 1842 neonates of which 10.9% were emergency surgeries. There were 120 postoperative severe complications and 965 nonsevere postoperative outcomes. Overall, 30-day mortality was 1.8% for the first procedure performed, with higher mortality seen on subgroup analysis for patients who underwent exploratory laparotomy (10.3%) and congenital lung lesion resection (4.9%). Postoperative areas for improvement included hyperglycemia (13.9%) and hypothermia (7.9%). DISCUSSION: The mortality rate in our study was comparable to other studies of neonatal surgery despite a high rate of emergency surgery and a high prevalence of prematurity in our cohort. The early outcomes data identified areas for improvement, including prevention of postoperative glucose and temperature derangements. CONCLUSIONS: Neonates in this cohort were at risk for severe and nonsevere adverse postoperative outcomes. Future studies are suggested to improve mortality and adverse event rates.

Eliminating Monitor Overuse (EMO) type III effectiveness-deimplementation cluster-randomized trial: Statistical analysis plan.

Background: Deimplementing overused health interventions is essential to maximizing quality and value while minimizing harm, waste, and inefficiencies. Three national guidelines discourage continuous pulse oximetry (SpO2) monitoring in children who are not receiving supplemental oxygen, but the guideline-discordant practice remains prevalent, making it a prime target for deimplementation. This paper details the statistical analysis plan for the Eliminating Monitor Overuse (EMO) SpO2 trial, which compares the effect of two competing deimplementation strategies (unlearning only vs. unlearning plus substitution) on the sustainment of deimplementation of SpO2 monitoring in children with bronchiolitis who are in room air. Methods: The EMO Trial is a hybrid type 3 effectiveness-deimplementation trial with a longitudinal cluster-randomized design, conducted in Pediatric Research in Inpatient Settings Network hospitals. The primary outcome is deimplementation sustainment, analyzed as a longitudinal difference-in-differences comparison between study arms. This analysis will use generalized hierarchical mixed-effects models for longitudinal clustering outcomes. Secondary outcomes include the length of hospital stay and oxygen supplementation duration, modeled using linear mixed-effects regressions. Using the well-established counterfactual approach, we will also perform a mediation analysis of hospital-level mechanistic measures on the association between the deimplementation strategy and the sustainment outcome. Discussion: We anticipate that the EMO Trial will advance the science of deimplementation by providing new insights into the processes, mechanisms, and likelihood of sustained practice change using rigorously designed deimplementation strategies. This pre-specified statistical analysis plan will mitigate reporting bias and support data-driven approaches. Trial registration: ClinicalTrials.gov NCT05132322. Registered on 24 November 2021.

Sustainment of continuous pulse oximetry deimplementation: Analysis of Eliminating Monitor Overuse study data from six hospitals.

Using continuous pulse oximetry (cSpO2 ) to monitor children with bronchiolitis who are not receiving supplemental oxygen is a form of medical overuse. In this longitudinal analysis from the Eliminating Monitor Overuse (EMO) study, we aimed to assess changes in cSpO2 overuse before, during, and after intensive cSpO2 -deimplementation efforts in six hospitals. Monitoring data were collected during three phases: "P1" baseline, "P2" active deimplementation (all sites engaged in education and audit and feedback strategies), and "P3" sustainment (a new baseline measured after strategies were withdrawn). Two thousand and fifty-three observations were analyzed. We found that each hospital experienced reductions during active deimplementation (P2), with overall adjusted cSpO2 overuse decreasing from 53%, 95% confidence interval (CI): (49-57) to 22%, 95% CI: (19-25) between P1 and P2. However, following the withdrawal of deimplementation strategies, overuse rebounded in all six sites, with overall adjusted cSpO2 overuse increasing to 37%, 95% CI: (33-41) in P3.

Measuring quality STI care among adolescent female primary care patients in Philadelphia.

OBJECTIVES: Engagement in guideline-recommended sexually transmitted infection (STI) care is fundamental to ending the STI epidemic in the USA. However, the US 2021-2025 STI National Strategic Plan and STI surveillance reports do not include a framework to measure quality STI care delivery. This study developed and applied an STI Care Continuum that can be used across settings to improve STI care quality, assess adherence to guideline-recommended care and standardise the measurement of progress towards National Strategic goals. METHODS: Review of the Centers for Disease Control and Prevention STI Treatment guidelines identified seven distinct steps of STI care for gonorrhoea, chlamydia and syphilis: (1) STI testing indication, (2) STI test completion, (3) HIV testing, (4) STI diagnosis, (5) partner services, (6) STI treatment and (7) STI retesting. Steps 1-4, 6 and 7 for gonorrhoea and/or chlamydia (GC/CT) were measured among females aged 16-17 years with a clinic visit at an academic paediatric primary care network in 2019. We used Youth Risk Behavior Surveillance Survey data to estimate step 1, and electronic health record data for steps 2, 3, 4, 6 and 7. RESULTS: Among 5484 female patients aged 16-17 years, an estimated 44% had an STI testing indication. Among those patients, 17% were tested for HIV, of whom none tested positive, and 43% were tested for GC/CT, 19% of whom were diagnosed with GC/CT. Of these patients, 91% received treatment within 2 weeks and 67% were retested within 6 weeks to 1 year after diagnosis. On retesting, 40% were diagnosed with recurrent GC/CT. CONCLUSIONS: Local application of an STI Care Continuum identified STI testing, retesting and HIV testing as areas for improvement. The development of an STI Care Continuum identified novel measures for monitoring progress towards National Strategic indicators. Similar methods can be applied across jurisdictions to target resources, standardise data collection and reporting and improve STI care quality.

The Relationship Between Directly Observed Therapy for Chlamydia Infections and Retesting Rates in an Adolescent Population.

BACKGROUND: Chlamydia trachomatis is the most common reportable sexually transmitted infection in the United States, with >60% of reported cases occurring in individuals aged 15 to 24 years. US practice guidelines recommend directly observed therapy (DOT) for the treatment of chlamydia in adolescents, but almost no research has been done to evaluate whether DOT results in improved outcomes. METHODS: We conducted a retrospective cohort study of adolescents who sought care at 1 of 3 clinics within a large academic pediatric health system for a chlamydia infection. The study outcome was return for retesting within 6 months. Unadjusted analyses were performed using χ2 , Mann-Whitney U , and t tests, and adjusted analyses were performed using multivariable logistic regression. RESULTS: Of the 1970 individuals included in the analysis, 1660 (84.3%) received DOT and 310 (15.7%) had a prescription sent to a pharmacy. The population was primarily Black/African American (95.7%) and female (78.2%). After controlling for confounders, individuals who had a prescription sent to a pharmacy were 49% (95% confidence interval, 31%-62%) less likely than individuals who received DOT to return for retesting within 6 months. CONCLUSIONS: Despite clinical guidelines recommending the use of DOT for chlamydia treatment in adolescents, this is the first study to describe the association between DOT and an increase in the number of adolescents and young adults who return for sexually transmitted infection retesting within 6 months. Further research is needed to confirm this finding in diverse populations and explore nontraditional settings for the provision of DOT.

Evaluating the Accuracy of Pulse Oximetry in Children According to Race.

This cross-sectional study investigates the association between race and pulse oximeter accuracy in children in the US.

Pediatric Characteristics Associated With Higher Rates of Monitor Alarms.

Background: Continuous physiologic monitoring commonly is used in pediatric medical-surgical (med-surg) units and is associated with high alarm burden for clinicians. Characteristics of pediatric patients generating high rates of alarms on med-surg units are not known. Objective: To describe the demographic and clinical characteristics of pediatric med-surg patients associated with high rates of clinical alarms. Methods: We conducted a cross-sectional, single-site, retrospective study using existing clinical and alarm data from a children's hospital. Continuously monitored patients from med-surg units who had available alarm data were included. Negative binomial regression models were used to test the association between patient characteristics and the rate of clinical alarms per continuously monitored hour. Results: Our final sample consisted of 1,569 patients with a total of 38,501 continuously monitored hours generating 265,432 clinical alarms. Peripheral oxygen saturation (SpO2) low alarms accounted for 57.5% of alarms. Patients with medical complexity averaged 11% fewer alarms per hour than those without medical complexity (P < 0.01). Patients older than 5 years had up to 30% fewer alarms per hour than those who were younger than 5 years (P < 0.01). Patients using supplemental oxygen averaged 39% more alarms per hour compared with patients who had no supplemental oxygen use (P < 0.01). Patients at high risk for deterioration averaged 19% more alarms per hour than patients who were not high risk (P = 0.01). Conclusion: SpO2 alarms were the most common type of alarm in this study. The results highlight patient populations in pediatric medical-surgical units that may be high yield for interventions to reduce alarms. Most physiologic monitor alarms in pediatric medical-surgical (med-surg) units are not informative and likely could be safely eliminated to reduce noise and alarm fatigue.1-3 However, identifying and sustaining successful alarm-reduction strategies is a challenge. Research shows that 25% of patients in pediatric med-surg units produce almost three-quarters of all alarms.4 These patients are a potential high-yield target for alarm-reduction strategies; however, we are not aware of studies describing characteristics of pediatric patients generating high rates of alarms. The patient populations seen on pediatric med-surg units are diverse. Children of all ages are cared for on these units, with diagnoses ranging from acute respiratory infections, to management of chronic conditions, and to psychiatric conditions. Not all patients on pediatric med-surg units have physiologic parameters continuously monitored,4 but among those who do, understanding patient characteristics associated with high rates of alarms may help clinicians, healthcare technology management (HTM) professionals, and others working on alarm management strategies to develop targeted interventions. We conducted an exploratory retrospective study to describe patient characteristics associated with high rates of alarms in pediatric med-surg units.

The Alarm Burden of Excess Continuous Pulse Oximetry Monitoring Among Patients With Bronchiolitis.

Guidelines discourage continuous pulse oximetry monitoring of hospitalized infants with bronchiolitis who are not receiving supplemental oxygen. Excess monitoring is theorized to contribute to increased alarm burden, but this burden has not been quantified. We evaluated admissions of 201 children (aged 0-24 months) with bronchiolitis. We categorized time ≥60 minutes following discontinuation of supplemental oxygen as "continuously monitored (guideline-discordant)," "intermittently measured (guideline-concordant)," or "unable to classify." Across 4402 classifiable hours, 77% (11,101) of alarms occurred during periods of guideline-discordant monitoring. Patients experienced a median of 35 alarms (interquartile range [IQR], 10-81) during guideline-discordant, continuously monitored time, representing a rate of 6.7 alarms per hour (IQR, 2.1-12.3). In comparison, the median hourly alarm rate during periods of guideline-concordant intermittent measurement was 0.5 alarms per hour (IQR, 0.1-0.8). Reducing guideline-discordant monitoring in bronchiolitis patients would reduce nurse alarm burden.

A combined computational-experimental approach to define the structural origin of antibody recognition of sialyl-Tn, a tumor-associated carbohydrate antigen.

Anti-carbohydrate monoclonal antibodies (mAbs) hold great promise as cancer therapeutics and diagnostics. However, their specificity can be mixed, and detailed characterization is problematic, because antibody-glycan complexes are challenging to crystallize. Here, we developed a generalizable approach employing high-throughput techniques for characterizing the structure and specificity of such mAbs, and applied it to the mAb TKH2 developed against the tumor-associated carbohydrate antigen sialyl-Tn (STn). The mAb specificity was defined by apparent KD values determined by quantitative glycan microarray screening. Key residues in the antibody combining site were identified by site-directed mutagenesis, and the glycan-antigen contact surface was defined using saturation transfer difference NMR (STD-NMR). These features were then employed as metrics for selecting the optimal 3D-model of the antibody-glycan complex, out of thousands plausible options generated by automated docking and molecular dynamics simulation. STn-specificity was further validated by computationally screening of the selected antibody 3D-model against the human sialyl-Tn-glycome. This computational-experimental approach would allow rational design of potent antibodies targeting carbohydrates.

Applying Pose Clustering and MD Simulations To Eliminate False Positives in Molecular Docking.

In this work, we developed a computational protocol that employs multiple molecular docking experiments, followed by pose clustering, molecular dynamic simulations (10 ns), and energy rescoring to produce reliable 3D models of antibody-carbohydrate complexes. The protocol was applied to 10 antibody-carbohydrate co-complexes and three unliganded (apo) antibodies. Pose clustering significantly reduced the number of potential poses. For each system, 15 or fewer clusters out of 100 initial poses were generated and chosen for further analysis. Molecular dynamics (MD) simulations allowed the docked poses to either converge or disperse, and rescoring increased the likelihood that the best-ranked pose was an acceptable pose. This approach is amenable to automation and can be a valuable aid in determining the structure of antibody-carbohydrate complexes provided there is no major side chain rearrangement or backbone conformational change in the H3 loop of the CDR regions. Further, the basic protocol of docking a small ligand to a known binding site, clustering the results, and performing MD with a suitable force field is applicable to any protein ligand system.

Vina-Carb: Improving Glycosidic Angles during Carbohydrate Docking.

Molecular docking programs are primarily designed to align rigid, drug-like fragments into the binding sites of macromolecules and frequently display poor performance when applied to flexible carbohydrate molecules. A critical source of flexibility within an oligosaccharide is the glycosidic linkages. Recently, Carbohydrate Intrinsic (CHI) energy functions were reported that attempt to quantify the glycosidic torsion angle preferences. In the present work, the CHI-energy functions have been incorporated into the AutoDock Vina (ADV) scoring function, subsequently termed Vina-Carb (VC). Two user-adjustable parameters have been introduced, namely, a CHI- energy weight term (chi_coeff) that affects the magnitude of the CHI-energy penalty and a CHI-cutoff term (chi_cutoff) that negates CHI-energy penalties below a specified value. A data set consisting of 101 protein-carbohydrate complexes and 29 apoprotein structures was used in the development and testing of VC, including antibodies, lectins, and carbohydrate binding modules. Accounting for the intramolecular energies of the glycosidic linkages in the oligosaccharides during docking led VC to produce acceptable structures within the top five ranked poses in 74% of the systems tested, compared to a success rate of 55% for ADV. An enzyme system was employed in order to illustrate the potential application of VC to proteins that may distort glycosidic linkages of carbohydrate ligands upon binding. VC represents a significant step toward accurately predicting the structures of protein-carbohydrate complexes. Furthermore, the described approach is conceptually applicable to any class of ligands that populate well-defined conformational states.

Specificity of furanoside-protein recognition through antibody engineering and molecular modeling.

Recognition of furanosides (five-membered ring sugars) by proteins plays important roles in host-pathogen interactions. In comparison to their six-membered ring counterparts (pyranosides), detailed studies of the molecular motifs involved in the recognition of furanosides by proteins are scarce. Here the first in-depth molecular characterization of a furanoside-protein interaction system, between an antibody (CS-35) and cell wall polysaccharides of mycobacteria, including the organism responsible for tuberculosis is reported. The approach was centered on the generation of the single chain variable fragment of CS-35 and a rational library of its mutants. Investigating the interaction from various aspects revealed the structural motifs that govern the interaction, as well as the relative contribution of molecular forces involved in the recognition. The specificity of the recognition was shown to originate mainly from multiple CH-π interactions and, to a lesser degree, hydrogen bonds formed in critical distances and geometries.

BFMP: a method for discretizing and visualizing pyranose conformations.

We report a new classification method for pyranose ring conformations called Best-fit, Four-Membered Plane (BFMP), which describes pyranose ring conformations based on reference planes defined by four atoms. The method is able to characterize all asymmetrical and symmetrical shapes of a pyran ring, is readily automated, easy to interpret, and maps trivially to IUPAC definitions. It also provides a qualitative measurement of the distortion of the ring. Example applications include the analysis of data from crystal structures and molecular dynamics simulations.

Predicting the Origins of Anti-Blood Group Antibody Specificity: A Case Study of the ABO A- and B-Antigens.

The ABO blood group system is the most important blood type system in human transfusion medicine. Here, we explore the specificity of antibody recognition toward ABO blood group antigens using computational modeling and biolayer interferometry. Automated docking and molecular dynamics simulations were used to explore the origin of the specificity of an anti-blood group A antibody variable fragment (Fv AC1001). The analysis predicts a number of Fv-antigen interactions that contribute to affinity, including a hydrogen bond between a His(L49) and the carbonyl moiety of the GalNAc in antigen A. This interaction was consistent with the dependence of affinity on pH, as measured experimentally; at lower pH there is an increase in binding affinity. Binding energy calculations provide unique insight into the origin of interaction energies at a per-residue level in both the scFv and the trisaccharide antigen. The calculations indicate that while the antibody can accommodate both blood group A and B antigens in its combining site, the A antigen is preferred by 4 kcal/mol, consistent with the lack of binding observed for the B antigen.

Importance of ligand conformational energies in carbohydrate docking: Sorting the wheat from the chaff.

Docking algorithms that aim to be applicable to a broad range of ligands suffer reduced accuracy because they are unable to incorporate ligand-specific conformational energies. Here, we develop a set of Carbohydrate Intrinsic (CHI) energy functions that quantify the conformational properties of oligosaccharides, based on the values of their glycosidic torsion angles. The relative energies predicted by the CHI energy functions mirror the conformational distributions of glycosidic linkages determined from a survey of oligosaccharide-protein complexes in the protein data bank. Addition of CHI energies to the standard docking scores in Autodock 3, 4.2, and Vina consistently improves pose ranking of oligosaccharides docked to a set of anticarbohydrate antibodies. The CHI energy functions are also independent of docking algorithm, and with minor modifications, may be incorporated into both theoretical modeling methods, and experimental NMR or X-ray structure refinement programs.