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The purpose of this study was to identify racial and ethnic differences in patient-reported rates of treatment for chronic pain and ratings of pain-treatment effectiveness among veterans treated in Veterans Affairs (VA) facilities. This was a cross-sectional analysis of data from 255,522 veterans who participated in the VA Survey of the Healthcare Experiences of Patients (SHEP) in Fiscal Year 2005. Measures included demographics, the Veterans Rand Health Survey-12, a single item inquiring if the patient received treatment for chronic pain in the VA within the prior 12 months, and a single item asking the patient to rate the effectiveness of chronic pain care. In a logistic model adjusting for demographics, pain interference, and mental health status, male and female veterans who were Hispanic (OR 1.39 [95%CI 1.26-1.53] and OR 1.57 [1.02-2.43], respectively) or non Hispanic black (OR 1.43 [1.33-1.54] and OR 1.35 [1.02-1.78], respectively) were more likely to report receiving treatment for chronic pain in the prior 12 months compared to non Hispanic white veterans. Among veterans who reported receiving treatment for chronic pain, non Hispanic black men were less likely to rate pain-treatment effectiveness as very good or excellent, compared to non Hispanic white men (OR .809 [.720-.910]). PERSPECTIVE: In our study, Hispanic and non Hispanic black veterans reported receiving chronic pain treatment more frequently than white veterans. Among veterans reporting pain treatment, non Hispanic black men were somewhat less likely to report receiving highly effective treatment than white men. Further research is needed to understand the reasons for these differences and their potential clinical implications. [ABSTRACT FROM AUTHOR]

Collecting clean-caught voided urine samples is minimally invasive, but contamination occurs when urine passes through the nonsterile urethra and external genitalia. Discarding the initial urine stream may reduce these contaminants. This study hypothesized that using a midstream urine collection device would decrease bacterial and cellular contamination as compared with cleanly caught voided urine. This descriptive cross-sectional study collected urine from dogs using standard clean-caught (SCC), midstream collection device (MCD), and cystocentesis (CYS) techniques. Urinalysis and aerobic urine culture characteristics were recorded with each characteristic's prevalence described using percentages and 95% confidence intervals for each mode of collection. Positive urine culture prevalence did not differ between SCC and MCD (adjusted P value = .099); however, CYS had a lower prevalence compared with SCC and MCD (adjusted P values of <.001 [CYS versus SCC] and 0.009 [CYS versus MCD]). For other variables, there was no difference in prevalence when comparing SCC with MCD. There was no identified advantage to collecting urine using an MCD as compared with the SCC technique. Either option is a suitable alternative when CYS is not practical; however, clinicians need to interpret results cautiously because bacterial contamination is more common as compared with CYS., (© 2024 by American Animal Hospital Association.)

Objective: To examine the effect of client presence on healing rates of spontaneous chronic corneal epithelial defect (SCCEDs) following debridement and anterior stromal puncture (ASP)., Animals Studied: Sixty-eight client-owned dogs., Procedures: Dogs presenting prior to the COVID-19 shutdown were assigned to the C group (client in the room, 31/68), while dogs presenting after were assigned to group NC (no client in the room, 37/68). Inclusion criteria were retention of fluorescein, non-adherent epithelium, persistence for at least 1 week, and recheck within 1 month. Exclusion criteria were concurrent ocular disorders and endocrinopathies. Success was defined as negative fluorescein retention at first recheck. t-Tests, rank-sum tests, and chi-squared or Fisher's exact tests were used to compare findings between groups. Logistic regression was used to determine whether odds of success at first recheck differed between groups or were modified by other characteristics., Results: Dogs in the NC group were older (9.9 vs. 8.7 years, p = .014) and had more bandage contact lenses (BCLs) placed (65% vs. 29%, p = .003). There were no other significant differences between groups. BCL placement was associated with significantly greater odds of healing by first recheck (OR = 4.00, 95% CI: 0.63-11.2; p = .008). The NC group initially had 2.5 times greater odds of healing than the C group; after adjusting for BCL placement, the association between client location and healing weakened (aOR = 1.80, 95% CI: 0.63-5.13; p = .277)., Conclusions: Healing was marginally associated with not having the client in the room, likely due to increased BCL use. BCL application improves SCCED healing rates following debridement/ASP., (© 2024 The Author(s). Veterinary Ophthalmology published by Wiley Periodicals LLC on behalf of American College of Veterinary Ophthalmologists.)

Macrophages are primary cells of the innate immune system that mediate tumor progression. However, the motile behavior of macrophages and interactions with tumor cells are not well understood. Here, we exploit the optical transparency of larval zebrafish and perform real-time imaging of macrophage-melanoma interactions. We found that macrophages are highly motile in the tumor microenvironment. Macrophages extend dynamic projections between tumor cells that precede invasive melanoma migration. Modulating macrophage motility with a dominant inhibitory mutation in Rac2 inhibits recruitment to the tumor and impairs tumor invasion. However, a hyperactivating mutation in Rac2 does not affect macrophage recruitment but limits macrophage projections into the melanoma mass and reduces invasive melanoma cell migration. Taken together, these findings reveal a role for Rac2-mediated macrophage protrusive motility in melanoma invasion., (© 2024 Ramakrishnan et al.)

Epithelial damage leads to early reactive oxygen species (ROS) signaling, which regulates sensory neuron regeneration and tissue repair. How the initial type of tissue injury influences early damage signaling and regenerative growth of sensory axons remains unclear. Previously we reported that thermal injury triggers distinct early tissue responses in larval zebrafish. Here, we found that thermal but not mechanical injury impairs sensory axon regeneration and function. Real-time imaging revealed an immediate tissue response to thermal injury characterized by the rapid Arp2/3-dependent migration of keratinocytes, which was associated with tissue scale ROS production and sustained sensory axon damage. Isotonic treatment was sufficient to limit keratinocyte movement, spatially restrict ROS production, and rescue sensory neuron function. These results suggest that early keratinocyte dynamics regulate the spatial and temporal pattern of long-term signaling in the wound microenvironment during tissue repair., Competing Interests: AF, AH, ML, AH No competing interests declared, (© 2024, Fister, Horn et al.)

Objectives: Sjögren disease (SjD) diagnosis often requires either positive anti-SSA antibodies or a labial salivary gland biopsy with a positive focus score (FS). One-third of patients with SjD lack anti-SSA antibodies (SSA-), requiring a positive FS for diagnosis. Our objective was to identify novel autoantibodies to diagnose 'seronegative' SjD., Methods: IgG binding to a high-density whole human peptidome array was quantified using sera from SSA- SjD cases and matched non-autoimmune controls. We identified the highest bound peptides using empirical Bayesian statistical filters, which we confirmed in an independent cohort comprising SSA- SjD (n=76), sicca-controls without autoimmunity (n=75) and autoimmune-feature controls (SjD features but not meeting SjD criteria; n=41). In this external validation, we used non-parametric methods for binding abundance and controlled false discovery rate in group comparisons. For predictive modelling, we used logistic regression, model selection methods and cross-validation to identify clinical and peptide variables that predict SSA- SjD and FS positivity., Results: IgG against a peptide from D-aminoacyl-tRNA deacylase (DTD2) bound more in SSA- SjD than sicca-controls (p=0.004) and combined controls (sicca-controls and autoimmune-feature controls combined; p=0.003). IgG against peptides from retroelement silencing factor-1 and DTD2 were bound more in FS-positive than FS-negative participants (p=0.010; p=0.012). A predictive model incorporating clinical variables showed good discrimination between SjD versus control (area under the curve (AUC) 74%) and between FS-positive versus FS-negative (AUC 72%)., Conclusion: We present novel autoantibodies in SSA- SjD that have good predictive value for SSA- SjD and FS positivity., Competing Interests: Competing interests: SMcC declares consulting for Novartis, Horizon, Target RWE, Otsuka/Visterra, Kiniksa, BMS and iCELL., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: Oxygen saturation profiles generated by pulse oximetry are used as a clinical tool in the neonatal intensive care unit (NICU). There is limited evidence on normal oxygen saturation profile values in term infants. This study aimed to determine oxygen saturation profiles over an 8-hour monitoring period among healthy term neonates between 24 and 48 hours after birth., Study Design: A prospective cohort study of healthy term neonates born at 37 to 41 weeks of gestation. Preductal oxygen saturations were continuously monitored for an 8-hour period between 24 and 48 hours of life using pulse oximetry. Oxygen profile histograms were recorded for analysis. The average percent oxygen saturation (SpO 2 ) was measured over the entire study duration for each neonate and was characterized as the fraction of time of their SpO 2 reading was in each of five intervals: ≤80, 81 to 84, 85 to 89, 90 to 94, and 95 to 100%., Results: Seventy-five neonates were included in the study. Median SpO 2 was 95.4%. Percentage time spent in each of the five SpO 2 intervals was as follows: 0.07 (≤80), 0.15 (81-84), 0.88 (85-89), 26.9 (90-94), and 67.3% (95-100%). Eighteen infants (24%) spent the highest percentage of time in SpO 2 of 90 to 94%., Conclusion: This study provides reference ranges for oxygen profiles in healthy term neonates during 24 to 48 hours of life. Nearly one-quarter of newborns spent the highest percentage of time in SpO 2 of 90 to 94%. This data is important when interpreting oxygen saturation profiles of term neonates admitted to the NICU., Key Points: · This study provide reference ranges for oxygen profiles in healthy term neonates during 24 to 48 hours.. · Median SpO2 was 95.4%.. · Nearly one quarter of newborns spent the highest percentage of time in SpO2 of 90 to 94%.., Competing Interests: None declared., (Thieme. All rights reserved.)

Objective: The aim of this study was to describe clinical outcomes of bridled nasogastric tube (NGT) program implementation for infants requiring assisted home feeding (AHF) to discharge from the neonatal intensive care unit (NICU)., Study Design: This was a descriptive prospective analysis of a pilot cohort of infants after implementation of a bridled NGT AHF program to facilitate discharge from level III and IV NICUs from March 2019 to October 2020., Results: Of 29 attempts in infants, 22 infants were discharged with bridled NGTs over 18 months. Bridle placement was unsuccessful in three patients, and four bridles were removed before discharge. Bridle use ranged from 7 to 125 days, with a median duration of 37 days. Dislodgement rate was 0.69 per 100 days. Seventeen infants (77%) achieved full oral feeds, while five (23%) discharged with bridled NGTs later converted to gastrostomy tubes., Conclusion: Implementation of a bridled NGT program is feasible for level III and IV NICUs to facilitate discharging infants who require feeding support to transition home., Key Points: · Bridled NGT use after NICU is typically 1 month.. · Infants have low bridle NGT dislodgement.. · Most bridled NGT NICU grads attain full oral feeds.., Competing Interests: None declared., (Thieme. All rights reserved.)

Objective:  Noninvasive respiratory support (NRS) failure is common in preterm infants with respiratory distress syndrome (RDS). We evaluated the utility of respiratory severity score (RSS) and oxygen saturation index (OSI) during the first 2 hours of life (HOL) as predictors for NRS failure in moderate preterm infants., Study Design:  We conducted a retrospective cohort study of infants born between 28 0/7 and 33 6/7 weeks with RDS. Univariate and multivariable logistic regression analyses were used to assess whether the RSS and OSI summary measures were associated with NRS failure., Results:  A total of 282 infants were included in the study. Median gestational age and birth weights were 32 weeks and 1.7 kg, respectively. Fifty-eight infants (21%) developed NRS failure at the median age of 10.5 hours. RSS and OSI summary measures in the first 2 HOL were associated with NRS failure within 72 HOL., Conclusion:  RSS and OSI during the first 2 HOL can predict NRS failure. Optimal RSS and OSI cutoffs for the prediction of NRS failure need to be determined in large cohort studies., Key Points: · Nearly one in five moderate preterm infants on NRS at 2 hours of life developed NRS failure.. · RSS and OSI during the first 2 HOL can predict NRS failure.. · Optimal RSS and OSI cutoffs for the prediction of NRS failure need to be determined.., Competing Interests: D.K. and S.G. serve as consultants for ONY Biotech. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Thieme. All rights reserved.)

Importance: Cellulitis is misdiagnosed in up to 30% of cases due to mimic conditions termed pseudocellulitis. The resulting overuse of antibiotics is a threat to patient safety and public health. Surface thermal imaging and the ALT-70 (asymmetry, leukocytosis, tachycardia, and age ≥70 years) prediction model have been proposed as tools to help differentiate cellulitis from pseudocellulitis., Objectives: To validate differences in skin surface temperatures between patients with cellulitis and patients with pseudocellulitis, assess the optimal temperature measure and cut point for differentiating cellulitis from pseudocellulitis, and compare the performance of skin surface temperature and the ALT-70 prediction model in differentiating cellulitis from pseudocellulitis., Design, Setting, and Participants: This prospective diagnostic validation study was conducted among patients who presented to the emergency department with acute dermatologic lower extremity symptoms from October 11, 2018, through March 11, 2020. Statistical analysis was performed from July 2020 to March 2021 with additional work conducted in September 2023., Main Outcomes and Measures: Temperature measures for affected and unaffected skin were obtained. Cellulitis vs pseudocellulitis was assessed by a 6-physician, independent consensus review. Differences in temperature measures were compared using the t test. Logistic regression was used to identify the temperature measure and associated cut point with the optimal performance for discriminating between cellulitis and pseudocellulitis. Diagnostic performance characteristics for the ALT-70 prediction model, surface skin temperature, and both combined were also assessed., Results: The final sample included 204 participants (mean [SD] age, 56.6 [16.5] years; 121 men [59.3%]), 92 (45.1%) of whom had a consensus diagnosis of cellulitis. There were statistically significant differences in all skin surface temperature measures (mean temperature, maximum temperature, and gradients) between cellulitis and pseudocellulitis. The maximum temperature of the affected limb for patients with cellulitis was 33.2 °C compared with 31.2 °C for those with pseudocellulitis (difference, 2.0 °C [95% CI, 1.3-2.7 °C]; P < .001). The maximum temperature was the optimal temperature measure with a cut point of 31.2 °C in the affected skin, yielding a mean (SD) negative predictive value of 93.5% (4.7%) and a sensitivity of 96.8% (2.3%). The sensitivity of all 3 measures remained above 90%, while specificity varied considerably (ALT-70, 22.0% [95% CI, 15.8%-28.1%]; maximum temperature of the affected limb, 38.4% [95% CI, 31.7%-45.1%]; combination measure, 53.9% [95% CI, 46.5%-61.2%])., Conclusions and Relevance: In this large diagnostic validation study, significant differences in skin surface temperature measures were observed between cases of cellulitis and cases of pseudocellulitis. Thermal imaging and the ALT-70 both demonstrated high sensitivity, but specificity was improved by combining the 2 measures. These findings support the potential of thermal imaging, alone or in combination with the ALT-70 prediction model, as a diagnostic adjunct that may reduce overdiagnosis of cellulitis.

Objective: Preterm infants often develop failure of noninvasive respiratory support. These infants miss the advantages of early rescue surfactant therapy. In this study, we evaluate the utility of respiratory severity score (RSS) during the first 3 hours of life (HOL) as a predictor for failure of noninvasive respiratory support., Study Design: We conducted a post hoc analysis of infants between 23 and 40 weeks' gestational age who received usual care in the AERO-02 clinical trial. Univariate and multivariable logistic regression analysis were used to assess whether the RSS summary measures were associated with the odds of surfactant administration., Results: Study involved 146 infants. Sixty-four infants (45%) received surfactant within the first 72 hours. Administration of surfactant was associated with the mean RSS ( p  < 0.01) and the linear trend ( p  < 0.01)., Conclusion: We demonstrated that RSS during the first 3 HOL can predict failure of noninvasive respiratory support and need for late rescue surfactant administration. Optimal RSS cutoffs for early rescue surfactant therapy need to be determined in large cohort studies., Key Points: · Early recognition of infants at risk of failure of noninvasive ventilation is important to prevent complications.. · It is desirable to identify patients who would benefit from early rescue surfactant treatment.. · RSS in first 3 hours can be used as a predictor of failure of noninvasive respiratory support.., Competing Interests: S.O.G., P.F., and D.C.K. serve as consultants for ONY Biotech. P.F. is also a consultant for Fisher-Paykel and Enalare., (Thieme. All rights reserved.)

Background: Optimal CPAP strategy to prevent CPAP failure defined as need for endotracheal intubation is unknown., Objective: To evaluate the risk of CPAP failure in infants treated with high vs low CPAP strategy while receiving aerosolized calfactant in the AERO-02 clinical trial and AERO-03 expanded access program., Methods: Infants born between 29 0/7 to 36 6/7 weeks were included. Comparisons were made between low and high CPAP groups (Low, 4-7 cm H 2 O; High, 8-10 cm H 2 O)., Results: CPAP failure and pneumothorax were not different between the groups. Odds of CPAP failure were not different after adjustment for baseline characteristics (OR = 0.61; 95% CI: 0.29, 1.24)., Conclusion: We found no difference in CPAP failure among infants who received aerosolized calfactant that were treated with high vs low CPAP strategy. Efficacy of high CPAP strategy with aerosolized surfactant treatment needs to be evaluated in future studies., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Females who are incarcerated are disproportionately burdened by cancer, particularly cervical cancer. We measured the odds of cervical cancer compared with nonscreenable cancers for females who were incarcerated before diagnosis. By comparing a cancer for which screening and vaccination are available with cancers for which neither are available, we aimed to assess the relationship of incarceration with diseases for which preventive care mitigates risk. We created a novel data set combining cancer data from a large cancer center with incarceration data from the state department of corrections. We then estimated the odds of cervical cancer relative to nonscreenable cancers for those with and without a history of incarceration. Females with a history of incarceration had greater odds of being diagnosed with cervical cancer compared with nonscreenable cancers (odds ratio = 7.04; 95% confidence interval [CI]: 4.4-11.0) relative to those who had not been incarcerated. Adjusting for race and age, the odds of cervical cancer remained significantly greater for those with a history of incarceration (adjusted odds ratio = 3.86; 95% CI: 2.3-6.3). Our findings support the need for expanded cervical cancer screening and vaccination opportunities for incarcerated females and increased access to preventive health care after release.

(1) Background: Near-infrared spectroscopy (NIRS) is a noninvasive tool frequently used during cardiac surgery and postoperatively in the cardiac intensive care unit to monitor regional tissue oxygen saturation. A relationship between trends of intraoperative renal oxygenation and the risk of developing cardiac surgery-associated acute kidney injury (AKI) post-operatively has not yet been established in the neonatal population. The objective of this study is to evaluate the relationship of cerebral and renal oxygenation during cardiopulmonary bypass with cardiac surgery-associated AKI in the first 72 h post-operation in neonates < 30 days of age. (2) Methods: A prospective cohort study at a tertiary care children's hospital was performed. Renal and cerebral oxygenation measured were collected intraoperatively from neonates < 30 days of age who underwent cardiopulmonary bypass for the correction of congenital heart disease. AKI was defined accordance with the Kidney Disease: Improving Global Outcomes criteria modified for neonates. Variables were compared between groups. (3) Results: 32 neonates with 35 cardiopulmonary bypass cases were included. AKI was diagnosed in 60% of cases. Intra-operative renal oxygenation, both on- and off-bypass, did not differ among the three AKI groups ( p > 0.19). Renal oxygenation after coming off, but not during, cardiopulmonary bypass steadily decreased with increasing levels of AKI (Jonckheere's test, one-sided p = 0.024). (4) Conclusions: Renal oxygenation decreased in proportion to AKI severity after coming off, but not during, cardiopulmonary bypass.

Objective: To evaluate the relationship between regional renal saturation of oxygen (RrSO 2 ) changes and serum creatinine (SCr) during the first eight days of age for preterm neonates born < 32 weeks' gestational age., Design: Post-hoc analysis of multicenter prospectively measured neonatal RrSO 2 values collected during the first 8 days of age in neonates born at < 32 weeks' gestation. Acute kidney injury (AKI) was defined by the neonatal modified Kidney Disease: Improving Global Outcomes (KDIGO) criteria. Variables were compared between groups of neonates with and with AKI., Results: One hundred nine neonates were included and 561 SCr values were obtained. Eight participants developed AKI by SCr criteria. A 10-percentage point increase in mean %RrSO 2 was associated with a 40% decrease in risk of AKI (95%CI: 9.6-61%; p = 0.016)., Conclusions: Increases in mean %RrSO 2 in neonates born at < 32 weeks' GA were associated with a decreased risk of AKI. These findings support the design of further prospective trials utilizing RrSO 2 monitoring to evaluate new therapies or clinical protocols to prevent and treat neonatal AKI., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Purpose: Cancer detection rate (CDR), an important metric in the mammography screening audit, is designed to ensure adequate sensitivity. Most practices use biopsy results as the reference standard; however, commonly ascertainment of biopsy results is incomplete. We used simulation to determine the relationship between the cancer ascertainment rate of biopsy (AR-biopsy), CDR estimation, and associated error rates in classifying whether practices and radiologists meet the established ACR benchmark of 2.5 per 1,000., Materials and Methods: We simulated screening mammography volume, number of cancers detected, and CDR, using negative binomial and beta-binomial distributions, respectively. Simulations were performed at both the practice and radiologist level. Average CDR was based on linearly rescaling a published CDR by the AR-biopsy. CDR distributions were simulated for AR-biopsy between 5% and 100% in steps of five percentage points and were summarized with boxplots and smoothed histograms over the range of AR-biopsy, to quantify the proportion of practices and radiologists meeting the ACR benchmark at each level of AR-biopsy., Results: Decreasing AR-biopsy led to an increasing probability of categorizing CDR performance as being below the ACR benchmark. Our simulation predicts that at the practice level, an AR-biopsy of 65% categorizes 17.6% below the benchmark (compared to 1.6% at an AR-biopsy of 100%), and at the radiologist level, an AR-biopsy of 65% categorizes 34.7% as being below the benchmark (compared to 11.6% at an AR-biopsy of 100%)., Conclusions: Our simulation demonstrates that decreasing the AR-biopsy (in currently clinically relevant ranges) has the potential to artifactually lower the assessed CDR on both the practice and radiologist levels and may, in turn, increase the chance of erroneous categorization of underperformance per the ACR benchmark., (Copyright © 2023 American College of Radiology. Published by Elsevier Inc. All rights reserved.)

Objective: To compare the effectiveness of preoperative bupivacaine inferotemporal retrobulbar blocks to postoperative liposome-encapsulated bupivacaine (Nocita) line blocks for analgesia following enucleation., Animals: 39 client-owned dogs (40 eyes) presenting to the Ophthalmology Service for enucleation., Methods: Dogs were randomly assigned to receive either a preoperative inferotemporal retrobulbar block with 0.5% bupivacaine or a peri-incisional line block with liposome-encapsulated bupivacaine (Nocita) at closure. Patients underwent unilateral enucleation and were hospitalized for 24 hours after surgery. Pain scores were performed by a masked observer with the Glasgow Composite Measure Pain Scale and the University of Wisconsin Ocular Pain Scale at 0.25, 0.5, 1, 2, 4, 6, 8, and 24 hours following surgery. Intraoperative use of blood pressure and anesthetic support mediations as well as need for rescue pain control were recorded and compared between groups., Results: There was no significant difference in rescue rates between treatment groups. When comparing the use of medical intraoperative heart rate, blood pressure, or anesthetic plane support, there were no significant differences in use between groups., Clinical Relevance: Use of preoperative bupivacaine retrobulbar blocks and postoperative Nocita line blocks were equally effective at postoperative pain control with similarly low complication rates.

Background: Factor (F)IXa activity has been detected in human plasma and may impact thrombotic risk. Current FIXa activity assays are complex and cumbersome., Objectives: To develop a reproducible enzyme-linked immunosorbent assay (ELISA) using a novel monoclonal antibody that detects total FIXa in human plasma., Methods: A monoclonal antibody was raised against the new N-terminus exposed upon activation of FIX to FIXa by cleavage after R226. This antibody is specific for FIXa protease and does not recognize FIX zymogen or FIXα. The antibody was used to develop a FIXa-specific ELISA capable of quantifying total FIXa (free FIXa and FIXa-antithrombin complex) in human plasma. Total FIXa quantified using the ELISA was compared to that of FIXa-antithrombin quantified using modifications of a previously described ELISA., Results: The FIXa-specific ELISA was reproducible and quantified total FIXa in human plasma. Total FIXa levels correlated with FIXa-antithrombin levels., Conclusion: A monoclonal antibody was developed that specifically detects human FIXa protease. A FIXa-specific ELISA using the new antibody is capable of reproducibly measuring total FIXa in human plasma (both free FIXa and FIXa-antithrombin). This assay should facilitate the evaluation of total FIXa levels in a variety of clinical circumstances., (© 2024 The Author(s).)

Purpose: Chest x-ray (CXR) is the standard imaging used to evaluate children in acute respiratory distress and failure. Our objective was to compare the lung-imaging techniques of CXR and lung ultrasound (LUS) in the evaluation of children with acute respiratory failure (ARF) to quantify agreement and to determine which technique identified a higher frequency of pulmonary abnormalities., Methods: This was a secondary analysis of a prospective observational study evaluating the sensitivity and specificity of LUS in children with ARF from 12/2018 to 02/2020 completed at the University of Wisconsin-Madison (USA). Children > 37.0 weeks corrected gestational age and ≤ 18 years of age admitted to the PICU with ARF were evaluated with LUS. We compared CXR and LUS completed within 6 h of each other. Kappa statistics (k) adjusted for maximum attainable agreement (k/k max ) were used to quantify agreement between imaging techniques and descriptive statistics were used to describe the frequency of abnormalities., Results: Eighty-eight children had LUS completed, 32 with concomitant imaging completed within 6 h are included. There was fair agreement between LUS and CXR derived diagnoses with 58% agreement (k/k max  = 0.36). Evaluation of imaging patterns included: normal, 57% agreement (k = 0.032); interstitial pattern, 47% agreement (k = 0.003); and consolidation, 65% agreement (k = 0.29). CXR identified more imaging abnormalities than LUS., Conclusions: There is fair agreement between CXR and LUS-derived diagnoses in children with ARF. Given this, clinicians should consider the benefits and limitations of specific imaging modalities when evaluating children with ARF. Additional studies are necessary to further define the role of LUS in pediatric ARF given the small sample size of our study., (© 2023. Società Italiana di Ultrasonologia in Medicina e Biologia (SIUMB).)

In 2022, National Comprehensive Cancer Network updated the phrase of "complete circumferential peripheral and deep margin assessment (CCPDMA)" to "peripheral and deep en face margin assessment (PDEMA)," which was meant to create more consistency across all treatment modalities and provide clarity to the meaning of total margin evaluation. The aim of this project was to investigate the interpretation of PDEMA across pertinent specialties and to identify any existing knowledge gaps in hopes of improving clinical performance of institutional practice. An electronic survey was administered to medical professionals within the divisions of dermatology and otolaryngology retrieving demographic data and assessing respondents' knowledge on tissue processing techniques and PDEMA. Of the four knowledge-based assessment questions administered, dermatology respondents answered three questions with > 80% accuracy and one question with < 65% accuracy. Otolaryngology respondents answered one question with > 80% accuracy and three with < 65% accuracy. Both groups answered the knowledge-based question evaluating the concept of "what must be true for Mohs or PDEMA to have value" with under 65% accuracy. When comparing dermatology and otolaryngology respondents, only one question which evaluated the proper methods to "achieve processing of the epidermal edge and the base of the tumor along a single plane in the lab" significantly differed between groups, with a percentage correct of 96% for dermatologists compared to 54% for otolaryngologists (p < 0.001). Results were found to be similar when resident physicians were removed from analysis. The overall percent correct for knowledge-based questions was shifted higher for dermatologists compared to otolaryngologists (p = 0.014). This trend was also redemonstrated when analyzing the data excluding residents (p = 0.053)., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Vitamin C levels are known rapidly decrease in adult critical illness. Vitamin C scavenges free radicals, provides critical protection of the endothelial barrier, and improves endothelial responsiveness to catecholamines. Children with congenital heart disease and undergoing cardiac surgery might be at increased risk for low circulating vitamin C levels. A prospective single-center observational study investigated perioperative changes in vitamin C levels in critically ill Children who underwent congenital heart surgery using CPB. Vitamin C serum levels were collected preoperatively and postoperatively (upon admission to the ICU, 24 and 72 h). Linear mixed-effect model was used to estimate mean circulating concentration of vitamin C and to estimate changes in concentration over time. Primary outcome was change in circulating levels of vitamin C before and after CPB. Secondary outcomes were hospital length of stay (LOS), acute kidney injury (AKI), and illness severity. Forty-one patients with a median age of 4.5 [interquartile range (IQR) 2.6-65.6] months at the time of surgery were consented and enrolled. Median CPB duration was 130 [90-175] minutes, and hospital LOS was 9.1 [5.2-19] days. Mean vitamin C levels (μmol/L) before CPB, at PICU admission, 24 h, and 72 h were 82.0 (95% CI 73.4-90.7), 53.4 (95% CI 44.6,62.0), 55.1 (95% CI 46.3,63.8), and 59.2 (95% CI 50.3,68.1), respectively. Upon postoperative admission to the PICU, vitamin C levels decreased by 28.7 (95% CI 20.6-36.8; p < 0.001) μmol/L, whereas levels at 24 and 72 h recovered and did not differ substantially from concentrations reported upon PICU admission (p > 0.15). Changes in vitamin C concentration were not associated with CPB time, STAT mortality category, age, or PIM3. Three patients had post-CPB hypovitaminosis C or vitamin C deficiency. Reduction in vitamin C levels was not associated with hospital LOS (p = 0.673). A 25 μmol/L decrease in vitamin C levels upon PICU admission was associated with developing AKI (aOR = 3.65; 95% CI 1.01-18.0, p = 0.049). Pediatric patients undergoing cardiac surgery with CPB showed decreased vitamin C levels during the immediate postoperative period. Effects of hypovitaminosis C and vitamin C deficiency in this population remain unclear., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: The aerosolized calfactant decreased the need for intubation in neonates with respiratory distress syndrome (AERO-02 trial)., Objective: To determine the oxygenation response to aerosolized calfactant among infants born 28 0/7-36 6/7 weeks with RDS in the AERO-02 trial., Methods: Trends in hourly fraction of oxygen (FiO 2 ), mean airway pressure (MAP) and respiratory severity score (RSS) were compared between the aerosolized calfactant (AC) and usual care (UC) groups from time of randomization for 72 h., Results: A total of 353 subjects were included in the study. FiO 2 , MAP, and RSS were lower in the UC group. FiO 2 decrease was seen after the first aerosolized calfactant dose., Conclusion: FiO 2 , MAP, and RSS were lower in the UC group. This is likely due to early and higher rate of liquid surfactant administration in the UC group. Decrease in FiO 2 was noted in the AC group after the first aerosolization., (© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Competing Interests: None disclosed.

Objective: This retrospective study aimed to measure rabbit laryngotracheal dimensions at different locations on computed tomography (CT), assess the relationship of these measurements with rabbit body weight, determine the most common narrowest measurement and assess its relationship with endotracheal tube (ETT) size and body weight., Animals: 66 adult domestic rabbits (Oryctolagus cuniculus) of different breeds and body weights., Procedures: CT laryngotracheal luminal height, width, and cross-sectional area measurements were made at the rostral thyroid cartilage at the level of the arytenoids, caudal thyroid cartilage/rostral cricoid cartilage, caudal cricoid cartilage/cranial trachea, and trachea at the level of the fifth cervical vertebra., Results: The data for every measurement of luminal airway dimensions revealed robust positive associations with body weight (P < .001). The narrowest laryngotracheal measurement was the width at the level of the caudal thyroid cartilage/rostral cricoid cartilage, and the smallest cross-sectional area was at the rostral thyroid cartilage at the level of the arytenoids. There was a strong association between body weight and the likelihood of appropriate ETT fit. To have at least an 80% chance of appropriate ETT fit with a 2.0, 2.5, and 3.0 mm ETT, the rabbits' weight predicted by the model (lower 95% confidence limit) were at least 2.99 (2.72) kg, 5.24 (4.65) kg, and 5.80 (5.21) kg, respectively., Clinical Relevance: The laryngotracheal lumen was narrowest at the level of the caudal thyroid cartilage in rabbits, which indicates this location may be the limiting factor in determining ETT size in rabbits.

Introduction: Continuous aerosolized β 2 agonist, namely albuterol, is the most commonly used therapy for critical asthma. Benzalkonium chloride is a preservative present in some formulations of aerosolized albuterol solutions that can induce bronchospasm. Recent studies have shown that inhalation of albuterol containing benzalkonium chloride might induce unintended bronchoconstriction and poor outcomes. This study aimed to investigate whether using albuterol solutions containing benzalkonium chloride results in prolonged hospital length of stay (LOS)., Methods: This was a retrospective cohort study of pediatric subjects admitted to the pediatric ICU (PICU) and treated with continuous albuterol. Data were collected and compared before and after a change to benzalkonium chloride-containing solutions. Subjects who were treated with preservative-free solutions were used as control. The primary outcome was PICU and hospital LOS; secondary outcomes included the duration of continuous albuterol and use of adjunctive therapies., Results: A total of 266 admissions were included in the study. One hundred forty subjects (52.6%) were exposed to benzalkonium chloride. Median age and severity of illness scoring were similar between groups. The initial dose of continuous albuterol was significantly higher in the benzalkonium chloride group (median 15 interquartile range [IQR] 10-20 mg/h) compared to the preservative-free group (median 10 IQR 10-20 mg/h) ( P < .001). PICU LOS was longer for the preservative-free group, 2.5 (IQR 1.4-4.6) d vs 1.8 (IQR 1.1-2.9) d for benzalkonium chloride group ( P = .002). There was no significant difference in duration of continuous albuterol therapy ( P = .16) or need for adjunctive respiratory support (heliox [ P = .32], noninvasive ventilation [ P = .81], and invasive mechanical ventilation [ P = .57])., Conclusions: In contrast to published literature showing that benzalkonium chloride may be associated with a longer duration of continuous albuterol nebulization and hospital LOS, our study demonstrated that benzalkonium chloride-containing albuterol is safe for continuous nebulization in critically ill children and not associated with worse outcomes., Competing Interests: Dr Al-Subu discloses a relationship with Edwards Lifesciences LLC. The remaining authors have disclosed no conflicts of interest., (Copyright © 2023 by Daedalus Enterprises.)

Objective: To characterize the incidence, contributing risk factors, and healing characteristics of immediate postoperative corneal erosions (IPCE) in dogs undergoing routine phacoemulsification., Animals Studied: Medical records of 313 canine eyes (159 dogs) undergoing routine phacoemulsification surgery., Procedures: Medical records of dogs undergoing planned cataract surgery at UW Veterinary Care were retrospectively reviewed. Patient-related variables including age, skull conformation, diabetes status, and cataract stage at the time of surgery were recorded. Intraoperative variables per eye were also recorded including surgical technique, surgeon expertise level, average phacoemulsification power, and phacoemulsification time. Diagnosis of IPCE ≤ 24 h after completion of surgery and time to IPCE healing were recorded where follow-up data were available., Results: Immediate postoperative corneal erosions were observed in 48/313 (15.3%) operated eyes. The presence of diabetes mellitus or brachycephalic skull conformation, preoperative Schirmer tear test (STT) value, surgical technique and surgeon experience level, phacoemulsification time, and absolute phacoemulsification time were not statistically significant risk factors for IPCE. Average phacoemulsification power was associated with IPCE (RR 1.52, p = .001). Time to IPCE healing was similar in diabetic and non-diabetic dogs (median [IQR] 8 [6-11] days and 8 [6-15] days, respectively). Diabetes mellitus, brachycephaly, and phacoemulsification parameters were not associated with IPCE healing at 7 or 14 days postoperatively., Conclusions: Higher average phacoemulsification power may be associated with the development of IPCE in canine eyes. The presence of diabetes mellitus or brachycephaly are not risk factors for the development of IPCE, nor are they factors that influence IPCE healing., (© 2022 The Authors. Veterinary Ophthalmology published by Wiley Periodicals LLC on behalf of American College of Veterinary Ophthalmologists.)

Amish and Mennonite (Plain) communities have increased prevalence of many recessively inherited disorders due to founder variants that can be identified using next-generation sequencing (NGS). We assessed newborn screening (NBS) utilization, prior genetic testing, and perceptions of genetic testing among Wisconsin Plain communities to guide implementation and utilization of a population-specific NGS gene panel testing. A mailed paper survey (N = 959) of demographics, NBS utilization, prior genetic testing, and preferences for categorical genetic disorder and defined clinical context testing was developed. Overall response rate was 39% (N = 378; 183 Amish, 193 Mennonite; 2 not Amish/Mennonite). Mennonites were more likely to respond in favor of carrier screening for metabolic disorders and other surgical conditions and less likely to respond in favor of asymptomatic testing for neurologic disorders and lethal disorders compared to Amish. Reported utilization of NBS was positively associated with stated interest in genetic testing for an asymptomatic child. Reported prior genetic testing was positively associated with stated interest in carrier screening and negatively associated with testing a symptomatic child. Although Plain community members share many common outward characteristics, our survey responses suggest diversity in their views of genetic testing and support laboratory methods that can be flexible to varied needs of individuals., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: An institution's tobramycin pharmacokinetics (PK) database was reviewed to evaluate the efficacy and safety of empiric tobramycin dosing and monitoring strategies used in pediatric patients with cystic fibrosis (CF). The relationship between patient age and tobramycin dosing needed to achieve the area under the curve (AUC) goal was investigated., Methods: Retrospective chart review was performed for patients who received tobramycin during a CF exacerbation from 2009 to 2019 who received PK monitoring by pediatric pharmacists. Tobramycin dosing needed to achieve an AUC of 100 mg·hr/L was calculated for each patient. Serum creatinine and concomitant nephrotoxin use were collected as surrogate nephrotoxicity endpoints to evaluate safety., Results: Goal AUC (100 ± 15 mg·hr/L) was achieved based on initial or repeat PK calculations in 43.5% (95% CI, 37.7-49.3) of 85 unique patients across 326 encounters. Patients with calculated recommended doses of 9.5 to 11.9 mg/kg every 24 hours empirically achieved goal AUC in 77% (78/101) of encounters. The odds of achieving goal AUC were 56% higher for children aged 10 vs 5 years (OR = 1.56; 95% CI, 1.04-2.34; p = 0.033) and 32% higher for children aged 15 vs 10 years (OR = 1.32; 95% CI, 1.07-1.61; p = 0.008). Overall rates of acute kidney injury and concomitant nephrotoxin use were 10.8% (95% CI, 6.2-15.5) and 80.7% (95% CI, 74.3-87.1), respectively., Conclusions: Desired AUC was achieved by 43.5% of pediatric patients with CF using tobramycin 10 mg/kg every 24 hours. Older patient age was associated with higher initial AUC attainment and fewer dose modifications. Younger children may require higher weight-based dosing to meet AUC goals., Competing Interests: Disclosures. The authors declare no conflicts. The authors had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis., (Copyright. Pediatric Pharmacy Association. All rights reserved. For permissions, email: membership@pediatricpharmacy.org 2023.)

Purpose: To describe point-of-care lung ultrasound (POC-LUS) artifact findings in children admitted to the pediatric intensive care unit (PICU) for acute respiratory failure (ARF)., Methods: This is a secondary analysis of a prospective observational study completed in a 21-bed PICU. Children > 37 weeks gestational age and ≤ 18 years were enrolled from December 2018 to February 2020. POC-LUS was completed and interpreted by separate physicians blinded to all clinical information. POC-LUS was evaluated for the presence of lung sliding, pleural line characteristics, ultrasound artifacts, and the ultrasound diagnosis., Results: Eighty-seven subjects were included. A-lines were the most frequent artifact, occurring in 58% of lung zones (163/281) in those with bronchiolitis, 39% of lung zones (64/164) in those with pneumonia, and 81% of lung zones (48/59) in those with status asthmaticus. Sub-pleural consolidation was second most common, occurring in 28% (80/281), 30% (50/164), and 12% (7/59) of those with bronchiolitis, pneumonia, and status asthmaticus, respectively. The pattern a priori defined as bronchiolitis, pneumonia, and status asthmaticus was demonstrated in 31% (15/48), 10% (3/29), and 40% (4/10) of subjects with bronchiolitis, pneumonia, and status asthmaticus, respectively., Conclusion: We found significant heterogeneity and overlap of POC-LUS artifacts across the most common etiologies of ARF in children admitted to the PICU. We have described the POC-LUS artifact findings in pediatric ARF to support clinicians using POC-LUS and to guide future pediatric POC-LUS studies. Determining the optimal role of POC-LUS as an adjunct in the care of pediatric patients requires further study., (© 2022. Società Italiana di Ultrasonologia in Medicina e Biologia (SIUMB).)

Introduction/Objective: Indomethacin is an effective tocolytic to prevent extremely preterm birth. Prior studies have associated antenatal indomethacin exposure with adverse preterm neonatal intestinal and neurological outcomes. Indomethacin is a nephrotoxic medication that may also affect preterm neonatal kidneys. We sought to evaluate the effect of antenatal indomethacin on extremely preterm neonatal kidney function and acute kidney injury (AKI) in the first week of age. Methods: A retrospective cohort study was conducted on neonates born < 29 weeks at a level III neonatal intensive care unit (NICU) from January 2018-April 2019. Serum creatinine (sCr) values and urine output (UOP) in the first seven days of age and the neonate's peak serum creatinine within the first 30 days were evaluated. Neonatal AKI was defined by the modified neonatal Kidney Disease Improving Global Outcomes (KDIGO) definition including urine output. Results: 17 of the 55 neonates meeting criteria for this study were exposed to indomethacin. The average gestational age at birth was similar between study groups. Maternal preeclampsia was more common among women who did not receive indomethacin ( p  = 0.021). Indomethacin exposed neonates received more gentamicin ( p  = 0.024). Overall, staging of the neonatal AKI did not differ significantly between the study groups, regardless of how it was quantified (sCr or UOP) or the duration of time in which the injury developed (7 days or 30 days). Separate analysis of sCr and UOP in the first seven days also failed to show any statistically significant differences between the two groups. Conclusion: In this small cohort study of extremely preterm neonates, those born to mothers treated with indomethacin did not have an increased incidence of AKI compared to neonates born to unexposed mothers. Although no statistically significant differences in UOP or sCr were found, they deserve further evaluation in adequately powered prospective clinical trials. Future prospective studies with long-term follow-up utilizing advanced biomarkers are needed to determine how antenatal indomethacin affects extremely preterm neonatal kidney function in the NICU, during childhood, and as adults.

Objective: To describe renal regional saturation of oxygen (RrSO 2 ) values during the first week of life for preterm neonates born at <32 weeks gestational age (GA)., Methods: RrSO 2 values recorded over the first week of life using near-infrared spectroscopy were retrospectively analyzed in this two-center cohort study of preterm infants without known congenital anomalies of the kidney., Results: A cohort of 109 neonates with a median GA of 26.9 weeks and a median of 120 (IQR: 87-141) hours of continuous RrSO 2 monitoring were included. Separately fitted trends in RrSO 2 did not differ (p = 0.52) between sites and demonstrated a consistent decrease in RrSO 2 by 20 points (95% CI: 9.6-30.1) during the first 60 h of life, followed by a stabilization of RrSO 2 thereafter. RrSO 2 baseline trends increased by 2.1 (95% CI: 0.8-3.3) percentage points for each additional week GA between 24 and 32 weeks GA., Conclusions: Despite differences in adjusted RrSO 2 values between sites, profiles over time are consistent, allowing for the determination of RrSO 2 trajectories in preterm infants. This expected pattern of RrSO 2 changes in the first week may help guide future investigations and interventions to identify and reduce kidney injury in the preterm neonate., Impact: Renal regional saturation of oxygen (RrSO 2 ) slowly decreases during the first 60 h of age in <32-week preterm neonates. While site differences were identified with respect to absolute values, RrSO 2 trends from two different centers were not different. Lower gestational age neonates have lower RrSO 2 levels during the first week., (© 2022. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)

Importance: Suicide is a significant public health burden in the United States. There is little understanding how policies regarding gun purchasing affects suicide rates. Wisconsin state legislature rescinded a 48-hour waiting period for handgun purchases, which took effect in June 2015., Objective: To determine whether firearm-related suicide increased with the repeal of the 48-hour waiting period for handgun purchases in 2015., Method: We obtained data through the Wisconsin Department of Health Services via the Wisconsin Interactive Statistics on Health Query System. Suicide rates were compared by Comparative Mortality Figures (CMF)., Results: We reviewed all suicides in Wisconsin between 2012-2014 and 2016-2018. The rate ratios ( R ) and second generation P values (p δ ) comparing deaths between 2012-2014 and 2016-2018 indicate significant increases in firearm-related suicide among people of color ( R  = 1.927; p δ = 0.0) and among Wisconsinites residing in urban counties ( R  = 1.379, p δ = 0.0). There was no significant increase in non-firearm-related suicide ( R  = 1.117, p δ = 0.092), nor in firearm-related suicide among White non-Hispanics ( R  = 1.107, p δ = 0.164) or Wisconsinites residing in rural counties ( R  = 1.085, p δ = 0.500)., Conclusion: Our findings suggest that the repeal of the 48-hour waiting period on handgun purchases in 2015 is correlated with the increase of firearm-related suicides among Wisconsin residents of color and Wisconsinites residing in urban counties.Key Messages:Firearm policies are associated with changes in suicide rates.

Background: Since 2018, the Centers for Medicare & Medicaid Services (CMS) guidelines have allowed teaching physicians to bill for evaluation and management services based on medical student documentation. Limited previous data suggest that medical student documentation suffers from a high rate of downcoding relative to faculty documentation. We sought to compare the coding outcomes of documentation performed by medical students, and not edited by faculty, with documentation edited and submitted by faculty., Methods: A total of 104 randomly selected notes from real patient encounters written by senior medical students were compared to the revised notes submitted by faculty. The note pairs were then split and reviewed by blinded professional coders and assigned level of service (LoS) codes 1-5 (corresponding to E&M CPT codes 99281-99285)., Results: We found that the LoS agreement between student and faculty note versions was 63%, with 23% of all student notes receiving lower LoS compared to faculty notes (downcoded). This was found to be similar to baseline variability in professional coder LoS designations., Conclusions: Notes from medical students who have completed a focused documentation curriculum have less LoS downcoding than in previous reports., Competing Interests: The authors have no potential conflicts to disclose., (© 2022 The Authors. AEM Education and Training published by Wiley Periodicals LLC on behalf of Society for Academic Emergency Medicine.)

Objectives: Compare prevalence of infusion reaction (IR) between infliximab (IFX) and infliximab biosimilar (IFX-abda) at standard and rapid rates and measure the impact on health care cost in children with inflammatory bowel disease (IBD)., Methods: Records of subjects receiving IFX and IFX-abda were reviewed over a 21-month period. Demographics and IRs were recorded. Cost analysis utilized average wholesale pricing, infusion duration, nursing time, and infusion center throughput., Results: Fifty-six subjects received 498 infusions. Sixteen subjects received both IFX and IFX-abda. Thirteen IRs occurred for an overall prevalence of 2.6%. One outlier subject accounted for 8 of 13 (62%) of IRs. Data were analyzed with and without the outlier. Standard rate infusion of both IFX and IFX-abda was associated with increased risk of IR compared with rapid rate but only reached significance for IFX when calculated with the outlier removed. Risk of IR was not statistically significant between IFX and IFX-abda for both standard and rapid rates. IFX-abda saved an average of $2,611 per infusion. Rapid infusion saved 70 minutes of infusion time, 20 minutes of estimated nursing time per infusion, and decreased infusion center appointment length by as much as 2 hours per infusion., Conclusions: Rapid IFX-abda appears safe without increased IRs and decreases cost., Competing Interests: The authors report no conflicts of interest., (Copyright © 2022 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Background: Pediatric sedation is a clinical activity with potential for serious but rare airway adverse events, particularly laryngospasm. Anticholinergic drugs, atropine and glycopyrrolate, are frequently used with the intention to improve sedation safety by virtue of their antisialagogue effects., Aims: The objective of this study is to describe the current practice of anticholinergic use in pediatric sedation and to compare the frequency of serious sedation-related adverse events in patients who received anticholinergics to those who did not., Methods: We examined prospectively collected data from the Pediatric Sedation Research Consortium database. Patient characteristics, procedure type, sedation provider, sedatives, location of sedation, anticholinergic administered, adverse events, and airway interventions were reported. Propensity score matching and multivariable logistic regression were used to test whether any association exists between anticholinergic use and serious sedation-related adverse events., Results: Anticholinergics were administered in 7.1% (n = 18 707) of all cases (n = 263 883) reported between November 2011 and October 2017. When anticholinergics were used, atropine was used in 22% (n = 4111) and glycopyrrolate in 78.1% (n = 14 601) of sedations. Use of anticholinergics was more common in patients with well-described risk factors for airway adverse events: active/history of upper respiratory infection, history of reactive airway disease/asthma, and exposure to smoke. However, infants and ASA 3 patients were not associated with higher rate of anticholinergic use. Anticholinergic use was independently associated with an increase in the odds of serious adverse events, OR 1.8 (95% CI 1.6-2.1), especially airway adverse events., Conclusions: In this large Pediatric Sedation Research Consortium study, we found the use of anticholinergic adjuvants independently associated with greater odds of serious adverse events, especially airway adverse events, after adjusting for well-known sedation risk factors using propensity score matching and multivariate analysis., (© 2022 John Wiley & Sons Ltd.)

Objectives: Use of point-of-care lung ultrasound (POC-LUS) has increased significantly in pediatrics yet it remains under-studied in the pediatric intensive care unit (PICU). No studies explicitly evaluate the reliability of POC-LUS artifact interpretation among critically ill children with acute respiratory failure (ARF) in the PICU. We thus designed this study to determine the inter-rater reliability of POC-LUS interpretation in pediatric ARF among pediatric intensivists trained in POC-LUS and an expert intensivist., Methods: We compared the interpretation of lung sliding, pleural line characteristics, ultrasound artifacts, and POC-LUS diagnoses among pediatric intensivists and an expert intensivist in a cohort of children admitted to the PICU for ARF. Kappa statistics (k) adjusted for maximum attainable agreement (k/k max ) were used to quantify chance-correct agreement between the pediatric intensivist and expert physician., Results: We enrolled 88 patients, evaluating 3 zones per hemithorax (anterior, lateral, and posterior) for lung sliding, pleural line characteristics, ultrasound artifacts, and diagnosis. There was moderate agreement between the PICU intensivist and expert-derived diagnoses with 56% observed agreement (k/k max  = 0.46, 95% confidence interval [CI] 0.31-0.65). Agreement in identification of lung sliding (k = 0.19, 95% CI -0.17 to 0.56) and pleural line characteristics (k = 0.24, 95% CI 0.08-0.40) was slight and fair, respectively, while agreement in the interpretation of ultrasound artifacts ranged from moderate to substantial., Conclusions: Evidence supporting the evaluation of neonatal and adult patients with POC-LUS should not be extrapolated to critically ill pediatric patients. This study adds to the evidence supporting use of POC-LUS in the PICU by demonstrating moderate agreement between PICU intensivist and expert-derived POC-LUS diagnoses., (© 2021 American Institute of Ultrasound in Medicine.)

Background: Due to the COVID-19 pandemic, many genetics clinics across the country were prompted to integrate telephone visits and videoconferencing into their practice to promote the safety of patients and clinic staff members. Our study examined providers' perspectives on the utility and effectiveness of these telehealth-based clinic visits in response to the COVID-19 pandemic in Wisconsin., Methods: An anonymous Qualtrics survey was distributed via email in October 2020 to all members of the Wisconsin Genetic Systems Integration Hub and the Wisconsin Genetic Counselor Association. Current clinical genetic providers were eligible to participate in the survey. The survey assessed providers' experiences and perceptions toward utilizing telehealth in delivering clinical genetic services to their patients during the pandemic., Results: Forty-seven currently practicing clinical genetic counselors in Wisconsin either partially or fully completed the survey. Nearly all respondents somewhat (23%) or strongly (75%) wanted to incorporate telehealth in the future, primarily because of perceived improvements in clinic functioning. Patients with suboptimal telecommunications capacities were considered the most challenging aspect of telehealth, and better technology support was the most frequently cited strategy for addressing current telehealth limitations., Conclusion: Clinical genetic counselors in Wisconsin generally reported positive experiences integrating telehealth into their patient care during the COVID-19 pandemic. Many counselors see telehealth as a way to increase access to genetic services and, with better technology support from their intuitions, would support utilizing telehealth in their clinical practice., (Copyright© Board of Regents of the University of Wisconsin System and The Medical College of Wisconsin, Inc.)

Recurrently mutated genes in acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) have proven useful in risk stratification and clinical decision-making. Sequencing technologies that detect these genetic mutations are now widely available, though there is variability in the use of such data among hematologists. Molecular genetic sequencing trends were assessed in 470 patients presenting to a single institution with AML or MDS to determine how molecular data impacts clinical management of patients with myeloid malignancies. Patients with AML were more likely to have molecular genetic sequencing performed compared to patients with MDS, and clinicians were more likely to reference molecular data in decision-making for patients with AML. Furthermore, the presence of molecular data was associated with an increased odd of bone marrow transplantation (BMT). This study demonstrates the real-world application of molecular data in the management of myeloid malignancies and also highlights disparities in the use of such data based on diagnosis.

Objectives: To assess whether 21-deoxycortisol (21deoxy) can be used to predict 21-hydroxylase deficiency (21OHD) in newborns and to evaluate the influence of gestational age and the timing of collection on 21deoxy concentrations., Study Design: 17-hydroxyprogesterone (17OHP) and 21deoxy levels were measured in 906 newborn screening specimens (851 unaffected newborns, 55 confirmed cases of 21OHD) to compare their ability to identify babies with 21OHD. In addition, these 2 steroids were assessed in the unaffected cohort to determine the influence of gestational age (ranging from 23 to 42 weeks) and the timing of specimen collection on the measured concentrations., Results: The gestational age of the newborn impacted both 17OHP and 21deoxy concentrations, but the degree of influence was more substantial for 17OHP. Timing of collection did not affect 21deoxy concentration. Moreover, 21deoxy was a better predictor of 21OHD status compared with 17OHP, with little overlap in concentrations between the unaffected population and confirmed cases of 21OHD. A streamlined decision tree using solely 21deoxy (cutoff value, 0.85 ng/mL) yielded a 91.7% positive predictive value for 21OHD screening., Conclusions: Our findings demonstrate that 21deoxy is a key disease marker of 21OHD and can be used to improve the accuracy of newborn screening for this disorder., (Copyright © 2021 Elsevier Inc. All rights reserved.)

The function of macrophages in vitro is linked to their metabolic rewiring. However, macrophage metabolism remains poorly characterized in situ. Here, we used two-photon intensity and lifetime imaging of autofluorescent metabolic coenzymes, nicotinamide adenine dinucleotide (phosphate) (NAD(P)H) and flavin adenine dinucleotide (FAD), to assess the metabolism of macrophages in the wound microenvironment. Inhibiting glycolysis reduced NAD(P)H mean lifetime and made the intracellular redox state of macrophages more oxidized, as indicated by reduced optical redox ratio. We found that TNFα+ macrophages had lower NAD(P)H mean lifetime and were more oxidized compared to TNFα- macrophages. Both infection and thermal injury induced a macrophage population with a more oxidized redox state in wounded tissues. Kinetic analysis detected temporal changes in the optical redox ratio during tissue repair, revealing a shift toward a more reduced redox state over time. Metformin reduced TNFα+ wound macrophages, made intracellular redox state more reduced and improved tissue repair. By contrast, depletion of STAT6 increased TNFα+ wound macrophages, made redox state more oxidized and impaired regeneration. Our findings suggest that autofluorescence of NAD(P)H and FAD is sensitive to dynamic changes in intracellular metabolism in tissues and can be used to probe the temporal and spatial regulation of macrophage metabolism during tissue damage and repair., Competing Interests: VM, KT, ML, EB, AW, LZ, CM, MC, JF, JS, MS, AH No competing interests declared, (© 2022, Miskolci et al.)

Objective. To evaluate the interrater reliability of a universal evaluator rubric used to assess student pharmacist communication skills during patient education sessions. Methods. Six US schools and colleges of pharmacy each submitted 10 student videos of a simulated community pharmacy patient education session and recruited two raters in each of the five rater groups (faculty, standardized patients, postgraduate year one residents, student pharmacists, and pharmacy preceptors). Raters used a rubric containing 20 items and a global assessment to evaluate student communication of 12 videos. Agreement was computed for individual items and overall rubric score within each rater group, and for each item across all rater groups. Average overall rubric agreement scores were compared between rater groups. Agreement coefficient scores were categorized as no to minimal, weak, moderate, strong, or almost perfect agreement. Results. Fifty-five raters representing five rater groups and six pharmacy schools evaluated student communication. Item agreement analysis for all raters revealed five items with no to minimal or weak agreement, 10 items with moderate agreement, one item with strong agreement, and five items with almost perfect agreement. Overall average agreement across all rater groups was 0.73 (95% CI, 0.66-0.81). The preceptor rater group exhibited the lowest agreement score of 0.68 (95% CI, 0.58-0.78), which significantly deviated from the overall average. Conclusion. While strong or almost perfect agreement scores were not observed for all rubric items, overall average interrater reliability results support the use of this rubric in a variety of raters to assess student pharmacist communication skills during patient education sessions., (© 2022 American Association of Colleges of Pharmacy.)

Objective: Data on free thyroxine (FT4) concentrations beyond first 2 weeks of preterm infants are limited. This study was aimed to describe the association between perinatal characteristics and FT4 concentrations and the incidence of hypothyroxinemia at 4 weeks., Study Design: Retrospective analysis of serum thyroid function tests at 4 weeks in preterm infants <30 weeks of gestation. Association between FT4 at 4 weeks of life and perinatal characteristics were determined by bivariate analysis and multivariable regression. Incidence of hypothyroxinemia was determined using a gestational age adjusted definition based on in utero levels at the equivalent postmenstrual age., Results: The study cohort consisted of 280 infants. FT4 concentrations at 4 weeks of life were significantly associated with gestational age, birth weight, gender, and maternal history of thyroid disease. Hypothyroxinemia was found in 32.8% of the study cohort., Conclusion: Perinatal characteristics are associated with FT4 concentrations at 4 weeks of life. Nearly one-third of infants born <30 weeks had hypothyroxinemia at 4 weeks of life when compared with in utero levels at the equivalent postmenstrual age., Competing Interests: None declared., (Thieme. All rights reserved.)

Objectives: Determine the sensitivity and specificity of point-of-care lung ultrasound in identifying the etiology of acute respiratory failure at admission to the PICU., Design: Prospective observational study., Setting: Tertiary PICU., Patients: Children older than 37 weeks gestational age and less than or equal to 18 years old admitted to the PICU with acute respiratory failure from December 2018 to February 2020., Intervention: Point-of-care lung ultrasound performed within 14 hours of admission to the PICU by physicians blinded to patient history and clinical course. Two physicians, blinded to all clinical information, independently interpreted the point-of-care lung ultrasound and then established a consensus diagnosis (ultrasound diagnosis). The ultrasound diagnosis was compared with an independent, standardized review of the medical record following hospital discharge (final diagnosis)., Measurements and Results: Eighty-eight patients were enrolled in the study. Forty-eight patients had a final diagnosis of bronchiolitis/viral pneumonitis (55%), 29 had pneumonia (33%), 10 had status asthmaticus (11%), and one was excluded because of an inability to differentiate the final diagnosis. Point-of-care lung ultrasound correctly identified the etiology of acute respiratory failure in 56% of patients (49/87; 95% CI, 46-66%). It identified bronchiolitis/viral pneumonitis with 44% sensitivity (95% CI, 0.31-0.58) and 74% specificity (95% CI, 0.59-0.85), pneumonia with 76% sensitivity (95% CI, 0.58-0.88) and 67% specificity (95% CI 0.54-0.78), and status asthmaticus with 60% sensitivity (95% CI, 0.31-0.83) and 88% specificity (95% CI, 0.79-0.94)., Conclusions: In contrast to literature demonstrating high utility differentiating the cause of acute respiratory failure in adults, blinded point-of-care lung ultrasound demonstrates moderate sensitivity and specificity in identifying the etiology of pediatric acute respiratory failure at admission to the PICU among children with bronchiolitis, pneumonia, and status asthmaticus., Competing Interests: The authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2021 by the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.)

Objective: Point of care ultrasound (POCUS) use is increasing in pediatrics and has been demonstrated to be superior in identifying central catheter tip location in neonatal intensive care units. However, limited data exist regarding cardiorespiratory changes secondary to POCUS in neonates., Study Design: A prospective observational equivalence study was performed on 50 POCUS assessments of central catheter tip location in 46 patients ≥23 weeks gestation. Heart rate (HR), respiratory rate (RR), and percent oxygen saturation (SpO2) levels were collected before and after POCUS. Limits of equivalence were set in advance., Result: Equivalence was demonstrated in HR, RR, and SpO2 before and after POCUS. HR decreased by 3.24 beats per minute (90% CI: -5.36, -1.14). RR increased by 0.71 breath/min (90% CI: -1.84, +3.27). SpO2 increased by 0.54 percentage points (90% CI: -0.23, +1.31)., Conclusion: Identifying central catheter tip location using POCUS in neonates appears safe without affecting cardiorespiratory stability.

Background: Farm exposures may reduce the risk of atopic dermatitis (AD) in children, but this is controversial and US data are limited., Objective: This study was conducted to identify patterns of farm exposure in Wisconsin family farms that modify AD incidence and prevalence in early childhood., Methods: Environmental exposures, health history, and clinical outcomes were prospectively recorded for 111 farm families and 129 non-farm families enrolled in the Wisconsin Infant Study Cohort birth cohort study. Exposures from the prenatal and early postnatal (2-month) visits were evaluated together with parental report of AD diagnosis by a health care provider through age 24 months. Latent class analysis was performed with prenatal and early postnatal farm-exposure variables to assign farm children to 3 classes., Results: Overall, children of farm families had reduced AD incidence (P = .03). Within farm families, exposures including poultry (3% vs 28%; P = .003), pig (4% vs 25%; P = .04), feed grain (13% vs 34%; P = .02), and number of animal species were inversely associated with AD incidence. Among the latent class groups, children in families with diverse or more intense farm exposures (classes A and B) had reduced AD incidence, whereas low-exposure (class C) infants had AD incidence similar to that in nonfarm children., Conclusions: Infants in Wisconsin farm families had reduced AD incidence, and patterns of farm exposures further defined AD risk. These findings suggest that exposure to diverse farm animals, feed, and bedding during the prenatal period and in early infancy reduce the risk of early-onset AD, a phenotype associated with multiple other atopic diseases., (Copyright © 2020 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: In humans, Enterococcus spp. urinary tract infections (UTI) are commonly associated with urinary catheter-induced urothelial inflammation but this is not the case in dogs., Hypothesis/objectives: To identify risk factors predisposing dogs to enterococcal bacteriuria., Animals: Seventy dogs with Enterococcus spp. bacteriuria (case) and 70 dogs with Enterococcus coli bacteriuria (control)., Methods: A single center retrospective case-control study with subjects and controls identified by a medical records search for Enterococcus spp. (subject) or E coli (control) bacteriuria from January 1, 2014 to December 31, 2017. Cases and controls were balanced with respect to average age and weight. Binary logistic regression was used to estimate and test whether the odds of having Enterococcus spp. bacteriuria (instead of E coli) were associated with the presence of any given characteristic., Results: A history of recurrent bacteriuria was significantly more common in Enterococcus spp. cases than in E coli controls (odds ratio [OR]: 2.07; 95% confidence interval [CI]: 1.04-4.16, P = .04). Comorbidities associated with the presence of Enterococcus spp. bacteriuria included lower urinary tract (LUT) anatomic abnormalities (OR: 2.94; 95% CI: 1.17-8.10, P = .02), urolithiasis (P = .01), and the presence of LUT neoplasia (P = .04). Small frequencies (n = 12 and n = 6, respectively) compromise our ability to precisely estimate the genuine OR for the latter 2 characteristics., Conclusions and Clinical Importance: If the identified risk factors promote Enterococcus spp. colonization in dogs via induced LUT inflammation similar to people then Enterococcus spp. bacteriuria could be a sentinel for underlying LUT inflammation., (© 2020 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.)

Background: High-flow nasal cannula (HFNC) is commonly used to provide respiratory support to pediatric patients with respiratory failure. Although the use of bronchodilators via HFNC has been described, the feasibility and safety of aerosolized bronchodilator delivery via HFNC are controversial. In this study, we sought to evaluate whether the HFNC system can be used to deliver nebulized bronchodilators at lower gas flow of 2-4 L/min, increase patient comfort, and minimize respiratory therapist (RT) bedside time when compared to traditional interfaces., Methods: A retrospective chart review of all pediatric subjects who were admitted to the pediatric ICU in a tertiary care children's hospital and required nebulized bronchodilators between December 2017 and June 2018., Results: A total of 205 nebulizations were administered to 28 children; 31% of nebulized bronchodilators were given using a nebulization system integrated into the HFNC. Nebulized treatments resulted in an average increase in heart rate of 9.98 (95% CI 3.72-16.2) beats/min when HFNC was used and 0.64 (95% CI -1.65 to 2.93) beats/min when traditional interfaces were used, a difference of 9.34 (95% CI 2.30-16.4) beats/min ( P < .001). RT bedside time was significantly longer for HFNC nebulized treatments ( P = .031). Subjective level of comfort was not statically different when nebulized bronchodilators were delivered via HFNC or via traditional interfaces. Length of pediatric ICU stay was not statistically different between subjects who received some aerosol nebulized bronchodilators via HFNC versus those who received all bronchodilators through traditional interfaces ( P = .11)., Conclusions: Aerosol bronchodilator delivery using HFNC is feasible at low gas flow (ie, 2-4 L/min). However, the use of HFNC did not improve subjects' comfort, and it increased RT bedside time. Further prospective randomized studies are needed to determine the efficacy and efficiency of aerosol therapy delivered through HFNC and potential patient-oriented outcomes., (Copyright © 2020 by Daedalus Enterprises.)

Objective: To investigate complications associated with, and without, bupivacaine retrobulbar local anesthesia in dogs undergoing unilateral enucleation surgery., Study Design: Retrospective, observational study., Animals: A total of 167 dogs underwent unilateral enucleation surgery via a transpalpebral approach., Methods: Records from 167 dogs that underwent unilateral enucleation surgery that did (RB) or did not (NB) include retrobulbar bupivacaine anesthesia were reviewed, including anesthetic record, daily physical examination records, surgery report, patient discharge report and patient notes within 14 days of the surgery. Specific complications and severity were compared between RB and NB using the Wilcoxon rank-sum test. A 'complication burden' (0-5) comprising five prespecified complications was assigned and tested using rank-sum procedures. Statistical significance was set to 0.05., Results: Group RB included 97 dogs and group NB 70 dogs. Dogs in NB had a 17.0 percentage points (points) greater risk for a postoperative recovery complication (38.6% versus 21.6%; 95% confidence interval: 3.0-30.6 points; p = 0.017). There was inconclusive evidence that dogs in group RB had a lower risk of requiring perioperative anticholinergic administration (12.4% versus 22.9%; 10.5 points; p = 0.073). Other complications were similar between groups RB and NB with risks that differed by <10 points. The risk of hemorrhage was similar between groups RB (22.7%) and NB (20.0%) with no significant difference in the level of severity (p = 0.664)., Conclusions and Clinical Relevance: In this retrospective study, the use of retrobulbar bupivacaine for enucleation surgery in dogs was not associated with an increased risk of major or minor complications., (Copyright © 2020 Association of Veterinary Anaesthetists and American College of Veterinary Anesthesia and Analgesia. Published by Elsevier Ltd. All rights reserved.)

Purpose: Newborn screening laboratories are challenged to develop reporting algorithms that accurately identify babies at increased risk for congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (21OHD). Screening algorithms typically use cutoff values for a key steroid(s) and include considerations for covariates, such as gestational age or birth weight, but false-positive and false-negative results are still too frequent, preventing accurate assessments. Principal component analysis (PCA) is a statistical method that reduces high-dimensional data to a small number of components, capturing patterns of association that may be relevant to the outcome of interest. To our knowledge, PCA has not been evaluated in the newborn screening setting to determine whether it can improve the positive predictive value of 21OHD screening., Methods: PCA was applied to a data set of 920 newborns with measured concentrations of 5 key steroids that are known to be perturbed in patients with 21OHD. A decision tree for the known outcomes (confirmed 21OHD cases and unaffected individuals) was created with 2 principal components as predictors. The effectiveness of the PCA-derived decision tree was compared with the current algorithm., Results: PCA improved the positive predictive value of 21OHD screening from 20.0% to 66.7% in a retrospective study comparing the current algorithm to a tree-based algorithm using PCA-derived variables. The streamlined PCA-derived decision tree, comprising only 3 assessment points, greatly simplified the 21OHD reporting algorithm., Conclusions: This first report of PCA applied to newborn screening for 21OHD demonstrates enhanced detection of affected individuals within the unaffected population., (© Endocrine Society 2020. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)