Novel autoantibodies help diagnose anti-SSA antibody negative Sjögren disease and predict abnormal labial salivary gland pathology.

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.

Cervical Cancer and a History of Incarceration: Examining a Social Determinant of Health.

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.

Validation of Thermal Imaging and the ALT-70 Prediction Model to Differentiate Cellulitis From Pseudocellulitis.

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.

A novel factor IXa-specific enzyme-linked immunosorbent assay detects factor IXa in human plasma.

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.

Decreased Intraoperative Renal Tissue Oxygenation after Cardiopulmonary Bypass Predicts Cardiac Surgery-Associated Acute Kidney Injury in Neonates.

(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.

Comparison of preoperative retrobulbar bupivacaine and postoperative subcutaneous liposome-encapsulated bupivacaine on postoperative analgesia in dogs undergoing enucleation.

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.

Renal tissue oxygenation and development of AKI in preterm neonates born < 32 weeks' gestational age in the first week of age.

OBJECTIVE: To evaluate the relationship between regional renal saturation of oxygen (RrSO2) 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 RrSO2 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 %RrSO2 was associated with a 40% decrease in risk of AKI (95%CI: 9.6-61%; p = 0.016). CONCLUSIONS: Increases in mean %RrSO2 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 RrSO2 monitoring to evaluate new therapies or clinical protocols to prevent and treat neonatal AKI.

The Importance of Outcomes Ascertainment for Accurate Assessment of the Mammography Screening Cancer Detection Rate: A Simulation Study.

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.

Comparison of chest radiograph and lung ultrasound in children with acute respiratory failure.

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/kmax) 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/kmax = 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.

Respiratory Severity Score during the First 3 Hours of Life as a Predictor for Failure of Noninvasive Respiratory Support and Need for Late Rescue Surfactant Administration.

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..

Risk of Hypovitaminosis and Vitamin C Deficiency in Pediatric Patients Undergoing Cardiopulmonary Bypass.

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.

Response to aerosolized calfactant in infants with respiratory distress syndrome; a post-hoc analysis of AERO-02 trial.

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 (FiO2), 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. FiO2, MAP, and RSS were lower in the UC group. FiO2 decrease was seen after the first aerosolized calfactant dose. CONCLUSION: FiO2, 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 FiO2 was noted in the AC group after the first aerosolization.

Computed tomographic laryngotracheal dimensions in adult domestic rabbits (Oryctolagus cuniculus) are positively associated with body weight and the laryngotracheal lumen is narrowest at the level of the thyroid cartilage.

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.

Exploring knowledge gaps in the understanding of peripheral and deep en face margin assessment.

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).

Review of Tobramycin Dosing in Pediatric Patients With Cystic Fibrosis.

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.

Effectiveness and Safety of Albuterol Solutions With and Without Benzalkonium Chloride.

INTRODUCTION: Continuous aerosolized ß2 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.

Retrospective investigation of perioperative risk factors for immediate postoperative corneal erosions in dogs undergoing phacoemulsification.

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.

Cross-sectional survey on genetic testing utilization and perceptions in Wisconsin Amish and Mennonite communities.

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.

Oxygen Saturation Profiles in Healthy Term Infants in Early Postnatal Life.

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 (SpO2) was measured over the entire study duration for each neonate and was characterized as the fraction of time of their SpO2 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 SpO2 was 95.4%. Percentage time spent in each of the five SpO2 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 SpO2 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 SpO2 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%..