Invasive haemodynamics predict outcomes in paediatric pulmonary artery hypertension.

BACKGROUND: Invasive haemodynamics are often performed for initiating and guiding pulmonary artery hypertension therapy. Little is known about the predictive value of invasive haemodynamic indices for long-term outcomes in children with pulmonary artery hypertension. We aimed to evaluate invasive haemodynamic data to help predict outcomes in paediatric pulmonary artery hypertension. METHODS: Patients with pulmonary artery hypertension who underwent cardiac catheterisation (2006-2019) at a single centre were included. Invasive haemodynamic data from the first cardiac catheterisation and clinical outcomes were reviewed. The combined adverse outcome was defined as pericardial effusion (due to right ventricle failure), creation of a shunt for pulmonary artery hypertension (atrial septal defect or reverse Pott's shunt), lung transplant, or death. RESULTS: Among 46 patients with a median [interquartile range (IQR)] age of 13.2 [4.1-44.7] months, 76% had CHD. Median mean pulmonary artery pressure was 37 [28-52] mmHg and indexed pulmonary vascular resistance was 6.2 [3.6-10] Woods units × m2. Median pulmonary artery pulsatility index was 4.0 [3.0-4.7] and right ventricular stroke work index was 915 [715-1734] mmHg mL/m2. After a median follow-up of 2.4 years, nine patients had a combined adverse outcome (two had a pericardial effusion, one underwent atrial level shunt, one underwent reverse Pott's shunt, and six died). Patients with an adverse outcome had higher systolic and mean pulmonary artery pressures, higher diastolic and transpulmonary pressure gradients, higher indexed pulmonary vascular resistance, higher pulmonary artery elastance, and higher right ventricular stroke work index (p < 0.05 each). CONCLUSION: Invasive haemodynamics (especially mean pulmonary artery pressure and diastolic pressure gradient) obtained at first cardiac catheterisation in children with pulmonary artery hypertension predicts outcomes.

Effect of a polyp detection poster on detection of sessile serrated lesions: a prospective controlled study.

Background and study aims Colonoscopy is effective in reducing the incidence of colorectal cancer, but interval cancers remain a concern and their occurrence mainly is thought to be due to poor detection of sessile serrated lesions (SSLs) and advanced neoplasia (AN). Currently there are no low-cost, easy-to-implement tools to improve detection of difficult-to-detect polyps. Our aims were to compare the detection rate for SSLs and AN between two groups of endoscopists at a large community practice, one of which received an intervention of a polyp detection poster displayed over the monitor in their endoscopy suite for 6 months. We compared preintervention and post-intervention detection rates in the intervention and control groups. Methods This was a convenience case control quality improvement project. For 6 months, a 2' × 3' poster of pictures of SSLs and advanced neoplasia was displayed over the monitor for 44 endoscopist in a large community gastroenterology practice in the Minneapolis/St.Paul area, while another 44 physicians performed colonoscopy in the usual fashion without the poster. The endpoints were improvement in detection rates for SSLs and AN preintervention and post-intervention between the control and intervention groups. Results During the study, 88 endoscopists performed 54,861 colonoscopies. At least one adenoma was detected in 41.3 % of patients, one or more SSLs in 11.4 %, and AN in 10.6 %. During the intervention period, the SSL detection rates were 10.9 % and 12.3 % for the control and intervention groups and for AN, the detection rates were 10.4 % and 10.75 % for the two groups, respectively. Exposure to the polyp detection poster significantly changed SSL detection for the intervention group relative to the control group (likelihood ratio test P  < 0.001). No significant effect of the intervention was observed for detection of AN, right-sided AN or left-sided AN, or adenoma detection rate. Conclusions Placement of a polyp detection poster above the endoscopy video monitor increased detection of SSL but not AN.

Local Tobacco 21 Policies are Associated With Lower Odds of Tobacco Use Among Adolescents.

INTRODUCTION: Tobacco 21 (T21) policies have shown promise in reducing cigarette use among adolescents. This study examined whether local T21 policies affected adolescent use of a variety of tobacco products and whether results differed by grade level. METHODS: We used repeated cross-sectional data from eighth, ninth, and eleventh-grade respondents to the 2016 (n = 107 981) and 2019 (n = 102 196) Minnesota Student Surveys. Generalized estimating equations modeled eight adolescent tobacco use outcomes in 2019 (past 30-day use of any tobacco, cigarettes, cigars, e-cigarettes, hookah, chewing tobacco, flavored tobacco, and multiple products) by T21 exposure, defined as respondents' attendance at a school within a jurisdiction with T21 policy implementation between the two surveys. Models controlled for demographic characteristics and product-specific baseline tobacco use at the school level in 2016 and were stratified by grade. RESULTS: After adjusting for baseline tobacco use and other demographics, T21-exposed eighth and ninth-grade students had significantly lower odds of tobacco use than unexposed peers in five of eight models, i.e. any tobacco (aOR = 0.80, 95% CI: 0.74, 0.87), cigarettes (aOR = 0.81, 95% CI: 0.67, 0.99), e-cigarettes (aOR = 0.78, 95% CI: 0.71, 0.85), flavored tobacco (aOR = 0.79, CI: 0.70, 0.89), and dual/poly tobacco (aOR = 0.77, 95% CI: 0.65, 0.92). T21-exposed eleventh-grade students did not differ significantly in their odds of any tobacco use outcomes relative to their unexposed peers. CONCLUSIONS: T21 exposure is associated with lower odds of multiple forms of tobacco use, particularly among younger adolescent populations, supporting the implementation of T21 policies to reduce tobacco use in this population.

A Randomized Trial of Nicotine versus No-nicotine E-cigarettes Among African American Smokers: Changes in Smoking and Tobacco Biomarkers.

INTRODUCTION: The objective of this clinical trial was to compare the effects of e-cigarettes with and without nicotine on patterns of combustible cigarette use and biomarkers of exposure to tobacco toxicants among African American smokers. METHODS: African American smokers (n = 234) were enrolled in a 12-week, single blind, randomized controlled trial and assigned to ad lib use of nicotine e-cigarettes with or without menthol (2.4% nicotine [equivalent to combustible cigarettes], n = 118), or no-nicotine e-cigarettes (n = 116) for 6 weeks. Surveys were administered at baseline, 2, 6, and 12 weeks, and urinary biomarkers 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) and total nicotine equivalents (TNE) were assessed at baseline and 6 weeks. RESULTS: Participants smoked an average of 11.4 cigarettes per day (CPD) and 88% used menthol cigarettes at baseline. At Week 6, the nicotine group reported using e-cigarettes 9.1 times per day compared to 11.4 times in the no-nicotine group (p = 0.42). Combustible cigarette smoking decreased 3.0 CPD in the nicotine group compared to 2.7 CPD in the no-nicotine group (p = 0.74). Neither TNE nor NNAL changed significantly between baseline and Week 6. There were no differences in nicotine withdrawal symptoms between treatment groups. Smoking reduction persisted in both groups at Week 12. CONCLUSIONS: Contrary to our hypotheses, nicotine e-cigarettes did not significantly reduce the use of combustible cigarettes compared to no-nicotine e-cigarettes in this cohort of African American smokers. Findings suggest e-cigarettes are modestly associated with the decreased use of combustible cigarettes among non-treatment seeking smokers, regardless of nicotine content, but without a reduction in tobacco toxicants. IMPLICATIONS: Although e-cigarettes have the potential to reduce harm if substituted for combusted cigarettes (or if they promoted cessation) because of lower levels of tobacco toxicants, this study suggests ad lib use of e-cigarettes among African American smokers, with or without nicotine, results in modest smoking reduction but does not change toxicant exposure in a cohort where smoking cessation or reduction is not the goal. These data suggest that testing future harm reduction interventions using e-cigarettes should include more specific behavioral change coaching, including substituting for or completely stopping combusted cigarettes. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov - NCT03084315.

Body composition assessment after pediatric liver transplant.

BACKGROUND: Pediatric liver transplantation generally restores metabolic function; yet after transplantation, some children remain malnourished, have increased adiposity, and develop obesity. Measurement of body composition in the assessment of nutrition status could reduce adverse consequences in children. METHODS: Anthropometric measurements, multiple-frequency bioelectrical impedance analysis, air displacement plethysmography, and ultrasound measurements were conducted on children recruited from the liver transplant program at the University of Minnesota Masonic Children's Hospital. A cross-sectional study was conducted to describe the quality of weight gain in post-liver transplant children between the ages of 2 and 17 years using multiple assessment tools (air displacement plethysmography, multiple-frequency bioelectrical impedance analysis, and ultrasound) and to determine whether multiple-frequency bioelectrical impedance analysis and ultrasound accurately describe body composition and quality of weight gain. RESULTS: Mean percent body fat by air displacement plethysmography and multiple-frequency bioelectrical impedance analysis was 18.4% (±3.3) and 19.0% (±3.9), respectively (P > .99). There were insufficient data to examine the relationship between summed muscle and adipose thickness measures by ultrasound and percent body fat determined by air displacement plethysmography or multiple-frequency bioelectrical impedance analysis. CONCLUSION: Percent body fat, fat mass, and fat-free mass measures determined by air displacement plethysmography and multiple-frequency bioelectrical impedance analysis were not statistically different, which suggests the stand-on device used in this study could be a useful body composition assessment tool for the pediatric population.

Night-time Screen Media Use in the Pediatric Intensive Care Unit.

This prospective observational study quantified screen media use within the night-time pre-sleep period in a pediatric intensive care unit and postulated possible implications. Seventy-five patients between the ages of newborn to 19 years old were observed 5 evenings per week for 3 weeks. Trained observers documented the patient's screen use, type of screen used, screen engagement, sleep state, light level, and parental presence. Patients in the ICU had on average 65 minutes of screen media use, per evening. The total screen media use averaged 59 minutes for the 0 to18-month age group; 83 minutes for the 18 to 24-month age group; 66 minutes for 2 to 6 year olds; 72 minutes for 6 to 13 year olds; and 74 minutes for those above 13. This research demonstrates that children are engaging in more screen time during the night hours than is recommended by the AAP.

Preoperative Factors Associated with Anesthesia Failure for Patients Undergoing Nonsurgical Root Canal Therapy: A National Dental Practice-Based Research Network Study.

INTRODUCTION: The aim of this study was to identify preoperative factors associated with local anesthesia failure. METHODS: The National Dental Practice-Based Research Network (www.NationalDentalPBRN.org) data from 534 patients who received a nonsurgical root canal treatment completed in a single appointment were included in this analysis. Three methods for defining anesthesia failure were used: definition 1, patient-reported level of numbness; definition 2, provider-reported quality of anesthesia; and definition 3, provider-reported use of supplemental anesthesia. Fifty-one preoperative factors were investigated and analyzed individually against the overall failure rate for each method, and multivariate generalized estimating equation logistic models were fit with predictors chosen using stepwise model selection to evaluate factors that may interact with each other. RESULTS: The overall anesthesia failure rates were 5%, 15%, and 30% for definitions 1, 2, and 3, respectively. Provider experience, diabetes, absence of sharp or aching pain, absence of smoking, and a fair expected outcome were associated with anesthesia failure (definition 1). Provider level of training, absence of a sinus tract, bite sensitivity, and stress making the pain worse were associated with anesthesia failure (definition 2). Provider level of training, pain provoked by stimulus, mandibular teeth, teeth with vital pulps, and pain interfering with daily activities were associated with the use of supplemental anesthesia (definition 3). CONCLUSIONS: With the range of 5%-30% of anesthesia failures, a few common factors across the models assessed were elucidated. Providers with higher levels of training had significantly fewer anesthesia failures. Patient self-reported history of diabetes and preoperative pain-related interference with daily activities were associated with more anesthesia failures. Greater severity of various tooth-related pain characteristics, as a group but not individually, accounted for more anesthesia failures.

Non-invasive Neurally Adjusted Ventilatory Assist (NAVA) in the pediatric ICU: assessing optimal Edi compliance.

BACKGROUND: Bronchiolitis patients are supported with non-invasive conventional modalities (HFNC, CPAP and BiPAP). Neurally Adjusted Ventilatory Assist (NAVA) is a newer mode which supports based on electrical activity of the diaphragm (Edi). It is unclear if non-invasive NAVA is used within optimal operational parameters. The study aim was to evaluate Edi compliance. METHODS: A retrospective chart review of bronchiolitis patients admitted to the PICU from January 2015 to January 2018 was undertaken. NAVA compliance within optimal parameters (defined as Edi peak values between 5-15 µV and Edi min < 1µV) was assessed as the primary outcome. Secondary outcomes included PICU length of stay (LOS), duration to minimal respiratory support (defined as 4 L/min or less on HFNC) and intubation rate in the conventional (non-NAVA) and non-invasive NAVA. RESULTS: Sixty-three patients with a mean age of 6.89 months with 30 on NAVA and 33 on non-NAVA support were analyzed. Compliance with optimal Edi peak and Edi min was 50.4% (±37.5%) and 33.8% (±26.2%) respectively. Regression models for PICU LOS with minimal respiratory support and for 1L/kg of HFNC showed adjusted R2= 0.96 and 0.92, respectively. The mean PICU stay for NAVA was 146.00 hrs. (±66.26) versus 69.58 hrs. (±57.69) for the non-NAVA group (p<0.001). Duration to minimal respiratory support was 125.40 hrs. (±54.90) for NAVA versus 58.03 hrs. (±58.97) for non-NAVA group (p<0.001). A higher intubation rate was found in the NAVA group (13.33% versus 3.03%, p=0.296). CONCLUSIONS: We found suboptimal compliance with operational parameters with non-invasive NAVA support. There was longer PICU LOS, time to minimal respiratory support in the NAVA compared to the non-NAVA support.

Predictors and Prospective Course of PANS: A Pilot Study Using Electronic Platforms for Data Collection.

Objectives: Little is known about the longitudinal course of pediatric acute-onset neuropsychiatric syndrome (PANS) because existing literature is primarily cross-sectional. To begin to address this gap, two digital platforms were used to prospectively monitor neuropsychiatric symptoms in children with PANS. The aim was to identify baseline clinical characteristics that would predict the course of neuropsychiatric symptoms over 12 weeks. We compared relative compliance between two electronic data acquisition platforms and evaluated agreement between parent-child ratings of symptoms. Methods: For 12 weeks, 20 children with PANS and their parents completed weekly rating scales of neuropsychiatric symptoms on Research Electronic Data Capture (REDCap) and concurrently parents completed tri-weekly ratings on My Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANDAS) Chart, a symptom monitoring website. Longitudinal data were analyzed by using regression analyses. Results: Greater duration of time between onset of PANS and study enrollment was associated with worsening of parent-rated neuropsychiatric symptoms over 12 weeks (p = 0.05). Higher scores on parents' Caregiver Burden Inventory at baseline predicted that children would report more severe symptoms over the 12-week period (p = 0.01). Compliance rates for parents were 86.3% for the weekly REDCap PANS Symptoms Rating Scale compared with 53.8% for the tri-weekly My PANDAS Chart ratings. There was moderate agreement between children and parents on the PANS Symptom Rating Scale (r = 0.55, p < 0.0001). Conclusion: Our study highlights the utility of electronic methods for tracking longitudinal symptoms in children with PANS and suggests that particular baseline characteristics (e.g., delay in identification and treatment of PANS, greater caregiver burden) may be indicative of a differential trajectory of PANS course, with more severe symptoms over the short term. clinicaltrials.gov NCT04382716.

Effects of Screening Compliance on Long-term Reductions in All-Cause and Colorectal Cancer Mortality.

BACKGROUND & AIMS: Randomized trials have shown that biennial fecal occult blood test (FOBT) screening reduces mortality from colorectal cancer (CRC), but not overall mortality. Differences in benefit for men vs women, and by age, are unknown. We sought to evaluate long-term reduction in all-cause and CRC-specific mortality in men and women who comply with offered screening, and in different age groups, using individual participant data from 2 large randomized trials of biennial FOBT screening, compared with an intention to treat analysis. METHODS: We updated the CRC and all-cause mortality from the Danish CRC screening trial (n = 61,933) through 30 years of follow up and pooled individual participant data with individual 30-year follow-up data from the Minnesota Colon Cancer Control trial (n = 46,551). We compared the biennial screening groups to usual care (controls) in individuals 50-80 years old using Kaplan Meier estimates of relative risks and risk differences, adjusted for study differences in age, sex, and compliance. RESULTS: Through 30 years of follow up, there were 33,478 (71.9%) and 33,479 (72.2%) total deaths and 1023 (2.2%) and 1146 (2.5%) CRC deaths in the biennial screening (n = 46,553) and control groups (n = 46,358), respectively. Among compliers, biennial FOBT screening significantly reduced CRC mortality by 16% (relative risk [RR], 0.84; 95% CI, 0.74-0.96) and all-cause mortality by 2% (RR, 0.98; 95% CI, 0.97-0.99). Among compliers, the reduction in CRC mortality was larger for men (RR, 0.75; 95% CI, 0.62-0.90) than women (RR, 0.91; 95% CI, 0.75-1.09). The largest reduction in CRC mortality was in compliant men 60-69 years old (RR, 0.59; 95% CI, 0.42-0.81) and women 70 years and older (RR, 0.53; 95% CI, 0.30-0.94). CONCLUSIONS: Long-term CRC mortality outcomes of screening among compliers using biennial FOBT are sustained, with a statistically significant reduction in all-cause mortality. The reduction in CRC mortality is greater in men than women-the benefit in women lags that of men by about 10 years.

Evaluation and Comparison of Performance Parameters and Impact of Telepathology and Operator Experience on Endobronchial and Endoscopic Ultrasound-Guided Fine-Needle Aspiration.

OBJECTIVES: Endobronchial ultrasound- and endoscopic ultrasound-guided fine-needle aspiration (EBUS-/EUS-FNA) are minimally invasive techniques of diagnosing and staging malignancies. The procedures are difficult to master, requiring specific feedback for optimizing yield. METHODS: Over 2 years, EBUS-/EUS-FNA cases were gathered using the institutional pathology database. Patient and specimen characteristics were collected from the pathology database and electronic medical record. RESULTS: In 2 years, 789 unique FNA specimens were collected (356 EBUS and 433 EUS specimens). The cohort and each subgroup had excellent performance, which was enhanced by telepathology. The discrepancy rate was satisfactorily low. Hematolymphoid neoplasms are overrepresented in discrepant EBUS cases. The malignancy rates of cytology diagnostic categories were comparable to the literature. CONCLUSIONS: Using diagnostic yield and concordance results allow for comprehensive evaluation of the entire process of EBUS-/EUS-FNAs. This study's findings can influence patient management, training methods, and interpretation of results, while also acting as a model for others to investigate their own sources of inadequacy, discrepancy, and training gaps.

Trabeculotomy Ab Interno With the Trab360 Device for Childhood Glaucomas.

PURPOSE: To report outcomes and complications of trabeculotomy ab interno using the Trab360 device (Trab360; Sight Sciences, Menlo Park, California, USA) in eyes with childhood glaucomas. DESIGN: Multicenter retrospective interventional case series. METHODS: Eyes with childhood glaucomas that underwent Trab360 with at least 3 months follow-up were evaluated. Postoperative intraocular pressure (IOP) less than or equal to 24 mm Hg with or without medications and no additional surgery defined success. RESULTS: Forty-six eyes of 41 patients were included. Median age at surgery was 12 months (range 1-325 months, mean 71 months); 54% prior to 20 months. A total of 48% were right eyes; 48% were male. Mean treatment was 290°. Median follow-up was 14.5 months (range 6-34 months, mean 16.2 months). Median preoperative IOP was 30 mm Hg (range 18-49 mm Hg, mean 30.9 mm Hg); median postoperative IOP was 18 mm Hg (range 5-40 mm Hg, mean 20.3 mm Hg]. Median number of preoperative glaucoma medications was 2.5 (range 0-5, mean 2.6); median number postoperatively was 1 (range 0-4, mean 1.6). Success was achieved in 67.4% (95% CI: 51.9%-80.0%) of eyes. Among 40 eyes for which Trab360 was the first glaucoma surgery, success rate was 70% (95% CI 53.3%-82.9%). Success was achieved in 81% (95% CI 57.4%-93.7%) of primary congenital glaucoma (PCG) eyes. Among 18 PCG eyes for which Trab360 was the first glaucoma surgery, success rate was 83.3% (95% CI 57.7%-95.6%). Two eyes (4.3%) suffered cyclodialysis. There were no other significant complications. CONCLUSIONS: Trab360 success resembles literature on other angle surgeries for childhood glaucomas. Good surgical technique and caution in high-risk angles is imperative to avoid cyclodialysis. Our study is limited by the imperfections inherent in any retrospective analysis. Single-incision ab interno trabeculotomy with the Trab360 device is effective and safe for treating childhood glaucomas, especially PCG.

An intramembrane sensory circuit monitors sortase A-mediated processing of streptococcal adhesins.

Bacterial adhesins mediate adhesion to substrates and biofilm formation. Adhesins of the LPXTG family are posttranslationally processed by the cell membrane-localized peptidase sortase A, which cleaves the LPXTG motif. This generates a short C-terminal peptide (C-pep) that remains in the cell membrane, whereas the mature adhesin is incorporated into the cell wall. Genes encoding adhesins of the oral bacterium Streptococcus gordonii were differentially expressed depending on whether the bacteria were isolated from saliva or dental plaque and appeared to be coordinately regulated. Deletion of sspA and sspB (sspAB), both of which encode LPXTG-containing adhesins, unexpectedly enhanced adhesion and biofilm formation. C-peps produced from a model LPXTG-containing adhesin localized to the cell membrane and bound to and inhibited the intramembrane sensor histidine kinase SGO_1180, thus preventing activation of the cognate response regulator SGO_1181. The absence of SspAB C-peps induced the expression of the scaCBA operon encoding the lipoprotein adhesin ScaA, which was sufficient to preserve and even enhance biofilm formation. This C-pep-driven regulatory circuit also exists in pathogenic streptococci and is likely conserved among Gram-positive bacteria. This quality control mechanism ensures that the bacteria can form biofilms under diverse environmental conditions and may play a role in optimizing adhesion and biofilm formation.