Protocol for the "magnitude of cigarette substitution after initiation of e-cigarettes and its impact on biomarkers of exposure and potential harm in dual users" (MAGNIFICAT) study.

Introduction: Many smokers who use e-cigarettes (ECs) to quit continue smoking alongside vaping. The impact on health among individuals who simultaneously smoke conventional cigarettes (CCs) and use ECs remains unclear. The varying patterns of dual use present differing levels of overall toxin exposure and relative risks concerning smoking-related diseases. Understanding these complexities is vital to assessing the implications for human health. Objective: Herein we describe a protocol designed to analyze the impact of different level of substituting CCs with ECs on exposure to toxicants. We'll use biomarkers to measure this exposure and assess harm reduction in dual users through clinical endpoints, harm-related biomarkers, and behavioral correlations. We expect to observe progressive changes with varying patterns of dual use. Methods and analyses: For this purpose, we planned to recruit a group of 250 smokers who will be asked to reduce their CC consumption by adopting ECs (intervention group). A separate group of 50 smokers will continue to smoke CC (reference group). Study groups will be followed up for 6 months during which biospecimens will be collected for biomarker analyses, and clinical endpoints will be assessed. The trial is structured to characterize subjects' usage patterns over time using robust biomarkers of exposure and a standardized mobile phone application to facilitate the precise categorization of dual users along the risk continuum based on their usage behaviors. Subject recruitment will start in February 2024 and enrolment is expected to be completed by August 2024. Results will be reported early in 2025. Study findings may provide valuable insights into health benefits or risks associated with varying patterns of dual use. Ethics and dissemination: The study protocol and informed consent forms will be approved by the local Ethical Review Boards. Study results will be disseminated through articles published in reputable, peer-reviewed, open access, scientific journals, presentations at conferences, and the University website.

A Global Health Survey of People Who Vape but Never Smoked: Protocol for the VERITAS (Vaping Effects: Real-World International Surveillance) Study.

BACKGROUND: There is only limited information about the health effects of regular vaping. Research on the health status of people who used to smoke faces the challenge that previous smoking may have caused unknown health effects. Only studies of people who vape but have never smoked combustible cigarettes can enable the detection of harms attributable to vaping. Large prospective studies of well-characterized electronic cigarette users with and without a history of combustible cigarette smoking are warranted to establish the long-term effects of regular vaping on respiratory health. OBJECTIVE: We will conduct a global cross-sectional survey of individuals from 6 world regions. Respiratory symptoms will be assessed using a validated questionnaire-the Respiratory Symptom Experience Scale (RSES). Current vapers who are nonusers of other tobacco or nicotine products will be compared with matched controls who are nonusers of vapes and other tobacco or nicotine products. METHODS: This will be a multicountry, cross-sectional internet-based survey of 750 adults aged ≥18 years who satisfy the criteria for inclusion in either a cohort of people who exclusively vape and who are nonusers of other tobacco or nicotine products ("vapers cohort"; target N=500) or a cohort of nonvapers who are also nonusers of other tobacco or nicotine products ("controls cohort"; target N=250). The primary end point of the study is the RSES score. RSES scores of people in the "vapers cohort" will be compared with those of people in the "controls cohort." Additionally, the study will collect data to characterize patterns of vaping product use among the vapers cohort. Data collection will include information about the age initiation of using vape products, reasons for starting and continuing the use of vape products, specific types of products used, flavors and nicotine strengths of recently used products, as well as the frequency and intensity of product use in the past 30 days. RESULTS: Participant recruitment started in April 2023, and enrollment was completed by November 2023 with 748 participants. Results will be reported in 2024. CONCLUSIONS: This will be the first study providing key insights into respiratory health effects associated with using electronic cigarettes in people who vape with no established use of combustible cigarettes or other tobacco or nicotine products. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/54236.

The impact of COVID-19 on racial and ethnic disparities in presentation with perforated appendicitis in children: A retrospective cohort study.

Background: Children from racial and ethnic minority groups have higher prevalence of perforated appendicitis, and the COVID-19 pandemic worsened racial and ethnic health-related disparities. We hypothesized that the incidence of perforated appendicitis worsened for children from racial and ethnic minorities during the COVID-19 pandemic. Methods: We performed a retrospective cohort study of the Pediatric Health Information System for children ages 2-18y undergoing appendectomy pre-pandemic (3/19/2019-3/18/2020) and intra-pandemic (3/19/2020-3/30/2021). The primary outcome was presentation with perforated appendicitis. Multivariable logistic regression with mixed effects estimated the likelihood of presentation with perforated appendicitis. Covariates included race, ethnicity, pandemic status, Child Opportunity Index, gender, insurance, age, and hospital region. Results: Overall, 33,727 children underwent appendectomy: 16,048 (47.6 %) were Non-Hispanic White, 12,709 (37.7 %) were Hispanic, 2261 (6.7 %) were Non-Hispanic Black, 960 (2.8 %) were Asian, and 1749 (5.2 %) Other. Overall perforated appendicitis rates were unchanged during the pandemic (37.4 % intra-pandemic, 36.4 % pre-pandemic, p = 0.06). Hispanic children were more likely to present with perforated appendicitis intra-pandemic versus pre-pandemic (OR 1.18, 95%CI: 1.07, 1.13). Hispanic children had higher odds of perforated appendicitis versus Non-Hispanic White children pre-pandemic (OR 1.10, 95%CI: 1.00, 1.20) which increased intra-pandemic (OR 1.19, 95%CI: 1.09, 1.30). Publicly-insured children had increased odds of perforated appendicitis intra-pandemic versus pre-pandemic (OR 1.14, 95%CI: 1.03, 1.25), and had increased odds of perforated appendicitis versus privately-insured children (intra-pandemic OR 1.26, 95%CI: 1.16, 1.36; pre-pandemic OR 1.12, 95%CI: 1.04, 1.22). Conclusions: During the COVID-19 pandemic, Hispanic and publicly-insured children were more likely to present with perforated appendicitis, suggesting that the pandemic exacerbated existing disparities in healthcare for children with appendicitis. Key message: We found that Hispanic children and children with public insurance were more likely to present with perforated appendicitis during the COVID-19 pandemic. Public health efforts aimed at ameliorating racial and ethnic disparities created during the COVID-19 pandemic should consider increasing healthcare access for Hispanic children to address bias, racism, and systemic barriers that may prevent families from seeking care.

Respiratory culture growth and 3-years lung health outcomes in children with bronchopulmonary dysplasia and tracheostomies.

BACKGROUND: While bacteria identification on respiratory cultures is associated with poor short-term outcomes in children with bronchopulmonary dysplasia (BPD) and tracheostomies, the influence on longer-term respiratory support needs remains unknown. OBJECTIVE: To determine if respiratory culture growth of pathogenic organisms is associated with ongoing need for respiratory support, decannulation, and death at 3 years posttracheostomy placement in children with BPD and tracheostomies. METHODS: This single center, retrospective cohort study included infants and children with BPD and tracheostomies placed 2010-2018 and ≥1 respiratory culture obtained in 36 months posttracheostomy. Primary predictor was any pathogen identified on respiratory culture. Additional predictors were any Pseudomonas aeruginosa and chronic P. aeruginosa identification. Outcomes included continued use of respiratory support (e.g., oxygen, positive pressure), decannulation, and death at 3 years posttracheostomy. We used Poisson regression models to examine the relationship between respiratory organisms and outcomes, controlling for patient-level covariates and within-patient clustering. RESULTS: Among 170 children, 59.4% had a pathogen identified, 28.8% ever had P. aeruginosa, and 3.5% had chronic P. aeruginosa. At 3 years, 33.1% of alive children required ongoing respiratory support and 24.8% achieved decannulation; 18.9% were deceased. In adjusted analysis, any pathogen and P. aeruginosa were not associated with ongoing respiratory support or mortality. However, P. aeruginosa was associated with decreased decannulation probability (adjusted risk ratio 0.48, 95% CI 0.23-0.98). Chronic P. aeruginosa was associated with lower survival probability. CONCLUSION: Our findings suggest that respiratory pathogens including P. aeruginosa may not promote long-term respiratory dysfunction, but identification of P. aeruginosa may delay decannulation.

Patterns of flavored e-cigarette use among adult vapers in the USA: an online cross-sectional survey of 69,233 participants.

BACKGROUND: Flavored e-cigarettes remain a controversial topic with regulators planning or already implementing restrictions worldwide. In this study, we examined patterns of flavor use in e-cigarettes among a convenience sample of US adult vapers. METHODS: Participants aged ≥ 18 years who reported ever using an e-cigarette were included in the study (N = 69,233) and responded to an online questionnaire. Their smoking status was recorded as well as patterns of flavor use at e-cigarette use initiation, at the time of the survey and at the time of smoking cessation (for participants who used to smoke and were using e-cigarettes at the time of quitting). RESULTS: The most popular flavors at e-cigarette use initiation were fruit (82.8%), followed by dessert/pastry/bakery (68.6%) and candy/chocolate/sweet (52.2%). Slightly higher prevalence of using fruit and dessert/pastry/bakery flavors was observed in those who never smoked compared to those who were currently and formerly smoking. Tobacco flavors were used by 20.8% of the participants and was by far the least prevalent among participants who never smoked. Similar patterns were observed with participants' choices at the time of the survey, but tobacco flavor use was substantially reduced (7.7%). Only 2.1% reported tobacco as the single most often used flavor. The most prevalent flavor at the time of quitting smoking was again fruit (83.3%), followed by dessert/pastry/bakery (68.0%) and candy/chocolate/sweet (44.5%). These flavors were considered the most helpful for quitting smoking. Tobacco flavor use at the time of smoking cessation was reported by 15.0%, while 9.3% considered it helpful for quitting smoking. CONCLUSION: Non-tobacco flavors were popular among the US adult vapers who participated in the study, and were popular choices at the time of quitting smoking for those who formerly smoked. Tobacco flavor use prevalence was low and was further reduced over time. Regulators should consider the flavor choice of adult consumers, especially those who quit smoking, when preparing legislation on flavored e-cigarettes.

Varenicline and counseling for vaping cessation: a double-blind, randomized, parallel-group, placebo-controlled trial.

BACKGROUND: Vaping cessation is virtually unexplored. The efficacy and safety of varenicline for vaping cessation has not been studied and rigorous research is required to advance best practice and outcomes for people who use electronic cigarettes (EC) and want to quit. The objective is to evaluate the efficacy and safety of varenicline (1 mg BID, administered for 12 weeks, with follow-up to week 24) combined with vaping cessation counseling in exclusive daily EC users intending to quit vaping. METHODS: Design: Double-blind, randomized, parallel-group, placebo-controlled trial. SETTING: The study took place at a University-run smoking cessation center. PARTICIPANTS: People who exclusively use ECs daily and intend to quit vaping. INTERVENTION: A total of 140 subjects were randomized to either varenicline (1 mg, administered twice daily for 12 weeks) plus counseling or placebo treatment (administered twice daily, for 12 weeks) plus counseling. The trial consisted of a 12-week treatment phase followed by a 12-week follow-up, nontreatment phase. MAIN OUTCOMES AND MEASURES: The primary efficacy endpoint of the study was biochemically validated continuous abstinence rate (CAR) at weeks 4 to 12. Secondary efficacy end points were CAR at weeks 4 to 24 and 7-day point prevalence of vaping abstinence at weeks 12 and 24. RESULTS: CAR was significantly higher for varenicline vs placebo at each interval: weeks 4-12, 40.0% and 20.0%, respectively (OR = 2.67, 95% CI = [1.25-5.68], P = 0.011); weeks 4-24, 34.3% for varenicline with counseling and 17.2% for placebo with counseling (OR = 2.52, 95% CI = [1.14-5.58], P = 0.0224). The 7-day point prevalence of vaping abstinence was also higher for the varenicline than placebo at each time point. Serious adverse events were infrequent in both groups and not treatment-related. CONCLUSIONS: The findings of the present RCT indicate that inclusion of varenicline in a vaping cessation program for people who use electronic cigarettes and intending to quit may result in prolonged abstinence. These positive findings establish a benchmark of intervention effectiveness, may support the use of varenicline combined with counseling in vaping cessation programs, and may also help guiding future recommendations by health authorities and healthcare providers. TRIAL REGISTRATION: The study has been registered in EUDRACT with Trial registration ID: 2016-000339-42.

Gabapentin is Associated With Decreased Postoperative Opioid Use and Length of Stay After Appendectomy in Children With Perforated Appendicitis: A Propensity Score-Matched Analysis.

BACKGROUND: Gabapentin is increasingly used as an off-label, opioid-sparing pain medication in children. We investigated perioperative gabapentin administration and postoperative opioid use in children who underwent appendectomy for perforated appendicitis. METHODS: A retrospective cohort study of healthy children ages 2-18 years undergoing appendectomy for perforated appendicitis from 2014 to 2019 was performed using the Pediatric Health Information System®. Propensity score matched (PSM) analysis was conducted with 1:1 matching based on patient and hospital characteristics. Multivariable linear regression analysis was used to evaluate an association between gabapentin, postoperative opioid use, and postoperative length of stay. RESULTS: Of 29,467 children with perforated appendicitis who underwent appendectomy, 236 (0.8%) received gabapentin. In 2014, <10 children received gabapentin, but by 2019, 110 children received gabapentin. On univariate analysis of the PSM cohort, children receiving gabapentin had decreased total postoperative opiate use (2.3 SD ± 2.3 versus 3.0 SD ± 2.5 days, p < 0.001). On adjusted analysis, children receiving gabapentin had 0.65 fewer days of postoperative total opioid use (95% CI: -1.09, -0.21) and spent 0.69 fewer days in the hospital after surgery (95% CI: -1.30, -0.08). CONCLUSION: While overall use is infrequent, gabapentin is increasingly administered to children with perforated appendicitis who undergo an appendectomy and is associated with decreased postoperative opioid use and reduced postoperative length of stay. Multimodal pain management strategies incorporating gabapentin may reduce postoperative opioid consumption, but further studies of drug safety are needed for this off-label use in children undergoing surgery. LEVEL OF EVIDENCE: III.

Behavioral intentions assessment of a disposable e-cigarette among adult current, former, and non-smokers in the United States.

Modeling the public health effects of e-cigarettes requires estimates of the likelihood that different individuals and population subgroups will start using e-cigarettes and subsequently transition to and from combustible cigarette use. To begin to generate input values for modeling efforts, this study assessed adults' behavioral intentions in relation to a disposable e-cigarette, "BIDI® Stick." An online questionnaire assessed intentions to try and use a BIDI® Stick regularly in 11 flavor variants among United States (U.S.) nationally representative samples of adult (21+ years) non-smokers (n = 2284), current smokers (n = 2391), former smokers (n = 2241), and young adult (21-24 years) non-smokers (n = 1140) of combustible cigarettes following exposure to product information and images. Current smokers rated their intentions to use a BIDI® Stick to partially or completely replace cigarettes. Positive intention to try a BIDI® Stick at least once was, for each flavor variant, highest among current smokers (22.4%-28.1%), lower among former smokers (6.0%-9.7%) and non-smokers (3.4%-5.2%), and lowest among never-smokers (1.0%-2.4%). Among current smokers, former smokers, and non-smokers, trial and regular use intentions were lowest among e-cigarette non-users and e-cigarette never-users. Approximately 23.6% of current smokers reported an intention to use a BIDI® Stick in at least one flavor to completely switch from cigarettes and/or to reduce cigarette consumption. Low trial and regular use intentions suggest that U.S. adults who do not currently smoke cigarettes and/or use e-cigarettes are unlikely to initiate use of the BIDI® Stick e-cigarette. Trial and regular use intentions are highest among adults who currently smoke cigarettes and/or use e-cigarettes. A moderate proportion of current smokers may try using a BIDI® Stick e-cigarette as a partial or complete replacement for combustible cigarettes.

Varenicline for smoking cessation in individuals who smoke cigarettes and use electronic cigarettes: a double-blind, randomised, placebo-controlled phase 3 trial.

Background: The efficacy and safety of varenicline for smoking cessation among individuals who smoke tobacco cigarettes and also use electronic cigarettes (known e-cigarettes or vapes) have not been studied. We aimed to address this knowledge gap and examine predictors for smoking abstinence. Methods: In this double-blind, placebo-controlled, single-centre randomised trial in Italy, we enrolled adults who had used an e-cigarette daily for at least 12 months and who also smoked at least one tobacco cigarette per day and had a willingness to quit smoking. 155 participants were randomly assigned to receive either varenicline (n = 78) or matched placebo (n = 77). Varenicline (1 mg, administered twice daily for 12 weeks) was given in combination with smoking cessation counseling in dual users with an intention to quit smoking. Participants in both treatment groups received the same smoking cessation counselling throughout the whole duration of the study. The trial consisted of a 12-week treatment phase followed by a 12-week follow-up. The primary efficacy endpoint was continuous abstinence rate (CAR) in weeks 4-12. Secondary efficacy endpoints were the CAR in weeks 4-24 and 7-day point prevalence of smoking abstinence at weeks 12 and 24. This study is registered in EUDRACT, 2016-000339-42. Findings: Between November 2018, and February 2020, 114 participants (61 in the varenicline group and 53 in the placebo group) completed the intervention phase at week 12 and 88 participants (52 in the varenicline group and 36 in the placebo group) completed the follow-up phase at week 24. CARs were significantly higher for the varenicline vs placebo at each time-point: 50.0% vs 16.9% (OR = 4.9; 95% CI, 2.3-10.4; P < 0.0001) between weeks 4 and 12; and 48.7% vs 14.3% (OR = 5.7; 95% CI, 2.6-12.3; P < 0.0001) between weeks 4 and 24. The 7-day point prevalence of smoking abstinence was also higher for the varenicline than placebo at each time point. Adverse events were rated as mild or moderate and rarely led to treatment discontinuation. Interpretation: Our findings indicate that inclusion of varenicline in a cessation programme for adults who smoke and use e-cigarettes with an intention to quit smoking could result in smoking abstinence without serious adverse events. In the absence of evidence from other smoking cessation methods, it could be useful to suggest the use of varenicline in cessation programmes specifically designed to help dual users stop smoking. Further research in larger and more generalisable populations is required to strengthen such a suggestion. Funding: Global Research Award for Nicotine Dependence, an independently reviewed competitive grants programmeme funded by Pfizer.

Tramadol Use in Pediatric Surgery: Trends After the Food and Drug Administration Black-Box Warning.

INTRODUCTION: The U.S. Food and Drug Administration (FDA) issued a black-box warning in 2017 contraindicating tramadol in children <12 y. Longitudinal trends and factors associated with perioperative tramadol use in children remain unclear. METHODS: A retrospective, multi-institutional cohort study utilizing the Pediatric Health Information System database was performed for children 2-18 y who underwent one of ten common surgeries from 1/2009-2/2020. Temporal trends correlated with the FDA tramadol contraindication were evaluated. Hierarchical multivariable logistic regression analysis identified factors associated with tramadol use. RESULTS: Of 477,153 children undergoing surgery, 5857(1.2%) received tramadol during hospitalization. Tramadol use occurred in 942 (16.1%) children after the black-box warning, 390 of whom were <12 y. For children <12 y, annual tramadol use peaked at 1.87% (2016) and decreased to 0.66% (2019). Female sex (odds ratio OR 1.32; 95% confidence interval CI:1.24,1.40), age ≥12 y (OR 2.79; 95%CI: 2.62,2.97), and Midwest location (OR 4.07; 95% CI:1.64,10.11) increased likelihood of receiving tramadol. Tramadol use was more likely after cholecystectomy (OR 1.17; 95% CI:1.04,1.32) and in children with gastrointestinal (OR 2.39; 95% CI: 2.19,2.60), metabolic (OR 1.39; 95% CI:1.26,1.53) or transplant-related (OR 1.82; 95% CI: 1.57,2.10) comorbidities. Children of Hispanic/Latino ethnicity and those with public insurance had decreased likelihood of receiving tramadol. Adjusting for patient and hospital characteristics, children <12 y were less likely to receive tramadol following the black-box warning (OR 0.65; 95% CI: 0.59,0.70). CONCLUSIONS: Despite the FDA contraindication, tramadol prescribing continues among children <12 y undergoing surgery, with use varying by patient and institutional factors. Interventions are required to reduce perioperative tramadol use in children.

Ketorolac use and risk of bleeding after appendectomy in children with perforated appendicitis.

BACKGROUND: Ketorolac is an opioid sparing agent commonly used in children. However, ketorolac may be avoided in children with peritonitis owing to a possible increased risk of bleeding. METHODS: A retrospective cohort study of healthy children 2-18 years who underwent appendectomy for perforated appendicitis was performed using the Pediatric Health Information System (2009-2019). Multivariable logistic regression was used to evaluate the association between perioperative ketorolac use and postoperative blood transfusions within 30 days of surgery, adjusting for patient and hospital level factors. An interaction between ketorolac and ibuprofen was evaluated to identify synergistic effects. RESULTS: Overall, 55,603 children with perforated appendicitis underwent appendectomy and 82.3% (N = 45,769) received ketorolac. Of those, 32% (N = 14,864) also received ibuprofen. Receipt of a blood transfusion was infrequent (N = 189, 0.3%). On multivariable logistic regression analysis, perioperative ketorolac administration was associated with decreased odds of a blood transfusion (OR 0.53, 95% CI: 0.35-0.79). However, children receiving ketorolac and ibuprofen were more likely to require a blood transfusion (OR 1.99, 95% CI: 1.42-2.79). In a subset of children receiving ketorolac, each additional day of ketorolac was associated with an increase odds of blood transfusion (OR 1.39, 95% CI: 1.30-1.49). CONCLUSION: Perioperative ketorolac alone is not associated with an increased risk of significant bleeding in children undergoing appendectomy for perforated appendicitis. However, use of both ketorolac and ibuprofen during hospitalization was associated with increased risk of bleeding, although precise timing of administration of these medications was unable to be determined. Extended ketorolac use was also associated with increased risk of bleeding requiring blood transfusion. LEVEL OF EVIDENCE: Level III.

Molecular Characterization of Clear Cell Renal Cell Carcinoma Reveals Prognostic Significance of Epithelial-mesenchymal Transition Gene Expression Signature.

BACKGROUND: There is an ongoing need to develop prognostic biomarkers to improve the management of clear cell renal cell carcinoma (ccRCC). OBJECTIVE: To leverage enriched pathways in ccRCC to improve risk-stratification. DESIGN, SETTING, AND PARTICIPANTS: We retrospectively identified two complementary discovery cohorts of patients with ccRCC who underwent (1) radical nephrectomy (RNx) with inferior vena cava tumor thrombectomy (patients = 5, samples = 24) and (2) RNx for localized disease and developed recurrence versus no recurrence (n = 36). Patients with localized ccRCC (M0) in The Cancer Genome Atlas (TCGA, n = 386) were used for validation. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: A differential expression gene (DEG) analysis was performed on targeted RNA next-generation sequencing data from both discovery cohorts. Using TCGA for validation, Kaplan-Meier survival analysis and multivariable Cox proportional hazard testing were utilized to investigate the prognostic impact of DEGs, cell cycle proliferation (CCP), and a novel epithelial-mesenchymal transition (EMT) score on progression-free (PFS) and disease-specific (DSS) survival. RESULTS AND LIMITATIONS: In the discovery cohorts, we observed overexpression of WT1 and CCP genes in the tumor thrombus versus the primary tumor, as well as in patients with recurrence versus those without recurrence. A hallmark pathway analysis demonstrated enrichment of the EMT- and CCP-related pathways in patients with high WT1 expression in the TCGA (validation) ccRCC cohort. CCP and EMT scores were derived in the validation cohort, which was stratified into four risk groups using Youden Index cut points: CCPlow/EMTlow, CCPlow/EMThigh, CCPhigh/EMTlow, and CCPhigh/EMThigh. The CCPhigh/EMThigh risk group was associated with the worst PFS and DSS (both p < 0.001). In a multivariable analysis, CCPhigh/EMThigh was independently associated with poor PFS and DSS (hazard ratio = 4.6 and 10.3, respectively; p < 0.001). CONCLUSIONS: We demonstrate the synergistic prognostic impact of EMT in tumors with a high CCP score. Our novel EMT score has the potential to improve risk stratification and provide potential novel therapeutic targets. PATIENT SUMMARY: Genes involved in epithelial-mesenchymal transition provides important prognostic information for patients with clear cell renal cell carcinoma.

Identifying Practices to Promote Inpatient Adolescent and Influenza Vaccine Delivery.

OBJECTIVES: Many hospitalized children are underimmunized. We assessed the association between hospital immunization practices and tetanus, diphtheria, and acellular pertussis (Tdap), meningococcal, human papillomavirus (HPV), and influenza vaccine delivery. METHODS: An electronic survey regarding hospital vaccine delivery practices was distributed via the Pediatric Health Information System (PHIS) and Pediatric Research in Inpatient Settings networks to PHIS hospitals. Number of vaccines delivered and total discharges in 2018 were obtained from the PHIS database to determine hospital vaccine delivery rates; patients 11 to 18 years old (adolescent vaccines) and 6 months to 18 years old (influenza vaccine) were included. Vaccine delivery rates were risk adjusted by using generalized linear mixed-effects modeling and compared with survey responses to determine associations between the number or presence of specific practices and vaccine delivery. Adjusted HPV and meningococcal vaccine delivery rates could not be calculated because of low delivery. RESULTS: Twenty-nine hospitals completed a survey (57%). 152 499 and 423 046 patient encounters were included for the adolescent and influenza vaccines, respectively. Unadjusted inpatient vaccine delivery rates varied. After adjustment, the number of practices was associated only with influenza vaccine delivery (P = .02). Visual prompts (P = .02), nurse or pharmacist ordering (P = .003), and quality improvement projects (P = .048) were associated with increased influenza vaccine delivery; nurse or pharmacist ordering had the greatest impact. No practices were associated with Tdap vaccine delivery. CONCLUSIONS: The number and presence of specific hospital practices may impact influenza vaccine delivery. Further research is needed to identify strategies to augment inpatient adolescent immunization.

Preformed fibrils generated from mouse alpha-synuclein produce more inclusion pathology in rats than fibrils generated from rat alpha-synuclein.

BACKGROUND: Alpha-synuclein (α-syn) preformed fibril (PFF)-induced pathology can be used to study the features and progression of synucleinopathies, such as Parkinson's disease. Intrastriatal injection of mouse α-syn PFFs produce accumulation of α-syn pathology in both mice and rats. Previous studies in mice have revealed that greater sequence homology between the α-syn amino acid sequence used to produce PFFs with that of the endogenous host α-syn increases α-syn pathology in vivo. NEW METHODS: Based on the prediction that greater sequence homology will result in more α-syn pathology, PFFs generated from recombinant rat α-syn (rPFFs) were used instead of PFFs produced from recombinant mouse α-syn (mPFFs), which are normally used in the model. Rats received unilateral intrastriatal injections of either rPFFs or mPFFs and accumulation of α-syn phosphorylated at serine 129 (pSyn) was examined at 1-month post-surgery. RESULTS: Rats injected with mPFFs exhibited abundant accumulation of α-syn inclusions in the substantia nigra and cortical regions, whereas in rats injected with rPFFs had significantly fewer SNpc neurons containing pSyn inclusions (≈60% fewer) and little, if any, pSyn inclusions were observed in the cortex. CONCLUSIONS: Our results suggest that additional factors beyond the degree of sequence homology between host α-syn and injected recombinant α-syn impact efficiency of seeding and subsequent inclusion formation. More practically, these findings caution against the use of rPFFs in the rat preformed fibril model.

The impact of intravenous acetaminophen pricing on opioid utilization and outcomes for children with appendicitis.

BACKGROUND: In 2014, the price of intravenous acetaminophen more than doubled. This study determined whether increased intravenous acetaminophen cost was associated with decreased utilization and increased opioid use for children undergoing appendectomy. METHODS: A multicenter retrospective cohort study using the Pediatric Health Information System database between 2011 and 2017 was performed. Healthy children 2 to 18 years undergoing appendectomy at 46 children's hospitals in the United States were identified. Intravenous acetaminophen use, opioid use, and pharmacy costs were assessed. Multivariable mixed-effects modeling was used to determine the association between postoperative opioid use, intravenous acetaminophen use, and postoperative length-of-stay. RESULTS: Overall, 110,019 children undergoing appendectomy were identified, with 22.5% (N = 24,777) receiving intravenous acetaminophen. Despite the 2014 price increase, intravenous acetaminophen use increased from 3% in 2011 to 40.1% in 2017 (P < .001), but at a significantly reduced rate. After 2014, adjusted median pharmacy charges decreased from $3,326.5 (interquartile range: $1,717.5-$6,710.8) to $3,264.1 (interquartile range: $1,782.8-$5,934.7, P < .001) for children who received intravenous acetaminophen. In 94,745 children staying ≥1 day after surgery, postoperative opioid use decreased from 73.6% in 2011 to 58.6% in 2017 (P < .001). Use of intravenous acetaminophen alone compared to opioids alone after surgery resulted in similar predicted mean postoperative length-of-stay. CONCLUSION: In children undergoing appendectomy, intravenous acetaminophen use continued to rise, but at a slower rate after a price increase. Furthermore, adjusted pharmacy charges were lower for children receiving intravenous acetaminophen, possibly secondary to a concurrent decrease in postoperative opioid use. These findings suggest intravenous acetaminophen may be more broadly used regardless of perceived costs to minimize opioid use after surgery.

The Adult JUUL Switching and Smoking Trajectories (ADJUSST) Study: Methods and Analysis of Loss-to-Follow-up.

Objectives: The Adult JUUL System User Switching and Smoking Trajectories (ADJUSST) study assessed the smoking and JUUL use trajectories of adults who purchased JUUL. In this paper, we describe study methods, characterize the sample, and assesses potential for bias due to loss to follow-up. Methods: We entered 55,414 US adults (≥ age 21) who purchased a JUUL Starter Kit for the first time (online or at retail) in 2018 into a naturalistic, longitudinal observational study, irrespective of baseline smoking status. Participants were invited for follow-ups 1, 2, 3, 6, 9, and 12 months later, focused on assessing past-30-day smoking and JUUL use. Analyses assessed potential bias due to non-response. Results: Over 90% of participants had a history of smoking; 62.8% were past-30-day smokers; 23.3% were former smokers. Participants' average age was 30; 75% were white. Most participants (77.6%) completed some follow-ups; 25% completed all follow-ups. Baseline differences among complete responders (N = 13,729), partial responders (N = 29,252), and complete non-responders (N = 12,433) were small. When recontacted, few 12-month non-responders said their non-response was due to smoking; many reported no past-30-day smoking. Conclusions: The study may elucidate smoking trajectories of adult JUUL users. The potential for bias due to loss to follow-up in ADJUSST was limited.

National Inpatient Immunization Patterns: Variation in Practice and Policy Between Vaccine Types.

BACKGROUND: Many hospitalized children are underimmunized, yet little is known about current systems supporting inpatient vaccination. We aim to describe national pediatric inpatient immunization practices and determine if variation exists among adolescent, childhood, and influenza vaccines. METHODS: An electronic survey regarding hospital vaccination practices was sent to physician, nurse, and pharmacy leaders via the Pediatric Research in Inpatient Settings Network in spring 2019. Hospitals reported the presence of various practices to support inpatient vaccination stratified by vaccine type: tetanus, diphtheria, and acellular pertussis, meningococcal, human papillomavirus, childhood series, and influenza. One-way analysis of variance testing compared differences in numbers of practices and χ2 tests compared proportions of sites reporting each practice between vaccine types. Qualitative responses were evaluated via content analysis. RESULTS: Fifty-one of 103 eligible hospitals completed the survey (50%). Standardized policies existed in 92% of hospitals for influenza, 41% for childhood, and 29% for adolescent vaccines. Hospitals identified an average of 5.1 practices to deliver influenza vaccines, compared with 1.5 for childhood; 0.9 for tetanus, diphtheria, and acellular pertussis; 0.7 for meningococcal; and 0.6 for human papillomavirus vaccines (P < .001). Standardized screening tools, visual prompts, standing orders, nurse- or pharmacy-driven screening or ordering, staff education, and quality improvement projects were reported more often for influenza vaccines than other vaccine types (P < .01 for all comparisons). Common barriers to delivery included communication difficulties, lack of systems optimization, and parent and provider discomfort with inpatient immunization. CONCLUSIONS: Existing hospital infrastructure supports influenza vaccine delivery over other vaccine types, potentially creating missed inpatient vaccination opportunities.

Impact of the MyProstateScore (MPS) Test on the Clinical Decision to Undergo Prostate Biopsy: Results From a Contemporary Academic Practice.

OBJECTIVE: To evaluate the association of the MyProstateScore (MPS) urine test on the decision to undergo biopsy in men referred for prostate biopsy in urology practice. METHODS: MPS testing was offered as an alternative to immediate biopsy in men referred to the University of Michigan for prostate biopsy from October 2013 through October 2016. The primary endpoint was the decision to perform biopsy. The proportion of patients undergoing biopsy was compared to predicted risk scores from the Prostate Cancer Prevention Trial risk calculator (PCPTrc). Analyses were stratified by the use of multiparametric magnetic resonance imaging (mpMRI). The associations of PCPTrc, MPS, and mpMRI with the decision to undergo biopsy were explored in a multivariable logistic regression model. RESULTS: Of 248 patients, 134 (54%) proceeded to prostate biopsy. MPS was significantly higher in biopsied patients (median 29 vs14, P < .001). The use of biopsy was strongly associated with MPS, with biopsy rates of 26%, 38%, 58%, 90%, and 85% in the first through fifth quintiles, respectively (P < .001). MPS association with biopsy persisted upon stratification by mpMRI. On multivariable analysis, MPS was strongly associated with the decision to undergo biopsy when modeled as both a continuous (odds ratio [OR] 1.05, 95%; confidence interval [CI] 1.04-1.08; <.001) and binary (OR 7.76, 95%; CI 4.14-14.5; P < .001) variable. CONCLUSION: Many patients (46%) undergoing clinical MPS testing as an alternative to immediate prostate biopsy were able to avoid biopsy. Increasing MPS was strongly associated with biopsy rates. These findings were robust to use of mpMRI.

Ethanol Conversion to Butadiene over Isolated Zinc and Yttrium Sites Grafted onto Dealuminated Beta Zeolite.

Zinc and Yttrium single sites were introduced into the silanol nests of dealuminated BEA zeolite to produce Zn-DeAlBEA and Y-DeAlBEA. These materials were then investigated for the conversion of ethanol to 1,3-butadiene. Zn-DeAlBEA was found to be highly active for ethanol dehydrogenation to acetaldehyde and exhibited low activity for 1,3-butadiene generation. By contrast, Y-DeAlBEA was highly active for 1,3-butadiene formation but exhibited no activity for ethanol dehydrogenation. The formation of 1,3-butadine over Y-DeAlBEA and Zn-DeAlBEA does not occur via aldol condensation of acetaldehyde but, rather, by concerted reaction of coadsorbed acetaldehyde and ethanol. The active centers for this process are ≡Si-O-Y(OH)-O-Si≡ or ≡Si-O-Zn-O-Si-O≡ groups closely associated with adjacent silanol groups. The active sites in Y-DeAlBEA are 70 times more active than the Y sites supported on silica, for which the Y site is similar to that in Y-SiO2 but which lacks adjacent hydroxyl groups, and are 7 times more active than the active sites in Zn-DeAlBEA. We propose that C-C bond coupling in Y-DeAlBEA proceeds via the reaction of coadsorbed acetaldehyde and ethanol to form crotyl alcohol and water. The dehydration of crotyl alcohol to 1,3-butadiene is facile and occurs over the mildly Brønsted acidic ≡Si-OH groups present in the silanol nest of DeAlBEA. The catalysts reported here are notably more active than those previously reported for both the direct conversion of ethanol to 1,3-butadiene or the formation of this product by the reaction of ethanol and acetaldehyde.

Fewer postoperative opioids are associated with decreased duration of stay for children with perforated appendicitis.

BACKGROUND: The impact of postoperative opioid use on outcomes for children with perforated appendicitis is unknown. METHODS: A retrospective cohort study was performed using the Pediatric Health Information System database from 2005 to 2015. Children 2 to 18 years with perforated appendicitis who underwent an appendectomy were identified. Postoperative day analgesic use was categorized as nonopioid analgesia alone, opioids (with or without nonopioid analgesia), or no analgesics. The impact of postoperative opioid use on postoperative duration of stay and 30-day readmission was evaluated using multivariable mixed-effects regression analysis. RESULTS: Overall, 47,726 children with perforated appendicitis were identified. On postoperative day 1, 17.7% received nonopioid analgesia alone, 77.6% received opioids, and 4.7% received no analgesics. On adjusted analysis, postoperative day 1 opioid use was associated with a 0.75-day (95% confidence interval: 0.54-0.96) increased postoperative duration of stay. Starting opioids after postoperative day 1 was associated with 2.21 days (95% confidence interval: 1.90-2.51) longer postoperative duration of stay. Among children who received opioids on postoperative day 1, continued use of opioids after postoperative day 1 was associated with a 1.88 day (95% confidence interval: 1.77-1.98) longer postoperative duration of stay. Postoperative day 1 opioid use did not significantly affect 30-day readmission. CONCLUSION: Early and continued postoperative opioid use is associated with prolonged postoperative duration of stay in children undergoing appendectomy for perforated appendicitis. Minimizing opioid use, even on postoperative day 2, may result in a decreased postoperative duration of stay.