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.

Fast Ion Isotropization by Current Sheet Scattering in Magnetic Reconnection Jets.

We present a statistical analysis of ion distributions in magnetic reconnection jets using data from the Magnetospheric Multiscale spacecraft. Compared with the quiet plasma in which the jet propagates, we often find anisotropic and non-Maxwellian ion distributions in the plasma jets. We observe magnetic field fluctuations associated with unstable ion distributions, but the wave amplitudes are not large enough to scatter ions during the observed travel time of the jet. We estimate that the phase-space diffusion due to chaotic and quasiadiabatic ion motion in the current sheet is sufficiently fast to be the primary process leading to isotropization.

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.

A Hemilabile NHC-Gold Complex and its Application to the Redox Neutral 1,2-Oxyarylation of Feedstock Alkenes.

We describe a AuI complex of a hemi-labile (C^N) N-heterocyclic carbene ligand that is able to mediate oxidative addition of aryl iodides. Detailed computational and experimental investigations have been undertaken to verify and rationalize the oxidative addition process. Application of this initiation mode has resulted in the first examples of "exogenous oxidant-free" AuI /AuIII catalyzed 1,2-oxyarylations of ethylene and propylene. These demanding yet powerful processes establish these commodity chemicals as nucleophilic-electrophilic building blocks in catalytic reaction design.

Migratory Insertion of CO into a Au-C Bond.

A MeDalPhos-ligated gold(III) metallafluorene complex, generated via C-C oxidative addition of biphenylene, reacts with CO to produce 9-fluorenone. Experimental and computational studies show that this proceeds via a hitherto unknown migratory insertion of CO into a Au(III)-C bond. This process is more energetically challenging compared to other M-C bonds, but once achieved, the product is comparatively stable with respect to retro-carbonylation. Exploiting migratory insertion of CO into Au-C bonds may extend the range of products that are accessible using gold chemistry.

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.

Constraining Cosmological Phase Transitions with the Parkes Pulsar Timing Array.

A cosmological first-order phase transition is expected to produce a stochastic gravitational wave background. If the phase transition temperature is on the MeV scale, the power spectrum of the induced stochastic gravitational waves peaks around nanohertz frequencies, and can thus be probed with high-precision pulsar timing observations. We search for such a stochastic gravitational wave background with the latest data set of the Parkes Pulsar Timing Array. We find no evidence for a Hellings-Downs spatial correlation as expected for a stochastic gravitational wave background. Therefore, we present constraints on first-order phase transition model parameters. Our analysis shows that pulsar timing is particularly sensitive to the low-temperature (T∼1-100 MeV) phase transition with a duration (ß/H_{*})^{-1}∼10^{-2}-10^{-1} and therefore can be used to constrain the dark and QCD phase transitions.

Acute respiratory infections in hospitalised infants with congenital heart disease.

OBJECTIVES: To assess the overall burden and outcomes of acute respiratory infections in paediatric inpatients with congenital heart disease (CHD). METHODS: This is a retrospective cross-sectional study of non-neonates <1 year with CHD in the Kid's Inpatient Database from 2012. We compared demographics, clinical characteristics, cost, length of stay, and mortality rate for those with and without respiratory infections. We also compared those with respiratory infections who had critical CHD versus non-critical CHD. Multi-variable regression analyses were done to look for associations between respiratory infections and mortality, length of stay, and cost. RESULTS: Of the 28,696 infants with CHD in our sample, 26% had respiratory infections. Respiratory infection-associated hospitalisations accounted for $440 million in costs (32%) for all CHD patients. After adjusting for confounders including severity, mortality was higher for those with respiratory infections (OR 1.5, p = 0.003), estimated mean length of stay was longer (14.7 versus 12.2 days, p < 0.001), and estimated mean costs were higher ($53,760 versus $46,526, p < 0.001). Compared to infants with respiratory infections and non-critical CHD, infants with respiratory infections and critical CHD had higher mortality (4.5 versus 2.3%, p < 0.001), longer mean length of stay (20.1 versus 15.5 days, p < 0.001), and higher mean costs ($94,284 versus $52,585, p < 0.001). CONCLUSION: Acute respiratory infections are a significant burden on infant inpatients with CHD and are associated with higher mortality, costs, and longer length of stay; particularly in those with critical CHD. Future interventions should focus on reducing the burden of respiratory infections in this population.

A Systematic Study of the Effects of Complex Structure on Aryl Iodide Oxidative Addition at Bipyridyl-Ligated Gold(I) Centers.

A combined theoretical and experimental approach has been used to study the unusual mechanism of oxidative addition of aryl iodides to [bipyAu(C2 H4 )]+ complexes. The modular nature of this system allowed a systematic assessment of the effects of complex structure. Computational comparisons between cationic gold and the isolobal (neutral) Pd0 and Pt0 complexes revealed similar mechanistic features, but with oxidative addition being significantly favored for the group 10 metals. Further differences between Au and Pd were seen in experimental studies: studying reaction rates as a function of electronic and steric properties showed that ligands bearing more electron-poor functionality increase the rate of oxidative addition; in a complementary way, electron-rich aryl iodides give faster rates. This divergence in mechanism compared to Pd suggests that Ar-X oxidative addition with Au can underpin a broad range of new or complementary transformations.

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.

Statistics of Kinetic Dissipation in the Earth's Magnetosheath: MMS Observations.

A familiar problem in space and astrophysical plasmas is to understand how dissipation and heating occurs. These effects are often attributed to the cascade of broadband turbulence which transports energy from large scale reservoirs to small scale kinetic degrees of freedom. When collisions are infrequent, local thermodynamic equilibrium is not established. In this case the final stage of energy conversion becomes more complex than in the fluid case, and both pressure-dilatation and pressure strain interactions (Pi-D≡-Π_{ij}D_{ij}) become relevant and potentially important. Pi-D in plasma turbulence has been studied so far primarily using simulations. The present study provides a statistical analysis of Pi-D in the Earth's magnetosheath using the unique measurement capabilities of the Magnetospheric Multiscale (MMS) mission. We find that the statistics of Pi-D in this naturally occurring plasma environment exhibit strong resemblance to previously established fully kinetic simulations results. The conversion of energy is concentrated in space and occurs near intense current sheets, but not within them. This supports recent suggestions that the chain of energy transfer channels involves regional, rather than pointwise, correlations.

In Situ Observation of Hall Magnetohydrodynamic Cascade in Space Plasma.

We present estimates of the turbulent energy-cascade rate derived from a Hall-magnetohydrodynamic (MHD) third-order law. We compute the contribution from the Hall term and the MHD term to the energy flux. Magnetospheric Multiscale (MMS) data accumulated in the magnetosheath and the solar wind are compared with previously established simulation results. Consistent with the simulations, we find that at large (MHD) scales, the MMS observations exhibit a clear inertial range dominated by the MHD flux. In the subion range, the cascade continues at a diminished level via the Hall term, and the change becomes more pronounced as the plasma beta increases. Additionally, the MHD contribution to interscale energy transfer remains important at smaller scales than previously thought. Possible reasons are offered for this unanticipated result.

Harm and Addiction Perceptions of the JUUL E-Cigarette Among Adolescents.

INTRODUCTION: This study assessed adolescents' harm and addiction perceptions of the highest-selling brand-JUUL-of the most commonly used tobacco product-electronic cigarettes (e-cigarettes)-among adolescents in the United States. METHODS: A cross-sectional online survey assessed use and perceptions of the harmfulness and addictiveness of the JUUL e-cigarette and conventional tobacco cigarettes in a nationally representative sample of 9865 adolescents aged 13-17 years in the United States. Associations between adolescents' harm and addiction perceptions and their use of a JUUL e-cigarette were examined through multinomial logistic regression models. RESULTS: Overall, 6.1% and 9.3% of adolescents believed daily use and occasional use of a JUUL e-cigarette, respectively, would cause them no harm. Around 11.3% believed they would either never experience harm from using a JUUL e-cigarette or they could use a JUUL e-cigarette for at least 20 years before experiencing any harm, and 7.3% believed they would be "very unlikely" to become addicted to using a JUUL e-cigarette. Overall, 39.3% and 29.3% of adolescents perceived the JUUL e-cigarette as "less harmful" and "less addictive" than conventional cigarettes, respectively. Compared to never users of the JUUL e-cigarette, current and former users held significantly lower harm and addiction perceptions of the JUUL e-cigarette on all measures. CONCLUSIONS: The majority of adolescents believed using a JUUL e-cigarette would put them at, at least, some risk for experiencing health problems and addiction. A smaller but significant proportion believed they could use a JUUL e-cigarette without ever being harmed by or becoming addicted to the JUUL e-cigarette. IMPLICATIONS: The study reports adolescents' perceptions of the harmfulness and addictiveness of the highest-selling brand of the most commonly used tobacco product among youth in the United States. Though the majority of adolescents correctly believed that using a JUUL e-cigarette would put them at, at least, some risk for experiencing health problems and addiction, a small proportion believed that using a JUUL e-cigarette would be risk free. Correcting such risk-free perceptions may reduce adolescents' interest in trying and continuing to use JUUL e-cigarettes.

Key Components of Traditional Consultation Letters and Their Relevance to Electronic Consultation Replies: A Systematic Review.

Background: Effective communication between primary care providers (PCPs) and specialists plays a key role in providing high-quality patient care. A high-quality referral process should involve referral letters containing all information that is necessary to support shared care between primary and specialty care. Introduction: There is no consensus on the optimal components of specialist-to-PCP communication after a face-to-face patient encounter or in the context of the emerging field of electronic consultations (eConsult). In this study, we aimed at synthesizing the evidence on key components of a traditional consultation letter and at determining whether they can be applied to eConsult replies. Methods: We conducted a systematic review by using a narrative synthesis approach. We searched Pubmed and Embase from inception to January/March 2016 (English). Included studies focused on features of specialists' responses to PCPs. We extracted components of a consultation letter that were identified to be of importance to PCPs and attempted to relate their applicability to eConsult replies. Results: The search revealed 744 potentially relevant citations, of which 65 were deemed eligible for full-text review. Forty-one papers were excluded on full-text review, resulting in 24 studies included in the final synthesis. Important components of consultation letters that were applicable to eConsults included: answering a direct question, providing a diagnosis, providing treatment options, providing education around the case, providing a prognosis, and arranging follow-up, clarity, and organization. Key differences between traditional and eConsult replies included the history and physical investigations, impression, plan, and rationale for plan/education. Conclusion: When seeking to improve the quality of specialist reply letters in both traditional and eConsult replies, one should consider differences in how information is collected and accessed, the role of each provider, and factors that impact specialist-to-PCP communication.

How long are Canadians waiting to access specialty care? Retrospective study from a primary care perspective.

OBJECTIVE: To calculate patient wait times for specialist care using data from primary care clinics across Canada. DESIGN: Retrospective chart audit. SETTING: Primary care clinics. PARTICIPANTS: A total of 22 primary care clinics across 7 provinces and 1 territory. MAIN OUTCOME MEASURES: Wait time 1, defined as the period between a patient's referral by a family physician to a specialist and the visit with said specialist. RESULTS: Overall, 2060 referrals initiated between January 2014 and December 2016 were included in the analysis. The median national wait time 1 was 78 days (interquartile range [IQR] of 34 to 175 days). The shortest waits were observed in Saskatchewan (51 days; IQR = 23 to 101 days) and British Columbia (59 days; IQR = 29 to 131 days), whereas the longest were in New Brunswick (105 days; IQR = 43 to 242 days) and Quebec (104 days; IQR = 36 to 239 days). Median wait time 1 varied substantially among different specialty groups, with the longest wait time for plastic surgery (159 days; IQR = 59 to 365 days) and the shortest for infectious diseases (14 days; IQR = 6 to 271 days). CONCLUSION: This is the first national examination of wait time 1 from the primary care perspective. It provides a picture of patient access to specialists across provinces and specialty groups. This research provides decision makers with important context for developing programs and policies aimed at addressing the largely ignored stage of the wait time continuum from the time of referral to eventual appointment time with the specialist.

Oxidative Addition of Alkenyl and Alkynyl Iodides to a AuI Complex.

The first isolated examples of intermolecular oxidative addition of alkenyl and alkynyl iodides to AuI are reported. Using a 5,5'-difluoro-2,2'-bipyridyl ligated complex, oxidative addition of geometrically defined alkenyl iodides occurs readily, reversibly and stereospecifically to give alkenyl-AuIII complexes. Conversely, reversible alkynyl iodide oxidative addition generates bimetallic complexes containing both AuIII and AuI centers. Stoichiometric studies show that both new initiation modes can form the basis for the development of C-C bond forming cross-couplings.

Observations of Electromagnetic Electron Holes and Evidence of Cherenkov Whistler Emission.

We report observations of electromagnetic electron holes (EHs). We use multispacecraft analysis to quantify the magnetic field contributions of three mechanisms: the Lorentz transform, electron drift within the EH, and Cherenkov emission of whistler waves. The first two mechanisms account for the observed magnetic fields for slower EHs, while for EHs with speeds approaching half the electron Alfvén speed, whistler waves excited via the Cherenkov mechanism dominate the perpendicular magnetic field. The excited whistler waves are kinetically damped and typically confined within the EHs.

Turbulence-Driven Ion Beams in the Magnetospheric Kelvin-Helmholtz Instability.

The description of the local turbulent energy transfer and the high-resolution ion distributions measured by the Magnetospheric Multiscale mission together provide a formidable tool to explore the cross-scale connection between the fluid-scale energy cascade and plasma processes at subion scales. When the small-scale energy transfer is dominated by Alfvénic, correlated velocity, and magnetic field fluctuations, beams of accelerated particles are more likely observed. Here, for the first time, we report observations suggesting the nonlinear wave-particle interaction as one possible mechanism for the energy dissipation in space plasmas.

Hydrofunctionalisation of an Aromatic Triphosphabenzene.

The aromatic heterocycle 2,4,6-tri-tert-butyl-1,3,5-triphosphabenzene reacts with a series of silanes, germanes and stannanes, with weaker E-H bonds reacting in an increasingly facile manner. All react by 1,4-addition to give bicyclic products with diastereomeric ratios varying with the substrate. Density functional theory (DFT) calculations show that activation of the E-H bond occurs across the 1,4-C/P axis of the triphosphabenzene, with the small energetic differences with respect to the stereochemistry of the addition offering insight into the experimentally observed diastereomeric ratios.

Development of Chronic Pseudomonas aeruginosa-Positive Respiratory Cultures in Children with Tracheostomy.

BACKGROUND: Up to 90% of children develop Pseudomonas aeruginosa (Pa)-positive respiratory cultures after tracheotomy. OBJECTIVE: To identify the factors associated with chronic Pa-positive respiratory cultures in the first 2 years after tracheotomy. METHODS: We conducted a retrospective cohort study of 210 children ≤ 18 years old who underwent tracheotomy at a single freestanding children's hospital that had two or more years of respiratory cultures post-tracheotomy available for analysis. We conducted multivariable logistic regression to test the association between demographic and clinical factors to our primary outcome of chronic Pa infection, defined as > 75% of respiratory cultures positive for Pa in the first 2 years after tracheotomy. RESULTS: Of the primarily male (61%), Hispanic (68%), and publicly insured (88%) cohort, 18% (n = 37) developed chronic Pa-positive respiratory cultures in the first 2 years. On multivariable logistic regression, pre-tracheotomy Pa-positive respiratory culture (aOR 11.3; 95% CI 4-1.5) and discharge on beta agonist (aOR 6.3; 95% CI 1.1-36.8) were independently associated with chronic Pa-positive respiratory cultures, while discharge on chronic mechanical ventilation was associated with decreased odds (aOR 0.3; 95% CI 0.1-0.7). On sensitivity analysis examining those without a pre-tracheotomy Pa-positive respiratory culture, discharge on MV continued to be associated with decreased odds of chronic Pa (aOR 0.1; 95% CI 0.02-0.4) and three other variables (male gender, chronic lung disease, and discharge on inhaled corticosteroids) were associated with increased odds of chronic Pa. CONCLUSION: Because pre-tracheotomy Pa growth on respiratory culture is associated with post-tracheotomy chronic Pa-positive respiratory cultures, future research should examine pre-tracheotomy Pa eradication or suppression protocols.