A multi-species, multi-pathogen avian viral disease outbreak event: Investigating potential for virus transmission at the wild bird - poultry interface.

AbstractA free-range organic broiler (Gallus gallus domesticus) premises in Staffordshire was infected by high pathogenicity avian influenza virus (HPAIV) H5N8 during the 2020-2021 epizootic in the United Kingdom (UK). Following initial confirmation of the infection in poultry, multiple wild bird species were seen scavenging on chicken carcasses. Detected dead wild birds were subsequently demonstrated to have been infected and succumbed to HPAIV H5N8. Initially, scavenging species, magpie (Pica pica) and raven (Corvus corax), were found dead on the premises but over the following days, buzzards (Buteo buteo) were also found dead within the local area with positive detection of HPAIV in submitted carcasses. The subacute nature of microscopic lesions within a buzzard was consistent with the timeframe of infection. Finally, a considerable number of free-living pheasants (Phasianus colchicus) were also found dead in the surrounding area, with carcasses having higher viral antigen loads compared to infected chickens. Limited virus dissemination was observed in the carcasses of the magpie, raven and buzzard. Further, an avirulent avian paramyxovirus type 1 (APMV-1) was detected within poultry samples as well as in the viscera of a magpie infected with HPAIV. Immunohistochemistry did not reveal colocalization of avian paramyxovirus antigens with lesions, supporting an avirulent APMV-1 infection. Overall, this case highlights scenarios in which bi-directional transmission of avian viral diseases between commercial and wild bird species may occur. It also underlines the importance of bio separation and reduced access when infection pressure from HPAIV is high.

Genetic Analysis of H5N1 High-Pathogenicity Avian Influenza Virus following a Mass Mortality Event in Wild Geese on the Solway Firth.

The United Kingdom (UK) and Europe have seen successive outbreaks of H5N1 clade 2.3.4.4b high-pathogenicity avian influenza virus (HPAIV) since 2020 peaking in the autumn/winter periods. During the 2021/22 season, a mass die-off event of Svalbard Barnacle Geese (Branta leucopsis) was observed on the Solway Firth, a body of water on the west coast border between England and Scotland. This area is used annually by Barnacle Geese to over-winter, before returning to Svalbard to breed. Following initial identification of HPAIV in a Barnacle Goose on 8 November 2021, up to 32% of the total Barnacle Goose population may have succumbed to disease by the end of March 2022, along with other wild bird species in the area. Potential adaptation of the HPAIV to the Barnacle Goose population within this event was evaluated. Whole-genome sequencing of thirty-three HPAIV isolates from wild bird species demonstrated that there had been two distinct incursions of the virus, but the two viruses had remained genetically stable within the population, whilst viruses from infected wild birds were closely related to those from poultry cases occurring in the same region. Analysis of sera from the following year demonstrated that a high percentage (76%) of returning birds had developed antibodies to H5 AIV. This study demonstrates genetic stability of this strain of HPAIV in wild Anseriformes, and that, at the population scale, whilst there is a significant impact on survival, a high proportion of birds recover following infection.

In vivo challenge studies on vaccinated chickens indicate a virus genotype mismatched vaccine still offers significant protection against NDV.

Although commercial vaccines against Newcastle Disease have been available for decades, outbreaks still occur in the face of vaccination Further vaccination may accelerate viral evolution resulting in a further reduction in vaccine efficacy. A key question is whether genotype-matched vaccines can confer better protection against contemporary type 1 Avian Paramyxoviruses. To assess this, an in vivo vaccine-challenge study was undertaken to assess protection afforded by 'genotype-matched' and commercial vaccine formulations. Groups of chickens were vaccinated twice (prime-boost) with an inactivated preparation of either La Sota Clone 30, AV632-chicken-Cyprus-13 (genotype VII.2), or mock vaccine, and later challenged with virulent AV632-chicken-Cyprus-13. Post vaccinal serological responses differed, although both vaccination/challenge groups showed similar levels of clinical protection compared to the unvaccinated group, where 100 % mortality was observed. Shedding was significantly reduced in the vaccinated groups compared to the unvaccinated group. Virus dissemination in the tissues of vaccinated birds was comparable, but onset of infection was delayed. Two mutations were observed in the HN gene of the heterologous vaccine group; H199N and I192M, the latter thought to be associated with increased fusogenic potential. These data demonstrate that existing vaccine formulations confer similar levels of clinical protection to contemporary strains and that the antigenic heterogeneity of circulating strains does not impact upon shedding profiles in immunised birds. In conclusion, the ability of virulent APMV-1 to cause disease in vaccinated flocks is unlikely to be the result of antigenic mismatch alone, and other factors likely contribute to vaccination failure and breakthrough.

Understanding the disease and economic impact of avirulent avian paramyxovirus type 1 (APMV-1) infection in Great Britain.

Newcastle disease (ND) is a notifiable disease affecting chickens and other avian species caused by virulent strains of Avian paramyxovirus type 1 (APMV-1). While outbreaks of ND can have devastating consequences, avirulent strains of APMV-1 generally cause subclinical infections or mild disease. However, viruses can cause different levels of disease in different species and virulence can evolve following cross-species transmission events. This report describes the detection of three cases of avirulent APMV-1 infection in Great Britain (GB). Case 1 emerged from the 'testing to exclude' scheme in chickens in Shropshire while cases 2 and 3 were made directly from notifiable avian disease investigations in chicken broilers in Herefordshire and on premises in Wiltshire containing ducks and mixed species, respectively). Class II/genotype I.1.1 APMV-1 from case 1 shared 99.94% identity to the Queensland V4 strain of APMV-1. Class II/genotype II APMV-1 was detected from case 2 while the class II/genotype I.2 virus from case 3 aligned closely with strains isolated from Anseriformes. Exclusion of ND through rapid detection of avirulent APMV-1 is important where clinical signs caused by avirulent or virulent APMV-1s could be ambiguous. Understanding the diversity of APMV-1s circulating in GB is critical to understanding disease threat from these adaptable viruses.

Investigating the Genetic Diversity of H5 Avian Influenza Viruses in the United Kingdom from 2020-2022.

Since 2020, the United Kingdom and Europe have experienced annual epizootics of high-pathogenicity avian influenza virus (HPAIV). The first epizootic, during the autumn/winter of 2020-2021, involved six H5Nx subtypes, although H5N8 HPAIV dominated in the United Kingdom. While genetic assessments of the H5N8 HPAIVs within the United Kingdom demonstrated relative homogeneity, there was a background of other genotypes circulating at a lower degree with different neuraminidase and internal genes.  Following a small number of detections of H5N1 in wild birds over the summer of 2021, the autumn/winter of 2021-2022 saw another European H5 HPAIV epizootic that dwarfed the prior epizootic. This second epizootic was dominated almost exclusively by H5N1 HPAIV, although six distinct genotypes were defined. We have used genetic analysis to evaluate the emergence of different genotypes and proposed reassortment events that have been observed. The existing data suggest that the H5N1 viruses circulating in Europe during late 2020 continued to circulate in wild birds throughout 2021, with minimal adaptation, but then went on to reassort with AIVs in the wild bird population. We have undertaken an in-depth genetic assessment of H5 HPAIVs detected in the United Kingdom over two winter seasons and demonstrate the utility of in-depth genetic analyses in defining the diversity of H5 HPAIVs circulating in avian species, the potential for zoonotic risk, and whether incidents of lateral spread can be defined over independent incursions of infections from wild birds. This provides key supporting data for mitigation activities. IMPORTANCE High-pathogenicity avian influenza virus (HPAIV) outbreaks devastate avian species across all sectors, having both economic and ecological impacts through mortalities in poultry and wild birds, respectively. These viruses can also represent a significant zoonotic risk. Since 2020, the United Kingdom has experienced two successive outbreaks of H5 HPAIV. While H5N8 HPAIV was predominant during the 2020-2021 outbreak, other H5 subtypes were also detected. The following year, there was a shift in the subtype dominance to H5N1 HPAIV, but multiple H5N1 genotypes were detected. Through the thorough utilization of whole-genome sequencing, it was possible to track and characterize the genetic evolution of these H5 HPAIVs in United Kingdom poultry and wild birds. This enabled us to assess the risk posed by these viruses at the poultry-wild bird and the avian-human interfaces and to investigate the potential lateral spread between infected premises, a key factor in understanding the threat to the commercial sector.

Identifying and describing trajectories of alcohol use frequency and binge drinking frequency among those aged 15-30 years in a national cohort of US adolescents: A group-based trajectory modeling approach.

BACKGROUND AND AIMS: Analyzing long-term trajectories of alcohol use has the potential to strengthen policy and intervention priorities and timing. We identified and described trajectories of alcohol use and binge drinking frequency from mid-adolescence to early adulthood and measured the association of the role of early drinking initiation with trajectory membership. DESIGN, SETTING, PARTICIPANTS: This was a longitudinal cohort study conducted in the United States. The National Longitudinal Survey of Youth 1997 is a nationally representative cohort of youth aged 12-16 years at baseline. The analytic sample included individuals who participated in two or more annual interviews between ages 15 and 30 years (n = 8809). MEASUREMENTS: Participants self-reported the number of days in the past 30 days they: (1) drank alcohol and (2) binge drank (five or more drinks on one occasion). We used group-based trajectory modeling to identify distinct trajectories from ages 15-30 years of past 30-day drinking and past 30-day binge drinking. Using multinomial logistic regression, we evaluated associations between early drinking initiation (≤ 14 years) and key demographics with trajectory membership. FINDINGS: We identified five past 30-day drinking groups: late-escalating (16.0%), moderate frequency (19.0%), high frequency (11.2%), low frequency (35.4%) and no/infrequent (18.4%). Early drinking initiation (versus later) was associated with higher odds of membership in the moderate [adjusted multinomial odds ratio (aMOR) = 4.88; 95% confidence interval (CI) = 4.00, 5.94] and high-frequency groups (aMOR = 4.68; 95% CI = 3.74, 5.86) than in the no/infrequent comparator trajectory. We identified five groups with distinct binge drinking frequency patterns: later escalating (9.9%), high frequency (3.9%), low frequency (28.7%), earlier onset (9.5%) and no/infrequent (48.0%). Early initiation was associated with increased odds of membership in earlier-onset and high-frequency groups compared with the no/infrequent group. For both outcomes, additional differences in probability of group membership were identified by gender, racial identity, parental factors (religiosity, high school completion) and household characteristics (household size, income, and region of residence). CONCLUSIONS: Youth in the United States appear to follow heterogeneous drinking and binge drinking trajectories from adolescence into adulthood. These may include higher-use trajectories as well as trajectories with different escalation timing (e.g. earlier versus later). Early initiation of drinking may increase risk of membership in higher- and earlier-use trajectory groups.

The production of Newcastle disease virus-like particles in Nicotiana benthamiana as potential vaccines.

Newcastle disease (ND) is a highly contagious viral respiratory and neurological disease that has a severe impact on poultry production worldwide. In the present study, an expression platform was established for the transient production in N.bethamiana of ND virus-like particles (VLPs) for use as vaccines against ND. The expression of the ND Fusion (F) and/or Hemagglutinin-neuraminidase (HN) proteins of a genotype VII.2 strain formed ND VLPs in planta as visualized under the transmission electron microscope, and HN-containing VLPs agglutinated chicken erythrocytes with hemagglutination (HA) titres of up to 13 log2.The immunogenicity of the partially-purified ND VLPs was confirmed in specific-pathogen-free White leghorn chickens. Birds receiving a single intramuscular immunization with 1024 HA units (10 log2) of the F/HN ND VLPs administered with 20% [v/v] Emulsigen®-P adjuvant, seroconverted after 14 days with F- and HN-specific antibodies at ELISA titres of 5705.17 and HI geometric mean titres (GMTs) of 6.2 log2, respectively. Furthermore, these ND-specific antibodies successfully inhibited viral replication in vitro of two antigenically closely-related ND virus isolates, with virus-neutralization test GMTs of 3.47 and 3.4, respectively. Plant-produced ND VLPs have great potential as antigen-matched vaccines for poultry and other avian species that are highly immunogenic, cost-effective, and facilitate prompt updating to ensure improved protection against emerging ND field viruses.

Game Birds Can Act as Intermediaries of Virulent Genotype VII Avian Orthoavulavirus-1 between Wild Birds and Domestic Poultry.

Newcastle Disease (ND), caused by virulent forms of Avian orthoavulavirus serotype-1 (AOAV-1) is an economically important avian disease worldwide. The past two incursions of ND into the United Kingdom occurred in game bird populations during 2005 and 2006. The nature of the game bird semi-feral rearing system, which can bring these birds into close contact with both wild birds and commercial or backyard poultry, has been hypothesized to act as a bridge between these two environments. As such, the risk that AOAV-1-infected game birds may pose to the UK poultry industry was investigated. Pheasants, partridges and chickens were experimentally infected with the virulent strain APMV-1/Chicken/Bulgaria/112/13, a genotype VII.2 virus associated with ND outbreaks in Eastern Europe. The study demonstrated that both chickens and pheasants are susceptible to infection with APMV-1/Chicken/Bulgaria/112/13, which results in high mortality and onward transmission. Partridges by contrast are susceptible to infection, but mortality was reduced, as was onward transmission. However, the data indicated that both pheasants and partridges may serve as intermediate hosts of AOAV-1 and may bridge the wild bird-domestic poultry interface enabling transmission into an economically damaging environment where morbidity and mortality may be high.

Comparative pathogenesis of two genotype VI.2 avian paramyxovirus type-1 viruses (APMV-1) in pheasants, partridges and chickens.

Newcastle disease (ND) is caused by virulent forms of avian paramyxovirus-1 (APMV-1) and is an economically important disease of poultry world-wide. Pigeon paramyxovirus 1 (PPMV-1), a sub-group of APMV-1 is endemic in Columbiformes and can cause infections of poultry. An outbreak of ND in partridges in Scotland, UK, in 2006 (APMV-1/partridge/UK(Scotland)/7575/06) was identified as a class II, genotype VI.2.1.1.2.1, more commonly associated with PPMV-1. It has been hypothesized that game birds may be a route of transmission into commercial poultry settings due to the semi-feral rearing system, which potentially brings them into contact with both wild-birds and poultry species. Therefore, the pathogenesis and transmission of APMV-1/partridge/UK(Scotland)/7575/06 in game birds and chickens was investigated, and compared to a contemporary PPMV-1 isolate, PPMV-1/pigeon/UK/015874/15. Viral shedding and seroconversion profiles demonstrated that pheasants were susceptible to infection with APMV-1/partridge/UK(Scotland)/7575/06 with limited clinical signs observed although they were able to excrete and transmit virus. In contrast, partridges and pheasants showed limited infection with PPMV-1/pigeon/UK/015874/15, causing mild clinical disease. Chickens, however, were productively infected and were able to transmit virus in the absence of clinical signs. From the data, it can be deduced that whilst game birds may play a role in the transmission and epidemiology of genotype VI.2 APMV-1 viruses, the asymptomatic nature of circulation within these species precludes evaluation of natural infection by clinical surveillance. It therefore remains a possibility that genotype VI.2 APMV-1 infection in game birds has the potential for asymptomatic circulation and remains a potential threat to avian production systems.RESEARCH HIGHLIGHTS Demonstration of infection of game birds with Pigeon paramyxovirus-1 (PPMV-1).There are differing dynamics of infection between different game bird species.Differing dynamics of infection between different PPMV-1 isolates and genotypes in game birds and chickens.

Shift in HPAI infection dynamics causes significant losses in seabird populations across Great Britain.

This focus article has been prepared by Marco Falchieri, Scott M. Reid, Craig S. Ross, Joe James, Alexander M. P. Byrne, Madalina Zamfir, Ian H. Brown and Ashley C. Banyard of the APHA; Glen Tyler and Emma Philip of NatureScot; and Will Miles of Scottish Oceans Institute, School of Biology, University of St Andrews.

Distinct groups of firearm owners with differential risk for suicide in the United States: A latent class analysis.

Suicide is a leading cause of mortality and firearm suicide accounts for the majority of fatalities. Firearm owners are a diverse population and firearm-specific suicide prevention programs should be tailored to distinct at-risk firearm-owning groups. This study set out to identify groups of firearm owners with differential suicide risk having unique characteristics that could be used to customize suicide prevention efforts. We conducted a nationally-representative survey of 2646 firearm owners to assess individual suicide risk, suicide risk factors, and demographic characteristics. A Latent Class Analysis identified unique segments of firearm owners at increased risk of suicide with similar underlying suicide risk factors and demographic characteristics. We found almost one in ten (9.6%) of firearm owners were at increased risk of suicide with 25% reporting suicide ideation, 6.6% reporting suicide planning, and 1.8% reporting previous suicide attempts. We identified three unique groups of firearm owners with higher than average suicide risk. Relative to other groups of firearm owners, one at-risk group were more affluent with a history of adverse experiences and mental health challenges, a second group had more male veterans with high levels of alcohol consumption, and third group had more non-heterosexual women who experienced trauma. We conclude that there are three unique groups of firearm owners with higher than average suicide risk with very different characteristics. In addition to broad suicide prevention efforts, customized firearm suicide prevention programs should be developed individually for these different firearm-owning populations, taking into consideration the unique suicide risk factors and demographics of each group.

Prospective association between e-cigarette use frequency patterns and cigarette smoking abstinence among adult cigarette smokers in the United States.

AIMS: To estimate the association of longitudinal patterns of e-cigarette use with cigarette smoking abstinence, after accounting for time-dependent confounding and selection bias. DESIGN: Secondary analysis of longitudinal national cohort data. Using marginal structural models and four waves of the population assessment of tobacco and health (wave 1, 2013-14; wave 2, 2014-15; wave 3, 2015-16; wave 4, 2016-18), we estimated the association of vaping frequency across waves 2 and 3 with 12-month sustained cigarette smoking abstinence at wave 4, adjusting for time-dependent confounders at waves 1 and 2 and selection bias due to drop-out with inverse probability of treatment and censoring weights. SETTING: United States. PARTICIPANTS/CASES: A total of 5699 adults (18+ years) who smoked cigarettes and did not vape at wave 1. MEASUREMENTS: The exposure was vaping frequency at waves 2 and 3 (non-use, non-daily use, daily use), representing nine possible combinations of vaping frequency across two waves. Non-use at both waves was the exposure reference group. The primary outcome was sustained 12-month cigarette smoking abstinence at wave 4. FINDINGS: Among 5699 adults who smoked cigarettes at wave 1, a total of 560 (9.8%) reported smoking abstinence at wave 4. Compared with nonuse at both waves, daily vaping at both waves [risk ratio (RR) = 3.82, 95% confidence interval (CI) = 2.59-5.64] and non-use at wave 2 followed by daily vaping at wave 3 (RR = 2.50, 95% CI = 1.66-3.77) were positively associated with smoking abstinence; non-daily vaping at both waves was inversely associated with smoking abstinence (RR = 0.28, 95% CI = 0.11-0.75). Results persisted after accounting for misclassification of e-cigarette use and cigarette smoking abstinence and after restricting to participants with plans to quit smoking. CONCLUSIONS: In a US cohort of adult smokers, longitudinal patterns of vaping frequency appear to predict smoking abstinence, even after accounting for several sources of systematic error. Consistent daily vaping is associated with increased chances of cigarette smoking abstinence, while consistent non-daily vaping is associated with decreased chances of smoking abstinence.

JMM Profile: Avian paramyxovirus type-1 and Newcastle disease: a highly infectious vaccine-preventable viral disease of poultry with low zoonotic potential.

Newcastle disease (ND) is a highly contagious disease of poultry caused by virulent avian paramyxovirus-1 (APMV-1) (previously termed avian avulavirus-1 and avian orthoavulavirus-1). APMV-1 is endemic in poultry in many developing countries, whilst outbreaks still occur in developed countries, affecting both commercial and backyard flocks. ND outbreaks can have substantial economic consequences due to high mortality rates and the imposition of trade restrictions. APMV-1 nucleic acid can be detected from swabs or tissues of suspected cases by PCR. Evidence of infection or vaccination may be demonstrated by the presence of specific antibodies against HN in serum samples. No anti-viral treatments exist, but vaccines are available, although there are currently concerns over their efficacy.

Smartphone-Guided Self-prone Positioning vs Usual Care in Nonintubated Hospital Ward Patients With COVID-19: A Pragmatic Randomized Clinical Trial.

BACKGROUND: Safe, effective, and easily implementable treatments that reduce the progression of respiratory failure in COVID-19 are urgently needed. Despite the increased adoption of prone positioning during the pandemic, the effectiveness of this technique on progression of respiratory failure among nonintubated patients is unclear. RESEARCH QUESTION: What is the effectiveness of smartphone-guided self-prone positioning recommendations and instructions compared with usual care in reducing progression of respiratory failure among nonintubated patients with COVID-19? STUDY DESIGN AND METHODS: Awake Prone Position for Early Hypoxemia in COVID-19 (APPEX-19) is a multicenter randomized clinical trial that randomized nonintubated adults with COVID-19 on < 6 L/min of supplemental oxygen to receive a smartphone-guided self-prone positioning intervention or usual care. The primary outcome was the composite of respiratory deterioration (an increase in supplemental oxygen requirement) or ICU transfer. Using a Bayesian statistical approach, the posterior probability of superiority within each treatment arm (superiority threshold 95%) was calculated. RESULTS: The trial was stopped early for slow enrollment. A total of 293 participants were included in the modified intention-to-treat analysis (159 self-prone positioning intervention and 134 usual care). Among participants who self-reported body positioning (n = 139 [70 intervention, 69 usual care]), 71.4% in the intervention arm and 59.4% in the usual care arm attempted prone positioning. Thirty-one participants (posterior mean, 24.7%; 95% credible interval, 18.6-31.4) receiving usual care and 32 participants (posterior mean, 22.1%; 95% credible interval, 16.6-28.1) receiving the self-prone positioning intervention experienced the primary outcome; the posterior probability of superiority for the self-prone positioning intervention was 72.1%, less than the 95% threshold for superiority. Adverse events occurred in 26.9% of participants in the usual care arm and in 11.9% of participants in the intervention arm. INTERPRETATION: Among nonintubated patients with COVID-19, smartphone-guided self-prone positioning recommendations and instructions did not promote strong adherence to prone positioning. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov; No.: NCT04344587; URL: www. CLINICALTRIALS: gov.

e-Cigarette Use and Combustible Cigarette Smoking Initiation Among Youth: Accounting for Time-Varying Exposure and Time-Dependent Confounding.

BACKGROUND: Youth e-cigarette use is associated with the initiation of combustible cigarette smoking, but prior studies have rarely accounted for time-varying measures of e-cigarette exposure or time-dependent confounding of e-cigarette use and smoking initiation. METHODS: Using five waves of the Population Assessment of Tobacco and Health (2013-2019), we estimated marginal structural models with inverse probability of treatment and censoring weights to examine the association between time-varying e-cigarette initiation and subsequent cigarette smoking initiation among e-cigarette- and cigarette-naïve youth (12-17 years) at baseline. Time-dependent confounders used as predictors in inverse probability weights included tobacco-related attitudes or beliefs, mental health symptoms, substance use, and tobacco-marketing exposure. RESULTS: Among 9,584 youth at baseline, those who initiated e-cigarettes were 2.4 times as likely to subsequently initiate cigarette smoking as youth who did not initiate e-cigarettes (risk ratio = 2.4, 95% confidence interval [CI] = 2.1, 2.7), after accounting for time-dependent confounding and selection bias. Among youth who initiated e-cigarettes, more frequent vaping was associated with greater risk of smoking initiation (risk ratio ≥3 days/month = 1.8, 95% CI = 1.4, 2.2; 1-2 days/month = 1.2; 95% CI = 0.93, 1.6 vs. 0 days/month). Weighted marginal structural model estimates were moderately attenuated compared with unweighted estimates adjusted for baseline-only confounders. At the US population level, we estimated over half a million youth initiated cigarette smoking because of prior e-cigarette use over follow-up. CONCLUSIONS: The association between youth vaping and combustible cigarette smoking persisted after accounting for time-dependent confounding. We estimate that e-cigarette use accounts for a considerable share of cigarette initiation among US youth. See video abstract at, http://links.lww.com/EDE/B937.

The association between depression symptom endorsement and glycemic outcomes in adolescents with type 1 diabetes.

OBJECTIVE: The prevalence of depression among adolescents with type 1 diabetes is estimated to be 2-3 times higher than in the general population. In adults with type 1 diabetes and depression, short-term outcomes are worse compared to individuals just diagnosed with type 1 diabetes. This study aims to determine if depressive symptom endorsement is associated with glycemic outcomes and short-term complications in adolescents with type 1 diabetes. RESEARCH DESIGN AND METHODS: Analysis was conducted using electronic medical records from the T1D Exchange Quality Improvement Collaborative. Adolescents with type 1 diabetes, aged 12-18, receiving treatment in a diabetes clinic who had been screened for depression with the PHQ-9 between 2016 and 2018 were eligible for inclusion. Individuals must have also had HbA1c data available from the day of depression screening and from 10 to 24 weeks after screening; the final sample size was 1714. RESULTS: Almost 30% of adolescents endorsed mild or greater (PHQ-9 ≥ 5) depressive symptoms. Endorsement of mild or greater depressive symptoms was associated with an 18% increased risk of an HbA1c ≥7.5% and a 42% increased risk of an HbA1c ≥9.0% on the day of screener administration. Depressive symptom endorsement was also associated with an 82% increased risk for DKA. CONCLUSIONS: This study suggests that depression symptoms are associated with an increased risk for elevated HbA1c and short-term complications. With the rising incidence of type 1 diabetes in youth, routine screening, and appropriate management of depression is needed.

Association of device type, flavours and vaping behaviour with tobacco product transitions among adult electronic cigarette users in the USA.

BACKGROUND: Few studies assess whether electronic cigarette (e-cigarette) device characteristics or flavours impact longitudinal patterns of cigarette and e-cigarette use. DESIGN: We examined data from waves 2-4 of the Population Assessment of Tobacco and Health Study (2014-2018). Among adult (≥18 years) current e-cigarette users at wave 2 who were current smokers (dual users; n=1759) and former smokers (exclusive e-cigarette users; n=470), we classified participants into four use patterns at wave 3 (~12 months later) and wave 4 (~24 months later): (1) dual use of e-cigarettes and cigarettes; (2) exclusive cigarette smoking; (3) exclusive e-cigarette use; (4) non-use of both products. We used multinomial logistic regression to assess correlates of changing use patterns at 24 months, relative to no change, adjusting for sociodemographic factors. RESULTS: At 24 months, 26.5% of baseline exclusive e-cigarette users, and 9% of baseline dual users, abstained from both vaping and smoking. Participants who vaped non-tobacco flavours (vs tobacco flavours), and used refillable tank or modifiable devices (vs disposable, cartridges and other devices) were less likely to transition to non-use of both products and to exclusive cigarette smoking. Baseline daily vaping (vs non-daily) was positively associated with exclusive e-cigarette use at 24 months for baseline daily cigarette smokers, but negatively associated with exclusive e-cigarette use and non-use of both products at 24 months for baseline non-daily smokers. CONCLUSIONS: Non-tobacco flavours, daily vaping and modifiable e-cigarette devices may help some smokers abstain from cigarette smoking via transitioning to exclusive e-cigarette use, but are also associated with ongoing exclusive e-cigarette use.

Comparison of Serological Assays for the Detection of SARS-CoV-2 Antibodies.

SARS-CoV-2 virus was first detected in late 2019 and circulated globally, causing COVID-19, which is characterised by sub-clinical to severe disease in humans. Here, we investigate the serological antibody responses to SARS-CoV-2 infection during acute and convalescent infection using a cohort of (i) COVID-19 patients admitted to hospital, (ii) healthy individuals who had experienced 'COVID-19 like-illness', and (iii) a cohort of healthy individuals prior to the emergence of SARS-CoV-2. We compare SARS-CoV-2 specific antibody detection rates from four different serological methods, virus neutralisation test (VNT), ID Screen® SARS-CoV-2-N IgG ELISA, Whole Antigen ELISA, and lentivirus-based SARS-CoV-2 pseudotype virus neutralisation tests (pVNT). All methods were able to detect prior infection with COVID-19, albeit with different relative sensitivities. The VNT and SARS-CoV-2-N ELISA methods showed a strong correlation yet provided increased detection rates when used in combination. A pVNT correlated strongly with SARS-CoV-2 VNT and was able to effectively discriminate SARS-CoV-2 antibody positive and negative serum with the same efficiency as the VNT. Moreover, the pVNT was performed with the same level of discrimination across multiple separate institutions. Therefore, the pVNT is a sensitive, specific, and reproducible lower biosafety level alternative to VNT for detecting SARS-CoV-2 antibodies for diagnostic and research applications. Our data illustrate the potential utility of applying VNT or pVNT and ELISA antibody tests in parallel to enhance the sensitivity of exposure to infection.

Evaluation of monitoring youth exposure to alcohol advertising on cable television, United States 2016-19.

BACKGROUND AND AIMS: Exposure to alcohol advertising is associated with underage drinking, which contributes to adolescent morbidity and mortality. Alcohol advertisements are regulated by the alcohol industry. Our research team has published reports monitoring alcohol advertisers' compliance with industry guidelines. In this study, we estimated: (1) changes in youth and adult exposure to alcohol advertisements on cable television from 2016-19 and (2) changes in youth exposure to types of non-compliant advertising highlighted in monitoring reports over the same period. DESIGN: Interrupted time-series analysis using data from Nielsen US national television audience estimates, 2012-19. MEASURES AND METHODS: Outcome was advertising impressions (the total number of times an alcohol advertisement was viewed by youth or adults) by month. Non-compliant exposure was impressions from advertisements that did not meet guidelines. Covariates were advertising spending in multiple media categories. Seasonal autoregressive integrated moving average models estimated trends in exposure before the publication of monitoring reports (2012-15 reference period) and during the monitoring period (2016-19). We compared the modeled exposure trend during the monitoring period to the reference period projected trend. SETTING: United States. PARTICIPANTS: A total of 57 000 Nielsen panel households FINDINGS: Non-compliant exposure declined 6158 [95% confidence interval (CI) = -11 406 to -911] million impressions, or -77.3% during the monitoring period compared with the reference period trend. Total youth exposure declined by 20 995 (CI = -34 701 to -7288) million impressions (27.0%). Non-compliant exposure on programs, network dayparts and brands highlighted in monitoring reports declined by -82.4, -79.0 and -82.2%-more than other programs (-52.7%), network dayparts (-71.0%) or brands (143%). Adult exposure declined by 9.3%. CONCLUSIONS: Publication of alcohol advertising monitoring reports appears to have been associated with a 27.0% decline in US youth exposure to alcohol advertising on cable television and a 77.3% decline in US youth exposure to non-compliant alcohol advertising.