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International time trends in asthma mortality have been strongly affected by changes in management and in particular drug treatments. However, little is known about how asthma mortality has changed over the past decade. In this study, we assessed these international trends. We collated age-standardised country-specific asthma mortality rates in the 5–34 year age group from the online WHO Mortality Database for 46 countries. To be included in the analysis, we specified that a country must have 10 years of complete data in the WHO Mortality Database between 1993 and 2012. In the absence of consistent and accurate asthma prevalence and prescribing data, we chose to use a locally weighted scatter plot smoother (LOESS) curve, weighted by the individual country population in the 5–34-year age group to show the global trends in asthma mortality rates with time. Of the 46 countries included in the analysis of asthma mortality, 36 were high-income countries, and 10 were middle-income countries. The LOESS estimate of the global asthma mortality rate was 0·44 deaths per 100 000 people (90% CI 0·39–0·48) in 1993 and 0·19 deaths per 100 000 people (0·18–0·21) in 2006. Despite apparent further reductions in some countries and regions of the world, there was no appreciable change in global asthma mortality rates from 2006 through to 2012, when the LOESS estimate was also 0·19 deaths per 100 000 people (0·16–0·21). The trend for reduction in global asthma mortality observed since the late 1980s might have stalled, with no appreciable difference in a smoothed LOESS curve of asthma mortality from 2006 to 2012. Although better implementation of established management strategies that have been shown to reduce mortality risk is needed, to achieve a further substantive reduction in global asthma mortality novel strategies will also be required. The Medical Research Institute of New Zealand, which is supported by Health Research Council of New Zealand Independent Research Organisation.

Studies exploring the effect of television viewing on obesity throughout childhood are conflicting. Most studies have been confined to single high-income countries. Our aim was to examine the association between television viewing habits and Body Mass Index (BMI) in adolescents and children in a multicentre worldwide sample. In the International Study of Asthma and Allergies in Children Phase Three, adolescents aged between 12 and 15 years completed questionnaires which included questions on television viewing habits, height and weight. Parents/guardians of children aged between 5 and 8 years completed the same questionnaire on behalf of their children. The questionnaire asked \"During a normal week, how many hours a day (24 hours) do you (does your child) watch television?\" Responses were categorised as; \"short\" (<1 hour), \"moderate\" (1 to ≤3 hours), \"long\" (3 to ≤5 hours) and \"prolonged\" (>5 hours). 207,672 adolescents from 37 countries and 77,003 children from 18 countries provided data. Daily television viewing in excess of one hour was reported in 89% of adolescents and 79% of children. Compared with adolescents in the short viewing group, those in the moderate, long and prolonged groups had BMIs that were 0.14 kg/m(2), 0.21 kg/m(2), 0.30 kg/m(2) and 0.08 kg/m(2), 0.16 kg/m(2) and 0.17 kg/m(2) larger for females and males respectively (both P<0.001). Compared with children in the short viewing group, those in the moderate, long and prolonged groups had BMIs that were 0.24 kg/m(2), 0.34 kg/m(2), 0.36 kg/m(2) and 0.19 kg/m(2), 0.32 kg/m(2) and 0.36 kg/m(2) larger for females and males respectively (both P<0.001). Increased television viewing hours were positively associated with BMI in both adolescents and children with an apparent dose response effect. These findings extend the evidence that television viewing contributes to increased BMI in childhood.

ObjectiveTo characterise the self-isolating household units (bubbles) during the COVID-19 Alert Level 4 lockdown in New Zealand.Design, setting and participantsIn this cross-sectional study, an online survey was distributed to a convenience sample via Facebook advertising and the Medical Research Institute of New Zealand’s social media platforms and mailing list. Respondents were able to share a link to the survey via their own social media platforms and by email. Results were collected over 6 days during Alert Level 4 from respondents living in New Zealand, aged 16 years and over.Main outcomes measuresThe primary outcome was the mean size of a self-isolating household unit or bubble. Secondary outcomes included the mean number of households in each bubble, the proportion of bubbles containing essential workers and/or vulnerable people, and the mean number of times the home was left each week.Results14 876 surveys were included in the analysis. The mean (SD) bubble size was 3.58 (4.63) people, with mean (SD) number of households 1.26 (0.77). The proportion of bubbles containing one or more essential workers, or one or more vulnerable persons was 45.3% and 42.1%, respectively. The mean number of times individual bubble members left their home in the previous week was 12.9 (12.4). Bubbles that contained at least one vulnerable individual had fewer outings over the previous week compared with bubbles that did not contain a vulnerable person. The bubble sizes were similar by respondent ethnicity.ConclusionIn this New Zealand convenience sample, bubble sizes were small, mostly limited to one household, and a high proportion contained essential workers and/or vulnerable people. Understanding these characteristics from a country which achieved a low COVID-19 infection rate may help inform public health interventions during this and future pandemics.

ObjectivesAs-needed low-dose combination budesonide-formoterol is recommended by asthma guidelines in many countries as an alternative to maintenance inhaled corticosteroids (ICS) for treatment of mild asthma, but there are few data on patient attitudes toward these regimens. This study explored the comparative implementation experiences and future treatment preferences of mild asthma patients who had experienced these two treatment regimens.SettingA subgroup of adults randomised to maintenance ICS or as-needed ICS-formoterol in a multinational, 52-week open-label randomised controlled trial (NovelSTART) in mild asthma patients were interviewed to explore their motivations for treatment use during the study and their preferences for future treatment.ParticipantsSemistructured interviews were conducted with 74 participants (Maintenance group: n=39, As-needed group n=35, mean age 38 (range 19–69)) and thematically analysed from transcribed audiorecordings.ResultsEmergent themes from analysis comprised: ‘How much my asthma affects me’ (how their asthma’s impact affected their self-management motivation); ‘What I know about asthma’ (limited knowledge impeded appropriate self-management decision making); ‘How much effort this treatment regimen involves for me’ (treatment complexity and/or difficulty establishing a medication routine impeded implementation, particularly in the Maintenance group); and ‘My beliefs about the benefits and risks of this treatment’ (patients who considered their treatment as ineffective, eg, limited difference in symptoms relative to salbutamol (both groups) or slower onset of relief (As-needed group) had poor motivation to use the treatment). Due to the simplicity of the as-needed combination strategy, this was the preferred future regimen, even by patients who had not yet tried it.ConclusionsKey patient perspectives on the implementation of preventer treatments for mild asthma included factors relating to perceived asthma burden, disease knowledge, treatment complexity and treatment usefulness or safety. The as-needed budesonide-formoterol regimen was preferred to maintenance ICS treatment in mild asthma though patient education is urgently needed to address implementation motivation.Trial registration numberACTRN12615000999538.

The increasing prevalence of overweight and obesity in childhood has implications for their future health. There are many potential contributors to overweight and obesity in childhood. The aim was to investigate the association between postulated risk factors and body mass index (BMI) in children and adolescents. Secondary analysis of data from a multi-centre, multi-country, cross-sectional study (ISAAC Phase Three). Parents/guardians of children aged 6-7 years completed a questionnaire about their child's current height and weight, and the postulated risk factors. Adolescents aged 13-14 years reported their own height and weight and answered questions about the postulated risk factors. A general linear mixed model was used to determine the association between BMI and the postulated risk factors. Imputation was used if there were missing responses for 3 or fewer explanatory variables. 65,721 children (27 centres, 15 countries) and 189,282 adolescents (70 centres, 35 countries) were included in the final analyses. Many statistically significant associations were identified, although for most variables the effect sizes were small. In children birth weight (for each kg increase in birth weight the BMI increased by +0.43 kg/m2, p<0.001), television viewing (5+ hours/day +0.33 kg/m2 vs. <1 hour/day, p<0.001), fast food (≥3 times/week +0.16 kg/m2 vs. never, p<0.001) vigorous physical activity (3+ hours/week 0.071 kg/m2 vs. never, p = 0.023) and maternal smoking in the first year of life (+0.13 kg/m2, p<0.001) were associated with a higher BMI in the adjusted model. Nut consumption (≥3 times/week -0.11 kg/m2 vs. never, p = 0.002) was associated with a lower BMI. Early life exposures (antibiotics, paracetamol and breast feeding) were also associated with BMI. For adolescents statistically significant associations with BMI and were seen with maternal smoking (+0.25 kg/m2, p<0.001), television viewing (5+ hours/day +0.23 kg/m2 vs. <1 hour/day, p<0.001), fast food (≥3 times/week -0.19 kg/m2 vs. never, p<0.001), vigorous physical activity (3+ hours/week 0.047 kg/m2 vs. never, p<0.001) and nuts (≥3 times/week -0.22 kg/m2 vs. never, p<0.001). Although several early life exposures were associated with small differences in BMI, most effect sizes were small. Larger effect sizes were seen with current maternal smoking, television viewing (both with higher BMI) and frequent nut consumption (lower BMI) in both children and adolescents, suggesting that current behaviours are more important than early exposures. Although many variables may influence BMI in childhood, the putative factors studied are not of sufficient magnitude to support major public health interventions.

We investigated the time course of change of type-2 asthma biomarkers after a severe asthma exacerbation. Blood eosinophils were lowest immediately after treatment was initiated (0.07 vs 0.33×109/L, p<0.001) while serum IgE levels were at their highest (339 vs 249 U/L, p<0.001). Fractional exhaled Nitric Oxide levels were lowest 2 weeks after treatment (23 vs 33 ppb, p=0.06) and serum periostin levels were lowest 1 week after treatment (45·9 vs 50·9 ng/mL, p<0.001). A delay of 4–8 weeks following a severe exacerbation is required if these biomarkers are used to guide the ongoing management of patients with asthma.Trial registration numberPost-results; The Australia New Zealand Trial Registry, >ACTRN12614000443695.

Background Literature on factors influencing medication adherence within paediatric clinical trials is sparse. The Paracetamol and Ibuprofen in the Primary Prevention of Asthma in Tamariki (PIPPA Tamariki) trial is an open-label, randomised controlled trial aiming to determine whether paracetamol treatment, compared with ibuprofen treatment, as required for fever and pain in the first year of life, increases the risk of asthma at age six years. To inform strategies for reducing trial medication crossovers, understanding factors influencing the observed ibuprofen-to-paracetamol crossovers (non-protocol adherence) is vital. The aim of this study was to investigate the factors influencing the decision-making process when administering or prescribing ibuprofen to infants that may contribute to the crossover events in the PIPPA Tamariki trial. Methods Constructivist grounded theory methods were employed. We conducted semi-structured interviews of caregivers of enrolled PIPPA Tamariki infants and healthcare professionals in various healthcare settings. Increasing theoretical sensitivity of the interviewers led to theoretical sampling of participants who could expand on the teams’ early constructed codes. Transcribed interviews were coded and analysed using the constant comparative method of concurrent data collection and analysis. Results Between September and December 2020, 20 participants (12 caregivers; 8 healthcare professionals) were interviewed. We constructed a grounded theory of prioritising infant welfare that represents a basic social process when caregivers and healthcare professionals medicate feverish infants. This process comprises three categories: historical , trusting relationships and being discerning ; and is modified by one condition: being conflicted . Participants bring with them historical ideas. Trusting relationships with researchers, treating clinicians and family play a central role in enabling participants to challenge historical ideas and be discerning. Trial medication crossovers occur when participants become conflicted, and they revert to historical practices that feel familiar and safer. Conclusions We identified factors and a basic social process influencing ibuprofen use in infants and trial medication crossover events, which can inform strategies for promoting adherence in the PIPPA Tamariki trial. Future studies should explore the role of trusting relationships between researchers and treating clinicians when conducting research.

Background Fluticasone furoate/Vilanterol trifenatate (FF/VI) is an inhaled corticosteroid/long-acting beta-agonist combination with a prolonged bronchodilator duration of action. We characterised the time-course of onset and offset of airway anti-inflammatory action of FF/VI, as assessed by fraction of exhaled nitric oxide (FeNO), and compared this to the bronchodilator duration of action. Methods A single-centre, randomised, double-blind, placebo-controlled, two-period, crossover study was undertaken in 28 steroid-naïve adults with asthma. Participants with an FEV 1  ≥ 60% predicted, reversible airway disease, and FeNO > 40 ppb received FF/VI 100/25 mcg or placebo once daily for 14 days. FeNO and peak expiratory flow were measured twice-daily during treatment and during a 21-day washout period. FEV 1 was measured for five days from treatment cessation. The primary outcome measure was FeNO change from baseline ratio for 21 days following treatment cessation. Results In the 27 subjects who completed the study, median (range) baseline FeNO was 87 ppb (42–212). FF/VI 100/25 mcg reduced FeNO by day 3, ratio FF/VI versus placebo 0.72 (95% confidence interval 0.61–0.86) with the maximum reduction occurring at day 14, 0.32 (0.27–0.37). Following cessation of treatment FeNO remained suppressed for 18 days, ratio on day 18 0.77 (0.59–1.00), whereas improvements in FEV 1 and peak flow were maintained for 3 to 4 days post-treatment. Conclusions The anti-inflammatory duration of action of FF/VI is consistent with the high glucocorticoid receptor affinity and long lung retention of fluticasone furoate. The anti-inflammatory effect of FF/VI was of greater duration than its bronchodilator effect in adults with mild asthma. Funding GlaxoSmithKline (201499). Trial registration Prospectively registered on ClinicalTrials.gov registry number NCT02712047 .

Influenza vaccination is an effective public health measure to reduce the risk of influenza illness, particularly when the vaccine is well matched to circulating strains. Notwithstanding, the efficacy of influenza vaccination varies greatly among vaccinees due to largely unknown immunological determinants, thereby dampening population-wide protection. Here, we report that dietary fibre may play a significant role in humoral vaccine responses. We found dietary fibre intake and the abundance of fibre-fermenting intestinal bacteria to be positively correlated with humoral influenza vaccine-specific immune responses in human vaccinees, albeit without reaching statistical significance. Importantly, this correlation was largely driven by first-time vaccinees; prior influenza vaccination negatively correlated with vaccine immunogenicity. In support of these observations, dietary fibre consumption significantly enhanced humoral influenza vaccine responses in mice, where the effect was mechanistically linked to short-chain fatty acids, the bacterial fermentation product of dietary fibre. Overall, these findings may bear significant importance for emerging infectious agents, such as COVID-19, and associated de novo vaccinations.