METHODS: We report the largest multicentre evaluation of the COPD airway mycobiome to date, including participants from Asia (Singapore and Malaysia) and the UK (Scotland) when stable (n=337) and during exacerbations (n=66) as well as nondiseased (healthy) controls (n=47). Longitudinal mycobiome analysis was performed during and following COPD exacerbations (n=34), and examined in terms of exacerbation frequency, 2-year mortality and occurrence of serum specific IgE (sIgE) against selected fungi.
RESULTS: A distinct mycobiome profile is observed in COPD compared with controls as evidenced by increased α-diversity (Shannon index; p<0.001). Significant airway mycobiome differences, including greater interfungal interaction (by co-occurrence), characterise very frequent COPD exacerbators (three or more exacerbations per year) (permutational multivariate ANOVA; adjusted p<0.001). Longitudinal analyses during exacerbations and following treatment with antibiotics and corticosteroids did not reveal any significant change in airway mycobiome profile. Unsupervised clustering resulted in two clinically distinct COPD groups: one with increased symptoms (COPD Assessment Test score) and Saccharomyces dominance, and another with very frequent exacerbations and higher mortality characterised by Aspergillus, Curvularia and Penicillium with a concomitant increase in serum sIgE levels against the same fungi. During acute exacerbations of COPD, lower fungal diversity associates with higher 2-year mortality.
CONCLUSION: The airway mycobiome in COPD is characterised by specific fungal genera associated with exacerbations and increased mortality.
METHODS: Patients with newly diagnosed AAC were identified prospectively over a 12-month period (November 2011 to October 2012) by active surveillance through the Scottish Ophthalmic Surveillance Unit reporting system. Data were collected at case identification and at 6 months follow-up.
RESULTS: There were 114 cases (108 patients) reported, giving an annual incidence of 2.2 cases (95% CI 1.8 to 2.6) or 2 patients (95% CI 1.7 to 2.4) per 1 00 000 in the whole population in Scotland. Precipitating factors were identified in 40% of cases. Almost one in five cases was associated with topical dilating drops. Best-corrected visual acuity (BCVA) at presentation ranged from 6/6 to perception of light. The mean presenting intraocular pressure (IOP) was 52 mm Hg (SD 11). Almost 30% cases had a delayed presentation of 3 or more days. At 6 months follow-up, 75% had BCVA of 6/12 or better and 30% were found to have glaucoma at follow-up. Delayed presentation (≥3 days) was associated with higher rate of glaucoma at follow-up (22.6% vs 60.8%, p<0.001), worse VA (0.34 vs 0.74 LogMAR, p<0.0001) and need for more topical medication (0.52 vs 1.2, p=0.003) to control IOP.
CONCLUSION: The incidence of AAC in Scotland is relatively low compared with the Far East countries, but in line with previous European data. Almost one in five cases were associated with pupil dilation for retinal examination.
METHODS: We did a retrospective observational cohort study. We included consecutive people with ACS who were discharged from Scottish hospitals between January 2008 and December 2013 and who received DAPT after discharge followed by antiplatelet monotherapy. The rates of cardiovascular events were assessed during each 90-day period of DAPT treatment and 90-day period after stopping DAPT. Cardiovascular events were defined as a composite of death, ACS, transient ischaemic attack or stroke. Cox regression was used to identify predictors of cardiovascular events following DAPT cessation.
RESULTS: 1340 patients were included (62% male, mean age 64.9 (13.0) years). Cardiovascular events occurred in 15.7% (n=211) during the DAPT period (mean DAPT duration 175.1 (155.3) days) and in 16.7% (n=188) following DAPT cessation (mean of 2.7 years follow-up). Independent predictors for a cardiovascular event following DAPT cessation were age (HR 1.07; 95% CI 1.05 to 1.08; p<0.001), DAPT duration (HR 0.997; 95% CI 0.995 to 0.998; p<0.001) and having revascularisation therapy during the index admission (HR 0.58; 95% CI 0.39 to 0.85; p=0.005).
CONCLUSIONS: The rate of cardiovascular events was not significantly increased in the early period post-DAPT cessation compared with later periods in this ACS population. Increasing age, DAPT duration and lack of revascularisation therapy were associated with increased risk of cardiovascular events during long-term follow-up after DAPT cessation.
METHODS: Oxy-PICU was a pragmatic, multicentre, open-label, randomised controlled trial in England and Scotland. Eligible children were older than 38 weeks and younger than 16 years and had been admitted for emergency care in one of 15 participating PICUs, where they received invasive respiratory support for abnormal gas exchange. Participants were randomly assigned (1:1) to either a conservative oxygenation target (SpO2 88-92%) or liberal oxygenation target (SpO2 >94%). Survival status was assessed at 90 days and 1 year, and health-related quality of life (HRQoL), quality-adjusted life-years (QALYs), health-care costs, and incremental net monetary benefit were assessed at 1 year after the index hospital admission and randomisation. HRQoL was measured with age-appropriate Paediatric Quality of Life Generic Core Scales and mapped onto the Child Health Utility 9D index score. HRQoL and survival data were combined to construct QALYs. Costs at 1 year were derived from use of hospital, outpatient, and community health services. The trial was registered in the ISRCTN registry (ISRCTN92103439).
FINDINGS: 2040 children were enrolled between Sept 1, 2020 and May 15, 2022. 1868 (91·6%) children were included in the 90-day survival analysis; of these 930 (49·8%) had been assigned liberal oxygen and 938 (50·2%) conservative oxygen. 1867 (91·5%) children were included in the 1-year survival analysis; 930 (49·8%) had been assigned liberal oxygenation and 937 (50·2%) conservative oxygen. At 90 days, 35 (3·7%) patients in the conservative oxygenation group and 45 (4·8%) patients in the liberal oxygenation group had died (adjusted hazard ratio [aHR] 0·75 [95% CI 0·48 to 1·17]). By 1 year, 52 (5·5%) patients in the conservative oxygenation group and 66 (7·1%) patients in the liberal oxygenation group had died (aHR 0·77 [95%CI 0·53 to 1·10]). Overall, mean HRQoL, life-years, and QALYs at 1 year were similar in the two groups. The adjusted incremental effect on cost of conservative oxygenation versus liberal oxygenation was -£879 (95% CI -9036 to 7278), whereas the incremental difference in QALYs was estimated at 0·001 (-0·010 to 0·011), leading to an incremental net monetary benefit of £894 (-7290 to 9078) associated with conservative oxygenation relative to liberal oxygenation. These results did not vary by age (<12 months vs ≥12 months), comorbidity at baseline, age-adjusted heart rate, or haemoglobin level at admission and were robust to alternative assumptions.
INTERPRETATION: Compared with usual care (SpO2 >94%) for invasively ventilated children who are admitted as an emergency to a PICU, conservative oxygenation (SpO2 88-92%) was not associated with differences in longer-term survival, costs, or cost-effectiveness. Taken together with previous findings of Oxy-PICU that conservative oxygenation compared with liberal oxygenation leads to better patient-centred and parent-centred outcomes at 30 days, these findings support the use of conservative oxygenation targets for this population.
FUNDING: UK National Institute for Health and Social Care Research Health Technology Assessment Programme.
METHODS: This study used data from 6524 participants of the 1970 British Birth Cohort Study, an ongoing population-based birth cohort of individuals born in England, Scotland and Wales. Participants' socioeconomic position was indicated by occupational social class at age 26 and 46 years (the first and latest adult waves, respectively). Self-rated oral health was measured at age 46 years. The association between social mobility and adult oral health was assessed using conventional regression models and diagonal reference models, adjusting for gender, ethnicity, country of residence and residence area.
RESULTS: Over a fifth of participants (22.2%) reported poor self-rated oral health at age 46 years. In conventional regression analysis, the odds ratios for social mobility varied depending on whether they were adjusted for social class of origin or destination. In addition, all social trajectories had greater odds of reporting poor oral health than non-mobile adults in class I/II. In diagonal reference models, both upward (Odds Ratio 0.79; 95% CI 0.63-0.99) and downward mobility (0.90; 95% CI 0.71-1.13) were inversely associated with poor self-rated oral health. The origin weight was 0.48 (95% CI 0.33-0.63), suggesting that social class of origin was as important as social class of destination.
CONCLUSION: This longitudinal analysis showed that intragenerational social mobility from young to middle adulthood was associated with self-rated oral health, independent of previous and current social class.