Growth to early adulthood following extremely preterm birth: the EPICure study.

OBJECTIVE: To investigate growth trajectories from age 2.5 to 19 years in individuals born before 26 weeks of gestation (extremely preterm; EP) compared with term-born controls. METHODS: Multilevel modelling of growth data from the EPICure study, a prospective 1995 birth cohort of 315 EP participants born in the UK and Ireland and 160 term-born controls recruited at school age. Height, weight, head circumference and body mass index (BMI) z-scores were derived from UK standards at ages 2.5, 6, 11 and 19 years. RESULTS: 129 (42%) EP children were assessed at 19 years. EP individuals were on average 4.0 cm shorter and 6.8 kg lighter with a 1.5 cm smaller head circumference relative to controls at 19 years. Relative to controls, EP participants grew faster in weight by 0.06 SD per year (95% CI 0.05 to 0.07), in head circumference by 0.04 SD (95% CI 0.03 to 0.05), but with no catch-up in height. For the EP group, because of weight catch-up between 6 and 19 years, BMI was significantly elevated at 19 years to +0.32 SD; 23.4% had BMI >25 kg/m2 and 6.3% >30 kg/m2 but these proportions were similar to those in control subjects. EP and control participants showed similar pubertal development in early adolescence, which was not associated with height at 19 years in either study group. Growth through childhood was related to birth characteristics and to neonatal feeding practices. CONCLUSIONS: EP participants remained shorter and lighter and had smaller head circumferences than reference data or controls in adulthood but had elevated BMI

Validation of chronic obstructive pulmonary disease recording in the Clinical Practice Research Datalink (CPRD-GOLD)

Objectives: The optimal method of identifying people with chronic obstructive pulmonary disease (COPD) from electronic primary care records is not known. We assessed the accuracy of different approaches using the Clinical Practice Research Datalink, a UK electronic health record database. Setting: 951 participants registered with a CPRD practice in the UK between 1 January 2004 and 31 December 2012. Individuals were selected for ≥1 of 8 algorithms to identify people with COPD. General practitioners were sent a brief questionnaire and additional evidence to support a COPD diagnosis was requested. All information received was reviewed independently by two respiratory physicians whose opinion was taken as the gold standard. Primary outcome measure: The primary measure of accuracy was the positive predictive value (PPV), the proportion of people identified by each algorithm for whom COPD was confirmed. Results: 951 questionnaires were sent and 738 (78%) returned. After quality control, 696 (73.2%) patients were included in the final analysis. All four algorithms including a specific COPD diagnostic code performed well. Using a diagnostic code alone, the PPV was 86.5% (77.5-92.3%) while requiring a diagnosis plus spirometry plus specific medication; the PPV was slightly higher at 89.4% (80.7-94.5%) but reduced case numbers by 10%. Algorithms without specific diagnostic codes had low PPVs (range 12.2-44.4%). Conclusions: Patients with COPD can be accurately identified from UK primary care records using specific diagnostic codes. Requiring spirometry or COPD medications only marginally improved accuracy. The high accuracy applies since the introduction of an incentivised disease register for COPD as part of Quality and Outcomes Framework in 2004

Does pay-for-performance improve patient outcomes in acute exacerbation of COPD admissions?

BACKGROUND: The COPD Best Practice Tariff (BPT) is a pay-for-performance scheme in England that incentivises review by a respiratory specialist within 24 hours of admission and completion of a list of key care components prior to discharge, known as a discharge bundle, for patients admitted with acute exacerbation of COPD (AECOPD). We investigated whether the two components of the COPD BPT were associated with lower 30-day mortality and readmission in people discharged following AECOPD. METHODS: Longitudinal study of national audit data containing details of AECOPD admissions in England and Wales between 01 February 2017 and 13 September 2017. Data were linked with national admissions and mortality data. Mixed-effects logistic regression, using a random intercept for hospital to adjust for clustering of patients, was used to determine the relationship between the COPD BPT criteria (combined and separately) and 30-day mortality and readmission. Models were adjusted for age, sex, socioeconomic status, length of stay, smoking status, Charlson comorbidity index, mental illness and requirement for oxygen or noninvasive ventilation during admission. RESULTS: 28 345 patients discharged from hospital following AECOPD were included. 37% of admissions conformed to the two COPD BPT criteria. No relationship was observed between BPT conforming admissions and 30-day mortality (OR: 1.09 (95% CI 0.92 to 1.29)) or readmissions (OR: 0.96 (95% CI 0.90 to 1.02)). No relationship was observed between either of the individual COPD BPT components and 30-day mortality or readmissions. However, a specialist review at any time during admission was associated with lower inpatient mortality (OR: 0.69 (95% CI 0.58 to 0.81)). CONCLUSION: Completion of the combined COPD BPT criteria does not appear associated with a reduction in 30-day mortality or readmission. However, specialist review was associated with reduced inpatient mortality. While it is difficult to argue that discharge bundles do not improve care, this analysis questions whether the pay-for-performance model improves mortality or readmissions

National clinical audit for hospitalised exacerbations of COPD

Introduction: Exacerbations of COPD requiring hospital admission are burdensome to patients and health services. Audit enables benchmarking performance between units and against national standards, and supports quality improvement. We summarise 23 years of UK audit for hospitalised COPD exacerbations to better understand which features of audit design have had most impact. / Method: Pilot audits were performed in 1997 and 2001, with national cross-sectional audits in 2003, 2008 and 2014. Continuous audit commenced in 2017. Overall, 96% of eligible units took part in cross-sectional audit, 86% in the most recent round of continuous audit. We synthesised data from eight rounds of national COPD audit. / Results: Clinical outcomes were observed to change at the same time as changes in delivery of care: length of stay halved from 8 to 4 days between 1997 and 2014, alongside wider availability of integrated care. Process indicators did not generally improve with sequential cross-sectional audit. Under continuous audit with quality improvement support, process indicators linked to financial incentives (early specialist review (55–66%) and provision of a discharge bundle (53–74%)) improved more rapidly than those not linked (availability of spirometry (40–46%) and timely noninvasive ventilation (21–24%)). / Conclusion: Careful piloting and engagement can result in successful roll-out of cross-sectional national audit in a high-burden disease. Audit outcome measures and process indicators may be affected by changes in care pathways. Sequential cross-sectional national audit alone was not generally accompanied by improvements in care. However, improvements in process indicators were seen when continuous audit was combined with quality improvement support and, in particular, financial incentives

National clinical audit for hospitalised exacerbations of COPD

Introduction: Exacerbations of COPD requiring hospital admission are burdensome to patients and health services. Audit enables benchmarking performance between units and against national standards, and supports quality improvement. We summarise 23 years of UK audit for hospitalised COPD exacerbations to better understand which features of audit design have had most impact. Method: Pilot audits were performed in 1997 and 2001, with national cross-sectional audits in 2003, 2008 and 2014. Continuous audit commenced in 2017. Overall, 96% of eligible units took part in cross-sectional audit, 86% in the most recent round of continuous audit. We synthesised data from eight rounds of national COPD audit. Results: Clinical outcomes were observed to change at the same time as changes in delivery of care: length of stay halved from 8 to 4 days between 1997 and 2014, alongside wider availability of integrated care. Process indicators did not generally improve with sequential cross-sectional audit. Under continuous audit with quality improvement support, process indicators linked to financial incentives (early specialist review (55-66%) and provision of a discharge bundle (53-74%)) improved more rapidly than those not linked (availability of spirometry (40-46%) and timely noninvasive ventilation (21-24%)). Conclusion: Careful piloting and engagement can result in successful roll-out of cross-sectional national audit in a high-burden disease. Audit outcome measures and process indicators may be affected by changes in care pathways. Sequential cross-sectional national audit alone was not generally accompanied by improvements in care. However, improvements in process indicators were seen when continuous audit was combined with quality improvement support and, in particular, financial incentives

Addressing a system failure to diagnose COPD and asthma

To provide high-quality guideline-based care for patients with asthma or chronic obstructive pulmonary disease (COPD) we must first establish the correct diagnosis. The National Asthma and COPD Audit Programme (NACAP) has highlighted an important issue across England, Scotland, and Wales that potentially undermines care for many people with airways disease

Impact of a functional polymorphism in the PAR-1 gene promoter in COPD and COPD exacerbations.

Proteinase-activated receptor-1 (PAR-1) plays a key role in mediating the interplay between coagulation and inflammation in response to injury. The aim of this study was to investigate the role of the promoter single-nucleotide polymorphism (SNP) rs2227744G>A in modulating PAR-1/F2R gene expression in the context of chronic obstructive pulmonary disease (COPD) and COPD exacerbations. The function of the rs2227744G>A SNP was investigated by using reporter gene assays. The frequency of the polymorphism in the UK population was assessed by genotyping 8,579 healthy individuals from the Whitehall II and English Longitudinal Study of Ageing cohorts. The rs2227744G>A SNP was genotyped in a carefully phenotyped cohort of 203 COPD cases and matched controls. The results were further replicated in two different COPD cohorts. The minor allele of the rs2227744G>A polymorphism was found to increase F2R expression by 2.6-fold (P A SNP was not significantly associated with COPD, or with lung function, in all cohorts. The minor allele of the SNP was found to be associated with protection from frequent exacerbations (P = 0.04) in the cohort of COPD patients for which exacerbation frequency was available. Considering exacerbations as a continuous variable, the presence of the minor allele was associated with a significantly lower COPD exacerbation rate (3.03 vs. 1.98 exacerbations/year, Mann-Whitney U-test P = 0.04). Taken together, these data do not support a role for the rs2227744G>A F2R polymorphism in the development of COPD but suggest a protective role for this polymorphism from frequent exacerbations. Studies in separate cohorts to replicate these findings are warranted

Bronchiectasis:an emerging global epidemic

Abstract Bronchiectasis has an increasing profile within respiratory medicine. This chronic and irreversible airways disease is common but suffers from a lack of evidenced based therapy for patients and, a lack of understanding of its inherent heterogeneity. Research focused on bronchiectasis must therefore be prioritized if we are to adequately address this evolving clinical problem. This special issue on bronchiectasis focuses on its clinical, microbiological and therapeutic aspects. By bringing together a unique collection of original research and review articles, we hope this issue will showcase international research efforts, encourage future research collaborations and stimulate debate. In doing so, we hope to bring greater attention to the urgent need for sustained investment into focused, dedicated and collaborative research platforms in bronchiectasis, an emerging “global epidemic”

Building toolkits for COPD exacerbations: lessons from the past and present

In the nineteenth century, it was recognised that acute attacks of chronic bronchitis were harmful. 140 years later, it is clearer than ever that exacerbations of chronic obstructive pulmonary disease (ECOPD) are important events. They are associated with significant mortality, morbidity, a reduced quality of life and an increasing reliance on social care. ECOPD are common and are increasing in prevalence. Exacerbations beget exacerbations, with up to a quarter of in-patient episodes ending with readmission to hospital within 30 days. The healthcare costs are immense. Yet despite this, the tools available to diagnose and treat ECOPD are essentially unchanged, with the last new intervention (non-invasive ventilation) introduced over 25 years ago. An ECOPD is ’an acute worsening of respiratory symptoms that results in additional therapy’. This symptom and healthcare utility-based definition does not describe pathology and is unable to differentiate from other causes of an acute deterioration in breathlessness with or without a cough and sputum. There is limited understanding of the host immune response during an acute event and no reliable and readily available means to identify aetiology or direct treatment at the point of care (POC). Corticosteroids, short acting bronchodilators with or without antibiotics have been the mainstay of treatment for over 30 years. This is in stark contrast to many other acute presentations of chronic illness, where specific biomarkers and mechanistic understanding has revolutionised care pathways. So why has progress been so slow in ECOPD? This review examines the history of diagnosing and treating ECOPD. It suggests that to move forward, there needs to be an acceptance that not all exacerbations are alike (just as not all COPD is alike) and that clinical presentation alone cannot identify aetiology or stratify treatment

Multifractality in Human Heartbeat Dynamics

Recent evidence suggests that physiological signals under healthy conditions may have a fractal temporal structure. We investigate the possibility that time series generated by certain physiological control systems may be members of a special class of complex processes, termed multifractal, which require a large number of exponents to characterize their scaling properties. We report on evidence for multifractality in a biological dynamical system --- the healthy human heartbeat. Further, we show that the multifractal character and nonlinear properties of the healthy heart rate are encoded in the Fourier phases. We uncover a loss of multifractality for a life-threatening condition, congestive heart failure.Comment: 19 pages, latex2e using rotate and epsf, with 5 ps figures; to appear in Nature, 3 June, 199