COPD exacerbation phenotypes in a real-world five year hospitalisation cohort

INTRODUCTION: COPD exacerbation phenotypes have been defined in research populations by predominantly infective or inflammatory aetiology. We sought to characterise this in patients admitted to our centre. MATERIALS AND METHODS: Case-notes of consecutive patients discharged alive after treatment for acute COPD exacerbations between December 2012 and January 2017 were analysed. Data were collected on treatment, length of stay, C-reactive protein (CRP), eosinophil count and bacterial sputum culture positivity for potentially pathogenic microorganisms (PPM). RESULTS: 1029 exacerbations were included. There was an inverse correlation between CRP and eosinophil count (rho = -0.277, p 100 mg/L (4d [3,8] vs 4d [2,7], p < 0.01) or when given antibiotics (4d [2,8] vs 3d [1,6], p < 0.001) and shorter if receiving corticosteroids (4d [2,6] vs 6d [3,7], p < 0.001). Being sputum culture positive on first exacerbation was associated with sputum culture positivity in subsequent exacerbations. Patients with PPM in sputum culture had a significantly higher median CRP than culture negative patients (38 mg/L [18.75, 57] v 18 mg/L [8.5,45.5] p < 0.05). Length of stay, eosinophil count and CRP were significantly correlated between exacerbation pairs. CONCLUSIONS: This real-world population found eosinophilic and high CRP exacerbations to be distinct and significantly stereotyped within individual patients across recurrent exacerbations. High CRP exacerbations are associated with greater healthcare utilisation and chance of sputum positivity with PPM. Eosinophilic exacerbations were associated with lower rate of readmission. Phenotype-driven treatment warrants further investigation in this population

The Blood Neutrophil Count After 1 Month of Treatment Predicts the Radiologic Severity of Lung Disease at Treatment End

BACKGROUND: Post-tuberculous lung disease confers significant morbidity. However, the determinants of persistent lung damage in tuberculosis are not well established. We investigated associations between tuberculosis-associated radiological changes and socio-demographic factors, surrogates of bacillary burden and blood inflammatory markers at initiation of therapy and after 1 month. RESEARCH QUESTION: What are the predictors of radiological severity at the end of tuberculosis treatment for tuberculosis? STUDY DESIGN AND METHODS: We collected data from patients treated for drug sensitive pulmonary tuberculosis at our centre over a 5.5-year period. We recorded age, sex, ethnicity, smoking status, symptom duration, sputum smear grade, time to culture positivity and blood results (C-reactive protein and neutrophil count) at baseline and after 1 month of treatment. Chest x-rays performed at baseline, 2 months and end of treatment were assessed independently by two radiologists and scored using a validated system. Relationships between predictor variables and radiological outcomes were assessed using linear or binary logistic regression. RESULTS: We assessed 154 individuals, mean age 37 years, 63% male. In multivariate analysis, baseline radiological severity correlated with sputum smear grade (p=0.003) and neutrophil count (p<0.001). At end of treatment, only the 1-month neutrophil count was significantly associated with overall radiological severity in multivariate analysis (r=0.34, p=0.003), and remained significant after controlling for baseline radiological scores. The 1-month neutrophil count was also the only independent correlate of volume loss and pleural thickening at end of treatment and was significantly higher in patients with persistent cavitation or effusion versus those without. INTERPRETATION: Persistent neutrophilic inflammation after 1 month of tuberculosis therapy is associated with poor radiological outcome, suggesting a target for interventions to minimise post-tuberculous lung disease

Alcohol, smoking, recreational drug use and association with virological outcomes among people living with HIV: cross-sectional and longitudinal analyses

Objectives: There is increasing evidence to suggest that people living with HIV (PLWH) have significant morbidity from alcohol, recreational drug use and cigarette smoking. Our aim was to report associations of these factors with antiretroviral therapy (ART) non-adherence, viral non-suppression and subsequent viral rebound in PLWH. / Methods: The Antiretroviral Sexual Transmission Risk and Attitudes (ASTRA) study recruited PLWH attending eight outpatient clinics in England between February 2011 and December 2012. Data included self-reported excessive drinking (estimated consumption of > 20 units of alcohol/week), alcohol dependency (CAGE score ≥ 2 with current alcohol consumption), recreational drug use (including injection drug use in the past 3 months), and smoking status. Among participants established on ART, cross-sectional associations with ART non-adherence [missing ≥2 consecutive days of ART on ≥2 occasions in the past three months] and viral-non suppression [viral load (VL) > 50 copies/mL] were assessed using logistic regression. In participants from one centre, longitudinal associations with subsequent viral rebound (first VL > 200 copies/mL) in those on ART with VL ≤ 50 copies/mL at baseline were assessed using Cox regression during a 7-year follow-up. / Results: Among 3258 PLWH, 2248 (69.0%) were men who have sex with men, 373 (11.4%) were heterosexual men, and 637 (19.6%) were women. A CAGE score ≥ 2 was found in 568 (17.6%) participants, 325 (10.1%) drank > 20 units/week, 1011 (31.5%) currently smoked, 1242 (38.1%) used recreational drugs and 74 (2.3%) reported injection drug use. In each case, prevalence was much more common among men than among women. Among 2459 people on ART who started at least 6 months previously, a CAGE score ≥ 2, drinking > 20 units per week, current smoking, injection and non-injection drug use were all associated with ART non-adherence. After adjusting for demographic and socioeconomic factors, CAGE score ≥ 2 [adjusted odds ratio (aOR) = 1.52, 95% confidence interval (CI): 1.09–2.13], current smoking (aOR = 1.58, 95% CI: 1.10–2.17) and injection drug use (aOR = 2.11, 95% CI: 1.00–4.47) were associated with viral non-suppression. During follow-up of a subset of 592 people virally suppressed at recruitment, a CAGE score ≥ 2 [adjusted hazard ratio (aHR) = 1.66, 95% CI: 1.03–2.74], use of 3 or more non-injection drugs (aHR = 1.82, 95% CI: 1.12–3.57) and injection drug use (aHR = 2.73, 95% CI: 1.08–6.89) were associated with viral rebound. / Conclusions: Screening and treatment for alcohol, cigarette and drug use should be integrated into HIV outpatient clinics, while clinicians should be alert to the potential for poorer virological outcomes

Genetic epidemiology of SARS-CoV-2 transmission in renal dialysis units - a high risk community-hospital interface

OBJECTIVES: Patients requiring haemodialysis are at increased risk of serious illness with SARS-CoV-2 infection. To improve the understanding of transmission risks in six Scottish renal dialysis units, we utilised the rapid whole-genome sequencing data generated by the COG-UK consortium. METHODS: We combined geographical, temporal and genomic sequence data from the community and hospital to estimate the probability of infection originating from within the dialysis unit, the hospital or the community using Bayesian statistical modelling and compared these results to the details of epidemiological investigations. RESULTS: Of 671 patients, 60 (8.9%) became infected with SARS-CoV-2, of whom 16 (27%) died. Within-unit and community transmission were both evident and an instance of transmission from the wider hospital setting was also demonstrated. CONCLUSIONS: Near-real-time SARS-CoV-2 sequencing data can facilitate tailored infection prevention and control measures, which can be targeted at reducing risk in these settings

Meta-analysis of individual-patient data from EVAR-1, DREAM, OVER and ACE trials comparing outcomes of endovascular or open repair for abdominal aortic aneurysm over 5 years.

BACKGROUND: The erosion of the early mortality advantage of elective endovascular aneurysm repair (EVAR) compared with open repair of abdominal aortic aneurysm remains without a satisfactory explanation. METHODS: An individual-patient data meta-analysis of four multicentre randomized trials of EVAR versus open repair was conducted to a prespecified analysis plan, reporting on mortality, aneurysm-related mortality and reintervention. RESULTS: The analysis included 2783 patients, with 14 245 person-years of follow-up (median 5·5 years). Early (0-6 months after randomization) mortality was lower in the EVAR groups (46 of 1393 versus 73 of 1390 deaths; pooled hazard ratio 0·61, 95 per cent c.i. 0·42 to 0·89; P = 0·010), primarily because 30-day operative mortality was lower in the EVAR groups (16 deaths versus 40 for open repair; pooled odds ratio 0·40, 95 per cent c.i. 0·22 to 0·74). Later (within 3 years) the survival curves converged, remaining converged to 8 years. Beyond 3 years, aneurysm-related mortality was significantly higher in the EVAR groups (19 deaths versus 3 for open repair; pooled hazard ratio 5·16, 1·49 to 17·89; P = 0·010). Patients with moderate renal dysfunction or previous coronary artery disease had no early survival advantage under EVAR. Those with peripheral artery disease had lower mortality under open repair (39 deaths versus 62 for EVAR; P = 0·022) in the period from 6 months to 4 years after randomization. CONCLUSION: The early survival advantage in the EVAR group, and its subsequent erosion, were confirmed. Over 5 years, patients of marginal fitness had no early survival advantage from EVAR compared with open repair. Aneurysm-related mortality and patients with low ankle : brachial pressure index contributed to the erosion of the early survival advantage for the EVAR group. Trial registration numbers: EVAR-1, ISRCTN55703451; DREAM (Dutch Randomized Endovascular Aneurysm Management), NCT00421330; ACE (Anévrysme de l'aorte abdominale, Chirurgie versus Endoprothèse), NCT00224718; OVER (Open Versus Endovascular Repair Trial for Abdominal Aortic Aneurysms), NCT00094575