[Show abstract][Hide abstract] ABSTRACT: There are no completed randomised trials of the use of corticosteroids in patients with severe influenza infection. Corticosteroid use in influenza is widespread, non-systematic and marked by controversy. A recent meta-analysis of observational studies of adjuvant corticosteroids in influenza found an association with increased mortality but there were important concerns regarding the risks of bias.
To (1) evaluate whether or not low-dose corticosteroids given as an adjunct to standard treatment is beneficial in patients who are hospitalised with severe pandemic influenza and (2) develop an 'off-the-shelf' clinical trial that is ready to be activated in a future pandemic.
Multicentre, pragmatic, blinded, randomised placebo-controlled trial.
Thirty to 40 hospitals in the UK.
Adults (≥ 16 years) admitted to hospital with an influenza-like illness during a pandemic.
Five-day course of dexamethasone (Dexsol®, Rosemont Pharmaceuticals Ltd) 6 mg daily, started within 24 hours of admission.
Admission to Intensive Care Unit, or death, within 30 days of admission to hospital.
This trial has not yet been activated. It is currently set up with full ethics and regulatory approvals in place, ready for rapid activation at the onset of the next pandemic. Hurdles to setting up a pandemic trial include planning for pandemic-level pressures on UK NHS resources and co-enrolment of patients to multiple pandemic studies, ensuring adequate geographical distribution of participating sites, maintaining long-term low-level engagement with site investigators, addressing future trial-specific training needs of local investigators and resilience planning in trial management. Identified threats to trial delivery include changes to research capabilities or policies during the hibernation phase, lack of staff resources during a pandemic and the influence of media at the time of a pandemic. A mismatch in the approach to informed consent required by current regulations to that preferred by patients and the public was identified.
This study demonstrates that advance set-up of a trial to be conducted during a pandemic, with full regulatory approvals in place, is possible. Regular review during the hibernation phase will be required. This study serves as a model for the development of other 'off-the-shelf' trials as part of preparedness planning for public health emergencies.
Current Controlled Trials ISRCTN72331452. European Union Drug Regulating Authorities Clinical Trials number: 2013-001051-12.
This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 19, No. 16. See the NIHR Journals Library website for further project information.
[Show abstract][Hide abstract] ABSTRACT: Objective To determine the association between 30-day inpatient mortality and route of admission to hospital, for adults with community acquired pneumonia (CAP).
Methods We studied 16 313 adults included in the British Thoracic Society (BTS) national CAP audit dataset. Comparisons were made between adults admitted via emergency departments (ED) with non-ED routes of admission, with regard to 30-day inpatient mortality. Secondary outcome measures were adherence to national CAP guidelines (time to first chest X-ray ≤4 h from admission; time to first antibiotic dose ≤4 h from admission; antibiotic choice; and antibiotic route of administration) by route of admission.
Results Of adults hospitalised with CAP, 75.6% were admitted via ED; these adults had a greater prevalence of comorbid illness and higher disease severity in comparison with non-ED admissions. Adjusted 30-day inpatient mortality was similar for ED versus non-ED route of admission (OR 1.10, 95% CI 0.96 to 1.25). Admissions via ED were associated with faster processes of care (time to chest X-ray ≤4 h, adjusted OR 3.39, 95% CI 2.79 to 4.12; time to first antibiotic ≤4 h, adjusted OR 1.62, 95% CI 1.42 to 1.84) and greater use of intravenous antibiotics regardless of disease severity (adjusted OR 1.58, 95% CI 1.43 to 1.74).
Conclusions Adults with CAP admitted via EDs have more comorbid illness and greater disease severity compared to those admitted via non-ED routes. Following adjustment for these differences, 30-day inpatient mortality was not associated with route of admission.
Emergency Medicine Journal 12/2014; 32(1). DOI:10.1136/emermed-2013-203494 · 1.84 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Tuberculosis (TB) incidence is rising globally, with drug resistance becoming increasingly problematic. Microbiological confirmation ensures correct anti-tuberculous chemotherapy.
We retrospectively analysed all TB cases diagnosed in Central Manchester in 2009 investigating how often we are not achieving microbiological diagnosis, factors influencing this and whether opportunities to obtain microbiological samples are missed.
128/156 (82%) cases had samples sent for microbiology. Factors affecting this included disease site, with ocular disease least likely to be sampled (p < 0.0001), and patient age (with children less likely to be sampled p = 0.002). Ethnicity did not affect sampling (n.s.). Overall, 92/156 (59%) cases were culture positive. Negative culture was related to specimen type (p < 0.0001) and patient age (p = 0.019), with children significantly less likely to have a positive culture. Ethnicity and disease site did not affect culture results. There was a trend towards culture positivity being more common in pulmonary (75%) than non-pulmonary (46%) disease (n.s.). In only 7 (4%), could samples have been sent where they were originally absent (3) or further samples obtained where the cultures proved to be negative (4).
Despite an overall culture positive rate of 59%, opportunities to achieve microbiological confirmation are seldom missed. In our centre, which is typical of UK practice, this lack of capacity to increase microbiological confirmation, particularly in an era of increasing importance of extra-pulmonary TB, is concerning. Improvements in sample acquisition and laboratory methods are urgently required.
Respiratory medicine 10/2013; 107(12). DOI:10.1016/j.rmed.2013.09.016 · 3.09 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: This article is a non-systematic review of selected recent publications in community-acquired pneumonia, including a comparison of various guidelines. Risk stratification of patients has recently been advanced by the addition of several useful biomarkers. The issue of single versus dual antibiotic treatment remains controversial and awaits a conclusive randomized controlled trial. However, in the meantime, there is a working consensus that more severe patients should receive dual therapy.
F1000 Prime Reports 10/2013; 5:43. DOI:10.12703/P5-43
[Show abstract][Hide abstract] ABSTRACT: The benefits of β-lactam/macrolide combination therapy over β-lactam therapy alone for the treatment of hospitalised community-acquired pneumonia (CAP) in relation to pneumonia severity are uncertain. We studied 5240 adults hospitalised with CAP from 72 secondary care trusts across England and Wales. The overall 30-day inpatient (IP) death rate was 24.4%. Combination therapy was prescribed in 3239 (61.8%) patients. In a multivariable model, combination therapy was significantly associated with lower 30-day IP death rate in patients with moderate-severity CAP (adjusted OR 0.54, 95% CI 0.41 to 0.72) and high-severity CAP (adjusted OR 0.76, 95% CI 0.60 to 0.96) but not low-severity CAP.
[Show abstract][Hide abstract] ABSTRACT: Patients with Chronic Obstructive Pulmonary Disease (COPD) are at higher risk of developing Community-Acquired Pneumonia (CAP) than patients in the general population. However, no studies have been performed in general practice assessing longitudinal incidence rates for CAP in COPD patients or risk factors for pneumonia onset.
A cohort of COPD patients aged ≥ 45 years, was identified in the General Research Practice Database (GPRD) between 1996 and 2005, and annual and 10-year incidence rates of CAP evaluated. A nested case-control analysis was performed, comparing descriptors in COPD patients with and without CAP using conditional logistic regression generating odds ratios (OR) and 95% confidence intervals (CI).
The COPD cohort consisted of 40,414 adults. During the observation period, 3149 patients (8%) experienced CAP, producing an incidence rate of 22.4 (95% CI 21.7-23.2) per 1000 person years. 92% of patients with pneumonia diagnosis had suffered only one episode. Multivariate modelling of pneumonia descriptors in COPD indicate that age over 65 years was significantly associated with increased risk of CAP. Other independent risk factors associated with CAP were co-morbidities including congestive heart failure (OR 1.4, 95% CI 1.2-1.6), and dementia (OR 2.6, 95%CI 1.9-3.). Prior severe COPD exacerbations requiring hospitalization (OR 2.7, 95% CI 2.3-3.2) and severe COPD requiring home oxygen or nebulised therapy (OR 1.4, 95% CI 1.1-1.6) were also significantly associated with risk of CAP.
COPD patients presenting in general practice with specific co-morbidities, severe COPD, and age >65 years are at increased risk of CAP.
Respiratory medicine 05/2012; 106(8):1124-33. DOI:10.1016/j.rmed.2012.04.008 · 3.09 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Tuberculosis (TB) has increased within the UK and, in response, targets for TB control have been set and interventions recommended. The question was whether these had been implemented and, if so, had they been effective in reducing TB cases.
Epidemiological data were obtained from enhanced surveillance and clinics. Primary care trusts or TB clinics with an average of > 100 TB cases per year were identified and provided reflections on the reasons for any change in their local incidence, which was compared to an audit against the national TB plan.
Access to data for planning varied (0-22 months). Sputum smear status was usually well recorded within the clinics. All cities had TB networks, a key worker for each case, free treatment and arrangements to treat HIV co-infection. Achievement of targets in the national plan correlated well with change in workload figures for the commissioning organizations (Spearman's rank correlation R = 0.8, P < 0.01) but not with clinic numbers. Four cities had not achieved the target of one nurse per 40 notifications (Birmingham, Bradford, Manchester and Sheffield). Compared to other cities, their loss to follow-up during treatment was usually > 6% (χ2 = 4.2, P < 0.05), there was less TB detected by screening and less outreach. Manchester was most poorly resourced and showed the highest rate of increase of TB. Direct referral from radiology, sputum from primary care and outreach workers were cited as important in TB control.
TB control programmes depend on adequate numbers of specialist TB nurses for early detection and case-holding.Please see related article: http://www.biomedcentral.com/1741-7015/9/127.
BMC Public Health 11/2011; 11:896. DOI:10.1186/1471-2458-11-896 · 2.26 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The updated British Thoracic Society (BTS) Guidelines for the management of community acquired pneumonia (CAP) in adults was published in October 2009. In conjunction with the Guidelines, the first national BTS audit of adult CAP was conducted.
An audit tool was developed as part of the Guidelines. Members of the BTS were invited to participate in the audit capturing data relating to acutely ill adults admitted to hospitals in the U.K. and treated for CAP within the period 1 December 2009 and 31 January 2010. Data entry using the web-based audit tool closed in May 2010.
Of 2749 submissions from 64 institutions; 8 were excluded due to inconsistent data. The mean age of patients was 71 years (range 16-105 years). The CURB65 score was 0 to 1 in 40% of patients, 2 in 30% and 3 to 5 in 30%. Five hundred and three (18.3%) patients died in hospital within 30 days, 101 (20.1%) within 1 day of admission. Initial empirical antibiotics were in accordance with local CAP guidelines in 1478 (55.5%) patients and were administered intravenously in 712 (65%), 603 (74%) and 743 (90%) patients with CURB65 scores 0 to 1, 2 and 3 to 5 respectively. Within 4 hours of admission, a chest x-ray was obtained in 83% of patients and the first dose of antibiotics was administered in 58%.
The burden of CAP is high. Efforts should be directed at improving adherence to local CAP guidelines and specific processes of care.
[Show abstract][Hide abstract] ABSTRACT: Four different rules have been suggested and validated for intensive care unit (ICU) admission for community-acquired pneumonia: modified American Thoracic Society (ATS) rule, Infectious Diseases Society of America (IDSA)/ATS rule, España rule, and SMART-COP. Their performance varies, with sensitivity of around 70% and specificity of around 80-90%. Only negative predictive values are consistently high. Critical methodological issues include the appropriate reference for derivation, the populations studied, the variables included, and the time course of pneumonia. Severe community-acquired pneumonia (SCAP) may evolve because of acute respiratory failure or/and severe sepsis/septic shock. Pneumonia-related complications and decompensated comorbidities may be additional or independent reasons for a severe course. All variables included in predictive rules relate to the two principal reasons for SCAP. However, taken as major criteria, they are of little value for clinical assessment. Instead, a limited set of minor criteria reflecting severity seems appropriate. However, predictive rules may not meet principal needs of severity assessment because of failure in sensitivity, ignorance of the potential contribution of complications or decompensated comorbidity to pneumonia severity, and poor sensitivity for the lower extreme in the spectrum of severe pneumonia, i.e., patients at risk of SCAP. We therefore advocate an approach that refers to the evaluation of the need for intensified treatment rather than ICU, based on a set of minor criteria and sensitive to the dynamic nature of pneumonia. Intensified treatment such as monitoring and treatment of acute respiratory failure or/and severe sepsis/septic shock is thought to improve management and possibly outcomes by setting the focus on both patients with severity criteria at admission and those at risk for SCAP.
Intensive Care Medicine 11/2010; 37(2):214-23. DOI:10.1007/s00134-010-2077-0 · 7.21 Impact Factor