Introducing RELAX: An automated pre-processing pipeline for cleaning EEG data - Part 1: Algorithm and application to oscillations.

OBJECTIVE: Electroencephalographic (EEG) data are often contaminated with non-neural artifacts which can confound experimental results. Current artifact cleaning approaches often require costly manual input. Our aim was to provide a fully automated EEG cleaning pipeline that addresses all artifact types and improves measurement of EEG outcomes METHODS: We developed RELAX (the Reduction of Electroencephalographic Artifacts). RELAX cleans continuous data using Multi-channel Wiener filtering [MWF] and/or wavelet enhanced independent component analysis [wICA] applied to artifacts identified by ICLabel [wICA_ICLabel]). Several versions of RELAX were compared using three datasets (N = 213, 60 and 23 respectively) against six commonly used pipelines across a range of artifact cleaning metrics, including measures of remaining blink and muscle activity, and the variance explained by experimental manipulations after cleaning. RESULTS: RELAX with MWF and wICA_ICLabel showed amongst the best performance at cleaning blink and muscle artifacts while preserving neural signal. RELAX with wICA_ICLabel only may perform better at differentiating alpha oscillations between working memory conditions. CONCLUSIONS: RELAX provides automated, objective and high-performing EEG cleaning, is easy to use, and freely available on GitHub. SIGNIFICANCE: We recommend RELAX for data cleaning across EEG studies to reduce artifact confounds, improve outcome measurement and improve inter-study consistency.

RELAX part 2: A fully automated EEG data cleaning algorithm that is applicable to Event-Related-Potentials.

OBJECTIVE: Electroencephalography (EEG) is often used to examine neural activity time-locked to stimuli presentation, referred to as Event-Related Potentials (ERP). However, EEG is influenced by non-neural artifacts, which can confound ERP comparisons. Artifact cleaning reduces artifacts, but often requires time-consuming manual decisions. Most automated methods filter frequencies <1 Hz out of the data, so are not recommended for ERPs (which contain frequencies <1 Hz). Our aim was to test the RELAX (Reduction of Electroencephalographic Artifacts) pre-processing pipeline for use on ERP data. METHODS: The cleaning performance of multiple versions of RELAX were compared to four commonly used EEG cleaning pipelines across both artifact cleaning metrics and the amount of variance in ERPs explained by different conditions in a Go-Nogo task. Results RELAX with Multi-channel Wiener Filtering (MWF) and wavelet-enhanced independent component analysis applied to artifacts identified with ICLabel (wICA_ICLabel) cleaned data most effectively and produced amongst the most dependable ERP estimates. RELAX with wICA_ICLabel only or MWF_only may detect effects better for some ERPs. CONCLUSIONS: RELAX shows high artifact cleaning performance even when data is high-pass filtered at 0.25 Hz (applicable to ERP analyses). SIGNIFICANCE: RELAX is easy to implement via EEGLAB in MATLAB and freely available on GitHub. Given its performance and objectivity we recommend RELAX to improve artifact cleaning and consistency across ERP research.

Isolated IgG2 deficiency is an independent risk factor for exacerbations in bronchiectasis.

BACKGROUND: Immunoglobulin G (IgG) subclass 2 deficiency is the most frequent IgG subclass deficiency identified in patients with bronchiectasis, but its clinical significance is not known. AIM: To analyse if bronchiectasis patients with isolated IgG2 deficiency at risk of recurrent exacerbations and/or hospitalization? Do patients with IgG2 deficiency have worse disease progression? DESIGN AND METHODS: This is a retrospective study (2015-20) exploring independent risk factors for recurrent exacerbations (3 or more per year) and/or hospitalization with bronchiectasis exacerbations using multivariable models using binary logistic regression. There was no patient with IgG deficiency, IgG 1, 3 or 4 deficiency, or IgA or IgM deficiency included. In this model, the authors included: serum IgG2 level; lung function; body mass index; MRC breathlessness scale; age; sex; number of bronchiectatic lobes; bacterial colonization; comorbidities; and the use of long-term immunosuppressant drugs or antibiotics for more than 28 days. Analysing 2-year longitudinal data, one-way ANOVA and Mann-Whitney U-test were used to compare bronchiectasis severity between patients with different IgG2 levels. RESULTS: Serum IgG2 levels (<2.68 g/l, 2.68-3.53 g/l and 3.54-4.45 g/l); hospital admission in the preceding 2 years; bacterial colonization with potentially pathogenic organisms and asthma were independent predictors for three or more bronchiectasis exacerbations. Those with low IgG2 levels (<2.68 g/l and 2.68-3.53 g/l), had worsening progression of their bronchiectasis, using the Bronchiectasis Severity Index, over 1 year compared with those who were IgG2 replete (>4.45 g/l) (P = 0.003, 0.013). CONCLUSION: Reduced IgG2 levels were an independent predictor for bronchiectasis exacerbations and have increased disease progression.

Role of Stenotrophomonas maltophilia isolation in patients with non-CF bronchiectasis.

INTRODUCTION: Stenotrophomonas maltophilia is a bacteria whose role in patients with cystic fibrosis (CF) bronchiectasis has been previously studied; little is known about its role in non-CF bronchiectasis. MATERIALS AND METHODS: Aim of our study is to investigate the risk factors for S. maltophilia acquisition and its clinical impact on bronchiectasis patients. A retrospective observational cohort study enrolling patients attending the Bronchiectasis Clinic at the Royal Infirmary of Edinburgh, Scotland, UK. A total of 167 bronchiectasis patients undergoing intravenous (IV) antibiotic therapy were selected and divided according to single or chronic S. maltophilia isolation in sputum. The risk factors and prognostic impact were studied. RESULTS: Single isolation was independently associated with lower baseline % predicted forced expiratory volume in 1 s [odds ratio (OR) 0.98; 95% confidence interval (CI) 0.970-1.044; P = 0.025] and with less radiological involvement (OR 0.379; 95% CI 0.175-0.819; P = 0.01). Chronic isolation was associated with the number of IV antibiotic courses in the year before and after the first isolation (OR 1.2; 95% CI 1.053-1.398; P = 0.007) and with the absence of Pseudomonas aeruginosa colonization (OR 0.207; 95% CI 0.056-0.764; P = 0.02). In the chronic isolation group, there were more exacerbations and more need of IV antibiotics in the year after the first isolation. CONCLUSIONS: Poor lung function is the main independent risk factor for single isolation of S. maltophilia. For chronic colonization, the main independent risk factor is the number of IV antibiotic courses and the absence of P. aeruginosa chronic colonization. Only when chronically present, S. maltophilia had a clinical impact with more exacerbations.

Quality control for multiple breath washout tests in multicentre bronchiectasis studies: Experiences from the BRONCH-UK clinimetrics study.

INTRODUCTION: Multiple Breath Washout (MBW) to measure Lung Clearance Index (LCI) is increasingly being used as a secondary endpoint in multicentre bronchiectasis studies. LCI data quality control or "over-reading" is resource intensive and the impact is unclear. OBJECTIVES: To assess the proportion of MBW tests deemed unacceptable with over-reading, and to assess the change in LCI (number of turnovers), LCI coefficient of variation (CV%) and tidal volume (VT) CV% results after over-reading. METHODS: Data were analysed from 250 MBW tests (from 98 adult bronchiectasis patients) collected as part of the Bronch-UK Clinimetrics study in 5 UK centres. Each MBW test was over-read centrally using pre-defined criteria. MBW tests with <2 technically valid and repeatable trials were deemed unacceptable to include in analysis. In accepted tests, values for LCI, LCI CV% and VT CV% before and after over-reading, were compared. RESULTS: Insufficient data was collected in 10/250 tests. With over-reading, 30/240 (12%) were deemed unacceptable to include in analysis. In those accepted tests, overall the change in LCI, LCI CV% and VT CV% with over-reading was not statistically significant. When MBW new sites were compared to MBW expert sites, the change in LCI with over-reading was significantly greater in MBW new sites (p = 0.047). Data suggests that over-reading could be important up to at least 12 months post initiation of MBW activity. CONCLUSION: MBW over-reading was important in this study as 12% of tests were considered unacceptable. Over-reading improved test result accuracy in sites new to MBW.

Risk factors for requiring intravenous antibiotic therapy in hospital and 30-day readmission for exacerbations of bronchiectasis.

BACKGROUND: The safety and efficacy of domiciliary intravenous (IV) antibiotic therapy compared to inpatient hospital treatment for exacerbations of bronchiectasis has been established. Factors that determine the setting for IV antibiotic therapy need to be characterized further. AIM: We aimed to identify factors at presentation that were associated with the requirement for IV antibiotic therapy delivered in hospital and 30-day readmission. DESIGN: Retrospective cohort study of all IV antibiotic courses administered to patients with bronchiectasis by a specialist respiratory unit over a 2-year period. METHODS: We assessed demographic data, treatment outcomes, morbidity, mortality, and 30-day readmission rates. Multiple linear regression analysis was performed to identify factors associated with inpatient IV antibiotics and 30-day readmission. RESULTS: One hundred six patients received 243 courses of IV antibiotic therapy in 2 years. Sixty-six cases (27.2%) were managed in hospital, 28 cases (11.5%) required initial admission prior to early supported discharge to complete IV antibiotics at home and 149 cases (61.3%) received domiciliary IV antibiotics. Bronchiectasis Severity Index (P < 0.0001) and emergency presentation with an exacerbation (P < 0.0001) were independent factors associated with the requirement for inpatient IV antibiotic therapy. There were no differences between mortality (P = 0.06) and morbidity (P = 0.1) between groups. Thirty-day readmission following early supported discharge was higher compared to inpatient or domiciliary therapy (P=0.0004). CONCLUSION: A higher Bronchiectasis Severity Index and emergency presentation with an exacerbation are independently associated with the need for IV antibiotics delivered in hospital. We could not identify any factors that predicted 30-day readmission in a multi-variable model.

Development of two real-time multiplex PCR assays for the detection and quantification of eight key bacterial pathogens in lower respiratory tract infections.

The frequent lack of a positive and timely microbiological diagnosis in patients with lower respiratory tract infection (LRTI) is an important obstacle to antimicrobial stewardship. Patients are typically prescribed broad-spectrum empirical antibiotics while microbiology results are awaited, but, because these are often slow, negative, or inconclusive, de-escalation to narrow-spectrum agents rarely occurs in clinical practice. The aim of this study was to develop and evaluate two multiplex real-time PCR assays for the sensitive detection and accurate quantification of Streptococcus pneumoniae, Haemophilus influenzae, Staphylococcus aureus, Moraxella catarrhalis, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Acinetobacter baumannii. We found that all eight bacterial targets could be reliably quantified from sputum specimens down to a concentration of 100 CFUs/reaction (8333 CFUs/mL). Furthermore, all 249 positive control isolates were correctly detected with our assay, demonstrating effectiveness on both reference strains and local clinical isolates. The specificity was 98% on a panel of nearly 100 negative control isolates. Bacterial load was quantified accurately when three bacterial targets were present in mixtures of varying concentrations, mimicking likely clinical scenarios in LRTI. Concordance with culture was 100% for culture-positive sputum specimens, and 90% for bronchoalveolar lavage fluid specimens, and additional culture-negative bacterial infections were detected and quantified. In conclusion, a quantitative molecular test for eight key bacterial causes of LRTI has the potential to provide a more sensitive decision-making tool, closer to the time-point of patient admission than current standard methods. This should facilitate de-escalation from broad-spectrum to narrow-spectrum antibiotics, substantially improving patient management and supporting efforts to curtail inappropriate antibiotic use.

The effect of a large Legionnaires' disease outbreak in Southwest Edinburgh on acute and critical care services.

OBJECTIVE: The largest outbreak of Legionnaires Disease (LD) in the UK for a decade occurred in Edinburgh in June 2012. We describe the clinical and public health management of the outbreak. SETTING: Three acute hospitals covering an urban area of ~480,000. METHODS: Data were collected on confirmed and suspected cases and minutes of the Incident Management Team meetings were reviewed to identify key actions. RESULTS: Over 1600 urine samples and over 600 sputum samples were tested during the outbreak. 61 patients with pneumonia tested positive for Legionella pneumophila serogroup 1 by urinary antigen detection, culture, respiratory PCR or serology. A further 23 patients with pneumonia were treated as suspected cases on clinical and epidemiological grounds but had no microbiological diagnosis. 36% of confirmed and probable cases required critical care admission. Mean ICU length of stay was 11.3 (±7.6) days and mean hospital length of stay for those who were admitted to ICU was 23.0 (±17.2) days. For all hospitalized patients the mean length of stay was 15.7 (±14) days. In total there were four deaths associated with this outbreak giving an overall case fatality of 6.5%. Hospital and critical care mortality was 6.1% and 9.1%, respectively. CONCLUSION: A significant proportion of patients required prolonged multiple organ support or complex ventilation. Case fatality compared favourably to other recent outbreaks in Europe. Access to rapid diagnostic tests and prompt antibiotic therapy may have mitigated the impact of pre-existing poor health among those affected.

Symptoms of airway reflux predict exacerbations and quality of life in bronchiectasis.

AIM: We have explored the association of the upper airway symptoms related to cough with exacerbation frequency, sputum microbiology and inflammatory markers in patients with non cystic fibrosis bronchiectasis. METHODS: Patients with bronchiectasis completed the Hull Airway Reflux Questionnaire (HARQ). A score of >13 was taken to indicate the presence of reflux. Patients were followed-up with longitudinal spirometry, sputum culture and Leicester cough questionnaire (LCQ). Myeloperoxidase (MPO), free neutrophil elastase (NE) activity, Interleukin (IL)-8 and Tumour Necrosis Factor (TNF)-α was measured from spontaneous sputum samples. RESULTS: 163 completed the study. 59.5% were female. Mean age was 65.7 years. 73.6% reported airway reflux using HARQ. Patients with airway reflux had more severe cough symptoms as assessed by the LCQ [15.2 (3.5) vs. 19.4 (1.9)], p < 0.001. Sputum levels of MPO, NE, IL-8 and TNF-α were all significantly higher in the reflux positive group (p < 0.05 for all comparisons). In a multivariable logistic regression, airway reflux was independently associated with cough severity (-3.27, standard error 0.81, p = 0.0002). Airway reflux, age, FEV1 % predicted and colonization with Pseudomonas aeruginosa were independently associated with an increased risk of ≥3 bronchiectasis exacerbations in one year. CONCLUSION: The symptoms of airway reflux independently predict severity and exacerbation frequency in non cystic fibrosis bronchiectasis.

An evaluation of clinical stability criteria to predict hospital course in community-acquired pneumonia.

A number of different methods exist to assess clinical stability, a key component of pneumonia management. We compared the prognostic value of different stability criteria through a secondary analysis of the Edinburgh pneumonia study database. We studied four clinical stability criteria (Halm's criteria, the ATS criteria, CURB and 50% or more decrease in C-reactive protein from baseline). Outcomes included 30-day mortality, need for mechanical ventilation or vasopressor support (MV/VS), development of a complicated pneumonia, and a combined outcome of the above. A total of 1079 patients (49.8% male), with a median age of 68 years (IQR 53-80), were included. Ninety-three patients (8.6%) died by day 30, 91 patients (8.4%) required MV/VS and 99 patients (9.2%) developed a complicated pneumonia. Patients with increasing severity of pneumonia on admission, assessed by both CURB-65 and PSI, took a progressively longer time to achieve clinical stability assessed by any method (p < 0.001 for all criteria). Halm's criteria had the highest area under the curve (AUC) for prediction of 30-day mortality (AUC 0.95 (0.94-0.96)), need for MV/VS (AUC 0.96 (0.95-0.97)) and combined adverse outcome (AUC 0.96 (0.95-0.97)). C-reactive protein had the highest area under the curve for complicated pneumonia (AUC 0.96 (0.95-0.97)). Adding C-reactive protein to Halm's criteria increased the area under the curve, but the difference was only statistically significant for complicated pneumonia. All of the criteria performed well in predicting adverse outcomes in patients with pneumonia. Halm's criteria performed best when identifying patients at low risk of complications.

Does an interferon-gamma release assay change practice in possible latent tuberculosis?

BACKGROUND AND AIMS: Suspected latent tuberculosis infection (LTBI) is a common reason for referral to TB clinics. Interferon-gamma release assays (IGRAs) are more specific than tuberculin skin tests (TSTs) for diagnosing LTBI. The aim of this study is to determine if IGRA changes practice in the management of cases referred to a TB clinic for possible LTBI. DESIGN AND METHODS: A prospective study was performed over 29 months. All adult patients who had TST, CXR & IGRA were included. The original decision regarding TB chemoprophylaxis was made by TB team consensus, based on clinical history and TST. Cases were then analysed with the addition of IGRA to determine if this had altered management. An independent physician subsequently reviewed the cases. RESULTS: Of 204 patients studied, 68 were immunocompromised. 120 patients had positive TSTs. Of these, 36 (30%) had a positive QFT and 84 (70%) had a negative QFT. Practice changed in 78 (65%) cases with positive TST, all avoiding TB chemoprophylaxis due to QFT. Of the immunocompromised patients, 17 (25%) underwent change of practice. No cases of active TB have developed. CONCLUSION: This study demonstrates a significant change of clinical practice due to IGRA use. Our findings support the NICE 2011 recommendations.

Eight-weekly intravenous antibiotics is beneficial in severe bronchiectasis.

AIM: The aim of our study was to assess the impact of 8-weekly intravenous (IV) antibiotics on exacerbation frequency and health-related quality of life in bronchiectasis. METHODS: Patients were recruited prospectively from June 2008 to December 2010. Patients with recurrent exacerbations (five or more exacerbations per year) and subjectively reporting ill health between antibiotic courses were recruited. Eight-weekly IV antibiotics (for 14 days) were initiated. Patients were followed up for 1 year. Main outcome was reduction in exacerbation frequency and improvement in health-related quality of life (HRQoL) at 1 year after starting intravenous antibiotic therapy. Other outcomes recorded were forced expiratory volume in 1 s (FEV(1)), forced vital capacity (FVC), incremental shuttle walk test (ISWT), 24-h sputum volume, sputum microbiology, body mass index (BMI), markers of inflammation--white cell count (WCC), C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR). RESULTS: In total, 19 patients were recruited. Mean age was 64.1 years and 52.6% were female. With 8-weekly antibiotics, there was a significant reduction in the number of exacerbations [mean (SE): 9.3 (0.5) in the year before vs. 8.0 (0.4) in the year after; P = 0.02]. In 63.2%, Leicester Cough Questionnaire (LCQ) improved by ≥1.3 U (P = 0.006)] and in 42.1% St. George's Respiratory Questionnaire (SGRQ) improved by ≥4 U (P = 0.03). Exercise capacity increased by 58.7 m (P = 0.004). There was no improvement in the other end points. CONCLUSION: Treatment with 8-weekly intravenous antibiotics in severe bronchiectasis reduced exacerbation frequency and improved exercise tolerance and health-related quality of life.

A pilot study of pulmonary rehabilitation and chest physiotherapy versus chest physiotherapy alone in bronchiectasis.

AIM: The aim of our study was to assess the efficacy of pulmonary rehabilitation in addition to regular chest physiotherapy in non cystic fibrosis bronchiectasis. METHODS: Thirty patients with clinically significant bronchiectasis and limited exercise tolerance were randomized into either the control group receiving chest physiotherapy (8 weeks) or into the intervention group, receiving pulmonary rehabilitation in addition to chest physiotherapy (8 weeks). Both groups were encouraged to maintain their exercise program and or chest physiotherapy, following completion of the study. RESULTS: End of training (8 weeks) No improvement in control group. In the intervention group, incremental shuttle walk test (ISWT) improved by 56.7 m (p = 0.03), endurance walk test (EWT) by 193.3 m (p = 0.01), Leicester Cough Questionnaire (LCQ) improved by 2.6 units (p < 0.001) and St. George's Respiratory Questionnaire (SGRQ) by 8 units (p < 0.001). At 20 weeks (12 weeks post end of training) No improvement in control group. In the intervention group, ISWT improved by 80 m (p = 0.04) and EWT by 247.5 m (p = 0.003). LCQ improved by 4.4 units (p < 0.001) and SGRQ by 4 units (p < 0.001). CONCLUSION: Pulmonary rehabilitation in addition to regular chest physiotherapy, improves exercise tolerance and health related quality of life in non cystic fibrosis bronchiectasis and the benefit was sustained at 12 weeks post end of pulmonary rehabilitation. Clinical trials regn no. NCT00868075.

Contact tracing in pulmonary and non-pulmonary tuberculosis.

AIM: The aim of our study was to determine the effectiveness of contact tracing for both pulmonary and non-pulmonary tuberculosis (TB). METHODS: The authors studied contact tracing in South East of Scotland, Edinburgh TB Clinic, UK, for 3 years. New index cases of both pulmonary and non-pulmonary TB were identified from reviewing TB nurses records. Pulmonary involvement was excluded from all non-pulmonary cases. Active TB was diagnosed as per the national TB guidelines. Latent TB was diagnosed based on history, tuberculin skin test and interferon γ release assay. TB contacts were identified from reviewing TB nurses notes on index TB patients. A positive screening episode was defined as identification of either active or latent TB in a contact following relevant investigations. RESULTS: Total number of positive screening episodes for pulmonary TB was 43.1% and non-pulmonary TB was 26.1%. Of these, 78.8% were household contacts and 21.2% were casual contacts. CONCLUSION: Contact tracing in low-prevalence TB countries, for both pulmonary and non-pulmonary TB, is an essential intervention to identify and reduce the number of infected patients that will progress to active disease. This is the key for effective TB control.

Seven-day antibiotic courses have similar efficacy to prolonged courses in severe community-acquired pneumonia--a propensity-adjusted analysis.

There are no studies to guide the optimal duration of therapy in severe community-acquired pneumonia (CAP). The aim of this study was to determine whether 7 days of antibiotic treatment is equivalent to longer-course therapy in severe CAP. In this prospective observational study, we included patients with severe CAP (CURB65 score 3-5) admitted to the hospital with signs and symptoms consistent with pneumonia. A propensity score, derived through multiple logistic regression, was used to match patients into two groups: treated for 7 days vs. treated for >7 days. Patients who died, were admitted to the intensive-care unit, developed complicated pneumonia, failed to reach clinical stability or had positive cultures for microorganisms requiring prolonged treatment within the first 7 days were excluded. Patients outside the mutual range of the propensity score were also excluded. The primary outcome of this study was 30-day mortality. Secondary outcomes were subsequent requirement for mechanical ventilation and/or inotropic support and the development of complicated pneumonia or re-admission within 30 days. Four hundred and twelve patients were suitable for derivation of the propensity score. After matching on propensity score, 164 patients treated for 7 days were compared with 164 treated for >7 days; they were well matched in terms of age, gender, comorbidities, and physiological parameters. The results showed no significant differences in the primary and the secondary outcomes between the two groups. This study therefore suggests that, in the majority of severe CAP patients who have clinically responded, antibiotics can be safely discontinued at 7 days.

Predicting mortality with severity assessment tools in out-patients with community-acquired pneumonia.

INTRODUCTION: In community-acquired pneumonia, severity assessment tools, such as CRB65, CURB65 and Pneumonia Severity Index (PSI), have been promoted to increase the proportion of patients treated in the community. The prognostic accuracy of these scores is established in hospitalized patients, but less is known about their use in out-patients. We aimed to study the accuracy of these severity tools to predict mortality in patients managed as out-patients. METHODS: We performed a systematic review and meta-analysis according to MOOSE guidelines. From 1980 to 2010, we identified 13 studies reporting prognostic information for the CRB65, CURB65 and PSI severity scores in out-patients (either exclusively managed in the community or discharged from an emergency department <24 h after admission). Two reviewers independently collected data and assessed study quality. Performance characteristics across the studies were pooled using a random-effects model. Relationships between sensitivity and specificity were plotted using summary receiver operator characteristic curves (sROC). RESULTS: Out-patient mortality ranged from 0% to 3.5%. Four studies were identified for CRB65, 2 for CURB65 and 10 for PSI. Mortality was low for out-patients in the low-risk CRB65 classes [CRB65 0 or 1: mortality occurred in 3 of 1494 patients (0.2%)] but higher in CRB65 Groups 2-4 [mortality 13 of 154 patients (8.4%)]. Similarly, mortality was low in PSI Classes I-III [mortality 8 of 3655 patients (0.2%)] managed as out-patients but higher in Classes IV and V [mortality 32 of 317 patients (10.1%)]. CRB65 showed pooled sensitivity of 81% (54-96%), pooled specificity of 91% (90-93%) and the area under the sROC was 0.91 [standard error (SE) 0.05]. For PSI, pooled sensitivity was 92% (64-100%), pooled specificity was 90% (89-91%) and area under the sROC was 0.92 (SE 0.03). There were insufficient studies to analyse CURB65. CONCLUSION: The limited data available suggest that CRB65 and PSI can identify groups of patients at low risk of mortality that can be safely managed in the community.

Physician judgement is a crucial adjunct to pneumonia severity scores in low-risk patients.

This study investigates the reasons for hospitalisation in patients with low-risk (CURB-65 score 0-1) community-acquired pneumonia (CAP), with a view to identifying the potential for improving outpatient management. As part of a prospective observational study of CAP, we evaluated reasons for hospitalisation in these low-risk patients. 565 patients had low-risk CAP and 420 of these were admitted (for >12 h). 39.3% had additional markers of severity justifying admission, 29.5% of the admissions were required for further management that could not be provided rapidly in the community, 11.9% had unsafe social circumstances and 19.3% had no clinical reason justifying hospitalisation. 30-day mortality was increased in patients with additional severity markers (6.7%), which was significantly higher compared with 0% for patients awaiting investigations (p=0.009) and 0% without a clear indication for hospitalisation (p=0.04). In a logistic regression analysis, parameters associated with 30-day mortality were chronic cardiac comorbidity (adjusted odds ratio (aOR) 5.73, 95% CI 1.52-21.6; p=0.01), acidosis (aOR 5.14, 95% CI 1.44-18.3; p=0.01), hypoxia (aOR 9.86, 95% CI 2.39-40.7; p=0.002) and multilobar chest radiograph shadowing (aOR 4.54, 95% CI 1.21-17.1; p=0.03). This study supports recommendations from international guidelines that pneumonia severity scores should be used as an adjunct to clinical judgement, when deciding on hospitalisation.

Impact of inhaled corticosteroid use on outcome in COPD patients admitted with pneumonia.

The aim of this study was to investigate whether inhaled corticosteroid (ICS) use affects outcome in patients with chronic obstructive pulmonary disease (COPD) admitted with community-acquired pneumonia (CAP). This was a prospective, observational study of patients with spirometry-confirmed COPD presenting with a primary diagnosis of CAP in Lothian, UK. Outcome measures were compared between ICS users and non-ICS users. Of 490 patients included in the study, 76.7% were classified as ICS users. ICS users had higher Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage compared with non-ICS users (mean ± sd 3.2 ± 0.8 versus 2.6 ± 0.9; p<0.0001). There were no significant differences in pneumonia severity (mean ± sd Pneumonia Severity Index (PSI) 4.2 ± 0.8 versus 4.3 ± 0.8 (p = 0.3); mean ± sd CURB-65 score 2.1 ± 1.3 versus 2.3 ± 1.3 (p = 0.07)) or markers of systemic inflammation (median C-reactive protein 148 (interquartile range 58-268) mg·L(-1) versus 183 (IQR 85-302) mg·L(-1); p = 0.08) between ICS users and non-ICS users. On multivariable analysis, after adjustment for COPD severity and PSI, ICS use was not independently associated with 30-day mortality (OR 1.71, 95% CI 0.75-3.90; p = 0.2), 6-month mortality (OR 1.62, 95% CI 0.82-3.16; p = 0.2), requirement for mechanical ventilation and/or inotropic support (OR 0.73, 95% CI 0.33-1.62; p = 0.4) or development of complicated pneumonia (OR 0.71, 95% CI 0.25-1.99; p = 0.5). Prior ICS use had no impact on outcome in patients with COPD admitted with CAP.