Pro-oxidant iron in exhaled breath condensate: a potential excretory mechanism.

AIMS: Pro-oxidant iron provides a potential measure of iron-catalysed oxidative stress in biological fluids. This study aimed, to investigate if the Bleomycin technique for measurement of pro-oxidant iron in biological fluids could be utilised for determinations in exhaled breath condensate (EBC). Secondly, to measure levels of pro-oxidant iron in EBC from asthmatics after exposure to polluting city environments. METHODS: Retrospective analysis of samples of EBC and bronchoalveolar lavage fluid (BALF). Pro-oxidant iron levels were determined by the Bleomycin method. Transferrin levels were determined by radial diffusion immunoassay and lactoferrin by ELISA. SUBJECTS: Patients undergoing surgery necessitating cardiopulmonary bypass, normal healthy controls, "healthy" smokers, and asthmatics (mild and moderate). RESULTS: Pro-oxidant iron was significantly decreased (p<0.05) post cardiac surgery in both EBC and BALF. In smokers levels of pro-oxidant iron in EBC were significantly (p<0.05) increased verses healthy controls. In asthmatics with more severe disease, there were significant increases in EBC pro-oxidant iron content post exposure to city environments (p<0.001), with levels most elevated after exposure to the most polluted setting. CONCLUSION: Similar patterns in the levels of pro-oxidant iron detectable in EBC and paired BALF from patients undergoing cardiopulmonary bypass (pre and post surgery) suggest a potential for EBC determinations. Significantly elevated levels in EBC from smokers relative to control subjects provide further support for this technique. In asthma disease severity and environmental exposure influenced levels of pro-oxidant iron measured in EBC indicating a potential for enhanced iron-catalysed oxidative stress.

Improving venous thromboembolic disease prophylaxis in medical inpatients: a role for education and audit.

BACKGROUND: Venous thromboembolic disease (VTED) prophylaxis is a key strategy in reducing preventable deaths in medical inpatients. We assessed compliance with internationally published guidelines for VTED prophylaxis in at-risk medical patients before and 1 month after an educational intervention to enhance compliance with such guidelines. RESULTS: One hundred and fifty patients were assessed on each occasion. Pre-intervention, VTED prophylaxis was prescribed in only 48% of at-risk cases. Compliance was best among patients under stroke services and worst for those under acute medical teams. Patients within specialist units were more likely to be prescribed prophylaxis than those in general wards (75 vs. 53%; p = 0.0019). Post-intervention, overall compliance improved to 63% (p = 0.041 for comparison). There was a significant improvement among general medical teams (48 vs. 75%; p = 0.001), and in general wards (52 vs. 74%; p = 0.003). CONCLUSIONS: Thromboprophylaxis is under-prescribed in medical inpatients, but compliance with international guidelines can be significantly enhanced with targeted educational intervention.

Endoscopic ultrasound with fine needle aspiration and biopsy in lung cancer and isolated mediastinal lymphadenopathy.

Endoscopic ultrasound with fine-needle aspiration and biopsy (EUS-FNAB) is well established in diagnosing and staging lung cancer in patients with mediastinal adenopathy. EUS-FNAB is highly sensitive, less invasive and has lower complication rates when compared to surgical staging of mediastinal nodes. In this study we describe our experience of EUS-FNAB in lung cancer and other causes of mediastinal lymphadenopathy. EUS-FNAB was performed for assessment of PET positive mediastinal lymph nodes between January 2007 and March 2009 in AMNCH. The endpoints of our study were sensitivity and specificity of EUS-FNAB, morbidity and length of hospital stay. Thirty four patients underwent EUS-FNAB during the study period for both diagnosis and staging. Thirty patients had positive lymph node invasion and 4 had no evidence of malignant invasion. In these 4 patients negative cytology was confirmed on mediastinoscopy giving EUS-FNAB a sensitivity and specificity of 100%. EUS-FNAB upstaged the disease in 12 patients. EUS-FNAB is a reliable tool for mediastinal staging in lung cancer, significantly reducing the need for surgical staging procedures in patients with suspected mediastinal involvement.

Impact of an acute medical admission unit on hospital mortality: a 5-year prospective study.

AIM: To determine the impact of the introduction of an acute medical admission unit (AMAU) on all-cause hospital mortality in unselected patients undergoing acute medical admission to a teaching hospital. DESIGN: Analysis of data recorded in the hospital in-patient enquiry (HIPE) system relating to all emergency medical patients admitted to St James's Hospital (SJH), Dublin between 1 January 2002 and 31 December 2006. METHODS: The reference year was 2002, during which patients were admitted to a variety of wards under the care of a named consultant physician. In 2003, two centrally located wards were re-configured to function as an AMAU, and all emergency medical patients were admitted to this unit following emergency department evaluation. Hospital mortality was obtained from a database of deaths occurring during this period and linked to HIPE data. RESULTS: Following the introduction of the AMAU process, all-cause hospital mortality decreased from 12.6% in 2002 to 7.0% in 2006 (P < 0.0001), representing a 44.4% relative reduction during the course of the 5-year observation period (P < 0.0001). The Odds ratio (95% confidence interval) for all-cause mortality in 2006 compared with 2002 was 0.28 (0.23, 0.35). This effect was powerfully independent of other covariates, including Charlson co-morbidity and illness severity score (APACHE II), in binary logistic regression analysis and was observed across a wide cross-section of diagnostic groups. CONCLUSION: The introduction of an AMAU significantly improved all-cause hospital mortality in acute unselected medical patients. The delivery of Acute Medicine may be enhanced by structural reform with emphasis on focus and volume. Prospective studies validating similar models elsewhere should be explored.

Emergency department census of patients awaiting admission following reorganisation of an admissions process.

OBJECTIVES: To determine the impact of reorganisation of an acute admissions process on numbers of people in the emergency department (ED) awaiting admission to a hospital bed in a major teaching hospital. METHODS: We studied all emergency medical patients admitted to St James' Hospital, Dublin, between 1 January 2002 and 31 December 2004. In 2002, patients were admitted to a variety of wards from the ED when a hospital bed became available. In 2003, two centrally located wards were reconfigured to function as an acute medical admissions unit (AMAU) (bed capacity 59), and all emergency patients were admitted directly to this unit from the ED (average 15 admissions per day). The maximum permitted length of stay on the AMAU was 5 days. We recorded the number of patients in the ED, who were awaiting the availability of a hospital bed, at 0700 and 1700 on the days of recording during the 36 month study period. RESULTS: The impact of the AMAU reduced overall hospital length of stay from 7 days in 2002 to 5 days in 2003 and 2004 (p<0.0001). The median number of patients waiting in the ED for a hospital bed reduced from 14 in 2002 to 9 in 2003 and 8 in 2004 (p<0.0001). While age and sex of patients did not differ over the years, the factors that independently contributed to the number of patients awaiting admission were the day of the week, the month of the year, and and the extent of the comorbidity index on the previous day's intake (p<0.0001). CONCLUSIONS: This study found that reorganisation of a system for acute medical admissions can significantly impact on the number of patients awaiting admission to a hospital bed, and allow an ED to operate efficiently and at a level of risk acceptable to patients.

Do consultants differ? Inferences drawn from hospital in-patient enquiry (HIPE) discharge coding at an Irish teaching hospital.

OBJECTIVE: To find out if there was a difference between hospital consultants, all trained in acute general medicine, in length of stay (LOS), re-admission rates, resource utilisation, and diagnostic coding, among patients admitted as emergencies to St James' Hospital (SJH) Dublin. METHODS: A retrospective analysis was performed of data on discharges from hospital, recorded in the hospital in-patient enquiry (HIPE) system, relating to 9204 episodes among 6968 emergency medical patients admitted to SJH between 1 January 2002 and 31 October 2003. For comparative analysis, four physician groups were defined consisting of gastroenterology (GI, n = 4), respiratory (n = 3), general internal medicine (GIM, n = 2), or specialty (n = 5). RESULTS: GIM consultants had the shortest LOS (median 5 days); GIM and respiratory consultants were less likely to have long stay patients (> 30 days, p<0.0001). Patients re-admitted under the same consultant had a longer LOS than those re-admitted under a different consultant (p<0.0001). Endoscopy and GI radiology investigations were used most by GI consultants, computed tomography of the thorax by respiratory, ECHO by respiratory and specialty, and computed tomography of brain by GIM and specialty consultants. GI diagnostic codings were more frequent with GI consultants (p<0.0001), respiratory diagnoses and malignancy with respiratory (p<0.0001 for both), diabetes and hypertension with specialty (p = 0.0017), and heart failure more with GIM consultants (p = 0.001). CONCLUSIONS: This study found that the HIPE database was very powerful in predicting differences between hospital consultants in LOS, re-admission rates, resource utilisation, and disease coding. It would be of interest to examine the extent to which protocols and guidelines could reduce such variations.

Impact of an acute medical admission unit on length of hospital stay, and emergency department 'wait times'.

BACKGROUND: While many UK hospitals have introduced an acute medical admissions unit (AMAU) to facilitate an efficient emergency admission process and reduce length of hospital stay (LOS), there is a lack of such data in the Republic of Ireland. AIM: To determine the impact of an AMAU on emergency department (ED) wait times for a hospital bed, consultant practice, and LOS. DESIGN: Retrospective analysis of data recorded in the hospital in-patient enquiry (HIPE) system. METHODS: We studied all emergency medical patients admitted to St James' Hospital Dublin between 1 January 2002 and 31 December 2003. In 2002, patients were admitted directly to a variety of wards, many of which were not affiliated with a medical specialty, under the care of a named consultant physician. In 2003, two centrally located wards were re-configured to function as an AMAU, and all emergency patients were admitted to this unit. RESULTS: For all physician teams, median LOS shortened significantly from 2002 to 2003 (6 vs. 5 days, p<0.0001). Overall, patients seen by general physicians had a shorter LOS (5 days) than that of those seen by sub-specialists (6 days) (p<0.0001). The number of patients waiting in the ED for a hospital bed was reduced by 30% from 2002 to 2003 (p<0.001). Extrapolated cost savings for the hospital with the introduction of the AMAU were estimated at approximately 4039 bed-days and 1 714 152. DISCUSSION: Introduction of the AMAU speeded access to acute medical service and reduced costs.

Length of hospital stay, diagnoses and pattern of investigation following emergency admission to an Irish teaching hospital.

Data on discharges from acute public hospitals in Ireland is recorded in the hospital in-patient enquiry (HIPE) system; its value in describing the casemix and pattern of resource utilization following emergency medical admissions has not been examined. We wished to determine whether there was a relationship between coded diseases at the time of discharge, patterns of investigation, and length of hospital stay (LOS) in a major teaching hospital. Data relating to emergency medical patients admitted to St James' Hospital Dublin between 1st January and 31st December 2002 was recorded. Of 5038 episodes evaluated, the median LOS was 6 days (IQR 3-13); this was significantly shorter when the patient was admitted under a general medical service (p<0.0001). There was also a positive correlation between patient age and LOS (r = 0.32; p<0.0001). No test request was associated with a shortened LOS. Prolonged LOS was associated with oesophago-gastro-duodenoscopy, echocardiography, computerised tomography, magnetic resonance imaging, and abdominal ultrasonography testing. Furthermore, prolonged LOS was associated with the following disease related groups (DRG) at discharge; codes related to heart failure, respiratory system, malignancy, stroke, diabetes, psychiatry, and anaemia. We found that clinical coding using the HIPE database strongly predicted hospital LOS for acute general medical admissions. Spare bed capacity is essential if an acute hospital is to operate efficiently and at a level of risk acceptable to patients. Therefore, determining major influences on hospital LOS is valuable, to develop potential strategies to optimise efficient utilization of acute bed capacity.

Patient and disease profile of emergency medical readmissions to an Irish teaching hospital.

OBJECTIVE: To determine whether there was a relationship between coded diseases at the time of hospital discharge, a pattern of ordering investigations, and hospital readmission in a major teaching hospital. DESIGN: Systematic review of data relating to emergency medical patients admitted to St James' Hospital Dublin between 1 January and 31 December 2002. DATA SOURCES AND METHODS: Data on discharges from hospital recorded in the Hospital In-Patient Enquiry (HIPE) system. The value of HIPE data in describing the relationship between the pattern of resource utilisation, diagnostic related groups, and hospital readmission has not previously been examined. RESULTS: Of 5038 episodes recorded among 4050 patients admitted, the number of readmissions was up to 15. Age and male gender were factors associated with readmission, and readmitted patients remained in hospital for longer. No particular test request predicted readmission, but computed tomography of the brain was associated with a reduced readmission rate. Discharge diagnostic related group coding at first discharge predicted readmission-codes related to heart failure, respiratory system, alcohol, malignancy, and anaemia. CONCLUSIONS: It was found that clinical coding using the HIPE database strongly predicted hospital readmission. It may be argued that early hospital readmission reflects unsatisfactory patient care, alternatively that many readmissions are not preventable, representing either new events in elderly patients with chronic illnesses and frequent co-morbidity or related to social factors. The utility of specific interventions, in patients at high risk for hospital readmission, could be explored.

Pharmacokinetics of sirolimus in heart transplant recipients with chronic renal impairment.

BACKGROUND: A common clinical problem following organ transplantation is the development of renal failure due to calcineurin inhibitors. Sirolimus offers the potential of providing appropriate immunosuppression without nephrotoxicity. This study evaluates the impact of sirolimus monotherapy on renal function in patients late following heart transplantation and correlates trough sirolimus levels with area-under-the-concentration time curve measurements. METHODS: Six male patients with renal impairment late following heart transplantation (mean 8 years) were offered sirolimus therapy. Calcineurin inhibition was discontinued in all patients on commencing sirolimus. Patients started on sirolimus 2 to 5 mg/d orally. Venous blood samples for pharmacokinetic studies and repeat creatinine clearance were performed before and 6 weeks after commencement of sirolimus in all subjects. RESULTS: Sirolimus trough levels accurately reflected sirolimus area-under-the-concentration time curve measurements. There was no change in renal function. Mean creatinine clearance prior to commencing sirolimus was 26.7 (12.2) mL/min and the post-sirolimus creatinine clearance performed 6 weeks later was 23.4 (11.7) mL/min (P = .64). CONCLUSIONS: Trough levels of sirolimus correlate with drug exposure and may be used to monitor sirolimus therapy. No improvement in renal function following calcineurin inhibitor withdrawal occurred in this cohort.

Protective ventilation of patients with acute respiratory distress syndrome.

The majority of patients with acute respiratory distress syndrome (ARDS) require mechanical ventilation. This support provides time for the lungs to heal, but the adverse effects of mechanical ventilation significantly influence patient outcome. Traditionally, these were ascribed to mechanical effects, such as haemodynamic compromise from decreased venous return or gross air leaks induced by large transpulmonary pressures. More recently, however, the ARDS Network study has established the clinical importance of lowering the tidal volume to limit overdistension of the lung when ventilating patients with ARDS. This study suggests that ventilator-associated lung injury (VALI) caused by overdistension of the lung contributes to the mortality of patients with ARDS. Moreover, the results from clinical and basic research have revealed more subtle types of VALI, including upregulation of the inflammatory response in the injured and overdistended lung. This not only damages the lung, but the overflow of inflammatory mediators into the systemic circulation may explain why most patients who die with ARDS succumb to multi-organ failure rather than respiratory failure. The results of these studies, the present understanding of the pathophysiology of VALI, and protective ventilatory strategies are reviewed.

Release of inflammatory mediators from eosinophils following a hyperosmolar stimulus.

Airway dehydration and subsequent hyperosmolarity of periciliary fluid are considered critical events in exercise-induced bronchoconstriction (EIB). It has been shown that an in vitro hyperosmolar stimulation of basophils and mast cells with mannitol can induce the release of histamine and leukotrienes. The aim of this study was to establish if a hyperosmolar challenge could trigger activation of eosinophils to release chemokines and lipid mediators. Peripheral blood eosinophils were isolated from seven asthmatic and six non-asthmatic subjects. Hyperosmolar stimulation of eosinophils with mannitol (0.7 M), resulted in a significant increase in LTC4 levels compared to baseline in both asthmatic (15.2+/-4.6 vs. 70.1+/-9.5; P = 0.0002) and control subjects (14.3+/-4.0 vs. 55.6+/-5.6; P = 0.0001). ECP levels did not increase significantly above baseline following mannitol stimulation in either group. This study shows that eosinophils can be activated by a hyperosmolar stimulus. Therefore it seems reasonable to suggest that eosinophils could contribute to EIB.

The shuttle walk exercise test in idiopathic pulmonary fibrosis.

The shuttle walk test (SWT) is a validated, incremental walking test for chronic obstructive pulmonary disease, but not for idiopathic pulmonary fibrosis (IPF). The measurement of maximal oxygen consumption (VO2 max) is considered to be the gold standard measurement of functional capacity. This study examines the relationship between IPF patients' performance on the SWT and VO2 max. Twenty patients were recruited for the study, which consisted of two separate experiments. Firstly, the relationship between SWT performance on a conventional corridor SWT, with that on a programmable treadmill SWT designed to reproduce the corridor SWT was examined (n=10). In the second experiment, the relationship between performance on the treadmill equivalent SWT and VO2 max measurements was studied (n=10). There was a significant correlation between distance walked on the corridor SWT, and that walked on the treadmill equivalent SWT without VO2 max measurements (367 m vs. 410 m) (r=0.91, P=0.0003). There was a significant correlation between distance walked on the treadmill equivalent SWT (277 m), and the directly determined VO2 max (14.87 ml/kg/min) (r=0.74, P=0.01). During both experiments, a significant correlation was also observed between baseline PaO2 and SWT performance, and between DLCO and SWT performance. The shuttle walk test is a simple objective measure of functional capacity in IPF patients, which should facilitate the evaluation of new therapeutic compounds for IPF.

Pathophysiology and pharmacological treatment of pulmonary hypertension in acute respiratory distress syndrome.

Pulmonary hypertension (PH) is a characteristic feature of the acute respiratory distress syndrome (ARDS). The magnitude of PH has been shown to correlate with the severity of lung injury in patients with ARDS independently of the severity of associated hypoxaemia and has an adverse prognostic significance. Early in the histopathological evolution of ARDS, pulmonary vasoconstriction, thromboembolism and interstitial oedema contribute to the development of PH, although pulmonary vascular remodelling probably occurs eventually. Intravenous vasodilator agents lead to an increase in intrapulmonary shunting and systemic hypotension, which can limit their therapeutic use, and have not been shown to improve survival. By contrast, rapidly metabolised vasodilators administered by inhalation induce selective pulmonary vasodilatation and decrease shunting, but again do not appear to confer a survival benefit. Research aimed at further understanding the mechanisms that underlie pulmonary hypertension, a characteristic feature of the acute respiratory distress syndrome, are expected to provide improvements in pharmacological interventions for the treatment of pulmonary hypertension in the acute respiratory distress syndrome.

Rapid dendritic cell recruitment to the bronchial mucosa of patients with atopic asthma in response to local allergen challenge.

BACKGROUND: Airway dendritic cells (DC) play an important role in chronic allergic airway inflammation in experimental animals, but a similar role for DC in human allergic asthma has been difficult to define. This pilot study was undertaken to elucidate the role of DC in allergic asthma by examining their potential to migrate to the lower airways in response to bronchial challenge with specific allergen. METHODS: Bronchial biopsy specimens were obtained from seven patients with allergic asthma before and 4-5 hours after allergen challenge. Multicolour immunofluorescence staining was performed on mucosal cryosections to identify changes in the number and phenotypes of DC. RESULTS: A dramatic increase in the number of CD1c+HLA-DR+ DC were observed in the lamina propria after challenge compared with baseline (22.4 v 7.8 cells/mm(2)). The rapid accumulation (within 4-5 hours) of these cells strongly suggests that they were directly recruited from peripheral blood. CONCLUSION: We have shown for the first time that a specific DC subset rapidly emigrates into the human bronchial mucosa during allergic inflammation. While this study is based on relatively few patients, the consistency of the overall results strongly suggests that the rapid population dynamics of human airway DC closely parallel those in animal models of acute inflammation. These findings support suggestions that DC have an important role in human airway allergy.

Controlled oxygen therapy and carbon dioxide retention during exacerbations of chronic obstructive pulmonary disease.

Hypoxaemic patients with exacerbations of chronic obstructive pulmonary disease (COPD) are at some risk of carbon dioxide (CO2) retention during oxygen therapy. We quantified the risk of CO2 retention with oxygen therapy in COPD in 24 consecutive patients presenting to the accident and emergency department with acute exacerbations associated with hypercapnic respiratory failure (partial arterial pressure of oxygen [PaO2] < 8 kPa and partial pressure of CO2 [PaCO2] > or = 6.5 kPa). Only three patients developed clinically important CO2 retention (defined as a rise in PaCO2 > 1 kPa) with controlled oxygen therapy (24-40% by Venturi mask to maintain the oxygen saturation at 91-92%). These patients presented with more severe hypercapnia, but all three required only low-flow oxygen (24-28%). These findings suggest only a small risk of aggravating hypercapnia with controlled oxygen supplementation.