Necrotising pneumonia due to influenza A (H1N1) and community-acquired methicillin-resistant Staphylococcus aureus clone USA300: successful management of the first documented paediatric case.

Necrotising pneumonia in young, previously healthy patients due to Panton–Valentine leucocidin (PVL) producing Staphylococcus aureus has been increasingly recognised. PVL pneumonia is often associated with influenza co-infection and high mortality. This case report describes the successful management of the first documented paediatric case of a previous healthy adolescent who developed necrotising pneumonia due to community-acquired methicillin-resistant (CA-MRSA) clone USA300 with pandemic influenza A (H1N1) co-infection, and highlights the importance of early recognition and initiation of appropriate therapy for this potentially fatal co-infection. PCR remains the gold standard to diagnose pandemic H1N1 since it may not be detected by rapid antigen tests. Bacterial necrotising pneumonia should be suspected in those presenting with worsening flu-like symptoms and clinical and/or radiological evidence of PVL infection (multifocal infiltrates, effusion and cavitation). These patients may benefit from the administration of toxin neutralising agents. In light of the current H1N1 pandemic, healthcare professionals will be increasingly confronted with this clinical scenario.

Treatment rationale and study design for a phase III, double-blind, placebo-controlled study of maintenance pemetrexed plus best supportive care versus best supportive care immediately following induction treatment with pemetrexed plus cisplatin for advanced nonsquamous non-small cell lung cancer.

BACKGROUND: To improve the efficacy of first-line therapy for advanced non-small cell lung cancer (NSCLC), additional maintenance chemotherapy may be given after initial induction chemotherapy in patients who did not progress during the initial treatment, rather than waiting for disease progression to administer second-line treatment. Maintenance therapy may consist of an agent that either was or was not present in the induction regimen. The antifolate pemetrexed is efficacious in combination with cisplatin for first-line treatment of advanced NSCLC and has shown efficacy as a maintenance agent in studies in which it was not included in the induction regimen. We designed a phase III study to determine if pemetrexed maintenance therapy improves progression-free survival (PFS) and overall survival (OS) after cisplatin/pemetrexed induction therapy in patients with advanced nonsquamous NSCLC. Furthermore, since evidence suggests expression levels of thymidylate synthase, the primary target of pemetrexed, may be associated with responsiveness to pemetrexed, translational research will address whether thymidylate synthase expression correlates with efficacy outcomes of pemetrexed. METHODS/DESIGN: Approximately 900 patients will receive four cycles of induction chemotherapy consisting of pemetrexed (500 mg/m2) and cisplatin (75 mg/m2) on day 1 of a 21-day cycle. Patients with an Eastern Cooperative Oncology Group performance status of 0 or 1 who have not progressed during induction therapy will randomly receive (in a 2:1 ratio) one of two double-blind maintenance regimens: pemetrexed (500 mg/m2 on day 1 of a 21-day cycle) plus best supportive care (BSC) or placebo plus BSC. The primary objective is to compare PFS between treatment arms. Secondary objectives include a fully powered analysis of OS, objective tumor response rate, patient-reported outcomes, resource utilization, and toxicity. Tumor specimens for translational research will be obtained from consenting patients before induction treatment, with a second biopsy performed in eligible patients following the induction phase. DISCUSSION: Although using a drug as maintenance therapy that was not used in the induction regimen exposes patients to an agent with a different mechanism of action, evidence suggests that continued use of an agent present in the induction regimen as maintenance therapy enables the identification of patients most likely to benefit from maintenance treatment.

Eosinophil cationic protein is not only a distinctive eosinophil protein

We read with interest the article by Qiu et al (Thorax 2007;62:475–82). In this paper, neutrophils and eosinophils were identified using mouse anti-human neutrophil elastase and anti-eosinophil cationic protein (ECP), both monoclonal antibodies (mAbs). mAbs against ECP have been used to detect total eosinophils, but immunostaining techniques evidenced that the number of ECP+ cells was higher than the number of eosinophils.1 Recent studies show that ECP is not only a distinctive eosinophil protein, but has been found in neutrophils.1–3

Intratracheal dopamine attenuates pulmonary edema and improves survival after ventilator-induced lung injury in rats

INTRODUCTION Clearance of alveolar oedema depends on active transport of sodium across the alveolar-epithelial barrier. beta-Adrenergic agonists increase clearance of pulmonary oedema, but it has not been established whether beta-agonist stimulation achieves sufficient oedema clearance to improve survival in animals. The objective of this study was to determine whether the increased pulmonary oedema clearance produced by intratracheal dopamine improves the survival of rats after mechanical ventilation with high tidal volume (HVT). METHODS This was a randomized, controlled, experimental study. One hundred and thirty-two Wistar-Kyoto rats, weighing 250 to 300 g, were anaesthetized and cannulated via endotracheal tube. Pulmonary oedema was induced by endotracheal instillation of saline solution and mechanical ventilation with HVT. Two types of experiment were carried out. The first was an analysis of pulmonary oedema conducted in six groups of 10 rats ventilated with low (8 ml/kg) or high (25 ml/kg) tidal volume for 30 or 60 minutes with or without intratracheally instilled dopamine. At the end of the experiment the animals were exsanguinated and pulmonary oedema analysis performed. The second experiment was a survival analysis, which was conducted in two groups of 36 animals ventilated with HVT for 60 minutes with or without intratracheal dopamine; survival of the animals was monitored for up to 7 days after extubation. RESULTS In animals ventilated at HVT with or without intratracheal dopamine, oxygen saturation deteriorated over time and was significantly higher at 30 minutes than at 60 minutes. After 60 minutes, a lower wet weight/dry weight ratio was observed in rats ventilated with HVT and instilled with dopamine than in rats ventilated with HVT without dopamine (3.9 +/- 0.27 versus 4.9 +/- 0.29; P = 0.014). Survival was significantly (P = 0.013) higher in animals receiving intratracheal dopamine and ventilated with HVT, especially at 15 minutes after extubation, when 11 of the 36 animals in the HVT group had died as compared with only one out of the 36 animals in the HVT plus dopamine group. CONCLUSION Intratracheal dopamine instillation increased pulmonary oedema clearance in rats ventilated with HVT, and this greater clearance was associated with improved survival.

Clinical presentation and time-course of postoperative venous thromboembolism: Results from the RIETE Registry

There is little literature about the clinical presentation and time-course of postoperative venous thromboembolism (VTE) in different surgical procedures. RIETE is an ongoing, prospective registry of consecutive patients with objectively confirmed, symptomatic acute VTE. In this analysis, we analysed the baseline characteristics, thromboprophylaxis and therapeutic patterns, time-course, and three-month outcome of all patients with postoperative VTE. As of January 2006, there were 1,602 patients with postoperative VTE in RIETE: 393 (25%) after major orthopaedic surgery (145 elective hip arthroplasty, 126 knee arthroplasty, 122 hip fracture); 207 (13%) after cancer surgery; 1,002 (63%) after other procedures. The percentage of patients presenting with clinically overt pulmonary embolism (PE) (48%, 48%, and 50% respectively), the average time elapsed from surgery to VTE (22 +/- 16, 24 +/- 16, and 21 +/- 15 days, respectively), and the three-month incidence of fatal PE (1.3%, 1.4%, and 0.8%, respectively), fatal bleeding (0.8%, 1.0%, and 0.2%, respectively), or major bleeding (2.3%, 2.9%, and 2.8%, respectively) were similar in the three groups. However, the percentage of patients who had received thromboprophylaxis (96%, 76% and 52%, respectively), the duration of prophylaxis (17 +/- 9.6, 13 +/- 8.9, and 12 +/- 11 days, respectively) and the mean daily doses of low-molecular-weight heparin (4,252 +/- 1,016, 3,260 +/- 1,141, and 3,769 +/- 1,650 IU, respectively), were significantly lower in those undergoing cancer surgery or other procedures. In conclusion, the clinical presentation, time-course, and three-month outcome of VTE was similar among the different subgroups of patients, but the use of prophylaxis in patients undergoing cancer surgery or other procedures was suboptimal.

Alveolar fluid clearance in healthy pigs and influence of positive end-expiratory pressure

INTRODUCTION The objectives were to characterize alveolar fluid clearance (AFC) in pigs with normal lungs and to analyze the effect of immediate application of positive end-expiratory pressure (PEEP). METHODS Animals (n = 25) were mechanically ventilated and divided into four groups: small edema (SE) group, producing pulmonary edema (PE) by intratracheal instillation of 4 ml/kg of saline solution; small edema with PEEP (SE + PEEP) group, same as previous but applying PEEP of 10 cmH2O; large edema (LE) group, producing PE by instillation of 10 ml/kg of saline solution; and large edema with PEEP (LE + PEEP) group, same as LE group but applying PEEP of 10 cmH2O. AFC was estimated from differences in extravascular lung water values obtained by transpulmonary thermodilution method. RESULTS At one hour, AFC was 19.4% in SE group and 18.0% in LE group. In the SE + PEEP group, the AFC rate was higher at one hour than at subsequent time points and higher than in the SE group (45.4% vs. 19.4% at one hour, P < 0.05). The AFC rate was also significantly higher in the LE + PEEP than in the LE group at three hours and four hours. CONCLUSIONS In this pig model, the AFC rate is around 20% at one hour and around 50% at four hours, regardless of the amount of edema, and is increased by the application of PEEP.

Asma en la edad pediátrica : proceso asistencial integrado

Este documento (2003), junto con el de Asma en la edad adulta (2004), han sido unificados en un único Proceso Asistencial Integrado: Asma (2012)[http://hdl.handle.net/10668/674]. Publicado en la página web de la Consejería de Salud y Bienestar Social: www.juntadeandalucia.es/salud (Consejería de Salud y Bienestar Social/ Profesionales / Nuestro Compromiso por la Calidad / Proceso Asistencial Integrado Asma / Histórico de documentos del PAI Asma)

Asma del adulto : proceso asistencial integrado

Este documento (2004), junto con el de Asma en la edad pediátrica (2003), han sido unificados en un único Proceso Asistencial Integrado: Asma (2012)[http://hdl.handle.net/10668/674]. Publicado en la página web de la Consejería de Salud y Bienestar Social: www.juntadeandalucia.es/salud (Consejería de Salud y Bienestar Social/ Profesionales / Nuestro Compromiso por la Calidad / Proceso Asistencial Integrado Asma / Histórico de documentos del PAI Asma)

Asma : proceso asistencial integrado

Este Proceso (2012) integra los dos publicados anteriormente de Asma en la edad pediátrica (2003) y Asma en la edad adulta (2004). Fichero en formato pdf, publicado en la página web de la Consejería de Salud y Bienestar Social: www.juntadeandalucia.es/salud (Consejería de Salud y Bienestar Social / Profesionales / Nuestro Compromiso por la Calidad / Procesos Asistenciales Integrados)

Conozca cómo vivir mejor con la EPOC : guía de información para pacientes

En la port.: Respuestas sencillas a las preguntas más frecuentes sobre la enfermedad pulmonar obstructiva crónica (EPOC)

High Prevalence of Systemic Autoimmune Diseases in Patients with Meniere's Disease

BACKGROUND. Autoimmunity appears to be associated with the pathophysiology of Meniere's disease (MD), an inner ear disorder characterized by episodes of vertigo associated with hearing loss and tinnitus. However, the prevalence of autoimmune diseases (AD) in patients with MD has not been studied in individuals with uni or bilateral sensorineural hearing loss (SNHL). METHODS AND FINDINGS. We estimated the prevalence of AD in 690 outpatients with MD with uni or bilateral SNHL from otoneurology clinics at six tertiary referral hospitals by using clinica criteria and an immune panel (lymphocyte populations, antinuclear antibodies, C3, C4 and proinflammatory cytokines TNFα, INFγ). The observed prevalence of rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and ankylosing spondylitis (AS) was higher than expected for the general population (1.39 for RA, 0.87 for SLE and 0.70 for AS, respectively). Systemic AD were more frequently observed in patients with MD and diagnostic criteria for migraine than cases with MD and tension-type headache (p = 0.007). There were clinical differences between patients with uni or bilateral SNHL, but no differences were found in the immune profile. Multiple linear regression showed that changes in lymphocytes subpopulations were associated with hearing loss and persistence of vertigo, suggesting a role for the immune response in MD. CONCLUSIONS. Despite some limitations, MD displays an elevated prevalence of systemic AD such as RA, SLE and AS. This finding, which suggests an autoimmune background in a subset of patients with MD, has important implications for the treatment of MD.

Municipal distribution of bladder cancer mortality in Spain: Possible role of mining and industry

BACKGROUND Spain shows the highest bladder cancer incidence rates in men among European countries. The most important risk factors are tobacco smoking and occupational exposure to a range of different chemical substances, such as aromatic amines. METHODS This paper describes the municipal distribution of bladder cancer mortality and attempts to "adjust" this spatial pattern for the prevalence of smokers, using the autoregressive spatial model proposed by Besag, York and Molliè, with relative risk of lung cancer mortality as a surrogate. RESULTS It has been possible to compile and ascertain the posterior distribution of relative risk for bladder cancer adjusted for lung cancer mortality, on the basis of a single Bayesian spatial model covering all of Spain's 8077 towns. Maps were plotted depicting smoothed relative risk (RR) estimates, and the distribution of the posterior probability of RR>1 by sex. Towns that registered the highest relative risks for both sexes were mostly located in the Provinces of Cadiz, Seville, Huelva, Barcelona and Almería. The highest-risk area in Barcelona Province corresponded to very specific municipal areas in the Bages district, e.g., Suría, Sallent, Balsareny, Manresa and Cardona. CONCLUSION Mining/industrial pollution and the risk entailed in certain occupational exposures could in part be dictating the pattern of municipal bladder cancer mortality in Spain. Population exposure to arsenic is a matter that calls for attention. It would be of great interest if the relationship between the chemical quality of drinking water and the frequency of bladder cancer could be studied.

Characterization of Mycobacterium tuberculosis Beijing isolates from the Mediterranean area

BACKGROUND. The Beijing lineage of Mycobacterium tuberculosis is causing concern due to its global distribution and its involvement in severe outbreaks. Studies focused on this lineage are mainly restricted to geographical settings where its prevalence is high, whereas those in other areas are scarce. In this study, we analyze Beijing isolates in the Mediterranean area, where this lineage is not prevalent and is mainly associated with immigrant cases. RESULTS. Only 1% (N = 26) of the isolates from two population-based studies in Spain corresponded to Beijing strains, most of which were pan-susceptible and from Peruvian and Ecuadorian patients. Restriction fragment length polymorphism typing with the insertion sequence IS6110 identified three small clusters (2-3 cases). Mycobacterial interspersed repetitive unit-variable number tandem repeat typing (MIRU-15) offered low discriminatory power, requiring the introduction of five additional loci. A selection of the Beijing isolates identified in the Spanish sample, together with a sample of Beijing strains from Italy, to broaden the analysis context in the Mediterranean area, were assayed in an infection model with THP-1 cells. A wide range of intracellular growth rates was observed with only two isolates showing an increased intracellular replication, in both cases associated with contained production of TNF-alpha. No correlation was observed between virulence and the Beijing phylogenetic group, clustered/orphan status, or resistance. The Beijing strain responsible for extensive spread on Gran Canaria Island was also identified in Madrid, but did not lead to secondary cases and did not show high infectivity in the infection model. CONCLUSIONS. The Beijing lineage in our area is a non-homogeneous family, with only certain highly virulent representatives. The specific characterization of Beijing isolates in different settings could help us to accurately identify the virulent representatives before making general assumptions about this lineage.

Assessment of Severe Apnoea through Voice Analysis, Automatic Speech, and Speaker Recognition Techniques

This study is part of an ongoing collaborative effort between the medical and the signal processing communities to promote research on applying standard Automatic Speech Recognition (ASR) techniques for the automatic diagnosis of patients with severe obstructive sleep apnoea (OSA). Early detection of severe apnoea cases is important so that patients can receive early treatment. Effective ASR-based detection could dramatically cut medical testing time. Working with a carefully designed speech database of healthy and apnoea subjects, we describe an acoustic search for distinctive apnoea voice characteristics. We also study abnormal nasalization in OSA patients by modelling vowels in nasal and nonnasal phonetic contexts using Gaussian Mixture Model (GMM) pattern recognition on speech spectra. Finally, we present experimental findings regarding the discriminative power of GMMs applied to severe apnoea detection. We have achieved an 81% correct classification rate, which is very promising and underpins the interest in this line of inquiry.

Lung function in idiopathic pulmonary fibrosis--extended analyses of the IFIGENIA trial.

BACKGROUND The randomized placebo-controlled IFIGENIA-trial demonstrated that therapy with high-dose N-acetylcysteine (NAC) given for one year, added to prednisone and azathioprine, significantly ameliorates (i.e. slows down) disease progression in terms of vital capacity (VC) (+9%) and diffusing capacity (DLco) (+24%) in idiopathic pulmonary fibrosis (IPF). To better understand the clinical implications of these findings we performed additional, explorative analyses of the IFGENIA data set. METHODS We analysed effects of NAC on VC, DLco, a composite physiologic index (CPI), and mortality in the 155 study-patients. RESULTS In trial completers the functional indices did not change significantly with NAC, whereas most indices deteriorated with placebo; in non-completers the majority of indices worsened but decline was generally less pronounced in most indices with NAC than with placebo. Most categorical analyses of VC, DLco and CPI also showed favourable changes with NAC. The effects of NAC on VC, DLco and CPI were significantly better if the baseline CPI was 50 points or lower. CONCLUSION This descriptive analysis confirms and extends the favourable effects of NAC on lung function in IPF and emphasizes the usefulness of VC, DLco, and the CPI for the evaluation of a therapeutic effect. Most importantly, less progressed disease as indicated by a CPI of 50 points or lower at baseline was more responsive to therapy in this study.