Suplementação oral de L-carnitina associada ao treinamento físico e muscular respiratório na doença pulmonar obstrutiva crônica: estudo preliminar

Avaliar os efeitos da suplementação oral de L-carnitina associada ao treinamento físico e muscular respiratório na doença pulmonar obstrutiva crônica (DPOC). Participaram 14 voluntários com idade de 65±10,4 anos e diagnóstico clínico de DPOC moderado, classificados de acordo com a espirometria prévia. Os voluntários foram divididos em grupo treino esteira (GTE) e grupo treino muscular respiratório (GTMR). Realizaram o teste de caminhada de seis minutos (TC6'), teste de caminhada com carga progressiva (TCP), avaliação nutricional do índice de massa corpórea (IMC), dose diária recomendada de L-carnitina, pressões inspiratórias (PImáx) e expiratórias máximas (PEmáx). Fizeram 30 min de caminhada em esteira, 3 vezes/semana por 10 semanas, e o GTMR realizou, ainda, 10 min de treinamento muscular inspiratório (Threshold® IMT) e 10 min de treinamento muscular expiratório (Threshold® PEP) à 50% da PImáx e PEmáx ajustados semanalmente. Após 10 semanas, foram reavaliados. No TC6' pré e pós-programa de treinamento físico, as variáveis alteradas foram: distância percorrida (DP), frequência cardíaca (FC) final, pressão arterial sistólica (PAS) final, pressão arterial diastólica (PAD) final e Borg final no GTMR, no GTE as variáveis alteradas foram FC repouso, FC final, PAS final, Borg repouso e DP. Comparando os grupos no TC6, o GTE apresentou FC final, PAD final e Borg final maiores do que o GTMR na reavaliação; já no TCP, a FC final, PAS final, Borg final foram maiores no GTE, e DP foi maior no GTMR. Na avaliação respiratória, a PEmáx foi maior no GTMR na reavaliação. O treino aeróbio e suplementação de L-carnitina na DPOC otimizou a performance, a capacidade física e a tolerância ao esforço.

The Integrated European Project "GEHA - GEnetics of Healthy Aging": recruitment, health status assessment and survival of the Italian 90+ sibpairs

The present study is part of the EU Integrated Project “GEHA – Genetics of Healthy Aging” (Franceschi C et al., Ann N Y Acad Sci. 1100: 21-45, 2007), whose aim is to identify genes involved in healthy aging and longevity, which allow individuals to survive to advanced age in good cognitive and physical function and in the absence of major age-related diseases. Aims The major aims of this thesis were the following: 1. to outline the recruitment procedure of 90+ Italian siblings performed by the recruiting units of the University of Bologna (UNIBO) and Rome (ISS). The procedures related to the following items necessary to perform the study were described and commented: identification of the eligible area for recruitment, demographic aspects related to the need of getting census lists of 90+siblings, mail and phone contact with 90+ subjects and their families, bioethics aspects of the whole procedure, standardization of the recruitment methodology and set-up of a detailed flow chart to be followed by the European recruitment centres (obtainment of the informed consent form, anonimization of data by using a special code, how to perform the interview, how to collect the blood, how to enter data in the GEHA Phenotypic Data Base hosted at Odense). 2. to provide an overview of the phenotypic characteristics of 90+ Italian siblings recruited by the recruiting units of the University of Bologna (UNIBO) and Rome (ISS). The following items were addressed: socio-demographic characteristics, health status, cognitive assessment, physical conditions (handgrip strength test, chair-stand test, physical ability including ADL, vision and hearing ability, movement ability and doing light housework), life-style information (smoking and drinking habits) and subjective well-being (attitude towards life). Moreover, haematological parameters collected in the 90+ sibpairs as optional parameters by the Bologna and Rome recruiting units were used for a more comprehensive evaluation of the results obtained using the above mentioned phenotypic characteristics reported in the GEHA questionnaire. 3. to assess 90+ Italian siblings as far as their health/functional status is concerned on the basis of three classification methods proposed in previous studies on centenarians, which are based on: • actual functional capabilities (ADL, SMMSE, visual and hearing abilities) (Gondo et al., J Gerontol. 61A (3): 305-310, 2006); • actual functional capabilities and morbidity (ADL, ability to walk, SMMSE, presence of cancer, ictus, renal failure, anaemia, and liver diseases) (Franceschi et al., Aging Clin Exp Res, 12:77-84, 2000); • retrospectively collected data about past history of morbidity and age of disease onset (hypertension, heart disease, diabetes, stroke, cancer, osteopororis, neurological diseases, chronic obstructive pulmonary disease and ocular diseases) (Evert et al., J Gerontol A Biol Sci Med Sci. 58A (3): 232-237, 2003). Firstly these available models to define the health status of long-living subjects were applied to the sample and, since the classifications by Gondo and Franceschi are both based on the present functional status, they were compared in order to better recognize the healthy aging phenotype and to identify the best group of 90+ subjects out of the entire studied population. 4. to investigate the concordance of health and functional status among 90+ siblings in order to divide sibpairs in three categories: the best (both sibs are in good shape), the worst (both sibs are in bad shape) and an intermediate group (one sib is in good shape and the other is in bad shape). Moreover, the evaluation wanted to discover which variables are concordant among siblings; thus, concordant variables could be considered as familiar variables (determined by the environment or by genetics). 5. to perform a survival analysis by using mortality data at 1st January 2009 from the follow-up as the main outcome and selected functional and clinical parameters as explanatory variables. Methods A total of 765 90+ Italian subjects recruited by UNIBO (549 90+ siblings, belonging to 258 families) and ISS (216 90+ siblings, belonging to 106 families) recruiting units are included in the analysis. Each subject was interviewed according to a standardized questionnaire, comprising extensively utilized questions that have been validated in previous European studies on elderly subjects and covering demographic information, life style, living conditions, cognitive status (SMMSE), mood, health status and anthropometric measurements. Moreover, subjects were asked to perform some physical tests (Hand Grip Strength test and Chair Standing test) and a sample of about 24 mL of blood was collected and then processed according to a common protocol for the preparation and storage of DNA aliquots. Results From the analysis the main findings are the following: - a standardized protocol to assess cognitive status, physical performances and health status of European nonagenarian subjects was set up, in respect to ethical requirements, and it is available as a reference for other studies in this field; - GEHA families are enriched in long-living members and extreme survival, and represent an appropriate model for the identification of genes involved in healthy aging and longevity; - two simplified sets of criteria to classify 90+ sibling according to their health status were proposed, as operational tools for distinguishing healthy from non healthy subjects; - cognitive and functional parameters have a major role in categorizing 90+ siblings for the health status; - parameters such as education and good physical abilities (500 metres walking ability, going up and down the stairs ability, high scores at hand grip and chair stand tests) are associated with a good health status (defined as “cognitive unimpairment and absence of disability”); - male nonagenarians show a more homogeneous phenotype than females, and, though far fewer in number, tend to be healthier than females; - in males the good health status is not protective for survival, confirming the male-female health survival paradox; - survival after age 90 was dependent mainly on intact cognitive status and absence of functional disabilities; - haemoglobin and creatinine levels are both associated with longevity; - the most concordant items among 90+ siblings are related to the functional status, indicating that they contain a familiar component. It is still to be investigated at what level this familiar component is determined by genetics or by environment or by the interaction between genetics, environment and chance (and at what level). Conclusions In conclusion, we could state that this study, in accordance with the main objectives of the whole GEHA project, represents one of the first attempt to identify the biological and non biological determinants of successful/unsuccessful aging and longevity. Here, the analysis was performed on 90+ siblings recruited in Northern and Central Italy and it could be used as a reference for others studies in this field on Italian population. Moreover, it contributed to the definition of “successful” and “unsuccessful” aging and categorising a very large cohort of our most elderly subjects into “successful” and “unsuccessful” groups provided an unrivalled opportunity to detect some of the basic genetic/molecular mechanisms which underpin good health as opposed to chronic disability. Discoveries in the topic of the biological determinants of healthy aging represent a real possibility to identify new markers to be utilized for the identification of subgroups of old European citizens having a higher risk to develop age-related diseases and disabilities and to direct major preventive medicine strategies for the new epidemic of chronic disease in the 21st century.

Über das Vermessen tubulärer Strukturen in der Computertomographie

Die chronisch obstruktive Lungenerkrankung (engl. chronic obstructive pulmonary disease, COPD) ist ein Überbegriff für Erkrankungen, die zu Husten, Auswurf und Dyspnoe (Atemnot) in Ruhe oder Belastung führen - zu diesen werden die chronische Bronchitis und das Lungenemphysem gezählt. Das Fortschreiten der COPD ist eng verknüpft mit der Zunahme des Volumens der Wände kleiner Luftwege (Bronchien). Die hochauflösende Computertomographie (CT) gilt bei der Untersuchung der Morphologie der Lunge als Goldstandard (beste und zuverlässigste Methode in der Diagnostik). Möchte man Bronchien, eine in Annäherung tubuläre Struktur, in CT-Bildern vermessen, so stellt die geringe Größe der Bronchien im Vergleich zum Auflösungsvermögen eines klinischen Computertomographen ein großes Problem dar. In dieser Arbeit wird gezeigt wie aus konventionellen Röntgenaufnahmen CT-Bilder berechnet werden, wo die mathematischen und physikalischen Fehlerquellen im Bildentstehungsprozess liegen und wie man ein CT-System mittels Interpretation als lineares verschiebungsinvariantes System (engl. linear shift invariant systems, LSI System) mathematisch greifbar macht. Basierend auf der linearen Systemtheorie werden Möglichkeiten zur Beschreibung des Auflösungsvermögens bildgebender Verfahren hergeleitet. Es wird gezeigt wie man den Tracheobronchialbaum aus einem CT-Datensatz stabil segmentiert und mittels eines topologieerhaltenden 3-dimensionalen Skelettierungsalgorithmus in eine Skelettdarstellung und anschließend in einen kreisfreien Graphen überführt. Basierend auf der linearen System Theorie wird eine neue, vielversprechende, integral-basierte Methodik (IBM) zum Vermessen kleiner Strukturen in CT-Bildern vorgestellt. Zum Validieren der IBM-Resultate wurden verschiedene Messungen an einem Phantom, bestehend aus 10 unterschiedlichen Silikon Schläuchen, durchgeführt. Mit Hilfe der Skelett- und Graphendarstellung ist ein Vermessen des kompletten segmentierten Tracheobronchialbaums im 3-dimensionalen Raum möglich. Für 8 zweifach gescannte Schweine konnte eine gute Reproduzierbarkeit der IBM-Resultate nachgewiesen werden. In einer weiteren, mit IBM durchgeführten Studie konnte gezeigt werden, dass die durchschnittliche prozentuale Bronchialwandstärke in CT-Datensätzen von 16 Rauchern signifikant höher ist, als in Datensätzen von 15 Nichtrauchern. IBM läßt sich möglicherweise auch für Wanddickenbestimmungen bei Problemstellungen aus anderen Arbeitsgebieten benutzen - kann zumindest als Ideengeber dienen. Ein Artikel mit der Beschreibung der entwickelten Methodik und der damit erzielten Studienergebnisse wurde zur Publikation im Journal IEEE Transactions on Medical Imaging angenommen.

The CFTR frameshift mutation 3905insT and its effect at transcript and protein level

Cystic fibrosis (CF) is one of the most common genetic diseases in the Caucasian population and is characterized by chronic obstructive pulmonary disease, exocrine pancreatic insufficiency, and elevation of sodium and chloride concentrations in the sweat and infertility in men. The disease is caused by mutations in the CF transmembrane conductance regulator (CFTR) gene, which encodes a protein that functions as chloride channel at the apical membrane of different epithelia. Owing to the high genotypic and phenotypic disease heterogeneity, effects and consequences of the majority of the CFTR mutations have not yet been studied. Recently, the frameshift mutation 3905insT was identified as the second most frequent mutation in the Swiss population and found to be associated with a severe phenotype. The frameshift mutation produces a premature termination codon (PTC) in exon 20, and transcripts bearing this PTC are potential targets for degradation through nonsense-mediated mRNA decay (NMD) and/or for exon skipping through nonsense-associated alternative splicing (NAS). Using RT-PCR analysis in lymphocytes and different tissue types from patients carrying the mutation, we showed that the PTC introduced by the mutation does neither elicit a degradation of the mRNA through NMD nor an alternative splicing through NAS. Moreover, immunocytochemical analysis in nasal epithelial cells revealed a significantly reduced amount of CFTR at the apical membrane providing a possible molecular explanation for the more severe phenotype observed in F508del/3905insT compound heterozygotes compared with F508del homozygotes. However, further experiments are needed to elucidate the fate of the 3905insT CFTR in the cell after its biosynthesis.

Nanotoxicology: a perspective and discussion of whether or not in vitro testing is a valid alternative

Despite the many proposed advantages related to nanotechnology, there are increasing concerns as to the potential adverse human health and environmental effects that the production of, and subsequent exposure to nanoparticles (NPs) might pose. In regard to human health, these concerns are founded upon the plethora of knowledge gained from research relating to the effects observed following exposure to environmental air pollution. It is known that increased exposure to environmental air pollution can cause reduced respiratory health, as well as exacerbate pre-existing conditions such as cardiovascular disease and chronic obstructive pulmonary disease. Such disease states have also been associated with exposure to the NP component contained within environmental air pollution, raising concerns as to the effects of NP exposure. It is not only exposure to accidentally produced NPs however, which should be approached with caution. Over the past decades, NPs have been specifically engineered for a wide range of consumer, industrial and technological applications. Due to the inevitable exposure of NPs to humans, owing to their use in such applications, it is therefore imperative that an understanding of how NPs interact with the human body is gained. In vivo research poses a beneficial model for gaining immediate and direct knowledge of human exposure to such xenobiotics. This research outlook however, has numerous limitations. Increased research using in vitro models has therefore been performed, as these models provide an inexpensive and high-throughput alternative to in vivo research strategies. Despite such advantages, there are also various restrictions in regard to in vitro research. Therefore, the aim of this review, in addition to providing a short perspective upon the field of nanotoxicology, is to discuss (1) the advantages and disadvantages of in vitro research and (2) how in vitro research may provide essential information pertaining to the human health risks posed by NP exposure.

The SerpinB1 knockout mouse a model for studying neutrophil protease regulation in homeostasis and inflammation

SerpinB1 is a clade B serpin, or ov-serpin, found at high levels in the cytoplasm of neutrophils. SerpinB1 inhibits neutrophil serine proteases, which are important in killing microbes. When released from granules, these potent enzymes also destroy host proteins and contribute to morbidity and mortality in inflammatory diseases including emphysema, chronic obstructive pulmonary disease, cystic fibrosis, arthritis, and sepsis. Studies of serpinB1-deficient mice have established a crucial role for this serpin in Pseudomonas aeruginosa infection by preserving lung antimicrobial proteins from proteolysis and by protecting lung-recruited neutrophils from a premature death. SerpinB1⁻/⁻ mice also have a severe defect in the bone marrow reserve of mature neutrophils demonstrating a key role for serpinB1 in cellular homeostasis. Here, key methods used to generate and characterize serpinB1⁻/⁻ mice are described including intranasal inoculation, myeloperoxidase activity, flow cytometry analysis of bone marrow myeloid cells, and elastase activity. SerpinB1-knockout mice provide a model to dissect the pathogenesis of inflammatory disease characterized by protease:antiprotease imbalance and may be used to assess the efficacy of therapeutic compounds.

Moraxella catarrhalis - pathogen or commensal?

Moraxella catarrhalis is an exclusively human commensal and mucosal pathogen. Its role as a disease-causing organism has long been questioned. Today, it is recognized as one of the major causes of acute otitis media in children, and its relative frequency of isolation from both the nasopharynx and the middle ear cavity has increased since the introduction of the heptavalent pneumococcal conjugate vaccine, which is associated with a shift in the composition of the nasopharyngeal flora in infants and young children. Although otitis media caused by M. catarrhalis is generally believed to be mild in comparison with pneumococcal disease, numerous putative virulence factors have now been identified and it has been shown that several surface components of M. catarrhalis induce mucosal inflammation. In adults with chronic obstructive pulmonary disease (COPD), M. catarrhalis is now a well-established trigger of approximately 10% of acute inflammatory exacerbations.Although the so-called cold shock response is a well-described bacterial stress response in species such as Escherichia coli, Bacillus subtilis or - more recently - Staphylococcus aureus, M. catarrhalis is the only typical nasopharyngeal pathogen in which this response has been investigated. Indeed, a 3-h 26°C cold shock, which may occur physiologically, when humans inspire cold air for prolonged periods of time, increases epithelial cell adherence and enhances proinflammatory host responses and may thus contribute to the symptoms referred to as common cold, which typically are attributed to viral infections.

Detection of erythropoietin in exhaled breath condensate of nonhypoxic subjects using a multiplex bead array

As a noninvasive method, exhaled breath condensate (EBC) has gained importance to improve monitoring of lung diseases and to detect biomarkers. The aim of the study was to investigate, whether erythropoietin (EPO) is detectable in EBC. EBC was collected from 22 consecutive patients as well as from healthy individuals. Using a multiplex fluorescent bead immunoassay, we detected EPO in EBC, as well as tumour necrosis factor-alpha (TNF-alpha) in 13 out of 22 patients simultaneously (EPO 0.21 +/- 0.03 in U/mL and TNF-alpha 34.6 +/- 4.2 in pg/mL, mean +/- SEM). No significant differences for EPO levels or correlation between EPO and TNF-alpha were found but TNF-alpha was significantly higher in patients with chronic obstructive pulmonary disease (COPD) than in non-COPD (obstructive sleep apnoea, OSA, and lung healthy patients). This is the first report of detection of EPO in EBC. Due to the small study size more data is needed to clarify the role of EPO in EBC.

Content comparison of health-related quality of life instruments for COPD

BACKGROUND: Due to the increasing importance of quality of life assessments in chronic obstructive pulmonary disease (COPD) patients, and the increased use of the International Classification of Functioning, Disability and Health (ICF) for comparative purposes it is essential to understand the relationship between health-related quality of life (HRQL) instruments and the ICF. OBJECTIVE: The objective of this study was to compare the content of recommended COPD-specific HRQL instruments using the ICF as reference. COPD-specific instruments mentioned in widely accepted guidelines were linked to the ICF using standardized linking rules. The degree of agreement between various health professionals was assessed by calculating the kappa statistic. RESULTS: Eleven instruments were included. They varied strongly in the number of concepts contained and the number of ICF categories used to map these concepts. A total of 548 concepts were identified and linked to 60 different ICF categories. Only the single category 'dyspnea' was covered by all instruments, whilst 21 categories were unique to specific instruments. The relationships of the measures with the ICF were identified. CONCLUSIONS: This study may aid researchers and clinicians to choose the most appropriate instrument for a specific purpose as well as help compare studies that have used different instruments for HRQL assessment.

Novel autoantigens immunogenic in COPD patients

Background Chronic obstructive pulmonary disease (COPD) is a respiratory inflammatory condition with autoimmune features including IgG autoantibodies. In this study we analyze the complexity of the autoantibody response and reveal the nature of the antigens that are recognized by autoantibodies in COPD patients. Methods An array of 1827 gridded immunogenic peptide clones was established and screened with 17 sera of COPD patients and 60 healthy controls. Protein arrays were evaluated both by visual inspection and a recently developed computer aided image analysis technique. By this computer aided image analysis technique we computed the intensity values for each peptide clone and each serum and calculated the area under the receiver operator characteristics curve (AUC) for each clone and the separation COPD sera versus control sera. Results By visual evaluation we detected 381 peptide clones that reacted with autoantibodies of COPD patients including 17 clones that reacted with more than 60% of the COPD sera and seven clones that reacted with more than 90% of the COPD sera. The comparison of COPD sera and controls by the automated image analysis system identified 212 peptide clones with informative AUC values. By in silico sequence analysis we found an enrichment of sequence motives previously associated with immunogenicity. Conclusion The identification of a rather complex humoral immune response in COPD patients supports the idea of COPD as a disease with strong autoimmune features. The identification of novel immunogenic antigens is a first step towards a better understanding of the autoimmune component of COPD.

Incidence and direct medical costs of hospitalizations due to osteoporotic fractures in Switzerland

The objective of this study was to estimate the annual direct medical costs of hospitalizations due to osteoporotic fractures in Switzerland. Days of hospital stay in 1992 were quantified using the casuistic of the medical statistics department of VESKA (Vereinigung Schweizerischer Krankenhäuser, the Swiss Hospital Association), which covers 43% of all hospital beds of that country. Number and incidence of total hospitalizations due to fractures were calculated by extrapolating to 100% the 43% VESKA-selected sample. To estimate number and incidence of hospitalizations due to osteoporotic fractures, internationally accepted age-specific osteoporosis attribution rates were applied. According to the latter the probability of a fracture being caused by osteoporosis increases with age. Mean length of stay for all fractures was calculated (= total hospital days divided by number of cases). By multiplying these mean lengths of stay by the number of osteoporosis-related fracture cases, the number of bed-days due to osteoporotic fractures was calculated. To compare the direct medical costs of hospitalization due to osteoporosis with those due to other frequent diseases, days of hospital stay caused by chronic obstructive pulmonary disease (COPD), stroke, acute myocardial infarction and breast cancer were estimated using the same methodology. A total estimate of 63,170 (f: 33,596, m: 29,574) hospitalizations due to fractures (and other osteoporosis-related diagnoses) was calculated, thus leading to overall annual incidence rates of hospitalizations for fractures of 950/100,000 women and 877/100,000 men. In women, 548,615 hospital days were found to be caused by osteoporosis, 353,654 days by COPD, 352,062 days by stroke, 200,669 days by breast carcinoma and 131,331 days by myocardial infarction. In men, COPD caused more hospitalization days (537,164) than myocardial infarction (196,793), stroke (180,524) or osteoporosis (152,857). Taking a mean price for a hospital day in Switzerland of 845 Swiss francs, the annual costs of acute hospitalizations due to osteoporosis and its complications were approximately 600 million Swiss francs (f: 464, m: 130 million Swiss francs) in 1992. We conclude that there is enough economic evidence to justify wide-scale interventions against osteoporosis in Switzerland.

Non-acute myocardial infarction-related causes of elevated high-sensitive troponin T in the emergency room: a cross-sectional analysis

To systematically investigate putative causes of non-coronary high-sensitive troponin elevations in patients presenting to a tertiary care emergency department. In this cross-sectional analysis, patients who received serial measurements of high-sensitive troponin T between 1 August 2010 and 31 October 2012 at the Department of Emergency Medicine were included. The following putative causes were considered to be associated with non-acute coronary syndrome-related increases in high-sensitive troponin T: acute pulmonary embolism, renal insufficiency, aortic dissection, heart failure, peri-/myocarditis, strenuous exercise, rhabdomyolysis, cardiotoxic chemotherapy, high-frequency ablation therapy, defibrillator shocks, cardiac infiltrative disorders (e.g., amyloidosis), chest trauma, sepsis, shock, exacerbation of chronic obstructive pulmonary disease, and diabetic ketoacidosis. During the study period a total of 1,573 patients received serial measurements of high-sensitive troponin T. Of these, 175 patients were found to have acute coronary syndrome leaving 1,398 patients for inclusion in the study. In 222 (30 %) of patients, no putative cause described in the literature could be attributed to the elevation in high-sensitive troponin T observed. The most commonly encountered mechanism underlying the troponin T elevation was renal insufficiency that was present in 286 patients (57 %), followed by cerebral ischemia in 95 patients (19 %), trauma in 75 patients (15 %) and heart failure in 41 patients (8 %). Non-acute coronary syndrome-associated elevation of high-sensitive troponin T levels is commonly observed in the emergency department. Renal insufficiency and acute cerebral events are the most common conditions associated with high-sensitive troponin T elevation.

Use of early corticosteroid therapy on ICU admission in patients affected by severe pandemic (H1N1)v influenza A infection.

INTRODUCTION Early use of corticosteroids in patients affected by pandemic (H1N1)v influenza A infection, although relatively common, remains controversial. METHODS Prospective, observational, multicenter study from 23 June 2009 through 11 February 2010, reported in the European Society of Intensive Care Medicine (ESICM) H1N1 registry. RESULTS Two hundred twenty patients admitted to an intensive care unit (ICU) with completed outcome data were analyzed. Invasive mechanical ventilation was used in 155 (70.5%). Sixty-seven (30.5%) of the patients died in ICU and 75 (34.1%) whilst in hospital. One hundred twenty-six (57.3%) patients received corticosteroid therapy on admission to ICU. Patients who received corticosteroids were significantly older and were more likely to have coexisting asthma, chronic obstructive pulmonary disease (COPD), and chronic steroid use. These patients receiving corticosteroids had increased likelihood of developing hospital-acquired pneumonia (HAP) [26.2% versus 13.8%, p < 0.05; odds ratio (OR) 2.2, confidence interval (CI) 1.1-4.5]. Patients who received corticosteroids had significantly higher ICU mortality than patients who did not (46.0% versus 18.1%, p < 0.01; OR 3.8, CI 2.1-7.2). Cox regression analysis adjusted for severity and potential confounding factors identified that early use of corticosteroids was not significantly associated with mortality [hazard ratio (HR) 1.3, 95% CI 0.7-2.4, p = 0.4] but was still associated with an increased rate of HAP (OR 2.2, 95% CI 1.0-4.8, p < 0.05). When only patients developing acute respiratory distress syndrome (ARDS) were analyzed, similar results were observed. CONCLUSIONS Early use of corticosteroids in patients affected by pandemic (H1N1)v influenza A infection did not result in better outcomes and was associated with increased risk of superinfections.

Association between intraoperative electroencephalographic suppression and postoperative mortality

BACKGROUND Low bispectral index values frequently reflect EEG suppression and have been associated with postoperative mortality. This study investigated whether intraoperative EEG suppression was an independent predictor of 90 day postoperative mortality and explored risk factors for EEG suppression. METHODS This observational study included 2662 adults enrolled in the B-Unaware or BAG-RECALL trials. A cohort was defined with >5 cumulative minutes of EEG suppression, and 1:2 propensity-matched to a non-suppressed cohort (≤5 min suppression). We evaluated the association between EEG suppression and mortality using multivariable logistic regression, and examined risk factors for EEG suppression using zero-inflated mixed effects analysis. RESULTS Ninety day postoperative mortality was 3.9% overall, 6.3% in the suppressed cohort, and 3.0% in the non-suppressed cohort {odds ratio (OR) [95% confidence interval (CI)]=2.19 (1.48-3.26)}. After matching and multivariable adjustment, EEG suppression was not associated with mortality [OR (95% CI)=0.83 (0.55-1.25)]; however, the interaction between EEG suppression and mean arterial pressure (MAP) <55 mm Hg was [OR (95% CI)=2.96 (1.34-6.52)]. Risk factors for EEG suppression were older age, number of comorbidities, chronic obstructive pulmonary disease, and higher intraoperative doses of benzodiazepines, opioids, or volatile anaesthetics. EEG suppression was less likely in patients with cancer, preoperative alcohol, opioid or benzodiazepine consumption, and intraoperative nitrous oxide exposure. CONCLUSIONS Although EEG suppression was associated with increasing anaesthetic administration and comorbidities, the hypothesis that intraoperative EEG suppression is a predictor of postoperative mortality was only supported if it was coincident with low MAP. CLINICAL TRIAL REGISTRATION NCT00281489 and NCT00682825.

Burden of serious fungal infections in Tanzania.

The incidence and prevalence of fungal infections in Tanzania remains unknown. We assessed the annual burden in the general population and among populations at risk. Data were extracted from 2012 reports of the Tanzanian AIDS program, WHO, reports, Tanzanian census, and from a comprehensive PubMed search. We used modelling and HIV data to estimate the burdens of Pneumocystis jirovecii pneumonia (PCP), cryptococcal meningitis (CM) and candidiasis. Asthma, chronic obstructive pulmonary disease and tuberculosis data were used to estimate the burden of allergic bronchopulmonary aspergillosis (ABPA) and chronic pulmonary aspergillosis (CPA). Burdens of candidaemia and Candida peritonitis were derived from critical care and/or cancer patients' data. In 2012, Tanzania's population was 43.6 million (mainland) with 1 500 000 people reported to be HIV-infected. Estimated burden of fungal infections was: 4412 CM, 9600 PCP, 81 051 and 88 509 oral and oesophageal candidiasis cases respectively. There were 10 437 estimated posttuberculosis CPA cases, whereas candidaemia and Candida peritonitis cases were 2181 and 327 respectively. No reliable data exist on blastomycosis, mucormycosis or fungal keratitis. Over 3% of Tanzanians suffer from serious fungal infections annually, mostly related to HIV. Cryptococcosis and PCP are major causes of mycoses-related deaths. National surveillance of fungal infections is urgently needed.