Neuraminidase Inhibitors and Hospital Length of Stay: A Meta-analysis of Individual Participant Data to Determine Treatment Effectiveness Among Patients Hospitalized With Nonfatal 2009 Pandemic Influenza A(H1N1) Virus Infection.

BACKGROUND: The effect of neuraminidase inhibitor (NAI) treatment on length of stay (LoS) in patients hospitalized with influenza is unclear. METHODS: We conducted a one-stage individual participant data (IPD) meta-analysis exploring the association between NAI treatment and LoS in patients hospitalized with 2009 influenza A(H1N1) virus (A[H1N1]pdm09) infection. Using mixed-effects negative binomial regression and adjusting for the propensity to receive NAI, antibiotic, and corticosteroid treatment, we calculated incidence rate ratios (IRRs) and 95% confidence intervals (CIs). Patients with a LoS of <1 day and those who died while hospitalized were excluded. RESULTS: We analyzed data on 18 309 patients from 70 clinical centers. After adjustment, NAI treatment initiated at hospitalization was associated with a 19% reduction in the LoS among patients with clinically suspected or laboratory-confirmed influenza A(H1N1)pdm09 infection (IRR, 0.81; 95% CI, .78-.85), compared with later or no initiation of NAI treatment. Similar statistically significant associations were seen in all clinical subgroups. NAI treatment (at any time), compared with no NAI treatment, and NAI treatment initiated <2 days after symptom onset, compared with later or no initiation of NAI treatment, showed mixed patterns of association with the LoS. CONCLUSIONS: When patients hospitalized with influenza are treated with NAIs, treatment initiated on admission, regardless of time since symptom onset, is associated with a reduced LoS, compared with later or no initiation of treatment.

Exopolysaccharides from Aspergillus terreus: Production, chemical elucidation and immunoactivity.

Aspergillus terreus, a fungus commonly used in pharmaceutical industry to produce lovastatin and other secondary metabolites, has been reported to have beneficial biological properties. In this study the exopolysaccharides (AT-EPS) produced by A. terreus were evaluated as potential modulators of certain functions of macrophages. The production parameters for EPS obtained from the liquid culture broth of the studied fungus were optimized using response surface methodology (RSM) and indicated good correlation between the experimental and predicted values. The optimum conditions for AT-EPS extraction included fermentation at 28 °C, pH 8.79, under 98 rpm of agitation, using 2.39% glucose (carbon source) and 0.957% ammonium nitrate (nitrogen source). Under these optimized conditions, AT-EPS production was 1.34 g/L medium. The chemical analyses showed that AT-EPS was composed by mannose (Man; 40.5 mol%), galactose (Gal; 35.2 mol%), and glucose (Glc; 24.3 mol%), and the spectroscopic (FTIR; NMR) and methylation analyses indicated the presence of galactomannans, ß-1,3-glucans, and glycogen-like glucans. AT-EPS was tested on murine macrophages to verify its immunoactivity and the treated cells were able to produce nitric oxide, superoxide anion, TNF-α and interleukin 6 similarly to the positive control cells. Furthermore, the macrophages treated with AT-EPS showed activated-like morphological alterations.

Surgical lung biopsy in onco-hematological patients with diffuse pulmonary infiltrates and mechanical ventilation in the ICU.

Among onco-hematological patients with acute respiratory failure (ARpF), surgical lung biopsy (SLB) could contribute to the medical management, by guiding initiation, maintenance or discontinuation of diagnostic and therapeutic interventions. The aim of the present study was to evaluate the results of SLB in these patients in an oncological center from a medium-income country, as well as analyze if this procedure is clinically useful in this context, and its impact on complications and mortality. This observational retrospective study analyzed onco-hematological patients with ARpF in the Intensive Care Unit (ICU) of a cancer center in southern Brazil between 2010-2016, who required mechanical ventilation and were submitted to open SLB. Among the studied population (n=17), the most commonly found etiology was infectious, present in ~50% of the biopsies, followed by unspecific inflammatory infiltrate acute respiratory distress syndrome and interstitial fibrosis, alveolar hemorrhage, neoplastic infiltrate and pulmonary embolism. Biopsy has led to a change of management in 63.3% of patients that were alive when results were available; however, 35% of patients succumbed prior to the pathological result. There was no requirement for re-operation or mortality attributable to the procedure. However, ICU mortality was elevated (88%). SLB in onco-hematological patients mechanically ventilated in the ICU is a safe procedure with few severe complications and that contributes for diagnosis and management in the majority of cases. Due to the high mortality of this population, controlled trials may be required to establish its benefit in mortality and ICU outcomes.

Corrigendum to "Factors Associated with the Incidence and Severity of New-Onset Atrial Fibrillation in Adult Critically Ill Patients".

[This corrects the article DOI: 10.1155/2017/8046240.].

ß-(1→6)-D-glucan secreted during the optimised production of exopolysaccharides by Paecilomyces variotii has immunostimulatory activity.

Paecilomyces variotii is a filamentous fungus that occurs worldwide in soil and decaying vegetation. Optimization of the fermentation process for exopolysaccharide (EPS) production from the fungus P. variotii, structure determination and immuno-stimulating activity of EPS were performed. Response surface methodology (RSM) coupled with central composite design (CCD) was used to optimize the physical and chemical factors required to produce EPS in submerged fermentation. Preliminary investigations to choose the three factors for the present work were made using a factorial experimental design. Glucose, ammonium nitrate (NH4NO3) and pH were used as variables for which, with constant temperature of 28 °C and agitation of 90 rpm, the optimal process parameters were determined as glucose values of 0.96%, NH4NO3 0.26% and pH 8.0. The three parameters presented significant effects. In this condition of culture, the main composition of the isolated EPS was a linear ß-(1 â†’ 6)-linked-D-glucan, as determined by Nuclear Magnetic Resonance (NMR) and methylation analysis. This polysaccharide is a very unusual as an EPS from fungi, especially a filamentous fungus such as P. variotii. Murine peritoneal macrophages cultivated with ß-glucan for 6 and 48 h showed an increase in TNF-α, IL-6 and nitric oxide release with increased polysaccharide concentrations. Therefore, we conclude that the ß-(1 â†’ 6)-linked-D-glucan produced in optimised conditions of P. variotii cultivation has an immune-stimulatory activity on murine macrophages.

Characteristics and Outcomes of Intensive Care Unit Survivors: Experience of a Multidisciplinary Outpatient Clinic in a Teaching Hospital

OBJECTIVES: To describe the experience of an outpatient clinic with the multidisciplinary evaluation of intensive care unit survivors and to analyze their social, psychological, and physical characteristics in a low-income population and a developing country. METHODS: Retrospective cohort study. Adult survivors from a general intensive care unit were evaluated three months after discharge in a post-intensive care unit outpatient multidisciplinary clinic over a period of 6 years (2008-2014) in a University Hospital in southern Brazil. RESULTS: A total of 688 out of 1945 intensive care unit survivors received care at the clinic. Of these, 45.2% had psychological disorders (particularly depression), 49.0% had respiratory impairments (abnormal spirometry), and 24.6% had moderate to intense dyspnea during daily life activities. Patients experienced weight loss during hospitalization (mean=11.7%) but good recovery after discharge (mean gain=9.1%), and 94.6% were receiving nutrition orally. One-third of patients showed a reduction of peripheral muscular strength, and 5.7% had moderate to severe tetraparesis or tetraplegia. There was a significant impairment in quality of life (SF-36), particularly in the physical and emotional aspects and in functional capacity. The economic impacts on the affected families, which were mostly low-income families, were considerable. Most patients did not have full access to rehabilitation services, even though half of the families were receiving financial support from the government. CONCLUSIONS: A significant number of intensive care unit survivors evaluated 3 months after discharge had psychological, respiratory, motor, and socioeconomic problems; these findings highlight that strategies aimed to assist critically ill patients should be extended to the post-hospitalization period and that this problem is particularly important in low-income populations.

Factors Associated with the Incidence and Severity of New-Onset Atrial Fibrillation in Adult Critically Ill Patients.

BACKGROUND: Acute Atrial Fibrillation (AF) is common in critically ill patients, with significant morbidity and mortality; however, its incidence and severity in Intensive Care Units (ICUs) from low-income countries are poorly studied. Additionally, impact of vasoactive drugs on its incidence and severity is still not understood. This study aimed to assess epidemiology and risk factors for acute new-onset AF in critically ill adult patients and the role of vasoactive drugs. METHOD: Cohort performed in seven general ICUs (including cardiac surgery) in three cities in Paraná State (southern Brazil) for 45 days. Patients were followed until hospital discharge. RESULTS: Among 430 patients evaluated, the incidence of acute new-onset AF was 11.2%. Patients with AF had higher ICU and hospital mortality. Vasoactive drugs use (norepinephrine and dobutamine) was correlated with higher incidence of AF and higher mortality in patients with AF; vasopressin (though used in few patients) had no effect on development of AF. CONCLUSIONS: In general ICU patients, incidence of new-onset AF was 11.2% with a high impact on morbidity and mortality, particularly associated with the presence of Acute Renal Failure. The use of vasoactive drugs (norepinephrine and dobutamine) could lead to a higher incidence of new-onset AF-associated morbidity and mortality.

Pressure ulcers in ICU patients: Incidence and clinical and epidemiological features: A multicenter study in southern Brazil.

OBJECTIVES: To evaluate the incidence and risk factors of pressure ulcers (PU) in adult patients admitted to intensive care units (ICUs), as well as the outcome (including ICU and hospital mortality) of these patients. METHODS: Epidemiological cohort multicenter prospective study, evaluating patients admitted for a period of 31days (June 01 to July 01, 2015) until hospital discharge. Epidemiological and clinical data were collected daily until ICU discharge, as was the incidence of PU, either new or present on admission. SETTING: 10 general adult ICUs. RESULTS: We evaluated 332 patients, 52.1% male, mean age 63.1 years. The most common cause of admission was medical diseases (50.3%), and the mean APACHE II score was 14.9. A total of 45 patients (13.6%) had PU; the most common sites were sacral, calcaneal, ears, and trochanter. The incidence of PU was related to predictive factors, such as the Braden Scale and length of lack of nutrition. The presence of PU was strongly related to unfavorable outcomes, such as Mechanical Ventilation (MV) duration and ICU and hospital mortality. CONCLUSIONS: PU incidence is related to severity of the patient's condition and predicted by Braden Scale score. The presence of PU is also related to adverse outcomes, such as MV duration and ICU and hospital mortality. It was also shown that patients with PU have a higher incidence of medical complications, such as acute renal failure, pneumonia, and the need for vasoactive drugs.

Characteristics and Outcomes of Intensive Care Unit Survivors: Experience of a Multidisciplinary Outpatient Clinic in a Teaching Hospital.

OBJECTIVES: To describe the experience of an outpatient clinic with the multidisciplinary evaluation of intensive care unit survivors and to analyze their social, psychological, and physical characteristics in a low-income population and a developing country. METHODS: Retrospective cohort study. Adult survivors from a general intensive care unit were evaluated three months after discharge in a post-intensive care unit outpatient multidisciplinary clinic over a period of 6 years (2008-2014) in a University Hospital in southern Brazil. RESULTS: A total of 688 out of 1945 intensive care unit survivors received care at the clinic. Of these, 45.2% had psychological disorders (particularly depression), 49.0% had respiratory impairments (abnormal spirometry), and 24.6% had moderate to intense dyspnea during daily life activities. Patients experienced weight loss during hospitalization (mean=11.7%) but good recovery after discharge (mean gain=9.1%), and 94.6% were receiving nutrition orally. One-third of patients showed a reduction of peripheral muscular strength, and 5.7% had moderate to severe tetraparesis or tetraplegia. There was a significant impairment in quality of life (SF-36), particularly in the physical and emotional aspects and in functional capacity. The economic impacts on the affected families, which were mostly low-income families, were considerable. Most patients did not have full access to rehabilitation services, even though half of the families were receiving financial support from the government. CONCLUSIONS: A significant number of intensive care unit survivors evaluated 3 months after discharge had psychological, respiratory, motor, and socioeconomic problems; these findings highlight that strategies aimed to assist critically ill patients should be extended to the post-hospitalization period and that this problem is particularly important in low-income populations.

Impact of neuraminidase inhibitors on influenza A(H1N1)pdm09-related pneumonia: an individual participant data meta-analysis.

BACKGROUND: The impact of neuraminidase inhibitors (NAIs) on influenza-related pneumonia (IRP) is not established. Our objective was to investigate the association between NAI treatment and IRP incidence and outcomes in patients hospitalised with A(H1N1)pdm09 virus infection. METHODS: A worldwide meta-analysis of individual participant data from 20 634 hospitalised patients with laboratory-confirmed A(H1N1)pdm09 (n = 20 021) or clinically diagnosed (n = 613) 'pandemic influenza'. The primary outcome was radiologically confirmed IRP. Odds ratios (OR) were estimated using generalised linear mixed modelling, adjusting for NAI treatment propensity, antibiotics and corticosteroids. RESULTS: Of 20 634 included participants, 5978 (29·0%) had IRP; conversely, 3349 (16·2%) had confirmed the absence of radiographic pneumonia (the comparator). Early NAI treatment (within 2 days of symptom onset) versus no NAI was not significantly associated with IRP [adj. OR 0·83 (95% CI 0·64-1·06; P = 0·136)]. Among the 5978 patients with IRP, early NAI treatment versus none did not impact on mortality [adj. OR = 0·72 (0·44-1·17; P = 0·180)] or likelihood of requiring ventilatory support [adj. OR = 1·17 (0·71-1·92; P = 0·537)], but early treatment versus later significantly reduced mortality [adj. OR = 0·70 (0·55-0·88; P = 0·003)] and likelihood of requiring ventilatory support [adj. OR = 0·68 (0·54-0·85; P = 0·001)]. CONCLUSIONS: Early NAI treatment of patients hospitalised with A(H1N1)pdm09 virus infection versus no treatment did not reduce the likelihood of IRP. However, in patients who developed IRP, early NAI treatment versus later reduced the likelihood of mortality and needing ventilatory support.

Effectiveness of neuraminidase inhibitors in reducing mortality in patients admitted to hospital with influenza A H1N1pdm09 virus infection: a meta-analysis of individual participant data.

BACKGROUND: Neuraminidase inhibitors were widely used during the 2009-10 influenza A H1N1 pandemic, but evidence for their effectiveness in reducing mortality is uncertain. We did a meta-analysis of individual participant data to investigate the association between use of neuraminidase inhibitors and mortality in patients admitted to hospital with pandemic influenza A H1N1pdm09 virus infection. METHODS: We assembled data for patients (all ages) admitted to hospital worldwide with laboratory confirmed or clinically diagnosed pandemic influenza A H1N1pdm09 virus infection. We identified potential data contributors from an earlier systematic review of reported studies addressing the same research question. In our systematic review, eligible studies were done between March 1, 2009 (Mexico), or April 1, 2009 (rest of the world), until the WHO declaration of the end of the pandemic (Aug 10, 2010); however, we continued to receive data up to March 14, 2011, from ongoing studies. We did a meta-analysis of individual participant data to assess the association between neuraminidase inhibitor treatment and mortality (primary outcome), adjusting for both treatment propensity and potential confounders, using generalised linear mixed modelling. We assessed the association with time to treatment using time-dependent Cox regression shared frailty modelling. FINDINGS: We included data for 29,234 patients from 78 studies of patients admitted to hospital between Jan 2, 2009, and March 14, 2011. Compared with no treatment, neuraminidase inhibitor treatment (irrespective of timing) was associated with a reduction in mortality risk (adjusted odds ratio [OR] 0·81; 95% CI 0·70-0·93; p=0·0024). Compared with later treatment, early treatment (within 2 days of symptom onset) was associated with a reduction in mortality risk (adjusted OR 0·48; 95% CI 0·41-0·56; p<0·0001). Early treatment versus no treatment was also associated with a reduction in mortality (adjusted OR 0·50; 95% CI 0·37-0·67; p<0·0001). These associations with reduced mortality risk were less pronounced and not significant in children. There was an increase in the mortality hazard rate with each day's delay in initiation of treatment up to day 5 as compared with treatment initiated within 2 days of symptom onset (adjusted hazard ratio [HR 1·23] [95% CI 1·18-1·28]; p<0·0001 for the increasing HR with each day's delay). INTERPRETATION: We advocate early instigation of neuraminidase inhibitor treatment in adults admitted to hospital with suspected or proven influenza infection. FUNDING: F Hoffmann-La Roche.

Taxa de mortalidade por asma de acordo com os atestados de óbito nos moradores em Cascavel/PR no período de jan/05 a dez/09 / Asthma mortality rates according to the death certifications among inhabitants of Cascavel, PR during 2005-2009

A prevalência estimada de asma no Brasil (21%) coloca-o em 8º lugar no ranking mundial. As taxas de mortalidade por asma costumam variar entre os países e são moduladas por fatores externos à doença, tais como o nível de desenvolvimento dos recursos de saúde disponíveis e a qualidade do sistema de registros de óbitos. Este trabalho teve como objetivo quantificar e analisar a taxa de mortalidade por asma nos moradores da cidade de Cascavel/PR. Os dados foram selecionados dos atestados de óbito dos moradores no município de Cascavel, PR, ocorridos de janeiro de 2005 a dezembro de 2009, sem limitação de faixa etária, que contivessem em qualquer das partes a citação de asma (J45), na 10ª revisão da Classificação Internacional de Doenças (CID 10). Os dados foram obtidos no Sistema de Informações sobre Mortalidade (SIM) da Secretaria Municipal de Saúde. A asma foi identificada como causa associada em 17 óbitos, correspondendo ao coeficiente médio de mortalidade de 1,11/100.000 habitantes, diferente do observado em outros países. Observou-se que a mortalidade associada à asma foi maior nas faixas etárias mais altas. O gênero não pareceu ser uma variável importante. A maioria das mortes ocorreu em hospitais e não houve maior ocorrência de óbitos em determinada época do ano. Não se pôde avaliar com acurácia o diagnóstico de asma dos óbitos, nem se a asma contribuiu ou não para o óbito, pois não se teve acesso à identificação e dados de internação dessas pessoas.

Brazil is the 8th country in the world in asthma prevalence (approximately 21%). Mortality rates for asthma vary among countries and are modulated by external factors, such as the level of development of health resources available and the quality of the system of death records. This study aimed to analyze and quantify the asthma mortality rate in people living in thecity of Cascavel, PR, from 2005 to 2009. Data were selected from death certificates of residents of Cascavel, PR, registered from January 2005 to December 2009, which contained in any field asthma (ICD 10, code J45), without limitation of age. Data were collected from Mortality Information System (SIM) in the Health secretary of Cascavel. Asthma was identified as an associated cause in 17 deaths, corresponding to an average mortality rate of 1.11 per 100,000 inhabitants, different from the observed in other countries. It can be observed that the mortality associated with asthma was higher in higher age groups. The genderdoes not seem to be an important variable. Most deaths occurred in hospitals and there was not a higher incidence of deaths related to certain period of the year. We were unable to assess accurately the diagnosis of asthma deaths, nor if asthma contributedto death or not, because there were no identification available and admission data of such people.