A new mass spectrometry-based method for the quantification of histones in plasma from septic shock patients.

The aim of this study was to develop a novel method to detect circulating histones H3 and H2B in plasma based on multiple reaction monitoring targeted mass spectrometry and a multiple reaction monitoring approach (MRM-MS) for its clinical application in critical bacteriaemic septic shock patients. Plasma samples from 17 septic shock patients with confirmed bacteraemia and 10 healthy controls were analysed by an MRM-MS method, which specifically detects presence of histones H3 and H2B. By an internal standard, it was possible to quantify the concentration of circulating histones in plasma, which were significantly higher in patients, and thus confirmed their potential as biomarkers for diagnosing septic shock. After comparing surviving patients and non-survivors, a correlation was found between higher levels of circulating histones and unfavourable outcome. Indeed, histone H3 proved a more efficient and sensitive biomarker for septic shock prognosis. In conclusion, these findings suggest the accuracy of the MRM-MS technique and stable isotope labelled peptides to detect and quantify circulating plasma histones H2B and H3. This method may be used for early septic shock diagnoses and for the prognosis of fatal outcomes.

Degree of adherence to recommended antiviral treatment during the pandemic and post-pandemic periods of influenza A(H1N1)pdm09 in 148 intensive care units in Spain.

OBJECTIVE: To determine the degree of antiviral treatment recommendations adherence and its impact to critical ill patients affected by influenza A(H1N1)pdm09 mortality. DESIGN: Secondary analysis of prospective study. SETTING: Intensive care (UCI). PATIENTS: Patients with influenza A(H1N1)pdm09 in the 2009 pandemic and 2010-11 post-Pandemic periods. VARIABLES: Adherence to recommendations was classified as: Total (AT); partial in doses (PD); partial in time (PT), and non-adherence (NA). Viral pneumonia, obesity and mechanical ventilation were considered severity criteria for the administration of high antiviral dose. The analysis was performed using t-test or «chi¼ square. Survival analysis was performed and adjusted by Cox regression analysis. RESULTS: A total of 1,058 patients, 661 (62.5%) included in the pandemic and 397 (37.5%) in post-pandemic period respectively. Global adherence was achieved in 41.6% (43.9% and 38.0%; P=.07 respectively). Severity criteria were similar in both periods (68.5% vs. 62.8%; P=.06). The AT was 54.7% in pandemic and 36.4% in post-pandemic period respectively (P<.01). The NA (19.7% vs. 11.3%; P<.05) and PT (20.8% vs. 9.9%, P<.01) was more frequent in the post-pandemic period. The mortality rate was higher in the post-pandemic period (30% vs. 21.8%, P<.001). APACHE II (HR=1.09) and hematologic disease (HR=2.2) were associated with a higher mortality and adherence (HR=0.47) was a protective factor. CONCLUSIONS: A low degree of adherence to the antiviral treatment was observed in both periods. Adherence to antiviral treatment recommendations was associated with lower mortality rates and should be recommended in critically ill patients with suspected influenza A(H1N1)pdm09.

Macrolide-based regimens in absence of bacterial co-infection in critically ill H1N1 patients with primary viral pneumonia.

PURPOSE: To determine whether macrolide-based treatment is associated with mortality in critically ill H1N1 patients with primary viral pneumonia. METHODS: Secondary analysis of a prospective, observational, multicenter study conducted across 148 Intensive Care Units (ICU) in Spain. RESULTS: Primary viral pneumonia was present in 733 ICU patients with pandemic influenza A (H1N1) virus infection with severe respiratory failure. Macrolide-based treatment was administered to 190 (25.9 %) patients. Patients who received macrolides had chronic obstructive pulmonary disease more often, lower severity on admission (APACHE II score on ICU admission (13.1 ± 6.8 vs. 14.4 ± 7.4 points, p < 0.05), and multiple organ dysfunction syndrome less often (23.4 vs. 30.1 %, p < 0.05). Length of ICU stay in survivors was not significantly different in patients who received macrolides compared to patients who did not (10 (IQR 4-20) vs. 10 (IQR 5-20), p = 0.9). ICU mortality was 24.1 % (n = 177). Patients with macrolide-based treatment had lower ICU mortality in the univariate analysis (19.2 vs. 28.1 %, p = 0.02); however, a propensity score analysis showed no effect of macrolide-based treatment on ICU mortality (OR = 0.87; 95 % CI 0.55-1.37, p = 0.5). Moreover, the sensitivity analysis revealed very similar results (OR = 0.91; 95 % CI 0.58-1.44, p = 0.7). A separate analysis of patients under mechanical ventilation yielded similar results (OR = 0.77; 95 % CI 0.44-1.35, p = 0.4). CONCLUSION: Our results suggest that macrolide-based treatment was not associated with improved survival in critically ill H1N1 patients with primary viral pneumonia.

[Consensus document on vaccination against influenza in health care workers]. / Consenso sobre la vacunación frente a la gripe en el personal sanitario.

Health care workers (HCW) are included each year among risk groups for vaccination against influenza. However, vaccination coverage among this group in our country is very low, not exceeding 25%. Convinced that one of the best tools to increase this coverage among professionals in our country are the scientific evidence, 19 scientific societies and associations professionals bringing together health professionals more directly related to influenza as an health problem, and the General Nursing Council, met to discuss and develop this consensus document in order to inform HCW about the appropriateness of their vaccination against influenza and the benefits that flow from it for themselves, for their patients and for the rest of the population. This recommendation is based on 3 pillars: argument of necessity, ethics and exemplary.

[Community infections that require admission to the ICU]. / Infecciones comunitarias que requieren ingreso en UCI.

The clinical and diagnostic characteristics and treatment of the most severe and frequent community-acquired infections in the Intensive Care Units are analyzed. These are serious community-acquired pneumonias, meningitis, encephalitis and urinary tract infections. Regarding the pneumonias, emphasis is placed on the use of the severity scales to evaluate admission in the critical units, on evolutive monitoring using biological markers and on the importance of initiating adequate early antibiotic treatment. The importance of the Gram staining of the cerebral spinal fluid in the etiological diagnosis of meningitis, of the polymerase chain reaction amplification techniques in real time and of the magnetic resonance imaging in the etiological diagnosis of the encephalitis. Furthermore, concern is expressed regarding the increase of the percentage of the strains of extended spectrum betalactamase-producing Escherichia coli and Klebsiella pneumoniae in our country.

[Pneumonia in the elderly population over 70 years with limited functional condition: case-control study of institutionalized patients]. / Neumonía en la población mayor de 70 años y con estado funcional limitado: estudio caso-control de pacientes institucionalizados.

OBJECTIVE: Community acquired pneumonia (CAP) of the elderly is an increasingly important growing health problem due to its prevalence and mortality. Among the factors that are usually related with poor evolution are advanced age, poor functional status and coming from a socio-health care institution such as residential homes for the elderly. In this study, we have chosen a population over 70 years of age with limited functional capacity (Barthel Index < 50) in order to know if coming from a residential home for the elderly is an isolated factor that is associated to worse prognosis of CAP. PATIENTS AND METHODS: We selected 87 patients over 70 years from a prospective and multicenter study of the hospitalized CAPs during one year. We analyzed the evolution and course of the CAP based on place or origin and then conducted a case-control study of the elderly over 70 years with the Barthel under 50, including 21 elderly from residences and 21 from the own home. RESULTS: In elderly patients over 70 years with CAP, those coming from the residence have a confusional picture more often and come to emergency with lower values of systolic and diastolic blood pressure, lower arterial oxygen saturation, greater involvement on the x-ray, Fine Index is worse and die more often. When we limit the population to those over 70 years with Barthel under 50, we do not find differences in institutionalized patients versus the others. CONCLUSION: In the elderly over 70 years with CAP, patients from assisted living residences have greater mortality. However, when functional capacity is bad (Barthel < 50), place or origin (community or elderly residence) loses importance and becomes a variable that has no more influence than others in the clinical evolution and course of the CAP.

Antibiotic prescription for community-acquired pneumonia in the intensive care unit: impact of adherence to Infectious Diseases Society of America guidelines on survival.

BACKGROUND: The purpose of our study was to analyze prognostic factors associated with mortality for patients with severe community-acquired pneumonia (CAP). METHODS: We conducted a prospective multicenter study including all patients with CAP admitted to the intensive care unit during a 15-month period in 33 Spanish hospitals. Admission data and data on the evolution of the disease were recorded. Multivariate analysis was performed using the SPSS statistical package (SPSS). RESULTS: A total of 529 patients with severe CAP were enrolled; the mean age (+/-SD) was 59.9+/-16.1 years, and the mean Acute Physiology and Chronic Health Evaluation (APACHE) II score (+/-SD) was 18.9+/-7.4. Overall mortality among patients in the intensive case unit was 27.9% (148 patients). The rate of adherence to Infectious Diseases Society of America (IDSA) guidelines was 57.8%. Significantly higher mortality was documented among patients with nonadherence to treatment (33.2% vs. 24.2%). Multivariate analysis identified age (odds ratio [OR], 1.7), APACHE II score (OR, 4.1), nonadherence to IDSA guidelines (OR, 1.6), and immunocompromise (OR, 1.9) as the variables present at admission to the intensive care unit that were independently associated with death in the intensive care unit. In 15 (75%) of 20 cases of Pseudomonas aeruginosa infection, the antimicrobial treatment at admission was inadequate (including 8 of 15 cases involving patients with adherence to IDSA guidelines). Chronic obstructive pulmonary disease (OR, 17.9), malignancy (OR, 11.0), previous antibiotic exposure (OR, 6.2), and radiographic findings demonstrating rapid spread of disease (OR, 3.9) were associated with P. aeruginosa pneumonia. CONCLUSIONS: Better adherence to IDSA guidelines would help to improve survival among patients with severe CAP. Pseudomonas coverage should be considered for patients with chronic obstructive pulmonary disease, malignancy, or recent antibiotic exposure.

[Guidelines for the management of community pneumonia in adult who needs hospitalization]. / Guías para el manejo de la neumonía comunitaria del adulto que precisa ingreso en el hospital.

Community acquired pneumonia is still an important health problem. In Spain the year incidence is 162 cases per 100,000 inhabitants with 53,000 hospital admission costing 115 millions of euros per year. In the last years there have been significant advances in the knowledge of: aetiology, diagnostic tools, treatment alternatives and antibiotic resistance. The Spanish Societies of Intensive and Critical Care (SEMICYUC), Infectious Diseases and Clinical Microbiology (SEIMC) and Pulmonology and Thoracic Surgery (SEPAR) have produced these evidence-based Guidelines for the management of community acquired pneumonia in Adults. The main objective is to help physicians to make decisions about this disease. The different points that have been developed are: aetiology, diagnosis, treatment and prevention.

Risk factors of treatment failure in community acquired pneumonia: implications for disease outcome.

BACKGROUND: An inadequate response to initial empirical treatment of community acquired pneumonia (CAP) represents a challenge for clinicians and requires early identification and intervention. A study was undertaken to quantify the incidence of failure of empirical treatment in CAP, to identify risk factors for treatment failure, and to determine the implications of treatment failure on the outcome. METHODS: A prospective multicentre cohort study was performed in 1424 hospitalised patients from 15 hospitals. Early treatment failure (<72 hours), late treatment failure, and in-hospital mortality were recorded. RESULTS: Treatment failure occurred in 215 patients (15.1%): 134 early failure (62.3%) and 81 late failure (37.7%). The causes were infectious in 86 patients (40%), non-infectious in 34 (15.8%), and undetermined in 95. The independent risk factors associated with treatment failure in a stepwise logistic regression analysis were liver disease, pneumonia risk class, leucopenia, multilobar CAP, pleural effusion, and radiological signs of cavitation. Independent factors associated with a lower risk of treatment failure were influenza vaccination, initial treatment with fluoroquinolones, and chronic obstructive pulmonary disease (COPD). Mortality was significantly higher in patients with treatment failure (25% v 2%). Failure of empirical treatment increased the mortality of CAP 11-fold after adjustment for risk class. CONCLUSIONS: Although these findings need to be confirmed by randomised studies, they suggest possible interventions to decrease mortality due to CAP.

Sepsis and SOFA score: related outcome for critically ill renal patients.

AIMS: To evaluate the influence of sepsis in critically ill patients with acute renal failure (ARF), and to analyze the value of the sequential organ failure assessment (SOFA) score for assessing the morbidity and related mortality of these patients. MATERIAL AND METHODS: A prospective observational study developed in a medical intensive care unit (ICU) of a tertiary care university hospital. Data were collected from January 1, 2001 - July 31, 2002. The inclusion criterion was either a creatinine plasma level > or = 2 mg/dl on ICU admission or increases > or = 30% from its initial value. Sepsis was evaluated at the time of study inclusion, and patients were distributed into 2 groups (septic and nonseptic patients). RESULTS: Two hundred patients with ARF were prospectively enrolled in the study (91 (45.5%) septic and 109 (54.5%) nonseptic patients). Median age was 68 years in septic patients and 72 in nonseptic ones while the percentage of males in both groups was 66% vs 69%, respectively. Septic patients showed more organ failures and more respiratory, cardiovascular and coagulation failures at the time of study admission as well as a worse mean SOFA score during the first 4 days after inclusion (p < 0.01). Mortality rate at the ICU was significantly higher in the septic group when compared to the nonseptic one (55% vs 19.3%, OR = 2.21 (1.65 - 2.97)). Using stepwise logistic regression, acute tubular necrosis and oliguria in septic patients as well as cardiovascular failure (evaluated by SOFA score) in nonseptic patients were identified as independent risk factors for mortality. CONCLUSIONS: Septic and nonseptic ICU patients with ARF have an increased risk of ICU mortality depending on the type of organ failure. Although SOFA score does not predict outcome, it is a useful tool to categorize these patients and to describe a sequence of complications in critically ill patients.

[Acute renal failure in critically ill patients. A prospective epidemiological study]. / Fracaso renal agudo en la unidad de cuidados intensivos. Estudio observacional prospectivo.

AIMS: To determine factors which may predict mortality in patients admitted to intensive care unit who present acute renal failure. METHODS: Prospective observational study of the patients admitted to a multidisciplinary intensive care unit over a year. The inclusion criteria were a creatinine plasmatic value > or = 2 mg/dl (177 micromol/l) or an increase (30% or higher) of its basal value on admittance. RESULTS: One hundred and twenty-seven patients (age = 65.83 +/- 15.06 years; 38% male) with acute renal failure, were prospectively enrolled in the study (13% of intensive care unit admissions). The univariate analysis showed that hospital origin, acute tubular necrosis, late ARF, oliguria, maintained hypotension, sedation or coma, oncological disease and need of mechanical ventilation were significantly associated with mortality (p < 0.05). This association was also found for sepsis (OR: 41.5), multiorganic failure (OR: 3.58) and respiratory, cardiovascular or haematological failure according to the SOFA score. The multivariate analysis found that four clinical variables had an independent predictive value for mortality risk: acute tubular necrosis [OR: 4.57 (2.32-9.00)], use of vasoactive drugs [OR: 2.32 (1.22-4.40)], oliguria [OR: 2.15 (1.12-4.13)] and the acute renal failure starting during admission [OR: 2.06 (1.09-3.88)]. CONCLUSION: Data related to renal failure have worse prognosis than other demographic or clinical data in critically ill patients with acute renal failure. Multicentric studies with unified criteria are needed to analyse the most important prognostic factors.

Community-acquired pneumonia in the elderly: Spanish multicentre study.

Community-acquired pneumonia (CAP) in the elderly has increased as a consequence of an overall increase of the elderly population. A controversy about the aetiology and outcome of CAP in this population still exists and more epidemiological studies are needed. A prospective, 12-month, multicentre study was carried out to assess the clinical characteristics, aetiology, evolution and prognostic factors of elderly patients (> or = 65 yrs) admitted to hospital for CAP. The study included 503 patients (age 76 +/- 7 yrs). The clinical picture lasted < or = 5 days in 318 (63%) and the main clinical features were cough (n = 407, 81%) and fever (n = 380, 76%). Aetiological diagnosis was achieved in 199 (40%) cases, with a definite diagnosis obtained in 164 (33%). Of the 223 microorganisms isolated the main agents found were Streptococcus pneumoniae in 98 (49%) and Haemophilus influenzae in 27 (14%). A total of 53 patients died (11%) and the multivariate analysis showed the following factors of bad prognosis: previous bed confinement, alteration in mental status, absence of chills, plasma creatinine > or = 1.4 mg x dL(-1), oxygen tension in arterial blood/inspiratorv oxygen fraction ratio < 200 at the time of admission, and shock and renal failure during the evolution. The results of this study may aid in the management of empiric antibiotic treatment in elderly patients with community-acquired pneumonia and the patients who have a greater probability of bad evolution may be identified based on the risk factors.

Use of venous thromboembolism prophylaxis for surgical patients: a multicentre analysis of practice in Spain.

OBJECTIVE: To assess the use of venous thromboembolism prophylaxis in surgical patients. DESIGN: Retrospective multicentre study. SETTING: Eight acute-care teaching hospitals with more than 400 beds, Spain. PATIENTS: Medical records of all consecutive patients undergoing operations in the general surgical and trauma and orthopaedic services during the month of April, 1997, were randomly selected. INTERVENTION: The sample size for each type of operation (general, trauma-orthopaedic) was calculated from the number of operations done at each hospital (with an absolute precision of 5%, and an alpha error of 5%) and the prevalence of the use of venous thromboembolism prophylaxis obtained from a random sample of 50 records (25 from patients in general surgery and 25 from patients in orthopaedic surgery) from each centre. MAIN OUTCOME MEASURES: Appropriate and inappropriate pharmacological prophylaxis defined according to a combination of risk categories for venous thromboembolism, doses of antithrombotic agents given, time of starting prophylaxis, and its duration. RESULTS: A total of 1848 medical records (general surgery, n = 1025; trauma-orthopaedic surgery, n = 823) were included. Physical methods (elastic stockings, intermittent pneumatic compression) were used in only 0.3% of patients. Pharmacological prophylaxis consisted of low molecular weight heparin in 99% of cases. The percentage given heparin-based prophylaxis was 54%. Overall, appropriate prophylaxis was given in 1175 patients (64%). Use of thromboprophylaxis ranged from 27% to 70% among the participating hospitals. Prophylaxis was more likely to be appropriate in orthopaedic patients (577, 70%) than in general surgical patients (598, 58%) in both the high and moderate risk categories. CONCLUSIONS: Given the large variability between the participating hospitals, more specific protocols and recommendations about prophylaxis of thromboembolism in surgical patients are needed.

Treatment of severe nosocomial pneumonia: a prospective randomised comparison of intravenous ciprofloxacin with imipenem/cilastatin.

BACKGROUND: A prospective multicentre study was undertaken to compare the efficacy of intravenous ciprofloxacin or imipenem in the treatment of severe nosocomial pneumonia requiring mechanical ventilation. METHODS: Patients with a clinical suspicion of pneumonia were randomised to receive either ciprofloxacin (800-1200 mg/day) or imipenem (2-4 g/day) in doses adjusted for renal function and specimens of the lower respiratory tract were taken. Patients were included in the study when specimens showed significant growth for potentially pathogenic microorganisms in quantitative bacterial cultures (n = 75, ciprofloxacin 41/75 (55%); imipenem 34/75 (45%)). The clinical and bacteriological success rates were the primary and secondary efficacy variables. An intent-to-treat analysis was performed for all randomised patients who received at least one dose of the study medication (n = 149, ciprofloxacin 72/149 (48%), imipenem 77/149 (52%)). RESULTS: The success rates were generally good, but neither the clinical success rates (ciprofloxacin, 29/41 (71%), imipenem, 27/34 (79%); 95% CI -10.8 to 28.1; p = 0.435) nor the bacteriological response rate (ciprofloxacin, 20/41 (49%), imipenem, 17/34 (50%); 95% CI -21.5 to 23.9; p = 1.0) were significantly different between the study arms. Pseudomonas aeruginosa was recovered in 26/75 patients (35%) and clinical (ciprofloxacin, 10/14 (71%), imipenem, 8/12 (67%); 95% CI -40.4 to 30.9; p = 1.0) and bacteriological response rates (ciprofloxacin, 7/14 (50%), imipenem, 3/12 (25%), 95% CI -60.9 to 10.9, p = 0.247) were not significantly different in this subgroup of patients. Resistance of Pseudomonas aeruginosa developed in 5/26 cases (19%), 1/14 (7%) to ciprofloxacin and 4/12 (33%) to imipenem (p = 0.147), and the mortality was 12/75 (16%) with no difference between treatment groups (ciprofloxacin, 8/41(24%), imipenem 4/34 (17%); p = 0.362). The clinical response was evaluable in 109/149 patients (73%) in the intent-to-treat analysis and was successful in 74/109 patients (68%). The clinical response rates were also not significantly different in the intent-to-treat analysis (ciprofloxacin, 34/52 (65%), imipenem, 40/57 (70%); 95% CI -12.8 to 22.3; p = 0.746). CONCLUSIONS: Treatment with either ciprofloxacin or imipenem was effective in a selected group of patients with microbiologically confirmed, severe nosocomial pneumonia requiring mechanical ventilation. Although no differences between the study medication could be documented in this trial, smaller differences between treatment arms may have been missed because of sample size limitations.

[Descriptive epidemiology of the vascular risk factors in Bañeres. Study group 'Bañeres Project']. / Epidemiología descriptiva de los factores de riesgo vascular en Bañeres. Grupo de Estudio 'Proyecto Bañeres'.

INTRODUCTION: Epidemiological studies of the risk factors of cerebrovascular disease are of great interest, particularly the identification of factors which may be modified. Previous studies carried out in the Alcoi region of Alicante province, showed a high prevalence of cerebrovascular disease. The town of Bañeres was therefore chosen for confirmation of this data and identification of the frequency of vascular risk factors. OBJECTIVE: To compare the group of patients with cerebrovascular disease with the remainder of the population interviewed. PATIENTS AND METHODS: In a door-to-door study in Bañeres 1,832 people were interviewed as part of the Bañeres Project. The population aged over 45 years was interviewed and filled in a questionnaire for diagnosis of transient ischemic accidents. RESULTS: Arterial hypertension: estimated prevalence 500/1,000 inhabitants, relative risk 3.24; diabetes mellitus: estimated prevalence 195/1,000, relative risk 2.18; coronary artery disease: estimated prevalence 58/1,000, relative risk 1.88; peptic ulcer: estimated prevalence 75/1,000, relative risk 1.23; smoking: estimated prevalence 110/1,000, relative risk 0.46; complete arrhythmia: prevalence 73/1,000, relative risk 5.23. Family histories of cerebrovascular accident, arterial hypertension, diabetes and coronary artery disease were not significant. CONCLUSIONS: Arterial hypertension, diabetes mellitus and arrhythmia were significantly more prevalent amongst patients with vascular disease in our setting. We found no association with the other risk factors analyzed.