Antibióticos empíricos para la neumonía adquirida en la comunidad en pacientes adultos: Una revisión sistemática y un metaanálisis en red

Objetivo: El objetivo principal de este metaanálisis en red es identificar el antibiótico empírico (Em-ATB) con mayor probabilidad de ser el mejor (HPBB) en términos de (1) tasa de curación y (2) tasa de mortalidad en pacientes hospitalizados con neumonía adquirida en la comunidad (NAC) . Método: Criterios de inclusión: (1) pacientes adultos (>16 años) diagnosticados de NAC que requirieron hospitalización; (2) aleatorizados a al menos dos Em-ATB diferentes, (3) que informen de la tasa de curación y (4) que estén escritos en inglés o español. Criterios de exclusión: (1) protocolo de antibióticos ambiguo y (2) publicados exclusivamente en formato resumen o carta. Fuentes de datos: Medline, Embase, Cochrane y revisiones de citas desde el 1 de enero de 2000 hasta el 31 de diciembre de 2018. Riesgo de sesgo: Herramienta de Cochrane. Calidad de la revisión sistemática (RS): A MeaSurement Tool to Assess systematic Reviews-2. Certeza de la evidencia: Grading of Recommendations Assessment, Development and Evaluation. Análisis estadísticos: método frecuentista realizado con la biblioteca 'netmeta', paquete R. Resultados: se incluyeron 27 ensayos controlados aleatorizados (ECA) de las 41.307 citas seleccionadas inicialmente. En cuanto al riesgo de sesgo, más de una cuarta parte de los estudios presentaron riesgo bajo y ningún estudio presentó riesgo alto en todos los dominios. La calidad de la RS es moderada. Para la curación, se construyeron dos redes. Así, dos Em-ATB tienen la HPBB: cetarolina 600 mg (dos veces al día) y piperacilina 2000 mg (dos veces al día). Para la mortalidad, se construyeron tres redes. Así, tres Em-ATB tienen la HPBB: ceftriaxona 2000 mg (una vez al día) más levofloxacino 500 (dos veces al día), ertapenem 1000 mg (dos veces al día) y amikacina 250 mg (dos veces al día) más claritromicina 500 mg (dos veces al día). La certeza de la evidencia para cada resultado es moderada. Conclusiones: Para la tasa de curación, ceftarolina y piperacilina son las opciones con la HPBB. Sin embargo, para la tasa de mortalidad, las opciones son ceftriaxona más levofloxacino, ertapenem y amikacina más claritromicina. Parece necesario realizar un ECA que compare los tratamientos con el HPBB para cada evento (curación o mortalidad) (CRD42017060692).Objective: The main aim of this network meta-analysis is to identify the empiric antibiotic (Em-ATB) with the highest probability of being the best (HPBB) in terms of (1) cure rate and (2) mortality rate in hospitalised patients with community acquired pneumonia (CAP) . Method: Inclusion criteria: (1) adult patients (>16 years old) diagnosed with CAP that required hospitalisation; (2) randomised to at least two different Em-ATBs, (3) that report cure rate and (4) are written in English or Spanish. Exclusion criteria: (1) ambiguous antibiotics protocol and (2) published exclusively in abstract or letter format. Data sources: Medline, Embase, Cochrane and citation reviews from 1 January 2000 to 31 December 2018. Risk of bias: Cochrane's tool. Quality of the systematic review (SR): A MeaSurement Tool to Assess systematic Reviews-2. Certainity of the evidence: Grading of Recommendations Assessment, Development and Evaluation. Statistical analyses: frequentist method performed with the 'netmeta' library, R package. Results: 27 randomised controlled trials (RCTs) from the initial 41 307 screened citations were included. Regarding the risk of bias, more than one quarter of the studies presented low risk and no study presented high risk in all domains. The SR quality is moderate. For cure, two networks were constructed. Thus, two Em-ATBs have the HPBB: cetaroline 600 mg (two times a day) and piperacillin 2000 mg (two times a day). For mortality, three networks were constructed. Thus, three Em-ATBs have the HPBB: ceftriaxone 2000 mg (once a day) plus levofloxacin 500 (two times a day), ertapenem 1000 mg (two times a day) and amikacin 250 mg (two times a day) plus clarithromycin 500 mg (two times a day). The certainity of evidence for each results is moderate. Conclusion: For cure rate, ceftaroline and piperaciline are the options with the HPBB. However, for mortality rate, the options are ceftriaxone plus levofloxacin, ertapenem and amikacin plus clarithromycin. It seems necessary to conduct an RCT that compares treatments with the HPBB for each event (cure or mortality) (CRD42017060692)

Land- and water-based exercise intervention in women with fibromyalgia: the al-andalus physical activity randomised controlled trial

Background The al-Andalus physical activity intervention study is a randomised control trial to investigate the effectiveness of a land- and water-based exercise intervention for reducing the overall impact of fibromyalgia (primary outcome), and for improving tenderness and pain-related measures, body composition, functional capacity, physical activity and sedentary behaviour, fatigue, sleep quality, health-related quality of life, and cognitive function (secondary outcomes) in women with fibromyalgia. Methods/Design One hundred eighty women with fibromyalgia (age range: 35-65 years) will be recruited from local associations of fibromyalgia patients in Andalucía (Southern Spain). Patients will be randomly assigned to a usual care (control) group (n = 60), a water-based exercise intervention group (n = 60) or a land-based exercise intervention group (n = 60). Participants in the usual care group will receive general physical activity guidelines and participants allocated in the intervention groups will attend three non-consecutive training sessions (60 min each) per week during 24 weeks. Both exercise interventions will consist of aerobic, muscular strength and flexibility exercises. We will also study the effect of a detraining period (i.e., 12 weeks with no exercise intervention) on the studied variables. Discussion Our study attempts to reduce the impact of fibromyalgia and improve patients' health status by implementing two types of exercise interventions. Results from this study will help to assess the efficacy of exercise interventions for the treatment of fibromyalgia. If the interventions would be effective, this study will provide low-cost and feasible alternatives for health professionals in the management of fibromyalgia. Results from the al-Andalus physical activity intervention will help to better understand the potential of regular physical activity for improving the well-being of women with fibromyalgia.This study was supported by the Consejeria de Turismo, Comercio y Deporte (CTCD-201000019242-TRA), the Spanish Ministry of Science and Innovation (I + D + I DEP2010-15639, grants: BES-2009-013442, BES-2011-047133, RYC-2010-05957, RYC-2011-09011), the Swedish Heart-Lung Foundation (20090635), the Spanish Ministry of Education (AP-2009-3173), Granada Research of Excelence Initiative on Biohealth (GREIB), Campus BioTic, University of Granada, Spain and European University of Madrid. Escuela de Estudios Universitarios Real Madrid. 2010/04RM

Acute Respiratory Distress Syndrome and Diffuse Alveolar Damage. New Insights on a Complex Relationship

Acute respiratory distress syndrome (ARDS) is a major clinical problem with high morbidity and mortality. Diffuse alveolar damage (DAD) is considered the histological hallmark for the acute phase of ARDS. DAD is characterized by an acute phase with edema, hyaline membranes, and inflammation, followed by an organizing phase with alveolar septal fibrosis and type II pneumocyte hyperplasia. Given the difficulties in obtaining a biopsy in patients with ARDS, the presence of DAD is not required to make the diagnosis. However, biopsy and autopsy studies suggest that only one-half of patients who meet the clinical definition of ARDS also have DAD. The other half are found to have a group of heterogeneous disorders, including pneumonia. Importantly, the subgroup of patients with ARDS who also have DAD appears to have increased mortality. It is possible that the response of these patients to specific therapies targeting the molecular mechanisms of ARDS may differ from patients without DAD. Therefore, it may be important to develop noninvasive methods to identify DAD. A predictive model for DAD based on noninvasive measurements has been developed in an autopsy cohort but must be validated. It would be ideal to identify biomarkers or imaging techniques that help determine which patients with ARDS have DAD. We conclude that additional studies are needed to determine the effect of DAD on outcomes in ARDS, and whether noninvasive techniques to identify DAD should be developed with the goal of determining whether this population responds differently to specific therapies targeting the molecular mechanisms of ARDS.Sin financiación4.006 JCR (2017) Q1, 13/60 Respiratory System1.797 SJR (2017) Q1, 14/152 Pulmonary and Respiratory MedicineNo data IDR 2017UE

Safety and Efficacy of Devices Delivering Inhaled Antibiotics among Adults with Non-Cystic Fibrosis Bronchiectasis : A Systematic Review and a Network Meta-Analysis

It remains unknown whether the type of aerosol generating device is affecting efficacy and safety among non-cystic fibrosis bronchiectasis (NCFB) adults. The proposal of this network meta-analysis (NMA) is to evaluate effectiveness and safety of inhaled antibiotics administered via dry powder inhaler (DPI) and via nebulizers (SVN) among adult patients with NCFB. Inclusion criteria were randomized-controlled trials, adults (≥18 years) with NCFB, and inhaled antibiotics administered via DPI as intervention. Search strategy was performed in PubMed, Web of Science, and Cochrane Library from 2000 to 2019. Sixteen trials (2870 patients) were included. Three trials (all ciprofloxacin) used DPIs and thirteen used SVN (three ciprofloxacin). Both DPI and SVN devices achieved similar safety outcomes (adverse events, antibiotic discontinuation, severe adverse events, and bronchospasm). Administration of ciprofloxacin via DPI significantly improved time to first exacerbation (87 days, 95% CI 34.3-139.7) and quality of life (MD −7.52; 95% CI −13.06 to −1.98) when compared with via SVN. No other significant differences were documented in clinical efficacy (at least one exacerbation, FEV% predicted) and microbiologic response (bacterial eradication, emergence of new potential pathogens, and emergence of antimicrobial resistance) when comparing devices. Our NMA documented that time to first exacerbation and quality of life, were more favorable for DPIs. Decisions on the choice of devices should incorporate these findings plus other criteria, such as simplicity, costs or maintenance requirements

Acute respiratory distress syndrome sub-phenotypes according to histological findings

The objective is to demonstrate that among patients with the clinical diagnosis of ARDS, the presence of diffuse alveolar damage (DAD) at histological examination, as compared to its absence, defines a clinical sub-phenotype. We studied patients that died in our ICU from 2000 to 2012 with the diagnosis of ARDS according to the Berlin definition and had autopsy. We excluded patients dying [14 days after the diagnosis of ARDS. The diagnosis of DAD required the presence of hyaline membranes plus at least one of the following: intra-alveolar edema, alveolar type I cell necrosis, alveolar type II cell proliferation, interstitial proliferation of fibroblasts or organizing interstitial fibrosis.7.214 JCR (2014) Q1, 3/27 Critical care medicineUE

Genetic predisposition to acute kidney injury induced by severe sepsis.

2.191 JCR (2013) Q3, 17/27 Critical care medicineUE

Genetic predisposition to acute respiratory distress syndrome in patients with severe sepsis

OBJECTIVE: The objective of this study was to analyze the association between candidate gene polymorphisms and susceptibility to acute respiratory distress syndrome (ARDS) in patients with severe sepsis. METHODS: Patients older than 18 years admitted to the intensive care unit (ICU) with the diagnosis of severe sepsis were prospectively included. A blood sample was drawn on the first day of ICU admission, and DNA was extracted. We genotyped the insertion/deletion polymorphism of the angiotensin-converting enzyme (ACE) gene (polymerase chain reaction) and the following single-nucleotide polymorphisms (TaqMan SNP genotyping assay): tumor necrosis factor α -376 G/A, -308 G/A, and -238 G/A; interleukin 8 -251 T/A; pre-B cell colony-enhancing factor -1001 G/T; and vascular endothelial growth factor +405 C/G and +936 C/T. Polymorphisms were selected based on reports on their association with ARDS. Variables associated in univariate analysis (P < 0.1) with the diagnosis of ARDS were included in a multiple logistic regression analysis. RESULTS: We studied 149 patients, of whom 35 presented ARDS. Variables included in the maximal multivariate model were male sex, chronic alcoholism, use of ACE inhibitors or angiotensin-receptor blockers, Simplified Acute Physiology Score II score, serum glucose concentration at ICU admission, and the presence of the allele D of the ACE gene. After adjustment for those variables, the presence of the allele D of the ACE gene (odds ratio, 4.75; 95% confidence interval, 1.02-22.20; P = 0.048) was significantly associated with the diagnosis of ARDS. CONCLUSION: The presence of the allele D of the ACE gene is associated with ARDS in patients with severe sepsis.2.732 JCR (2013) Q2, 11/27 Critical care medicine, 27/68 Hematolog

Identification and validation of a mirna as a diagnostic biomarker of diffuse alveolar damage in an animal model of acute lung injury and adult respiratory distress syndrome in mechanically ventilated patients

The objective is to discover a miRNA with diagnostic characteristics for diffuse alveolar damage (DAD) in an animal of acute lung injury (ALI) and in patients with the ARDS. Male rats (325-372 gr) underwent mechanical ventilation for 2.5 h with VT=9 ml/kg + PEEP=5 cm H2O (low VT, LV, n=10); or VT=25 ml/kg + PEEP=0 cm H2O (high VT, HV, n=19) (11 of 19 developed DAD at histological examination). Whole miRNA expression (RNA-seq-Single Read, 72 cycles, Illumina GaIIx) was analyzed in lung parenchyma. miRNA expression in LV vs. HV and in HV-DAD vs. HV-no-DAD was compared. We used a data mining strategy to prioritize the most relevant miRNA within the miRNAs differentially expressed. Prioritized miRNAs were validated in (1) serum from the same group of rats (RT-PCR); (2) human lung tissue (preserved at -80º after sampling) from autopsies of patients with ARDS (RT-PCR and in situ hybridization) (n=20); (3) human serum from mechanically ventilated patients obtained during the first 24 hours of ICU admission (n=66, 14 nonsurvivors). A p value < 0.05 was considered statistically significant. Results are median (IQR), and odds ratio (OR [95% confidence interval]). RT-PCR results were expressed x10-4. Categorical and continuous variables were compared with χ2 and Mann-Whitney, respectively. Predictive multivariate logistic analysis was used to identify independent risk factors. The area under ROC curve (AUROC, mean±SEM) was used to assess the discriminatory capacity. Multiple-comparison was adjusted by FDR. The local Ethics Committee approved this study.7.214 JCR (2014) Q1, 3/27 Critical care medicineUE

Acute respiratory distress syndrome in patients with and without diffuse alveolar damage: an autopsy study

Objective To demonstrate that among patients with acute respiratory distress syndrome (ARDS), the presence of diffuse alveolar damage (DAD) at histological examination, as compared to its absence, defines a specific subphenotype. Methods We studied 149 patients who died in our ICU with the clinical diagnosis of ARDS according to the Berlin Definition (BD) and who had autopsy examination. We compared the change over time of different clinical variables in patients with (n = 49) and without (n = 100) DAD. A predictive model for the presence of DAD was developed and validated in an independent cohort of 57 patients with ARDS and postmortem examination (21 of them with DAD). Results Patients with DAD, as compared to patients without DAD, had a lower PaO2/FiO2 ratio and dynamic respiratory system compliance, and a higher SOFA score and INR, and were more likely to die of hypoxemia and less likely to die of shock. In multivariate analysis, variables associated with DAD [odds ratio, 95 % confidence interval (CI)] were PaO2/FiO2 ratio [0.988 (0.981–0.995)], dynamic respiratory system compliance [0.937 (0.892–0.984)] and age [0.972 (0.946–0.999)]. Areas under the ROC curve (95 % CI) for the classification of DAD using the regression model or the BD were, respectively, 0.74 (0.65–0.82) and 0.64 (0.55–0.72) (p = 0.03). In the validation cohort, the areas under the ROC curve for the diagnosis of DAD were 0.73 (0.56–0.90) and 0.67 (0.54–0.81) for the regression model and the BD, respectively. Conclusions The presence of DAD appears to define a specific subphenotype in patients with ARDS. Targeting patients with DAD within the population of patients with the clinical diagnosis of ARDS might be appropriate to find effective therapies for this condition