Project description:BackgroundLower respiratory tract infections (LRTI) are a leading cause of critical illness and mortality in mechanically ventilated children; however, the pathogenic microbes frequently remain unknown. We combined traditional diagnostics with metagenomic next generation sequencing (mNGS) to evaluate the cause of LRTI in critically ill children.MethodsWe conducted a prospective, multicentre cohort study of critically ill children aged 31 days to 17 years with respiratory failure requiring mechanical ventilation (>72 h) in the USA. By combining bacterial culture and upper respiratory viral PCR testing with mNGS of tracheal aspirate collected from all patients within 24 h of intubation, we determined the prevalence, age distribution, and seasonal variation of viral and bacterial respiratory pathogens detected by either method in children with or without LRTI.FindingsBetween Feb 26, 2015, and Dec 31, 2017, of the 514 enrolled patients, 397 were eligible and included in the study (276 children with LRTI and 121 with no evidence of LRTI). A presumptive microbiological cause was identified in 255 (92%) children with LRTI, with respiratory syncytial virus (127 [46%]), Haemophilus influenzae (70 [25%]), and Moraxella catarrhalis (65 [24%]) being most prevalent. mNGS identified uncommon pathogens including Ureaplasma parvum and Bocavirus. Co-detection of viral and bacterial pathogens occurred in 144 (52%) patients. Incidental carriage of potentially pathogenic microbes occurred in 82 (68%) children without LRTI, with rhinovirus (30 [25%]) being most prevalent. Respiratory syncytial virus (p<0·0001), H influenzae (p=0·0006), and M catarrhalis (p=0·0002) were most common in children younger than 5 years. Viral and bacterial LRTI occurred predominantly during winter months.InterpretationThese findings demonstrate that respiratory syncytial virus, H influenzae, and M catarrhalis contribute disproportionately to severe paediatric LRTI, co-infections are common, and incidental carriage of potentially pathogenic microbes occurs frequently. Further, we provide a framework for future epidemiological and emerging pathogen surveillance studies, highlighting the potential for metagenomics to enhance clinical diagnosis.FundingUS National Institutes of Health and CZ Biohub.

Project description:BackgroundRecruitment manoeuvres involve transient elevations in airway pressure applied during mechanical ventilation to open ('recruit') collapsed lung units and increase the number of alveoli participating in tidal ventilation. Recruitment manoeuvres are often used to treat patients in intensive care who have acute respiratory distress syndrome (ARDS), but the effect of this treatment on clinical outcomes has not been well established. This systematic review is an update of a Cochrane review originally published in 2009.ObjectivesOur primary objective was to determine the effects of recruitment manoeuvres on mortality in adults with acute respiratory distress syndrome.Our secondary objective was to determine, in the same population, the effects of recruitment manoeuvres on oxygenation and adverse events (e.g. rate of barotrauma).Search methodsFor this updated review, we searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (OVID), Embase (OVID), the Cumulative Index to Nursing and Allied Health Literature (CINAHL, EBSCO), Latin American and Caribbean Health Sciences (LILACS) and the International Standard Randomized Controlled Trial Number (ISRCTN) registry from inception to August 2016.Selection criteriaWe included randomized controlled trials (RCTs) of adults who were mechanically ventilated that compared recruitment manoeuvres versus standard care for patients given a diagnosis of ARDS.Data collection and analysisTwo review authors independently assessed trial quality and extracted data. We contacted study authors for additional information.Main resultsTen trials met the inclusion criteria for this review (n = 1658 participants). We found five trials to be at low risk of bias and five to be at moderate risk of bias. Six of the trials included recruitment manoeuvres as part of an open lung ventilation strategy that was different from control ventilation in aspects other than the recruitment manoeuvre (such as mode of ventilation, higher positive end-expiratory pressure (PEEP) titration and lower tidal volume or plateau pressure). Six studies reported mortality outcomes. Pooled data from five trials (1370 participants) showed a reduction in intensive care unit (ICU) mortality (risk ratio (RR) 0.83, 95% confidence interval (CI) 0.72 to 0.97, P = 0.02, low-quality evidence), pooled data from five trials (1450 participants) showed no difference in 28-day mortality (RR 0.86, 95% CI 0.74 to 1.01, P = 0.06, low-quality evidence) and pooled data from four trials (1313 participants) showed no difference in in-hospital mortality (RR 0.88, 95% CI 0.77 to 1.01, P = 0.07, low-quality evidence). Data revealed no differences in risk of barotrauma (RR 1.09, 95% CI 0.78 to 1.53, P = 0.60, seven studies, 1508 participants, moderate-quality evidence).Authors' conclusionsWe identified significant clinical heterogeneity in the 10 included trials. Results are based upon the findings of several (five) trials that included an "open lung ventilation strategy", whereby the intervention group differed from the control group in aspects other than the recruitment manoeuvre (including co-interventions such as higher PEEP, different modes of ventilation and higher plateau pressure), making interpretation of the results difficult. A ventilation strategy that included recruitment manoeuvres in participants with ARDS reduced intensive care unit mortality without increasing the risk of barotrauma but had no effect on 28-day and hospital mortality. We downgraded the quality of the evidence to low, as most of the included trials provided co-interventions as part of an open lung ventilation strategy, and this might have influenced results of the outcome.

Project description:ObjectivesInappropriate antibiotic use for respiratory tract infection (RTI) is an ongoing problem linked to the emergence of drug resistance and other adverse effects. Less is known about the prescribing practices of individual physicians or the impact of physician prescribing habits on patient outcomes. We studied the prescribing practices of providers for acute RTIs in an integrated health system, identified patient factors associated with receipt of an antibiotic and assessed the relation between providers' adjusted prescribing rates and a number of patient outcomes.MethodsThis was a retrospective analysis of adults with an RTI visit to any primary care providers across the Cleveland Clinic Health System in 2011-2012. Patients with a history of chronic obstructive pulmonary disease or immunocompromised status were excluded. Logistic regression was used to examine patient factors associated with receipt of an antibiotic.ResultsOf 31,416 patients with an RTI, 54.8% received an antibiotic. Patient factors associated with antibiotic prescribing included white race (odds ratio [OR] 1.35, P < 0.001), presence of fever (OR 1.66, P < 0.001), and a diagnosis of bronchitis (OR 10.98, P < 0.001) or sinusitis (OR 33.85, P < 0.001). Among 290 providers with ≥10 RTI visits, adjusted antibiotic prescribing rates ranged from 0% to 100% (mean 49%). Antibiotics were prescribed more often for sinusitis (OR 33.85, P < 0.001), bronchitis (OR 10.98, P < 0.001), or pharyngitis (OR 1.76, P < 0.001) compared with upper respiratory tract infection. Patients who were prescribed antibiotics at the index visit were more likely to return for RTI within 1 year (adjusted OR 1.26, P < 0.001). Emergency department visits for respiratory complications were rare and not associated with antibiotic receipt.ConclusionsAntibiotic prescribing for RTI varies widely among physicians and cannot be explained by patient factors. Patients prescribed antibiotics for RTI were more likely to return for RTI.

Project description:PurposeExperimental animal models of acute respiratory distress syndrome (ARDS) have shown that the updated airway pressure release ventilation (APRV) methodologies may significantly improve oxygenation, maximize lung recruitment, and attenuate lung injury, without circulatory depression. This led us to hypothesize that early application of APRV in patients with ARDS would allow pulmonary function to recover faster and would reduce the duration of mechanical ventilation as compared with low tidal volume lung protective ventilation (LTV).MethodsA total of 138 patients with ARDS who received mechanical ventilation for <48 h between May 2015 to October 2016 while in the critical care medicine unit (ICU) of the West China Hospital of Sichuan University were enrolled in the study. Patients were randomly assigned to receive APRV (n = 71) or LTV (n = 67). The settings for APRV were: high airway pressure (Phigh) set at the last plateau airway pressure (Pplat), not to exceed 30 cmH2O) and low airway pressure ( Plow) set at 5 cmH2O; the release phase (Tlow) setting adjusted to terminate the peak expiratory flow rate to ≥ 50%; release frequency of 10-14 cycles/min. The settings for LTV were: target tidal volume of 6 mL/kg of predicted body weight; Pplat not exceeding 30 cmH2O; positive end-expiratory pressure (PEEP) guided by the PEEP-FiO2 table according to the ARDSnet protocol. The primary outcome was the number of days without mechanical ventilation from enrollment to day 28. The secondary endpoints included oxygenation, Pplat, respiratory system compliance, and patient outcomes.ResultsCompared with the LTV group, patients in the APRV group had a higher median number of ventilator-free days {19 [interquartile range (IQR) 8-22] vs. 2 (IQR 0-15); P < 0.001}. This finding was independent of the coexisting differences in chronic disease. The APRV group had a shorter stay in the ICU (P = 0.003). The ICU mortality rate was 19.7% in the APRV group versus 34.3% in the LTV group (P = 0.053) and was associated with better oxygenation and respiratory system compliance, lower Pplat, and less sedation requirement during the first week following enrollment (P < 0.05, repeated-measures analysis of variance).ConclusionsCompared with LTV, early application of APRV in patients with ARDS improved oxygenation and respiratory system compliance, decreased Pplat and reduced the duration of both mechanical ventilation and ICU stay.

Project description:ObjectiveTo assess the overall effect of delayed antibiotic prescribing on average symptom severity for patients with respiratory tract infections in the community, and to identify any factors modifying this effect.DesignSystematic review and individual patient data meta-analysis.Data sourcesCochrane Central Register of Controlled Trials, Ovid Medline, Ovid Embase, EBSCO CINAHL Plus, and Web of Science.Eligibility criteria for study selectionRandomised controlled trials and observational cohort studies in a community setting that allowed comparison between delayed versus no antibiotic prescribing, and delayed versus immediate antibiotic prescribing.Main outcome measuresThe primary outcome was the average symptom severity two to four days after the initial consultation measured on a seven item scale (ranging from normal to as bad as could be). Secondary outcomes were duration of illness after the initial consultation, complications resulting in admission to hospital or death, reconsultation with the same or worsening illness, and patient satisfaction rated on a Likert scale.ResultsData were obtained from nine randomised controlled trials and four observational studies, totalling 55 682 patients. No difference was found in follow-up symptom severity (seven point scale) for delayed versus immediate antibiotics (adjusted mean difference -0.003, 95% confidence interval -0.12 to 0.11) or delayed versus no antibiotics (0.02, -0.11 to 0.15). Symptom duration was slightly longer in those given delayed versus immediate antibiotics (11.4 v 10.9 days), but was similar for delayed versus no antibiotics. Complications resulting in hospital admission or death were lower with delayed versus no antibiotics (odds ratio 0.62, 95% confidence interval 0.30 to 1.27) and delayed versus immediate antibiotics (0.78, 0.53 to 1.13). A significant reduction in reconsultation rates (odds ratio 0.72, 95% confidence interval 0.60 to 0.87) and an increase in patient satisfaction (adjusted mean difference 0.09, 0.06 to 0.11) were observed in delayed versus no antibiotics. The effect of delayed versus immediate antibiotics and delayed versus no antibiotics was not modified by previous duration of illness, fever, comorbidity, or severity of symptoms. Children younger than 5 years had a slightly higher follow-up symptom severity with delayed antibiotics than with immediate antibiotics (adjusted mean difference 0.10, 95% confidence interval 0.03 to 0.18), but no increased severity was found in the older age group.ConclusionsDelayed antibiotic prescribing is a safe and effective strategy for most patients, including those in higher risk subgroups. Delayed prescribing was associated with similar symptom duration as no antibiotic prescribing and is unlikely to lead to poorer symptom control than immediate antibiotic prescribing. Delayed prescribing could reduce reconsultation rates and is unlikely to be associated with an increase in symptoms or illness duration, except in young children.Study registrationPROSPERO CRD42018079400.

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Topical antibiotic prophylaxis to reduce respiratory tract infections and mortality in adults receiving mechanical ventilation.

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