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Oral steroids for long-term use in cystic fibrosis.

Oral steroids for long-term use in cystic fibrosis.

Cochrane Database Syst Rev. 2011;(10):CD000407

Authors: Cheng K, Ashby D, Smyth RL

Abstract
BACKGROUND: In cystic fibrosis (CF) airway obstruction and recurrent respiratory infection lead to inflammation, long-term lung damage, respiratory failure and death. Anti-inflammatory agents, e.g. oral corticosteroids are used since inflammation occurs early in disease.
OBJECTIVES: To assess the effectiveness of oral corticosteroids in respiratory complications in CF, particularly lung function and adverse events. We examined long-term use (over 30 days) only.
SEARCH STRATEGY: We searched the Cochrane CF and Genetic Disorders Group Trials Register comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings.Most recent search: 06 April 2011.
SELECTION CRITERIA: Randomised trials comparing oral corticosteroids given for more than 30 days with placebo or no additional therapy in people with CF.
DATA COLLECTION AND ANALYSIS: Two authors independently assessed study eligibility and quality.
MAIN RESULTS: Of nine studies identified, three (354 participants) were included: two with four-year follow up and one with 12-weeks follow up. Data were lacking on predefined outcomes; common outcomes were examined at different time-points and presented differently. Meta-analyses were not possible.In one study, oral corticosteroids at prednisolone-equivalent dose of 1 mg/kg alternate days slowed progression of lung disease; at two and four years, % predicted FEV(1) in the 1 mg/kg group changed significantly more than in the placebo group (P < 0.02). During the first two years, the 2 mg/kg group was not significantly different from the placebo group. Linear growth retardation was observed from six months in the 2 mg/kg alternate days prednisolone group and from 24 months in the 1 mg/kg alternate days prednisolone group.Adverse events terminated one four-year study early. Year 10 follow up showed catch-up growth started two years after treatment ceased. Alternate-day treatment with oral corticosteroids may have impaired growth until adulthood in boys.
AUTHORS' CONCLUSIONS: Oral corticosteroids at prednisolone-equivalent dose of 1 to 2 mg/kg alternate days appear to slow progression of lung disease in CF; benefit should be weighed against occurrence of adverse events. Risk-benefit analysis of low-dose alternate days corticosteroids is important and the short-term use of oral corticosteroids should be better evaluated.

PMID: 21975730 [PubMed - indexed for MEDLINE]

Short-course versus prolonged-course antibiotic therapy for hospital-acquired pneumonia in critically ill adults.

Pneumonia is the most common hospital-acquired infection affecting patients in the intensive care unit (ICU). However, the optimal duration of antibiotic therapy for hospital-acquired pneumonia (HAP) is uncertain.

OBJECTIVES: To assess the effectiveness of short versus prolonged-course antibiotic administration for HAP in critically ill adults, including patients with ventilator-associated pneumonia (VAP).

SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2011, Issue 1), which includes the Cochrane Acute Respiratory Infections Group's Specialised Register, MEDLINE (1950 to February week 4, 2011), EMBASE (1974 to March 2011), LILACS (1985 to March 2011) and Web of Science (1985 to March 2011).

SELECTION CRITERIA: We considered all randomised controlled trials (RCTs) comparing fixed durations of antibiotic therapy, or comparing a protocol intended to limit duration of therapy with standard care, for HAP (including patients with VAP) in critically ill adults.

DATA COLLECTION AND ANALYSIS: Two review authors conducted data extraction and assessment of risk of bias. We contacted trial authors for additional information.

MAIN RESULTS: Eight studies (1703 patients) were included. Methodology varied considerably and we found little evidence regarding patients with a high probability of HAP who were not mechanically ventilated. For patients with VAP, a short seven to eight-day course of antibiotics compared with a prolonged 10 to 15-day course (three studies, N = 508) increased 28-day antibiotic-free days (odds ratio (OR) 4.02; 95% confidence interval (CI) 2.26 to 5.78) and reduced recurrence of VAP due to multi-resistant organisms (OR 0.44; 95% CI 0.21 to 0.95), without adversely affecting other outcomes. However, for cases of VAP due to non-fermenting Gram-negative bacilli (NF-GNB), recurrence was greater after short-course therapy (OR 2.18; 95% CI 1.14 to 4.16; two studies, N = 176), though other outcome measures did not significantly differ. Discontinuation strategies utilising clinical features (one study; N = 302) or procalcitonin (three studies; N = 323) led to a reduction in duration of therapy and, in the procalcitonin studies, increased 28-day antibiotic-free days (mean difference (MD) 2.80; 95% CI 1.39 to 4.21) without negatively affecting other outcomes.

AUTHORS' CONCLUSIONS: We conclude that for patients with VAP not due to NF-GNB, a short fixed-course (seven or eight days) antibiotic therapy may be more appropriate than a prolonged course (10 to 15 days). Use of an individualised strategy (incorporating clinical features or serum procalcitonin) appears to safely reduce duration of antibiotic therapy for VAP.

Referral to an extracorporeal membrane oxygenation center and mortality among patients with severe 2009 influenza A(H1N1).

Extracorporeal membrane oxygenation (ECMO) can support gas exchange in patients with severe acute respiratory distress syndrome (ARDS), but its role has remained controversial. ECMO was used to treat patients with ARDS during the 2009 influenza A(H1N1) pandemic.

OBJECTIVE: To compare the hospital mortality of patients with H1N1-related ARDS referred, accepted, and transferred for ECMO with matched patients who were not referred for ECMO.

DESIGN, SETTING, AND PATIENTS: A cohort study in which ECMO-referred patients were defined as all patients with H1N1-related ARDS who were referred, accepted, and transferred to 1 of the 4 adult ECMO centers in the United Kingdom during the H1N1 pandemic in winter 2009-2010. The ECMO-referred patients and the non-ECMO-referred patients were matched using data from a concurrent, longitudinal cohort study (Swine Flu Triage study) of critically ill patients with suspected or confirmed H1N1. Detailed demographic, physiological, and comorbidity data were used in 3 different matching techniques (individual matching, propensity score matching, and GenMatch matching).

MAIN OUTCOME MEASURE: Survival to hospital discharge analyzed according to the intention-to-treat principle.

RESULTS: Of 80 ECMO-referred patients, 69 received ECMO (86.3%) and 22 died (27.5%) prior to discharge from the hospital. From a pool of 1756 patients, there were 59 matched pairs of ECMO-referred patients and non-ECMO-referred patients identified using individual matching, 75 matched pairs identified using propensity score matching, and 75 matched pairs identified using GenMatch matching. The hospital mortality rate was 23.7% for ECMO-referred patients vs 52.5% for non-ECMO-referred patients (relative risk [RR], 0.45 [95% CI, 0.26-0.79]; P = .006) when individual matching was used; 24.0% vs 46.7%, respectively (RR, 0.51 [95% CI, 0.31-0.81]; P = .008) when propensity score matching was used; and 24.0% vs 50.7%, respectively (RR, 0.47 [95% CI, 0.31-0.72]; P = .001) when GenMatch matching was used. The results were robust to sensitivity analyses, including amending the inclusion criteria and restricting the location where the non-ECMO-referred patients were treated.

CONCLUSION: For patients with H1N1-related ARDS, referral and transfer to an ECMO center was associated with lower hospital mortality compared with matched non-ECMO-referred patients.

Changes in forced expiratory volume in 1 second over time in COPD.

BACKGROUND: A key feature of chronic obstructive pulmonary disease (COPD) is an accelerated rate of decline in forced expiratory volume in 1 second (FEV(1)), but data on the variability and determinants of this change in patients who have established disease are scarce.

METHODS: We analyzed the changes in FEV(1) after administration of a bronchodilator over a 3-year period in 2163 patients. A random-coefficient model was used to evaluate possible predictors of both FEV(1) levels and their changes over time.

RESULTS: The mean (±SE) rate of change in FEV(1) was a decline of 33±2 ml per year, with significant variation among the patients studied. The between-patient standard deviation for the rate of decline was 59 ml per year. Over the 3-year study period, 38% of patients had an estimated decline in FEV(1) of more than 40 ml per year, 31% had a decline of 21 to 40 ml per year, 23% had a change in FEV(1) that ranged from a decrease of 20 ml per year to an increase of 20 ml per year, and 8% had an increase of more than 20 ml per year. The mean rate of decline in FEV(1) was 21±4 ml per year greater in current smokers than in current nonsmokers, 13±4 ml per year greater in patients with emphysema than in those without emphysema, and 17±4 ml per year greater in patients with bronchodilator reversibility than in those without reversibility.

CONCLUSIONS: The rate of change in FEV(1) among patients with COPD is highly variable, with increased rates of decline among current smokers, patients with bronchodilator reversibility, and patients with emphysema.

British Thoracic Society guidelines for the management of community acquired pneumonia in children: update 2011.

The British Thoracic Society first published management guidelines for community acquired pneumonia in children in 2002 and covered available evidence to early 2000. These updated guidelines represent a review of new evidence since then and consensus clinical opinion where evidence was not found.

This document incorporates material from the 2002 guidelines and supersedes the previous guideline document.

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