Enfermedad pulmonar crónica: revisiones sistemáticas y meta análisis

Neuraminidase inhibitors for treatment and prophylaxis of influenza in children: systematic review and meta-analysis of randomised controlled trials.

BMJ. 2009;339:b3172

Authors: Shun-Shin M, Thompson M, Heneghan C, Perera R, Harnden A, Mant D

OBJECTIVE: To assess the effects of the neuraminidase inhibitors oseltamivir and zanamivir in treatment of children with seasonal influenza and prevention of transmission to children in households. DESIGN: Systematic review and meta-analysis of data from published and unpublished randomised controlled trials. DATA SOURCES: Medline and Embase to June 2009, trial registries, and manufacturers and authors of relevant studies. Review methods Eligible studies were randomised controlled trials of neuraminidase inhibitors in children aged </=12 in the community (that is, not admitted to hospital) with confirmed or clinically suspected influenza. Primary outcome measures were time to resolution of illness and incidence of influenza in children living in households with index cases of influenza. RESULTS: We identified four randomised trials of treatment of influenza (two with oseltamivir, two with zanamivir) involving 1766 children (1243 with confirmed influenza, of whom 55-69% had influenza A), and three randomised trials for postexposure prophylaxis (one with oseltamivir, two with zanamivir) involving 863 children; none of these trials tested efficacy with the current pandemic strain. Treatment trials showed reductions in median time to resolution of symptoms or return to normal activities, or both, of 0.5-1.5 days, which were significant in only two trials. A 10 day course of postexposure prophylaxis with zanamivir or oseltamivir resulted in an 8% (95% confidence interval 5% to 12%) decrease in the incidence of symptomatic influenza. Based on only one trial, oseltamivir did not reduce asthma exacerbations or improve peak flow in children with asthma. Treatment was not associated with reduction in overall use of antibiotics (risk difference -0.30, -0.13 to 0.01). Zanamivir was well tolerated, but oseltamivir was associated with an increased risk of vomiting (0.05, 0.02 to 0.09, number needed to harm=20). CONCLUSIONS: Neuraminidase inhibitors provide a small benefit by shortening the duration of illness in children with seasonal influenza and reducing household transmission. They have little effect on asthma exacerbations or the use of antibiotics. Their effects on the incidence of serious complications, and on the current A/H1N1 influenza strain remain to be determined.

PMID: 19666987 [PubMed - indexed for MEDLINE]

A clinical practice guideline for physiotherapists treating patients with chronic obstructive pulmonary disease based on a systematic review of available evidence.

Clin Rehabil. 2009 May;23(5):445-62

Authors: Langer D, Hendriks E, Burtin C, Probst V, van der Schans C, Paterson W, Verhoef-de Wijk M, Straver R, Klaassen M, Troosters T, Decramer M, Ninane V, Delguste P, Muris J, Gosselink R

PURPOSE: Update of a clinical practice guideline for the physiotherapy management of patients with chronic obstructive pulmonary disease supporting the clinical decision-making process. METHODS: A systematic computerized literature search was performed on different modalities for improving physical exercise capacity, reducing exertional dyspnoea, improving airway clearance and encouraging changes in physical activity behaviour. Methodological quality was scored with the PEDro Scale. Scientific conclusions were graded according to the criteria of the; Dutch Evidence Based Guideline Development Platform'. These, together with practical considerations, were used to formulate recommendations for clinical practice. RESULTS: A total of 103 studies were included in the systematic review, consisting of five meta-analyses of randomized controlled trials, 84 randomized controlled trials and 14 uncontrolled studies. Twenty scientific conclusions supported six recommendations on physical exercise training. Nineteen scientific conclusions supported eight recommendations on interventions for reducing dyspnoea. Five scientific conclusions supported seven recommendations concerning treatment modalities to improve mucus clearance, and two scientific conclusions supported two recommendations on strategies for encouraging permanent changes in physical activity behaviour. CONCLUSIONS: Strong recommendations support the use of physical exercise training to improve health-related quality of life and functional exercise capacity. Future research should investigate whether additional interventions for reducing exertional dyspnoea have a place as adjuncts to physical exercise training in selected patients. In addition, treatment of impaired mucus clearance, especially during acute exacerbations, requires further research. With the advance of new technologies for objective measurements of physical activities in daily life more research is needed concerning interventions to initiate and maintain physical activity behaviour change during and after supervised physical exercise training programmes.

PMID: 19389745 [PubMed - indexed for MEDLINE]

Antiinflammatory effects of long-acting beta2-agonists in patients with asthma: a systematic review and metaanalysis.

Chest. 2009 Jul;136(1):145-54

Authors: Sindi A, Todd DC, Nair P

BACKGROUND: Long-acting beta(2)-agonists (LABAs) are recommended as add-on therapy to antiinflammatory treatment in patients with chronic persistent asthma. Results from individual studies evaluating the in vivo antiinflammatory effect of LABAs are conflicting. The purpose of this metaanalysis was to determine whether LABAs have an in vivo antiinflammatory effect compared to placebo and whether the addition of a LABA to therapy with inhaled corticosteroids (ICSs) has a synergistic or additive antiinflammatory effect. METHODS: A systematic search was performed of online databases for randomized controlled trials evaluating the antiinflammatory effects of the following: (1) LABAs compared to placebo; and (2) a LABA plus ICS vs ICS alone in adults and children with asthma. Inflammatory outcome measures included cell counts and markers of cell activation in sputum, BAL fluid, bronchial biopsy specimens, serum, and exhaled nitric oxide (ENO). Data were independently extracted by two study investigators and analyzed to generate standardized mean differences using either a fixed or random-effects metaanalysis depending on the degree of heterogeneity. RESULTS: Thirty-two studies (n = 1,105 participants) met the inclusion criteria. The mean number of participants and mean number of studies for each inflammatory outcome in the metaanalysis was 113.1 (SD, 46.2) and 3.5 (SD, 1.3), respectively. There was no effect of LABA therapy on sputum, BAL fluid, or mucosal inflammatory cells in adults or in children. LABA therapy decreased ENO levels and BAL fluid albumin levels in adults. In children, LABA therapy was associated with a small decrease in serum eosinophils and interleukin-4. CONCLUSION: LABA therapy does not appear to have any clinically important antiinflammatory or proinflammatory effect. LABA therapy decreases BAL fluid albumin levels, suggesting a possible modulating effect on microvascular leakage.

PMID: 19255288 [PubMed - indexed for MEDLINE]

Tiotropium and risk for fatal and nonfatal cardiovascular events in patients with chronic obstructive pulmonary disease: Systematic review with meta-analysis.

Respir Med. 2009 Jun 23;

Authors: Rodrigo GJ, Castro-Rodriguez JA, Nannini LJ, Moral VP, Schiavi EA

BACKGROUND: There are safety concerns regarding the use of anticholinergics in the COPD patient population. The purpose of this review was to evaluate the cardiovascular risk of regular use of inhaled tiotropium bromide in patients with COPD of any severity. METHODS: Systematic searches were conducted in MEDLINE, EMBASE, the Cochrane Controlled Trials Register, manufactures' trial register, and FDA databases, without language restriction. Primary outcomes were a composite of major adverse cardiovascular events, cardiovascular mortality, and nonfatal myocardial infarction (MI) or stroke during the treatment period. Relative risks (RR) were estimated using fixed-effects models and statistical heterogeneity was estimated with the I(2) statistic. RESULTS: Nineteen randomized controlled trials (18,111 participants) were selected. There was no difference in the incidence of adverse cardiovascular events (RR=0.96; 95% CI, 0.82-1.12, I(2)=6%). Among individual components of the composite outcome, tiotropium did not significantly increase the risk of cardiovascular death (RR=0.93; 95% CI, 0.73-1.20, I(2)=1%), nonfatal MI (RR=0.84; 95% CI, 0.64-1.09, I(2)=0%), and nonfatal stroke (RR=1.04; 95% CI, 0.78-1.39, I(2)=0%). A smoking history of >/=55 pack-years presented a trend to a higher rate of cardiovascular adverse events in patients receiving tiotropium. CONCLUSIONS: Compared with control (placebo or salmeterol), tiotropium did not significantly increase the risk of adverse major cardiovascular events among COPD patients. Subgroup analysis suggested that smoking history can modify the risk of cardiovascular adverse events.

PMID: 19556116 [PubMed - as supplied by publisher]

Use of non-invasive ventilation to wean critically ill adults off invasive ventilation: meta-analysis and systematic review.

BMJ. 2009;338:b1574

Authors: Burns KE, Adhikari NK, Keenan SP, Meade M

OBJECTIVE: To summarise the evidence for early extubation with immediate application of non-invasive ventilation compared with continued invasive weaning on important outcomes in intubated adults with respiratory failure. DESIGN: Systematic review and meta-analysis of randomised and quasi-randomised controlled trials. SETTING: Intensive care units. PARTICIPANTS: Critically ill adults receiving invasive ventilation. Study selection criteria We searched Medline, Embase, and CENTRAL, proceedings from four conferences, and reference lists of relevant studies to identify relevant trials. Two reviewers independently selected trials, assessed trial quality, and abstracted data. RESULTS: We identified 12 trials enrolling 530 participants, mostly with chronic obstructive pulmonary disease. Compared with invasive weaning, non-invasive weaning was significantly associated with reduced mortality (relative risk 0.55, 95% confidence interval 0.38 to 0.79), ventilator associated pneumonia (0.29, 95% 0.19 to 0.45), length of stay in intensive care unit (weighted mean difference -6.27 days, -8.77 to -3.78) and hospital (-7.19 days, -10.80 to -3.58), total duration of ventilation, and duration of invasive ventilation. Non-invasive weaning had no effect on weaning failures or weaning time. Benefits on mortality and weaning failures were non-significantly greater in trials that exclusively enrolled patients with chronic obstructive pulmonary disease versus mixed populations. CONCLUSIONS: Current trials in critically ill adults show a consistent positive effect of non-invasive weaning on mortality and ventilator associated pneumonia, though the net clinical benefits remain to be fully elucidated. Non-invasive ventilation should preferentially be used in patients with chronic obstructive pulmonary disease in a highly monitored environment.

PMID: 19460803 [PubMed - indexed for MEDLINE]

Omega 3 and 6 oils for primary prevention of allergic disease: systematic review and meta-analysis.

Allergy. 2009 Jun;64(6):840-8

Authors: Anandan C, Nurmatov U, Sheikh A

BACKGROUND: There is conflicting evidence on the use of omega 3 and omega 6 supplementation for the prevention of allergic diseases. We conducted a systematic review evaluating the effectiveness of omega 3 and 6 oils for the primary prevention of sensitization and development of allergic disorders. METHODS: We searched The Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, LILACS, PsycInfo, AMED, ISI Web of Science and Google Scholar for double-blind randomized controlled trials. Two authors independently assessed articles for inclusion. Meta-analyses were undertaken using fixed effects modelling, or random effects modelling in the event of detecting significant heterogeneity. RESULTS: Of the 3129 articles identified, 10 reports (representing six unique studies) satisfied the inclusion criteria. Four studies compared omega 3 supplements with placebo and two studies compared omega 6 supplements with placebo. There was no clear evidence of benefit in relation to reduced risk of allergic sensitization or a favourable immunological profile. Meta-analyses failed to identify any consistent or clear benefits associated with use of omega 3 [atopic eczema: RR = 1.10 (95% CI 0.78-1.54); asthma: RR = 0.81 (95% CI 0.53-1.25); allergic rhinitis: RR = 0.80 (95% CI 0.34-1.89) or food allergy RR = 0.51 (95% CI 0.10-2.55)] or omega 6 oils [atopic eczema: RR = 0.80 (95% CI 0.56-1.16)] for the prevention of clinical disease. CONCLUSIONS: Contrary to the evidence from basic science and epidemiological studies, our systematic review and meta-analysis suggests that supplementation with omega 3 and omega 6 oils is probably unlikely to play an important role as a strategy for the primary prevention of sensitization or allergic disease.

PMID: 19392990 [PubMed - indexed for MEDLINE]

Critical analysis of the factors associated with enteral feeding in preventing VAP: a systematic review.

J Chin Med Assoc. 2009 Apr;72(4):171-8

Authors: Chen YC

Ventilator-associated pneumonia (VAP) is a common cause of morbidity in critically ill patients. Appropriate enteral feeding is the most important factor associated with the prevention of VAP. However, the standardization of enteral feeding methods needs clarification. The purpose of this systematic review was to synthesize the factors associated with enteral feeding in order to prevent VAP and to describe the characteristics of these factors. A comprehensive search was undertaken involving all major databases from their inception to September 2008 using medical subject heading terms associated with enteral feeding in relation to VAP. The overall reference list of identified studies was audited, and eligible studies included randomized controlled trials, controlled before-and-after (pre-post) studies and meta-analyses. To generate the characteristics of the factors associated with VAP, the reported components of these trials were pinpointed and categorized. A total of 14 papers were found that had investigated the factors linking enteral feeding and VAP. For these, 11 were randomized controlled trials, 1 was a meta-analysis and 2 were case-controlled analyses. Twelve of these 14 studies were conducted at a single institute and 2 were conducted at multiple institutes. The sample sizes varied from 10 to 2,528 subjects. Three major issues were identified based on the purpose of study interventions, and these were the effects of feeding method (continuous vs. intermittent), feeding site on aspiration (gastric vs. small bowel), and the timing of enteral feeding (early vs. late). The evidence suggests that a correct choice of enteral feeding method can effectively reduce complications due to aspiration. Furthermore, intermittent enteral feeding and with a small residual volume feed can reduce gastroesophageal reflux, and increased total intake volume and early feeding can reduce ICU mortality. Nonetheless, the effects of these choices on preventing VAP still need further evaluation. A set of clinical guidelines based on these evidence-based findings with respect to enteral feeding is required, particularly one that covers all aspects of the enteral feeding process.

PMID: 19372071 [PubMed - indexed for MEDLINE]

Interventions for educating children who are at risk of asthma-related emergency department attendance.

Cochrane Database Syst Rev. 2009;(2):CD001290

Authors: Boyd M, Lasserson TJ, McKean MC, Gibson PG, Ducharme FM, Haby M

BACKGROUND: Asthma is the most common chronic childhood illness and is a leading cause for paediatric admission to hospital. Asthma management for children results in substantial costs. There is evidence to suggest that hospital admissions could be reduced with effective education for parents and children about asthma and its management. OBJECTIVES: To conduct a systematic review of the literature and update the previous review as to whether asthma education leads to improved health outcomes in children who have attended the emergency room for asthma. SEARCH STRATEGY: We searched the Cochrane Airways Group Trials Register, including the MEDLINE, EMBASE and CINAHL databases, and reference lists of trials and review articles (last search May 2008). SELECTION CRITERIA: We included randomised controlled trials of asthma education for children who had attended the emergency department for asthma, with or without hospitalisation, within the previous 12 months. DATA COLLECTION AND ANALYSIS: Two authors independently assessed trial quality and extracted data. We contacted study authors for additional information. We pooled dichotomous data with a fixed-effect risk ratio. We used a random-effects risk ratio for sensitivity analysis of heterogenous data. MAIN RESULTS: A total of 38 studies involving 7843 children were included. Following educational intervention delivered to children, their parents or both, there was a significantly reduced risk of subsequent emergency department visits (RR 0.73, 95% CI 0.65 to 0.81, N = 3008) and hospital admissions (RR 0.79, 95% CI 0.69 to 0.92, N = 4019) compared with control. There were also fewer unscheduled doctor visits (RR 0.68, 95% CI 0.57 to 0.81, N = 1009). Very few data were available for other outcomes (FEV1, PEF, rescue medication use, quality of life or symptoms) and there was no statistically significant difference between education and control. AUTHORS' CONCLUSIONS: Asthma education aimed at children and their carers who present to the emergency department for acute exacerbations can result in lower risk of future emergency department presentation and hospital admission. There remains uncertainty as to the long-term effect of education on other markers of asthma morbidity such as quality of life, symptoms and lung function. It remains unclear as to what type, duration and intensity of educational packages are the most effective in reducing acute care utilisation.

PMID: 19370563 [PubMed - indexed for MEDLINE]

Second-line treatments in non-small cell lung cancer. A systematic review of literature and metaanalysis of randomized clinical trials.

Chest. 2009 Jun;135(6):1596-609

Authors: Tassinari D, Scarpi E, Sartori S, Tamburini E, Santelmo C, Tombesi P, Lazzari-Agli L

BACKGROUND: To assess the efficacy of second-line treatments in non-small cell lung cancer (NSCLC). METHODS: A systematic review of literature with metaanalysis of randomized clinical trials (RCTs) was independently performed by three authors. A primary analysis included all RCTs comparing any approach (chemotherapy or therapy with epidermal growth factor receptor [EGFR] inhibitors) with placebo; a secondary analysis included all RCTs comparing any treatment with docetaxel therapy every 3 weeks. The 1-year survival rate (SR) of the primary analysis was the primary outcome of the study; the 1-year SR of the secondary analysis, response rate (RR), and time to progression of primary and secondary analyses were the secondary end points. RESULTS: Fourteen RCTs met the selection criteria. The outcomes of 2,627 and 5,952 patients were analyzed in the primary and secondary analysis, respectively. A significant heterogeneity was documented in the primary analysis for 1-year SR with odd ratio [OR] = 0.763 (p = 0.029). No heterogeneity was documented for RR in the primary analysis, with OR = 0.165 (p < 0.001). A modest heterogeneity was documented in the secondary analysis for 1-year SR and RR, with 1-year SR OR = 0.924 (p = 0.122) and RR OR = 1.069 (p = 0.643). CONCLUSION: Second-line treatments in NSCLC seem to improve the main outcomes better than supportive care. Docetaxel administration every 3 weeks probably remains the "gold standard" because at present the data in literature are not enough to support a greater efficacy of other alternative options. Further trials are needed to identify a clinical and biological profile that could predict the response to treatments and a criterion to select the patients to be treated with chemotherapy or EGFR inhibitors.

PMID: 19225067 [PubMed - indexed for MEDLINE]

Diuretics in acute kidney injury.

Minerva Anestesiol. 2009 May;75(5):251-7

Authors: Karajala V, Mansour W, Kellum JA

BACKGROUND: In an acute care setting, diuretics are often prescribed to maintain or increase urine output in patients presenting with acute kidney injury (AKI). The rationale behind giving diuretics is that they may protect the kidney from ischemic injury by maintaining a nonoliguric state. There have been many studies both supporting and criticizing diuretic use in AKI for improving overall patient outcomes. METHODS: A systematic review of the literature was conducted to evaluate the role of diuretics including osmotics, loop diuretics, and nesiritide in modifying AKI. RESULTS: There was no evidence to suggest that the use of loop diuretics in AKI reduces mortality, the need for dialysis, the number of dialysis sessions, or length of Intensive Care Unit/hospital stay or that it increases the recovery of renal function. There is no benefit for the use of mannitol as an osmotic diuretic over hydration in rhabdomyolysis. In contrast, mannitol was found to cause more harm and to induce nephropathy. Nesiritide did not improve renal function in patients with decompensated heart failure and mild chronic renal insufficiency. Nesiritide may be effective in the prevention of AKI when applied in lower doses for a prolonged period of time in patients with mild to moderate renal insufficiency. CONCLUSIONS: Diuretics have been shown to be ineffective in the prevention of AKI or for improving outcomes once AKI occurs. At best, diuretics can help decrease symptoms of pulmonary edema secondary to volume overload.

PMID: 18636060 [PubMed - indexed for MEDLINE]

Does a higher positive end expiratory pressure decrease mortality in acute respiratory distress syndrome? A systematic review and meta-analysis.

Anesthesiology. 2009 May;110(5):1098-105

Authors: Phoenix SI, Paravastu S, Columb M, Vincent JL, Nirmalan M

BACKGROUND: Positive end expiratory pressure (PEEP) is an important component of therapy in patients with acute lung injury or acute respiratory distress syndrome. The independent effect of PEEP on mortality is currently unknown. METHODS: A systematic review and meta-analysis of randomized controlled clinical trials comparing the use of higher and lower levels of PEEP. RESULTS: Six trials with a total of 2,484 patients from 102 intensive care units and 9 countries met the eligibility criteria. In three trials, the effect of different levels of PEEP was compared in groups receiving comparable tidal volumes. Three trials accounted for more than 85% of total weighting in the meta-analyses. The pooled relative risk obtained from these three trials showed a trend towards improved mortality with high PEEP, even though the difference did not reach statistical significance: Pooled cumulative risk of 0.90 (95% CI 0.72-1.02, P = 0.077). The reduction in absolute risk of death was approximately 4%. There was no evidence of a significant increase in baro-trauma in patients receiving high PEEP, with a pooled risk of 0.95 (95% CI 0.62-1.45, P = 0.81). CONCLUSION: High PEEP strategy may have a clinically relevant independent mortality benefit. Despite a possible increase in baro-trauma, the benefits far outweigh potential risks. Current evidence therefore favors the use of high PEEP as the preferred option when ventilating patients with severe acute respiratory distress syndrome. As the reduction in absolute risk of death is less than 5%, a future clinical trial aimed at demonstrating statistical significance is likely to pose considerable financial and ethical burdens.

PMID: 19352160 [PubMed - indexed for MEDLINE]

Short-term efficacy of upper-extremity exercise training in patients with chronic airway obstruction: a systematic review.

Phys Ther. 2009 May;89(5):443-55

Authors: Costi S, Di Bari M, Pillastrini P, D'Amico R, Crisafulli E, Arletti C, Fabbri LM, Clini EM

BACKGROUND, OBJECTIVES, AND MEASUREMENTS: Patients with chronic airway obstruction (CAO) frequently experience dyspnea and fatigue during activities performed by accessory muscles of ventilation, which competitively participate in arm elevation. This systematic review of randomized controlled trials (RCTs) concerning patients with CAO addresses the effects of upper-extremity exercise training (UEET), added to lower-extremity training or comprehensive pulmonary rehabilitation, on the following patient-centered outcomes: exercise capacity, symptoms, ability to perform daily activities, and health-related quality of life. METHODS: Studies were retrieved using comprehensive database and hand-search strategies. Two independent reviewers determined study eligibility based on inclusion criteria. A detailed description of treatments was mandatory. Reviewers rated study quality and extracted information on study methods, design, intervention, and results. RESULTS: Forty publications were evaluated. Four RCTs met the inclusion criteria but had serious methodological limitations, which introduce possible biases that reduce their internal validity. The outcomes measured were heterogeneous, and the results were inconsistent regarding maximal exercise capacity, dyspnea, and health-related quality of life. No effect of UEET was demonstrated for measures of arm fatigue. LIMITATIONS AND CONCLUSIONS: The limited methodological quality of the studies retrieved prevented us from performing a meta-analysis, the results of which could be misleading. This systematic review shows that there is limited evidence examining UEET and that the evidence available is of poor quality. Therefore, a recommendation for the inclusion or exclusion of UEET in pulmonary rehabilitation programs for individuals with CAO is not possible. Further research is needed to definitively ascertain the effects of this training modality on patient-centered outcomes.

PMID: 19282362 [PubMed - indexed for MEDLINE]