Efficacy of heat and moisture exchangers in preventing ventilator-associated pneumonia: meta-analysis of randomized controlled trials

Objective Several randomized controlled trials (RCT) have examined the effect of antibacterial humidification strategies, particularly the replacement of heated humidifiers (HH) by heat and moisture exchangers (HME), in preventing ventilator-associated pneumonia (VAP). The present meta-analysis reviews these RCTs.Methods RCTs were identified by searching the Medline and Cochrane Central Register of Controlled Trials databases from 1990 to 2003. We included RCTs using HMEs in the treatment group and HHs in the control group and reporting the incidence of pneumonia as a study outcome. Two investigators independently abstracted key data on design, population, intervention and outcome of the studies.Results Between 1990 and 2003 eight RCTs met the inclusion criteria of this analysis. Pooling the results from these studies revealed a reduction in the relative risk of VAP in the HME group (0.7), particularly in MV with a duration of at least 7 days (five RCTs, relative risk 0.57).Conclusions This meta-analysis found a significant reduction in the incidence of VAP in patients humidified with HMEs during MV, particularly in patients ventilated for 7 days or longer. This finding is limited by the exclusion of patients at high risk for airway occlusion from some of the studies. Moreover, contraindications (tenacious secretions, airway obstructive disease, hypothermia) and technical issues of HMEs must be considered. Further RCTs are necessary to examine the wider applicability of HMEs and their extended use.     

Nesiritide: trials and tribulations

Standard therapy for acute decompensated heart failure, a major health problem, consists of intravenous diuretics, vasodilators, and positive inotropic agents. Nesiritide, a recombinant form of human B-type natriuretic peptide, is the only drug specifically approved for this indication. Recent meta-analyses have reported an increased risk of worsening renal function and 30-day mortality with nesiritide administration. These data understandably require physicians to carefully reevaluate their current use of nesiritide in patients with acute decompensated heart failure. In performing this reevaluation, it is important to consider our understanding of the underlying disease state, the limitations and results of these meta-analyses, and new data that provide additional insight into the possible risks and benefits associated with nesiritide therapy. Until additional therapeutic trials are conducted, therapeutic choices must be based on symptomatic and hemodynamic improvement and limited, imperfect available data, which may continue to support the use of nesiritide for its established indication.     

Widening eligibility to phase II trials: constant arcsine difference phase II trials

This paper presents a method for undertaking Phase II trials in which not all patients are considered equally likely to respond to treatment. In ovarian cancer, for example, it has been shown that response is less likely in patients who have failed the previous treatment after only a short interval compared to those who have a protracted failure-free interval [Gynecol. Oncol. 36 (1990) 207]. The method is analogous to those used in phase III trials which estimate relative rather than absolute effects; a constant odds ratio, for example, encompasses multiple relationships between response rates. Phase II trials commonly test the null hypothesis H(0): Por=p(1), where the response rate p(1) is the minimum required level of efficacy and p(0) the highest level which would indicate that the treatment is of no further interest. This approach can be extended by using the arcsine transformation to allow p(0) and p(1) to vary between patients, thus for the ith patient p(0i)=(sin c(i))(2) and the efficacy level is set to p(1i)=(sin (c(i)+b))(2). The value of the arcsine parameter b therefore determines efficacy and the test for efficacy in the trial then becomes a test of the null hypothesis H(0): Bor=b. The value of b is determined by considering representative values of p(0) and p(1) and setting b=(sin(-1) radical p(1)-sin(-1) radical p(0)); b is thus the constant arcsine difference (CAD) between p(0i) and p(1i). The variance of B is 1/4n, which is independent of P, trial designs are therefore independent of P, implying that all patients for whom this difference is identical can be entered into the same trial. This paper considers single-stage and two-stage CAD Phase II trials.     

Inept media trials of clinical trials

The Indian media in general, with the exception of a few domain expert journalists, have failed to comprehend the complexities involved in the clinical trial process. In the run up to the deadline-based coverage of a story, a majority of them fall short in conveying the right perspective to readers, but nevertheless they have been successful in sensationalizing an event in this arena. Possibly by unintended misrepresentation, or mostly out of ignorance of the nuances involved in the clinical trials process, the media has done more harm than good, and got away with it. On the other side, the industry has been reluctant to engage with the media in a meaningful dialog for too long now. It bears not only the consequences of damage to its professional reputation following such reportage, but also the repercussions of unnecessary clampdowns by the regulators. Science journalism in India has yet to rise as a profession.     

Behavioral therapies trials: a case example

BACKGROUND: Behavior change is integral to the prevention and treatment of many disorders associated with deleterious lifestyles. Rigorous scientific testing of behavior change interventions is an important goal for nursing research. APPROACH: The stage model for behavioral therapy development is recommended as a useful framework for evaluating behavior change strategies. The NIH model specifies three stages from initial testing of novel behavioral therapies to their dissemination in community settings. Definitions of each step in a Stage I trial and a case example of Mindfulness-Based Stress Reduction (MBSR) in therapeutic community treatment are provided. RESULTS: It is feasible to adapt a behavioral therapy such as MBSR using the stage model framework. Steps in the process include: (a) determining pilot study design and describing the population; (b) modifying the intervention and developing the manual; (c) training the teachers; (d) implementing a pilot study; and (e) monitoring treatment integrity. DISCUSSION: The development of behavior therapies requires the same scientific rigor used in pharmacotherapy research. Stage I of the model enables consideration of the "dose" of a behavioral intervention necessary to achieve behavior change in a defined population. The stage model offers an excellent approach to achieving rigor in a variety of potentially useful therapies of interest to nurse researchers.     

Randomized clinical trials: issues for researchers

The clinical trial is a randomized prospective study of human subjects in which the effectiveness of an intervention is compared against a control. Such a trial is considered to be a critical test of an innovative therapy. Trials require careful design and planning to be scientifically valid and clinically pertinent. In this review the clinical trial and its role in research are defined, and major ethical, methodological, and feasibility issues associated with trial design and organization are described.     

单个大样本随机对照试验与小样本随机对照试验Meta分析的比较

在缺乏针对临床干预措施的大样本、决定性的随机对照试验的情况下,基于小样本随机对照试验的Meta分析是否能够替代大样本随机对照试验,为临床实践提供最佳证据,是值得探讨的。本文对大样本随机对照试验和Meta分析的原始文献质量、方法学质量进行分析和讨论,并比较单个大样本随机对照试验(RCT)和Meta分析优缺点,以供循证医学研究者参考。     

Gene therapy trials: a patient pathway

This article describes ongoing gene therapy trials at University Hospital Birmingham NHS Trust for liver, head and neck and prostate cancer treatment. The authors suggest that this research programme might become an alternative option for patients who have not responded to conventional treatments.