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Importance of a registered and structured protocol when conducting systematic reviews: comments about nebulized antibiotics for ventilator-associated pneumonia

We appreciate Gu’s [1] interest in our study. We apologize and agree with his comment about attributing units to standardized mean difference (SMD). Nevertheless, similar to the SMD, results in mean difference (control – nebulized) were unaffected by nebulized antibiotics (2.67 days, 95 % confidence interval (CI) –2.89, 8.23 for ICU length of stay (LOS); and 0.70 days, 95 % CI −3.40, 4.80 for mechanical ventilation). However, we strongly disagree with other points raised by the letter.

First, the study protocol was defined a priori [2]. We disagree that combining observational studies with intervention studies is reserved only for safety evaluation. This topic has been discussed in the literature and combining both types of studies was adequate for our aim [3]. Furthermore, we presented the main results separating interventional studies from observational studies, thereby allowing the reader to interpret both analyses independently.

Second, both of the studies cited as “case–control studies” [1] received this denomination in their title and abstract. However, by reading their methods it becomes clear that they are actually matched cohort studies [4, 5]. Indeed, they matched exposed patients (“nebulized group”) to unexposed patients (“no-nebulized group”). A case–control design starts with the outcome (case = “clinical success”) and matches them with controls (“clinical failures”). Therefore, our measure of effect was correct [5]. For exploration, we report the analysis for clinical cure using the odds ratio (OR) (Fig. 1). The results are unchanged.

Fig. 1
figure1

Forest plot for clinical cure using odds ratios (OR). P for overall effect = 0.015. CI confidence interval

Third, Kalin’s study was included because it fulfilled our inclusion/exclusion criteria [2]. Gu’s suggestion to exclude this study based solely on its effects in heterogeneity could be considered selective reporting [1].

Our study provided data for further trials aiming to evaluate the effect of nebulized antibiotics in ventilator-associated pneumonia (VAP) [2].

Abbreviations

CI:

Confidence interval

LOS:

Length of stay

OR:

Odds ratio

SMD:

Standardized mean difference

VAP:

Ventilator-associated pneumonia

References

  1. 1.

    Gu WJ. Nebulized antibiotics for ventilator-associated pneumonia: misleading analysis and interpretation of the data. Crit Care. 2015;19:236.

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    Zampieri FG, Nassar AP, Gusmao-Flores D, Taniguchi LU, Torres A, Ranzani OT. Nebulized antibiotics for ventilator-associated pneumonia: a systematic review and meta-analysis. Crit Care. 2015;19:150.

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Authors

Corresponding author

Correspondence to Otavio T. Ranzani.

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Competing interests

The authors declare that they have no competing interests.

Author contributions

FGZ conceived the study, participated in data acquisition, data analysis, and interpretation, and helped to revise the manuscript for important intellectual content. APN participated in conception of the study, data acquisition, data analysis, and interpretation, and helped to revise the manuscript for important intellectual content. DG-F participated in conception of the study and interpretation, and helped to revise the manuscript for important intellectual content. LUT participated in conception and design of the study and interpretation, and helped to revise the manuscript for important intellectual content. AT participated in conception and design of the study and interpretation, and helped to revise the manuscript for important intellectual content. OTR conceived the design of the study, participated in data acquisition and interpretation, and wrote the draft of the manuscript. All authors read and approved the final manuscript.

See related Letter by Gu, http://www.ccforum.com/content/19/1/236, and related research by Zampieri et al., http://ccforum.com/content/19/1/150.

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Zampieri, F.G., Nassar, A.P., Gusmao-Flores, D. et al. Importance of a registered and structured protocol when conducting systematic reviews: comments about nebulized antibiotics for ventilator-associated pneumonia. Crit Care 19, 298 (2015). https://doi.org/10.1186/s13054-015-1020-8

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Keywords

  • Confidence Interval
  • Observational Study
  • Mechanical Ventilation
  • Control Design
  • Clinical Success