Summary

-This paper presents a Systematic-Review with Meta-Analysis focusing on Cohort Studies of prevalently North-American and Sub-Saharan infant populations, receiving a combinative treatment of ETV and CPC.Authors included 11 Retrospective Cohorts addressing the aforementioned questions, employing Meta-Analysis of Observational Studies in Epidemiology (MOOSE) guidelines. The primary target was to assess the efficacy and safety of the procedure, while the secondary was the comparison of results between the aforementioned populations, as well as, morbidity, mortality, and complications. The outcome was set as the interval to repeated CSF diversion or death. Comparators of included studies consist of ETV alone or VP-hunt placement.

Strong points

• Study is presented with a clearly focused question, investigating outcomes and complications between initial treatment with ETV+CPC or any other accepted type of surgical treatment of infant congenital hydrocephalus.
• A search was conducted employing MEDLINE, Scopus, Web of Science and Cochrane Central Registry of Controlled Trials databases, without any restrictions or language filtration. Search lines are provided in Appendix A and can be reproduced.
• Merging of duplicates was assessed by two reviewers.
• Title/abstract/full-text screening was performed by two researchers, while contradicting opinions were resolved through discussion. Kappa coefficient was presented as an agreement strength evaluation tool, which was found substantial.
• Identified data were assessed taking into consideration random sequence generation, allocation concealment, blinding of participants/personnel, incomplete outcome data, selective reporting, etc. A graph with the results was provided, as well as rates, employing a guide developed by the team a priori (due to lack of a standardized one, as stated in the manuscript). An online the search confirmed the absence of a generally accepted assessment tool in observational retrospective studies.
• Publication bias was assessed, employing I2 statistic, Egger, and Begg-Mazumbar tests, while heterogeneity was evaluated by Cochran Q, Tau2, and funnel plot/funnel plot regression.
• Limitations are clearly stated (hospital-based, retrospective, short duration, no patient-important data uniformity).
• Authors combined shunt-free rates, mortality, and complications employing a random effect model as per Der-Simonian-Laird pooling method, due to significant heterogeneity variable (e.g. efficacy assessment) and preference.
• A sensitivity analysis was performed to evaluate the geographical impact.
• Authors present aquired data in form of Forest Plots event rate (95%CI) and Funnel Plots of Standard Error by Logit event rate (95%CI).
• Taking into consideration the Confidence Intervals and presented graphics, we conclude that results regarding efficacy have high precision (narrow values) and as a result, they are presented with short lines and big squares/rhombus. On the contrary, the CI of morbidity is wide, thus results present a lower precision and subsequently the plot lines are wider, while symbols are presented small (Figure 3).

Limitations

• Employment of RCTs would be preferable, however, authors highlight the lack of them.
• Neglect of “grey” literature, that would be a valuable enhancement. However, taking into consideration that the aforementioned databases were employed, we cannot consider this as a major fault in the search methodology, according to the Cochrane “Searching for and selecting studies” guidelines.
• The search was performed by only one researcher. No matter how experienced a researcher is, the search has to be performed by two independent individuals, in order to ensure the majority of papers is found, due to variating search in methodology and/or employed terms. The authors themselves state that some of the existing papers may be left unidentified, due to indexing or screening errors.
• Cochrane tools, are meant for prospective research, thus use in this case may produce a high risk of bias.
• Pooling data in non-standardized treatment strategies, with infant hydrocephalus of various aetiologies and surgical approaches (rigid/flexible endoscopes) and a wide range of study qualities included may predispose bias. However, the methodology may be rated as acceptable in this situation, due to the lack of prospective technically uniform and etiology-specific RCTs.
• Mortality was not analyzed.
• No secondary outcomes were Meta-Analyzed.
• Failure of reproducibility between them, as stated by the authors, causes the arousing of a problematization, regarding the possibility of application of this procedure to the local population.
• It would be valuable to assess additional ventricle size, developmental delay, quality of life, and cost-effectiveness. Authors, however, state the lack of information regarding the aforementioned outcomes in the enrolled literature.
• This systematic review does not provide the reader with a clear conclusion, thus the data should be cautiously interpreted.

It is my belief that we cannot use this article as a foundation in order to build upon an evidence-based decision. In conclusion, further research is mandatory.