In Reply: Letter: Central Nervous System Infections in Patients With Ventriculoperitoneal Shunts Admitted for Primary Abdominal Infections: A US Nationwide Cohort Analysis

To the Editor: We appreciate the authors' response1 to our study. Although our manuscript2 was not a meta-analysis, we agree that the significant heterogeneity in studies of shunt-related infections is an important consideration. Variability in infection rates can arise from differences in patient populations, institutional practices, and infection definitions. A critical factor contributing to this variability is the length of follow-up, with longer periods more likely to capture late-onset infections. Although the I2 statistic helps quantify the heterogeneity, bias can occur when meta-analyses include a small number of studies,3 potentially overestimating the heterogeneity. Time-dependent biases can also affect I2 calculations, which is why 95% CIs are often reported.4 These issues highlight the importance of standardized infection definitions, consistent follow-up periods, and rigorous study design in meta-analyses. Cochrane methodology provides valuable guidance in addressing some of these concerns. Cochrane reviews focus on minimizing bias by ensuring comprehensive and systematic inclusion of studies, setting clear criteria for study selection, and assessing the risk of bias across studies.5 Importantly, Cochrane reviews typically include sensitivity analyses to explore the impact of follow-up duration and study characteristics on overall results.6 By rigorously addressing the methodological quality of the included studies, Cochrane reviews help mitigate some of the concerns regarding heterogeneity and time-dependent biases. The letter also highlights the lack of meta-analyses regarding pooled infection rates on lumboperitoneal shunts (LPS) placed for all indications1; however, for communicating hydrocephalus and idiopathic intracranial hypertension, there are recent meta-analyses comparing infection rates for ventriculo-peritoneal shunt (VPS) and LPS.7,8 Both studies reported significantly lower infection rates for LPS compared with VPS, and both used standardized risk of bias assessment tools, including the Cochrane-provided ROB 2 for randomized trials and Risk Of Bias In Non-randomized Studies-I (ROBINS-I) for nonrandomized studies. In support of these standardized tools, both studies reported I2 of 0% for the outcome of infection rates. As the field evolves, further multicenter, long-term studies are needed to better define infection risks for different types of shunts. We thank the authors for their valuable feedback and contribution to this important discussion. Sincerely, Cameron P. Beaudreault, MD, Eris Spirollari, BA, Sabrina Zeller, MD, Fawaz Al-Mufti, MD