**4. Discussion**

SSIs primarily result from the disruption of the equilibrium between the quantity of inoculated microorganisms, their virulence, and the ability of the immune system to clear them. TCS, which are coated in a broad-spectrum antimicrobial agent, reduce the bacterial load at the wound site, thereby potentially helping to reduce the risk of SSIs.

Meta-analysis is a useful tool in that it allows for data pooling from multiple trials and thus provides a more comprehensive estimation of treatment effects. However, this approach only partially restricted the confounding effect of the differences and heterogeneity among the included studies

and populations. Among the available meta-analyses and in accordance with the defined inclusion criteria, we assessed and estimated the results of the 2017 meta-analysis reported by Henriksen et al. [28] as the most recently available evidence that fulfilled our clinical focus. The authors included all RCTs that evaluated the e ffect of TCS in patients who underwent abdominal surgery. The e ffect of TCS was evaluated in several studies that enrolled subjects with distinct patient-related and operation-related risk factors. There was heterogeneity between trials in terms of surgery type which included elective colorectal surgeries, elective procedures through midline laparotomy, elective and emergency laparotomies for any type of target organ, emergency surgery for fecal peritonitis, and open appendectomy. The pooled results yielded a significant 33% reduction in the odds of having an SSI after surgery for patients who received a wound closure with TCS versus CS. However, it should be noted that intervention type (elective versus emergency), target organs, and the lack of implementation of recognized peri-operative strategies to reduce SSI likely limit the ability to define the true e ffect of TCS, adding high heterogeneity and possible confounders. Two additional RCTs [40,41] that were published afterwards did not contribute to solving these uncertainties.

The e ffect of TCS should, ideally, be evaluated in a population with a fixed risk of SSI and, importantly, in a setting where all the WHO recommendations [16] (Table 4) are fulfilled to assess the true "over the top" protective e ffect of this strategy. The heterogeneity of studies' settings in terms of adherence to SSI prevention guidelines can therefore be considered as an additional bias; however, these limitations notwithstanding, all nine published meta-analyses reported a consistent decrease in the risk of having an SSI with the use of the used TCS (Table 2). Despite the fact that some of the available meta-analyses did not demonstrate significant di fferences compared to the control arms, the decrease in the SSI rate can still be considered important as it may result in a net financial saving even if the cost of TCS is higher than CS.

> **Table 4.** World Health Organization recommendations for SSI prevention, 2016 version.


Administration of oxygen with 80% FiO2 for 2–6 h post-op Appropriate wound evaluation and managemen<sup>t</sup>

Not use

advanced dressing of any sort, prefer standard dressing

> Abbreviations: SSI, surgical site infection.

A budget impact analysis was performed to evaluate the economic impact of adopting TCS into clinical practice from the perspective of a general surgery unit in an Italian hospital. The model demonstrated that the incremental cost of adopting TCS was o ffset by the cost of SSI episodes that were avoided. Despite an upfront incremental acquisition cost of €600, the use of TCS resulted in an overall annual net saving of €14,785 for the institution. Furthermore, sensitivity analyses demonstrated that, across a broad variation in the ranges for each parameter, the annual savings remained positive with a 98% probability that TCS was cost-saving.

Leaper et al. [44], by using a deterministic decision-tree, a stochastic cost model, and the National Health Service (NHS England)-based cost of inpatient admissions for infections and di fferential costs of TCS versus CS, estimated a significant mean saving of £91.25 per surgical procedure from using antimicrobial sutures across all surgical wound types. This is aligned with the findings in this analysis, where the overall saving was split for single hospitalization with a saving of €147.85. This was further supported by three trials that were published between 2007 and 2013 that evaluated the clinical e fficacy and economic impact of TCS and which demonstrated a net economic saving resulting from adopting TCS rather than CS [26,45,46].

The relevance of this study to the Italian healthcare system lies in the use of Italian-specific input data for SSI risk and SSI cost. This analysis could therefore be valuable to support decision-making processes at the hospital level in Italy. The robustness of the model is increased by the performed sensitivity analyses; however, the limitations of the model lie in some of the inputs being extrapolated from literature research, not being real-world data, or being inflated to current values from outdated data like the SSI cost. To alleviate this, additional analyses, based on recent real-world data from one or more Italian hospitals could be performed to demonstrate the real budget impact of adopting TCS into Italian clinical practice.

Hence, in the decision-making process to adopt a new technology or device, a robust economic analysis should always couple the clinical results to gather additional and essential information on the potential dominant cost-e ffectiveness ratio.
