## 2 Method
### Data Collection and Synthesis  
Using a pre-set list of potential information about the significant characteristics and results of studies (Supplementary Material, Table S2), relevant data were extracted from the validated studies. Results were combined in a narrative synthesis subdivided into five sections that comment on main findings, namely the PR concentrations in influents  
\begin{table}
\begin{tabular}{l l l l} \hline
**Bias** & **Study** & **Bias** & **Bias** \\
**Domain** & **Parameter** & **Assessment** & **Score** \\ \hline Selection Bias & PRs sampling & Authors attempted to analyse all the PRs in WW & Yes = 2, No = 0, Unclear = 1 \\  & & samples (wide-scope screenings preceded the detection and quantification of examined PRs) & \\  & & If not, the number of PRs analysed was less or more than 10 & \(\leq\)10 = 0, \(\geq\)10 = 1, \(\geq\)50 = 2 \\  & & Authors explained reasons for their selection of & Yes = 2, No = 0, Unclear = 1 \\  & & PRs, WW, WWTPs & \\ \hline PRs detection & Period of sampling campaigns & \(\leq\)1 week = 0, \(\geq\)1 week = 1, \\  & & \(\geq\)1 year = 2 \\  & & Composite samples & Yes = 2, No = 0, Unclear = 1 \\  & & Volume analysed during the detection phase & \(\leq\)50 mL = 0, \(>\)50 mL = 1, \\  & & \(\geq\)250 mL = 2 \\ \hline Performance Bias & Sampling and & Samples stored on ice and in dark conditions & Yes = 2, No = 0, Unclear = 1 \\  & analytical techniques & Samples stored for less or more than 24 h before & \(\leq\)24 h = 2, \(>\)224 h/unclear = 1, \\  & & the analytical phase & \(\geq\)72 h = 0 \\  & & Description and correct preparation and & Yes = 2, No = 0, Unclear = 1 \\  & & preservation of reagents and solutions & \\ \hline Detection Bias & Sample pre-treatment & Solid-phase extraction (SPE) during the & Yes = 2, No = 0, Unclear = 1 \\  & PRs detection technique & Gas or Liquid chromatography coupled to mass & Yes = 2, No = 0, Unclear = 1 \\  & & spectrometry & \\  & Sampling and & Validation of the analytical method (MDL or & Yes = 2, No = 0, Unclear = 1 \\  & detection technique & LOD, MQL or LOQ \({}^{*}\), recovery) & \\ \hline Attrition Bias & Data analysis & Missing data & Yes = 0, No = 2, Unclear = 1 \\  & & If so, the authors explained with appropriate & Yes = 2, No = 1, Unclear = 1 \\  & & reasons the lack of data & \\ \hline Reporting Bias & Data presentation & Presentation and description of & Yes = 2, No = 0, Unclear = 1 \\  & & Statistical Analyses & \\  & & Authors reported only statistically & Yes = 0, No = 2, Unclear = 1 \\  & & significant data & \\  & & Standard Deviation values represented & Yes = 2, No = 0, Unclear = 1 \\  & & Authors selectively reported only a part of & Yes = 0, No = 2, Unclear = 1 \\  & & the results & \\  & & Risk assessment of PRs (Risk quotient: RQ) & Yes = 2, No = 0, Unclear = 1 \\ \hline Other Bias & Sponsor & Status of funding & Clear = 2, Unclear = 1 \\ \hline \end{tabular}
\end{table}
Table 1: Pre-set list of bias assessment for internal and external validity.  
and effluents of the treatment facilities, seasonal variations of PRs, differences between hospital and municipal WW, environmental risk assessment of the antimicrobial substances and removal efficiencies of the plants (Supplementary Material, Data_extraction.xlsx). Sub-group analyses were performed to investigate significant differences between PR concentrations in effluents and influents, or municipal and hospital WWTPs, and between seasons. Statistical analyses were performed using Microsoft Excel 2016 (Microsoft Corporation, Washington, DC, USA) and SPSS Statistics V26.0 (IBM SPSS Statistics, Armonk, NY, USA). The independent \(t\)-test, based on Levene's Test for equality of variances, was used to determine differences in PR concentrations between effluents and influents and municipal and hospital WWTPs. One-way ANOVA, following the Bonferroni correction method, was used to determine differences between seasons.