Emerging research has provided evidence suggesting the potential influence of governance on the development and spread of antimicrobial resistance (AMR), accounting for significant disparities observed both between and within countries. In our study, we conducted an ecological analysis to investigate the relationship between governance quality, antibiotic consumption, and AMR across Italian regions.By leveraging data from three distinct sources at the regional level, we compiled a comprehensive dataset comprising: AMR proportions for three specific pathogen-antibiotic combinations in the year 2021, antibiotic consumption data for systemic use in the year 2020, and the 2021 European Quality of Government Index (EQI) and its corresponding pillars. Employing mediation analysis, we investigated the potential mediating role of antibiotic consumption in the association between the EQI and an average measure of AMR.Our analysis revealed substantial variation in the percentages of AMR across different regions in Italy, demonstrating a discernible North-to-South gradient concerning both antibiotic usage and governance quality. The EQI exhibited a statistically significant negative correlation with both antibiotic consumption and AMR percentages, encompassing both specific combinations and their average value. Regions characterized by higher levels of governance quality consistently displayed lower values of antibiotic consumption and AMR, while regions with lower governance quality tended to exhibit higher levels of antibiotic use and AMR. Furthermore, we observed a significant total effect of the EQI on average AMR . Notably, this effect was found to be mediated by antibiotic consumption, as evidenced by a significant indirect effect .These findings draw attention to the regional disparities observed in AMR levels, antibiotic consumption patterns, and governance quality in Italy. Our study also highlights the mediating role of antibiotic consumption in the relationship between governance quality and AMR. This underscores the significance of implementing focused interventions and policies aimed at improving governance quality and promoting responsible antibiotic use.The online version contains supplementary material available at 10.1186/s13756-023-01337-6. Antimicrobial resistance (AMR) has emerged as a pressing global health threat, undermining the effectiveness of antibiotics and posing significant challenges to healthcare systems worldwide –4. The oWhile numerous studies have focused on individual-level determinants of antibiotic use –16, therDespite this imperative, the association between governance and both antibiotic consumption and AMR has received limited attention, particularly at the local and national levels. Our study focused on Italy, a country that faces significant challenges related to the overuse of antibiotics and high AMR rates. The healthcare landscape in Italy is characterized by variations in healthcare practices, governance structures, and patient populations –26, presBy conducting an analysis using datasets that include antibiotic consumption data, AMR surveillance data, and indicators of governance quality, our aim is to study potential connections between governance quality, variations in antibiotic use and the prevalence of AMR in Italy.A cross-sectional analysis was conducted on ecological data obtained from 19 Italian regions and the two autonomous provinces of Bolzano and Trento. The dataset was constructed by integrating variables related to AMR percentages, antibiotic consumption, and governance indicators, which were sourced from three different data sources.Staphylococcus aureus (MRSA), carbapenem-resistant Klebsiella pneumoniae (CRKP), and third-generation cephalosporin-resistant Escherichia coli (CREC). The percentage of methicillin resistance in S. aureus refers to the resistance to at least one antibiotic among oxacillin and cefoxitin. The percentage of carbapenem resistance in K. pneumoniae refers to the resistance to at least one antibiotic among imipenem and meropenem. The percentage of third-generation cephalosporin resistance in E. coli refers to the resistance to at least one antibiotic among cefotaxime, ceftazidime, and ceftriaxone [We utilized regional-level data on AMR proportions in Italy for the year 2021. These data were provided by the Italian AMR surveillance project of the Istituto Superiore di Sanità (AR-ISS), which focuses on selected isolates and specific periods across the country . For thetriaxone . In addiWe collected data on the consumption of antibacterials for systemic use  at the regional level for the year 2020, as well as the ratio between broad- and narrow-spectrum antibiotics. The inclusion of data from the year prior to the collection of AMR data is driven by the recognition of the potential influence of antibiotic consumption on AMR proportions. By considering the antibiotic consumption data from the previous year, we can evaluate the potential impact of this factor on the observed AMR proportions. To obtain information on antibiotic consumption, we referred to the 2020 National Report on Antibiotic use in Italy, which was published by the Italian Medicines Agency and made accessible through the Medicines Utilisation Monitoring Centre in 2022 . AntibioWe used data on the European Quality of Government Index (EQI) and its pillars, which comprehensively assess citizens' perceptions and experiences regarding corruption, quality, and impartiality in essential public services . The latThe EQI serves as a composite indicator, amalgamating data from seventeen survey items to estimate the level of quality of government at the regional level. The aggregation process involved standardizing and centering the data using World Governance Indicators measures pertaining to corruption, government effectiveness, rule of law, and voice and accountability. To ensure representativeness, the study incorporated weighting and post-stratification techniques. The regional data were combined, resulting in a singular EQI score for each region. This composite score, expressed as numerical value, serves as a comprehensive indicator of overall regional performance based on citizens' perceptions and experiences. Higher EQI scores indicate a better perceived quality of government, including lower corruption levels, heightened impartiality, and superior quality in public service delivery. Conversely, lower EQI scores indicate areas where improvements in these dimensions are necessary .Descriptive analysis was performed on the individual variables to summarize their characteristics. The data concerning antibiotic consumption, the EQI and its pillars, and the percentages of AMR for specific pathogen-antibiotic combinations were processed in their original form, as provided by their respective sources , 31, 33.We examined the relationships between the variables using bivariate analysis, employing Spearman's correlation coefficient. Subsequently, after verifying the statistical assumptions, we utilized simple linear regression models to evaluate the association between the EQI (as the independent variable) and both antibiotic consumption and the average AMR measure (as the dependent variables). In each model, the variables were included as continuous numeric variables.Lastly, mediation analysis was performed to explore the mediating role of antibiotic consumption between the EQI and AMR. This approach provides a robust method to assess both the direct and indirect effects of the independent variable on the dependent variable, mediated through the proposed mediator. In general, based on the framework proposed by Baron and Kenny , there aIn the year 2021, AMR data at the regional level are accessible for eighteen regions and two autonomous provinces (Bolzano and Trento). Figure Significant variability among the regions was also observed regarding antibiotic consumption, exhibiting a clear increasing gradient from northern to southern Italy Fig. B. Apart A pronounced North-to-South gradient was instead apparent in terms of governance quality, evaluated through the EQI. In general, the regions in Northern Italy reported higher levels of governance quality, as reflected by higher EQI scores, while the scores were comparatively lower for the Central and Southern regions of Italy. Specifically, the highest EQI scores were observed in the autonomous provinces of Trento, Friuli Venezia Giulia, and Veneto, while the lowest scores were reported in Calabria, Campania, Basilicata, and Sicily Fig. C. ComparExpanding on this scenario, we conducted an analysis to examine the correlation between the EQI and its respective pillars and sub-pillars, along with antibiotic consumption and AMR data. The EQI displayed a statistically significant negative correlation with both antibiotic consumption and AMR, for both the specific combinations and their average measure. However, there was no significant correlation observed between the EQI and the ratio of broad-spectrum to narrow-spectrum antibiotics. Comparable results were obtained when considering the pillars and sub-pillars of the EQI, except for the experienced corruption, which did not show a significant correlation Table .Table 1Tp < 0.001 and β = − 0.97; SE = 0.25; p = 0.001, respectively). Furthermore, by stratifying the regions into tertiles based on the EQI distribution, we categorized them into those with low governance quality (1st tertile), moderate quality (2nd tertile), and high quality (3rd tertile). Upon comparing these groups (Fig. Hence, our attention was directed towards exploring the association of the EQI with antibiotic consumption and the average AMR measure Fig. A, B. ThrBy visually representing antibiotic consumption and average AMR on a graph Fig. , a quadrTo the best of our knowledge, this study is the first examining the relationships between governance quality and regional variations in antibiotic consumption and AMR across Italian regions. By adopting a regional perspective, we enhance our understanding of the factors that contribute to antibiotic use and AMR, specifically focusing on the level of quality, impartiality, and corruption in essential public services.Through the analysis of surveillance data pertaining to specific pathogen-antibiotic combinations , 29, ourThe observed regional disparities in AMR levels across Italian regions may be associated with variations in antibiotic consumption, which is a relationship that has been extensively reported and well-established , 60–62. On the other hand, our study provides further evidence that regions with lower AMR levels tend to exhibit lower rates of antibiotic consumption. It would be plausible to hypothesize that these regions exhibit lower levels of AMR also due to reduced antibiotic consumption –7.In addition to the observed regional disparities in AMR and antibiotic consumption, our findings also report a North-to-South gradient in governance quality. The association between governance quality, as measured by the EQI, and both antibiotic consumption and AMR suggests the potential role of effective governance in addressing AMR. Regions characterized by lower governance quality exhibited elevated levels of both antibiotic consumption and AMR. This hypothesis was substantiated by the mediation analysis conducted in our study, which offered additional insights into the interplay between governance, antibiotic consumption, and AMR. The significant indirect effect of governance on AMR, mediated through antibiotic consumption, hints the influence of governance on antibiotic utilization, which subsequently affects AMR outcomes. These findings highlight the importance of comprehensive strategies that target governance issues to effectively address AMR –73. InteOur findings seem in line with previous evidence from ecological analyses conducted at the global and European levels. Studies examining various indicators of governance, including voice and accountability, government effectiveness, regulatory quality, rule of law, and control of corruption, consistently demonstrate an inverse relationship with both antibiotic consumption and AMR –13, 17. While our study contributes to the growing body of evidence on the association between governance quality, antibiotic consumption, and AMR, it is important to acknowledge its limitations. Firstly, the study was based on ecological and cross-sectional data, which restricts our ability to establish causality. More specifically, the absence of a control group could potentially impact the reliability and validity of our findings. It makes it difficult to discern whether the observed outcomes are a direct result of the factors we are investigating or if they are influenced by unrelated variables. Secondly, our analysis centered around three pathogen-antibiotic combinations that pose significant public health challenges and for which regional-level data are accessible. In the context of our analysis, it would have provided valuable insights to have access to the ECDC composite index, which incorporates data on MRSA, vancomycin-resistant E. faecium and E. faecalis, third-generation cephalosporin-resistant Enterobacteriaceae, as well as carbapenem-resistant P. aeruginosa and A. baumannii.When examining antibiotic consumption, we utilized data from the year 2020, which preceded the AMR proportion data for 2021. In contrast, for the EQI, we had access to 2021 data, as it was not available on an annual basis. The additional data on the EQI from the years 2010, 2013, and 2017 were not considered for the present analysis. Therefore, future longitudinal studies are warranted to explore the temporal relationship between governance, antibiotic use, and AMR. Furthermore, the limited dataset size constrained our ability to incorporate additional factors that may be involved in the observed relationships. Although antibiotic consumption plays a significant role as a mediator in the governance-AMR relationship, it is important to acknowledge the presence of other complex dynamics that may influence AMR outcomes. For instance, certain cultural dimensions, such as uncertainty avoidance and individualism, have been identified as social factors that contribute to AMR. Notably, these dimensions may exhibit diverse patterns among various regions within Italy. Addressing these factors in future studies will enable a more precise assessment of the intricate relationship between governance, antibiotic consumption, and AMR. Finally, the study focused on regional-level data and did not examine individual-level factors that may contribute to AMR. Future research should investigate the individual determinants of antibiotic consumption and AMR to gain a more comprehensive understanding of the underlying factors.On the other hand, the study has some strengths. It utilized data from multiple sources, allowing for an analysis of the association between governance, antibiotic consumption, and AMR. By incorporating data from various dimensions, our study adopted a multidimensional approach that helps provide an understanding of the dynamics in play. Additionally, our study incorporated the EQI as a measure of governance quality, providing a multidimensional perspective on governance beyond the healthcare sector. This approach allows us to examine the broader context in which antibiotic consumption and AMR occur, considering factors such as corruption, public service quality, and impartiality.This ecological study contributes additional insights into the intricate interplay among governance, antibiotic consumption, and AMR. Italy, in particular, presents an authentic research environment owing to the significant variations in AMR prevalence, antibiotic consumption levels, and governance indices observed across its diverse regions. If regions characterized by high governance quality showed reduced antibiotic consumption and lower levels of AMR, contrastingly, regions marked by poorer governance exhibited elevated rates of both. Specifically, our findings suggest the mediating effect of antibiotic consumption in the relationship between governance quality and AMR. This aligns with earlier research findings indicating that governance can primarily impact antibiotic consumption, subsequently affecting AMR levels. However, the limitations of our study strongly advocate for additional longitudinal investigations that take into account individual-level factors and account for potential confounding variables. These efforts will provide a deeper understanding of the intricate mechanisms that underlie the connection between governance, antibiotic use, and AMR.Additional file 1. Regional coverage of surveillance data on antimicrobial resistance in 2021Additional file 2. Percentages of AMR for specific pathogen-antibiotic combinations and the average AMR measure across Italian regions in 2021Additional file 3. Pillars and sub-pillars of the European Quality of Government Index across Italian regions in 2021


A prediction model was established to obtain a formula for the PPF-MSC carbonization depth in terms of the content and length of PPF and the carbonization time. The following results were obtained from the RSM: compared to the PPF length, the PPF content has a larger impact on the PPF-MSC bending strength and a smaller impact on the PPF-MSC carbonization resistance; there is no significant interaction between the content and length of PPF; and the predicted and measured values are close, indicating that the model is highly reliable. A comparison of the XRD patterns and SEM micrographs of PPF-MSC and MSC after 28 days of carbonization show a lower peak intensity of CaCO3 in the pattern for the carbonized area for PPF-MSC than for MSC and considerably fewer surface pores and cracks in PPF-MSC than in MSC. These results indicate that the addition of PPF increases the compactness of MSC and creates an effective resistance to the erosion by water molecules and carbon dioxide (CO2), thus enhancing the bending strength and carbonization resistance of MSC. To popularize the complete replacement of natural sand with manufactured sand, a study was performed to determine the effect of adding polypropylene fibres (PPFs) to increase the bending strength and carbonization resistance of manufactured sand concrete (MSC). A 2 × 3 factorial design with the content and length of PPF as variables was used to establish a carbonization depth prediction model and a response surface model (RSM). The phase composition and microstructure of polypropylene-fibre-reinforced manufactured sand concrete (PPF-MSC) were analysed using X-ray diffraction (XRD) and scanning electron microscopy (SEM). The results show the addition of PPF with different contents and lengths increases the bending strength of PPF-MSC to varying degrees, while reducing the carbonization depth and increasing the dynamic elastic modulus after 28 days of carbonization. The highest bending strength (6.12 MPa) and carbonization resistance of PPF-MSC are obtained by the addition of 1 kg/m The escalating global environmental crisis has created a growing demand for sustainable building materials, making it crucial to design novel types of sustainable concrete ,2,3. Con2) in the air inside the numerous capillary pores in concrete reacts with free carbon hydroxide (Ca(OH)2) in concrete to generate calcium carbonate (CaCO3), causing loosening of the concrete structure and falling off of concrete pieces. Carbonization can reduce the alkalinity of concrete. When the carbonization depth exceeds the thickness of the concrete protection layer, the concrete can no longer protect steel bars against the action of water and air, leading to a series of problems, such as rusting, shrinkage cracking, and even disintegration of the gel structure in concrete [2, promotes carbonization reactions, and increases the vulnerability of the concrete protection layer to environmental attack, ultimately increasing the rusting of reinforcing steel.Carbonization is one of the influencing factors for the durability of building structures. Carbonization, also known as concrete neutralization, is a term used to describe a failure mode in concrete. During the carbonization of concrete, carbon dioxide  have mainly focused on the material mechanical properties, and more research needs to be conducted on the durability of PPF-MSC. Therefore, in this study, natural sand in MSC was completely replaced with manufactured sand with different contents of PPF (of various lengths). The influence of the content and length of PPF on the bending strength and carbonization resistance of MSC was studied. The changes in the carbonization depth of MSC were used to establish a carbonization depth prediction model. The changes in the bending strength, dynamic elastic modulus, and carbonization depth of MSC were used to establish a response surface model (RSM). The phase composition and microstructure of PPF-MSC were determined using X-ray diffractometry (XRD) and SEM. The analysis of the bending strength and carbonization resistance of PPF-MSC performed in this study is highly relevant for practical applications.Tests were performed on P·O 42.5 cement, a mineral admixture of Grade I fly ash, natural coarse aggregates with particle sizes ranging from 5 mm to 33 mm, and Zone II medium sand as manufactured sand. According to Sand for Construction (GB/T14684-2011), the megabyte (MB) value and stone powder content of the manufactured sand meet the requirements of Grade II manufactured sand. The cumulative screen residue and main performance indicators of the manufactured sand are shown in 3, 1.0 kg/m3, and 1.2 kg/m3; 6 mm, 12 mm, and 19 mm. The following contents and lengths of PPF were used to fabricate a concrete specimen with a design strength grade of C30 following the Specification for Mix Proportion Design of Ordinary Concrete (JGJ55-2011): 0.8 kg/mFirst, a single horizontal shaft forced concrete mixer (HJW-60) was used to mix coarse aggregate, fine aggregate, and cement for 60 s. Next, a polycarboxylate superplasticizer and water were added to the mixer, and the mixture was homogenized. Finally, PPF was added and evenly dispersed into the concrete matrix by 3 min of mixing. The schematic figure is shown in Following the Standard for Test Methods of Long-term Performance and Durability of Ordinary Concrete (GB/T50082-2009), the test specimen was removed from the curing room two days before the carbonization test to be performed and dried for 48 h at 60 °C. The two opposite side surfaces of the specimen were left untreated, and the other surfaces were sealed with heated paraffin. Parallel lines were drawn on the side surfaces of the specimen along the length at 10 mm intervals for measuring the carbonization depth.2 concentration was 20 ± 3%, the relative humidity was 70 ± 5%, and the temperature was 20 ± 5 °C. At 3, 7, 14, and 28 days after carbonization, the test specimen was removed from the test box and broken using a DYE-2000S compression testing machine. A specimen cross section was sprayed with a 1% phenolphthalein alcohol solution. A KS-105 wireless crack-width gauge was used to measure the carbonization depth as the distance from each point on both sides of the specimen to the purple boundary, as shown in id denotes the carbonization depth (mm) measured for each of the two side surfaces, and n denotes the total number of measurement points on the two side surfaces. The test described above was performed on three specimens of each group, and the measurements were averaged.Next, the test specimen was placed in a TH-B concrete carbonization test box, as shown in An MTS compression testing machine was employed to measure the bending strength, as shown in 1L12)-MSC (which has a bending strength of 6.12 MPa). This result is obtained because PPF of a moderate length and content disperses effectively and uniformly in the concrete, and PPF has good bridging ability that enables a tight combination with the matrix, maximizing the increase in the MSC bending strength. An excessively high PPF content results in a narrow spacing between the fibres in the concrete, increasing the tendency of the fibres to knot and agglomerate. The PPF-MSC bending strength consequently decreases. When the fibre length is too large, the longer fibres cannot completely fill the internal pores of the concrete, thus reducing the compactness of the concrete, resulting in lower bending strength.1L12)-MSC (which has a dynamic elastic modulus of 38 GPa). Both the bending strength and dynamic elastic modulus of MSC and PPF-MSC increase after 28 days of carbonization. This result is obtained because CaCO3 generated by the carbonization reaction fills the small pores in the concrete surface to compactify the concrete structure, thereby increasing the dynamic elastic modulus. 1L12)-MSC and largest (5.6%) for MSC. The increase in the dynamic elastic modulus of PPF(C1L12)-MSC is 59.64% lower than that of MSC. Carbonization can cause a decrease in the permeability and porosity of concrete, which is particularly significant for concrete with poor performance. Comparing the increases in the dynamic elastic modulus for MSC and PPF-MSC shows a larger decrease in the internal porosity after 28 days of carbonization for MSC than for PPF-MSC, indicating that carbonization has a larger impact on MSC than on PPF-MSC. There are two main reasons for this phenomenon. First, PPF can resist cracking and is randomly distributed in the concrete, thereby blocking the capillary channels and affecting the movement of water molecules. Consequently, the number of connected voids created by water seepage are effectively reduced, the formation of internal cracks in the concrete is hindered, and the propagation rate of CO2 in the concrete is decreased. Second, PPF can support aggregates, which effectively prevents segregation in concrete caused by aggregate settling. Consequently, the porosity is reduced and the pore structure is improved, providing effective resistance against the invasion of CO2 into the concrete and decreasing the carbonization rate.2 enters the concrete and reacts rapidly with Ca(OH)2 on the surface, generating a large quantity of CaCO3. During the late stages of carbonization, the formation of a thin CaCO3 layer on the surface of the Ca(OH)2 crystal causes the carbonization rate to decrease. The quantity of carbonization products increases and fills the pores on the concrete surface, which blocks the invasion of CO2 and decreases the carbonization rate. As the CaCO3 product layer gradually thickens, contact between the uncarbonized part of the concrete and water is increasingly inhibited, making it difficult for H2CO3 to be generated by the invasion of CO2. Consequently, the rate of the carbonization reaction between Ca(OH)2 and the hydration product (C-S-H gel) decreases. Thus, the carbonization rate first increases and then decreases. However, the change in the carbonization depth of PPF-MSC during the early and late stages of carbonization is considerably lower than that of MSC, indicating that PPF addition decreases the carbonization rate of MSC. This result is obtained because PPF can both inhibit cracking and enhance interfacial effects, that is, the formation of a cement mortar fibre structure in the concrete creates many interfaces that effectively relax stress on the material. When a microcrack appears, an interface can effectively alleviate the stress at the crack tip to delay crack expansion [2 and the carbonization depth.xpansion , thereby1L12)-MSC, which is 61.58% lower than the corresponding value for MSC. The average carbonization depth for the PPF-MSC specimens is 38.02% lower than that of MSC, indicating an improvement in the carbonization resistance of MSC.2 are widely accepted by researchers. The carbonization depth is determined using the following formula:H denotes the carbonization depth (mm), k denotes the carbonization coefficient, and t denotes the carbonization time (d).The assumptions that concrete is an isotropic continuous medium material and that steady-state diffusion theory can be used to simulate the diffusion process of CO2) for the fit are shown in 2 value is >0.95 for all the fitting results, indicating a good fit. MSC has the largest carbonization coefficient and the lowest resistance to carbonization. As the content and length of PPF increase, the carbonization coefficient of PPF-MSC first decreases and then increases. The lowest carbonization coefficient is obtained for PPF(C1L12)-MSC, which indicates that the highest carbonization resistance of PPF-MSC is obtained for a PPF content of 1 kg/m3 and a PPF length of 12 mm.The data for the carbonization depth with time were fitted. The corresponding formula and coefficient of determination (Rx) and length (y) of PPF, whereCombining Equations (2) and (3) yields a prediction formula for the carbonization depth in terms of the PPF content, PPF length, and carbonization time:The RSM is a commonly used method for multi-factor experimental design that has been widely applied to optimize industrial formulas and production conditions. However, the RSM has seldom been applied to concrete. An experiment was performed with the PPF content as Factor A and the PPF length as Factor B using Design Expert 10 to establish a multiple regression equation and regression model. The bending strength of PPF-MSC, the carbonization depth, and the increase in the dynamic elastic modulus after 28 days of carbonization were taken as the response values. The RSM was used to analyse the bending strength and carbonization resistance of PPF-MSC. To reduce errors, four sets of repeated experiments were designed for the RSM. That is, four sets of test blocks were reproduced according to p values are <0.01 for the model of the PPF bending strength, as well as for the models of the carbonization depth and the increase in the dynamic elastic modulus after 28 days of carbonization, demonstrating that the models are extremely significant. The p values for Factor A in the model are 0.013 (<0.05), 0.626 (>0.05), and 0.049 (<0.05), indicating that the PPF content significantly affects the models for the bending strength and carbonization depth after 28 days of carbonization but does not significantly affect the model for the increase in the dynamic elastic modulus after 28 days of carbonization. The p values for Factor B in the model are 0.102 (>0.05), 0.0002 (<0.05), and 0.026 (<0.05), indicating that the PPF content significantly affects the models for the increase in the dynamic elastic modulus and carbonization depth after 28 days of carbonization but has an insignificant effect on the model for the bending strength. This result demonstrates that compared to the PFF length, the PPF content has a larger impact on the bending strength of PPF-MSC but a smaller impact on the carbonization resistance of PPF-MSC. The AB values in the model are 0.285 (>0.05), 0.136 (>0.05), and 0.397 (>0.05), showing an insignificant interaction between the content and length of PPF.The multiple regression equations and variance analysis of the regression model are shown in In 3 and a PPF length of 12.152 mm, the PPF bending strength reaches a maximum of 6.114 MPa, and the increase in the dynamic elastic modulus and carbonization depth after 28 days of carbonization decrease to a minimum of 2.296% and 1.955 mm, respectively. At this point, PPF-MSC exhibits the highest bending strength and carbonization resistance and the model prediction is close to the measured value with a reliability of 0.949, indicating high accuracy for the RSM prediction.The RSM prediction results are shown in 1L12)-MSC (which was found to exhibit the highest resistance to carbonization) after 28 days of carbonization were determined using a German Bruker D8 Advance 25 XRD. The obtained XRD patterns presented in 1L12)-MSC contain CaCO3, Ca(OH)2, C-S-H, and SiO2. In particular, in the diffraction patterns for the carbonized areas of MSC and PPF(C1L12)-MSC, the peak intensities are higher for CaCO3 and SiO2 and lower for Ca(OH)2 and C-S-H than those for the non-carbonized areas. However, compared to the peak intensities in the PPF(C1L12)-MSC patterns, the peak intensities in the MSC patterns are higher for CaCO3 and SiO2 and lower for Ca(OH)2 and C-S-H. This result indicates that during CO2 corrosion, more Ca(OH)2 and C-S-H are consumed to react with CO2 and more CaCO3 and SiO2 are produced in MSC than in PPF(C1L12)-MSC. The addition of PPF can effectively slow MSC carbonization, thus improving the resistance of MSC to carbonization.The phase compositions of the carbonized and non-carbonized areas of MSC and PPF(C1L12)-MSC (which was found to exhibit the highest bending strength and carbonization resistance). Two observation areas, labelled A and B, were randomly selected from the two specimens.A Czech TESCAN MIRA LMS SEM was used to determine the microstructure of MSC and PPF (C1L12)-MSC microstructure, where the matrix surface appears relatively smooth and flat with few pores and cracks. 2 is reduced, and the carbonization reaction is slowed. Therefore, PPF addition to MSC can improve the pore structure and density while enhancing the bending strength and carbonization resistance.(1) In general, the addition of PPF to MSC results in an increase in the bending strength, while reducing the increase in the dynamic elastic modulus and carbonization depth after 28 days of carbonization. Thus, PPF addition enhances the bending strength and carbonization resistance of MSC.3 of 12 mm long PPF to MSC, whereas the increase in the dynamic elastic modulus and carbonization depth after 28 days of carbonization are maintained at a minimum of 2.26% and 1.94 mm, respectively, i.e., the highest bending strength and carbonization resistance of MSC are obtained.(2) The maximum enhancement of the bending strength of MSC (to 6.12 MPa) is obtained by the addition of 1 kg/mH = (−9.28x − 0.07y + 4.75x2 + 0.003y2 − 0.01xy + 5.44)(3) A prediction model for the carbonization depth is established to obtain a formula for predicting the MSC carbonization depth using the PPF content, PPF length, and carbonization time: 3 and higher for C-S-H than in that of MSC. The PPF-MSC matrix is smoother and denser with fewer pores and cracks than MSC.(4) XRD and SEM results show that after 28 days of carbonization, the diffraction peak intensity in the pattern for the carbonized area of PPF-MSC is lower for CaCO


The creep of concrete is one of the main problems threatening concrete structural development and the stability and safety of structures. However, the nonlinear theory is the key to solving the problem of taking into account the physical and mechanical properties of concrete creep in shell structures. To create such a theory, the original shell is replaced by a continuous equivalent elastic shell. To determine the stress–strain state of the structure, the equations of nonlinear creep and crack growth are derived, and a deformation model of the section is created. The behavior of the structure at all stages of the life cycle is investigated by solving the solving systems of differential equations of equilibrium, motion, and perturbation of the equivalent shell. The values of the ratios of dependence of long-term and short-term critical loads on deformations, forces, cracks, etc., are given. The accuracy of the solution of the developed nonlinear theory is compared with the linear theory of concrete creep as well as experimental data. The results show that, according to the linear theory, for the values for the short term and long term, up to 56% and up to 39% of critical loads are overestimated, respectively. The creep process in practical engineering can be effectively controlled by the results of the proposed theory. The phenomenon of metal creep at high temperatures is one of the reasons for the destruction of the Twin Towers in New York (USA) . Due to The development of creep increases the stress loss in the concrete structure and redistributes the internal force of statically indeterminate structures. In turn, excessive deformation of the structure significantly reduces the overall strength and even causes loss of bearing capacity. With the modern, wide range, high-quality, and common use of concrete materials, concrete creep has become one of the main problems threatening structural composition, the quality characteristics of concrete, as well as the safety and long-term stability of concrete structures ,4,5.The creep of concrete elements can weaken the greatest tensile stress, which reduces the risk of the early cracking of concrete ,10,11,12Taking into account the creep of concrete under axial compression in calculations within the framework of the classical theoretical approach was first proposed by A.R. Rzhanitsyn and subsequently developed by Y.N. Rabanov, S.A. Shestikov, L.B. Bunyatyan, V.B. Kolmanovsky, I.E. Prokopovich, E.A. Yatsenko, and I.I. Ulitsky for linear creep problems of concrete ,20,21,22Creep deformation has a linear dependence on the applied stress in the case of a low stress level (compressive strength less than 30%). However, creep is an unstable phenomenon, since time and stress increase in the case of a high stress level (from 30% to 80% compressive strength); that is, it is a nonlinear dependence that is found in specific creep theories and experimental research data ,27,28,29A review of the literature shows that the development of effective unified computational algorithms for solving physically nonlinear problems of the dynamics of short-term and long-term deformation of shells and plates made of composite materials is an urgent problem today ,31.L is the length of the column for the core elements, and The value of long-term resistance anitsin) , E is a The value of long-term resistance contains deviations from the results. With the prolonged action of the load, the empirical method dangerously overestimates the conditional critical force by several times concerning the value of the limiting elasticity of concrete. Formula (2) shows the modulus of deformation of concrete and the numerical values of the ultimate creep characteristic The principles of the general nonlinear theory of the calculation of structures are the basis of European standards ,32. FiguThe theory of limit equilibrium excludes the indicator tructure . This coContradictions between the limit state of the structure, established by the nonlinear theory of the calculation of structures, and the limit state are presented in the building codes:Point The nonlinear theory of the calculation of structures recognizes the unsatisfactory state of the structure, corresponding to the site  is the modulus of deformations at the initial moment of time, and The nonlinear creep equation for concrete, which describes the biaxial stress state, has the form :(3)ε11t=The equation of the nonlinear creep of concrete has the form :(4)εt,t0s record . C0*t, τndrovsky .E(t) is the modulus of elastic-instantaneous deformations, The equation of nonlinear creep of concrete  for the The nonlinear creep of concrete  is writtt, t, The equation of the nonlinear creep of concrete takes into account the nonlinearity of the instantaneous deformation of concrete and has the form :(7)ε˙bt=harovsky  notationA general theory of calculation of composite physically and geometrically nonlinear thin-walled systems is proposed, extending to a fairly wide class of smooth and reinforced shell and plate structures, including during their reconstruction, operating in a complex stress state at real loading levels, as well as under conditions of nonlinear creep of the material and the presence of cracks.A mathematical model of the behavior of the mentioned structures at all stages of loading is constructed within the framework of unified systems of differential equations and an algorithm for their solution at different points in time.A new method for calculating inelastic shell structures with cracks is proposed, and relations for equivalent elasticity parameters are given, which implement quite strictly the problem of taking into account plasticity, half-strength, and cracks in stretched and compressed cross-section zones. The main idea is to replace an inelastic shell with cracks—a solid equivalent elastic shell structure with equivalent elasticity parameters determined by comparing its deformations with similar deformations of a nonlinear model.Building codes ensure that the general criteria and design methods comply with the requirements of the nonlinear theory of structural analysis.Practical adaptation requires overcoming existing inconsistencies in the building codes, the calculated position of which is based on an erroneous model of a plastic hinge ,41,42. IThe construction of a nonlinear theory for the calculation of reinforced concrete shells and plates based on generally accepted assumptions is shown. The well-known models of concrete deformation under short-term and long-term loading are considered, disobedient to Hooke’s law The nonlinear relationship between stresses and deformations was first considered by G. Bulfinger and F. Gerstner. The power law at The following equations are also used to describe the nonlinear relationship between stresses and strains.F. Gerstner describes the nonlinearity of materials by parabolic dependence:The functional relationship between stress intensity and strain intensity in the material deformation diagram pendence  in the fThe polynomial function is taken as:Within the framework of the hypothesis of the linear creep of concrete, the creep of particular importance is in the form of:The simplified Maxwell–Kachanov concrete creep formula is taken in differential form:Next, the problems of constructing a nonlinear theory for the calculation of reinforced concrete shells and plates are considered.In the first stage, a deformed thin-walled element and its cross-section of unit length are considered, receiving displacements with these 2 shifts .The hypotheses of the theory of plasticity are accepted, and specific equations of fiber deformation in the differential form are obtained with increasing load for the case of short-term loading in the form:For research on the processes of the creep of materials in structures, any of the equations of creep theories are used; exactly, equations of the theory of ageing in differential form, which have the form:The combination of these two laws of short-term and long-term deformation is applicable at all stages of the structure’s existence.Geometric relations are obtained based on a Timoshenko-type shift model:Transverse shear stresses are distributed according to the parabola law in the following form:In this case, the following conditions are met:The shape coefficient at shift is derived to obtain shear stresses at the center of gravity of the shell cross-section with cracks, depending on the shape of the section.The main vector and the main moment of the stress diagram in a linear section are compiled in the form:The fixed ultimate deformations in the section are taken subject to the strength condition in the form:With numerical integration, the boundary of the occurrence of plastic deformations in the reinforcement corresponds to the achievement of yield strains When creating a deformation model of the cross-section, the condition for the appearance of a crack during compression and tension was adopted in the form of a condition (criterion) of strength by G. Geniev (21) :(21)σr12To relate the stresses and strains in the fibers, there are equations of the forms (14) or (15). The specific equilibrium equations in the cross-section with cracks are compiled in differential form. A linear system of differential equations with time-varying coefficients is obtained in the form:The solution of Equation (22) makes it possible to find edge deformations with the help of which all parameters of the stress–strain state of the section are determined.Equivalent elastic parameters are obtained based on te calculated edge deformations of the section.To achieve this, As a result of the integral representation of material properties (24), physical equations of a nonlinear model with load-dependent parameters The shell calculation model is constructed according to a deformed scheme based on differential equilibrium equations.The features of deformation and the existence of the shell are accounted for. Functional dependencies of changes in external influences and/or the rheological properties of materials corresponding to the real process of loading and deformation are set:A resolving system of quasi-static equations of shell motion due to changes in external load or geological processes is constructed. All relations used are differentiated once in time, including physical relationships with equivalent elasticity parameters, taking into account variability. As a result, a linear system of differential equations is obtained concerning the generalized velocities of the deformation parameters:To check the stability of the equilibrium of the structure, its varied state is considered. A system of linear equations in variations of the desired quantities is derived. As a result, a homogeneous system of linear equations in variations is obtained with coefficients recalculated at each calculation step:The equality of the determinant of this system to zero determines the condition for the loss of stability of the equilibrium of the structure.The proposed mathematical model and algorithm for solving nonlinear problems are implemented in the form of a compiled set of computer programs. The developed software systems have been tested on solving test problems, with satisfactory comparison of shell calculation results with known solutions ,47 and eBased on the developed software systems, the operation of structures at all stages of the life cycle is studied. Various effects of the influence of nonlinearities on the behavior of structures are revealed. A study established the dependence of the equivalent parameters of elasticity on the level of loading, the percentage of reinforcement, the cracks formation scheme, and other factors .Solutions for the development of practical recommendations have been obtained on the effective calculation of composite shells and plates in a nonlinear formulation in the concept of European standards.Short-term ultimate loads for P-1 with the following parameters: In The general figures and explanations for The following initial parameters are set: ovoselov  , which will require significant material costs and organizational efforts . However


Antimicrobial Stewardship (AMS) requires effective teamwork between healthcare professionals, with patients receiving consistent messages from all healthcare professionals on the appropriate antimicrobial use. Patient education may reduce patients’ expectations to receive antibiotics for self-limiting conditions and reduce the pressure on primary care clinicians to prescribe antibiotics. The TARGET Antibiotic Checklist is part of the national AMS resources for primary care and aims to support interaction between community pharmacy teams and patients prescribed antibiotics. The Checklist, completed by the pharmacy staff with patients, invites patients to report on their infection, risk factors, allergies, and knowledge of antibiotics. The TARGET antibiotic checklist was part of the AMS criteria of England’s Pharmacy Quality Scheme for patients presenting with an antibiotic prescription from September 2021 to May 2022. A total of 9950 community pharmacies claimed for the AMS criteria and 8374 of these collectively submitted data from 213,105 TARGET Antibiotic Checklists. In total, 69,861 patient information leaflets were provided to patients to aid in the knowledge about their condition and treatment. 62,544 (30%) checklists were completed for patients with an RTI; 43,093 (21%) for UTI; and 30,764 (15%) for tooth/dental infections. An additional 16,625 (8%) influenza vaccinations were delivered by community pharmacies prompted by discussions whilst using the antibiotic checklist. Community pharmacy teams promoted AMS using the TARGET Antibiotic Checklist, providing indication-specific education and positively impacting the uptake of influenza vaccinations.  Antimicrobial resistance (AMR) is defined as the loss of antimicrobial effectiveness against microorganisms and, although it develops naturally, this process is accelerated by the inappropriate or incorrect use of antimicrobials . AMR is reducing need for, and unintentional exposure to, antimicrobials;optimising use of antimicrobials;investing in innovation, supply and access .Antimicrobial stewardship (AMS) refers to an organisational or healthcare system-wide approach to promoting and monitoring the judicious use of antimicrobials to preserve their future effectiveness . The UK Although a reduction in the prescribing of antimicrobials in primary care has been observed in England, the majority of antibiotics are still prescribed in this sector . In 2020In the UK, community pharmacies are recognised as a first port of call for healthcare advice and services because of the convenient access to a health care professional for managing minor ailments and self-limiting illnesses . They haThe UK AMR National Action Plan has recognised that one of the most successful initiatives used to embed AMS into practice has been the use of the TARGET Antibiotic Toolkit jointly produced by the UK Health Security Agency (UKHSA) and the Royal College of General Practitioners (RCGP) . The tooThe Pharmacy Quality Scheme (PQS) is part of the community pharmacy contractual framework (CPCF) for England . The schSince 2020, the scheme has incentivised AMS activities in community pharmacies . These iEvaluation of the clinical findings and implementation barriers are reported separately .This is a service evaluation of the scaling of the use of the TARGET Antibiotic Checklist in community pharmacies via the national incentive scheme. In this structured observational study, researchers assessed the outcomes of how community pharmacists implemented the criteria within the AMS domain of the PQS criteria. Data were collected as a part of England’s Pharmacy Quality Scheme (PQS) 2021–22 . The schThe PQS is a voluntary scheme and all community pharmacies in England providing NHS services are eligible to participate . IncentiPharmacy teams were asked to use the TARGET Antibiotic Checklist within their current AMS practice for four weeks with a minimum of 25 patients, or up to eight weeks if the minimum number of patients was not achieved within four weeks . ContracThe online Snap Survey  portal digitalised the questions from the TARGET Antibiotic Checklist as well as included demographic information such as the pharmacy’s Organisation Data Service (ODS) code and address . A singlThe data was analysed using Microsoft Excel for descriptive analysis. As the tool allowed multiple answers to be ticked simultaneously, the research team agreed that reports of two or more concurrent infections were likely to be erroneous data entries. Therefore, after the initial analysis, the data were cleaned and re-analysed to only include patients reported to have been prescribed up to two antibiotics for a maximum of two indications at that specific point in time. Further ambiguous data were removed along the way—e.g., if both options (yes and no) were ticked for subsequent questions, these data were removed from the analysis. From the 213,105 checklists reported, 208,858 (98%) were included in the final data analysis. As this study is a service evaluation, NHS ethical approval is not required . InstituThe total number of community pharmacy contractors who claimed to be for the PQS prevention domain was 9950  out of the 11,232 community pharmacies listed on the pharmaceutical list in March 2022. Pharmacy contractors collectively submitted data for 213,105 TARGET Antibiotic Checklists. A total of 163,446 (78%) of the submitted TARGET Antibiotic Checklists were completed for patients who were collecting their own antibiotics, and the remainder on behalf of patients for whom a representative was collecting their antibiotics. From the submitted checklists, 107,360 (51%) patients reported taking other medications alongside their antibiotics  and 165,The most common indication for which a checklist was completed  was for a respiratory tract infection (RTI), representing 62,664 (29%) of submissions, followed by a urinary tract infection (UTI) with 43,093 (20%) submissions, and tooth infections with 31,198 (14%) submissions see . The most frequently prescribed antibiotics were amoxicillin, accounting for 73,921 (35%) submissions, followed by nitrofurantoin , flucloxacillin , doxycycline , and metronidazole  see . Where tPharmacy teams reported providing 69,861 patient information leaflets with patients’ dispensed antibiotics to aid with patients’ knowledge about their condition and treatment See . The majThe TARGET Antibiotic Checklist aims to facilitate targeted information sharing between patient and pharmacist to address concerns and give appropriate counselling. Patients most frequently selected that they did not understand the following side effects of their antibiotics , how to take their antibiotics with food , and how long their symptoms would last . There was selection for information about why they must take their antibiotics according to healthcare professional instruction , why they must never share or keep their antibiotics for later use , and knowing when to seek further help with their infection  See .In the patient section of the TARGET Antibiotic Checklist, the patient reported in 36,097 (17%) of cases that they had previously received the same antibiotic in the last three months. Pharmacy staff discussed antibiotic resistance with patients for 87,975 (42%) checklists See .Overall, 97,463 (47%) of the submitted checklists confirmed that the patient had already received the influenza vaccination, of which 53,592 (25%) were eligible for a free NHS influenza vaccination See ). All a. As a reThe initiative proved successful in terms of both uptake and sharing information with patients. In total, 89% of all community pharmacies in England participated in the Pharmacy Quality Scheme AMS criteria in 2021–22, which is consistent with previous pharmacy quality schemes . As expeResearch has demonstrated that the TARGET resources facilitate pharmacist–patient communication ,26. In tCommunity pharmacies have been administering influenza vaccinations as an advanced service since 2015 . As wellThe initiative highlighted the risks of relying on patient recall alone when establishing medication history as only 17%  of patients confirmed they had taken the same antibiotic in the past 3 months when the rate indicated from the pharmacy staff counselling records was 42% . Whilst it can be argued that most patients are unlikely to have medical training to remember the exact name of their antibiotic and then make the association that it was the same antibiotic, pharmacy teams should take care if relying on patient recall to provide information and consider confirming with dispensing system records when appropriate. Community pharmacy teams provided advice to 59,168 (28%) patients collecting an antibiotic as to why unused antibiotics need to be returned to a community pharmacy for disposal. It is unclear the extent of patient comprehension, i.e., whether patients understood that if antibiotics are not used responsibly, they can lead to dangerous side effects, a delay to an accurate diagnosis, contribute to antimicrobial resistance (AMR), and/or whether inappropriate disposal of unused antibiotics also damages the environment, impacting water quality and wildlife . RegardlMany patients attend community pharmacies for the treatment and management of lower acuity health issues or minor ailments. In fact, the development of the Community Pharmacist Consultation Service (CPCS) has diverted many patients from NHS 111 (telephone triage), out-of-hours services, and from GP practices to community pharmacies for management of these minor ailments . The topResearch has shown that individuals prescribed an antibiotic in primary care for a RTI or UTI are more likely to harbour bacteria resistant to that antibiotic . The effContinuing the initiative alongside evaluation will contribute to reinforcing AMS principles through the continued practice of using the TARGET Antibiotic Checklist for patients prescribed antibiotics as well as promoting sustained change for its use. The success of the TARGET Antibiotic Checklist in the community pharmacy setting has led to the development of a new community pharmacy section on the TARGET Antibiotic Toolkit website: Resources for community pharmacy setting to aid pharmacy teams in promoting AMS . The dedMuch like the study “Evaluation of the England Community Pharmacy Quality Scheme (2018–2019 and 2019–2020) in reducing harm from Non-Steroidal Anti-inflammatory Drugs in older patients” where the PQS was used to promote medicines safety, the dataset has a high ecological validity as data have been collected from every day practice, giving a snapshot of community pharmacy AMS activities . Over 200,000 data entries were collected as part of this PQS criteria from all over England, one of the largest studies conducted on community pharmacies to date . This quA study limitation is that the data were self-reported by community pharmacy teams without independent validation, so both inconsistent or inaccurate reporting cannot be ruled out. Data cleaning helped to remove duplicate entries, erroneous entries, and data absence. It could also be argued that pharmacy teams may behave differently to usual practice when taking part in an incentivised scheme such as the PQS, with potential temporary changes in behaviours; however, more checklists were submitted than were required for the purposes of the PQS and there is a known continuation of resource use post intervention period . AdditioPharmacy teams were allowed to check multiple response options simultaneously on the data collection tool as some patients could have multiple infections. This, however, may have led to erroneous data entry, for example, checklist data suggesting nitrofurantoin and trimethoprim, antibiotic items typically prescribed for UTIs, being prescribed for chest infections. However, after data cleaning, 208,858 (98%) out of the 213,105 checklists were included in the analysis, suggesting limited human error. The upcoming PQS will use the findings from this study to refine the data collection process and data collection tool.All major AMR control and AMS strategies recommend ongoing education for patients, children, the public, and relevant healthcare professionals  regarding unique features of bacterial infections and antibiotics, prudent antibiotic prescribing as a positive construct, and personal hygiene  . AMR canThe majority of antimicrobial drugs are prescribed and dispensed in primary care, hence the structured and ongoing education on AMS for primary care healthcare professionals and patients is paramount . CommuniPrevious research has demonstrated the value of using the TARGET Antibiotic Checklist to support community pharmacy teams who play a crucial role in AMS by using targeted patient education and addressing patients’ concerns about antibiotic use ,10. ThisWhilst engaging in conversations about their antibiotic prescriptions, community pharmacy teams have provided additional indication-specific education materials to reinforce their counselling and increased the influenza vaccinations uptake. In light of this, the initiative has been renewed as part of the NHS England Community Pharmacy Quality Scheme 2023–24, which will support embedding the use of the TARGET resources into day-to-day practice and reinforcing AMS behaviours within community pharmacies . AMR is an issue of international concern. This intervention could be adapted for international use as it would be suitable for use for all patients  presenting with an antibiotic prescription. The TARGET Antibiotic Checklist is available digitally and translated in multiple languages . In addiThis study highlights the vital role that community pharmacy teams have in promoting AMS initiatives, including educating the public to ensure the safe and appropriate use of antibiotics.


There are growing concerns with rising antimicrobial resistance (AMR) across countries. These concerns are enhanced by the increasing and inappropriate utilization of ‘Watch’ antibiotics with their greater resistance potential, AMR is further exacerbated by the increasing use of antibiotics to treat patients with COVID-19 despite little evidence of bacterial infections. Currently, little is known about antibiotic utilization patterns in Albania in recent years, including the pandemic years, the influence of an ageing population, as well as increasing GDP and greater healthcare governance. Consequently, total utilization patterns in the country were tracked from 2011 to 2021 alongside key indicators. Key indicators included total utilization as well as changes in the use of ‘Watch’ antibiotics. Antibiotic consumption fell from 27.4 DIDs (defined daily doses per 1000 inhabitants per day) in 2011 to 18.8 DIDs in 2019, which was assisted by an ageing population and improved infrastructures. However, there was an appreciable increase in the use of ‘Watch’ antibiotics during the study period. Their utilization rose from 10% of the total utilization among the top 10 most utilized antibiotics (DID basis) in 2011 to 70% by 2019. Antibiotic utilization subsequently rose after the pandemic to 25.1 DIDs in 2021, reversing previous downward trends. Alongside this, there was increasing use of ‘Watch’ antibiotics, which accounted for 82% (DID basis) of the top 10 antibiotics in 2021. In conclusion, educational activities and antimicrobial stewardship programs are urgently needed in Albania to reduce inappropriate utilization, including ‘Watch’ antibiotics, and hence AMR. There are concerns with rising rates of antimicrobial resistance (AMR) globally, increasing morbidity, mortality, and costs ,3,4,5,6.We have seen a number of Central and Eastern European (CEE) countries, as well as former Soviet Union Republics, which are not included in CEE countries, introduce or plan to introduce a number of initiatives and activities to reduce inappropriate utilization of antibiotics and ultimately AMR ,24,25,26Albania is an upper middle-income country in South-East Europe with a population of just under three million in recent years . HoweverConsequently, in view of ongoing concerns in Albania, we believe there is a need to build on previous publications that have tracked antibiotic utilization patterns in Albania, including high rates of ‘Watch’ antibiotics. ,45,46. TAlongside this, we are aware that there has been an appreciable increase in the use of antibiotics in patients with COVID-19 across countries and sectors despite limited evidence of bacterial infections or co-infections ,51,52,53In view of this, the objectives of this study were to measure and analyze antibiotic utilization patterns in Albania in recent years alongside possible factors influencing these patterns. Potential factors include an ageing population, increasing GDP, as well as current levels of corruption. The findings, along with exemplars from other countries, can subsequently be used to give guidance to key stakeholder groups in Albania and beyond.We will first discuss the broader antibiotic utilization patterns in Albania during the past 11 years using a traditional drug utilization approach before looking critically at their composition, including trends in the utilization of ‘Watch’ antibiotics. In addition, we assess the possible impact of key factors, including an ageing population and governance, on utilization patterns. There is no attempt to look critically at the utilization of individual antibiotics because there is no diagnostic or indication data in the data sets used for analysis. In addition, the lack of specific demand-side measures at set times precludes the use of sophisticated statistical analyses, including time series analyses.Total antibiotic consumption fell in Albania between 2011 and 2019 but increased thereafter until 2021, which coincided with the COVID-19 pandemic . There wOverall, in 2011 only two antibiotics from the ‘Watch’ list were present in the list of the top 10 most utilized antibiotics in 2011. This had appreciably changed by 2021 when only two of the antibiotics in the top 10 were from the ‘Access’ list; the remainder were from the ‘Watch’ list . Table 1There is a significant correlation between the decrease in antibiotic use and an increase in median age for the period 2011–2020. A similar significant correlation is observed between the decrease in antibiotic use and the growth in GDP per capita. It must be noted that these correlations are significant only when the 2021 values, which we considered outliers, are excluded .The scatter plots in We believe this is the first study undertaken in Albania in recent years to document current antibiotic consumption through an 11-year study as well as changes in utilization patterns prior to the introduction of the NAP. This includes changes in patterns following the recent COVID-19 pandemic. Prior to the pandemic, we saw a decreasing trend in the overall utilization of antibiotics in Albania from 27.2 DIDs in 2011 to 18.8 DIDs in 2019. We believe this is primarily due to ageing populations with less childhood respiratory illnesses. Such a correlation is supported by the fact that over 90% of antibiotic utilization globally is in ambulatory care, with only a minority in hospital care, especially in LMICs ,55. AlonThese pressures, coupled with increasing concerns with AMR, may have also contributed to the increasing use of ‘Watch’ antibiotics in recent years. In 2011, only two antibiotics from the ‘Watch’ list were in the top 10 most utilized antibiotics in Albania . HoweverIt is difficult to also comment on trends in the utilization of antibiotics in hospitals in Albania during the study years, including IV versus oral use, as we were unable to disaggregate the utilization data into separate sectors and components. However, there have been concerns in previous studies with prolonged antibiotic administration post-surgery to reduce SSIs in Albania . This maAnother identified concern is the increased utilization of antibiotics following the COVID-19 pandemic, which reversed the downward utilization trend that was seen . Such anThe increasing use of ‘Watch’ antibiotics, now accounting for 82% of total antibiotic utilization among the top 10 most utilized antibiotics during the pandemic, is also a considerable concern. This excessive use may have been driven by physicians feeling more comfortable with prescribing ‘Watch’ antibiotics to feel safer in the absence of resistance data with limited testing in reality. However, again, we cannot comment further without additional research. In any event, this trend also needs to be urgently reversed. We are also likely to see a greater use of prescribing indicators across countries, including Albania, centered on the AWaRe book with their treatment suggestions for a number of infections routinely seen across sectors ,55. ThisWe are aware of a number of limitations with this study. These include the fact that we could not split the utilization data down into ambulatory and hospital sectors for comparison purposes. In addition, since the data were aggregated, we were unable to break this down into the different formulations. There were also no diagnostic or resistance data to assess the appropriateness of prescribing, especially the ‘Watch’ antibiotics. Alongside this, data sets post pandemic were limited to undertake sophisticated statistical analysis of any trends. Despite these limitations, we believe our findings are robust based on the length of this longitudinal study and breaking antibiotic utilization patterns down into the different AWaRe components. Alongside this, potential different hypothesis and factors should be tested to guide all key stakeholders in Albania going forward when the NAP will be launched.Antibiotic utilization patterns for the total population of Albania from 2011 to 2021 are documented as DIDs (defined daily doses per 1000 inhabitants per day). DIDs are an internationally recognized metric used by the WHO for undertaking drug utilization studies to meaningfully document drug utilization patterns across countries, including European countries, where there are appreciable differences in population sizes ,26,45,69The AWaRe classification is important given previously high rates of ‘Watch’ antibiotics being prescribed and dispensed in Albania . In thisWe also listed the number of antibiotics in the ‘Watch’ vs. ‘Access’ categories each year in the top 10 most utilized antibiotics since these are the most prescribed. We chose the top 10 as this usually encompasses most of the utilized antibiotics and gives a good focus for future ASPs. Examples of successful ASPs will also be documented to give guidance to all key stakeholder groups across the sectors in Albania to improve future antibiotic prescribing and dispensing where concerns have been identified. This though will not be a systematic review of successful examples in the three key situations, e.g., hospital antibiotic prescribing to prevent SSIs, initiatives to improve physician prescribing, as well as initiatives to appreciably reduce the purchasing of antibiotics without a prescription. This is because one of the primary objectives of this paper is to provide examples to key stakeholder groups in Albania regarding successful approaches that have been implemented in other LMICs to address concerns with utilization patterns where these are seen rather than undertake full systematic reviews. These examples from the literature are based on the considerable experiences of the co-authors publishing in this area ,56,58,73The source of the antibiotic utilization data was the import records provided from the Drug Agency and Customs in Albania combined with the sales records from local manufacturers. This encompasses the total population of Albania.EUROSTAT with INSTAT (Albanian Institute for Statistics) provided population data , with thp-values < 0.05 were considered statistically significant. Scatterplots were subsequently created using Microsoft Excel to illustrate potential associations.The Kendall’s tau-b correlation coefficient with 95% confidence interval (two-tailed) was calculated to test potential associations between antibiotic utilization patterns and potential key factors using IBM SPSS Statistics (version 26). Two-sided There was no ethical approval for this study as no patients were involved. In addition, data was extracted from publicly available datasets. This is in line with institutional guidance.In conclusion, there are principally three challenges to address in Albania to improve future antibiotic use given current concerns, especially with the growing use of ‘Watch’ antibiotics. Firstly, key stakeholders need to reinforce and implement the draft NAP leveraging multi-sectorial. Secondly, ASPs need to be urgently introduced in hospitals to address concerns with excessive prescribing of antibiotics. This includes any prolonged use to prevent SSIs, any prolonged IV administration, or excessive prescribing in patients with COVID-19. Thirdly, universities need to make sure in their curricula that all key HCP students are fully conversant with the rationale for prescribing antibiotics, especially ‘Watch’ antibiotics’, as well as undertaking ASPs post-graduation.Lastly, the MoH in Albania will need to reinforce the routine monitoring of prescribing and utilization of antibiotics across sectors as well as provide the necessary equipment and tools to HCPs to increase prescription accuracy and protocol compliance in line with AWaRe guidance.


Composed of rod building blocks (RBBs) cross-linked by bipy linkers,the activated form of CMOM-5 adapted its pore structureto bind four guest molecules, 1-phenyl-1-butanol (1P1B), 4-phenyl-2-butanol(4P2B), 1-(4-methoxyphenyl)ethanol (MPE), and methyl mandelate (MM),making it an example of a chiral crystalline sponge (CCS). Chiralresolution experiments revealed enantiomeric excess, ee, values of 36.2–93.5%. The structural adaptability of CMOM-5 enabled eight enantiomer@CMOM-5 crystalstructures to be determined. The five ordered crystal structures revealedthat host–guest hydrogen-bonding interactions are behind theobserved enantioselectivity, three of which represent the first crystalstructures determined of the ambient liquids R-4P2B,S-4P2B, and R-MPE.Chiral metal–organicmaterials (CMOMs), can offer molecularbinding sites that mimic the enantioselectivity exhibited by biomoleculesand are amenable to systematic fine-tuning of structure and properties.Herein, we report that the reaction of Ni(NO Anew chiral metal−organic material provides a blueprintfor the design of families of chiral crystalline sponges that enableenantiomeric selectivity, and the determination of the crystal structuresof liquid enantiomers. Of these,101 are homochiral, whereas only nine are racemic. This can causechallenges for purification as the identical physical properties ofenantiomers mean that separation of racemic mixtures into their enantiomericallypure components is difficult and costly, tending to rely upon enantiomericseparation7 and/or asymmetric synthesis.9Enantiomers of chiral molecules can behavevery differently inbiological systems, e.g., one enantiomer might drive a physiologicalfunction, while the other is toxic. This means that high enantiomericpurity can be a requirement in specialty chemicals such as pharmaceuticals,fragrances, condiments, and agrochemicals.10 Chiral porous materials have the potential to overcome these challengesif they exhibit the right pore size and chemistry to enable effectivechiral separation performances. Further, they can afford insight intoselective binding mechanisms.15In the context of separations, the early promise of chiral cyclodextrinand polysaccharide derivatives as scaffolds for separating racematesthrough supramolecular chemistry has not been fully realized, withpoor stability and high cost handicapping their commercial utility.17 it is not always possible to readily obtainsuitable single crystals, especially when one is dealing with liquidsor solid compounds that are only available in small quantities.18 In this context, the introduction of “crystallinesponges” represents a seminal breakthrough that offerspromise to address the limitations of SCXRD.24 This is because, in a typical crystalline sponge experiment, guest-accessiblemetal–organic materials (MOMs) can adsorb and orient theirpores to accommodate organic molecules in an ordered manner, therebyenabling spatial precision.25 The prototypalcrystalline sponges were metal–organic frameworks (MOFs),20 but other classes of compounds such as hydrogen-bondedorganic frameworks (HOFs) and metal–macrocycle frameworks canalso function as crystalline sponges.28Single-crystal X-ray diffraction (SCXRD) studies can offerdirectstructural information with atomic-level precision. Although absolutestructure determination of crystalline chiral compounds is feasibleby SCXRD,2)3(tpt)2x(solvent)]n (tpt = tris(4-pyridyl)-1,3,5-triazine), ZnI2-tpt, enabled structuraldetermination of several chiral molecules.33 To observe the effective anomalous scattering fromthe host, ZnI2-tpt was preinstalled with a chiral reference, following which the absoluteguest molecule configurations could be determined.34 Our group has developed chiral crystalline sponges (CCSs)based on homochiral MOMs (CMOMs) for the structure determination ofchiral compounds, and chiral separation performances thereof.37The prototypalcrystalline sponge, the achiral MOF [Cd(bipy)(H2O)][NO3], CMOM-5, and its CCS properties , 4-phenyl-2-butanol(4P2B), 1-(4-methoxyphenyl)ethanol (MPE), and methyl mandelate (MM)are key enantiopure reagents for the total synthesis of chiral pharmaceuticalsor bioactive nature products, e.g., corticotropin-releasing factors,chiral arylamines, fluorohexestrol, and (−)-disorazole C1.80 Under ambient conditions, all six isomers of 1P1B, 4P2B, and MPEare liquids, and only one enantiomer, S-1P1B, hashad its structure crystallographically determined, in S-1P1B@CMOM-3S (Table S4).36That the coordination geometry in  S-IDECH 1a, rightoperties 1b. We weSupporting Information (SI).All reagents and solvents were obtained from commercialvendorsand used without further purification. More details of the experimentalprocedures are described in the F2.83 Electron densitycorresponding to highly disordered guest molecules was addressed byPLATON SQUEEZE.85 Occupancy of chiral guest moleculeswas determined by considering the MASK-calculated electrons and theratios among the guests and the ligands reflected in the corresponding 1H nuclear magnetic resonance (NMR) spectra.86SCXRD data were collected at 150 Kusing a Bruker D8 Quest diffractometer equipped with a Cu KαIμS micro-focus source (λ = 1.54178 Å) and PhotonII detector. Temperature was controlled by an Oxford Cryosystem withliquid nitrogen flow. In all cases, the data was indexed by APEX4(v2021.10–0). Integrations were conducted by SAINT V8.40A inAPEX4. Absorption corrections were performed by SADABS in APEX4. Spacegroup determination was performed by XPREP in APEX4. Structures weresolved using the Olex2–1.5 software package and SHELXT throughIntrinsic Phasing. Refinement was conducted by SHELXL through full-matrixleast-squares on 3)2·6H2O and S-indoline-2-carboxylicacid  was mixedwith an N,N-dimethylformamide (DMF)solution of bipy in a 15 mL glass vial. The reaction mixture was heatedat 60 °C for 24 h. Blue single crystals of CMOM-5 were obtained upon cooling to RT. Single crystals of CMOM-5 were soaked in acetonitrile (MeCN) for 5 days, with fresh solventexchanged daily, before proceeding with crystalline sponge and chiralresolution experiments.An ethanolic solutionof Niof the racemates. The screw cap was loosened to enable slow evaporationof MeCN over 5 days. Crystals were then filtered and washed with ethylacetate and then n-hexane to remove the residualchiral molecules on the surface of the crystals. Guest molecules in CMOM-5 were extracted by soaking the crystals in 10 mL ofmethanol (MeOH) for 3 days, following which the crystals were filteredand washed with MeOH. The filtrates were combined, and the solventwas removed by a rotary evaporator. The dried fractions were dissolvedin 1 mL of MeOH for ee analysis.90 mg of MeCN-exchanged CMOM-5 crystalswere soaked in 0.5 mL of MeCN containing 40 mg of isomers of MM, or40 μL of isomers of 1P1B, 4P2B, and MPE. The screw cap was loosenedto enable slow evaporation of MeCN over 3 days; single crystals wereisolated for SCXRD experiments; see Figure S1.MeCN-exchanged 1, X2, X3 = N, A = O, cbnn topology net.35 With respect to the 14 RBB structures involving prolinato ligands,the coordination geometries were found to be octahedral  or pyramidal . Thirteen one-dimensionalRBB structures are comprised of Cu2+ or Zn2+ central cations that are also coordinated to terminal ligands besidesprolinato. Perhaps the most relevant example is the coordination network l-prolinato)(bipy)(NO3)] 6H2O -6,6-dimethylbiphenyl-2,2-diol),which preferred S-MM with 93.1% ee (Table S27).90 Relative to CMOM-5, (Δ12)-PCC-57 and [DyNaL(H2O)4] 6H2O require more complexsynthesis conditions for their preparation.To thebest of our knowledge, there are no previous reports ofchiral resolution experiments involving 1P1B.R-1P1B was found to interact with a nitrate anionthrough O–H···O hydrogen bonding . R-1P1B also formedhost–guest and guest–guest C–H···πinteractions . In CMOM-5-S-1P1B, guest moleculeswere disordered in the channel .84 That the unit cellof CMOM-5-R-1P1B is different than CMOM-5-S-1P1B, a and b longerby 0.20 and 1.03 Å, respectively, and c shorterby 1.13 Å (Table S8), reveals theadaptive nature of CMOM-5. 1H NMR spectraof digested CMOM-5-S-1P1B crystals revealed a 1:1.01:1.15 ratio of bipy/S-IDEC/1P1B, consistent with the crystal structure  and surface bound R-1P1B. A 1:1.01:0.5 ratio was found for CMOM-5-S-1P1B . The higher loading of R isomer loadedcould be ascribed to guest–guest C–H···πinteractions.93We next analyzedthe guest-loaded crystal structures to gain insightinto the observed chiral resolution performance. The hydroxy groupof CMOM-5-R-MPE, the methylene C–Hmoiety from S-IDEC interactswith the hydroxy group of R-MPE through C–H···OH-bonds (3.28 Å), and the hydroxy group interacts with a nitrateanion through O–H···O H-bonds (2.84 Å).The oxygen atom in the ether group of R-MPE exhibitsguest–guest C–H···O H-bonds (3.25 Å)and MeCN molecules reside in channels (Table S23). Bipy and S-IDEC ligands of the host frameworkexhibit C–H···π interactions with thechiral guest R-MPE. Further, there are guest–guestC–H···π interactions between R-MPE molecules . For the structures with ordered chiral guests and solventmolecules, CMOM-5-R-MPE exhibited the largest unit cell volume . The a, b, and c axes in CMOM-5-S-MPE are 0.07, 0.15, and 0.41 Å, respectively,less than those of CMOM-5-R-MPE (Table S10). Additionally,unlike the other chiral guest-loaded structures, the dihedral angleformed by the two pyridine rings in CMOM-5-R-MPE orients in the opposite direction. In CMOM-5-S-MPE, the 42.1% void volume ofthe unit cell  is occupied by S-MPE and MeCN molecules.83 Thenitrate anion interacts with the aqua ligand through O–H···OH-bonding . 1H NMR data revealed the ratio of bipy/S-IDEC/MPEin CMOM-5-R-MPE and CMOM-5-S-MPE to be 1:0.99:0.96 and 1:1.01:0.5, respectively . The higher uptake of R isomer and the guest–guest interactions could explain thehigher ratio of R isomer from the chiral resolutionexperiments.93In CMOM-5-R-4P2B and CMOM-S-4P2B, R-4P2B and S-4P2B were boundin a similar manner. The hydroxy groups of R-4P2Band S-4P2B interact nitrate anions through O–H···OH-bonds of 2.72 and 2.66 Å, respectively, while the channel watermolecules interact with the hydroxy groups of R-4P2Band S-4P2B through O–H···OH-bonds of 2.73 and 2.76 Å, respectively (Tables S21 and S22). In CMOM-5-R-4P2B, bipy ligands interact with R-4P2B through C–H···O H-bonds of 3.35 Å(Table S21). The occupancy of both isomers was100% in the corresponding structures, as supported by 1H NMR data revealing that the bipy/S-IDEC/4P2B ratiois 1:0.98:1.07 and 1:0.99:1.15 in CMOM-5-R-4P2B and CMOM-5-S-4P2B, respectively . Compared to CMOM-R-4P2B, the unit cellparameters of CMOM-5-S-4P2B are reduced by 0.13 and 0.65 Å along a and c, respectively, whereas b is increased by 0.6 Å (Table S9),resulting in a reduced unit cell volume for CMOM-5-S-4P2B. C–H···πinteractions were found between R-4P2B molecules. C–H···πinteractions between S-4P2B molecules of 3.73 and3.45 Å were observed .Stronger guest–guest C–H···π interactionsin CMOM-5-S-4P2B could explain the higher loading of S-4P2B in thechiral resolution experiments.93In CMOM-5-R-MM, the chiral guestmolecules and solvent molecules were found tobe disordered in channels . 1H NMR data revealed the ratio of bipy/S-IDEC/MM in CMOM-5-R-MM to be 1:1.03:0.52 , while in CMOM-5-S-MM, the ratio was 1:1:1.01 . The unit cell volume of CMOM-5-S-MM was determined to be smaller than the otherchiral guest-loaded structures . Compared to CMOM-5-R-MM, a and c in CMOM-5-S-MM werefound 0.12 Å and 0.44 Å shorter, respectively, while b increased by 0.12 Å. (Table S11). S-MM was bound to the host framework throughO–H···O H-bonds from the hydroxy moiety to theaqua ligand (2.81 Å) and C–H···πinteractions with bipy and S-IEDC . Intermolecular C–H···OH-bonds between the chiral guest molecules were observed (3.26 Å, S-MM moleculesformed infinite chains (CMOM-5-S-MM exhibited guest–guest H-bonding could bebehind the strong separation performance.95In S-IDECHis introduced as a homochiral ligand for MOMs, affording CMOM-5. Thanks to the adaptive properties of CMOM-5, it functionsas a CCS for several solvents and chiral guests, enabling us to observeordered enantiomers in five crystal structures for five of the eightguests studied, i.e., R-1P1B, R-4P2B, S-4P2B, R-MPE, and S-MM.This report also represents the first time that the crystal structuresof R-1P1B, R-4P2B, S-4P2B, and R-MPE have been determined. Overall,our study shows that a crystal engineering approach to the developmentof families of CMOMs from naturally abundant homochiral ligands couldovercome the high cost55 of alternative approaches.In this work, the low-cost natural product