The present study focuses on the investigation of the interfacial bond behavior of carbon fiber-reinforced polymer (CFRP)-concrete under dry–wet sulfate cycles by double-sided shear testing. Besides, the effects of fly ash content on the interfacial failure characteristics, interfacial debonding bearing capacity, CFRP strain distribution, and interfacial shear stress peak were analyzed. The interfacial debonding capacity, maximum CFRP strain, and peak value of interfacial shear stress of the CFRP-concrete interface decreased with increasing erosion time under the sulfate dry–wet cycle's action, according to the sulfate dry–wet cycle test results. The sulfate resistance of the CFRP-concrete interface increased after the addition of fly ash. However, the final decrease amplitude of interfacial debonding capacity, CFRP maximum strain, and maximum interfacial shear stress all reduced as the fly ash content increased. The effective bond length of the interface gradually increased with increasing erosion time; however, the change in fly ash content had little effect on the effective bond length, and the final effective bond length of the samples with different fly ash content was the same. Moreover, the CFRP-concrete interfacial bearing capacity model under the sulfate dry–wet cycle was established by introducing sulfate's comprehensive influence coefficient and considering fly ash content's influence. In conclusion, the comparative analysis of the prediction model and test results revealed that the prediction model could well reflect the degradation law of interfacial debonding bearing capacity with sulfate attack time. However, most of the CFRP-reinforced structural members of infrastructures are exposed to harsh environmental influences in practical engineering. The bonding performance of the CFRP-concrete interface is directly related to the exposure time to environmental influences, which reduces the bearing capacity of the reinforced elements9. Therefore, the durability of the CFRP-concrete interface in harsh environments directly affects the long-term mechanical properties of CFRP-reinforced concrete structures. Many scholars14 have conducted extensive studies on the FRP-concrete interface, resulting in a vast amount of experimental data and helpful conclusions, as well as the development of a more mature interface mechanics model. However, the existing interface mechanics model rarely considers the influence of the erosion environment and cannot accurately express the degradation of FRP-concrete interface performance under an erosion environment.Carbon fiber-reinforced polymer (CFRP) is widely used to support existing reinforced concrete structures by taking its advantages such as a lightweight, not bulky, high strength, easy construction, corrosion resistance, fire resistance, considerable geometric plasticity, and easy tailoring18. In one of these studies, Al-Rousan et al. reported that sulfate had a great impact on the interfacial bonding performance of FRP-concrete and that the interfacial bonding performance of FRP-concrete showed significant deterioration after sulfate attack7. Zhou et al. studied the effect of sulfate dry–wet cycles on the mechanical properties of CFRP-concrete interface16. The test results showed that the interfacial bonding performance decreased significantly under the sulfate dry–wet cycles, indicating that the main factor for the deterioration of the CFRP-concrete interface performance was the deterioration in the mechanical properties of the concrete. The peeling capacity and peak shear stress of the interface declined gradually with the increase in erosion time, according to the experimental results in Reference15, and the peeling capacity reduced by around 52% after 150 days of sulfate dry–wet cycle. In addition, it was found that the trend exhibited by the interface peel strength was consistent with the concrete strength based on the change in erosion time. This also indirectly reflects the decrease of concrete mechanical properties under the sulfate attack environment, which is the main reason for the reduction in CFRP-concrete interface bonding performance.Sulfate attack is one of the main reasons for the deterioration of mechanical properties of the FRP-concrete interface, according to many studies27. A large number of sulfate ions react with the hydration products of cement, resulting in the decomposition and dissolution significant amount of calcium hydroxide and C-S-H gel material in concrete, which leads reduction in strength properties and cohesiveness of concrete. In addition, the expansion stress generated by these expansion products causes concrete cracking27. The development of cracks creates a vicious cycle that leads to a sharp decrease in the strength of the concrete, which is sustained by the erosion boundary continually moving towards the interior of the concrete. Although the situation looks underwhelming, some mineral admixtures can improve the resistance of concrete to sulfate attack29. Among these, fly ash stands out with its advantages such as improving and refining the pore structure of concrete, preventing the penetration of sulfate-containing medium, and slowing the exposure of concrete to sulfate attack33, thereby effectively increasing the sulfate attack resistance of the FRP-concrete interface. Therefore, investigating the effect of fly ash content on the interfacial bonding performance of CFRP-concrete in a sulfate attack environment is essential for guiding the durability design and assessment of CFRP-reinforced concrete structures.Sulfate attack of concrete is one of the most complex and harmful environmental water physical and chemical erosion, which involves the transmission of sulfate ions in concrete, the reaction between sulfate ions and cement hydration products, and the destruction of concrete structure by the generated expansion productsIn this paper, the influence of fly ash content on the bonding properties of CFRP-concrete interface under sulfate dry–wet cycle is studied by double-sided shear test. The mechanical model of CFRP-concrete interface considering the influence of fly ash content under sulfate dry–wet cycle is established.The materials used in the study are as follows: Qilianshan grade 42.5 ordinary Portland cement; natural river sand as fine aggregate with a fineness modulus of 3.0; gravel with a maximum particle size of 20 mm as coarse aggregate (the weight ratio of 5–10 mm particle size to 10–20 mm particle size is 1:2); fly ash with good quality class II fly ash; the tap water as mixing water, and UNF-I as the high performance water reducing agent. The indexes of cement and fly ash are shown in Tables Double-sided shear specimens were used in the experiments. The size of the concrete prism was 100 mm × 100 mm × 220 mm, and 18 prism specimens were prepared for each mixture ratio. The prism specimens are shown in Fig. The production process and requirements of the double shear specimen: 1) The concrete specimen is first polished to remove the floating slurry layer and uneven part of the specimen surface at the CFRP paste part until the coarse aggregate is exposed; (2) Cleaning the concrete surface with a blower and then wiping it with anhydrous ethanol; (3) Using the transparent tape to isolate the adhesive area and non-adhesive area, so as to avoid the overflow of resin glue in the process of brushing into the non-adhesive area and affect the test results; (4) Compressing back and forth with rollers in order to eliminate the gaps between the concrete surface and the carbon fiber fabric by the resin-impregnated on the carbon fiber fabric after bonding of CFRP sheets; (5) Curing of the prepared samples at room temperature for 7 days before performing the tests. The field condition of prism specimens bonded with CFRP is shown in Fig.  The conc36. The test was carried out with 10% Na2SO4 solution. The dry–wet cycle process was as follows: Soaking in sulfate solution for 12 h, then discharging the solution, drying for 2 h, heating the test box, drying for 8 h at 40 °C, and finally shutting down the heating system for natural cooling for 2 h. After one cycle is complete, the sample is placed in solution for the next 24-h cycle. The temperature of the test box is maintained at 40 ± 2 °C during drying operation due to the softening temperature of the adhesive resin is 45–80 °C38. The solution is renewed every other month to maintain the constant concentration. A double set of shear specimens and a cube specimen were produced, with three specimens in each group, at five mixing ratios, to be tested every 30 days.The dry–wet cycle system was carried out according to the sulfate resistance test standard of GB/T50082-2009In order to facilitate the analysis of test results, all specimens were grouped. In this grouping, while DW represents the sulfate dry–wet cycle environmental effect; F0, F10, F15, F20 and F25 represent concrete fly ash content of 0%, 10%, 15%, 20% and 25%, respectively. Sulfate attack time was directly marked by digital. For example, DW-F10-60 represents a group of specimens with 10% fly ash content and 60d erosion time under sulfate dry–wet cycle. The specific specimen grouping is shown in Table The electronic universal testing machine for the CFRP-concrete double shear test is shown in Fig. The residual strength ratio of concrete is utilized to more clearly articulate the attenuation law of concrete strength with erosion time under the sulfate dry–wet cycle. The expression of residual strength ratio of concrete is as follows:26. Furthermore, the expansion stress caused by these expansion products leads concrete to crack. The development of cracks leads the erosion boundary to advance continually to the interior of the concrete, resulting in a vicious cycle in which the concrete's strength is dramatically reduced27. According to the results, after 150 days of erosion, the strength of concrete without fly ash decreased by 41.2%.The variation of compressive strength of concrete with erosion time under sulfate dry–wet cycle is presented in Fig. 31. In addition, the substitution of fly ash to cement reduces the 33. It can also be seen from Fig. 39.As shown in Fig. After sulfate dry–wet cycles, the specimen's failure mode changed significantly from the failure of the concrete layer without erosion to the failure of the interface between colloid and concrete. The specimen's failure surface occurs in the concrete layer underneath the adhesive layer without sulfate attack or with a short erosion period. During failure, a large number of pulled concrete debris and particles adhered to the CFRP, and the concrete surface was in a rough state. At the loading end, a triangular shear zone with an angle of about 45 degrees with the CFRP axis appeared, called type I failure. The failure surface occurred at the concrete surface or the bonding interface for the specimens exposed to a long sulfate attack. The CFRP sheet was no longer bonded with concrete debris but only a small amount of concrete particles and the triangular shear zone at the loading end could not be observed, as identified as a type II fault. Typical failure characteristics of specimens are shown in Fig. 15. Therefore, the change in the failure mode of the CFRP-concrete interface was mainly caused due to the degradation of concrete and the deterioration of the contact surface. Based on the analysis in “The mechanical properties of CFRP sheets showed a slight decrease under sulfate dry–wet cycles. However, because the strength of CFRP and bond resin was much higher than that of concrete, the decrease in the performance of CFRP and bond resin had little effect on the degradation of the bond performance of the CFRP-concrete interfaceWith increasing sulfate attack time, the interface bearing capacity of CFRP-concrete will deteriorate. To eliminate the problem that the test results due to the heterogeneity of the concrete show variations, the effect of the fly ash content and the drying-wetting cycle time of the sulfate on the interfacial bearing capacity of CFRP-concrete are examined as follows: While the erosion time T was taken as the abscissa, the ratio of the interfacial abrasion bearing capacity obtained with different erosion durations to the interfacial wear bearing capacity of the same type samples at room temperature,  is used to represent the change of the interface shear stress with erosion time in order to more intuitively express the influence of fly ash content and erosion time on the maximum shear stress of the interface. Figure 40; however, measuring the effective bond length directly when reaching the ultimate load is difficult. Nakaba et al. recommended that the effective bond length is taken as the distance between the two points on both sides of the peak shear stress distribution (the coordinate point corresponding to the peak shear stress of 10%)41, that is, the effective stress transfer length. Because the stress transfer length is consistent with the length corresponding to the inclined section of the strain curve, the effective bond length is defined as the bond length corresponding to the inclined section of the strain curve.The bond strength between CFRP and concrete does not always increase with the increase of bond length. Many investigations have revealed that at the CFRP-concrete interface, there is an effective bond length, The presence of interfacial friction causes the CFRP strain to increase somewhat following interfacial debonding, as seen from the specimen's strain curve analysis. As a result, the effective bond length is calculated as the length of an inclined section between two points on the fitting curve with maximum strain values of 2% and 98%. According to the strain curve analysis, the effective bond length of the FRP interface at room temperature is 60–70 mm, and the fly ash content has little effect on the effective bond length. The effective bond length of FRP will grow as the sulfate dry–wet cycle time increases. The effective bond length of specimens with different fly ash yields at room temperature was normalized to minimize the heterogeneity of concrete and the discreteness of test results induced by the difference in specimen production. The change in effective bond length of the interface between distinct specimens throughout dry and wet sulfate cycles is depicted in Fig. The effective bond length of the interface increases as the erosion duration increases, as shown in Fig. ηL under sulfate dry–wet cycle is obtainedFigure 42, Tanaka model43, Chaallal et al. model44, Sato model45, Izumo model46, Iso model46, Neubauer and Rostasy model47, Khalifa model48, Chen and Teng model49, Lu Xinzheng model50. However, the existing interfacial bearing capacity models are mainly proposed without taking environmental factors into account. The analysis of the existing interfacial bearing capacity models showed that the interfacial bearing capacity is closely related to the stiffness of fiber sheets and the strength of concrete. However, after sulfate dry–wet cycles, the mechanical properties of the constituent materials will deteriorate with the extension of erosion time. Therefore, the existing interfacial bearing capacity models cannot accurately reflect the loss of interfacial bearing capacity after sulfate erosion. This paper presents an interfacial bearing capacity model for sulfate erosion based on the existing interfacial bearing capacity model by introducing the comprehensive effect coefficient Domestic and foreign scholars have established some bearing capacity models through a large number of experimental research and theoretical analyzes, such as: Hiroyuki and Wu modelThe constant coefficient into Eq. . The impAs the sulfate dry–wet cycle time increases, the interfacial bearing capacity of CFRP-concrete decreases. The effect of erosion time on the interfacial bearing capacity of specimens without fly ash is investigated using the change in interfacial debonding bearing capacity of specimens without fly ash with sulfate dry–wet cycle time. Similarly, the interfacial debonding bearing capacity obtained at different erosion durations is normalized with the average value of the specimen at room temperature to eliminate the large discreteness of test findings caused by concrete heterogeneity and differences in specimen preparation. The variation trend of interface debonding bearing capacity with erosion time can be calculated using erosion time mentclasspt{minimamentclasspt{minimaThe bonding performance of the CFRP-concrete interface under sulfate assault has improved to some extent after adding fly ash to concrete.The interface bearing capacity diminishes as the amount of fly ash in the mixture increases. As a result, the comprehensive effect coefficient of sulfate will also change as the fly ash content changes. The complete effect coefficient of sulfate in a sulfate environment must be rectified. When Eq.  is used Figure with Eq. . The corThe expression of the complete effect coefficient ing Eqs.  into 7)\documentSubstituting Eqs.  into 5)5), the bThe interface bearing capacity under different working conditions was calculated according to the Eqs.  and 9)..9). A coAfter the sulfate dry–wet cycles, the interfacial failure gradually changed from the concrete layer below the adhesive layer to the damage at the interface between the adhesive layer and the concrete, with increasing erosion time. However, the addition of fly ash improved the sulfate resistance of concrete, thus improving the corrosion resistance of the interface. With the increase of fly ash content, the failure mode of the specimen changed from type I failure to type II failure for a prolonged duration.The decrease in the mechanical properties of concrete was the main reason for reducing CFRP-concrete interface bearing capacity. With the increase of erosion time, the interfacial bond separation carrying capacity decreased; however, with the increase of fly ash content, the time required for the interfacial bond separation carrying capacity to begin to decrease gradually was prolonged, and the final decrease gradually decreased.Under the sulfate dry–wet cycle, the maximum strain value of CFRP and the peak value of interfacial shear stress gradually reduced as erosion duration increased. However, the sulfate resistance of the CFRP-concrete interface improved after the addition of fly ash, and the final state of maximum strain and interfacial shear stress of CFRP gradually decreased with the increase of fly ash content.With the increase of sulfate dry–wet cycle time, the effective bond length of the interface gradually increased. On the other hand, the impact of the fly ash content on the variation of the effective bond length was not notable. The final effective bond length of the samples with different fly ash content was detected to be basically the same.The interface bearing capacity model of CFRP-concrete under the dry–wet cycle of sulfate was established by introducing the comprehensive influence coefficient of sulfate and considering the influence of fly ash content. Through the comparative analysis of the prediction model and the experimental results, it has been revealed that the prediction model can well reflect the degradation law of interface stripping bearing capacity with sulfate attack time.In the current study, the effect of fly ash content on the bonding performance of the CFRP-concrete interface was studied by the sulfate dry–wet cycle accelerated erosion test. The specific conclusions are as follows:


Blast furnace slag (BFS) and fly ash (FA), as mining-associated solid wastes with good pozzolanic effects, can be combined with superplasticizer to prepare concrete with less cement utilization. Considering the important influence of strength on concrete design, random forest (RF) and particle swarm optimization (PSO) methods were combined to construct a prediction model and carry out hyper-parameter tuning in this study. Principal component analysis (PCA) was used to reduce the dimension of input features. The correlation coefficient (R), the explanatory variance score (EVS), the mean absolute error (MAE) and the mean square error (MSE) were used to evaluate the performance of the model. R = 0.954, EVS = 0.901, MAE = 3.746, and MSE = 27.535 of the optimal RF-PSO model on the testing set indicated the high generalization ability. After PCA dimensionality reduction, the R value decreased from 0.954 to 0.88, which was not necessary for the current dataset. Sensitivity analysis showed that cement was the most important feature, followed by water, superplasticizer, fine aggregate, BFS, coarse aggregate and FA, which was beneficial to the design of concrete schemes in practical projects. The method proposed in this study for estimation of the compressive strength of BFS-FA-superplasticizer concrete fills the research gap and has potential engineering application value. Concrete is a widely used building material containing a high proportion of artificially manufactured stone, generally mixed with cement, coarse aggregates , fine aggregates , admixture, and water. The strength of concrete is related to that of cement. However, cement has a high cost and is also the main cause of concrete’s environmental impacts. With the growth of the cement industry, carbon dioxide CO emissionemerging . Althougmissions , studies2, CaO and Al2O3 in its major composition , with values closer to 1 indicating more similar dispersion between the predicted and actual values; this scenario indicates that the results obtained through the model will be better at explaining the variance of the input variables, whereas smaller values indicate poorer results.3. MAE : The MAE4. MSE: The MSE parameter is the most commonly used evaluation metric in regression models. This metric calculates the mean of the sum of squares of the errors between the fitted data and the original data corresponding to the sample points. The closer the MSE is to zero, the more accurate the model.In this study, the RF-PSO model was used to predict concrete strength by combining RF with PCA and PSO techniques. To reduce the dimensionality of the input variables before applying the RF, the PCA approach was employed for dimension reduction. The data were split randomly into two subsets: a training set and a testing set, comprising 85% and 15% of the total data, respectively, based on a sensitivity analysis. PSO was used to optimize the model’s hyper-parameters to achieve the optimum model performance.Having obtained an accurate compressive strength prediction model, it is crucial to understand which variables have a major impact on the compressive strength of high-performance concrete. Sensitivity analysis was performed in this study by changing one input variable at a time while keeping the others constant . The preAs shown, the most important variable was identified as curing age, which contributed 33.536%, followed by cement (23.964%) and water (12.689%). Superplasticizer, fine aggregate, BFS, coarse aggregate, and FA contributed relatively less, with values of 8.055%, 6.133%, 6.128%, 5.139%, and 4.356%, respectively. On this basis, the influence of BFS, FA, and superplasticizer on concrete strength was explained as follows.BFS improves the mechanical characteristics of concrete by reducing its porosity and increasing its resilience to weak acids and salts . In compThe pozzolanic effect and cementitious properties of FA are primarily responsible for the influence of FA on concrete strength. Young Keun Cho et al. reported that after 91 days of curing time, the strength of FA-based concrete increased due to the pozzolanic effect . In shorSeveral studies have shown that adding superplasticizer to concrete decreases the quantity of water required for mixing, thus lowering the water–cement ratio and porosity and improving the superplasticizer concrete performance ,60,61. S(1)The R, EVS, MAE and MSE values on the original dataset were 0.954, 0.901, 3.746 and 27.535, respectively, indicating that the ML model constructed in this study can accurately predict the strength of concrete prepared with BFS, FA, and superplasticizer, which has potential engineering application value.(2)After PCA processing, the prediction accuracy decreased , indicating that PCA dimension reduction has a negative impact on ML modeling and cannot be adopted. However, there is no doubt that the combination of the two has exploratory significance.(3)The sensitivity analysis showed that curing time has the greatest influence on the compressive strength of concrete, followed by cement > water > superplasticizer> fine aggregate > blast furnace slag > coarse aggregate > fly ash. This provided potential ideas for further improving the strength of concrete.In this study, ML techniques were used to construct a model for the precise and rapid prediction of the concrete strength. The influences of BFS, FA, and superplasticizer on concrete strength were key target variables during dataset collection. The content of cement, water, coarse aggregate, and fine aggregate, as well as age and a variety of chemical additives, were selected as model inputs. The RF algorithm was utilized in combination with PCA and PSO for the concrete strength prediction. The specific conclusions are as follows:However, this study still had some limitations, such as the size of the dataset on the compressive strength of concrete was still a little small to be representative. The positive and negative effects of cement, water and superplasticizer on compressive strength have not been specified, and how to improve the compressive strength of concrete based on post-model analysis also needed to be further explored.


Evidence from clinical studies on biofilm-active antibiotics in PJI will be highlighted, mainly focusing on the role of rifampicin for Gram-positive microorganisms and fluoroquinolones for Gram-negative microorganisms. The optimal treatment duration will be discussed as the timing of switching to oral antibiotic therapy.The antibiotic treatment of periprosthetic joint infections (PJI) is complicated by the presence of biofilm produced by bacteria on the abiotic surface of the implant. Bacteria within the deeper layers of the biofilm become metabolically less active, resulting in antibiotic tolerance due to several mechanisms. This review describes the basic principles of antibiotic treatment in PJI in relation to the behavior of bacteria within the biofilm. The concept of biofilm-active antibiotics will be explained from an  Periprosthetic joint infection (PJI) is characterized by the formation of biofilm on the implanted foreign body . Biofilmin vitro and clinical data. We will also focus on the current state of knowledge of treatment duration and the role of intravenous (IV) vs. oral antibiotic therapy in treating biofilm infections.The inherent properties of biofilm have led to the emergence of several principles for the treatment of PJI. First, surgical source control with extensive debridement is an essential part of treatment. Obtaining source control for biofilm infections presenting in an early stage  may be restricted to surgical debridement with implant retention (DAIR) . Achievie.g., in the case of a mounted immune response [Biofilm is a complex network formed between bacteria, the prosthetic material and the host. Aggregates of bacteria (possibly multiple species) form a polymer matrix, which consists of excreted polysaccharides, proteins and DNA. This matrix may also be supplemented by materials from the host, response . Biofilmresponse . Bacteriresponse . Biofilmresponse .Antibiotics may have difficulty diffusing through the matrix of the biofilm and reaching effective concentrations, especially in the inner core. This, however, is a temporary effect as an equilibrium is eventually reached with antibiotic treatment. Nevertheless, slowly rising antibiotic concentrations may facilitate the build-up of antibiotic tolerance .Pseudomonas aeruginosa and tobramycin [Components of the matrix of the biofilm may scavenge antibiotics, rendering them inactive. This has been described with alginate polysaccharides produced by bramycin .The biochemical conditions in the biofilm may result in reduced activity of antibiotics . For exaMicroorganisms inside the biofilm are dormant and do not divide actively . This mae.g., by upregulating β-lactamase production or efflux pumps. These mechanisms are generally not biofilm-specific, although circumstances may facilitate their emergence, and biofilm-specific adaptive resistance mechanisms have been described [Microorganisms in the biofilm may show adaptive resistance, escribed .Lastly, acquired resistance may play a role in biofilm infections as in any other infections. In the case of biofilm infections, the issue is complicated by the fact that the environment may increase the frequency of genetic mutations and facilitate horizontal gene transfer .Due to these characteristics, there are several factors that contribute to the antibiotic tolerance of bacteria in biofilm:Pseudomonas aeruginosa, due to its role in biofilms in cystic fibrosis [P. aeruginosa has an impressive arsenal of adaptive resistance mechanisms available, but relatively little is known about how well the resistance mechanisms apply to the much more commonly encountered Gram-positive and other Gram-negative microorganisms than P. aeruginosa in PJI [These mechanisms of antibiotic tolerance have been particularly well studied in fibrosis . P. aerua in PJI .An "anti-biofilm active" antibiotic is classically considered as an antibiotic that penetrates well into the biofilm and demonstrates its capability to eradicate the bacteria embedded within it. In addition, for PJI treatment, it is important that the antibiotic penetrates well into the bone and, for oral antibiotics, has adequate bio-availability . For exaSeveral biofilm models have been developed to assess the property of antibiotic tolerance of microorganisms in biofilms. Concentrations at which antibiotics show efficacy within a biofilm can be quantified by using parameters such as the minimal biofilm inhibitory concentration (MBIC) and minimal biofilm eradication concentration (MBEC) .Staphylococcus epidermidis and Staphylococcus aureus, respectively. These concentrations are nowhere near feasible with systemic therapy in in vivo situations.Molina-Manso et al. quantified MBEC's for several antibiotics used in the treatment of staphylococci on a collection of 32 clinical isolates from PJI . Their sin vivo condition. In the commonly used Calgary Biofilm Device (nowadays known as MBEC® assay), biofilm matured during an overnight incubation on an abiotic surface, in a situation with continuous exposure to the medium, but without the complex host anatomy and immune response [in vivo conditions [It is important to recognize the shortcomings of such quantifications to mimic the response . In addinditions .in vivo situations [Nevertheless, these in vitro quantifications have made important contributions. For example, they have drawn attention to providing high local concentrations of antibiotics as a part of biofilm treatment regimens, as these may approximate MBEC's in tuations . Also, ttuations .Over the last decades, rifampicin has emerged as a cornerstone in the treatment of staphylococcal PJIs. Rifampicin penetrates well into tissues, including bone, achieves good intracellular concentrations, and has bactericidal activity in bacteria that are not dividing . It can in vitro studies, animal studies and non-experimental clinical studies for staphylococcal PJI [Rifampicin has shown its activity in ccal PJI . The cliccal PJI . Howeverccal PJI .t.i.d. instead of more commonly 450 mg b.i.d.), (4) a lack of monitoring compliant intake of rifampicin, (5) the low statistical power of the study, (6) a lack of detailed description of the failures, and (7) the choice of the companion antibiotic of rifampicin (vancomycin or cloxacillin) [in vitro data and the RCT by Zimmerli et al., many observational studies indicated a clear benefit of rifampicin on clinical outcomes in staphylococcal PJIs [A second RCT on rifampicin combination therapy for acute staphylococcal PJI was published in 2020 and questioned the need for rifampicin. This study did not show a benefit compared to vancomycin or cloxacillin monotherapy . The triacillin) . Apart fcal PJIs , 25. LikCutibacterium spp. PJIs. Commonly, β-lactams and clindamycin are used for these infections, but they demonstrated limited in vitro activity against biofilm-embedded bacteria, while rifampicin showed better in vitro activity [Cutibacterium spp. PJIs, the only available clinical studies are observational.Rifampicin has also been considered as a treatment adjunct in streptococcal and activity –29. For et al. performed a multinational study of 462 cases of streptococcal PJI treated with DAIR, of which 52% were hematogenous infections and the remainder were post-surgical ones [Lora-Tamayo cal ones . The autet al. analyzed 187 cases of Cutibacterium spp. PJI, of which 85% was C. acnes. The infections generally involved the shoulder or hip, and 95% presented with a chronic infection at least a month after implantation [In another multinational study, Kusejko antation . In eachin vitro and animal studies. In vitro data in which fluoroquinolones showed the highest biofilm eradication rate when compared to other antibiotics was mostly demonstrated in Pseudomonas aeruginosa biofilms [Escherichia coli [Stenotrophomonas maltophilia [In Gram-negative PJI, the use of ciprofloxacin is generally considered pivotal for eradication of biofilm, although there is limited evidence from biofilms , 33, buthia coli  and Stentophilia .et al. and included 174 cases treated with DAIR, of which 78% were caused by Enterobacterales, and 20% by Pseudomonas aeruginosa [P < 0.001). It is important to note that only ten patients in this study were treated with co-trimoxazole, and therefore, the comparative effectiveness of ciprofloxacin and co-trimoxazole as oral alternatives remains to be established. A smaller observational study (n = 47) confirmed the inferiority of other oral antibiotics to ciprofloxacin [The largest observational study has been published by Rodriguez-Pardo ruginosa . Treatmefloxacin . The onlfloxacin . In thisTraditionally, treatment duration for PJI has been at least 3 months, which is substantially more than the 4 to 6 weeks that is generally advised in the case of the absence of orthopedic hardware . This iset al. performed the multicenter DATIPO RCT in France, in which 410 patients with a PJI of the hip or knee were randomized to either 6 or 12 weeks of antibiotic therapy after surgical source control [vs. 9.4% of those treated for 12 weeks, with the confidence interval of the risk difference excluding the non-inferiority of 6 weeks of treatment. In subgroup analyses, the inferiority of a 6-week antibiotic regimen was particularly evident in patients treated with DAIR, with an absolute risk difference of 16.2%. The primary endpoint was not significantly different for patients who were treated with a one- or two-stage revision. This finding supports the notion that the presence of infected orthopedic hardware is an important factor in the prognosis of PJI treatment. The RCT performed by Benkabouche et al. even demonstrated that recurrences did not differ between 4 and 6 weeks of antibiotic treatment after the removal of orthopedic hardware [Bernard  control . The prihardware . HoweverA Spanish multicenter RCT by Lora-Tamayo compared an 8-week antibiotic regimen with 3- or 6-month regimens for staphylococcal PJI of the hip or knee treated with DAIR . In the Although uncertainties remain based on the above-mentioned studies, all in all, there is potential for shortening antibiotic treatment duration to 6 weeks, in particular, for selected groups of patients with an acute PJI and a low risk of failure after DAIR, and for chronic infections treated with revision surgery. Results are awaited of the SOLARIO trial. This trial evaluates whether 7 or fewer days of systemic antibiotics is non-inferior to a long course of antibiotic treatment if local antibiotics have been applied. Although the study is designed for orthopedic infections in general, making it more difficult to evaluate subgroups with sufficient statistical power, cases with a PJI are included as well .A final recurring question with regard to the treatment of PJI is at what time point a switch from intravenous to oral treatment is justified. Traditionally, osteomyelitis and PJI were considered an entity that should be treated with intravenous antibiotics only . HoweverEarly oral therapy in the cases of osteomyelitis and PJI has received momentum in recent years through the OVIVA trial. In this British multicenter RCT, 1054 patients with bone and/or joint infection were randomized to either a switch to oral therapy within 7 days after surgery, or a full 6-week course of intravenous antibiotics and, if needed, followed by additional oral therapy . In 61% Antimicrobial tolerance, developing during maturation of the biofilm, makes PJIs difficult to treat and necessitates adequate source control, antimicrobial therapy with "anit-biofilm active" antibiotics and prolonged courses of antibiotic therapy.Applying biofilm models for susceptibility testing in routine laboratory testing is currently not clinically useful. Ideally, though, in the future, individual characteristics of the biofilm related to the bacterial strain and the manner of the biofilm being embedded into the host would shape antibiotic choices.Staphylococci consists of rifampicin, supplemented with a second antibiotic to prevent resistance formation. Most experience exists with using fluoroquinolones with proper Gram-positive action as companion drugs , but other antibiotics with good bio-availability and bone penetration may just be as adequate.Biofilm-active therapy in the case of Streptococci and Cutibacterium spp. showed good activity in in vitro biofilms. Observational studies suggested that it might increase clinical cure, but the surgical strategy might be a more important predictor for clinical outcomes. Routine use is not recommended, but it might be considered in certain subgroups of patients.Rifampicin for in vitro activity against biofilms produced by certain Gram-negative organisms. In addition, observational studies reported good outcomes using this compound, and is, therefore, still the first-line antibiotic treatment for PJIs caused by Gram-negatives.Fluoroquinolones show good Antibiotic treatment duration should be 3 months for acute PJIs treated with DAIR but may be shortened for the cases with a low risk of failure. In the case of revision surgery, 6 weeks of antibiotic treatment probably suffice.IV antibiotics can be switched early to an oral treatment regimen, provided that an antibiotic with anti-biofilm properties and adequate bioavailability is available.


The developed method worked with a rectangular counter electrode without a guard ring assist, during an individual impedance measurement. The impact of the counter electrode size on the impedance spectra was verified in the first stage by tests conducted with ten types of counter electrodes. The obtained results in the form of empirical spectra were represented by theoretical spectra using the 3D model and the matching degrees were within a range of 0.96–1.73 at the expected level of 1.00. The obtained results in the form of spectra distribution were accurately represented by simulations with the 3D model. In the second stage, the iterative procedure for determining the polarization area of reinforcement in concrete was positively verified for additional test elements. Electrochemical parameters of the steel-concrete system were determined on the basis of the 3D model with a simultaneous adjustment of the polarization area on the rebar. In this case, the expected matching degree of 1.00 was obtained for each tested system after more than ten iterations starting from matching the model spectra to the empirical spectra at the level of 0.31–0.93.A new method is proposed for determining the test surface of steel rebar in concrete during polarization measurements of corrosion rate of reinforcement using the method of Electrochemical Impedance Spectroscopy. The methodology was based on the original  The operational safety of large concrete structures can be provided by their administrators, who should have detailed knowledge of their technical conditions . FacilitThe most popular method consists of the application of twin counter electrodes placed in one head on the surface of the concrete cover over reinforcement. The auxiliary electrode is described as a guard ring that is used to confine distribution of polarization currents on the side surface of cylindrical reinforcement. The idea of guard ring has been repeatedly described and experimentally verified ,45,46,47The second method of identifying the polarization surface of reinforcement, which is also described in the available literature, is to perform a series of measurements, each time using a counter electrode of a different size. Finally, the distribution of outcomes of polarization resistance against the counter electrode surface can be analysed by extrapolating true values of polarization resistance for the projected unlimited polarization surface of the test electrode. The above testing method was described in the paper  as a conThe third, a laboratory and in situ verified method of identifying the polarization surface of reinforcement, is based on cutting a cylindrical core with part of the support rebar from the reinforced concrete structure. Then, a three-electrode system composed of an auxiliary electrode, a reference electrode, and a working electrode, which is a part of the cut rebar from the core, is arranged on the cylindrical core under laboratory conditions. Because geometry of the cut rebar is known, its side surface is also defined. Additionally, this side surface can be verified after crushing the core in the testing machine. Key information for testing the polarization surface of reinforcement is automatically acquired during the EIS measurements on such a core. Additionally, a possibility for simulating variable thermal and humidity conditions in the environment of the structure in a climatic and corrosion chamber provides a range of extreme values of the corrosion ratio instead of a single value obtained from traditional measurements. The above methodology for polarization tests on concrete cores was patented in 2012 and is also presented in the papers ,49,50,51Another, fourth, method of identifying the polarization surface of reinforcement covered with concrete is to make a cylindrical cut in the concrete cover to a depth corresponding to its thickness prior to the EIS measurements. This circular cut should have a diameter equivalent to a cross-sectional diameter of the counter electrode, which is placed on the concrete surface through wet felt. The cut, which is recommended to be filled with liquid insulator, ensures relatively effective confinement of distribution of polarization currents over the side surface of steel reinforcement. The test surface of reinforcement can be estimated because the effects of the insulator are known. This methodology was patented in 2020, and its experimental verification is discussed in the papers ,52,533D model of the steel-concrete system. The model, which is a base of the proposed methodology, has already been described and partially verified during tests concerning the impact of diameters [3D model.In the search for non-destructive methods for identifying the polarization surface of reinforcing steel in concrete, this paper suggests a new methodology that requires only one EIS measurement with a single counter electrode and the analysis of results is enhanced with an original iameters  and the iameters , the thiiameters , and theiameters  on the rφ and concrete cover of thickness The steel–concrete system composed of a rectangular concrete body 1 with a singular smooth rebar 2 of diameter ckness c  was consThe counter electrode 3, the reference electrode 4, and the working electrode 2 that was a steel rebar, formed a three-electrode system that was connected to the potentiostat.CPE, described by the parameters CPE  is determined using the algorithms of the Gaussian method for estimating the volume for a triple integral [3, whereas the volume of the solid element was expressed as the quotient of the dry concrete mass Definitions of local coefficients of concrete and steel geometry were introduced to map the irregular geometry of the flow area of polarization currents between the counter electrode 3 and the working electrode 2 in the he paper .(1)γi,juctivity b, given integral . The solD. The approximated value of that integral was determined using the algorithms of the Gaussian method for estimating the volume for a double integral [D with a surface area of The local coefficient for steel geometry he paper (6)γi,jsectrical b. The suintegral . The flation cf. . ParametFinally, the defined local coefficients of concrete steel γs 3D model. The total equivalent impedance They comprehensively describe the flow area of polarization currents between the counter electrode 3 and the working electrode 2 with reference to geometry of that area. The representative form of the expressions (7) resulted from two planes of symmetry included in the concrete  is given3D model were divided into two stages. At first, assumptions made for the 3D model were empirically verified with reference to the impact of the rectangular geometry of the counter electrode on shapes of impedance spectra.Experimental tests related to the computational analysis with the S1 and S2. Concrete mix S1 with the ratio of w/c = 0.43 was prepared from 489 kg/m3 of Portland cement 32.5R, 501 kg/m3 of fine aggregate with fraction to 2 mm, 1168 kg/m3 of coarse aggregate with fraction of 2–8 mm, and 212 L/m3 of water. Another mixture S2 differed from the mixture S1 only in the presence of an additive in the form of 3% NaCl dissolved in batched water. Smooth rebars with a diameter φ12 mm and φ16 mm, which were made from stainless steel of grade S235JR, were used as reinforcement in concrete elements. Test elements were prepared from two concrete mixes, –/AgCl,Ag electrode was used as the reference electrode.The three-electrode system for the EIS measurements on reinforced concrete elements was prepared from a set of rectangular counter electrodes cut from a stainless steel sheet of grade X5CrNi18-9 . The couThe photo of a test stand for performing impedance tests on the impact of the rectangular counter electrode width on the shape of impedance spectra of steel in concrete is shown in S1, which is characterized by high protective properties against steel. Two other elements were also made from concrete of series S2 (with chloride additives) with reduced protective properties.The impact of width In accordance with the assumptions described in point 2, the test stand shown in 5 on each side to minimize the effect of a gradual change in moisture content in concrete cover.The working electrode in each case was the rebar 1 in concrete element, and the counter electrode 2 and the reference electrode 3, which were placed on the top surface of concrete through wet felt 6 to provide electric contact. Moisture content in concrete cover was measured with the dielectric method prior to each impedance measurement. The obtained results and the methodology for converting dielectric moisture into mass moisture are presented in LM1, LM3 and LM5), which were selected from analysed five models presented in 4 between the counter electrode 2 and the working electrode 1. Hence, the flow of alternating current through concrete during the impedance measurements was maximal at the longest counter electrode, and minimal at the shortest one. Similarly, BM1, BM3 and BM5) of the three-electrode system, representing the test stand from 3D model assumptions describe in point 2 and to empirical equations given in Three characteristic models  in terms of the impact of a changing length S1 was within a range of 5.8–21.5 kΩ  on the Nyquist plots –(10) electrochemical parameters determined from S1 obtained from the counter electrodes of EL = 200, 150, 100 and 50 mm in length, at the average mass moisture of concrete midw = 4.8%. The spectra in S2 corresponding to the following lengths: EL = 246, 200, 150 and 50 mm, obtained at the measured average moisture content in concrete midw = 5.0%—cf. Dashed lines in LM2, LM3, LM4 and LM5 of the test element of series S1, while spectra LM1, LM2, LM3 and LM5 in S2. As in the previous analysis of the impact of the counter electrode width, the adjusted model spectra are additionally shown on the Bode plots—Δw in moisture content against mass moisture, at which the initial spectra LM1 and LM4 were obtained. An increase in moisture content in concrete element of series S1 was observed within a relatively narrow range of +0.2–+0.9%, whereas moisture content in concrete of series S2 was close to the absolute value and ranged from −0.1 to 0.9%. As in the case of analysing the impact of the counter electrode width, the non-uniform moisture content in concrete was the reason for varying theoretical values of average moisture content in concrete per the element volume. In relation to the simulated distribution of current lines shown in The solid line in 3D model-based simulation of effects on the impedance shapes produced by the reinforcement diameter and length, concrete cover, and limited polarization range forced by an electrical insulator. The experimental verification presented in S1, an elongated test element with the dimensions of 1000 × 100 × 56 mm was prepared That element was reinforced with a bar φ16 mm, 1030 mm long, made of smooth steel of S235JR grade. A substantial length of the reinforced concrete element, in the context of the electrochemical tests, was to simulate measurements on real elements from concrete structures under laboratory conditions. Additionally, this element could prevent polarization of the whole rebar covered with concrete at the considerably small size of the counter electrode. Otherwise, the method functionality could not be effectively assessed.For the purpose of showing the functionality of the elaborated iterative method of determining polarized area of reinforcement in concrete of series Gamry Reference 600, which was used in the testing procedure for measuring impedance at a rage of frequencies of 1 mHz–1 MHz at the potential amplitude 20 mV in potentiostatic mode.A view of the test stand for impedance measurements of long test elements 1 is presented in The EIS measurements were taken for comparative analysis of two counter electrodes with a length of Electrochemical parameters of the model were determined in the first stage of tests using the equivalent electrical circuit, as shown in In the second stage, these Formulas (1)–(7) were used to calculate local and global coefficients of concrete and steel geometry, for which lengths of polarization ranges The coefficient 3D model for the shorter counter electrode The selected values of the coefficient Regarding the corrosion evaluation of reinforced concrete, density of corrosion current Equation ,60 was unsfer Rt . The coeto 52 mV ,62,63,642, and for the longer one was 2. As can be seen, the values Taking into account the above assumptions and substituting values of the charge transfer resistance To summarise the above iterative procedure for determining the polarized area of reinforcement during the measurements on reinforced concrete corrosions by the EIS method, the schematic presentation of key elements and stages of this methodology are shown in 3D model, which could include and separate at the analysis stage features of impedance spectra not related to electrochemical effects. The development of an iterative methodology for determining the polarized area of reinforcement in a single rebar in concrete highlighted the practical functionality of the model.This paper supplements multi-thread experimental tests that verify the original 3D model was to define the area of electrically conductive concrete within the developed three-electrode system (with a rebar as the working electrode) and route theoretical paths of current in that area. Basic equivalent electrical circuits, which were connected in parallel, were assigned to each current path, which was a curved block of concrete between the counter electrode and the working electrode. By introducing the geometric coefficient for concrete and steel into Formulas expressing the overall impedance of the system, electrochemical parameters of equivalent circuits were coupled with geometric parameters.A novelty of the experimentally verified 3D model. The future transition into solutions related to the method of finite elements would lead to increased accuracy of modelling the steel-concrete systems; however, it will be a difficult task.Relying on empirical Formulas  to deter3D model; that is, the dimensions of the rectangular counter electrode. Other geometric parameters of the analysed steel-concrete system; that is, a diameter and length of the rebar, thickness of the cover, and polarization range, have already been positively verified and documented in the papers [Results of impedance tests described in this paper referred to the experimental verification of the final, not tested up to then, geometric parameter of the e papers ,55,56,573D model represented tendencies for impedance shapes to change, which was observed during the EIS measurements. However, a slight adjustment of model spectra by a relevant selection of the theoretical moisture content in concrete had a significant impact on the matching degree.The discussed impedance tests performed for different widths and lengths of the rectangular counter electrode indicated a strong relationship between the spectra shapes and variable geometry of the analysed steel-concrete system. The verified The tests employed a simplified method of measuring moisture content in concrete with a dielectric method and converting this parameter into mass moisture . If the 3D model and the relevant formulas. Hence, a description of this method required a complex presentation of the model (The main objective of this paper was to present and experimentally verify the original iterative method for determining the polarized area of reinforcement in concrete. Based on the developed methodology, the initial matching degree of model spectra to the empirical spectra was he model . 3D model, was found to be important in this paper.The iterative method for determining the reinforcement polarization involved the use of a single counter electrode in the three-electrode system and the possible identification of the test area, including electrochemical parameters obtained from a single EIS measurement. Therefore, the experimental tests to verify the simulated impact of varying sizes of the counter electrodes on the spectra shapes, based on the It is difficult to compare this new method of determining polarization surface of reinforcement in concrete with other methods that include the analysed surface in measurements of the reinforcement corrosion rate, which were specified in the Introduction section, in a measurable way without additional tests. The proposed approach seems to be closest to a common solution based on measurements using a counter electrode with guard ring.Looking ahead to further developments of this model to associate it with the method of finite elements, there is the possibility of implementing the described algorithms into the software of testing devices that could be used to provide a more precise in situ evaluation of risk corrosion of reinforcement in concrete.


Little is known about the pattern and appropriateness of antibiotic prescriptions in patients with acute respiratory tract infections (ARTIs).Describe the antibiotics used to treat ARTIs in Tunisian primary care offices and emergency departments (EDs), and assess the appropriateness of their use.It was a prospective multicenter cross-sectional observational clinical study conducted at 63 primary care offices and 6 EDS during a period of 8 months. Appropriateness of antibiotic prescription was evaluated by trained physicians using the medication appropriateness index (MAI). The MAI ratings generated a weighted score of 0 to 18 with higher scores indicating low appropriateness. The study was conducted in accordance with the Declaration of Helsinki and national and institutional standards. The study was approved by the Ethics committee of Monastir Medical Faculty.p < 0.001), asthma , diabetes , history of COPD  and age > 65 years  were associated with a higher likelihood of inappropriate prescribing.From the 12,880 patients screened we included 9886 patients. The mean age was 47.4, and 55.4% were men. The most frequent diagnosis of ARTI was were acute bronchitis (45.3%), COPD exacerbation (16.3%), tonsillitis (14.6%), rhinopharyngitis (12.2%) and sinusitis (11.5%). The most prescribed classes of antibiotics were penicillins (58.3%), fluoroquinolones (17.6%), and macrolides (16.9%). Antibiotic therapy was inappropriate in 75.5% of patients of whom 65.2% had bronchitis. 65% of patients had one or more antibiotic prescribing inappropriateness criteria as assessed by the MAI. The most frequently rated criteria were with expensiveness (75.8%) and indication (40%). Amoxicillin-clavulanic acid and levofloxacin were the most inappropriately prescribed antibiotics. History of cardiac ischemia . Respiratory tract infections (RTIs) are the most common reason for antibiotic prescription in primary care , 2. AlthThis is an observational, cross-sectional, multicenter, national clinical study. The study was carried out from January 2018 to August 2018 in Tunisian population involving 63 primary care outpatient offices  and 6 EDs. The sampling was planned to cover most of Tunisian areas. In total, 20 counties were selected to reflect the national picture of antibiotic use.We performed an exhaustive search by consulting the different available sources as Medline (PubMed), Embase (Ovid), Global Health (Ovid), and CENTRAL (Cochrane Library) of studies conducted in primary care or in the emergency departments to estimate the prevalence of antibiotic prescriptions and first choice antibiotics for ARTIs. The search strategy was built using key terms for “antibiotic,” “primary healthcare,” “emergency”, “prescribing,” and “acute respiratory tract infections”. Bibliographies of retrieved articles were also searched for further studies, and we consulted the annual Tunisian health ministry reports.The study was conducted in accordance with the Declaration of Helsinki and national and institutional standards. The study was approved by the Ethics committee of Monastir Medical Faculty and is registered at Clinicaltrials.gov registry (NCT04482231). We obtained free and informed consent of all included patients.We included patients over the age of 18 years presenting to the EDs or to primary care offices and received antibiotic treatment for lower or upper ARTIs, according to the International Classification of Primary Care. Lower ARTIs include pneumonia and acute bronchitis. Acute upper ARTIs include rhinitis, pharyngitis/tonsillitis, sinusitis, and laryngitis. Each patient was included in the study only once and only antibiotics for oral systemic use were recorded. We excluded any visit that resulted in admission to the hospital, patients with additional diagnoses requiring antibiotherapy, patients with history of immunodeficiency  or active pulmonary tuberculosis. Patients who received antibiotics or who were discharged from the hospital within the preceding two weeks were also excluded. There were no standard antimicrobial order sets at the participating sites during the time of this study.For each patient, the general practitioner or EDs physician registered baseline demographics including age, sex, race, body weight, smoking status, diagnosis of ARTI type, symptoms, duration of symptoms and which antibiotics were prescribed. Additional data collected included comorbid conditions, including heart failure (HF), chronic obstructive pulmonary disease (COPD), asthma, and diabetes. We used the medication appropriateness index (MAI) , 16 whicp value < 0.05 was considered a level of statistical significance. Data were analyzed using SPSS version 20 .Qualitative variables were expressed as frequencies and percentage. Continuous variables were presented as means ± standard deviations or median and interquartile range as appropriate. We calculated the mean MAI for each antibiotic class and ARTI type. The normality of the continuous quantitative variables was verified with the Shapiro–Wilk test. To identify factors associated with inappropriate prescription we tested the univariable relationship between the independent variables for inappropriate prescribing of antibiotics using logistic regression. Those that were significant at an alpha of 0.1 or less were included in a multivariable logistic regression model. Independent variables were demographic characteristics including gender, age, comorbidities, and clinical variables. A n = 1365), lack of clinical data (n = 490), and impossibility to calculate the medication appropriateness index (n = 1139) , asthma , diabetes , history of COPD  and age > 65 years .Of the total prescriptions included, 1621 24.5%) received no inappropriate ratings, 62.1% had one, 10.3% had two, and 3.1% had three or more. Table .5% receiOur study showed that most ARTIs treated with antibiotics in primary care and EDs were bronchitis, tonsillitis, COPD exacerbation, rhinopharyngitis and sinusitis. The most used classes of antibiotics were penicillins accounting for more than 58% of the total antibiotics prescribed for ARTIs. Among these, the most commonly prescribed penicillin was amoxicillin clavulanate followed by amoxicillin. Fluoroquinolones accounted for 17.6% of all antibiotic prescriptions, and 49% of these were levofloxacin. Macrolides and cephalosporins were far less frequently prescribed. In 75.8% of cases, antibiotic therapy should not be prescribed. Inappropriate antibiotic prescription as assessed by MAI was mostly observed in acute bronchitis and in patients treated with amoxicillin-clavulanic acid or levofloxacin. Comorbidities were significantly associated with inappropriate antibiotic prescription.There is clear evidence that antibiotics are heavily overprescribed for respiratory infections because most of these infections are of viral origin and self-limited conditions , 3, 19. There are a number of potential limitations to note. First, although our study included a large sample representing overall clinical practice in Tunisia, we acknowledge that we did not include children who represent some of the highest users of antibiotic prescriptions. Second, in this study we applied the MAI score to assess prescribing appropriateness in primary care and ED practice. Whether this score is optimal when antibiotic inappropriateness is addressed is a question that should be clarified. Of note, this index is generally considered among the most acceptable available tools for implicit measurement of inappropriate prescribing. It was initially validated in geriatric outpatient population but has since been validated for use in inpatient settings. It was found to have good interrater and intrarater reliability. It has undergone extensive validity testing, in the USA, UK and, more recently, in Europe , 34. MAIOur study demonstrated that there is a high rate of inappropriate antibiotic prescribing for patients diagnosed with ARTIs in primary care and EDs. Incorrect indications such as acute bronchitis and choosing expensive and broad spectrum antibiotics were the most common reasons for inappropriate prescribing in particular for old patients with comorbid conditions. The potential for reducing rates of antibiotic prescription is therefore substantial. Future research should include interventions to improve the use of antibiotics in ARTIs.


Ground blast-furnace slag is one of the waste products available in Ukraine and other countries. It is obtained at metallurgical enterprises in huge quantities and can be efficiently used for concrete production. The article is devoted to obtaining experimental-statistical models of the influence of technological factors that determine the composition of self-compacting concrete (SCC) based on ground blast-furnace slag and polycarboxylate superplasticizer on compressive strength, tensile strength, prismatic strength, elastic modulus and crack resistance. Analysis of the investigated factors’ influence on the specified SCC properties is carried out and positive influence of blast-furnace slag and superplasticizer simultaneous action on durability and deformation characteristics is studied. A design method of SCC composition design using the obtained mathematical models is developed. It allows for the consideration of a set of necessary parameters simultaneously. A numerical example is given. Applying effective plasticizers and superplasticizers in concrete compositions enable to obtain concrete mixtures with high workability (cast mixtures) and hardened concrete with high physical, mechanical and operational characteristics based on ordinary Portland cement and aggregates ,2. At thWide use of self-compacting concrete (SCC) in construction is quite attractive, but it is limited by the need to use highly active mineral admixtures and the lack of sufficient experimental basis for predicting its properties . In turnOne of the widespread active mineral additives for concrete is ground domain granular slag . Of all Blast-furnace slag is formed in large quantities at metallurgical enterprises. It is an artificial silicate material formed during smelting metals from ore due to the high-temperature interaction of ore, fuel, floodplains and gaseous medium. For many years, a significant amount of blast-furnace slag has accumulated in dumps, occupied agricultural land and polluted the environment. Therefore, disposal of metallurgical slag is important for environmental protection and resource reuse worldwide.SCC is usually characterized by high cement consumption , so the In order to use SCC in structural elements, the influence of technological factors on concrete deformability, crack resistance and behavior under loading is important. Development of proper methodology for predicting the SCC deformability at the concrete composition design stage is also relevant.One of the most important and well-predictable concrete deformation characteristics is its modulus of elasticity. It is known  that ordAs known, due to the lower content of coarse aggregate, which creates a rigid frame, SCC has lower modulus-of-elasticity values . For lowIn order to design composition of SCC with blast-furnace slag, taking into account a set of specified properties, it is important to obtain mathematical dependences allowing evaluation of technological and concrete composition factors’ impact on the required properties. The method of mathematical experiments planning ,14 is efIn order to identify the complex effect of active mineral additives and polycarboxylate-type superplasticizers on SCC strength and deformable properties in a wide range of strength classes, as well as to establish mathematical relationships between properties and technological factors, a planned experiment was conducted.The novelty of this study is that based on the experimental results, mathematical models of strength and deformation characteristics of SCC based on blast-furnace slag are obtained. These models allow for a design of concrete composition that provides the required concrete characteristics at different hardening stages with minimum possible cement consumption.3 (X1), superplasticizer content SP, % (X2) and consumption of mineral additives (blast-furnace granulated slag) Sl, kg/m3 (X3). The concrete-mixture workability at the points of the experiment was maintained at the level of S5 , splitting tensile strength  and modulus of elasticity  under a single short-term load were determined by standard methods [As variable factors were selected Portland cement consumption C, kg/mrding to ). 204 cu methods .3 [1…X3 are variables, b0…b23 are the equation coefficients.For determining the strength of concrete cubic specimens, the experiment was performed according to a three-level three-factor plan B3  to obtaiInvestigation of deformation characteristics was carried out in accordance with the two-level plan of the three-factor plan . The typThe planning conditions are given in f = 2.0, locally available granite crushed-stone fraction 5–20 mm, blast-furnace granular slag, polycarboxylate-type superplasticizer PCE50 . The experiment-planning matrix and the concrete composition at the experimental points are given in The following materials were used in the research: Portland cement CEM I 42.5 , sand wiBy statistical analysis of the experimental results , mathema1 (cement consumption) and X2 (SP content), which cause a significant decrease in W/C, contribute to a significant increase in strength at 1 day.SCC with organic-mineral modifier, which includes polycarboxylate SP and blast-furnace granulated slag, had compressive strength in the range from 3.6 to 51 MPa after 1 day of hardening. As expected, factors XThe optimal content of the SP additive is significantly related to the cement consumption—at a minimum content of C just 0.5% of SP is enough to maximize the strength; at a maximum cement consumption the optimal SP content is 0.8–1.1. With the increase in the slag content, the optimal content of the additive and its effectiveness slightly decreases .3) mostly reduces the strength at 1 day of SCC hardening by 40–70%. As known [cm1 by 20–25%.Increasing the blast-furnace-slag content  becomes higher. The extreme influence of blast-furnace-slag content becomes more noticeable, which makes it possible to determine its optimal amount from the position of achieving maximum strength: at a cement consumption of 600 kg/m3 the optimal slag content from the strength viewpoint is 40–50 kg/m3 and it is 120–150 kg/m3 at cement consumption of 200 kg/m3.The concrete classes by strength at 28 days that were investigated in the frame of the present research ranged from C8/10 to C 70/85. In general, the tendencies of the factors affect, detected for strength at 1 day, are similar to those at 28 days . It shouctm1) varied from 0.4 to 5.44 MPa and at 28 days (fctm28), from 1.35 to 8.9 MPa. Following the mathematical models, the nature of the variable factors’ influence on splitting tensile strength is almost the same as for compressive one  at a minimum cement consumption (X1) (One of the criteria for crack resistance of concrete is the ratio between compressive and tensile strengths fcracking . Using tobtained . The maiion (X1) . Accordi1) C, kg/m3, superplasticizer content (X2) SP, %, blast-furnace granular-slag consumption (X3) Sl, %) was studied according to the linear plan of the full factorial experiment [Prismatic strength and modulus of deformation of SCC with organic-mineral modifier were studied by testing 100 mm × 100 mm × 400 mm prisms. The influence of the same three factors (cement consumption (Xperiment . The coe1 (C) and X2 (SP), which first of all cause a decrease in W/C in transition from the lower to the upper level (3 (content of blast-furnace granulated slag) has little effect on the prismatic strength after one day of hardening.The prismatic strength after one day of hardening ranged from 2 to 32 MPa, which corresponded to 78% of concrete cubes’ strength at the same age. The highest influence on the prismatic strength is caused by factors Xer level . Factor 3 (slag content) with X1 (cement consumption) becomes more noticeable: for low cement consumption, an increase in slag content has a positive effect on concrete prismatic strength, while at high cement consumption the same increase in slag consumption causes a decrease in strength. As known [After 28 days of hardening  interactAs known , concretThe influence of other factors (cement consumption and SP content) on the prismatic strength at 28 days is similar to that after 1 day of hardening. The strength varies from 11 to 85 MPa. The mean value of the ratio between cubic and prismatic strength at 28 days is like after one day of hardening: 78%. The correlation between these concrete characteristics is shown in The values of concrete modulus of elasticity at the first day were in the range from 10,000 to 27,000 MPa, at the 28th day—from 19,000 to 50,000 MPa. Analyzing the mathematical models, it should be noted that all three investigated factors significantly affect the SCC modulus of elasticity. The interactions between these factors are also significant.1  and X2  from the lower level to the upper one the SCC modulus of elasticity increases on average from 10,000–12,000 to 20,000–26,000 MPa at 1 day and from 20,000–30,000 to 40,000–50,000 MPa at 28 days. The positive interaction coefficient of these factors  on average has less effect on the modulus of elasticity than X1 and X2, but its effect is significantly enhanced by the simultaneous influence of other factors. At low cement consumption (C = 200 kg/m3) the increase in slag consumption increases Epr by 1.5–1.7 times both at early hardening stages and at 28 days; however, at high cement consumption the same factor causes a significant reduction in SCC modulus of elasticity ; Em and S are empirical constants. Modern codes for structural design recommend the following values: Em = 52,000; S = 23 [For predicting the concrete modulus of elasticity under loading at the age of τ days the most used dependencies have the following form:; S = 23 .According to the European Concrete Committee recommendation , the folDifferent modifications of Equation (4) and coefficient values were proposed . AccordiFor high-strength concrete, the American Concrete Association has proposed a different equation :(6)E=332Deformability characteristics of concrete with modifying additives differ from the usual one. Elastic properties of modified concrete, including SCC, increase 1.4 times, and plastic ones decrease twice . For modThis dependence is fundamentally similar to Equations (3) and (4) and differs by a refined coefficient for modified high-strength concrete. The difference between the values of E calculated by Equations (3)–(7) increases (up to 35%) as the concrete strength increases .-after 1 day of hardening:Based on the obtained data, the dependence between the modulus of elasticity of self-compacting concrete with a multifunctional modifier containing blast-furnace slag and superplasticizer was approximated . The obt-after 28 days of hardening:A method of creating and using multifactor dependences obtained, for example, by mathematical experiments planning has a higher resolution to perform tasks of predicting concrete properties at the composition design stage. The obtained experimental-statistical models with coefficients given in Numerical example. Calculate composition of high-strength SCC (Slump—250–270 mm) using ground blast-furnace slag with a specific surface area of 270 m2/kg and polycarboxylate superplasticizer. The required indicators are that concrete class C40/50 (cubic strength at 28 days at least 64.3 MPa), cubic strength and modulus of elasticity at 1 day must meet the normative indicators for class C12/15: at least 19.3 MPa and 27,000 MPa, respectively.3, 2900 kg/m3, 2650 kg/m3, 2700 kg/m3. The part of crushed stone in the SCC should not exceed 0.35.Characteristics of raw materials: true densities of cement, slag, sand and crushed stone are 3100 kg/m1.cm1, fcm28, Epr1 (see According to experimental statistical models of fEpr1 see  using thEpr1 see . For cal2.According to the mathematical model of W/C see , calcula3.Find the crushed stone consumption from the condition that its volume should be 0.35 of concrete volume:4.Find the sand consumption:5.Find the superplasticizer content:3 is:Concrete composition per 1 ml; SP—4.92 kg; slag—200 kg; sand—780 kg; crushed stone—945 kg. A spreadsheet with the calculation performed can be viewed in Cement—492 kg; water—128 When using raw materials that differ from those used in the obtaining models , it is eThe properties of self-compacting concrete with organic-mineral modifier, including blast-furnace granulated slag and polycarboxylate-type superplasticizer, have been studied. Mathematical models of cubic and prismatic strength, as well as modulus of elasticity at different concrete ages were obtained.The combined action of blast-furnace slag and polycarboxylate superplasticizer contributes to an increase in the self-compacting concrete elasticity modulus by 1.5–1.7 times. A method for composition design of self-compacting concrete using blast-furnace slag and polycarboxylate superplasticizer is proposed. The method allows for the consideration of the strength of prisms and also the influence of technological factors that characterize the SCC composition when determining its modulus of elasticity.The use of the obtained mathematical models enables the optimization of the SCC composition in order to provide the necessary strength and deformability characteristics at minimum cost of the final product.


Cascade reporting is an antimicrobial stewardship strategy that has been successfully implemented in inpatient settings, but evidence of its impact on outpatient settings is scarce. We report on the impact on fluroquinolone prescribing at a network of urgent care clinics following the implementation of cascade reporting of Enterobacterales in urine cultures. The use of cascade reporting has been supported by the IDSA guidelines as an element of an antimicrobial stewardship program. Currently, however, there is no standardized guidance for the implementation of cascade reporting by microbiology laboratories.Cascade susceptibility reporting is defined by the Infectious Diseases Society of America (IDSA) as a type of selective reporting in which antimicrobial susceptibility results of secondary antibiotics are only reported if an organism is resistant to primary antibiotic choices within the antibiotic class. Furthermore, the number of urgent care clinic visits has rapidly increased in the United States and significant antibiotic prescribing variability has been noted in this setting. Urgent care clinics have seldom been the target of antimicrobial stewardship interventions. Therefore, the objective of our study was to evaluate the impact of cascade reporting of fluoroquinolone antimicrobial susceptibility on antibiotic prescribing rates in urgent care and express care clinics.More than 50% of antibiotic expenditures in the United States occur in the outpatient setting.The intervention was conducted at a network of urgent care and express care clinics that are part of an integrated health system in Des Moines, Iowa. Urine samples are collected in the clinics and processed for culturing and susceptibility testing at an off-site centralized microbiology laboratory. Once available, urine culture results are displayed in the electronic medical record . Prior to the intervention, cascade reporting was in place for urine cultures with growth of Enterobacterales and was limited to third- and fourth-generation cephalosporins, β-lactam–β-lactamase inhibitor combinations, and carbapenems. In July 2019, antimicrobial susceptibility reporting for Enterobacterales was modified to follow the rules displayed in Figure For the purposes of the study, the preintervention period was June 1, 2018, to June 30, 2019, and the postintervention period was August 1, 2019, to December 31, 2020. We performed an interrupted time series analysis (ITSA) by measuring monthly antibiotic prescriptions per 1,000 patient encounters (PE). All encounters regardless of final diagnosis were included. Data for the number of patient encounters were obtained from central administration and antibiotic prescribing data were abstracted from pharmacy prescribing records, including all initial and subsequent prescriptions. Antibiotic orders included in the analysis included all orders for fluoroquinolones, cephalexin, nitrofurantoin, and trimethoprim-sulfamethoxazole. Although we initially planned to include cefdinir and ceftriaxone in the analysis, these antibiotics were seldom used in the participating clinics and thus were not analyzed. All liquid antibiotic formulations were excluded. We decided a priori to evaluate a change in prescribing rates immediately after implementation of the intervention (change in level) as well as a change in the slope. Individual models were built for each antibiotic. Each antibiotic model was assessed for autocorrelation and seasonality. All statistical analysis were performed using Stata version 14.2 software .P < .0001), and no change in slope was subsequently detected .Data from 7 urgent care clinics and 2 express care clinics were included. Rates of antibiotic prescribing during the study period are displayed in Figure P = .06), with a median of 41.12  prescriptions per 1,000 PE. During the preintervention period, the median prescribing rate of nitrofurantoin was 28.27 prescriptions per 1,000 PE , and the postintervention rate was 35.84 prescriptions per 1,000 PE . No immediate or slope changes were identified by the ITSA. The median prescribing rates for trimethoprim-sulfamethoxazole were 38.98 prescriptions per 1,000 PE  and 38.59  for the pre- and postintervention periods, respectively, without any immediate or slope changes noted in the ITSA.The median prescribing rate of cephalexin was 37.10 prescriptions per 1,000 PE  during the preintervention period. No change in cephalexin prescribing was immediately seen, but there was a nonsignificant change in slope toward monthly increase in prescribing of 4% in the postintervention period (IRR, 1.00–1.09; Our results show that after implementation of cascade reporting of fluoroquinolones, a significant and sustained decrease in prescribing of this antibiotic class was seen at the urgent care and express care clinics affected by the intervention. and can prompt de-escalation in cases of gram-negative bacteremia. Regarding outpatient settings, Tan et al conducted a survey of prescribing practices in England and found that prescribing volumes were higher for antibiotics reported by local microbiology laboratories. In a study by Langford et al among outpatients aged >65 years in Ontario, Canada, reporting antibiotic susceptibility was associated with increased odds of prescribing the reported antibiotic. We now show that implementation of cascade reporting in outpatient settings can lead to sustained reductions in fluoroquinolone use. Moreover, the Centers for Disease Control and Prevention Core Elements of Outpatient Antibiotic Stewardship identify microbiology laboratories as potential partners for outpatient stewardship activities, and our results suggest that cascade reporting of urine cultures collected in clinics can be implemented as an action for practice to improve antibiotic prescribing.Previous studies have shown that cascade reporting in inpatient settings can lead to sustained reductions in the use of the targeted antibioticsOur study had several limitations. The study was conducted in a mid-size city with a relatively homogeneous population and low baseline prevalence of antimicrobial resistance. Although the microbiology laboratory is centralized, it is still part of an integrated health system and therefore communication with laboratory personnel is easy. Furthermore, we did not capture clinic or provider-level characteristics nor individual patient-level data to assess diagnostic indication for antibiotics or treatment failure rates associated with specific antibiotic classes. Importantly, from March to September 2020, multiple urgent care and express care clinics had to halt clinical services due to the COVID-19 pandemic. However, the impact on our results is mitigated by using rates in our analysis, as well as seeing the effect of the intervention many months prior to the onset of the pandemic. We also noted that fluoroquinolone use showed a downward trend prior to onset of intervention. Considering that education and cascading were deployed concomitantly, the impact of each individual component of the intervention could not be separated. Lastly, given the quasi-experimental design, we were unable to control for variability in the characteristics of individuals treated at the clinics; however, these factors would not be expected to have significantly changed throughout the study period.In conclusion, cascade reporting of antimicrobial susceptibility of Enterobacterales in urine cultures is a feasible and sustainable antimicrobial stewardship that can be applied in urgent care and express care clinics in an integrated health system.


TO THE EDITOR,,2 It is estimated that 0.8% to 59.0% of the patients admitted to an ICU require renal replacement therapy (RRT) at some point during hospitalization. Nevertheless, these patients have worse short- and long-term outcomes. The main modalities of RRT used in the ICU are intermittent hemodialysis, extended hemodialysis, and continuous therapy . Neurocritical issues and dysnatremias are the main formal indications for continuous therapies; however, from a practical perspective, centers that have continuous therapies available also use them in patients in need of vasoactive drugs since the fluid removal rate per hour is lower than that in intermittent therapies, generating less hemodynamic instability.Acute kidney injury is a common organ dysfunction observed in intensive care units (ICUs), with a prevalence ranging from 2.5% to 92.2%, according to the population studied. Due to operational and clinical facilities, the National Institute of Health (NIH) recommended the preferential use of continuous therapies over intermittent therapies in these patients. This further increased the demand for trained professionals and supplies. Given this scenario, tools that can predict the time a patient spends in RRT have become necessary, either for clinical purposes or supply and therapy planning purposes.The coronavirus 2019 (COVID-19) pandemic caused approximately 22% of critically ill patients to need RRT, resulting in a greater demand for beds capable of offering RRT in ICUs.timing prediction for the transition between the therapies (continuous to intermittent) could enable improved management of therapy resource allocations in ICUs. Thus, the present study included 480 patients diagnosed with septic shock (norepinephrine-dependent ≥ 0.5µg/kg/minute) who required continuous RRT . Data were collected retrospectively from a single ICU, and the time in continuous therapy was evaluated according to the number of organ dysfunctions present in the first 72 hours of admission. The organ dysfunctions were classified as follows: gastrointestinal , neurological , respiratory (need for invasive or noninvasive ventilatory support), and hematological (need for transfusion of blood products). The ICU in the study already used continuous RRT as the first choice for patients with classical indications and for those who require moderate doses of vasoactive drugs during dialysis sessions. Therefore, there was no limitation due to a lack of expertise or resources that could impact the prescription of therapy.Thus, since the supplies used for these therapies are different from each other, as well as the needs related to logistical planning for their acquisition, an adequate In the study, the quantitative variables were described as medians and interquartile ranges. The comparison between the time on continuous hemodialysis, in days, and the presence or absence of each organ dysfunction was performed using the Mann-Whitney U test. The comparison between the number of days on continuous hemodialysis and the number of organ dysfunctions was performed with the Kruskal-Wallis test, treating the number of days categorically, and the relationship between the variables was also verified using the Spearman’s correlation.Individually, all organ dysfunctions were related to a longer duration on continuous dialysis therapy . Two orgThus, from the data obtained, it is believed that the number of organ dysfunctions present within the first 72 hours of admission of patients with septic shock can predict the duration of continuous RRT. Although incipient, this could be a useful and practical tool for the organization of an ICU and its dialysis resources. Although retrospective, the objective of this study was to provide a foundation for assisting resource management based on clinical criteria focused on nephrointensivism.