Conversation aids can facilitate shared decision-making and improve patient-centered outcomes. However, few examples exist of sustained use of conversation aids in routine care due to numerous barriers at clinical and organizational levels. We explored factors that will promote the sustained use of two early-stage breast cancer conversation aids. We examined differences in opinions between the two conversation aids and across socioeconomic strata.We nested this study within a randomized controlled trial that demonstrated the effectiveness of two early-stage breast cancer surgery conversation aids, one text-based and one picture-based. These conversation aids facilitated more shared decision-making and improved the decision process, among other outcomes, across four health systems with socioeconomically diverse patient populations. We conducted semi-structured interviews with a purposive sample of patient participants across conversation aid assignment and socioeconomic status (SES) and collected observations and field notes. We interviewed trial surgeons and other stakeholders. Two independent coders conducted framework analysis using the NOrmalization MeAsure Development through Normalization Process Theory. We also conducted an inductive analysis. We conducted additional sub-analyses based on conversation aid assignment and patient SES.We conducted 73 semi-structured interviews with 43 patients, 16 surgeons, and 14 stakeholders like nurses, cancer center directors, and electronic health record (EHR) experts. Patients and surgeons felt the conversation aids should be used in breast cancer care in the future and were open to various methods of giving and receiving the conversation aid . Patients of higher SES were more likely to note the conversation aids influenced their treatment discussion, while patients of lower SES noted more influence on their decision-making. Intervention surgeons reported using the conversation aids did not lengthen their typical consultation time. Most intervention surgeons felt using the conversation aids enhanced their usual care after using it a few times, and most patients felt it appeared part of their normal routine.Key factors that will guide the future sustained implementation of the conversation aids include adapting to existing clinical workflows, flexibility of use, patient characteristics, and communication preferences.NCT03136367, registered on May 2, 2017ClinicalTrials.gov Identifier: The online version contains supplementary material available at 10.1186/s13012-021-01115-1. Contributions to the literatureBoth surgeons and patients, regardless of conversation aid used and socioeconomic status, recommended the early-stage breast cancer conversation aids be used in future breast cancer care.Tailoring the use of conversation aids to existing clinical workflows, flexibility of use, and taking into account patient characteristics and preferences, like health literacy, can facilitate sustained implementation.Normalization Process Theory  can also feasibly be used to analyze the patient perspective about the sustainable implementation of conversation aids into diverse practices.Conversation aids help patients compare treatment options using evidence-based information to support them and their families in making a decision that is aligned with their preferences and values –3. HowevIn breast cancer care, clinicians tend to feel they communicate well with their patients and are reluctant to modify aspects of their usual care . CliniciPatients with early-stage breast cancer are faced with a preference-sensitive decision, where their treatment options (mastectomy or breast-conserving surgery with radiation) need to be deliberated, ideally using shared decision-making –22. PatiGiven evidence of the effectiveness of conversation aids, including the two from our parent trial, it is imperative to understand the factors and facilitators for routine implementation and sustainability of conversation aids in diverse clinical contexts for early-stage breast cancer, and particularly for patients of lower SES , 30. WhiThe protocol for the parent study, What Matters Most, is published elsewhere . We condThe Option Grid conversation aid for early-stage breast cancer presents evidence-based information on breast-conserving surgery with radiation and mastectomy in a comparative table . Prior to starting the trial, all surgeons underwent training that included information about the trial protocol, shared decision-making, and communication skills. Training for surgeons in intervention arms included videos and role plays on how to use their assigned conversation aid and when . Surgeons in intervention arms were also provided feedback on their use of the conversation aid throughout the trial period, during scheduled supervision visits. As decided by the parent trial team (including patient partners), we included usual care surgeons to understand their experience in the trial and gauge their interest in using the conversation aids once the trial was over.All participating surgeons after trial involvement  specialists. Most interviewed clinical stakeholders and one non-clinical stakeholder were part of integrating the trial activities in the clinics where they worked. Some non-clinical stakeholders, in administration, provided initial support for the conversation aids’ use.We interviewed:p < 0.05 ) would present the information. — Patient, Picture Option Grid, Higher SESMost intervention surgeons had to use the conversation aid a few times before using it with ease. After a few uses, they felt the conversation aid became part of their normal routine . For both interventions, all surgeons thought the training on shared decision-making and how to use their assigned intervention was sufficient and did not recommend any changes (Skillset workability).Well, it became pretty much second-hand for me actually. I got really used to using it. It just became part of my routine. — Surgeon, Picture Option GridI had a lumpectomy instead of a mastectomy because the information contained in the grid helped me understand that I didn’t need one [mastectomy]. — Patient, Picture Option Grid, Higher SESFor both interventions, over half of patients felt the conversation aid affected their treatment decision (Systemization)....as I got faster, I got more used to it. It did help the rhythm. At first, it took me a little bit longer than I think it would’ve been, but not much. Then, at the end, I think it ultimately helped structure things. It might have made things as efficient or more efficient. — Surgeon, Option GridSurgeons understood the conversation aids were designed to help structure their conversation with eligible patients and help them make a treatment decision. For both interventions, all surgeons felt that the time it took to use the conversation aid did not change the typical time they spend with patients in the surgical consultation .See Additional file I interacted with the piece of paper a hundred times more than I would with the downloaded file if somebody had just sent that to me to look at before my appointment. — Patient, Option Grid, Higher SESI’d say it really influenced it [my decision]. — Patient, Option Grid, Lower SESI would recommend it to everybody. — Patient, Option Grid, Lower SESPatients of higher SES, for both interventions, were more likely to find the conversation aid easier to understand than materials they had received before. They found the conversation aid concise and understood it was designed to help them compare their treatment options (Coherence). For patients of lower SES in the Picture Option Grid group who found the conversation aid easy to understand, all found the pictures played a significant role in their understanding (Coherence). Patients of lower SES who received Picture Option Grid and patients of higher SES who received Option Grid had a preference for paper-based conversation aids. Patients of higher SES reported more willingness to hypothetically receive the conversation aid ahead of their appointment  compared with patients of lower SES, who were more likely to mention that receiving it directly from their surgeon would be best (Cognitive participation). Patients of higher SES, for both interventions, mentioned more often that the conversation aid affected the discussion with their surgeon compared with patients of lower SES were more likely to mention it influenced their treatment decision (Reflexive monitoring).Additional file Completely influenced [my decision] — Patient, Option Grid, Higher SESIt needs to be something they can see online in MyChart. It should also be in a doctor’s office so that a woman can, you know, “Let me read this.” — Patient, Picture Option Grid, Lower SESPatients who received Picture Option Grid reported more willingness to hypothetically receive the conversation aid in advance of their appointment. Patients who received Option Grid were more likely to mention that receiving the conversation aid from their surgeon, and paper-based, would be best (Cognitive participation). Patients who received Option Grid found that using the conversation aid did not feel awkward (Collective action). Patients who received Option Grid were slightly more likely to feel the conversation aid influenced their discussion with their surgeon (Reflexive monitoring).All surgeons who used Option Grid felt using the conversation aid did not feel different from their usual practice compared with only half of surgeons who used Picture Option Grid (Coherence). Surgeons who used Picture Option Grid were more likely to mention the conversation aid should be given at the surgical consultation, as was done in the RCT. They were also more comfortable with their nurse or other qualified clinic personnel giving the conversation aid (Cognitive participation). Surgeons who used Picture Option Grid found they were able to integrate the conversation aid into their normal practice, especially after a few uses (Collective action). Some Picture Option Grid surgeons found the pictures not helpful, but most had no concerns with patients using the conversation aid.Well, it became pretty much second-hand for me actually. I got really used to using it so I don’t know. It just became part of my routine. — Surgeon, Picture Option GridAdditional file The future implementation of the early-stage breast cancer Option Grid conversation aids across diverse practices shows promise for sustainability. Key facilitators include adapting the conversation aids to existing clinical workflows, using them in an adaptable manner that fits best within a surgeon’s consultation, and recognizing patient characteristics and communication preferences. No major barriers were reported by patients, surgeons, or stakeholders in sustainably implementing these conversation aids in diverse practices.Over half of patients thought their surgeons used the conversation aids as part of their usual care. Almost all recommended others like them use the conversation aids. Patients of higher SES were more likely to note the conversation aids influenced their treatment discussion, while patients of lower SES noted more influence on their decision-making. Patients were open to receiving the conversation aids in various ways . For all intervention surgeons, using the conversation aids did not change the typical time they spent with their patients. Most intervention surgeons felt using the conversation aids enhanced their usual care , became part of their normal routine, and took a few times before using the conversation aid with ease. Most surgeons recommended other surgeons like them use these conversation aids in the future. Overall, there were no noted major downsides to using the conversation aids, thus facilitating future adoption and potential sustainability of these conversation aids in diverse clinical settings.A strength of our study is the large number of interviews conducted with a diverse group of stakeholders. We had diversity in type of interviewee  and in demographics . A researcher not affiliated with What Matters Most conducted interviews with the surgeons and stakeholders to minimize positive response bias. Using NPT with multiple perspectives provided a holistic picture of the implementation and sustainability factors of the conversation aids. As a novel approach, we analyzed the patient perspective using NPT as it is important to understand patients’ opinions regarding the implementation of conversation aids with diverse patient groups.One limitation is the discrepancy in patient interview lengths across sites potentially resulting in more site representation than others. However, the same training materials, protocols, and transcript review mechanisms were used across all sites to promote consistency and quality control. There were significant differences between patients who agreed to the interview compared with those who declined, which might limit the generalizability of our findings. Decliners were more likely to be Hispanic and Spanish-speaking, although they were offered to complete the interviews in Spanish with a translator present. Decliners were also more likely to have less education and be of lower SES. Further, our results should be interpreted with caution as we conducted an implementation and sustainability assessment using an implementation framework in a comparative effectiveness trial . There mOur findings align with existing evidence, including in early-stage breast cancer, that it takes flexibility of use and a few tries for a clinician to become comfortable using a conversation aid , 49. WhiSurgeons who were able to integrate the conversation aid in their clinical practice mentioned the conversation aid was similar to their usual consultation content, also seen in a similar study on contraceptive counseling . Some paOur results coincide with another study on a different surgical conversation aid that most patients mentioned the best place to use the conversation aids was during the surgical consultation . HoweverAccording to patients and surgeons who liked using the conversation aids, they mentioned that Picture Option Grid appeared particularly powerful with the inclusion of images. Research shows that pictures in health communication may help better facilitate knowledge for disadvantaged patients than words alone –43. A syBarriers to implementing similar conversation aids continue to exist despite a general understanding that these conversation aids are helpful for patients –66. We fThis study is novel in our effort to understand the experiences and opinions of implementation and sustainability factors of two conversation aids for early-stage breast cancer with multiple stakeholder perspectives, including the patient perspective. We found that in order to successfully implement and ensure sustainability, the conversation aids must be skillfully adapted to clinical workflows and integrated flexibly in health professionals’ usual care. Individual patient characteristics, like health literacy and existing knowledge about breast cancer, and communication preferences are important factors in determining which conversation aid to use. However, we also recommend that patients are given a choice between the two or given both. Patients and surgeons agreed that the conversation aids should be used in breast cancer care in the future and were open to various methods of giving and receiving the conversation aid, allowing for adaptability of future implementation efforts. In this study, the future implementation of the early-stage breast cancer Option Grid conversation aids across diverse clinical practices shows promise for sustainability.Additional file 1.Additional file 2.Additional file 3.Additional file 4.Additional file 5.Additional file 6.Additional file 7.Additional file 8.Additional file 9.Additional file 10.Additional file 11.Additional file 12.Additional file 13.


Scientific Reports 10.1038/s41598-020-80504-w, published online 21 January 2021Correction to: The original version of this Article contained errors.Author names Yoshihiro Araki, Norio Yamamoto, Katsuhiro Hayashi, Akihiko Takeuchi, Shinji Miwa, Kentaro Igarashi, Takashi Higuchi, Kensaku Abe, Yuta Taniguchi, Hirotaka Yonezawa, Sei Morinaga, Yohei Asano, Hiroko Ikeda, Takayuki Nojima, Hiroyuki Tsuchiya were incorrectly given as Y. Araki, N. Yamamoto, K. Hayashi, A. Takeuchi, S. Miwa, K. Igarashi, T. Higuchi, K. Abe, Y. Taniguchi, H. Yonezawa, S. Morinaga, Y. Asano, H. Ikeda, T. Nojima, H. Tsuchiya.In addition, the Article contains a typographical error in the Results section, in the number of years in the ROC curve analyses for the optimal cut-off values.“The optimal cut-off values were as follows: age, 47 years old ; size, 93 mm ; number of osteoclasts in the biopsy specimen, 5 , number of courses of DOX as neoadjuvant chemotherapy, 3 ; number of courses of CDDP as neoadjuvant chemotherapy, 3 ; number of courses of IFO as neoadjuvant chemotherapy, 4 , and number of courses of MTX as neoadjuvant chemotherapy, 1  (Table 1).”now reads:“The optimal cut-off values were as follows: age, 46 years old ; size, 93 mm ; number of osteoclasts in the biopsy specimen, 5 , number of courses of DOX as neoadjuvant chemotherapy, 3 ; number of courses of CDDP as neoadjuvant chemotherapy, 3 ; number of courses of IFO as neoadjuvant chemotherapy, 4 , and number of courses of MTX as neoadjuvant chemotherapy, 1  (Table 1).”The number of years has been correctly shown in Table 1.Furthermore, in Table 2, in the subcategory Stage,“II/IV”now reads:“III/IV”These errors have now been corrected in the PDF and HTML versions of the Article.


The reuse of waste in civil construction brings environmental and economic benefits. However, for these to be used in concrete, it is necessary a previous evaluation of their physical and chemical characteristics. Thus, this study aimed to characterize and analyze the waste foundry exhaust sand (WFES) for use in self-compacting concrete (SCC). Foundry exhaust sand originates from the manufacturing process of sand molds and during demolding of metal parts. It is a fine sand rich in silica in the form of quartz collected by baghouse filter. Characterization of WFES was conducted through laser granulometry, scanning electron microscopy (SEM) in the energy dispersive spectroscopy (EDS) mode, X-ray diffraction (XRD), X-ray fluorescence (XRF), Fourier transform infrared spectroscopy (FTIR), thermogravimetry (TG) and derivative thermogravimetry (DTG) techniques. The waste was classified as non-hazardous and non-inert, with physical and chemical properties suitable for use in SCC composition, as fine aggregate or mineral addition. Five mixtures of SCC were developed, in order to determine the waste influence in both fresh and hardened concrete. The properties in the fresh state were reached. There was an increase in compressive strength and sulfate resistance, a decrease in water absorption of self-compacting concrete by incorporating WFES as 30% replacement. The properties of a material and its microstructure are closely related. In general, microstructural characterization involves the determination of crystalline structure, chemical composition, particle size and morphology, as well as phase distribution . The traCement manufacturing and aggregates extraction for concrete production cause negative impacts on the environment. In light of this, investigations have analyzed alternative materials, which could partially replace the main constituents of concrete, since that they meet the requirements for acceptable structural, construction and safety performance. Also, they must present characteristics required by the current standards .Filling Ability: Ability of SCC to flow into a mold and fill it completely only by its own weight;Passing Ability: Ability of SCC to flow through the steel reinforcing bars without segregation or blocking;Segregation Resistance: Ability of SCC to remain homogeneous during mixing, transport and placement.Self-Compacting Concrete (SCC) was developed in Japan by Okamura in 1986, with the intention to obtain a more durable concrete . As a vaSCC composition is the same of conventionally vibrated concrete (CVC), which consists of cement, fine and coarse aggregates, water, mineral and chemical admixtures. The most significant difference between the two concretes is that SCC requires less coarse aggregates and a higher quantity of fine materials, as well as a higher dosage of water reducing agents, superplasticizer admixtures (SP) and sometimes, viscosity modifying agents (VMA), to ensure adequate filling and passing abilities and segregation resistance . AggregaThe use of cementitious materials such as blast furnace slag, microsilic, fly ash, metakaolin, limestone filler, rice husk ash, among others, has witnessed significant growth in recent years. This is due to the fact that these materials can provide cost reductions, decrease in environmental impact and pronounced improvement of the material final structural performance, such as in the case of compressive strength. In addition, some materials can help with issues of segregation and loss of workability, caused by overdose of superplasticizer .Mineral additions are fine and inorganic materials incorporated into the concrete with intention to achieve or enhance specific properties. They can improve thermal cracking and reduce alkali-aggregate expansion, sulfate attacks and also, costs. The addition of these fine materials to the mixture, which are mostly industrial by-products, decreases their landfill disposal . Multipl2, Al2O3 and Fe2O3 percentages, a loss limit to flame of 6%, moisture content without exceeding 3%, and percentage of material retained in the 45 µm sieve less or equal to 34%.Chemical evaluation of the waste was performed by X-ray diffraction (XRD), X-ray fluorescence (XRF) and scanning electron microscopy (SEM) in energy dispersive spectroscopy (EDS) mode. Thermal analysis of thermogravimetry (TG) and differential scanning calorimetry (DSC) were used to determine if the material can assist in cement hydration processes and if pozzolanic properties are present . These tPhysical, chemical and mineralogical characteristics of the concrete constituent materials have a great influence on its mechanical properties , as wellWaste foundry sands (WFS) are a serious waste management problem for foundry industry, due to their high volume generated  . Althoug2, by 20.000 tons. It generates savings of 20 million British Thermal Unit, BTU, of energy and 7.8 million liters of water 67]. For 2, Fe2O3 and Al2O3 was equal to 98.27% and therefore, higher than 70% as indicated in [As for pozzolanicity, the sum of the compounds SiOcated in . HoweverThermal analysis is a grouping of techniques operates as a function of time and temperature to measure, mass variation (TG/DTG), temperature (DTA) and energy (DSC). It makes it possible to identify melting points, boiling points and phase diagrams, as well as patterns decomposition. Through Thermogravimetry (TG) technique, thermal decomposition, metal corrosion, calcination and other phenomena can be identified.During thermogravimetry analysis, the residue was subjected to a temperature variation from 25° to 1000° C with a heating rate of 10°C/min. TG/DTG curves showed intervals associated with mass loss .The waste showed a total mass loss around 6.1%, which was associated with decomposition of the constituents of free water residue and oxidation of organic matter, such as coal and disintegration of clay minerals. Santos, Dalla Valentina and Souza  state th−1, 796.67 cm−1 and 778.44 cm−1 could be seen, being correspondent to peaks of silica oxide (SiO2) in the form of quartz. The 693.61 cm−1 band was referent to Al2O3, and other peaks were not representative.Foundry exhaust sand was analyzed through infrared spectroscopy, in order to determine its chemical bonds. In the FTIR spectrum , peaks o−1 were found referring to Si-O bonds and may refer to quartz. Santos [−1. The bands corresponding to Al2O3 were identified at 980 and 684 cm−1 in [This result is very similar to that found by Santos, Dalla Valentina, and Souza . In Souz. Santos  identifiLeaching and solubilization tests were performed and provided by the foundry industry. The parameters analyzed showed appropriated concentrations, according to those indicated in . Thus, tSome elements solubilized in aqueous extract were obtained as described in  and the With respect to the residue, the analyzed parameters of aluminum, barium, lead, total chrome, iron, manganese and nitrate exhibited higher concentrations than those presented in , which c2). No chemical compounds have been identified to cause the alkali-silica reaction that causes expansion and cracking and consequently penetration of harmful agents.The applied techniques help to elucidate the chemical composition of materials. When applied together, these techniques provide a range of information that is extremely useful in identifying and characterizing materials, and can be complementary. About chemical properties and SCC characteristics: the composition of Waste Foundry Exhaust Sand is similar to natural sand and is classified as non-hazardous, non-inert and non-corrosive. The WFES mineralogical composition identified was quartz  at 7 and 28 days can be seen in Continuous particle size distribution and spherical shape of the aggregates provided packing density between particles, which favored lower water demand and consequently, provided higher compressive strength with advancing ages for all mixtures. At 28 days, M30 mixture presented higher compressive values when compared to M0 mixture. This fact can be explained because the waste WFES is thinner than natural sand, which makes the composition denser. This result is similar to that obtained by Bilal et al. .In Siddique et al  strengthIt appears that the mixtures M0, M20, M30 could be classified in the category of low absorption and good quality, that is, absorption percentage lower than 3%, according to the comité européen du béton (CEB) . The mixThe resistance to magnesium sulfate attack after 180 days is shown in the 2SO4 solution, the minimum loss percentage in compressive strength was observed for R30, of 1.51% at 90 days. They affirmed that the use of treated used foundry sand (TUFS) as replacement material enhances the sulfate resistance of concrete. It was observed by Siddique and Sandhu [It was observed that there was an increase of 4.5% in compressive strength for M30 in comparison to control mixture after sulfate attack. These results can be attributed to internal porosity, shape and better packing of particles that improved the density of concrete, making it difficult for aggressive agents to penetrate. Gurumoorthy and Arunachalam  remarkedd Sandhu  that for2 as shown in Sulfate attack resistance was related to water absorption of SCC mixtures. Correlation between these properties was verified using a linear equation, evaluating the coefficient R2 = 0.8403 for linear equations, indicating respectively, a high correlation between these properties.The sulfate resistance curve showed RThe penetration of harmful agents in concrete does not only depend on the pore volume, but also on the connectivity between them. The results showed that, with 30% of sand replacement by WFES, SCC presented smaller void ratio and greater sulfate attack resistance. WFES fine particles acted as a packing material, and consequently, generated a concrete with denser matrix.Self-compacting concrete is a relatively new material when compared to conventional vibrated concrete. The properties of fresh concrete such as fluidity, workability and viscosity depend very much on the characteristics and properties of its components.Understanding the waste characteristics, it is possible to identify its influence on fresh and hardened concrete properties, such as compressive strength, water absorption, permeability and durability, shrinkage, and potential reactions when subjected to sudden changes in temperature.Waste foundry exhaust sand is a low-particle waste with a chemical composition similar to natural sand and it is classified as non-hazardous, non-inert and non-corrosive. No chemical compounds that cause alkali-silica reaction were identified, which could lead to expansion and cracking, and consequently, penetration of harmful agents. WFES is considered an alternative material to replace natural sand in the construction industry.The use of WFES as a partial replacement for fine aggregate in conventional concrete can increase water absorption and make the concrete less plastic. Therefore, its application is more suitable for SCC, since that it uses superplasticizer admixture, to increase fluidity, and fine materials, to improve viscosity and particles cohesion.Due to its fineness, rounded shape and good packing between particles, WFES increases compressive strength, reduces water absorption and permeability of concrete mixtures and consequently, increases durability by making mixtures denser, thus reducing pore size and hindering penetration of harmful agents.SCC mixtures using WFES as a partial substitute for natural sand presented appropriate required properties for fresh state such as fluidity, viscosity and segregation resistance. Good results were achieved for compressive strength and durability indicators. The best outcomes were obtained with 30% of residue.This waste can be reused as mineral additive or fine aggregate in SCC. In this way, it can contribute to the development of sustainable concrete, since that it helps to reduce the use of cement and natural aggregates, and decreases the volume of waste in landfills.


Introduction: Online sales of antibiotics have increased public access to these medicines. This study aimed to analyze the online antibiotic purchase behavior of the Chinese residents and identify its associated factors.Methods: We conducted a nationwide cross-sectional online survey among Chinese community residents from January 20 to February 28, 2019. A structured questionnaire was used to collect data on their sociodemographic characteristics, health-related variables, and the online antibiotic purchase behavior in the past 3 months. Descriptive statistics and logistic regression analyses were used. The statistical analyses were performed using SAS version 9.4 (SAS Institute Inc.).Results: A total of 101,120 respondents were included in the analysis. The weighted prevalence of antibiotic purchase online was 3.71% . Residents who purchased antibiotics online were more likely to be older (age≥65 years), be a male, live in rural areas, have a higher education level, report an excellent economic status, suffer from chronic diseases, and search for health information on the internet.Conclusion: Numerous residents had purchased antibiotics online in the past 3 months throughout China. We should pay more attention to this behavior. There is a need to strengthen regulation of antibiotic sales online and improve public education on antibiotic purchase online. More comprehensive information on antibiotic purchase online as well as the advantages and disadvantages of online sales of antibiotics should be investigated in the future studies. Irrational use of antibiotics and the antibiotic resistance it has caused pose a serious threat to globe health . The irrWith the development of electronic commerce, online sales of antibiotics have increased public access to these medicines, which is an enormous challenge for antibiotic stewardship . As a neChina is one of the countries with a serious problem of irrational use of antibiotics . In addiA nationally cross-sectional study on the online antibiotic purchase behavior was designed and conducted among Chinese residents. The data was collected as a part of the community survey module of the undergraduate students of Hainan Medical College using a web-based questionnaire. From January 20 and February 28, 2019, participants were recruited from these student’s native place communities, using the convenience sampling method. The inclusion criteria for the subjects were: 1) 18 years and older 2) those who could read Chinese and 3) able to use smartphone. We also excluded those with severe mental/cognitive problems.n = z2p(1-p)/d2, where n is the sample size, p is the proportion of purchasing antibiotic online, z is the normal deviation (1.96) and d is the margin of error (5%p). There was no previous study on the prevalence of antibiotic purchase online, therefore, we replaced the proportion with that of purchasing medicine online to calculate the sample size. Previous research on medicine purchase online had reported a prevalence of 0.45–12.80% (p = 5%) and set the confidence interval (CI) at 95%. The sample size calculated was 29,196. Furthermore, a study on the sample size estimation showed that the research design efficiency value should be considered when calculating the sample size in a sampling survey. The efficiency value of research design is the ratio of the variance of the planned sampling method estimator to the variance of the simple random sampling method estimator, when the survey unit is the same for the same target quantity .” Only respondents who chose “Yes” were directed to the questionnaire page. Considering that some respondents are not familiar with antibiotics, we set a screening item at the beginning of the questionnaire: “Do you know the term of “antibiotic” or drugs like penicillin, amoxicillin, cephalosporin, and roxithromycin? (Yes/No).” If the screening item was answered with “No,” the survey ended, and if the screening item was answered with “Yes,” the survey continued. In addition, we set up three quality control questions at different places in the questionnaire to identify the respondents who filled the questionnaire at random. The three questions were “Where is the capital of China?”, “What is 7 minus 2?”, and “What is 1 plus 3?”. Each question had 4 alternative answers, of which only one was correct, and the correct alternatives for the 3 questions were inconsistent. After answering all the questions, respondents were directed to submit the questionnaire. The questionnaire system would mark the questionnaire as invalid if any of the three answers of the quality control questions was incorrect. Additionally, to prevent multiple submissions, each mobile phone or computer was eligible to answer only once. The answers to all respondent’s questionnaires were automatically entered into a data file and checked by two independent researchers. Respondent’s information was completely confidential and recorded anonymously. This study is a joint research project of Tongji Medical College, Huazhong University of Science and Technology and Hainan Medical College. The former institution was responsible for the study design and the latter was responsible for the data collection. The Medical Research Ethics Committee of Tongji Medical College, Huazhong University of Science and Technology approved the study [no. IEC (S175)] on March 1, 2018.Our primary outcome variable was the purchase of antibiotics online. Respondents were asked whether they bought any antibiotics online in the past 3 months. We defined respondents as purchasers of antibiotics online if they answered yes to the question.These variables included age , gender , ethnicity (Han or minority), geographic location , residence , education level , marital status , employment status (employed or not employed), self-reported economic status , health insurance status (insured or uninsured), whether suffering from physician-diagnosed chronic diseases (yes or no), and whether searching for health information online in the past 3 months (yes or no).p was less than 0.05.To account for the oversampling and the nonresponse, we used post-stratification weights, which corrected the distribution of respondents to match the known distribution of the Chinese population on age group, gender, residence, and geographic location . We calcDuring the study period, we distributed 171,335 questionnaire links, and 107,650 participants from 31 Chinese mainland provinces  completed the online questionnaire, with a response rate of 62.83%. Of them, 6530 who failed to pass the quality control questions were excluded. Finally, 101,120 respondents were included in the analysis. The mean age of the respondents was 30.43 (standard deviation: 13.12) years. Over half were female (58%), unmarried (63%), and living in urban area (60%). As for geographic location, 55, 22, and 23% lived in the eastern, central, and western China, respectively. Furthermore, 68% had an associate or bachelor degree, 91% had health insurance, 50% was employed, as well as 59% reported that their economic status was fair. Nearly one seventh of them (14%) suffered from physician-diagnosed chronic diseases, and 42% had searched for health information online in the past 3 months. Respondent’s characteristics are detailed in The overall weighted prevalence of antibiotic purchase online in the past 3 months was 3.71% . Additionally, the weighted prevalence was more than 6%  among those who were aged 65 years or older, and who had a graduate degree or higher education level, reported an excellent economic status, or searched for health information online. Whereas, there was no difference in the prevalence among residents with different marital or insurance status, as well as among those who lived in different regions of China. The crude and adjusted OR (aOR) for factors associated with antibiotic purchase online are shown in Additionally, residents who lived in rural areas , or suffered from chronic diseases  had higher odds of purchasing antibiotics online. Compared with those having a high school or lower degree, residents who had an associate or bachelor degree  as well as a graduate or higher degree  were more likely to purchase antibiotics from online pharmacies. In the past 3 months, those had searched for health information on the internet were more than three times  more likely to purchase antibiotics online.Our study showed that 3.71% of Chinese residents had purchased antibiotics on the internet in the past 3 months. Currently, few study on online antibiotic purchase behavior of residents has been conducted in other countries, but studies on prescription medicine purchase online have been carried out. Relevant studies showed that 0.45 and 5.00% of residents have purchased prescription medicines on the internet in Malta and the United States in the past year, respectively . Though The current study found that the female was less likely to buy antibiotics on the internet, which may be due to that they were more cautious about medicine purchase online. A study on the online medicine purchase behavior of Chinese residents reported that women were less inclined to buy medicines in online pharmacies due to their cautiousness . AdditioIn our study, residents with higher education level were more prone to purchase antibiotics online. This is consistent with the result of studies on factors related to self-medication with antibiotics, which found that higher education level was associated with irrational use of antibiotics . People In the past 3 months, nearly half of the residents had searched for health information on the internet, and they were more likely to purchase antibiotics online. This may be due to that they usually chose to seek information online to self-diagnose and self-medication when they suffered from illness. Information obtained online and internet usage habits may encourage them to purchase medicines online. It is very important to ensure that the internet provides correct health information and medication knowledge in the information age.To our knowledge, this is the first study to explore the prevalence of antibiotic purchase online among residents and identify its associated factors. We considered that this study will help the researchers and policymakers worldwide understand the online antibiotic purchase behavior of residents, as well as provide evidence for antibiotic stewardship. This study has several limitations. First, this study was conducted by using a convenience sampling method and web-based survey. These may affect the sample’s representativeness. However, the survey was conducted by trained investigators in urban and rural communities all over the country, the sample size was large, and post-stratification weights were used to correct the distribution of the respondents, which can make the results more nationally representative. Second, we investigated the online antibiotic purchase behavior in the past 3 months, and therefore, recall bias may exist. Third, we did not collect the information on types of antibiotics purchased online, medical conditions that required antibiotics, whether residents purchased antibiotics with a prescription or not, and other possible factors influencing the purchase behavior, which limited our more comprehensive understanding of the online antibiotic purchase behavior of residents.Our study investigated the online antibiotic purchase behavior of residents, which could provide evidence for researchers and policymakers worldwide to understand this behavior. Additionally, the study results showed that the prevalence of antibiotic purchase online was relatively high among Chinese residents. This implied that, on the one hand, the regulation of antibiotic sales online should be strengthened; on the other hand, there is a need to improve public education on antibiotic purchase online, so as to promote purchases of antibiotics with a prescription and rational use of antibiotics.As a new channel to obtain antibiotics, online antibiotic purchase has rarely been studied. Therefore, it is necessary to pay attention to this purchase behavior, and carry out more relevant researches. For the future studies, more detailed information of antibiotic purchase online should be collected, such as types of antibiotics purchased and whether residents purchased antibiotics with a prescription or not, so as to provide a more comprehensive reference for antibiotic stewardship. In addition, antibiotic is an important kind of medicines for the treatment of acute bacterial diseases. Online sales of antibiotics have improved the accessibility of these medicines among residents. However, considering that antibiotics should be used accurately and timely for patients when needed, whether online purchases of antibiotics will result in delay in treatment is a matter of concern. Extensive researches and discussions should be conducted to reveal the advantages and disadvantages of online sales of antibiotics.Our study found that numerous Chinese residents had purchased antibiotics on the internet. Age, gender, residence, education level, economic status, suffering from chronic diseases, and searching for health information on the internet were all significantly associated with the purchase behavior. Therefore, it is necessary to strengthen the regulation of antibiotic sales on the internet, and improve public education on antibiotic purchase online. In the future studies, more comprehensive information on antibiotic purchase online should be collected, as well as the advantages and disadvantages of online sales of antibiotics should be investigated.


Two eco-friendly healing bioproducts generated from microbial mixed cultures (MMC) for the production of polyhydroxyalkanoates (PHA) were used as surface treatments, with two residual materials used as the substrates, namely crude glycerol and pinewood bio-oil. Their ability to improve the durability of concrete samples containing recycled aggregates was assessed. To determine this protective capacity, 180 samples were analyzed using different tests, such as water penetration under pressure, capillary absorption, freeze–thaw and water droplet absorption test. Three types of conditions were used: outdoor–indoor exposure, re-application of biopolymers and application in vertical exposure conditions. The results showed reductions of up to 50% in the water penetration test and a delay in the water droplet absorption test of up to 150 times relative to the reference. The surface application of these bioproducts significantly reduced the degree of water penetration in recycled concrete, increasing its useful lifespan and proving to be a promising treatment for protecting concrete surfaces. The global population growth over the past 100 years has resulted in rapid industrial and urban development. Considering the properties of concrete, namely its versatility, resistance and low cost, a large increase in the demand for this material has been occurring, making it the second most extensively used material worldwide, only behind water  ,67 29,67Some researchers ,96,97,982O) in all tests, although the improvements were particularly noticeable in the pressurized water penetration and water drop absorption tests;The treatments with the bioproducts showed significant improvements relative to the reference concrete  and pinewood bio-oil (SP) as the carbon sources, were applied on the surfaces of concrete samples produced with partially recycled aggregate. The protective effects of the bioproducts were evaluated experimentally through six different tests. The conclusions obtained were as follows:The incorporation of two waste materials such as crude glycerol and pinewood bio-oil to produce the bioproducts used to improve the capacity and durability of recycled concrete has a positive environmental impact. This strategy involves two routes leading to a more circular economy, both by reducing waste and improving waste management, thereby reducing the consumption of energy and natural resources.In summary, this research shows the effectiveness of both bioproducts in protecting the surfaces of recycled aggregate concrete samples against water penetration and the consequent risk of deterioration and decrease in their useful lifespan; that is, the useful lifespan and performance of recycled concrete are increased, encouraging the use of construction wastes as aggregates, thereby reducing the volume of such waste.


Objective: This study aimed to evaluate the effects of intensified Chinese special rectification activity on clinical antibiotic use (CSRA) policy on a tertiary-care teaching hospital.Methods: A 48-month longitudinal dataset involving inpatients, outpatients, and emergency patients were collected. Study period included pre-intervention stage (adopting soft measures like systemic training) and post-intervention stage (applying antibiotic control system to intensify CSRA policy). Antibiotic use was evaluated by antibiotic use rate (AUR) or antibiotic use density (AUD). Economic indicator was evaluated by antibiotic cost in prescription or antibiotic expenditure in hospitalization. Data was analyzed by interrupted time series (ITS) analysis.Results: The medical quality indicators remained stable or improved during the study period. AUR of inpatients (AURI) declined 0.553% per month (P = 0.025) before the intervention and declined 0.354% per month (P = 0.471) after the intensified CSRA policy was implemented. AUD, expressed as defined daily doses per 100 patients per day (DDDs/100PD), decreased by 1.102 DDDs/100PD per month (P = 0.021) before and decreased by 0.597 DDDs/100PD per month (P = 0.323) thereafter. The ratio of antibiotic expenditure to medication expenditure (AE/ME) decreased by 0.510% per month (P = 0.000) before and fell by 0.096% (P = 0.000) per month thereafter. AE per patient decreased by 25.309 yuan per month (P = 0.002) before and decreased by 7.987 yuan per month (P = 0.053) thereafter. AUR of outpatient (AURO) decreased by 0.065% per month before (P = 0.550) and decreased by 0.066% per month (P = 0.994) thereafter. The ratio of antibiotic cost to prescription cost in outpatient (ACO/PCO) decreased by 0.182% per month (P = 0.506) before and decreased by 0.216% per month (P = 0.906) thereafter. AUR of emergency patient (AURE) decreased by 0.400% per month (P = 0.044) before and decreased by 0.092% per month (P = 0.164) thereafter. The ratio of antibiotic cost to prescription cost in emergency patient (ACE/PCE) decreased by 0.616% per month (P < 0.001) before and decreased by 0.151% per month (P < 0.001) thereafter.Conclusions: Implementation of CSRA policy was associated with declining antibiotic use and antibiotic expenditure in inpatients, outpatients, and emergency patients. However, it is also important to note that the declining trend of antibiotic consumption slowed due to the limited capacity for decline in the later stages of CSRA intervention. Antibiotics have been widely used for more than 70 years. During this time, inappropriate or excessive use of antibiotics has accelerated antibiotic resistance. Substantial reports have demonstrated the causal relationships between antibiotic consumption and selective pressure in resistant organisms –4. HenceThe overuse of antibiotics is also a serious problem in China . The perMany Chinese studies have evaluated the impact of CSRA guidelines on antibiotic use in hospitals and affirmed the positive outcomes yielded by this policy –18. HoweChangzhou No. 2 People's Hospital, a 2,200-bed tertiary general hospital affiliated with a medical university in Jiangsu, began to implement CSRA guidelines in 2011. First, the implementation of the policy consisted of soft measures such as founding an AMS team, implementing systemic training, and strengthening the education of healthcare providers. By April 2012, an antibiotic control system (ACS) was constructed in this hospital which integrated specific targets of the CSRA policy into the original Hospital Information System (HIS). Rigid measures have been deployed over the entire hospital to intensify the AMS since April 2012.Here, we conducted an interventional study in this hospital from 2011 to 2014, with a focus on how antibiotic use and economic indicators differed before and after the intensified intervention. Combined with interrupted time series (ITS) analysis, the strongest and quasi-experimental approach for evaluating longitudinal effects of intervention , and the post-intervention period was defined as from April 2012 to December 2014 .First, we briefly introduce the Chinese special rectification activity on clinical antibiotic use (CSRA) initiated by the Chinese government in 2011. This policy strengthens the clinical antibiotic management in thirteen detailed ways. The five most important ones are as follows: (1) antibiotics are categorized into three classifications, namely, unrestricted, restricted, and special level. For each level of antibiotics, they can only be prescribed by clinicians who have been authorized according to their technical titles; (2) limit the number of antibiotics used in hospitals. In a general tertiary hospital, the total number of unique antibiotic cannot exceed 50; (3) set a specific target for antibiotic use. Antibiotic use rate (AUR) of inpatients, emergency patients, and outpatient cannot exceed 60, 40, 20%, respectively. AUD should be controlled under 40 DDDs/100PD in a general tertiary hospital; (4) microbial specimen detection is required before antibiotic use and detection rate of inpatients must exceed 30%; (5) vetting exercises should be carried out periodically by infectious disease experts or clinical pharmacists. In response to the policy of the government, Changzhou No. 2 People's Hospital began to implement the CSRA policy in 2011. At first, soft measures such as founding an AMS team , systemic training, and education were only adopted. Thus, we defined the period from January 2011 to March 2012 as pre-intensified policy stage.Here, we emphatically introduced the intensified CSRA policy. In April 2012, rigid measures were deployed over the entire hospital to intensify AMS. We developed an ACS and integrated it into HIS. In ACS, the classification of antibiotics and prescription authorization are computerized. Data related to AUR, AUD, and microbial specimen detection rates of each ward can be easily retrieved from the ACS. Clinicians in each ward would receive bonuses if they met the quota, or penalties if the quota was not met. In addition, for each inappropriate prescription, there was a penalty of 50 yuan, and for each inappropriate medical record, the penalty increased to 500 yuan. In short, ACS, along with awards and penalties, offered better opportunities and incentives to optimize antibiotic use. Thus, we called it intensified CSRA policy. We defined the period from April 2012 to December 2014 as post-intensified policy stage.In this study, four items, namely, antibiotic use rate of inpatients (AURI), AUD, the ratio of antibiotic expenditure to medication expenditure (AE/PE), and antibiotic expenditure per patient (AE per patient) were selected as indicators of inpatient antibiotic use. AUD is defined as the number of defined daily doses/100 patient-days (DDDs/100PD) according to the anatomical therapeutic chemical (ATC)/DDD classification stated by WHO. DDD is the average daily dose in grams of a specific agent given to an average adult patient.We selected three indicators to evaluate antibiotic use of outpatients, namely, antibiotic use rate of outpatients (AURO), antibiotic cost of outpatient/total prescription cost of outpatient (ACO/PCO), and antibiotic cost per patient in outpatient (ACO per patient).Similarly, we selected three indicators to evaluate antibiotic use of emergency patient which include antibiotic use rate of emergency patients (AURE), antibiotic cost of emergency patient/total prescription cost of emergency patient (ACE/PCE), and antibiotic cost per patient in emergency patient (ACE per patient).The values of outcome variables were calculated at the hospital level every month, and the measurement is explained in detail in During the study period, medical quality indicators were also captured in hospital-wide population level every year. They were the number of hospitalizations, patient-days, recovery rate, improvement rate, invalid rate, mortality rate, and nosocomial infection rate.We briefly describe ITS analysis, the strongest quasi-experimental approach, for evaluating the longitudinal effects of intervention when a control group is unavailable or unethical . This tyIn this model, the results of each variable are presented in three parts as described in our previous study . They arY is the main outcome indicator, such as the AURI; T is a continuous time variable, assigning 1–48 in this study; D is a dummy variable assigned a value of 0 before intervention and 1 after the intervention; P is a time variable counting the number of months after the intervention—for the time before the intervention, P = 0, and after the intervention, P is assigned a value from 1 to 34 in this study; ε is a random variable which cannot be explained in the linear model, which we designate the “error term”; β0 is the baseline level of the outcomes when T = 0; β1 is an estimate of changing trends during the pre-intervention period; β2 is the level of changes in the policy intervention; β3 is the trend change of the outcome caused by the policy intervention. Here, β1 + β3 represents the final trend of the outcome variable after policy intervention, which we call the net effect. A graphical illustration of the ITS model is shown in where Linear regression was carried out in order to assess the changes in trends of medical quality indicators during the study period. The linear trend by year is defined as the slope of the response over time, expressed by a coefficient (β).p-value of ≤ 0.05.The Durbin–Watson test is the most commonly used method for testing first-order autocorrelation of data . GeneralP = 0.011 and 0.012, respectively). Simultaneously, the average length of stay and recovery rate both significantly decreased , and the incidence of mortality mildly decreased . There was no significant change in the invalid rate . Meanwhile, the nosocomial infection rate appeared to be declining, however, the results was not statistically significant . In summary, medical quality indicators remained stable or improved during and after the implementation of CSRA policy.As shown in P < 0.001) after the implementation of the intensified CSRA policy. AUD dropped from 87.02 to 58.26 DDDs/100PD (P < 0.001) after intervention. AE/ME was significantly decreased, from 24.04 to 17.49% (P < 0.001). Moreover, AE per patient decreased, resulting in a savings of 322.56 yuan per patient after intervention (P < 0.001). Overall, the intensified CSRA policy had a positive effect on reducing antibiotic use in inpatients.The overall changes in the three indicators with regard to antibiotic use in outpatient are displayed in The overall changes in the three indicators with regard to antibiotic use in emergency patients are displayed in P = 0.037). However, after that, the downward trend gradually slowed down, decreasing at 0.597 DDDs/100PD (P = 0.323) per month. (3) AE/ME: AE/ME decreased before the intensified CSRA policy was implemented, and the rate of decrease was 0.510% per month (P = 0.000). The ratio dropped by 1.344% (P = 0.123) in the first month of intervention. Subsequently, AE/ME fell at a rate of 0.096% (P = 0.000) per month, which was significantly lower than that in the previous period. (4) AE per patient: AE per patient decreased at the rate of 25.309 yuan (P = 0.002) per month during the pre-intervention period. After the intensified CSRA policy was executed, no significant decline was noted immediately. In the post-intervention period, AE per patient decreased by 7.987 yuan (P = 0.053) per month, and the rate was significantly lower than before. In general, antibiotic use and expenditure in inpatients notably decreased during the pre-intervention period and the declining trend gradually tapered after the intensified CSRA policy was implemented.The ITS analysis and the changing trend of four indicators with regard to inpatient antibiotic use are displayed in P = 0.550) per month before the intervention. An immediate drop of 1.731% (P = 0.097) was observed at the beginning month of intervention. After the intervention, the decreasing trend seemed to become slightly sharper at a rate of 0.066% (P = 0.994) per month, although this decrease was not statistically significant. (2) ACO/PCO: ACO/PCO declined at a rate of 0.182% (P = 0.506) per month before the intensified policy was implemented. The ratio instantly increased by 0.892% (P = 0.744) in the first month of intervention. After the intervention, the declining trend accelerated to a rate of 0.216% (P = 0.906) per month. (3) ACO per patient: Surprisingly, ACO per patient increased at a rate of 1.965 yuan per month (P = 0.003) before the intervention. At the beginning of the intervention, this indicator increased to a level of 14.623 yuan (P = 0.021) immediately. After that, the increasing trend of ACO per patient slowed down, increased by 0.320 yuan (P = 0.021) per month. In general, AURO and ACO/PCO gradually decreased before the intervention and the intensified CSRA policy accelerated the downward trend. Although ACO per patient significantly increased during the pre-intervention period, the intensified CSRA policy curbed the rapid increase of this indicator.P = 0.044) per month. At the beginning month of the intervention, there was a notable decrease in the level of 4.817% (P = 0.009). After the intervention, the declining trend gradually slowed down, decreasing by 0.092% (P = 0.164) per month. (2) ACE/PCE: ACE/PCE decreased before the intervention, and the rate of decrease was 0.616% (P <0.001) per month. At the beginning of the intervention, the ratio dropped greatly by 2.492% instantly (P = 0.020). However, the downward trend slowed down after the intervention, and decreased at a rate of 0.151% (P <0.001) per month. (3) ACE per patient: ACE per patient increased at a rate of 0.208 yuan (P = 0.591) per month before the intervention. At the beginning month of the intervention, this indicator increased to a level of 11.398 yuan (P = 0.005) immediately. After that, ACE per patient began to decrease at a rate of 0.422 yuan (P = 0.133) per month. In general, AURE and ACE/PCE notably decreased before the intervention, and the declining trend gradually tapered after the intensified CSRA policy was implemented. Although ACE per patient increased during the pre-intervention period, intensified CSRA policy stopped this increasing trend and showed a positive effect on reducing the antibiotic cost in the emergency patient.The ITS analysis results and the changing trend of antibiotic use with regard to emergency patients are shown in During and after the study period, the rate of nosocomial infection remained stable, and the rate of mortality mildly decreased, which indicates that the continued decline in antibiotic use is unlikely to negatively impact the quality of medical care provided.The findings of this study demonstrate that antibiotic use of inpatients (AURI and AUD), outpatient (AURO), and emergency patients (AURE) notably decreased in the pre-intervention period from January 2011 to March 2012. Thus, it was apparent that soft measures such as systemic training and education play an important role in reducing antibiotic use. Similarly, a study by Onorato et al.  also conThe impact of intensified CSRA policy on antibiotic expenditure  is almost the same as that of antibiotic use. The growth trajectories of the cost indicators changed from a steep descending trend to a softened descending trend. As stated above, there is little room for a further decline in the later stages of intervention. We were even delighted to see that the downward trend of ACO/PCO sharpened after the intensified CSRA policy was implemented. But to our surprise, ACO per patient increased by 36.05 yuan and ACE per patient increased by 5.51 yuan in pre- post-comparisons. In the ITS analysis, ACO per patient also greatly increased prior to the full implementation of the intensified CSRA policy, which is inconsistent with other indicators. Maybe we can interpret this phenomenon from the policy itself. The CSRA policy only imposed quotas of AUR and AUD, but no claims were made about the cost of antibiotics. Thus, physicians might prescribe expensive antibiotics to ease the impact of the policy in the short term. Additionally, drug price inflation may also contribute to the increase of antibiotic cost during the whole study period. Similar findings have been reported in other studies where antibiotic expenditure fluctuated before reaching a stable status over a prolonged period , 29. EncAfter 4 years of CSRA implementation in this hospital, AURO decreased from 25 to 22%, and AURI decreased from 65 to 54% in the last month of the study period. These two indicators are quite close to the goals set by the CSRA policy. However, AURE gradually approached 55% and AUD approached 52 DDDs/100PD in the last month of the study period, which far exceeded target values (AURE of 40% and AUD of 40DDDs/100PD). This begs several questions: are the goals of AURE and AUD set by the CSRA policy reasonable? To what extent is further reduction achievable without endangering the quality of care in this hospital? In China, data from 114 general tertiary-care hospitals in 30 provinces showed that the rate of antibiotic prescription was 27.82% in emergency departments in 2016 . AnotherWe acknowledge that there are some limitations to our study. First, this study was a single-center study without a control group. Although ITS analysis was applied to minimize the threats to internal validity, we still could not ensure that CSRA policy implementation was the only reason for the changes we report in our findings. A concurrent control hospital can be implemented in future studies to account for simultaneous secular trends in antibiotic use . Second,In summary, this study provides detailed ITS analysis of the impact of CSRA policy (soft measures and intensified rigid measures) on antibiotic use in a single teaching hospital. Implementation of CSRA policy was associated with declining antibiotic use and antibiotic expenditure in inpatients, outpatients, and emergency patients. However, it is also important to note that the declining trend of antibiotic consumption slowed down due to the limited capacity for a decline in the later stages of CSRA intervention.The original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding author/s.Institutional Ethics Committee approval was obtained from the Nanjing Medical University Ethics Committee . Due to this being a retrospective study, the patient data were aggregated and the individual patients' information was not reported in this study. Therefore, the study was approved with a waiver for informed consent.XQ and XL initiated the study concept. XQ conducted data analysis and wrote the first draft of the manuscript. YP and JG collected the data of inpatients. SX and YL led the data collection of outpatients and emergency patients. XL and DS contributed to the data analysis and interpretation of the data and also revised the draft of the manuscript. All the authors read and approved the final manuscript.This study was supported by the National Natural Science Foundation of China (Grant No: 71673147), the Jiangsu Pharmaceutical Association Aosaikang Hospital Pharmaceutical Fund (Grant No: A201621), the China Medical Board (Grant No: 17-277), and the Joint Project between Southeast University and Nanjing Medical University (Grant No: 2018DN0023).The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Alkali-activated concrete (AAC) could be a solution to use a cement-less binder and recycled materials for producing concrete reducing the carbon dioxide emission and the demand for raw materials, respectively. In addition to the environmental aspect, AACs can achieve mechanical characteristics higher than those of ordinary Portland concrete (OPC) but also an improvement of the thermal insulation capacity. Despite the positive results available in the scientific literature, the use of AACs in construction practice is still limited mainly due to the absence of codification for the mix design and consequently of specific design rules. In this paper, AAC produced by ground-granulated blast-furnace slag (GGBFS) and silica fume is investigated for the production of structural elements and to discuss the reliability of formulations for evaluating mechanical properties, necessary for structural design. The mechanical strengths  are evaluated by experimental tests according to different curing times  in ambient conditions and the thermal conductivity is measured to understand the effect that the material could have on thermal losses for a sustainable building perspective. The results showed that AAC strengths depend on the curing time and the exposure conditions, and the insulation properties can be improved compared to the traditional Portland cement with the proposed composition. The environmental and economic concerns associated with conventional cement-based building materials have led the scientific and technical community to explore possibilities in the use of alternative materials.2 emissions originate from the manufacturing of Portland cement [Currently, the concrete industry faces two main challenges that are the increasingly limited limestone reserves and the carbon taxes increase because of the growing demand for Portland cement (OPC) and the greenhouse gas emissions resulting from the production of OPC, respectively . Indeed,d cement , and itsd cement .2 emissions lower than those necessary to produce OPC [These issues require the development of alternative binders, such as alkali-activated cement (AAC), with the aim of reducing the environmental impact of buildings, the use of a greater percentage of pozzolan waste and improving concrete performance . From thduce OPC ,7, with duce OPC . Other rduce OPC  and therduce OPC ,11. Baseduce OPC . In addiduce OPC .Despite the advantages mentioned above, the use of alkali-activated materials in buildings and civil engineering, that is, as structural material, is limited by the lack of consistent guidelines for the mixture proportioning design ; furtherThis study was a part of a research activity that was aimed to evaluate the performance of ground-granulated blast-furnace slag (GGBFS) and silica fume-based alkali-activated concrete for the application as structural elements . During the research activity, many mixtures were developed and the most promising is the one discussed herein. The main scope of the paper was to discuss the reliability of formulations for evaluating mechanical properties necessary for structural design. The mixture was mainly designed to obtain good structural performance, but considering the current attention to the multifunctional use of new materials and the sustainability of the buildings, the thermal behaviour is worthy of investigation, especially for realizing blocks. It is known that the improvement of the thermophysical properties is usually matched with a reduction of the density and thus of the mechanical performance, therefore finding a mix design that provides a material with good structural and thermal performance is the current challenge. Hence, experimental tests carried out at the Laboratory of Materials and Structures (LAMAS) of the University of Sannio  were performed to evaluate the main structural strengths, such as the compression strength, the splitting tensile strength and the flexural strength, according to different curing time; in addition, the characterisation of the material was completed with the tests for determining the thermal conductivity performed in the Insulating Material Thermal Analysis laboratory (IMATlab) of the University of Naples Federico II . In the available literature, very few researchers consider the combined effect of slag and silica fume on the mechanical and thermal parameters of alkali-activated concrete, instead, the evaluation of thermal behaviour is usually investigated for lightweight aggregate foamed geopolymer concrete whose insulation properties can be attributed to the porosity and voids of the microstructure.The experimental evaluation of the mechanical strength allowed us to analyse the reliability between measured values and those prevised by standards provisions for OPC, which usually provide the relationship for tensile and flexural strength as a function of the compression one, pointing out the unsuitableness of the current codes in describing the AAC behaviour. Formulations developed by previous authors specifically for AAC were also considered.Alkali-activated materials (AAMs) are formed by the reaction between alumino-silicates precursors with an alkaline chemical activator. These products are also named geopolymers (GPC), but even if chemically similar they are based on different aluminosilicate precursors. Indeed, geopolymers are viewed as a subset of AAM with the highest Al and lowest Ca concentrations . In this2SiO3), sodium silicate (Na2SiO3), sodium carbonate (Na2CO3) or a combination of these alkalis [Specifically, the typical precursors for the alkali-activated systems are cementitious materials such as steel and blast furnace slag (SG), or pozzolanic materials such as fly ash (FA), metakaolin (MK), silica fume (SF), rice husk ash (RHA). Various alkali activators can be used to activate the binder, such as potassium hydroxide (KOH), sodium hydroxide (NaOH), potassium silicate  and type of alkaline activator;Si/Al ratio of precursor materials and quantity of available calcium sources such as Portland cement, blast furnace slag and lime;Total water/solids ratio ;Curing conditions.Research on the AAC has shown that the main parameters affecting the fresh and hardened properties include:It should be clarified that the exact contributions of these parameters to the strength are still not fully clear, consequently the various mixture design methods proposed in the literature are usually empirical or experimental .Regarding the precursor materials, mixtures with fine particles activated with alkali exhibit greater workability and require less water due to the reduction of porosity and to the increase of the surface in the finer particles ,25. The The water to geopolymer solids ratio has been observed to have an inverse relationship with the compressive strength of concrete, instead, it has a direct relationship with the workability, similar to that observed between water/cement ratio and behaviour of OPC concrete .Curing temperature has a significant effect on the microstructural and mechanical strength development of the geopolymer system. Generally, the geopolymerisation is accelerated at a higher temperature than the ambient one: it was observed the existence of an optimum curing temperature (60 °C) that allows the achievement of the best physical and mechanical properties .Several mixes of geopolymer concrete based on low calcium FA activated by solutions of sodium silicates and sodium hydroxide were analysed by various authors ,37,38,39In contrast to the case of elastic modulus, previous studies showed that the tensile strength of GPC was usually higher than that of the OPC concrete at the same compressive strength. In particular, the tensile strength of geopolymer concrete is affected by the type of raw materials: for instance, the decrease in the amount of additional water , the incSimilarly, to the tensile strength, geopolymer concretes exhibit higher flexural strength than ordinary ones ,48, and Several researchers are focused on the evaluation of the incidence of the geopolymeric process on other properties as thermal conductivity, sound absorption and durability. However, the main results regard the geopolymer foam concrete  for whic2SiO3) have found a maximum of compressive strengths at 1.7 MPa and the minimum thermal conductivity at 0.31 W/m K. Baran et al. [It is worthy of investigation the analysis of the thermal behaviour of not aerated geopolymer concrete that can also show high structural characteristics. More in general it has been obtained that for the metakaolin-derived Na, NaK, and K geopolymers, the thermal conductivity is closely linked with the specific heat, with little variation in thermal diffusivity observed in different conditions . The sann et al.  have indn et al.  have ind2O2) and decreases with increasing bagasse ash content. The increase in porosity resulted in a decrease in compressive strength but with a significant reduction in thermal conductivity from 0.3194–0.4519 to 0.1532–0.1857 W/m K with 1–1.5 wt% H2O2 addition and 10–20 wt% bagasse ash replacement.Pantongsuk et al.  have fouThe alkali-activated concrete used in these experimental tests included gravel (4–14 mm), sand (<4 mm), filler power with limestone and gypsum (<0.07 mm), grand granulated blast furnace slag (by-product of iron and steel-making) and silica fume  as solid part . The che2/Na2O) of 1.6 with 27.50% by weight SiO2, 17.19% by weight Na2O, and a solid content of 44.69% by weight; water was used to complete the mix design. The addition of a naphthalene-based superplasticizer with a dosage of 2% by weight with respect to the binder improved its workability. Details of the mixture proportions used in this study are shown in The alkaline activator consisted of a commercially available sodium silicate (SS) solution having a modulus  were poured over the solids and then they were mixed for about four minutes until a homogeneous compound was obtained;Step 3: the freshly prepared geopolymer concrete was poured into different type molds  in three layers and vibrated by means of a vibrating table to remove any entrapped air;Step 4: specimens were demolded within 48 h after casting and were stored in ambient conditions until the test day.The mixing protocol applied in this study included the following steps:During the casting procedure, it was observed a fast setting of the mixture adhered strongly to the mold. The workability of AAC is generally lower than that of OPC concrete due to the presence of silicate in AAC would provide a sticky characteristic , therefoHence, it is noted that the specimen’s preparation is a crucial phase that needs to be performed accurately for the correct success of the experimental program. The test program consists of mechanical and thermal characterisation. In Mechanical characterisation was carried out according to the standards EN 12390-3 , EN 1239cf of the specimens was determined as follows:In particular, the compression tests were performed on cylinders with height-to-diameter ratio As for the compression test, cylindrical specimens  instrument is used for the measurement of the thermal conductivity (λ) of two specimens according to the standard ISO 8302 . Several® system, high-temperature version [® machine used in the above test.More in detail, The GHP principle is based on an absolute measurement method and therefore requires no calibration standards. The NETZSCH GHP 456 Titan version  was usedt. Thus, the samples are placed between two heated plates set to different temperatures. These temperatures are regulated by means of the heating  and cooling (liquid nitrogen) systems. During the test, the desired temperature difference ΔT is established between the hot and the cold plates. The guard ring has the aim to minimize lateral heat losses. When the steady-state conditions are reached, the thermal conductivity is calculated according to the Fourier law, as reported in Equation (4) where the factor 2 is present because the measure is performed on two samples:T is the temperature difference;the factor 2 is present because the measure is performed on two samples.The measurement is done by means of two plates with different temperatures and a guard ring that must host two samples of the material with the same thickness 3, which is slightly lower than the density of OPC concrete.The mass and the dimensions of the specimens were measured before conducting the tests in order to calculate the average unit weight of the geopolymer concrete that resulted in approximately 2300 kg/mcmf approximately doubled from tests performed at 7 days of curing to those at 14 days and improved from 7 days to the long-time, but a reduction of about 16% and 43% has been observed at 28 and 90 days compared to 14 days, respectively. Regarding the dispersion of the data, a higher value of COV (up to 23%) affected the measures at curing times greater than 14 days.According to previous studies ,73,74, tAll the measured properties at 90 days showed a degradation of the strength; this effect could be related to the curing conditions in environments with high humidity or with uncontrolled humidity, as happened for the tested specimens, which played an important role in the development of compressive strength . Indeed,2 = 0.94) that is equal to 25.2 MPa.As the reduction of compression strength was observed for curing times greater than 14 days, the experimental mean values of compression strength, also indicating the standard deviation for each experimental value, are plotted with reference to the inverse of the test age . This alThe behaviour of the AAC identified in this study does not reflect that of the ordinary concrete cured in standard conditions for which the increase in strength is expected over time. Therefore, the qualification rules in terms of control times and environmental conditions used for the ordinary concrete cannot be applied to this material, but new procedures need to be developed especially for the identification of the design strength. In particular, if standardised mixtures are defined a specific set of tests in compression at different curing times can be established (three ages at least) to extrapolate the effective resistance at a long time by the proposed procedure.In addition, the reduction of the compressive strength is relatively more considerable than that of the tensile and flexural strength; the latter varies much lower compared to the tensile strength showing also lower dispersion of data.However, further analyses by monitoring the microstructural and mineralogical developments are needed to better understand the behaviour of the material also for durability issues in the long term.Eurocode 2 (EN 1992)  for streAmerican Standards (ACI 318) (6)fctm=In order to analyse the tensile and bending resistance of AAC, it is useful to compare the experimental results reported in Various studies have acknowledged that geopolymer concrete shows a better performance in tension compared to the provisions for OPC ,48,49,81 363R-92  and Mode 363R-92 , proposiOther formulations based on experimental investigations were suggested by Lee-Lee   that is also safe because the raw materials used and the curing conditions applied in this study are similar to those reported in Ref. . Instead2 = 0.91, which confirm the efficiency of the type of formulation.Considering the experimental measures from Regarding the tensile resistance in flexure, o et al. . These ro et al. , the useT) of 6 °C between the hot plate and cold ones is set in all cases. Thermal conductivity is the most important thermal property that affects heat transfer by conduction through concrete. The adoption, also for structural elements, of concrete with low thermal conductivity, contributes to reducing the heat losses of the building envelope and thus the building energy consumptions. Specifically, the thermal conductivity indicates the quantity of heat transmitted through a unit thickness in a direction perpendicular to a surface of the unit area, due to a unit temperature gradient under given conditions. It influences the conduction heat transfer. Two geopolymer panels have been used for the measurement of thermal conductivity. The operation temperature of such panels, considering typical ranges for the buildings, can generally vary between −10 °C and 50 °C in most climatic zones, worldwide. Therefore, this latter property is measured at three temperature (T) levels, i.e., −10 °C, 20 °C and 50 °C. In this regard, a temperature difference . For instance, Wang et al.  for the TC: traditional concrete with high density ;MT: traditional mortar ;CF1: modified concrete with fly ash (FA1) ;OPSNFGC and OPSFGC15: oil palm shell respectively non-foamed and foamed geopolymer concrete  utilizinFA30: concrete with fly ash in 30% cement replacement ;FA+BSF: concrete with fly ash and blast furnace in 30% cement replacement ;FC: foamed concrete with medium density ;SF+SI: concrete containing 2% silane and 15% silica fume as admixture .The value of measured thermal conductivity is influenced by the spatial spreading and volume ratio of mixed elements and voids created during the process also of a high-density material. For understanding the effect of adding slag and silica fume to the production process, the value measured at 20 °C is compared with the thermal conductivity of other geopolymer concrete (foamed or not) and traditional materials as reported in the scientific literature. As seen from Moreover, it can be noted that the measured conductivity is comparable to non-foamed geopolymer concretes (lower than −2.0%) and to foamed concrete but the density is higher respectively of 28% and 44%. The improvement compared with the foamed concrete is not expected because in this case, the improvement of thermal conductivity is due to foaming agents that generate a large volume of artificial pores in hardened pastes, leading to increasing the thermal resistance. However, the foamed binder pastes are usually not suitable for structural purposes, due to their significantly low strength. Moreover, literature findings indicate that for reducing the thermal conductivity of concrete two solutions can be adopted, or the replacement of normal weight aggregates by lightweight aggregates or the replacement of Ordinary Portland Cement by supplementary cementing materials; however, these techniques generally compromise the mechanical properties as in the case of foamed concrete.Thus, the purpose of the proposed experiment is to demonstrate that the obtained mixture conjugates good thermal and mechanical properties.In addition to affecting the structural behavior, the higher value of density positively influences the thermal inertia/capacity enhancement of the building envelope, which is highly effective during the cooling season because it increases lag and attenuation of the heatwave.Finally, it wants to be remarked that this comparison is affected by several factors that can modify the mix design of a specific mixture, and the final results can be largely get affected by such parameters. In the future, some other mixes will be prepared and utilised for comparison under the same thermal testing conditions.A rapid setting of the mixture has been observed during the manufacturing process, therefore, the difficult workability can be a challenge to face during casting;The compression strength of alkali-activated concrete is affected by test age and significant performance is obtained already in the early days of curing;The long-term measured properties showed a degradation of the strength probably due to the curing conditions in humid environments that could favor the development of the sub fluorescence phenomenon and the carbonatation causing internal damage to the material. In addition, it is necessary to define new qualification procedures and identify more standard mixtures because AAC is sensitive to the curing regime. The proposal could be a procedure with a fixed number of tests for various curing ages and the extrapolation of the long-term resistance;The measured values of tensile strength The experimental flexural strength resulted much greater (quite double) than the values calculated applying the formulations of codes as a function of the compressive strength or strength in pure tension. This phenomenon is due to a higher interparticle bond between geopolymer binder and aggregate, but also in this case the result cannot be generalised for all the mix designs. Anyway, the relation of the tensile strength in flexure with the strength in compression is well fitted by a formula as The measured thermal conductivity is affected by the test temperature but the reference value at 20 °C is 0.57 W/m K. This value is about 60% lower than traditional products with the same density and 14% higher compared with foamed geopolymer concrete with half the density value. The adoption of structural and non-structural building components would help to reduce the heat losses  but also the overheating problem during the summer period (thanks to high density) and thus the yearly energy consumption.In this research, the mechanical and thermal properties of alkali-activated concrete produced by silica fume and GGBFS were investigated by experimental tests. The main results are summarised below:Finally, the results of the experimental campaign give preliminary information on the potential of the proposed mix for the application in the construction sector as bearing block or blocks for infill walls due to high compressive strength, good performance in tension and lower thermal conductivity. Additional experimental and simulation studies are needed both to complete the understanding from the mechanical side, such as in the fields of multiaxial stress states and long-term mechanical properties, both to evaluate the effect of different environmental conditions on the thermal conductivity and also to test the amount of energy savings. Nevertheless, a standardisation of the mix design supported by specific procedures of qualification  and design formulations are necessary to really employ the material.