Patients in the case group had a higher level of serum IgG4 , IgE  and ESR . High IgE level ) and other types of allergic disease ) were risk factors for patients in the case group, in which most patients had nasal manifestations before the diagnosis of IgG4-RD. The median time interval from nasal symptoms appearance to IgG4-RD diagnosis was − 120 and − 90 months for patients complicated with AR and CRS, respectively. IgG4-RD patients are often complicated with AR/CRS and have distinct characteristics, which appear to be a subgroup of IgG4-RD. The data suggests a pathogenic association of IgG4-RD and AR/CRS.In clinical practice, we found that IgG4-related disease (IgG4-RD) patients complicated with allergic rhinitis (AR)/chronic rhinosinusitis (CRS) seemed to have unique characteristics different from patients with IgG4-RD alone. In this study, demographic, clinical and laboratory characteristics of IgG4-RD patients complicated with AR/CRS were investigated. We retrospectively analyzed 756 IgG4-RD patients who were recruited in four medical centers from 2009 to 2021. We divided 756 IgG4-RD patients into 2 groups: the case group included IgG4-RD patients complicated with AR/CRS, and the control group included IgG4-RD patients without AR/CRS. 411 patients were complicated with AR/CRS among 756 IgG4-RD patients. Multiple organs involvement (≥ 3,  The characteristic pathological features of IgG4-RD are lymphocyte and plasmacyte infiltration, storiform fibrosis, and obliterative phlebitis5. IgG4-RD was recognized as isolated entities incipiently and was first described in pancreas in a cohort of Japanese patients in 20016. Subsequent studies found that it was a systemic condition and could affect nearly any anatomic site8.IgG4-related disease (IgG4-RD) is an immune-mediated systemic disorder that is typified by sclerosing lesions in multiple organs10. AR diagnosis is based on clinical manifestations, signs, and skin prick test as well as serum specific IgE detection indicating allergen-specific IgE. Chronic rhinosinusitis (CRS) is the mucosal inflammation of paranasal sinuses12. The cardinal manifestations of CRS are mucopurulent drainage, nasal obstruction, decreased sense of smell and facial pain-pressure-fullness.Allergic rhinitis (AR) is an inflammatory condition that is resulted from immunoglobulin E (IgE)-mediated mucosal inflammation to inhaled allergens, presenting nasal symptoms like sneezing, nasal obstruction, rhinorrhea and nasal itching13. Subsequent studies demonstrated that immunohistochemical examination in some IgG4-RD patients with nasal symptoms showed abundant IgG4-positive plasma cell infiltration in the nasal and paranasal sinus mucosa15. However, studies about the nasal involvement of IgG4-RD had limited samples and mainly focused on CRS17. In clinical practice, we found that IgG4-RD patients complicated with AR/CRS seemed to have unique characteristics different from patients with IgG4-RD alone. In this study, we retrospectively analyzed the demographic, clinical and laboratory disparities in the 756 IgG4-RD patients. To our knowledge, this is the largest cross-sectional cohort study comparing the two phenotypes of IgG4-RD with and without CRS/AS. Confirming the characteristics of these two groups could refine the classification of IgG4-RD and suggest the pathogenic association of IgG4-RD and AR/CRS.Sinusitis was first recognized as a complication of extra-pancreatic lesions of autoimmune pancreatitis in 201118, and 479 (63.4%), 96 (12.7%) and 181 (23.9%) cases were diagnosed as definite , probable  and possible IgG4-RD  in all enrolled patients, respectively. The exact clinical, serological and pathological diagnosis criteria are18: (1) Clinical diagnosis criteria: One or more organs show diffuse or localized swelling or a mass or nodule characteristic of IgG4-RD. In single organ involvement, lymph node swelling is not included; (2) Serological diagnosis criteria: Serum IgG4 levels greater than 135 mg/dl; (3) Pathological diagnosis criteria: Positivity for two of the following three criteria . All of the patients enrolled in this study were diagnosed as IgG4-RD based on their extra-nasal symptoms and/or extra-nasal biopsy results, since there is no unified definition of IgG4-related nasal disease. All the patients were recruited in 4 medical centers  from 2009 to 2021. AR was diagnosed according to the Allergic Rhinitis and its Impact on Asthma (ARIA) 2008 and BSACI guideline 201720: AR diagnosis is based on the concordance between a typical history of allergic symptoms and diagnostic tests. (1) Typical symptoms: Including two or more symptoms such as sneezing, watery mucus, nasal congestion, and nasal itching, and the symptoms persist or accumulate for more than 1 h per day. May be accompanied by eye symptoms such as itching and conjunctival congestion. (2) Signs: Nasal mucosa pale, edema, nasal watery secretions. Nasal endoscopy and sinus CT examinations were performed as appropriate. (3) Diagnostic tests: Skin prick test or serum specific IgE detection were done to assist diagnosis. CRS was diagnosed according to the EPOS 2012 criteria21: (1) Having two or more symptoms of nose and the paranasal sinuses inflammation, one of which should be either nasal blockage/obstruction/congestion or nasal discharge , ± facial pain/pressure, ± reduction or loss of smell; (2) Either endoscopic signs  or CT/MRI changes  that support CRS diagnosis. The clinical diagnosis of AR/CRS was made by otolaryngologists. Due to the retrospective nature, we collected patient nasal manifestations through combination of medical records and questionnaires. Patients diagnosed as IgG4-RD were categorized into the case group if they met the diagnostic criteria of AR19 and/or CRS21. The control group included IgG4-RD without AR/CRS. In the case group, patients with AR were categorized into Group A, patients with CRS were categorized into Group B, and patients with both AR and CRS were categorized into Group C. 46 patients in the case group underwent nasal tissue biopsies. Among them, 28 patients had numerous IgG4-positive plasma cell infiltration, and 4 patients had storiform fibrosis and/or obliterative phlebitis.We retrospectively analyzed 756 IgG4-RD patients fulfilled 2020 revised comprehensive diagnostic criteria for IgG4-RDDemographic features like age and gender, and clinical characteristics including clinical manifestation, disease duration and organ involvement were recorded. The time interval from disease onset to diagnosis was defined as the time interval from symptoms onset to the diagnosis of IgG4-RD. Other types of allergic disease included atopic dermatitis, asthma etc. This study was approved by Medical Ethics Committees of the four medical centers that were responsible for patient enrollment . Data protection authority and medical research ethical committee gave their approval according to national regulations and in accordance with the Declaration of Helsinki. All methods were performed in accordance with the relevant guidelines and regulations. Informed consent was obtained from all patients enrolled in this study.Laboratory studies including serum IgG4 level, serum IgE level, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), eosinophilia, C3, C4 and autoantibodies (including RF and ANAs) were retrospectively collected.All patients received radiological examinations comprising of ultrasonography, Computed Tomography (CT), or Magnetic resonance imaging (MRI); and partial patients underwent 18F-fuorodeoxyglucose PET-CT for systematic examination.575 patients carried out tissue biopsy and all tissue biopsy samples were fixed in formalin and embedded in paraffin wax. Then all samples were stained with hematoxylin and eosin and immunocytochemistry .23. Student’s t test was used for differences for continuous, normally distributed data; Mann–Whitney test was used for differences for continuous, non-normally distributed data. Categorical variables were processed by X2 or Fisher's exact tests. Logistic regression analysis with enter method was performed to compare the patients in the case group and control group. Factors with P < 0.05 and clinical significance in the univariate analysis were included in the multivariate analysis. P-value < 0.05 was deemed as statistically significant.All statistical analyses were performed by GraphPad Prism 8.0 using descriptive methods, with standard summary statistics including mean (S.D.), median, interquartile range (IQR), and proportions as previously reportedThis study was approved by Medical Ethics Committees of the four medical centers that were responsible for patient enrollment .All authors of this study have their consent for publication.Demographic characteristics of a total of 756 patients diagnosed as IgG4-RD were listed in Table p = 0.0089), longer disease duration  and longer follow-up period  compared with patients in the control group  as shown in Table p < 0.0001), lung , salivary gland , lacrimal gland  and parotid gland  involvement than the control group. The most frequently involved organs in the case group were salivary gland (63.26%), lacrimal gland (52.07%) and lymph node (41.12%). In contrast, salivary gland (42.32%), pancreas (27.54%) and lymph node (26.96%) were the most frequently involved organs in the control group.In general, the proportion of number of involved organs ≥ 3 in the case group was higher than that in the control group  and ESR  than control group, as shown in Table p < 0.0001) and hypocomplementemia  were more common in the case group, too.Patients in the case group had higher level of serum IgG4 , serum IgE  infiltration as shown in Fig. 14.The main clinical nasal manifestations of patients in Group A were sneezing 29.04%), nasal obstruction (27.47%), nasal itching (20.57%) and rhinorrhea (20.09%) as shown in Fig. 9.04%, naIn univariate analysis, disease duration, other types of allergic disease, number of involved organs ≥ 3, lymph node involvement, salivary gland involvement, thyroid gland involvement, lung involvement, biliary system involvement, gallbladder involvement, salivary gland involvement, lacrimal gland involvement, parotid gland involvement, higher level of serum IgG4, higher level of serum IgE, higher level of ESR, eosinophilia and hypocomplementemia were associated with higher rate of IgG4-RD complicated with AR/CRS .As shown in Fig. In the present study, we described the clinical manifestations of IgG4-RD patients complicated with AR/CRS in a large cross-sectional cohort. Moreover, we compared the demographic, clinical and laboratory disparities of 408 IgG4-RD patients complicated with AR/CRS and 348 IgG4-RD patients without AR/CRS. The chronological relationship of complication of AR/CRS and IgG4-RD disease diagnosis was analyzed. To our current knowledge, this is the first and largest cross-sectional cohort study focusing on the complications of both AR and CRS of IgG4-RD, and exploring the differences of IgG4-RD with and without AR/CRS phenotypes.23. However, few studies have discussed nasal involvement in IgG4-RD, which is mainly because there is no classification diagnostic criterion for IgG4-related rhinitis or IgG4-related rhinosinusitis. Clinical symptoms of exocrine gland involvement are common in IgG4-RD patients8 and secretory gland is a major part of the nasal membrane, which indicates that the nasal membrane may be theoretically involved in IgG4-RD17. Moreover, patients with IgG4-RD do have a higher proportion of complication of AR/CRS based on previous study13 and our clinical practice experiences. Therefore, this study retrospectively analyzed the demographic, clinical and laboratory characteristics of IgG4-RD patients complicated with AR/CRS, which could be conducive to better understanding of the pathogenesis of IgG4-RD.IgG4-RD is an immune-mediated systemic disorder that is typified by sclerosing lesions in multiple organs. Organs in the head and neck region are commonly involved in IgG4-RD, such as salivary gland, lacrimal gland and parotid gland15, 37.0%14 and 32.3%13). The different inclusion criteria may explain for the discrepancy. IgG4-RD patients complicated with AR/CRS seemed to have longer time interval from disease onset to diagnosis. Multiple organs involvement (≥ 3 organs) was more common in patients complicated with AR/CRS than patients without AR/CRS, and the distribution of involved organs were also different, suggesting different underlying pathogenesis.The percentage of complication of AR/CRS in the present study was 54.0%, which was higher than previous studies ; (2) IgG4-RD patients with AR/CRS showed different demographic, clinical and laboratory characteristics than patients without AR/CRS; (3) IgG4-RD patients with AR/CRS in our study were sensitive to glucocorticoid therapy and their nasal symptoms alleviated or disappeared after treatment, while CRS alone is insensitive to glucocorticoid therapy. Although AR alone is sensitive to glucocorticoid therapy, IgG4-RD patients complicated with AR had outstanding allergic symptoms and showed different laboratory characteristics than patients with IgG4-RD alone. Therefore, we consider AR may be related to IgG4-RD. However, we couldn’t draw a definite conclusion from the data. Our study may draw attention to the nasal involvement of IgG4-RD, which was barely reported before. Future studies should focus more on the pathological changes between IgG4-RD complicated with AR/CRS, IgG4-RD alone, and AR/CRS alone, which may lead to the recognition of a new clinical entity of IgG4-RD.Our research supports the hypothesis that IgG4-RD patients with AR/CRS may have distinctive characteristics, which is supported by several findings: (1) 54.0% patients (408) in our study had AR/CRS , which was higher than the morbidity of general population(20.2% for ARThere are several limitations of this study. First, although most cases underwent general examinations, its retrospective nature made some involved organs neglected. Second, due to the long time-interval of complication of AR/CRS and IgG4-RD diagnosis, some nasal manifestations of IgG4-RD patients with AR/CRS may be neglected because of recall bias.In the present study, we compared the demographic, clinical and laboratory differences between IgG4-RD patients with and without AR/CRS. IgG4-RD patients with AR/CRS had longer time interval from onset to diagnosis. Other types of allergic disease and multiple organs involvement were more common in these patients. IgG4-RD patients with AR/CRS showed higher levels of serum IgG4 and IgE, and higher percentages of ESR elevation, eosinophilia and hypocomplementemia. Physicians should pay attention to the medical history of AR/CRS because AR/CRS could occur several years earlier than IgG4-RD diagnosis in the present study. IgG4-RD patients are often complicated with AR/CRS, which may have distinctive characteristics. The data in this study suggests a pathogenic association of IgG4-RD and AR/CRS.


In this paper, we evaluated the applicability of the minimum required compressive strength for cold weather concreting based on winter meteorological factors. In this study, a compressive strength test, dynamic elastic modulus test, hydration degree test, underwater weighing test, and freeze–thaw test were performed to investigate the effect of compressive strength development at early ages on frost resistance of concrete. In particular, the ASTM equivalent number of cycles ( The most critical factors in cold weather concreting are early age frost damage and the normal development of strength ,2. EarlyThe minimum required compressive strength is a reference value defined by experimental results. Previous studies ,17,18,19However, according to recent studies, even once concrete has reached a compressive strength of 5.0 MPa, freezing and multiple freeze–thaw cycles still have adverse effects on its durability. Koh et al.  verifiedAccording to the Guide to Cold Weather Concreting of American Concrete Institute Committee 306 , the conGenerally, under experimental conditions, evaluation of frost resistance performed well on completely hardened concrete. The test method to determine the frost resistance of concrete is to place concrete into temperature-adjustable equipment, such as the ASTM C 666 , JIS A 1Furthermore, to connect with concrete structures in the natural environment, the frost damage deterioration behavior of concrete at early ages can be estimated by meteorological factors. Considerable progress has already been made in estimating the frost damage deterioration behavior of concrete based on meteorological factors ,27,28. H C 666 A  method tAs mentioned above, an unclear relationship exists between the minimum required compressive strength and frost resistance at early ages of concrete. Moreover, there is no study using meteorological factors to evaluate the applicability of minimum required compressive strength. Therefore, this study aimed to investigate the effect of compressive strength development at early ages on frost resistance of concrete and perform an objective and correct evaluation of the applicability of minimum compressive strength for cold weather concreting according to meteorological factors.In the Recommendation for Practice of Cold Weather Concreting of Architectural Institute of Japan , the minAs shown in From the summary, it can be established that there is a positive correlation between compressive strength and frost resistance of concrete. However, the effect of compressive strength development at early ages on the frost resistance of concrete is not clear. It is also still unknown that concrete can against how many freeze–thaw cycles with the minimum required compressive strength value. Therefore, the main workflows in this study are, firstly, summarizing the current regulation content of the minimum required compressive strength for cold weather concreting in different guidelines of various countries; secondly, conducting experiments to investigate the effect of compressive strength development at early ages on frost resistance of concrete based on the summary of different guidelines; thirdly, collecting the winter meteorological factors data in a few cold regions from various countries and estimating their 3. The density and water absorption of fine aggregate were 2.73 g/cm3 and 1.72%, respectively. For the coarse aggregate, the density and water absorption were 2.68 g/cm3 and 1.78%, respectively. The concrete mix proportions are listed in Concrete specimens in this study were manufactured by ordinary Portland cement (OPC), land sand, coarse aggregate, and tap water. The density of ordinary Portland cement was 3.16 g/cmIt is necessary to conduct the pre-experiment first before carrying out the main experiments in order to grasp the curing time of different values of the minimum required compressive strength. The concept of concrete maturity indicates that the combination of curing time and temperature produces a specific strength for a given concrete mixture. The maturity method is used to develop relationships between time-temperature history and concrete compressive strength. Saul  originalM=∑0tTc+1After estimating the curing time of each specimen and verifying the actual compressive strength using the JIS A 1108 , the resIn Series 1, it contained the case of early age frost damage of concrete (F-T12) and the conditions of concrete with different compressive strength values , which is aimed at evaluating the physical recovery performance of concrete that was subjected to several freeze–thaw cycles at early ages. Based on the pre-experiment results, the compressive strength values of the frozen specimens in Series 1 were determined by the compressive strength test after 20 °C sealing curing for 12 h, 24 h, 44 h, 50 h, and 75 h, respectively. After confirming the compressive strength, the specimens of Series 1 were transferred to an adjustable temperature chamber for freeze–thaw cycles in air condition for 3 cycles, and one cycle was 12 h −20 °C and 12 h +5 °C, which was used to simulate the daytime and nighttime temperatures in the Hokkaido of Japan during winter. After 3 freeze–thaw cycles, the specimens were returned to a room at 20 °C and 60% relative humidity to perform the recovery curing until 31 days. Experimental items were performed, and the freeze–thaw test was conducted until 300 cycles in accordance with the JIS A 1148 A method.Series 2 was designed to investigate the effect of different compressive strength values on frost resistance of concrete at early ages and assess the deterioration behaviors in 300 freeze–thaw cycles. Before the freeze–thaw test, the 20 °C sealing curing ages of specimens were 24 h, 44 h, 50 h, and 75 h, respectively. Measurement items were carried out after the pre-curing, then the specimens were subjected to 300 freeze–thaw cycles according to JIS A 1148 A method.The slump, air content, and temperature of fresh concrete were measured according to the JIS A 1101 , JIS A 1After the specified curing time, the samples were cut into 5 mm cube samples from the central area of the specimens. Acetone was used to stop the hydration process of samples for 1 day, and then the samples were dried using the F-drying method . The sam3); 3); 3).The underwater weighing test was conducted to determine the total porosity of the concrete. Samples were used as a whole specimen without cutting. After boiling the samples in hot water for 6 h, the fire was turned off, and the water was gradually cooled at room temperature. The samples were continued to be kept in the container for 24 h. Subsequently, samples were removed from the container, and the surface moisture was wiped so as to measure the mass of a saturated surface-dry specimen. The mass of the sample underwater was determined by putting the sample into the equipment for underwater weighing. And then, the sample mass of the absolute dry specimen was measured after drying at 105 °C for 24 h. The following Equations (8)–(10) were used to calculate the total porosity:Compressive strength test was conducted using a ∅ 100 × 200 mm cylinder specimen in accordance with JIS A 1108 .The freeze–thaw test was determined according to the JIS A 1148 A method  on speciIn this study, several locations in cold regions from different countries were selected for the investigation to comprehensively evaluate the applicability of the minimum required compressive strength for cold weather concreting. The selected locations and meteorological data types are given in It is well known that In addition, because the winter meteorological data were mainly used in this study, the calculation conditions were considered as insolation condition of the northern side (a et al. , these eDue to the limitations of the experimental conditions, the concrete specimens of Series 1 and 2 were manufactured in two batches. It is necessary to determine whether the specimens attain the expected compressive strength values before performing the test items. The compressive strength test was measured for F-S5, F-S12, F-S18, and F-S25 in Series 1 and 2. The results of the hydration degree and the total porosity in Series 2 before the freeze–thaw test are shown in According to The results of the RDM and weight loss in Series 2 are shown in According to 2 was greater than 0.9, which implied that there is a high positive correlation between compressive strength and durability factor. Besides, the compressive strength of N can also represent that of all F specimens in Series 1 because they had almost the same degree of compressive strength as that of N. Hence, it was demonstrated that the frost resistance of concrete at early ages depends on the pre-curing time and the hydration degree.From the above results, it was confirmed that air-entrained concrete could withstand several freeze–thaw cycles at early ages and prevent early age frost damage by ensuring a compressive strength of 5.0 MPa. However, because the hydration reaction process of cement, which is during the compressive strength development at early ages, was not sufficiently advanced, the frost resistance of concrete at early ages was low. On the other hand, the freeze–thaw action from the natural environment in the cold weather concreting period or winter cannot cause damage equivalent to the 300 freeze–thaw cycles in JIS A 1148 A test method. Concrete structures after construction in winter would be expected to get a recovery curing from spring to autumn.Besides, the numbers of freeze–thaw cycles that the RDM remained above 90% for F specimens in Series 2 were determined that F-S5 at 18 freeze–thaw cycles, F-S12 at 55 cycles, F-S18 at 90 cycles, and F-S25 at 124 cycles. According to the survey results of In this study, the applicability of 5.0 MPa as the minimum required compressive strength for cold weather concreting was determined for the first time with the combination of experiments and estimation based on meteorological factors. Moreover, the findings of this study were persuasive by investigating guidelines for cold weather concreting in different countries and winter meteorological data from various locations in the world.Air-entrained concrete that reaches a compressive strength of 5.0 MPa can withstand several freeze–thaw cycles and effectively prevent early age frost damage.Recovery curing significantly improves the compressive strength and frost resistance of early frozen concrete. It can make frozen concrete attain normal strength development and achieve the same degree of frost resistance as non-frozen concrete.For early age concrete subjected to repeated freeze–thaw cycles in a critical water-saturated environment, the frost resistance increases with the increase in compressive strength. For OPC concrete with w/c of 0.5, the numbers of freeze–thaw cycles of the concrete with compressive strength values of 5.0, 12.0, 18.0, and 25.0 MPa that can maintain the relative dynamic modulus of elasticity above 90% were about 18, 55, 90, and 124 cycles, respectively.Using winter meteorological factors from various locations to estimate In this paper, the effect of compressive strength development at early ages on the frost resistance of concrete was investigated, and the


This study aimed to carry out a scientometric review of rice husk ash (RHA) concrete to assess the various aspects of the literature. Conventional review studies have limitations in terms of their capacity to connect disparate portions of the literature in a comprehensive and accurate manner. Science mapping, co-occurrence, and co-citation are a few of the most difficult phases of advanced research. The sources with the most articles, co-occurrences of keywords, the most prolific authors in terms of publications and citations, and areas actively involved in RHA concrete research are identified during the analysis. The Scopus database was used to extract bibliometric data for 917 publications that were then analyzed using the VOSviewer (version: 1.6.17) application. This study will benefit academics in establishing joint ventures and sharing innovative ideas and strategies because of the statistical and graphical representation of contributing authors and countries. This has resulted in significant environmental problems on Earth . The mantruction . The buitruction ,6,7,8,9.truction ,11,12,13missions ,15,16,17missions . These Gmissions ,20,21. Imissions ,25,26,27missions . Industrmissions ,31,32,33missions ,35,36,37missions ,39. Utilmissions . This nomissions . Numeroumissions ,43. The missions . Agriculmissions ,47,48,49missions . Globallmissions . Rice humissions . This prmissions . The ashmissions . Utilizimissions . This de process . Given R process ,59,60,612 discharges [The key properties of SCMs are their compatibility with aggregates (similar to OPC) and their better pozzolanic nature ,63. The scharges . As a reAs research on RHA concrete develops in response to the expanding environmental concerns, scientists face information constraints that may stymie creative investigation and scholarly collaboration. As a result, it is vital to create and apply a method that enables researchers to obtain critical information from the most reliable sources feasible. A scientometric method may assist in overcoming this shortcoming via the software application. The intention of this work is to conduct a scientometric analysis of bibliographic records published on RHA concrete up to 2021. Using a proper software tool, a scientometric analysis may undertake a quantitative examination of massive bibliometric data. Conventional review studies are weak in their ability to connect diverse sections of the literature in a complete and accurate manner. Science mapping, co-occurrence, and co-citation are a few of the most demanding parts of modern-day exploration ,85,86. TFor the quantitative evaluation of the various features of the bibliographic data, this study carried out the scientometric analysis of the bibliographic data ,88,89. NScientometric investigations employ scientific mapping, a technique developed by academics for the purpose of analyzing bibliometric information . Scopus The Scopus analyzer was employed to carry out this analysis to discover the most pertinent study fields. Engineering, materials science, and environmental science were found to be the leading three document-producing areas, with around 39, 27, and 10% of documents, respectively, accounting for a total 76% of contributions based on document count, as seen in The assessment of publication sources was carried out using the VOSviewer on the collected bibliographic data. During the analysis, “bibliographic coupling” was selected as the “kind of analysis”, while “sources” were retained as the “unit of analysis”. At least ten papers per source restraint were set, and 14 of the 265 publication sources met these criteria. Keywords are important in research because they define and highlight the study domain’s fundamental subject . The “anCitations indicate a researcher’s influence within a certain study domain . For theThe amount of citations a document obtains reflects its influence on a certain area of research. Papers with a high citation count are recognized as pioneers in their respective fields of research. For the assessment of documents, the “kind of analysis” was set to “bibliographic coupling” and “unit of analysis” to “documents”. The least citations requirement for a document was 50, and 121 of 917 documents satisfied this requirement. The top ten papers in the area of RHA concrete by citations are included in Several countries have contributed more to current research than others have and are expected to contribute further. The network map was created to allow readers to view areas committed to the research of RHA concrete. “Bibliographic coupling” was selected as the “kind of analysis”, and “countries” as the “unit of analysis”. The minimum document limit for a nation was set at 10, and 27 countries met this requirement. The nations listed in 2 emissions [This study provided a statistical overview and mapping of various aspects of the literature on RHA concrete. Previous manual review studies have limitations in terms of their ability to comprehensively and accurately connect diverse sections of the literature. This study identified sources  that published most articles, most commonly employed keywords in the published papers, articles and authors having most citations, and countries actively involved in the research of RHA concrete. The analysis of keywords identified that RHA had been examined for its possible applications as SCM in conventional concrete, self-compacting concrete, and high-performance concrete due to the presence of high silica content in its chemical composition ,117,118.missions . As a comissions . By incomissions . In addiMost of the RHA applications stated above are still in their development, and more in-depth analyses are necessary before broadening their applicability . FurtherAn analysis of publication sources containing documents on RHA concrete research exposed that the topmost three sources are “Construction and building materials”, “IOP conference series: materials science and engineering”, and “Materials today: proceedings”, with 110, 48, and 45 papers, respectively, Also, the leading three publication sources in terms of overall citations are “Construction and building materials” with 6797, “Cement and concrete composites” with 2268, and “Journal of cleaner production” with 1579.A keyword analysis of the subject study field shows that the five most-often appearing keywords are rice husk ash, compressive strength, concretes, fly ash, and cements. The keyword analysis revealed that RHA had been studied primarily as a supplemental cementitious material (SCM) in concrete.Author analysis revealed that only 50 writers had published at least five publications on RHA concrete research. The top writers were classified according to their number of publications, citations, and average citations. Nuruddin M.F., with 16, Zain M.F.M., and Mahmud H.B., with 14 each, and Shafiq N., with 13 papers, are the top three authors in terms of overall publications. With 973 citations, Jaturapitakkul C. leads the field, followed by Zain M.F.M. with 738 and Chindaprasirt P. with 668 citations until 2021. In addition, when the average number of citations is compared, the following authors stand out: C. Jaturapitakkul has around 97, P. Chindaprasirt has approximately 84, and D.D. Bui has approximately 82 average citations.According to an analysis of papers providing data on RHA concrete, Ganesan K.  receivedThe leading nations were assessed based on their participation in RHA concrete research, and it was determined that only 27 countries published at least ten papers. India, Malaysia, and Thailand each delivered 293, 133, and 48 papers, respectively. In addition, these nations received the most citations, with Malaysia receiving 3104, India receiving 3098, and Thailand receiving 2049 citations.RHA has been investigated for its potential uses as SCM in conventional concrete, self-compacting concrete, and high-performance concrete because of the high silica concentration in its chemical composition. Furthermore, RHA is being investigated for application in the production of geopolymer concrete.The application of RHA in the construction sector will result in green construction by reducing cement demand and conserving natural sources when used as a substitute for cement and fine aggregate.The majority of the RHA applications are still under investigation, and further analysis is required before widening their effectiveness.The objective of this study was to conduct a scientometric analysis of the available literature on rice husk ash (RHA) concrete in order to assess various measures. The Scopus database was queried for 917 relevant papers, and the results were analyzed using the VOSviewer program. The following findings were drawn from this study:


Dentin is a permeable tubular composite and complex structure, and in weight, it is composed of 20% organic matrix, 10% water, and 70% hydroxyapatite crystalline matrix. Demineralization of dentin with gradient concentrations of ethylene diamine tetraacetic acid, 0.6 N hydrochloric acid, or 2% nitric acid removes a major part of the crystalline apatite and maintains a majority of collagen type I and non-collagenous proteins, which creates an osteoinductive scaffold containing numerous matrix elements and growth factors. Therefore, demineralized dentin should be considered as an excellent naturally-derived bioactive material to enhance dental and alveolar bone tissues regeneration.The PubMed and Midline databases were searched in October 2021 for the relevant articles on treated dentin matrix (TDM)/demineralized dentin matrix (DDM) and their potential roles in tissue regeneration.Several studies with different study designs evaluating the effect of TDM/DDM on dental and bone tissues regeneration were found. TDM/DDM was obtained from human or animal sources and processed in different forms  and different shapes , with variable sizes measured in micrometers or millimeters, demineralized with different protocols regarding the concentration of demineralizing agents and exposure time, and then sterilized and preserved with different techniques. In the act of biomimetic acellular material, TDM/DDM was used for the regeneration of the dentin-pulp complex through direct pulp capping technique, and it was found to possess the ability to activate the odontogenic differentiation of stem cells resident in the pulp tissues and induce reparative dentin formation. TDM/DDM was also considered for alveolar ridge and maxillary sinus floor augmentations, socket preservation, furcation perforation repair, guided bone, and bioroot regenerations as well as bone and cartilage healing.To our knowledge, there are no standard procedures to adopt a specific form for a specific purpose; therefore, future studies are required to come up with a well-characterized TDM/DDM for each specific application. Likely as decellularized dermal matrix and prospectively, if the TDM/DDM is supplied in proper consistency, forms, and in different sizes with good biological properties, it can be used efficiently instead of some widely-used regenerative biomaterials.The online version contains supplementary material available at 10.1007/s13770-022-00438-4. Dentin is chemically composed of approximately 70% mineral phase (40%–45% in vol), 20% organic matrix (30% in vol), and 10% water (20–25% in vol). Additionally, the organic component of dentin consists of 18% collagen and 2% noncollagenous proteins (NCP), proteoglycans, growth factors, phospholipids, and enzymes  in the crown and till the dentino-cemental junction (DCJ) in the root. Dentin exhibits regional differences in tubule density and diameter wherein tubule diameter can vary from 0.9 µm peripherally to 2.5 µm at the pulp side. In the meantime, density is approximately 59,000–76,000 tubules/mmr dentin .The dentinal tubule contains an odontoblast cell process, which is an extension of an odontoblast cell, and serum-like fluid which contains a mixture of proteoglycans, tenascin, transferrin, and albumin. Interestingly, odontoblast processes were seen only in the tubules near the pulp. Further, odontoblasts differentiate from ectomesenchymal cells of the dental papilla and are organized at the periphery of the pulp as a cellular palisade. They form the dentin matrix (predentin) by synthesizing collagen types I, III, and V; noncollagenous proteins as integrin-binding sialoprotein, matrix extracellular phosphoglycoprotein, osteopontin, dentin matrix protein 1, and sialophosphoprotein; glycoproteins as dermatan sulfate, keratan sulfate, heparan sulfate, and chondroitin sulfate . They arDuring tooth development and organogenesis, odontoblasts form the primary dentin which comprises the main bulk of the circumpulpal dentin. After root completion and throughout the life of the tooth, odontoblasts form secondary dentin bordering the pulp at a slow rate Fig. C. This tAt the micron length scale, crown dentin is similar to root dentin; however, unlike root dentin, the proportion of the tubular area is higher and tubules follow a gentle S-shaped curve in the crown part while they are straight in the root area. The dentinal tubules are surrounded by a 2–6 µm dense cuff of peritubular dentin, which suggests that the dentin mineral density is higher in the crown than in the root and the predentin is significantly wider in the crown than in the root .Considering the physical and biological properties of dentin, the thickness is approximately 3–10 mm or even more, and this thickness differs in the regional parts of the same tooth, among different teeth and as a result of aging. The color of dentin greatly affects the color of the tooth due to the translucency of enamel as dentin is a yellowish-hued material that becomes darker with age. In radiographic images, dentin is more radiolucent than enamel due to its lower mineral content whereas it is more radiopaque than cementum and bone. Dentin has no replacement mechanism for biologic turnover but it can be remodeled to a certain degree as odontoblasts and pulpal resident stem cells can produce secondary and tertiary dentin when it is damaged by excessive tooth wear, carious lesion, trauma, or through iatrogenic insult, such as accidental exposure. Dentin is a bone-like matrix that is a vital, sensitive and porous tissue, capable of responding to mechanical, thermal, chemical, evaporative, and osmotic environmental stimuli. Dentin can be regarded as both a barrier and permeable structure, depending upon its thickness, age, and other variables. The permeability to fluid flow through the dentinal tubules, as well as a directional design of these tubules, suggests that dentin has a sensory hydrodynamic function. Micropore-sized dentinal tubules that measure 0.9–2.5 µm diameter provide micropore spaces of 3.70%–5.88% porosity that increases the surface contact area of dentin ) AND (regeneration [Title/Abstract])/ AND (regeneration [Title/Abstract])} and the following one for Medline (OVID) databases)treated dentin matrix and regeneration).af  and .af. Figure in vitro and in vivo animal and human studies and excluding narrative reviews, systematic reviews, and meta-analyses.The relevant studies were selected according to the inclusion and exclusion criteria. The searches were not restricted by language type, however, were limited to original researches including A template was established and reviewed by each author. The authors were calibrated to extract the following data; authors, publication year, country of origin, study design, source of TDM/DDM , tooth part (crown or root), matrix form, matrix size, demineralization protocol, ways of sterilization, and preservation and the outcome.Meta-synthesis and integration of findings from qualitative studies were performed to provide a new and more comprehensive interpretation of the findings.Degree of chance–adjusted agreement  was used to determine the inter-reviewer reliability.in vitro, in vivo animal and human studies were obtained and were included in the present review  whereas the lowest ones were published in 2014 (1.47%), 2008 (1.47%), 2005 (1.47%), 2002 (1.47%), and 2001 (1.47%). The percentage of articles published in 2020, 2019, 2018, 2017, 2016, 2015, 2013, 2012, 2011, and 2009 were 8.82%, 5.88%, 8.82%, 10.29%, 10.29%, 13.23%, 5.88%, 4.41%, 2.94%, and 2.49%, respectively. No articles were published in 2010, 2007, 2006, 2004, and 2003. Regarding the country of origin, most of the studies were performed in China (50%), Republic of Korea (16.17%), Japan (10.29%), Brazil (7.35%), Iran (4.41%), Egypt (2.94%), Sweden (2.49%), Taiwan (1.47%), UK (1.47%), USA (1.47%), and Thailand (1.47%). The study designs were Is there a difference betweenTDM and DDM?3. In our opinion, it is devisable to use the term DDM for the dentin matrices prepared for regenerative purposes that obtained from different sources, fabricated in different forms and shapes, and demineralized with different protocols as the term TDD could mean physical treatment using laser therapy or mechanical one by means of abrasives.The search strategy of PubMed and Medline (OVID) databases using the appropriate search terms yielded 55 articles for PubMed database and 13 articles for Midline (OVID). Among them, there were 32 articles for TDM and 36 articles for DDM. Both terms were used interchangeably despite that the matrices were fabricated with the same protocols using gradient concentrations of EDTA, 0.6 N-HCl or 2% HNOTeeth and tooth parts involved in study designsThe majority of the published studies relied on harvesting vital and nonvital human permanent teeth. The human teeth were maxillary and mandibular premolars extracted for orthodontic reasons, nonfunctional third molars requiring removal for clinical reasons and exfoliated deciduous teeth. In addition, teeth obtained from other animal species were involved in a few study designs such as porcine deciduous incisors, rabbit permanent incisors, rat permanent molars, dog permanent premolars and rat permanent incisors, that were frequently selected whereas goat incisors, bovine posterior teeth, ovine lower anterior teeth and pig unerupted developing teeth were selected to less comparatively Fig. .Primarily and with the use of proper dental instruments, enamel, cementum, and periodontal tissues of the extracted teeth were completely removed from the outer tooth surface, and pulp tissue with predentin was completely removed from the internal one. Root dentin is the tooth part that is commonly used whereas crown dentin was used to a lesser degree Fig. .Forms and sizesThe TDM/DDM were produced in different forms likely as particles, liquid extract, hydrogel, and paste, and in different shapes such as sheets, slices, chips, blocks, discs, root-shaped, barrier membranes, and press-fitted according to the defect shape.2 solution. The paste form [Dentin grinder and ball mill machines were used for preparing particulate dentin , 77, 80.ste form  was prepSheets , 44, 78 Methods of demineralization, sterilization and preservation3 [51, , 55, To our knowledge, no standard protocol for demineralization was established for the different forms and shapes of dentin matrices used for tissue regeneration. Therefore, the protocol requires optimization of the concentration and pH of the demineralizing agent, and the exposure time needs to be properly adjusted for each form and shape. Before demineralization, it is necessary to prepare dentin matrix to remove the debris resulting from mechanical instrumentation. Accordingly, the dentin matrices were soaked in deionized water for 5–6 h and a cleaning cycle of 5–20 min was performed every hour using an ultrasonic cleaner , 40, 43.3 51, , 55, 62 Human-derived particles used for preparing liquid extracts were demineralized with 17%, 10%, and 5% EDTA with two different time frames as 5 min, 5 min, 10 min , 30 min,3 for 30 min [Human-derived sheet scaffolds were demineralized with 17% and 5% with two different time frames as 5 min, 5 min  and 4 mir 30 min  whereas r 30 min , 28, 30 r 30 min , or for r 30 min , respectr 30 min , or for r 30 min , respectr 30 min . Human-dr 30 min . Scaffolr 30 min , respectSterilization was performed by maintaining the matrices in sterile phosphate-buffered saline (PBS) with 100 units/ml of penicillin and 100 μg/ml of streptomycin at 37 °C, for 72 h and then washed in sterilized deionized water for 5 min , 38–44, The matrices were preserved in α-MEM media containing 50 units/ml of penicillin and 50 μg/ml of streptomycin or in 0.1 x PBS and kept in refrigerator at 4 °C , 44, 47 OutcomeThe TDM/DDM were considered for osteogenic differentiation , 49, 50 in vivo dentin defects. In addition, Mehrvarzfar et al. [Regarding dentin-pulp complex regeneration, Holiel et al.  evaluater et al.  comparedConsidering alveolar bone regeneration, Um et al.  evaluateRegenerative dentistry has widely been recognized as a promising field in the provision of functional and biocompatible dental tissues as alternatives for conventional materials. Current progress in tissue engineering has offered new methods and technologies for dentin-pulp complex and bone regeneration. As there are several reasons for dental extraction, including caries, mobility, orthodontic tooth reasons, and trauma, DDM can be prepared with low risks of infection and rejection with non-invasive attainability; thus, it should be considered as a natural resource to be used to full advantage for other applications.DDM is autogenous tooth dentin that has osteoconductive and osteoinductive potential since dentin contains extracellular COL-1 and various growth factors. Based on the demineralization process, the factors remain available to the host environment; however, extracting proper concentrations of collagen and bioactive molecules from the extracted teeth is a challenging task and requires meticulous preparation of the tooth dentin. DDM is used in dental surgery in the treatment of extraction socket preservation and guided bone regenerations. It functions in a dual capacity: First as a scaffold to support bone regeneration and second as a carrier for bone morphogenic protein (BMP-2). When DDM serves as a carrier, it combines the properties of the grafting material with those of the delivered substances .The type of demineralizing agents and time frames used to prepare DDM are dissimilar in different studies, and therefore they affect the amount of the mineral percentage remaining in the DDM. The DDM components have different inorganic/organic ratios compared to those originally found in the dentin matrix. Approximately, the powder form has mineral content of about 5%–10%, whereas block form has a mineral content of about 10%–30% . COL-1 wThe degree of demineralization is critical for optimal dentin regeneration; the partially demineralized dentin matrix (PDDM) is thought to have optimal conditions for dentin regeneration. Partial demineralization results in the elimination of the major part of the mineral phase and immunogenic components while retaining a very low fraction of minerals (5–10 wt%), providing an osteoconductive and osteoinductive scaffold containing several growth factors . On the In terms of particle size, the dentinogenic properties of DDM were greatly affected by the size and shape of dentin matrix particles. The larger-sized particles of the DDM, whose sizes ranged between 350 μm and 800 μm, were found to have better bone regeneration results than the smaller-sized particles that had more resorbability in the defect site before the initiation of new bone formation . PDDM wiDentin and bone are mineralized tissues known to be an organic–inorganic hybrid. They are almost similar.n their biochemical components but dentin is acellular matrix, while bone includes osteocytes. Autogenous bone is an ideal bone graft material as it has osteoconductive, osteoinductive and osteogenic capabilities but the major drawbacks of autogenous bone are that it requires a secondary donor site with an increase in the susceptibility risk of infection, therefore clinicians prefer commercially available non-autogenous graft materials. Allogenic and xenogeneic bone grafts have osteoinductive ability, but risk of viral infection still remains a considerable problem. Alloplastic bone grafts are clinically used, but they have disadvantages such as limited osteoinductivity and high cost . Among tIt is beneficial to utilize extracted teeth as bone substitutes in implant dentistry, even though there are limited cases with available teeth, in addition to a limited volume. However, there is no risk of transmitting diseases as it is autogenous tissue and no additional surgery is needed to harvest tissues since unwanted teeth are utilized and this raises the need for tooth banking. The Korea Tooth Bank, which was established in Seoul in 2009, is one such tooth-banking facility that can procure and store teeth, and then process them into bone graft substitutes. The Hospital Tooth Bank at Seoul National University Bundang Hospital, which was established in 2010 for performing storage and grafting of auto-tooth bone grafts based on experimental and clinical research.Before clinical application and for each specific purpose, optimizing protocols of demineralization, characterization, developing a proper consistency, and applying a proper handling technique are necessary for standardization. Further studies are required to determine the most suitable conditions of demineralization and particle sizes for clinical application in implant dentistry.Supplementary file1 (PDF 239 kb)Below is the link to the electronic supplementary material.


To evaluate oral antibiotic prescribing for common infections at hospital discharge before and after implementation of a pharmacist-driven transitions-of-care (TOC) program.Single-center before-and-after study.Acute-care, academic, community hospital in Santa Barbara, California.Eligible adult patients prescribed oral antibiotics at hospital discharge for community-acquired pneumonia, skin and soft-tissue infections, and urinary tract infections between September 2019 and December 2019 (preimplementation period) and between March 2021 and May 2021 (postimplementation period).Antimicrobial stewardship–initiated, department-wide, TOC program requiring all clinical pharmacists to review discharge antibiotic prescriptions in real time.P = .005). Inappropriate rates decreased in all assessment categories: dosing , treatment duration , antibiotic selection based on infection type or microbiology , and antibiotics not indicated . Median total antibiotic days decreased by 1 day after implementation , and 30-day readmission rates were similar between both phases.In total, 260 antibiotic prescriptions were assessed for appropriateness: 140 before implementation and 120 after implementation. After implementation, the number of prescriptions considered inappropriate significantly decreased by 18% (52% vs 34%; A real-time, pharmacist-driven, TOC program for oral antibiotic prescriptions had a significant impact in reducing inappropriate prescribing of antibiotics at hospital discharge for common infections. Incorporating discharge antibiotic prescription review into pharmacist daily workflow may be a sustainable approach to outpatient antimicrobial stewardship in a setting with limited resources. Clostridioides difficile infections. According to the Centers for Disease Control and Prevention (CDC), ∼30% of all antibiotics prescribed in the United States hospital setting are unnecessary or suboptimal, with 20% of those patients subsequently experiencing adverse effects. The most common inappropriate prescribing patterns have been related to excessive treatment duration, inappropriate antibiotic selection, incorrect doses, and conditions not warranting antibiotic treatment. Antimicrobial stewardship efforts have helped reduce antibiotic days of therapy and the associated risks during hospitalization, but an opportunity exists to expand these efforts to the community setting. As part of a multifaceted approach, the CDC “Core Elements of Hospital Antibiotic Stewardship Programs, 2019” recommends that antimicrobial stewardship programs (ASPs) also assess how often patients are discharged on the correct antibiotics for the appropriate duration.Antimicrobials are powerful medications that can be used to treat life-threatening infections. However, inappropriate prescribing can result in negative consequences such as emergence of antibiotic resistance and adverse reactions. Antibiotic resistance developing from inappropriate antibiotic use has been identified as one of the greatest public health threats, as well as increased risk of  Furthermore, community-acquired pneumonia (CAP), skin and soft-tissue infection (SSTI), and urinary tract infection (UTI) account for most inappropriate prescriptions. Therefore, assessing current prescribing practices and optimizing antibiotic discharge prescriptions for these infections could be an effective intervention in antimicrobial stewardship. Based on evaluation of our hospital discharge antibiotic prescriptions, we identified a need to optimize oral antibiotic prescriptions for common infections. Although antimicrobial stewardship needs continue to grow, many acute-care facilities are ill-equipped to support all the recommended initiatives due to inadequate resources among antimicrobial stewardship pharmacists, antimicrobial stewardship physicians, and transitions-of-care (TOC) pharmacists. We implemented a pharmacy department–wide protocol for real-time assessment of oral discharge antibiotic prescriptions, and we evaluated its impact on appropriate antibiotic usage for CAP, SSTI, and UTI at hospital discharge.Recent studies have shown that many hospital-initiated antibiotic courses are completed after hospital discharge.In this single-center, quasi-experimental study, we compared appropriate antibiotic usage at hospital discharge before and after implementation of a department-wide program requiring all pharmacists to conduct real-time assessment of antibiotic prescriptions filled through the hospital-operated outpatient pharmacy. The study was approved by the organization’s institutional review board as a quality improvement project. The study site is a 519-bed, acute-care, community-based, teaching hospital and level 1 trauma center, and >50% of all discharge prescriptions are typically filled at the hospital outpatient pharmacy. The outpatient pharmacist provides medication reconciliation and discharge counseling upon the patient’s request. However, due to staffing limitations, pharmacists, inpatient or outpatient do not routinely conduct critical assessment of all discharge prescriptions. To further promote consistency, a recommended “duration of therapy” handout was created. Discharge prescriptions were configured by the information technology team to show as a stat order on the inpatient pharmacist’s order-verification queue. The pharmacist was responsible for reviewing the patient’s hospitalization medical record to verify the indication and overall appropriateness of the discharge prescription. If intervention was required, the pharmacist contacted the prescribing physician to make a recommendation or to obtain clarification. Once verified, the prescription was sent electronically to the hospital outpatient pharmacy.The antimicrobial stewardship team developed a TOC policy requiring inpatient pharmacists to review all oral discharge antibiotic prescriptions sent to the hospital-operated outpatient pharmacy in real time. This department-wide TOC policy was approved by the antibiotic subcommittee of pharmacy and therapeutics committee and by the chief medical officer. Informational notification was sent to the prescribers regarding the new policy for inpatient pharmacists to review discharge antibiotic prescriptions being sent to the hospital-operated outpatient pharmacy. The antimicrobial stewardship pharmacist provided education to all inpatient pharmacists on the TOC policy, institutional guidelines adapted from the Infectious Diseases Society of America treatment guidelines, and clinical parameters to determine the appropriateness of the prescriptions.The patients who were prescribed 1 or more oral antibiotics at hospital discharge were identified through the prescriptions filled at the hospital outpatient pharmacy during 2 phases: between September 16, 2019, and December 16, 2019 (preimplementation period) and between March 1, 2021, and May 31, 2021 (postimplementation period). Subsequently, adult patients discharged with oral antibiotic prescriptions for primary indications of CAP, SSTI, and UTI were eligible for inclusion. We excluded patients who were aged <18 years; those admitted to the emergency department only; those diagnosed with endocarditis, osteomyelitis, central nervous system infections or infections with nonbacterial pathogens; those who left the hospital against medical advice; patients discharged with parenteral antimicrobials; and patients receiving chronic immunosuppressive therapy or antibiotics for long-term suppression or prophylaxis. For quasi-random selection, the first 5 consecutive prescriptions were included for analysis, the next 5 consecutive prescriptions were excluded, and the process was repeated.The prescriptions were assessed for appropriateness in the following 4 areas: antibiotic dose, treatment duration, antibiotic selection, and need for antibiotic at discharge. Appropriate dosing was based on indication and dosing recommendations listed in Lexicomp  and the institutional guidelines. Prescriptions were defined as having an appropriate duration if the total number of days of antibiotics, including the days during hospitalization, fell within 1 day of the recommended duration based on the guidelines and based on clinical parameters including vital signs, resolution of symptoms, white blood cell count, procalcitonin, C-reactive protein, lactate, urinalysis, imaging, and microbiology results. Appropriateness of antibiotic selection was determined based on approved indications, institutional treatment guidelines, allergies, local antibiogram, or any antibiotic exhibiting susceptibility on microbiological results. Finally, the ongoing need for antibiotics at the time of discharge was based on the total number of days of antibiotics and patient’s clinical response during hospitalization. Discharge prescriptions deemed excessive duration of therapy in the absence of any clinical reason were considered inappropriate. In addition, asymptomatic bacteriuria was considered an inappropriate indication for antibiotics. The prescription was assessed for each category of inappropriateness; however, the prescription was counted as inappropriate only once. Along with discharge antibiotic prescription data, patient demographics, comorbidities, and 30-day readmission data were collected.Our primary objective was to compare pre- and postimplementation inappropriate antibiotic prescribing rates for CAP, SSTI, and UTI indications. Secondary objectives included comparing the types of prescribing pattern change  and 30-day readmission rates.2 test of homogeneity. Post-hoc analyses using the Bonferroni correction were conducted to identify which category significantly changed in infection types. The Mann-Whitney U test was used to test for significance in overall antibiotic days of therapy.To compare pre- and postimplementation data, statistical analysis was performed using R version 3.5.1 software . Prescription inappropriateness for overall prescribing, dosage, duration, selection, need at time of discharge, and 30-day readmission were compared using the χIn total, 861 prescriptions identified during the preimplementation phase were filtered to include indications for CAP, SSTI, and UTI and removal of those meeting the exclusion criteria resulted in 280 prescriptions included in this study. Subsequent quasi-randomization resulted in 140 prescriptions for 140 patients. During the postimplementation phase, 619 prescriptions were identified, among which 225 prescriptions met the inclusion criteria. Finally, 120 prescriptions from 113 patients were randomly selected. Baseline patient characteristics overall were similar between groups with a few differences. The patients in the preimplementation group were older than those in the postimplementation group, with the mean ages of 66 and 60 years, respectively (Table P = .005). Overall rates of inappropriate prescriptions decreased in all assessment categories of dosage, treatment duration, antibiotic selection, and continued need for antibiotic at the time of discharge . Common reasons for dosing errors were related to not adjusting the dose based on patient’s renal function and selecting incorrect dose for the infection type. Excessive treatment duration showed a downward trend overall, but there was a significant reduction in the number of inappropriate prescriptions for SSTI after implementation of the TOC policy . The median total antibiotic days decreased by 1 day after implementation of the TOC policy  was the most common reason for inappropriateness, followed by no indication for antibiotic 16%), incorrect dose (15%), and incorrect antibiotic selection (8%) . The most isolated organisms were Escherichia coli, methicillin-susceptible Staphylococcus aureus, and Streptococcus spp. Based on available microbiology data, an appropriate antibiotic was chosen most of the time in both the pre- and postimplementation periods . In 8 cases, the appropriate antibiotics were selected based on the susceptibility report but were not de-escalated. Inappropriate antibiotic selection was often due to a culture result returning after the patient was discharged. Continuing antibiotics after completion of therapy and achieving clinical resolution during hospitalization were the primary reasons for patients not needing antibiotic prescription at discharge.Regarding selection of discharge antibiotics, amoxicillin-clavulanate, sulfamethoxazole-trimethoprim, cephalosporins, and fluoroquinolones were the most-prescribed agents in both periods. Notably, both levofloxacin and ciprofloxacin prescriptions decreased after implementation by approximately 40% and 50%, respectively. Positive microbiology data were available in approximately half of the patients in both study periods to assist in antibiotic selection , among whom 6 patients  were readmitted for reasons related to the previous discharge conditions. C. difficile was not reported among these subgroups.Overall, 30-day readmission rates were comparable in the pre- and postimplementation groups . Interestingly, we noted a slight increase in the number of prescriptions with inappropriate treatment durations for CAP during the postimplementation period . This finding may be related to empiric treatment of bacterial superinfections in the setting of coronavirus disease 2019 (COVID-19). Most prescriptions were appropriately selected. However, stewardship opportunities were identified for timely de-escalation of therapy based on the susceptibility during hospitalization as well as follow-up of microbiology results that are reported after patient discharge. Readmission rates remained similar, suggesting that improved prescribing patterns, including reduction in the total antibiotic days, did not affect patient safety. Ultimately, these improvements align with national goals to reduce inappropriate prescribing to combat the emergence of antibiotic resistance without further complications to patients.In this quasi-experimental study of oral discharge antibiotic prescriptions for common infections requiring hospitalization at a community hospital, we demonstrated a successful implementation of a pharmacist-led TOC program. After the implementation of real-time pharmacist assessment and intervention, the inappropriate prescription rate significantly decreased by 18%. The number of inappropriate prescriptions decreased across all subcategories of dosing, treatment duration, antibiotic selection, and need for antibiotic at discharge. The most significant impact was in antibiotic dosing, which is not surprising given that pharmacists have specialized knowledge to effectively review patient information and to determine appropriate doses. Excessive treatment duration was the most common reason for inappropriate prescribing in both study phases. This finding is similar to the findings of Vaughn et al, In a retrospective descriptive study of 1,100 adult patients at high risk for readmission and mortality, TOC pharmacists intervened in 298 discharge antimicrobial medications. Common intervention types were dosing (30%) and treatment duration (25%), most of which were accepted by the discharging prescribers. Parsels et al evaluated the impact of an antimicrobial stewardship team consisting of a full-time adult infectious disease (ID) pharmacist, a full-time pediatric ID pharmacist, a pharmacy school-funded ID pharmacist faculty, and a postgraduate year ID pharmacy resident on discharge oral antimicrobial prescriptions in a retrospective, single-center study. Among 438 interventions by the antimicrobial stewardship team, a significant impact was demonstrated in the median number of antimicrobial days, which decreased from 8 days  to 4 days . Despite the positive impact demonstrated by the specialty-trained pharmacists, limited resources have been mentioned in the literature. In a retrospective audit of 236 discharge antibiotic prescriptions at a 300-bed regional hospital, appropriateness of dosing , microbiological specimens , and targeted antibiotic selection  were more likely when an antimicrobial stewardship team of an ID physician and a dedicated antimicrobial stewardship pharmacist was involved. However, due to limitations in the existing resources, only 18% of discharge antibiotic prescriptions were reviewed during the study period. Barnett et al reported an opportunity for antimicrobial stewardship intervention at hospital discharge by 1 or more antimicrobial stewardship members  in a retrospective cohort study at a small Veterans’ Affairs Hospital. However, the antimicrobial stewardship reviews occurred only twice weekly due to limited resources. In a multicenter, quality improvement study of 800 patients, utilizing pharmacists to proactively identify soon to be discharged patients and to create optimal oral discharge prescriptions for final approval provided effective TOC at hospital discharge. However, this practice model requires multiple clinical pharmacists who are already integrated within the medical teams. There is a critical need for a practical approach to stewardship, especially at a community hospital with limited resources. Our TOC policy leveraging all inpatient pharmacists was unique in expanding antimicrobial stewardship services during hospital discharge without requiring additional resources. A mean of 7 prescriptions each day required additional dedicated time to review and intervene. In place of having one or more specialty-trained TOC or antimicrobial stewardship pharmacists, training all pharmacists and incorporating antimicrobial stewardship into their daily workflow results in continuity in patient care and sustainability of a successful program.A limited number of studies have shown the impact of discharge antibiotic prescriptions stewardship by specialty-trained pharmacists.Given the nature of the retrospective review at a single center, this study had several limitations. We lacked the opportunity or documentation to further clarify specific prescribing by physicians during the preimplementation period. Implementation of the policy was delayed due to the COVID-19 pandemic. As such, the postimplementation analysis period could not be matched seasonally with the preimplementation period. Prescribing behavior may have been altered due to the unfolding COVID-19 pandemic. However, overall antibiotic susceptibility for common pathogens remained stable, and similar antibiotics were prescribed during the pre- and postintervention periods. Finally, many interventions were incompletely documented, which may have been due to the staffing shortages and frequent changes in workflow during COVID-19. Due to the lack of documentation, we may have missed prescriptions that were discontinued based on pharmacist recommendation as unnecessary at hospital discharge.In summary, implementation of a pharmacy department–wide, real-time assessment of discharge antibiotic prescriptions had a significant impact on reducing the number of inappropriate prescriptions for common infections at hospital discharge. This study provides an example of a practical and sustainable TOC program leveraging existing pharmacist staff that can be implemented at other community hospitals with limited resources.


This study analysed the processes of damage formation and development in early age unloaded concrete using the acoustic emission method (IADP). These are of great importance in the context of the durability and reliability of a structure, as they contribute to reducing its failure-free operation time. Concrete made with basalt aggregate and Portland or metallurgical cement cured under different conditions after demoulding was the test material. The obtained damage values were compared with the measured concrete shrinkage, and a shrinkage strain–acoustic emission signal (resulting from damage) correlation was found. The correlation allows easy measurement of damage level in the early period of concrete hardening, and consequently can be the basis of a non-destructive method. Concrete, especially reinforced concrete (RC), is currently the most commonly used material for the construction of buildings and engineering structures. It is subjected to various effects, i.e., mechanical loads (static and dynamic) ,2, variaAn important aspect is not only the current strength of elements or entire structures but also their durability .Increasingly complex and ambitious design challenges and sustainable development goals require using concrete and steel with new properties that significantly impact the behaviour of structures ,9. TightUndoubtedly, the width and growth of cracks are crucial parameters in diagnosing buildings . For thiThe cracks observed in the structures are the final result of a more complex process of the formation and development of damage in early age concrete . When haStress concentration, caused by heterogeneous and often excessive temperature and humidity fields, is also a factor in microcracking ,35. MicrNon-destructive or semi-destructive methods ,39,40,41One of the non-destructive methods (used in this paper) is the acoustic emission (AE) method—IADP (identification of active destructive processes), which has been successfully used to analyse the development of cracks resulting from loads on the structure, including the service load ,45,46,47The objective of this paper is to analyse AE signals caused by destructive processes in unloaded early age concrete, detected using the AE IADP technique, and their correlation with the measured shrinkage strains.In the papers ,53, AE sThis paper attempts to determine the correlation between the strain values and the destructive processes recorded in the hardening concrete. The tests were performed on unloaded concrete that varied in the type of cement and maintenance conditions after removal from the moulds. The strains and the course of the destructive processes in concrete were tested for 56 days. Furthermore, the shrinkage strains were estimated according to three standard approaches: Eurocode 2 (EC2) , Model CDestructive processes in the material  are accompanied by a rapid release of energy, generating elastic (acoustic) waves in the material. These waves  graduallIn this study, the IADP method was used to measure destructive processes. The method does not rely on the selected parameters of the AE signal, but is based on the reference signals created with the use of 12 parameters of the recorded electric signal: counts, counts to peak, duration, rise time, amplitude in mV or dB, energy, strength, root mean square, mean level, mean frequency, reverberation frequency, and initial frequency. The use of this method for the evaluation of reinforced concrete structures (bridges) is presented in ,46,47.The signal is measured when an active destructive process occurs in a given element during the measurement, e.g., a crack is formed or propagated . Damage Using AE signals, it is also possible to analyse other destruction processes. In the case of prestressed elements, these are ,43: micrmicrocracks in the cement paste and at the aggregate-paste interface (Class 1),internal propagation of microcracks (Class 2),formation of microcracks on the concrete surface (Class 3), andgrowth of microcracks (Class 4).In ,55, the A destructive process in concrete  is an acoustic wave sources. Twelve parameters of the AE wave  are recorded by the AE sensors and compared with the base of reference signals, which allows us to determine the destructive process  and its location based on the arrival time of the AE signal.Although microcracks and damage in early age concrete do not have a direct impact on the safety of the structure  (unless Nine concrete samples (three series of three samples) with dimensions of 150 × 150 × 600 mm were used in the tests. The samples varied in terms of selected parameters described below and summarised in The composition of individual concrete mixes is shown in An 8 inch (~20 cm) demountable mechanical strain gauge was used for the strain test b. The meStrains were measured on four faces of each specimen and the basic statistical parameters were calculated, i.e., mean value, coefficient of variation, and variance. The strain results obtained for three series of specimens at varied curing conditions are shown in The strains (shrinkage) from the tests were compared with the results predicted according to the following standards: Eurocode 2 (EC2)—PN-EN−1992−1−1 , Model CThe strain values obtained in the C−I (MC) and C−III (MC) concrete  are shown in The strains estimated according to the EC2, MC90–99, and B3 approaches in water-cured samples C−I (MC) (with Portland cement) and C−III (MC)  fell within the range of +/− 20% in relation to the values obtained in the laboratory tests. In the first week of the test, swelling of concrete C−I (MC) and C−III (MC) was observed. The phenomenon was most likely due to the higher humidity in the thermal chamber than the ambient humidity in the laboratory hall where the samples were prepared for testing.Higher ambient humidity in the climatic chamber resulted from samples with higher humidity being placed there. With the same number of samples and the volume of the climatic chamber, the result was a significant increase in humidity inside the chamber. As a result, the humidity of the samples themselves increased, and, as a result, their volume increased. Over time, the humidity decreased, contributing to the recorded shrinkage deformations, not swelling. This was largely due to the low humidity of the environment in which the chamber itself was located, which contributed to the final decrease in the level of humidity.In the case of the non-moisture-cured C−III (AC) concrete with metallurgical cement, the strain values predicted according to the standards were lower than the values obtained from laboratory tests.The impact of not curing and curing errors in the initial stage of hardening on the shrinkage strains are not taken into account in the adopted standards ,28,29, wThe tests were carried out using the IADP acoustic emission method, validated, among others, in . The floConcrete samples C−I (MC) and C−III (MC) were removed from the moulds after 10 days of cure. C−III (AC) samples were tested without curing. Two Vallen VS30-V sensors were placed on one side of each sample. The concrete surface was cleaned before the sensors were attached to the surface with a thermally conductive silicone paste and elastic rubber.The calibration before the start of the test consisted of checking the amplitude of the recorded AE signal from breaking the graphite of a pencil with a hardness of 2H, diameter 0.3 mm, length 3 mm  inclIf the amplitude of the signal excited by breaking the pencil recorded on each sensor reached 100 dB, calibration was performed successfully. If a lower amplitude was recorded, the amount of thermal paste was added to improve the contact between the sensor and the concrete surface.Before the test, an input data file was created in the Mistras program. The dimensions of the tested element, the spacing, and number of AE sensors as well as measurement parameters were set. AE signals were recorded in the samples in 12 h cycles preceding the measurement at 1–8, 12, 16, 20, 24, 28, 38, and 46 days at the points where strain values were taken, the samples were weighed, and cracks were observed.The test results were analysed using Noesis software and the reference signal database . Based oThe classification involved comparing the registered AE signals with the previously prepared reference base. It was developed in the research described in .They werThe correlation between the strains obtained from the tests and the number of AE signals (destructive processes such as microcracks in the cement paste and at the aggregate-paste interface (Class 1), the internal microcrack propagation (Class 2), and the formation of microcracks on the concrete surface (Class 3) was recorded in concrete series C−I (MC)–C−III (AC), and as shown in In the presented graphs on the horizontal axis, the values of shrinkage strains are shown, while the vertical axes show the number of class 1 signals on the left axis, and the number of class 2 and 3 signals on the right axis. The use of two vertical axes is due to significant differences between the quantities of class 1, 2, and 3 signals. Presenting them on one axis would make their analysis impossible. However, if class 3 signals were not recorded in a sample, no additional vertical axis was added.From the results in Equations of linear functions shown in In a paper , the uniThe obtained correlation between the unit energy of the signals of individual classes (representing damage) and the strains is shown in From the results in The equations of linear functions shown in One of the objectives of the study was an attempt to develop a relationship that would allow the prediction of the number of AE signals due to damage and processes in time.On the basis of the trend lines in the graphs showing the increase in both shrinkage strains and acoustic emission signals, a natural logarithm function was adopted as the base function modified with adjustment coefficients.α, β—estimated correction factors,skA, skB—coefficients of the logarithmic trend line of the additional shrinkage strain for the tested sample, andx—time in days.α and β, were adopted to better match the results. The coefficients were estimated as the ratios of the A and B coefficients read from the trend line (logarithm functions) of the increase in shrinkage strains (SKA and SKB) and the acoustic emission signals (AEA and AEB).Correction factors, α and β coefficients were estimated with two methods (API and APII) based on the results obtained from the concrete series. In the first approach (API), the AE/ASKA and AE/BSKB ratios were determined for each concrete series (C−I (MC) to C−III (AC) separately, and then the values were averaged, obtaining α and β coefficients, respectively. The second approach (APII) consisted of determining the average AEA, SKA, AEB, and BSK coefficients from the C−I (MC) to C−III (AC) concrete series. Then, α and β coefficients were calculated from AE/ASKA and AE/BSKB relationships. The parameters adopted to estimate the theoretical values of AE signal increase are presented in The values of the The initial verification of the results was carried out based on the calculated coefficients (α and β) and the values of experimental shrinkage strains from the C−I (MC) to C−III (AC) concrete series. The course of the predicted increase in acoustic emission signals over time in relation to their experimental values is shown in I and βI coefficients, while the dashed red line represents the theoretical gain of the AE signals estimated from the αII and βII correction factors. Both lines were developed on the basis of the shrinkage strains of the examined concrete, i.e., the trend line in the diagram of the actual strain increment. The analysis showed that the predicted values of the increase in the number of AE signals were consistent with those obtained experimentally and, therefore, the adopted algorithm of the procedure can be considered properly matched.The dotted lines (with markers at measurement points) show the real increase in AE signals for the C−I (MC) to C−III (AC) concrete series over time, while the dashed lines show the increase in predicted course of the AE signals. The black dashed line represents the theoretical gain estimated from the αAs has been shown, it is possible to describe the number of AE signals as a function of shrinkage strains, which is the basis for the wide testing program taking into account various parameters that affect the shrinkage in concrete.Using the AE technique, a very strong correlation, in the range of 0.91 to 0.99, between the strain values and the number of AE signals related to destructive processes in early age concrete was found. Additionally, the recorded processes were divided into three classes, i.e., microcracks in the cement paste and at the grain boundaries in the cement paste (Class 1), the formation of microcracks in the cement paste (Class 2), and the formation of microcracks on the concrete surface (Class 3). The indicated correlation was described using a simple logarithm function.Additionally, a very strong correlation was found between the increase in strain and the increase in energy of the AE signals, which can be described using a similar logarithm function.Hence, by measuring shrinkage strains and knowing experimentally defined factors, one can estimate the theoretical range of AE signals. On this basis, one can determine whether, in addition to the basic processes, there are also those indicative of progressive internal micro-damage. This is important, as they can reduce the structure’s durability and reliability.Additionally, a comparative analysis of experimental shrinkage strains and strains estimated according to selected calculation models, including those used in the relative standards shown in o Class 1—microcracks in the cement paste and at the aggregate-paste interface,o Class 2—internal propagation of microcracks, ando Class 3—formation of microcracks on the concrete surfaceThe increase in the number of AE signals resulting from damage:is strongly correlated with the increase in strain over time and can be described by logarithmic function. Simple logarithm functions describing this relation were developed for C−I (MC), C−III (MC), and C−III (AC) concrete with specific parameters and variables.Presented results show that:The increase in the energy of Class 1, 2, and 3 signals over time is strongly correlated with the increase in strain over time and functions describing this relation were developed.The results presented may form the basis for simple diagnostics of new elements. It means that by knowing the early age shrinkage strains (easy to measure), one can estimate the early age damage.More concrete tests should be performed to optimise the function formula and other variables should be added, e.g., aggregate, admixtures, and concrete strength.It was also shown that:Experimental shrinkage strains and those estimated according to selected standards show a strong correlation in the case of cured concrete C−I (MC) and C−III (MC)).In the case of non-cured concrete (C−III (AC)), the shrinkage strains estimated according to the standards are lower than those measured in the laboratory tests.The obtained results are very promising, in particular due to the diagnostic possibilities they offer. For this reason, an extended program to verify these findings on other specimens made with a different concrete composition is being prepared.