Preoperative antibiotic prophylaxis is essential for preventing surgical site infection (SSI). The aim of this study was to evaluate compliance with international and local recommendations in caesarean deliveries carried out at the Obstetrics and Gynaecology Service of the Ambato General Hospital, as well as any related health and economic consequences.A retrospective indication-prescription drug utilization study was conducted using data from caesarean deliveries occurred in 2018. A clinical pharmacist assessed guidelines compliance based on the following criteria: administration of antibiotic prophylaxis, antibiotic selection, dose, time of administration and duration. The relationship between the frequency of SSI and other variables, including guideline compliance, was analysed. The cost associated with the antibiotic used was compared with the theoretical cost considering total compliance with recommendations. Descriptive statistics, Odds Ratio and Pearson Chi Square were used for data analysis by IBM SPSS Statistics version 25.2 = 8.08, P = 0.036). The mean expenditure on antibiotics per patient was 5.7 times greater than that the cost derived from compliance with international recommendations.The study included 814 patients with an average age of 30.87 ± 5.50 years old. Among the caesarean sections, 68.67% were emergency interventions; 3.44% lasted longer than four hours and in 0.25% of the deliveries blood loss was greater than 1.5 L. Only 69.90% of patients received preoperative antibiotic prophylaxis; however, 100% received postoperative antibiotic treatment despite disagreement with guideline recommendations (duration: 6.75 ± 1.39 days). The use of antibiotic prophylaxis was more frequent in scheduled than in emergency caesarean sections . Nevertheless, the timing of administration, antibiotic selection and dose were more closely adhered to guideline recommendations. The incidence of surgical site infection was 1.35%, but tended to increase in patients who had not received preoperative antibiotic prophylaxis . Also, a significant relationship was found between SSI and patient age (χSurgical antibiotic prophylaxis compliance was far below guideline recommendations, especially with respect to implementation and duration. This not only poses a risk to patients but leads to unnecessary expenditure on medicines. Therefore, this justifies the need for educational interventions and the implementation of institutional protocols involving pharmacists. Caesarean section is one of the most frequent obstetric surgeries in the world and its use has increased exponentially in recent years ; it alloComplications of caesarean delivery include surgical site infections (SSIs), which are among the leading causes of maternal death . MorbidiAppropriate preoperative antibiotic prophylaxis (PAP), defined by the World Health Organization (WHO) as "administering an effective antimicrobial agent prior to exposure to contamination during surgery", is necessary to prevent SSI .Although multiple studies have shown the importance of the PAP in minimising risks and optimising available institutional resources, recommendations are often not followed  –8.In Ecuador, there is a Clinical Practice Guide for Caesarean Delivery Care (CPG—Ecuador)   that addBased on the above, the objective of this study is to assess compliance with international and local recommendations on PAP in caesarean delivery at the Obstetrics and Gynaecology Service of Ambato General Hospital as well as its economic impact.A retrospective indication-prescription drug utilization study was conducted. All women who, irrespective of the cause, underwent a caesarean birth in the Obstetrics and Gynaecology Service at the Ambato General Hospital in the year 2018 were considered as the study population. However, some of them were excluded: patients lacking an agreed diagnosis or personal data at the time of the review; patients with Premature Rupture of Membranes (PROM) remote from term (from 24 to 34.6 weeks), as they required another type of prophylaxis not studied in the present study ; and patThe information of the patients was obtained from the review of medical records through the file of hospital discharge reports of the Obstetrics and Gynaecology Service from the Medical Information System (MIS/AS400). It included the following data: age, origin, dates of admission and hospital discharge, date and type of surgery (scheduled or emergency), estimated blood loss and SSI.The following aspects were recorded in relation to PAP: whether or not it was applied, antibiotics used, dose, timing of administration and duration.A clinical pharmacist retrospectively assessed whether preoperative prophylaxis had been adequately used, considering the directives stated in the CPG—Ecuador  and the Appropriate indication: administering preoperative prophylactic antibiotic treatment before making the skin incision, unless the patient has an active infection for which she is already receiving antibiotic treatment  , 11.Inappropriate indication: when the above is not complied with.Appropriate selection of antibiotic: using first generation cephalosporins (cefazolin) or joint treatment of gentamicin and clindamycin in patients allergic to beta-lactams  .Inappropriate antibiotic selection: using any antibiotic other than those mentioned above. Also included in this category is the use of combination therapies by two or more antibiotics with similar activity spectra for which there is no evidence demonstrating synergistic activity.Appropriate dose: cefazolin IV at 2 g (3 g for patients weighing more than 120 kg), clindamycin IV at 900 mg and gentamicin IV at 5 mg/kg  .Inappropriate dose: using antibiotics at doses other than those referred to above.Appropriate timing of administration: receiving the antibiotic intravenously during the 60 min prior to the surgical incision. In the case of emergency surgery, administration up to the point of incision was considered appropriate  , 11.Inappropriate administration time: receiving an intravenous antibiotic at any other time before or after the incision.Appropriate duration: administering a single dose of intravenous antibiotic or, in the case of operations longer than 4 h or blood loss greater than 1.5 L, prolonging treatment by no more than 24 h after surgery  .Inappropriate duration: prolonging the administration of antibiotics for more than 24 h after the end of surgery.For the cost analysis, only the expenditure associated with the use of antibiotics was taken into account. The unit price of each of the drugs used for PAP was defined based on the information provided by the Pharmacy Department of the institution under study.The cost of treatment was obtained from the dosage schedule used in each of the patients studied. On the other hand, the ideal cost was calculated considering the compliance with the PAP as established in the reference guidelines and the PAP cost/patient ratio.The difference between the real cost of the treatments administered and the ideal cost obtained in the research indicates the savings that would have been made by optimising compliance with the recommendations.IBM SPSS Statistics version 25.0 was used for data analysis. Categorical/Binary variables were presented as frequency and percentage while continuous variables were reported as mean ± standard deviation. Association between categorical variables was determined using Pearson Chi Square; the Odds Ratio was used to report the statistical association between binary variables. P value < 0.05 was considered as statistically significant.Prior to the start of the study, the protocol was reviewed by the relevant authorities at Ambato General Hospital, who approved the study as meeting the ethical requirements of the institution.Data analysis was performed in a coded file to preserve patient anonymity.Table Table All patients received postoperative antibiotics, with a mean duration of 6.75 ± 1.39 days. Thus, 88.67% of them were prescribed parenteral antibiotics during the 24 to 72 h after surgery following 25 different therapeutic schemes, and in the rest the oral route was used. The most prescribed intravenous antibiotics were cefazolin, clindamycin and ampicillin/sulbactam. After the first 24–72 h, 95.75% of the patients continued the treatment orally in the form of 21 therapeutic schemes; in nine patients, eight schemes combining oral and parenteral medicines were used. The most prescribed oral antibiotics were cephalexin, clindamycin and amoxicillin/clavulanic acid. Upon discharge from the hospital, the patients received, free of charge, the medicines to complete the treatment.Table With regard to costs associated with treatment, which are reflected in Table The ideal cost of the PAP, assuming that the recommendations of the ASHP had been followed in all the patients studied, would be USD 476.52. Therefore, compliance would result in savings of USD 2 266,83 . The ideal PAP/patient ratio is 0.59 cents, but the actual average expenditure per patient was USD 3.37, almost six times more than would have been necessary if the protocols had been followed.Compliance with PAP is an important factor in reducing the incidence of SSI and avoiding the costs associated with it  . As in oPAP was administered to a higher percentage of patients in scheduled caesarean Sects. (83.14%) than in emergency caesarean Sects. (63.83%) . No data have been found in the literature to corroborate this observation.Furthermore, all women, including those who did not receive PAP, received post-surgical antibiotic treatment, something which is non-compliant with the guidelines recommendations. This is the most relevant result of the study and is consistent with that obtained by Saied et al. in Egypt  . Other sSeveral studies have shown that there is no significant difference in the incidence of postpartum infectious morbidity between the use of single and multiple doses of PAP  , 20–23. On the other hand,other variables studied showed compliance with the reference guidelines recommendations such as: the timing of administration, the selection of antibiotic and the dose administered Table .New research continues to recommend that PAP be administered within 60 min before the incision and, in the case of emergency surgery, as soon as possible after the incision,  , 16, 17.Antibiotic selection was consistent with ASHP in 98.07% of patients receiving PAP and the correct drug dose was administered to 94.27%; these results were similar to those obtained by Abdel Jalil et al.  . CPG-EcuThere is widespread agreement on the use of first generation cephalosporins (cefazolin), or a combination of aminoglycosides and clindamycin for patients with a history of severe reaction to cephalosporins, to avoid SSI in most surgical procedures  , 24, 25.vs 1.23%). At the sample level it is observed that the ratio between presence and absence of SSIs is 1.33 times higher in subjects without PAP as compared to subjects with PAP . This difference increases (1.14 vs 1.74) if we compare patients who received the correct antibiotic at the appropriate dose (6 cases in 526) with those who did not receive PAP or who did not receive an appropriate choice of antibiotic and/or dose administered (5 cases in 288) . These results may indicate a tendency to decrease the development of SSI when there is greater compliance with the guidelines' recommendations. It should be taken into account, however, that in all patients a post-surgical antibiotic was used for several days, which makes it difficult to statistically demonstrate the benefits of PAP on this variable.The incidence of SSI in this study (1.35%) is lower than in other similar studies, where it reaches up to 40%  , 28–31. 2 = 8.08, P = 0.036), which is in line with similar data reported in other studies  [2 = 1.59, P = 0.44).It has also been observed that the incidence of SSIs increases with the age of the patients . Thus, a significant relationship was found between these variables  than needed (Table Unfortunately, little research addresses the issue of costs of noncompliance with the PAP in caesarean sections. Instead, studies generally address the average cost of a patient receiving PAP and how cost-effective it is compared to a patient who does not receive it  –34. JansThe participation of the pharmacist within the health care team translates into a decrease in unnecessary costs, an increase in the quality of care and an improvement in the patient's quality of life. These results have led to the acceptance of this professional by other members of the health team  –41. To dThe fact that the study conducted was retrospective is one of its limitations, as it made it difficult to analyse variables that would allow the risks associated with inappropriate duration of antibiotic use to be assessed.The study shows a low compliance with the recommendations of the reference guidelines and the general literature in terms of application, selection and duration of antibiotic prophylaxis, which poses a risk to the health of patients and unnecessary expenses for the institution. In addition, it could have a negative effect on public health through increased bacterial resistance.The analysis of the PAP in the study sample allowed the detection of weaknesses in CPG-Ecuador, which will serve as a basis for the design of institutional preoperative antibiotic prophylaxis policies that clearly detail which antibiotics to use and at what dose, time and duration.We believe that the intervention of the pharmacist in the process of design, implementation and assessment of PAP protocols could improve the use of antibiotics and their cost effectiveness.


Early-onset sepsis (EOS) is a potentially life-threatening complication of birth. Clinical symptoms are often unspecific and biomarkers have low predictive values for EOS. Therefore, clinical suspicion often leads to antibiotic therapy in neonates with a negative blood culture. In the study we evaluated if a quality improvement initiative could reduce unwarranted antibiotic use in a safe way in term neonates with culture-negative sepsis.The quality improvement initiative included new treatment guidelines and were introduced on 11 June 2018. The guidelines included C-reactive protein- and clinical symptoms-guided decision-making and shorter intravenous antibiotic therapy. All term neonates treated for EOS at Ryhov Hospital, Jönköping, Sweden were studied before (period 1: 2016–2017) and after the introduction of the new guidelines (period 2: 11 June 2018 to 30 Sept 2019).Laboratory and clinical data were analysed.p < 0.001) and hospital stay  as well as healthcare costs  was reduced in the group who met the criteria after the introduction of the guidelines.There were 7618 term neonates in period 1 and 5005 term neonates in period 2. We identified 140 (1.8%) EOS in period 1 and 97 (1.9%) EOS in period 2. During period 1 and 2, there were 61  and 59  EOS neonates, respectively, who met the criteria for shorter antibiotic treatment. The number of positive blood cultures were seven (0.92/1000 live births) and five (1.0/1000 live births) in period 1 and 2. The median C-reactive protein were 52 mg/L (37–62) in period 1 and 42 mg/L (31–56) in period 2 in the group who met the criteria of the guidelines. The duration of antibiotic therapy (Median: seven vs. five days, C-reactive protein- and clinical symptoms-guided decision-making for EOS significantly decreased the duration of antibiotic therapy and hospital stay, and hence reduced healthcare costs, with no reinfection in a cohort of term infants.ISRCTN29535824. Date of registration: 28 May 2020. Retrospectively registered.Trial registration number: The online version contains supplementary material available at 10.1186/s12887-020-02426-w. This study compared antibiotic therapy and hospital stay in early-onset sepsis before (period 1) and after (period 2) the introduction of new guidelines including CRP- and clinical symptoms-guided decision-making.The study included 61 neonates in period 1 and 59 neonates in period 2 who met the criteria of the guidelines.The duration of antibiotic therapy and hospital stay as well as healthcare costs decreased between the periods without any reinfection.Early-onset sepsis (EOS) is a potentially life-threatening complication of birth . DelayedConsequently, neonates with culture-negative sepsis are associated with high antibiotic use in neonatal units , 14. OveHence, it is important to minimise unnecessary antibiotic treatment. One way to decrease the antibiotic exposure is to discontinue antibiotic therapy in the absence of a culture-confirmed infection.C-reactive protein (CRP) is one of the most widely used and studied acute-phase reactants for neonatal sepsis as it is fast, cost-effective and simple . Using CIn order to discontinue antibiotic therapy earlier in term neonates and reduce unwarranted antibiotic use the neonatal intensive care unit (NICU) in Jönköping implemented a quality improvement (QI) project including a modified version of the clinical guidelines from the NICU of Queen Silvia’s Children’s Hospital in Gothenburg, Sweden. This local guideline is now in clinical use in Jönköping. National guidelines are under development but not yet implemented.The aim of this study was to evaluate whether the introduction of the new treatment guidelines in the NICU resulted in a decreased number of days with antibiotic treatment without increasing the rate of reinfection or readmission.This QI project compared antibiotic use of term neonates treated for EOS before and after the introduction of new treatment guidelines (introduced 11 June 2018) at one single centre level 2 NICU in Jönköping, Sweden. The new guidelines were developed in order to help physicians´ decision to discontinue antibiotics in term infants when they met the criteria of the guidelines. In the study we decided a priori to evaluate the guidelines by comparing data from 24 months before and 15–16 months after the introduction of the guidelines. Period 1 was between 1 January 2016 and 31 December 2017 and period 2 was between 11 June 2018 and 30 September 2019. Infants born during period 1 were considered a baseline group. The period from 1 Jan 2018 to 10 June 2018 was considered an educational period where local physicians modified the clinical guidelines from the NICU of Queen Silvia’s Children’s Hospital in Gothenburg, Sweden. This was made within the QI framework. The physicians and nursing staff where educated about the new treatment guidelines and therefore the implementation went smoothly.The primary outcome was number of days with antibiotic treatment. The secondary outcome was reinfection or readmission to hospital within three days after completed antibiotic treatment. Other outcomes were hospital stay and healthcare costs. Healthcare costs were calculated based on the cost per day of care .There is no screening for maternal GBS bacteriuria or rectovaginal colonisation with GBS in asymptomatic pregnant women. Only women with clinical symptoms are evaluated with a urine culture and if they have GBS bacteriuria they are treated with antibiotics. Intrapartum prophylactic antibiotics is routinely given to mothers if there is prolonged rupture of membranes (> 18 h), GBS bacteriuria, a previous GBS infected child and maternal fever. There is no specific guideline at the unit when to start antibiotic therapy in term infants with symptoms and/or risk factors for EOS, but both clinical symptoms and a significant increase of CRP or Interleukin-6 (IL-6) are needed. Antibiotic therapy is never started only based on risk factors alone. In the study there were no specific time for CRP measurements after onset of therapy, it was up to the attending physician to decide when it was appropriate.At the neonatal unit in Jönköping antibiotic treatment is routinely discontinued after 36–72 h if symptoms and laboratory findings are not in accordance with EOS. Those infants where not diagnosed with any infection, and therefore not included in the present study. If the blood culture was negative after 48–72 h, antibiotic treatment continued only if the physician had strong clinical reasons to believe it was an EOS.The unit provides a regional service for preterm neonates with a GA of ≥27 weeks. The unit aimed to obtain a minimum blood volume of 1 mL for blood cultures.In the study, EOS was defined as onset of symptoms within 72 h of life. Culture-positive EOS in neonates was defined as growth of a recognised pathogen in blood cultures in combination with clinical signs of infection. Culture-negative EOS in neonates was defined, in the study, as infants who were diagnosed with an infection and had clinical signs of infection , elevated biomarkers for infection with CRP > 20 mg/L and, or, IL-6 > 350 ng/L and subsequent antibiotic therapy. No sepsis was defined as cases who received antibiotics but were never diagnosed with an infection. The attending physician decided whether it was an infection or not.All neonates who were admitted to the neonatal unit at the Ryhov County Hospital during period 1 and 2 with any antibiotic treatment during the first three days of life, and the diagnostic codes for neonatal sepsis P36 (P36.0–36.9) or infection specific for the perinatal period P39 (P39.8–39.9), according to the International Classification of Diseases, 10th revision (ICD-10-SE) were included in the study. The neonates were identified by using the Region Jönköping County electronic medical record searching tool (Diver) and the Swedish Neonatal Quality Register (SNQ).Before the new guidelines were introduced, neonates with both culture-positive and culture-negative EOS used to be treated with at least seven days of intravenous antibiotics at the NICU. In neonates where intravenous access was not accessible infants received oral suspension antibiotics instead.According to the new treatment guidelines the intravenous antibiotic therapy can be withdrawn after three days followed by administration of oral suspension antibiotic  for two more days in term neonates meeting the criteria of the new treatment guidelines.term neonate (week 37 + 0 to week 41 + 6), andno need of intensive care (including invasive respiratory support or cardiovascular support) initially when the antibiotic treatment started, andthe neonate appeared well on day 3, andthe blood culture was not positive on day 3, andmaximum CRP-value of 80 mg/L decreasing by at least 50% during the first three days.The new guidelines contained the following criteria;For extra safety, the infants included in the study also received a routine visit on day 7 for clinical assessment and control of CRP.In the study infants with EOS received penicillin G 50 mg/kg every 8–12 h and amikacin 15 mg/kg every 24 h.The following details were reviewed from the medical record: when the antibiotic treatment was initiated and terminated, drugs prescribed, duration of antibiotic treatment and hospital stay, any readmission or reinfection within three days after ending antibiotic treatment, clinical symptoms at initiation of antibiotic treatment, whether the neonate appeared well on day 3, 30-day mortality and relevant laboratory data .Background data were collected on: sex, birthweight, gestational age (GA), Apgar scores, time of rupture of the membranes and arterial pH at birth. A positive blood culture was categorised either as a proven infection or as a contamination. If a positive blood culture result was noted in the patient record as a contaminant it was defined as a contaminant. Growth of two or more species in a blood culture was considered as contamination.Inclusion criteria: Term neonates in gestational week 37 + 0 to week 41 + 6 and clinically diagnosed as EOS that had initiated antibiotic treatment within 72 h of life. Exclusion criteria: Term neonates who received prophylactic antibiotic treatment and not because of an EOS.In the study population we were primarily interested in the group who met the criteria of the new treatment guidelines referred to as the new guideline group.Length of antibiotic treatment as well as hospital stay were counted in days. When the neonate received only one dose of intravenous antibiotic or one dose of oral suspension antibiotic during a day, it was counted as one day with antibiotic treatment. On occasions when the neonate received both intravenous and oral suspension antibiotic treatment during the same day it was counted as one day with intravenous antibiotic treatment. Regardless of when the neonate was admitted or discharged from the NICU, it was counted as a full day of care.isrctn.com, number ISRCTN29535824.The regional ethical committee of Linköping approved this study, dnr 2018/503–31. Data were analysed using SPSS version 25  and Statistica version 13.3 . The study was registered at Comparison between groups was calculated with the Mann-Whitney U-test and Chi-square test. Data are shown using medians and interquartile ranges (IQR) and also means and standard deviations (SD). Categorical data are shown as percentages. This study was designed to obtain a power of 90% and a significance level of 5%, in order to detect a reduction from seven to five days of antibiotic therapy. To obtain this power, significance level and desired effect size, a sample of 60 patients in each treatment group were required.In the Region Jönköping County 7618 term infants (week 37 + 0 to week 41 + 6) were born during period 1 and 5005 term infants during period 2  or they only received prophylactic antibiotics (n = 2). During period 2 we identified 128 term neonates who were admitted to the NICU in the first three days of life and treated with antibiotic therapy (Table During period 1 we identified 185 term neonates who were admitted to the NICU in the first three days of life and treated with antibiotic therapy Table . There wtics n = . During tics n = . During There were 61 infants in period 1 who met the criteria of the guidelines (not yet implemented guidelines)  and one  patients, respectively, who got shorter antibiotic therapy than five days due to clinical improvements.Among the patients who met the criteria for the new guidelines there was a significant difference between period 1 and 2 in the number of days of antibiotic therapy Table . The medThere was no reinfection within three days after discontinuation of antibiotics in period 1 or 2 among patients who met the criteria for shorter antibiotic therapy. There was only one reinfection in period 1 in one neonate who did not meet the criteria. There was one readmission in Period 2. This neonate had no clinical symptoms but had a rising CRP (8-17 mg/L) at the routine visit on day 6. During observation at hospital for one night no antibiotics were given and CRP decreased to 10 mg/L the following day. It was the only one of all neonates who had an elevated CRP at the return visit. There was one infant who died during period 2 at the age of 10 h because of an intrauterine infection, multi-organ failure and severe asphyxia in the group that did not meet the criteria; otherwise there were no deaths in any group within 30 days of birth.In the new guideline group there was a significant difference between period 1 and period 2 in the median number of days of the hospital stay Table . The medConsequently there were in median two days saved per patient, and at a cost of €1350 per day this corresponds to €2700 per patient. During period 2, a total of 59 patients met the criteria, resulting in a total saving of €159,000, which corresponds to an annual saving of about €122,000.This study showed that new treatment guidelines including CRP- and clinical symptoms-guided decision-making significantly reduced the duration of antibiotic therapy and hospital stay in term infants with culture-negative EOS. There was no reinfection or study-related mortality in the groups who met the criteria. Combining CRP measurements, negative blood culture, the neonate’s symptoms and clinical signs supports antimicrobial stewardship and helps physicians to decide whether to discontinue antibiotic treatment earlier during the disease course in neonates who meet the criteria.Proven neonatal infection is quite unusual, but antibiotic treatment for culture-negative EOS is more common . One stuOne of the reasons could be that there is no consensus definition for culture-negative neonatal sepsis . This leA number of studies have previously been carried out using different methods, all trying to reduce the antibiotic treatment in a safe way in neonates receiving antibiotic therapy because of culture-negative EOS. We found only two studies using CRP-guided decision-making to reduce the duration of antibiotic therapy in neonates. One study had a cut-off value for CRP of less than 10 mg/L  and the Stocker and colleagues conducted a multicentre, randomised trial and used procalcitonin-guided decision-making to reduce antibiotic therapy in neonates with suspected EOS, and showed a significant reduction in the duration of antibiotic therapy (55 h vs. 65 h) and length of stay between the procalcitonin-guided therapy group and the standard therapy group, with no proven reinfection or study-related deaths in either group . In theiStocker and collegues found 27 proven bacterial infections in 1710 neonates treated with antibiotics (Number needed to treat (NNT) = 63) . A natioIf continuing with antibiotic therapy for longer than 36 h despite negative blood cultures, there is a recommendation, according to the National Institute of Health and Care Excellence (NICE) guidelines, to review the infant at least every 24 h. Also the level of the initial clinical suspicion of infection, the infant’s clinical progress and current condition should be reconsidered each day, including assessment of “reassuring” levels and trends of CRP when deciding timepoint for withdrawing of antibiotic treatment .Consequently, there are different approaches to safely reducing antibiotic therapy in neonates with culture-negative sepsis, although not all of them lead to reduced antibiotic therapy. Our study showed one way to reduce antibiotic therapy, length of hospital stays, and the cost of care.The incidence of blood culture positive EOS (0.92/1000 live births in period 1 and 1.0/1000 live births in period 2) was higher in our study compared to other studies from high-income countries, although the incidence of GBS was 0.13/1000 live births in period 1 and 0.40/1000 live births in period 2 which is similar to or lower than the reported in other studies . An obviThe QI-project was implemented smoothly in our NICU without any extra staffing or cost. One explanation could be that we are a relatively small NICU with physicians who are used to follow new guidelines. However, we acknowledge that this could be a challenge in other units.There are several limitations to our study. The QI study design has inherent limitations. The power calculation was calculated on an expected reduction in the duration of antibiotic treatment and therefore does not rule out rare side effects, which would have required a much larger population.The arbitrary chosen level of 80 mg/L in CRP as a cut-off, was used in the present study and is still in use in the local clinical guideline. The upcoming Swedish national guidelines have suggested 60 mg/L in CRP as a cut-off as an extra precaution. We did not see any negative consequences of including patients up to 80 mg/L in CRP in our study. We also took into account the dynamics of CRP development, symptoms at disease onset, the blood culture result and the clinical condition of the infant when deciding to discontinue intravenous antibiotic treatment. Additionally, CRP values up to at least 40–50 mg/L in non-infected neonates have been seen , which rThe strength of the study is that we included all neonates attending the NICU and receiving antibiotic therapy for EOS during the study period.In our study, the infants received oral solution antibiotic treatment after the initial intravenous antibiotic therapy as an extra precaution. However, the effect of oral solution antibiotic treatment is uncertain. In future studies we intend to evaluate the effect of exclusively intravenous antibiotic therapy for 48–72 h in a similar group of patients as in this study.CRP- and clinical symptoms-guided decision-making for EOS significantly decreased the duration of antibiotic therapy and hospital stay, and hence reduced healthcare costs, with no reinfection in a cohort of term neonates in Sweden.Additional file 1. Patients characteristics on all infants with early-onset sepsis. Term infants treated for early-onset sepsis (EOS) pre- and post-implementation of new antibiotic treatment guidelines. Period 1 and 2 include term infants with both culture positive and culture-negative sepsis. Data are median (IQR) or n/total (%) except for birthweight which is mean (SD). Numbers are less than n in each group where data were not available. CRP=C-reactive protein; IL-6 = Interleukin-6.Additional file 2. Antibiotic therapy and length of hospital stay in patients with early-onset sepsis. Term infants treated for early-onset sepsis (EOS) pre- and post-implementation of new antibiotic treatment guidelines. Period 1 and 2 include term infants with both culture positive and culture-negative sepsis. Data are median (IQR). AB-days = days with antibiotic treatment; IV-days = days with intravenous antibiotic treatment; Oral-days = days with oral solution antibiotic treatment; H-days = Hospital stay in days.


Polymer Flexible Joint (PFJ) is a method for repairs of concrete elements, which enables carrying loads and large deformations effectively. This article presents the possibility of applying PFJ on beams subjected to bending and describes the influence of such joints on concrete elements. An experimental investigation was conducted to determine the behavior of concrete in a four-point bending test. The research program included flexural tests of plain concrete elements with a notch, as well as tests of elements which were repaired with PFJ after failure. Based on the experimental results, the numerical characteristics of analyzed polymer and concrete were calibrated. A nonlinear numerical model is developed, which describes the behavior of concrete elements and polymer in the experiments. The model is used to numerically analyze deformations and stresses under increasing load. The influence of flexible joint on concrete elements is described and behavior of elements repaired with PFJ is compared to original elements. Particular attention was paid to the stress redistribution in concrete. The application of flexible joint positively influences load capacity of the connected concrete elements. Furthermore, because of stress redistribution, connected elements can bear larger deformations than original ones. PFJ can therefore be considered an efficient repair method for connecting concrete elements. Early-age shrinkage as well as mechanical cracks in concrete are common problems in constructions. Deformations caused by concrete shrinkage or temperature changes leads to local stress concentrations in the concrete. This results in damage of concrete components such as floors or roadways ,2. In adCommon joint materials, such as epoxy resins, have high stiffness and low deformability, which can be a disadvantage, since new cracks often appear after repair, close to the repaired one. On the contrary, sealants or mortars which are also used for such repairs do not have sufficient strength to carry internal forces  11,12,1,112,13. Polymer flexible joint is a method that allows effectively bearing the loads and absorbing large deformations at the same time . TherefoThis article presents experimental and numerical investigations of the most effective PT-type polymer for concrete repair. It can be applied in cracks of concrete and RC elements making elastic (or nonlinear elastic) hinge, which is able to transfer bending loads and high deformation simultaneously, also under cyclic loads. It can be used for the repair of cracked concrete surfaces . MoreoveThe aim of the research presented in this article is to investigate the possibility of the application of PFJ on beams subjected to bending. Until now, PT-type polymer was not thoroughly investigated in flexure. The four main objectives of this work are: (1) to describe the influence of PFJ on concrete elements and stress redistribution, (2) to determine the behavior of concrete in four-point bending tests, including digital image correlation analysis, (3) to perform a numerical analysis of the experimental work, describe the behavior of concrete elements and polymer and analyze deformations and stresses under increasing load, and (4) to assess the influence of flexible joint on concrete elements and compare the behavior of elements repaired with PFJ to original elements, focusing on joint effectiveness.w/c ratio of 0.45 and a maximum aggregate size of 16 mm. To determine the compressive strength of the concrete, 150 mm cubes were used, while the tensile strength was measured in the uniaxial tensile test on prisms with dimensions of b × h × L = 100 × 100 × 200 mm3 with a notch a = 25 mm on both sides in the center of each prism. These tests were carried out 60 days after casting [CONCRETE. All concrete specimens were made of one concrete mixture: normal concrete based on Portland cement with a E = 700 MPa, almost two orders lower than the applied concrete [POLYMER. A two-component PT-type polymer was used in the research program. It is an elasto-visco-plastic material with good bonding properties. The tensile test was carried out according to EN ISO 527-1  at the sconcrete . Table 1The experimental investigations consist of 63 four-point bending tests (4PB) with various structural materials. The test specimens were divided into 21 series, each containing 3 test specimens. The aim of this research program was to analyze the influence of the polymer PT on joint effectiveness (JE) ,24 in coJoint effectiveness was defined as a ratio of load-bearing capacity or elongation capacity of the elements after the repair and before the repair. In this paper, experimental and numerical analysis of one series (3 test specimens before and after repair) for concrete and polymer PT cooperation is presented.L = 400 mm and a square cross-section with b × h = 100 × 100 mm2. Each specimen was provided with a notch of a = 30 mm depth at the bottom, in the middle of its length  was applied. The bending tests of the repaired elements were carried out 16–20 h after the polymer application (a kind of emergency repair).The specimens used in 4PB tests were prismatic, with a length of ngth see . Such elMaximum force:     100 kN,Initial force:       0.80 kN,Test displacement rate:  0.10 mm/min,Span length:       300 mm,Distance between loads: 100 mm.The bending tests were performed with a Zwick/Roell Z100 testing machine . The test parameters are as follows:Three measurement methods were used simultaneously in all 4PB tests: (1) extensometer for the crack width displacement (CMOD), (2) extensometer for the vertical deformation, (3) digital image correlation (DIC) to measure the strain field on the side surface of the specimens . For DICb × h = 100 × 100 mm2. The curve is linear up to the maximum load for both original and repaired elements. It is noted that repaired specimens, where the polymer was used, have a lower bending stiffness than original specimens. Therefore, higher CMOD values were observed for repaired specimens at the same load levels. The load-bearing capacity of original elements reached higher values in most cases. Before maximum nominal stress σmax ), no cracks were detected with the unarmed eye. However, crack formation was observed in the post-critical phase (≥σmax).All specimens had a similar type of failure—a crack occurred along the notch where the stresses reached the highest values. Furthermore, the failure was sudden and brittle. Cracks run not only through the cementitious matrix but also through aggregates . In the Using digital image correlation method (DIC), first cracks were already observed before reaching the maximum load. A development of the horizontal strains (X-axis) of the original and repaired specimens is shown in maxF of the repaired specimens was about 2.5-times higher than of the original specimens.Repaired specimens had a different mechanism. The first cracks appeared much earlier, which was a consequence of the already weakened cross-section . In the repaired specimen several main cracks developed further (load step 29/110) on the left side of the notch. However, halfway through the test a new crack developed on the other side of the notch (load step 71/110). From this point on, the previous, initial cracks did not develop further, and the new crack caused the failure. This sidewise shift of the damage process is visible between the last steps (load step 68/110 and 71/110). The horizontal strain at The phenomenon above confirms observation presented in  for tensAs mentioned above, the load-bearing capacity of the repaired elements was generally lower than the original ones. The average values of maximum stress for original and repaired elements are 5.28 MPa  and 4.60 MPa  respectively. On the other hand, the average values of CMOD are 47.7 μm  and 132.7 μm  respectively. The repaired specimens manifested load bearing capacity of 87% of the original elements, but ductile behavior increased almost three times.A comparison of maximum stresses and maximum CMODs for the original and repaired specimens is shown in E = 30,000 ÷ 40,000 MPa) than the applied PT-type polymer (E = 700 MPa). On the other hand, ability of PT-type polymer to deform up to 10% of ultimate strain with hyperelastic characteristic results in stress redistribution, thus the PFJ can act as a load-bearing connection and absorb large deformations at the same time.In terms of maximum stress, the repaired specimens achieved only 13% lower strength than the original specimens. In terms of deformability, the repaired specimens achieved significantly higher deformation at break than the original ones. This is explained by the substantially higher deformability of polymer of the hyperelastic characteristic when compared to brittle concrete. In general, the specimens repaired with a 10 mm polymer layer had the average CMOD value 2.78 times higher than the specimens before the repair. These two joint effectiveness values indicate increase in global fracture energy of the specimens after repair, what is not observed when brittle materials (cracked) are repaired (bonded) using stiff and high strength materials . TypicalCQ16M) of eight nodes [CL12I) with zero thickness at the contact area with 95% tensile strength of the concrete were used. Boundary conditions were defined as rigid supports. The right support was modelled as a sliding type in the horizontal direction without taking any possible friction effect.The numerical analysis of the 4PB test was performed with the DIANA Finite Element Software  in 2D asht nodes . The maxh is a crack bandwidth, which is assumed here as the square root of a finite element area. The constitutive model for concrete used in the analysis is based on a smeared crack model  and was ctf << ptf).The maximum tensile stresses in the system were equal to the concrete tensile strength; in this range, the polymer behaved as a linear-elastic material . TherefoTo take this into account, the influence of the primer layer between the damaged concrete and the polymer, a zero thickness interface layer was modelled. A non-linear model of the interface was adopted with a strength equal to 95% of the concrete tensile strength. The remaining parameters were calibrated empirically on the basis of experimental results .F = 6000 N) a load control procedure was carried out; the load step in this phase was equal to 200 N. After reaching load F = 6000 N and before the cracking load, the system switched to an arc-length control procedure with load step of 100 N. Convergence criteria assumed the force and displacement norm. Due to the relatively small deformations, the analysis only took into account material non-linearity, while non-linear geometrical analysis was excluded. Two master control nodes were located at the lower edge of the specimens next to the notch. The results of these nodes shift were called CMOD deformation.An incremental-iterative solution approach according to the Newton–Raphson method was used. For the first steps of analysis , the difference between experimental results and calculation was 43% for the original test specimens and 1% for the repaired specimens. Such a high difference in deformation results was due to the stiffness of the test bench. It should be noted that the difference of the CMOD at cracking load between original and repaired specimen in the numerical analysis was 4.8 times.1 ran along the curve line (vault effect) and near the supports their direction was not parallel to the edge of the element. It should be emphasized, however, that the numerical model correctly reproduces the pre-critical phase and failure mechanism.Similar to the original specimens, the behavior of the repaired specimens in the FE-analysis is comparable to the experimental results. It is pointed out that not only the pre-critical path was reproduced correctly, but also for the post-critical phase the numerical results are satisfactory. Probably, using of hyperelastic model for the polymeric material (instead of the linear one)  can predComparison of initial  and subsequent (repaired specimen) damage energy, evaluated by the area under curves in The numerical model could also predict the crack formation . The spe(1)The joint effectiveness of Polymer Flexible Joint with PT-type polymer in terms of load-bearing capacity is 87% (on average) in the experiments and 88% in the numerical analysis.(2)For specimens repaired with PT-type polymer, the polymer is decisive for the experimental and numerical results in terms of CMOD values. It was observed that the strain capacity of the repaired specimens was more than 280% higher than that of the original specimens.(3)The repaired specimens were able to manifest higher damage energy than the original ones; the area under stress-CMOD curve for repaired specimens was more than 2× higher than that of the original ones.(4)It is emphasized that the specimens repaired with PFJ have the load-bearing capacity of more than 80% of the original ones. In this way the PFJ can be used as a load-bearing connection. In addition, the higher flexibility of the connection leads to a reduction of possible imposed stresses and introduces additional ductile behavior of structural elements after repair.(5)Using DIC method, the phenomenon of stress redistribution around a flexible joint was documented.(6)The comparison between experimental and numerical analysis shows a good agreement of the results in terms of failure load and deformation .(7)The numerical model correctly reproduces the pre-critical phase and failure mechanism. It was proven that presented numerical simulations can be a useful and suitable tool for the analysis of pre-critical phase of a four-point bending test of concrete bonded with a polymer flexible compound.(8)However, the post-critical path was not satisfactory . Experimental results show much smoother curves during failure and in the post-critical phase than numerical calculations. The reason for this may be the friction of the support during the test, where a quasi-arch effect might have occurred. Further investigations are required to adequately describe the mechanism in the post-critical phase.The experimental results of the four-point bending tests on plain concrete beams and beams repaired with PFJ specimens were presented together with the numerical analysis based on FE-modelling. The following conclusions can be drawn from a comparative analysis of the experimental and numerical results:


Cpaste, 420, 450, 480, 500 kg/m3), and color of powder (green (G) and colorless (C)). The alkali–silica reaction (ASR) expansion risk of WGS-blended mortar was assessed. The experimental results indicated that WGP after 0.5 h grinding could be used as substituted cement in mortar and help to release potential ASR expansion. The replacement rate played a dominant role on strength at both the early or long-term age. The water/binder ratio of 0.35 was beneficial to the compressive strength at three days and 0.50 was better for strength at 60 and 90 days. An optimal value of cementitious material dosage (450 Kg/m3) exited in view of its strength, while the effect of the color of WG was minor. WGS could be graded as standard construction sand and no ASR expansion risk was found even for 100% replacement of regular sand in mortar. Through the comprehensive reuse of waste glass, this study could provide basic knowledge and a concept for the sustainable development of building materials.The purpose of this study is to investigate the availability of waste glass as alternative materials in sustainable constructions. Collected waste glass was ground into waste glass powder (WGP) with similar particle size distribution as Portland cement (PC) and waste glass sand (WGS) with similar grade as sand. The compressive strength was investigated through the Taguchi test to evaluate the effect of different parameters on WGP-blended mortar, which include WG-replacement rate , water/binder ratio , cementitious material dosage ( Howev2-Al2O3) .2) and various metal oxides, that is, Ca, Al, and Fe, among others [Except for the aforementioned materials, the growing demand of SCMs is pushing industry and academia to explore more alternatives from a practical point of view , for exag others . In theog others . Howeverg others . A majorg others ,17,18,192) in WG could react with calcium hydroxide solution (Ca(OH)2) to generate an expansive reaction product [WG was firstly proposed as a coarse aggregate in construction concrete. By optimizing the mixture proportion, the negative effect of WG on mechanical strength can be predicted and accepted. However, non-negligible alkali–silica reaction (ASR) expansion was the main concern for re-utilization of WG. This is because active silicon oxide  were generated during the grinding process. Recently, support has been growing for the utilization of WGP as SCMs to replace part of ordinary Portland cement (OPC). Owing to the complex sorting process and similar composition character, mixed colorful WGP was usually used as SCMs in previous research ,26. Shi,Cpaste, 420, 450, 480, 500), replacement rate (glass/cement (G/B), 0%, 10%, 20%, 30%), and color of glass powder (green and colorless). Finally, glass culets were ground and graded into waste glass sand (WGS) according to American Society for Testing and Materials (ASTM) C1260 [To the best of our knowledge, previous works have focused on the effect of the replacement rate of WG to cement or aggregates. From the previous results, we can observe the non-negligible effect of the cement dosage and the water/binder ratio on properties of WGP blended samples. In this study, three waste glasses with different colors were collected and tested. Firstly, the pozzolanic activity of WGPs and its effect on ASR expansion was evaluated. Then, a Taguchi test was designed to assess the effect of water/binder , cementitious material dosage (M) C1260 , and the2O + 0.658K2O ≤ 0.6%, Shanshui, Qingdao, China) was used for the volume stability test to reduce ASR expansion caused by OPC to the greatest extent possible. The chemical composition as well as physical and mechanical properties of these two PCs are given in Ordinary Portland cement (OPC) Type 42.5  was used for the activity rate index test and Taguchi mixture design. Low alkali cement Type 52.5 , colorless glass powder (CP), and brown glass powder (BP) after 2.5 h milling is shown in and Kazi  also fouound 80% . Howeveround 80% .WGS was prepared according to the Chinese standard for building sand GB/T 14684-2011 ,40. The 2 and pozzolanic activity) and the physical property  were recorded. The ASR test of WGP blended mortar could help to verify the suitability of the chosen grinding time. The last part aimed to check the potential ASR of WGS as supplemental fine aggregate in mortar. ISO standard sand was used as the control group. To effectively utilize WG as construction materials, WG was separated into two parts: fine powders (WGP) as supplementary cement and coarse particles (WGS) as construction sand. Before evaluating the effect of different parameters on the optimal mixture design of WGP blended mortar, chemical properties  was measured according to the content of active SiO2 of WGPs, as the low content contribution of Al2O3 and Fe2O [2 could react with Ca(OH)2 (2), and the reaction product 3) dissolved in hydrochloric acid (HCl) solution (3). The reaction product (SiCl4) could react with sodium hydroxide (NaOH) solution to achieve flocculated white precipitate, that is, H2SiO3 (4). After calcined above precipitate at 950 °C for 2 h, the weight of active SiO2 could be calculated (5).The pozzolanic activity 2 powder was dissolved in distilled water until no more dissolution occurred. Saturated NaOH solution was prepared as it is. It was allowed to stand still until the precipitate sunk to the bottom of the volumetric flask. The supernatant was the saturated Ca(OH)2 and NaOH solution.Prepare saturated Ca(OH)2 solution (Solution 1). To accelerate the full reaction between active SiO2 and Ca(OH)2, alcohol lamp boiling and condensing reflux were applied in this contribution.Mixed WGP and saturated Ca(OH)Concentrated hydrochloric acid titration. Then, 8 mL HCl solution (12 mol/L) was added into the above cooling Solution 1 to get Solution 2. The, it was boiled again for 5 min, cooled down, and allowed to stand still. Solution 3 was obtained by filtering Solution 2.Saturated NaOH solution titration. Saturated NaOH solution was added into the above Solution 3 until no more flocculated white precipitate occurred. It was filtered again and the filter paper and sediment were kept.2SiO3.High temperature furnace ashing. The filter paper and sediment were placed in high-alumina crucible, and then the crucible was placed in a high-temperature furnace. Then it was calcined at a set temperature of 950 °C for 2 h, including heating for 1 h while warming up. The residue was pure HKc) of WGP was measured according to ASTM C 618. Mortar samples (40 mm × 40 mm × 160 mm) were prepared using 70% OPC and 30% WGP. The ratio of water/binder and binder/sand was 0.5 and 0.33, respectively, with a contrast sample that consisted of 100% OPC. Kc could be calculated using Equation (6), where cnf was the compressive strength of mortar after n days curing and cf0 was the compressive strength of contrast sample at same curing age:The compressive strength in the name of the activity rate index , replacement rate (glass/cement ratio (G/B), 0%, 10%, 20%, 30%), and color of glass powder  array. The component parameters for each trial mixture are given in In this contribution, four factors were investigated, that is, the water/binder ratio , cementitious material dosage , as shoK value is the average value of each factor with same level; the R value is the range of K value at each factor. The key factors and the effect of each factor could further analyzed based on the K value and R value [K value and R value could help to find the dominant factor that affect the strength performance of WGP blended mortar. This contributed to figuring out the optimum combination of factors and levels [The  R value . The K vd levels . HoweverTGA-DTG test is an analytical method recording the relationship  between mass and temperature on a thermal balance. The following is a detailed operating procedure: turn on the TA Instruments TGA Q 650; adjust the pressure of the nitrogen bottle to 0.1–0.2 MPa; balance the empty crucible, and add around 10–15 mg sample powder into the balanced crucible; set the temperature from room temperature to 1400 °C; start the test. After the differential quotient with temperature, a differential quotient thermogravimetric curve (DTG) was obtained. The weight change percentage of calcium hydroxide in samples was determined by the tangent method ,46. The 2 (Ka) was measured according to the method mentioned in 2 amount increased continually with the grinding time, as shown in Ka(BP) closed to Ka(GP), although it was much higher than Ka(CP). However, the total amount of SiO2 in CP was highest from the XRF result  of WGP was given based on the change of compressive strength. The samples were prepared with 70% PC and 30% glass powder. From Kc of the three glass powders under the same curing age is brown > green > colorless. It was assumed that the active SiO2 was one of the reasons. The influence was significant at an earlier age, rather than after 28 days’ curing.The pozzolanic activity rate (16 ≤ 0.20%) at 16 days of age, meaning it is hard to determine the risk of ASR. The samples containing 10% WGP, 20% WGP, and 30% WGP showed a lower expansion rate than OPC of 0.08%, 0.05%, and 0.02%, respectively. These results suggested that there was no ASR risk of mortars with the partial replacement of WGP. With the increasing substituted ratio of WGP, the relevant expansion rate decreased. This was because WGP could help to reduce the pH inside mortar by consuming calcium hydroxide, which was generated by cement hydration, and thereby reducing the ASR risk [As shown in ASR risk . Thomas ASR risk  reviewedCpaste. The influence of Cpaste was significant on the effect of the substitution rate. When Cpaste was 420 kg/m3 and 450 kg/m3, samples with 10% WGP had comparable strength performance to controls (0% WGP) from the earlier curing age to 90 days. When Cpaste was 480 kg/m3, there was a big drop from controls to WGP blended samples. After Cpaste increased to 500 kg/m3, samples with 10% and 20% WGP showed minor higher compressive strength compared with controls. Cpaste had a trivial influence on samples with a higher substitution rate (30%). A lower substation of WGP in cement mortar was helpful to improve the compressive strength, which was consistent with previous studies [2 and Ca(OH)2, which was produced by cement hydration [The compressive strength value of mixtures is recorded in both  studies ,52. Therydration . The reaydration .K value  of the substituted rate (G/B) gradually deepened from 10.47 to 19.11, while the R value of the water/binder (w/b) ratio kept fluctuating around 10. However, the optimal w/b value changed (w/b = 0.35) from low at 3 d to high (w/b = 0.50) at 60 d and 90 d. This result suggested that a lower water/binder ratio had better performance for earlier properties, while a higher and critical value had better performance in the long-term.Cpaste had a small change with different curing ages. At earlier ages, smaller cementitious dosage displayed better performance. At 28 days, different Cpaste had a similar effect, while this effect became significant at 90 days. It was interesting to find that, when Cpaste was 480 kg/m3, the compressive strength decreased obviously at the long-term curing age. From the above experiments, colorless glass powder with a slightly better strength performance might have contributed to the lower test number. However, the R value of color was so small that the influence of color in strength properties could be ignored based on results from this experiment.The effect of pasteC = 420 kg/m3) and TM14 . There was a significant loss of weight in different temperature ranges, that is, 120–150 °C for water loss, 440–460 °C for decomposition of Ca(OH)2, 700–730 °C for decomposition of CaCO3, and 1200–1400 °C for decomposition of sulphate [Two mixtures were selected for the TGA test, that is, TM1 . This value increased to 1.806% at 28 days. The Ca(OH)2 as one of main products of cement hydration continued increasing with the reaction process [3 increased from 1.071% to 1.143% of TM1 owing to the carbonation of Ca(OH)2 occurring during the curing. The total molar amount of Ca(OH)2 from 3 d to 28 d increased from 0.027 mol to 0.035 mol with the processing of hydration [2 amount of TM14 (2 decreased from 0.038 mol to 0.033 mol from 3 d to 28 d. This was because active silicon oxide in WGP in mortar could react with Ca(OH)2, thereby causing the consumption of Ca(OH)2 [As shown in  process ,64. The ydration . The Ca( of TM14  was high Ca(OH)2 .16 of the OPC sample was 0.11%. The WGS substituted samples both displayed minor expansion, less than 0.10%. According to standard specification, the WGS blended samples had no potential ASR risk. Even after 56 days’ curing, the expansion rate of the WGS-blended samples (except 30% WGS) was less than 0.20%. From the collected results, we could infer that the expansion rate of the WGS-blended samples decreased with the amount of the substituted rate (from 10% to 30%). The results obtained from this experiment were contrary to the principle that the increase of the active aggregate content leads to an increase in the expansion rate [As one can see, ion rate ,67. The ion rate . Figure ion rate  and partion rate .Waste glass could be effectively used as construction materials. The ground glass powder could be used as supplementary cementitious materials. The remaining glass cullet could be used as standard sand.2 (Ka) and particle size distribution of WGP. In terms of green glass powder, 0.5 h of grinding was enough to achieve a suitable particle size distribution to replace PC in mortar.Grinding time played a dominant role in percentage of active SiOThe ASR test results of WGP-blended samples with different substituted rates were encouraging. There was no potential ASR risk presented.Cpaste), replacement rate (G/B), and color of glass powder had different impact proportions on the properties of WGP-blended mortars. The effect of Cpaste and w/b had a notable difference between the earlier and long-term curing ages. Therefore, in terms of practical application, the optimum design for WGP substituted samples should take account to the influence of curing age.The effect of the water/binder (w/b) ratio, cementitious material dosage (Optimal mixture design could not be addressed from this contribution, owing to the decrease of compressive strength. However, future studies should focus on the optimal mixture design depending on different compressive strength levels.After being graded into standard sand, the WGS could substitute construction sand in cement mortar without an ASR expansion risk.The utilization of WGS as construction blended sand in mortar and a composition design of WGP as substituted cementitious materials was presented in this paper. The following conclusions were drawn according to the above results obtained from the specimens and work in this paper:


Central sensitization is thought to be an important contributing factor in many chronic pain disorders. The Central Sensitization Inventory (CSI) is a patient-reported measure frequently used to assess symptoms related to central sensitization. The aims of the study were to translate and cross-culturally adapt the CSI into Nepali (CSI-NP) and assess its measurement properties.2,1), (3) measurement errors, and (4) construct validity testing five a priori hypotheses. Confirmation of construct validity was determined if a minimum of 75% of the hypotheses were met.The CSI was translated into Nepali using recommended guidelines. The CSI-NP was then administered on 100 Nepalese adults with sub-acute and chronic musculoskeletal pain with additional demographic and pain-related questions. The CSI-Nepali was administered again about 2 weeks later. Four measurement properties of the CSI-NP were evaluated: (1) internal consistency using Cronbach’s alpha, (2) test-retest reliability using intraclass correlation coefficient (ICCr = 0.50); moderately with the total number of pain descriptors (r = 0.35); weakly with the Numerical Rating Scale (r = 0.25); and women had significantly higher CSI scores than men. However, the CSI scores did not correlate significantly with the total duration of pain, as hypothesized (r = 0.10).The CSI was successfully translated into Nepali. Internal consistency and test-retest reliability were both excellent . The standard error of measurement was 0.31 and the smallest detectable change was 0.86. Four out of five (80%) a priori hypotheses were met, confirming the construct validity: the CSI-NP correlated strongly with the Pain Catastrophizing Scale total scores (The Nepali translation of the CSI demonstrated excellent reliability and construct validity in adults with musculoskeletal pain. It is now available to Nepali health care providers to help assess central sensitization-related signs and symptoms in individuals with musculoskeletal pain in research or clinical practice to advance the understanding of central sensitization in Nepalese samples. Musculoskeletal pain is a highly prevalent condition. It is estimated that at least one in three persons experiences it . It is oCS involves the amplification of pain, and hypersensitivity to other environmental stimuli, within the central nervous system . The CenPain is influenced by culture –22. TherTherefore, we aimed to translate and culturally adapt the CSI into Nepali (CSI-NP), using recommended guidelines , and to This research was conducted in two steps. In the first step, we performed a translation and cross-cultural adaptation of the CSI into Nepali. In the second step, we assessed the measurement properties of the Nepali version of the CSI. A longitudinal observational study design was used to evaluate the measurement properties of the CSI-NP. Data were collected from two sources: (1) the outpatient Physiotherapy Department of Dhulikhel Hospital, a tertiary care Hospital in Dhulikhel, Nepal, which is 30 km from Kathmandu, and (2) from the community of Bhaktapur, Kathmandu, Lalitpur, and Kavre districts from July to October in 2016.A consecutive sampling method was used at the hospital, so that every patient presenting with musculoskeletal pain was invited to participate in the study, and those who met the inclusion criteria and consented to participate were included. A purposive sampling method was used to collect data from participants in the community. Participants were recruited door-to-door, and data were collected in their homes from the community sample. The protocol for this study was approved by the Institutional Review Committee of Kathmandu University School of Medical Sciences (ref number 76/16) before data collection began. Informed consent was obtained from every individual before administration of questionnaires. This study was a part of Bachelor of Physiotherapy degree thesis of the second author of this study. All data, including responses to CSI items, were collected in interview format to account for the high rate of illiteracy in Nepal .A sample size of more than 50 participants is usually considered adequate for assessing measurement properties of a patient-reported outcome measure , 32. OurFor the evaluation of measurement properties portion of the study, a total of 115 individuals with self-reported and/or physician-diagnosed musculoskeletal pain were screened for eligibility. Eligible subjects were (1) able to understand and speak Nepali; (2) at least 18 years old; (3) having musculoskeletal pain for at least 1 month ; and (4) having a self-reported pain intensity of at least 3 out of 10 on a 11-point numeric pain rating scale for a minimum of 4 days in the past week . ParticiIn addition, a sample of 20 individuals with sub-acute or chronic musculoskeletal pain was recruited from the outpatient Physiotherapy Department of Dhulikhel Hospital, Nepal for the pretesting and cognitive debriefing portion of this study. All study participants consented to participate. No participants were excluded based on low literacy skills.The original 25 items of the English version of the CSI Part A were translated into Nepali using recommended guidelines  using a The translation of the Part B of the CSI was deemed “untranslatable” during the preliminary “translatability assessment” of the scale. Translatability assessment is an important pre-requisite of translation and cross-cultural adaptation of outcome measures , 37. ThiA translator without a medical background, who was blind to the original English version of the CSI, translated the synthesized Nepali translation (T4) back into English.An expert committee was comprised of the researchers and the translators involved in the translation processes. All translation versions were discussed in this meeting, and after the consensus from the committee members, a pre-final Nepali version of the CSI (T5) was created with minimal modification on the choices of words and sentence structure on the T3 version. The English back-translation of this version was then sent to two of the original CSI developers (author RN and Prof Robert Gatchel) for review of the items. Minor changes were made in some items after suggestions from the developers, resulting in a T6 version, which was used for pretesting.The Nepali version of the CSI was tested on 20 individuals with sub-acute or chronic musculoskeletal pain, representing different age categories, both sexes, and a variety of education levels. Guidelines recommend from five to 30 participants adequate for pre-testing and cognitive debriefing , 38. We After the translation and pre-testing processes were completed, data were collected for assessment of the measurement properties of the CSI-NP. We followed the methodological quality, proposed by the COSMIN recommendations . To accoInformation regarding participants’ age, gender, marital status, religion, ethnicity, education and occupation were collected to describe the participant characteristics.Duration of pain was recorded as the number of weeks since the onset of current pain. Pain intensity was assessed using the Nepali version of the 11-point Numerical Rating Scale (NRS), which has been shown to be valid and reliable, with excellent test-retest reliability  . Three mQuality of pain was assessed with a list of descriptors, which we previously identified as the most common pain quality descriptors in Nepal . These dSites of pain were assessed using a pain diagram. Participants were asked to mark their painful sites on a body chart. The sites of pain were categorized as pain in the neck, shoulder and arm, elbow and forearm, wrist and hand, upper back, lower back, hip and thighs, knee and leg, and ankle and foot.Pain catastrophizing was assessed using the Nepali version of 13-item Pain Catastrophizing Scale (PCS) . Each itPart A of the CSI  includesThe raw data were entered into SPSS 24.0 for analyses, and descriptive statistics were computed for demographic and pain variables.The internal consistency of the CSI-NP was computed using Cronbach’s alpha. We considered Cronbach’s alpha between 0.80–0.89 to be good, and values equal to 0.90 or more as excellent internal consistency .2,1) was used to compute the two-week test-retest reliability using two way mixed model and absolute agreement. The ICC value of more than 0.75 was considered to be excellent test-retest reliability [The Intraclass Correlation Coefficient , where SD = standard deviation of change of CSI-NP from baseline to follow-up.The SDC for 95% confidence interval was computed using the formula SEM × Z × √2; where Z is the Z value for the 95% CI and √2 is used to account for the variance of two measurements .The Bland-Altman Plot was created to visualize systematic errors in the baseline and final time-point scores of the CSI .r values of less than 0.30 as a weak correlation, 0.30–0.49 as a moderate correlation and values of 0.50 or higher as a strong correlation [t-test was used to assess if women had significantly higher CSI score than men. The results are reported as “hypothesis confirmed” or “hypothesis not confirmed”. The total number of met hypotheses were added and reported as percentages. If the total percentage was more than 75%, we confirmed the construct validity of the CSI-NP as per the COSMIN recommendations [As indicated earlier, a total of five hypotheses were tested to evaluate the construct validity of the CSI-NP, using a standard hypothesis testing methodology , 50. Sperelation . An unpandations .Three items required cross-cultural adaptation during the translation phase, with input from two of the developers of the CSI. Item 19, “I have pain in my jaw,” was difficult to translate because a single Nepali word for “jaw” does not exist. After discussion within the translation team and a dentist, the item was translated as “I have pain in the muscles and joints around my molar teeth.” Item 25, “I have pain in my pelvic area,” was translated as “I have pain between my hips (near my private body parts)” because there was no agreement on a Nepali word for pelvic area that is easily understandable. Finally, the Nepali translation of item 24, “I suffered trauma as a child,” only reflected physical trauma in the initial Nepali translation. Therefore, to assure the conceptual equivalence we explicitly added “physical or psychological” before “trauma” to clarify that trauma could be either physical or psychological. Translation of the part B of the CSI was difficult because Nepali words for most of the medical conditions were not available in Nepali, therefore the vigorous forward and backward translation of part B of the CSI was not performed.The mean age of the study participants was 42.01 (14.61 SD) years. The majority of participants were female (67%), married (76%), and Hindu by religion (79%). Almost half of the participants were unemployed (47%). The mean duration of pain was 111 weeks, the median was 24 weeks, and the range was 4 to 1280 weeks. The most common sites of pain were the knee (32%) followed by the low back (24%). Additional socio-demographic details are presented in Table Total mean score for the CSI-NP was 22.85 (SD 12.35) with scores ranging from 0 to 59. A majority of the sample (75%) scored in the subclinical severity range (scores < 29). Only 14% were categorized as mild, 8% as moderate, and 3% as severe central sensitization related symptoms. No subjects scored in the extreme category. The total mean score for the PCS was 18.51  and the NRS was 5.17 .Internal consistency of the CSI-NP was good . Test-retest reliability of the CSI-NP was excellent with ICC = 0.98 ., presents the distribution and variability in the CSI scores in the baseline and final measurements for each study participant.Standard error of measurement was 0.31. Smallest detectable change (SDC) was 0.86. The Bland-Altman Plot, shown in Fig. 1r = 0.50, P < 0.001), moderately with the total number of pain descriptors , and weakly with NRS pain intensity . Mean CSI-NP scores were significantly higher in women  compared to the men . The correlation of the CSI-NP with pain duration  was weak and non-significant.As shown in Table Exploratory analysis revealed that CSI-NP scores were frequently and significantly associated with three pain descriptors, including heavy, tingling, and infection-like pain (throbbing pain), but not with other types of pain, including achy, piercing, stretching, numb, cramping, and burning  smaller than other language versions (SEM = 1.84 to 3.16) , 54, 55.Eighty percentage (four of five) of a priori hypotheses were met, which support the construct validity of the CSI-NP based on criteria proposed by Terwee and colleagues . Construr = 0.51 and 0.42 respectively) [r = 0.50) was similar to the Dutch version (r = 0.52) but lesser than Brazilian Portuguese version (r = 0.68). Our hypothesis that women experience more CS related symptoms is consistent with previous literature [The hypotheses were made based on the direction and magnitude of associations. Due to lesser number of similar associations being tested in previous research, the magnitude of association hypothesized were open wider. Although the hypotheses on the association of the CSI-NP with pain intensity, pain catastrophizing were met as hypothesized, the strength of correlations we found are varied. For example, the correlation of the CSI-NP with pain intensity (r = 0.25) was lower than the Dutch and Japanese versions (ctively) , 18. Simterature –30. The Exploratory analyses for the association of CSI scores with heavy pain, tingling pain, and throbbing pain is interesting, and should be confirmed in further studies to assess if particular types of pain are associated more strongly with central sensitization signs and symptoms than the other types of pain. If this is the case, type of pain then could help flag central sensitization related signs and symptoms.Despite the methodological strengths, i.e. adoption of standard recommended guidelines to translate and cross-culturally adapt CSI into Nepali , and comThe CSI was successfully translated into Nepali for the first time. The CSI scores were shown to be reliable and valid and that it can be used to assess signs and symptoms related to central sensitization in adults with musculoskeletal pain in Nepal in clinical practice or research. Future studies on the CSI-NP should assess treatment responsiveness, compute a minimum important change score, compare if that score is larger than the values of measurement errors, and validate the CSI in other pain populations to extend its clinical and research use.Additional file 1. Nepali-CSI final version.Additional file 2. CSI English version.


We study the continuity of many channel parameters and operations under various topologies on the space of equivalent discrete memoryless channels (DMC). We show that mutual information, channel capacity, Bhattacharyya parameter, probability of error of a fixed code and optimal probability of error for a given code rate and block length are continuous under various DMC topologies. We also show that channel operations such as sums, products, interpolations and Arıkan-style transformations are continuous. This paper is an extended version of our paper that is published in the International Symposium on Information Theory 2017 (ISIT 2017) (o) . TherefoNoisiness metric: For every W (see [The quantity f W (see ). TherefDefine the noisiness distance We have shown in  that (DMThe space of channels with input alphabet We define the equivalence relation The space of equivalent channels with input alphabet W with the For every Since any two equivalent channels have the same Blackwell measure, we can define the Blackwell measure of We have:A topology Every natural topology is onnected . On the anywhere . This imStrong topology on We associate -compact .The strong topology A is a subset of A is strongly open if and only if A is strongly closed if and only if We call open and closed sets in We have shown in  that Ts,d and T4 . On the anywhere ; hence, Noisiness metric: Define the noisiness metric on The metric topology on shown in  that TX,Topologies from Blackwell measures: The mapping Since In , we studThe total-variation metric distance The total-variation topology roved in  that if X is distributed as p and Y is the output of W when X is the input. The mutual information is computed using the natural logarithm. The capacity of W is defined as Let W under prior p is defined as:For every Clearly, W as:For every It is easy to see that It was shown in ,11 that n is the block length of M is the size of the code. The rate of An W is given by:The optimal error probability of The following proposition shows that all the above parameters are continuous:Proposition 2.We have:For every code For every Proof. I, its concavity in p and its convexity in W [C is the supremum of a family of mappings that are convex in W, it is also convex in W. For a proof of the continuity of C, see Z, p and in W can also be easily seen from the definition. ☐These facts are well known, especially the continuity of ity in W . Since CW and V as follows:If For every function It is easy to see that if For every two channels We define the channel product annon in .For every Channel interpolation arises when a channel behaves as  used in  to constNow, fix a binary operation ∗ on These operations generalize Arıkan’s polarization transformations .Proposition 3.We have:The mapping The mapping The mapping The mapping For any binary operation ∗ on For any binary operation ∗ on Proof. The continuity immediately follows from the definitions. ☐W. Therefore, we can define those parameters for any It is well known that the parameters defined in Proposition 4.We have:For every code For every Proof. I and Z. We will only prove the continuity of I since the proof of continuity of Z is similar.Since the corresponding parameters are continuous on R on Define the relation R-equivalence class of I is continuous on I is continuous on I is continuous on It is easy to see that With the exception of channel composition, all the channel operations that were defined in Let annon in .Therefore, if With the exception of channel composition, we can “quotient” all the channel operations of Proposition 5.We have:The mapping The mapping The mapping For any binary operation ∗ on For any binary operation ∗ on Proof. We only prove the continuity of the channel sum because the proof of continuity of the other operations is similar.f is continuous.Let R on Now, define the equivalence relation R-equivalence class of f defined on The discussion before the proposition shows that f on Notice that f on Now, since the mapping The following lemma provides a way to check whether a mapping defined on Lemma 6.Let Proof. I, C, Z, Since the channel parameters  n≥1 see , they arProposition 6.Let For every code For every Proof. I and Z are similar, we only prove the continuity for I.The continuity of Due to the distributivity of the product with respect to disjoint unions, we have:I is continuous on I is continuous on Therefore, R on R-equivalence class of I is a continuous mapping from I is continuous on Define the relation It is also possible to extend the definition of all the channel operations that were defined in Proposition 7.Assume that all equivalent channel spaces are endowed with the strong topology. We have:The mapping The mapping The mapping For any binary operation ∗ on For any binary operation ∗ on Proof. We only prove the continuity of the channel interpolation because the proof of the continuity of other operations is similar.Let Therefore, the space For every n is the unique integer satisfying Define the mapping f is continuous on f is continuous on Due to Proposition 3 and due to the continuity of R on Let R-equivalence class of f is continuous on Since Since Corollary 3.Proof. H is continuous by Proposition 7. We also have Fix The reader might be wondering why channel operations such as the channel sum were not shown to be continuous on the whole space R be the equivalence relation on One potential method to show the continuity of the channel sum on It was shown in  that theWe need to express the channel parameters and operations in terms of the Blackwell measures.The following proposition shows that many channel parameters can be expressed as an integral of a continuous function with respect to the Blackwell measure:Proposition 8.For every where Proof. By choosing any representative channel Proposition 9.Let For every code For every Proof. I is continuous on Z similarly.We associate the space Now, define the mapping Fix C is continuous on Similarly, we can show that For every Now for every Clearly It is worth mentioning that Proposition 6 can be shown from Proposition 9 because the noisiness topology is coarser than the strong topology.Corollary 4.All the mappings in Proposition 9 are also continuous if we replace the noisiness topology Proof. This is true because In the following, we show that we can express the channel operations in terms of Blackwell measures. We have all the tools to achieve this for the channel sum, channel product and channel interpolation. In order to express the channel polarization transformations in terms of the Blackwell measures, we need to introduce new definitions.Let o itself . For eveshown in  that a bBinary operations that are not uniformity preserving are not interesting for polarization theory because they do not preserve the symmetric capacity . TherefoLet ∗ be a fixed uniformity preserving operation on The probability distribution Clearly, gies see . For eveSince the product of meta-probability measures is continuous under both the weak-∗ and the total variation topologies , the (−,For every The probability distribution Define the mapping If For every Since the product of meta-probability measures is continuous under both the weak-∗ and the total variation topologies , the (+,Proposition 10.We have:For every where For every For every For every uniformity preserving binary operation ∗ on For every uniformity preserving binary operation ∗ on Proof. See Note that the polarization transformation formulas in Proposition 10 generalize the formulas given by Raginsky in  for binaProposition 11.Assume that all equivalent channel spaces are endowed with the noisiness/weak-∗ or the total variation topology. We have:The mapping The mapping The mapping For every uniformity preserving binary operation ∗ on For every uniformity preserving binary operation ∗ on Proof. The proposition directly follows from Proposition 10 and the fact that all the meta-probability measure operations that are involved in the formulas are continuous under both the weak-∗ and the total variation topologies. ☐Corollary 5.Both Proof. We can use the same proof of Corollary 3. ☐The continuity of the channel sum and the channel product on the whole product space