Antibiotic overuse is one of the main drivers of antimicrobial resistance (AMR), especially in low-income and middle-income countries. This study aimed to understand the perceptions and views towards AMR, antibiotic prescribing practice and antimicrobial stewardship (AMS) among hospital physicians in Jakarta, Indonesia.Cross-sectional, self-administered questionnaire-based survey, with descriptive statistics, exploratory factor analysis (EFA) to identify distinct underlying constructs in the dataset, and multivariable linear regression of factor scores to analyse physician subgroups.Six public and private acute-care hospitals in Jakarta in 2019.1007 of 1896 (53.1% response rate) antibiotic prescribing physicians.Physicians acknowledged the significance of AMR and contributing factors, rational antibiotic prescribing, and purpose and usefulness of AMS. However, this conflicted with reported suboptimal local hospital practices, such as room cleaning, hand hygiene and staff education, and views regarding antibiotic decision making. These included insufficiently applying AMS principles and utilising microbiology, lack of confidence in prescribing decisions and defensive prescribing due to pervasive diagnostic uncertainty, fear of patient deterioration or because patients insisted. EFA identified six latent factors : awareness of AMS activities; awareness of AMS purpose; views regarding rational antibiotic prescribing; confidence in antibiotic prescribing decisions; perception of AMR as a significant problem; and immediate actions to contain AMR. Factor scores differed across hospitals, departments, work experience and medical hierarchy.AMS implementation in Indonesian hospitals is challenged by institutional, contextual and diagnostic vulnerabilities, resulting in externalising AMR instead of recognising it as a local problem. Appropriate recognition of the contextual determinants of antibiotic prescribing decision making will be critical to change physicians’ attitudes and develop context-specific AMS interventions. The self-developed questionnaire in this study identified a relevant set of attributes through a factor analysis optimisation process, with adequate content, face and construct validity and internal reliability. This study adds important value in the absence of adequately validated instruments regarding antimicrobial resistance and stewardship, with particular applicability for low-income and middle-income countries.This study had a large, varied respondent sample and high response rate among physicians at six public and private hospitals in Jakarta, Indonesia, and identified differences between physicians across hospitals, departments, work experience and medical hierarchy, which can guide priority-setting and tailoring of stewardship interventions.However, non-participation and the convenient hospital sample could have introduced selection bias, and the data are not necessarily representative for Jakarta or Indonesia.Factor analysis is based on using a ‘heuristic’, which leaves room to more than one interpretation of the same data and cannot identify causality.The global rise in drug-resistant infections is one of the leading threats to public health globally, with increasing rates of morbidity, mortality and escalating healthcare costs.6Patients infected with drug-resistant bacteria causing common bacterial infections in hospitalised populations are more likely to receive inappropriate antibiotic therapy resulting in higher mortality rates and opportunities for spreading to other patients.12The global push to enact effective AMS requires detailed, context-specific data on physicians, given their central role in the complex process of antibiotic prescribing in hospitals, which can inform on how antimicrobial resistance (AMR) is conceived, how current prescribing is rationalised, and how broad AMS principles may be experienced across contexts and nations.4 5Indonesia, a diverse lower-middle-income country in Southeast Asia with the world’s fourth largest population (275 million), is particularly vulnerable for AMR, ranked among the greatest risers (29th of 76 countries) in antibiotic consumption, estimated at 2.5-fold between 2000 and 2015.To identify context-specific opportunities for AMS interventions, we conducted a questionnaire-based survey among antibiotic-prescribing physicians in hospitals in Jakarta, Indonesia, to evaluate their perceptions of AMR, antibiotic prescribing practice, and views on AMS, and explore differences between physician subgroups. The study also aimed to evaluate the construct validity and psychometric properties of the questionnaire, and explore differences between physician subgroups.We conducted a cross-sectional survey between March and August 2019 among all antimicrobial prescribing physicians at six acute-care hospitals in Jakarta, Indonesia, as part of a mixed-method study to identify targets for quality improvement in antibiotic prescribing practices (EXPLAIN study).All qualified physicians prescribing antibiotics on a regular basis working were eligible for the survey and were approached to participate. The survey intended to include physicians across all clinical departments, work experience and professional hierarchy, to ensure representation of different antibiotic practices and views, perceptions and experiences related to AMR and AMS.Patients or the public were not involved in the design, conduct or reporting of the research.We developed a two-page anonymous, self-administered, paper-based questionnaire, which was easy to complete and based on a conceptual framework that included attributes related to prescribers’ perceptions, views and practices. Good practice recommendations for questionnaire design and existing questionnaires in the literature were reviewed and discussed with several experts. The Clinician Pre/Post Perception Survey of the Greater New York Hospital Association United Hospital FundThe final questionnaire included an explanation of study purpose and completion instructions; 40 short statements (items) to which participants were asked to indicate the extent to which each reflected their own opinion on a 5-point Likert scale, divided into three sections: scope of the AMR problem and key contributors; antibiotic prescribing practices; AMS and respondent sociodemographics .10.1136/bmjopen-2021-054768.supp1Supplementary dataThe hospital management provided the total number of prescribing physicians for each department. The questionnaires were delivered to the head of each unit who then distributed the survey to all eligible staff. The study coordinator kept a record of numbers of physicians approached and participated. On survey completion, respondents could enter a raffle to win one of three gift cards in each hospital (US$14 each); there were no other incentives for participation.The percentage of respondents selecting each answer choice was calculated using the total number of responses as the denominator. For an exploratory factor analysis (EFA), a common lower bound for sample size is 10 cases per variable, suggesting a minimum sample size of 400; to allow for meaningful subgroup comparisons and minimise selection bias, we targeted a>50% response rate and a sample size of >1000 across the six hospitals.paran package in Stata). Parallel analysis adjusts the original eigenvalues for sampling error induced collinearity among the variables to arrive at adjusted eigenvalues. Analogous to the Kaiser criterion, only factors with adjusted eigenvalues >1 were retained. The scree plot of eigenvalues and the scree plot of parallel analysis were visually inspected and factors were retained above the inflection. To interpret the factor solutions, we examined the factor loadings, and assigned each item to a certain factor based on the highest absolute factor loading (minimum loading 0.30), and then produced an umbrella label for each factor that best characterised the joint meaning of all the variables associated with it. If a certain item did not fit with the factor structure , the analysis was rerun without the pertinent item(s). After the optimal factor solution had been achieved, we used the regression scoring method to compute the factor scores based on the factor loadings, and Cronbach’s α coefficient to test internal reliability. Using the factor scores as the dependent variable, we developed six (one for each factor score) multivariable linear regression models to assess associations with key physician characteristics (‘subgroups’) as the following five independent variables, that is, hospital sector and care level, grouped departments, work experience and medical hierarchy. Given the hierarchical structure of the data  we applied multilevel (two-level) modelling to control for possible clustering within hospitals. We also adjusted for possible confounders. Values of p<0.05 were considered statistically significant. All analyses were done with Stata/IC v16.1 (StataCorp).We performed EFA to identify underlying distinct constructs, using factor, pcf command in Stata with orthogonal (varimax) rotation. For this analysis, the eight items worded in the negative were reverse-coded, and missing data for categorical variables were treated as a separate category. The Kaiser-Meyer-Olkin (KMO) was calculated to ensure EFA requirements were met. Each item was assigned to a certain factor based on the highest absolute factor loading of the rotated solution. To determine the optimal factor solution, we used the Kaiser criterion, scree plot of eigenvalues, and Horn’s parallel analysis  participated in the survey. 10.1136/bmjopen-2021-054768.supp2Supplementary dataMost respondents agreed that AMR is an important problem in Indonesia  (Q2); in communities outside of the hospital  (Q6); and at their hospital  (Q1), with 30.9% (311/1005) agreeing that patients are likely to develop an infection with a multidrug-resistant infection (Q10). Most acknowledged as key contributing factors: overuse of antimicrobial drugs  (Q3), lack of hand hygiene  (Q4), use of broad-spectrum antibiotics  (Q5). Current infection and prevention control (IPC) practices at their hospital were regarded as suboptimal: 64.8% (651/1004) thought that patient rooms are cleaned according to hospital protocol after discharge of a patient with a multidrug-resistant organism (Q7); 56.9% (570/1002) thought adherence to hand-hygiene protocols to be excellent (Q8); and 22.5% (226/1005) felt that their hospital does not provide adequate staff education regarding multidrug-resistant organisms (Q9).Whereas most respondents  agreed that antibiotics are overused in Indonesia (Q11), only 35.5% (357/1005) acknowledged this to be case at their hospital (Q12). Most agreed that more judicious antimicrobial prescribing practices would decrease AMR  (Q17) and that following evidence-based antibiotic guidelines will help optimise treatment outcomes  (Q18). Most gave high priority to rational antibiotic prescribing to their patients  (Q19), and considered developing hospital antibiotic guidelines more useful than applying international guidelines  (Q20). Nearly a quarter of respondents indicated to be often unsure if a patient needs an antibiotic or not  (Q21) or which antibiotic to prescribe  (Q22). A small but considerable fraction expressed lack of confidence in prescribing decisions, that is, 12.2% (123/1005) prescribed in patients with just a high fever (≥39°C) (Q24), 36.6% (368/1005) when they felt uncertain about the diagnosis of infection (Q25), 35.0% (352/1006) prescribed more freely because of fear of clinical failure (Q26), and 9.8% (98/1005) frequently prescribed antibiotics because patients or their relatives insist (Q27). Just more than half of the respondents reported that microbiology laboratory results are efficiently communicated to the treating physician  (Q13), considered the hospital antibiogram when empirically prescribing antibiotics  (Q14), and would stop antibiotics that others have prescribed in the absence of an appropriate indication  (Q23). Most  agreed that, if medically appropriate, intravenous antibiotics should be stepped down to an oral alternative after 3 days (Q15). Notably, 33.6% (338/1006) felt that restrictions on antibiotics impaired their ability to provide good patient care (Q16).When asked about AMS in general, most respondents were aware that their hospital had an AMS programme  (Q28), they reported they understood its purpose  (Q29), and they agreed that AMS can improve patient care  (Q30), reduce AMR  (Q31) and hospital-acquired infections  (Q32). When asked about the usefulness of specific AMS activities, most respondents acknowledged that additional education on antibiotic prescribing was needed  (Q33), regular audit and feedback encouraged them to prescribe antibiotics prudently  (Q34), rapid and accurate diagnostic tests are useful for diagnosis of infectious diseases and guidance on antibiotic therapy  (Q35), implementation of antibiotic restriction  can reduce antibiotic overuse in hospitals  (Q36), regular consultations or ward rounds with a clinical microbiologist or infectious disease physician can curb AMR  (Q37), timely access to microbiological test results is needed to guide antibiotic therapy  (Q38), and IPC in the hospital can reduce AMR  (Q40).The KMO was 0.8773 overall and >0.5 for all items, suggesting the data were suitable for EFA. Analysis of the scree plot  indicateStatistically significant differences were identified between hospitals for awareness of AMS purposes (factor 2), views regarding rational antibiotic prescribing (factor 3), perception of AMR as a significant problem (factor 5) and immediate actions to contain AMR (factor 6), but not for awareness of AMS activities (factor 1) and confidence in antibiotic prescribing decisions (factor 4). None of the factor scores differed between prescribers in public vs private, or secondary vs tertiary hospitals.For awareness of AMS activities (factor 1), consultants, GPs and residents scored higher than interns. For awareness of AMS purposes (factor 2), consultants scored lower than interns and residents. For views regarding rational antibiotic prescribing (factor 3), consultants scored higher than GPs. For confidence in antibiotic prescribing decisions (factor 4), consultants scored lower than residents, whereas for immediate actions to contain AMR (factor 6), consultants scored higher than residents. No differences were identified for perception of AMR as a significant problem (factor 5).For awareness of AMS activities (factor 1) and purpose (factor 2), physicians in surgery and medicine scored higher than the acute specialties, whereas for awareness of AMS activities (factor 1), medicine scored higher than surgery. For views regarding rational antibiotic prescribing (factor 3), surgery scored higher than acute specialties. For confidence in antibiotic prescribing decisions (factor 4), medicine scored lower than surgery and other specialties. For perception of AMR as a significant problem (factor 5), surgery scored lower than medicine. For immediate actions to contain AMR (factor 6), surgery scored higher than medicine and other specialties and the acute specialties scored higher than surgery and medicine.Physicians with little (0–5 years) work experience scored lower than more experienced colleagues, for awareness of AMS purpose (factor 2); for perception of AMR as a significant problem (factor 5); and for immediate actions to contain AMR (factor 6). No differences were identified for factors 1, 3 and 4.This survey, among over 1000 physicians in Indonesian hospitals, assessed their perceptions and views regarding the AMR problem and its key contributors, antibiotic prescribing practices and AMS. Starting from those three broad themes, we used EFA to identify distinct underlying constructs in the dataset, that is, (1) awareness of AMS activities; (2) awareness of AMS purposes; (3) views regarding rational antibiotic prescribing; (4) confidence in antibiotic prescribing decisions; (5) perception of AMR as a significant problem and (6) immediate actions to contain AMR. The survey findings thus outline a series of dynamics around AMR and AMS in the Indonesian context. Spanning issues around awareness (education)In this respect, an important finding was that only few physicians recognised that antibiotic overuse was an issue at their own hospital, that many physicians were hesitant to stop antibiotics without an appropriate indication that others had prescribed, and that many felt that antibiotic restrictions impaired their ability to provide good patient care. Lack of confidence in prescribing decisions and defensive prescribing were common due to diagnostic uncertainty, fear of patient deterioration or complications, or because patients or their relatives insisted. These views and perceptions concur with the observed overuse of broad-spectrum antibiotics, the underuse of diagnostic stewardship to guide antibiotic decisions and poor guideline compliance of antibiotic prescribing in the same hospitals, described in our recent paper, which identified several priority areas for stewardship.17Based on the survey data, we considered that an important obstacle that hinders effective AMS implementation in this context could be linked to perceived ‘externality of AMR’ as a problem.35The identified differences between hospitals regarding awareness of AMS purposes, views regarding rational antibiotic prescribing, perception of AMR as a significant problem and immediate actions to contain AMR could not be attributed or related to the pertinent hospital sector (public vs private) or healthcare level (secondary vs tertiary), but they were found to be associated with several differences between the physician subgroups. First of all, work experience and medical hierarchy were found to influence the awareness of AMS purpose, AMR as a significant problem, and immediate actions to contain AMR. Interestingly, compared with junior physicians, specialists/consultants expressed lower confidence to make antibiotic decisions in uncertain situations while showing higher confidence in actions to contain AMR. Possible explanations include that specialists/consultants have a better recognition of the ‘unknowns’  and that they bear final patient responsibility, introducing the fear of losing a patient or legal consequences,38 39Furthermore, the acute specialties  and anaesthesiology) had lower awareness of AMS activities and purposes, compared with surgery or medicine, but scored higher for immediate actions to contain AMR. Compared with surgeons, physicians in medicine had a greater awareness of AMS activities and recognition of AMR as a significant problem, but they had lower confidence in antibiotic prescribing decisions and immediate actions to contain AMR. These observations are in line with a UK study that found that emergency physicians experienced pressure for immediate action out of fear of losing a patient and a lack of ownership of antibiotic decision making due to the patient transitioning to inpatient care, that medical doctors adopted a more policy-informed, interdisciplinary approach and that senior surgeons left complex antibiotic decisions to junior staff, resulting in potential defensive and inappropriate antibiotic use.Our study had several strengths and weaknesses. First, we were able to identify a relevant set of attributes through a factor analysis optimisation process, with adequate content, face and construct validity and internal reliability. In the absence of adequately validated instruments regarding AMR and AMS,AMS implementation in Indonesian hospitals is likely highly dependent on institutional, contextual and diagnostic vulnerabilities. These may result in the problem of AMR being externalised, instead of recognised as a local hospital problem. Current AMS strategies may be insufficiently successful in promoting prudent antibiotic use, due to lack of systematic engagement with and feedback to prescribers, aimed at building confidence in antibiotic decision making and ownership of the AMR problem. Appropriate recognition of the contextual and social determinants of antibiotic prescribing decision making, including hospital factors, dynamics in medical hierarchy and experience, among others, will be critical to design context-specific AMS interventions that are adopted by healthcare professionals and successfully influence behaviours.14


Globally, the prevalence of allergic diseases remains high, as does the level of environmental antibiotics. It has been found that clinical antibiotic application may increase preschool allergy risk. However, few biomonitoring studies have been conducted about the association between early life environmental trace dose antibiotic exposure and preschool allergy.To analyze the association between prenatal environmental antibiotic levels and allergic diseases using logistic regression models.A total of 743 pregnant women and their offspring from the Shanghai Allergy Birth Cohort completed five years follow-up, and 251 mother-infant pairs were finally included. Maternal urine samples were collected for 15 antibiotic quantitative measurements using liquid chromatography-tandem mass spectrometry. The high-antibiotic group was defined as having at least half of antibiotics exceeding the median concentration. Allergic diseases were assessed by clinicians through clinical history, standardized questionnaires, and annual physical examinations until the age of five. Skin-prick-test (SPT) was performed at 5 years old.The incidence of allergic diseases was generally higher in the high-antibiotic than that in the low-antibiotic group. Compared to the low-comprehensive antibiotic group, children in the high-antibiotic group were weakly associated with allergic diseases but had a 6-fold increased risk of food allergens sensitivity . Association of above-median single prenatal antibiotic concentration exposure and allergic diseases was also observed . Moreover, children with higher prenatal norfloxacin levels were more sensitive to food allergens .Early-life environmental antibiotic exposure may be correlated with an increased risk of asthma, wheeze, atopic dermatitis, and SPT positivity for food allergens in 5-year-old children. Because samples –9. These samples .At the same time, the prevalence of allergic diseases has remained continuously high in recent years. Approximately one-third of children worldwide develop allergies, inevitably leading to global economic burdens , 12. TheThe Shanghai Allergy Birth Cohort is an ongoing prospective birth cohort that recruited pregnant women from June 2012 from two tertiary-level hospitals in Shanghai, Xinhua Hospital and the International Peace Maternity and Child Health Hospital. Third-trimester pregnant women  who underwent routine prenatal examinations at the two hospitals were considered for this cohort. Eventually, 1,143 mother-infant pairs participated in the cohort as a baseline, and 743 pairs (65%) completed each scheduled follow-up until their children were 5 years old. A total of 198 pairs were followed up only by telephone and did not fill out the standard questionnaire in the field and were therefore excluded. Moreover, 294 pairs whose biological samples were missing; hence, 251 mother-infant pairs were finally included in the study . Most ofParticipants completed standard questionnaires upon enrollment and at 6 months, 1 year, 2 years, and 5 years of the child's age. The initial questionnaire collected information on maternal age, weight, parental education levels, and parental atopic-disease history . The subsequent questionnaires at 6 months, 1 year, 2 years, and 5 years of the age focused on the children's fundamental conditions and allergic diseases (including cough and wheeze) and covered the International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire. All participants signed an informed consent form at enrollment. The study was approved by the Ethics Committees of the involved research institutions and hospitals.In this study, maternal urine samples collected 1–3 days before delivery were assessed for antibiotic exposure. According to previous studies regarding environmental antibiotic exposure , 7, 20, 4, sulfadiazine-13C6, ciprofloxacin-d8, enrofloxacin-d5, trimethoprim-d3, chloramphenicol-d5, azithromycin-d3, and tetracycline-d6). Quality control samples were randomly included among samples in each batch and the purity of all the standards was strictly maintained at ≥ 94%. The limit of detection (LOD) was set at 0.1–1.0 ng/mL for the selected antibiotics, with a signal-to-noise ratio of 3.Specimens were stored at Xinhua Hospital's biobank at −80°C. The urine samples were preprocessed , and liqUrinary creatinine levels were detected using the enzymatic method . The creatinine-corrected urinary antibiotic concentrations (ng/g creatinine) were considered the internal exposure levels, which were calculated using volume-based urinary antibiotic concentrations divided by urinary creatinine concentrations.via repeated symptoms (wheeze and cough), history of allergy to dust mites, and clinical examination (immunoglobulin E [IgE] level and pulmonary function tests), based on the Global Initiative for Asthma guidelines (via the symptom of an itchy rash and at least three of the following characteristics: (1) history of flexural involvement; (2) onset under 2 years old; (3) medical history of asthma or allergic rhinitis; (4) ever had dry skin; and (5) visible flexural dermatitis. Parents reported information on diarrhea during the second year after birth. The definition of diarrhea depended on the change of stool characteristics and frequency: the formation of loose stools, watery stools, egg-patterned stools, or stools with mucus or pus and blood; the number of stools is more than usual or more than three times.Asthma was diagnosed by professional pediatric respiratory physicians at 1, 2, 3, 4, and 5 years of age idelines . Wheeze idelines . Accordiidelines , atopic Dermatophagoides pteronyssinus and Dermatophagoides farina), cat/dog dander, Aspergillus niger, ragweed/indus/birch tree/willow pollen, egg, cow's milk, mango, sea shrimp, sea crab, beef, mutton, cashew nut, and walnut. In this study, SPT for common inhalants and nine food allergens were performed by pediatricians at 5 years old according to the European standardization SPT procedures, with histamine and physiologic saline as positive and negative controls, respectively. A positive result was confirmed after 15–20 min of application when the wheal diameter was at least 3 mm larger than that of the negative control (Skin prick test (SPT) was conducted for nine common inhalants and nine food allergens, including dust mites , and frequency  were calculated for sociodemographic characteristics, antibiotic concentrations in maternal urine samples, and allergy-related health outcomes among group participants. Furthermore, corresponding-antibiotic-category detection in maternal urine samples was defined as the overall antibiotic detection in that category covered in this study. Multivariate logistic regression was used to analyze the associations between antibiotic exposure in utero and allergy-related health outcomes. Three analyses were mainly conducted: (1) based on the concentrations and detection frequencies of 13 antibiotics, the total population was classified into binaries, and children in the high-antibiotic group were regarded as having higher comprehensive prenatal environmental antibiotic exposure. A globally accepted definition of high-antibiotic exposure is not available currently. Thus, the high-antibiotic group was defined as (1) having at least half of antibiotics exceeding the median out of eight antibiotics whose detection frequency exceeded 25%; (2) for five single antibiotics whose frequency was above 50%, antibiotic concentrations were divided into binaries by their medians. Antibiotic exposure concentrations (≥ median) were regarded as having higher single prenatal environmental antibiotic exposure; (3) concerning six single antibiotics whose frequency below 50%, the population was spilled into binaries (concentrations: < 90th percentile and ≥ 90th percentile). Antibiotic exposure concentrations (≥ 90th percentile) were considered as higher single environmental antibiotic exposure in utero. The results are presented as adjusted odd ratios (ORs) and 95% confidence intervals (CIs). The following potential confounders were selected: offspring sex, maternal education status at delivery, gestational age, breastfeeding during the first 6 months, and offspring body mass index (BMI) at 5 years of age. Data were missing in 0.7–2.1% of the mother-infant pairs for one or more potential confounders. Additionally, regarding SPT positivity for common inhaled allergens or food allergens, 10.4–17.9% of the participants lacked corresponding data. Despite partial data loss in some participants, they were included in this study's analysis.Mean values (standard deviations [SDs]), medians (Phttp://www.T-project.org). P ≤ 0.05 was considered statistically significant.All analyses were performed using Empower R  and R software   .P < 0.05) . However, no statistically significant differences in the incidence of allergy-related outcomes were observed between the low-antibiotic group and the high-antibiotic group, except for SPT being sensitive to food allergens  . The ris < 0.05) . Moreove < 0.05) .In the analysis of each class of antibiotics, VA exposure above the median showed an 84% higher risk  of wheeze than lower concentration exposure; there was no significant association between the allergic diseases and the concentrations of other categories of antibiotics .Regarding five specific antibiotics whose frequency was above 50%, compared to those with low-antibiotic exposure, children with exposure to above-median prenatal enrofloxacin  and trimethoprim  concentrations appeared 2.22-times  and 2.00-times  more likely to develop wheeze and atopic dermatitis, respectively. Furthermore, the risk of SPT positivity for food allergens in children with norfloxacin exposure concentrations above the medians  increased 4.52 times  compared with children with lower antibiotic exposure concentrations . A higheWe further analyzed the six single antibiotics whose frequency was below 50% by grouping the population into two sets (< 90th percentile and ≥ 90th percentile) . Among tMoreover, SPT-positive individuals were found to have considerably greater IgE levels than negative individuals among children whose mothers had lower concentrations of antibiotics found in their urine. When exposed to higher single antibiotic levels , children who tested positive for SPT had noticeably higher IgE levels than those who tested negative for SPT .in utero and allergy-related health outcomes in preschool children until the age of 5 years and found that compared to the comprehensive antibiotic low-exposure group, children with higher comprehensive prenatal environmental antibiotic exposure were not associated with allergic diseases but may be more liable to test positive for SPT for food allergens. Children exposed to higher environmental enrofloxacin and trimethoprim in utero were correlated with an increased risk of wheeze and atopic dermatitis, respectively. Children with higher prenatal norfloxacin levels were more sensitive to food allergens than lower-concentration exposure. Furthermore, prenatal environmental azithromycin exposure was related to the susceptibility to asthma compared to children with lower exposure.This study assessed the associations between environmental antibiotic exposure in utero, which may have resulted in exposure to doses heavier than their body weight can withstand and may adversely affect children's health   summarizin utero leading to increased allergic disease risk remains unclear. There is a potential explanation that environmental antibiotic exposure could damage the immune defense and inflammatory response, impacting the gut microbiome and metabolic pathways, thereby mediating allergic diseases, which are closely related to immune defense and inflammation. Several experimental studies demonstrated that antibiotic exposure would eventually threaten human health by disrupting the balance maintained by the microbiota and damaging immune defense  was associated with an increased risk of subsequent asthma, wheeze, atopic dermatitis, and positive results of SPT to food allergens in preschool children. In this respect, more evidence is needed to clarify the association and the specific pathway it affects.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The studies involving human participants were reviewed and approved by Xinhua Hospital and International Peace Maternity and Infant Health Hospital Affiliated with the Shanghai Jiao Tong University School of Medicine. Written informed consent to participate in this study was provided by the participants' legal guardian/next of kin.HZ and XZ contributed equally for formal analysis, roles and writing—original draft, and writing—review editing. QX, YW, QL, and QC were responsible for data curation. WZ and LH contributed equally to project administration and supervision. All authors contributed to the article and approved the submitted version.This research was supported by the National Natural Science Foundation of China (grant numbers 81874265 and 82073561), Shanghai Science and Technology Commission (grant numbers 18411966600 and 19410740800), Shanghai Jiao Tong University School of Medicine (grant number 2020002), Key Discipline Construction Plan from Shanghai Municipal Health Commission (GWV-10.1-XK01), and National Key Specialty of Children's Respiration.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Urinary tract infection (UTI) is considered to be a major problem in pregnant women. It is also one of the most prevalent infections during pregnancy, being diagnosed in as many as 50–60% of all gestations. Therefore, UTI treatment during pregnancy is extremely important and management guidelines have been published worldwide to assist physicians in selecting the right antibiotic for each patient, taking into account the maternal and fetal safety profile. A review of the literature was carried out and all international guidelines giving recommendations about antibiotic treatments for pregnancy-related UTI were selected. The search came back with 13 guidelines from 4 different continents . Our review demonstrated concordance between guidelines with regard to several aspects in the antibiotic treatment of UTI during pregnancy and in the follow-up after treatment. Nonetheless, there are some areas of discordance, as in the case of antenatal screening for bacteriuria and the use of fluoroquinolones in lower or upper UTI. Given the current evidence that we have from international guidelines, they all agree on several key points about antibiotic use. Urinary tract infection (UTI) is considered to be a major problem in pregnant women ,2,3. It Enterobacteriaceae, commonly found in the gastrointestinal tract, with Escherichia coli (E. coli) being responsible for 80–90% of cases. However, we can find other bacteria such as Group-B Streptococcus saprophyticus (GBSS), Klebsiella pneumoniae, coagulase-negative Staphylococcus, Staphylococcus aureus and Proteus mirabilis in a lower percentage [UTIs can be classified as lower urinary tract infections, including both asymptomatic bacteriuria (ASB) or acute cystitis (AC), and upper urinary tract infections or acute pyelonephritis (APN) . Most inrcentage ,6.In pregnant women, ASB occurs in an estimated 2–10% , and if Therefore, UTI treatment during pregnancy is extremely important and management guidelines have been published worldwide to assist physicians in selecting the right antibiotic for each patient, taking into account the maternal and fetal safety profile ,6,9.The aim of this study is to review the concordance in recommendations between evidence-based guidelines for antibiotic treatment of pregnancy-related UTI developed by different authorities around the world. Additionally, we will review their concordance in terms of ASB screening and follow-up after treatment.A literature review was carried out in August 2021 using the PubMed and Scopus databases for clinical guidelines covering the topic of pregnancy-related UTI. An additional search was performed in the Guidelines International Network (G-I-N) for any relevant guidelines not identified by our PubMed and Scopus database search. Exclusion criteria included guidelines that did not include recommendations about antibiotic treatments for pregnancy-related UTI. This review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement .Different searches were carried out with the following medical subject heading (MeSH) terms and keywords: “urinary tract infection”, “UTI”, “pregnancy”, “woman”, “guideline”, “asymptomatic”, “bacteriuria”, “cystitis” and “pyelonephritis”. Boolean operators  were used to refine the search. The references of each included guideline were also reviewed. No time period nor language restrictions were applied.The PubMed and Scopus search returned 386 results and 20 additional guidelines were added after the G-I-N search. After duplicate removal and review of results, a total of 20 guidelines were selected of which 7 were excluded leaving 13 guidelines that fulfilled our inclusion criteria. The summary of the selection process is represented in Of the 13 guidelines coming from 4 different continents , 8 came For better understanding of the main purpose of the present report, the obtained results have been divided into different sections. Those sections are organized as follows: screening for ABU, antibiotics in ABU, antibiotics in cystitis, antibiotics in APN, urine culture follow-up and prophylaxis follow-up.Key points of antibiotic use in pregnancy according to international guidelines  are summarized in A total of 11 out of 13 guidelines (85%) recommended systematic screening for ABU bacteriuria in pregnant women. All guidelines coming from South America ,20,21, NMost guidelines recommended to conduct this screening by a UC ,20,21,225 colony-forming units (CFU)/mL without symptoms of UTI [Almost all guidelines defined ASB as a urine sample showing ≥10s of UTI ,20,21,22s of UTI ,13,20,21s of UTI ,15,16,22Colombia and Brazil recommended to repeat this screening in the third trimester of pregnancy ,21, espeWithout specifying the hierarchy of preference, the recommended antibiotics were: nitrofurantoin ,18,19,20When referring to lines of treatment, as first line, nitrofurantoin ,21, fosfResults are summarized in Without specifying the hierarchy of preference, the recommended antibiotics were: nitrofurantoin ,15,19,20When referring to lines of treatment, as first line, nitrofurantoin ,16,21, fResults are summarized in For APN treatment, most guidelines recommended as a first-line treatment a monotherapy with 3rdGC ,14,15,20Second-line treatment included cefuroxime , gentamiE. coli (ESBLE). Ciprofloxacin, levofloxacin or TMP-SMX was the first-line choice, amoxicillin–clavulanate was the second-line choice and cefoxitin, piperacillin–tazobactam or temocillin was the third-line choice.As a third-line option, France proposed ciprofloxacin in case of beta-lactamase allergy . The AFURecommendations for oral therapy switch were: amoxicillin ,22, amoxA couple of European guidelines proposed oral antibiotics for uncomplicated AP: cephalexin (1stGC)  or amoxiResults are summarized in After lower UTI treatment (ABU or cystitis), 8 out of 13 guidelines (62%) remarked the need of a UC follow-up after 7–14 days ,20,21,22After treating APN, 4 out of 13 guidelines (31%) remarked the need for a UC after 7–14 days ,14,20,22Prophylaxis was suggested in persistence of bacteriuria after full treatment , ≥2 episAfter one episode of APN, prophylaxis with nitrofurantoin was recommended by Irish guidelines When choosing antimicrobials during pregnancy, safety considerations for both mother and fetus must be considered. Most of the antibiotics recommended by international guidelines are category B according to the United States Food and Drug Administration (FDA), meaning that there are no adverse effects in well-controlled studies of human pregnancies. However, some of the antibiotics used for UTI in pregnancy such as trimethoprim, TMP/SMX, gentamicin and ciprofloxacin are FDA category C, and must be used with caution .Our review demonstrated concordance between guidelines with regard to several aspects in the antibiotic treatment of UTI during pregnancy and in the follow-up after treatment. Nonetheless, there are some areas of discordance, as in the case of antenatal screening for bacteriuria. There is adequate evidence showing that ASB is associated with an increased risk of APN, preterm labor and an increased risk of delivering a low-birth-weight infant, among other adverse fetal outcomes ,24,25,26The only two European guidelines that do not recommend this screening anymore are the ones from Germany and Switzerland ,12, withE. coli, followed by Klebsiella sp., two bacterial agents that were highly susceptible to nitrofurantoin [E. coli is also sensitive to 1stGC but extremely resistant to ampicillin and to other aminopenicillins worldwide [Concerning antibiotic therapy for lower UTI, it was similar around the world. Few guidelines gave specific lines of treatments for ASB and cystitis. This may be related to variable patterns of antimicrobial resistance worldwide, meaning that treatment should be based on UC and sensitivities recommended by the laboratory report, taking into account the antibiotics allowed during the trimester of pregnancy. We remarked that only two European guidelines ,16 and ourantoin . This maorldwide ,33. Due orldwide . InsteadThe use of ciprofloxacin was another area of discordance in this review. French guidelines were the only ones that recommended ciprofloxacin as a third-line treatment for cystitis in pregnancy and as a first-line choice for ESBLE, together with levofloxacin or TMP-SMX . In spitIn terms of therapy duration for lower UTI in pregnancy, all guidelines recommended the shortest possible duration, varying from 3 to 7 days for all antibiotics but fosfomycin. Recent publications show that there is no clear difference between a single dose vs. a 4–7 day short course of antibiotics for lower UTI treatment, in terms of progression to pyelonephritis  and preterm birth  . This woOn the other hand, focusing on APN, it is well known that initial antimicrobial therapy is empiric and should be modified according to the UC results . All guiGuidelines from South America and Europe specified the need for a second UC 1–2 weeks after the antibiotic course has been completed. This is in line with previous recommendations ,43. ThosThe main strength of our review lies in the inclusion of guidelines from different continents, which can give us un idea about the worldwide management of pregnancy-related UTI. However, this study is not devoid of limitations. First, we acknowledge that some guidelines might have not been included because they were not found in our database search or because they vaguely mentioned the antibiotic treatment. Nonetheless, the aim of our study was to specifically present the antibiotic recommendations for UTIs. Second, the lack of specifications of certain guidelines in terms of dosage and optimal duration of antibiotic courses in pregnancy made the results more general.Antibiotics selected for UTI during pregnancy should be safe for both mother and unborn child. Guidelines from the four selected continents agree on several key points about antibiotic use. First lines of treatment are similar for lower and upper UTI around the world; however, before selecting the antibiotic of choice, it is mandatory to know the AMR in the local population.


The superior mechanical characteristics of ultra-high-performance concrete (UHPC) have attracted the interest of many researchers worldwide. Researchers have attempted to perform comparative analyses on the behavior of UHPC versus conventional and high-strength concrete, with their aim being to gain more insights into the difference between different types of concrete. However, the current state-of-the-art revealed no direct comprehensive comparisons between their behaviors in ductile coupled shear walls under seismic loading. This paper explores a comprehensive side-by-side comparison in terms of seismic behavior and cost analysis for four 60-story archetype buildings. The reference building was designed using high-strength concrete with a strength of 60 MPa. The other three archetype variations incorporated three different UHPC grades: 150 MPa, 185 MPa, and 220 MPa. The plan configuration and the lateral force-resisting system (LFRS) were chosen according to the most common practice in the UAE. The main objective is to report the effect of UHPC on the LFRS . Moreover, a simplified initial cost analysis  design was performed. The findings of this paper indicate that the use of UHPC is capable of improving the seismic performance behavior of the lateral system as well as reducing the total initial costs. In recent decades, the number of high-rise buildings has increased all over the world. They are designed and built using innovative structural systems and lighter materials. So, these structures tend to be more flexible with lower damping than previous constructions. However, these buildings are more sensitive to dynamic excitation caused by strong earthquake loads in comparison to older structures. The majority of tall structures are prone to seismic loads and vibrations, and, hence, it is essential to design these structures appropriately. The mass, stiffness, natural period, and damping coefficient are the main dynamic characteristics of these structures. If a structure has a lower natural frequency, then it vibrates significantly under seismic loading. In addition, the structural design response is considered an important factor in the design of tall structures . There hRecently, several studies compared different techniques used to optimize the seismic response of RC structures. In other words, using alternative materials such as FRP bars instead of conventional steel reinforcement led to a significant improvement in different aspects, as reported in ,52,53,54Despite the advanced behavior of UHPC in the construction and design industry, no guidance yet exists for the ways in which a designer can optimize the use of UHPC in structural designs. Numerous studies have investigate UHPC ,83,84,85Naeimi and Moustafa  studied Azmee and Shafiq  discusseOesch et al.  examinedValikhani et al.  discusseSince the flexural capacity of reinforced columns deteriorates with underground motion due to the crushing of the concrete and the buckling of longitudinal steel bars, research has focused on lessening the damage at the plastic hinge regions of bridge columns in order to develop bridge columns that are seismic-resistant. In their efforts to mitigate this issue, Ichikawa et al.  studied Wille et al.  tested tArora et al.  exploredMany researchers have studied the performance of UHPC, focusing on its development and behavior from a materials-related perspective. Dong  examinedNumerous computational methods exist for describing the behavior of UHPC structures under seismic loading. Wang et al.  studied Experimental and numerical investigations were carried out by Ren et al.  to descrThis study investigates the feasibility of using UHPC in tall buildings located in moderate seismicity regions in terms of seismic performance and cost-effectiveness. UHPC demonstrates enhanced properties such as a higher compressive strength, a higher ductility and durability, and a better tensile strength ,16,17,18There is a research gap regarding the influence of UHPC on the seismic performance of tall buildings. In addition, there are no codes or standards developed explicitly for structural design using UHPC. UHPC has been found to be an efficient alternative to conventional concrete. Since the Dubai Municipality published its most recent Seismic Code , buildinSince many high-rise buildings worldwide, especially in the UAE, have a typical number of stories ranging from 40 to 80, the average number of 60 floors was chosen in this research to study the effect of the concrete type. Typically, a 60-story building is considered a tall building, and, particularly in the UAE, plenty of buildings with 60 stories or more exist . HoweverThe purpose of this research paper was to assess and compare difference in terms of structural performance as well as cost when using high-strength concrete or ultra-high-performance concrete in a 60-story building. First, four buildings with different concrete grades  were modeled and analyzed using ETABS software  to meet 3. The high-strength concrete had a compressive strength equal to 60 MPa and the UHPC had three different compressive strength values; 150 MPa; 185 MPa; and 220 MPa. Practically, some engineers consider 60 MPa as a conventional reinforced concrete compressive strength for tall buildings, while others consider it the strength of high-strength concrete. Meanwhile, concrete is considered UHPC if it has a compressive strength greater than or equal to 150 MPa [2], a live load of 50 psf [2.394 kN/m2], a roof live load of 20 psf [0.958 kN/m2] and wall perimeter (cladding) load of 7.5 psf [0.359 kN/m2]. Other parameters such as the Ss and S1 were set equal to 0.935 and 0.365, respectively. These values were obtained based on the Ss and S1 values for moderate seismic regions. The long period was set equal to 8 s. The building was designed to meet the seismic requirements of ASCE 7-16 and IBC-18. The layout of each floor of the building being modeled is shown in According to the formula mentioned in ACI 318-19 , section 150 MPa . Other p 150 MPa ,98,99. A20 psf 0.8 kN/m2 aGravity loads such as self-weight, dead, live, and roof live loads were evaluated using the equivalent lateral force (ELF) method. A linear static load case type was used for these loads. For the seismic load, four load cases were produced, namely, seismic load (E), seismic drift (E-Drift), response spectrum without eccentricity (E_RS_X), and response spectrum with eccentricity (E_RS_X-ecc). Seismic load (E) and seismic drift (E-Drift) load cases were analyzed using the equivalent lateral force (ELF) method, while response spectrum without eccentricity (E_RS_X) and response spectrum with eccentricity (E_RS_X-ecc) load cases were evaluated for response spectrum analysis. The main difference between the two response spectrum load cases is that the response spectrum without eccentricity (E_RS_X) has no diaphragm eccentricity, but the response spectrum with eccentricity (E_RS_X-ecc) has a diaphragm eccentricity of 0.05.The design of the gravity system included both a slab and columns design. The thickness of slabs was determined based on the applied gravity loads as well as the span between vertical elements. In other words, a serviceability check (deflection and vibration) and strength design were performed to calculate the minimum slab thickness to minimize the building’s weight. The building’s weight significantly affects the seismic analysis, as will be discussed in the coming sections. Thus, a flat plate with a thickness of 0.2 m was selected for all stories. The building was supposed to move laterally under seismic events. Therefore, the gravity system had to be designed to resist this movement without losing its functionality. ASCE 7-16  mentionsSpecial coupled shear walls were used to resist the seismic forces. In ETABS models, all columns were released laterally to consider only the special coupled shear wall in the lateral design. The total dead mass, which includes the self-weight of the entire building and the superimposed loads for finishes, cladding, and brick walls, was used to determine the base shear in ETABS according to ASCE 7-16 . A stiffd/I, where Cd is the deflection amplification factor taken as per ASCE 7-16 [For the drift design, the ETABS software has been used to design the lengths and thicknesses of the shear walls. Several iterations were performed for each model in order to obtain the optimum model in terms of drift-design limits. During these iterations, certain limitations were considered, such as the structure’s natural period being kept in the range of 0.1–0.15 N to prevent the structure from being excessively rigid or flexible. Furthermore, the aspect ratio of the spandrels was kept between 3 to 5. According to Ghosh , maintaiSCE 7-16 .Both the ETABS and Quick Concrete Wall (QCW) programs were utilized for the strength design. ETABS was used in the design of the columns, shear walls, and coupling beams. Moreover, QCW was used to review the design of shear walls in addition to calculating the boundary elements requirements according to ACI 318-19 . Due to The subsequent sections report the results of this investigation. Furthermore, they provide a detailed comparison of the seismic performances and cost-effectiveness of the high-strength concrete and the UHPC models.s,H). It can be noticed that, by increasing the compressive strength of the concrete, most of the cross-sections become smaller. For example, pier P1 at story 1–5 had a length and thickness of 4.55 and 0.65 m, respectively, at 60 MPa concrete strength, but the pier length and thickness reduced to 3.75 and 0.6 m, respectively, at 150 MPa. In addition, the reinforcement ratios also decrease. This reduces the cost of steel reinforcement used in the building and accordingly decreases the amount of work and manpower needed at the construction site. be), thickness (bbe), and horizontal reinforcement in long  and short  directions. The pier boundary element sizes and the horizontal reinforcement in the long direction were observed to have reduced with an increase in concrete compressive strength. As at story 1–5, the length and thicknesses of pier P1 for 60 MPa, 150 MPa, 185 MPa, and 220 MPa were found to be about 2.05 and 1.3 m, 1.6 and 0.6 m, 1 and 0.6 m, and 0.75 and 0.55 m, respectively. However, the horizontal reinforcement in the short direction increased with an increase in concrete strength, but at higher stories, the requirement of boundary elements reduced with higher concrete strengths. Hence, for the overall building, an increase in concrete strength led to a reduction in the boundary element requirements. Moreover, at a higher concrete strength of 220 MPa, the boundary elements were required only for pier P1 at the base stories, while the P2 and P3 piers did not require any boundary elements throughout the building. It shows that using concrete with a higher compressive strength leads to a significant reduction in the boundary element sizes, which, in turn, enhances the functionality of the free space in the building from an architectural perspective. In general, the reduction in the cross-section of the elements reduces the total building weight, decreasing the foundation’s cost. s,T), bottom , vertical , and horizontal  reinforcement areas. In general, the reinforcement areas reduced with an increase in concrete compressive strengths, validating the previous pier design and boundary element design results. A reduction in reinforcement ratios were also noticed with an increase in the story levels. This reduction occurred since higher story levels are susceptible to lower loading compared to base stories. Modal analysis was performed using the Eigen method. The induced overturning moment (OTM) was calculated by multiplying each story force, calculated from ETABS, by the corresponding story height to the foundation level. 3 (78.3 USD/m3) and that of UHPC as 550, 600, and 650 AED/m3 , for 150, 185, and 220 MPa, respectively, based on the UAE market value at the time of the study. In addition, the cost of steel in the UAE market ranges between 2800 and 3000 AED/m3 (756–810 USD/m3). Thus, an average value of 2900 AED/m3 (783 USD/m3) was used in this study. As discussed in El-Tawil et al. [In this section, detailed quantity surveying was conducted. The results are summarized in l et al. , UHPC cal et al. . MoreoveWhen substituting the cost of the reference concrete (HSC) in place of X, the indirect costs were evaluated as AED (USD) 11,430,022 , 5,868,620 , 4,708,592 , and 4,273,390  for the high-strength concrete and UHPC 150, 185, 220 MPa, respectively. The results show that using UHPC can save up to around AED (USD) 5,500,000  from the indirect cost, as shown in This proves that the model used for UHPC 220 MPa may not be the most optimum design and further modeling could be performed in order to achieve a more efficient and optimum design for UHPC 220 MPa. However, since the total cost of the UHPC 220 MPa model is lower than the high-strength concrete model and the UHPC 150 MPa model, the UHPC 220 MPa design is in fact not overly inefficient and can be used for the analysis of this study. A significant reduction in total cost in AED and USD can be noticed clearly in All buildings exhibited a similar seismic response but with smaller structural elements in UHPC buildings.A reduction in the dead weight of the building was observed, in addition to a lower value for overturning moments, for the UHPC building compared to the high-strength concrete building, which results to cost-saving in the design of the foundation.The results showed that by increasing the strength of concrete from high-strength concrete of 60 MPa to the UHPC of 150, 185, and 220 MPa, the total initial costs were reduced by 25%, 31%, and 26%, respectively.In terms of seismic performance and cost analysis, the best results were observed when using the UHPC of 185 MPa. Therefore, this study recommends using the UHPC in tall buildings instead of high-strength concrete.The reduction in the cost can be attributed to the decrease in the dead load of the structure, the smaller sizes of the required structural elements for lateral load resistance , and lower manpower transportation costs.Future nonlinear analysis  is highly recommended to validate the assumed parameters  for UHPC tall buildings.In this paper, four models for a 60-story building were developed to quantify the effect of using UHPC as a replacement for high-strength concrete. The modal analysis results and the design summary of the columns and the special concrete coupled shear walls were presented and discussed. The main findings of this study are summarized as follows:


Have you ever tried to enter a new field of research or to get a basic overview? Of course, we all have. However, where does one begin when entering a new field of research? This mini-review offers a concise (and certainly not comprehensive) overview on the fast-evolving field of ethnopharmacology. Based on a survey in which researchers provided feedback on the publications they find most relevant in the field and an assessment of what publications have been particularly relevant in the field, this paper offers a review of the 30 best papers and books for newcomers in the field. They cover the relevant areas within ethnopharmacology and give examples from all the core regions where ethnopharmacological research is being conducted. Different and sometimes contrasting approaches and theoretical frameworks are included, as well as publications reviewing important methods. With this, basic knowledge on related fields such as ethnobotany, anthropology, fieldwork methods and pharmacognosy is also incorporated. This paper is an invitation to explore fundamental aspects of the field and to understand the particular challenges faced by researchers newly entering this multi- and transdisciplinary field, and to provide them with examples of particularly stimulating research. Getting started in any field of research can be a daunting task to a ‘newcomer’. Ethnopharmacology is no exception. Ethnopharmacology studies ‘traditional medicines’, i.e., plants, fungi and other natural substances used as medicines. It is made more complicated by its multi- and transdisciplinary nature, covering such diverse fields like pharmacology, botany, pharmacognosy, analytical and natural product chemistry, anthropology/sociology, biomedical research, toxicology, clinical research, as well as history, environmental science, various areas of biology, climate research and numerous others. The number of publications in the field is impressive. For example, on the Web of Science, as seen in the changes over 10-year periods in annual publications, the keyword ‘traditional medicine’ shows 28532 (2022), 9026 (2012), 2375 (2002), 844 (1992), 49 (1982) and 6 (1972) publications. These numbers show that the science of ethnopharmacology today continues to be a thriving and fast-developing field of research. If one focuses specifically on scientific approaches labelled ‘ethnopharmacology’, for 2022, the Web of Science lists 895 publications, again with an enormous increase over the last 55 years with the specific keyword ‘ethnopharmacology’: 720 (2012), 225 (2002) 62 (1992), 48 (1982) and 0 (1972) publications. With such a large number of publications annually, one can easily get lost in the field.So, where to begin? In several fields of research, mini-reviews have been published, presenting the most relevant publications , offering a basis for understanding this specific field of research. Examples include pharmacoepidemiology and medicinal chemistry . Other oEthnopharmacology is – in its initial scope and focus a ‘child of the 1960’s in the global West, i.e., North America and Western Europe. The first use of the term ‘ethnopharmacology’ in writing is linked to a symposium ‘Ethnopharmacological Search for Psychoactive Drugs’ in 1967 and the resulting publications  and Hol. This isNumerous studies exemplify the (most notably European) interest in exotic medicines resulting from the colonial expansion of European empires and the United States . Of courIn such an overview, the aim is to present publications which are widely accessible, written in such a way that they are understandable to a wide range of researchers, representative of the field both present and past, and especially addressing newcomers to the field of ethnopharmacology.via a range of scientific society websites, official social media platforms , and through personal networks of academics . All nominations were then solicited between November and December 2022. Our call received considerable attention from ethnopharmacologists all over the world. During data analysis (of responses received), duplicates were merged. Each of the assessors, the authors of the present work, then discussed the remaining nominations focussing on those selected papers or books with three or more votes. This was followed by rounds of adjustments to prioritise between partially overlapping nominations, resulting in a final selection of 30 publications in ethnopharmacology.Initially, emails were sent out to all editors and associate editors at the Frontiers in Pharmacology section Ethnopharmacology to invite nominations  of the most important papers or books in the field of ethnopharmacology. Next, an online survey was also conducted to invite global nominations of important papers or books and those with the greatest influence. Participants were asked explicitly to also include ‘overlooked’ papers or books which are considered important but which should receive more attention since they are fundamental contributions to the field. The online survey comprised one main section with three questions covering (1) full bibliographic details of the nominated paper or book; (2) a short justification of why this paper or book is so essential; and (3) a summary of the main findings of the nominated paper or book. The survey was designed to be short and take 3–5 min to complete  be in English, published as an article  or as a book; (b) be of general interest to the field because of their approach, topic or methodology; (c) be published after the term ‘ethnopharmacology’ was coined; and (d) there was no direct overlap with other studies, i.e., a similar theme. Papers and books listed more than three times in the survey were all included. Papers with a lower frequency of mention were included on a selective basis. In general, preference was given to more widely cited publications.In the initial round, we received 185 nominations. After the merging of duplicates, 110 nominations remained. 15 books and papers suggested three or more times were included in the list of the 30 most relevant publications. The authors then selected 15 additional publications to ascertain a global coverage that the various approaches in ethnopharmacology are represented. This selection is a mix of publications that have had a high impact  and a selection of classical publications of fundamental contribution to the field covering the period since 1967 .Bencao Gangmu (Compendium of Materia Medica) [orig. completed 1578], first printed in 1596, first English translation in 2003  by Ibn Sina    [orig. 1The 19th century saw a flourishing of studies focusing on botanical drugs and their potential based on the colonial expansion and subsequent exploration combined with the fast development of pharmacological studies of these ‘new’ resources . In thisArtemisia annua L.  indicating an interest in the larger commercial development of such health food or medicinal plants. Another core area are emerging areas of pharmacological focus, most notably diabetes, The 2000s see a massive flourishing of studies . SeveralAt least since the 2000‘s there has been a very strong shift of focus and a rise of research on medicinal plants used in numerous Asian traditions, most importantly in the People’s Republic of China, e.g., Safety and, specifically, drug interactions remain an area which has received comparatively little attention, despite of calls to focus more on it , includiTextbooks providing fundamental knowledge on neighbouring fields involved in ethnopharmacological research were not included in the list of the 30 most relevant publications. Yet, these publications can be of great help to newcomers entering the field of ethnopharmacology. Some excellent examples focusing on (a) drug discovery and pharmacognosy ; (b) ethThis mini-review is intended to enable newcomers to the field to understand the wide conceptual basis and the diverse general methodologies and approaches in this large field of research. As such, it is an orientation driven by feedback received from the scientific community. There remain some limitations of the approach, for example, due to the way the questionnaire was disseminated , limited feedback was received from some countries, most notably the PR China. We, therefore, searched core journals for widely cited publications with a broad scope, but clearly, this is somewhat based on personal choice. Since this review is intended to be a starting point to understand the field, this is not a major limitation. We also acknowledge the numerous gaps, but by highlighting the top 30 publications, we can only offer a starting point for further exploring the field.in vitro or in vivo tools for assessing pharmacological, toxicological and microbiological activities or the study of clinical aspects. It was our aim to represent examples of the diversity of views within the field, and as such, we also showcase some of the important debates in the field.There is an element of personal choice and a focus on best practices in research. We have to refer colleagues to specialist publications for specific methods like The authors of this paper consider a strong social science element (esp. anthropology) to be a core element of ethnopharmacology. The wider context of biodiversity research, drug discovery, natural product research and other core fields of research, including the policies relevant to ethnopharmacological research , have only been touched upon briefly. For modern studies, we limited ourselves to publications in English, and it is essential to remember that a field like ethnopharmacology is driven by national, regional and local developments with a rich body of literature in many languages.We hope that this paper will serve as an orientation and as a basis for giving and developing postgraduate and undergraduate courses. However, in the end, readers should and must make their own choices and select what is most relevant to them and their specific interests. The most important benefit of this overview is that it enables readers to delve into aspects of ethnopharmacology they have not yet explored.