Symptom checkers (SCs) for laypersons’ self-assessment and preliminary self-diagnosis are widely used by the public. Little is known about the impact of these tools on health care professionals (HCPs) in primary care and their work. This is relevant to understanding how technological changes might affect the working world and how this is linked to work-related psychosocial demands and resources for HCPs.This scoping review aimed to systematically explore the existing publications on the impacts of SCs on HCPs in primary care and to identify knowledge gaps.We used the Arksey and O’Malley framework. We based our search string on the participant, concept, and context scheme and searched PubMed (MEDLINE) and CINAHL in January and June 2021. We performed a reference search in August 2021 and a manual search in November 2021. We included publications of peer-reviewed journals that focused on artificial intelligence- or algorithm-based self-diagnosing apps and tools for laypersons and had primary care or nonclinical settings as a relevant context. The characteristics of these studies were described numerically. We used thematic analysis to identify core themes. We followed the PRISMA-ScR  checklist to report the study.finding prediagnosis comprised the comparison between SCs and physicians. We identified the performance of the diagnosis and the relevance of human factors as topics. In the theme layperson-technology relationship, we identified potentials for laypersons’ empowerment and harm through SCs. Our analysis showed potential disruptions of the physician-patient relationship and uncontested roles of HCPs in the theme (impacts on) physician-patient relationship. In the theme impacts on HCPs’ tasks, we described the reduction or increase in HCPs’ workload. We identified potential transformations of HCPs’ work and impacts on the health care system in the theme future role of SCs in health care.Of the 2729 publications identified through initial and follow-up database searches, 43 full texts were screened for eligibility, of which 9 were included. Further 8 publications were included through manual search. Two publications were excluded after receiving feedback in the peer-review process. Fifteen publications were included in the final sample, which comprised 5 (33%) commentaries or nonresearch publications, 3 (20%) literature reviews, and 7 (47%) research publications. The earliest publications stemmed from 2015. We identified 5 themes. The theme The scoping review approach was suitable for this new field of research. The heterogeneity of technologies and wordings was challenging. We identified research gaps in the literature regarding the impact of artificial intelligence– or algorithm-based self-diagnosing apps or tools on the work of HCPs in primary care. Further empirical studies on HCPs’ lived experiences are needed, as the current literature depicts expectations rather than empirical findings. Dr. Google  generally provide people with possible alternative diagnoses based on their reported symptoms and/or suggest a course of action  appointment or go to an emergency department [ED])” .From the perspective of occupational health, we are particularly interested in understanding how technological changes might affect the working world and how this is linked to work-related psychosocial demands and resources . The JoiAs SCs are a rather new technology, we expected limited knowledge and heterogeneous sources with regard to our research interests. Therefore, we chose to conduct a scoping review as a suitable method to gain an overview of existing knowledge . Even thWhat is known from the literature about the impact of SC on HCPs in general practice, especially with regard to work content and work organization, HCP-patient interaction and relationship, professionals’ identity, job satisfaction, and perceived stress?This scoping review aimed to systematically explore the existing knowledge on the impacts of SC on HCPs in general practice and to identify gaps in knowledge. This review was guided by the following research question: A scoping review approach allowed us to identify, retrieve, and summarize publications relevant to a particular topic and to identify the key concepts underpinning a research area and the main sources and types of evidence available . We chosOur scoping review included the following key phases : (1) ideWe followed the population, concept, and context scheme  to definWe included publications in peer-reviewed journals and did not restrict by study design to capture the wide array of relevant publications. The time frame from 2000 to 2021 was chosen to minimize the inclusion of irrelevant publications of older tools for self-diagnosis. The publications included were published in English, German, French, Turkish, or Russian and were obtainable in full text. We excluded studies that did not fit the topic and setting or focused on technologies that were designed for a professional target group such as tools for clinical decision support  and 3.PublicationPublication date from 2000 to 2021Languages: English, German, French, Turkish, and RussianAll study types, views, editorials, etcTopicSymptom checkers for general conditionsSettingGeneral practice and primary careHealth care professionals and physicians in generalDigital technologyUsed by lay public or patient-facingArtificial intelligence– or algorithm-basedFor self-diagnosis or self-triagePublicationFor example, blogs, thesis, and dissertationsTopicSymptom checkers focused on specific medical conditionsSettingHospitalDigital technologyUsed by physicians, nurses, etcDiagnostics with sensors, wearables, etcClinical decision support systems, etcAs we expected limited results with regard to our specific research interests, we conceptualized a broad search strategy. We considered 2 medical databases, PubMed (MEDLINE) and CINAHL, as comprehensive databases for our research question and searched them systematically. We worked with a librarian at the University of Tübingen to construct a search term to ensure comprehensive results. We developed the search term using keywords and MeSH  terms from thematically relevant empirical studies ,27. BecaJournal of Medical Internet Research, European Journal of General Practice, or Deutsches Ärzteblatt) and in Web of Science, ScienceDirect (June 2021), Google Scholar, and Google (November 2021) using keywords “symptom checker” and “self-diagnosis.”The initial database search was conducted in January 2021, and the follow-up search was conducted in June 2021 to identify the publications published after the initial search. Subsequently, we reviewed the reference lists of the included publications and references of known relevant reviews on SCs ,27 to idRayyan Systems Inc) [We imported the database search results into the reference management system Citavi  and remoems Inc)  to screeThe whole process (screening and selection) was conducted and constantly discussed by independent reviewers (NR and EÖ) to assess interrater reliability . To ensuWe developed the data charting form following the Arksey and O’Malley framework . NR and We extracted key information from the included publications pertaining to publication information ; study information, if applicable ; main findings; and implications related to our research question. All findings concerning the impact of SCs on GPs or HCPs were included. The main outcomes of interest were (impacts on) work content, organization or service use, job satisfaction of HCPs, perceived stress, HCP-patient or lay interaction or relationship and communication, and professional identity. Data extraction was performed simultaneously by 2 reviewers (NR and CP) and checked reciprocally for accuracy and consistency.We used thematic analysis  to strucA numerical analysis of the selection process and the included publications is presented. Of the 2729 publications found in the database search, 385 (14.11%) duplicates and an additional 211 (7.73%) publications with unsuitable publication types were removed. Of the remaining 78.16% (2133/2729) of publications, 2090 (97.98%) articles were removed after screening for inclusion, and 43 (2.02%) articles were screened for eligibility, of which 9 (21%) publications were considered eligible. A total of 69 publications were included through manual search and screened for eligibility, which resulted in further 8 (12%) included publications. The number of included publications for data extraction was 17. On the basis of the detailed feedback during the peer-review process in this journal, we excluded 2 more publications. The final number of included publications was 15 .Most publications 5/15, 33%) were published in 2019 ,15,34-36, 33% werWe identified 5 themes in the heterogeneity of the included publications. The charting table  providesperformance of diagnosis and the relevance of the human factor. We see the former as part of the work content and the latter as the basis for the quality of performing the work content.One theme that repeatedly occurred in the publications can be grouped under the lower accuracy in diagnostics [triage, understood as an evaluation of urgency [they consider various sources of information and contextual factors [a first sense of urgency [Some authors attested that SCs have a gnostics ,37,40,43 urgency ,36,37,40 urgency , holisti urgency , or indi urgency ,38 knowl urgency .lack a human factor. SCs do not have “tacit knowledge such as how to gain an individual’s confidence” [human factor as a strength of physicians to whom they ascribed a “6th sense” and “respectful,” individualized care [According to some authors, SCs fidence” . The lacfidence”  as well fidence” ,44, and fidence” . Unlike fidence”  and provfidence” . Some auzed care  as well zed care .Some authors addressed the impacts of SCs on layperson users as  patients. We consider this relevant to our research question, as it might indirectly transform HCPs’ work content.provide laypersons with knowledge, as they might function as a better alternative concerning health-related issues, for example, in comparison with Google and Wikipedia [layperson activating potential of SCs, as laypersons might switch into a more active role through self-management and responsibility [Authors saw the potential of SCs to ikipedia . Some adsibility .issues of quality and liability are still unclear [might increase anxieties in laypersons [According to some authors, SCs could be potentially harmful for laypersons, as the  unclear . The autypersons .Some authors addressed the impacts of SCs on the physician-patient relationship. We consider this to be relevant because the physician-patient relationship is also part of the HCPs’ work content .potential of changing roles in the physician-patient relationship. The authors depicted the patient-physician relationship as relying on trust and face-to-face conversation [Some authors addressed the ersation , which iersation . SCs couersation . The ampersation  and chalersation ,39,41.positive effects on the physician-patient relationship. SCs can enable and intensify necessary physician-patient contact [remain the primary source of trustworthy information; GPs were favored over technology, especially in conditions perceived as highly severe [Some authors indicated that SCs might have an impact but that the roles of HCPs would remain unchallenged. Some authors voiced that SC might have  contact . Accordiy severe . In addiy severe .The impacts of SCs on HCPs’ tasks is another theme in the literature relevant to our research question, as it is linked to work content. We included those parts that might have an impact on HCPs’ work.supporting repetitive and less-complicated tasks for the HCPs such as “initial triage of uncomplicated patients” [enable physicians to concentrate on other tasks such as verification and interpretation of the provided information [In some publications, SCs were seen as reducing HCPs’ workload through providing or atients” , “self aatients” , “patienatients” , and “adatients” . This coormation  and to formation . Generalormation ,45.Unnecessary contacts might increase [additional tasks during consultation. HCPs might need to explain the conflicting results between their assessments and those of SCs [Some authors assumed that SCs might increase HCPs’ workload. increase  as patieincrease  or as SCincrease . The wore of SCs . HCPs mie of SCs .Some authors made prognoses for the future of SCs and their impacts on health care. We consider those visions, which indicate an impact on HCPs’ work, as relevant to our topic.transform the roles of HCPs, as they might “overhaul general practice” [SCs complement HCPs, as they cannot and will not replace consultations with GPs [competition with HCPs. They might replace GPs in the context of the tasks that they are able to perform [Some publications addressed the future role that SCs could play in health care with regard to HCPs and the health care system. SCs might ractice”  in termsractice” . Some auwith GPs  and facewith GPs . SCs canwith GPs ,34,41,43with GPs  HCPs. Ne perform .improved supply. SCs might help to overcome supply issues associated with inaccessible or unaffordable health care services [potential overuse of services and the wastage of scarce resources of HCPs. Unnecessary medical visits resulting from the use of SCs might cause unnecessary costs [Some authors addressed the potential impacts of SCs on the health care system. Some assumed the potential for services . Furtherservices ,45. Othery costs .Looking beyond the respective themes, we identified a spectrum of 4 main discourses in which SCs were discussed as inferior, harmful, beneficial, or superior to humans .SCs as inferior, SCs are depicted as deficient in comparison with human physicians or unable to replace human physicians. The discourse of SCs as harmful centers the negative effects of SCs on humans such as anxiety and fear among users. The discourse of SCs as beneficial contains the positive effects of SCs, for example, for users (knowledge), physicians (relief of repetitive tasks), and the physician-patient relationship in general. In the discourse of SCs as superior, they are discussed as potentially outperforming humans or causing effects that are allegedly beyond human reach such as changing the roles of physicians. Thus, our results depict SCs as a double-edged sword in the physicians’ work.In the discourse of SCs are designed for laypersons but might have direct and indirect impacts on HCPs, as patients may use SCs instead of, before, or in addition to the consultation with an HCP. We conducted a scoping review to identify existing knowledge about the impacts of SCs on HCPs in primary care, especially with regard to work content and organization, HCP-patient or lay interaction or relationship, professionals’ identity, job satisfaction, and perceived stress of HCPs. We derived these perspectives from established models of work-related stress and mental health in the workplace ,17.layperson-technology relationship and (impacts on) physician-patient relationship were not addressed by research publications, whereas almost all subtopics were covered in literature reviews. This implies that there is a scientific discourse about these topics and that our search strategy was able to find it. Consequently, we assume that there is a lack of empirical knowledge about the experiences of and impacts on laypersons and physicians regarding SCs. In the few research publications included, the physicians expressed expectations about SCs [We included 15 publications and identified 5 main themes concerning the impacts of SCs on physicians in general practice and other settings. The literature in our scoping review consists of research publications, literature reviews, and nonresearch publications such as commentaries. We found the main themes across all 3 types of literature, with clear differences in the levels of the subtopics. Most subtopics in the themes bout SCs ,35 rathebout SCs  in dailySCs might cause unnecessary contacts or SCs might cause additional tasks during consultation might be potential indicators of perceived stress. Subtopics such as potential of changing roles in the physician-patient relationship as well as SCs in competition with HCPs and SCs transform the roles of HCPs in health care might affect HCPs’ professional identities. The reason that these dimensions are addressed rather implicitly might be due to the limited lived experience of HCPs with SCs in the daily routines mentioned in the previous paragraph and the lack of the perspective of occupational health in the context of SCs in health care.Interestingly, we could see that SCs entering the field of (pre)diagnosis was not enlarged from the perspective of “professionals’ identity,” “job satisfaction,” and “perceived work-related stress” that were further perspectives on our research question. Subtopics such as The existing literature turned out to be heterogeneous and inconsistent with regard to the concepts and wording that are used  patients might thus also affect HCPs’ work content and workload . An ambiThe impact of SCs on the physician-patient relationship is prominently addressed in the publications included in our scoping review and centers on the question of whether the roles of physicians and patients might change through SCs. According to a study on the impacts of patients’ use of social media on their interaction with HCPs, discussing health information collected on the web with HCPs led to perceived “tacit opposition” . This inThe publications in our scoping review show that SCs are expected to transform the roles of GPs. This is similar to the expected impacts of AI on the roles of HCPs . TransfoWith regard to future roles in health care systems, publications on COVID-19–related SCs show that unnecessary in-person visits may be eliminated . NeverthOn the basis of the literature, SCs can partially outsource and improve preliminary diagnoses and enhance diagnostic decision-making. Furthermore, they could become tools for “appropriate triage advice” by the patients themselves  and a “fSCs are currently not integrated into daily routines; therefore, GPs cannot control patient risks from using SCs for self-diagnosis and evaluation of a suggested course of action . In addiAlthough the topic of bias reduction on HCPs’ side has been addressed, there is a research gap concerning exacerbating inequalities  through This is the first scoping review that centers on the perspective of occupational health in the context of the potential impacts of SCs on the work of physicians in primary care. A current ethical reflection on SC chatbots in clinical settings indicates potential impacts on the work of HCPs such as impacts on HCPs’ practical wisdom, workload, and motivation at work . Our res


Results: The general search term “prostate cancer race” yielded 4507 publications. More specific search terms with ≥12 publications showing a higher scientific interest were found after 2005. The terms with the most publications when added to the general term were “genetic” (n = 1011), “PSA” (n = 995), and “detection” (n = 861). There was a linear increase in publications for “prostate cancer race” (R2 = 0.75) since 1980. Specific terms added to the general terms with a high linear increase (R2 ≥ 0.7) were “screening” (R2 = 0.82), “detection” (R2 = 0.72), “treatment access” (R2 = 0.71), and “trial underrepresentation” (R2 = 0.71). However, only a few studies have investigated its association with sexual activity. A combination with “sexual” showed 157 publications but only two years with ≥12 publications/year. Conclusion: The terms “genetic”, “PSA”, and “detection” have been the focus of recent research on racial differences in prostate cancer. We found that old stereotypes are still being mentioned but seem to find little interest in the current literature. Further research interest was found in “treatment access”. Recently, interest in socioeconomic factors has decreased.Background: Despite recent awareness of institutional racism, there are still important racial disparities in prostate cancer medical research. We investigated the historical development of research on racial disparities and bias. Methods: PubMed was searched for the term ‘prostate cancer race’ and added key terms associated with racial disparity. As an indicator of scientific interest in the topic, we analyzed whether the number of publications increased linearly as an indicator of growing interest. The linearity is expressed as R There are large disparities in the incidence and mortality rates of prostate cancer among Black men ,2. It haScientific literature as far back as the 1930s has investigated the difference in the incidence of prostatic blockage between Black and White men. When reviewing the literature, it seems that in the 1980s and the 1990s there were few studies investigating racial disparities, and the few articles investigating the subject were probably written mainly by White authors, focusing on biological differences in testosterone levels and sexual activity or sexually transmitted infections (STIs). This focus was based on the understanding that Black men have higher serum and intraprostatic tissue androgen concentrations ,5,6.Race and ethnicity are social constructs with limited utility in understanding medical research, but these terms may be useful for studying and viewing racism and disparities . HistoriFirst, we provide an overview of how the medical literature has evolved in recent years. Then, we investigate the factors over time that were of interest in explaining racial disparities in the medical community. Research on etiological factors for prostate cancer was analyzed and how it has changed over the years by analyzing differences in culture and sexual behavior in more scientific subjects, such as genetic and socioeconomic disparities.In the second section, research papers on racial differences were cited, which in our opinion, are particularly biased. Racially biased research was frequent in the past but has continued to play a role until today.First, we reviewed the literature to find common key words associated with “prostate cancer” and “race”. We then identified several historical articles in key publications that were among the first to report racial inequality in cancer detection and survival.https://pubmed.ncbi.nlm.nih.gov/) on 19 and 22 May 2023 and entered different search terms that have been in the past or are still attributed to racial disparities in prostate cancer.We accessed PubMed  deemed the scientific and editorial character and quality of a journal as meriting inclusion. We searched for each term, and recorded the number of publications. The year in which the term was first listed on PubMed was recorded, and then was analyzed at ≥6 and ≥12 publications. These numbers represent a certain interest in the scientific community in a subject indicated by there being at least one publication per month or per every other month in a year. We calculated the number of years between publication of ≥6 and ≥12 publications. A shorter time represents a rapid increase in interest in the subject’s knowledge.2, a measure of how well a linear regression model “fits” a dataset. The strong linearity was R2 > 0.7, moderate 0.5–0.7, and weak was R2 = 0.3–<0.5.Then, a graph based on the number of publications per year was created. The number of publications per year can easily be exported from PubMed to an Excel spreadsheet. Finally, Excel was used to calculate whether the increase in publications was linear. A linear increase represented an increase in interest and knowledge of the subject. Linearity is expressed as RFirst, we researched when awareness of racial differences must have begun. While reviewing the literature, we found that in general, the fact that there was an increasing incidence of prostate cancer in Black patients had been well-documented in large studies since at least 1980. Increasing incidence of prostate cancer in Black patients has been reported in several epidemiologic studies. An analysis of voluntary data supplied by hospitals in 1979 showed that Black patients presented with more advanced clinical stage and poorer survival rates. The first listed publication on “prostate cancer black mortality increase” appeared in PubMed in 1977. And the first time that there were >1 publications on the subject was in 1985. But only from 2008 on were there consistently >12 publications per year.In our analysis of the literature in PubMed, we found among the 4507 publications on “prostate cancer race”, most of the analyzed terms reached ≥6 publications/year beginning in 1994 . Most seIn general, terms investigating an association with sexual activity, a term that could indicate a bias towards Black men, had few publications. Only two terms associated with sexual activity had >50 publications: the combination with “sexual” had 157 publications but only in two years (2011 and 2022) with exactly 12 publications, and “sexual factors” had 93 publications, but always <12 publications/year and a maximum of eight publications per year in 2013. The term “genetics testosterone” has been used in only 36 publications. This term is sometimes used to investigate genetic differences between the testosterone receptors. First publications about “testosterone”, “sexual”, and “marital” could be found in the 1970s , while s2 > 0.7) in publications, representing a continuous interest, such as the general search term “prostate cancer race” (R2 = 0.75), “socioeconomic” , and a strong linear increase (R2 = 0.80). Other specific terms added to the general term with a strong linear increase were “screening” (R2 = 0.82), “detection” (R2 = 0.72), “treatment access” (R2 = 0.71), and “trial underrepresentation” (R2 = 0.71). Interest in “genetics” has plateaued (R2 = 0.65), but with more than 50 publications every year since 2015, after reaching ≥12 publications in 1997. Several search terms showed a strong linear increase  [Compared to prostate cancer, cervical cancer is clearly associated with STIs such as us (HPV) . InteresWe examined the historical development of research on racial disparity. The opinion that hormonal and sexual factors play a role in the differences between Black and White men probably originated in the fact that since the early 1940s it has been known that prostate cancer is hormonally dependent . AdditioAnother factor contributing to the bias in the medical establishment regarding Black men is that Black patients are sometimes seen as more tolerant to pain in general  and urinEven back then, the much more obvious cause of delayed doctor visits would have likely been restricted access to the medical system or the perception of unequal treatment by Black patients, resulting in distrust in the system.A factor that has gained little interest today is that Black men seem, despite similar care settings, to be generally less satisfied with their treatment . In theiOne could argue that the fact that they were treated in a trial could have created mistrust in patients, that their interaction with the research staff was not optimal, or that there were other cultural or socioeconomic differences in Black patients .Journal of Urology [Some of the biased literature may stem from previous research on benign prostatic hyperplasia (BPH) in Black men. Derbes et al. in their findings published in 1937 in the  Urology  showed tThere were studies without any racial prejudice such as the publication by Burns, read before the Southeastern Section, American Urological Association, in Biloxi, Miss, in 1939 . Journal of the National Cancer Institute [Ross et al. published a rather strongly biased example in May 1987 in the nstitute . They stIn 2022, Basourakos et al.  found thThe limitation of our study is that we did not separate publications about Black men only but included the term “race” without specifying further. It would have been a herculean task to analyze 4500 abstracts and classify each publication according to one main topic. Therefore, some publications have appeared in several searches although they have no direct importance to the subject of the publication. Furthermore, we did not include the search term “ethnicity” with nearly 4000 publications. We have, therefore, included some patients of origins other than African, although most studies on race and prostate cancer deal with disparities between Black men and other races. In general, little research has been conducted on other racial disparities outside North America. Therefore, our data are mostly US-specific and cannot necessarily be applied to other countries. There is a growing number of journals, and therefore, publications and research, over the years. Therefore, more recent topics have more publications and a faster uptake per definition than older topics. Healthcare professionals have been shown to exhibit the same level of implicit bias as that of the wider population. It has been observed that patients who experience racism lack trust and experience a delay in seeking healthcare .In conclusion, interest in the influence of race on prostate cancer began in the mid-1990s and has become a more researched subject since 2005. Biased terms dealing with racial sex differences have gained little but persistent interest. Recently, terms such as “genetic”, “PSA”, and “detection” have become the focus of research.


Escherichia coli and other Enterobacterales to fluoroquinolones, trimethoprim-sulfamethoxazole (TMP-SMX), and beta-lactams has left patients without reliable oral antibiotic treatment options for APN. This narrative review proposes using precision medicine concepts to improve empirical antibiotic therapy for APN in ambulatory settings. Whereas resistance rates to a particular antibiotic class may exceed 10% at the population-based level, the predicted antibiotic resistance rates based on patient-specific risk factors fall under 10% in many patients with APN on the individual level. The utilization of clinical tools for the prediction of fluoroquinolones, TMP-SMX, and third-generation cephalosporin resistance improves the ambulatory antibiotic management of APN. It may also reduce the need to switch antibiotic therapy later based on the in vitro antibiotic susceptibility testing results of bacterial isolates in urinary cultures. This approach may mitigate the burden of increasing antibiotic resistance in the community by ensuring that the initial antibiotic prescribed has the highest likelihood of treating APN appropriately.Acute pyelonephritis (APN) is a relatively common community-acquired infection, particularly in women. The early appropriate antibiotic treatment of this potentially life-threatening infection is associated with improved outcomes. The international management guidelines for complicated urinary tract infections and APN recommend using oral antibiotics with <10% resistance among urinary pathogens. However, increasing antibiotic resistance rates among  Escherichia coli is the predominant bacteria in both uncomplicated cystitis and acute pyelonephritis (APN), followed by other Enterobacterales such as Klebsiella spp. and Proteus mirabilis. In a population-based study over a 5-year period, the annual rate of outpatient pyelonephritis among the female population in the United States was 12 to 13 cases per 10,000 people [Urinary tract infections (UTIs) represent one of the most common outpatient infections treated with antibiotics, primarily affecting young women. With the increase in antibiotic resistance rates among community-onset urinary tract isolates, it is imperative to consider additional treatment strategies. The goal of this proposed strategy is to improve the selection of antibiotic therapy in individuals with APN and reduce the likelihood of antibiotic resistance transmission at the population level. This narrative review outlines key perspectives and considerations of applied precision medicine as a tool to manage APN when the selection of the antibiotic regimen is stratified to the host, microbiome, and pathogen characteristics.The 2010 IDSA and ESCMID guidelines recommend the use of oral ciprofloxacin, levofloxacin, or TMP-SMX for the management of APN . These gE. coli resistance to fluoroquinolones in the United States was <7%, although certain regions  had an elevated resistance rate of up to 20% [E. coli, that accounts for 85% of these infections through the production of CTX-M-15 beta-lactamases [Studies from the early 2000s demonstrated that the rate of p to 20% . In a mop to 20% ,5. Similp to 20% ,7. WhilePrecision medicine applied in infectious diseases is a relatively new concept that proposes the customization of therapeutics and medical decisions based on an individual’s clinical and environmental characteristics rather than a one-size-fits-all approach . When seIn a study by Dunne and colleagues that included 15 institutions in the United States, based on urinary isolates of Enterobacterales from over 5000 patients, investigators found resistance rates of >20% to fluoroquinolones, TMP-SMX, and beta-lactam antibiotics . This stWhile the selection of an empiric antibiotic regimen is often guided by the appropriate minimum acceptable susceptibility (MAS) based on a local antibiogram, other patient-specific markers should also be factored into the threshold of MAS. Haggard and colleagues demonstrated a proportional increase in the median MAS target among a cohort of clinically trained pharmacists with an increasing severity of Gram-negative infections and poor clinical prognoses. Specifically, the median MAS for critically ill patients with bloodstream infections and a poor or guarded prognosis was 90%, whereas the MAS for patients with APN and a good prognosis was 85% . AnotherEstablishing an institutional antibiogram may not always be feasible, especially at smaller hospitals where there may be a lack of personnel and resources. Similarly, the outpatient setting also lacks resources to complete an antibiogram. Non-variable challenges include few pathogen isolates and therefore do not meet the CLSI standard of 30 isolates per species. Microbiologic testing may not be widely available in rural areas or may be limited to send out testing, creating a barrier to the primary source data . Once an antibiogram is completed, if not appropriately analyzed and distributed, it may send the wrong message to prescribers and influence antibiotic ordering incorrectly. There may be a lack of knowledge on interpreting and utilizing the antibiogram effectively. Education is key for prescribers to enact change in prescribing patterns based on an antibiogram.If a hospital chooses to complete an institutional antibiogram, ensuring correctness is of utmost importance. Upon a review of 37 hospitals in the Duke Antimicrobial Stewardship Outreach Network (DASON) group, the authors found that 25% of hospitals reported antibiograms with only >30 isolates per species. Additionally, CLSI required standards were observed correctly in only 9% of antibiograms . If a hoWhile an antibiogram is an important antimicrobial stewardship tool that can aid in the selection of empiric antibiotic regimens, there are limitations with the applicability of traditional antibiograms. Most hospitals typically distribute a general antibiogram that includes isolates from all sources and all units, which may be difficult to interpret as different units may have different resistance rates owing to the complexity of patients served . Secondly, antibiograms do not distinguish between community-acquired versus hospital-acquired infections, whereby the latter are generally associated with higher rates of resistance. Thirdly, outpatient physician offices do not have clinic-specific antibiograms available for patients that have routine visits. Fourthly, a traditional antibiogram may include colonizing organisms, which could influence the susceptibility rates. Fifthly, the distribution of quantitative data such as the minimum inhibitory concentration (MIC) is not represented by the antibiogram, which is pertinent for the optimization of antibiotic dosing, especially in individuals with altered pharmacokinetic parameters . Lastly, static antibiograms may be of limited use in empiric antibiotic selection in patients with recurrent or recent infections.Pathogen susceptibility may be incorrectly interpreted when isolates from all units within an institution are combined as a cumulative antibiogram. Pathogens recovered from intensive care units (ICUs) typically have significantly higher rates of resistance compared to those from non-ICU locations due to the inherent risk for the repeated, prolonged exposure to broad-spectrum antibiotics and the severity of illness ,14. TherE. coli isolates was greater in the urinary antibiogram versus the standard  [E. coli isolates alone versus all urinary isolates  [Creating a urine-specific antibiogram may be helpful for determining empiric therapy, especially in outpatient and ED settings. In a study by Rabs and colleagues, 2284 pathogens were isolated from a urinary source. Overall, the antibiotic susceptibility increased; however, the prevalence of ESBL < 0.001) . In a ve< 0.001) . These fContrary to the traditional antibiogram, a patient-specific antibiogram accounts for numerous variables that are known to impact a patient’s risk of having a resistant organism. Overly and colleagues demonstrated that a patient-specific antibiogram based on the inclusion of key elements, including prior antibiotic exposure, prior microbiology, a history of resistant pathogens, diagnoses, age, and location in the hospital, provided a better prediction of antibiotic susceptibility compared to the traditional antibiogram . More imTwo single-center studies conducted in the United States examined independent risk factors for UTIs due to fluoroquinolone-resistant bacteria. Shah and colleagues identified multiple variables associated with fluoroquinolone resistance including the male sex, residence at a skilled nursing facility, an outpatient procedure within 1 month of the index infection, and prior fluoroquinolone use within 3 months and within 3 to 12 months of the index infection . In addiE. coli community-acquired complicated UTIs (61%), the authors found that a prior UTI or urinary colonization with TMP-SMX resistant isolates and prior use of TMP-SMX within the past 12 months of the index infection were associated with a risk of TMP-SMX resistance [E. coli in Michigan. The findings suggested that the recent use of TMP-SMX was associated with a higher risk of TMP-SMX resistance than the recent use of any other antibiotic  [E. coli, recruited from a Veterans Affair ambulatory clinic, also found that prior exposure to antibiotics including TMP-SMX, fluoroquinolones, and tetracyclines within the past 6 months increased the risk of TMP-SMX resistance. Furthermore, the study also demonstrated that as the number of previous antibiotic courses increased, the frequency of TMP-SMX resistance also increased. This ranged from a TMP-SMX resistance of 8% to 39% for patients with no prior antibiotics vs. patients with three or more prior antibiotics, respectively [The independent risk factors predicting TMP-SMX resistance in UTIs have been reported by several studies ,21. In asistance . Anotherctively) . AnotherThe increasing rates of ESBL-producing Enterobacterales detected in the community is concerning to all clinicians. In a large, multicenter, retrospective case–control study of adult patients admitted with community-acquired UTIs due to ESBL-producing Enterobacterales, those with a history of repeated UTIs, the presence of a urinary catheter at the time of admission, and prior exposure to outpatient antibiotics within the past 3 months had an increased risk for UTI due to ESBL-producing Enterobacterales after controlling for the acute severity of illness and comorbid conditions . AnotherIn a study by Goodman and colleagues, a clinical risk score with 14 variables was compared to a 5-variable decision tree model to predict patients’ risk of ESBL bacteremia. While this study focused on BSI, the authors found that the decision tree model, which included variables such as a history of infection due to ESBL-producing bacteria, local ESBL rates, indwelling hardware, prior antibiotic courses, and age, was more user-friendly but had lower discrimination when compared to the clinical risk score. This is important to consider when developing a risk score tool for the empiric selection of antibiotics based on predicted resistance .Clostridioides difficile infection. Frequent switches in ambulatory antibiotic prescriptions may also lead to a reduction in patients’ compliance with therapy due to cost and other logistical barriers to the second prescription. In addition, multiple antibiotic prescriptions may lead to a higher likelihood of developing an adverse drug reaction.A patient-specific risk factor evaluation would lead to a higher likelihood of selecting the appropriate antibiotic agent upon the initial patient presentation in the ambulatory setting. This would likely lead to faster clinical improvement in patients with APN. It may also result in a reduced risk of clinical deterioration, ultimately leading to hospitalization. This approach would also reduce the likelihood of future antibiotic switches that may be required if the bacterial isolate in the urine was resistant to the prescribed antibiotic. This will reduce the risk of exposure to multiple classes of antibiotics for the treatment of the same infection, which may subsequently reduce the risk of colonization with multi-drug resistant pathogens and As demonstrated in the study by Dunne and colleagues, patients with resistant pathogens often need an alternative prescription, which places strain on the healthcare system . AnotherEscherichia coli has a susceptibility to ciprofloxacin and levofloxacin at 75%.A 47-year-old woman is seen at an outpatient primary care clinic with complaints of dysuria, increased urinary frequency, and flank pain. The provider orders a urinalysis (UA) with culture, and the UA results are below . The patAllergies: penicillin (hives)Metformin 1000 mg twice daily;Lisinopril 20 mg daily;Atorvastatin 40 mg daily.Medication list:Utilizing the 2010 IDSA Guidelines for APN , after eUtilizing the precision medicine approach, the risk scores are relied on to direct the provider to the most appropriate antibiotic choice. First, the probability of fluoroquinolone resistance must be evaluated in this particular patient. Based on a fluoroquinolone resistance score of <2 (one point for diabetes mellitus), the predicted risk of fluoroquinolone resistance in this patient is <10%. This would place the patient in the category of “low risk of fluoroquinolone resistance”. Accordingly, there will be no need for the administration of IV or IM ceftriaxone or an aminoglycoside. This will spare the patient from additional costs, potential antibiotic adverse effects, and infusion-related complications. The patient may be prescribed oral ciprofloxacin or levofloxacin. The probability that the patient will need a second antibiotic prescription due to the growth of a fluoroquinolone-resistant urinary bacteria is <10%.Pharmacists play integral roles in antimicrobial stewardship in the community and large academic hospitals. The application of precision medicine would largely benefit the antimicrobial stewardship and ambulatory care pharmacists in optimizing empiric treatment for the management of APN. Integrating guidelines with the technology that is already implemented at institutions is necessary to allow for utilization by prescribers. A few ways to implement these risk factor tools include smart phone applications, as well as embedding them into the drug ordering pathway itself within the electronic health record (EHR) system. Disseminating these risk factor tools and education to prescribers will increase the utilization of local guidelines and risk factor prediction models. Pharmacists are well equipped to deliver this education to prescribers of all stages including attendings and trainees.E. coli isolates decreased by 1.6% for levofloxacin and 1.4% for ciprofloxacin each year (p < 0.01 and p < 0.001) [In a study conducted by Wang and colleagues at a 1400 bed tertiary hospital in China, interventions made by antimicrobial stewardship pharmacists had tremendous impacts on antibiotic consumption and antibiotic resistance. The authors found that the number of antibiotic prescriptions in the outpatient and inpatient settings decreased, and the amount of antibiotic prophylaxis also decreased. Pharmacists also play key roles in the appropriate dosing and timing of antibiotic administration in the hospital setting. Along with a decrease in antibiotic consumption, the study demonstrated that the fluoroquinolone resistance rates of < 0.001) .While the value of antimicrobial stewardship pharmacists in the inpatient, hospitalized setting is becoming well known and attributable to patient outcomes, the outpatient setting may be an untapped area for potential opportunities. In a cross-sectional, multicenter survey study conducted by Eudy and colleagues, the authors demonstrated that antimicrobial stewardship pharmacists were present in 7% 9 of 129) of ambulatory settings. This was compared to an 88% (114 of 129) presence in hospital settings [ of ambulThere are several limitations to this narrative review. First, articles examining the risk factors for fluoroquinolone-, TMP/SMX-, or ceftriaxone-resistant uropathogens are based on single-center retrospective studies. Therefore, the results are limited by its lack of external validation. Secondly, this paper does not address the outpatient management of APN in pregnant patients. The use of fluoroquinolones and trimethoprim–sulfamethoxazole is generally discouraged in pregnancy . The guiIn conclusion, the application of patient-specific precision medicine algorithms, such as the one proposed in this article, will optimize the ambulatory antibiotic management of APN. Providing the most effective, optimal therapy while minimizing consequences, such as side effects and further resistance, is crucial to patient care and antimicrobial stewardship initiatives. This algorithm provides a framework for healthcare systems to develop institution-specific protocols for the ambulatory antibiotic management of APN based on local antibiotic resistance data. Targeting patient-specific risk factors allows for a patient-centered approach to medicine, which is encouraged throughout the 2010 IDSA and ESCMID guidelines on APN. The application of precision medicine concepts improves the appropriateness of the first ambulatory antibiotic prescribed for APN and reduces the probability of clinical deterioration due to delayed appropriate therapy. It also reduces the risks of providing multiple antibiotic prescriptions for the treatment of the same infection and the associated adverse effects from these antibiotics.


N = 39) and found that ecological rather thansocial characteristics best predicted patterns of cognitive control across thesespecies. This highlights the importance of integrating cognitive data withspecies’ natural history to understand the origins of complex cognition.Cognitive control, or executive function, is a key feature of human cognition,allowing individuals to plan, acquire new information, or adopt new strategieswhen the circumstances change. Yet it is unclear which factors promote theevolution of more sophisticated executive-function abilities such as thosepossessed by humans. Examining cognitive control in nonhuman primates, ourclosest relatives, can help to identify these evolutionary processes. Here, wedeveloped a novel battery to experimentally measure multiple aspects ofcognitive control in primates: temporal discounting, motor inhibition,short-term memory, reversal learning, novelty responses, and persistence. Wetested lemur species with targeted, independent variation in both ecological andsocial features (ruffed lemurs, Coquerel’s sifakas, ring-tailed lemurs, andmongoose lemurs;  Weassessed four taxonomic groups: ruffed lemurs , Coquerel’s sifakas , ring-tailed lemurs, and mongoose lemurs. Ruffed lemursconsisted of both red-ruffed and black-and-white-ruffed lemurs, but we collapsedanalyses across both groups given their socioecological similarity andclassification as subspecies until recently (Table S1). All behavioral tests were approved by DukeUniversity’s Institutional Animal Care and Use Committee (Protocol No.A268-16-12).We tested 39 lemurs living at the Duke Lemur Center .In the basic procedure for the cognitive tasks, an experimenter sat across fromthe lemur at a sliding table and placed options containing hidden treats on thetable; lemurs could indicate their choice by either touching or approaching oneof the containers. All lemurs completed the tasks in the same order, typicallycompleting one session per day and at most two tasks with a break in between. Insome tasks, subjects had to first meet criteria on a pretest to demonstratebasic comprehension of the setup before proceeding to the main test, and theycould repeat sessions until they passed before proceeding. If the subject didnot choose one of the options within 15 s when responses involved makingchoices, the trial was stopped and repeated up to a maximum of four times. Ifthe subject continued to not make a choice, the session was halted and repeatedon a different day . The side of thedelayed option on the table was counterbalanced and quasirandomized acrosstrials , with a 30-sintertrial interval. We measured the lemurs’ choices for the largerreward.The ability to delay gratification for future rewards is a key component ofhuman executive functions . Toassehttps://doi.org/10.5061/dryad.6hdr7sr2k). The same procedurewas repeated three more times with visually distinct sets of containers anddifferent hiding locations , for a total of fourtest trials. The order of presentation of the container sets was fixedacross subjects, and the initially baited container (left or right) wascounterbalanced across trial blocks and subjects. We measured lemurs’choices of the correct container.The ability to inhibit ineffectual motor responses is another key componentof executive functions . Toassehttps://doi.org/10.5061/dryad.6hdr7sr2k). Although this taskdoes not require retaining information while performing a secondary task, asis the case for many measures of working memory used with humans . In the session,lemurs first completed two exposure trials, in which the experimenter putthe food under the correct learning-phase container in full view of thesubjects. Then they completed at least six (out of a maximum of 10) learningtrials in which that container was baited behind an occluder. Once lemursconsistently chose the baited container , they completed 10 test trials in which the rewardcontingencies were switched. The assignment of the baited side and of thecorresponding container for the learning phase was counterbalanced acrosssubjects. We measured lemurs’ choices for the correct container.The ability to flexibly update responses is another key component ofexecutive functions . Totesthttps://doi.org/10.5061/dryad.6hdr7sr2k). Each lemur waspresented with four stimuli in a fixed order: (a) baseline with table only,(b) baseline with a person sitting at the table, (c) novel stationaryobject, and (d) novel moving object . On each trial, wemeasured how long the lemur spent in close proximity to the stimuli.We also measured two aspects of temperament in the lemurs because responsesto novel or difficult situations may constrain cognitive control. Forexample, species might show poorer performance if they are more neophobic orless motivated to participate . To assehttps://doi.org/10.5061/dryad.6hdr7sr2k). We measured howlong subjects manipulated the box when attempting to retrieve the food; themaximum time allowed was 3 min.In the second temperament task, we presented lemurs with an inaccessible foodreward to measure their motivation to retrieve it. First, one experimenterpositioned a clear box containing a piece of food on a table inside thelemur’s room. For two consecutive solvable trials, the box’s lid was leftunsealed so the box could be easily opened to retrieve the food. In thethird, unsolvable trial, the lid was closed so it was impossible for thelemurs to open it . The study design andstatistical-analysis approach were preregistered (https://aspredicted.org/iv9tb.pdf). We used generalized linearmixed models to analyze trial-by-trial responses and compare species’performance for most tasks . Models always included subject as arandom factor to account for repeated trials when relevant, as well as age, sex,and trial number; we also accounted for pretest performance and the number ofsessions each individual completed before reaching criterion . Then weadded species as a factor to examine evolutionary variation. We compared modelfit using likelihood-ratio tests, and we computed post hoc pairwise comparisonswith a Tukey correction. In a final analysis, we compared species’ integrativeperformance across tasks using principal components analysis (PCA).All tasks were videotaped, and a coder blind to the study’s hypotheses coded atleast 20% of tasks with high reliability  = 11.97,p = .002 . Furthermore, all speciesselected the larger reward significantly more often than chance in the numberpretest, in which the larger reward entailed no delay . This shows that lemurs accounted for the presence of delaycosts in their choices. In the main analysis of the discounting task, all speciesexcept sifakas selected the longer-delayed option more often than chance in bothdelay conditions . To compare performance acrossspecies, we included subject, age, sex, trial number, and discrimination score  in a base model. Adding delay (15 s and 30 s) in the secondmodel did not improve model fit, χ2(1) = 0.88, p = .347,indicating that lemurs responded similarly to delay conditions. Adding species,however, significantly improved model fit, χ2(4) = 14.56,p = .006 ; post hoc comparisons showedthat ring-tailed lemurs were more willing to wait for a larger reward than bothmongoose lemurs and sifakas, and ruffed lemurs were more willing to wait thansifakas . These results support both the social- andecological-intelligence hypotheses, as the more socially complex ring-tailed lemursoutperformed mongoose lemurs, and the more ecologically complex ruffed lemursfurther outperformed sifakas.An initial comparison of performance in the temporal-discounting task examining delayduration  indicated a linear effect of delay: As expected, lemurschose the larger reward less often as the delay increased, χp < .05), andperformance of mongoose lemurs showed a trend toward doing so (p =.07); performance of ring-tailed lemurs and sifakas did not differ from chance . To compare performance, we included subject,age, sex, trial number, and number of sessions each individual needed to completebefore reaching criterion  in a base model. Inclusion of species improved model fit,χ2(3) = 11.52, p = .009 . Post hoc comparisonsrevealed a trend for mongoose lemurs and ruffed lemurs to outperform sifakas(p = .09) and for ruffed lemurs to outperform ring-tailedlemurs , whereas in the delay trials, only ring-tailed lemurs’ performance wasmarginally above chance . In the comparison of species, abase model accounting for subject, age, sex, trial number, number of sessions eachindividual needed to complete before reaching criterion  and condition (immediate or delayed choice) confirmedthat lemurs performed better when they could retrieve the food immediately. Addingspecies as a predictor in a second model showed a trend toward significantlyimproved model fit, χ2(3) = 6.35, p = .096, as didadding the interaction between species and condition, χ2(6) = 11.44,p = .076 . We further explored thisresult by analyzing lemurs’ performance only in the no-delay trials, given thelemurs’ poor performance in delay trials. We found that adding species as apredictor in a second model improved model fit, χ2(3) = 10.67,p = .014. Post hoc comparisons in this analysis revealed thatring-tailed lemurs outperformed sifakas . Noother differences among species were found. Overall, this suggests that lemurs havefairly poor short-term memory overall, but there was no evidence in support of thesocial-intelligence hypothesis. Rather, the folivorous sifakas’ relatively lowperformance was most in line with the ecological-intelligence hypothesis.In the short-term-memory task, all species selected the correct option at anabove-chance level on no-delay trials (p ≤ .05 for significant comparisons);note that individuals were expected to start below chance and improve over reversaltrials in this task as they learned the correct response after the contingencyswitches. Here, the base model accounted for subject, age, sex, trial number, andlearning trials needed to reach criterion  and showed that performance overall improved overreversal trials, as expected. Inclusion of species improved model fit,χ2(3) = 19.08, p < .001 . Post hoc comparisonsindicated that sifakas showed worse performance than all other species. Adding species to a base model includingsubject, age, sex, and trial type improved model fit, χ2(3) = 26.75,p < .001 ; sifakas spent more time nearthe novel items than both ring-tailed and mongoose lemurs (p <.05 for both comparisons), and ruffed lemurs spent more time than ring-tailed lemurs(p < .05). No other differences among species were found.Additional comparisons showed that these results were driven primarily bydifferences in responses to the stationary and moving objects . In the persistence task, the inclusion ofspecies in a base model accounting for sex and age also improved model fit,χ2(3) = 14.65, p = .002 ; sifakas and ruffed lemursspent more time manipulating the box compared with ring-tailed lemurs(p < .05 for significant comparisons). No other differencesamong species were found. Overall, these results indicate that sifakas, the specieswith the worst cognitive performance in general, were quite bold and willing toengage in tasks, and they generally had similar temperament outcomes to the morecognitively successful ruffed lemurs. Thus, neophobic responses or low levels ofmotivation did not seem to constrain performance across the cognitive-controltasks.Some proposals suggest that temperament may constrain performance in cognitive tasks, so we nSupplemental Material). The PCA yielded two principal unrotatedcomponents that best explained variation in lemurs’ performance, on the basis of ananalysis that compared eigenvalues from actual data with randomly resampled andsimulated correlation matrices . We then compared species’scores on these two dimensions and found that the sifakas were significantlydifferent from the other species in Dimension 1, reflecting an overall lowerperformance in the cognitive-control tasks . The ring-tailed lemurs alsoshowed a pattern more like sifakas on Dimension 2, which primarily tracks A-not-Bperformance . Thus, results from the PCAcomplement the results seen in each individual task: We found that the leastecologically complex species (sifakas) showed the worst performance across tasks onboth dimensions. In contrast, there was again limited or even negative support forthe social-intelligence hypothesis, given that the most socially complex species(ring-tailed lemurs) actually showed a decrement in performance on Dimension 2.As a final test of the social- and ecological-intelligence hypotheses, we implementeda PCA to extract summary scores of each species’ responses across the fourcognitive-control tasks. We then compared variation in these extracted scores acrossthe species to test for differences (for details, see the matrices . The temWe examined the evolution of cognitive control in lemurs using a novel battery ofcognitive tasks, and we found that ecological complexity more consistently predictedcognition across species than did social complexity across contexts. In particular,the sifakas—the only obligate folivore in our study—showed the worst performanceacross multiple measures and specifically were often outperformed by the highlyfrugivorous ruffed lemurs in the temporal-discounting, A-not-B, andreversal-learning tasks. Crucially, these species exhibit similar social systems butdiffer in the complexity of their diets. In contrast, there was no consistentpattern of variation related to sociality. Ring-tailed lemurs, who live in largesocial groups with dominance hierarchies, were quite successful at delayinggratification and successful to a lesser extent in the short-term-memory task.However, they did not otherwise consistently outperform the pair-bonded mongooselemurs or the other species in general; indeed, the mongoose lemurs showed strongerperformance in both the A-not-B task and the reversal-learning task. The PCA furtherindicated that the sifakas showed worse performance overall across both extracteddimensions and that the ring-tailed lemurs also had worse performance in Dimension2. Crucially, the novel-object and persistence measures indicated that thesepatterns of cognitive performance were not due to temperamental constraints. Thus,our study indicates that ecology rather than sociality plays a more fundamental rolein shaping cognitive control in lemurs.These results align with prior work showing that spatial memory and decision-makingvary according to ecology in primates e.g., . Yet theAnother important question concerns the mechanistic basis of cognitive control inprimates. In adult humans, different components of inhibition, working memory, andshifting represent distinct, dissociable components of executive control . Our PCAA final point concerns the fundamental problem of how to best conceptualizeecological and social complexity across species. Here, we took the approach ofcomparing species that differed across broad, widely accepted metrics of ecologicaland social complexity—degree of frugivorous versus folivorous diet and the size andcomplexity of social groups. Yet there are alternative approaches to this problem.Although frugivory diets are generally considered more ecologically complex thanfolivory diets in primates , other mIn conclusion, we examined cognitive control across lemurs using measures of temporaldiscounting, motor inhibition, short-term memory, and reversal learning. Our resultsshow that cognitive-control capacities consistently varied according to thesespecies’ feeding ecology but not according to their social complexity. Thus, ourfindings align with accumulating evidence that ecological complexity can be animportant driver of both cognitive and brain evolution in lemurs and acroClick here for additional data file.Supplemental material, sj-docx-1-pss-10.1177_09567976221082938 for The Evolutionof Cognitive Control in Lemurs by Francesca De Petrillo, Parvathy Nair, AverillCantwell and Alexandra G. Rosati in Psychological Science


This research concerns the possibility of using reclaimed asphalt pavement as a substitute for conventional aggregate in cement concrete mixtures for roads and airfield applications. The advantages of using reclaimed asphalt pavement as a replacement for natural aggregates are presented. Economic and environmental aspects are indicated, including the reduction in the consumption of natural non-renewable sources of mineral aggregates, as well as reduction in transport costs and emissions of harmful greenhouse gases. The consistency of this recycled material with the idea of sustainable development in the construction industry is emphasized. The test results of the used reclaimed asphalt and the assessment of the effect of its amount on the change in mechanical, physical and strength parameters of cement concrete are presented. It has been shown that the addition of reclaimed concrete reduces selected parameters of cement concrete, but it is possible to use it in structures with less traffic load, taking into account the sustainable development policy. Technological development is closely related to and dependent on transport possibilities, especially in terms of the economics of given projects. Transport safety is the most important element that should be ensured at the stage of management of highway infrastructure  butThe results presented in  indicateIt is estimated that in Europe the average production and consumption of natural aggregates is about 6.5 tons per capita . Such a In the article authors consider the possibility of reusing the aggregate from recycled pavement. The use of recycled materials in transportation infrastructure corresponds with the sustainability concept due to its environmental and economic benefits.Reclaimed asphalt pavement (RAP) is the material created in the process of demolition or milling of a distressed flexible pavement which is an integral part in pavement renovation works. Asphalt destruct in its composition contains about 88% mineral aggregate, 7% filler and about 5% asphalt binder, thus it gives opportunities to reuse such amounts of mineral material . The autThe beginnings of work on the possibilities of using reclaimed asphalt pavement in cement concrete mixes date back to the 1990s. Delwar et al., 1997  investigIn laboratory research Hassan et al., 2000  analyzedThe research of  concerneThe use of reclaimed asphalt in concrete mixes is a promising material solution; therefore, the global interest in developing this technology is visible. The publications on this subject that have been published in recent years focus not only on the strength properties of the concrete, but more and more new aspects are analyzed. Brand and Al-Quadi  focused Reducing the consumption of natural aggregates—destruct can be used both as a replacement for fine and coarse aggregate, and replacing natural aggregate with it in the amount of up to 50% does not cause a significant decrease in concrete properties ,25,36.Reduction in greenhouse gas emissions—it is estimated that the production of 1 ton of aggregate generates about 1% of greenhouse gases .Conducting a sustainable concrete production process . SustainSavings in transport costs ,36—this 3 of concrete by up to 45% by using reclaimed asphalt as a substitute for natural aggregate in the concrete mix [Savings in production costs—the amount of expenditure related to transport, extraction and preparation of natural aggregate significantly affects the cost of concrete production, it is estimated that it is possible to reduce the production cost of 1 mrete mix .The use of reclaimed asphalt as a substitute for natural aggregate brings many benefits, not only in terms of the natural environment, but also economic aspects :ReducingDespite the indicated advantages of using an alternative material in the form of reclaimed asphalt, the authors of the related publications indicate the lack of clear guidelines as to the possibility of using this additive in concrete mixes. An additional problem is the lack of awareness and concerns of contractors and investors regarding the quality and durability of objects made of cement concrete with reclaimed asphalt. However, the growing interest of scientists and the amount and scope of research work on the properties and possibilities of using reclaimed asphalt in cement concrete may, however, increase the interest in this technology .In order to systematize the knowledge gained so far in the experimental field, selected parameters of the concrete mix and the concrete composite were compiled, which were the results of the analyses of researchers dealing with the issue of using reclaimed asphalt in concrete mixes.Recent publications also focus on possible applications of reclaimed asphalt for rolled concrete (RCC-Roller-Compacted Concrete), research in this area was conducted by Debbarma, Ransinchung and Singh . The posObtained results indicated that further research on use of reclaimed asphalt in rigid surfaces made of cement concrete is justified.This research is aimed at checking the possibility of using reclaimed asphalt pavement for concrete mixtures in relation to polish road national standards.The aim of this research was to demonstrate the consistency between the internal structure of the concrete composite containing reclaimed asphalt and its mechanical parameters.Safe exploitation of concrete pavements is possible in terms of concrete that meets the functional, strength and durability requirements during the expected life cycle of the structure. In the context of road pavements, the static and dynamic loads generated by vehicles in conjunction with the stresses occurring in concrete slabs are included in the scope of structure design. In the airport systems, the forced thermal loads generated during the take-off stage of the aircraft are additionally taken into account. In terms of durability, these are multi-criteria issues that should be considered individually, as pointed out by the authors of ,43,44,45Laboratory tests included determination of the impact of the use of reclaimed asphalt on the change in selected paving concrete parameters. The reclaimed material selected in the exploratory tests (discussed in ) was useDensity and water absorption were determined for aggregates according to PN-EN 1097-6  using thC85/20 and for natural sand is GF85. The percentage share of individual grain sizes is summarized in The grain composition of the aggregates was determined in accordance with the requirements of PN-EN 12620  and PN-ESpecific selected parameters of reclaimed asphalt and asphalt extracted from it are summarized in For reclaimed asphalt, the grain composition and the maximum U size of the aggregate were determined. The reclaimed asphalt was classified as FM1/0.1 . The grain size of the used reclaimed asphalt is shown in 3. The composition of the mix uses tap water that meets the requirements of [3, pH of 5.5 and chloride ion content below 0.10% was used. An air-entraining admixture based on modified tensides and root resins was also used, in which the content of chloride ions was less than 0.10%. The compositions of concrete mixes are presented in In the composition of the concrete mix, cement CEM I 42.5 was used as a binder, which meets the standard requirements for reduced alkalinity. The cement content was determined on the basis of the adopted design assumptions and standard requirements ,11,13 inments of , and admThe concretes were made in accordance with the requirements of a series of standards ,59,60,61The compared series of C-C and C-RA concretes were analyzed in accordance with the assumptions of the Student’s t-test, each time for at least six samples in one test series. It was assumed that the number of series is constant and the distribution of results in each of the analyzed groups is compared with the normal distribution. The basic statistical parameters, arithmetic mean, standard deviation and coefficient of variation were determined according to the procedure presented in .In the research process, various types of samples were investigated, depending on their purpose and the test performed, which, together with the geometric characteristics, are summarized in It was found that the concrete with the addition of reclaimed asphalt of the C-RA series was characterized by a lower density compared to the control concrete .The depth of water penetration under pressure is one of the durability parameters of structural concrete in a road engineering structure. At the same time, a beneficial effect of reclaimed material on the reduction in water absorption under pressure and the depth of concrete penetration was found . This isIn the case of mechanical parameters, a decrease in the examined features was found, regardless of the analyzed parameter. The decrease in compressive strength was found in all three test periods . The highest decrease was recorded in the case of early ripening, after 7 and 14 days, which was about 15% . AnalyseStatistical parameters characterizing individual series are presented in The results obtained from the compressive strength test were characterized by low values of the standard deviation, which means that the average values obtained in laboratory tests are statistically representative.Similar dependencies occurred in the assessment of average flexural strength and average tensile splitting strength of the C-RA series concrete in relation to the C-C series concrete. A decrease in strength of more than 11% in the first case and 7% in the second case was found .Approximately 30% higher values of Young’s modulus results were measured in concrete C-C. The results were characterized by a slight differentiation, the coefficient of variation for concrete C-C was 1.3%, and 4.0% for concrete C-RA .The stress–strain dependence for the analyzed concrete series C-C and C-RA is shown in The presented test results clearly indicate that the fracture toughness of C-RA concrete is higher than that of C-C concrete. The index for the C-C series concrete was 0.115, and for the C-RA concrete it was 0.120. These results are also consistent with the specified brittleness coefficients of the analyzed concretes, as shown in The pull-off method is a measure of the concrete’s pull-off strength and is one of the methods for evaluating the durability of a structure. Based on the obtained results , a lowerThe assessment of concrete resistance to freezing and thawing cycles showed that both concrete series meet the requirements for traffic surfaces .By analyzing the durability parameters, it was shown that the C-C series concrete obtained a higher durability factor than the C-RA series concrete.The CT observation enabled a detailed assessment of changes in the total porosity content of C-C and C-RA series cement concrete. The obtained parameters are summarized in Based on the analysis of the obtained results, it was found that the total content of air voids in the C-C series concrete is higher than in the C-RA concrete. However, the content of pores with diameters below 300 µm and round pores, which increase the level of frost resistance in cement concrete, is higher in the C-RA series concrete.The differences in the frequency of air pores of different volumes and diameters are shown in The use of reclaimed asphalt in the concrete mix allows for comparable air-entrainment parameters, density and consistency classes.Based on the obtained results and their analysis, the following conclusions were formulated:The air content determined by the pressure method for the C-C reference mixture was 4.6% and for the C-RA series mixture it was 4.8%. Both series of mixtures met the minimum content requirements ranging from 4.5% to 6%. The used reclaimed asphalt consisted of visible agglomerations of aggregate combined with an asphalt binder, which contributed to an increase in the air content in the C-RA mix.3 for the C-C series to 2370 kg/m3 for the C-RA series). This is due to the fact that reclaimed asphalt has a lower density than the granite aggregate used in this experimental program.The use of reclaimed asphalt reduces the density of the concrete mix (from 2389 kg/m2.3 to 2407 kg/m3 for the C-RA series is related to the difference in the density of granite aggregate (2.65 kg/m3) and reclaimed asphalt (2.56 kg/m3).The use of reclaimed material reduces the density of hardened concrete in all analyzed periods. Reducing the density of C-C series concrete from 2430 kg/m3.In the case of physical parameters, a beneficial effect of the addition of reclaimed material was observed. Water absorption of the C-RA series concrete (3.9%) was lower than that of the control concrete (4.2%). A similar relationship occurred with regard to testing the depth of water penetration under pressure. The tested feature for the C-RA series was 12 mm and for the C-C series it was 23 mm.4.In the case of mechanical parameters, a decrease in the tested concrete properties was observed due to the presence of reclaimed material.The compressive strength of the C-RA series concrete was significantly lower than that of the C-C series control concrete in all analyzed research periods. In the case of the first 7 days, this decrease was about 15%, after 14 days it was also 15% and after 28 days it was 12%. The use of reclaimed material resulted in a reduction in the strength class from C40/50 for the C-C series to C35/45 for the C-RA series.Similar relationships were also observed for the characteristics of bending strength (decrease of more than 7%) and tensile strength at splitting (decrease of more than 11%). For the latter feature, both series of concretes meet the requirements for road surface concretes with traffic categories from KR1 to KR4. However, the C-RA series does not meet the requirements for airport pavements.5.In the case of durability features, no significant effect on the change in the tested concrete parameters due to the addition of reclaimed material was observed.The frost resistance parameters of both concrete series are comparable and meet the requirements for road and airport pavements.The lower values of the peel strength of the surface layer of the C-RA series concrete (2.35 MPa) in relation to the C-C series concrete (2.92 MPa) indicate a potentially lower resistance of the surface concrete. Especially in the case of more heavily loaded surfaces, such as airport pavements, this may shorten the service life of the structure. It should be noted, however, that in the case of both concrete series, the minimum required value of 2.0 MPa was achieved.


The management protocols will be pre-defined, but the selection of the protocol will be at the clinicians’ discretion. Patients will be followed for 12 months from the onset of the prophylaxis protocol. The primary outcome is to identify the incidence of breakthrough infections. The secondary outcomes are adverse events associated with the prophylaxis regimens and the severity of breakthrough infections. Other outcomes include the exploration of change in susceptibility pattern via the optional rectal and perineal swab, as well as health-related quality of life over time (HRQoL), which will be measured in a random subgroup of 30 patients. Ethics and dissemination: Ethical approval for this study has been granted by the ethical review board of the University Medical Centre Rostock (A 2021-0238 from 28 October 2021). The results will be published in a peer-reviewed journal and presented at relevant meetings. Study registration number: German Clinical Trials Register: Number DRKS00029142.Introduction: Patients with neurogenic lower urinary tract dysfunction (NLUTD) reliant on intermittent self-catheterization for bladder emptying are at an increased risk of recurrent urinary tract infections (rUTI). So far, the most common practice in the prevention of rUTIs is long-term low-dose antibiotic prophylaxis, phytotherapy, and immunomodulation, whereby antibiotic prophylaxis inevitably leads to the emergence of drug-resistant pathogens and difficulty in treating infections. Therefore, non-antibiotic alternatives in the prevention of rUTIs are urgently required. We aim to identify the comparative clinical effectiveness of a non-antibiotic prophylaxis regimen in the prevention of recurrent urinary tract infections in patients with neurogenic bladder dysfunction who practice intermittent self-catheterization. Methods and analysis: In this multi-centre, prospective longitudinal multi-arm observational study, a total of 785 patients practising intermittent self-catheterisation due to NLUTD will be included. After inclusion, non-antibiotic prophylaxis regimens will be instilled with either UroVaxom An increased risk of rUTIs is known in patients with neurogenic lower urinary tract dysfunction (NLUTD) due to the impairment in the urinary tract’s physical protective mechanisms. The cause of NLUTD and how it can manifest as a UTI are heterogeneous. Patients with NLUTD have an annual incidence of 54.9% of developing UTIs . UnfortuTo break the vicious cycle of recurrent UTIs (rUTI), prophylactic measures are propagated, albeit with limited evidence to support one intervention over the other. So far, the most common practice in the prevention of rUTIs is long-term low-dose antibiotic prophylaxis, phytotherapy, and immunomodulation. The antibiotic prophylaxis option exacerbates the emergence of difficult-to-treat drug-resistant infections. Therefore, non-antibiotic alternatives in the prevention of rUTIs are urgently required. ®) and the bacterial lysate vaccine Strovac® have been diligently tested and proven to lower the rate of UTI [We have recourse to a broad armamentarium of non-antibiotic options, whereby significant evidence is limited. Several viable and readily available options have been shown to yield consistent results. Main alternatives to antibiotic prophylaxis include vaccines, antiseptics, urine-specific antimicrobials, and direct mechanic washouts of the bladder. A variety of vaccines have been used in the prevention of rUTIs. Especially OM-89 . The primary outcome is depicted by the number of breakthrough infections. Secondarily adverse events associated with the prophylaxis regimens and the severity of breakthrough infections must be investigated. Change in susceptibility pattern via the optional rectal and perineal swab, as well as health-related quality of life over time (HRQoL) outcomes, will be measured in a random subgroup of 60 patients.The primary objective is to identify the clinical effectiveness of different prophylactic regimens. The secondary objective is to determine the adverse events related to prophylaxis and the severity of breakthrough infections. Patients unable to empty their bladder to completion due to a neurogenic disorder require adjunct management options to ensure a low-pressure urinary tract as well as sufficient emptying of the bladder. The most common way of achieving bladder emptying in patients with manual dexterity or with a carer to support is CISC. In this population, the rate of rUTI is significantly high at 9.4 episodes per year ,15. ○2 CFU/mL (Colony forming units);Positive urine culture with typical bacteria in UTI with >10○Urinary urgency;○Urinary frequency;○Dysuria;○Fever/chills;○Worsening of a neurological condition;○Altered mental status;○De novo incontinence.In our study, UTIs in this challenging collection of patients are defined as follows:Diagnosis of UTI is fulfilled if patients suffer from two or more of the above symptoms with positive urine culture (mandatory) . There are very few publications on the specific bacterial spectrum in rUTI in NLUTD. Mainly the bacterial spectrum of complicated and nosocomial acquired UTI is taken as representative of rUTI as well .Escherichia coli, Enterococcus faecalis, Klebsiella pneumoniae/variicola, Streptococcus viridans, Pseudomonas aeruginosa, and coagulase-negative Staphylococci have been detected. To date, unfortunately, fluoroquinolones are the most frequently used antibiotic in the management of UTI, whereby no considerable increase in resistance could be observed. Identified E. coli strains showed a noteworthy resistance increase against amoxicillin/clavulanic acid from 26 to over 38% [Recent data show a similar bacterial spectrum to other populations suffering from rUTI. Most frequently, over 38% .Treatment regimens in handling rUTI are highly individual and often challenging. Due to a lack of clinical information, grading of severity and, therefore, indication for antibiotic treatment is often unclear. Even though we usually have specific information concerning causative organisms for individual patients, empiric treatment regularly fails the patient. A multitude of antibiotic and non-antibiotic prophylaxis regimens have been tested to date, yet missing conclusive evidence ,19,20,21To our knowledge, there is limited evidence on prophylaxis to prevent rUTIs in NLUTD patients practising CISC. Long-term health outcomes and quality of life are significantly impaired in our population of interest, and increasing antibiotic consumption, as well as rising resistance rates against our antibiotic armamentarium, necessitates a controlled evaluation of non-antibiotic alternatives in the reduction of UTI frequency. Few trials support the use of non-antibiotic prophylaxis, but further investigation in a prospective manner is demanded eventually. If solid data supports any kind of named non-antibiotic alternative, this could serve to lower the burden on our healthcare system financially on the hand, and on the other hand, the even more pressing question of how to offer an evidence-based substitute in prophylaxis and therefore lowering exposure in the worldwide development of antibiotic resistance.The aim of this prospective observational cohort study is to investigate the impact of five different non-antibiotic prophylaxis regimens over the course of one year on predefined time points. Our long-term goal is to identify safe and effective candidate regimens that could be carried to a randomised controlled trial (RCT) to establish clinical and cost-effectiveness. To identify the clinical effectiveness of non-antibiotic prophylaxis regimens in the prevention of episodes of UTIs in NLUTD patients managing their bladder with CISC and having rUTIs. ○Number of UTIs under non-antibiotic prophylaxis necessitating antibiotic treatment;○Evaluation of antibiotic resistance of inherent microbial flora and acquired urine cultures;○Evaluation of antibiotic consumption (DDD-defined daily doses) under non-antibiotic prophylaxis;○Evaluation of quality of life in patients undergoing non-antibiotic prophylaxis.Escherichia coli viva OM-89 (UroVaxom®), bacterial lysate vaccine (StroVac®), nasturtium and horseradish root powder (Angocin®), D-Mannose or bladder irrigation with saline once daily. Occurring complications under named prophylaxis will be treated according to the current standard of care. This is a prospective, longitudinal, multi-arm, multi-centre, observational, clinical cohort study. Patients will receive approved non-antibiotic UTI prophylaxis with either Primary Outcome Measure: Incidence of symptomatic breakthrough infections.Secondary Outcomes: Severity of infectious breakouts with antibiotic use, development of antibiotic-resistant (AMR) flora, number of antibiotics used, quality of life, and exploration of health economic assessment variables. Adult patients with neurogenic bladder dysfunction, practising clean intermittent self-catheterization, who suffer from recurrent UTI (used definition: more than 3 episodes in the last 12 months) and who failed conservative measures. Non-antibiotic prophylaxis  will be offered to these patients per-protocol basis. The data of the bacterial isolates and their susceptibility results used in this study will be obtained as part of routine clinical care. The necessity of informed patient consent is at the discretion of the participating institution. All patient data will be analysed anonymously.Microbiologically proven UTI according to Age > 18;Ability to consent;NLUTD with practised ISC;rUTI (used definition: more than 3 infections per year) independent from a bacterial spectrum of infection;Failed conservative measures ;Previous episodes of UTIs do not show multi-drug-resistant bacteria;Non-antibiotic prophylaxis with UroVaxom, StroVac, Angocin, D-Mannose or bladder irrigation with saline;Signed informed consent form.Patients practising ISC with augmented bladder or continent pouches;Inability to consent;Intention-to-treat analysis for dropouts;Failure to provide consent;MDR pathogens in previous episodes of UTIs;Antibiotic prophylaxis in the months before study enrolment.Data collection in centres in Germany and Switzerland will fall under general consent. If necessary, because of country-specific ethical board requirements, patients will need to give written consent. Consent will be obtained by the primary physician. Identification of observations: Patients to be observed will be identified through participating clinicians in either an outpatient setting, hospitalised patients or follow-up visits after symptomatic infections. The eligibility criteria checklist of all cases considered to be observed will be filled in by participating principal investigators (PI). Clinical information from the initial diagnosis should be used to assess eligibility.A logbook of patient screening will be kept to keep track of the number of patients per unit who are eligible and who are not. We will also keep track of those who are eligible and refuse to participate. If recruitment rates are slower than the anticipated trajectory, the logbook will be reviewed to identify obstacles in recruitment. Patients will be stratified to balance our groups according to age, sex, underlying neurological condition and number of infections prior to study inclusion. Age;Country;Sex;BMI;Underlying neurological disease;Date of initial diagnosis;Charlson Comorbidity Index;Medication;ACSS score;Practice of sterile intermittent self-catheterization;Practice of clean intermittent self-catheterization;Duration of practised catheterisation in months;Number of catheterisations per day;Number of UTIs in last 12 months;Hospitalisation due to UTI;Earlier prophylaxis regimens/sufficiency of prophylaxis ;Appropriateness of intermittent self-catheterization  via ultrasound, which should be less than 100–150 mls).UroVaxom (OM-89) will be administered as a standard regimen: once daily for three months with a three-month pause following and three ten-day cycles at 7, 8 and 9 months.,StroVac  standard regimen: three vaccines in 6–12 weeks with two weeks between each vaccination *.Angocin twice daily for the duration of the study.D-mannose  once daily for the duration of the studyBladder irrigation with saline  once per day for the duration of the study.* In case of restricted drug availability due to country-specific authorisation of vaccines, additional treatment arms with similar mechanisms of action will be opened and analysed as a subgroup. If necessary, amendments to the protocol will be issued, and additional ethics approval will be requested.Number of UTI ;Hospital admission due to UTI or severe systemic infection ;Antibiotic treatment/ treatment with a reserve antibiotic;Urine culture, including susceptibility profile;Rectal swab ;Perineal swab ;ACSS score;Adverse events during intake;HRQoL measures (subgroup of 30 patients);End at 12 months: patient impression .Reason for dropout;Time Point of dropout;UTI;Sepsis;Adverse events;Problems of administration of the drug;Duration of non-antibiotic regimen;Switch to another prophylaxis regimen/which one.Study assessors will not be blinded.Power analysis was performed to determine an adequate sample size. We considered that these patients suffer 9.4 UTIs per year with an SD of 5.414. Furthermore, we assumed that a reduction of 3 UTIs per year is clinically significant. In order to achieve an effect size of 0.1, 785 participants are necessary . Furthermore, to achieve an effect size of 0.2, 197 participants are necessary, or for an effect size of 0.3, 88 participants are required, respectively. Data measured on a continuous scale will be expressed as mean, standard deviation, range, and median. Counts and percentages of patients in the categories will be used to convey categorical data. When necessary, T- or Mann-Whitney tests will be performed to determine statistical differences in continuous variables, and Chi-square or Fisher’s tests will be used to test for statistical differences in categorical variables.Patients with a minimum follow-up of 6 months who remained on the same prophylaxis regimen will be eligible for the final statistical analysis. Patients or the public were not involved in the design, conduct, reporting, or dissemination plans of our research.If protocol amendments are necessary, all involved parties  will be notified before relevant changes come into place.The trial will be audited by primary investigators after each data collection point. If any adverse events occur in between, those will be investigated, addressed, and reported accordingly.The Global Prevalence Study on Infection (GPIU) study team and platform will provide adequate data management.The collection of observational data will be performed using electronic (e) case report forms (CRF). Sites will receive direction from the study coordinator to help them complete the eCRFs. The research team retains the right to modify or enhance the eCRF template as necessary. Sites should utilise revised or extra forms, as these changes do not constitute a protocol amendment.The study coordinator will examine the completed eCRFs for consistency with the protocol, protocol compliance and missing variables. If any data gaps or anomalies are discovered, the site will raise questions for resolution. It is possible to query any systemic discrepancies found through central data monitoring.The end of the study will be the date of the last observation captured of our last enrolled participant.To date, no sponsors have been named.Responsibilities delegated to participating sites are defined in an agreement between the Sponsor and the individual site.The cohort study is designed longitudinal, observational with no intervention with no patient identifiable data and, generally, should not need ethics review. As this might differ between countries, the investigating sites should retrieve ethical consent according to their local needs. Ethical approval was granted in Germany by the ethical review board of the University Medical Centre Rostock (A 2021-0238 from 28 October 2021). In case of a change of protocol, amendments from country-specific ethical committees will be requested. This registry will be conducted according to the approved protocol and its amendments, supplementary guidance, and manuals supplied by potential sponsors.Data collected during the course of the study will be kept strictly confidential and accessed only by members of the team. Participants’ details will be stored on a secure database under the guidelines of the 1998 Data Protection Act, and regular checks and monitoring are in place to ensure compliance. Data are stored securely in accordance with the Act and archived in a secure data storage facility. The IT manager at Rostock University, Germany (in collaboration with the Study Directors and study coordinator) will manage access rights to the data set. Participants will be allocated an individual-specific number, and their details will be anonymised on the secure database. We anticipate that anonymised data may be shared with other researchers to enable international prospective meta-analyses. To comply with the 5th Principle of the Data Protection Act 1998, personal data will not be kept for longer than is required for the purpose it has been acquired.The main results will be published in peer-reviewed journals on behalf of all collaborators. The manuscript will be prepared by a writing group of members of the scientific committee and the European Section of Infections in Urology. Group authorship will be inserted under the collective title of ‘the NAPRUN Study Management Group’. If one or more individuals have made a significant contribution above and beyond other group members, but where all group members fulfil authorship rules, authorship will be attributed to the named individual(s) and the NAPRUN Group. Participating clinicians may be selected to join the writing group based on intellectual and time input. All participating clinicians will be acknowledged in the publications. Any presentations and publications relating to the data must be authorised by the GPIU group.