Endoscopic balloon dilation (EBD) is an effective, minimally invasive treatment for Crohn's disease (CD) related intestinal strictures. However, restenosis frequently occurs and requires repetitive EBD or surgical resection. Since previous studies could not evaluate restenosis based on stricture diameter, factors affecting restenosis after EBD were unclear. This study aimed to identify these factors by precisely measuring the diameter of small intestinal strictures in patients with CD.This single‐center retrospective study enrolled patients with CD with de novo small intestinal strictures who underwent two double‐balloon enteroscopy sessions (EBD and follow‐up) between January 2016 and October 2021. Clinical and endoscopic data were obtained from electronic medical records. A calibrated small‐caliber‐tip transparent hood was used to precisely measure stricture diameters. Multivariate analysis was performed to identify factors associated with restenosis.p = 0.01). Patients with complete mucosal healing at both sessions (n = 21) showed significant improvement in the narrowest stricture .Forty‐eight patients  were analyzed. The total number of strictures detected decreased from 162 to 143. The mean diameter of all strictures and the narrowest stricture in each patient increased significantly from 8.6 to 9.8 mm and from 7.6 to 8.7 mm, respectively. Thirty‐two (67%) patients developed endoscopic restenosis. Multivariate analysis showed that the presence of ulcers at the follow‐up session was a risk factor for restenosis (odds ratio 9.4, Maintenance of complete mucosal healing is significantly associated with avoiding restenosis after EBD in CD‐related small intestinal strictures. Crohn's disease (CD) is a phenotype of inflammatory bowel disease characterized by repeated episodes of clinical remission and relapse. CD‐specific lesions can lead to fibrotic intestinal strictures, which are the most common complication of CD.EBD is less invasive and relatively safe and effective for uncomplicated and short strictures (<5 cm).Annually scheduled DBE is performed for most patients with CD to monitor and optimize medications in our institution. When a stricture is found during the DBE, EBD is performed to pass through the stricture and observe further areas. This retrospective cohort study initially reviewed data from 113 patients with CD who underwent two serial sessions of scheduled DBE with EBD between January 2016 and October 2021. Patients who met the following inclusion criteria were then selected: (1) patients with ileal or ileocolonic CDA series of DBE during one hospitalization was considered “one session of DBE” in this study. At the EBD session and the follow‐up session, all detected strictures were evaluated and treated by EBD as indicated. Patients gave written informed consent for DBE, EBD, and conscious sedation before the procedures.DBE: The presence of ulcers and strictures were evaluated by therapeutic‐type DBE  with an over‐tube . An ulcer was defined as a mucosal defect, not depending on size or depth, and includes very tiny mucosal defects. A stricture was defined as a narrowed lumen with an inner diameter of 13 mm or less than the endoscope or over‐tube that could not pass through at the EBD session.Measuring stricture diameter: Stricture diameters were measured by using a calibrated small‐caliber‐tip transparent hood  and the through‐the‐scope balloon catheter  were inserted through the stricture lumen and inflated up to the target diameter under fluoroscopic guidance. The dilating balloon was then pressurized for one minute. Other subsequent strictures were measured and treated with EBD in patients with multiple strictures. Although EBD for mild strictures was not necessary to pass the endoscope, it was often performed to pass the over‐tube depending on needs. A 12–15 mm balloon catheter was generally used for moderate and mild strictures. A 10–12 mm or 8–10 mm balloon catheter was mainly used for severe strictures. The target diameter of EBD was adjusted considering the balance of risks and benefits based on various factors, including the presence of ulceration, the diameter and length of the stricture, and the necessity of passing the scope or the overtube.Endoscopic findings, including the frequency and diameters of strictures at both sessions, were compared to assess the effect of one EBD session. Since most patients had multiple strictures and some strictures became unrecognizable at the follow‐up session, we selected the diameter of the narrowest stricture in each session from each patient to define restenosis and improvement of stricture after EBD. In accordance with this definition, improvement was defined as a change of +2 mm or more in the diameter of the narrowest strictures, whereas restenosis was defined as a change of +1 mm or less. Patients were classified into improved and restenosis groups. Factors associated with restenosis after EBD were then analyzed.p‐value < 0.1 in univariate analysis were included in the multivariate analysis. A p‐value < 0.05 was considered statistically significant.All statistical analyses were performed using STATA 16.1 . Fisher's exact test was used for group comparison of categorical variables. Student's t‐test or a paired t‐test was used to compare quantitative variables. Logistic regression analysis was used to identify factors associated with restenosis. Variables with a n = 36) of patients underwent the follow‐up session 10–14 months after the EBD session, and the mean interval between the sessions was 12.8 months. Most patients were asymptomatic and serologically in remission, with no significant differences in abdominal symptoms or laboratory data  and immunomodulators . Medical treatment was modified in 15 patients (31%) after the EBD session due to the presence of ulcers and severe strictures, including the introduction of biologics (n = 5) and a dose escalation of immunomodulators and/or biologics (n = 7) (Table n = 24), the ulcer healing rate tended to be higher in the group who underwent treatment modification (4/9) than in those who did not (4/15); Figure Among 113 patients, 65 patients were excluded, and 48  were finally analyzed in this study Figure . GeneralOne hundred and twenty DBE procedures were performed during both sessions. Two episodes of post‐procedural bleeding were observed and treated conservatively. Perforation or acute pancreatitis was not observed.p = 0.04). The number of strictures decreased in 16 (33%) patients, six of whom had no stricture that warranted treatment. Patients with ulcerative strictures decreased from 24 (50%) to 19 (40 %). The frequency of severe and moderate strictures decreased from 57 to 40 and from 75 to 46, respectively. The mean diameter of detectable strictures increased significantly from 8.7 to 9.7 mm (p = 0.0004). The mean diameter of strictures in each patient increased in 33 (70%) patients, and the mean diameter of all strictures and the narrowest stricture in each patient improved significantly from 8.6 to 9.8 mm (p < 0.0001) and 7.6 to 8.7 mm .At the EBD session, 162 strictures were detected and dilated (≤13.5 mm for 104 and 15 mm for 58). At the follow‐up session, 143 strictures were detected, and 111 strictures were dilated. The mean number of detectable strictures per patient decreased from 3.4 to 3.0 (p = 0.03), and a long interval to follow‐up session after EBD and 15 mm sized dilation balloon were negatively associated with restenosis  patients had restenosis, and 16 (33%) were improved Tables . Multivap = 0.01). Of the narrowest strictures, 67 % (n = 32) were dilated by balloons 13.5 mm or less in diameter, and the remaining 33 % (n = 16) were treated with 15 mm balloons. Additionally, patients whose narrowest stricture was treated with 15 mm balloons tended to improve, whereas those treated with ≤13.5 mm balloons did not. Although there were no significant differences between the restenosis and improved patients, 69% of multiple stricture patients (25/36) and 74% of patients with severe strictures (20/27) developed restenosis.Patients with restenosis had a history of undergoing significantly more EBD procedures  compared to the improvement group. (Table n = 16), ulcer‐developed (n = 3), ulcer‐healed (n = 8), and no‐ulcer  and ulcer‐remaining  patients, while ulcer‐healed  and the no‐ulcer  groups had a lower rate.There were significantly more patients with ulcers at the follow‐up session in the restenosis group , similar to that in other studies with a different definition of restenosis.To evaluate long‐term outcomes after EBD, symptom‐free remission rate and surgery‐free rate were usually assessed in previous studies.EBD up to 15 mm was negatively associated with restenosis. This suggests that EBD for moderate to mild strictures is more effective than EBD for severe strictures and supports the advantage of scheduled maintenance EBD.The presence of small ulceration at the follow‐up session was identified as a risk factor for restenosis based on multivariate analysis in the present study. These results suggest that maintaining complete mucosal healing is important to improve the long‐term outcomes of EBD.A systematic review by Schulberg et al. concluded that effective anti‐inflammatory drug therapy combined with optimal endoscopic therapy for strictures provides the most effective non‐surgical treatment of strictures.This study has several limitations. First, it is a single‐center retrospective study with a relatively small number of patients. Therefore, the influence of the choice of medical treatment could not be evaluated. Secondly, it is possible that the comparison may not be of exactly the same stricture, although comparing the diameters of strictures one‐to‐one was ideal. Most patients had multiple strictures, and some mild strictures became unrecognizable at the follow‐up session. Comparing them one‐to‐one becomes very complicated. The narrowest stricture in each patient is often responsible for symptoms and rarely changes at the two sessions. For these reasons, we considered it better to compare the narrowest stricture for this analysis.In conclusion, maintenance of complete mucosal healing is significantly associated with avoiding restenosis after EBD for CD‐related small intestinal strictures.Hironori Yamamoto has patents for the calibrated small‐caliber‐tip transparent hood. Hironori Yamamoto has patents for double‐balloon endoscopy and a consultant relationship with Fujifilm. Tomonori Yano and Hirotsugu Sakamoto have received research funding and honoraria from Fujifilm.No other authors have personal financial relationships with a commercial entity producing healthcare‐related products and/or services relevant to this article.


This paper provides a step-by-step guide for organizing the scientific program (OSP) of international conferences. Through informal discussions, a panel of experts organizing international conferences came up with this guide, which includes a flowchart, checklist, and detailed discussions of each step. Subsequently, additional specialists were invited to evaluate this synopsis and provide their input. All of the participants approved the final version after the outline was improved. This guide proposes the following six steps: 1) preparation, 2) recruitment, 3) building the agenda, 4) cross-checking the program, 5) reviewing and finalizing, and 6) in-conference refining. Thirteen items are specified across the six main steps in a detailed checklist. This OSP guide includes a flowchart and a checklist for providing a comprehensive manual for establishing, conducting, and organizing international scientific conferences. Understanding the procedures that are expected to be followed when holding a scientific conference enables the involved parties to organize and assign tasks to one another as well as create a schedule that allows them to finish their work on time. This guide can be used at any kind of scientific conference to describe an organized process, resulting in a professional and distinguished scientific program. Conferences are an integral part of the scientific enterprise. “Scientific conference” has been defined as a meeting that invites submissions for presenting research results . The corGathering scientists of diverse backgrounds at conferences results in an enriching learning experience for both the audience and the participants . ConfereConducting national and international conferences is becoming a routine role for scientific professionals and societies . ScientiAchieving a good scientific program for international conferences requires collaborative efforts between qualified professionals with extensive experience in communication, organization, and knowledge about the targeted attendees, their needs, and their interests. The execution of this task can be described in multiple orderly steps to simplify the implementation. This study tries to elaborate on the steps of organizing the scientific program of international conferences in a manner that can be used as a guide. To reach this guide, a panel of experts, in organizing international conferences through informal discussions, has outlined a flowchart and a checklist and discussed each step in detail. Further experts were then included and asked to review this outline and give their feedback. The outline was refined, and the final version was approved by all the participants.Organizing scientific program flowcharts and checklistThis article provides a flowchart Fig.  and a chPreparationGeneral Theme and Target AudienceBefore starting the process of conducting a conference, there should be a clear vision of what the conference will be about: what is the aim of the conference? Who is the target audience? One of the key decisions is to give the conference a clear and attractive title. This will help give the conference its identity.TimingTiming of the ConferenceChoosing the appropriate timing for the conference is an essential element for ensuring good attendance by both the speakers and the audience. Care must be taken to avoid national holidays and events and to avoid any other conferences with the same target audience and society.Local tourism is one of the encouraging aspects of attendance, and choosing a season with more welcoming weather is advised.Timing of the PreparationPreparing a successful international scientific program requires substantial time and effort. For a large international conference, approximately more than one year of preparation time is mandatory and an acceptable duration to go stepwise through the whole process from the first advert to the final conference. As there are a large number of annual conferences, planning for the next conference should be started as early as possible after finishing the last conference. Time will be needed to promote the conference and attract the audience. The organizers need time for preparation during their workload. Dividing the preparation process into phases with specific tasks and amount of work can help the organizers fit these tasks into their daily workload. Speakers and attendees need time to schedule their travel arrangements and, thus, need to be informed about the confirmation of their participation well beforehand.Organizing the committeeThe organizing committee is responsible for the conference. This includes conducting and executing the scientific program as well as choosing a professional conference organizer (PCO) for executing the actual tasks of the organization. This includes (but is not limited to) setting the date of the conference, creating the budget, creating the website and submission portal, arranging the Continuous Medical Education (CME) certification, registering the attendees, selecting and preparing the venue including the necessary audio-visual/IT requirements and catering, finding sponsorship, and conducting marketing for the conference .The organizing committee needs to take into consideration the recognizability of the conference by using the same logo for recurring editions of the same conferences.The details of the organizing committee’s work are beyond the scope of this article.RecruitmentRecruiting Scientific CommitteesThe organizing committee needs to recruit a group of committed members to prepare the scientific program. To do so, it is first needed to have a vision of the scientific background and a vision of the conference. If necessary, depending on the general content of a conference, it may be necessary to divide the scientific program into subspecialties and assign committee members to subcommittees for each subspeciality (conference in conference principle). Each subcommittee should be composed of both senior members, who play a more supervisory role, and active energetic junior members, who complete the time-consuming tasks. Being a member of a scientific committee at an international conference is a great honor and a prestigious duty.Recruitment of the committee members should be based on merit. To resolve this issue, we propose the following process to provide a fair opportunity for all the scientific society members. An opening for the scientific committee can be advertised to society members. For medical scientific conferences, committee members should be, at minimum, a consultant with a fellowship training subspecialty. Prior participation in scientific conferences and each potential participant’s scientific CV can be objective measures in prioritizing the selection of subcommittee members. In addition, the scientific subcommittees should encourage the participation of well-known figures because their presence adds value due to their position in the scientific community.All the members need to be active in the scientific society of their field; that is, they have attended and participated in recent conferences or have published substantially in well-known journals and should be ready and willing to work collaboratively with their fellow committee members. Commitment and enthusiasm are imperative for adhering to timelines and fulfilling responsibilities . Each scThe scientific committee should include enough members to be able to perform all tasks without adding extra members who are not performing actual tasks. Having a large number of members can also complicate decision-making due to conflicting ideas.Setting terms of reference (TOR)The Scientific Committee is composed of the 1) Scientific Committee Chair, 2) Deputy Chair, 3) Subcommittee Chairs, and 4) Members. Each has their own responsibilities and duties.The Scientific Committee Chair is responsible for organizing and chairing the main scientific committee conference, including the meetings needed for the organization process. The Scientific Committee Chair will determine the agenda for each meeting, facilitating communication between the Scientific Committee and the Organizing Committee. They will be delegating responsibilities to the Deputy Chair, as appropriate.The Deputy Chair is responsible for assisting the Scientific Committee Chair in carrying out the duties listed above. The Deputy Chair will be deputizing for the Scientific Committee Chair at meetings, as necessary.The Subcommittee Chairs are responsible for calling a meeting with the Members regularly and delivering the minutes of the meetings to the main Scientific Committee Chair. The Subcommittee Chairs will be giving tasks to each member, setting deadlines for their completion, and raising proposals of suggestions to be discussed with the main Scientific Committee. Additionally, they will review the inputs received from the members for a final decision.Members are responsible for completing the tasks assigned to them by their Subcommittee Chair and actively raising their concerns and recommendations to the chair for improving each step they are participating in.Before proceeding to the details of the scientific program, the hours and number of rooms allotted in the scientific program for each subcommittee should be determined.Building the agendaBuilding the Scientific Program AgendaAfter having a defined structure of the conference, including the topic, number of rooms, and duration of the conference, each subcommittee should start by setting a broad agenda for their program. The agenda topics should cover three main categories: the basics and fundamentals of the scientific topic covered in traditional routine teaching, the recent advances in the area of interest, and the controversial topics.The agenda for the first category can be found in the table of contents of basic textbooks and targets the more junior and less experienced audience. The second and third categories can be found through extensive literature review, focusing on recent articles published in top-ranked journals. These categories target the more subspecialized, senior audience and give vision to juniors who are new in the field.For some conference topics, it may also be helpful to include the latest industrial developments. However, it is imperative that the scientific program of a conference should be created in full independence of business interests . Companies can bring their research and development insights and progress to the audience through satellite sessions. In creating the scientific program, first arrange the main agenda then add the detailed subtopics. This should ensure that no major agenda item will be missing. The program cannot be created solely based on the speakers’ preferences and their recommendations because this can lead to repetition of the topic and a lack of focus on new advances. Instead, the agenda should cover a variety of topics and be decided upon by the scientific committee. Setting the main agenda can help determine which areas are insufficiently covered so that this may be corrected, with specific speakers in those areas.An additional advantage is that appropriate time can be allocated to each topic on the agenda. When a topic is not filled out, a substitute subtopic of the same main agenda can be used.Furthermore, the attendees can easily choose their topics of interest so as to arrange their schedule accordingly .While arranging the program, it should be remembered that early morning and late afternoon sessions usually have lower attendance. Arranging high-impact, interesting, and interactive sessions and/or those given by key opinion leaders at these times will encourage better attendance . HoweverAudiences tend to stay in the larger rooms. Thus, arranging the elite speakers to present talks in these rooms can encourage more attendance in subsequent talks given in these rooms.Types of sessionsSessions of the scientific conferences usually contain the categories mentioned in Table DefinitionFree paper: This session presents a research work.Keynote lecture: It is a detailed presentation of a specific topic in a comprehensive scholastic manner by an expert. This session usually takes longer time than the free paper session.Round table: It contains short, individual, presentations by a number of experts on a specific topic.Panel discussion: An open discussion between the experts (panelists) on a specific topic is carried on with questions directed by a moderator who tries to share all the options and different aspects of decision-making.Debate: Two or more different or opposing opinions on the same topic are debated in which each expert illustrates the pros and cons of his opinion.Types of streamingIn the recent era of remote communication, conferences are not bound by physical presence. Streaming can be physical, digital via a video conference, or hybrid.The digital type can be either live streaming or recorded videos that are available for the audience for a period of time.In this article, we are most focused on in-person, physical conferences.Recruiting the speakersThe speakers are divided into two categories: invited speakers and speakers who submitted their work through the submission portal. The scientific committee needs to decide which of these two categories they are going to base their program on. This decision is also influenced by the session formats, which are to be used in the conference and covered by key persons. However, key persons are needed as lighthouses to promote the conference. This decision will define the next steps.There are benefits to having the invited speakers make up the majority of the scientific program. This can help in having control over the quality of the program. The lengthy portions of the program such as the keynote presentations, panel discussions, and instructional courses need carefully selected and well-known speakers. The scientific committee can control who these speakers are, if they are chosen by invitation instead of a more passive submission portal candidate. Moreover, personal invitations can lead to participation in cases where speakers do not know about the conference or forget to submit their work. Inviting elite speakers should increase the likelihood they present and this, in turn, could attract a greater number of conference attendees.Distinguished speakers to invite can be identified through the following pathways: First, an extensive literature review can identify authors with numerous publications on highly specialized topics . These pContinual follow-up (monitoring and plotting the progress)Scientific subcommittee members should hold regularly scheduled meetings, according to the workload, to follow up on the progress.There is a need to follow how many hours are confirmed by the speakers, track the number of submissions, and implement the confirmed speakers’ suggestions into the agendas. This will reveal the shortcomings in each agenda area. Scientific subcommittee members can then direct the invitation process to build a more comprehensive program; for example, they plan the steps of building the scientific program.This task is accomplished by revising the recruitment process through the previously mentioned pathway to ensure that all agendas are complete and that there is a fair global contribution by the speakers.Some speakers may accept the invitation without providing their topics. If this occurs, follow-up emails will need to be sent.It is also possible to send tailored invitations to highly specialized speakers to present on topics/areas that are missing or underrepresented in the scientific program. Using the pathways mentioned, potential speakers are more likely to accept invitations to speak on subtopics they are familiar with and enthusiastic about.The main Scientific Committee will receive the weekly report about the progress of each subcommittee to plot the difference between each subcommittee and create more engagement.Evaluating the submitted abstracts through the submission portalThe submission portal needs to be implemented into the conference website in the early phase of the process to allow enough time for possible participants to know about the conference and prepare and submit their work. The rules and regulations for submission need to be stated clearly and simply. The submission portal needs to be smoothly accessible through the website and through the links that are distributed to the community.A primary deadline for submission needs to be set from the beginning. By setting a primary deadline, potential participants will be encouraged to submit their work early, which will allow the scientific committee to know what action they need to take. If the submitted manuscripts are of adequate quality and length to fill in the gaps that are not covered by the invited speakers, extending the deadline will not be necessary.Cross-checking the programCross-checking with Other SubcommitteesIt is not uncommon that some agendas of subcommittees overlap. The invited speakers may respond to one subcommittee’s invitation, but their suggested topics fit another subcommittee better. The same issue may occur with submitted manuscripts through the submission portal. Subcommittees, therefore, need to be in close communication so that they can transfer the submitted work to the most suitable subcommittee.This can be made by a program planning software for automated checkups. However, it is also important to have a manual checkup to ensure there is nothing missed by the software.Promoting the conferenceTo encourage submissions and attendance to the program, the committee should announce the conference at an early stage and according to the time course left to the conference dates in a proper way . This program should consist of interesting and attractive topics presented by distinguished speakers whose participation is confirmed. The preliminary program should then be distributed for advertisement by the organizing committee that handles social promotions and by the PCO for administrative issues.Reviewing and finalizing the programTo ensure that there is no human error or typos, the final program should be reviewed in multiple rounds by more than one person. Each subcommittee’s final program should be first reviewed by each subcommittee and then by the main Scientific Committee as follows:The subcommittee ensures that, either through email or the submission portal, every subtopic in the program is based on a documented speaker submission.The subcommittee ensures that every speaker’s slot in the program is as appropriate to their significance.The main Scientific Committee ensures that there is no repetition in the program across the various subcommittees and that each subtopic is handled by the most appropriate subcommittee.The main Scientific Committee ensures that speakers are not scheduled for different rooms at the same time.Formally, the final program should be printed, and the schedule should be prepared carefully to allow a quick overview.In-conference refiningThe speakers in the program can make numerous requests for last-minute changes or cancellations. This needs to be addressed by the scientific subcommittee members, as per their judgment and knowledge of the program and relations to other speakers. A good rapport can be of critical value in these situations.Subcommittee members and their secretaries must be easily accessible and follow their communication portals regularly. There should also be close communication with the organizing committee to ensure speakers’ attendance beforehand to be able to plan any changes in advance.Interactivity During SessionsOne of the vital sections of each session is the questions asked by the attendees, which opens the door for interaction and a deeper understanding of the material presented. New technologies such as using applications that allow the audience to write down their questions can help a lot in easier and more organized questioning. The time allowed for the questions must be pre-defined by the scientific committee while making the program schedule and be maintained by the session moderators to avoid being behind schedule.The panel of experts included five participants who conducted an open-ended discussion on the details of conducting and organizing the scientific program of international conferences. An extensive literature review revealed the paucity of published material discussing the same process in detail. The panel finally decided on six fundamental steps and a 13-item checklist. These steps and items were then sent to an additional 12 experts, who critically reviewed and revised these steps and items and provided their feedback. These feedbacks were implemented on the primary steps and checklist, and the final version was formulated, as illustrated in the next section. The final version was approved by all the experts. The panel also decided on a flowchart summarizing the steps needed to be taken by the scientific committee to establish the scientific program (Figure In this article, we introduce a good practice guide for OSP of international conferences. Developing a good practice guide is a complex process that requires the cooperation of a panel of experts. First, the need for developing the guide was identified and justified. Then, the literature was reviewed to identify similar work and the evidence needed to make the guide. Rigor must be applied to assessing the published studies to utilize any previous efforts. However, the current literature was found to be limited in describing the process of OSP ,18.The use of expert opinion has been justified by Warsh , as the Warsh defined the principles of developing a good practice guide as having clarity in the definitions, compatibility of each attribute and its definition with professional usage, clear rationales or justifications, and sensitivity to practical issues. Any guide needs to be practical and informative. The instructions should be feasible and replicable. These principles were considered in developing this guide .Organizers of international scientific programs need to have a team of dedicated, knowledgeable experts. We believe that scientific programs of the conferences need to be conducted in an organized manner. This guide summarizes the collective experience of the authors, with their diverse backgrounds and long history of conducting numerous international conferences. This guide also provides a practical, detailed, and step-by-step process for conducting and organizing international scientific conferences. Knowing the steps anticipated in conducting a scientific conference helps the participating parties plan and divide the workload among themselves and prepare a timely schedule for accomplishing their tasks. Additionally, this guide could be applied to any type of scientific conference. The definitions used in this guide help in assigning the appropriate person for each task, while the flowchart and the checklist illustrated in this guide can help in evaluating the progress of the organization process.


Engineering excitation wavelength of photosensitizers (PSs) for enhanced reactive oxygen species (ROS) generation has inspired new windows for opportunities, enabling investigation of previously impracticable biomedical and photocatalytic applications. However, controlling the wavelength corresponding to operating conditions remains challenging while maintaining high ROS generation. To address this challenge, we implement a wavelength-engineerable imidazolium-based porous organic photocatalytic ROS generation system (KUP system) via a cost-effective one-pot reaction. Remarkably, the optimal wavelength for maximum performance can be tuned by modifying the linker, generating ROS despite the absence of metal ions and covalently attached heavy atoms. We demonstrate that protonated polymerization exclusively enables photosensitization and closely interacts with oxygen related to the efficiency of photosensitizing. Furthermore, superior tumor eradication and biocompatibility of the KUP system were confirmed through bioassays. Overall, the results document an unprecedented polymerization method capable of engineering wavelength, providing a potential basis for designing nanoscale photosensitizers in various ROS-utilizing applications. Engineering excitation wavelength of photosensitizers allows to enhanced reactive oxygen species but controlling the wavelength corresponding to operating conditions remains challenging. Here, the authors implement a wavelength-engineerable imidazolium-based porous organic polymer and demonstrate tuning of the optimal wavelength for maximum performance by modifying the linker system. ROS can include chemically reactive radicals (type I), such as superoxide (O2•–) or hydroxyl radicals, and molecular oxygen-driven non-radical molecules (type II), such as singlet oxygen (1O2)3. With a focus on their characteristic reactivity, numerous ROS-related studies have been reported in chemical and biological research for therapeutic and photocatalytic applications5. For example, photodynamic therapy (PDT) is one of the representative non-invasive remedies that attack malignant cells through ROS-induced cell death mechanisms3. In addition, ROS can be harnessed in various photocatalytic applications, including chemical bond generation8, photoelectrolytic reduction10, and photolysis, which can detoxify chemicals harmful to humans, such as chemical warfare agents (CWA) and factory pollutants15.Reactive oxygen species (ROS) are one of the most common chemicals in living organisms and industrial fields that respond to normal cellular functioning and catalytic process17.In general, ROS can be generated by transferring energy from excited photons of the photosensitizer (PS) and can be utilized in chemical reactions. Efficiency of a PS directly governs the amount and types of ROS generated. Therefore, the type and role of PSs are quite important in pertinent reactions. In particular, PS with a peculiar wavelength according to specific activation conditions, such as deeply placed cancer or realistic conditions like sunlight, is needed but engineering the corresponding wavelength while maintaining high ROS generation efficiency is very challenging. This is because ROS generation relies heavily on the slight differences in energy levels induced by the structure of the PSs. Thus, it is difficult for conventional PSs to simply adjust their operating wavelengths, so their use is limited because new PSs that meet each condition must be newly synthesized and prepared Fig. . Therefo21. Interestingly, their tailorable structure can absorb the light of various wavelengths, depending on the change of the organic linker to the framework22, and their well-developed porous environment can accelerate the rapid transport of ROS whose lifetime is too short to activate where it is intended23. In particular, nanoscale POPs are expected to have the combined advantages of low-toxicity molecular organic photosensitizers and nano-sized metallic nanoparticles with larger external surface areas, improved permeability, and increased retention effects. However, most of the reported POP-based photosensitizers are mainly composed of boron-dipyrromethene or porphyrin cores, which are well known for their 1O2 generation motif but exhibit heavy atomic effects, such as metal ion loading and covalent bonding with halogens26. Despite their excellent 1O2-generating ability, the toxicity of metal ions is a formidable obstacle for practical applications in humans and ecosystems. To overcome these fundamental limitations, it is highly sought to discover a new class of PSs based on heavy atom-free POPs that are environmentally friendly and biocompatible.Recently, porous materials such as metal-organic frameworks (MOFs), covalent-organic frameworks (COFs), and porous organic polymers (POPs) have been reported as novel classes of nano-photosensitizersKUP-1 and its extended version, KUP-2), which has never been used in ROS-utilizing applications, including photocatalysis and therapy  dominance by protonated polymerization. Finally, biological experiments demonstrated the biocompatibility of these materials. This system can be harnessed in various chemical and biological fields, such as photocatalysts and PDT agents.Herein, we report a wavelength-engineered imidazolium-based porous organic polymeric photocatalytic ROS generation system  were prepared by the reaction of 1,3,5-triformlybenzene (tb) or tris(4-formylphenyl)amine (ta) with ammonium chloride in N,N-dimethylformamide (DMF) at 150 °C for 5 days via a one-pot reaction  moieties in the framework. Detailed information on the atomic composition of the compounds was obtained using X-ray photoelectron spectroscopy (XPS), as shown in Fig. KUP-2 was higher than that in KUP-1 owing to the difference in the nitrogen content of each starting material’s composition. Interestingly, the presence of chloride was commonly corroborated in the XPS survey scans of KUP-1 and KUP-2. We suggested that the chloride attached to the protonated nitrogen in the imidazolium core act as a counter-anion. The XPS narrow scan of the N1s peak was conducted to investigate the chemical environment of nitrogen  can be deconvoluted to three subpeaks centered at 401.02 (399.67), 399.30 (399.07), and 398.60 (398.37) eV, which correspond to the binding energies of N+–H, C–N–C, and C–N=C, respectively28. This observation indicates two different chemical environments (sp2 C–N and sp3 C–N states) of nitrogens in the framework. In fact, two recognizable peaks in the solid-state 15N NMR (15N ssNMR) data of KUP-1 were observed at 43.58 and 123.78 ppm, revealing nitrogens of quaternary ammonium and imine, respectively  and tunneling electron microscope (TEM) images , which is suitable for ROS-utilized applications30.Thermogravimetric analysis (TGA) was conducted in the temperature range of 25–900 °C, under Nges Fig. –14, the KUP-1 was at 200–400 nm, but the peak range shifted to longer wavelengths (250–500 nm) in the extended system. Thus, the full UV–Vis range of imidazoline-based POPs is available, and the maximum absorbance range can be designed simply by extension of the framework.To scan the absorbance region of the KUP systems, we performed solid-state UV–Vis (ssUV) spectroscopy dimalonic acid (ABDA), in phosphate-buffered saline (PBS) solution   higher than O2-containing water without KUP systems (~1.1 mg L−1). The difference between oxygen levels with/without KUP systems was calculated to be 2.7 mg L−1 for KUP-1 and ~3.1 mg L−1 for KUP-2. This value is significantly higher than that of O2 self-sufficient fluorinated polypeptide PHFB nanoparticles (~575 µM at 3 mg mL−1)35. In addition, we measured the zeta potential after incubation of O2@KUP-1 in an aqueous solution to check the O2 transport performance of the KUP system. As a result, the surface charge of O2@KUP-1 is still kept even after 24 h, indicating that oxygen content in O2@KUP-1 will not drop significantly during O2 delivery  measurements were performed with 2,2,6,6-tetramethylpiperidine (TEMP) and 5,5-dimethyl-1-pyrroline N-oxide (DMPO) as a ely Fig. e and f. KUP-1 and 2.34 eV for KUP-2. The potential level of the KUP systems was estimated using Ag/AgCl as the reference electrode  and −5.49 eV (KUP-2) vs. vacuum levels from the oxidation data. From these values, a schematic band diagram of the KUP systems is shown in Fig. 2, which is converted into O2•–39.To understand the ROS generation mechanism, the band gap of each KUP system in Fig. KUP-2 was obtained at a longer wavelength overall than KUP-1 when the TRPL signals were measured at 78 K. To measure the triplet state lifetime of the KUP-1 and KUP-2, we compared the KUP-1 TRPL signal at 530 nm and the KUP-2 at 550 nm by plotting. Thus, we confirmed that the lifetime of the KUP-2 is longer than that of the KUP-1  signal to demonstrate the existence of triplet state population on KUP systems. As shown in Supplementary Fig. 2, the KUP-1 powder was soaked in a 1 M NaOH aqueous solution and stirred at 50 °C for 12 h . The IR spectrum of KUP-1(OH) showed that the broad band associated with N–H stretching around 3375 cm−1 was significantly weakened compared with the IR peak of KUP-1. On the contrary, the other peaks in the fingerprint region for KUP-1(OH) were almost identical to those for KUP-1   was measured as a negative charge , with a representative valence band level of −5.54 eV vs. vacuum level. This value is similar to that of KUP-1. However, the 1O2 generation test of KUP-1(OH) under the same experimental procedure led to an absolute suppression of the performance, as shown in Fig. KUP-1 played an essential role in the generation of 1O2.To gain insight into the role of the charged section in the imidazoline core with respect to photosensitization of O2 h Fig. . The resOH) Fig. . In addirge Fig. , the solrge Fig. . We drew1O2 generation ability of KUP-1 and KUP-1(OH) via electron transfer, the excited-state dynamics should be investigated. Therefore, we performed density functional theory (DFT) calculations to support the reason behind the comparison experiment results on 1O2 generation using KUP-1 and KUP-1(OH). After the photosensitizer is excited to the S1 state by the irradiated light, the excited system can be relaxed through a non-radiative process such as internal conversion (IC) and ISC processes. These two processes are competitive, and their relative relationship affects the electron population in the T1 state, which is an important factor for 1O2 generation due to the intrinsic triplet multiplicity of the oxygen molecule. As a result, we calculated and compared the IC and ISC rates of the excited KUP-1 and KUP-1(OH) systems.To understand the difference in the KUP-1 monomer and oligomer systems with seven monomer units due to the practical limitation of computational costs for polymer systems. For the KUP-1(OH) system, monomer and analogous oligomer systems were investigated. In the case of the KUP-1 oligomer, positively charged model systems, excluding counter anions , were calculated due to the impractical high computational cost for the oligomer KUP-1 system, including counter anions. All the systems investigated are shown in Fig. Since the ROS generation-capable KUP system is in polymeric frameworks, we demonstrated the changing trend of the relative excited-state dynamics with respect to the size of the system used in this study. We performed calculations for the S1 and T1 was computed from the semiempirical Marcus theory (Eq. (1))40.h, λ, kB, T, 〈S1|HSOC|T1〉, MECP are the plank constant, reorganization energy, Boltzmann constant, temperature, spin–orbit coupling (SOC) constant, and minimum energy crossing point respectively, which are listed in Supplementary Table S1 and T1 states (KUP-1m and KUP-1(OH). According to the calculated results, during oligomerization in KUP-1(OH), the IC rate became faster (1.65 times) and the ISC rate became slower (0.64 times). However, during oligomerization in KUP-1m, the IC rate became slower (0.56 times) and the ISC rate became faster (7.87 times). These tendencies for KUP-1(OH) and KUP-1m might be larger in practical polymeric systems. Based on this expectation, contrasting dynamic changes indicate that the KUP-1(OH) polymer would have faster IC than the ISC process and that the KUP-1 polymer would have comparable rates of IC and ISC processes. This suggests that the electronic population in the triplet state might accumulate only in KUP-1, resulting in exclusive 1O2 generation on protonated KUP system. This agrees with the experimental results for the formation of the triplet state of KUP-1  with oxygen molecules to obtain the adsorption energy per oxygen molecule according to the increasing number of that and compared variation of adsorption energies. As shown in Fig. KUP-1m positively increase as the number of oxygen molecules increases  while the adsorption energies of KUP-1(OH) show relatively similar and smaller value , which indicates that the protonated KUP system might be more favorably adsorb O2 molecules than neutral KUP(OH) system.Furthermore, we confirmed how well the hem Fig. . Adsorpt2 molecules and outstanding ability to generate ROS, we investigated the cellular effects of KUP-1 and O2@KUP-1. First, the photo-induced cytotoxicity assay for U87MG was evaluated under irradiation at 530 nm after treatment with KUP-1 and O2@KUP-1 for 12 h incubation. Next, the toxicity was evaluated at 30 h from the time of treatment. As expected from the preceding data, the cytotoxicity of U87MG increased with photoirradiation at 530 nm after treatment with KUP-1 or O2@KUP-1, compared with non-irradiated cells after treatment. Therefore, the cytotoxicity results indicate that KUP-1 and O2@KUP-1 could be utilized as photosensitizers that exhibit off-on cytotoxicity in the absence and presence of photoirradiation at 530 nm  more than that of the KUP-1 due to the increased generation of ROS via the number of oxygen molecules interacting with PS enhanced by high O2 affinity. Hence, the results mean that the O2 impregnated on KUP-1 could boost 1O2 generation and act as one of the 1O2 generator ingredients, attracting the 1O2-induced apoptosis pathway41. Unlike KUP-1 and O2@KUP-1, we could not observe the positive results using KUP-2 and O2@KUP-2 in diverse cell lines  as shown in Supplementary Fig. KUP-1 and O2@KUP-1 in the presence of photoirradiation at 530 nm, we used luciferase-containing U87MG cells (Luc-U87MG). Live-cell imaging analysis was performed after treatment with KUP-1 or O2@KUP-1 at 12 h and photo-irradiated at 530 nm for 3 min. As seen in Fig. O2@KUP-1, compared with the group treated with KUP-1. In particular, the cytotoxicity of O2@KUP-1 was confirmed by live-cell imaging. After pretreatment with O2@KUP-1 for 12 h and post-treatment with 530 nm irradiation, the live-cell images showed a marked difference in terms of the number of live cells. Generally, lactate dehydrogenase (LDH), an intracellular enzyme, is released upon cell death (apoptosis or necrosis) due to the destruction of the cell membrane by ROS-induced phototoxicity42. As seen in Fig. KUP-1 or O2@KUP-1 did not differ from the untreated group, but interestingly, laser irradiation at 530 nm in these groups induced an increase in LDH release. These results thus support selective phototoxicity that KUP-1 and O2@KUP-1 produce enough ROS to be toxic in a short time (exposure time <3 min). Based on these results, we next evaluated the hemolysis induced by KUP-1 and O2@KUP-1 under irradiation at 530 nm  , showed negative hemolysis of RBCs, indicating high biocompatibility while having potential as photosensitizers. Based on these results, we conclude that the superior ROS-induced cancer cell eradication and biocompatibility of imidazolium-based porous organic photosensitizers potentially provide new insights into the advantages of the photosensitizing system in future clinical fields.Given that the KUP system has a high capability for oxygen due to the favorable adsorption toward O nm Fig. . A notew nm Fig. . KUP-2 aKUP-1 and O2@KUP-1, KUP-2, and O2@KUP-2 with a cycle of 2 days of photo-induced treatment to confirm the possibility of inhibiting tumor proliferation . As a result, the tumor size was markedly diminished in the group of KUP-1 and O2@KUP-1 with light irradiation, and no substantial body weight loss was observed during the whole therapeutic course  and high concentration (8 mpk), KUP-1 and O2@KUP-1 showed no remarkable toxicity symptoms in mice during the experimental period (16 days)  for accurate tumor eradication and manifested that the newly introduced imidazolium-based photosensitizers (KUP-1 and KUP-2) are state-of-the-art oxygen-appended PDT agents.Based on our strategy, readily found to suppress the tumor growth in vitro, we next verified the antitumor potency of the KUP system. The BALB/c mice were first gifted with a U87MG cell line on the dorsal side and their vital were monitored by measuring their body weight every 3–4 days. After 3 days, the tumor-inoculated mice were treated with on Figs. . Given trse Fig. . In addiys) Fig. . These rays Fig. i and j. KUP-1) and an extended version (KUP-2) through a cost-effective one-pot reaction, a new type of POP-based PS that has never been used in therapeutic and photocatalytic applications using ROS. A key design component incarnated in the KUP system is the use of an appropriately modified organic linker to control the wavelength corresponding to specific operating conditions while maintaining high ROS generation efficiency and biocompatibility. Therefore, the KUP system can be harnessed with tunability in the visible range by simply modulating the components of PSs. Photophysical analysis of the KUP system proved effective at promoting both type I and II ROS generation mechanisms under light irradiation, and remarkably, 1O2 (type II ROS) was strongly generated under photoirradiation with weak power (1 mW cm−2). These results indicate that the KUP system enables the design of PS with peculiar excitation wavelengths according to specific activation conditions for optimal performance and type I and II photosensitizing, which are crucial factors in constructing PSs for various ROS-utilizing applications. We found that the charged component of the materials exhibited excellent wettability, dispersibility, and O2 affinity that enhanced the amount of dissolved oxygen. Theoretical calculations suggest that the mechanism of ROS generation, only in the protonated system, is associated with ISC dominance triggered by the polymerization of a porous framework with charged moieties. In addition, the adsorption energy calculations on KUP-1m and KUP-1(OH) with an increasing number of oxygen molecules presented that the protonated system is the key factor for high affinity with oxygen, which can influence the efficiency of 1O2 generation. With such a unique photocatalytic ROS generation mode of action, excellent selective antitumor efficiency and non-invasive biocompatibility were elucidated through biological experiments. Furthermore, the protein profiling assay demonstrated the tumor suppression effect underlying photo-induced tumor eradication of the KUP system, which induces the immune activity to control the release of cytokines. Overall, these protonated POP-based photosensitizing systems, with tunable excitation wavelengths, could provide a potential basis for designing nanoscale porous organic photosensitizers for a variety of ROS-enabled applications.We prepared a wavelength-engineerable imidazolium-based porous organic polymeric photocatalytic ROS generator  and used without further purification.KUP-1 powder was dried at 100 °C under vacuum for 10 h. Yellowish KUP-2 powder was prepared according to the same synthetic procedure as KUP-1, except that ta was used instead of tp. The elemental analysis of the sample (%) is as follows: Found for KUP-1  and KUP-2 .A 23 mL Teflon-lined cup was charged with tb , ammonium chloride , and DMF (10 mL). The cup was mounted in an autoclave and heated at 150 °C for 5 days. The precipitated solid was filtered and washed thoroughly with DMF, water, acetone, and methanol. The resultant pale-yellow KUP-1 and 50 mL of 1 M NaOH solution. After the vial was sealed, the mixture was stirred at 50 °C for 12 h. The solid was filtered and washed thoroughly with water, acetone, and methanol. The washed powder was dried at 100 °C in a drying oven for 12 h to obtain KUP-1(OH).A 70 mL vial was charged with ~100 mg of 1O2 generation ability of POPs was assessed by UV–Vis absorbance spectra of ABDA (100 μM), a 1O2 capture agent, in PBS solution . For UV–Vis spectroscopy, POPs (0.2 mg mL−1) were sonicated for 1 min and dispersed well in PBS solution. The resulting solution was irradiated with a xenon lamp (1 mW cm−2) at a target wavelength for 10 min. The corresponding absorption spectra were recorded immediately after light irradiation. As a result of 1O2 generation derived by POPs, the absorbance of ABDA was greatly reduced due to the oxidative decomposition effect of 1O2 on ABDA.UV–Vis absorbance spectra were obtained using a Jasco V-750. The 45 was performed to calculate the IC rate using the PYXAID software package47, which manages the motion of lighter electrons quantum mechanically and heavier nuclei classical mechanically. This package implements decoherence-induced surface hopping (DISH)48 to describe the dynamics of charge in the excited state. The electronic state and adiabatic MD trajectories were obtained from ab initio molecular dynamics (AIMD), which were performed using the Vienna Ab initio Simulation Package (VASP)49 based on the projector-augmented wave (PAW) pseudopotential theory, using a plane-wave basis set with Perdew, Burke, and Ernzerhof (PBE)50. The AIMD simulation was performed for 1 ps with a 1 fs time interval. The SOC constant between the S1 and T1 states was calculated using the Q-Chem 5.3 software packages51, using the B3LYP hybrid functional52 with the 6-31G(d) basis set. The system total energy, reorganization energy, ΔEST, excitation energy, and oscillator strength were calculated using the Gaussian16 software package53, using the B3LYP hybrid functional with 6-31G(d) basis sets. In this study, optimization and time-dependent DFT (TDDFT)55 calculations were performed.Non-adiabatic molecular dynamics (NAMD) simulation based on the Kohn–Sham density functional theory (DFT) framework3) were plated on a 96-well plate with a flat-bottom plate  for 24 h. When the confluency of cells reached 80%, the culture medium  was changed to serum-free (SF) media to enhance the efficiency of the uptake of materials. After incubation for 30 min, the cells were treated with KUP-1 and O2@KUP-1. Irradiation at 530 nm  was performed after treatment with KUP-1 and O2@KUP-1 for 12 h on fresh SF media. The phototoxicity of KUP-1 and O2@KUP-1 was evaluated using a cell counting kit-8 , according to the manufacturer’s protocols after incubation for 30 h.U87MG cells (5 × 10KUP-1 (0.4 mg mL−1) and O2@ KUP-1 (0.4 mg mL−1) under irradiation at 530 nm (60 mW cm-2) for 3 min, U87MG cells (2 × 104) were plated on a 35-mm confocal dish . When the cells were plated on the dish, they were treated with KUP-1 and O2@ KUP-1 in SF media. After incubation for 12 h, the cells were rinsed twice with 1 × PBS and irradiated with SF media at 530 nm. The cells on SF media were irradiated at 530 nm (60 mW cm−2) for 3 min, and the cells were incubated for 30 h at 37 °C with 5% CO2. The frequency of live cells was determined according to the manufacturer’s protocol .To visualize the frequency of live cells after treatment with 2). To evaluate LDH release  in supernatants, the assay was conducted according to the manufacturer’s protocols after incubation with KUP-1 (0.4 mg mL−1) and O2@KUP-1 (0.4 mg mL−1) for 30 h. The release of LDH was measured by measuring the absorbance at 492 nm. Irradiation condition: 530 nm, 60 mW cm−2, and 3 min.The U87MG cells were seeded into 96-well plates for 24 h at 37 °C . The KUP-1 and O2@KUP-1 samples were then exposed to photoirradiation at 530 nm (60 mW cm−2) for 3 min. The KUP-2 and O2@KUP-2 samples were exposed to photoirradiation at 660 nm (75 mW cm−2) for 5 min. After incubation for 1 h at 37 °C, the prepared samples were centrifuged at 3000 rcf at 4 °C. The absorbance of the supernatant was measured at 492 nm.Blood was extracted from the hearts of mice anesthetized with isoflurane. At 4 °C, whole blood was centrifuged at 1.4 rcf to obtain RBCs. The purified RBCs were treated with BALB/c mice  were obtained commercially from DBL . Five mice were randomly divided and housed per cage (20 × 26 × 13 cm) with free food and water intake in the room under a 12 h light/dark cycle . All experiments performed with mice were carried out in accordance with the National Institute of Health Guide for the Care and Use of Laboratory Animals  and protocols approved by the Institutional Animal Care and Use Committee of Kyung Hee University for each experiment (KHUASP-(SE)-19-002 and KHUASP(SE)-19-003) and institutional guidelines (assigned no. 2015-020).6 U87MG cells (subcutaneous injection on back) and Matrigel Membrane Matrix as 1:1 ratio (injected volume: 50 μL). After GBM implantation, the mice were recovered in a constant temperature chamber (30 °C) and placed in individual cages.The implantation of U87MG cells was performed using Matrigel Membrane Matrix . Briefly, each mouse  anesthetized with isoflurane has implanted a mixture with 5 × 10n = 5 per group) were used to evaluate the effect of PDT. The in vivo photodynamic therapy was carried out using the PBS (control), KUP-1, KUP-2, O2@KUP-1, and O2@KUP-2 in the GBM-xenograft model during the 16 days. The irradiation process  was performed 1 day after administration (8 mpk) of KUP-1, KUP-2, O2@KUP-1, and O2@KUP-2. This experiment was repeatedly performed with independent conditions.The groups (W (width) × D (depth) × H (height), to assume the volume of the tumor.The GBM xenograft mice were weighed every 3–4 days until 16 days. The tumor size was measured by using a caliper. The size was calculated using a standard formula, such as At the point of 16 days, the blood of GBM xenograft mice was extracted from the hearts of mice anesthetized with isoflurane. At 4 °C, whole blood was centrifuged at 3000 rcf to obtain the serum protein. The prepared samples were kept at −21 °C and then melted at 4 °C for 1 h before being used. The protein mapping analysis  was performed at the manufacturer’s recommendation. Briefly, the protein in blood was quantified using BCA  assay and then was loaded on a membrane coated by some antibodies for 1 h at 25 °C after washing and blocking the membrane. As a final step, the reaction with the antibody mixture was incubated overnight (about 12 h) at 25 °C. The antigen–antibody reaction on the membrane was measured by washing and reacting with enhanced chemiluminescence (ECL) solution in dark conditions.KUP-1, and O2@KUP-1 for 24 h. The concentration of administration was 8 mpk. The images were obtained 1 day after administration via subcutaneous injection under the tumor. [Setting information] zoom: 1×, focus: 109 steps, iris: F2.8, filter: excitation (540–569 nm), emission: (692–742 nm), light intensity: middle, exposure: 0.5 s, HDR: low gain mode.The U87MG-xenograft mice were measured by VISQUE InVivo Elite  after administration with PBS, P < 0.0001; ***P < 0.001; **P < 0.01; *P < 0.05; P values > 0.05 was considered not statistically significant (n.s.). Statistical tests were conducted using GraphPad InStat version 8.0.1 .The data were expressed as the mean ± standard error of the mean (SEM) unless stated otherwise. Statistical comparisons of the toxicity analyses were performed using two-way ANOVA. For all test significance is defined as ****Further information on research design is available in the Supplementary InformationPeer Review FileReporting Summary


Pre-traumatic frailty in geriatric trauma patients has caught attention from emergency medical workers and the assessment of it thus become one of the important aspects of risk management. Several tools are available to identify frailty, but limited tools have been validated for geriatric trauma patients in China to assess pre-traumatic frailty.The aim of this study is to translate the Trauma-Specific Frailty Index(TSFI) into Chinese, and to evaluate the reliability and validity of the translated version in geriatric trauma patients.A cross-sectional study was conducted. The TSFI was translated with using the Brislin model, that included forward and backward translation. A total of 184 geriatric trauma patients were recruited by a convenience sampling between October and December 2020 in Hospital of Chengdu University of Traditional Chinese Medicine, Sichuan. Using reliability or internal consistency tests assessed with Cronbach’s alpha coefficient, split-half reliability and test-retest reliability. Content validity and construct validity analysis were both performed. Sensitivity, specificity and maximum Youden index(YI) were used to determine the optimal cut-off value. The screening performance was examined by Kappa value.P < 0.05), the maximum YI was 0.725, the sensitivity was 80.2%, the specificity was 92.3%, and the critical value was 0.31. Kappa value was 0.682 (P < 0.05).The total study population included 184 subjects, of which 8 participants were excluded, resulting in a study sample size of 176 elderly trauma patients (the completion rate was 95.7%). The Chinese version of Trauma-Specific Frailty Index(C-TSFI) have 15 items with 5 dimensions. Cronbach’s alpha coefficient of the C-TSFI was 0.861, Cronbach’s alpha coefficient of dimensions ranged from 0.837 to 0.875, the split-half reliability of the C-TSFI were 0.894 and 0.880 respectively, test-retest reliability ranged from 0.692 to 0.862. The correlation coefficient between items and the C-TSFI ranged from 0.439 to 0.761. The content validity index for items (I-CVI) of the C-TSFI scale was 0.86~1.00, and the scale of content validity index (S-CVI) was 0.93. The area under curve (AUC) of the C-TSFI was 0.932 (95%CI 0.904–0.96, The Chinese version of TSFI could be used as a general assessment tool in geriatric trauma patients, and both its reliability and validity have been demonstrated.The online version contains supplementary material available at 10.1186/s12877-023-04243-z. Trauma, a global public health problem , refers In recent decades, more and more studies have shown that frailty is closely related to the adverse outcomes of elderly trauma patients. It is very important for the post-traumatic outcome of the elderly whether they have frailty before the trauma. And by evaluating frailty, whose predictive power of adverse outcomes is superior than that of age and trauma severity scores for elderly trauma patients , 14. TheTaking these aspects into account, together with the fact that in China few validated instruments for assessing geratric trauma patients pre-traumatic frailty status.Therefore, the study has two objectives: (1) to translate the English version of the TSFI into the Chinese and make necessary adaptaion, to enrich relevant scales to provide a wider range of choices ; (2) to evaluate the reliability and validity of the Chinese version of the TSFI in geriatric trauma patients from Chinese emergency departments.This is a descriptive cross-sectional study that included 184 participants from the Hospital of Chengdu University of TCM, Sichuan, China between October and December 2020. The sample was selected by means of a convenience method and the participants’ consent has been obtained. According to Kendall’s guidelines , Since tIn order to be included and be able to participate in the study, the participants had to meet the following inclusion criteria: (1) be of either sex, aged 60 years or over; (2) trauma patients whose integrity of body tissues and organs is destroyed due to various reasons ; (3) the time of admission after trauma is less than 24 h; (4) voluntarily signing the informed consent form.The exclusion criteria are: (1) elderly trauma patients with Injury Severity Score(ISS) at 25 or more in the emergency department, (2) not being able to read and having sever hearing loss, (3) disturbance of consciousness, with severe organ failure and end-stage disease, equal to the clinical type of brain death.The following withdrawal criteria are also considered after inclusion:1) abandoning the study anytime in the process despite having signed of informed consent form, 2) and completion of less than 50% of the scales administered.The research stages are as follows: First, the TSFI was converted from the English version through forward- and backward- translation procedure into the Chinese version; secondly, the reliability, validity and feasibility of the Chinese version of TSFI were tested by cross-sectional research design .The TSFI, which developed by Professor Bellal Joseph of the University of Arizona in the United States in 2014, is specific to assess eldely trauma patients’ frailty status.The questionnaire includes 15 items in 5 aspects describing comorbidities, social activities, daily activities, nutritional status and health attitudes. The score of each item of the TSFI scale ranges from 0 (representing non-frail state) to 1 (representing severe frail state). Most of the 15 variables included in TSFI are dichotomous variables (yes or no), while other items are of multiple levels. The TSFI score is average score of the 15 items, ranging from 0 to 1. The higher the score, the weaker the body .The FRAIL Scale is a frailty assessment scale developed by a team of geriatric experts from the International Working Group on Nutrition, Health and Aging in 2008. It has good reliability and validity in Chinese hospitalized geriatric patients, with Cronbach’s alpha coefficient of 0.826, Kappa coefficient of 0.892, and S-CVI/Ave of 0.98 .The self-designed General Condition Questionnaire was used to evaluate the demographic data, and the content includes: (a)sex; (b)age; (c)degree of education; (d)marital status; (e)income and expenses; (f)smoking; (g)drinking. Clinical data: (a)cause of injury; (b)location of injury; (c)nature of injury;(d)ISS score.The research group first contacted the TSFI group in America by E-mail and obtained authorization for the scale. Then the translation of the scale was conducte by using the Brislin model.The translation procedure was as follows:Two Chinese native speakers proficient in English translated the original version of TSFI into Mandarin (simplified) Chinese version independently. The first translator was a clinical nurse with master degree from hospital of Chengdu University of TCM who was invited to translate the questionnaire from clinical perspective. The second one was a non-medical translator who was translated the questionnaire by language aspect only.The research team held the discussion to review the two Chinese versions of TSFI in comparison with the original English version. Chinese words were carefully chosen from both translations and some modifications were made to construct a single version of the questionnaire finally.Another two Chinese-English translators who had never seen the original English version were asked to translate the reconciled Mandarin (simplified) Chinese version back into English. The research team held the discussion to compare the original English version with the backward translated English version, and then made further modifications. After that, the modified reconciled Chinese version was once again translated back into English. With several forwards and backwards, the backward-translated English version got as close to the original as possible, and up till now, a pre-investigation Chinese version of TSFI was finally formed.The pre-investigation Chinese version of TSFI was first tested on 30 selected patients. The necessary modifications were then made based on their suggestions and the Chinese version of TSFI finally came out.This study followed all principles outlined in the Declaration of Helsinki. Patients were informed about the aims of the study, confidentiality of the data and voluntary participation. All participants signed informed consent. Each participant did the General Condition Questionnaire, TSFI and Frail Scale during hospital admission.All statistical analyses were conducted via SPSS 21.0. Number (percentage) was used to describe enumeration data, and mean ± standard deviation (SD) was adopted to describe continuous data. Internal consistency reliability for each domain and total of the scale was determined with Cronbach’s α coefficient. According to the literature, Cronbach’s α greater than 0.9 was considered as excellent, 0.8–0.9 as good, 0.7–0.8 as acceptable, 0.6–0.7 as questionable, 0.5–0.6 as poor and lower than 0.5 as unacceptable .Split-haContent validity was assessed. The C-TSFI were evaluated by four clinical emergency specialists and three geriatric care specialists who were not involved in the translation process. Each item of the translated questionnaire was rated in a 4-point scale of ‘1 = not relevant’, ‘2 = somewhat relevant’, ‘3 = quite relevant’ and ‘4 = highly relevant’.To analyse the construct validity of the C-TSFI, correlation tables were used, which were resolved using Pearson’s Correlation Coefficient. Correlations were made between the scores of each item and the total score the of the C-TSFI.Pearson’s correlation coefficient between the FRAIL scale and the C-TSFI scale was calculated to test the correlation validity of the criterion. The Frailty were screened with scores ≥ 3 on the Frailty scale. The elderly emergency trauma patients were divided into frailty group and non-frailty group. And then by plotting the ROC curve, sensitivity, specificity and maximum Youden index were used to determine the optimal cut-off value of the C-TSFI screening for frailty. In addition, the screening performance of the C-TSFI was investigated by calculating the Kappa value.A total of 184 elderly truama patients were enrolled into the study, 176 questionnaires were effectively recovered, with an effective recovery rate of 95.7%. 8 participants were excluded because they met some withdrawal criteria. The mean age of patients was 72.13years(± 7.85years), 77 males and 99 females. The education of the majority was junior high school or below, accounting for 63.1% to evaluate the TSFI reliability. Reliability of internal consistency includes Cronbach alpha coefficient and split-half reliability. The Cronbach alpha coefficient of TSFI was 0.861Table . The splIt is determined that the I-CVI of the C-TSFI scale is 0.86~1, and the S-CVI of the TSFI is 0.93.P < 0.001)..The Receiver Operating Characteristic (ROC) curve was drawn to calculate the sensitivity, specificity and critical value of the Chinese version of TSFI for frailty to test the screening performance of the scale.The AUC of the C-TSFI scale was 0.932 , the Youden index was 0.725, the sensitivity was 0.802, the specificity was 0.923, and the best critical value was 0.31 (Table P < 0.05).The C-TSFI was positively correlated with the total score of FRAIL  for elderly trauma patients based on electronic hospital records, and has been proven to be useful in China . Both ofEven so, we consider it is essential to introduce the TSFI in China. Firstly, GTFI is constructed based on the patients’ ICD-10 diagnostic code, While the TSFI based on multi-dimensional health status. Not hard to find, when we use the GTFI, more attention to obvious trauma and chronic diseases, while ignoring some defects in psychological and social adaptation , 30. TheP < 0.05). The result was inconsistent with Heather Jarman’s group research, they reported that, compared with the CFS  and PRISMA7 (Program of Research to Integrate Services for the Maintenance of Autonomy 7), the TSFI showed the slightest agreement with geriatrician assessment of frailty [This study is the first to explore the screening value of the C-TSFI and determine critical value. We investigated the correlation with the reference standard, The C-TSFI was positively correlated with the total score of the FRAIL. As we kown, There is no gold standard for the assessment of frailty. The FRAIL as the reference standard in our study based on International clinical practice guidelines .Finally, frailty . Such reThe Chinese version of TSFI is a specific scale dedicated to the assessment of geriatric adult trauma patients. It has good reliability and validity.However, the sample size included in this study is relatively small, and the survey scope is limited to Chengdu area of Sichuan, China, which may affects the universality of the results. Because, the environment, cultural customs, health cognition and psychological characteristics are diverse in different regions in China.The next step should be to expand the range of sample sources and further verify the Chinese version of TSFI, which can ultimately provide a scientific reference standard for early intervention of traumatic geriatric patients.Below is the link to the electronic supplementary material.Supplementary Material 1


Background: The residency interview is a crucial step that helps the program identify potential new trainees while the trainees find out more about the program. With the onset of the COVID-19 pandemic, it became essential to hold interviews virtually.Objective: Here, we conducted a questionnaire-based study to identify areas of improvement in the virtual interview process in our program.Methods: The study was conducted among the residency interview applicants of the 2022 match cycle. A questionnaire was sent via email to all applicants who were invited to our residency program for an interview. Out of the 600 applicants who were interviewed in our program, 230 applicants answered the survey, an 11-point questionnaire pertaining to the various aspects of the interview process.Results: A virtual interview with an option of in-person is the most favored answer among the different groups, i.e., American Medical Graduates (AMGs), International Medical Graduates (IMGs) without need for a visa, and IMGs with a need for a visa, respectively, were, 37.5%, 42.8%, and 38.65%, respectively. An updated website with all required information was a top resource used by 95%, 84.5%, and 89.6% of the different groups of candidates. American medical graduates (32.50%) place high importance on resident interaction, while international medical graduates want the programs to focus on their website and provide more information about all aspects of the program during the virtual interview.Conclusions: In the post-COVID-19 era, Internal Medicine programs will need to improve several aspects of virtual interviews while assessing what is important to candidates. The residency interview is a crucial step that acts as the meeting point for the applicant and the residency program. It helps the program identify potential new trainees while the trainees find out more about the program and if they would like to train at the program for their residency. Coronavirus disease COVID-19), while having a great impact on medicine, has also ushered in a new era of virtual interviews. The interviews season in 2020 was the first time programs across the country had to resort to the use of virtual interviews based on recommendations of the Coalition for physician accountability 9, while . HoweverInternational Medical Graduates (IMGs) are an important part of the continued Graduate medical education (GME) and hospitals across the country contributing to relieving the linguistic and cultural barriers to receiving healthcare . The hurA questionnaire, which was designed to focus on key aspects of interviews, was sent via email to all applicants who were invited to the SUNY Downstate residency program for an interview. The questionnaire, which was designed to be anonymous, was sent after the national residency matching program (nrmp) rank list deadline submission day to prevent any bias in answering questions related to their interviews. The study was also Institutional Review Board (IRB) exempt as deemed by the IRB at SUNY Downstate. The number of candidates who were interviewed for the 2022 match at our program was approximately 600. Two hundred thirty candidates answered the questionnaire (Appendix) between March to July 2022. The 11-point questionnaire pertained to the various aspects of the interview process. Among the 230 respondents to our questionnaire, there were no candidates who had applied to primary care, and hence the subgroup has not been included in our analysis and discussion. Analysis was carried out using StataCorp. 2017. Stata Statistical Software: Release 15. College Station, TX: StataCorp LLC. Likert scales were converted to numerical scores (1-5), and Microsoft Excel  was utilized to generate graphs. Frequencies and percentages were used to summarize categorical variables. Among the 230 candidates, there were 40 AMGs, 84 IMGs without the need for a visa, and 106 IMGs with a need for a visa. More than 50% of candidates among all groups have indicated that they would like a virtual interview or a virtual interview with an option of in-person  of candidates responded with a 4 or 5 on a scale when asked if they would recommend our program to a junior or a colleague at the next match cycle. Two hundred and seventeen (94.35%) of candidates did not experience any technical difficulties during their interview. The limitations of the study include the following: i) the survey was sent to all applicants who interviewed at the program, so there is a potential for bias in their answers; however, we sent the survey after the rank order list deadline to avoid any kind of bias ii) the demographics of the candidates who participated in the survey is not available, but the survey avoided questions about demographics as we did not think it was an important criteria to group candidates answers based on their gender or race.Virtual interviews are likely to become the norm for all residency programs across the country despite the COVID-19 pandemic being less pathogenic. Applicants and PDs view the benefits of virtual interviews to outweigh the benefits of the in-person interview. Programs must work together with the applicants to help each other find their most suitable match. Programs must update their website with all required information as required by the applicants if they want to attract the most competitive applications. Applicants have consistently placed aspects such as presentation of the curriculum, information about the hospital and its affiliates, faculty and resident information, and research activities as important aspects in their evaluation of a program, and hence PDs must work to provide information on all these categories. Our institution undertook this survey to address aspects ranked high by the respondents to our survey. AMGs and our institution place high importance on resident interaction, which can be made possible by having more resident interaction time with virtual happy hours or allotting more time during the interview for the applicants to talk to current residents. PDs can help IMGs by updating the program website and providing more information about all aspects of the program during the virtual interview. Finally, programs can be applicant-centric by focusing on aspects considered important by preliminary applicants in addition to their categorical counterparts.


The Take Kare Safe Space (TKSS)), and (2) the strengths and weaknesses of TKSS from the perspective of key stakeholders.Safe Spaces are a harm reduction approach commonly utilised in nightlife and festival settings to address alcohol and other drug-related harms. Despite increasing use, there has been little independent evaluation of safe space programs. This study aimed to explore (1) program user satisfaction with and use of a safe space program implemented in Sydney, Australia (n = 4), ambulance (n = 4), a local hospital accident and emergency room (n = 4), local council (n = 2), city ‘rangers’ (n = 2), the TKSS program (n = 4), licensed venues and other nightlife service providers (n = 4), and program users (n = 14). Purposive sampling was used to identify key stakeholders to participate in interviews.Semi-structured, in-depth, interviews lasting between 30 min to 1 h were conducted with 38 key program stakeholders, including staff from police (Stakeholders stated that the TKSS program had a number of core benefits, including that it filled a service gap in nightlife settings; improved the efficiency and effectiveness of emergency services and other stakeholders operating in nightlife precincts; provided welfare services through proactive and non-judgmental interventions; and facilitated a means to de-escalate conflict without engaging police. Perceived weaknesses of the program included a lack of public awareness about the program; staff and volunteer levels; and misunderstandings regarding the scope and function of the TKSS program by some stakeholders.This study demonstrates the complex relationships that exist around the delivery of harm reduction in nightlife settings. In particular, it highlights the relative lack of servicing of public nightlife settings and the value of safe spaces/peer-to-peer safety ambassador programs in linking up care and filling this service gap. Further, it documents the extended benefit across key stakeholder groups of delivering proactive and non-judgemental harm reduction services and, in doing so, provides critical evidence around their efficacy in reducing AOD-related harms in the night-time economy. The ‘night-time economy’ (NTE) is an important part of contemporary social and economic life, referring to the mix of business, leisure, social and cultural activities that take place in the evening, generally from 6 pm onwards –5. In thLicensed entertainment precincts and venues are high risk settings for AOD-related violence, with a significant proportion of assaults occurring in or within close proximity to these locations –32. LinkB =  − 1.66, 95% confidence interval − 3.02, − 0.30)  team when they call an ambulance, we will be receiving a patient that is intoxicated, drugged, call it whatever you want, but there is a chance that we would have received that patient later for doing something silly or being hit by a car or getting involved in a fight. So, that’s a main impact that we see, that we might see that patient intoxicated because it’s not safe to be in the street but that [major incident] didn’t happen. If no one called the ambulance, we would be seeing a different patient hours later.’ (A&E Staff Member #3)Stakeholders also perceived the TKSS program as key to identifying and offering early intervention to individuals who may be at risk of harm. A&E and NSW Ambulance staff reported that the interventions by the TKSS program regularly resulted in a substantial reduction in the potential harm they may have experienced.Improving efficiency and effectiveness of emergency and other services operating in nightlife settings Stakeholders regularly asserted that the TKSS program had been valuable in acting as an intermediary between service providers, often functioning as a critical triage service for serious incidents. The TKSS program was praised by emergency medical professionals and police for its ability to manage ‘at risk’ individuals and escalate the incident with emergency services as or if necessary. In providing this service, police, ambulance, and A&E staff reported that presence of the TKSS program allowed them to better manage their own resources by freeing them from the workload of dealing with high volumes of purely alcohol-intoxicated nightlife revellers. Program users and stakeholders noted that without the TKSS program, many more intoxicated revellers would end up in ‘risky’ and vulnerable situations, in hospital beds or in police stations simply because they didn’t have anywhere else to go for appropriate care:‘There is just no one out there who is really well equipped to deal with heavily intoxicated people. Like, we do it all the time, but are we really the best people to be doing this? Most of the time they end up with us simply because there is no one else to take care of them…The Take Kare program is providing options that are much more appropriate for the level of care needed in most cases’ (NSW Ambulance #4)'It’s definitely assisted police I believe with taking some of the workload off the police who can be doing other things, dealing with other matters. For all police I think young persons are high care, no doubt about that, especially if they’re intoxicated, all that sort of thing, and it takes hours and hours and hours of police time to get that person home safely.' (NSW Police #4)3. ‘From the point of view of looking at better communication and coordination between stakeholders in the city at night. So, the program coming on board was an opportunity to go, "Okay. These guys are a conduit."... I mean, they're not coordinators but they're sort of a conduit to sort of bring it all together’ (City of Sydney Staff #1)Look, we haven’t always had a great working relationship with the police, for many reasons and I think because of that we haven’t always wanted to contact the police, and some people don’t want to involve an ambulance if they are just drunk, or feeling off. What having the TKSS program has meant is that we have someone else to turn to, and when police come by, they see that we are working to get a good outcome for our clients, and I think they are less suspicious of us. (Licensee #3)The nature of the TKSS program and its interaction with other stakeholders in Sydney’s NTE led many interviewees to view the service as a ‘hub’, acting as a conduit between different agencies operating in nightlife settings. Stakeholders felt that the presence of the TKSS program had been significant in developing relationships between organisations that previously had minimal or less established levels of communication, creating a cooperative eco-system of service providers that better worked together to meet the needs of its users. Facilitating this coordination and collaboration with other service providers operating in Sydney’s key nightlife precincts was seen as a strength of the program and something that ultimately improved safety in the city at night.I think it is great that venues are directing people to the Safe Spaces. Like, before, venues use to just kick people out and hope for the best. This created really unsafe situations and we saw it go wrong a lot in Kings Cross. People would pass out, get caught in bad situations. There are a lot of people out there who prey on these people, and so having a space and service where people can go is a really good thing. (NSW Police #3)The role of TKSS in linking together licensees, emergency services, the City of Sydney CCTV control room and other welfare services was seen as contributing to the efficiency and effectiveness with which each of these services function and fostered more productive working relationships between groups that have not always worked closely together:Stakeholders revealed several perceived weaknesses of the TKSS program including: (1) a lack of public awareness around the program; (2) the ability of the program to service its current localities given staff and volunteer levels; and (3) misunderstandings regarding the scope and function of the TKSS program by some stakeholders.A lack of public awareness around the program. The most consistently identified weaknesses of the program across stakeholders related to a lack of public awareness of the program and its role. Here, interviewees regularly noted that most people out in nightlife precincts simply didn’t know that TKSS existed or, if they did, they weren’t sure what service it provided. Many program users, for example, said that they were not aware of the Program before their initial contact with the Ambassadors:‘I had no idea they existed, so I think it would be good if that was more known, just to give people that kind of sense of a bit of security. Like, I don’t want it to encourage people to get, you know, more drunk just because they know that someone’s there but I think it would be good to advertise there's like a safe space, even for people who aren’t drinking, so to speak.’ (TKSS Program User #8)‘I guess the biggest question I would have is do enough people know about the program and what it does?...A program like Take Kare is probably limited in its impact because enough young people just don’t know about it… young people who need help still might not know it is there and that means they are not as effective as they might be if more people knew where they could go for help.’(NSW Ambulance #4)1. The ability of the program to service its current localities given staff and volunteer levels. It was asserted by stakeholders that the size of the locations the TKSS program services is a major challenge given the staff and volunteer resources available to the program, ultimately limiting the impact that the program can have. This was noted as critical given the proactive nature (and noted benefits detailed above) of the roving teams, with stakeholders stipulating that either an expansion of the program or a re-evaluation of its geographical reach was necessary. These operational issues were of particular concern to stakeholders working within the TKSS program.‘Operationally what could be improved? I think that it should be reconsidered around the footprint of the CBD site, what kind of area they're looking to cover. I think it's too big, in my opinion. Trying to survey a range from as far north as The Rocks, to as far south as Central Train Station, and to as far east as Taylor Square, and Oxford Street…it’s just too big’ (TKSS Staff #1)‘I think again what's unique is the ambassadors sort of roving around the city. I guess it's something about not just waiting for people to come to you, but being really proactive and going out looking in the dark alleys where crimes might often happen. Or looking yeah, in the gutter or on a side street where someone might be vomiting or vulnerable. I think that's where a lot of our incidences really actually come from. Like if you stay in the one spot you don’t see that much, but when you are roving you do ... I think we've noticed it sometimes in King's Cross or in the city where we haven't had enough teams to rove in every direction.’ (TKSS Staff #3)2. Misunderstandings regarding the scope and function of the TKSS program by some stakeholders Some stakeholders and program users identified concerns regarding the sometimes-misplaced enthusiasm of TKSS staff and volunteers in situations that required more formal service responses. In some cases, it was perceived that TKSS staff had attended incidents where emergency health services should have been engaged immediately. Some stakeholders suggested that this issue may be the product of a misunderstanding of the role and scope of the TKSS program amongst other services and organisations, resulting in either the overuse or underuse of the program. While the limited authority the volunteers hold makes them more approachable to revellers, it also has the potential to place them at risk when referred to an incident they may not be equipped to handle. Likewise, it was indicated that some stakeholders may not have a complete understanding of the resources that the TKSS program has access to, and that this lack of knowledge has the potential to promote negative outcomes for users of the program.‘Maybe there's like a misunderstanding of our role by different stakeholders. Like I know we've been called in situations where there's like a first aid situation where really an ambulance should've been called straight away. And it's kind of ... Well that, five, 10 minutes between when you called and got there, like they could've been an ambulance’ (TKSS Staff #1)3. This study provides important qualitative insight into the strengths, weaknesses and stakeholder perspectives related to the operation of a safe space and roaming ambassador nightlife HR service that operated in Sydney between 2014 and 2022. The TKSS program aimed to improve the safety and amenity of the urban public domain by providing a HR service where vulnerable people in nightlife settings could access support and a safe place. Critically, this study both supports and extends the current evidence base around the efficacy and impact of peer-to-peer HR services deployed in nightlife settings. In particular, this study demonstrates the role that safe space programs can play in relation to supporting safety and wellbeing in the public domain and connecting-up other nightlife services critical to the delivery of a safe and vibrant night-time economy. Such service provision is particularly needed given the widespread use of liquor regulation around the “responsible” service of alcohol (itself widely considered a form of harm reduction policy) that requires licensed premises in many countries to cease service to and evict people showing obvious signs of intoxication. In fact, international research has shown that some the most severe incidents of physical harm can result from these eviction practices and subsequent patron conflict outside venues . FindingThis study also highlights the important role of roving HR services in providing triage and mitigation against more intensive intervention for intoxicated nightlife revellers. It is widely and routinely reported that night-time AOD use and attending harms are associated with significant costs to individuals, businesses, and the state through provision of health care, policing services, and other impacts on the economy –78. FindProviding an alternative to police in the regulation and de-escalation of conflict in nightlife settings not only has the direct benefit of preventing the criminalisation of revellers, but also in reducing injury. The ability of TKSS ambassadors to identify vulnerable situations and people and provide early intervention minimised the potential for future harm and was frequently identified as the greatest value-generating activity of the program. Drug and alcohol affected program users felt comfortable and willing to divulge information to TKSS ambassadors they wouldn’t readily tell other service providers. The provision of non-judgemental support assisted uptake of the service, enhanced the ability to deliver important messages about risk reduction, and, in doing so, allowed action and relations that minimised harm. Again, these findings mirror those of other research that have highlighted how drug-affected young people often actively avoid police and medical services for of fear of judgement or arrest, or engage in more harmful consumption practices to avoid contact/detection by them , 39. TheThe role of the TKSS program in increasing communication and cooperation between service providers was a clearly stated strength that allowed key service providers to conduct their work more efficiently. Ensuring a safe night-time economy requires the collaboration of a range of sectors to provide a co-ordinated approach to management , 81–84. This study was completed in Sydney, Australia, during a period of highly restrictive regulations governing nightlife and the service of alcohol in licensed premises in the areas in which the TKSS program was operating. While it cannot be fully known how this regulatory context may have impacted the data collected, there is no doubt that engagement in Sydney nightlife was significantly impacted by the “lockout laws” and so issues reported may have been influenced by this operational context, and may therefore limit the transferability of these findings to other locations. Further, recruitment of program users was difficult and slow given that many who used the service during data collection were heavily intoxicated and unable to engage with advertising materials. This issue undoubtedly impacted on the final number of program users who took part in interviews, but the level of data saturation achieved with only this relatively small number of participants and the consistency with findings from the survey (reported elsewhere) indicated that it was sufficient to be considered a good reflection of program user sentiment regarding the TKSS service.This study demonstrates the complex relationships that exist around the delivery of harm reduction in nightlife settings. In particular, it highlights the relative lack of servicing of public nightlife settings and the value of safe spaces/ peer-to-peer safety ambassador programs in linking up care and filling this service gap. It documents the extended benefit across key stakeholder groups for the delivery of proactive and non-judgemental harm reduction and, in doing so, provides critical evidence around their efficacy in reducing AOD-related harms in the night-time economy.