Adverse events (AEs) during intensive care unit (ICU) rehabilitation and serious AEs during acute care hospital stays have been reported previously. However, no AEs have been reported for all patients needing rehabilitation in a non-ICU setting at an acute care hospital. This study aimed to investigate all AEs during acute-phase rehabilitation. Reports of AEs occurring during acute-phase rehabilitation in a university hospital from 1 April 2021 to 31 March 2022 were retrospectively analyzed. Minor and severe AEs were defined as those that did not require new treatment and those that required intensive treatment and/or prolonged hospitalization, respectively. There were 113 incidences of AEs during rehabilitation. The majority of AEs were minor (93.8%) and did not require new treatment. Only one serious AE was documented. The most common AEs were peripheral intravenous tube removal, decreased level of consciousness, poor mood due to low blood pressure, and falling down. There was no significant correlation between years of experience and the frequency of AEs. The neurosurgery department had the highest cases of AEs. Physical, occupational, and speech-language-hearing therapists had different characteristics and experiences of AEs. Risk management strategies should consider exercise load and targeted disorders due to differences in therapists’ specialties. The effectiveness of providing early rehabilitation for patients with many diseases has been demonstrated in recent years ,2,3,4, aIt has been reported that most AEs occurring during rehabilitation in the intensive care unit (ICU) setting did not warrant additional treatment, cost, or prolonged hospitalization ,12,13,14The purpose of this study was to retrospectively evaluate all AEs that occurred during rehabilitation and to obtain detailed information to improve risk management strategies in future acute care settings.Our study revealed that the majority of AEs that occur during rehabilitation in acute care settings have a minor impact on the patient, and the length of working experience of the therapist does not appear to affect the occurrence and frequency of AEs.As of 2022, Wakayama Medical University hospital had 760 general beds (including 10 ICU beds) and 40 psychiatric beds, serving 27 clinical departments and 28 central medical treatment sections. Rehabilitation began upon request from the physicians in various departments to the department of rehabilitation.Physiatrists examined inpatients prior to starting rehabilitation and evaluated their diagnosis, disease state, and physical condition. Registered and skilled therapists then commenced exercise therapy. A team meeting was held on the evening of the referral day of the patient to identify challenges and consider solutions, with the aim of improving rehabilitation safety and efficacy. For all patients participating in rehabilitation sessions, a physiatrist and therapist visited the patient’s room each morning to check vitals, consciousness, and any worsening of cognitive or motor impairments, and to assess the patient’s condition to determine if rehabilitation could continue. Therapists measured vital signs pre- and post-rehabilitation.In this retrospective cohort study, we analyzed AE reports that had been submitted by the Department of Rehabilitation Medicine to the Medical Safety Promotion Department at our hospital between April 2021 and March 2022. The AE reports were reviewed by the Risk Manager of the Rehabilitation Department and the Medical Safety Promotion Department, who also review the patient’s post-AE status and complaints. During the study period, one author (S.H.) worked as the department’s patient safety manager.At our hospital, all staff are required to report an AE to their corresponding risk manager. An AE during rehabilitation means any instance that has caused or may have caused further physical or psychological injury to the patient. AEs include damage to the patient’s clothing and belongings. A decision is made by the Medical Safety Promotion Department concerning the impact of the AE level. According to the National Coordination Council for Medication Error Reporting and Prevention index , the impThe rehabilitation period was defined as the period when a therapist provided rehabilitation in a patient’s bedroom, corridor, training room, or outdoors. Specific definitions of the period include duration (1) from when a therapist enters a patient’s room until leaving, (2) from when a patient enters a training room until leaving, or (3) if a surveillance and/or assistance patient was moved with a transfer staff; duration was defined as the time from when a therapist received a patient to when a patient was handed over to a transfer staff member.The survey items included the number of hospitalized patients, number of patients referred to the department of rehabilitation (inpatients), total number of AEs, degree of impact of AE on the patient, primary department of the patient who suffered from AE, content of the case, specialization of the in-charged therapist, and years of experience as a therapist.p  <  0.05. Statistical evaluations were performed using the Graph Pad Prism 6 software .The values of the variables are given as numbers and means ± standard deviations (SD), where applicable. The hospital accepts residents in 2- to 6-month increments, and for residents, 12 months was calculated as 1. Thus, 6 months of residency was calculated as 0.5. Pearson was used to examine the correlation between years of experience and the number of AEs. Differences were considered statistically significant at The hospital’s division of rehabilitation had a total of 38 regular staff comprising 26 physical therapists, 8 occupational therapists, and 4 speech-language-hearing therapists. Our hospital accepts training for therapists who are licensed and already working in other facilities for studying in an acute care hospital. There were a total of 18 residents during the study period: 14physical therapists, 3occupational therapist, and 1 speech-language-hearing therapist. The number of years of experience was 10.1 ± 6.3 (mean ± SD) for regular staff. The total number of inpatients during the study period was 18,724, with an average length of stay of 12.2 days. There were 6945 patients referred to the department of rehabilitation, of whom 6400 and 545 were inpatients and outpatients, respectively. The most frequently referred clinical departments were Emergency Medicine (1050), Gastrointestinal, Endocrine, and Pediatric Surgery (1001), Orthopedic Surgery (611), Cardiovascular Medicine (458), Neurosurgery (386), Hematology (270), Cardiovascular, Respiratory, and Breast Surgery (261), Gastrointestinal Medicine (219), Diabetes, Endocrine and Metabolic Medicine (210), and Pulmonary Medicine and Medical Oncology (207) .There were 3403 AEs (including 51 SAEs) in the entire hospital during the study period, and 113 (including 1 SAE) were recorded in the division of rehabilitation. In addition, all reports from the division of rehabilitation were on inpatients. The degree of impact of the AEs on the patients, as well as the corresponding contents and the number of occurrences, are shown in p = 0.1263). The clinical departments with the most AEs recorded were Neurosurgery at 36 cases, Emergency Medicine at 16 cases, and Orthopedic Surgery at 14 cases  SAEs occurred during rehabilitation, all of which occurred in either the physical therapy room or the general ward . Thus, SA previous study on AEs in the ICU reported 34 cases occurring in 5276 sessions of rehabilitation, with 23 incidents of blood pressure instability or arrhythmia, 3 falls, and 2 tube problems . KatsukaIn this study, the number of AEs was not particularly high among therapists with few years of working experience. In our previous report, there was no relationship between the occurrence of SAEs and the number of working years of the therapist in charge of the patient, indicating the need to be aware of the incidence regardless of experience . In addiThe occurrence of AEs differed among physical therapists, occupational therapists, and speech-language-hearing therapists. Physical therapists perform loading methods, mainly gait and endurance training , and in This study was limited in that it was a single-center, retrospective cohort study, and thus affected the generalizability of this study. Moreover, information concerning a non-adverse event group was not available. Consequently, it was not possible to analyze differences between patients without AEs. In the future, it is critical to conduct large-scale surveys across multiple facilities.The majority of AEs that occur during rehabilitation in acute care settings have a minor impact on the patient, and the length of working experience of the therapist does not appear to affect the occurrence and frequency of AEs. In addition, peripheral intravenous tube removal and attention to patients with cerebrovascular disease are important to reduce AEs, as well as devising measures that consider exercise load and targeted disorders due to differences in therapists’ specialties.


Applying rehabilitation research knowledge in practice is challenging due to a gap between scientific knowledge produced by researchers and the needs of practical rehabilitation. This study describes the current and future knowledge needs of rehabilitation research from the perspectives of professionals and service users. We conducted a qualitative study with inductive content analysis from nine focus group interviews with rehabilitation stakeholders. The results show that current knowledge needs are strongly related to the meaningful and inclusive life of service users, the promotion of multi- and interprofessionalism in rehabilitation, and transdisciplinary applied research on rehabilitation. The future knowledge needs were related to the changing needs of rehabilitation and remote rehabilitation based on rapid change in society and digitalisation and on different rehabilitation practices and contexts. The results of the study can be used to enable favorable conditions for reciprocal research, development, and innovation (RDI) activities and research networks in transdisciplinary rehabilitation. In Finland, good rehabilitation practice is based on the needs and the individually tailored rehabilitation plan of a service user (SU) as well as on the knowledge from empirical practice and evidence of effective rehabilitation from research , 2. HoweIn order to apply the evidence from research to rehabilitation, the importance of many underlying factors must be understood. Rehabilitation is an interactive process in which the relationships between professionals and SUs are crucial and collaborative. According to Vingerhoets, Hay-Smith, and Graham , it is cAccording to Sarkies et al. , EBP impIntegrated knowledge translation (IKT) is a research method that brings together researchers and stakeholders with experience and knowledge of a research topic. Within IKT, partnerships have been developed that enhance the relevance of research results among rehabilitation professionals and SUs . In thisIn Finland, rehabilitation is financed through several channels, mainly in accordance with the Nordic welfare state principle with public funds, but also through insurance companies and private financing. The rehabilitation system is decentralized to many areas, such as health care, social care, school, labor administration, and prison management . BecauseIn the field of rehabilitation, multidisciplinary research have been discussed for over 30 years . AccordiIn Finland, a nationwide strategic research and development program for rehabilitation is lacking . In the As previously described, nationwide multi-professional rehabilitation requires extensive collaboration in the field. This study bridges rehabilitation practice and research by studying the current and future knowledge needs of professionals and SUs in two different regions in Finland: Jyväskylä and Helsinki. Jyväskylä is located in central Finland, surrounded by sparsely populated rural communes and towns, and Helsinki is located in southern Finland, where the Helsinki metropolitan area consists of a concentration of major cities.The purpose of the study is to describe the current and future knowledge needs of rehabilitation from professionals' and SUs' perspectives to enhance the implementation of research. This study describes and compares regional knowledge needs in rehabilitation research. The specific study question is: What transdisciplinary rehabilitation knowledge needs do professionals and SUs in rehabilitation practice have?The study is part of the Platform Ecosystem for Strengthening of Research, Development, and Innovation (RDI) Activities in Multidisciplinary Rehabilitation' (REcoRDI) project. REcoRDI aims to improve research result utilization and the impact of applied research on rehabilitation by strengthening network collaboration and developing a roadmap for applied research on multidisciplinary rehabilitation. The project is being conducted in collaboration with JAMK University of Applied Sciences, Jyväskylä, and Metropolia University of Applied Sciences, Helsinki, between April 1, 2019 and March 31, 2022 .The knowledge needs of rehabilitation practice were collected through focus group (FG) discussions, using a qualitative research approach to gain an understanding. FG interviews were selected as a data collection method enabling the construction of information from professionals' and SUs' discussions. An FG is a group of people with interest, expertise, and experience of the research phenomenon . AccordiThe participants for the FG were recruited through purposive selection from the regional partners of the universities of JAMK and Metropolia. The regional rehabilitation partners of JAMK and Metropolia, were contacted through email and were asked for their consent to take part in the study. The purpose was to gather a group who were  multi-prThe study was conducted in accordance with the Declaration of Helsinki and good scientific practice. It included no invasive or potentially physically or psychologically harmful elements that would exceed the limits of normal daily life. Due to the COVID-19 pandemic, the interviews were performed online, all participants were informed about the study by email, and they gave their written consent for participation by responding by email. In addition, they received oral information supported by written slides at a Zoom meeting before the interview started. According to Finnish legislation and guidelines of the Finnish National Board on Research Integrity (TENK), an ethical review was not required. A confirmation statement from the TENK is included as The study data consists of nine FG interviews, five conducted by Metropolia in the Helsinki area and four by JAMK in the Jyväskylä area, all organized remotely by the Zoom application between April 2, 2020 and May 5, 2020. Each interview was conducted by two interviewers who were experienced in interviewing and work in JAMK or Metropolia. The first two interviews conducted by Metropolia served as pilots. They were included as research data because they did not justify any significant changes to the themes or the protocol.There were three to five  participants in each FG discussion. Five discussions were conducted in the Helsinki area (22 participants) and four in the Jyväskylä area (15 participants), with a total of 37 participants. The audio-recorded interviews lasted 56–89 min (mean time of 69 min). The recordings were transcribed verbatim in a total of 87 pages , and the transcription service was purchased. The interviews had three main themes concerning , algorithms, and bots in searching and getting scientific information that is personalized. In research, there is a need to get data automatically from the everyday life of rehabilitees.The future knowledge needs of applied research on interdisciplinary rehabilitation were related to six topics: knowledge on the changing needs of rehabilitation, the individual needs of SUs, rehabilitation as an interactive process between an SU and his or her environment, rehabilitation practices, the effectiveness and benefits of rehabilitation, and supporting and promoting the development and management of rehabilitation.In the future, knowledge is needed on the changing need for rehabilitation because the problems of SUs have become more complex. The next generations will have more and varying problems than previous generations. Knowledge concerning challenges affecting health and functioning is needed in relation to changing society and the future.Knowledge that originates from an SU's individual need is needed and meaningful in the future. Individual knowledge arises from the SU's personal needs alongside the diagnosis-specific knowledge. One participant described knowledge that is needed as “Personalized knowledge, in a way, individually for everyone's needs”. In the future, SUs will also need knowledge to promote their ability to function on their own.It is important to strengthen the knowledge of rehabilitation as an interactive process of the SU and environment. Knowledge about rehabilitation or habilitation processes is needed as well as research about building up and supporting one's agency. In the future, more knowledge is needed about the impacts of the environment—attitudes and physical environment—on the rehabilitation process. As one participant said:I'd be interested in knowing how people's attitudes and the changing of attitudes affect the rehabilitation process. We'll all encounter some phases in our lives—and I'm wondering how attitudes and atmosphere have an impact on how we all are capable of and able to participate equally in society.Also, information is needed about enablers of rehabilitation.There are many knowledge needs concerning rehabilitation practices. In the future, it will be important to increase knowledge about prevention, early-stage guidance, rehabilitation in everyday life, the use of International Classification of Functioning (ICF), peer support, and expert-by-experience services. Regarding the research on remote rehabilitation, digitalisation and technology are highlighted. In the future, knowledge about rehabilitation will be needed for political decision-making on the one hand and for information guidance on the other. The knowledge also needs to include collaboration between professionals as well as interaction between professionals and SUs.Knowledge about the effectiveness and benefits of rehabilitation is needed in the future. It is important to be able to demonstrate the impacts of rehabilitation as well as provide evidence of the introduction of new technology. It is also important to be able to justify rehabilitation on a personal and societal level.Knowledge is needed to develop rehabilitation and its administration. Research on strategic management and networks is needed. Research on professionals' knowledge and skills in rehabilitation is important for transferring tacit knowledge. To this end, it is increasingly important that rehabilitation professionals and SUs are involved in the conduction of the study, as described in one discussion: “And I am convinced that information is needed on how SUs are involved in the development of rehabilitation”. Future research should be able to utilize big data from people's daily lives and to study the uptake of research findings. Participants also discussed the use of technology to aid in the implementation of research results.The current and future knowledge needs in Helsinki  reflecteProfessionals and SUs in the field of rehabilitation need more knowledge about how the information is designed in an individually understandable way to meet the needs of the rehabilitee. In the future, rapid changes in society and technology will put pressure, as well as opportunities for the development of rehabilitation practices. Therefore, more knowledge to support development and decision-making is needed. Knowledge about the effectiveness of rehabilitation and its factors is required in the future. Currently, evidence is used and needed to maintain and demonstrate professional competence to different parties. Technical solutions, digitalisation, and AI were seen as key factors in remote rehabilitation, knowledge implementation, and research. In addition, more transdisciplinary knowledge is needed about practitioners' and SUs' roles in rehabilitation and its research.Study 2 brought together a multidisciplinary group of professionals working in different areas and sectors of rehabilitation, including those working with unemployed people and families. The current knowledge needs of applied research in multidisciplinary rehabilitation covered five interrelated topics. Evidence about methods and best practice is needed in the practice of rehabilitation for several purposes. Knowledge needs concerning other professions is a prerequisite for collaboration within rehabilitation in the health and social service field; relating to the SUs, it is necessary to understand the individual's situation; and regarding societal phenomena, it is needed to understand socially influencing factors. Besides knowledge needs, the utilization of scientific knowledge was also brought up.Regarding evidence about the effectiveness of methods and best practice, professionals face competing demands within their organization and need to have justification and reasoning internally for their work or work methods, or in situations that require more human or financial resources. For example, one participant explained the need for scientific knowledge as a justification to their employer by saying, ‘All situations where you need to justify your actions, are those. For example, at the workplace, I need to have good support for everything I suggest to the managers. I can't just say “I feel this would be nice”'. Therefore, the requirement for evidence-based practice is essential. Furthermore, some suggested that there may be competing views among colleagues on the “right” methods of rehabilitation, and sometimes reaffirming the overall practices of everyday life is needed. Vocational rehabilitation requires knowledge about SUs' re-employment pathways. Mentioned in particular were vocational re-education, employment-promoting institutions, the labor market and working life, the future of work, changes in occupations, and work ability.Furthermore, some participants stated that they need knowledge to justify their actions to managers and policy makers. Evidence-based information on effective rehabilitation is also used to influence local welfare policy and the division of resources; this requires evidence about the services. In Finland, rehabilitation services are increasingly provided by the private sector. Among those working in the private sector, the need for knowledge was for marketing purposes, to attract possible SUs, and to have research-based working methods to stand out among other service providers.The participants brought up evidence of rehabilitation as an important knowledge need in general. This concerned various topics on rehabilitation, methods and measures used to evaluate effectiveness, and best practice. As raised in the interviews, efficient rehabilitation practice includes information on the right timing of rehabilitation. This should be included in the knowledge on rehabilitation services in general. For example, the discussion brought up the justification for organizing preventive work that is often cut down to save financial resources.As rehabilitation requires collaboration between various professionals, multi-professional work requires knowledge on the collaboration, methods, services, and theoretical foundations of other professional groups, and an extensive understanding of those. Participants reflected on the need to learn and get extensive knowledge on the practices of medicine, psychology, and social work, for example. A physiotherapist may have knowledge needs related to the holistic view of an SU. For example, back pain and fear of pain is the cause-and-effect relationship between body and mind, which needs to be paid attention to. This kind of knowledge builds shared understanding to support work in the overall social and health care services and to serve the needs of the SU.Various knowledge needs relating to the SUs were considered: individual characteristics are related to the physical condition and health of the SUs, the significance of rehabilitation, and knowledge of the overall life span and various contexts of daily life. Professionals require knowledge to evaluate these as part of their daily work.Participants brought up the knowledge needs on societal phenomena, such as inequality, socio-economic class differences, knowledge of disadvantaged groups, and unemployment. In their daily work, inequality was noted in the practices of obtaining appropriate services for the SUs. Professionals need extensive knowledge on these phenomena to best support SUs.The interviews also discussed the utilization of scientific knowledge. Factors that advanced the use of research relate to accessibility of research findings, both in terms of usability and accessing the journals and books where the research is presented in detail. Many of the participants working in small non-research–focused organizations brought up that the lack of sufficient access to knowledge is the greatest obstacle to following research in their professional field. Organizations do not necessarily have resources to pay for the fees to access research publications. Another important factor is that concepts, expressions, and terminology used in research need to be accessible to both professionals and SUs. Participants also raised a concern that scientific knowledge of rehabilitation is fragmented and scattered across various communication channels, leading to difficulties in finding the right information and a delay in the implementation of the scientific knowledge into practice.The future knowledge needs covered six interrelated topics. The vivid discussions concerned digitalisation and remote rehabilitation, multi-professionalism, the contexts of rehabilitation, the change process of the individual SU, impact and effectiveness, and work ability and functional capacity. The pace of rapid change in society, such as digitalisation, was also brought up in the discussions, as was urbanization and immigration.Opportunities offered by digitalisation and technological development, as well as remote rehabilitation, formed essential knowledge needs for the future of rehabilitation research. One participant reflected on the topic by saying:We are going toward remote rehabilitation. Rehabilitation does not only take place face-to-face with the rehabilitee. Now it would be a good time to study the effectiveness of remote rehabilitation. We need knowledge about what remote rehabilitation is, what it brings, what is good, and its effectiveness.Some participants called for controlled trials to evaluate the differences in the effects of face-to-face and remote rehabilitation methods. While remote rehabilitation was extensively discussed, digitalisation did not only relate to remote rehabilitation; participants also discussed other developments, such as the use of AI. The participants brought up the need to understand how AI will affect work processes and working with SUs. For example, it was seen as a tool to manage service paths in the complex service system, but the participants called for more information.The need to understand work and pre-assumptions of various disciplines and across rehabilitation practice in the future was important for the participants. One participant reflected on this saying:In practice you note, it is great to note this, that “wow! He or she is thinking like that”. And often we have these stereotypes of different professions and what they do. It is really rewarding to note that someone thinks totally different from you. It would be beneficial to know about these presumptions much more.Rehabilitation takes place in a specific context, and the discussions reflected the need to gain knowledge on the various contexts and significance of rehabilitation. More knowledge is needed on reablement. Participants discussed, for example, what needs to be considered to gain effective results within the reablement process. Significant knowledge needs noted not only concern of the micro-level factors, but also how meso- and macro-level development affects rehabilitation practices. The living environment, such as urbanization and its significance, was raised, as well as inequality more generally.The core of effective rehabilitation is providing the right services at the right time. This requires from the SU readiness and motivation for the rehabilitation process. At the micro-level, the participants brought up that they need more information on the change process of the individual rehabilitee to gain the best possible outcomes.Current and future knowledge needs in Jyväskylä  reflecteThis study uncovered the current and future knowledge needs of rehabilitation research from the perspectives of professionals and SUs. Two separate studies from two regions, Helsinki and Jyväskylä, showed that there are more common knowledge needs than regional differences. The current and future information needs of both regions are strongly related to enabling and understanding the needs of SU individuals for a meaningful and inclusive life and thus correspond well to current perceptions of good rehabilitation practices , 2.Another general need for knowledge in both areas concerns the promotion of multiprofessional and multidisciplinary rehabilitation and rehabilitation research, as described by Grigorovich et al. . The preThe future knowledge needs in both regions were related to the changing needs of rehabilitation and remote rehabilitation based on rapid change in society and digitalisation. Both results emphasized that more knowledge is needed about the individuality of the SUs and the significance of their environment for rehabilitation. More scientific knowledge is needed on the different rehabilitation practices and contexts that are expected to play an even greater role in the success of rehabilitation in the future. In Jyväskylä, future knowledge needs are also focused on the work and functional capacity of the SUs. In the Helsinki metropolitan area, more information was needed regarding the development and administration of rehabilitation in the future .Studies 1 and 2 produced similar and complementary results on the current and future information needs of rehabilitation research. In Both now and in the future, the scientific knowledge needs in Finnish rehabilitation will be emphasized in justifying the effectiveness, impact, benefits, competence, and use of resources for financiers and other parties. From the perspective of rehabilitation, this is an external need for information that does not directly aim to promote rehabilitation, but to justify existing rehabilitation. The situation is understandable through the ongoing reform of the social and health sector, the shrinking economy in the sector, and the consequent intensification of competition.The knowledge needs reiterate the importance of an SU's individuality and meaningful life for rehabilitation, as well as the importance of different environments, contexts, and rapid change. Applied rehabilitation research faces major challenges in meeting these information needs. In practice, this requires that professionals and users of practical rehabilitation work be interested in and have the opportunity to participate in the conduction of the study. Therefore, in the future, there will be a need to develop participatory research methods and inclusive research approaches.Ideally, the knowledge needs of the professionals and SUs should guide the research activities in rehabilitation. The current and future knowledge needs reflected a great variability and multiplicity of research subjects, and what the research needs should thematically address. The use of concepts by the participants may at some instances be less detailed. Some specifications, such as robotisation as part of digitalisation or specific measures at the workplace to enhance employability, may have not been explicitly pointed out.Scientific knowledge needs of rehabilitation should be viewed at different levels, and at a specific temporal and physical place and setting. First, professionals and SUs contemplated knowledge needs on the individual level. This study confirms the previously known notion that there is a need for research concerning a better understanding of individual needs and environments. For practical purposes, this will require research-based development of sensitive tools and methods for understanding individual preferences and needs. Second, at the professional level, there is a need for effective methods and practices, as well as a need to understand the role of SUs and their ownership of and possibilities to participate in the rehabilitation process. The involvement of the SUs also concerns knowledge creation: there is a need for research knowledge on participatory and democratic methods of knowledge creation, and especially about collaborative knowledge creation and activities, as well as reciprocal communication. Third, there is a knowledge need related to the wider societal level, such as the service environment, and particularly on the marketisation of the service and the austerity politics of public services. Rehabilitation practitioners need to have selling points to promote their work within and outside their organization.Technical solutions, digitalisation, and AI were seen as key factors both in remote rehabilitation practice and in research. Remote rehabilitation was brought up as an important field of urgent research; not enough is known on the practices and effectiveness of remote solutions, and rapid development of digital tools and programs calls for research on the topic. The interviews took place in the time of COVID-19 that perhaps raised the question of remote services more strongly compared to if there had not been a pandemic.Study 1 and study 2 brought together multi- and transdisciplinary groups of professionals, SUs, and students working in different areas and sectors of rehabilitation, including those working with unemployed people and families. They had long experiences of rehabilitation in different organizations. Some of them pointed out knowledge needs relating to individual characteristics, while others further identified extensive societal themes as knowledge needs of professionals. Private sector workers are faced with the demand to respond to the market, while those working in the public sector face municipal austerity politics that they wish to influence. According to Charmaz , the criThis study has some limitations. Given the multiplicity of professionals working in rehabilitation, and even the ambiguousness of the field, it was not possible to include all professions, which may hinder external validity. A more extensive and versatile selection of informants might have brought up new topics. Some professions (for example physiotherapists) are highlighted in the sample which may emphasize their knowledge needs in the results. However, the focus groups were multidisciplinary including several professions to even out the differences of knowledge needs of certain professions. Another obvious limitation concerns the choice of participants: study 2 included only professionals, while study 1 also included SUs. This is a significant difference between the groups, and its significance in terms of the diversity of perspectives enriches the material. Thus, its impact on the quality of research has been positive rather than restrictive. It should also be noted that in studies 1 and 2, different researchers acted as data collectors, analysts, and reporters. Because researchers' own perceptions can never be completely ruled out, they can be reflected in the content, interpretations, and perceptions of the interviews. To minimize this weakness, there were several investigators in both studies who discussed their interpretations together and, in addition, the investigator groups discussed both interpretations together. As noted, regardless of the differences between the FGs and regions in which the group discussions took place, there were no significant differences between the regional data collections.Finally, in this study, researchers have extensive experience in practical rehabilitation work. They have surrendered, through critical review and discussion, to an ongoing and long-term process in which previous experiences with perceptions of rehabilitation and its research have provided a background for understanding the phenomena. Scholars have been open to new ideas, which has helped to gradually break the boundaries of previous perceptions and see their shortcomings .Rehabilitation has received increasing global attention . It is aAccording to Peirce , the priThe raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.MT, EJ, NV, and TH conducted the interviews. MT, EJ, TH, SH, and SS analyzed the data. All authors contributed to the interpretation of data for the article, contributed to the drafting of the article, revising it critically for important intellectual content, provided final approval of the version to be published, made substantial contributions to the conception or design of the work, and agreed to be named on the author list and approved the full author list.This study was funded by the Ministry of Education and Culture (Grant Number 411287).The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Biomarker in metastatic castration resistant prostate cancer (mCRPC) treatment are rare. We aimed to compare the clinical value of circulating tumor cells (CTCs) and androgen receptor splice variant 7 (AR-V7) as biomarker in mCRPC patients undergoing androgen receptor-targeted agent (ARTA) treatment. Overall cohort (65 patients) was stratified regarding either CTC or AR-V7 status followed by further sub-stratification of the respective other marker. Subsequently, prostate specific antigen (PSA) response, progression free survival (PFS) and overall survival (OS)) of subgroups was compared. CTCs and AR-V7 were detected in 54 (83%) and 33 (61%) patients, respectively. All AR-V7 + were CTC +. We detected PSA response in all subgroups. For PFS and OS, biomarker stratification revealed differences between all subgroups. Interestingly, no significant differences of AR-V7 transcript copy numbers were detected between responding and non-responding patients. Additionally, multivariable analysis revealed no independent prognostic value of AR-V7 positivity. Both biomarkers show clinical value in prognosticating clinical outcome. Nonetheless, AR-V7 stratification underestimates the heterogenous subgroup of CTC − and CTC + patient, the latter requiring more intense clinical surveillance. Additionally, AR-V7 level does not correlate with clinical response. Thus, the value of AR-V7 as a clinical biomarker must be considered skeptically. Large patient analyses of CTCs revealed a prognostic threshold of CTCs in prostate cancer3.Studies on circulating tumor cells (CTCs) have significantly increased knowledge of dissemination of tumor cells from primary and metastatic tumor sites7. However, there are inconsistencies among study designs analyzing the correlation between AR-V7 and treatment response. Initially, correlation analysis was performed solely in CTC + patients, further subdivided into AR-V7- and AR-V7 + subgroups4. A follow-up study then included CTC − patients, resulting in three groups 7. Further studies stratified AR-V7- and AR-V7 + only, without determination of the CTC status12. Of note, all studies showed a subset of AR-V7- patients not responding to ARTA treatment, demonstrating additional resistance mechanisms other than AR-V7.Besides analysis of CTCs, expression of androgen receptor splice variant 7 (AR-V7) in CTCs of prostate cancer patients has gained clinical interest for prediction of non-response to androgen receptor-targeted agents (ARTAs), i.e., abiraterone or enzalutamideThus, both, CTCs as well as AR-V7, have been demonstrated to be potential clinical biomarkers. Nonetheless, both stratification approaches lack the integration of the other marker. Therefore, we aimed to comprehensively compare the risk assessment of CTC and AR-V7 stratification on clinical outcome in a defined cohort of mCRPC patients undergoing ARTA treatment.14. Briefly, blood samples of mCRPC patients (5 ml of each patient) were processed using the Dynabeads™ Epithelial Enrich Kit followed by mRNA isolation using the Dynabeads™ mRNA DIRECT™ Purification Kit . Complementary DNA (cDNA) synthesis was performed using the SuperScript™ IV VILO™ Master Mix  according to manufacturer’s recommendation, except for using a temperature of 55 °C.Blood sample preparation and CTC analysis have been described previously15. Thus, determination of KLK3-PSA transcript copy numbers can be used as a semi-quantitative tool to dissect CTC distribution. AR-V7 status was analyzed using a previously described custom-made AR-V7 TaqMan PCR assay, demonstrating identical performance compared to the Johns Hopkins University (JHU) AR-V7 assay14. All qPCR runs were performed along with TaqMan qPCR assays for housekeeping genes RPL37A (Hs01102345_m1) and HPRT1 (Hs99999909_m1) .For determination of CTCs, patient samples were processed followed by qPCR using a KLK3-PSA TaqMan assay (Hs03063374_m1) . A patient sample was determined CTC + when displaying a qPCR signal for KLK3-PSA. Given the nature of our CTC detection system, we are not able to determine the actual number of CTCs. However, patients display similar expression levels of KLK3-PSA in single CTCsFor comparative biomarker stratification and clinical outcome analyses the overall cohort was sub-grouped based on either KLK3-PSA mRNA detection as a surrogate for CTCs or AR-V7 mRNA expression into CTC − and CTC + as well as AR-V7- and AR-V7 + groups, respectively. The CTC + subgroup was further subdivided into CTC +/AR-V7- and CTC +/AR-V7 + patients. Also, the AR-V7- subgroup was further subdivided into CTC −/AR-V7- and CTC +/AR-V7- patients Fig. .Figure 1The primary endpoint was clinical or radiographic PFS. The assessment of response status took place at each routinely planned visit and was independently performed by experienced experts in the field of mCRPC. For the classification of response status, general condition (ECOG), presence of pain, laboratory constellations (mainly PSA) as well as imaging were considered. Clinical progression was defined as symptomatic progression (worsening or new prostate cancer-related symptoms). PSA progression was defined as confirmed increase of 25% or greater from baseline in case of no prior PSA decline and an absolute increase of 2 ng/ml or more from nadir (Prostate Cancer Working Group 3 criteria). During clinically and biochemically stable disease, imaging consisting of CT- or MRI-scans of thorax, abdomen, and pelvis as well as bone scans, was not performed routinely. When biochemical progression occurred or PD was otherwise presumed, soft tissue metastases were evaluated by CT- and MRI-scans and bone metastases were assessed by bone scans. For all patients, PD was defined according to RECIST 1.1 criteria for cross-sectional imaging and by PCWG3 criteria for bone scans.Secondary endpoints included PSA response and OS. PSA response was defined as a PSA decline of 50% or more from baseline at any time under therapy; best PSA response (maximum percentage decrease from baseline) was also determined. OS was defined as the interval from start of ARTA to death from any cause.p values are two-sided and statistical relevance was assumed with a p value > 0.05.Statistical analyses were performed using SPSS-Statistics V28.0  and Prism 8 V8.4.3 . The descriptive statistics are reported as medians with interquartile ranges (IQR). Uni- and multivariate analyses were done by Cox-regression-models. Hazard ratios (HR) are given with 95% confidence intervals (CI). All reported Further detailed information can be found in the Supplementary Material.The study was approved by the local Ethics committee  and all patients provided written informed consent. The study was conducted with provisions of the Declaration of Helsinki.The authors agree the terms of conditions for publication.Between June 2016 and December 2020, we prospectively enrolled 65 patients who started on either abiraterone (n = 46) or enzalutamide (n = 19). At the time of study closure in March 2021, the median follow-up was 14.0 (IQR 8–31) months. 33 (50.8%) patients started as first-line treatment, 15 (23.1%) patients as a second-line treatment and 17 (26.2%) patients were treated in a third- or higher line of treatment (Table Eleven (17.0%) patients of the overall cohort were found to be negative for KLK3-PSA expression, i.e., absence of CTCs, whereas 54 (83.0%) patients were found to be positive for CTCs. We did not notice AR-V7 expression in any CTC − patient. Within the subgroup of CTC + patients, we detected AR-V7 in 33 (61.1%) patients (CTC +/AR-V7 +) whereas 21 (38.9%) patients did not display AR-V7 expression (CTC +/AR-V7-). In the AR-V7- subgroup, 11 patients (33.3%) displayed absence of CTCs, 21 patients were found to be positive for CTCs (66.7%).p = 0.10)   in 31 (47.7%) patients of the overall cohort. Compared to the CTC + group (23/54 (42.6%)), more CTC − patients showed a PSA response   . By comparing CTC + versus CTC − patients, PFS was significantly longer for CTC − patients with 22 months (CI not estimable) versus 8 months (CI 5.5–10.5) for CTC + patients (p < 0.01)   versus AR-V + patients (6 months CI 3.6–8.4)) (.6–8.4) (p < 0.01), Hb ≤ 12 g/dl at baseline (p = 0.01), absence of PSA decline ≥ 50% (p < 0.01), CTC positivity (p < 0.01) and AR-V7 positivity (p < 0.01) were statistically prognostic for PFS (Table p < 0.01), PSA doubling time < 3 months (p = 0.04) and absence of PSA decline ≥ 50% (p < 0.01) were significantly associated with worse PFS, whereas AR-V7 positivity did not show association with an inferior PFS (p = 0.09) (Table p < 0.01), absence of PSA decline ≥ 50% (p < 0.01) and CTC positivity (p < 0.05) were significantly associated with worse PFS  Table . Within FS Table .p = 0.01) was independently prognostic (Table p = 0.02) was independently prognostic   . By comparing CTC + versus CTC − patients, median OS was not reached for CTC − patients compared to 15 months (CI 8.7–21.3) for CTC + patients (p < 0.01)  ) compared to AR-V7 + patients (13 months (CI 9.2–16.8)) (p < 0.01), bone metastases (p = 0.03), ALP elevated at baseline (p < 0.01), Hb ≤ 12 g/dl at baseline (p < 0.01), absence of PSA decline ≥ 50% (p < 0.01), CTC positivity (p < 0.01), AR-V7 positivity (p < 0.01) were prognosticators of worse OS , prior abiraterone or enzalutamide (p < 0.01), Hb ≤ 12 g/dl at baseline (p < 0.01), PSA doubling time < 3 months (p = 0.03) and AR-V7 positivity (p = 0.04) were prognosticators of inferior OS (Table p < 0.01) and CTC positivity (p = 0.03) were significantly associated with worse OS , prior abiraterone or enzalutamide (p = 0.02) and Hb ≤ 12 g/dl at baseline (p < 0.01) were independent prognosticators for worse OS (Table p < 0.01) was independently prognostic for worse OS (Table p = 0.04) and Hb ≤ 12 g/dl at baseline (p < 0.01) were independent prognosticators for worse OS  and non-responding (N) subgroups.For PSA response, no significant difference of KLK3-PSA transcript copy number was detected between responders and non-responders in the CTC + subgroup, whereas AR-V7 transcript levels were significantly lower in responding patients compared to non-responding patients Fig. A. By appWe next aimed to perform a more conservative estimation by using the upper confidence interval as threshold to stratify patients into responders (above upper limit) and non-responders (below upper limit). By this, significant differences in KLK3-PSA transcript copy numbers were observed for both PFS and OS. However, for AR-V7, we did not detect any significant differences Fig. C. This vBy dissecting distribution of biomarker positive patients (CTC + and AR-V7 +) among distinct lines of treatment, we detected a significant increase of AR-V7 + patients during disease progression, while the number of CTC + patients tend to stay similar Fig. D. ContraWe next intended to correlate biomarker subgroups and criteria of an advanced stage of disease . We detected a significantly higher number of criteria representing a more advanced stage of disease within both, CTC + compared to CTC − and AR-V7 + compared to AR-V7- subgroups Fig. A. WhereaIn this study, we comprehensively compare the correlation of both, CTC and AR-V7 status, with clinical parameters in a cohort of mCRPC patients undergoing ARTA treatment. The results of our study indicate that both, CTC + versus CTC − and AR-V7 + versus AR-V7- stratification, can effectively prognosticate clinical outcome. Nonetheless, we demonstrate potential flaws by focusing on AR-V7 as a sole biomarker.20. The number of more than 5 CTCs per 7.5 ml blood sample highly correlates with a worse prognosis21. Furthermore, CTC analyses not only determine CTC counts at baseline but might also be applicable during treatment. A decrease of CTC count of more than 30% during the first 12 weeks of treatment is associated with a good prognosis19. Also, PCWG3 guidelines recommend CTC counts as an endpoint in patients with unfavorable counts at baseline in clinical trials22. Our results validate the prognostic power of CTC determination by demonstrating a worse clinical outcome in CTC + versus CTC − patients with respect to PSA response, PFS and OS. When semi-quantifying the number of KLK3-PSA transcripts as a potential surrogate for actual number of CTCs, we detected a significant increase in transcript copy numbers in non-responding patients. This demonstrates the value of CTC number determination to prognosticate clinical outcome. Additionally, CTC positivity is associated with a more advanced stage of disease. Our results therefore underscore the validity of CTC detection approaches for clinical applications.The presence of CTCs vividly holds the potential of a prognostic biomarker in mCRPC4. Although clinical outcome was worse in AR-V7 + patients, results might have been overestimated as AR-V7 + patients tend to suffer from an advanced stage of disease, e.g., higher number of previous treatments, higher serum PSA levels, and alkaline phosphatase levels. An extended follow-up study thus included CTC − patients and stratified patients into three categories: CTC −, CTC +/AR-V7- and CTC +/AR-V7 + 7. Within this study, significant differences were observed among the three subgroups, demonstrating the worst clinical outcome in CTC +/AR-V7 + patients. Consequently, the authors concluded, that AR-V7 analysis might be applied for prediction of ARTA treatment response. A biomarker-based application would imply clinical testing of AR-V7 status of all patients. Most recent studies then integrated dichotomous stratification of AR-V7 + or AR-V7- patients, without previous determination of CTC status12. In case of a strong predictive biomarker this stratification might be adequate. However, sole AR-V7 discrimination might be at risk of mis-consideration of severe clinical factors.Besides, AR-V7 has been discussed as both, a prognostic and predictive biomarker in mCRPC. Initially, expression of AR-V7 has been correlated to non-response to ARTA in CTC + patients23. When focusing on the CTC + cohort, no significant differences in PFS were observed between CTC +/AR-V7- and CTC +/AR-V7 + patients. Additionally, we did not notice differences in AR-V7 transcript levels between patients responding and non-responding to ARTA treatment. Thus, the actual levels of AR-V7 seem not to correlate with either response or non-response. Hence, our results challenge the clinical value of AR-V7 as a predictive biomarker for ARTA treatment.First, although PSA response is lower in AR-V7 + compared to CTC + patients, we show a substantial PSA response even in AR-V7 + patients. This is in line with previous reports demonstrating PSA response to ARTA even in AR-V7 + patients24. Given the lack of independent prognostic validity along with the fact, that a set of distinct criteria to stage patients into a high-risk subgroup, are already used in clinical routine, it remains unclear whether AR-V7 detection can add further information to improve patient treatment.Second, in case of OS, we detected a significant difference between CTC +/AR-V7- and CTC +/AR-V7 + patients, demonstrating a prognostic value of AR-V7. However, for neither PFS nor OS, AR-V7 positivity was found to be an independent prognostic factor for both the overall cohort as well as the CTC + subgroup. Appearance of AR-V7 increases over different lines of treatment. Furthermore, AR-V7 positivity is associated with presence of criteria related to a later stage of disease as well as a more aggressive subtype of prostate cancer. These results are in line with a recent study by Sharp et al., demonstrating a correlation of AR-V7 and a more advanced stage of diseaseThird—and presumably of highest clinical impact, focusing on AR-V7 neglects the heterogeneity of the AR-V7- cohort consisting of both CTC − and CTC + patients. A sole focus on AR-V7 would thus overlook the heterogeneity of this subgroup of CTC + and CTC − patients. As discussed earlier, CTC + patients display a higher probability of worse prognosis compared to CTC − patients and thus, need accurate and frequent clinical surveillance. Indeed, we detected significant differences between AR-V7-/CTC − and AR-V7-/CTC + patients with respect to both PFS and OS. Additionally, in terms of OS, presence of CTCs is an independent prognostic factor for both the overall cohort and the AR-V7 + subgroup. Therefore, sole AR-V7 stratification is of risk of underestimating the risk of rapid disease progression in a subset of AR-V7- yet CTC + patients.A limitation of this study is the relatively small number of included patients. Nonetheless, differences within the two biomarkers are obvious and significant.25.Conclusively, our results demonstrate a prognostic value of mCRPC patient stratification regarding both, CTC and AR-V7 status. However, CTC status is clinically more meaningful in prognostication, whereas AR-V7 status is of risk of underestimating the clinical differences in AR-V7- patients by not discriminating between AR-V7-/CTC − and AR-V7-/CTC + patients. Ultimately, similar PFS outcomes of AR-V7 + and AR-V7- patients within the subgroup of CTC + patients strongly question the power of AR-V7 as a predictive biomarker for non-response to ARTAs. Thereby, our study underscores recent expert opinion neglecting the usage of AR-V7 for clinical decision makingSupplementary Figure S1.Supplementary Figure S2.Supplementary Legends.Supplementary Information.Supplementary Tables.


Trichosurus vulpecula). Glucocorticoids (major hormones involved in stress responses) are metabolised in the body and excreted in the form of faecal glucocorticoid metabolites, which can be measured as a way of evaluating the response of animals to potential stressors. Comparing five enzyme immunoassay options, we found that the 11-oxoaetiocholanolone (abbreviation: 72a) EIA was the most suitable for measuring these metabolites in brushtail possums. This assay was then used to measure faecal glucocorticoid metabolite concentrations in 20 possums during rehabilitation. The probability of a physiological “stress” response occurring within five days of a potentially stressful event was about 50%, regardless of the type of event. There was a high level of variation in hormone profiles between possums. Our study has demonstrated that injured and orphaned possums show detectable changes in faecal glucocorticoid metabolites during captivity and rehabilitation, and has identified events that can induce a physiological response in some individuals. This is the first step toward understanding the relationship between these responses during rehabilitation and survival.Little is known about how exposure to novel stimuli during rescue and rehabilitation could affect the physiology of native wildlife. We investigated this question in a species commonly rescued for rehabilitation, the common brushtail possum (Trichosurus vulpecula). We evaluated five enzyme immunoassays (EIA) to determine the most suitable for measuring faecal glucocorticoid metabolites (FGM) as a proxy for evaluating the response of brushtail possums to potential stressors during rehabilitation. An adrenocorticotrophin hormone (ACTH) challenge was conducted on wild-caught possums to determine the best-performing EIA based on the successful detection of FGM peaks in at least two of three possums. While a number of assays met these criteria, the 11-oxoaetiocholanolone (abbreviation: 72a) EIA was selected as it had the largest amplitude of change in response to the ACTH challenge. This assay was then used to measure FGM concentrations in 20 possums during rehabilitation. There was high variation in baseline FGM concentrations and response to captivity between possums. Significant changes in FGM levels were detected in most possums during captivity, but were not reliably associated with potentially stressful events that were identified by rehabilitators. The probability of an FGM peak occurring within five days of a potentially stressful event was about 50%, regardless of the type of event. Our study has demonstrated that injured and orphaned possums show changes in FGMs during captivity and rehabilitation and has identified events that can induce a physiological response in some individuals. We recommend that research now focus on the relationship between these responses during rehabilitation and pre- and post-release survival.Volunteer wildlife rehabilitators rescue and rehabilitate thousands of native animals every year in Australia. However, there is little known about how exposure to novel stimuli during rehabilitation could affect the physiology of wildlife. We investigated this question in a species that commonly enters rehabilitation, the common brushtail possum ( Thousands of native animals are rescued and admitted for rehabilitation by volunteer wildlife rehabilitators every year in Australia ,2,3. TheA stressor is an event or stimulus that triggers a physiological response in the animal mediated by the hypothalamic–pituitary–adrenal (HPA) axis with the goal of resuming homeostasis, which can be accompanied by behavioural and autonomous nervous system responses ,17. The Circulating GCs in the bloodstream are metabolised into a range of molecules in the liver and gut which are excreted in faeces after a variable lag time. Faecal glucocorticoid metabolites (FGMs) are therefore a useful proxy measure for circulating GCs and can be quantified using an appropriate enzyme immunoassay (EIA) for the relevant metabolites ,34. ThisTrichosurus vulpecula)  are in the top 10 most-rescued species in NSW, Australia, with 5273 individuals rescued in the 2019–2020 financial year [Common brushtail possums  in rehabilitation had higher levels of faecal corticosterone metabolites and saliva corticosterone than wild hedgehogs [Phascolarctos cinereus) in rehabilitation found that faecal glucocorticoids increased on days when a stressor was recorded in two of three studied koalas [The relationship between captivity and the physiological response to stressors, as evidenced by changing GC concentrations, has been studied in several species ,50,51,52edgehogs , highligd koalas . HoweverThis study aimed to investigate the physiological response of brushtail possums to captivity associated with rehabilitation or hand-rearing. However, an appropriate FGM EIA has not been validated in this species ,54. HencTrapping was carried out over two consecutive nights (16–17 April 2018) at Macquarie University North Ryde campus (33°46′07.7″ S 151°06′47.5″ E). Eighteen Tomahawk live cage traps (65 × 24 × 24 cm) were covered with hessian and plastic bags and baited with half a peanut-butter sandwich and a quarter slice of apple. The traps were strategically placed around the campus on flat ground approximately one hour before sundown (16:30 to 17:30 AEST). All of the traps were checked 6–7 h after being set (23:30 to 00:30 AEST). Two female brushtail possums carrying back-riding young were immediately released at their site of capture. Adult brushtail possums in a healthy condition (body mass > 1.5 kg) of either sex were transferred from the site of capture in the hessian covered trap (maximum 5 min in transport) to their temporary housing for the challenge.n = 3 adult female, n = 1 adult male) used for the ACTH challenge were housed at the Macquarie University Fauna Park in individual wire enclosures  for nine nights. PIT tags (Biomark GPT12 pre-load sterile) were implanted under the skin between the shoulders for the identification of possums that were not previously tagged. The possums were housed individually in randomly assigned enclosures with an empty pen in between to reduce negative interactions that could affect their stress response. Plywood sheets were attached to the back half sides of the enclosures to separate them, and concrete flooring and steel roofing provided weather protection. The front half of the enclosure was unsheltered, exposed to adjacent pens, and laid with mulch. Tree branches were provided as enrichment, and wooden nest boxes were supplied. Food and water were provided daily (midday) ad libitum in bowls placed on top of a large plastic tub (60 × 43 × 33 cm) facing away from adjacent pens. This was undertaken to encourage the brushtail possums to leave their nest boxes to eat and drink as they would in the wild. A mixed diet of vegetables , fruit , nuts  and local native foliage was given. A small amount of supplementary food  was also given as enrichment. Food intake was recorded daily (in grams) as the amount of food eaten and the amount remaining from the previous day. The brushtail possums were weighed on entry into captivity (day zero), day two, day five, and upon release by suspending them in a hessian handling bag from a spring balance (Pesola Macroline 80005). Any individual showing poor food intake or a 7–10% reduction in body mass in the first 3–5 days was released from captivity at their original capture site  received an intramuscular injection to the thigh of 1 mL of synthetic ACTH, Synacthen , using a sterile 19 mm, 22-gauge Terumo needle. Fresh faecal scats were collected from each enclosure on day zero as a baseline measure. Samples were collected up to twice daily on days one through nine and stored at −20 °C. The ground was swept clean after each sample collection.On the night of capture (day zero), each brushtail possum  pellets each, from a discrete pile) were collected from 3 of 4 individuals prior to administration of ACTH (Day 0), from all possums within 24 h of ACTH administration, and on each day in captivity. Brushtail possums reportedly produce an average of 70 faecal pellets per day . One faeTo quantify FGM levels from faecal samples, frozen samples were heat dried for approximately 18 h in a laboratory oven  set at 60 to 70 °C. They were then crushed using a mallet and sieved through fine mesh. The sieved faecal powder was stored in vials at −20 °C until steroid extraction took place. For steroid extraction, the samples were weighed  and transferred into test tubes, then 2.5 mL of 80% methanol was added to each tube. The tubes were vortexed for 15 s and then shaken on an orbital shaker  at 210 rpm for 1 h at room temperature before being centrifuged at 2500 g for 15 min. The supernatant was transferred into labelled glass vials and stored at −20 °C.®, Ann Arbor, MI, USA) (hereafter referred to as AA-corticosterone) was run as per the manufacturer’s instructions [The Arbor Assays corticosterone EIA mini-kit  (hereafter referred to as CJM006) was run as reported elsewhere with faecal extracts diluted to 1:16 in assay buffer prior to analysis . The polThe 11-Oxoaetiocholanolone (72a) EIA produced in Vienna  has previously been used in broad-spectrum FGM investigations . The assThe cortisol EIA (hereafter referred to as R4866) was originally developed by Coralie Munro  and was used as described previously  with fae®, Ann Arbor, MI, USA) (hereafter AA-cortisol) was run as per the manufacturer’s recommendations with faecal extracts diluted to 1:12 in assay buffer prior to analysis. It has a reported cross-reactivity of 100% for cortisol, 42.08% for dehydocortisol, 26.53% for cortisone, 4.1% for dexamethasone, 3.37% for prednisone, 0.35% for corticosterone and 0.18% for desoxycorticosterone (as per the manufacturer).The Arbor Assays cortisol mini-kit EIA .EIAs in the validation analysis were evaluated using a 450 nm filter on an ELx808 BioTek microplate reader using Gen5 Software at the time of plate reading, and the intra- and inter-assay coefficients of variation were <10% and <15% respectively for all assays. All samples from an individual were run on the same plate. Parallelism was demonstrated for serial dilutions of pooled samples relative to the standard curve for each EIA  branches in and around the Greater Sydney region in NSW were recruited to take part in the study. Rehabilitators were provided with a sampling kit containing plastic zip-lock bags, labels, gloves, and data sheets. They were instructed to collect fresh scat samples from animals on arrival into care, followed by collections every day for a week, then once or twice a week for individually housed possums. The samples were kept frozen to preserve the integrity of the faecal constituents . RehabilA total of 221 samples were analysed from 20 individual brushtail possums. The possums were classified based on the length of care and severity of ailment as (a) orphan: juvenile possums hand-reared by a rehabilitator; (b) short-term: possums that were in care for less than 14 days and did not suffer from a long-term disease or injury  and (c) long-term: possums that were in care for more than 14 days or suffered from a long-term disease or injury. In each classification, the possums were then divided by sex  and by life stage . Juveniles were still dependent on their mother or wildlife rehabilitator, sub-adults were no longer dependent on their mother but were not sexually mature, and adults were independent and sexually mature. The 20 possums in this study included nine orphans , two short-term individuals , and nine long-term individuals .® 800 TS Absorbance Reader and analysed with a 4-parametric logistic fit using MyAssays Analysis Software Solutions (www.myassays.com (accessed on 23 October 2019)). The mean intra- and inter- assay coefficients of variation were 18.3% and 12.6%, respectively. All of the samples from an individual were run on the same plate.Scat samples from four of the 20 possums in rehabilitation  were sent to the University of Queensland, Gatton, for extraction and analysis to initially confirm that the 72a EIA would detect FGM changes in possums during rehabilitation . The extraction protocols described above for the ACTH challenge samples were followed. The samples from the remaining 16 possums in rehabilitation were analysed at The University of Sydney and the extraction protocol was modified slightly due to an increased amount of faecal matter available; in brief, the faeces were dried as described above, weighed at 0.2 g (range 0.18 g to 0.22 g) and extracted with 5 mL of 80% methanol. EIA analyses for all 20 possums’ samples followed the above protocol for 11-Oxoaetiocholanolone (72a) EIA and were read at 450 nm using a BioTekAll statistical analyses were completed in R version 4.0.5 . ParalleThe data were highly unbalanced across age , sex  and type of care  groups. Therefore, we tested for effects of age, sex, and type of rehabilitation on baseline threshold using separate ANOVAs with subsets of data that had sufficient sample sizes as follows: adult females (short-term versus long-term rehabilitation); long-term females (adult versus sub-adult age); orphan juveniles ; all females ; all females .Events that were identified by rehabilitators as potential stressors during the sampling period were categorised into Enter Rehabilitation and Other Events. We combined all events other than entering rehabilitation  was released from captivity on day four due to declining weight (6.4% body mass loss) and poor food intake. The results for this possum are presented, but not included in the EIA validation analysis due to lack of sample days.All five EIAs detected peaks in at least two of three possums . The detSix rehabilitators from three WIRES branches  provided samples from 34 possums. However, only 20 possums were included in this study due to insufficient sample numbers for 14 possums (≤ four samples). Rehabilitators described 10 event types that may have induced distress in the possums, including entry into rehabilitation, moving cages, escape from the cage, the introduction of new animals, administration of oral medicines, injecting medicines, handling, removing the cover from the cage, another possum riding their back and separation from buddy animals. = 4.97, p = 0.076); adult or sub-adult age of long-term females  = 0.667, p = 0.451); male or female sex for orphan juveniles  = 0.878, p = 0.380); short-term, long-term or orphan rehabilitation for females  = 0.411, p = 0.673); or adult, sub-adult or juvenile age for females  = 0.106, p = 0.900)  to 2409 ng/g , with a mean of 748 ng/g (SD 599) for the 20 possums. There were no significant effects on baseline threshold of: short-term or long-term rehabilitation for adult females (F= 0.900) .n = 6 of 15), the cover of the cage being removed (n = 1 of 1), being moved to a new cage (n = 4 of 5), a new possum entering the same cage (n = 1 of 2), handling (n = 2 of 2), being separated (1 of 2), and receiving an injection , escape from the cage (n = 0 of 1) or receiving oral medication . The mean probability of an FGM response occurring within 5 days of an event was 47.7% (s.e. 7.4%).Eighteen of the 20 possums had increases in FGM concentrations (above baseline) after entering rehabilitation. Of these, 11 possums had peaks that occurred within five days of recorded potential stress events. Some possums expressed an FGM response soon after entry into rehabilitation . Interestingly, the possum that was released from the study due to declining body condition showed a rapid increase in FGM of a large magnitude, suggesting that it was not coping with the captive environment. The sample size of three possums present for the validation process was sufficient for selecting an appropriate EIA but limited our ability to assess a wide range of individual animal responses. Similarly, few individuals per species were used in Fanson, et al.  to effecLasiorhinus krefftii), yellow-bellied glider , long-nosed potoroo (Potorous tridactlus), woylie (Bettongia penicillata), southern bettong (B. gaimardi), eastern grey kangaroo (Macropus giganteus) and western grey kangaroo (M. fuliginosus) [The 72a EIA was selected as the best option for further study of the GC response to rehabilitation in brushtail possums as it measured the greatest range of FGM concentrations and expressed the clearest increase and peak in FGMs in response to the ACTH challenge. The 72a EIA was the only assay to detect peaks in all three possums, likely because it is a group-specific assay, and these have been found to yield a stronger signal than cortisol or corticosterone assays . A recenginosus) . The 72aNotamacropus eugenii) increased by between 59% and 226% [Gorilla gorilla gorilla) increased in response to relocation, health checks, and introduction to other animals [The possums involved in the ACTH challenge were exposed to both a natural stressor (capture and captivity) and a synthetic stressor (injection of exogenous ACTH) concurrently. Natural stressors are known to increase FGMs in wildlife, for example, following isolation and movement, baseline corticosterone of tammar wallabies  [The FGM peak times post ACTH challenge were highly variable across EIAs, even for the same individual. As faecal samples were only collected up to twice daily, the exact time between defecation and collection was unknown. In koalas, there was no effect of time since defecation for up to seven days for either faecal cortisol or corticosterone metabolite concentrations . So, altampling)  to 24 anampling) . An IV iampling) . A previampling) . TherefoEudyptula minor), there were no long-term effects of rehabilitation on adrenal responses to humans in comparison to wild penguins [Loxodonta africana) showed that FGMs were elevated during translocation but returned to baseline levels within 23 days [The initial response to entry into rehabilitation could differ depending on the possum’s existing condition at the time of rescue, although there was too much variation in FGM responses in our study to draw any conclusions. There was a decrease from above baseline FGMs for one of eight adults without exudative dermatitis and two of three sub-adults with dermatitis, also known colloquially as stress dermatitis due to its possible association with environmental stressors ,73 or inpenguins , and a s 23 days . Acute s 23 days ,77 and c 23 days . For exa 23 days . TherefoThe events that were recorded by rehabilitators as potential stressors were followed by an FGM response within five days in about 50% of cases. Previous studies have shown that captivity is associated with stressors for wildlife including capture and handling, social stress, and unfamiliar sensory stimuli ,80,81. HRattus norvegicus and Rattus rattus) did not observe any chronic stress due to captivity [Lontra canadensis) found that FGM did not increase over the first 10–12 days in captivity [There is some evidence that holding wild animals in captivity can induce chronic stress  and theraptivity , and a saptivity . FurtherPseudocheirus peregrinus), and assessing the relationship between the physiological GC response during rehabilitation and post-release survival.Future studies can build on our dataset by increasing the timespan of sample collection, recruiting a larger sample size, assessing the effects of seasonality ,91,92, aIt is widely accepted that minimising stressful stimuli experienced by wildlife in captivity is important for their welfare. However, we need to determine what constitutes stressful stimuli for wildlife and whether this can change depending on the species, the context, or the characteristics of the individual. We have provided evidence that brushtail possums exhibit changes in FGMs during captivity and rehabilitation with a high level of individual variability, and our findings are a starting point for assessing the link with potentially stressful stimuli. We also need to know if there could be any disadvantages of removing potential stressors, such as reduced fitness after release. To reduce stressful stimuli, rehabilitators are trained to cover an animal’s head when handling it to keep it calm, decrease noise, use slow movements, and cluster activities to reduce the number of human interactions ,95. HoweOur study has successfully identified a suitable EIA for measuring FGMs in common brushtail possum faeces and has detected physiological GC changes in possums in rehabilitation. We recommend that future studies examine how specific stressors affect physiological changes. We have developed a list of potentially stressful stimuli that preceded a transient rise in FGMs in captivity for some possums, and this builds upon previous work in other species ,80. We d


Motor function rehabilitation training is to restore the motor function of hand injury to the maximum extent and meet the needs of patients' daily behavior. At present, motor function evaluation and rehabilitation training work have disadvantages such as relying on the subjective experience of physicians, unable to quantitatively assess the loss of motor function, and single rehabilitation training method. Most of these methods only focus on the independent motion range of a single organ, lack of consideration of the constraint relationship between adjacent fingers, and do not build a visual model for it. To end this issue, for the purpose of sports rehabilitation, combined with the status and application of rehabilitation machines, this paper proposed a cycling rehabilitation training system based on physiological signal extraction of ensemble empirical mode decomposition (EEMD) algorithm. Results compared with the previous rehabilitation training, the muscle tension level of patients' upper limbs decreased, and the strength of some muscles also increased. With the progress of rehabilitation training, the contralateral dominance coefficient showed an upward trend, which further confirmed the role of the proposed method in sports rehabilitation, and also provided a new idea for the evaluation of rehabilitation training effect of patients in the future. According to the data of the sixth national census in 2010, the population aged 60 years and over accounted for 13.26% of the total population in China, among which the population aged 65 years and over accounted for 8.87%, up 2.93 percentage points and 1.91 percentage points, respectively, compared with 2000. With the rapid development of population aging, many countries in the world have also entered the aging society. In modern society, with the increase of the number of elderly people, the health status and disease care of the elderly are more and more concerned by the society .Long ago in our country, many institutions have been carried out on lower limb rehabilitation robot research, the purpose is to gradually replace the traditional medical division as the core of rehabilitation. According to the different degree of rehabilitation of lower limb movement disorders, lower limb rehabilitation robot can provide incremental training mode, from auxiliary training to active rehabilitation training . The lowMany clinical patients have motor dysfunction to a certain extent. How to restore their motor skills has always been a difficult problem in the field of rehabilitation training. However, traditional rehabilitation training methods are often unable to fully mobilize the enthusiasm of patients, and there are safety risks, such as hand arm rehabilitation training is easy to cause new injuries due to collisions, and patients cannot complete complex movements through the mechanical arm to adapt to daily life. The results show that a large number of repetitive and high-density rehabilitation training can maximize the recovery of patients' physical functions, improve their quality of life, and improve their ability to live, work, and study. The traditional rehabilitation training method is mainly carried out by auxiliary massage, which is required to be carried out in professional locations , 9. The At present, hand robots, data gloves, and virtual reality technology are mostly used for hand rehabilitation –14. HandWe designed a cycling rehabilitation training system based on physiological signal extraction of ensemble empirical mode decomposition (EEMD) algorithm.The muscle tension level of patients' upper limbs decreased and the strength of some muscles also increased.We provided a new idea for the evaluation of rehabilitation training effect of patients in the future.Based on the above discussion, the main contributions of this paper are given as below:The traditional rehabilitation monitoring is in rehabilitation doctor handy or with the help of a simple instrument to assist patients complete the process of rehabilitation training, in the process of rehabilitation training rehabilitation doctor based on their experience of the patient's physical condition after training the stand or fall of the degree and the rehabilitation effect of evaluation, the monitoring and evaluation method is largely dependent on been physician experience, level and state, low efficiency, have greater limitations. Some teams have carried out researches on home nursing and remote health monitoring and developed the home intimate little nurse system. The system is composed of a home monitor and a hospital console. The home monitor can record the ECG, EEG, and dynamic blood pressure of patients in the process of rehabilitation in real time . The hosThe nodes developed in the wireless monitoring system were significantly improved in mobility compared with wired physiological monitoring. However, there are still many deficiencies in comfort and convenience. In order to solve the above problems, people begin to combine the emerging wearable technology and wireless sensor network technology and gradually apply it to the design of physiological parameter monitoring system. Wireless body area network is a new wireless communication technology developed in recent years, which combines the advantages of wearable and wireless sensor network, and has become one of the frontiers and hotspots in the field of information research. Limb rehabilitation robots are military exoskeleton research and application based on the exoskeleton of features should be used on the rehabilitation medicine helps lower limbs dyskinesia patients with rehabilitation training, lower limbs dyskinesia patients go CCB ability. In recent years, some research institutions launched a lower limb rehabilitation robot product, but because of the lack of research on sensor technology information fusion technology and machine learning, the functions of rehabilitation robot products are still not perfect. The rehabilitation training system can adjust the pull value of the rope and change the size of the patient's lower limb support force according to the force of patients with different lower limb movement disorders. The system by stimulating the quadriceps femoris two receptors and adjust the patient's gait and posture, so that the patients completely simulate the normal gait trajectory, so as to help patients in the cerebral cortex to rebuild or rebuild the walking posture functional area with the help of the system, according to the rehabilitation degree of patients with lower limb movement disorders to choose the corresponding recovery pattern, make exercise treadmill lead the limb implement step the passive training and training, and other rehabilitation mode, provide more suitable for patients with lower limb dyskinesia rehabilitation plan, can also be suitable for more of the lower limbs dyskinesia patients rehabilitation training, at the same time, the system can timely feedback to the effect of rehabilitation training rehabilitation evaluation system, to the patients. The effect of complex training for health evaluation and identification of abnormalities and other functions.Sensor signals in recent years have been widely applied in the extraction and state recognition of human movement information, through the installation of different functional rehabilitation robot motion sensor's patients data, to identify different human body movement patterns to achieve higher recognition rate and more motion pattern recognition, many researchers around the feature extraction method research. However, from a single common in sensor signal can only identify a limited number of sports mode, switch signal recognition results only as a robot, so multiple sensor information fusion become another hot point in the robot technology, it can be partial data provided by the comprehensive analysis of multiple sensor information, keep the cross department between sensors. Divide and remove the conflicting information between them, based on sensor data between complement each other, reduce the uncertainty information systems, human-computer complete description of the consistent state can be formed, thus improve the robot intelligent decision-making and rapid response performance of industrial robot information fusion method including estimate class methods, such as mobile robot information theory method and statistical method artificial intelligence methods. In addition, machine learning has been widely used in various fields –25, by gHowever, there are few or even no rehabilitation monitoring systems for rehabilitation training occasions of stroke patients. In addition, the most physiological parameters monitoring system still stays on the physiological parameter data collection, and for data processing and analysis is not in real time, in the process of rehabilitation training, to achieve the best effect of rehabilitation, real-time control of the patient's body recovery, rehabilitation doctor must accordingly adjust training mode and training intensity. Therefore, it is very practical and necessary to research and develop a monitoring system for rehabilitation training.The system designed in this paper is a platform capable of 3D robot kinematics and dynamics simulation and the interface of the system designed in this paper for sports rehabilitation, which is shown in Compared with traditional hand function evaluation and rehabilitation training, the functional evaluation and rehabilitation training system based on EEMD has prominent advantages, which are embodied in the objectivity of evaluation process and results, the interest of rehabilitation training, the improvement of the efficiency of medical resource allocation, and cost saving, etc. Specific analysis is as follows: all evaluation indexes are expressed in the form of joint angle values, and the quantified evaluation results can more objectively reflect the patient's hand motor function, and also help to compare the evaluation results with each standard index to find out the specific problems of motor dysfunction. On one hand, the physical movement skills learned by users in the virtual environment can be better transferred to real life; On the other hand, virtual games can greatly stimulate the initiative and enthusiasm of patients to participate in rehabilitation training. On the one hand, this system is based on the ROS distributed architecture and publishers—subscriber information communication mechanism, for evaluation and rehabilitation training data exchange and storage convenience, rehabilitation trainer can prompt understanding through the network to the patient's recovery and give guidance, shortens the recovery period, improve the efficiency of rehabilitation treatment. On the other hand, patients can conduct evaluation and rehabilitation training in the community street or at home, which not only solves the problem of lack of medical resources at the present stage but also greatly saves human and material resources and financial resources, avoiding patients to run repeatedly between family and hospital.In the common empirical mode decomposition (EMD) method, obtaining a reasonable intrinsic mode function (IMF) depends on the distribution of signal extreme points. If the signal extreme points are not evenly distributed, mode aliasing will occur. For low signal-to-noise ratio and the diesel engine vibration signal are nonstationary characteristics, etc., adopt EEMD, adding white noise to decompose signals, using the uniform distribution of white noise spectrum, when the signal on consistent throughout the time-frequency spatial distribution of white noise background. After multiple averaging, the noise will cancel each other, and the result of the integrated mean can be used as the final result. In addition, EEMD decomposition method is also adaptive, which is superior to wavelet analysis:h1(t) two conditions of IMF component are not met, the above steps should be repeated as the original signal to obtain the data sequence as h11(t), i.e.,If the c1 from the signal X(t)It is going to be separated In order to ensure that each IMF has the physical significance of amplitude and frequency modulation, the conditions are transformed into the following formula:Then the classification decision values of a user's offline training model are calculated by  as belowThe average envelope of the last cycle is as follows:The ideal SD value should be between 0.2 and 0.3 so that the original data can be represented by the sum of the IMF component and the residual term:The designed system can be divided into four main modules  selects two sub-band signals , , decomposes by EMD and selects the first two order IMFs. The data obtained from each test were decomposed by WPT, sub-band signals were selected, EMD decomposition was performed, IMF was selected, and the first two IMF components were combined and reconstructed. Then, CSP was used for feature extraction. Before using EMD, this paper extracts relevant EEG signals, selects the data of C3 and C4 channels, obtains a series of narrowband signals through WPT, and then performs EMD decomposition of corresponding sub-band signals to obtain multiple IMFs. The first two orders are selected as new inputs, forming 8 (channel) 2000 The matrix Finger horizontal rehabilitation assessment is to evaluate the rehabilitation of finger extension and abduction motor function assessment of finger extension and abduction motor function assessment is divided into static motor function assessment and dynamic motor function assessment static motor function assessment is independent motor function assessment of finger extension and abduction. Dynamic motor function assessment was used to assess the combined adduction and abduction of the index finger and middle finger.The percentage of the independent range of motion in the horizontal direction of the injured finger is the comparison of the standard range of motion in the extension and abduction of the injured finger. The comparison of the range of motion in the extension and abduction of the three patients is shown in Considering the efficiency and accuracy of real-time operation of online system, the separability of data classification results of offline training is discussed below. To test the electrical control clinical training operation performance, functional electrical stimulation recovery system to recruit two stroke patients  participated in the neurological rehabilitation clinical rehabilitation training test machine. As a reference, 2 healthy volunteers may also participate in the clinical test, training in the process of synchronization acquisition EEG data. In addition, in order to verify the rehabilitation effect of the system, a long-term rehabilitation training tracking was conducted for one of the patients, and the data collected during the process were analyzed for individual cases. Rehabilitation training was conducted 2–3 times a week, with each training lasting about 40 min. EEG data were collected synchronously during the experiment and the tracking process lasted for 3 months, among which the first months and 3 months for upper limb rehabilitation training (wrist and training), the second month for lower limb rehabilitation training, and record related clinical common rehabilitation rating scale. Functional electrical stimulation of rehabilitation in addition to the electrical control system, the whole process of rehabilitation training in patients with only accepted according to the traditional treatment, and no drug rehabilitation training in rehabilitation process. All 4 volunteers performed the right wrist extension exercise task.As can be seen from In order to prove the effectiveness of the proposed method in different states of exercise rehabilitation. As shown in With the continuous improvement of living standards, the poor diet and the aging of the population have led to an increase in the number of patients with impaired motor function year by year, and the social burden has become increasingly heavy in order to help these patients recover or recover the motor ability of limbs to a certain extent.In this paper, EEG signal processing methods are studied, including pretreatment, EEMD combined with WPD and CSP for feature extraction of EEG signals, and SVM method are used for pattern classification of extracted feature EEG signals, and the progress of this method is verified by experimental data. An online brain-computer interface (BCI) upper limb rehabilitation system based on motor imagination was designed, and several experiments were carried out. The system can control the robot arm in real time based on EEG signals of the experimenter and can realize the synchronization of EEG signals with the robot arm Experimental results show that the brain-controlled online arm rehabilitation system designed in this paper can fully improve the rehabilitation effect of patients with impaired motor ability.In this paper, an online MI-BCI upper limb rehabilitation system is designed based on the research of EEMD processing method. Based on my limited knowledge and ability level, and the rapid development of EEG signal processing technology, in view of these situations, the directions to be improved in the research of this paper are envisaged: The improvement of EEG collection method and equipment can improve the accuracy of EEG collection without noise interference. However, the research in this paper is only limited to the exercise rehabilitation training system of EEG signal, and the amount of data and data types involved are small. Big data and multiple kinds of data will be the focus of future research.