To evaluate the effectiveness of a tailored intervention to reduce low value MRIs and arthroscopies among patients ≥ 50 years with degenerative knee disease in 13 Dutch orthopaedic centers (intervention group) compared with all other Dutch orthopaedic centers (control group).All patients with degenerative knee disease ≥ 50 years admitted to Dutch orthopaedic centers from January 2016 to December 2018 were included. The tailored intervention included participation of clinical champions, education on the Dutch Choosing Wisely recommendation for MRI’s and arthroscopies in degenerative knee disease, training of orthopaedic surgeons to manage patient expectations, performance feedback, and provision of a patient brochure. A difference-in-difference analysis was used to compare the time trend before (admitted January 2016–June 2017) and after introduction of the intervention (July 2017–December 2018) between intervention and control hospitals. Primary outcome was the monthly percentage of patients receiving a MRI or knee arthroscopy, weighted by type of hospital.β =  − 0.15, P < 0.001) and by 0.19% per month for arthroscopy . However, these changes over time did not differ between intervention and control hospitals, neither for MRI  nor arthroscopy .136,446 patients were included, of whom 32,163 were treated in the intervention hospitals. The weighted percentage of patients receiving a MRI on average declined by 0.15% per month (The extent to which patients ≥ 50 years with degenerative knee disease received a MRI or arthroscopy declined significantly over time, but could not be attributed to the tailored intervention. This secular downward time trend may reflect anoverall focus of reducing low value care in The Netherlands.III. Due to the ageing population, more people will suffer from degenerative knee disease in the future , 48. NowSince 2014, clinical practice guidelines from professional orthopaedic associations , 7 as weNevertheless, many patients are still referred for a MRI or knee arthroscopy for symptomatic degenerative knee complaints , 42, 44.To create more awareness and reduce the routine use of MRI and knee arthroscopy in degenerative knee disease, “Choosing Wisely” recommendations were developed in several countries , 9, 47. n = 49; 2017: n = 55, 2018: n = 54).The Medical Ethical Committee (CME P16.190/NV/nv) of the Leiden University Medical Center waived the need for ethical approval for this study under Dutch law. A difference-in-difference design was used to compare the change in time trend before and after introduction of the intervention between intervention and control hospitals. Anonymized patient-level data were extracted from the Dutch National Basic Registration of Hospital Care (LBZ)  for all For each anonymized patient and care trajectory, information was obtained on patient characteristics , type of orthopaedic center , Diagnosis Treatment Code (1801–1899), group (intervention or control), MRI conducted (yes/no), arthroscopy conducted (yes/no), number of MRIs conducted, number of arthroscopies conducted, month and year care trajectory opened and closed, date of MRI, date of arthroscopy, number of other care trajectories open at that time point, and type of care trajectory . It was defined the period January 2016–June 2017 as before the intervention, and July 2017–December 2018 as during/after the intervention. If patients had multiple care trajectories for the same DTC (e.g. for every visit and/or treatment), it is likely that these all belong to the same care path so only the DTC for the last opened care trajectory were then used.A local clinical leader who encouraged colleagues to follow the clinical practice guidelines (July 2017),Education for orthopaedic surgeons to increase their knowledge about the Dutch Choosing Wisely recommendation (July 2017),Training to improve their skills to manage patient expectations (September 2017),Feedback of performance data to orthopaedic surgeons , andA patient brochure that professionals could use in their consultations (January 2018).A tailored intervention was developed and implemented from July 2017 to February 2018 in the 13 intervention hospitals that participated in the ‘SMART’ (Step-down MRI’s and ARThroscopies) study. This intervention consisted of the following five components that were geared at previously identified barriers and facilitators  and baseThe primary outcome was the monthly percentage of patients receiving a MRI or knee arthroscopy in their care trajectory. Patients with degenerative knee disease were identified by diagnostic codes: arthrosis (DTC 1801) or meniscus lesion (DTC 1805). As a secondary outcome the monthly percentage of patients aged 50 years and over with a cruciate ligament injury (DTC 1820 and 1830) receiving a MRI or knee arthroscopy was calculated, which was expected not to be influenced by the tailored intervention.Descriptive statistics were used to compare characteristics of patients treated in intervention or control hospitals, stratified by type of hospital  as this is known to affect the hospitals’ patient-mix.A difference-in-difference approach was used to examine the change in monthly percentage of patients receiving a knee arthroscopy/MRI before and after introduction of the intervention between intervention and control hospitals . The monα + β1time + β2introduction + β3group + β4introduction × group, using linear regression analysis. In this equation, time covers 36 months, introduction refers to the period of introduction of the intervention , and group indicates intervention or a control hospital . The interaction term introduction x group therefore indicates whether the difference before and after introduction of the intervention differed between intervention and control hospitals. The same analyses were carried out for the secondary outcome in cruciate ligament injured patients, to assess whether there was a change in use of MRI or arthroscopy for a patient group not targeted by the intervention.For the difference-in-difference analysis, the following formula was used: weighted monthly % patients receiving a MRI or Arthroscopy = p value < 0.05 was considered significant in all analyses.Since the components of the intervention were implemented over a period of time, these may not all have resulted in an immediate effect. Sensitivity analyses were therefore employed assuming different lag periods after the introduction of the intervention in July 2017 to account for the time it takes an intervention to affect care delivery: 3 months, 6 months, and 8 months. In addition, sensitivity analyses were performed excluding patients with a start of the initial care trajectory before January 2016, and excluding patients with a start of the initial care trajectory in November–December 2018. These analyses were done since only partial care trajectories might have been included in the data, resulting in missing MRIs or arthroscopies. All analyses were carried out with R statistics (version 3.6.2). A 215,293 records for patients ≥ 50 years and over with degenerative knee disease were identified, which involved 136,446 patients with a care trajectory. Table introduction x group is the variable of interest to show the effect of the intervention, which is non-significant meaning that the change in percentage of patients receiving a MRI or arthroscopy before and after the introduction of the intervention, did not differ significantly between intervention and control group. In other words, the intervention did not significantly change the time trend in intervention hospitals beyond what already occurred elsewhere.Figures These analyses were repeated for patients with a cruciate ligament injury (diagnosis code 1820/1830) who were not targeted by the intervention (Appendix A). Again, a significant reduction in patients receiving a MRI was shown of 0.29% per month, but was non-significant for arthroscopy. As expected because the intervention was not targeted at these patients, no effect of the intervention was found as shown by the non-significant interaction term (introduction x group).Sensitivity analyses for the different lag periods  showed similar results (Appendix B and C). Other sensitivity analyses excluding patients with a DTC open before January 2016 and excluding patients with a DTC open in November 2018 or December 2018, also showed similar results (data not shown).The most important finding of the present study was that a secular time trend reduced the weighted monthly percentage of patients with degenerative knee disease receiving a MRI and arthroscopy across both intervention and the control hospitals. The tailored intervention designed to reduce low value care did not further reduce the percentage of patients receiving a MRI or arthroscopy.Previous research has shown that de-implementation of low value care in orthopaedic surgery is challenging and that providing a substitute will likely be more effective than doing nothing . This miIncreasing awareness among clinicians has been shown previously to result in changes in clinical practice, particularly for issues receiving widespread attention. For instance, Kiadaliri et al.  showed tOther studies have identified additional barriers that may influence decisions around performing MRI or arthroscopy, which may have been insufficiently addressed with the tailored intervention in the present study. Barlow et al.  found, fA strength of this study is that to a control group was included to take into account any secular time trends and separate this for the intervention effect. In the absence of such a control group, the change over time might be incorrectly attributed to the introduction of the intervention, as may have been the case in previous studies . HoweverThe findings of this study emphasize that it is unclear when additional quality improvement interventions are needed to reduce low value care, and when the ‘rising-tide’ phenomenon is enough to increase awareness and to implement new insights from trials or guideline recommendations. More qualitative research is needed to gain further insight into the ‘rising tide’ phenomenon, identifying when interventions are needed to de-implement low value care. Based on the findings of the study, orthopaedic surgeons are advised to improve their care by considering for which patients MRI or arthroscopy has limited value and by explaining to patients why MRI or arthroscopy has limited value, potentially supported by patient brochures.This study showed that the weighted monthly percentage of patients ≥ 50 years with degenerative knee disease who receive a MRI or arthroscopy was reduced across both intervention and control hospitals as part of a secular trend. The tailored intervention did not have an additional effect beyond this secular downward time trend.Box 1. SMART interventionClinical champions (July 2017): local clinical leaders who encouraged colleagues to follow the clinical practice guidelines developed for diagnosing and treating patients aged 50 years and over with degenerative knee disease (e.g. during team meetings about patients).Education to increase knowledge about the Dutch Choosing Wisely recommendation (July 2017): to increase knowledge of orthopaedic surgeons about the Dutch Choosing Wisely recommendation against the use of low value MRIs and knee arthroscopies for diagnosis and treatment of degenerative knee disease in patients aged 50 years and over, clinical champions were educated about this recommendations and the corresponding literature. Clinical champions subsequently disseminated this information among their colleagues using a power point presentation that was prepared by the research team.Training to improve skills to manage patient expectations (September 2017)): to improve orthopaedic surgeons’ skills to manage expectations regarding the value of MRI and arthroscopy within diagnosis and treatment of degenerative knee disease, orthopaedic surgeons and residents were trained how to explain patients why it is not recommended to perform an MRI or knee arthroscopy for patients with degenerative knee disease. This was done in a meeting in each hospital/private clinic making use of videos of a consultation with a patient with degenerative knee disease. These videos included were developed in collaboration with specialised Dutch orthopaedic surgeons , and included scenarios in which an orthopeadic surgeon prescribed an MRI or arthroscopy, but also scenarios in which the orthopaedic surgeons succeeded to explain to the patients that a MRI and/ or arthroscopy were not indicated. These videos were used to initiate a discussion among colleagues.Feedback of data regarding MRI and arthroscopy use : data about the total number of patients with degenerative knee disease (including diagnosis code 1801 arthrosis and 1805 meniscus lesion), and the number of patients with degenerative knee disease who received a MRI and/ or arthroscopy was requested from each participating hospital/private clinic from 2016 until 2018. The data were analysed and presented twice to all orthopaedic surgeons in the participating hospitals/private clinics with a specialization in the treatment of knee injuries and to the residents (September 2017 and February 2018). Feedback was presented once by a researcher and once by the clinical champion or by e-mail.Patient Brochure (January 2018): a patient brochure was developed to provide patients information about degenerative knee complaints, recommended treatments and an explanation why and in which cases MRI’s and arthroscopies can be regarded as low value care in diagnosis and treatment of degenerative knee disease. The patient brochure could be used during the consultation or could be given after the consultation to provide information about a stepped care strategy and the risks of an MRI and knee arthroscopy.


To describe a protocol for the pilot phase of a trial designed to test the effect of an mHealth intervention on representation and readmission after adult cardiac surgery.A multisite, parallel group, pilot randomized controlled trial .Adult patients scheduled to undergo elective cardiac surgery  will be recruited from three metropolitan tertiary teaching hospitals. Patients allocated to the control group with receive usual care that is comprised of in‐patient discharge education and local paper‐based written discharge materials. Patients in the intervention group will be provided access to tailored ‘GoShare’ mHealth bundles preoperatively, in a week of hospital discharge and 30 days after surgery. The mHealth bundles are comprised of patient narrative videos, animations and links to reputable resources. Bundles can be accessed via a smartphone, tablet or computer. Bundles are evidence‐based and designed to improve patient self‐efficacy and self‐management behaviours, and to empower people to have a more active role in their healthcare. Computer‐generated permuted block randomization with an allocation ratio of 1:1 will be generated for each site. At the time of consent, and 30, 60 and 90 days after surgery quality of life and level of patient activation will be measured. In addition, rates of representation and readmission to hospital will be tracked and verified via data linkage 1 year after the date of surgery.Interventions using mHealth technologies have proven effectiveness for a range of cardiovascular conditions with limited testing in cardiac surgical populations.This study provides an opportunity to improve patient outcome and experience for adults undergoing cardiac surgery by empowering patients as end‐users with strategies for self‐help.Australian New Zealand Clinical Trials Registry (ANZCTR): ACTRN12621000082808. When readmission rates have been investigated there are consistent features evident in the literature. Literature is generally focused on the efficacy of readmission rates as a quality of care metric . Readmission rates vary widely from 39% in a large multicentre study of patients having surgery in the late 1980s  in those settings  Victoria, Westmead or Liverpool hospitals, in NSW. The two NSW sites service a similar demographic to RMH. The RMH provides services to the western and northern suburbs of Melbourne, extending to Shepparton, Bendigo, Ballarat and Horsham. The RMH provides specialist services including adult congenital cardiac surgery and has an international reputation in valvular surgery and total arterial revascularization. Annually there are approximately 600 cardiac surgery cases performed at this site. The Western Sydney Local Health District (WSLHD) in NSW is the second most populous and has one of the fastest growing populations, expected to increase by almost half a million people by 2036. The catchment includes more than 120 suburbs, over a million residents and the healthcare provided equates to more than $1.8 billion dollars annually. In this district more than 600 cardiothoracic procedures are performed at Westmead hospital annually. Similarly, the South West Sydney Local Health District (SWSLHD) will have over a million residents by 2021, an increase of 21% since 2011. The population is culturally diverse and the district houses some of the poorest communities in NSW. Liverpool Hospital performs between 350 and 400 cardiothoracic procedures annually.The liaison nurse at each site leads initial contact with patients and placement on elective surgical waiting lists following referral receipt. They explain next steps and processes for preoperative preparation for surgery. They are also the point of contact for patients and families in the lead up to a date being booked for surgery and after the booking is confirmed. Waiting times on elective surgical lists are variable but most cardiac surgery cases are classified as either category 1 or 2 patients, with a median waiting time of 16–19 days in 2017–2018  undergoing elective CABGS, valve surgery, CABGS and valve or aortic surgery, discharged home in 30 days, able to understand spoken English, and they own and use a smartphone, tablet or computer. Exclusion criteria are patients 18 years of age or younger, patients undergoing thoracic, transplant or non‐elective surgery, not discharged in 30 days, not discharged to their home/primary residence, and unable to understand spoken English without an interpreter.2.5The intervention has been designed by Healthily, a nurse led organization that provides a range of health resources for consumers and clinicians focused on building patient knowledge and capacity for self‐help. GoShare Healthcare is Healthily's flagship product and a customized content distribution platform for health professionals to share up‐to‐date, accurate and engaging healthcare resources tailored to the needs of individual patients. An extensive process of consultation and content development is undertaken with clinician and patient involvement to ensure that materials are appropriate, informative and reliable. The cardiac surgery platform contains a patient narrative library with a series of videos describing patient and carer experiences, in addition to animations and links to reputable on‐line resources. Evidence indicates patient narratives have a positive impact on patient education because the information they provide is vivid, engaging, relatable and understandable  Database Registry, is approximately 4% annually. Each site performs an average of 10–15 cases per week. The aim is to recruit 20 patients from each site to a total of 60 patients, allowing for loss to follow up, prior to interim analyses in this pilot study. If two patients per week from each site can be recruited the trial should take approximately 10–12 weeks.RA‐1 will maintain an electronic randomization schedule, and using a computer‐generated permuted block randomization schedule, randomize the patient to intervention or control. The enrolment, randomization and follow‐up schedules will be housed in separate sheets in REDCap to ensure liaison nurses and RA‐2 are blinded to allocation. It is not possible to blind patients to the intervention, and they may disclose allocation to RA‐2. Data analyses will be complete by an investigator not involved in recruitment, allocation or outcome measurement.2.7REDCap  for analysis. Preoperative, intraoperative and perioperative data will be extracted from the ANZSCTS repository following 90‐day follow up. A minimum of 12 months after the date of surgery for the last enrolled patient, ANZSCTS data linked to the National Death Index will be accessed for the study cohort and combined with existing data that will then be screened for inconsistencies and errors. On completion of cleaning, linking variables will be removed, data will become non‐identifiable and aggregate analyses will be undertaken. Categorical data will be presented as frequency and proportion and continuous data as mean and standard deviation where normally distributed, or median with quartiles.2) or two‐tailed Fisher's exact test with appropriate degrees of freedom to test for equality of proportions. Independent samples t‐tests (two‐tailed) will be used to test for equality of means for continuous variables or the non‐parametric equivalent Kruskal–Wallis test. Univariate factors with a p value ≤0.25 will be considered eligible for multivariate analysis. Multivariate logistic regression will be used to identify predictors of readmission. Direct entry techniques will be contrasted with backward stepwise selection to build a parsimonious explanatory model of association. Model sensitivity and specificity will be reviewed using receiver operating characteristic curve analysis with 95% confidence intervals calculated.Preoperative demographic data, operative data and early postoperative complications will be compared between intervention and control group. Frequency of representation, readmission and mHealth metrics will be reported as proportions and the EQ5D‐5L and PAM endpoints are scale measures that will also be compared between intervention and control groups. The approach to analysis of repeated measures results from the EQ5D‐5L and PAM will be dependent on loss to follow up and normality of distribution. Categorical variables will be analysed using chi‐square . The trial poses low or minimal risk to participants and verbal informed consent has been approved in the context of COVID‐19 restrictions and a concomitant reduction in preoperative face‐to‐face appointments. Patients will be agreeing to an opportunity to access GoShare materials and receive the follow‐up phone calls from an expert cardiothoracic nurse (RA‐2). GoShare access further implies patients’ agreement. At the time of each follow‐up phone call RA‐2 will again confirm that the patient agrees to answers questions about their quality of life and level of activation in healthcare.The point at which the greatest patient burden or risk of discomfort is anticipated during the follow‐up phone calls. To counteract this risk an expert cardiothoracic nurse will conduct these calls. Should there be any concerns raised that warrant further investigation RA‐2 is well placed to provide appropriate advice to patients that may need to referral to support services. Liaison nurses, RA‐2 and the study PI will have monthly team meetings to ensure streamlined processes are in place and to ensure concerns are effectively addressed. If a patient chooses to withdraw from the study, data collected to date will be non‐identifiable and retained for the purposes of aggregate analyses.3Data from the Independent Hospital Pricing Authority indicates that in 2017 the average cost of a patient re‐presenting to an Australian Emergency Department was $533 and, if subsequently admitted, $969. In 2019 there were over 15,000 adult cardiac surgery procedures performed in Australia. Readmission was on average 10.2% for isolated CABG patients, 10.4% for isolated aortic valve surgery and 10.9% for combined CABG and valve. In 2017 the average rate of readmission for all case types was approximately 14%  not involved in follow‐up and the collection of outcome measures. Patients who are allocated to the intervention may reveal that to the investigator (RA‐2) collecting outcomes but valid, reliable objective instruments are being used to capture outcomes that should eliminate any risk of response bias.4Representation and readmission after cardiac surgery are potentially avoidable and costly. Interventions using mHealth technologies have demonstrated effectiveness for a range of cardiovascular conditions with limited evaluation in cardiac surgical populations. Findings from this study will establish whether improved self‐efficacy enhances self‐management and as such, the capacity to make decisions that reduce the likelihood of representing to hospital or requiring readmission. Patient participation and experience during the trajectory of recovery from cardiac surgery are neglected aspects of research in this specialty. This study will provide evidence to substantiate the value of mHealth and self‐efficacy for self‐management in patients undergoing cardiac surgery. Findings will also provide longitudinal representation and readmission data for quality benchmarking. A model of prediction will be built to inform preoperative risk assessment and discharge planning processes. In combination, outcomes from this research will provide a platform from which a program of research focused on future interventional studies augmenting patient patient‐led recovery can be developed.No conflict of interest has been declared by the author(s).http://www.icmje.org/recommendations/):Substantial contributions to conception and design, acquisition of data or analysis and interpretation of data;Drafting the article or revising it critically for important intellectual content.All authors have agreed on the final version and meet at least one of the following criteria (recommended by the ICMJE: https://publons.com/publon/10.1111/jan.15104.The peer review history for this article is available at


The transport of coronavirus‐2019 (COVID‐19) patients on extracorporeal membrane oxygenation (ECMO) is a challenging situation, especially for healthcare workers (HCWs), due to the risk of cross‐infection. Hence, certain precautions are needed for their safety. The study aims to evaluate the risk of COVID‐19 transmission to HCWs who transport COVID‐19 patients on ECMO device.A retrospective review of adult patients with COVID‐19 infection supported with ECMO and transported by ground route to the Medical Intensive Care Unit (MICU) at Hamad General Hospital (HGH) and a survey of HCWs involved in those cases.A total of 63 HCWs of the mobile ECMO team were exposed to COVID‐19‐positive patients on 199 occasions. HCWs exposure time was nearly 110 h, and the total transport distance was 1018 km. During the study period, only two of the mobile ECMO HCWs tested positive for COVID‐19. There was zero incidence of transfer‐associated injuries or accidents to HCWs.The risk of COVID‐19 cross‐infection to the mobile ECMO team seems to be very low, provided that strict infection prevention and control measures are applied. As of September 2022, over 600 million confirmed SARS‐CoV‐2 infections leading to coronavirus disease 2019 (COVID‐19) had been reported, with over 6.46 million related deaths.The SARS‐CoV‐2 transmission and significant risk to healthcare workers (HCWs) caring for patients with COVID‐19 have been reported worldwide.Whilst protecting healthcare professionals performing their duty is extremely important, solutions also need to be found to maximize the chances of survival of critically ill COVID‐19 patients. Extracorporeal membrane oxygenation (ECMO) has been suggested for severe acute respiratory distress syndrome (ARDS) secondary to SARS‐CoV‐2 infection.Dissemination of infection to transport team members and staff from other facilities is a major concern. Direct and close patient contact, mechanical ventilation, airway suctioning, accidental disconnection of the breathing system, or extubation are all potential AGP and may be encountered during transport.Transport and retrieval of COVID‐19 patients, particularly those critically ill who are put on ECMO, is challenging. The risk of HCWs cross‐infection may be considerable; hence, specific guidance for HCWs' safety during transfer has been issued.The mobile ECMO service at Hamad General Hospital (HGH) ; the premier healthcare provider in Qatar) was established in 2014 in preparation for the Middle East Respiratory Syndrome‐Coronavirus (MERS‐CoV) outbreak.The mobile ECMO activation and mobilization is following the local and international guidance.When possible, all cannulations were percutaneous, ultrasound‐guided, at the bedside or in the operating theatre with fluoroscopic guidance. After stabilization, patients were transferred with ECMO for pan‐CT scan at the referring facility, to the ambulance, and finally, to the Medical Intensive Care Unit (MICU) at HGH.We hypothesized that frequent, repeated, and prolonged exposures to COVID‐19 increase the risk of HCWs co‐transmission; thus, this retrospective study investigates the transmission of the novel SARS‐CoV‐2 to HCWs undertaking transport and retrieval on ECMO of COVID‐19 patients. The current study aims to investigate the incidence rate of COVID‐19 among mobile ECMO team members in the State of Qatar over a 10‐month period.22.1This retrospective cohort study was approved by the institutional review board MRC‐01‐21‐029). The STROBE checklist was followed to guide the reporting of the study findings . Categorical variables are expressed as numbers and proportions.2.5Statistical analysis was conducted using Excel version 16.45 (Microsoft Corporation).3During the study period, 34 mobile ECMO activations and cannulations were performed for patients with confirmed COVID‐19 infection. Patients were predominantly males (30/34) and of relatively young age . Patients were critically ill with high acute physiology and chronic health evaluation‐II (APACHE‐ II) score  and sequential organ failure assessment (SOFA) score . Thirty‐three successful veno‐venous and one veno‐arterial ECMO cannulation were accomplished. Patients' demographics, the severity of illness, and clinical characteristics are presented in Table A total of 63 different mobile ECMO team members were exposed to COVID‐19 patients in a total of 199 episodes of treatment. All of them consented to receiving and completing the online survey for the study. The frequency of mobile ECMO team exposure to patients with COVID‐19 encountered during transport and retrieval missions is summarized in Table During the study period, only two of the mobile ECMO team members tested positive for COVID‐19 by the lateral flow immunoassay rapid test. In addition, none of the HCWs reported an injury or incident associated with the missions. No untoward patient transport incidents were reported to the ECMO Transport program lead (Ahmed Labib).4Our report demonstrates a low risk of COVID‐19 cross‐infection to HCWs undertaking cannulation and transporting patients with COVID‐19 supported with ECMO. Over 10 months period, only two out of 63 members of the interprofessional mobile ECMO team tested COVID‐19 positive. Transportation and retrieval on ECMO are challenging and necessitate the implementation of the interprofessional, well‐trained team, checklists, and dedicated equipment. Current guidelines also recommend a hub‐and‐spoke model to better utilize resources and centrcentralizealise this highly demanding service.The risk of transmission of COVID‐19 infection to HCWs cannot be underestimated. Globally, nearly 4% of patients reported to be infected with COVID‐19 were HCWs.It is crucial to maintain staff safety and implement appropriate measures to prevent cross infection at all times and particularly during a pandemic where the number of cases is soaring, and the need for workforce across the health system is at a maximum. Transportation of COVID‐19 supported with ECMO presents the team with a multitude of practical, technical, logistical, and resource management challenges. Prior planning, effective communication, checklists, policies, training, and education are key elements to ensure staff safety and sustain the service.In a recent Italian report of VV‐ECMO cannulation and interhospital transfer of 36 COVID‐19‐positive cases, none of the HCWs reported COVID‐19 infection. However, the authors did not explain how this was investigated.Another report from the USA concerning 19 road and 3 air transfers after ECMO implantation for severe COVID‐19 ARDS stated that staff involved tested negative during routine screening , but there was a limited description of the transport process and duration of exposure.Another study demonstrated a very low risk of COVID‐19 contamination to EMS and reported an incidence of 0.57 infections/10,000 person‐days over a similar study period.Our study, however, is based on a higher number of COVID‐19 ECMO patients transport missions and provides a more detailed description of the transport process, time of exposure, and examination of possible risk factors for HCWs cross‐infection. We report over a period during which vaccines were not yet available in the State of Qatar to protect the general population and HCWs, and hence should make everyone more cautious. Only two of the HCWs involved in our mobile COVID‐19 ECMO program tested positive for the virus during the study period. No HCW injury or incident associated with the missions was reported. This is despite a high number of missions and prolonged and repeated encounters with COVID‐19 patients.5Our study has several limitations; it is a single‐center, retrospective observational study and subject to all biases associated with such design. Second, the number of cases and subjects is small, which makes the generalisability of the findings less likely. Akin to other studies, it was not possible to determine if those infections occurred during the transport missions, during other interactions with COVID‐19 patients in the ICU, or outside of the work context due to the prevalence of COVID‐19 within the community at the time. Ultimately, we hope that our retrospective cohort study can be complemented by further similar studies from other ECMO centers to help identify best practices and formulate further recommendations in relation to handling COVID‐19 patients in an ECMO transport context.6Transport of COVID‐19 patients on ECMO is challenging and requires meticulous attention to detail to ensure the safety of the patient and the whole team involved in the process. Aspects of cannulation and transportation involve potentially aerosol‐generating procedures that are undertaken under stressful conditions of hypoxia and clinical instability, which may add to the risk of virus transmission. Therefore, strict measures of PPE usage should be observed before, during, and after patient transportation to maintain staff and public safety. The safety measures make the process more complex than with other ECMO patients and could increase the duration of the missions but they are crucial. Our study demonstrates that COVID‐19 patients can be safely transported. Training and strict adherence to the safety measures presented above ensured that of the 63 different healthcare professionals involved in the transport and retrieval of the 34 COVID‐19 ECMO patients, only two eventually tested positive to COVID‐19, although we cannot determine for sure when and how they contracted COVID‐19. This satisfactory outcome was achieved while keeping these acutely ill patients safe from any untoward event.Rabee Tawel: Data curation; investigation; methodology; writing – original draft; writing – review and editing. Lubna Altawil: Data curation; formal analysis; validation; writing – original draft; writing – review and editing. Sunil Hassan Koya: Writing – original draft; writing – review and editing. Hani Jaouni: Writing – original draft; writing – review and editing. Guillaume Alinier: Investigation; methodology; validation; writing – original draft; writing – review and editing. Abdulqadir J. Nashwan: Investigation; methodology; writing – original draft; writing – review and editing. Ahmed Labib: Conceptualization; data curation; formal analysis; methodology; supervision; writing – original draft; writing – review and editing.Abdulqadir J. Nashwan is an Editorial Board member of Health Science Reports and coauthor of this article. He is excluded from editorial decision‐making related to the acceptance of this article for publication in the journal. The authors declare no conflict of interest.The study was approved by the Medical Research Center (MRC)—Institutional Review Board (IRB) at Hamad Medical Corporation (MRC‐01‐21‐029). The study has been conducted in accordance with the ethical standards noted in the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards.The lead author Abdulqadir J. Nashwan affirms that this manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as planned  have been explained.Supplementary information.Click here for additional data file.


To determine whether UK optometrists and ophthalmologists provide target refraction advice to patients prior to cataract surgery, and when this should first be discussed.Optometrists and ophthalmologists were asked to complete a survey of two clinical vignettes , plus multiple choice and short answer questions either using hard copy or online.Responses were obtained from 437 optometrists and 50 ophthalmologists. Optometrists who reported they would provide target refraction advice were more experienced (median 22 years) than those who would leave this to the Hospital Eye Service (median 10 years). The former group reported it was in the patients’ best interest to make an informed decision as they had seen many myopic patients who read uncorrected pre‐operatively, and were unhappy that they could no longer do so after surgery. Inexperienced optometrists reported that they did not want to overstep their authority and left the decision to the ophthalmologist. The ophthalmologists estimated their percentage of emmetropic target refractions over the last year to have been 90%.Currently, some long‐term myopes become dissatisfied after cataract surgery due to an emmetropic target refraction that leaves them unable to read without glasses as they did prior to surgery. Although experienced optometrists are aware of this and attempt to discuss this issue with patients, less experienced optometrists tend not to. This suggests that target refraction needs greater exposure in university training and continuing professional development. To provide patients with the knowledge to make informed decisions regarding their surgery, we suggest an agreed protocol within funded direct referral schemes of initial target refraction discussions by optometrists to introduce the idea of refractive outcomes and outline options, with further discussion with the ophthalmologist to clarify understanding. Many experienced optometrists reported long‐term myopic patients were dissatisfied with a target refraction of emmetropia due to the need to wear reading glasses following cataract surgery.Less experienced optometrists discussed target refraction much less with cataract surgery patients, suggesting this needs further exposure in university education and continuing professional development.The inclusion of initial target refraction discussions by optometrists within funded direct referral schemes seem to be a useful step forward.Cataract surgery is a commonly performed procedure, with an estimated 25 million cataract operations performed each year worldwide.A focus group study exploring patients’ experiences of their vision following cataract surgery found a lack of knowledge among patients of how their final prescription would impact the type of spectacles worn post‐surgery.To determine if optometrists and ophthalmologists provide advice regarding post‐operative target refraction.To determine the optimum time target refraction should first be discussed with the patient.This is an exploratory study using a survey sent to UK optometrists and ophthalmologists and a mixture of vignette case scenarios, plus multiple choice and short answer questions. The aims of the study were:As previous studies have shown differences in optometric referrals and NHS sight test outcomes depending on optometrist experience and practice type  versus independents),Ethical approval was gained from the Chair of the Biomedical, Natural, Physical and Health Sciences Research Ethics Panel at the University of Bradford on 08/04/2020 (EC26122). The survey gathered background information regarding the number of years qualified, the work setting  and resident  or locum practitioner status for optometrists. It was then split into two sections: the first consisted of two vignette clinical case scenarios (Patients A and B) and the second consisted of follow up questions regarding when target refraction should be discussed, and what percentage of patients receive an emmetropic target refraction (see Appendix 1). The survey included free text questions to give practitioners the opportunity to explain their answers. The number of questions were kept to a minimum to allow the survey to be completed in approximately 10 min in order to gain a good response rate.The optometrist years qualified data were described using non‐parametric statistics, as the data were shown not to be normally distributed by Kolmogorov‐Smirnov tests. A Fisher's Exact test was used to compare target refraction discussion rates among large multiple and independent practice types. A multinomial logistic regression was used to assess if any of the three variables (i) practice type, (ii) years qualified or (iii) resident/locum were associated with discussing target refraction. First, a main effects model was used to assess the effect of each independent variable upon the answer chosen. Then, a full factorial model was conducted to investigate interactions between the independent variables. The ophthalmologist years qualified data were described using parametric statistics, as the data followed a normal distribution.The vignette case scenarios were agreed by three optometrists  and an ophthalmologist . The scenarios were identical for both the ophthalmologist and optometrist questionnaires, but the questions surrounding the scenario were different to fit the role of each profession. The scenarios were written to assess a key theme identified in the focus group study by Webber et al.Patient A and Patient B both had bilateral cataracts. Patient A was a pre‐operative myope (−2.50DS) who wore distance single vision spectacles for everyday wear, taking the spectacles off to read. This prescription was chosen as it allowed the patient to be able to read comfortably without their spectacles and addresses the issue of some myopic patients struggling with post‐surgical emmetropia.Part B consisted of further questions and asked when practitioners thought a patient's target refraction should be discussed. The options were: (i) by the optometrist at the point of referral , (ii) by the optometrist at the point of referral  and (iii) by the ophthalmologist. Ophthalmologists were asked one additional question, investigating the percentage of patients in which they aimed for an emmetropic target refraction in the last year.Postal and online recruitment methods were used from the start of the study in an attempt to recruit as many optometrists as possible. The questionnaires were distributed between December 2019 and March 2020. A prospective sample size of 411 was determined following the method of IsraelThe questionnaires were distributed between August 2020 and December 2020. A prospective sample size of 326 was determined following the method of Israel.p < 0.001).A total of 437 questionnaires were returned consisting of 359 online responses and 78 paper replies (a response rate of 33%). 78.5% of the responses (343) were from resident optometrists and 21.5% (94) from locum optometrists. Table Patient A was a simple myope of −2.50DS in both eyes who took their spectacles off to read. Optometrists were asked, “At the point of referral, would you discuss with the patient their target refraction options? ”. Three options were available: (i) yes, discuss in person (34% of responses), (ii) yes, and state preference in referral letter (28% of responses) or (iii) no, leave the patient to discuss this with the ophthalmologist/ hospital eye service (38% of responses). Responses to Patient A were further divided into practice type and can be seen in Table p < 0.0001). Multinomial logistic regression found a statistically significant association between discussing target refraction and years qualified (χ2(2) = 21.2 p < 0.0001), with a non‐significant interaction between practice type and whether the optometrist was a resident/locum, (χ2(2) = 0.47 p = 0.80). This suggests that differences were due to years of experience and not practice type. Binary logistic regression produced an odds ratio of 1.07 (95% CI 1.05–1.09) indicating a 6.6% increase in discussion rates per year of experience.When comparing results from practice type, four options included small amounts of data (<10%) and were considered too small for meaningful analysis. We compared data from the two largest groups of large multiple (N = 195) and independent (N = 169). The results showed highly significant differences Table , with “DPatient B was a habitual monovision contact lens wearer with his right eye for distance vision and his left for near vision and spectacle independence was important to them. The importance of spectacle independence made the situation unique, potentially making it more obvious to the respondent that they should discuss target refraction with the patient. Optometrists were asked the same question, “At the point of referral would you discuss with the patient their target refraction options? ”. The same three options were available: (i) yes, discuss in person compromising (26% of responses), (ii) yes, and state preference in referral letter (46% of responses), and (iii) no, leave the patient to discuss this with the ophthalmologist/ hospital eye service (28% of responses). Responses to Patient B were further divided into practice type and can be seen in Table p < 0.0001). A full factorial, multinomial logistic regression showed a statistically significant association between discussing target refraction and years qualified (χ2(2) = 11.9 p = 0.003), with a non‐significant interaction between practice type and whether the optometrist was a resident/locum, (χ2(2) = 0.30 p = 0.86). This suggests that differences were due to years of experience and not practice type.A Fisher's Exact test showed that the distribution of those who would discuss or not discuss target refraction with Patient B were significantly different from each other in large multiple and independent practices  – Respondent 52I have had too many myopes disappointed with their emmetropia (and therefore need for readers!) and know that I too would prefer to be left myopic, so always try to inform the patient at this point. – Respondent 335Many optometrists reported a history of examining patients dissatisfied with the refractive outcome of cataract surgery, and this was their main motivation in discussing target refractions. Some felt patients may not be given a choice about their target refraction as all options may not be offered, or it may not be explained in a way the patient understands. In particular, some optometrists worried that some (particularly myopic) patients could accept an emmetropic target refraction without fully understanding its consequences on their visual needs and lifestyle.Part of the referral processIt’s important, and necessary, I believe, our responsibility as a primary care professional to discuss different possible outcomes with the patient and discuss patient preferences. I also think it’s important to pass this information to the ophthalmologist in writing.‐ Respondent 117We have a funded extended counselling service for cataract referral and this would be a part of it. – Respondent 30Some optometrists reported that discussing target refraction was part of their referral process. This included optometrists that felt they had a duty of care to discuss options and outcomes of surgery with patients, and those where this was part of a funded cataract referral pathway. Many felt they were in a good position to discuss and advise patients on this topic as they have a good understanding of patients’ refractive history and visual needs.Do not want to over‐step authorityThe reasons why optometrists who reported they would not discuss target refraction, did not do so could be explained by three themes.I am not operating or choosing the lens power of the implant. It may be different if a long term monovision contact lens wearer but I would not patronise the surgeon into telling them which refractive result to aim for in this case. – Respondent 136I do not make a recommendation at the risk of stepping on ophthalmologist’s toes. – Respondent 268Some optometrists felt that discussing target refractions with a patient could be over‐stepping their authority.Lack of confidenceWould not feel confident offering the patient other options when I am not sure that the ophthalmologist is happy to agree to it. – Respondent 21I wouldn't want to create expectations that were then changed @ HES for a reason. Also not confident in discussing what could be achieved. – Respondent 347Some felt a lack of confidence in what options were available, and others were unsure if the ophthalmologist had any specific preferences. Some highlighted that they would not feel confident to have the discussion in practice, as there may be clinical factors they are not aware of that may limit target refraction. A few described how having this discussion with patients could lead to disappointment if a patient chooses a target refraction that the ophthalmologist later decides is not an option. Others lacked confidence that their recommendations would be seen by the ophthalmologist or would be ignored.Ophthalmologist rolenot required as part of the referral process. This reinforces the idea that a discussion is not part of the optometrist's professional role and will be covered by the ophthalmologist.This decision needs to be made between the ophthalmologist and the patient. We can refer but ultimately, it's the surgeon's decision whether he performs surgery. It's their responsibility to discuss the pros, cons and risks of the procedure and the potential outcome for the patient. – Respondent 210It is down to what the surgeon thinks is suitable for the patient as they will do further tests to determine what is the correct IOL power, axial length, etc which we as optometrist cannot do so. – Respondent 124This included all responses believing that the responsibility to discuss the target refraction lies with the ophthalmologist rather than themselves (optometrists). Many talked about how the ophthalmologist makes clinical decisions about which target refraction to offer, and extra examinations and tests are often conducted at the hospital before a target refraction discussion can occur. Some thought that the discussion about target refraction best takes place alongside a wider discussion of the risks of surgery and what the patient will experience. Some described how it had never occurred to them that they would have this discussion with the patient, as everything to do with surgery is handled by the hospital. Several optometrists noted that they did not discuss target refraction with the patient as it is Optometrists who sometimes reported that they would discuss target refraction said they would do so for the monovision patient but were less likely to do so for the myopic patients, and that they would also provide information if, and when, asked.Not often time to discuss fully in hospital, and good that the patient is fully aware of their options – Hospital optometrist – Respondent 96Local ophthalmologists have requested this as it means their time is better spent with the patient if options have been discussed – Respondent 25Time was an encompassing theme for all three groups. In those that discussed target refraction with patients, they did so because they felt they had the time to discuss different options with the patient. Some felt they had more time than would be available to the ophthalmologist at the hospital, and that ophthalmologists may not spend sufficient time on the discussion due to time limitations. One hospital optometrist stated there was not enough time to discuss target refraction options at the hospital, and some mentioned that local ophthalmologists requested that optometrists have this discussion with patients, further demonstrating that the time available during hospital appointments was limited.Time constraints in practice do not allow enough time to spend with patients to go through different correction options. – Respondent 135We have no time to discuss further options due to a 25‐minute slot to complete an eye‐test – Respondent 124Of those that do not discuss target refraction, many mentioned this was due to time limitations in practice.Will only discuss if I'm running on time. If not then I'll briefly mention that it's something to talk about with your consultant. – Respondent 159Time issue ‐ have discussed with patients when he/she wants more information. – Respondent 318Of those optometrists who would only discuss target refraction sometimes, time availability was one of the main contributing factors. They noted they would only discuss target refraction with the patient if they had time but if not, they would advise the patient to discuss this when they saw their ophthalmologist. Some felt they did not have sufficient time to have an in‐depth discussion, but would briefly mention the options available if time allowed.A total of 50 questionnaires were completed, of which all were completed online. Ophthalmologists working in the NHS completed 54% of responses, 6% worked in private practice, and 40% worked a combination of NHS and private practice. The average number of years qualified was 18.3 years (SD 7.3 years). The sample size is much lower than our target number of 326, and subgroup sample sizes  are too small for meaningful analyses. Table Ophthalmologists were asked over the past year what percentage of patients they aimed for an emmetropic target refraction. The median response was 90%, range 80%–100%.Important to explain options to the patient and allow own decision based on their visual requirements and preferences … in my experience not all low myopes are happy with emmetropia – Respondent 30Would not make decision based on what patient had discussed with their optometrist. Would have discussion with the patient and together we would make the decision. Nine times out of ten, emmetropia is chosen – Respondent 17Many ophthalmologists highlighted the importance of discussing target refraction with the patient to ensure they are satisfied with the outcome of surgery, and saw this as best practice.I tend to say that we usually aim for emmetropia but offer myopia if they wish ‐ they tend to go for emmetropia – Respondent 26The refractive aim will depend on the patient’s daily activities, e.g., some myopes read unaided, and may want to continue to do this. If they are unsure I would suggest a contact lens trial to simulate the outcome, informing them of the degree of prediction error in outcomes. – Respondent 26This category covers ophthalmologists who would discuss available options with the patient and then recommend a target refraction. The target refraction advised was for several reasons: some advised a specific target refraction due to the patient's lifestyle or hobbies, and some based on their past clinical experience. Several suggested discussing all options with the patient, and then trialling different refractive errors with contact lenses to ensure the patient is happy with their choice before making a recommendation. This latter approach seems problematic as although post‐operative emmetropia with ready‐made readers for near might be easily simulated, post‐operative myopia would also require new distance spectacles that they would remove for near work.Normally aim at ‐0.75 to ‐1.0 as myopes ‘hate’ ending up on hypermetropic side of emmetropia – Respondent 15Low myopia and reading glasses are acceptable for most patients. Taking off glasses to read appears to be a new practice for this teacher. If they are clear about their needs and have had a robust discussion with their optom and is documented in the referral letter then I would go with, ‘usually accept the patients decision based on the discussion they had with their optometrist‐ Respondent 11This category covered ophthalmologists who make a target refraction recommendation for the patient but did not mention discussing options. Of those that recommended a target refraction for the myopic Patient A, 57% reported that they would recommend an emmetropic target . Most of the responses were based upon clinical experience and satisfaction of previous patients.Finally, both optometrists and ophthalmologists were asked when they thought target refraction should first be discussed with the patient, with the results shown in Figure I currently work for an AQP  doing cataract surgery. Community optometrists discussing refractive targets is a big problem we face. The reason for this is because community optometrists don't tend to explain that the reason for cataract surgery is to improve vision whether they need specs for distance vision and near vision post operatively or not. The patient doesn't understand the ±1.00 tolerance of the operation (because it is often not explained) and when we try and discuss with the patient a number of them are upset and say, 'Well my optometrist said … '. Not only does this make the Community optometrist look like they don't know what they are doing it leaves patients very unhappy.‐ Respondent 196When discussing target refraction with patients, it is important that the patient's expectations are managed. While the patient has a choice when deciding upon their final target refraction, they should be made aware that this is within a tolerance and cannot always be guaranteed. National biometry audits suggest a benchmark of 85%–90% of patients undergoing routine cataract surgery should achieve a final spherical equivalent refraction within 1 dioptre of the predicted value, and 55% of patients should be within 0.5 dioptres.n = 26) found 27% of patients had no discussion regarding their target refraction or were not given sufficient time or information to make an informed choice, and therefore deferred to the ophthalmologist's recommendation.Target refraction discussions are vital to ensure patient satisfaction post‐operatively. Current advice from the NHS states, “Providers must ensure that patients have sufficient time to consider these complex issues, and decisions such as post‐operative target refraction should be determined and agreed with the patient well in advance of the scheduled surgery date.”Optometrists and ophthalmologists participating in our survey were found to have more agreement for the monovision patient (Patient B) and typically felt that a full discussion and possibly contact lens trials were warranted for this patient. The pre‐operative low myope (Patient A) provided more differing views. Less experienced optometrists were found to not discuss target refraction for two reasons. Firstly, they were not familiar with previously myopic patients being unhappy with their final refraction (emmetropia) because they had now lost their ability to read without spectacles. Secondly, they reported a lack of confidence and knowledge and a desire not to over‐step their authority. The multinomial logistic regression results suggested that the reason that optometrists in large multiples discussed target refraction much less than those in independent practices is that these groups employ far more inexperienced clinicians. The driver appears to be years of experience and not practice type.Only a small number of responses were received from ophthalmologists (50) and much lower than our target size (326), so the results cannot be generalised and must be treated with caution. The majority of ophthalmologists  reported they would discuss the available options with the myopic patient and then allow them to make an informed decision, while 42% (21/50) reported that they would recommend either emmetropia  or myopia , although the comments provided suggested that the latter was low myopia of about −0.75 to −1.00DS. Five out of the nine ophthalmologists who would recommend myopia would advocate low myopia, which would still require patients to use reading glasses rather than a higher myopic distance correction (≈ −2.00D) that would allow reading without glasses. Ophthalmologists reported targeting an emmetropic refraction in 90% of their patients in the past year, with the remaining 10% consisting of mainly myopic patients with some monovision target refractions. It is difficult to estimate how many myopic patients who read uncorrected are obtaining an emmetropic target refraction. In Europe, those born between 1940 and 1979 have been shown to have a myopic prevalence of 23.5% pre cataract surgery.p < 0.0001) and discussion rates were shown to increase 6.6% per year of experience. To improve the discussion rate in this group, including this topic in optometric education would raise awareness of the issues patients face post‐surgery, and improve confidence for the more inexperienced. Continued professional development could be provided for qualified optometrists.Target refraction discussions are essential for every patient, and our results highlighted several barriers to patients receiving these discussions. We discuss below how these barriers can potentially be overcome. Firstly, education. The 44% (191/437) of optometrists who believe target refraction should be discussed by the ophthalmologist were significantly less experienced  the time constraints of ophthalmologists, (ii) the changing of NHS email addresses making it harder for us to contact ophthalmologists and (iii) some ophthalmologists reporting NHS firewalls blocking our emails. The ophthalmic directory from the Royal College of Ophthalmologists was used to contact all of the ophthalmologists with an available email address, and they were asked to respond and circulate. An ophthalmologist was part of the study team (AC) and attempted to obtain responses from colleagues and several other ophthalmologists helped with circulations, along with promoting the study on social media platforms. Despite these attempts, the response rate remained low. Although the results should be interpreted with caution, we believe that the data are valuable in helping to demonstrate that the great majority of patients have an emmetropic target refraction  and 12 of the 50 ophthalmologists (24%) reported that they would aim for a target refraction of emmetropia for the moderate myope who read without spectacles pre‐surgery. Finally, as the respondents were self‐selecting these clinicians may have had an interest in target refraction, and this may have influenced the results and introduced bias.p < 0.0001), with less experienced optometrists choosing not to due to lack of experience, confidence and wishing to avoid patronising the ophthalmologist. We assume that the view of experienced optometrists, with their knowledge of the unhappy patients produced under the current system, is the approach to follow. This suggests that this issue needs greater exposure in university training and continuing professional development. Both optometrists and ophthalmologists raised time constraints as a barrier to having comprehensive discussions concerning target refraction. Funded direct referral schemes are likely to be a useful step forward so that optometrists are provided with the extra time to discuss this with patients, who will then be more informed for the discussion they will have with their ophthalmologist and will allow them sufficient time to consider their decision. Despite many optometrists already discussing target refraction options with patients, within our study, 76% of ophthalmology respondents thought target refraction should first be discussed by themselves. Guidelines developed between optometrists and ophthalmologists would both provide optometrists with the confidence and correct information of what to include in patient discussions, and provide confidence to ophthalmologists that the patient is correctly informed before they attend the Hospital Eye Service. An agreed protocol of initial target refraction discussions by optometrists to introduce the idea of refractive outcomes, and outline options with further discussion with the ophthalmologist to clarify understanding and make a decision, will help to provide patients with the knowledge and time to make informed decisions regarding their surgery.Opinions differed between optometrists and ophthalmologists of when target refraction should first be discussed with patients when referring for cataract surgery. Experienced optometrists were much more likely to discuss target refraction with their patients ; Data curation (lead); Formal analysis (lead); Investigation ; Methodology ; Project administration (lead); Visualization ; Writing – original draft (lead); Writing – review & editing . Alison Alderson: Conceptualization ; Investigation ; Methodology ; Supervision (supporting); Visualization ; Writing – review & editing . Fiona Fylan: Formal analysis ; Validation ; Writing – review & editing . Richard A Armstrong: Formal analysis ; Validation ; Writing – review & editing . Aman Chandra: Methodology (supporting); Project administration (supporting); Resources (supporting); Writing – review & editing ; Writing – review & editing . David Elliott: Conceptualization ; Data curation ; Formal analysis ; Investigation ; Methodology ; Supervision (lead); Validation ; Visualization ; Writing – original draft (supporting); Writing – review & editing .Figure S1Click here for additional data file.Figure S2Click here for additional data file.Table S1Click here for additional data file.Table S2Click here for additional data file.Table S3Click here for additional data file.Table S4Click here for additional data file.Table S5Click here for additional data file.


Organismal traits are presumed to be well suited for performance in the tasks required for survival, growth, and reproduction. Major injuries to such traits should therefore compromise performance and prevent success in the natural world; yet some injured animals can survive for long periods of time and contribute to future generations. We here examine 3 years of camera trap observations along a remote trail through old‐growth forest in northern British Columbia, Canada. The most common observations were of moose (2966), wolves (476), and brown bears (224). The moose overwhelmingly moved in one direction along the trail in the late fall and early winter and in the other direction in the spring. This movement was clustered/contagious, with days on which many moose traveled often being interspersed with days on which few moose traveled. On the video recordings, we identified 12 injured moose, representing 1.4% of all moose observations. Seven injuries were to the carpus, three were to the antebrachium, and two were to the tarsus—and they are hypothesized to reflect damage to ligaments, tendons, and perhaps bones. The injured moose were limping in all cases, sometimes severely; and yet they did not differ noticeably from uninjured moose in the direction, date, contagiousness, or speed of movement along the trail. We discuss the potential relevance of these findings for the action of natural selection in the evolution of organismal traits important for performance. Major injuries should compromise organismal performance and prevent success in the natural world. Using camera trap video recordings along a remote trail in northern British Columbia (Canada), we identified 12 moose with leg injuries, including 7 to the carpus, 3 to the antebrachium, and 2 to the tarsus. The injured moose were limping in all cases, sometimes severely. However, we here show that these moose did not differ noticeably from uninjured moose in the direction, date, contagiousness, or speed of movement along the trail. We discuss implications for the efficacy of natural selection. As suchSeveral situations arise, however, where outlier or “exceptional” phenotypes are produced more naturally, and thus can be assessed for their effects on performance, survival, reproductive success, or fitness. One situation occurs when individuals with phenotypes that evolved in one environment naturally disperse to a different type of environment. Studies examining such out‐of‐place individuals often document reduced survival or reproductive success  can do the same for their claws, and some sea cucumbers can eject parts of their gut to distract predators  healed injuries on the performance of individual organisms Lovell, ? In humaOur study was motivated by observations of moose with leg injuries recorded on camera traps in a remote area of northwestern British Columbia, Canada. These injuries were typically evident as enlarged joints or limbs, and/or striking angular limb deviations . Most of the injuries caused the moose to limp moderately to severely (at least to our subjective interpretation), and yet we observed the same injured moose passing multiple camera traps, and at least some of those moose appear to have been present in multiple years. The current study takes advantage of a recent 2017–2020) deployment of high‐quality camera traps along a well‐defined trail passing through old‐growth forest to examine the movement patterns of injured moose under natural conditions. Observations of 12 injured moose  of six camera traps (numbered 1–6) was deployed on August 8, 2017. These traps were placed facing obvious splits in the trail in order to record the side of the split taken by each animal (side‐biases at these trail splits will be the focus of a subsequent paper). When referring to the different “sides” of each split, we use “left” and “right” in reference to the downstream direction of flow in the adjacent river. Two different groups of trail splits were instrumented with the cameras  of four camera traps  was first deployed on August 10, 2018. Trap 12 was placed facing a short steep hill where the trail descended to the upstream river flats. The other three traps were placed to record both the trail and a bear‐rubbing tree immediately beside the trail. Trap 11 was placed at the upstream end of the trail, 72 m upstream of Trap 12. Trap 9 was placed at the downstream end of the trail, 470 m after it descended to the downstream river flats. Trap 13 was placed between the two groups of splits that had been instrumented in the first set of traps , maximum video length of 30 s, and a delay between consecutive recordings of 5 s. However, three deviations from standard settings arose owing to battery differences, apparent programming differences between some cameras, and adjustments to problems encountered. (1) Over the first year , the cameras would turn off the video whenever an animal stopped moving during the 30 s recording interval. In subsequent years, all cameras were programmed to record for 30 continuous seconds regardless of whether or not the animal continued moving. (2) The second set of cameras insisted on taking a single picture before each video recording, and we were unable to remove this setting. Hence, both the initial photo and the subsequent video from these cameras needed to be examined to identify the animals. (3) The first set of cameras was equipped with Energizer Ultimate Lithium AA‐cell batteries, which worked continuously for the entire time period . In hopes of improving sustainability, the second set of cameras was equipped with Tenergy NiMH rechargeable AA‐cell batteries, which were often drained before the spring . Additional information recorded will be discussed below in the context of research questions we sought to answer. Several potential limitations were revealed during this video screening process. First, some recordings did not capture any animal—seemingly because the animal passed by too quickly between when the camera was triggered and when it started recording (about 1 s). This fact was usually evident based on branches moving in the video, or fresh tracks in the snow relative to the previous recording. Second, the videos were foggy in some instances, which precluded the accurate collection of some information. Third, martens and fishers were difficult to distinguish as they moved rapidly through the videos and so are grouped for analysis.When viewing the videos, the following baseline information was recorded for each individual animal: date, time, direction of movement , and the species of animal  of our friends and family, and also 25 observations (0.6% of 4341) of other humans. The observations of other humans were all from Trap 9, which is located at downstream end of the trail and is therefore more accessible. In short, beyond a few recordings at the first trap on the trail, no humans other than ourselves were observed over the entire 3 year period. Of the remaining 4075 observations, we next excluded 128 (3.1% of 4075) “immediate repeat” observations: that is, instances where sequential recordings from a single camera trap were clearly of the same individual animal. We could not exclude potential “later repeats,” which could include the same individual animal recorded on different camera traps, or the same individual recorded hours later on the same camera trap. Of the remaining 3947 observations, we next excluded nine observations (0.2% of 3947) of domestic dogs, which were always with humans, as well as 164 recordings (4.2% of 3947) where no animal could be seen. In nearly all of these latter cases, moving branches indicated that an animal had passed too quickly to be recorded. Finally, we removed all observations of birds because they were too few to be worth analyzing: three observations of grouse and one of a Stellar's Jay. The remaining 3770 observations were used for subsequent analyses.Our camera trap deployments were optimized for studying animal movement along a single trail and, hence, several other types of inferences would not appropriate. First, we do not estimate population sizes because doing so requires other designs for camera placement  and time (different seasons and years). Hence, the tallies reflect general use of the trail, rather than any sort of population size estimate. These tallies revealed that moose were the primary users of the trail , followed by wolves (12.6%) and brown bears (5.9%), and then by lower numbers of many other species Figure . SeveralQualitative observations from lower‐quality camera traps deployed in previous years suggested that moose were using the trail for continuous  transit along the ridge connecting the upstream and downstream river flats. Furthermore, those transits appeared to be primarily downstream in the late fall and early winter but primarily upstream in the spring. To here quantify those patterns, we examined data from the five camera traps (traps 2–6 in set 1) that had continuous recordings for the entire three‐year period Figure . Camera These new quantitative data confirmed our earlier qualitative observations. That is, moose typically transit the trail without lengthy pauses (see estimated rates of transit below) and that—overwhelming—they moved downstream in the late fall and early winter but then upstream in the spring Figure . FurtherAnother striking pattern was that—within a season—the movement of moose was strongly clustered or “contagious” Figure . That is4We observed some instances of cuts or sores on moose, but we here focus on obvious structural leg injuries that are readily identifiable across video recordings on multiple camera traps. We first screened all recordings on all camera traps to note such injuries. We then carefully re‐screened all other videos within 12 h of a given observation of an injured moose. This re‐screening was helpful because an injury sometimes was not immediately noticed during initial screening, and yet could be confirmed via slow motion and magnification of the videos. In all cases, we only retained videos of injured moose where the injury was visible, and where we were confident that it was the same individual moose with the same injury within a given season.www.youtube.com/watch?v=ly1jVA6w5WM. Seven of the injuries were to the right carpus, which is homologous to the human wrist, and these were characterized by lateral displacement and possible hyperextension (6 injuries) or medial displacement (1 injury). Three of the injuries were to the antebrachium, which is homologous to the human lower arm, and were characterized by swelling and possible bone remodeling. The remaining two injuries were to the left hock (tarsus), which is homologous to the human ankle, and were characterized by enlargement near the Achilles tendon attachment. These 12 injured moose were distributed across all years and both seasons , and the total number of confirmed observations (33) plus the total number of additional likely observations (8) together represented 1.4% of the total number of moose observations (2966).This screening procedure identified 12 moose with obvious leg injuries , acquired , and acute/traumatic . However, without being able to examine internal anatomy of the injuries, it is important to outline the alternatives. First, certain diseases or parasites can cause “infectious lameness” evident as an altered gait even in the absence of musculoskeletal damage  and one of those moose was also recorded at the downstream end of the trail (trap 9). (Note: detectability appears lower at these upstream‐most and downstream‐most locations because moose sometimes there divert from the trail into the surrounding river flats.) Given that these upstream‐most and downstream‐most traps were >2 km apart, they presumably yield best estimates of the average rate of movement along the entire trail. The rate estimates for these five injured moose over this longer distance averaged 0.70 ± 0.11 m/s. . For 11 of the 12 injured moose, we were able to identify a "paired" uninjured moose passing the same traps within at least 4 days; and, for 3 of those 11 injured moose, we could identify two individual uninjured moose—one moving before and one moving after the injured moose. We then calculated the travel time between the two most widely spaced traps on which the injured and uninjured moose in each pair were recorded.Over short distances (the core area of the set 1 traps 1–6), no obvious difference was evident in the rate of travel of injured and uninjured moose Figure . Over lot10 = 0.147, p = .886).As noted previously, most of our data do not meet the assumptions required for inferential statistics, and so the above interpretations are based on qualitative assessment of descriptive statistics and visual examination of data distributions—as seen in the figures. However, we appreciate that some readers might chafe at the absence of formal statistical support for our assertion that injured and uninjured moose do not differ in their movement. The one type of data that we feel can be formally analyzed is the relative rate of movement of injured and uninjured moose—that is, the 11 injured/uninjured pairs that are independent of each other, at least within a season. Hence, we analyzed the movement times shown in Figure Overall, then, we suggest no detectable effect of these injuries on the transit of moose along the trail. Of course, we have not assessed other aspects of movement, such as whether injured or uninjured moose are more or less likely to use the trail that we instrumented with our camera traps. Furthermore, we cannot assess the movement of injured moose when they are not transiting between the upper and lower parts of the river, nor can we assess other components of their fitness, such as reproductive success or lifespan. Such comparisons would require other camera trap deployments and additional methodologies.5Major structural  injuries to moose limbs would seem incompatible with survival in the wild—and yet 1.4% of all observations of moose revealed such limb injuries.  This injury percentage is much lower than those reported for structural limb injuries in other animals, such as 47.9% limb abnormalities in bonobos Kano, , 5.9% liThe relatively low rate of injuries in moose presumably reflects the difficulty of post‐injury survival for such a heavy prey animal that sometimes needs to move quickly. Indeed, the observed frequency of injuries in moose  is not a measure of the frequency at which such injuries occur. We would expect the latter frequency to be much higher because most moose suffering from them would die quickly due to predation or starvation—before our cameras could record them. On the other hand, some moose with such injuries might recover so well that their injuries are no longer detectable by the time our cameras recorded them. Regardless, the frequency of seemingly severe injuries on ambulatory moose in nature was surprising—at least to us. The location and nature of these injuries was variable Figure  and theiOur identification of injured moose was based on obvious physical signatures  rather than on how they were moving. And yet those injuries did influence immediate movement behavior because every injured moose was limping and one (moose H) showed—in all observations—the expected behavioral signs of pain, such as flattened ears and extended nostrils ; data curation (lead); formal analysis (lead); funding acquisition (lead); investigation ; methodology ; project administration (lead); resources (lead); supervision (lead); visualization (lead); writing – original draft (lead); writing – review and editing (lead). Aspen Sierra Hendry: Conceptualization ; data curation (supporting); investigation (supporting); methodology ; writing – original draft (supporting); writing – review and editing (supporting). Heather Lynn Roffey: Conceptualization ; data curation (supporting); investigation ; methodology ; writing – original draft (supporting); writing – review and editing (supporting). Cedar Alyce Hendry: Conceptualization ; data curation (supporting); investigation (supporting); methodology ; writing – original draft (supporting); writing – review and editing (supporting). Michael Hendry: Conceptualization ; methodology ; resources (supporting); writing – original draft (supporting); writing – review and editing (supporting).The authors are all members of the same family—but did not receive any financial support from research grants, government agencies, NGOs, or businesses.Video S1Click here for additional data file.


The Mo‐dependent formate dehydrogenase (FDH) from Rhodobacter capsulatus catalyzes reversible formate oxidation to CO2 at a bis‐molybdopterin guanine dinucleotide (bis‐MGD) cofactor. To elucidate potential substrate binding sites relevant for the mechanism, we studied herein the interaction with the inhibitory molecules azide and cyanate, which are isoelectronic to CO2 and charged as formate. We employed infrared (IR) spectroscopy in combination with density functional theory (DFT) and inhibition kinetics. One distinct inhibitory molecule was found to bind to either a non‐competitive or a competitive binding site in the secondary coordination sphere of the active site. Site‐directed mutagenesis of key amino acid residues in the vicinity of the bis‐MGD cofactor revealed changes in both non‐competitive and competitive binding, whereby the inhibitor is in case of the latter interaction presumably bound between the cofactor and the adjacent Arg587.Biological carbon dioxide  are capable of oxidizing formate to CO2 reversibly. Here, we compared IR spectroscopic data with DFT calculations and inhibition kinetics to study the putative binding mode of CO2/formate at the bis‐MGD cofactor with the help of isoelectronic and charged product analogues. Experimental and theoretical data exclude a direct binding of the inhibitor molecules to the bis‐MGD. Both have been proposed to ensure optimal substrate binding to and proton transfer away from the active site Figure .6a, 6a, 72 analogues with RcFDH. The negative charge and hence the large transition dipole moment of the inhibitory anions causes high extinction coefficients of the antisymmetric stretching modes, which are exceptionally well‐suited for IR measurements as they are located in a spectral region free of any protein or water absorptions.RcFDH and associated variants, potential interaction sites at the bis‐MGD and in its secondary coordination sphere could be identified. In addition, we have investigated the azide inhibition of the inactive oxo‐ligated bis‐MGD that was produced in absence of its maturation precursor, RcFDHΔFdsC.In the present study, infrared (IR) spectroscopy was employed in combination with density functional theory (DFT) and inhibition kinetic studies to elucidate the specific interaction of such inhibitory CORcFDH proteins incubated with 10‐fold excess inhibitor in which contributions of free inhibitors in solution were subtracted. The spectra of the as isolated protein sample treated with azide and cyanate   and the detected band shape suggest a conformation of the azide, which is more similar to that of free azide in water . The second distinct band, observed at 2031 cm−1 for azide, and 2153 cm−1 for cyanate treatment, could only be detected in the bis‐MGD‐containing enzyme .The small frequency shift (ΔAint) within a semi‐quantitative evaluation . They were found to be in a similar order of magnitude as the protein concentration, yielding in sum values about 0.5 anions per RcFDH molecule. As this observation was consistent for all azide‐incubated samples, it rather points to a modified extinction coefficient due to the interaction with the protein environmentTo elucidate the specific role of the different binding sites, the concentrations of both types of bound azide molecules were estimated from their band intensities Aint withi−1, forms the binding site indicated by the band at 2031 cm−1. This finding is supported by the fact that the overall integrated absorbance Aint of both bands (Aint(2031+2040 cm−1)) in the RcFDHWT sample is equivalent to the total integral Aint of the band at 2040 cm−1 in the apoenzyme, RcFDHΔbis−MGD. The calculated difference spectrum, in which spectral contribution of the apoenzyme with respect to the Mo loading are subtracted, shows exclusively the remaining bis‐MGD dependent band centered at 2031 cm−1 . This observation suggests that the two observed bands represent two populations of potential binding sites within the sample (apo‐ and holoenzyme), to which in total only one inhibitory molecule can bind.Moreover, this result indicates that in presence of the bis‐MGD cofactor, the azide molecule from the interaction site, related to the absorption at 2040 cmVI), the ligated Cys386, and an additionally incorporated inhibitor anion were conducted . The corresponding Mo coordination geometry was derived from the oxidized structure of the related bis‐MGD of the nitrate‐inducible formate dehydrogenase (FDH−N) from E. coli.VI oxidation state and the respective inhibitor was kept in an energetically favored position near the MoVI ion but excluding a covalent Mo−N bond . DFT calculations were also performed for the corresponding interactions with isotopically labeled azide (15N=N=N−) and cyanate (O=13C=15N−) for a proper comparison with the experimental spectra , whereas the lower frequency band appears to refer to a specific interaction site in the RcFDHWT (holoenzyme). Notably, the observed binding‐site‐specific bands remain independent from the cofactor's oxidation state, indicating that none of the inhibitors coordinate directly the Mo ion. This has been also recently proposed within a combined quantum mechanical and molecular mechanic calculations.Enzyme reduction is illustrated in the corresponding UV‐visible absorption spectra by the respective intensity loss of bands characteristic for Fe−S clusters and FMN . In addition, previous XAS and EPR spectroscopic studies have proven that such treatments change the oxidation state of the Mo ion to MoRcFDHH387M and RcFDHR587K  as an electron acceptor at the bis‐MGD‐site, kcat values of about 1800 min‐1 were obtained for RcFDHWT, while lowered kcat values were observed for the RcFDHH387M and RcFDHR587K variants.KM (formate) value was obtained, displaying a significantly lower binding affinity. While RcFDHWT and RcFDHH387M revealed a mixed‐type inhibition for azide and cyanate, the amino acid exchange in the RcFDHR587K variant resulted in a strictly competitive inhibition, which underlines the importance of Arg587 for both substrate and competitive inhibitor binding.In catalytic assays for formate oxidation, using NADKi (azide) of RcFDHWT, the Ki (azide) of the active site variants RcFDHH387M and RcFDHR587K increased by a factor of ∼10 and 120, respectively (Table Ki (cyanate) of the RcFDHWT has increased by a factor of ∼15 relative to Ki (azide). This suggests a stronger influence of these amino acids on the binding of azide compared to cyanate. Furthermore, azide is also a more efficient inhibitor as reflected by the lowered Ki and αKi values.Notably, significant differences were observed for the inhibition constants of azide and cyanate. In comparison to Ki values was observed in experiments using DCPIP  as electron acceptor at the bis‐MGD, confirming that both forms of inhibition rather occur near the active site instead of being related to an interruption of the intramolecular electron transfer.Additionally, no influence on the RcFDHH387M variant for each of the two inhibitors, albeit slightly shifted compared to the WT protein, only the higher frequency component, as found for the RcFDH▵bis−MGD, was detected in the spectrum of the RcFDHR587K variant at 2042 and 2157 cm−1 for azide and cyanate, respectively. These data suggest that the binding site of the inhibitor, giving rise to the lower frequency IR bands at 2031 and 2153 cm−1 for azide and cyanate, respectively, is localized between the bis‐MGD cofactor, presumably the sulfido ligand, and the Arg587 in a more defined manner. This binding site would correspond to the competitive inhibition mode component as derived from the kinetic experiments of RcFDHWT and RcFDHH387M.Complementary to the biochemical assays, IR spectra of the azide‐ and cyanate‐treated variants were recorded Figure . While tRcFDHΔFdsC with the active RcFDHWT enzyme  . Presumably, it is bound to the protein in a manner, which provides a higher degree of translational freedom. This assumption would explain the small spectral shifts in the inhibitor‐treated RcFDHWT, RcFDHR587K and RcFDHH387M holoenzyme variants  should be addressed to the authors.Supporting InformationClick here for additional data file.