Frailty increases vulnerability to dependency and death.1 With Singapore’s ageing population, early frailty identification in the emergency department (ED) is critical yet constrained by time and resources. Clinical Frailty Score (CFS) is a validated 9-point tool used for frailty identification, with scores 5 indicating frailty (Supplementary materials Appendix S1).2 In Singapore, the CFS algorithm (CFS-A) (Supplementary materials Appendix S2) showed comparable performance against the gold-standard Frailty Index (FI)3 in hospitalised older persons and predicted outcomes, such as mortality and institutionalisation.4 However, there is currently no validated frailty tool for the ED in Singapore.

Background: Functional dependency may serve as a marker for positive SARC-F screen (Strength, Assistance with walking, Rise from a chair, Climb stairs and Falls) among older adults at the Emergency Department (ED). We compared functional dependency between SARC-F– (<4) and SARC-F+ (≥4) groups at the ED. Methods: A secondary analysis of cohorts from two quasi-experimental studies among patients aged ≥65 years old presenting to the ED of a 1,700-bed tertiary hospital. We compared both groups for baseline characteristics using univariate analyses, and performed multiple linear regression to examine the association between Modified Barthel Index (MBI) and Lawton’s instrumental activities of daily living (IADL) against SARC-F, and binary logistic regression to examine the associations between individual ADL domains and SARC-F+. We compared the area under receiver operating characteristic curves (AUC) to detect SARC-F+ for MBI, IADL, frailty, age, cognition and comorbidity. Results: SARC-F+ patients were older (86.4±7.6 years), predominantly female (71.5%) and frail (73.9%), more dependent on walking aids (77.2%), and had lower premorbid MBI (median 90.0 [interquartile range 71.0–98.0]) and IADL (4.0 [2.0–5.0]) (both p<0.001). MBI (β=–0.07, 95% confidence interval [CI] –0.086 to –0.055) and IADL (β=–0.533, 95% CI –0.684 to –0.381) were significantly associated with SARC-F. Dependency in finances (odds ratio [OR]=14.7, 95% CI 3.57–60.2, p<0.001), feeding (OR=12.4, 95% CI 1.45–106, p=0.022), and stair-climbing (OR=10.49, 95% CI 4.96–22.2, p<0.001) were the top three functional items associated with SARC-F. MBI (AUC=0.82, 95% CI 0.77–0.84) and IADL (AUC=0.78, 95% CI 0.72–0.84) showed superior discrimination for SARC-F+ compared to other measures (AUC=0.58–0.70). Conclusion: Functional dependency is strongly associated with positive SARC-F screen among older adults at the ED. This highlights the need for increased vigilance, especially in the presence of dependency in relevant domains such as managing finances, feeding, and stair-climbing.

Introduction: Hospitalisations can pose hazards and may not be an appropriate care setting for frail nursing home (NH) residents. Few studies have quantified the extent of NH resident hospitalisations in Singapore, hence we aimed to address this knowledge gap by studying characteristics of unplanned hospitalisations over a 1-year period. Method: This was a retrospective cohort study of 9922 subsidised residents across 59 NHs in Singapore, with analysis using administrative healthcare data. Key measures included inpatient admission and emergency department visit rates, final discharge diagnoses and estimated costs. We examined correlates of inpatient admissions with a multivariable zero-inflated negative binomial regression model incorporating demographics, institutional characteristics and Charlson Comorbidity Index. Results: There were 6620 inpatient admissions in 2015, equivalent to 2.23 admissions per 1000 resident days, and the majority were repeat admissions (4504 admissions or 68.0%). Male sex (incidence rate ratio [IRR] 1.23), approaching end-of-life (IRR 2.14), hospitalisations in the past year (IRR 2.73) and recent NH admission within the last 6 months (IRR 1.31-1.99) were significantly associated with inpatient admission rate. Top 5 discharge diagnoses were lower respiratory tract infections (27.3%), urinary tract infection (9.3%), sepsis (3.1%), cellulitis (1.9%) and gastroenteritis (1.1 %). We estimated the total system cost of admissions of subsidised residents to be SGD40.2 million (USD29.1 million) in 2015. Conclusion: We anticipate that unplanned hospitalisation rate will increase over time, especially with an increasing number of residents who will be cared for in NHs. Our findings provide a baseline to inform stakeholders and develop strategies to address this growing problem.

We refer to our article entitled ‘Emergency Department Interventions for Frailty (EDIFY): frontdoor geriatric care can reduce acute admissions’, which reported a success rate of up to 81.4% in preventing acute hospital admissions in older adults, with no compromise in health outcomes such as rehospitalisation, institutionalisation and mortality. In this letter, we present our novel transdisciplinary care model, describing the unique role of the EDIFY pharmacist. Frontloading geriatric assessments and interventions right from the emergency department (ED), to meet multidimensional needs of vulnerable older adults and to reduce adverse outcomes, have been coined as ‘frontdoor geriatrics’. At our centre, the EDIFY programme aims to minimise potentially avoidable acute admissions and deliver early integrated geriatric interventions at the ED. Team members consist of professionals trained in geriatric care, including a geriatrician, specialist registrar, geriatric advanced practice nurse (APN), boardcertified geriatric pharmacist, and a physiotherapist. Planned admissions to inpatient geriatrics were routinely screened and reviewed by the APN, and patients identified for potential discharge from the ED or transfer to lowacuity care areas (eg, shortstay observation units, subacute care units, or community hospitals) were highlighted to a geriatrician for further review. Care planning, discharge education, and telephonic followup consultation are provided to those who are discharged. Patients who are deemed unfit will proceed with acute admission as planned. Using a novel transdisciplinary care model, the role of the EDIFY pharmacist transcends traditional boundaries of pharmacy practice. In addition to providing standard pharmacy services, including medication reconciliation, medication review, and patient education, the EDIFY pharmacists are trained to perform similar duties as the APN, such as identifying patients at the ED who are suitable for discharge or stepdown care; obtaining histories and performing physical examinations; reviewing and ordering investigations; escalating ill cases for urgent doctor review; and prescribing of inpatient/ discharge medications (table 1). Regular workbased assessments were conducted with a geriatrician to ensure satisfactory competencies in performing the abovementioned clinical work. Between June 2020 and June 2022, 3300 patients were screened by the EDIFY team and 217 cases were deemed suitable for intervention. The EDIFY pharmacist screened 704 cases, of which 26 patients were identified for potential acute admissions avoidance. Five patients were successfully discharged from ED, 19 patients were transferred to loweracuity care areas, and two patients were admitted to the acute ward as planned. Due to constraints on healthcare resources and changing landscapes amid the pandemic, the statistics may not be reflective of the true potential of our service as reported in our study. To our knowledge, our centre is the first to pioneer such transformative care between the geriatric APN and pharmacist in the ED. This care model has helped EDIFY provide sustainable and effective care at times of pandemic and during staff shortages with high caseloads. Patients do not need to see multiple healthcare professionals, comprehensive assessments can be done timely, and deployment of personnel/resources can be made flexibly. We believe that transdisciplinarity is a key milestone in transforming healthcare delivery, especially in the ED. Tingting Selina Cheong , Birong Zhu, Edward Chong Pharmacy, Tan Tock Seng Hospital, Singapore Nursing Service, Tan Tock Seng Hospital, Singapore Geriatrics Medicine, Tan Tock Seng Hospital, Singapore

Background. Blockade of interleukin-6 (IL-6) has emerged as a promising therapeutic option for antibody-mediated rejection. Subtherapeutic anti-IL-6 antibody level or treatment cessation following prolonged cytokine neutralization may result in proinflammatory rebound phenomena via accumulation of IL-6 and/or modulated gene expression of major components of the IL-6/IL-6 receptor (IL-6R) axis. Methods. We evaluated biologic material obtained from a randomized controlled, double-blind phase 2 trial designed to evaluate the safety and efficacy of the anti-IL-6 monoclonal antibody clazakizumab in late antibody-mediated rejection. Twenty kidney transplant recipients, allocated to clazakizumab or placebo, received 4-weekly doses over 12 wks, followed by a 40-wk extension where all recipients received clazakizumab. Serum proteins were detected using bead-based immunoassays and RNA transcripts using quantitative real-time polymerase chain reaction (peripheral blood) or microarray analysis (serial allograft biopsies). Results. Clazakizumab treatment resulted in a substantial increase in median total (bound and unbound to drug) serum IL-6 level (1.4, 8015, and 13 600 pg/mL at 0, 12, and 52 wks), but median level of free (unbound to drug) IL-6 did not increase (3.0, 2.3, and 2.3 pg/mL, respectively). Neutralization of IL-6 did not boost soluble IL-6R or leukocyte or allograft expression of IL-6, IL-6R, and glycoprotein 130 mRNA. Cessation of treatment at the end of the trial did not result in a meaningful increase in C-reactive protein or accelerated progression of graft dysfunction during 12 mo of follow-up. Conclusion. Our results argue against clinically relevant rebound phenomena and modulation of major components of the IL-6/IL-6R axis following prolonged IL-6 neutralization with clazakizumab.

We refer to our article entitled "Brief Aids to Guide Clinical Frailty Scale Scoring at the Front Door of Acute Hospitals," 1 Chong E. Tham A. Chew J. et al. Brief aids to guide clinical frailty scale scoring at the front door of acute hospitals. J Am Med Dir Assoc. 2021; 22: 1116-1117.e2 Abstract Full Text Full Text PDF PubMed Scopus (1) Google Scholar which reported the potential utility of the Clinical Frailty Scale–Emergency Department (CFS-ED) that promotes fast and accurate frailty screening in the ED setting. 1 Chong E. Tham A. Chew J. et al. Brief aids to guide clinical frailty scale scoring at the front door of acute hospitals. J Am Med Dir Assoc. 2021; 22: 1116-1117.e2 Abstract Full Text Full Text PDF PubMed Scopus (1) Google Scholar ,2 Rockwood K. Song X. MacKnight C. et al. A global clinical measure of fitness and frailty in elderly people. CMAJ. 2005; 173: 489-495 Crossref PubMed Scopus (4767) Google Scholar The CFS-ED was first developed by our emergency physicians for easy CFS scoring by triage nurses. It has since been established as standard practice for frailty screening among ED attendees aged ≥65 years at our institution.

Background The Emergency Department Interventions for Frailty (EDIFY) program was developed to deliver early geriatric specialist interventions at the Emergency Department (ED). EDIFY has been successful in reducing acute admissions among older adults. Objectives We aimed to examine the effectiveness of EDIFY in improving health-related quality-of-life (HRQOL) and length of stay (LOS), and evaluate EDIFY's cost-effectiveness. Design A quasi-experiment study. Setting The ED of a 1700-bed tertiary hospital. Participants Patients (≥85 years) pending acute hospital admission and screened by the EDIFY team to be potentially suitable for discharge or transfer to low-acuity care areas. Intervention EDIFY versus standard-care. Measurements Data on demographics, comorbidities, premorbid function, and frailty status were gathered. HRQOL was measured using EQ-5D-5L over 6 months. We used a crosswalk methodology to compute Singapore-specific index scores from EQ-5D-5L responses and calculated quality-adjusted life-years (QALYs) gained. LOS and bills in Singapore-dollars (SGD) before subsidy from ED attendances (including admissions, if applicable) were obtained. We estimated average programmatic EDIFY cost and performed multiple imputation (MI) for missing data. QALYs gained, LOS and cost were compared. Potential uncertainties were also examined. Results Among 100 participants (EDIFY=43; standard-care=57), 61 provided complete data. For complete cases, there were significant QALYs gained at 3-month (coefficient=0.032, p=0.004) and overall (coefficient=0.096, p=0.002) for EDIFY, whilst treatment cost was similar between-groups. For MI, we observed only overall QALYs gained for EDIFY (coefficient=0.102, p=0.001). EDIFY reduced LOS by 17% (Incident risk ratio=0.83, p=0.015). In a deterministic sensitivity analysis, EDIFY's cost-threshold was SGD$2,500, and main conclusions were consistent in other uncertainty scenarios. Mean bills were: EDIFY=SGD$4562.70; standard-care=SGD$5530.90. EDIFY's average programmatic cost approximated SGD$469.30. Conclusions This exploratory proof-of-concept study found that EDIFY benefits QALYs and LOS, with equivalent cost, and is potentially cost-effective. The program has now been established as standard-care for older adults attending the ED at our center.

OBJECTIVES:emergency department interventions for frailty (EDIFY) delivers frailty-centric interventions at the emergency department (ED). We evaluated the effectiveness of a multicomponent frailty intervention (MFI) in improving functional outcomes among older persons.DESIGN:a quasi-experimental study.SETTING:a 30-bed ED observation unit within a 1,700-bed acute tertiary hospital.PARTICIPANTS:patients aged ≥65 years, categorised as Clinical Frailty Scale 4-6, and planned for discharge from the unit.METHODS:we compared patients receiving the MFI versus usual-care. Data on demographics, function, frailty, sarcopenia, comorbidities and medications were gathered. Our primary outcome was functional status-Modified Barthel Index (MBI) and Lawton's iADL. Secondary outcomes include hospitalisation, ED re-attendance, mortality, frailty, sarcopenia, polypharmacy and falls. Follow-up assessments were at 3, 6 and 12 months.RESULTS:we recruited 140 participants (mean age 79.7 ± 7.6 years; 47% frail and 73.6% completed the study). Baseline characteristics between groups were comparable (each n = 70). For the intervention group, MBI scores were significantly higher at 6 months (mean: 94.5 ± 11.2 versus 88.5 ± 19.5, P = 0.04), whereas Lawton's iADL scores experienced less decline (change-in-score: 0.0 ± 1.7 versus -1.1 ± 1.8, P = 0.001). Model-based analyses revealed greater odds of maintaining/improving MBI in the intervention group at 6 months [odds ratio (OR) 2.51, 95% confidence interval (CI) 1.04-6.03, P = 0.04] and 12 months (OR 2.98, 95% CI 1.18-7.54, P = 0.02). This was similar for Lawton's iADL at 12 months (OR 4.01, 95% CI 1.70-9.48, P = 0.002). ED re-attendances (rate ratio 0.35, 95% CI 0.13-0.90, P = 0.03) and progression to sarcopenia (OR 0.19, 95% CI 0.04-0.94, P = 0.04) were also lower at 6 months.CONCLUSIONS:the MFI delivered to older persons at the ED can possibly improve functional outcomes and reduce ED re-attendances while attenuating sarcopenia progression.

OBJECTIVES: We designed this study to test whether clazakizumab, a direct interleukin-6 inhibitor, benefits patients hospitalized with severe or critical COVID-19 disease accompanied by hyperinflammation. DESIGN: Multicenter, randomized, double-blinded, placebo-controlled, seamless phase II/III trial. SETTING: Five U.S. medical centers. PATIENTS: Adults inpatients with severe COVID-19 disease and hyperinflammation. INTERVENTIONS: Eighty-one patients enrolled in phase II, randomized 1:1:1 to low-dose (12.5 mg) or high-dose (25 mg) clazakizumab or placebo. Ninety-seven patients enrolled in phase III, randomized 1:1 to high-dose clazakizumab or placebo. MEASUREMENTS AND MAIN RESULTS: The primary outcome was 28-day ventilator-free survival. Secondary outcomes included overall survival, frequency and duration of intubation, and frequency and duration of ICU admission. Per Data Safety and Monitoring Board recommendations, additional secondary outcomes describing clinical status and status changes, as measured by an ordinal scale, were added. Bayesian cumulative proportional odds, logistic, and Poisson regression models were used. The low-dose arm was dropped when the phase II study suggested superiority of the high-dose arm. We report on 152 patients, 74 randomized to placebo and 78 to high-dose clazakizumab. Patients receiving clazakizumab had greater odds of 28-day ventilator-free survival (odds ratio [OR] = 3.84; p [OR > 1] 99.9%), as well as overall survival at 28 and 60 days (OR = 1.75; p [OR > 1] 86.5% and OR = 2.53; p [OR > 1] 97.7%). Clazakizumab was associated with lower odds of intubation (OR = 0.2; p [OR] < 1; 99.9%) and ICU admission (OR = 0.26; p [OR < 1] 99.6%); shorter durations of ventilation and ICU stay (risk ratio [RR] < 0.75; p [RR < 1] > 99% for both); and greater odds of improved clinical status at 14, 28, and 60 days (OR = 2.32, p [OR > 1] 98.1%; OR = 3.36, p [OR > 1] 99.6%; and OR = 3.52, p [OR > 1] 99.8%, respectively). CONCLUSIONS: Clazakizumab significantly improved 28-day ventilator-free survival, 28- and 60-day overall survival, as well as clinical outcomes in hospitalized patients with COVID-19 and hyperinflammation.

We refer to our recent article entitled 'Emergency Department Interventions for Frailty (EDIFY): Front-Door Geriatric Care Can Reduce Acute Admissions', which reported on the successful implementation of a program with the dual purpose of reducing the number of potentially avoidable acute admissions, and delivering frailty-centric care through interprofessional geriatric interventions (Chong et al., 2021). In this letter, we wish to highlight that the success of the program is a result of collaborative efforts from an interprofessional team of geriatric experts, one of which is the geriatric advanced practice nurse (APN). APNs are registered nurses who have acquired expert knowledge, complex decision-making skills and the relevant clinical competencies that result in the expansion of their roles beyond basic nursing care (Fougere et al., 2018). Within the scope of their practice, APNs with advanced skills can perform comprehensive clinical assessments, order and interpret investigations, diagnose medical conditions, develop care plans, and even prescribe appropriate medications. Additionally, APNs are responsible for promoting high quality care and leading training programs, which can potentially improve patient safety across the healthcare continuum (Fougere et al., 2018). Hence, an APN requires the amalgamation of good leadership, professional autonomy, advanced skills in their given specialty, together with collaboration and communication skills for effective teamwork with other healthcare professionals. There are rising demands to deliver safe and effective care to frail older persons with multidimensional and complex care needs, which commonly include medical, functional, psychological and social needs (Conroy & Parker, 2017; Foo et al., 2014). Furthermore, the added risk of functional dependency, morbidity and mortality among these individuals have been well established and efforts to mitigate these unwanted outcomes must be put in place. At present, numerous APN care models have been demonstrated to effectively reduce rehospitalization rates, lower healthcare costs, and improve patient satisfaction (Fougere et al., 2018). Hence, APNs are in an ideal position to contribute to better care for this vulnerable group across various clinical settings. In particular, geriatric APNs can attend to these individuals and provide targeted geriatric assessments, identify and manage frailty timely, and develop care plans to promote effective continuity of care in the community. In light of the global surge in the volume of frail older persons attending the emergency departments (ED), there is a call for EDs to be better equipped to cope with these rising demands. Whilst, there is limited data to support the role of APNs at the ED, it is increasingly evident that geriatric APNs play a crucial role in the delivery of frailty-centric care at the ED. Geriatric nurses at the ED have demonstrated favourable patient outcomes among frail older persons, which include reduced ED re-attendances and hospital admissions, reduced complications associated with ED presentations such as delirium, fall, functional decline and incontinence (Conroy & Parker, 2017), and reduced inappropriate hospitalizations in a cost-effective manner (Fougere et al., 2018). At our centre, the EDIFY program comprises of a team of geriatric experts including a geriatrician, senior resident, geriatric APN, pharmacist and physiotherapist. EDIFY significantly reduces potentially avoidable acute admissions without escalating the risk of rehospitalization, ED re-attendance or mortality, and with possible benefit in attenuating frailty progression (Chong et al., 2021). The program, which is led by a consultant geriatrician, empowers the APN to screen patients at the ED who meet criteria for EDIFY interventions. Once identified, the APN proceeds to review suitable patients by initiating the comprehensive geriatric assessments. If required, the APN can prescribe or adjust medications following a discussion with the EDIFY doctors. For patients who are deemed suitable for acute admission avoidance, the APN would communicate the plans with the patients or their caregiver and initiate appropriate plans for continuity of care on discharge. The APN also provides discharge advice, frailty education and counselling, and telephonic follow-up consultation, when indicated. Moreover, the APN has an established collaborative and consultative relationship with the ED staff and regularly provides expert advice and support to geriatric emergency medicine (GEM) nurses (Foo et al., 2014) and other healthcare staff at the ED (Table 1). In conclusion, hospitals must be prepared to embrace frailty-centric care models to provide optimal care to older persons presenting to the ED. The geriatric APN, along with collaborative efforts with other healthcare professionals, play an essential role in delivering timely geriatric care, and is potentially an important piece of the puzzle in realizing a frailty-ready ED. The authors express their gratitude to the staff of the Emergency Department of Tan Tock Seng Hospital for their unwavering support in the EDIFY program. In addition, the authors thank Dr. E. Chong, Ms S. Cheong, Ms B.Y. Ooi, Ms A. Ho, Dr. J.Q. Chia, Dr. C.L. Foo and Ms Y.C. Yeoh for playing a vital role in the success of the EDIFY program. No conflict of interest has been declared by the authors. Birong Zhu: conceptualization, drafting and writing; Selina Cheong: revision and editing; Edward Chong: conceptualization, critical revision and editing.

The microvascular endothelium of the renal transplant is the first site of graft interaction with the host immune system and is often injured in chronic Antibody Mediated Rejection (AMR). Microvascular inflammation is an independent determinant of AMR and heightens endothelial expression of human leukocyte antigen (HLA) molecules thereby increasing the possibility of Donor Specific Antibody (DSA) binding. Endothelial cells (ECs) produce IL-6 in the steady-state that is increased by inflammation or by HLA-DR antibody binding in an allogeneic setting. Because IL-6 has been implicated in AMR, IL-6 blockade is currently under investigation as a therapeutic target. To further understand the role of IL-6 in EC immunogenicity, we have examined whether humanized antibody blockade of IL-6 altered EC interactions with allogeneic PBMC and after anti-HLA or DSA binding to ECs in an in vitro human experimental model. Soluble factors, endothelial phenotype, Stat-3 activation, CD4+ -T differentiation and C4d deposition were examined. Blockade of IL-6 reduced EC secretion of IL-6 and of the monocyte chemoattractant MCP-1. Pre-activation of ECs by anti-HLA or DSA binding increased IL-6 secretion, that was further increased by concurrent binding of both antibodies and this was inhibited by IL-6 blockade. Activation of Stat-3 in CD4+ -T mediated by soluble factors produced in endothelial-PBMC interactions, and endothelial differentiation of CD4+ -T cell subsets (Th1, Treg), were impaired whereas activation of Complement by anti-HLA antibody binding remained unchanged by IL-6 blockade. Together, these data identify EC-mediated pro-inflammatory responses (T cell expansion, EC auto-activation, chemokine secretion) targeted by IL-6 blockade.

We refer to our article entitled “Emergency Department Interventions for Frailty (EDIFY): Front-Door Geriatric Care Can Reduce Acute Admissions.”1Chong E. Zhu B. Tan H. et al.Emergency Department Interventions for Frailty (EDIFY): front-door geriatric care can reduce acute admissions.J Am Med Dir Assoc. 2021; 22: 923-928.e5Abstract Full Text Full Text PDF PubMed Scopus (8) Google Scholar Although we have described clinical effectiveness of the EDIFY program, a deeper appreciation of emergency department (ED) staff perceptions of geriatric care and support was needed to ascertain overall quality of the program. EDIFY was designed for the dual purpose of reducing the number of potentially avoidable acute admissions and delivering interprofessional geriatric interventions through comprehensive geriatric assessments, and promoting awareness and education on frailty.2Conroy S. Parker S. Acute geriatrics at the front door.Clin Med (Lond). 2017; 17: 350-353Crossref PubMed Scopus (11) Google Scholar,3Jay S. Whittaker P. Mcintosh J. Hadden N. Can consultant geriatrician led comprehensive geriatric assessment in the emergency department reduce hospital admission rates? A systematic review.Age Ageing. 2017; 46: 366-372PubMed Google Scholar The program significantly reduced acute admissions without escalating the risk of rehospitalization, ED re-attendance, or mortality.1Chong E. Zhu B. Tan H. et al.Emergency Department Interventions for Frailty (EDIFY): front-door geriatric care can reduce acute admissions.J Am Med Dir Assoc. 2021; 22: 923-928.e5Abstract Full Text Full Text PDF PubMed Scopus (8) Google Scholar We conducted a survey among ED staff aimed at assessing their perceptions of knowledge and confidence in managing older persons and to explore their satisfaction with current geriatric expert support. In the absence of suitable survey instruments, a survey questionnaire was crafted by members of the study team comprising 2 geriatricians and an advanced practice nurse. The questionnaire underwent multiple rounds of pretesting, which led to multiple revisions before a final version was ready. It comprises 3 subsections: (1) demographics, (2) knowledge and confidence in managing older persons, and (3) satisfaction with current geriatric expert support. Each question is scored on an 8-point Likert scale ranging from 0 (strongly disagree) to 7 (strongly agree) to avoid participants selecting the neutral option. Participants were introduced to the survey during department meetings and were informed that participation was voluntary. Written consent was obtained and ethical approval was granted by the institutional review board. Descriptive analysis was performed and we reported categorical variables as number (percentage) and continuous variables as mean and median. Total scores for individual questionnaire items were derived with reverse ordering of scores applied to selected items to ensure consistent directionality. Between-group comparisons were then performed using unpaired t-test. Statistical analysis was performed using SPSS V21.0 (SPSS, Inc, Chicago, IL), and statistical significance was assessed using a threshold of 5%. We recruited a total of 78 participants (34.7% doctors and 62.7% nurses). Most were women (58.1%), aged 20 to 30 years old (37.7%), Chinese (49.4%), and had <5 years working experience at the ED (44.9%). Only a minority received training in geriatric care (Supplementary Table 1). Responses scored as 0 to 3 and 4 to 7 were taken as disagree and agree, respectively (Table 1). Our results revealed inconsistencies in staff perceptions of knowledge and confidence in delirium and dementia management. More than half lacked confidence in diagnosing delirium (Q1 and Q3; median = 3), agreed that restraints used on patients with delirium would protect them from harm (Q7; median = 4), and were not familiar with advanced dementia care services (Q8; median = 3). Participants were well aware of the role of advanced care planning (Q14 and Q15; median = 5) and felt they had good understanding of frailty (Q17 and Q18; median = 5). Although 62.8% of participants agreed that the current geriatric expert support is adequate (Q20; median = 4.5), only 26.9% felt well equipped to care for older persons (Q21; median = 2). Overall, 84.6% were satisfied with the current geriatric expert support (Q24; median = 5).Table 1Summary of Results From the Survey Questions Using an 8-Point Likert ScaleSurvey QuestionsScore Range 0 (Strongly Disagree) to 7 (Strongly Agree)nAgree∗“Disagree” if score is 0–3; “agree” if score is 4–7. (%)Mean (SD)Median (IQR)A. Understanding/Confidence in managing older persons at the EDDisagree vs Agree∗“Disagree” if score is 0–3; “agree” if score is 4–7. Delirium and dementiaQ1. I would be able to identify if my patients had delirium by administering the Confusion Assessment Method (CAM).7748.73.5 (1.9)3 (2–5)Q2. I would be able to distinguish the difference between delirium and dementia.7867.94.3 (1.6)4.5 (3–6)Q3. I am familiar with the DELIRIUM acronym in identifying possible delirium risk factors/causes.7848.73.3 (1.9)3 (2.-5)Q4. Delirium does not lead to significant adverse outcomes for hospitalized older patients.7719.22.0 (1.7)1 (1–3)Q5. All delirium cases should not be managed at home or in the community.7862.84.0 (1.9)4 (3–6)Q6. I would be able to manage behavior-related issues due to delirium/dementia in the ED setting.7850.03.4 (1.6)3.5 (2–5)Q7. Physical and/or chemical restraints used on a patient with delirium will protect them from harming themselves.7862.83.8 (1.8)4 (2–5)Q8. I am familiar with advanced dementia care and the relevant resources available in the hospital and in the community.7837.22.9 (1.6)3 (2–4) Falls, function, and community resourcesQ9. I would be able to identify older patients with high falls risk.7891.05.2 (1.2)5 (5–6)Q10. I would be able to know the difference between predisposing and precipitating factors leading to falls in the elderly.7882.14.7 (1.3)5 (4–6)Q11. I would be able to assess older patients' functional status and decide on further treatment plans.7870.54.2 (1.5)4 (3–5)Q12. Older patients presenting with functional decline will always require admission.7855.13.7 (1.7)4 (2–5)Q13. I am familiar with the available community resources and confident in allocating the right resource for my patients.7765.43.8 (1.5)4 (3–5) Advanced care planningQ14. I am aware the existence of Advanced Care Planning (ACP) and the potential impact on care planning.7787.25.1 (1.5)5 (4–6)Q15. If a patient's ACP decision was for “limited interventions,” there is a chance that the patient can be discharged from the ED if appropriate community support is rendered.7785.94.9 (1.5)5 (4–6) Continence careQ16. I would be able to manage patients with issues pertaining to urinary and bowel control.7666.74.1 (1.5)4 (3–5) FrailtyQ17. I am well informed about the concept of frailty and its impact on my patients.7773.14.4 (1.4)5 (3–5.5)Q18. I would be able to identify frailty in older patients presenting to the ED.7779.54.7 (1.3)5 (4–6) Geriatric careQ19. My knowledge in geriatric care will allow me to provide the best care for my patients in ED.7778.24.6 (1.5)5 (4–6)Total Score (range: 0–133)†Reverse ordering of scores applied for Q4, Q5, Q7, and Q12.77.0 (15.2)78 (66–88)B. Satisfaction with current geriatric expert support at the ED Q20. I feel that the care of my older patients in the ED is adequate with the current geriatric support.7662.84.2 (1.5)4.5 (3–5) Q21. I am well equipped to care for my older patients and do not need additional geriatric support.7826.92.5 (1.7)2 (1–4) Q22. I am comfortable in communicating with the geriatric team for advice on the care of my patients in the ED.7874.44.6 (1.5)5 (3–6) Q23. The geriatric team has been very helpful in explaining and teaching me about my patients' conditions and the rationale for their management plans.7780.85.0 (1.4)5 (4–6) Q24. Please rate your current satisfaction level with your current geriatric support in ED.7784.65.1 (1.2)5 (4–6)Total Score (range: 0–35)†Reverse ordering of scores applied for Q4, Q5, Q7, and Q12.21.2 (5.4)21 (17.8–25)IQR, interquartile range; Q, question.∗ “Disagree” if score is 0–3; “agree” if score is 4–7.† Reverse ordering of scores applied for Q4, Q5, Q7, and Q12. Open table in a new tab IQR, interquartile range; Q, question. Between-group comparisons revealed that geriatric-trained staff had greater confidence in differentiating predisposing and precipitating factors for falls, assessment of functional status, allocating the right community resources, and frailty identification (all P < .05). Doctors were also more aware of the potential sequelae of delirium (Q3; P < .001) and the impact of advanced care planning (Q14; P = .011); however, there were no differences in total scores between groups (Supplementary Table 2). Our findings show that most ED staff valued having additional geriatric expert support and highlights the need to improve delirium management and knowledge on advanced dementia care at the ED. Because of time pressures at the ED, addressing complex multidimensional needs of older persons often do not take precedence.2Conroy S. Parker S. Acute geriatrics at the front door.Clin Med (Lond). 2017; 17: 350-353Crossref PubMed Scopus (11) Google Scholar,3Jay S. Whittaker P. Mcintosh J. Hadden N. Can consultant geriatrician led comprehensive geriatric assessment in the emergency department reduce hospital admission rates? A systematic review.Age Ageing. 2017; 46: 366-372PubMed Google Scholar Hence, care models designed specifically to deliver frailty-centric care at the ED are needed to improve functional outcomes and reduce ED re-attendance among older persons.1Chong E. Zhu B. Tan H. et al.Emergency Department Interventions for Frailty (EDIFY): front-door geriatric care can reduce acute admissions.J Am Med Dir Assoc. 2021; 22: 923-928.e5Abstract Full Text Full Text PDF PubMed Scopus (8) Google Scholar,4Foo C.L. Siu V.W. Tan T.L. et al.Geriatric assessment and intervention in an emergency department observation unit reduced re-attendance and hospitalisation rates.Australas J Ageing. 2012; 31: 40-46Crossref PubMed Scopus (52) Google Scholar, 5Foo C.L. Siu V.W. Ang H. et al.Risk stratification and rapid geriatric screening in an emergency department - a quasi-randomised controlled trial.BMC Geriatr. 2014; 14: 98Crossref PubMed Scopus (22) Google Scholar, 6Devriendt E. De Brauwer I. Vandersaenen L. et al.Geriatric support in the emergency department: A national survey in Belgium.BMC Geriatr. 2017; 17: 68Crossref PubMed Scopus (11) Google Scholar, 7Ang S.H. Rosario B.H. Ngeow K.Y.I. et al.Direct admission from the emergency department to a subacute care ward: An alternative to acute hospitalization.J Am Med Dir Assoc. 2020; 21: 1346-1348Abstract Full Text Full Text PDF PubMed Scopus (4) Google Scholar Our study had a number of limitations. First, most participants had fewer than 5 years of working experience at the ED and most had no training in geriatric care. Hence, our findings may not be reflective of EDs with a larger proportion of staff experienced in geriatric care. Second, our results are reflective of an ED that has received support from the EDIFY program for more than a year. Therefore, no comparisons can be made before the introduction of the EDIFY program to the ED. Third, the large number of tests performed for between-group comparisons may have resulted in some observed differences occurring purely by chance. Hence, these findings should be interpreted with caution. In conclusion, the rising trend of older persons making up a significant proportion of ED attendances calls for EDs to better equip themselves in the provision of geriatric care. The EDIFY program is noticeably an important piece of the puzzle in realizing a frailty-ready ED. We express our deepest gratitude to the staff of the Emergency Department of Tan Tock Seng Hospital for their unwavering support in the EDIFY program and their participation in this survey study. We also thank Ms E.F. Goh, Ms H. Tan, Dr J.D.C. Molina, Ms S. Cheong, Ms P. Kaur, Dr M.J. Pereira, Ms S.H.X. Ng, Dr J.Q. Chia, Dr A. Chong, Dr C.L. Foo, and Dr M. Chan for playing a vital role in the success of the EDIFY program and study, and Professor W.S. Lim for providing advice on data analysis. Last but not least, we thank the Ng Teng Fong Healthcare Innovation Programme (Project Code: NTF_JUL2017_I_C2_CQR_02), National Healthcare Group, Singapore, for funding this study. Supplementary Table 1Baseline Demographics of all ED Staff ParticipantsnAll ParticipantsAge range, n (%)77 20–3029 (37.7) 31–4028 (36.4) 41–5017 (22.1) 51 and older3 (3.9)Gender, n (%)77 Male32 (41.6) Female45 (58.1)Ethnicity, n (%)77 Chinese38 (49.4) Malay13 (16.9) Filipino17 (22.1) Indian7 (9.1) Burmese1 (1.3) Others1 (1.3)Occupation, n (%)76 Doctor26 (34.7) Nurse47 (62.7) Allied health2 (2.7)Years of service in the ED, n (%)77 < 535 (44.9) 5–1021 (26.9) 11–1513 (16.7) 16–207 (9) >211 (1.3)GDGM trained, n (%)74 No71 (95.9) Yes3 (4.1)GEMS trained, n (%)77 No59 (76.6) Yes18 (23.4)GDGM, graduate diploma in geriatric medicine; GEM, geriatric emergency medicine. Open table in a new tab Supplementary Table 2Comparison in Results of Survey Questions Between Geriatric-Trained and Non–Geriatric-Trained, and Between Doctors and Nurses/Allied Health Staff at the EDSurvey QuestionsScore Range 0 (Strongly Disagree) To 7 (Strongly Agree)Geriatric-Trained (n = 18)Non–Geriatric-Trained (n = 59)Doctors (n = 26)Nurses or Allied Health Professionals (n = 49)Mean (SD)Mean (SD)P Value∗Unpaired t-test performed.Mean (SD)Mean (SD)P Value∗Unpaired t-test performed.A. Knowledge/Confidence in managing older persons at the ED Delirium and dementiaQ1.I would be able to identify if my patients had delirium by administering the Confusion Assessment Method (CAM).3.9 (1.9)3.3 (1.9).2524.1 (1.5)3.3 (2.0).088Q2.I would be able to distinguish the difference between delirium and dementia.4.8 (1.3)4.2 (1.6).1994.7 (1.3)4.2 (1.6).153Q3.I am familiar with the DELIRIUM acronym in identifying possible delirium risk factors/causes.3.9 (1.8)3.1 (1.9).0873.4 (1.7)3.3 (2.0).896Q4.Delirium does not lead to significant adverse outcomes for hospitalized older patients.†Reverse ordering of scores applied for Q4, Q5, Q7, and Q12.4.4 (1.8)5.2 (1.7).1086.2 (1.0)4.4 (1.7)<.001Q5.All delirium cases should not be managed at home or in the community.†Reverse ordering of scores applied for Q4, Q5, Q7, and Q12.2.3 (1.3)3.1 (2.0).1122.8 (2.1)3.0 (1.8).616Q6.I would be able to manage behavior-related issues due to delirium/dementia in the ED setting.3.7 (1.7)3.3 (1.5).3403.6 (1.5)3.3 (1.6).390Q7.Physical and/or chemical restraints used on a patient with delirium will protect them from harming themselves.†Reverse ordering of scores applied for Q4, Q5, Q7, and Q12.2.7 (1.5)3.4 (1.8).1243.4 (1.7)3.1 (1.9).496Q8.I am familiar with advanced dementia care and the relevant resources available in the hospital and in the community.3.5 (1.5)2.7 (1.5).0512.6 (1.3)3.0 (1.7).290 Falls, function, and community resourcesQ9.I would be able to identify older patients with high falls risk.5.6 (1.0)5.1 (1.2).1225.0 (1.3)5.4 (1.1).256Q10.I would be able to know the difference between predisposing and precipitating factors leading to falls in the elderly.5.2 (1.1)4.5 (1.4).0444.7 (1.4)4.7 (1.2).959Q11.I would be able to assess older patients' functional status and decide on further treatment plans.5.0 (1.1)3.9 (1.6).0064.2 (1.4)4.2 (1.6).975Q12.Older patients presenting with functional decline will always require admission.†Reverse ordering of scores applied for Q4, Q5, Q7, and Q12.2.7 (1.3)3.5 (1.8).0593.3 (1.7)3.4 (1.7).815Q13.I am familiar with the available community resources and confident in allocating the right resource for my patients.4.6 (1.1)3.6 (1.6).0153.8 (1.7)3.8 (1.5).944 Advanced care planningQ14.I am aware the existence of advanced care planning (ACP) and the potential impact on care planning.5.2 (1.3)5.1 (1.6).7395.7 (0.9)4.8 (1.7).011Q15.If a patient's ACP decision was for “limited interventions,” there is a chance that the patient can be discharged from the ED if appropriate community support is rendered.5.1 (1.4)4.9 (1.5).6615.3 (1.4)4.7 (1.5).139 Continence careQ16.I would be able to manage patients with issues pertaining to urinary and bowel control.4.4 (1.5)4.0 (1.5).3644.0 (1.6)4.2 (1.5).505 FrailtyQ17.I am well informed about the concept of frailty and its impact on my patients.4.9 (1.2)4.2 (1.4).0514.7 (1.1)4.3 (1.5).257Q18.I would be able to identify frailty in older patients presenting to the ED.5.3 (1.0)4.5 (1.4).0214.7 (0.9)4.6 (1.5).765 Geriatric careQ19.My knowledge in geriatric care will allow me to provide the best care for my patients in ED.5.3 (1.1)4.4 (1.5).0344.7 (1.2)4.6 (1.6).870Total Score (range: 0–133)†Reverse ordering of scores applied for Q4, Q5, Q7, and Q12.82.2 (12.6)75.3 (15.8).09280.8 (11.5)76.1 (15.4).180B. Satisfaction with current geriatric expert support at the ED Q20.I feel that the care of my older patients in ED is adequate with the current geriatric support.4.5 (1.4)4.1 (1.6).3584.6 (1.3)4.0 (1.6).147 Q21.I am well equipped to care for my older patients and do not need additional geriatric support.2.9 (1.6)2.3 (1.7).2062.3 (1.4)2.6 (1.8).426 Q22.I am comfortable in communicating with the geriatric team for advice on the care of my patients in ED.4.9 (1.3)4.6 (1.5).3304.9 (1.4)4.5 (1.5).320 Q23.The geriatric team has been very helpful in explaining and teaching me about my patients' conditions and the rationale for their management plans.5.5 (1.0)4.9 (1.5).0955.1 (1.5)5.0 (1.3).676 Q24.Please rate your current satisfaction level with your current geriatric support in the ED.5.3 (1.1)5.0 (1.2).4615.3 (1.1)5.0 (1.3).233Total Score (range: 0–35)†Reverse ordering of scores applied for Q4, Q5, Q7, and Q12.23.1 (4.5)20.7 (5.5).09221.8 (5.0)21.1 (5.6).614IQR, interquartile range; Q, question.One missing response for whether participant is geriatric trained and 3 missing responses for participant's occupation. Hence, excluded from this analysis.∗ Unpaired t-test performed.† Reverse ordering of scores applied for Q4, Q5, Q7, and Q12. Open table in a new tab GDGM, graduate diploma in geriatric medicine; GEM, geriatric emergency medicine. IQR, interquartile range; Q, question. One missing response for whether participant is geriatric trained and 3 missing responses for participant's occupation. Hence, excluded from this analysis.

Background Chronic active antibody-mediated rejection (AMR) is a major cause of graft loss with no approved drugs for its treatment. Currently, off-label regimens are used, reflecting the high unmet need for effective therapies based on well-controlled trials. Clazakizumab is a high-affinity, humanized monoclonal antibody that binds interleukin-6 and decreases donor-specific antibody (DSA) production and inflammation. Phase 2 pilot studies of clazakizumab in kidney transplant recipients with chronic active AMR suggest modulation of DSA, stabilization of glomerular filtration rate (GFR), and a manageable safety profile. We report the design of the Phase 3 IMAGINE study (NCT03744910) to evaluate the safety and efficacy of clazakizumab for the treatment of chronic active AMR. Methods IMAGINE is a multicenter, double-blind trial of approximately 350 kidney transplant recipients with chronic active AMR (Banff chronic glomerulopathy [cg] >0 with concurrent positive human leukocyte antigen DSA) randomized 1:1 to receive clazakizumab or placebo (12.5 mg subcutaneous once every 4 weeks). The event-driven trial design will follow patients until 221 occurrences of all-cause graft loss are observed, defined as return to dialysis, graft nephrectomy, re-transplantation, estimated GFR (eGFR) <15 mL/min/1.73m 2 , or death from any cause. A surrogate for graft loss (eGFR slope) will be assessed at 1 year based on prior modeling validation. Secondary endpoints will include measures of pharmacokinetics/pharmacodynamics. Recruitment is ongoing across North America, Europe, Asia, and Australia. Discussion IMAGINE represents the first Phase 3 clinical trial investigating the safety and efficacy of clazakizumab in kidney transplant recipients with chronic active AMR, and the largest placebo-controlled trial in this patient population. This trial includes prognostic biomarker enrichment and uniquely utilizes the eGFR slope at 1 year as a surrogate endpoint for graft loss, which may accelerate the approval of a novel therapy for patients at risk of graft loss. The findings of this study will be fundamental in helping to address the unmet need for novel therapies for chronic active AMR. Trial registration ClinicalTrials.gov NCT03744910 . Registered on November 19, 2018.

OBJECTIVES:The EDIFY program was developed to deliver early geriatric specialist interventions at the emergency department (ED) to reduce the number of acute admissions by identifying patients for safe discharge or transfer to low-acuity care settings. We evaluated the effectiveness of EDIFY in reducing potentially avoidable acute admissions. DESIGN:A quasi-experimental study. SETTING:ED of a 1700-bed tertiary hospital. PARTICIPANTS:ED patients aged ≥85 years. MEASUREMENTS:We compared EDIFY interventions versus standard care. Patients with plans for acute admission were screened and recruited. Data on demographics, premorbid function, frailty status, comorbidities, and acute illness severity were gathered. We examined the primary outcome of "successful acute admission avoidance" among the intervention group, which was defined as no ED attendance within 72 hours of discharge from ED, no transfer to an acute ward from subacute-care units (SCU) within 72-hours, or no transfer to an acute ward from the short-stay unit (SSU). Secondary outcomes were rehospitalization, ED re-attendance, institutionalization, functional decline, mortality, and frailty transitions at 1, 3, and 6 months. RESULTS:We recruited 100 participants (mean age 90.0 ± 4.1 years, 66.0% women). There were no differences in baseline characteristics between intervention (n = 43) and nonintervention (n = 57) groups. Thirty-five (81.4%) participants in the intervention group successfully avoided an acute admission (20.9% home, 23.3% SCU, and 44.2% SSU). All participants in the nonintervention group were hospitalized. There were no differences in rehospitalization, ED re-attendance, institutionalization and mortality over the study period. Additionally, we observed a higher rate of progression to a poorer frailty category at all time points among the nonintervention group (1, 3, and 6 months: all P < .05). CONCLUSIONS AND IMPLICATIONS:Results from our single-center study suggest that early geriatric specialist interventions at the ED can reduce potentially avoidable acute admissions without escalating the risk of rehospitalization, ED re-attendance, or mortality, and with possible benefit in attenuating frailty progression.

Objectives: The FRAIL-NH was originally developed for frailty assessment of nursing home (NH) residents. We aimed to compare concurrent, predictive, and known-groups validity between FRAIL-NH and FRAIL, using the Frailty Index (FI) as gold standard reference. We also examined for ceiling effect of both measures in the detection of severe frailty. Design: A secondary analysis of a prospective cohort study. Setting & Participants: Older adults (mean age 89.4 years) hospitalized for an acute medical illness in a 1300-bed tertiary hospital. Measurements: Baseline data on demographics, comorbidities, severity of illness, functional status, and cognitive status were gathered. We also captured outcomes of mortality, length of stay (LOS), institutionalization, and functional decline. For concurrent validity, we compared areas under the operating characteristic curves (AUCs) for both measures against the FI. For predictive validity, univariate analyses and multiple logistic regression were used to compare both measures against the adverse outcomes of interest. For known-groups validity, we compared both measures against comorbidities and functional status via 1-way analysis of variance, and dementia diagnosis via independent t test. Box plots were also derived to investigate for possible ceiling effect. Results: Both measures had good concurrent validity (both AUC > 0.8 and P < .001), with FRAIL-NH detecting more frailty cases (79.5% vs 50.0%). Although FRAIL-frail was superior for in-hospital mortality [6.7% vs 1.0%, P = .031, odds ratio (OR) 9.29, 95% confidence interval (CI) 1.09-79.20, P < .042] and LOS (10 vs 8 days, P = .043), FRAIL-NH-frail better predicted mortality (OR 6.62, 95% CI 1.91-22.94, P = .003) and institutionalization (OR 6.03, 95% CI 2.01-18.09, P = .001) up to 12 months postenrollment. Known-groups validity was good for both measures with FRAIL-NH yielding greater F values for functional status and dementia. Lastly, box plots revealed a ceiling effect for FRAIL in the severely frail group. Conclusions and Implications: This exploratory study highlights the potential for expanding the role of FRAIL-NH beyond NH to acute care settings. Contrasted to FRAIL, FRAIL-NH had better overall validity with less ceiling effect in discrimination of severe frailty. (C) 2021 AMDA - The Society for Post-Acute and Long-Term Care Medicine.

Frailty is a clinical syndrome characterized by increased vulnerability to functional dependency and/or mortality attributable to 1 or more stressors. 1 Morley J.E. Vellas B. van Kan G.A. et al. Frailty consensus: a call to action. J Am Med Dir Assoc. 2013; 14: 392-397 Abstract Full Text Full Text PDF PubMed Scopus (1839) Google Scholar Given that the Emergency Department (ED) stands as a portal to multiple health care settings, the identification of frailty at the ED represents a pivotal component of care and risk assessment among older adults. 2 Brousseau A.A. Dent E. Hubbard R. et al. Identification of older adults with frailty in the Emergency Department using a frailty index: Results from a multinational study. Age Ageing. 2018; 47: 242-248 Crossref PubMed Scopus (32) Google Scholar , 3 Conroy S. Thompson D. Griffiths S. et al. Improving acute care for older people at scale - the Acute Frailty Network. Acute Med. 2016; 15: 185-192 Crossref PubMed Google Scholar , 4 Theou O. Campbell S. Malone M.L. Rockwood K. Older adults in the emergency department with frailty. Clin Geriatr Med. 2018; 34: 369-386 Abstract Full Text Full Text PDF PubMed Scopus (28) Google Scholar Nonetheless, the implementation of frailty screening and frailty-centered care at the ED remains challenging owing to limitation of resources and manpower, prioritization of disease-specific care, time-pressured environment to assess and transfer patients to the next care area, and limited opportunities to train staff in frailty indentification. 2 Brousseau A.A. Dent E. Hubbard R. et al. Identification of older adults with frailty in the Emergency Department using a frailty index: Results from a multinational study. Age Ageing. 2018; 47: 242-248 Crossref PubMed Scopus (32) Google Scholar , 3 Conroy S. Thompson D. Griffiths S. et al. Improving acute care for older people at scale - the Acute Frailty Network. Acute Med. 2016; 15: 185-192 Crossref PubMed Google Scholar , 4 Theou O. Campbell S. Malone M.L. Rockwood K. Older adults in the emergency department with frailty. Clin Geriatr Med. 2018; 34: 369-386 Abstract Full Text Full Text PDF PubMed Scopus (28) Google Scholar , 5 Kajsa E. Katarina W. Sten L. Synneve I.D. Screening for frailty among older emergency department visitors: Validation of the new FRESH-screening instrument. BMC Emerg Med. 2016; 16: 27 Crossref PubMed Scopus (29) Google Scholar Hence, frailty screening tools at the ED must be brief, easy to use, valid, and highly sensitive. 4 Theou O. Campbell S. Malone M.L. Rockwood K. Older adults in the emergency department with frailty. Clin Geriatr Med. 2018; 34: 369-386 Abstract Full Text Full Text PDF PubMed Scopus (28) Google Scholar ,5 Kajsa E. Katarina W. Sten L. Synneve I.D. Screening for frailty among older emergency department visitors: Validation of the new FRESH-screening instrument. BMC Emerg Med. 2016; 16: 27 Crossref PubMed Scopus (29) Google Scholar

Sarcopenia is associated with adverse health outcomes including mortality, functional loss, falls, and poorer quality of life. However, the value of screening sarcopenia at the Emergency Department (ED) remains unclear. We aimed to examine the SARC-F questionnaire for its (1) diagnostic ability in identifying frailty, and (2) predictive ability for adverse health outcomes. A secondary analysis of a quasi-experimental study. Setting: An ED within a 1700-bed tertiary hospital. ED patients aged ≥85 years (mean age 90.0 years) recruited into the Emergency Department Interventions of Frailty (EDIFY) study. Data of demographics, premorbid function, frailty status [Frailty Index (FI), Clinical Frailty Scale (CFS), FRAIL], comorbidities, medications, and cognitive status were gathered. We also captured outcomes of mortality, acute hospitalization, and ED reattendance at 3-, and 6-month. We then compared area under the operating characteristic curves (AUCs) for the abovementioned measures against the FI (reference) for diagnosis of frailty. Lastly, we performed univariate analyses and logistic regression to compare SARC-F and other measures against the adverse outcomes of interest. RESULTS: Amongst the various instruments, the SARC-F (AUC 0.92, 95% Confidence Interval (CI) 0.86-0.98, P<0.001; Sensitivity 79.0%, and Specificity 88.9%) performed best for frailty detection as defined by FI. Optimal cutoff was ≥3 (Sensitivity 91.4%, Specificity 83.3%, and Negative Predictive Value 68.2%). Only SARC-F was predictive of acute hospitalization [Adjusted Odds Ratio (OR) 4.00, 95% CI 1.47-10.94, P=0.007] and ED-reattendance [Adjusted OR 3.29, 95% CI 1.26-8.56, P=0.015] at 3-month. The SARC-F demonstrated excellent diagnostic ability for frailty detection and predictive validity for ED reattendance and acute hospitalization at 3 months. Lowering cutoff score to ≥3 may improve case-finding at the ED to facilitate early identification and management of sarcopenia. Further studies are required to validate the diagnostic and predictive performance of SARC-F at ED settings.

Targeting interleukin-6 (IL-6) is a promising strategy to counteract antibody-mediated rejection (ABMR). In inflammatory states, IL-6 antagonism was shown to modulate cytochrome P450 (CYP), but its impact on drug metabolism in ABMR treatment was not addressed so far. We report a sub-study of a phase 2 trial of anti-IL-6 antibody clazakizumab in late ABMR (ClinicalTrials.gov, NCT03444103). Twenty kidney transplant recipients were randomized to clazakizumab versus placebo (4-weekly doses; 12 weeks), followed by a 9-month extension where all recipients received clazakizumab. To study CYP2C19/CYP3A4 metabolism, we administered pantoprazole (20 mg intravenously) at prespecified time points. Dose-adjusted C0 levels (C0 /D ratio) of tacrolimus (n = 13) and cyclosporin A (CyA, n = 6) were monitored at 4-weekly intervals. IL-6 and C-reactive protein were not elevated at baseline, the latter was then suppressed to undetectable levels under clazakizumab. IL-6 blockade had no clinically meaningful impact on pantoprazole pharmacokinetics (area under the curve; baseline versus week 52: 3.16 [2.21-7.84] versus 4.22 [1.99-8.18] μg/ml*h, P = 0.36) or calcineurin inhibitor C0 /D ratios (tacrolimus: 1.49 [1.17-3.20] versus 1.37 [0.98-2.42] ng/ml/mg, P = 0.21; CyA: 0.69 [0.57-0.85] versus 1.08 [0.52-1.38] ng/ml/mg, P = 0.47). We conclude that IL-6 blockade in ABMR - in absence of systemic inflammation - may have no meaningful effect on CYP metabolism.