Performance of Panel-Estimated GFR Among Hospitalized Older Adults.

RATIONALE & OBJECTIVE: Older adults represent nearly half of all hospitalized patients and are vulnerable to inappropriate dosing of medications eliminated through the kidneys. However, few studies in this population have evaluated the performance of equations for estimating the glomerular filtration rate (GFR)-particularly those that incorporate multiple filtration markers. STUDY DESIGN: Cross-sectional diagnostic test substudy of a randomized clinical trial. SETTING & PARTICIPANTS: Adults≥65 years of age presenting to the emergency department of Copenhagen University Hospital Amager and Hvidovre in Hvidovre, Denmark, between October 2018 and April 2021. TESTS COMPARED: Measured GFR (mGFR) determined using 99mTc-DTPA plasma clearance compared with estimated GFR (eGFR) calculated using 6 different equations based on creatinine; 3 based on creatinine and cystatin C combined; and 2 based on panels of markers including creatinine, cystatin C, ß-trace protein (BTP) and/or ß2-microglobulin (B2M). OUTCOME: The performance of each eGFR equation compared with mGFR with respect to bias, relative bias, inaccuracy (1-P30), and root mean squared error (RMSE). RESULTS: We assessed eGFR performance for 106 patients (58% female, median age 78.3 years, median mGFR 62.9mL/min/1.73m2). Among the creatinine-based equations, the 2009 CKD-EPIcr equation yielded the smallest relative bias (+4.2%). Among the creatinine-cystatin C combination equations, the 2021 CKD-EPIcomb equation yielded the smallest relative bias (-3.4%), inaccuracy (3.8%), and RMSE (0.139). Compared with the 2021 CKD-EPIcomb, the CKD-EPIpanel equation yielded a smaller RMSE (0.136) but larger relative bias (-4.0%) and inaccuracy (5.7%). LIMITATIONS: Only White patients were included; only a subset of patients from the original clinical trial underwent GFR measurement; and filtration marker concentration can be affected by subclinical changes in volume status. CONCLUSIONS: The 2009 CKD-EPIcr, 2021 CKD-EPIcomb, and CKD-EPIpanel equations performed best and notably outperformed their respective full-age spectrum equations. The addition of cystatin C to creatinine-based equations improved performance, while the addition of BTP and/or B2M yielded minimal improvement. FUNDING: Grants from public sector industry (Amgros I/S) and government (Capital Region of Denmark). TRIAL REGISTRATION: Registered at ClinicalTrials.gov with registration number NCT03741283. PLAIN-LANGUAGE SUMMARY: Inaccurate kidney function assessment can lead to medication errors, a common cause of hospitalization and early readmission among older adults. Several novel methods have been developed to estimate kidney function based on a panel of kidney function markers that can be measured from a single blood sample. We evaluated the accuracy of these new methods (relative to a gold standard method) among 106 hospitalized older adults. We found that kidney function estimates combining 2 markers (creatinine and cystatin C) were highly accurate and noticeably more accurate than estimates based on creatinine alone. Estimates incorporating additional markers such as ß-trace protein and ß2-microglobulin did not further improve accuracy.

Estimated glomerular filtration rate based on creatinine, cystatin C, ß-trace protein and ß2 microglobulin in patients undergoing nontraumatic lower extremity amputation.

AIMS: The study's aim is to compare current and new equations for estimating glomerular filtration rate (GFR) based on creatinine, cystatin C, ß-trace protein (BTP) and ß2 microglobulin (B2M) among patients undergoing major amputation. METHODS: This is a secondary analysis of data from a prospective cohort study investigating patients undergoing nontraumatic lower extremity amputation. Estimated GFR (eGFR) was calculated using equations based on creatinine (eGFRcre[2009] and eGFRcre[2021]), cystatin C (eGFRcys), the combination of creatinine and cystatin C (eGFRcomb[2012] and eGFRcomb[2021]) or a panel of all 4 filtration markers (eGFRpanel). Primary outcome was changed in eGFR across amputation according to each equation. Two case studies of prior amputation with GFR measured by 99mTc-DTPA clearance are described to illustrate the relative accuracies of each eGFR equation. RESULTS: Analysis of the primary outcome included 29 patients (median age 75 years, 31% female). Amputation was associated with a significant decrease in creatinine concentration (-0.09 mg/dL, P = 0.004), corresponding to a significant increase in eGFRcre[2009] (+6.1 mL/min, P = 0.006) and eGFRcre[2021] (+6.3 mL/min, P = 0.006). Change across amputation was not significant for cystatin C, BTP, B2M or equations incorporating these markers (all P > 0.05). In both case studies, eGFRcre[2021] yielded the largest positive bias, eGFRcys yielded the largest negative bias and eGFRcomb[2012] and eGFRcomb[2021] yielded the smallest absolute bias. CONCLUSION: Creatinine-based estimates were substantially higher than cystatin C-based estimates before amputation and significantly increased across amputation. Estimates combining creatinine and cystatin were stable across amputation, while the addition of BTP and B2M is unlikely to be clinically relevant.

Using soluble urokinase plasminogen activator receptor to stratify patients for medication review in the emergency department.

AIMS: To investigate whether the association between levels of medication use (including polypharmacy and potentially inappropriate medications [PIMs]) and health outcomes such as readmission and mortality is dependent on baseline soluble urokinase plasminogen activator receptor (suPAR). METHODS: This registry-based cohort study included medical patients admitted to the emergency department at Copenhagen University Hospital Hvidovre, Denmark. Patients were grouped according to their admission suPAR levels: low (0-3 ng/mL), intermediate (3-6 ng/mL), or high (>6 ng/mL). Hyper-polypharmacy was defined as ≥10 prescribed medications. PIMs were identified based on the EU(7)-PIM list, and data on admissions and mortality were obtained from national registries. Risk of 90-day readmission and mortality was assessed by Cox regression analysis adjusted for sex, age and Charlson comorbidity index. Results were reported as hazard ratios within 90 days of index discharge. RESULTS: In total, 26 291 patients (median age 57.3 y; 52.7% female) were included. Risk of 90-day readmission and mortality increased significantly for patients with higher suPAR or higher number of medications. Among patients with low suPAR, patients with ≥10 prescribed medications had a hazard ratio of 2.41 (95% confidence interval = 2.09-2.78) for 90-day readmission and 8.46 (95% confidence interval = 2.53-28.28) for 90-day mortality compared to patients with 0 medications. Patients with high suPAR generally had high risk of readmission and mortality, and the impact of medication use was less pronounced in this group. Similar, but weaker, association patterns were observed between suPAR and PIMs. CONCLUSION: The association between levels of medication use and health outcomes is dependent on baseline suPAR.

Alterations of monocyte NF-κB p65/RelA signaling in a cohort of older medical patients, age-matched controls, and healthy young adults.

BACKGROUND: Altered monocyte NF-κB signaling is a possible cause of inflammaging and driver of aging, however, evidence from human aging studies is sparse. We assessed monocyte NF-κB signaling across different aging trajectories by comparing healthy older adults to older adults with a recent emergency department (ED) admission and to young adults. METHODS: We used data from: 52 older (≥65 years) Patients collected upon ED admission and at follow-up 30-days after discharge; 52 age- and sex-matched Older Controls without recent hospitalization; and 60 healthy Young Controls (20-35 years). Using flow cytometry, we assessed basal NF-κB phosphorylation (pNF-κB p65/RelA; Ser529) and induction of pNF-κB following stimulation with LPS or TNF-α in monocytes. We assessed frailty (FI-OutRef), physical and cognitive function, and plasma levels of IL-6, IL-18, TNF-α, and soluble urokinase plasminogen activator receptor. RESULTS: Patients at follow-up were frailer, had higher levels of inflammatory markers and decreased physical and cognitive function than Older Controls. Patients at follow-up had higher basal pNF-κB levels than Older Controls (median fluorescence intensity (MFI): 125, IQR: 105-153 vs. MFI: 80, IQR: 71-90, p < 0.0001), and reduced pNF-κB induction in response to LPS (mean pNF-κB MFI fold change calculated as the log10 ratio of LPS-stimulation to the PBS-control: 0.10, 95% CI: 0.08 to 0.12 vs. 0.13, 95% CI: 0.10 to 0.15, p = 0.05) and TNF-α stimulation (0.02, 95% CI: - 0.00 to 0.05 vs. 0.10, 95% CI: 0.08 to 0.12, p < 0.0001). Older Controls had higher levels of inflammatory markers than Young Controls, but basal pNF-κB MFI did not differ between Older and Young Controls (MFI: 81, IQR: 70-86; p = 0.72). Older Controls had reduced pNF-κB induction in response to LPS and TNF-α compared to Young Controls (LPS: 0.40, 95% CI: 0.35 to 0.44, p < 0.0001; and TNF-α: 0.33, 95% CI: 0.27 to 0.40, p < 0.0001). In Older Controls, basal pNF-κB MFI was associated with FI-OutRef (p = 0.02). CONCLUSIONS: Increased basal pNF-κB activity in monocytes could be involved in the processes of frailty and accelerated aging. Furthermore, we show that monocyte NF-κB activation upon stimulation was impaired in frail older adults, which could result in reduced immune responses and vaccine effectiveness.

A characterization of patients with low soluble urokinase plasminogen activator receptor who died within 90 days of hospital discharge.

Soluble urokinase plasminogen activator receptor (suPAR) is a marker of systemic chronic inflammation. Elevated suPAR levels are associated with adverse clinical outcomes, but a small subset of patients with low suPAR also experience poor outcomes. Therefore, we aimed to characterize patients presenting to the emergency department with low suPAR (<3 ng/mL) who died within 90 days after discharge in a registry-based study. Compared to patients with low suPAR who survived (n = 15 122), those who died within 90 days (n = 87) had higher age (75.4 years), higher medication use (7.0; 71.3% with polypharmacy) and more blood tests outside reference intervals (5.0) (including C-reactive protein, neutrophils and albumin), and the most common diagnoses were chronic pulmonary disease (27.6%), cerebrovascular disease (18.4%) and dementia (11.5%). Patients with low suPAR were more morbid than what was reflected by suPAR alone. Future studies must determine which factors that contribute the most to potential algorithms when stratifying patients based on their risk of adverse clinical outcomes. These data indicate that inclusion of medication data could be relevant.

Inappropriate prescribing in patients with kidney disease: A rapid review of prevalence, associated clinical outcomes and impact of interventions.

BACKGROUND: The prevalence of patients with chronic kidney disease (CKD) and polypharmacy is increasing and has amplified the importance of examining inappropriate prescribing (IP) in CKD. This review focuses on the latest research regarding the prevalence of IP in CKD and the related adverse clinical effects and explores new interventions against IP. METHOD: A literature search was performed using PubMed, EMBASE and the Cochrane Library searching articles published between June 2016 and March 2022. RESULTS: Twenty-seven studies were included. An IP prevalence of 12.6% to 96% and 0.3% to 66% was reported in hospital and outpatient settings, respectively. In nonhospital settings, the prevalence of IP varied between 3.9% and 60%. IP was associated with higher risk of hospitalisation (HR 1.46, 95% CI 1.17-1.81), higher bleeding rate (HR 2.34, 95% CI 1.32 to 3.37) and higher risk of all-cause mortality (OR 1.07, 95% CI 1.02 to 1.13). Three studies reported the impact of interventions on IP. CONCLUSION: This review highlights widespread IP in CKD patients across healthcare settings, with varying prevalence rates. IP is substantially linked to adverse outcomes in patients. While limited interventions show promise, urgent research is needed to develop effective strategies addressing IP and improving CKD patient care.

Growth differentiation factor 15 (GDF15) levels are associated with malnutrition in acutely admitted older adults.

BACKGROUND AND AIMS: The aging process is often accompanied by high risk of malnutrition and elevated levels of growth differentiation factor 15 (GDF15). GDF15 is an increasingly recognized biomarker for regulation of metabolism, but few studies have investigated the connection between GDF15 and malnutrition in older age and how it relates to other features of aging such as decreased appetite and physical function. Therefore, we investigated the associations between GDF15 levels and nutritional status, appetite, and physical function in acutely admitted older adults. METHODS: Plasma GDF15 levels were measured using immunoassays in 302 older adults (≥65 years) admitted to the emergency department (ED). Nutritional status was evaluated with the Mini Nutritional Assessment Short-Form (MNA®-SF), appetite was evaluated with the Simplified Nutritional Appetite Questionnaire (SNAQ), and physical function was evaluated with handgrip strength (HGS), 30-s chair stand test (30s-RSS), and gait speed (GS). Associations between GDF15 and each outcome was determined by logistic regression adjusted for age, sex, and C-reactive protein (CRP). RESULTS: Each doubling in plasma GDF15 level was associated with an adjusted odds ratio (OR) (95% confidence interval) of 1.59 (1.10-2.29, P = 0.01) for risk of malnutrition compared to normal nutrition and 1.19 (0.85-1.69, P = 0.3)) for malnutrition compared to risk of malnutrition. Each doubling in GDF15 was associated with an adjusted OR of 1.63 (1.21-2.23)) for having poor appetite, 1.46 (1.07-1.99) for having low HGS, 1.74 (1.23-2.51) for having low 30s-RSS, and 1.99 (1.39-2.94) for having low GS. CONCLUSION: Among older adults admitted to the ED, higher GDF15 levels were significantly associated with malnutrition, poor appetite, and low physical function independent of age, sex, and CRP.

Development of a quick guide for assessment of the most frequently used renal risk medication in Danish hospitals and primary care.

Due to changes in pharmacokinetics and pharmacodynamics, patients with impaired renal function suffer an increased risk of suboptimal and potentially harmful medication treatment. This necessitates careful consideration of medications affected by impaired renal function when performing medication reviews. The aim of this study was to develop a quick guide (a list of recommendations) for assessing renal risk medications in medication reviews led by hospital pharmacists. The list was based on the 100 most frequently used medications in Danish hospitals and primary care. After combining the 200 records, 29 duplicates were excluded resulting in a pool of 171 medications. Assessment by two clinical pharmacists led to the exclusion of 121 medications. Of the remaining 50 medications, seven were discussed among the two pharmacists, and two of these were also in the research group to reach a consensus. The renal risk quick guide comprised 50 medications. The most prevalent medications on the list were from Anatomical Therapeutic Chemical Classification System (ATC)-group N, C and L. Recommendations from two databases were included in the quick guide in order to provide clinical pharmacists with existing, updated evidence on medication use in impaired renal function. The next step is to test the feasibility of the quick guide in daily practice when performing medication reviews.

Optimization of the Danish National Electronic Prescribing System to Improve Patient Safety: Development of a User-Friendly Prototype of the Digital Platform Shared Medication Record.

This study uses a participatory design to develop a user-friendly prototype of the current Danish digital platform, Shared Medication Record (SMR), to improve patient safety and minimize medication errors for patients with multimorbidity. A fundamental challenge for medication prescribing is the lack of access to an accurate medication list, which impairs effective communication between healthcare professionals and increases the risk of medication errors. We used a participatory design to identify the major problems with the existing SMR and develop a prototype for a redesigned SMR that addresses these problems. We argue that this prototype will improve communication between healthcare providers, promote patient involvement in their own care, and ultimately reduce medication errors related to the SMR. Moreover, we argue that the participatory design with its emphasis on user involvement and design iterations is a strong approach when designing IT solutions for complex problems in healthcare.

Evaluation of Multi-Frequency Bioelectrical Impedance Analysis against Dual-Energy X-ray Absorptiometry for Estimation of Low Muscle Mass in Older Hospitalized Patients.

The accuracy of multi-frequency (MF) bioelectrical impedance analysis (BIA) to estimate low muscle mass in older hospitalized patients remains unclear. This study aimed to describe the ability of MF-BIA to identify low muscle mass as proposed by The Global Leadership Initiative on Malnutrition (GLIM) and The European Working Group on Sarcopenia in Older People (EWGSOP-2) and examine the association between muscle mass, dehydration, malnutrition, and poor appetite in older hospitalized patients. In this prospective exploratory cohort study, low muscle mass was estimated with MF-BIA against dual-energy X-ray absorptiometry (DXA) in 42 older hospitalized adults (≥65 years). The primary variable for muscle mass was appendicular skeletal muscle mass (ASM), and secondary variables were appendicular skeletal muscle mass index (ASMI) and fat-free mass index (FFMI). Cut-off values for low muscle mass were based on recommendations by GLIM and EWGSOP-2. MF-BIA was evaluated against DXA on the ability to estimate absolute values of muscle mass by mean bias, limits of agreement (LOA), and accuracy (5% and 10% levels). Agreement between MF-BIA and DXA to identify low muscle mass was evaluated with sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV). The association between muscle mass, dehydration, malnutrition, and poor appetite was visually examined with boxplots. MF-BIA overestimated absolute values of ASM with a mean bias of 0.63 kg (CI: -0.20:1.46, LOA: -4.61:5.87). Agreement between MF-BIA and DXA measures of ASM showed a sensitivity of 86%, specificity of 94%, PPV of 75% and NPV of 97%. Boxplots indicate that ASM is lower in patients with malnutrition. This was not observed in patients with poor appetite. We observed a tendency toward higher ASM in patients with dehydration. Estimation of absolute ASM values with MF-BIA should be interpreted with caution, but MF-BIA might identify low muscle mass in older hospitalized patients.

Comparison of 24-hour urinary creatinine clearance and estimated glomerular filtration rate based on a panel of filtration markers in patients with chronic kidney disease.

Diagnosis and management of chronic kidney disease (CKD) requires accurate assessment of glomerular filtration rate (GFR). In practice, GFR is typically estimated by equations based on creatinine concentration in blood, but creatinine is affected by non-GFR factors such as age and sex. Alternative filtration markers such as cystatin C, beta-trace protein (BTP), and beta-2 microglobulin (B2M) may be less dependent on age and sex, but equations combining these markers have not been investigated in patients with chronic kidney disease (CKD). In this cross-sectional study of 50 patients with CKD stage 3-4, we compared kidney function estimates based on creatinine, cystatin C, BTP, B2M, or a combination of markers. Compared to the creatinine/cystatin C combination equation, the panel equation yielded a mean difference of only 2.8 ml/min/1.73 m2 , indicating that switching to the panel equation would be unlikely to affect management.

Medicines Reconciliation in the Emergency Department: Important Prescribing Discrepancies between the Shared Medication Record and Patients' Actual Use of Medication.

Medication reconciliation is crucial to prevent medication errors. In Denmark, primary and secondary care physicians can prescribe medication in the same electronic prescribing system known as the Shared Medication Record (SMR). However, the SMR is not always updated by physicians, which can lead to discrepancies between the SMR and patients' actual use of medication. These discrepancies may compromise patient safety upon admission to the emergency department (ED). Here, we investigated (a) the occurrence of discrepancies, (b) factors associated with discrepancies, and (c) the percentage of patients accessible to a clinical pharmacist during pharmacy working hours. The study included all patients age ≥ 18 years who were admitted to the Hvidovre Hospital ED on three consecutive days in June 2020. The clinical pharmacists performed medicines reconciliation to identify prescribing discrepancies. In total, 100 patients (52% male; median age 66.5 years) were included. The patients had a median of 10 [IQR 7-13] medications listed in the SMR and a median of two [IQR 1-3.25] discrepancies. Factors associated with increased rate of prescribing discrepancies were age < 65 years, time since last update of the SMR ≥ 115 days, and patients' self-dispensing their medications. Eighty-four percent of patients were available for medicines reconciliations during the normal working hours of the clinical pharmacist. In conclusion, we found that discrepancies between the SMR and patients' actual medication use upon admission to the ED are frequent, and we identified several risk factors associated with the increased rate of discrepancies.