Measures Of Function Research Articles

#1023 Patient outcomes and graft survival among kidney transplant recipients with chronic hepatitis C infection: a single center study

Abstract Background and Aims Previous studies have shown that kidney transplant_(KT) recipients with chronic hepatitis C (HCV) infection have lower survival rates after transplantation. With the emergence of direct-acting antiviral therapy for HCV infection, the long-term outcomes for these patients are still unknown. This aims to evaluate the 5-year graft and patient outcomes of kidney transplant recipients with HCV infection at the National Kidney and Transplant Institute. Method A retrospective cohort study of HCV-positive KT recipients which were compared to HCV-negative patients in the same post-transplantation period. Data gathered from the patient's in-hospital and outpatient records and MEDSYS database. Results Twelve(12) out of 117 KT recipients with HCV infection were included. Half of these patients had detectable HCV RNA before KT. There was no difference in recipients' age, gender, and donor type between the groups. HCV infection is significantly associated with and an independent predictor of graft loss, rejection, and mortality. Patient survival between groups did not show any significant difference. Rates of graft rejection, graft loss, and patient mortality among HCV-positive recipients did not show statistically significant difference between groups. Graft survival rates at 6 months, 1-, 3-, and 5 years post KT were significantly lower among HCV-positive KT recipients compared to HCV-negative recipients. There were no significant differences in renal function, presence of proteinuria, liver enzyme levels, and incidence of cirrhosis between the groups. Conclusion Graft survival was shorter in HCV-positive KT recipients. Patient survival, measures of kidney function, and liver-related complications were similar between HCV-positive and HCV-negative KT recipients after transplantation.

Arrow of time and gravitational entropy in collapse

We investigate the status of the gravitational arrow of time in the case of a spherical collapse of a fluid that conducts heat and radiates energy. In particular, we examine the results obtained by W. B. Bonnor in his 1985 paper where he found that the gravitational arrow of time was opposite to the thermodynamic arrow of time. The measure of gravitational epoch function P used by Bonnor was given by the ratio of the Weyl square to the Ricci square. In this paper, we have assumed the measure of gravitational entropy (GE) P 1 to be given by the ratio of the Weyl scalar to the Kretschmann scalar. Our analysis indicates that Bonnor’s result seems to be validated, i.e. the gravitational arrow and the thermodynamic arrow of time point in opposite directions. This strengthens the opinion that the Weyl proposal of GE applies only to the Universe as a whole (provided that we exclude the white holes).

#2832 Lean tissue mass is associated with mortality across different stages of chronic kidney disease: a systematic review and meta-analysis

Abstract Background and Aims Loss of lean tissue mass (LLTM) commonly occurs in multiple long-term conditions (LTC), including chronic kidney disease (CKD), and is thought to be associated with adverse outcomes including mortality, frailty surrogates and poor quality of life. It remains unclear whether LLTM is directly associated with mortality in CKD after adjusting for the severity of CKD or the degree of multimorbidity, and whether such associations remain in other LTC with similar levels of multimorbidity, such as heart failure (HF). Method A systematic review was conducted in adult CKD [kidney transplant (KT), CKDG3-5 or dialysis treated kidney failure (D-KF)] and HF patients who had whole body bioimpedance defined lean tissue mass (BI-LTM). The primary outcome was mortality, with secondary outcomes including hospitalisation and health related quality of life (HRQoL). The review was registered with PROSPERO (CRD42021240688) and was conducted according to PRISMA guidelines. Electronic database searches of MEDLINE, EMBASE, AMED, CINAHL, PsychInfo, Web of Science, CENTRAL, ICTRP and ISRCTN were searched from inception until June 2023. Data extraction and risk of bias assessments, using the Quality in Prognosis Studies (QUIPS) tool, was performed by two independent reviewers. Random effects meta-analysis was conducted using STATA SE16.2 using restricted maximum likelihood (REML) estimation. Results From 10,024 citations, 126 studies were identified (100 D-KF, 12 CKDG3-5, 2 KT, 3 mixed CKD and 9 HF) reporting outcomes on 143,053 D-KF, 15,164 CKDG3-5, 346 KTR and 3716 HF patients respectively. There were 1,227 deaths (over 2-5 years) in the HF studies and 16,471 deaths (over 1-20 years) in the CKD studies. The weighted mean eGFRCreat was 54 and 42 ml/min/1.73 m2 in the KT and CKDG3-5 studies, with only 3 HF studies reporting any measure of renal function (all using categorical cut offs). In 87 studies survival analyses of all-cause mortality (ACM) showed that BI-LTM was associated with mortality in 67%, 100%, 85% and 74% of the HF, KT, CKDG3-5 and D-KF studies respectively after adjusting for age, sex, diabetic status, comorbidity score, CRP / IL-6, albumin and bioimpedance defined fluid measures in 93%, 77%, 64%, 17%, 32%, 59% and 24% of analyses. Meta-analysis within D-KF studies reporting MVA revealed a 1-degree decrease in phase angle (pooled HR 1.82, 95% CI 1.50-2.20: Fig. 1A) and lean tissue index <10th percentile (pooled HR 1.48, 95% CI 1.31-1.66: Fig. 1B) was associated with ACM. Leave one out meta-analysis and sensitivity analyses removing studies at high-risk of statistical analysis and study confounding bias confirmed these pooled estimates were robust. Of the studies reporting secondary outcomes including hospitalisation and HRQoL (including the Short Form-36 and Kidney Disease Quality of Life Instrument), 67% showed associations with BI-LTM. Conclusion LLTM is associated with mortality across all stages of CKD and in heart failure. Furthermore, LLTM is associated with adverse outcomes such as hospitalisation and poor quality of life. This study confirms that LLTM potentially has an important role in the explanatory pathway for adverse outcomes in patients with LTCs, including CKD. Using BI-LTM may provide a way to identify early LLTM and target interventions to reduce the risk of adverse outcomes in these multimorbid cohorts.

Financial and numerical abilities: patterns of dissociation in neurological and psychiatric diseases.

The present work investigates whether financial abilities can be associated with numerical abilities and with general cognitive abilities. We compared performance on numerical and financial tests, and on tests routinely used to measure general cognitive performance, in healthy controls and in a group of people with heterogeneous pathological conditions including mild cognitive impairment, amyotrophic lateral sclerosis, traumatic brain injury, and schizophrenia. Patients showed lower performances in both numerical and financial abilities compared to controls. Numerical and financial skills were positively correlated in both groups, but they correlated poorly with measures of general cognitive functioning. Crucially, only basic financial tasks -such as counting currencies- but not advanced ones -like financial judgments- were associated with numerical or general cognitive functioning in logistic regression analyses. Conversely, advanced financial abilities, but not basic ones, were associated with abstract reasoning. At a qualitative analysis, we found that deficits in numerical and financial abilities might double dissociate. Similarly, we observed double dissociations between difficulties in financial abilities and cognitive deficits. In conclusion, financial abilities may be independent of numerical skills, and financial deficits are not always related to the presence of cognitive difficulties. These findings are important for both clinical and legal practice.

#2459 Matching-adjusted indirect comparison of eGFR in patients with immunoglobulin A nephropathy treated with Nefecon (TRF budesonide) or sparsentan

Abstract Background and Aims Primary immunoglobulin A nephropathy (IgAN) is an immune-mediated disease that can lead to kidney failure, need for dialysis and kidney transplantation, and early death. IgAN is the most common type of primary glomerulonephritis globally, with an estimated worldwide incidence of 2.5 per 100 000 individuals per year. Estimated glomerular filtration rate (eGFR) is a measure of renal function and is accepted as a surrogate endpoint for clinical trials evaluating kidney function deterioration. In December 2023, the US Food and Drug Administration (FDA) granted full approval to Nefecon (marketed as Tarpeyo® by Calliditas Therapeutics), a targeted-release formulation of budesonide, to reduce the loss of kidney function in adults with IgAN at risk of disease progression, based on the Phase 3 NefIgArd clinical trial. In February 2023, sparsentan (marketed as Filspari™ by Travere Therapeutics) was granted accelerated approval by the FDA to reduce proteinuria in adults with primary IgAN at risk of rapid disease progression, generally a urine protein–creatinine ratio (UPCR) ≥1.5 g/g, based on the Phase 3 PROTECT study. Matching-adjusted indirect comparison (MAIC) is a widely accepted and relevant methodology for comparing treatments across trials in the absence of head-to-head comparisons. In this analysis, we aimed to compare the effects of Nefecon and sparsentan on kidney function deterioration in patients with IgAN, as assessed by eGFR. Method An anchored MAIC was performed to estimate the relative effect of Nefecon and sparsentan on the absolute eGFR change from baseline at 9, 12 and 24 months, with common comparators of optimized renin–angiotensin system inhibition for NefIgArd and irbesartan for PROTECT. Patient-level data from NefIgArd were used to select a population matched to PROTECT, and the following baseline characteristics were used to determine the weights: mean age (years), sex (% male), race (% white), mean eGFR (mL/min/1.73 m2), mean UPCR (g/g), urine albumin–creatinine ratio (UACR) (% with UACR >1.1 g/g), and urinary protein excretion (% with urinary protein excretion >1.8 g/day). Absolute change in eGFR was analyzed using a mixed model for repeated measures (MMRM) method, including baseline, 3-, 6-, 9-, 12-, 18- and 24-month data, baseline eGFR, baseline eGFR-by-time interaction, treatment, and treatment-by-time interaction. The MAIC weights were incorporated into the MMRM. A Bayesian fixed-effects network meta-analysis was performed on the relative effect from PROTECT and the weighted relative effect from NefIgArd, measured by the estimated absolute change from baseline in eGFR. Results The matching-adjustment of the NefIgArd patient population to the PROTECT population is shown in Table 1. The weighted NefIgArd population exhibits very similar baseline characteristics to the PROTECT population. The effective sample size of the weighted NefIgArd population is 208. Results from the anchored MAIC showed statistically and clinically significant favorable effects of Nefecon versus sparsentan on eGFR for all time points analyzed (Fig. 1). Mean differences in the absolute change in eGFR of 5.68 mL/min/1.73 m2 (95% credible interval [Crl] 3.14, 8.20; p < 0.001), 3.48 mL/min/1.73 m2 (95% Crl 0.97, 5.97; p = 0.006) and 3.28 mL/min/1.73 m2 (95% Crl 0.02, 6.51; p = 0.048) were observed when comparing Nefecon with sparsentan at 9 months vs 36 weeks, 12 months vs 48 weeks, and 24 months vs 106 weeks, respectively. Conclusion After accounting for differences in the patient populations from the NefIgArd and PROTECT trials, the anchored MAIC showed that treatment with Nefecon 16 mg/day for 9 months was associated with greater eGFR benefit compared with continuous treatment with sparsentan 400 mg/day over 2 years, with significant differences observed as early as 9 months after treatment initiation and sustained up to 2-years of follow-up.

#1321 Long term outcomes in people with fluctuating criteria for the diagnosis of chronic kidney disease

Abstract Background and Aims The diagnostic criteria for chronic kidney disease (CKD) recognise that measures of kidney function may fluctuate in the short term by requiring that abnormalities must persist for at least 90 days to support the diagnosis. Nevertheless, studies have reported that even people who meet the diagnostic criteria may have transient or prolonged improvement in kidney function in the absence of specific treatment. In this study we used the opportunity afforded by long term follow-up of a cohort recruited from primary care to assess the impact on outcomes of fluctuations in CKD diagnostic criteria. Method Participants with confirmed CKD stage 3 were recruited from primary care practices in 2008-2010. Clinical assessment and protocol laboratory tests were performed at baseline, 1 and 5 year study visits. In 2019-20, information on deaths and latest available outpatient estimated GFR (eGFR) and urine albumin to creatinine ratio (UACR) values was obtained from electronic records. Participants with eGFR ≥60 ml/min/1.73 m2 and UACR <3 mg/mmol were regarded as being in “remission” at each time point. CKD progression was defined as a decline in eGFR of ≥25% and progression to a more advanced stage (KDIGO definition). Results The cohort included 1741 participants with median (IQR) age 74 (67-79) years, eGFR 53.8 (45.3-61.7) ml/min/1.73 m2 and UACR 0.3 (0.001-1.5) mg/mmol at baseline. During a median observation period of 9.8 (9.2-10.0) years, 680 participants (39.1%) died and CKD progression was observed in 430 of 1402 (30.6%) but only 24 (1.4%) progressed to CKD stage 5. The prevalence of remission was 495/1737 (28.5%) at baseline, 424/1618 (26.2%) at year 1, 335/1236 (27.1%) at year 5 and 176/1190 (14.8%) at year 10. Remission was present at all three visits in 15.4%, two visits in 13.0% and one visit in 15.8%. Participants with diabetes and those treated with a renin-angiotensin system inhibitor evidenced a lower prevalence of remission at all time points. Blood pressure control to <130/80 mmHg was not associated with remission. Evidence of remission at 1, 2 or 3 study visits was associated with progressively lower incidence of persistent CKD, CKD progression and death at 10 years (Table, p < 0.001 for all trends). No participants with an episode of remission had progressed to CKD stage 5 at 10 years. Conclusion A substantial minority of people diagnosed with CKD in primary care exhibit fluctuating diagnostic criteria. People with one or more episodes of remission appear to have a better prognosis than those with persistent CKD but remain at risk of CKD progression. They can therefore be reassured that an episode of remission is associated with an improved prognosis but long-term monitoring of kidney function is still warranted.

Responsiveness and construct validity of two outcome measures of bilateral upper limb function in patients with chronic stroke

BackgroundStroke is a leading cause of long-term disability among stroke survivors. Despite the availability of numerous stroke rehabilitative therapies, such as mirror therapy, bilateral arm training, and robot-assisted therapy, the recovery of motor function after stroke remains incomplete. Bilateral arm function is a key component in stroke patients to perform activities of daily living and to reflect their functional autonomy.ObjectiveThis clinimetric study investigated and compared the construct validity and responsiveness of 2 bimanual activity outcome measures, the Chedoke Arm and Hand Activity Inventory (CAHAI) and the ABILHAND Questionnaire, in individuals receiving stroke rehabilitation.MethodsThe present study is a secondary analysis following the framework of the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN). Individuals with chronic stroke (N = 113) were recruited from outpatient rehabilitation settings. Participants received 18 to 20 sessions of robot-assisted therapy, mirror therapy, combined therapy, or conventional rehabilitation for 4 to 6 weeks. The CAHAI, ABILHAND Questionnaire, and a comparison instrument, the Motor Activity Log (MAL), were administered twice at a 4- to 6-week interval to all participants. ABILHAND scores, in logits, were converted from raw ordinal scores into a linear measure.ResultsThere was medium to large correlation of the CAHAI and the MAL (ρ = 0.60–0.62, p < 0.01) as well as the ABILHAND Questionnaire and the MAL (ρ = 0.44–0.51, p < 0.01). Change scores from the initial measurement to the post-intervention measurement demonstrated small to medium correlation of the CAHAI and the MAL (ρ = 0.27–0.31, p < 0.01) and medium to large correlation of the ABILHAND Questionnaire and the MAL (ρ = 0.37–0.41, p < 0.01). Overall, 7 of 8 hypotheses were supported. The hypothesis testing regarding the construct validity and responsiveness of the CAHAI and ABILHAND Questionnaire was confirmed.ConclusionThe CAHAI and ABILHAND Questionnaire are both responsive and suitable to detect changes in bilateral arm functional daily activities in individuals with chronic stroke. Patient-reported outcome measures are recommended to use along with therapist-rated outcome measures for upper limb capacity evaluation in stroke rehabilitation. Further study with a prospective study design to capture specific clinical features of participants and the use of body-worn sensors, such as the arm accelerometer, is suggested.

Co-occurring Chronic Pain and PTSD Among US Military Veterans: Prevalence, Correlates, and Functioning.

The prevalence of co-occurring chronic pain and posttraumatic stress disorder (PTSD) has yet to be established in a nationally representative sample of US veterans, and little is known about the individual contributing roles of these disorders to the psychiatric and functional burden of this comorbidity. To determine the prevalence of chronic pain, PTSD, and co-occurring chronic pain and PTSD, and psychiatric comorbidities and psychosocial functioning in these groups. Data were analyzed from the National Health and Resilience in Veterans Study, which surveyed a nationally representative sample of US veterans. Veterans (n=4069) were classified into four groups: control (i.e., no PTSD or chronic pain), chronic pain only, PTSD only, and co-occurring chronic pain and PTSD. A probable PTSD diagnosis was established using the PTSD Checklist for DSM-5, and a chronic pain diagnosis using a self-report item that queried health care professional diagnoses. Psychiatric and functional status were assessed using the Patient Health Questionnaire-4, Alcohol Use Disorders Identification Test, Screen of Drug Use, Suicide Behaviors Questionnaire-Revised, Short Form Health Survey-8, Brief Inventory of Psychosocial Functioning, and Medical Outcomes Study Cognitive Functioning Scale. A total of 3.8% of veterans reported both probable PTSD and a diagnosis of chronic pain. Relative to veterans with chronic pain alone, those with co-occurring chronic pain and probable PTSD were more likely to screen positive for psychiatric disorders (odds ratios [ORs]=2.59-9.88) and scored lower on measures of psychosocial functioning (Cohen's ds=0.38-1.43). Relative to veterans with probable PTSD only, those with co-occurring chronic pain and probable PTSD were more likely to have attempted suicide (OR=4.79; 95%CI, 1.81-12.69). Results underscore the importance of whole health care that considers a broad range of health and functional domains in the assessment and treatment of co-occurring chronic pain and PTSD in veterans.

A Potential Measure of Premorbid Functioning: Evaluating the Construct Validity of the Author and Magazine Recognition Tests.

To establish convergent and discriminant validity for a combined measure of print exposure (i.e., Author Recognition Test and Magazine Recognition Test [ART/MRT]) and assess its potential utility for estimating premorbid cognitive functioning. Community-dwelling older adults (N = 84; 95% non-Hispanic White) completed the ART/MRT, Test of Premorbid Functioning (ToPF), Dementia Rating Scale - 2nd Edition (DRS-2), Hopkins Verbal Learning Test - Revised (HVLT-R-DR), and select subtests from the Delis-Kaplan Executive Functioning System (D-KEFS) as measures of executive functioning (i.e., D-KEFS-EF) and processing speed (i.e., D-KEFS-PS). Pearson correlations and linear regressions were used to examine the relationships between the ART/MRT, cognition, and demographics. Cognitive scores, with the exception of HVLT-R-DR, were positively correlated with ART/MRT score such that better cognitive performance was associated with greater print exposure (range r = 0.39-0.49). ART/MRT score was positively correlated with years of education and negatively correlated with age. ToPF and DRS-2 differentially and uniquely predicted ART/MRT score beyond the other cognitive and demographic variables and beyond each other. Findings indicate that measures of print exposure reflect crystallized knowledge but may also capture fluid abilities that may be more vulnerable to age-related decline or neurodegeneration. Assessment of print exposure may offer an alternative to word reading measures that may be inappropriate for translation into other languages and for use with individuals with certain language difficulties.

Neural correlates of response to joint attention in 2-to-5-year-olds in relation to ASD and social-communicative abilities: An fNIRS and behavioral study.

Autism spectrum disorder (ASD) is associated with life-long challenges with social cognition, and one of its earliest and most common manifestations is atypical joint attention, which is a pivotal skill in social-cognitive and linguistic development. Early interventions for ASD children often focus on training initiation of joint attention (IJA) and response to joint attention bids (RJA), which are important for social communication and cognition. Here, we used functional near-infrared spectroscopy and behavioral measures to test typically developing (TD, n = 17) and ASD children (n = 18), to address the relationship between the neural correlates of RJA and social-communicative behavior. Group-level differences were present for RJA-specific activation over right temporal sites, where TD children showed higher levels of activation during RJA than ASD children, whereas the two groups did not differ in the control condition. Correlations between neural activation and behavioral traits suggest that, in ASD children, neural activation during RJA is related to the frequency of RJA behavior when the former is measured over left temporal sites, and to social affect symptoms when considered for right temporal sites. Possible implications of the evidenced correlations are discussed.

#1559 Using nephrology clinic data to emulate cohorts: a comparison between an electronic health records service and Chronic Renal Insufficiency Cohort

Abstract Background and Aims The amount of data contributed to evidence-synthesis is inequitably distributed among various countries in a way that most of the data is emerged from developed and/or upper middle and high income countries. One efficient and low-cost solution can be the implementation of scattered electronic health records (EHR) sources in those countries into emulated cohort studies. We aim to compare the characteristics of a custom-built nephrology clinic electronic health records (CBNC-EHR) service that is in practice for more than 13 years with Chronic Renal Insufficiency Cohort (CRIC) study which has approximately the same span and enrollment to find out about the feasibility, strengths, and challenges of the proposition. Method We compared measured variables of baseline characteristics and follow-up strategy of CRIC study with the data provided by CBNC-EHR to estimate if the care-centered database is capable of emulating a cohort study. Results Among variables of socioeconomic information at CRIC study, CBNC-EHR provides 33% at full, 33% are “partially available or easily accessible” (PAEA), and 33% are not available. 71% of variables of medical history are fully available for all patients, while only 14% are PAEA, and 14% are not available. For kidney function measures, CBNC-EHR provides 55% of variables completely, while the remaining 45% are PAEA. Obviously, no blood or urine sample were collected during ambulatory care, and no questionnaire on different aspects of health were used to gather supplementary data, contrary to CRIC study. Compared to follow-up strategy of CRIC study, which indicated Annual visits and laboratory tests and 6-month telephone follow-ups, CBNC-EHR yields data only upon personally-decided attention of patients for follow-up care, which varies widely from one patient to another. Nevertheless, the majority of patients have at least one office visit in a year, accompanied by relevant laboratory tests. CBNC-EHR provides a complete list of risk factors and comorbidities of each patient, which makes it suitable for subgrouping, as was designed in CRIC study regard the diabetes status of patients. CBNC-EHR currently has data of 6481 individuals with renal failure, compared to 3000 enrollment goal of CRIC study. However, much higher rates of dropout (estimated to be approximately 20%) and utilization of inclusion and exclusion criteria will contribute to the actual available cases to emulate a cohort study. Conclusion Implementing a care-centered database into emulation of a cohort study, is challenging and complicated. Lack of consistency, high dropout rates, imperfect baseline and complementary information, and need for extensive data cleaning are all difficulties. However, contribution to equitability of data share in evidence-synthesis, extremely lower cost of conduction, and less heterogeneity are strengths of this procedure which can have a remarkable effect on transforming medical data from less-developed countries (which understandably prioritize healthcare to research due to scarcity of resources) to effective research studies. In this paper, we compared a renowned nephrology cohort with a private nephrology clinic EHR in a developing country and showed virtual availability of data to emulate a cohort study based on the care-centered database.

#1311 Cardiac damage in a multifactorial DKD/CKD mouse model resembles HFpEF and can be reduced by standard-of-care treatment

Abstract Background and Aims We developed a diet-induced hypertension-accelerated mouse model of diabetic kidney disease characterized by progressive loss of GFR resulting in chronic kidney disease. Since cardiovascular disease is the major cause of death in CKD, we characterized the functional and structural cardiac damage in this model. Additionally, we studied the efficacy of combination therapy with an ACE-inhibitor (Lisinopril) and SGLT2-inhibitor (Dapagliflozin) on cardiac histopathology. Method Male KKAy mice underwent uninephrectomy. After recovery mice received high fat diet (45% LARD) and drinking water with or without 50 mg/L LNNA (wk0). At 12 weeks, imaging was performed to study cardiac function and mice were terminated at week 13. In the intervention study, at week 4, lisinopril (2.5 mg/kg/day; drinking water) and at week 8 dapagliflozin (5 and 20 mg/kg/day; foodadmix) treatment were started. At week 16 mice were terminated and lung and heart weight and cardiac histology were determined. Results Upon termination, macroscopic evaluation of the hearts showed extensive scar tissue formation on the outside of the left ventricle. Histological evaluation showed the presence left ventricular hypertrophy, coronary calcification and myocardial fibrosis in male KKAy mice with UNX, HFD and LNNA. KKAy mice with UNX and HFD but without LNNA also showed myocardial fibrosis, monocyte infiltration and focal mineralization. Imaging showed preserved ejection fraction, a significant reduction, increased left ventricle posterior wall thickness and decrease left ventricle inner diameter. Treatment with combination therapy reduced lung wet weight, significantly reduced heart weight and significantly decreased cardiac fibrosis. Macroscopically, less scar tissue was observed after treatment. Conclusion This multifactorial mouse model shows cardiac damage on a background of hypertension, diabetes, renal dysfunction and obesity. Functional measurement including preserved ejection fraction, left ventricle hypertrophy, diastolic dysfunction and increased fibrosis resembling the clinical HFpEF phenotype. Combination therapy with Lisinopril and Dapagliflozin reduced cardiac weight and cardiac fibrosis. This indicates cardiac involvement in the DKD mouse model which confirms that this multifactorial model is clinically relevant.

#2022 Clinical outcomes in US patients initiating finerenone – a report from the FOUNTAIN platform

Abstract Background and Aims Evidence from clinical trials demonstrates that finerenone reduces the risk of cardiovascular and renal complications among patients with chronic kidney disease (CKD) and type 2 diabetes (T2D). What is lacking is the evidence on finerenone use in real-world clinical practice. Method The present analysis is based on a longitudinal single-arm cohort study of patients initiating finerenone between July 2021 and August of 2023 and with prior diagnoses of CKD and T2D. Data were obtained from US electronic health records and insurance claims (OM1 Real-World Data CloudTM). CKD was defined as either having 1 diagnostic code for CKD stage 2-4 or unspecified stage, two estimated glomerular filtration rate (eGFR) measurements between 15 and 60 ml/min/1.73 m2, or two urine albumin to creatinine ratio (UACR) measurements over 30 mg/g; T2D was defined as having a diagnostic code for T2D. We described patient demographics, comorbidities, and comedications at baseline (365 days prior and including index date), and incidence rates of cardiovascular and renal outcomes, including eGFR and UACR changes over time. The presented analysis (NCT05703880) is part of the multi-national, multi-database observational research platform FOUNTAIN. Results We identified 28,056 new users of finerenone with prior CKD and T2D. The users had a mean (SD) age of 68.8 (10.8) years and 44.8% were female. Comorbidities of interest at baseline were hypertension (89.8%), cardiovascular disease (21.2%), neuropathy (13.4%), retinopathy (8.1%), heart failure (7.9%), and cerebrovascular disease (4.2%). Assessment of comedication use at baseline indicates that patients who initiate finerenone had exposure to renin–angiotensin system inhibitors (52.5%), sodium-glucose cotransporter-2 inhibitors (39.2%), or glucagon-like peptide-1 receptor agonists (27.4%) within 180 days prior to initiating finerenone. Overall, 82.5% of patients initiated finerenone at 10 mg/d, while 17.5% of patients started with 20 mg/d. Complete results including incidence rates of cardiovascular and renal outcomes, hyperkalemia events, and changes in kidney function measures (eGFR, UACR) during follow-up will be presented as part of the conference presentation. Conclusion Data from patients receiving finerenone as part of clinical practice in the USA suggest that finerenone is used concurrently with other renal and cardiovascular protective medication-classes recommended for patients with CKD and T2D.

Is Revision Arthroscopic Bankart Repair a Viable Option? A Systematic Review of Recurrent Instability following Bankart Repair.

Background/Objectives: Recurrent shoulder instability following Bankart lesion repair often necessitates surgical revision. This systematic review aims to understand the failure rates of arthroscopic revision Bankart repair. Methods: Following the PRISMA guidelines and registered on PROSPERO, this systematic review examined twenty-five articles written between 2000 and 2024. Two independent reviewers assessed eligibility across three databases, focusing on recurrent instability as the primary endpoint, while also noting functional measures, adverse events, revision operations, and return-to-sport rates when available. Results: The key surgical techniques for recurrent instability post-Bankart repair were identified, with revision arthroscopic Bankart being the most common (685/1032). A comparative analysis revealed a significantly lower recurrence for open coracoid transfer compared to arthroscopic revision Bankart repair (9.67% vs. 17.14%; p < 0.001), while no significant difference was observed between remplissage plus Bankart repair and Bankart repair alone (23.75% vs. 17.14%; p = 0.24). The majority of studies did not include supracritical glenoid bone loss or engaging Hill-Sachs lesions, and neither subcritical nor non-engaging lesions significantly influenced recurrence rates (p = 0.85 and p = 0.80, respectively). Conclusions: Revision arthroscopic Bankart repair remains a viable option in the absence of bipolar bone loss; however, open coracoid transfer appears to have lower recurrence rates than arthroscopic Bankart repair, consistent with prior evidence. Further studies should define cutoffs and investigate the roles of critical glenoid bone loss and off-track Hill-Sachs lesions. Preoperative measurements of GBL on three-dimensional computed tomography and characterizing lesions based on glenoid track will help surgeons to choose ideal candidates for arthroscopic revision Bankart repair.

#3042 Prevalence and associations of impaired cognitive function for people with chronic kidney disease: baseline findings from the NURTuRE-CKD cohort study

Abstract Background and Aims Chronic kidney disease (CKD) is known to be associated with impaired cognitive function, with lower estimated glomerular filtration rate (eGFR) associated with poorer cognitive performance [1]. Though CKD prevalence increases with age, the association with cognitive disorders is not entirely explained by age distribution. Cognitive impairment in CKD is multifactorial with potential biochemical, cardiovascular, medication and socio-economic mediators. As with other long-term conditions, self-management of kidney disease becomes more difficult in the context of cognitive impairment. The prevalence and associations of cognitive impairment in people referred to secondary care with CKD is not well described. This study therefore aimed to identify the prevalence and associations of impaired cognitive function among a referred population of people with CKD. Method The NURTuRE-CKD cohort recruited 2996 people with an estimated Glomerular Filtration Rate (eGFR) of 15-59 ml/min/1.73 m2 (CKD-EPI equation) or ≥60 ml/min/1.73 m2 with a urine albumin to creatinine ratio (uACR) of more than 30 mg/mmol referred to one of 16 secondary care nephrology clinics. Baseline data were collected between 2017-2019 including sociodemographic, anthropometric, biochemical, and clinical information and included the 6-item cognitive impairment test (6-CIT), a commonly used cognitive screening instrument. Other scores collected included the Hospital Anxiety and Depression score (HADS), EQ-5D-5L as a health-related quality of life (HRQoL) measure and Single Item Literacy Screener (SILS). Prevalence of impaired cognitive function (defined as 6-CIT score of 8 or more out of 28) was calculated and multivariable mixed effects logistic regression models used to identify associations with impaired cognitive function. The multivariable model was adjusted for known factors impacting cognitive impairment and recruitment region as a random effect. Results A total of 2743/2996 (91.6%) participants had complete 6-CIT data. Median age was 66 years and 41% were female. Median eGFR was 34 ml/min/1.73 m2. Prevalence of cognitive impairment was 8.7% (240/2743), rising from 5.3% in those &amp;lt;65 to 10.6% in those ≥65 years. eGFR was not associated with cognitive impairment on univariate analysis. After adjustment, greater likelihood of cognitive impairment was independently associated with older age, Asian and Black ethnicity (compared to white), and limited health literacy. Lower likelihood of cognitive impairment was associated with better HRQoL and higher education attainment (Figs 1 and 2). Conclusion Cognitive impairment was relatively common in this cohort of people with CKD. Similar associations for cognitive impairment with age and education in a CKD population had also been identified in CKD-REIN—a prospective cohort of CKD patients recruited from secondary care in France, though using a different cognitive function measure. Associations of limited health literacy, ethnicity, and HRQoL with cognitive impairment were identified risk factors that could aid clinicians in recognising high risk patients to prompt screening and improve management. Follow-up data will allow longitudinal analyses to explore associations between impaired cognitive function and health-related outcomes, between kidney function and change in cognitive function and risk factors for change in cognitive function, including the role of inflammatory markers. Limitations: this analysis only used baseline data so causality cannot be established, 6-CIT is a screening rather than diagnostic tool for cognitive impairment.

Psychometric testing of the Chinese version of the International Classification of Functioning, Disability, and Health Measure of Participation and Activities Screener in people with stroke.

Clinicians need a validated measure to assess the activity and participation of Chinese people with stroke. To culturally adapt and psychometrically test the Chinese (Cantonese) version of the International Classification of Functioning, Disability and Health Measure of Participation and Activities (C-IMPACT-S) in community-dwelling people with stroke. We followed the standard translation procedures to culturally adapt the C-IMPACT-S. Then we administered the C-IMPACT-S to 100 people with stroke and 50 healthy counterparts for psychometric testing, including the ceiling and floor effects, internal consistency, test - retest, measurement error, minimal detectable change, correlations with other outcome measures, known-group validity and optimal cutoff scores. The C-IMPACT-S has no floor effects but ceiling effects in item 5. It has poor to excellent (Cronbach's α = 0.56-95) internal consistency and fair to excellent (Intraclass correlation coefficients = 0.58-1.00) test-retest reliability. The overall C-IMPACT-S mean score and activity and participation component mean scores had statistically significant no to weak correlations with the Fugl-Meyer Assessment, the Chinese versions of Geriatric Depression Scale, Fatigue Assessment Scale, Lawton Instrumental Activities of Daily Living Scale and Community Integration Measure. The stroke participants had lower C-IMPACT-S scores then their health counterparts. The optimal cutoff scores of the overall C-IMPACT-S and activity and participation domains were 88.02% (sensitivity 72%, specificity 80%), 80.56% (sensitivity 86%, specificity 68%) and 91.67% (sensitivity 68%, specificity 80%), respectively. C-IMPACT-S is a reliable and valid measure for assessing the levels of activity and participation of people with chronic stroke.

Right Atrial Strain in Pediatric Pulmonary Hypertension-A Prospective Observational Study.

Right ventricular (RV) afterload due to elevated pulmonary arterial (PA) pressure in pulmonary hypertension (PH) causes long-term right atrial (RA) remodeling and dysfunction. RA function has been shown to correlate with PA pressures and outcome in both adult and pediatric patients with PH. We studied the role of RA strain in estimating PA pressures in congenital heart disease (CHD)-associated PH. Children below 12years undergoing elective repair of CHD with left-to-right shunts and echocardiographic evidence of PH were included. RA reservoir, conduit and contractile strain along with conventional measures of RV function and PA pressure were measured using transthoracic echocardiography after induction of anaesthesia. Pre-and post-repair invasive PA pressures were measured after surgical exposure. 51 children with a median age of 24months (range 4-144months) were included, most of whom were undergoing VSD closure. Contractile RA strain showed good correlation with pre-repair systolic PA pressure in mmHg (r = 0.59, 95%CI 0.37-0.75) or expressed as a percentage of SBP (r = 0.67, 95%CI 0.49-0.80). It also predicted persistent postoperative PH as well as pre-repair pulmonary artery acceleration time and right ventricular systolic pressure measured from tricuspid regurgitation jet. The trends of correlation observed suggest a possible prognostic role of RA strain in ACHD with PH and potential utility in its echocardiographic assessment. The observed findings merit deeper evaluation in larger cohorts.

Automatic quantification of REM sleep without atonia reliably identifies patients with REM sleep behavior disorder: a possible screening tool?

REM Sleep Behavior Disorder (RBD) is characterized by absence of physiological muscle atonia during REM sleep (REM sleep without atonia, RWA). Nigro-striatal dopaminergic impairment is a feature of Parkinson disease (PD) and can be identified in prodromal stages as well, such as idiopathic RBD (iRBD). Aims of this study are to explore the efficacy of an automatic RWA quantification in identifying RBD patients and the correlation between RWA and nigro-striatal dopaminergic function. Forty-five iRBD, 46 PD with RBD, 24 PD without RBD patients and 11 healthy controls were enrolled in the Genoa Center (group A) and 25 patients with iRBD (group B) were enrolled in the Danish Center. Group A underwent brain [123I]FP-CIT-SPECT and group B underwent brain [18F]PE2I-PET as measures of nigro-striatal dopaminergic function. Chin muscle activity was recorded in all subjects and analyzed by applying a published automatic algorithm. Correlations between RWA and nigro-striatal dopaminergic function were explored. The automatic quantification of RWA significantly differentiated RBD from non-RBD subjects (AUC = 0.86), although with lower accuracy compared with conventional visual scoring (AUC = 0.99). No significant correlation was found between RWA and nigro-striatal dopaminergic function. The automatic quantification of RWA is a reliable tool to identify subjects with RBD and may be used as a first-line screening tool, but without correlations with nigro-striatal dopaminergic functioning.

Is shockwave therapy effective in the management of greater trochanteric pain syndrome? A systematic review and meta-analysis.

Evidence is lacking for the efficacy of shockwave therapy (SWT) in the treatment of greater trochanteric pain syndrome (GTPS). To investigate the efficacy of SWT on pain and function in the management of GTPS. A systematic search of electronic databases and grey literature was conducted up to May 2023. Studies utilising SWT on adults for GTPS, providing measures of pain and/or function at baseline and at follow-up were considered for inclusion. Meta-analysis was undertaken using converted pain and functional outcomes. Studies were assessed for quality and risk of bias, and assigned a level of evidence as per the Grading of Recommendations, Assessment, Development and Evaluations criteria. Twelve articles (n=1121 subjects) were included, including five randomised controlled trials (RCTs) and seven non-RCTs. No statistical differences were observed for pain over time f(1,5)=1.349 (p=0.298) or between SWT and control f(1,5)=1.782 (p=0.238). No significant differences in functional outcomes in short- (H=2.591, p=0.181) and medium-term follow-up (H=0.189, p=0.664) were identified between SWT and control. Moderate magnitude treatment effects for pain (Hedges-G [HG] 0.71) favouring SWT groups over control was identified, decreasing to low for function (HG 0.20). Further pain and functional treatment effects were identified at higher magnitudes across follow-up time-points in SWT groups compared to control. Moderate-quality evidence demonstrated no statistically significant improvements in pain and function post-SWT compared to control. Low-quality evidence established clinical improvements throughout all included studies favouring SWT over control. Consequently, owing to relatively low incidence of side effects, SWT should be considered a viable option for the management of GTPS. Issues with both clinical and statistical heterogeneity of studies and during meta-analysis require consideration, and more robust RCTs are recommended if the efficacy of SWT for the management of GTPS is to be comprehensively determined.

Relationship Between Hand Strength and Function in Duchenne Muscular Dystrophy and Spinal Muscular Atrophy: Implications for Clinical Trials.

Measurement of muscle strength and motor function is recommended in clinical trials of neuromuscular diseases, but the loss of hand strength at which motor function is impacted is not documented. To establish the relationship between hand strength and function, and to determine the strength threshold that differentiates normal and abnormal hand function in individuals with Duchenne Muscular Dystrophy (DMD) or Spinal Muscular Atrophy (SMA). Maximal handgrip and key pinch strength were measured with the MyoGrip and MyoPinch dynamometers, respectively. Hand function was assessed using the MoviPlate, the Motor Function Measure items for distal upper limb (MFM-D3-UL) and the Cochin Hand Function Scale (CHFS). Data from 168 participants (91 DMD and 77 SMA, age 6-31 years) were analyzed. Relationships between strength and function were significant (P < 0.001). Hand function was generally preserved when strength was above the strength threshold determined by Receiver-Operating Characteristic (ROC) analysis: For MFM-D3-UL, the calculated handgrip strength thresholds were 41 and 13% of the predicted strength for a healthy subject (% pred) and the key pinch strength thresholds were 42 and 26% pred for DMD and SMA, respectively. For the MoviPlate, handgrip strength thresholds were 11 and 8% pred and key pinch strength thresholds were 21 and 11% pred for DMD and SMA, respectively. For participants with sub-threshold strength, hand function scores decreased with decreasing strength. At equal % pred strength, individuals with SMA had better functional scores than those with DMD. Hand function is strength-dependent for most motor tasks. It declines only when strength falls below a disease-specific threshold. Therefore, therapies capable of maintaining strength above this threshold should preserve hand function.