Increased Risk Of Death Research Articles

Using Electrocardiogram to Assess Diastolic Function and Prognosis in Mitral Regurgitation

BackgroundThe determination of left ventricular diastolic function (LVDF) in patients with significant (≥moderate) mitral regurgitation (MR) poses a complex challenge. We recently validated an artificial intelligence–enabled electrocardiogram (AI-ECG) algorithm to estimate LVDF. ObjectivesThis study sought to evaluate the risk of all-cause mortality across AI-ECG LVDF-derived myocardial disease (MD) grades in MR. MethodsThis was a retrospective study including all patients in the AI-ECG LVDF study testing group who underwent comprehensive transthoracic echocardiography confirming significant MR and electrocardiogram within 14 days of each other at the Mayo Clinic between September 2001 and April 2023. AI-ECG LVDF status was determined based on the index electrocardiogram and used to categorize patients into 3 stages of MD: MD-1, normal or grade 1 LVDF; MD-2, grade 2 LVDF; and MD-3, grade 3 LVDF. ResultsOf 4,019 patients with significant MR (mean age 69.8 years; 49.0% women), 1,175 (29.2%), 1,881 (46.8%), and 963 (24.0%) were classified by AI-ECG as MD-1, MD-2, and MD-3, respectively. The median mitral effective regurgitant orifice area was 26 mm2 (Q1-Q3: 20-36 mm2). Over a median follow-up of 3.5 years, 1,636 (40.7%) patients died. In multivariable survival analysis adjusted for multiple risk factors, a higher diastolic function grade was independently associated with an increased death risk (MD-2, adjusted HR [aHR]: 1.99; 95% CI: 1.62-2.45; MD-3, aHR: 2.65; 95% CI: 2.11-3.34). These findings were consistent when accounting for mitral valve intervention and across various sensitivity and subgroup analyses. ConclusionsIn patients with significant MR, the grading of LVDF by AI-ECG is independently associated with all-cause mortality.

Smoking and outcomes in candidates for Liver Transplantation: Analysis of the pulmonary vascular complications of liver disease 2 (PVCLD2).

Patients with chronic liver disease commonly have abnormal lung function, however the impact of smoking on outcomes in these patients is unknown. We hypothesized current or past smoking would be associated with worse survival in patients with advanced liver disease. The Pulmonary Vascular Complications in Liver Disease Study 2 (PVCLD2) was a prospective cohort of patients with advanced liver disease undergoing evaluation for liver transplantation (LT). Patients were classified by self-report as a "non-smoker", "past smoker", or "current smoker". We used Cox proportional hazards models and Fine-Gray models with LT as a competing risk. Models were adjusted for age, sex, body mass index, race, family income, liver disease etiology, and Model for End-Stage Liver Disease-Sodium (MELD-Na) score. Of the 410 patients included, most (65%) were male with mean age at enrollment was 56.5 years. 160 (39%) patients were non-smokers, 183 (45%) were past smokers, and 67 (16%) were current smokers. In total, 151 (37%) patients received a LT, and 88 (20%) patients died. When compared to non-smokers, current smokers had a 2.17-fold increase in risk of death overall (95% CI 1.12-4.18, p=0.02). There was a 7% increase in overall risk of death for every 5 pack-years increase (95% CI 1.01-1.13, p=0.02). With LT as a competing risk, the sub-distributional hazard ratio (sHR) of current smokers versus non-smokers for death was 2.45 (95% CI 1.31-4.60, p=0.005). In this model, past smokers displayed a non-significant increase in risk of death compared to non-smokers (sHR1.58, 95% CI 0.91-2.72, p=0.10). Patients with advanced liver disease undergoing evaluation for LT who smoke have an increased risk of death. Smoking cessation could lead to improved overall survival with or without LT.

Prognostic stratification of patients with mitral regurgitation using artificial intelligence-enhanced electrocardiogram for left ventricular diastolic function assessment

Abstract Background The determination of left ventricular diastolic dysfunction (LVDD) and filling pressure in patients with significant (>moderate) mitral regurgitation (MR) poses a complex challenge. We recently validated an artificial intelligence-enabled electrocardiogram (AI-ECG) algorithm to detect LVDD and estimate LV filling pressures. Methods This retrospective study sought to examine the risk of all-cause mortality across AI-ECG LVDD grades. Patients from the AI-ECG LVDD study test cohort who underwent transthoracic echocardiography confirming significant MR and an ECG within fourteen days of each other at Mayo Clinic between 09/2001 and 06/2022 were included. LVDD status was determined based on the index ECG, and patients were categorized into groups representing normal diastolic function (NDF) or LVDD grades 1 (G1), 2 (G2), or 3 (G3). Results Of 4,019 patients with significant MR (mean age 69.8, 49.0% women), 1,175 (29.2%), 1,881 (46.8%), and 963 (24.0%) were classified by AI-ECG as NDF/G1-LVDD, G2-LVDD, and G3-LVDD, respectively. The median mitral effective regurgitant orifice area was 26 mm² (interquartile range 20-36 mm²). Over a median follow-up of 3.5 years, 1,636 (40.7%) patients died. In multivariable survival analysis adjusted for multiple risk factors, a worse AI-ECG LVDD grade was independently associated with an increased death risk [G2DD: adjusted hazard ratio (aHR) 1.98 (95% confidence interval (95% CI) 1.63-2.40), G3DD: aHR 2.59 (95% CI 2.09-3.20)]. These findings were consistent when accounting for mitral valve intervention and among patients with >moderate MR or after mitral valve intervention. Conclusion In patients with significant MR, the grading of LVDD by AI-ECG is independently associated with all-cause mortality.

COVID-19 vaccination and lethality reduction: a prospective observational study in Venezuela during the last two waves

BackgroundIn Venezuela, the predominant vaccines administered are BBIBP-CorV and Gam-COVID-Vac. Despite robust evidence from randomized clinical trials validating the effectiveness of COVID-19 vaccines in mitigating hospitalization and mortality, there is still a lack of post-authorization safety studies conducted within this demographic population.MethodsA prospective observational study from October 5, 2021 to March 31, 2022 encompassed COVID-19 vaccinated and unvaccinated patients from four sentinel hospitals in Venezuela. Patient lethality was predicted using Charlson Comorbidity index. Clinical outcomes were assessed through WHO’s COVID-19 Clinical Progression Scale.ResultsOut of the 175 patients assessed, 85 (48.6%) were vaccinated. The median Charlson Comorbidity index was 3 points, with no statistically significant differences observed between the groups (p = 0.2). A total of 50 (28.6%) patients died during the study period, with higher proportion of deaths in unvaccinated patients (35.6% vs. 21.2%, p = 0.035). Advanced age (OR = 1.043, 95% CI = 1.015–1.071, p = 0.002) was associated with increased death risk, whereas vaccination against COVID-19 (OR = 0.428, 95% CI = 0.185–0.99, p = 0.047), high oxygen saturation (OR = 0.964, 95% CI = 0.934–0.995, p = 0.024), and enoxaparin administration (OR = 0.292, 95% CI = 0.093–0.917, p = 0.035) were associated with decreased death risk.ConclusionDuring the third and fourth waves of the pandemic, COVID-19 vaccination was associated with a 57% reduction in lethality among patients in four public hospitals in Venezuela.

Impact of the Preservation of Residual Kidney Function on Hemodialysis Survival: Results from the BISTRO Trial.

Preservation of residual kidney function (RKF) in dialysis patients has been associated with improved survival. RKF in the BISTRO trial was relatively well preserved and here we describe its association with survival during the trial and extended follow-up. RKF, measured as the average urea and creatinine clearance (GFR) or 24-hour urine volume was assessed at baseline, one, two and three months and three-monthly up to 2 years in incident haemodialysis patients. Time to event survival data or competing events (transplantation, modality change) were obtained for 50 months post enrolment via data linkage with the UK Renal Registry. Cox proportional hazards regression survival models, including those incorporating change in GFR from baseline as a time-varying variable and joint regression models for longitudinal and survival data (longitudinal models for GFR or urine volume) were used to explore the relationship of RKF preservation with survival. Analyses were adjusted for age, sex, comorbidity and ethnicity. 2919 measures of RKF were made in 387 patients from 32 UK dialysis units. Higher age and comorbidity score associated with increased mortality in all models. Baseline GFR reduced the risk of death (Hazard Ratio: 0.918 95%CI: 0.844, 0.999) per ml/min/1.73m2. A greater fall in GFR and urine volume from baseline was associated with a non-significant increased risk of death as visualised on spline plots. In the joint survival models higher GFR (adjusted HR: 0.88 95%CI 0.80, 0.97) or urine volume (adjusted HR: 0.75 95%CI 0.57, 0.95 per L) at any time point associated with better survival. Lower RKF during the first two years of haemodialysis is associated with an increased death risk for up to 50 months following dialysis initiation. This adds to a growing body of evidence that interventions to preserve RKF should be developed and tested in clinical trials.

Predictors of death without prior appropriate therapy in ICD recipients: the comorbidities, frailty and functional status (COMFFORT study)

ObjectiveMost patients who have an implantable cardioverter-defibrillator (ICD) implant do not receive life-prolonging therapy from it. Little research has been undertaken to determine which patients benefit the least from ICD...

Survival Risk Score for Invasive Nonmetastatic Breast Cancer: A Real-World Analysis.

This study aimed to develop a multivariable, weighted overall survival (OS) risk score (SRS) for nonmetastatic (M0) invasive breast cancer (M0-BC, SRSM0-BC). This study included a training (1,890 patients) and a validation cohort (850 patients) from the Reggio Emilia Cancer Registry (RE-CR). Ten traditional prognostic variables were evaluated. In the training set, all the variables but the human epidermal growth factor receptor were significantly associated with OS at univariable analysis. A multivariable model identified an increased death risk for estrogen receptor (hazard ratio [HR], 2.0 [95% CI, 1.1 to 3.1]; P = .021), tumor stages T2-T3 (HR, 2.4 [95% CI, 1.3 to 4.7]; P = .009) and T4 (HR, 5.1 [95% CI, 2.0 to 13.0]; P < .001), and age >74 years (HR, 5.7 [95% CI, 4.0 to 8.2]; P < .001). By assigning scores according to HRs, four risk categories were generated (P for trend <.001). The HRs of death in the high- (282 patients, 15.6%), intermediate-high (275 patients, 15.2%), and intermediate-risk (349 patients, 19.2%) categories patients were, respectively, 27.3, 12.9, and 3.5 times higher, compared with the low-risk (909 patients, 50%) group. Harrell'C index was 81.1%, and the explained variation in mortality was 66.6. Internal cross-validation performed on the accrual index dates yielded a Harrell'C index ranging from 79.5% to 82.3% and an explained variation in mortality ranging from 60.3% to 69.4%. In the validation set, the same risk categories (P for trend <.001) were devised. The Harrell'C index and the explained variation in mortality were 76.1% and 53.7%, respectively, in the whole cohort, maintaining an elevated percentage according to the two accrual index dates. SRSM0-BC using the real-world RE-CR data set may represent a low-cost, accessible, globally applicable model in daily clinical practice, helping to prognostically stratify patients with invasive M0-BC.

Identification of poor prognosis predictors in patients with pulmonary embolism

Aim. To identify the predictors of poor prognosis in patients with pulmonary embolism (PE).Material and methods. The study included 120 patients with verified PE. The analysis included the clinical evidence collection, paraclinical investigations (including echocardiography) and genetic analysis. Cox regression analysis was used to assess mortality predictors. Statistical data processing was performed using Excel 2019, SPSS Statistica v. 26 (IBM, USA), MedCalc v. 20.104 and JMP Pro 17 (SAS, USA) software.Results. The following independent mortality predictors were identified using multivariate regression analysis: age (odds ratio (OR) 1,051, p=0,0002), prior venous thromboembolism (OR 2,090, p=0,0117), TT genotype of the F13A1 rs5985 polymorphism (OR 2,820, p=0,0427) and anteroposterior right ventricular size (OR 1,043, p=0,0294). Right ventricular wall hypokinesis (OR 5,040, p=0,0285), submassive pulmonary artery involvement (OR 2,714, p=0,0025), prior myocardial infarction (OR 2,839, p=0,0028) and other factors were significantly associated with an increased death risk. Based on these predictors, a prognostic model was developed that allows for effective stratification of the death risk.Conclusion. The predictors identified in the study can be used for risk stratification and optimization of patient management with PE, which can improve the prognosis and treatment outcomes.

Household Latrine Utilization Behavioral Model as an Effort to Improve Open Defecation-Free Program

Background: Healthy latrine-using behavior indicates healthy behavior. However, many people still practice open defecation, which can cause illness and increase death risk. Self-efficacy is a dominant predictor of health behavior change. Aims: The study aims to develop a household latrine utilization behavior model based on self-efficacy to improve an open defecation-free (ODF) program. Method: The study was a descriptive-analytic with a cross-sectional design. The sample size was 138 respondents with cluster random sampling. The study variables were endogenous (household latrine utilization), exogenous (predisposing, enabling, and reinforcing factors), and intervening variables (self-efficacy). Data were collected by questionnaire and analyzed using SEM-PLS. Result: The household latrine utilization behavior-based self-efficacy model is fit (SRMR=0.098; NFI= 0.910; Q2=0.334). Valid and reliable indicators were education (predisposing), clean water availability and latrine maintenance (enabling), and health worker and family support (reinforcing). Path analysis showed exogenous factors, directly and indirectly, influence latrine utilization behavior through self-efficacy. Predisposing and reinforcing factors had a direct and significant effect (p = 0.025; p = 0.001) while enabling factors were insignificant (p = 0.438). Enabling and reinforcing factors indirectly and significantly affected latrine utilization behavior through self-efficacy (p = 0.033; p = 0.004), while predisposing factors were insignificant (p = 0.141). Self-efficacy significantly influenced latrine-using behavior (p = 0.023). Conclusion: The household latrine utilization behavior-based self-efficacy model is a fit model with good predictive relevance in predicting household latrine use behavior. Health workers can use the model to enhance household latrine utilization behavior and improve the ODF program and public health status.

Amyotrophic lateral sclerosis patients with various gene mutations show diverse motor phenotypes and survival in China

BackgroundAmyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disorder characterised by progressive degeneration of motor neurons. Genetic factors have a substantial impact on ALS. Therefore, this study aimed to explore...

Nursing Team Composition and Mortality Following Acute Hospital Admission

Many studies show the adverse consequences of insufficient nurse staffing in hospitals, but safe and effective staffing is unlikely to be just about staff numbers. There are considerable areas of uncertainty, including whether temporary staff can safely make up shortfalls in permanent staff and whether using experienced staff can mitigate the effect of staff shortages. To explore the association of the composition of the nursing team with the risk of patient deaths. This patient-level longitudinal observational study was conducted in 185 wards in 4 acute hospital trusts in England between April 2015 and March 2020. Eligible participants were patients with an overnight stay and nursing staff on adult inpatient wards. Data analysis was conducted from month April 2022 to June 2023. Naturally occurring variation during the first 5 days of hospital admission in exposure to days of low staffing from registered nurses (RNs) and nursing support (NS) staff, the proportion of RNs, proportion of senior staff, and proportion of hospital-employed (bank) and agency temporary staff. The primary outcome was death within 30 days of admission. Mixed-effect Cox proportional hazards survival models were used. Data from 626 313 admissions (319 518 aged ≥65 years [51.0%]; 348 464 female [55.6%]) were included. Risk of death was increased when patients were exposed to low staffing from RNs (adjusted hazard ratio [aHR], 1.08; 95% CI 1.07-1.09) and NS staff (aHR, 1.07; 95% CI, 1.06-1.08). A 10% increase in the proportion of temporary RNs was associated with a 2.3% increase in the risk of death, with no difference between agency (aHR, 1.023; 95% CI, 1.01-1.04) and bank staff (aHR, 1.02; 95% CI, 1.01-1.04). A 10% increase in the proportion of agency NS was associated with a 4% increase in risk of death (aHR, 1.04; 95% CI, 1.02-1.06). Evidence on the seniority of staff was mixed. Model coefficients were used to estimate the association of using temporary staff to avoid low staffing and found that risk was reduced but remained elevated compared with baseline. This cohort study found that having senior nurses in the nursing team did not mitigate the adverse outcomes associated with low nurse staffing. These findings indicate that while the benefits of avoiding low staffing may be greater than the harms associated with using temporary staff, particularly for RNs, risk remains elevated if temporary staff are used to fill staffing shortages, which challenges the assumption that temporary staff are a cost-effective long-term solution to maintaining patient safety.

Overall and cause-specific mortality among patients diagnosed with gastric precancerous lesions in Sweden between 1979 and 2014: an observational cohort study

BackgroundThe Correa’s cascade, encompassing chronic non-atrophic gastritis, atrophic gastritis, intestinal metaplasia, and dysplasia, represents the well-recognized pathway for the development of non-cardia gastric cancer. Population-based studies on all-cause and cause-specific mortalities among patients with gastric lesions in Correa’s cascade are scarce.MethodsWe compiled a cohort of 340 744 eligible patients who had undergone endoscopy with biopsy for non-malignant indications during the period 1979–2011, which was followed up until 2014. Standardized mortality ratios (SMRs) with 95% confidence intervals (CIs) provided estimation of the relative risk, using the general Swedish population as reference. Cox regression model was used to estimate hazard ratios (HRs) of death for internal comparison.ResultsA total of 306 117 patients were included in the final analysis, accumulating 3,049,009 person-years of follow-up. In total 106,625 deaths were observed during the study period. Compared to the general population, excess risks of overall mortality were noted in all subgroups, with SMRs ranging from 1.11 (95% CI 1.08–1.14) for the normal mucosa group to 1.54 (95% CI 1.46–1.62) for the dysplasia group. For cause-specific mortalities, mortality from gastric cancer gradually increased along Correa’s cascade, with excess risk rising from 105% for patients with chronic gastritis to more than 600% for the dysplasia group. These results were confirmed in the comparison with the normal mucosa group. For non-cancer conditions, increased death risks were noted for various diseases compared to the general population, especially among patients with more severe gastric precancerous lesions. But the results were confirmed only for “infectious diseases and parasitic diseases”, “respiratory system diseases”, and “digestive system disease”, when using the normal mucosa group as reference.ConclusionsIncreased mortality from gastric cancer suggests that early recognition and intervention of gastric precancerous lesions probably benefit the patients. Excess mortality due to non-cancer conditions should be interpreted with caution, and future studies are warranted.

46 Radiological tumor burden is an independent risk factor for survival in patients with metastatic clear cell renal cell carcinoma (mccRCC) treated with first line immunotherapy (IO)-based regimens

Abstract Background IO-based regimens (IO + IO or IO + VEGF inhibitor) represent current standard of care systemic therapies for the management of patients with mRCC. IMDC is the current standard to assess prognosis in patients with mRCC of clear cell histology. Baseline radiological tumor burden (BRTB) is a readily available measurement to calculate using routine CT-scans. Here we describe the utility of BRTB as prognostic factor in patients with mccRCC treated with first line IO-based regimens. Methods We reviewed data of 183 patients with mccRCC treated at Dana-Farber Cancer Institute from August 2014 to October 2023 and who received ≥ 1 dose of an IO-based regimen (IO + IO or IO + VEGF inhibitor). Patients with available CT-scan reports within 1 month prior to first line treatment initiation were included in our analysis. BRTB was assessed by a single operator as the sum of all measurable lesions as listed on the RECIST v1.1 report. The primary outcome was overall survival (OS), and secondary outcomes were time to treatment failure (TTF) and time to next therapy (TTNT). To evaluate the impact of BRTB on OS, TTF and TTNT, we used univariable and multivariable Cox regression models accounting for IMDC risk group, history of nephrectomy, and presence of either bone, liver, or brain metastases prior to first line initiation. Results A total of 150 patients satisfied the inclusion criteria and were included in our final analysis, of which 80% of patients were male (120/150). 9% (13/150) had favorable risk, 51% (77/150) had intermediate risk and 20% (30/150) had poor risk by IMDC criteria. Overall, 73% (109/150) of patients had nephrectomy prior to first line therapy initiation and 41% (61/150) had either brain, bone, or liver metastasis. Median follow-up was 44.8 months. Every 1 cm increase in BRTB was associated with a 5% increase in risk of death (HR: 1.05; 95% CI: 1.03 – 1.08; p &amp;lt; 0.0001). On multivariable analysis, radiological tumor burden was significantly associated with OS (HR: 1.04; 95%CI: 1.00 – 1.08; p = 0.03). After categorizing BRTB by tertiles, tertile 1 included 0 - 7.5 cm, tertile 2: 7.6– 15.3 cm and tertile 3: 15.4 – 47.7 cm. The 4-year OS estimates were 84% (95%CI: 74 – 97%), 60% (95%CI: 45 – 81%) and 43% (95%CI: 29 – 66%), respectively, for the 1st, 2nd and 3rd tertile (log-rank P &amp;lt; 0.0001). BRTB did not show a significant association with TTF on univariable (HR: 1.00; 95%CI: 0.99 – 1.01; p = 0.783), or multivariable analysis (HR: 0.99; 95%CI: 0.97 – 1.01; p = 0.428). As for TTNT, BRTB also did not show a significant association on univariable (HR: 1.01; 95%CI: 1.0 – 1.02; p = 0.234) or multivariable analysis (HR: 1.01; 95%CI: 0.99 – 1.03; p = 0.453). Conclusions Baseline radiological tumor burden is an independent prognostic factor for OS in patients with mccRCC treated with first line immunotherapy-based regimens. However, tumor burden is not significantly associated with TTF or TTNT. Figure: Kaplan-Meier curves representing OS based on baseline radiological tumor burden assessed by RECIST v1.1 (Tertile 1: 0 - 7.5 cm; Tertile 2: 7.6 - 15.3 cm; Tertile 3: 15.4 – 47.7 cm). P value is derived from the log-rank test.

Prognostic value of blood GRHL2 in patients with non-small-cell lung cancer after radiotherapy and chemotherapy.

Aim: We aimed to investigate the predictive value of the Grainyhead-like 2 (GRHL2) expression from circulating blood for recurrence, metastasis and overall death on patients with non-small-cell lung cancer (NSCLC).Materials & Methods: We collected blood samples from 122 patients who were admitted to our hospital for NSCLC.Results: Multivariable Cox proportional-hazards analysis in adjusted Model II showed that compared with GRHL2-negative expression, positive expression in patients with NSCLC was associated with increased death risk (HR=7.0, 95% CI: 2.1-20.9, p=0.03) and risk for composite end point (HR=8.2, 95% CI: 4.0-27.1, p <0.01).Conclusion: This study supported that elevated circulating GRHL2 expression might be considered as a candidate prognostic biomarker for poor prognosis among these NSCLC patients.

The inverted U-shaped association between blood fibrinogen and rehospitalization risk in patients with heart failure

Fibrinogen, a biomarker of thrombosis and inflammation, is related to a high risk for cardiovascular diseases. However, studies on the prognostic value of blood fibrinogen concentrations for heart failure (HF) patients are few and controversial. We performed a retrospective analysis among acute or deteriorating chronic HF patients admitted to a hospital in Sichuan, China, between 2016 and 2019, integrating electronic health care records and external outcome data (N = 1532). During 6 months of follow-up, 579 HF patients were readmitted within 6 months, and 46 of them died. Surprisingly, we found an inverted U-shaped association of blood fibrinogen levels with risk of readmission within 6 months but not with risk of death within 6 months. It was found that HF patients had the highest risk for readmission within 6 months after reaching the turning point for blood fibrinogen (2.4 g/L). In HF patients with low fibrinogen levels < 2.4 g/L, elevated fibrinogen concentrations were still significantly associated with a higher risk for readmission within 6 months [OR = 2.3, 95% CI (1.2, 4.6); P = 0.014] after controlling for relevant covariates. There was no significant association between blood fibrinogen and readmission within 6 months [(OR = 1.0, 95% CI (0.9, 1.1); P = 0.675] in HF patients with high fibrinogen (> 2.4 g/L). The effect difference for the two subgroups was significant (P = 0.014). However, we did not observe any association between blood fibrinogen and death within 6 months stratified by the turning point, and the effect difference for the stratification was not significant (P = 0.380). We observed an inverted U-shaped association between blood fibrinogen and rehospitalization risk in HF patients for the first time. Additionally, our results did not support that elevated blood fibrinogen was related to increased death risk after discharge.

Analyses of academician cohorts generate biased pandemic excess death estimates

ObjectiveDeath data from cohorts of academicians have been used to estimate pandemic excess deaths. We aimed to evaluate the validity of this approach. Study Design and SettingData were analyzed from living and deceased member lists from Mainland China, UK and Greece academies; and Nobel laureates (and US subset thereof). Samples of early elected academicians were probed for unrecorded deaths; datasets overtly missing deaths were excluded from further analyses. Actuarial risks were compared against the general population in the same country in respective age strata. Relative incidence risk increases in death in active pandemic periods were compared to population-wide pandemic excess death estimates for the same country. ResultsRoyal Society and Academy of Athens datasets overtly missed deaths. Prepandemic death rates were 4- to 12-fold lower in the Chinese Academy of Engineering (CAE) vs respective age strata of the Mainland China population. A +158% relative increase in death risk was seen in CAE data during the first 12-month of wide viral spread. Both increases (+34% in British Academy) and decreases (−27% in US Nobel laureates) in death rates occurred in pandemic (2020-22) vs prepandemic (2017-19) years; point estimates were far from known excess deaths in the respective countries (+6% and +14%, respectively). Published excess death estimates for urban-dwelling Mainland China selectively analyzed CAE that had double the pandemic death rates than another Chinese academy (Chinese Academy of Sciences). ConclusionMissingness, lack of representativeness, large uncertainty, and selective analysis reporting make data from academy rosters unreliable for estimating general population excess deaths.

Circulating Chemokines and Short- and Long-Term Outcomes After Ischemic Stroke

AbstractChemokines are vital in post-cerebral ischemia inflammatory reactions. We investigate the possible relationship between plasma chemokines and short-term and long-term outcomes after stroke. This study included 235 patients (median age, 72 years; 49.8% female) suffering from ischemic stroke, or transient ischemic attack admitted to the hospital within 24 h of onset. We evaluated chemokines CCL2, CCL5, CXCL8, CXCL9, and CXCL10 in plasma samples collected upon admission. Further, we assessed functional outcomes at 3- and 12-months, all-cause fatality over 5 years, and episodes of delirium within the first 7 days of admission. Multivariate analysis revealed an association between higher CXCL10 levels and an increased risk of poor functional outcomes at 3 months (OR: 3.02, 95%CI: 1.22–7.46, p = 0.016) and 12 months (OR: 2.32, 95%CI: 1.03–5.26, p = 0.043), as well as an increased death risk (HR: 1.79, 95%CI: 1.04–3.07, p = 0.036). High CXCL8 levels independently predicted poor functional outcomes at 12 months (OR: 2.69, 95%CI: 1.39–6.31, p = 0.005) and a higher 5-year case fatality rate (HR: 1.90, 95%CI: 1.23–2.93, p = 0.004). Elevated CXCL9 levels also predicted unfavourable functional outcomes at 12 months (OR: 2.45, 95%CI: 1.07–5.61, p = 0.034). In univariate analysis, increased levels of CXCL8, CXCL9, and CXCL10 showed an association with delirium, although this link was not evident in the multivariate analysis. Plasma CXCL8 and CXCL10 show potential as prognostic biomarkers for stroke outcomes and as therapeutic targets suitable for reverse translation.

Association of quality of life (QoL) with mortality in patients with adenoid cystic carcinoma using an internationally validated QoL questionnaire (EQ-5D-5L): A new baseline.

6097 Background: An evaluation of impact on quality of life (QoL) is required for regulatory approval and reimbursement of new drug therapies. Almost all studies of new therapies in adenoid cystic carcinoma (ACC) are non-randomised with no comparator QoL measure. To support Health Technology Assessments and the evaluation of the clinical utility of these therapies, we sought to determine the QoL measures in a cohort of ACC patients and to assess for change over time and associations with clinical or prognostic factors. Methods: An internationally validated QoL questionnaire (EQ-5D-5L) was completed by ACC patients referred to an experimental medicine centre between 2019 and 2024, who provided written informed consent to analysis. EQ-5D value scores (EQV) were calculated from each questionnaire using the EuroQol England value set. A Cox proportional hazards model was built with EQV as a time dependent variable, with a variant using penalised smoothing splines to assess linearity. A base non-linear mixed effects (nlme) model was constructed between time and EQV. The relationship between EQV and other predictors (NOTCH1 alteration status, age at diagnosis, sex, local and/or metastatic recurrence, and primary site of disease) were tested against the base model using variant models built for each predictor. Both analyses used R Statistical Software (v4.3.2) with survival and nlme packages in Rstudio (v2023.12.0.0). Results: Between 2019 and 2023, 563 EQ-5D-5L questionnaires were completed by 161 patients with ACC (median 2 responses/patient, range 1 to 20). NOTCH1 alteration was seen in 8% (13/161), median age at diagnosis 49 years (range 17 to 81), 40% male, 36% (58/161) had a major salivary gland as primary site, and 14% had local recurrence, 46% metastatic recurrence and 26% both for 86% total with recurrent disease (139/161). For all 161 patients, median EQV was 0.81 (range -0.22 to 1.0); an EQV of 1 is ideal QoL and 0 is QoL as bad as death. The median EQV for the clinical subgroups were 0.83 (NOTCH1, IQR 0.74-0.87), 0.84 (no recurrence, IQR 0.75-0.92), 0.80 (local recurrence only, IQR 0.70-0.86), 0.81 (distant metastasis only, IQR 0.70-0.92), 0.83 (distant and local, IQR 0.75-0.92), 0.84 (major primary site, IQR 0.75-0.92), 0.81 (other primary site, IQR 0.70-0.89), and no statistical differences were identified between these groups. However, a decrease in EQV from 1 to 0 was associated with an eightfold increase in risk of death in the total population (HR= 0.118, 95% CI 0.057 to 0.244, p= &lt;0.001). There was a significant non-linear relationship between EQV and survival over time (p=0.011), with a greater marginal effect on survival for EQVs &gt;0.81. Conclusions: For patients with ACC, a worse QoL as measured by EQ-5D-5L was associated with a significantly increased risk of death. NOTCH1 and disease recurrence were not associated with a worse QoL.

#1441 COVID-19 vaccination and risk of infection and subsequent death in patients with kidney disease

Abstract Background and Aims The effect of vaccinations against SARS-CoV-2 on risk of infection and subsequent adverse outcomes in patients with kidney dysfunction beyond end-stage kidney disease remains uncertain. Based on nationwide data from multiple health care registers, the study aims to evaluate vaccination effect on rates of SARS-CoV-2 infection and subsequent risk of associated mortality in patients with kidney disease beyond end-stage kidney disease. Method A population-based retrospective cohort study on all Danish residents ≥18 years with an eGFR ≤90 ml/min/1.73 m2 identified between February 1st 2021 and June 27th 2022 corresponding to predominance of Alpha-, Delta-, and Omicron-variant. Outcomes compared based on vaccination state (unvaccinated, vaccinated, and booster vaccinated) across predefined eGFR categories (eGFR 60-90 mL/min/1.73 m2; eGFR 45-59 mL/min/1.73 m2, eGFR 30-44 mL/min/1.73 m2; eGFR &amp;lt;30 mL/min/1.73 m2). Risk of infection reported as age- and gender-standardized rate ratios of positive SARS-CoV-2 PCR and subsequent risk of death reported as age- and gender standardized 30-day mortality risk. Standardized risks computed based on hazards obtained in multiple cause-specific Cox regression models. Results A total of 982,047 adults with eGFR ≤90 ml/min/1.73 m2 identified. Gender distribution was 43.9% male, median age was 71 [IQR 61–78] years, median eGFR 75 [IQR 63-84], and 13.1% diabetes. Population rates of vaccination were 3.5%, 80.1%, and 95.4% for Alpha-, Delta-, and Omicron-variant, with 66.2% booster vaccinated at Omicron-variant baseline (Pfizer BionTech 88.3%, Moderna 9.4%, other vaccinations 2.3%). In total 359,428 SARS-CoV-2 infections were identified (Alpha: n = 7,861, Delta: n = 27,868, Omicron: n = 323,699), corresponding to a crude rate of positive SARS-CoV-2 PCR test of 629.0 per 100,000 person-weeks overall. Vaccination and booster vaccination were associated with progressively lower rate of SARS-CoV-2 infection. Age- and gender-standardized rate ratios are shown in Fig. 1. Overall, mean 30-day risks of death were 7.1‰ [95% CI 6.7-7.6], 3.8‰ [95% CI 3.5-4.0], and 1.4‰ [95% CI 1.3-1.4] in unvaccinated, vaccinated, and booster vaccinated persons, respectively. Vaccination and booster vaccination were associated with benefit on 30-day mortality across all strata of eGFR despite progressive increase in risk of death observed with declining kidney function. Age- and gender standardized 30-day mortality rates following a positive PCR for SARS-CoV-2 across granular eGFR are shown in Fig. 2. Conclusion Based on comprehensive nationwide data covering Alpha-, Delta-, and Omicron-variant predominance in Denmark, vaccination and booster vaccination against COVID-19 were associated with lower rates of SARS-CoV-2 infection and benefit on subsequent risk of 30-day mortality across all strata of eGFR.

#559 Validation of the Kidney Failure Risk Equation (KFRE) in individuals with chronic kidney disease and multimorbidity

Abstract Background and Aims Increasing numbers of individuals with chronic kidney disease (CKD) experience multiple long-term conditions (multimorbidity). Clinical guidance recommends the use of validated risk prediction equations, such as the kidney failure risk equation (KFRE), to guide referral to specialist kidney care services. However, multimorbidity may impact the accuracy of creatinine-based eGFR and bias the prognostic utility of KFRE. Equations with alternative filtration markers, such as Cystatin C eGFR (eGFRcys) or the combined creatinine and Cystatin C eGFR (eGFRcrcys), may improve KFRE's risk stratification and discrimination of future kidney failure risks. This study aimed to validate the four-variable KFRE in individuals with CKD, with and without multimorbidity in a research-based cohort (UK Biobank) and a population-based cohort (Stockholm Creatinine Measurements project (SCREAM)). The study also assessed the performance of KFRE when using eGFRcr, eGFRcys and eGFRcrcys. Method Individuals from both cohorts were included if they had CKD, defined as eGFR&amp;lt;60 mL/min/1.73 m2 by any of the three eGFR equations (eGFRcr, eGFRcys and eGFRcrcys), and had available proteinuria measurement at time of testing or within the previous 12 months. Multimorbidity was defined as the presence of two or more long-term conditions in addition to CKD and was grouped into multimorbidity clusters based on previous research. The outcome was kidney failure, defined as the need for long-term dialysis or kidney transplantation. KFRE performance at 2- and 5-years was assessed using the area under the receiver operating characteristic curve and c-index for discrimination and calibration curves for calibration. Results We included 24 489 individuals from UK Biobank and 42 902 individuals from SCREAM (mean age 62.8 (SD 5.6) and 70.1 (SD14.1), 54% and 66% female, respectively). In UK biobank, 14 998 individuals had multimorbidity, of which 5 375 had cardiometabolic multimorbidity. In SCREAM, 30 147 had multimorbidity and 17 854 cardiometabolic multimorbidity. Overall, there were 252 and 312 kidney failure events and 1 108 and 1 471 death events in UK Biobank and 918 and 1 098 kidney failure events and 8 785 and 10 152 death events in SCREAM within 2- and 5-years respectively. Model performance was consistent across both cohorts. Discrimination power of KFRE was good in individuals with and without multimorbidity and across the 2-year and 5-year models (Table 1). Calibration plots revealed over-estimation of risk at 2-years in both cohorts and under-estimation of risk at 5-years in patients with multimorbidity in UK Biobank. There was no improvement in model performance when using eGFRcys or eGFRcrcys compared to eGFRCr. There was a higher cumulative incidence of both kidney failure and death in the multimorbidity group, with a prominent increase in risk of death over time compared to the no multimorbidity group. This was most evident in the SCREAM cohort (Fig. 1). Conclusion KFRE adequately predicts kidney failure in individuals with multimorbidity and either creatinine or cystatin C can be used. Given the high rates of mortality amongst people with multimorbidity, exploration of models that account for the competing risk of death is warranted.