Multicenter Observational Study Research Articles

Effect of comorbidity classes on survival of patients with gastrointestinal tract cancer

BackgroundComorbidities may complicate medical situations and have an impact on the treatment decisions and poor survival of cancer patients. How comorbidities cluster together and ultimately affect patients’ outcomes in gastrointestinal tract cancer (GTC) is a poorly understood area.MethodsIn a multicenter prospective observational study from 2012 to 2021, we grouped the comorbidities of patients with GTC by latent class analysis, obtaining two comorbidity classes. Cox regression models were initially used to predict mortality. LASSO techniques were used to reduce the dimension. The final model included the comorbidity classes and nine more predictors. Additionally, the performance of different simple multimorbidity measures were compared using the Bayesian information criterion (BIC), ROC curves and C-index. Finally, the performance of the final model was analyzed using ROC curves, calibration curves and decision curves. The nomogram was drawn to evaluate the model.ResultsWe included 10,019 patients and obtained two comorbidity classes. Class 2 patients have a higher incidence of comorbidities, and a lower survival rate compared to Class 1 (P < 0.001). Compared to models containing the number of comorbidities or only a single comorbidity, the final model with the comorbidity classes has the highest AUC and C-index, as well as the lowest BIC, indicating this model has the best predictive performance.ConclusionWe identified two classes of comorbidities that were associated with overall survival in patients with GTC. The combination of different comorbidities class plays a vital role in the prognosis of GTC.

Comparative Outcomes of Glucagon-Like Peptide-1 Receptor Agonists to Dipeptidyl Peptidase 4 Inhibitors in Patients With Heart Failure and Type 2 Diabetes.

Clinical trials showed that glucagon-like peptide-1 receptor agonist (GLP1-RA) significantly improved the control of diabetes and reduced body weight compared with dipeptidyl peptidase 4 inhibitor (DPP-4i). However, it is unclear whether GLP1-RA is effective compared with DPP-4i in patients with heart failure (HF) with type 2 diabetes (T2D). The purpose of this study was to evaluate the risk of GLP1-RA compared with DPP-4i in all-cause death and hospitalization in patients with HF and T2D. This multicenter retrospective observational study using TriNetX, a global health care data and analytics platform, included patients with HF and T2D who had received GLP1-RA or DPP-4i from January 1, 2018, to December 31, 2022. Primary outcome was 12-month incidence of all-cause death. Secondary outcome was hospitalization. We used odds ratios (ORs) and 95% CIs to evaluate outcome measures. Among 1 005 097 patients with HF and T2D, 57 965 initiated GLP1-RA and 77 098 initiated DPP-4i. After propensity score matching, the number of participants in both the GLP1-RA group and the DPP-4i group was 36 557. The proportion of 12-month incidence of all-cause death was lower in the GLP1-RA group than in the DPP-4i group (5.9% [2140/36 557] versus 8.5% [3103/36 557]; OR, 0.67 [95% CI, 0.63-0.71]).The proportion of 12-month incidence of hospitalization was also lower in the GLP1-RA group than in the DPP-4i group (42.3% [15 455/36 557] versus 48.5% [17 733/36 557]; OR, 0.78 [95% CI, 0.76-0.80]). Use of GLP1-RA for patients with HF and T2D was associated with reduced 12-month incidence of all-cause death and hospitalization compared with DPP-4i.

Profiling the persistent and episodic nature of long COVID symptoms and the impact on quality of life and functional status: a cohort observation study.

Post-viral issues following acute infection with coronavirus disease 2019 (COVID-19), referred to widely as long COVID, are associated with episodic, persistent, and disabling symptoms affecting quality of life and functional status. Evidence demonstrates a significant impairment and long disease course, but there remains limited empirical data to profile and determine the fluctuating symptom profile of long COVID. We devised a 16-week, multicentre prospective cohort observation study to profile changes in patient-reported outcomes, and biological, physiological, psychological, and cognitive parameters following diagnosis and/or referral to an established long COVID clinic. Following baseline assessments, participants completed four face-to-face visits interspersed with telephone consultations. Face-to-face visits included physiological assessment, patient-reported outcome measures (PROMs), functional status, and respiratory function. Telephone consultations involved PROMs and symptom profiling. Patient-reported outcomes improved from baseline to week sixteen, but demonstrated between visit fluctuations in frequency and severity. Further findings highlight the severity and frequency of long COVID symptom profiles and the extent of quality of life and functional status impairment. The data presented here highlight the episodic and relapsing nature and should be used to help characterise long COVID disability. They can inform the development of long COVID-specific guidelines and support services that can adequately respond to the reductions in patient well-being.

Prognostic utility of neutrophil gelatinase-associated lipocalin (NGAL) levels for cardiovascular events in patients with stable coronary artery disease treated with percutaneous coronary intervention: a prospective longitudinal cohort study

IntroductionNeutrophil gelatinase-associated lipocalin (NGAL) modulates the enzymatic activity of matrix metalloproteinase-9, which is an important mediator of plaque instability in atherosclerosis. High NGAL levels can independently predict all-cause mortality and major adverse cardiac events (MACE) in patients with acute myocardial infarction (AMI). However, studies that have measured NGAL levels in patients with stable coronary artery disease (CAD) are limited. Furthermore, no significant prognostic predictive value between NGAL levels and stable CAD has been established.HypothesisWe aimed to investigate the prognostic role of NGAL levels in a prospective cohort study of patients with stable CAD treated with percutaneous coronary intervention (PCI).MethodsA total of 2,238 stable patients with CAD and a previous PCI were enrolled in a multicenter prospective observational study (The National Taiwan Biosignature Research, NTBR) in Taiwan. The primary outcome was the occurrence of MACE (cardiovascular death, nonfatal myocardial infarction, and ischemic stroke). The secondary outcome was a composite of cardiovascular events (cardiovascular death, nonfatal MI, nonfatal stroke, and hospitalization for heart failure).ResultsDuring the mean follow-up period of 4.6 ± 1.7 years, 441 patients reached the primary endpoints. Kaplan-Meier analysis showed that event-free survival was significantly different between the first and third tertile groups (log-rank test, p < 0.001) in subjects categorized by NGAL levels. In a multivariate Cox proportional hazard regression analysis, plasma NGAL levels were independently associated with an increased risk of MACE [adjusted hazard ratio (aHR) = 1.35; 95% confidence interval (CI) = 1.18–1.54, p < 0.001], AMI (aHR = 1.34; 95% CI = 1.12–1.59, p < 0.001), and target vessel revascularization (aHR = 1.35; 95% CI = 1.19–1.53, p < 0.001). Addition of serum NGAL levels to the traditional risk model improved its prediction value for future cardiovascular events.ConclusionsHigh plasma NGAL levels were independently associated with the occurrence of MACE and composite cardiovascular events in patients with stable PCI-treat CAD.

Intravenous tranexamic acid and reduction in blood loss and perioperative transfusion requirements in adult spinal deformity: a multicenter propensity-scored observational study.

Intraoperative antifibrinolytic therapy with tranexamic acid (TXA) is a focus of interest for blood loss reduction in multilevel adult spinal deformity (ASD) correction surgery. There is considerable heterogeneity in the reported findings regarding the safety and efficacy of this therapy. In the present study, the authors aimed to rigorously investigate the safety and efficacy of TXA in multilevel ASD correction surgery and to explore secondary perioperative outcomes. This retrospective cohort study used data from the authors' institutional spine deformity database, including records of surgeries performed between January 1, 2013, and December 13, 2021, with a minimum follow-up of 2 years. Adult patients undergoing elective thoracolumbosacral posterior spinal fusion involving 6 or more vertebrae were included. The primary outcome was the safety and efficacy of TXA, with secondary outcomes including postoperative complications and overall outcomes. Propensity-scored stabilized inverse probability of treatment weighting was used to adjust for confounding factors. Subsequent weighted analysis of the treatment effect was performed using regression models for hypothesis testing, with 95% confidence intervals calculated based on weighted means, variances, and standard errors. The p values of primary outcomes and subgroup analyses were adjusted for multiplicity testing with the Benjamini-Hochberg correction at a false discovery rate of 0.05. The conduct and reporting of this study were supported by the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines. The study included 598 patients, with 257 receiving TXA and 341 controls. Weighted analysis revealed that TXA administration was associated with significant reductions in estimated blood loss (p = 0.007), percentage of estimated blood volume lost (p = 0.035), intraoperative total red blood cell transfusion volume (p = 0.035), and postoperative packed red blood cells transfusion volume (p = 0.035). No significant differences were observed in postoperative thromboembolic events (p = 0.397). TXA was significantly associated with reduced blood loss and transfusion requirements in multilevel ASD correction surgery without increasing the risk of thromboembolic complications.

Two-year trajectory of functional recovery and quality of life in post-intensive care syndrome: a multicenter prospective observational study on mechanically ventilated patients with coronavirus disease-19

BackgroundPost-intensive care syndrome (PICS) affects the quality of life (QOL) of survivors of critical illness. Although PICS persists for a long time, the longitudinal changes in each component and their interrelationships over time both remain unclear. This multicenter prospective study investigated the 2-year trajectory of PICS and its components as well as factors contributing to deterioration or recovery in mechanically ventilated patients with coronavirus disease 2019 (COVID-19), and also attempted to identify possible countermeasures.MethodsPatients who survived COVID-19 requiring mechanical ventilation completed questionnaires on the Barthel index, Short-Memory Questionnaire, Hospital Anxiety and Depression Scale, and EuroQol 5 dimensions 5-level every six months over a two-year period. Scores were weighted to account for dropouts, and the trajectory of each functional impairment was evaluated with alluvial diagrams. The prevalence of PICS and factors impairing or restoring function were examined using generalized estimating equations considering trajectories.ResultsAmong 334 patients, PICS prevalence rates in the four completed questionnaires were 72.1, 78.5, 77.6, and 82.0%, with cognitive impairment being the most common and lower QOL being noted when multiple impairments coexisted. Physical function and QOL indicated that many patients exhibited consistent trends of either recovery or deterioration. In contrast, cognitive function and mental health revealed considerable variability, with many patients showing fluctuating ratings in the later surveys. Delirium was associated with worse physical and mental health and poor QOL, while prolonged ventilation was associated with poor QOL. Living with family was associated with the recovery of all functions and QOL, while extracorporeal membrane oxygenation (ECMO) was associated with the recovery of cognitive function and mental health.ConclusionsCritically ill patients had PICS for a long period and followed different trajectories for each impairment component. Based on trajectories, known PICS risk factors such as prolonged ventilation and delirium were associated with impaired recovery, while ECMO and the presence of family were associated with recovery from PICS. In critically ill COVID-19 patients, delirium management and family interventions may play an important role in promoting recovery from PICS.Trial registration number: UMIN000041276, August 01, 2020.

Short-term complications of internal versus external fixation of closed diaphyseal tibial fractures in 95 skeletally immature dogs.

To determine the influence of fixation method (internal vs. external) on short-term postoperative complications of closed diaphyseal tibial fractures in skeletally immature dogs. Retrospective observational multicenter study. Skeletally immature dogs stabilized with internal fixation (IF) via plate osteosynthesis (n = 59) and external skeletal fixation (ESF) (n = 36). Medical records from skeletally immature dogs with closed tibial diaphyseal fractures were reviewed. Data collected included signalment, fracture morphology, etiology, fixation technique, surgeon status, complications, time to discharge and time to final discharge. The total complication rate for IF was lower at 20.3% (p < .001, CI: 11.0-32.8) compared to ESF at 55.6% (CI: 38.1-72.1). A total of 95% of complications were considered major for external fixation versus 75% for internal fixation. Multivariable analysis revealed decreased odds of a postoperative short-term complication when a closed tibial diaphyseal fracture was stabilized with IF compared to ESF (p = .004, OR: 0.2, CI: 0.09-0.63). The median time to final discharge for ESF was 4 weeks (range: 2-13) and for IF was 6 weeks (range: 4-32) (p = .01). ESF had a higher rate of short-term complications than IF, primarily due to pin-tract morbidity. The complication rate was 35.3% higher for ESF than for IF. Surgeons should consider the use of IF over ESF for skeletally immature dogs to reduce the risk of major complications.

Ten-Year Surveillance of RSV Hospitalizations in Adults: Incidence Rates and Case Definition Implications.

The impact of RSV in older adults is under-recognized, and the limited existing studies on the incidence of hospitalizations show great variability. This study aims to estimate the seasonal incidence rates (IRs) of RSV hospitalizations among adults aged 60 and older (≥60) and evaluate how different case definitions influence these estimates. A prospective, multicentre observational study with active monitoring conducted over 10 seasons (2010/2011 to 2019/2020) in 4-10 hospitals (depending on the season) that covered 21-46% of the region's total population (around 5 million people). RSV-hospitalization IRs per 100,000 person-years (p-y) and 95% confidence intervals (CI) were calculated by the Exact Poisson method, and were stratified by age group (≥60, ≥70, and ≥80), RSV season, sex, and the entire study period. Two case definitions were compared: influenza-like illness (ILI) and the combined use of ILI and extended severe acute respiratory infection (ILI/SARI). A total of 40,600 hospitalizations of individuals aged ≥60 were included. The RSV-hospitalization IRs ranged from 21 to 402 per 100,000 p-y, varying by season, age group and case definition. The highest IRs were observed in those aged 80 and older. The ILI case definition underestimated RSV hospitalizations by 13% to 40% when compared to the ILI/SARI case definition. On average, approximately 1 every 1,000 adults ≥60 is hospitalized due to RSV. The risk of a severe RSV infection increases with age and varies significantly between seasons. These are key results for the estimation of the potential impact of the new available RSV vaccines.

Real-world effectiveness and retention rate of upadacitinib in patients with rheumatoid arthritis: results from a multicentre study

This study evaluates upadacitinib (UPA) effectiveness and drug retention rate (DRR) in patients with rheumatoid arthritis (RA). Multicentre prospective observational study. Consecutive patients with RA receiving UPA were evaluated at 0, 3, 6, 12, 18, and 24 months of treatment. Key outcomes included UPA DRR and changes in clinical and serological measures over time. The study included 215 patients (72.6% female sex, mean age 60.1 ± 11.7 years). The DRR of UPA was 91.6% (95% CI 88.0–95.4%) at 6 months, 84.6% (95% CI 79.8–89.7%) at 12 months, 80.3% (95% CI 75.0–86.0%) at 18 months and 80% (95% CI 75.0–86.0%) at 24 months. UPA DRR was similar between monotherapy and methotrexate combination (p = 0.47), and across different treatment lines (p = 0.58). A statistically significant improvement from baseline was observed over 24 months considering erythrocyte sedimentation rate, C-reactive protein (CRP), Health Assessment Questionnaire (HAQ), Disease Activity Score (DAS)28-CRP, Physician’s (Ph) and Patient’s (Pt) Global Assessment (GA), Visual Analogue Scale (VAS) Pain, Simplified and Clinical Disease Activity Index (SDAI and CDAI) (p < 0.00 for all of them). Patients discontinuing UPA were more likely to be male (p = 0.02), with a longer disease duration (p = 0.03), higher baseline values of VAS Pain (p < 0.00), PtGA (p < 0.00), PhGA (p < 0.00), CDAI (p < 0.00), SDAI (p < 0.00) and corticosteroid dosage (p = 0.04). This study confirms UPA effectiveness in managing RA in the real-world practice, demonstrating sustained drug retention and improvements in clinical and laboratory measures over time. Also, UPA could be a valuable option for patients with multi-refractory RA and when monotherapy is preferred.

A normal electrocardiogram indicates a better prognosis in patients with moderate to very severe chronic obstructive pulmonary disease

The role of electrocardiography (ECG) in predicting mortality in patients with chronic obstructive pulmonary disease (COPD) has not been sufficiently established. Research question: Is a normal ECG associated with a better prognosis than an abnormal ECG in patients with COPD? ECG parameters were assessed in patients enrolled in the Czech Multicenter Research Database of COPD. We assessed ECGs from baseline (August 2013) until December 31, 2019, or until death. The primary endpoint was 5-year overall survival depending on the ECG findings. A total of 300 subjects were enrolled in the study and 143 died during follow-up. This multicenter noninterventional observational prospective study revealed a significant difference in 5-year overall survival between COPD patients with normal ECGs and those with prognostically significant or other ECG abnormalities (76.8%, 38.2%, and 63.4%, respectively; P < 0.001). Patients with prognostically significant ECG abnormalities had a 2.537-fold greater mortality risk at 5 years than those with normal ECGs. In the COPD setting, patients with normal ECGs had a better prognosis than those with prognostically significant abnormalities suggesting that ECG may be a valuable tool for predicting mortality risk in these patients.

Frequent detection of anti-nuclear antibodies and low-titer rheumatoid factor in female patients with undifferentiated peripheral spondyloarthritis in Japan: a prospective observational study.

Studies on the clinical features of undifferentiated peripheral spondyloarthritis (upSpA) are limited. This study explores sex-based manifestations of upSpA and compares upSpA with rheumatoid arthritis (RA) under conditions of low human leukocyte antigen B27 positivity in Japan. In this multicenter prospective observational study, physical and laboratory findings from 29 upSpA cases (19 females, 10 males) were collected to investigate sex differences. Fourteen patients with RA were also enrolled as a control group to evaluate clinical parameters distinguishing upSpA and RA. Tenderness at the humeral epicondyles and the Achilles tendon were more common in female patients with upSpA than in males. Serum C-reactive protein (CRP) levels were lower in female patients with upSpA than in male patients. Serum rheumatoid factor (RF) levels were lower in upSpA cases than in RA, with a cut-off value of 84 IU/mL differentiating RA from upSpA. An anti-nuclear antibodies (ANA) test at a dilution of ≥1:160 was detected in about half of the female upSpA cases but not in male cases. Among upSpA and RA cases, female patients with upSpA frequently present with multiple enthesitis, low serum CRP levels, low-titer RF positivity, and a high incidence of ANA positivity.

Phenotypic Trajectories From Acute to Stable Phase in Heart Failure With Preserved Ejection Fraction: Insights From the PURSUIT-HFpEF Study.

Using machine learning for the phenotyping of patients with heart failure with preserved ejection fraction (HFpEF) has emerged as a novel approach to understanding the pathophysiology and stratifying the patients. Our objective is to perform phenotyping of patients with HFpEF in stable phase and to investigate the phenotypic trajectory from acute worsening phase to stable phase. The present study is a post hoc analysis of the PURSUIT-HFpEF (Prospective Multicenter Observational Study of Patients with Heart Failure with Preserved Ejection Fraction) study. We applied the latent class analysis to the discharge data of patients hospitalized for acute decompensated heart failure. We finally included patient data of 1100 cases and 63 features in the latent class analysis. All patients were subclassified into 5 phenogroups as follows: Phenotype 1, characterized by better renal function and lower NT-proBNP (N-terminal pro-B-type natriuretic peptide) level [N=325 (29.5%)]; Phenotype 2, higher blood pressure, sinus rhythm, and poor renal function. [N=242 (22.0%)]; Phenotype 3, higher prevalence of atrial fibrillation, higher tricuspid pressure gradient, and lower tricuspid annular plane systolic excursion [N=214 (19.5%)]; Phenotype 4, higher C-reactive protein level and higher tricuspid pressure gradient [N=245 (22.3%)]; and Phenotype 5, poor nutritional status, poor renal function, and higher NT-proBNP level [N=74 (6.7%)]. A particular phenotype observed at the time of discharge was correlated with a distinct phenotype of acute worsening. We identified 5 distinct stable phase phenotypes of the patients with HFpEF from the data at discharge. A specific phenotype at discharge was associated with a particular phenotype of acute worsening. This grouping can be a basis for future precision medicine of patients with HFpEF. URL: https://www.umin.ac.jp/ctr/; Unique identifier: UMIN000021831.

Validation of a biomarker-based mortality score for cardiogenic shock patients: Comparison with a clinical risk score.

Cardiogenic shock (CS) is the deadliest manifestation of acute heart failure, with persistently high mortality rates and a lack of recent therapeutic breakthroughs. Accurate risk prediction is crucial in clinical decision-making and the design of future clinical trials. We aimed to validate the CLIP score, a biomarker-based risk score comprising cystatin C, lactate, interleukin-6 and NT-proBNP, for predicting mortality in acute coronary syndrome (ACS) related CS, and to compare its predictive value with the previously published CardShock risk score. The study is a post hoc analysis of the CardShock Study, a prospective, observational European multicentre study on CS. The CLIP score was calculated 12h after hospital admission, and its ability to predict 90-day mortality was assessed using are under the curve (AUC) of the receiver-operating characteristics (ROC) curve analysis. The discriminative ability of the CLIP score was compared with the CardShock risk score by comparing the AUC's. The cohort was dichotomized into low and high risk groups by the optimal cut-off value derived from the ROC analysis of the CLIP score. Kaplan-Meier curves were constructed to evaluate risk stratification when combining the CLIP and CardShock risk scores. The cohort (n=121) comprised 77% (n=93) men and the median age was 67years (IQR 61-76). A total of 21% (n=25) of the patients had non-ACS related CS. The CLIP score demonstrated appropriate predictive accuracy for 90-day mortality (AUC 0.84, 95% CI 0.77-0.91), comparable with the CardShock risk score (AUC 0.77 [95% CI 0.69-0.85]; P=0.064 for comparison). A CLIP score cut-off of 0.28 stratified patients into high risk (65% mortality) and low risk (16% mortality) groups. In addition, incorporating the CLIP score enhanced risk stratification in all CardShock risk score categories. The CLIP score, calculated within 12h of hospital admission, accurately predicted 90-day mortality in CS and complemented the CardShock risk score. The biomarker-based score has potential utility in dynamic mortality risk assessment and could inform clinical management and trial design.

Real-world outcomes of generic elexacaftor/tezacaftor/ivacaftor (gETI) in South Africans (SA) with CF using standard versus clarithromycin-boosted gETI, modulator-sparing strategies to reduce cost.

Access to highly effective modulator therapies (HEMT) in resource-limited countries is limited by prohibitive cost and restrictive patents. We report the clinical outcomes of a cost-reduction strategy in South Africa (SA), where generic elexacaftor/tezacaftor/ivacaftor (gETI) was pharmacokinetically enhanced with clarithromycin (gETI/c) for people with CF (pwCF) eligible for HEMT. A multi-center observational study from December 2021 to May 2024. Analysis of variance (ANOVA) and linear mixed effects analyses were conducted to describe and compare change in sweat chloride (SC), FEV1pp, BMI (m/kg2) and adverse events (AE) over 18-months follow-up for different gETI dose categories: a) standard, full or b) modulator sparing dose (gETI/c at 25-50 % recommended dose, twice/thrice weekly). 70/413 (17 %) eligible pwCF [median age 27 years (range 6-52); 68 (97 %) with ≥ one copy F508del] received gETI with standard (n = 38) or modulator-sparing doses (n = 32); 29 changed dosing regimens across the study period. The overall mean (SD) reduction in SC after 1-month of treatment was -52.9 (16.9) mmol/L (p < 0.001), with no evidence of difference between dose groups (p = 0.2). Overall mean (SD) FEV1pp and BMI increased at 1-month by 14.9 (95 % CI 11.49-18.40) and 0.84 (95 % CI 0.16-1.49), respectively. Improvements in FEV1pp and BMI were sustained throughout follow-up, with no evidence of difference between dosing groups. No serious AEs were reported. Our experience with gETI is similar to real-world reports using the originator product. Boosting ETI with CYP3A-inhibitors is a safe and effective strategy to increase access to ETI in settings where access to HEMT is restricted.

Abstract 13: Intravenous Tirofiban as An Adjunct to Endovascular Therapy for Posterior Circulation Strokes with Tandem Lesions: One-Year Outcomes

Background: The effectiveness and safety of intravenous Tirofiban as an adjunct to endovascular therapy (EVT) in posterior circulation patients with tandem lesions (PCTL) remain uncertain. Methods: This study utilized individual patient data pooled from two multicenter observational studies: the BASILAR and the PERSIST registries. We included patients with acute ischemic stroke due to PCTLs who were treated with EVT. The patients were divided into two groups based on whether they received adjunctive intravenous Tirofiban therapy or not. The primary efficacy outcome was favorable functional outcome, defined as modified Rankin Scale (mRS) scores of 0-3 at one year. Secondary outcomes included safety assessments, such as rates of symptomatic intracerebral hemorrhage (sICH), early neurological deterioration (defined as a decline in National Institutes of Health Stroke Scale [NIHSS] score by ≥4 points within 72h), and all-cause mortality at one year. We also evaluated procedural outcomes, including successful reperfusion, defined as modified Thrombolysis in Cerebral Infarction (mTICI) grade 2b-3, and complete reperfusion, defined as mTICI 3. Results: Among 210 patients treated with EVT (126 Tirofiban, 84 Non-Tirofiban), successful reperfusion (mTICI 2b-3) was achieved in 109 (86.5%) Tirofiban patients versus 64 (76.2%) non-Tirofiban patients (Adjusted OR 1.75, 95%CI [0.76-4.03], P=0.19). Complete reperfusion (mTICI 3) was achieved in 74 (58.7%) Tirofiban patients versus 36 (42.9%) non-Tirofiban patients (Adjusted OR 2.08, 95%CI [1.04-4.14], P=0.04). Rates of sICH were 6 (4.8%) in the Tirofiban group versus 9 (10.7%) in the non-Tirofiban group (Adjusted OR 0.24, 95%CI [0.04-1.36], P=0.11). Early neurological deterioration occurred in 18 (14.3%) Tirofiban patients versus 32 (38.1%) non-Tirofiban patients (Adjusted OR 0.20, 95%CI [0.09-0.46], P&lt;0.001). One-year mRS 0-3 was achieved in 48/119 (40.3%) Tirofiban patients versus 24/82 (29.3%) non-Tirofiban patients (Adjusted OR 5.38, 95%CI [2.21-13.06], P&lt;0.001). One-year mortality was 45/119 (37.8%) in the Tirofiban group versus 43/82 (52.4%) in the non-Tirofiban group (Adjusted OR 0.26, 95%CI [0.12-0.59], P=0.001). Conclusion: Intravenous Tirofiban as an adjunct to EVT may improve long-term functional outcomes in acute ischemic stroke patients due to PCTLs without significantly increasing the risk of hemorrhagic complications. Further prospective studies are warranted to validate these findings.

Five-year efficacy and safety of pembrolizumab as first-line treatment in patients with non-small cell lung cancer with PD-L1 tumor proportion score ≥50 %: A multicenter observational study

Five-year efficacy and safety of pembrolizumab as first-line treatment in patients with non-small cell lung cancer with PD-L1 tumor proportion score ≥50 %: A multicenter observational study

Abstract 32: Ischemic and hemorrhagic risks of patients with Basal Ganglia Perivascular Spaces on Antithrombotic Therapy

Background: Enlarged perivascular spaces (PVS), a marker of cerebral small vessel disease (SVD), are considered to increase the risk of stroke. However, there is limited data on the benfits and harms of antithrombotic agents in patients with PVS. We assessed the association of PVS with the risk of hemorrhagic or ischemic events in patients receiving antithrombotic agents. Methods: This is an investigator-initiated, prospective, multicenter observational study that enrolled patients with cerebrovascular or cardiovascular diseases who were taking oral antithrombotic agents from 52 hospitals across Japan between 2016 and 2019. All participants underwent baseline multimodal MRI. The MRI scans were centrally evaluated for radiologic indicators related to SVD, including white matter hyperintensities (WMH), cerebral microbleeds (CMBs), lacunes, basal ganglia enlarged-perivascular spaces (BGPVS), cortical superficial siderosis, using a visual scale. The outcomes included major bleeding, intracranial hemorrhage, ischemic events, ischemic stroke, and mortality. Results: Of the analyzed 5,250 patients (1,736 women; median age 73 [IQR 66–79] years), antiplatelets and anticoagulants were administered at baseline in 3,948 (75.2%) and 1,565 (29.8%), respectively. During a median 2 (IQR1.8–2.0) years, 278 ischemic events, 197 ischemic strokes, 93 major bleeding, 55 intracranial hemorrhage, and 217 deaths were observed. The distribution of BGPVS was as follows: 0 BGPVS in 475 patients (9.4%), 1-10 BGPVS in 2615 patients (51.6%), and 11+ BGPVS in 1975 patients (39.9%). A higher BGPVS burden was associated with older age, a lower proportion of women, higher rates of hypertension and smoking, lower eGFR values, and a higher prevalence of lacunes, CMBs, and WMH. A higher burden of BGPVS was associated with a higher risk of major bleeding (1–10 BGPVS: adjusted hazard ratio (aHR) 1.49, [95% confidence interval CI 0.76–7.92], 11+ BGPVS: aHR 3.27 [1.09–11.57] versus 0 BGPVS; p trend = 0.035) and ischemic stroke (1–10 BGPVS: aHR 1.79 [0.90–3.57], 11+ BGPVS: aHR 2.39 [1.19–4.81]; p trend = 0.014). In contrast, higher BGPVS burden was not significantly associated with an increased risk of ischemic events, intracranial hemorrhage, or mortality. Conclusions: A higher burden of BGPVS was associated with an increased risk of ischemic stroke and major bleeding in patients taking antithrombotic medication and might be useful in clinical decision making.

The relationship between hypomagnesemia and ICU mortality in severe hemorrhagic stroke patients: an observational multicentre study on eICU database

BackgroundHemorrhagic stroke is a potentially fatal condition with high mortality and morbidity. However, there is a lack of evidence for this relationship in critically ill patients with hemorrhagic stroke. This study aims to explore the relationship between hypomagnesemia and ICU mortality in severe hemorrhagic stroke patients.MethodsThe study included 2,026 severe hemorrhagic stroke patients from the Electronic Intensive Care Unit Collaborative Study database, categorized into hypomagnesemia and non-hypomagnesemia groups based on serum magnesium levels. Primary outcome was ICU mortality. Secondary outcome was mechanical ventilation use. Multivariate Cox proportional hazards regression analyses were used to study the relationship between hypomagnesemia and the outcomes. We also performed a cumulative survival rate analysis by Kaplan–Meier curves.ResultsA total of 2,026 severe hemorrhagic stroke patients, aged over 16 and hospitalized in the ICU for more than 24 h, were enrolled. Among them, 277 (13.7%) died in the ICU, and hypomagnesemia was observed in 489 patients. Multivariable Cox regression analyses demonstrated that hypomagnesemia was related to a 28% increased risk of ICU mortality (HR 1.28, 95% CI [1.02–1.68], p = 0.035) and a 15% increased risk of mechanical ventilation use (HR 1.15, 95% CI [1.04—1.33], p = 0.010) in severe hemorrhagic stroke patients.ConclusionsOur findings suggested that hypomagnesemia is associated with increased risks of ICU mortality and mechanical ventilation use in severe hemorrhagic stroke patients. Future randomized, prospective studies are needed to elucidate the role of hypomagnesemia and explore potential interventions.

Clinical Predictors of Mortality in People With Severe Behavioral and Psychological Symptoms of Dementia

Dementia significantly impacts quality of life, health care costs, and caregiver burden, being a leading cause of death among older adults. We investigated predictors of mortality in people with severe behavioral and psychological symptoms of dementia (BPSD). A multicentric longitudinal observational study was conducted, comprising clinical assessments at baseline and every 6 months for 3 years. People with severe BPSD (Neuropsychiatric Inventory, NPI ≥32) living at home. Data on demographics and clinical characteristics were collected at baseline and during 6-monthly follow-ups over 3 years. The main outcome was mortality, documented over a total period of 4 years and analyzed using the Cox proportional hazards model. Of the 508 patients with dementia with severe BPSD, 165 (32.5%) died during the 4-year follow-up. Non-survivors were older (79.8 ± 7.7 vs 77.3 ± 8.0; P < .001), more likely to be male (58.8% vs 38.5%; P < .001), and had higher BPSD severity (NPI: 57.2 ± 20.2 vs 50.3 ± 17.9; P < .001), lower cognitive function according to the Mini-Mental State Examination (MMSE) (13.5 ± 6.6 vs 16.4 ± 5.9; P < .001), and worse functional status according to the Alzheimer's Disease Cooperative Study - Activities of Daily Living Scale (ADCS) (28.8 ± 16.4 vs 36.3 ± 17.2; P < .001) at baseline. Significant predictors of mortality included male sex [hazard ratio (HR), 2.03; 95% confidence interval (95% CI), 1.46-2.82; P < .001], older age at diagnosis (HR, 1.05; 95% CI, 1.03-1.07; P < .001), higher NPI scores (HR, 1.01; 95% CI, 1.01-1.02; P= .002), lower MMSE (HR, 0.95; 95% CI, 0.93-0.98; P= .001), lower ADCS (HR, 0.98; 95% CI, 0.98-0.99; P= .015), and lower quality of life rated by proxy (HR, 0.97; 95% CI, 0.95-0.99; P= .021). The use of antidepressants (HR, 0.69; 95% CI, 0.48-0.98; P= .038) was associated with increased survival. Delusions (HR, 1.0; 95% CI, 1.03-1.12; P < .001), hallucinations (HR, 1.07; 95% CI, 1.02-1.11; P= .002), and agitation/aggression (HR, 1.05; 95% CI, 1.01-1.09; P= .021) were significantly linked to increased mortality. Older age, male sex, severe BPSD, and lower cognitive and quality of life scores significantly predict increased mortality in patients with severe BPSD.

The impact of summative, formative or programmatic assessment on the Dutch National Pharmacotherapy assessment: A retrospective multicentre study.

The Dutch National Pharmacotherapy Assessment (DNPA), which focuses on assessing medication safety and essential drug knowledge, was introduced to improve clinical pharmacology and therapeutics education in the Netherlands. This study investigated how the performance of final-year medical students on the DPNA was affected by the assessment programme (traditional with summative or formative assessment, and programmatic assessment). This multicentre retrospective longitudinal observation study (2019-2023) involved final-year medical students from four medical schools in the Netherlands. The DNPA was used in different ways - either as a summative or formative assessment in a traditional assessment programme or as a non-high-stakes assessment in a programmatic assessment programme. Three medical schools changed from assessment programme over time. This study involved 1894 students. Summative assessment resulted in significantly higher scores and pass rates than formative assessment in a traditional assessment programme (mean score of 84.3% vs. 67.5%, and pass rate of 60.4% vs. 5.9%). In contrast, slightly lower scores were obtained when the assessment was non-high-stakes as part of a programmatic assessment programme rather than a summative assessment in a traditional assessment programme (mean score of 81.% vs. 84.3%, pass rate of 51.8% vs. 60.4%). In curricula where the assessment became summative instead of formative, scores and pass rates significantly improved (mean increase of +14.4% and 42.3%, respectively), when the assessment programme changed from traditional with summative assessment to programmatic with non-high-stakes assessment, scores and pass rates modestly decreased (decrease of 3.3% and 14.2%, respectively). Integrating the DNPA within a traditional assessment programme is most effective when assessed summatively, as it results in significantly higher scores compared to formative assessment. In the context of a programmatic assessment programme, the scores may be slightly lower. Changing assessment programmes within a medical school influences DNPA scores. Scores increase when the assessment is summative rather than formative within a traditional assessment programme. Conversely, scores mildly decrease when the assessment programme shifts from traditional with summative assessment to non-high-stakes programmatic assessment.