Higher Risk Of Adverse Events Research Articles

Mining and analysis of amphotericin B adverse reaction signals: a real-world study based on the FAERS database.

Invasive fungal infections (IFIs) have become an increasingly serious public health problem. Amphotericin B (AmB) remains the important component in the treatment of IFIs. But its clinical application is limited due to its adverse reactions. In this study we mined the adverse drug event signals of AmB based on the Food and Drug Administration Adverse Event Reporting System (FAERS) from the first quarter of 2004 to the third quarter of 2023, using the Reported Odds Ratio, Proportional Reporting Ratio, Bayesian Confdence Propagation Neural Network and Multi-item Gamma Poisson Shrinker methods to provide a reference for the safe clinical use. A total of 3597 adverse event (AE) reports for the primary suspect drug AmB were obtained, involving 22 system organ classes (SOCs), 1355 AEs. Patients aged 18-60 (47.93%) and female patients (53.82%) were at a higher risk of AEs with AmB. High risk signals in the report include hypokalemia, pyrexia, chill, renal failure. Additional high risk signals not mentioned in the instructions conclude respiratory failure, tachycardia, deafness. Mining the adverse reaction signal study of AmB based on the FAERS database provides support for the clinical monitoring and risk identification of this drug.

Klotho: Potential Marker of High Cardiovascular Risk in Patients With Acute Coronary Syndrome and Chronic Kidney Disease

Abstract Aim Recently it was established that the deficit of Klotho morphogenetic protein in serum is one of the most likely predictors of cardiovascular mortality. Purpose of the Study to examine the association of Klotho with adverse prognosis factors in patients with acute non-ST-segment elevation myocardial infarction and chronic kidney disease. Materials and Methods of the Study The analysis included patients with acute myocardial infarction without ST-segment elevation and chronic kidney disease. Inclusion criteria: AMI without persistent ST-segment elevation that underwent coronary artery stenting after coronary angiography; presence of chronic kidney disease diagnosed as a decrease in glomerular filtration rate less than 60 ml/min/1.73m2. Exclusion criteria: terminal CKD or patients on program hemodialysis, presence of acute kidney injury, cancer, refusal to participate in the study. Results Initial analysis showed that decreased Klotho levels were common among elderly patients, and among these patients there was more frequent history of myocardial revascularization, as well as a higher risk of adverse events according to the GRACE scale. The association of Klotho level with three cardiovascular complications risk factors—age (β = −9.884 (SD 1.667), p = 0.000), C-reactive protein level (β = −0.661 (SD 0.205), p = 0.002) and troponin (β = −0.07 (SD 0.031), p = 0.026)—was determined by multiple linear regression method. Conclusion The prospective study demonstrated that Klotho may act as one of the markers of cardiovascular risk in patients with non-ST elevation myocardial infarction and chronic kidney disease. Its independent association with three risk factors of cardiovascular risk – age, C-reactive protein level and troponin was established.

Transcatheter Aortic Valve Implantation and Replacement: The Latest Advances and Prospects

Transcatheter aortic valve replacement (TAVR) has revolutionized the treatment of aortic stenosis, particularly in patients at high risk of adverse events for traditional open-heart surgery. Since the early 2000s, TAVR has evolved rapidly with advancements in device technology, procedural techniques, and patient selection criteria. Over the past 20 years, this catheter-based procedure has significantly improved patient survival and quality of life, demonstrating both the safety and efficacy of TAVR, even in patients at low surgical risk. This paper reviews the latest advances in valve design and strategies for treating aortic stenosis. It explores the challenges with long-term outcomes given the younger age of patients undergoing TAVR and the prospects of emerging technologies to improve long-term outcomes.

Perceived Connections Between Personal Values and Health in High-Risk Patients with Multimorbidity: A Qualitative Study.

Aligned with increasing organizational and policy focus on whole person care, particularly for patients with multimorbidity, health systems are operationalizing how to assess what patients find meaningful in life for personalized health planning. Few studies have examined how patients with multimorbidity at high risk of adverse events perceive connections between what is most important in life (i.e., personal values) and health, healthcare, and healthcare decisions. This knowledge is critical to optimizing how, when, and under what circumstances the topics are addressed in healthcare settings. To understand how high-risk patients with multimorbidity perceive connections between personal values and health, healthcare, and healthcare decisions. Qualitative study. Patients ≥ 75th percentile risk of hospitalization or mortality using a validated prediction score, with ≥ 2 diagnoses among depression, hypertension, chronic kidney disease, or diabetes, engaged in Veterans Health Administration primary care. Individual semi-structured telephone interview, analyzed with content analysis. Patients (N=27) averaged 68 years old; 17 (63%) were male. Three main themes emerged: (1) personal values were rarely discussed in healthcare settings or reflected in healthcare decision-making, sometimes given perceived lower relevance by patients; (2) when personal values were perceived as affecting health decisions, it was within specific contexts or circumstances (e.g., deciding on surgery); (3) eliciting personal values in healthcare settings could have positive or negative consequences, related to conditions of disclosure and resultant action taken in the care plan, and not all patients wanted to disclose values. In this study, high-risk patients with multimorbidity reported rarely discussing values in healthcare settings, and if so, only perceived relevant connections between values and health in specific contexts. While some participants felt sharing values benefitted care, not all felt comfortable with disclosure. Patient preferences for eliciting and incorporating values are relevant to integrating patient personal values in healthcare settings.

Risk scores inconsistently predict sudden death and ventricular arrhythmias in repaired tetralogy of Fallot.

Risk scores inconsistently predict sudden death and ventricular arrhythmias in repaired tetralogy of Fallot.

Neoadjuvant Treatment in Localized Pancreatic Cancer of the Elderly: A Systematic Review of the Current Literature

Background/Objectives: Neoadjuvant therapy (NAT) improves surgical outcomes in pancreatic cancer, but its role in elderly patients remains unclear. Due to comorbidities and lower chemotherapy tolerance, assessing NAT’s benefits and risks in this population is essential. This systematic review assesses the impact of NAT on overall survival (OS), surgical resection rates, and treatment-related toxicities(G3-4) in elderly patients with resectable, borderline, or locally advanced pancreatic cancer. Methods: A systematic search was conducted in PubMed, MEDLINE, EMBASE, Scopus, and Cochrane databases according to PRISMA guidelines. Studies reporting that NAT outcomes in elderly patients (≥70 years) were included. The Newcastle–Ottawa scale was used to assess study quality. Subgroup analyses compared NAT versus upfront surgery and outcomes in elderly versus younger patients. Results: Twelve studies (four prospective and eight retrospective) including 11,385 patients met the inclusion criteria. Among 9580 elderly patients, only 24% underwent NAT. NAT significantly improved R0 resection rates compared to upfront surgery (p < 0.001), and elderly patients receiving NAT had a median OS of 26.5 (range 15.7–39.1) months versus 20.3 months (range 11.5–23.8) of upfront surgery and versus 36.2 months (range 23.6–43.0) of NAT in young patients. Elderly patients experienced higher rates of major toxicities (17–57.5%). Personalized regimens, such as gemcitabine/nab-paclitaxel, were better tolerated than FOLFIRINOX. Conclusions: NAT is associated with improved survival and surgical outcomes in elderly pancreatic cancer patients, despite a higher risk of adverse events. Patient selection based on performance status rather than age alone is essential to optimize treatment benefits. Further prospective trials are needed to refine treatment approaches in this population.

Apixaban in patients with nonvalvular atrial fibrillation, heart failure and low body weight: A report from a global federated research dataset.

Atrial fibrillation (AF) and low body weight (BW, <60 kg) are common in patients with heart failure (HF). However, the safety and effectiveness of direct oral anticoagulants (DOACs) in this group remain unclear. This study compares the efficacy and safety of apixaban versus vitamin K antagonists (VKAs) in patients with nonvalvular AF, low BW and HF. We analysed 155,152 patients with HF and AF, weighing ≤100 kg and treated with oral anticoagulants (apixaban 86,493; VKA 68,659), from the TriNetX Global Research Network. Outcomes included ischaemic stroke/systemic embolism (SEE), clinically relevant bleedings, intracranial haemorrhage (ICH), all-cause death and net clinical benefit (composite of stroke/SEE, bleedings and all-cause death) across three BW categories: 60-100 kg (reference), 50-60 kg (low BW) and ≤50 kg (very low BW). Propensity score matching was used to balance the treatment groups. Patients with low BW had a higher risk of adverse events compared to those with reference BW, regardless of treatment. Apixaban consistently reduced the risk of ischaemic stroke/SEE and bleeding (including ICH) across all BW ranges (all p-interaction >.10), and improved net clinical benefit compared to VKA (reference BW: HR .82 [95% CI: .80-.84]; low BW: HR .79 [95% CI: .74-.85]; very low BW: HR .86 [95% CI: .78-.95], p-interaction = .366). However, a significant BW-treatment interaction was observed for all-cause mortality, indicating reduced relative effectiveness of apixaban vs. VKA as BW decreases. In this large real-world analysis, treatment with apixaban was associated with a superior effectiveness and safety profile compared to VKA in patients with AF, HF and low BW. These results remained consistent, albeit slightly attenuated, in patients with very low BW. These findings provide preliminary evidence supporting the use of apixaban in this high-risk population.

Upadacitinib Dose Reduction Regimen in Elderly Patients with Atopic Dermatitis, Guided by Treat-to-Target Consensus Recommendations.

The effectiveness of Janus kinase (JAK) inhibitors in treating atopic dermatitis (AD) is well established. However, little is known about whether disease control can be maintained with longer dosing intervals, especially in older patients who are at higher risk of adverse events from JAK inhibitors. The treat-to-target (T2T) consensus was established to guide systemic treatment in adults with AD, aiming to achieve disease control promptly and sustain it in the long term. The aim of this study was to evaluate the efficacy and safety of extended JAK inhibitor dosing intervals based on the T2T consensus in older adults. A prospective observational cohort study was conducted from July 2022 to February 2024. Fifty-eight elderly patients (aged ≥ 65 years) were included in the study and received upadacitinib with gradually longer dosing intervals. The primary outcome was the proportion of patients maintaining different treatment dosing intervals at the end of the follow-up, as well as the assessment of six scales at every visit. Among the 58 patients (median [IQR] age, 70 [68-77] years) included in the study, 86.2% completed the 1-year follow-up. By the last visit, among those who completed the follow-up, 26.0% maintained a dosing interval of every 3 days, and 72.0% maintained a dosing interval of every 2 days. The overall incidence of adverse events (AEs) was 29.3% among all patients, with the most common AE reported being herpes virus infection (13.8%). The dose reduction regimen guided by the T2T consensus was well tolerated in elderly patients with moderate-to-severe AD. Prolonging dosing intervals offers potential benefits for both patients and socioeconomic outcomes.

Impact of amyloidosis on outcomes after transcatheter aortic valve implantation.

Data on the impact of amyloidosis on outcomes after transcatheter aortic valve implantation (TAVI) are limited. The objective of this study was to evaluate the 1-year risk of adverse events post-TAVI in patients with amyloidosis. Patients undergoing TAVI (between 2005 and 2023) were categorized into 2 groups based on the presence of amyloidosis. The primary outcome was the 1-year risk of a composite endpoint: heart failure (HF), ischemic stroke, pacemaker implantation, acute kidney injury, and all-cause death. Secondary outcomes assessed the individual components of the composite. Propensity score matching was used to balance the groups, and Cox regression was used to assess the risk of adverse outcomes associated with amyloidosis. Composite outcomes were analyzed for early (30-day) and long-term (30-day to 1 year) follow-up. Data from 589 TAVI patients with amyloidosis (mean age 78.9 ± 8.2 years, 31.9% female) were compared with 52 296 individuals without amyloidosis (mean age 78.1 ± 8.8 years, 40.3% female). After propensity score matching, patients with amyloidosis had a significantly higher 1-year risk of adverse events (HR, 1.27; 95%CI, 1.08-1.49). Specifically, patients with amyloidosis showed an increased risk of HF (HR, 1.37; 95%CI, 1.10-1.70). Stroke risk (HR, 1.67; 95%CI, 1.16-2.40) and pacemaker implantation (HR, 2.25; 95%CI, 1.15-4.41) were higher during long-term follow-up, while no differences were found for acute kidney injury or all-cause mortality between the 2 groups. Among patients undergoing TAVI, those with amyloidosis are at a higher risk of adverse events, particularly HF, and have an increased risk of pacemaker implantation and stroke in the long-term.

Efficacy and safety of systemic targeted therapies for atopic dermatitis in children: A systematic review and meta-analysis.

Efficacy and safety of systemic targeted therapies for atopic dermatitis in children: A systematic review and meta-analysis.

Nanotechnological approaches to improve corticosteroids ocular therapy.

Nanotechnological approaches to improve corticosteroids ocular therapy.

Potential of 6-mm-diameter fully covered self-expandable metal stents for unresectable malignant distal biliary obstruction: a propensity score-matched study.

To date, only thinner-diameter metal stents have been evaluated for unresectable malignant distal biliary obstruction (UR-MDBO). This study investigated the outcomes and optimal cohorts for a 6-mm-diameter fully covered self-expandable metal stent (FCSEMS) compared with those for a 10-mm-diameter FCSEMS. This single-center retrospective cohort study included patients who underwent initial transpapillary metal stenting for UR-MDBO. Propensity score matching (1:1) analysis was performed. Of 133/68 patients who underwent 6-mm/10-mm-diameter FCSEMS deployment, 59 in each group were selected. The median time to recurrent biliary obstruction was not significantly different between the groups (p=0.46). In contrast, use of the 6-mm-diameter FCSEMS resulted in a significantly reduced incidence of stent-related adverse events (AEs) (p=0.016), especially cholecystitis (p=0.032), and patients aged <70 years were particularly affected by this significant reduction. Among the patients in the end-stage cohort who were unable to continue chemotherapy after FCSEMS deployment, the free rate of stent-related events, including recurrent biliary obstruction and stent-related AEs, was significantly higher in the 6-mm group (p=0.027). For UR-MDBO, a 6-mm-diameter FCSEMS can be an optimal and safe option in the younger cohort with a relatively high risk of AEs and in the end-stage cohort requiring safer drainage without interference from stent-related events during times of poor prognosis.

Decreased Homeostasis Model Assessment of β-Cell Function in Patients Without Diabetes Can Predict Future Events in Patients With Cardiovascular Disease

Reduced insulin secretion is linked to diabetes and cardiovascular disease (CVD), but its role in non-diabetic CVD patients is unclear. The homeostasis model assessment of β-cell function (HOMA-β) measures pancreatic β-cell function. This study investigated the association between HOMA-β and adverse cardiovascular events in non-diabetic CVD patients. This study included 1301 non-diabetic CVD patients who underwent cardiac catheterization at the University of Yamanashi Hospital. HOMA-β was calculated based on fasting blood glucose and insulin levels. Patients were followed for 3 years to track adverse events, such as all-cause death, myocardial infarction, angina pectoris requiring percutaneous coronary intervention, and heart failure. Receiver operating characteristic curve analysis established a HOMA-β cut-off value of ≤49.3%. Kaplan-Meier analysis indicated that patients with HOMA-β ≤49.3% had a significantly higher risk of adverse events (P <0.001), with a 2.65-fold increased risk (hazard ratio 2.65; 95% confidence interval 1.97-3.57). Adding HOMA-β to traditional risk factors such as age, sex, estimated glomerular filtration rate, and left ventricular ejection fraction significantly improved risk prediction, as demonstrated by net reclassification improvement and integrated discrimination improvement. Decreased HOMA-β is a significant predictor of adverse cardiovascular events in CVD patients without diabetes. These findings suggest reduced insulin secretion contributes to worse outcomes, underscoring the importance of monitoring HOMA-β in this population.

Efficacy and safety of combination of semaglutide and basal insulin in patients with of type 2 diabetes mellitus: A systematic review and meta-analysis.

Efficacy and safety of combination of semaglutide and basal insulin in patients with of type 2 diabetes mellitus: A systematic review and meta-analysis.

Valvular heart disease in transthyretin cardiac amyloidosis

Abstract Introduction Amyloidosis cardiomyopathy (CM) is known to be associated with valvular heart disease (VHD) and particularly with aortic stenosis (AS). However, previous studies included both immunoglobulin light-chain CM and transthyretin amyloid CM (ATTR-CM), with limited data focussing specifically on ATTR-CM. Furthermore, VHD assessment was mostly limited to isolated significant VHD, and the difference in outcome between isolated and multiple VHD is largely unknown. Aim To evaluate the prevalence and prognostic value of significant VHD in ATTR-CM patients, including the differences in outcome between isolated and multiple significant VHD, with or without AS. Methods Patients with ATTR-CM were retrospectively included in this multicentric study. Significant VHD was defined as at least moderate VHD. The study endpoint was a composite of heart failure hospitalisations and all-cause death. Results A total of 694 ATTR-CM patients (mean age 75 ±13 years, 74% male) were included, and 302 (44%) presented with significant VHD (Figure 1). These patients were older (81±9 vs. 71±13, p&amp;lt;0. 001), had more cardiovascular risk factors, lower left ventricular ejection fraction (50±12 vs. 54±12, p&amp;lt;0.001) and more pulmonary arterial hypertension (76% vs. 45%, p&amp;lt;0.001), as compared to patients without significant VHD. Among patients with significant VHD, only 98 patients had VHD including AS (isolated AS in 45%; multiple VHD with AS in 55%), while the majority (n=204) had VHD without AS (isolated in 64%, multiple VHD in 36%) (Figure 1). During a median follow-up of 16 (6 - 33) months, 214 (31%) patients reached the study endpoint. Univariable Cox regression analysis identified significant VHD as a predictor of worse outcomes (HR: 3.486; 95% CI: 2.627 - 4.626; p &amp;lt; 0.001), which remained significant in the multivariable Cox regression analysis (HR: 1.879;95%CI:1.182 - 2.987;p=0.008), after adjusting for transthyretin amyloid cardiomyopathy phenotype, disease-modifying treatment, coronary artery disease, atrial fibrillation, renal function, New York Heart Association III-IV, polyneuropathy, electrocardiographic abnormalities, left ventricular stroke volume, interventricular septum thickness, left atrial dilatation, tricuspid annular plane systolic excursion, and arterial pulmonary hypertension(Figure2). Further stratification based on the presence of significant AS, and according to isolated or multiple VHD, revealed that patients isolated significant AS (HR:2.399;95%CI 1.179 – 4.884;p=0.016), and patients with multiple VHD including significant AS, had the highest risk for adverse outcomes (HR:3.542; 95%CI: 1.809 - 6.935;p&amp;lt;0.001)(Figure 2). Conclusion In ATTR-CM, significant VHD is strongly associated with poor prognosis, with the highest risk for adverse events in patients with significant multiple VHD including AS. These findings underscore the importance of VHD assessment for risk stratification and possibly targeted treatment in this patient population. The distribution of significant VHD.

Diabetes and Untoward Outcomes after ACL Reconstruction

Background Diabetes affects approximately 536.6 million adults worldwide and 32.2 million in the United States. Prior studies across multiple specialties have reported the presence of diabetes is associated with adverse outcomes following surgical operations. While several studies have identified diabetes as a risk factor for adverse outcomes following ACL reconstruction (ACLR), literature evaluating the relationship between diabetes status and outcomes after ACLR is lacking. Purpose We aimed to study surgical outcomes following primary ACLR among patients with diabetes compared to those without diabetes. Study Design Retrospective Cohort Study Methods We conducted a cohort study using data from an integrated healthcare system’s ACLR registry. Patients aged ≥12 receiving a primary unilateral ACLR were included (2005–2020). Preoperative diabetes status was the exposure of interest. The two primary outcomes were revision surgery and ipsilateral reoperation following primary ACLR, modeled using multivariable Cox proportional hazards regression that followed patients until an adverse event or loss to follow up. We also examined hospital readmission within 90 days post-surgery, modeled using logistic regression. All models compared patients with diabetes to those without diabetes, adjusting for age, gender, race, smoking status, body mass index, American Society of Anesthesiologist’s score, comorbid conditions, education level, income level, exercise, and graft type. Results There were 18,797 primary ACLR in the study sample with 383 (2.0%) occurring in patients with diabetes. The diabetes group exercised about 90 minutes less per week than the non-diabetes group. In unadjusted bivariate descriptive analyses, patients with diabetes had a lower rate of revision surgery (1.6% vs. 3.6%, p = 0.037) but a higher rate of ipsilateral reoperation (10.7% vs. 8.0%, p = 0.051). The 90-day readmission rate was higher among patients with diabetes compared to those without diabetes (1.8% vs. 0.7%, p = 0.016). However, after adjusting for covariates, these associations were no longer statistically significant. Conclusion After controlling for patient characteristics and other risk factors, the presence of diabetes was not associated with a higher risk of adverse events following primary ACLR.

Electrocardiogram-based machine learning for risk stratification of patients with suspected acute coronary syndrome.

The importance of risk stratification in patients with chest pain extends beyond diagnosis and immediate treatment. This study sought to evaluate the prognostic value of electrocardiogram feature-based machine learning models to risk-stratify all-cause mortality in those with chest pain. This was a prospective observational cohort study of consecutive, non-traumatic patients with chest pain. All-cause death was ascertained from multiple sources, including the CDC National Death Index registry. Six machine learning models were trained for survival analysis using 73 morphological electrocardiogram features (80% training with 10-fold cross-validation and 20% testing), followed by a variational Bayesian Gaussian mixture model to define distinct risk groups. The resulting classification performance was compared against the HEART score. The derivation cohort included 4015 patients (age 59 ± 16 years, 47% women). The mortality rate was 20.3% after a median follow-up period of 3.05 years (interquartile range 1.75-5.32). Extra Survival Trees outperformed other forecasting models, and the derived risk groups successfully classified patients into low-, moderate-, and high-risk groups (log-rank test statistic = 121.14, P < .001). This model outperformed the HEART score, reducing the rate of missed events by >90% with a negative predictive value and sensitivity of 93.4% and 85.9%, compared to 89.0% and 75.0%, respectively. In an independent external testing cohort (N = 3095, age 59 ± 15 years, 44% women, 30-day mortality 3.5%), patients in the moderate [odds ratio 3.62 (1.35-9.74)] and high [odds ratio 6.12 (2.38-15.75)] risk groups had significantly higher odds of mortality compared to those in the low-risk group. The externally validated machine learning-based model, exclusively utilizing features from the 12-lead electrocardiogram, outperformed the HEART score in stratifying the mortality risk of patients with acute chest pain. This may have the potential to impact the precision of care delivery and the allocation of resources to those at highest risk of adverse events.

Unsupervised clustering of intraventricular hemodynamic forces for the phenotyping of left-ventricular function in non-ischemic left ventricular cardiomyopathy.

Cardiac magnetic resonance (CMR) is essential for diagnosing cardiomyopathy, serving as the gold standard for assessing heart chamber volumes and tissue characterization. Hemodynamic forces (HDF) analysis, a novel approach using standard cine CMR images, estimates energy exchange between the left ventricular (LV) wall and blood. While prior research has focused on peak or mean longitudinal HDF values, this study aims to investigate whether unsupervised clustering of HDF curves can identify clinically significant patterns and stratify cardiovascular risk in non-ischemic LV cardiomyopathy (NILVC). A retrospective cohort of 279 patients with NILVC who underwent cardiac CMR at Vall d'Hebron University Hospital (Barcelona) was examined. Unsupervised clustering of longitudinal and transversal HDF curves was performed using Dynamic Time Warping for dissimilarity measurement and the Partitioning Around Medoids algorithm. Outcomes were defined as a composite of cardiovascular mortality, heart failure hospitalization, and ventricular arrhythmias. Median age was 65[57.0;74.0] years, with 27.2% females and 35.5% showing late gadolinium enhancement (LGE). Unsupervised clustering identified three distinct clusters, delineating risk groups with worsening LA and LV function, indicating a stepwise increase in cardiovascular risk profile. Over a median follow-up of 40 months, 60 patients experienced the composite outcome. After adjusting for LGE, LVEF and LV size, clusters 2 and 3 demonstrated a significantly higher risk of adverse events (both p<0.05) compared to cluster 1. Analyzing both longitudinal and transversal HDF throughout the cardiac cycle enables the identification of distinct phenotypes with prognostic value beyond ejection fraction and LGE in NILVC patients.

Blood pressure targets, medication considerations and special concerns in elderly hypertension III: Focus on stroke and neurodegenerative disorders.

Blood pressure targets, medication considerations and special concerns in elderly hypertension III: Focus on stroke and neurodegenerative disorders.

Patient and family engagement interventions for enhancing patient safety in the perioperative journey: a scoping review

BackgroundSurgical procedures present intricate challenges within healthcare delivery, often associated with higher risks of adverse events compared with non-surgical contexts. Patient and family engagement (PFE) throughout the perioperative journey is...