Occurrence Of Adverse Events Research Articles

Long-term safety and efficacy of filgotinib for the treatment of moderately to severely active ulcerative colitis: Interim analysis from up to 4 years of follow-up in the SELECTION open-label long-term extension study.

Filgotinib, an oral, once-daily, Janus kinase 1 preferential inhibitor, is an approved treatment for moderately to severely active ulcerative colitis. The aim of this study is to assess the safety and efficacy of continued filgotinib therapy over ~4 years in the long-term extension of the phase 2b/3 SELECTION trial (SELECTIONLTE; NCT02914535). In this interim analysis of SELECTIONLTE, SELECTION completers (week 10 responders to filgotinib who completed the maintenance study) continued their assigned treatment (double-blind filgotinib 200 mg [FIL200] or filgotinib 100 mg) and SELECTION week 10 non-responders received open-label FIL200. We assessed safety by adverse events (AEs), and efficacy by partial Mayo Clinic Score (pMCS), inflammatory biomarkers and health-related quality of life (HRQoL). We compared safety and efficacy between achievers and non-achievers of a multi-component endpoint, comprehensive disease control (CDC), comprising symptomatic, endoscopic, inflammatory biomarker and HRQoL improvements. Data for completers (n = 250) and non-responders (n = 372) were reported for ≤202 weeks. AE occurrences were low and consistent with previous analyses. The as-observed proportion of FIL200-treated patients in pMCS, biomarker and HRQoL remission during SELECTIONLTE remained high among completers (week 144: 80.0%, 86.4% and 86.0%, respectively) and increased among non-responders (week 192: 62.1%, 76.7% and 59.3%, respectively). Significantly higher proportions of CDC achievers at SELECTION week 58 achieved pMCS, IBDQ and corticosteroid-free pMCS remission than non-achievers, up to LTE week 96. Filgotinib induced and maintained symptomatic remission and improved HRQoL over 4 years. Safety results showed a proven long-term benefit-risk profile. FIL200-treated CDC achievers had better long-term outcomes than non-achievers.

Counterproductive Behaviors in the Healthcare Setting: History and Recommended Approaches for Addressing Disruptive Physician Behaviors

Healthcare is a complex multidimensional delivery system that depends on effective communication and collaboration between all health team members. The goal is to provide safe, high-quality, appropriate, and effective care that results in the best possible patient outcomes. When individuals act in an unprofessional, inappropriate, counterproductive manner, it can negatively affect team focus and concentration that can impair healthcare relationships which can affect roles, responsibilities, and task completion, all of which may lead to the occurrence of adverse medical events that can hurt patient safety and quality of care. In the healthcare setting, this counterproductive work behavior often is categorized as disruptive behavior, and it can cause a toxic medical environment that prevents individuals from doing their jobs. Gaining a better understanding of these types of behaviors, their causes, and their consequences will help raise awareness and lead to the development of policies and procedures that can address these issues and prevent emotional and physical harm to both staff and patient. Early recognition and early intervention can reduce the likelihood and impact of disruptive events.

Do nonfatal events during the first 5 years after coronary artery bypass surgery influence 10 year outcomes?

ObjectiveFew have examined the influence of early adverse events after coronary artery bypass grafting (CABG) on long-term survival. We sought to determine if the occurrence of nonfatal major adverse cardiac and cerebrovascular events (MACCE) during the first 5 years after CABG influences survival and adverse events at 10 years. MethodsAll patients who underwent isolated CABG from 1990 to 2014 at a single center in Ontario, Canada, were included. Primary end point was all-cause mortality. The secondary end point of interest was MACCE, a composite of mortality, nonfatal myocardial infarction, stroke, and repeat revascularization. ResultsA total of 20,444 cases of elective primary isolated CABG were identified as being alive at 5 years, with 11% of patients developing nonfatal MACCE within the first 5 years after CABG (MACCE group) and the remaining 89% were alive without a MACCE event at 5 years (non-MACCE group). Following propensity score matching, 2167 patient-pairs were formed. Among the MACCE group, 972 out of 2167 (44.9%) developed a myocardial infarction, 519 out of 2167 (24.0%) had a stroke, and 946 out of 2167 (43.7%) required a repeat revascularization within the first 5 years after CABG. Non-MACCE was associated with better overall survival (hazard ratio, 1.42; 95% CI, 1.25-1.63; P < .01) and freedom from MACCE (hazard ratio, 1.61; 95% CI, 1.45-1.79; P < .01) up to 10 years after CABG compared with MACCE cases. ConclusionsPatients who experienced nonfatal MACCE during the first 5 years after CABG experienced worse survival and more MACCE at 10 years. Prevention of major adverse events during the first 5 years after surgical revascularization may be an important strategy to improve late outcomes.

The Performance of Peroral Endoscopic Myotomy in Sigmoid-Type Achalasia

Objective: Sigmoid-type achalasia represents an advanced stage of achalasia characterized by significant dilation and tortuosity of the esophageal lumen. Considering the demonstrated efficacy of peroral endoscopic myotomy (POEM) in treating early-stage achalasia, this procedure may offer an alternative therapeutic approach for sigmoid-type achalasia. This study aimed to assess POEM’s feasibility and short-term efficacy in patients with sigmoid-type achalasia. Materials and Methods: We enrolled 16 consecutive patients with sigmoid-type achalasia (eight with type 1 and eight with type 2). The anticipated outcomes were symptom relief during the 12-month follow-up period (evaluated through a reduction in Eckardt symptom scores), an acceptable incidence of procedure-related adverse events, and a decrease in esophageal diameter and barium height. Results: POEM was successfully performed in all cases, with a median operative time of 118.50 minutes (range: 52–206 minutes). No serious complications associated with POEM were observed. During the 12-month follow-up period, the median Eckardt symptom score decreased from 6 (2-10) preoperatively to 1 (0-3) (P = 0.008). Complications were mucosal injuries (31.25% of cases), pneumoperitoneum (12.5%), and minor bleeding (6.25%), although no interventions were needed. Conclusion: POEM procedure has exhibited favorable treatment outcomes, showcasing a high clinical success rate in addressing sigmoid-type achalasia. Despite the occurrence of acceptable adverse events, the procedure remains a viable alternative treatment or bridging therapy for sigmoid-type achalasia. Nonetheless, it is crucial to acknowledge that this procedure presents greater challenges in comparison to the treatment of typical achalasia.

Efficacy of revascularization in CTO patients based on hibernating myocardium therapy.

The effectiveness of percutaneous coronary intervention (PCI) for chronic total occlusion (CTO) is still uncertain, especially for patients with ischemic left ventricular dysfunction. This study aimed to assess hibernating myocardium (HM), as determined by single-photon emission computed tomography (SPECT) and 18F-FDG positron emission tomography (PET), and to compare the benefits of PCI and optimal medical therapy (OMT). A retrospective study collected data from 332 patients with CTO and ischemic left ventricular dysfunction. The study compared patients who underwent PCI or OMT via propensity score matching (PSM) analysis which was performed with a 1:2 matching protocol using the nearest neighbour matching algorithm. The primary endpoint of the study was the occurrence of major adverse cardiac events (MACE), defined as a composite of cardiac death, readmission for worsening heart failure (WHF), revascularization and myocardial infarction (MI). After PSM, there were a total of 246 individuals in the PCI and OMT groups. Following Cox regression, hibernating myocardium/total perfusion defect (HM/TPD) was identified as an independent risk factor (hazard ratio (HR): 1.03, 95% confidence interval (CI): 1.008-1.052, p = .007). The cut-off value of HM/TPD was 38%. The results of the subgroup analysis suggest that for patients with HM/TPD >38%, the OMT group had a greater risk of MACE (p = .035). A sensitivity analysis restricting patients with single-vessel CTO lesions, HM/TPD remained an independent predictor (HR 1.025, 95% CI 1.008-1.043, p = .005). HM/TPD is an independent predictor of MACE, and for patients with HM/TPD > 38%, CTO-PCI had a lower risk of MACE compared with OMT. However, further validation is still needed through large-scale studies.

Prognostic impact of right atrial strain in systemic lupus erythematosus with pulmonary arterial hypertension.

The aim of this study was to assess right atrial (RA) function, including RA phase strain, via speckle-tracking echocardiography (STE) in a cohort of systemic lupus erythematosus (SLE) patients with pulmonary arterial hypertension (PAH) and in particular to explore the relationship between RA phase strain and the occurrence of cardiovascular events. STE analyses of RA function were evaluated in patients with SLE-PAH and in 33 healthy control subjects. Clinical associations, serum biomarkers, echocardiographic data, survival times, and adverse cardiovascular events were evaluated. A total of 66 patients with SLE-PAH were enrolled; they were divided into two groups based on the occurrence of adverse clinical events. RA phase strain was significantly reduced in patients with events than in patients without events. The endpoint was defined as the combined outcome of all-cause mortality, right heart failure, and rehospitalization due to disease progression. During a mean follow-up of 17.2±9.9 months, 23 patients (35%) reached the endpoint. Compared with patients with RA reservoir strain (RASr) ≥33.45%, patients with RASr<33.45% had more adverse long-term outcomes (log rank p<.0001). RASr was independently associated with adverse clinical outcomes according to multivariate analysis (p=.010). Our data suggest that RA function has prognostic value for SLE-PAH patients, and strain analysis revealed that the worse the RA function is, the worse the prognosis.

571. A PHASE I/II MULTICENTER STUDY EVALUATING THE EFFICACY AND SAFETY OF INDUCTION IMMUNOCHEMOTHERAPY FOLLOWED BY CONCURRENT IMMUNO-CHEMORADIOTHERAPY IN UNRESECTABLE LA-ESCC

Abstract Background Despite advances in radiotherapy techniques, the prognosis for patients undergoing definite chemoradiotherapy remains suboptimal. There exists an urgent and unmet need to enhance the efficacy of concurrent chemoradiotherapy for patients with unresectable Locally Advanced Esophageal Squamous Cell Carcinoma (LA-ESCC). Immunotherapy, when combined with chemotherapy, has emerged as the established first-line treatment for advanced esophageal cancer. Significant tumor shrinkage and reduced tumor residual observed after induction immunotherapy might provide the potential to enhance locoregional control of radiotherapy as well as better protection of critical organs and circulating lymphocytes. Methods We conducted a multicenter, phase I/II study aiming to assess the efficacy and safety of induction immunochemotherapy followed by immuno-chemoradiotherapy (ICRT) for unresectable LA-ESCC (SCR-ESCC-002, NCT06173986) (Figure 1). Eligible patients will initiate treatment with 2-3 cycles of immunochemotherapy. Within 4 weeks after completing the induction treatment, patients without disease progression will proceed to receive concurrent radiotherapy (45-50Gy in 25 fractions), weekly chemotherapy, and PD-1 inhibitor on day1,22. Following immuno-chemoradiotherapy, patients will continue with immunotherapy maintenance until disease progression or unacceptable toxicity, for a maximum duration of one year. The study's dual primary endpoints are progression-free survival and treatment completion rate. Results As of January 2024, 13 eligible patients were enrolled in our trial, with median follow-up of 7.8 months. Due to tumor shrinkage of induction immunochemotherapy, radiation doses to normal tissues were significantly reduced, particularly for the lungs, heart, and vertebrae. All 13 patients completed the planned induction treatment and radiotherapy, with 8 completing more than 4 weekly chemotherapies. During ICRT, 10 of 13 patients experienced grade 3-4 adverse events. These included lymphopenia (69.23%), myelosuppression (46.15%), hepatitis (7.69%), esophagitis (7.69%), and pneumonitis (7.69%). Nine patients achieved a complete response, and 3 partial response 4 weeks after ICRT according to RECIST v1.1. Conclusion Decreased radiation volumes due to tumor regression brought by induction immunochemotherapy diminish the occurrence of non-hematological adverse events during ICRT. Preliminary analysis suggests that this therapeutic modality exhibits favorable safety profiles and yields a superior clinical complete response rate compared to definitive chemoradiotherapy alone. The trial is presently enrolling participants, and the confirmation of efficacy and survival outcomes necessitates larger sample sizes and extended follow-up durations.

813. SELF-DILATATION FOR THE MANAGEMENT OF REFRACTORY BENIGN OESOPHAGEAL STRICTURES: OUTCOMES FROM THE LARGEST EUROPEAN TERTIARY CENTRE EXPERIENCE TO DATE

Abstract Background Benign oesophageal strictures are commonly encountered in endoscopy and are often effectively managed with endoscopic dilatation. However, up to 40% of patients may develop refractory benign oesophageal strictures (RBES), necessitating frequent endoscopic interventions that are often challenging, pose a greater risk of complications, and negatively impact quality of life. Oesophageal self-dilatation (SD) offers an alternative treatment that potentially reduces the need for repeat hospital visits while allowing patients greater autonomy in managing their condition. We describe the efficacy and safety of oesophageal SD at a tertiary referral centre. Methods We retrospectively reviewed the electronic records of patients with RBES (n=43) who were referred for SD to our centre between 2013 and 2024. The primary outcomes were the endoscopic dilatation-free interval (EDFI; longest period of time patients did not require endoscopic dilatation) and the number of endoscopic procedures performed within 12 months of starting SD. Secondary outcomes included the technical success rate of learning SD, improvement in the Dakkak and Bennett dysphagia score, and complications. Results are reported as median (interquartile range). Results 41/43 patients (median age 57 years) with various RBES aetiologies (32% peptic, 19.5% post-radiation, 12% post-surgical, 11.6% post-endoscopic resection, 24.9% other) and locations (24.4% proximal, 29.3% middle, 34.1% lower, 12.2% multi-segment) successfully learned SD. Median follow-up was 23.2 months. The EDFI increased from 68.5 (41-106) to 161 (121-279) days (P&amp;lt;0.001) while endoscopic interventions decreased from 7 (4.7-10) to 1 (0.75-3) (P&amp;lt;0.001) within 12 months before and after SD. The all-time EDFI was 405 days (130-705) and dysphagia score improved from 2 at baseline to 0 after SD. One patient experienced clinically significant haematemesis and one presumed SD-related oesophageal perforation. Conclusion To our knowledge, we have described the largest European case series of oesophageal SD that has been published to date. Oesophageal SD appears to be an effective, well-tolerated, and safe approach in managing often complex patients with RBES providing a viable alternative to conventional endoscopic interventions. However, the occurrence of adverse events highlights the importance of careful patient selection and ongoing monitoring. Further research is warranted to validate these findings and identify predictive factors for treatment success.

Effect of Tryptophan Restriction in the Therapy of Irritable Bowel Syndrome: a Systematic Review.

The metabolic pathways of tryptophan (TRP) have been implicated in the pathophysiology of irritable bowel syndrome (IBS), positing that the strategic modulation of TRP consumption may exert regulatory effects on serotonin levels, consequently altering the clinical manifestation of IBS. This systematic review was meticulously orchestrated to evaluate the effect of TRP restriction on IBS. A comprehensive search of the MEDLINE/PubMed, Cochrane Library, and Embase databases was conducted. Controlled trials that compared the efficacy of TRP restriction in IBS patients were scrutinized. The primary outcomes were gastrointestinal symptoms, quality of life, and pain, whereas the secondary outcomes included anxiety, mood, and safety. The risk of bias was meticulously assessed according to the guidelines recommended by the Cochrane Collaboration. A total of five trials, enrolling 135 participants, were incorporated into the qualitative synthesis. Low-TRP intake attenuated gastrointestinal discomfort and enhanced psychological well-being in IBS patients, while the effects of acute TRP depletion were controversial. Safety data from one randomized controlled trial reported no occurrence of adverse events. This systematic review suggests that moderating, rather than depleting, TRP intake may potentially be a feasible and safe adjunctive treatment for patients with IBS. Future research incorporating a high-quality study design and consensus on clinical outcome measurements for IBS is warranted.

Medical Treatment of Graves’ Disease: Benzylthiouracil vs. Methimazole, What to Choose?

Introduction: The management of Graves’ disease (GD) typically involves the use of synthetic antithyroid drugs (ATDs), primarily Methimazole (MMI) and Carbimazole (BTU), which aim to inhibit thyroid hormone synthesis and restore normal thyroid function. There are uncertainties regarding the choice of the most appropriate synthetic antithyroid drug (ATD) for the treatment of hyperthyroidism related to GD. This study aims to evaluate the efficacy and tolerance of MMI compared to BTU in patients diagnosed with GD. Patients and Methods: This cross-sectional analytical study included 121 patients diagnosed with GD. The patients were divided into two groups: Group 1 (G1, n=77), consisting of patients treated with Carbimazole (BTU), and Group 2 (G2, n=44), consisting of patients treated with Methimazole (MMI). We compared the efficacy and tolerance of the two drugs. Results: Adverse effects (AE) related to the ATDs were more frequent with MMI (18.2%) than with BTU (10.4%), but without a significant difference. The decrease in fT4 levels was significantly earlier and more pronounced with MMI compared to BTU. After a standard treatment duration (12 to 18 months), the remission rate was significantly higher with MMI than with BTU (58.3% vs. 31.9%; p=0.012). The relapse rate was comparable between the two groups (14.5% in G1 vs. 11.1% in G2; p=0.76). Conclusion: MMI is more effective than BTU in reducing fT4 levels and achieving remission in GD after a standard treatment duration. However, its contribution to the occurrence of adverse effects warrants further investigation.

Explainable machine learning prediction of edema adverse events in patients treated with tepotinib.

Tepotinib is approved for the treatment of patients with non-small-cell lung cancer harboring MET exon 14 skipping alterations. While edema is the most prevalent adverse event (AE) and a known class effect of MET inhibitors including tepotinib, there is still limited understanding about the factors contributing to its occurrence. Herein, we apply machine learning (ML)-based approaches to predict the likelihood of occurrence of edema in patients undergoing tepotinib treatment, and to identify factors influencing its development over time. Data from 612 patients receiving tepotinib in five Phase I/II studies were modeled with two ML algorithms, Random Forest, and Gradient Boosting Trees, to predict edema AE incidence and severity. Probability calibration was applied to give a realistic estimation of the likelihood of edema AE. Best model was tested on follow-up data and on data from clinical studies unused while training. Results showed high performances across all the tested settings, with F1 scores up to 0.961 when retraining the model with the most relevant covariates. The use of ML explainability methods identified serum albumin as the most informative longitudinal covariate, and higher age as associated with higher probabilities of more severe edema. The developed methodological framework enables the use of ML algorithms for analyzing clinical safety data and exploiting longitudinal information through various covariate engineering approaches. Probability calibration ensures the accurate estimation of the likelihood of the AE occurrence, while explainability tools can identify factors contributing to model predictions, hence supporting population and individual patient-level interpretation.

Differences in fluidity and viscosity of brand-name and generic injectable ointment.

Generic medications contain the identical active ingredient in the same concentration as their branded counterparts and are administered in the same manner, aiming to deliver comparable efficacy, dosage, and clinical outcomes. Nevertheless, variations in additives and formulation processes, particularly noticeable in topical medications, can influence factors like ease of use and patient adherence. Therefore, in this study, we aimed to compare the rheological attributes of branded and generic injectable ointments, assessing disparities in formulation performance and their impact on patient care. Posterisan® Forte and Hemoporison® ointments were used as the branded and generic versions, respectively, and their viscosity, ductility, and viscoelastic properties were evaluated. Posterisan® Forte showcased enhanced spread ability, maintaining uniform flow characteristics across varying temperatures, whereas Hemoporison® displayed pronounced thixotropic properties and stiffness, suggesting potential benefits for applications necessitating reversible viscosity adjustments and heightened rigidity. Despite sharing identical additives, observable differences in physical characteristics highlight the necessity of understanding formulation traits, which could influence ointment behavior. Alterations in fluidity and viscosity may affect how patients perceive and apply the medication, potentially influencing treatment outcomes and the occurrence of adverse effects.

Efficacy and safety of immune checkpoint inhibitors plus platinum-etoposide vs. platinum-etoposide in the first-line treatment of extensive-stage small cell lung cancer: a systematic review and a meta-analysis.

Currently, immune checkpoint inhibitors (ICIs) combined with platinum-etoposide (EP) are gradually becoming the first-line standard treatment for extensive-stage small cell lung cancer (ES-SCLC). This meta-analysis aims to compare the efficacy and safety of ICIs combined with EP vs. EP alone in the first-line treatment of ES-SCLC. We searched PubMed, Embase, and Cochrane Library databases for phase II/III randomized controlled trials (RCTs) that met inclusion criteria from January 2016 to November 2023. Outcome measures included progression-free survival (PFS), overall survival (OS), objective response rate (ORR), treatment-related adverse events (TRAEs), treatment-related serious adverse events (TRSAEs), and immune-related adverse events (IRAEs). The effect analysis statistics of the outcome indicators were expressed with hazard ratio (HR) and odds ratio (OR) and their 95% confidence interval (CI). This study included nine RCTs with a total of 4,711 patients. Compared to EP, ICIs plus EP improved patients' PFS (HR =0.71; 95% CI: 0.64-0.79; P<0.001), OS (HR =0.79; 95% CI: 0.74-0.84; P<0.001), and ORR (OR =1.27; 95% CI: 1.12-1.44; P=0.001), but increased the incidence of adverse events (AEs): TRAEs (OR =1.45; 95% CI: 1.20-1.76; P<0.001), IRAEs (OR =3.97; 95% CI: 2.49-6.32; P<0.001), and grade 3-4 IRAEs (OR =6.17; 95% CI: 2.36-16.15; P<0.001). However, there was no significant difference in the incidence of grade 3-4 TRAEs (OR =1.05; P=0.54), TRSAEs (OR =1.40; P=0.13), and grade 3-4 TRSAEs (OR =1.17; P=0.72). Subgroup analysis found that patients with brain metastasis did not benefit from ICIs combined with EP therapy, and patients with programmed cell death ligand 1 (PD-L1) expression ≥1% had poorer survival benefits compared to patients with PD-L1 expression <1%. In the first-line treatment of ES-SCLC, compared to EP chemotherapy, ICIs with EP can benefit patients in terms of PFS, OS, and ORR, but it will increase the occurrence of AEs.

Identification of risk factors for adverse drug events in a general hospital.

Adverse events (AEs), and particularly adverse drug events (ADEs), represent a health problem as they can cause permanent damage or death. Understanding the frequency, location, and causes of ADEs can prevent harm to patients. The Global Trigger Tool, produced by the Institute for Healthcare Improvement (GTT/IHI), is widely used to identify AEs. Recognizing the profile of patients who suffer ADEs can reveal clinical or individual characteristics that predispose to the occurrence of AEs. A cross-sectional study was carried out through a retrospective analysis of 120 medical charts of patients discharged from hospital between October 2020 and April 2021. Patients over 18 years old, with a length of stay of more than 24 h, were included. The list of triggers used was from the medication module of the GTT/IHI, which was adapted for use in the institution. Two primary reviewers and a medical reviewer applied this tool. The primary reviewers independently assessed the randomized charts. A meeting to achieve consensus among the reviewers was held every 2 weeks to validate the identified ADEs; classifications were based on harm severity. Multivariate logistic regression was utilized to assess the variables that predicted the occurrence of ADEs, using the backward stepwise method. A total of 43 ADEs were identified, with a frequency of 36 per 100 admissions (43/120). Of these, five ADEs (12%) were responsible for patients being admitted to hospital. In the case of in-hospital ADEs, there were 42.2 per 1000 patients/day. The clinical manifestation of altered kidney function (16%) and the anatomical drug group of the nervous system (33%) were the most frequent ADEs. The multivariate logistic regression model was significant (×2 = 44.960, P < .001), indicating that factors such as: known drug allergy [odds ratio 5.728; 95% confidence interval (CI): 1.249, 26.274, P = .025]; being clinically hospitalized (odds ratio 7.504; 95% CI: 1.654, 34.037; P = .009); number of medicines used (odds ratio 1.100; 95% CI: 1.054, 1.148; P < .001); and being under the care of internal medicine (odds ratio 3.633; 95% CI: 1.257, 10.511; P = .017) were predictor variables associated with the occurrence of ADEs. A significant percentage of hospitalized patients experienced at least one ADE, with rates surpassing those found in similar studies. The GTT/IHI effectively assessed medication-related harm, emphasizing the need for tailored triggers based on population characteristics. Predictor variables can inform preventive strategies. Overall, the tool facilitated a localized risk assessment of medication use.

Systemic inflammation and health outcomes in patients receiving treatment for atherosclerotic cardiovascular disease.

The burden and outcomes of inflammation in patients with atherosclerotic cardiovascular disease (ASCVD) are not well defined beyond the controlled settings of trials and research cohorts. This was an observational study of ASCVD adults undergoing C-reactive protein testing in Stockholm's healthcare (2007-21). After excluding C-reactive protein tests associated with acute illness or medications/conditions that bias C-reactive protein interpretation, systemic inflammation was evaluated over a 3-month ascertainment window. Determinants of C-reactive protein ≥ 2 mg/L were explored with logistic regression. C-reactive protein categories were compared via negative-binomial/Cox regression for subsequent healthcare resource utilization and occurrence of major adverse cardiovascular events, heart failure hospitalization, and death. A total of 84 399 ASCVD adults were included (46% female, mean age 71 years, 59% with C-reactive protein ≥ 2 mg/L). Female sex, older age, lower kidney function, albuminuria, diabetes, hypertension, and recent anaemia were associated with higher odds of C-reactive protein ≥ 2 mg/L. The use of renin-angiotensin system inhibitors, antiplatelets, and lipid-lowering therapy was associated with lower odds. Over a median of 6.4 years, compared with C-reactive protein < 2 mg/L, patients with C-reactive protein ≥ 2 mg/L had higher rates of hospitalizations, days spent in hospital, outpatient consultations, and dispensed medications (P < .05 for all). They also had a higher rate of major adverse cardiovascular events [hazard ratio (HR) 1.30; 95% confidence interval (CI) 1.27-1.33], heart failure (HR 1.24; 95% CI 1.20-1.30), and death (HR 1.35; 95% CI 1.31-1.39). Results were consistent across subgroups and granular C-reactive protein categories and robust to the exclusion of extreme C-reactive protein values or early events. Three in five adults with ASCVD have systemic inflammation, which is associated with excess healthcare resource utilization and increased rates of cardiovascular events and death.

The prognostic role of remnant cholesterol in Asian menopausal women received percutaneous coronary intervention with acute coronary syndrome

BackgroundRemnant cholesterol (RC) exert a significant influence on atherosclerotic cardiovascular disease development. However, the prognostic implications of RC in menopausal women received percutaneous coronary intervention (PCI) who experiencing acute coronary syndrome (ACS) remain uncertain.MethodsRC was derived by subtracting the sum of high-density lipoprotein cholesterol and low-density lipoprotein cholesterol from the total cholesterol. Kaplan-Meier survival and Cox regression analysis were employed for assessing the correlation between continuous RC levels and composite and individual adverse events in Q1-Q4 quartiles. Receiver operator characteristic (ROC) curves, derived from Cox regression, were employed for analyzing the relationship between RC and both composite and individual adverse events.Results1505 consecutive menopausal women who underwent PCI and diagnosed with ACS were included. Kaplan-Meier survival analysis demonstrated a progressive reduction in composite adverse event survival rates across the four groups, observed in both the general population and among diabetic individuals, as RC values increased (Log-rank P < 0.001). The analysis of multivariate Cox regression indicated RC remained independently associated with both composite and individual adverse events. ROC analysis showed that RC enhanced the area under the curve both in total and diabetic populations for composite adverse events.ConclusionAmong menopausal women diagnosed with ACS who underwent PCI, heightened levels of RC were found to be independently correlated with an increased occurrence of adverse events.

Comparison of exsanguination and hemostasis devices for Limb surgery: a multicenter randomized controlled study

BackgroundExcessive intraoperative bleeding remains a challenge in limb surgeries. The exsanguination tourniquet ring has emerged as a potential solution for effective exsanguination and hemostasis. This study aims to evaluate its efficacy and safety compared to the conventional exsanguination and hemostasis approach (pneumatic tourniquet combined with Esmarch bandage).MethodsThis randomized controlled trial evaluates the exsanguination tourniquet ring’s effectiveness and safety versus the conventional approach in 220 participants undergoing various limb surgeries. Allocation included experimental and control groups, assesses through efficacy (including intraoperative and total blood loss, hemoglobin levels, and exsanguination and hemostasis effectiveness) and safety (adverse event occurrence) indicators.ResultsThe experimental group (n = 110) utilizes the exsanguination tourniquet ring, while the control group (n = 110) employs the conventional approach. As for intraoperative blood loss, the experimental group is non-inferior to the control group (p-value < 0.001). While no significant difference is found in total blood loss (for the full analysis set, p-value = 0.442; for the per protocol set, p-value = 0.976) and differences in postoperative and preoperative hemoglobin levels (for the full analysis set, p-value = 0.502; for the per protocol set, p-value = 0.928). Regarding exsanguination and hemostasis effectiveness, the full analysis set reveals significantly superior ratings in the experimental group compared to the control group (p-value = 0.002 < 0.05), while the per protocol set analysis indicates no significant difference between the groups (p-value = 0.504). As for safety indicators, adverse events related to the device are minimal in two groups, with only one severe event unrelated to the device.ConclusionsThe exsanguination tourniquet ring is an effective and safe device for intraoperative blood loss control in various limb surgeries.Trial registrationComparison of Exsanguination and Hemostasis Devices for Limb Surgery A Prospective Multicenter Randomized Controlled Study, ChiCTR2300077998, 11/27/2023.

Non-linear associations between night shifts and adverse events in nursing staff: a restricted cubic spline analysis

IntroductionExisting studies suggest that the number of night shifts may impact the occurrence of adverse events. However, while this relationship is well-documented, previous research has not thoroughly examined the non-linear associations between night shifts and adverse events among nursing staff, which remains a gap in our understanding.MethodsParticipants were 1,774 Chinese nurse staff. Psychosocial characteristics were screened by The Chinese version of the multidimensional scale of perceived social support (MSPSS) for social support, the 9-item Patient Health Questionnaire (PHQ-9) for depressive symptoms, the Generalized Anxiety Disorder-7 (GAD-7) for anxiety symptoms. Binary logistic regression and restricted cubic splines were applied to analyze the data. The statistical software used were R version 3.6.2 and SPSS version 22.0.ResultsOver the past year, 325 cases (18.3%) were classified as adverse events. Logistic regression unveiled that social support played a protective role against adverse events, with an OR of 0.991 (95% CI: 0.983, 0.999). Furthermore, night shifts continued to surface as a substantial risk factor for adverse events, with an OR to 1.300 (95% CI: 1.181, 1.431). The restricted cubic spline regression model highlights a nonlinear relationship between night shifts and adverse events (P for non-liner < 0.001). The probability of adverse events increases with the number of night shifts, but compared to individuals working 3–4 night shifts per month, those working 5–6 night shifts per month have a lower probability of adverse events.ConclusionOur findings indicate a non-linear relationship between the frequency of night shifts and adverse events, suggesting a complex interplay of factors. This highlights the need for nursing practice and policy to consider the intricacies of night shift scheduling and explore more reasonable rostering strategies to mitigate the probability of adverse events.

Mental health related adverse events of cytisine and varenicline in smokers with and without mental health disorders: Secondary analysis of a randomized controlled trial

IntroductionLittle is known about the adverse events (AEs) of cytisine versus varenicline among individuals with mental health disorders (MHDs), highlighting the necessity for further exploration to inform clinical practice. This secondary analysis of clinical trial data aimed to investigate the effect of varenicline vs. cytisine regarding mental-health-related AEs (MH-related AEs) on smokers with and without MHDs. MethodsAustralian daily smokers interested in quitting were randomised to varenicline (84 days) or cytisine (25 days) and categorised by self-reported MHD diagnosis or treatment in the past year (MHD or non-MHD groups). Treatment adherence was assessed by self-reported number of doses taken during the active treatment phase via two check-in calls (at one month), while AEs were evaluated through four phone interviews: two check-in calls (one month) and follow-up calls at four and seven months. Logistic regression analysis compared MH-related AEs between groups, including only participants taking at least one dose. ResultsOf 1452 smokers 246 reported MHDs, 725 received cytisine and 727 received varenicline. Median number of doses taken was comparable between MHD (34 cytisine and 12 varenicline) and non-MHD (33 cytisine and 13 varenicline) groups. MH-related AEs were: 14.1 % (n = 30) in MHD (12.5 % in cytisine and 15.4 % in varenicline), and 11.8 % (n = 126) in non-MHD group (10.9 % in cytisine and 13.7 % in varenicline). No significant difference in MH-related AE occurrence was identified between medication groups (aOR=0.96, 95 % CI 0.4 to 2.2, p-value = 0.94). ConclusionComparable MH-related AEs were observed between smokers with and without MHDs, suggesting that cytisine, like varenicline, may be well-tolerated by those with MHDs. However, larger clinical trials focused on MH-related AEs are needed for more conclusive evidence.

Hemoglobin glycation index and cardiovascular outcomes in patients with diabetes and coronary artery disease: insights from a large cohort study

Background/objectivesThe hemoglobin glycation index (HGI) has been demonstrated to serve as a substitute for the individual bias in glycosylated hemoglobin A1c (HbA1c). Our objective was to assess the correlation between HGI and cardiovascular (CV) outcomes in patients with diabetes and coronary artery disease (CAD).Subjects/methodsWe sequentially recruited 11921 patients with diabetes and CAD at Fuwai Hospital. The patients were categorized into five groups based on their HGI quintiles, ranging from Q1 to Q5. The primary endpoint was the occurrence of major adverse cardiac events (MACEs), which included CV death and nonfatal myocardial infarction.ResultsDuring the median 3-year follow-up, 327 (2.7%) MACEs were observed. A U-shaped relationship between HGI and 3-year MACEs was demonstrated by restricted cubic spline (RCS) after multivariable adjustment (nonlinear P = 0.014). The Kaplan-Meier curves demonstrated that the Q2 group had the lowest risk of MACE (P = 0.006). When comparing the HGI Q2 group, multivariable Cox regression models showed that both low (Q1) and high (Q4 or Q5) HGI were linked to a higher risk of MACEs (all P < 0.05). Patients with a low HGI (Q1) had a significantly increased risk of all-cause and CV death, with a 1.70-fold increase in both cases (both P < 0.05).ConclusionsIn individuals with diabetes and established CAD, HGI levels were found to have a U-shaped relationship with the occurrence of MACEs over a period of three years. Significantly, those with low HGI had an increased risk of CV death.