Higher Risk Of Adverse Events Research Articles

Bispectral index monitoring for sedation in scheduled adult colonoscopy: A randomized controlled trial

Bispectral index monitoring for sedation in scheduled adult colonoscopy: A randomized controlled trial

Patient-specific ascending aortic intervention criteria.

Ascending aortic aneurysms pose a different risk to each patient. We aim to provide personalized risk stratification for such patients based on sex, age, body surface area and aneurysm location (root versus ascending). Root and ascending diameters, and adverse aortic events (dissection, rupture, death) of ascending thoracic aortic aneurysm patients were analysed. Aortic diameter was placed in context vis-a-vis the normal distribution in the general population with similar sex, age and body surface area, by conversion to z scores. These were correlated of major adverse aortic events, producing risk curves with 'hinge points' of steep risk, constructed separately for the aortic root and mid-ascending aorta. A total of 1162 patients were included. Risk curves unveiled generalized thresholds of z = 4 for the aortic root and z = 5 for the mid-ascending aorta. These correspond to individualized thresholds of less than the standard criterion of 5.5 cm in the vast majority of patients. Indicative results include a 75-year-old typical male with 2.1 m2 body surface area, who was found to be at increased risk of adverse events if root diameter exceeds 5.15 cm, or mid ascending exceeds 5.27 cm. An automated calculator is presented, which identifies patients at high risk of adverse events based on sex, age, height, weight, and root and ascending size. This analysis exploits a large sample of aneurysmal patients, demographic features of the general population, pre-dissection diameter, discrimination of root and supracoronary segments, and statistical tools to extract thresholds of increased risk tailor-made for each patient.

A practical guide to selecting and using new ulcerative colitis therapies.

Several new biologics (mirizikizumab) and small molecules (upadacitinib, ozanimod, etrasimod) are approved for the treatment of moderate-to-severe ulcerative colitis. To date, there are no head-to-head trials to guide positioning and use of these newer agents. From phase III clinical trials, in the biologic experienced patient, induction with ozanimod, etrasimod, and mirizikizumab had lower clinical remission rates, whereas upadacitinib's clinical remission rates remained similar. Indirect evidence using network meta-analysis suggests upadacitinib may be more efficacious than other advanced therapies for the treatment of ulcerative colitis in both the bio-naive and experienced patient. Upadacitinib was found to have the highest risk for adverse events. These newer agents add novel mechanisms of action to the expanding therapeutic armamentarium of advanced therapies to treat ulcerative colitis. Based on expert opinion and available data to date, we propose a practical guide on positioning of these new agents for the treatment of ulcerative colitis. In mild-to-moderate disease, one should consider using ozanimod or etrasimod as first-line agents. In moderate-to-severe disease, we favor using mirizikizumab as first-line agent. In patients who have failed an anti-tumor necrosis factor agent, upadacitinib or mirizikizumab should be considered using patient factors and safety to guide one's decision between these two agents.

Neonatal Outcomes of Early Term Versus Late-Term Births in a University Teaching Hospital in Lagos, Nigeria.

There is increasing evidence of an association between early term birth and adverse neonatal outcomes. However, there is a paucity of data on the true neonatal outcomes following term deliveries in lower-income countries, including Nigeria. This study compared the neonatal outcomes of early and late-term deliveries in a tertiary hospital in Lagos, Nigeria. This was a five-year retrospective cohort study of all term deliveries between January 2013 and December 2017. Data were obtained from the labour ward and neonatal ward admission registers and medical records of the hospital.Descriptive and inferential statistics were computed for all relevant data. Statistical significance was reported at a p-value < 0.05. Of the 1,001 deliveries reviewed and analysed for this study, 215 recorded adverse neonatal events, with a significantly higher proportion of these occurring in early term compared to late-term delivered pregnancies (75.8% versus 24.2%, p < 0.001).There was a statistically higher rate of NICU admission in early term neonates than in late-term neonates (14.3 versus 3.9%, p < 0.001). Respiratory complications were the most common adverse outcomes experienced by neonates in both groups. However, the early term neonates had a higher risk even when adjusted for sex, birth weight, and mode of delivery. Our study highlights the substantial impact of gestational age on neonatal outcomes, with early term neonates at a significantly higher risk of adverse events compared to late-term neonates. Strategies aimed at reducing the rates of elective early term induction of labour and caesarean deliveries may help minimize the occurrence of adverse neonatal outcomes in our setting.

Alternative Therapy to Intravesical Bacillus Calmette–Guerin in Nonmuscle Invasive Bladder Cancer

Summary Intravesical Bacillus Calmette-Guerin (BCG) is recommended as an adjuvant therapy for intermediate and high-risk bladder cancers following complete resection. However, up to 45% of patients receiving BCG experience treatment failure. High failure rates along with increased toxicity and a global shortage of BCG availability have led to the search for alternative agents which can replace BCG. These agents can be used as second-line therapies after BCG failure before considering patients for radical cystectomy. Intravesical chemotherapeutic agents such as gemcitabine, docetaxel, valrubicin, sequential gemcitabine-docetaxel, and sequential valrubicin-docetaxel have been shown to yield comparable or better outcomes compared to BCG with low toxicity. Newer methods of drug delivery such as chemohyperthermia (CHT), electromotive drug administration (EMDA) and targeted releasing system 200 (TAR-200) have been reported to amplify drug delivery and enhance outcomes. The immune checkpoint inhibitor pembrolizumab has been used for BCG unresponsive disease with satisfactory response rates but with a higher risk of adverse events. A newer immunotherapeutic agent, ALT-803/N-803, which is an interleukin 15 superagonist, has shown promising short-term results. Novel oncolytic viral delivery systems such as nadofaragene-firadenovac, CG0070, CG0070-pembrolizumab have been shown to alter immune response and destroy malignant cells with good short-term outcomes. The number of BCG alternatives has surged in the recent past and newer agents continue to emerge. Expanding the study populations and long-term follow-up will enable affirming these alternatives as BCG equivalents in the future.

Inappropriate Underdosing of Direct Oral Anticoagulants in Atrial Fibrillation Patients: Results from the START2-AF Registry.

Background: Direct oral anticoagulants (DOACs) are recommended for stroke prevention in non-valvular atrial fibrillation (NVAF) patients. We aimed to describe the prevalence of inappropriate DOACs dose prescription in the START2-AF Registry, the outcomes according to the appropriateness of the dosage, and the factors associated with inappropriate dose prescription. Methods: Patients' demographics and clinical data were prospectively collected as electronic files in an anonymous form on the website of the START2-Registry; DOACs dosage was determined to be appropriate when prescribed according to the European Heart Rhythm Association Guidelines. Results: We included 5943 NVAF patients on DOACs; 2572 (46.3%) were female patients. The standard dose (SD) was prescribed to 56.9% of patients and the low dose (LD) was prescribed to 43.1% of patients; 38.9% of all NVAF patients received an inappropriate LD DOAC and 0.3% received inappropriate SD. Patients treated with LD DOAC had a significantly higher rate of all bleedings (RR 1.5; 95% CI 1.2-2.0), major bleedings (RR 1.8; 95% CI 1.3-1.7), and mortality (RR 2.8; 95% CI 1.9-4.1) with respect to patients treated with SD DOAC. No difference was found among patients treated with appropriate and inappropriate LD regarding bleeding, thrombotic, and mortality rates. Age, body weight <60 kg, and renal failure were significantly associated with inappropriate LD DOAC prescription. Conclusions: Inappropriate LD DOACs in NVAF patients is not associated with a reduction in bleeding risk, nor with an increased thrombotic risk. Instead, it is associated with higher mortality rate, suggesting that, in clinical practice, underdosing is preferred for patients at particularly high risk for adverse events.

Treatment Efficacy of Plasmapheresis Versus Intravenous Immunoglobulin in Guillain-Barré Syndrome Management: A Systematic Review.

Guillain-Barré syndrome (GBS) is a rare and debilitating autoimmune disorder that affects the peripheral nervous system. Although the exact etiology of GBS is still unknown, it is thought to be triggered by a preceding gastrointestinal infection in most of the cases. Clinical manifestations include limb weakness, areflexia, and sensory loss that can further progress to neuromuscular paralysis affecting the respiratory, facial, and bulbar functions. Both plasmapheresis (PE) and intravenous immunoglobulin (IVIG) have shown effectiveness in the treatment of GBS, but it is still unclear which treatment approach is superior in terms of therapeutic efficacy. This systematic review acts per Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) 2020 guidelines. For appropriate studies and research, we searched PubMed, PubMed Central (PMC), Medical Literature Analysis and Retrieval System Online (MEDLINE), Science Direct, and Google Scholar. Screening of articles was performed based on relevance and inclusion and exclusion criteria. To check for bias, we used relevant quality appraisal tools. Initially, we found 2454 articles. After removing duplicates and irrelevant papers, we finalized 31 studies based on titles, abstracts, and reading entire articles. We excluded 14 studies because of poor quality; the remaining 17 papers were included in this review. IVIG is equally efficacious as PE in improving primary outcomes and secondary outcomes. IVIG showed a slight advantage over PE in reducing the need for mechanical ventilation (MV) and hospital stay duration. However, in children, PE demonstrated a slight edge in improving secondary outcomes. PE was associated with a slightly higher risk of adverse events and post-treatment worsening symptoms compared to IVIG. IVIG is considered more user-friendly with a significantly lower patient discontinuation rate than PE. IVIG treatment was found to be significantly more expensive than PE.

Monitorización del índice biespectral para sedación en colonoscopias electivas de pacientes adultos: ensayo controlado aleatorizado

Monitorización del índice biespectral para sedación en colonoscopias electivas de pacientes adultos: ensayo controlado aleatorizado

Intraoperative Hemodynamic Instability and Higher ASA Classification Increase the Risk of Developing Non-Surgical Complications following Orthopedic Surgeries.

(1) Background: Either pre-operative physical status or unstable hemodynamic changes has been reported to play a potential role in causing vital organ dysfunction. Therefore, we intended to investigate the impact of the American Society of Anesthesiologist (ASA) classification and intraoperative hemodynamic instability on non-surgical complications following orthopedic surgery. (2) Methods: We collected data on 6478 patients, with a mean age of 57.3 ± 16, who underwent orthopedic surgeries between 2018 and 2020. The ASA classification and hemodynamic data were obtained from an anesthesia database. Non-surgical complications were defined as a dysfunction of the vital organs. (3) Results: ASA III/IV caused significantly higher odds ratios (OR) of 17.49 and 40.96, respectively, than ASA I for developing non-surgical complications (p < 0.001). Non-surgical complications were correlated with a 20% reduction in systolic blood pressure (SBP), which was intraoperatively compared to the pre-operative baseline ((OR) = 1.38, p = 0.02). The risk of postoperative complications increased with longer durations of SBP < 100 mmHg, peaking at over 20 min ((OR) = 1.33, p = 0.34). (4) Conclusions: Extended intraoperative hypotension and ASA III/IV caused a significantly higher risk of adverse events occurring within the major organs. The maintenance of hemodynamic stability prevents non-surgical complications after orthopedic surgeries.

CAR T cells and T cells phenotype and function are impacted by glucocorticoid exposure with different magnitude.

Chimeric antigen receptor (CAR) T cell therapy is associated with high risk of adverse events. Glucocorticoids (GCs) are cornerstone in the management of high-grade cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). Given the potentially deleterious effects of GCs on CAR T cells anti-tumor activity, increasing our understanding of GCs impact on CAR T cells is crucial. Using several CAR T cells i.e., CD19, mesothelin (MSLN)-CD28 and MSLN-41BB CAR T cells (M28z and MBBz), we compared phenotypical, functional, changes and anti-tumor activity between i) transduced CD19 CAR T cells with untransduced T cells, ii) M28z with MBBz CAR T cells induced by Dexamethasone (Dx) or Methylprednisolone (MP) exposures. Higher levels of GC receptor were found in less differentiated CAR T cells. Overall, Dx and MP showed a similar impact on CAR T cells. Compared to untreated condition, GCs exposure increased the expression of PD-1 and TIM-3 and reduced the expression of LAG3 and function of T cells and CAR T cells. GC exposures induced more exhausted (LAG3 + PD1 + TIM3 +) and dysfunctional (CD107a-INFγ-TNF-IL2-) untransduced T cells in comparison to CD19 CAR T cells. GC exposure impaired more CD4 + than CD8 + CD19 CAR T cells. GC exposures increased more PD-1 expression associated with reduced proliferative capacity and function of M28z as compared to MBBz CAR T cells. CAR T cells anti-tumor activity was greatly affected by repeated GC exposure but partly recovered within 48h after GCs withdrawal. In summary, GCs impacted phenotype and function of untransduced and CAR T cell with different magnitude. The nature of the CAR costimulatory domain influenced the magnitude of CAR T cell response to GCs.

(259) Comparison of Dapoxetine vs Paroxetine vs Clomipramine for Premature Ejaculation Patients

(259) Comparison of Dapoxetine vs Paroxetine vs Clomipramine for Premature Ejaculation Patients

Usability of the 4Ms Worksheet in the Emergency Department for Older Patients: A Qualitative Study.

Older adults often have multiple comorbidities; therefore, they are at high risk for adverse events after discharge. The 4Ms framework-what matters, medications, mentation, mobility-has been used in acute and ambulatory care settings to identify risk factors for adverse events in older adults, although it has not been used in the emergency department (ED). We aimed to determine whether 1)use of the 4Ms worksheet would help emergency clinicians understand older adult patients' goals of care and 2)use of the worksheet was feasible in the ED. We conducted a qualitative, descriptive study among patients aged ≥60years and emergency clinicians from January-June 2022. Patients were asked to fill out a 4Ms worksheet; following this, semi-structured interviews were conducted with patients and clinicians separately. We analysed data to create codes, which were divided into categories and sub-categories. A total of 20 older patients and 19 emergency clinicians were interviewed. We identified two categories based on our aims: understanding patient goals of care (sub-categories: clinician/ patient concordance; understanding underlying goals of care; underlying goals of care discrepancy) and use of 4Ms Worksheet (sub-categories: worksheet to discussion discrepancy; challenges using worksheet; challenge completing worksheet before discharge). Rates of concordance between patient and clinician on main concern/goal of care and underlying goals of care were 82.4% and 15.4%, respectively. We found that most patients and emergency clinicians agreed on the main goal of care, although clinicians often failed to elicit patients' underlying goal(s) of care. Additionally, many patients preferred to have the interviewer fill out the worksheet for them. There was often discrepancy between what was written and what was discussed with the interviewer. More research is needed to determine the best way to integrate the 4Ms framework within emergency care.

Aortic Elasticity and Cardiovascular Risk Stratification: A Narrative Review on the Current Understanding

Cardiovascular risk stratification is a cornerstone of preventive cardiology, aiming to identify individuals at a higher risk for adverse events. In line with this, aortic elastic properties have gained recognition as crucial indicators of vascular health and predictors of cardiovascular outcomes. This narrative review delves into the significance of aortic stiffness, compliance, and distensibility in risk assessment, shedding light on their associations with cardiovascular diseases, such as hypertension, atherosclerosis, and coronary artery disease. This review aims to provide an overview of the current knowledge regarding aortic elastic properties and their role in cardiovascular risk stratification. The exploration of potential mechanisms and clinical implications outlines the need for further research to establish precise links between aortic elasticity and cardiovascular risk. Furthermore, the integration of advanced imaging, genetic factors, and personalized medicine is suggested to refine risk assessment strategies and enhance patient care. Ultimately, this review underscores the importance of aortic elastic properties in cardiovascular risk prediction, opening avenues for future research and clinical application.

Advanced-Therapy Medicinal Products: Challenges for Implementation in Pediatric Clinical Practice

The article discusses classifications of medicines for gene and cell therapy. Data on medicinal products registered in Russia, as well as in the European Union countries, Great Britain, USA, and Japan is presented. The limitations on using such medicinal products were considered, including their high utilitarian cost and high risk of adverse events. The potential for increasing clinical efficacy and economic feasibility of advanced therapies (pediatrics included) has been analyzed.

Сопроводительная терапия при множественной миеломе: практические рекомендации

Supportive therapy is becoming increasingly important for the state-of-the-art algorithm of multiple myeloma (MM) treatment. The introduction of innovative drugs and transplantation methods into clinical practice considerably improved the disease-free and overall survival rates. However, in the vast majority of cases, MM still remains an incurable malignant plasma cell tumor. It is often treated on a continuous basis with a succession of targeted drugs and integration of glucocorticosteroids and conventional cytostatic agents into the program therapy. All of these together with immunodeficiency, bone lesions, and myeloma nephropathy lead to a high risk of adverse events and cumulative toxicity of treatment. At the same time, one of the main goals at all MM therapy stages is to maintain quality of life. The characteristics of clinical symptoms, the nuances of targeted therapy and chemotherapy-associated adverse events justify the need for further development of supportive MM therapy algorithms which remain to be a matter of current concern. They should be mainly aimed at preventing the therapy complications, reducing the rate of adverse events and clinical manifestations of side effects as well as developing a treatment strategy for cumulative toxicity. In the state-of-the-art algorithm of program MM treatment, supportive therapy-related knowledge is of no less value than the information on antitumor drugs and their efficacy. This paper reports the personal experience and provides recommendations mostly based on the results of clinical studies or views of expert panels. It also offers practical recommendations for supportive therapy in symptomatic MM which include prevention of skeletal complications, thromboses, and infections, nausea and vomiting management, vaccination, pre-medication and the algorithm of monoclonal antibody administration, anesthesia, peripheral polyneuropathy treatment, correction of secondary immunodeficiency, nutritional support, fatigue assessment and countermeasures.

Outcomes of management strategies in patients with prior coronary artery bypass grafting presenting with an acute coronary syndrome

Outcomes of management strategies in patients with prior coronary artery bypass grafting presenting with an acute coronary syndrome

Fibrinogen contribution to clot strength in patients with sepsis and hematologic malignancies and thrombocytopenia—a prospective, single-center, analytical, cross-sectional study

Fibrinogen contribution to clot strength in patients with sepsis and hematologic malignancies and thrombocytopenia—a prospective, single-center, analytical, cross-sectional study

Arterial Hypertension, Heart Failure, Angina Pectoris, Myocardial Infarction, and Atrial Fibrillation after COVID-19: A Narrative Review

COVID-19 infection is associated with significant complications affecting multiple organs other than the respiratory system. In fact, there seems to be a bidirectional relation between cardiovascular disease and viral infection, as patients with prior cardiac comorbidities are at a higher risk of adverse events during infection, and COVID-19 infection seems to exponentiate the risk of acute and long-term cardiac events. In this review, the authors will discuss the acute and long-term impact of COVID-19 infection in arterial hypertension, heart failure, angina pectoris, myocardial infarction, and atrial fibrillation.

Prevalence of iron deficiency in patients admitted to a geriatric unit: a multicenter cross-sectional study

BackgroundIron deficiency (ID) is often associated with other comorbidities in older patients and is a factor of morbimortality. However, the prevalence of ID remains poorly documented in this population.MethodsThe CARENFER PA study was a French multicenter cross-sectional study whose objective was to evaluate ID in patients (> 75 years) admitted to a geriatric unit. The primary endpoint was the ID prevalence defined as: serum ferritin < 100 µg/L and/or transferrin saturation coefficient (TSAT) < 20%. The Short Physical Performance Battery (SPPB) test was used to identify older patients at high risk of adverse events (e.g., disability, falls, hospitalization, death).ResultsA total of 888 patients (mean age, 85.2 years; women, 63.5%) from 16 French centers were included from October 2022 to December 2022. The prevalence of ID was 57.6% (95% CI, 54.3–60.9) in the cohort of older patients (62.6% in anemic and 53.3% in non-anemic patients; p = 0.0062). ID prevalence increased significantly with the presence of more than three comorbidities (65.6% vs. 55.9%; p = 0.0274), CRP ≥ 12 mg/L (73.0% vs. 49.3%; p < 0.001) and treatment that may influence ID/anemia (60.5% vs. 49.6%; p = 0.0042). In multivariate analysis, only CRP ≥ 12 mg/L was an independent predictive factor of ID (odds ratio, 2.78; 95% CI, 1.92–4.08; p < 0.001). SPPB scores were low (0–6) in 60.5% of patients with ID versus 48.6% of patients without ID (p = 0.0076).ConclusionMore than half of older patients had ID, including non-anemic patients. ID was associated with the presence of inflammation and a low SPPB score.Trial registrationNCT05514951.

Pulmonary arterial hypertension associated with type II Abernethy malformation in an adolescent: a case report

The article provides a case of pulmonary arterial hypertension (PAH) associated with congenital extrahepatic portocaval shunt (CEPS), or Abernethy malformation, in a 17-year-old female patient. CEPS, which remained undiagnosed for a long time, manifested with severe encephalopathy at an early age. By the age of 6 years, it was complicated by PAH, and by the age of 9 years — by hepatic focal nodular hyperplasia. In the absence of timely surgical treatment and adequate therapy of CEPS, PAH progressed. Combined dual therapy for PAH, prescribed only at age 14, was ineffective. Despite the potential for clinical and functional improvement documented with combination triple therapy at 17 years of age, the patient continued to meet criteria for a high risk of adverse events, including mortality. Two months after the initiation of triple therapy for PAH, not achieving the target hemodynamic characteristics that would reduce operative and perioperative risks lead to an attempt of surgical treatment of CEPS, which led to the patient death in the early postoperative period. The description of this case report shows the difficulties of diagnosing a rare form of portopulmonary hypertension, the modern possibilities of drug therapy for a severe, potentially curable PAH in the early stages.