Are all erythropoiesis-stimulating agents created equal?

2020 ◽  
Author(s):  
Francesco Locatelli ◽  
Lucia Del Vecchio ◽  
Luca De Nicola ◽  
Roberto Minutolo
Keyword(s):  
Randomized Clinical Trials ◽  
Hypoxia Inducible Factor ◽  
Patient Characteristics ◽  
Common Mechanism ◽  
Mortality And Morbidity ◽  
Erythropoiesis Stimulating Agents ◽  
Increased Risk ◽  
Morbidity Risks ◽  
Factor Α ◽  
Effective Drugs

Abstract Erythropoiesis-stimulating agents (ESAs) are effective drugs to correct and maintain haemoglobin (Hb) levels, however, their use at doses to reach high Hb targets has been associated with an increased risk of cardiovascular adverse events, mortality and cancer. Presently used ESAs have a common mechanism of action but different pharmacokinetic and pharmacodynamic characteristics. Accordingly, the mode of activation of the erythropoietin (EPO) receptor can exert marked differences in downstream events. It is unknown whether the various ESA molecules have different efficacy/safety profiles. The relative mortality and morbidity risks associated with the use of different types of ESAs remains poorly evaluated. Recently an observational study and a randomized clinical trial provided conflicting results regarding this matter. However, these two studies displayed several differences in patient characteristics and ESA molecules used. More importantly, by definition, randomized clinical trials avoid bias by indication and suffer less from confounding factors. Therefore they bring a higher degree of evidence. The scenario becomes even more complex when considering the new class of ESAs, called prolyl-hydroxylase domain (PHD) inhibitors. They are oral drugs that mimic exposure to hypoxia and stabilize hypoxia-inducible factor α. They profoundly differ from presently used ESAs, as they have multiple targets of action, including the stimulation of endogenous EPO synthesis, direct mobilization/absorption of iron and a higher reduction of hepcidin. Accordingly, they have the potential to be more effective in inflamed patients with functional iron deficiency, i.e. the setting of patients who are at higher risk of cardiovascular events and mortality in response to present ESA use. As for ESAs, individual PHD inhibitors differ in molecular structure and degree of selectivity for the three main PHD isoforms; their efficacy and safety profiles may therefore be different from that of presently available ESAs.

Antenatal glucocorticoids: where are we after forty years?

2014 ◽  
Vol 6 (2) ◽  
pp. 127-142 ◽  
Author(s):  
C. J. D. McKinlay ◽  
S. R. Dalziel ◽  
J. E. Harding
Keyword(s):  
Clinical Trials ◽  
Randomized Clinical Trials ◽  
Later Life ◽  
Current Evidence ◽  
Mortality And Morbidity ◽  
Increased Risk ◽  
Elective Cesarean ◽  
Short And Long Term ◽  
Synthetic Glucocorticoids

Since their introduction more than forty years ago, antenatal glucocorticoids have become a cornerstone in the management of preterm birth and have been responsible for substantial reductions in neonatal mortality and morbidity. Clinical trials conducted over the past decade have shown that these benefits may be increased further through administration of repeat doses of antenatal glucocorticoids in women at ongoing risk of preterm and in those undergoing elective cesarean at term. At the same time, a growing body of experimental animal evidence and observational data in humans has linked fetal overexposure to maternal glucocorticoids with increased risk of cardiovascular, metabolic and other disorders in later life. Despite these concerns, and somewhat surprisingly, there has been little evidence to date from randomized trials of longer-term harm from clinical doses of synthetic glucocorticoids. However, with wider clinical application of antenatal glucocorticoid therapy there has been greater need to consider the potential for later adverse effects. This paper reviews current evidence for the short- and long-term health effects of antenatal glucocorticoids and discusses the apparent discrepancy between data from randomized clinical trials and other studies.

L-arginine effect on inflammatory mediators: A systematic review of randomized controlled clinical trials

2019 ◽  
pp. 1-9 ◽  
Author(s):  
Seyed Reza Mirhafez ◽  
Mitra Hariri
Keyword(s):  
Systematic Review ◽  
Clinical Trials ◽  
Inflammatory Mediators ◽  
Randomized Clinical Trials ◽  
Randomized Controlled Clinical Trials ◽  
Patients With Cancer ◽  
Reactive Protein ◽  
Randomized Controlled ◽  
Human Adults ◽  
Factor Α

Abstract. L-arginine is an important factor in several physiological and biochemical processes. Recently, scientists studied L-arginine effect on inflammatory mediators such as C-reactive protein (CRP), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). We conducted a systematic review on randomized controlled trials assessing L-arginine effect on inflammatory mediators. We searched data bases including Google scholar, ISI web of science, SCOPUS, and PubMed/Medline up to April 2019. Randomized clinical trials assessing the effect of L-arginine on inflammatory mediators in human adults were included. Our search retrieved eleven articles with 387 participants. Five articles were on patients with cancer and 6 articles were on adults without cancer. L-arginine was applied in enteral form in 5 articles and in oral form in 6 articles. Eight articles were on both genders, two articles were on women, and one article was on men. L-arginine could not reduce inflammatory mediators among patients with and without cancer except one article which indicated that taking L-arginine for 6 months decreased IL-6 among cardiopathic nondiabetic patients. Our results indicated that L-arginine might not be able to reduce selected inflammatory mediators, but for making a firm decision more studies are needed to be conducted with longer intervention duration, separately on male and female and with different doses of L-arginine.

Circulating Stem/Progenitor Cells as Prognostic Biomarkers in Macro- and Microvascular Disease: A Narrative Review of Prospective Observational Studies

2018 ◽  
Vol 25 (35) ◽  
pp. 4507-4517 ◽  
Author(s):  
Mauro Rigato ◽  
Gian Paolo Fadini
Keyword(s):  
Cardiovascular Disease ◽  
Progenitor Cells ◽  
Cardiovascular Events ◽  
Observational Studies ◽  
English Language ◽  
Microvascular Disease ◽  
Patient Characteristics ◽  
Diabetic Patients ◽  
Increased Risk ◽  
Cell Phenotypes

Background: Circulating progenitor cells (CPCs) and endothelial progenitor cells (EPCs) are immature cells involved in vascular repair and related to many aspects of macro and microvascular disease. <p> Objective: We aimed to review studies reporting the prognostic role of CPCs/EPCs measurement on development of cardiovascular disease and microangiopathy. <p> Methods and Results: We reviewed the English language literature for prospective observational studies reporting the future development of cardiovascular disease or microangiopathy in patients having a baseline determination of CPCs/EPCs. We retrieved 34 studied reporting on cardiovascular outcomes and 2 studies reporting on microvascular outcomes. Overall, a reduced baseline level of CPCs/EPCs was associated with a significant increased risk of cardiovascular events, all-cause death, and onset/progression of microangiopathy. The most predictive phenotypes were CD34+ and CD34+CD133+. The main limitation was related to the high heterogeneity among studies in terms of patient characteristics and cell phenotypes. <p> Conclusion: The present review shows that a reduced level of circulating progenitor cells is a risk factor for the development of future cardiovascular events and death. In addition, low CPCs/EPCs levels predict the onset or worsening of microalbuminuria and retinopathy in diabetic patients.

Molecular Mechanisms of Curcumin in Neuroinflammatory Disorders: A Mini Review of Current Evidences

2019 ◽  
Vol 19 (3) ◽  
pp. 247-258 ◽  
Author(s):  
Mahsa Hatami ◽  
Mina Abdolahi ◽  
Neda Soveyd ◽  
Mahmoud Djalali ◽  
Mansoureh Togha ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
English Language ◽  
Molecular Mechanisms ◽  
Randomized Clinical Trials ◽  
Mitochondrial Dynamics ◽  
Nuclear Factor Κb ◽  
General Term ◽  
Neuroinflammatory Disease ◽  
Tnf Α ◽  
Factor Α

Objective: Neuroinflammatory disease is a general term used to denote the progressive loss of neuronal function or structure. Many neuroinflammatory diseases, including Alzheimer’s, Parkinson’s, and multiple sclerosis (MS), occur due to neuroinflammation. Neuroinflammation increases nuclear factor-κB (NF-κB) levels, cyclooxygenase-2 enzymes and inducible nitric oxide synthase, resulting in the release of inflammatory cytokines, such as interleukin-6 (IL-6), interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α). It could also lead to cellular deterioration and symptoms of neuroinflammatory diseases. Recent studies have suggested that curcumin (the active ingredient in turmeric) could alleviate the process of neuroinflammatory disease. Thus, the present mini-review was conducted to summarize studies regarding cellular and molecular targets of curcumin relevant to neuroinflammatory disorders. Methods: A literature search strategy was conducted for all English-language literature. Studies that assessed the various properties of curcuminoids in respect of neuroinflammatory disorders were included in this review. Results: The studies have suggested that curcuminoids have significant anti- neuroinflammatory, antioxidant and neuroprotective properties that could attenuate the development and symptom of neuroinflammatory disorders. Curcumin can alleviate neurodegeneration and neuroinflammation through multiple mechanisms, by reducing inflammatory mediators (such as TNF-α, IL-1β, nitric oxide and NF-κB gene expression), and affect mitochondrial dynamics and even epigenetic changes. Conclusion: It is a promising subject of study in the prevention and management of the neuroinflammatory disease. However, controlled, randomized clinical trials are needed to fully evaluate its clinical potential.

scholarly journals Association between Intraoperative Blood Transfusion and Mortality and Morbidity in Patients Undergoing Noncardiac Surgery

2011 ◽  
Vol 114 (2) ◽  
pp. 283-292 ◽  
Author(s):  
Laurent G. Glance ◽  
Andrew W. Dick ◽  
Dana B. Mukamel ◽  
Fergal J. Fleming ◽  
Raymond A. Zollo ◽  
...  
Keyword(s):  
Blood Transfusion ◽  
Noncardiac Surgery ◽  
Pulmonary Complications ◽  
Wound Complications ◽  
Severe Anemia ◽  
Thromboembolic Complications ◽  
Mortality And Morbidity ◽  
Risk Of Death ◽  
Increased Risk ◽  
The Impact

Background The impact of intraoperative erythrocyte transfusion on outcomes of anemic patients undergoing noncardiac surgery has not been well characterized. The objective of this study was to examine the association between blood transfusion and mortality and morbidity in patients with severe anemia (hematocrit less than 30%) who are exposed to one or two units of erythrocytes intraoperatively. Methods This was a retrospective analysis of the association of blood transfusion and 30-day mortality and 30-day morbidity in 10,100 patients undergoing general, vascular, or orthopedic surgery. We estimated separate multivariate logistic regression models for 30-day mortality and for 30-day complications. Results Intraoperative blood transfusion was associated with an increased risk of death (odds ratio [OR], 1.29; 95% CI, 1.03-1.62). Patients receiving an intraoperative transfusion were more likely to have pulmonary, septic, wound, or thromboembolic complications, compared with patients not receiving an intraoperative transfusion. Compared with patients who were not transfused, patients receiving one or two units of erythrocytes were more likely to have pulmonary complications (OR, 1.76; 95% CI, 1.48-2.09), sepsis (OR, 1.43; 95% CI, 1.21-1.68), thromboembolic complications (OR, 1.77; 95% CI, 1.32-2.38), and wound complications (OR, 1.87; 95% CI, 1.47-2.37). Conclusions Intraoperative blood transfusion is associated with a higher risk of mortality and morbidity in surgical patients with severe anemia. It is unknown whether this association is due to the adverse effects of blood transfusion or is, instead, the result of increased blood loss in the patients receiving blood.

scholarly journals Incidence, characteristics, determinants and prognostic impact of recurrent syncope

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
T Zimmermann ◽  
J Du Fay De Lavallaz ◽  
T Nestelberger ◽  
D Gualandro ◽  
P Badertscher ◽  
...  
Keyword(s):  
Patient Characteristics ◽  
Coronary Intervention ◽  
Final Diagnosis ◽  
Major Adverse Cardiovascular Events ◽  
Unknown Etiology ◽  
Funding Source ◽  
Prognostic Impact ◽  
Lasso Regression ◽  
Recurrence Rates ◽  
Increased Risk

Abstract Background The incidence, characteristics, determinants, and prognostic impact of recurrent syncope are largely unknown, causing uncertainty for both patients and physicians. Methods We characterized recurrent syncope including sex-specific aspects and its impact on death and major adverse cardiovascular events (MACE) in a large prospective international multicenter study enrolling patients ≥40 years presenting with syncope to the emergency department (ED). Syncope etiology was centrally adjudicated by two independent and blinded cardiologists using all information becoming available during syncope work-up and 12-month follow-up. MACE were defined as a composite of all-cause death, acute myocardial infarction, surgical or percutaneous coronary intervention, life-threatening arrhythmia including cardiac arrest, pacemaker or implantable cardioverter defibrillator implantation, valve intervention, heart-failure, gastrointestinal bleeding or other bleeding requiring transfusion, intracranial hemorrhage, ischemic stroke or transient ischemic attack, sepsis and pulmonary embolism. Results Incidence of recurrent syncope among 1790 patients was 20% (95%-confidence interval (CI) 18% to 22%) within 24 months. Patients with an adjudicated final diagnosis of cardiac syncope (hazard ratio (HR) 1.50, 95%-CI 1.11 to 2.01) or syncope of unknown etiology even after central adjudication (HR 2.11, 95%-CI 1.54 to 2.89) had an increased risk for syncope recurrence (Figure). LASSO regression fit on all patient information available early in the ED identified more than three previous episodes of syncope as the only independent predictor for recurrent syncope (HR 2.13, 95%-CI 1.64 to 2.75). Recurrent syncope within the first 12 months after the index event carried an increased risk for all-cause death (HR 1.59, 95%-CI 1.06 to 2.38) and MACE (HR 2.24, 95%-CI 1.67 to 3.01), whereas recurrences after 12 months did not have a significant impact on outcome measures. Conclusion Recurrence rates of syncope are substantial and vary depending on syncope etiology. There seem to be no reliable patient characteristics available early on the ED that allow for the prediction of recurrent syncope with only a history of more than three previous syncope being associated with a higher risk for future recurrences. Importantly, recurrent syncope within the first 12 months carries an increased risk for death and MACE. Figure 1 Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): Swiss National Science Foundation, Swiss Heart Foundation

ECG-guided PICC insertion using a new silicon catheter with a conductive tip: A retrospective clinical study

2021 ◽  
pp. 112972982110025
Author(s):  
Yu-Xia Yin ◽  
Wei Gao ◽  
Sheng-Yu Feng ◽  
Deng-Xu Wang ◽  
Min Wan ◽  
...  
Keyword(s):  
Clinical Study ◽  
Daily Practice ◽  
Patient Characteristics ◽  
Mobile App ◽  
High Rate ◽  
Exit Site Infection ◽  
Increased Risk ◽  
Retrospective Clinical Study ◽  
Operation Rate ◽  
Catheter Tip

Objective: Safety and efficacy of ECG-guided PICC insertion using a new silicon catheter with a conductive tip was evaluated in daily practice. Methods: A retrospective study was conducted on 1659 patients who accepted successful tip-conductive PICC placement and clinically followed-up until the catheter removal between January 2018 and April 2019. Baseline of patient characteristics, catheter placement characteristics, date of dressing changes as well as records of catheter-related complications were extracted from a special designed mobile APP. Results: The first-attempt success (success of placing catheter tip to the ideal position by primary indwelling operation) rate of PICC placement was 99.3%. The average duration of PICC placement was 128.7 ± 39.5 days and 1535 patients (92.5%) reached the therapy end-point without any complications and removed the catheter normally. The cumulative rates of total complications were 7.5%, including exit site infection (2.5%), phlebitis (0.9%), DVT (1.0%), catheter malposition (1.1%), catheter breakage (0.1%), and liquid extravasation (1.8%). In multivariable logistic regression analyses, hyperlipidemia, diabetes mellitus, lung cancer, stomach cancer, and lymphoma were significantly associated with increased risk of complications, as the independent risk factors. Conclusions: This retrospective clinical study demonstrates that ECG-guided insertion of a new tip-conductive PICC is associated with a high rate of first-attempt success and low rate of catheter related complications.

scholarly journals Newborns at risk of Covid-19 ― lessons from the last year

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Malika D. Shah ◽  
Ola Didrik Saugstad
Keyword(s):  
Horizontal Transmission ◽  
Mode Of Delivery ◽  
Newborn Infants ◽  
World Health ◽  
Premature Delivery ◽  
Mortality And Morbidity ◽  
Skin Contact ◽  
Cord Clamping ◽  
Increased Risk ◽  
Health Organization

Abstract After more than 1 year of the SARS-CoV-2 pandemic, a great deal of knowledge on how this virus affects pregnant women, the fetus and the newborn has accumulated. The gap between different guidelines how to handle newborn infants during this pandemic has been minimized, and the American Academy of Pediatrics (AAP)’s recommendations are now more in accordance with those of the World Health Organization (WHO). In this article we summarize present knowledge regarding transmission from mother to the fetus/newborn. Although both vertical and horizontal transmission are rare, SARS-CoV-2 positivity is associated with an increased risk of premature delivery and higher neonatal mortality and morbidity. Mode of delivery and cord clamping routines should not be affected by the mother’s SARS-CoV-2 status. Skin to skin contact, rooming in and breastfeeding are recommended with necessary hygiene precautions. Antibodies of infected or vaccinated women seem to cross both the placenta and into breast milk and likely provide protection for the newborn.

scholarly journals Comparing Patient Characteristics, Clinical Outcomes, and Biomarkers of Severe Asthma Patients in Taiwan

Biomedicines ◽  
2021 ◽  
Vol 9 (7) ◽  
pp. 764
Author(s):  
Shih-Lung Cheng ◽  
Kuo-Chin Chiu ◽  
Hsin-Kuo Ko ◽  
Diahn-Warng Perng ◽  
Hao-Chien Wang ◽  
...  
Keyword(s):  
Severe Asthma ◽  
Clinical Characteristics ◽  
Linear Models ◽  
Patient Characteristics ◽  
Emergency Department Visits ◽  
Receiver Operating Characteristic Curves ◽  
Increased Risk ◽  
Significant Difference ◽  
Asthma Patients ◽  
Patients At Risk

Purpose: To understand the association between biomarkers and exacerbations of severe asthma in adult patients in Taiwan. Materials and Methods: Demographic, clinical characteristics and biomarkers were retrospectively collected from the medical charts of severe asthma patients in six hospitals in Taiwan. Exacerbations were defined as those requiring asthma-specific emergency department visits/hospitalizations, or systemic steroids. Enrolled patients were divided into: (1) those with no exacerbations (non-exacerbators) and (2) those with one or more exacerbations (exacerbators). Receiver operating characteristic curves were used to determine the optimal cut-off value for biomarkers. Generalized linear models evaluated the association between exacerbation and biomarkers. Results: 132 patients were enrolled in the study with 80 non-exacerbators and 52 exacerbators. There was no significant difference in demographic and clinical characteristics between the two groups. Exacerbators had significantly higher eosinophils (EOS) counts (367.8 ± 357.18 vs. 210.05 ± 175.24, p = 0.0043) compared to non-exacerbators. The optimal cut-off values were 292 for EOS counts and 19 for the Fractional exhaled Nitric Oxide (FeNO) measure. Patients with an EOS count ≥ 300 (RR = 1.88; 95% CI, 1.26–2.81; p = 0.002) or FeNO measure ≥ 20 (RR = 2.10; 95% CI, 1.05–4.18; p = 0.0356) had a significantly higher risk of exacerbation. Moreover, patients with both an EOS count ≥ 300 and FeNO measure ≥ 20 had a significantly higher risk of exacerbation than those with lower EOS count or lower FeNO measure (RR = 2.16; 95% CI, 1.47–3.18; p = < 0.0001). Conclusions: Higher EOS counts and FeNO measures were associated with increased risk of exacerbation. These biomarkers may help physicians identify patients at risk of exacerbations and personalize treatment for asthma patients.

scholarly journals An Emulation of Randomized Trials of Administrating Antipsychotics in PTSD Patients for Outcomes of Suicide-Related Events

2021 ◽  
Vol 11 (3) ◽  
pp. 178
Author(s):  
Noah R. Delapaz ◽  
William K. Hor ◽  
Michael Gilbert ◽  
Andrew D. La ◽  
Feiran Liang ◽  
...  
Keyword(s):  
Randomized Clinical Trials ◽  
Previous History ◽  
Current Treatment ◽  
Careful Consideration ◽  
P Value ◽  
Post Traumatic Stress ◽  
Increased Risk ◽  
History Of ◽  
Almost All

Post-traumatic stress disorder (PTSD) is a prevalent mental disorder marked by psychological and behavioral changes. Currently, there is no consensus of preferred antipsychotics to be used for the treatment of PTSD. We aim to discover whether certain antipsychotics have decreased suicide risk in the PTSD population, as these patients may be at higher risk. A total of 38,807 patients were identified with a diagnosis of PTSD through the ICD9 or ICD10 codes from January 2004 to October 2019. An emulation of randomized clinical trials was conducted to compare the outcomes of suicide-related events (SREs) among PTSD patients who ever used one of eight individual antipsychotics after the diagnosis of PTSD. Exclusion criteria included patients with a history of SREs and a previous history of antipsychotic use within one year before enrollment. Eligible individuals were assigned to a treatment group according to the antipsychotic initiated and followed until stopping current treatment, switching to another same class of drugs, death, or loss to follow up. The primary outcome was to identify the frequency of SREs associated with each antipsychotic. SREs were defined as ideation, attempts, and death by suicide. Pooled logistic regression methods with the Firth option were conducted to compare two drugs for their outcomes using SAS version 9.4 (SAS Institute, Cary, NC, USA). The results were adjusted for baseline characteristics and post-baseline, time-varying confounders. A total of 5294 patients were eligible for enrollment with an average follow up of 7.86 months. A total of 157 SREs were recorded throughout this study. Lurasidone showed a statistically significant decrease in SREs when compared head to head to almost all the other antipsychotics: aripiprazole, haloperidol, olanzapine, quetiapine, risperidone, and ziprasidone (p < 0.0001 and false discovery rate-adjusted p value < 0.0004). In addition, olanzapine was associated with higher SREs than quetiapine and risperidone, and ziprasidone was associated with higher SREs than risperidone. The results of this study suggest that certain antipsychotics may put individuals within the PTSD population at an increased risk of SREs, and that careful consideration may need to be taken when prescribed.

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