9 research outputs found
Riociguat treatment in patients with chronic thromboembolic pulmonary hypertension: Final safety data from the EXPERT registry
Objective: The soluble guanylate cyclase stimulator riociguat is approved for the treatment of adult patients with pulmonary arterial hypertension (PAH) and inoperable or persistent/recurrent chronic thromboembolic pulmonary hypertension (CTEPH) following Phase 3 randomized trials. The EXPosurE Registry RiociguaT in patients with pulmonary hypertension (EXPERT) study was designed to monitor the long-term safety of riociguat in clinical practice. Methods: EXPERT was an international, multicenter, prospective, uncontrolled, non-interventional cohort study of patients treated with riociguat. Patients were followed for at least 1 year and up to 4 years from enrollment or until 30 days after stopping riociguat treatment. Primary safety outcomes were adverse events (AEs) and serious adverse events (SAEs) coded using Medical Dictionary for Regulatory Activities preferred terms and System Organ Classes version 21.0, collected during routine clinic visits and collated via case report forms. Results: In total, 956 patients with CTEPH were included in the analysis. The most common AEs in these patients were peripheral edema/edema (11.7%), dizziness (7.5%), right ventricular (RV)/cardiac failure (7.7%), and pneumonia (5.0%). The most common SAEs were RV/cardiac failure (7.4%), pneumonia (4.1%), dyspnea (3.6%), and syncope (2.5%). Exposure-adjusted rates of hemoptysis/pulmonary hemorrhage and hypotension were low and comparable to those in the long-term extension study of riociguat (Chronic Thromboembolic Pulmonary Hypertension Soluble Guanylate Cyclase-Stimulator Trial [CHEST-2]). Conclusion: Data from EXPERT show that in patients with CTEPH, the safety of riociguat in routine practice was consistent with the known safety profile of the drug, and no new safety concerns were identified
Riociguat treatment in patients with pulmonary arterial hypertension: Final safety data from the EXPERT registry
Objective: The soluble guanylate cyclase stimulator riociguat is approved for the treatment of adult patients with pulmonary arterial hypertension (PAH) and inoperable or persistent/recurrent chronic thromboembolic pulmonary hypertension following Phase 3 randomized trials. The EXPosurE Registry RiociguaT in patients with pulmonary hypertension (EXPERT) study was designed to monitor the long-term safety of riociguat in clinical practice. Methods: EXPERT was an international, multicenter, prospective, uncontrolled, non-interventional cohort study of patients treated with riociguat. Patients were followed for at least 1 year and up to 4 years from enrollment or until 30 days after stopping riociguat treatment. Primary safety outcomes were adverse events (AEs) and serious adverse events (SAEs) coded using Medical Dictionary for Regulatory Activities preferred terms and System Organ Classes version 21.0, collected during routine clinic visits (usually every 3-6 months) and collated via case report forms. Results: In total, 326 patients with PAH were included in the analysis. The most common AEs in these patients were dizziness (11.7%), right ventricular (RV)/cardiac failure (10.7%), edema/peripheral edema (10.7%), diarrhea (8.6%), dyspnea (8.0%), and cough (7.7%). The most common SAEs were RV/cardiac failure (10.1%), pneumonia (6.1%), dyspnea (4.0%), and syncope (3.4%). The exposure-adjusted rate of hemoptysis/pulmonary hemorrhage was 2.5 events per 100 patient-years. Conclusion: Final data from EXPERT show that in patients with PAH, the safety of riociguat in clinical practice was consistent with clinical trials, with no new safety concerns identified and a lower exposure-adjusted rate of hemoptysis/pulmonary hemorrhage than in the long-term extension of the Phase 3 trial in PAH
TREM-1 expression on neutrophils and monocytes of septic patients: relation to the underlying infection and the implicated pathogen
<p>Abstract</p> <p>Background</p> <p>Current knowledge on the exact ligand causing expression of TREM-1 on neutrophils and monocytes is limited. The present study aimed at the role of underlying infection and of the causative pathogen in the expression of TREM-1 in sepsis.</p> <p>Methods</p> <p>Peripheral venous blood was sampled from 125 patients with sepsis and 88 with severe sepsis/septic shock. The causative pathogen was isolated in 91 patients. Patients were suffering from acute pyelonephritis, community-acquired pneumonia (CAP), intra-abdominal infections (IAIs), primary bacteremia and ventilator-associated pneumonia or hospital-acquired pneumonia (VAP/HAP). Blood monocytes and neutrophils were isolated. Flow cytometry was used to estimate the TREM-1 expression from septic patients.</p> <p>Results</p> <p>Within patients bearing intrabdominal infections, expression of TREM-1 was significantly lower on neutrophils and on monocytes at severe sepsis/shock than at sepsis. That was also the case for severe sepsis/shock developed in the field of VAP/HAP. Among patients who suffered infections by Gram-negative community-acquired pathogens or among patients who suffered polymicrobial infections, expression of TREM-1 on monocytes was significantly lower at the stage of severe sepsis/shock than at the stage of sepsis.</p> <p>Conclusions</p> <p>Decrease of the expression of TREM-1 on the membrane of monocytes and neutrophils upon transition from sepsis to severe sepsis/septic shock depends on the underlying type of infection and the causative pathogen.</p
Riociguat treatment in patients with chronic thromboembolic pulmonary hypertension: Final safety data from the EXPERT registry
Objective: The soluble guanylate cyclase stimulator riociguat is approved for the treatment of adult patients with pulmonary arterial hypertension (PAH) and inoperable or persistent/recurrent chronic thromboembolic pulmonary hypertension (CTEPH) following Phase
Procalcitonin-guided algorithms of antibiotic therapy in the intensive care unit: A systematic review and meta-analysis of randomized controlled trials
Objective: There is increasing interest for strategies that could
curtail antibiotic resistance in the critical care setting. We sought to
determine the effectiveness and safety of procalcitonin-guided
algorithms in the management of septic patients in the intensive care
unit.
Data Sources: MEDLINE, Scopus, Cochrane Central Register of Controlled
Trials (through April 2010), reference lists of retrieved publications,
and queries of corresponding authors. No language restrictions were
applied.
Study Selection: We included only randomized controlled studies
reporting on antibiotic use and clinical outcomes of intensive care unit
patients managed with a procalcitonin-guided algorithm or according to
routine practice.
Data Extraction: Data on study characteristics, interventions, and
outcomes were retrieved by two independent reviewers. Pooled odds
ratios, weighted mean differences, and 95% confidence intervals were
calculated by implementing both the Mantel-Haenszel fixed effect model
and the DerSimonian-Laird random effects model.
Data Synthesis: Seven randomized controlled studies involving 1131
intensive care unit patients (adults = 1010; neonates = 121) were
included. In comparison with routine practice, the implementation of
procalcitonin-guided algorithms decreased the duration of antibiotic
therapy for the first episode of infection by approximately 2 days
(weighted mean difference = -2.36 days; 95% confidence interval, -3.11
to -1.61) and the total duration of antibiotic treatment by 4 days
(fixed effect model: weighted mean difference: -4.19 days; 95%
confidence interval, -4.98 to -3.39). The comparison between the
procalcitonin and the routine practice group was not associated with any
apparent adverse clinical outcome: 28-day mortality (fixed effect model:
odds ratio = 0.93; 95% confidence interval, 0.69 to 1.26), intensive
care unit length of stay (fixed effect model: pooled weighted mean
difference = -0.49 days, 95% confidence interval, -1.55 to 0.57), and
relapsed/persistent infection rate (fixed effect model: odds ratio =
0.97; 95% confidence interval, 0.56 to 1.69).
Conclusions: The implementation of a procalcitonin-based algorithm may
reduce antibiotic exposure in critically ill, septic patients without
compromising clinical outcomes, but further research is necessary before
the wide adoption of this strategy. (Crit Care Med 2010; 38: 2229-2241
Clinical Usefulness of Novel Serum and Imaging Biomarkers in Risk Stratification of Patients with Stable Angina
Inflammatory mediators appear to be the most intriguing yet confusing subject, regarding the management of patients with acute coronary syndromes (ACS). The current inflammatory concept of atherosclerotic coronary artery disease (CAD) led many investigators to concentrate on systemic markers of inflammation, as well as imaging techniques, which may be helpful in risk stratification and prognosis assessment for cardiovascular events. In this review, we try to depict many of the recently studied markers regarding stable angina (SA), their clinical usefulness, and possible future applications in the field
COVID-19 Infection-Related Coagulopathy and Viscoelastic Methods: A Paradigm for Their Clinical Utility in Critical Illness
Hypercoagulability and thrombosis remain a challenge to diagnose and treat in severe COVID-19 infection. The ability of conventional global coagulation tests to accurately reflect in vivo hypo- or hypercoagulability is questioned. The currently available evidence suggests that markedly increased D-dimers can be used in identifying COVID-19 patients who may need intensive care unit (ICU) admission and close monitoring or not. Viscoelastic methods (VMs), like thromboelastography (TEG) and rotational thromboelastometry (ROTEM), estimate the dynamics of blood coagulation. The evaluation of coagulopathy by VMs in severe COVID-19 infection seems an increasingly attractive option. Available evidence supports that COVID-19 patients with acute respiratory failure suffer from severe hypercoagulability rather than consumptive coagulopathy often associated with fibrinolysis shutdown. However, the variability in definitions of both the procoagulant profile and the clinical outcome assessment, in parallel with the small sample sizes in most of these studies, do not allow the establishment of a clear association between the hypercoagulable state and thrombotic events. VMs can effectively provide insight into the pathophysiology of coagulopathy, detecting the presence of hypercoagulability in critically ill COVID-19 patients. However, it remains unknown whether the degree of coagulopathy can be used in order to predict the outcome, establish a diagnosis or guide anticoagulant therapy