scholarly journals Early use of remdesivir and risk of disease progression in hospitalized patients with mild-to moderate COVID-19

2022 ◽  
Author(s):  
Marco Falcone ◽  
Lorenzo Roberto Suardi ◽  
Giusy Tiseo ◽  
Chiara Barbieri ◽  
Lisa Giusti ◽  
...  
Keyword(s):  
Disease Progression ◽  
Hospitalized Patients ◽  
Early Use ◽  
Risk Of Disease

scholarly journals The Genetics of Myelodysplastic Syndromes: Clinical Relevance

Genes ◽  
2021 ◽  
Vol 12 (8) ◽  
pp. 1144
Author(s):  
Chiara Chiereghin ◽  
Erica Travaglino ◽  
Matteo Zampini ◽  
Elena Saba ◽  
Claudia Saitta ◽  
...  
Keyword(s):  
Disease Progression ◽  
Myelodysplastic Syndromes ◽  
Clinical Relevance ◽  
Driver Mutations ◽  
Significant Information ◽  
Hematopoietic Stem ◽  
Probability Of Survival ◽  
Mutational Status ◽  
Increased Risk ◽  
Risk Of Disease

Myelodysplastic syndromes (MDS) are a clonal disease arising from hematopoietic stem cells, that are characterized by ineffective hematopoiesis (leading to peripheral blood cytopenia) and by an increased risk of evolution into acute myeloid leukemia. MDS are driven by a complex combination of genetic mutations that results in heterogeneous clinical phenotype and outcome. Genetic studies have enabled the identification of a set of recurrently mutated genes which are central to the pathogenesis of MDS and can be organized into a limited number of cellular pathways, including RNA splicing (SF3B1, SRSF2, ZRSR2, U2AF1 genes), DNA methylation (TET2, DNMT3A, IDH1/2), transcription regulation (RUNX1), signal transduction (CBL, RAS), DNA repair (TP53), chromatin modification (ASXL1, EZH2), and cohesin complex (STAG2). Few genes are consistently mutated in >10% of patients, whereas a long tail of 40–50 genes are mutated in <5% of cases. At diagnosis, the majority of MDS patients have 2–4 driver mutations and hundreds of background mutations. Reliable genotype/phenotype relationships were described in MDS: SF3B1 mutations are associated with the presence of ring sideroblasts and more recent studies indicate that other splicing mutations (SRSF2, U2AF1) may identify distinct disease categories with specific hematological features. Moreover, gene mutations have been shown to influence the probability of survival and risk of disease progression and mutational status may add significant information to currently available prognostic tools. For instance, SF3B1 mutations are predictors of favourable prognosis, while driver mutations of other genes (such as ASXL1, SRSF2, RUNX1, TP53) are associated with a reduced probability of survival and increased risk of disease progression. In this article, we review the most recent advances in our understanding of the genetic basis of myelodysplastic syndromes and discuss its clinical relevance.

Early vs Late Use of Anti-TNFa Therapy in Adult Patients With Crohn Disease: A Systematic Review and Meta-Analysis

2020 ◽  
Vol 26 (12) ◽  
pp. 1808-1818
Author(s):  
Shadi Hamdeh ◽  
Muhammad Aziz ◽  
Osama Altayar ◽  
Mojtaba Olyaee ◽  
Mohammad Hassan Murad ◽  
...  
Keyword(s):  
Systematic Review ◽  
Clinical Response ◽  
Disease Progression ◽  
Crohn Disease ◽  
Meta Analysis ◽  
Adult Patients ◽  
Cochrane Central Register ◽  
Significant Difference ◽  
Clinical Series ◽  
Early Use

Abstract Objectives While anti-tumor necrosis factor alpha (anti-TNFa) therapies for Crohn disease (CD) were initially introduced in 1998 for biologic therapies are often introduced after a minimum of 6 years after diagnosis. The benefit of anti-TNFa early in the course of CD is still controversial, with some studies showing better outcomes but others not. To determine whether earlier introduction of anti-TNFa therapy improves efficacy in clinical trials or clinical series, we aimed to perform a meta-analysis comparing early vs late anti-TNFa use in the management of CD. Methods A comprehensive search of MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, the Cochrane Database of Systematic Reviews, and Scopus was conducted from each database’s inception to November 3, 2019. We included comparative studies of early vs late use of anti-TNFa therapy in adult patients with CD. Results Eleven studies were included in the analysis, with a total of 2501 patients. Meta-analysis demonstrated that the early use of anti-TNFa was associated with a statistically significant decrease in the need for surgery (relative risk [RR] = 0.43; 95% confidence interval [CI], 0.26–0.69; I2 = 68%) and disease progression (RR = 0.51; 95% CI, 0.35–0.75; I2 = 61%). Early use also showed an increase in early remission (RR = 1.94; 95% CI, 1.54–2.46; I2 = 0%) and clinical response. There was no statistically significant difference in achieving late remission (RR = 1.39; 95% CI, 0.94–2.05; I2 = 65%) or mucosal healing (RR = 1.10; 95% CI, 0.63–1.91; I2 = 0%). Conclusion This systematic review suggests that using anti-TNFa earlier in the treatment of CD (within 3 years) may improve clinical outcomes compared to late administration in terms of achieving early clinical remission, clinical response, disease progression, and the need for surgery.

scholarly journals Impact of early vs. delayed initiation of dutasteride/tamsulosin combination therapy on the risk of acute urinary retention or BPH-related surgery in LUTS/BPH patients with moderate-to-severe symptoms at risk of disease progression

2020 ◽  
Author(s):  
Salvatore D’Agate ◽  
Chandrashekhar Chavan ◽  
Michael Manyak ◽  
Juan Manuel Palacios-Moreno ◽  
Matthias Oelke ◽  
...  
Keyword(s):  
At Risk ◽  
Combination Therapy ◽  
Disease Progression ◽  
Urinary Retention ◽  
Acute Urinary Retention ◽  
Treatment Algorithm ◽  
Phase Iii ◽  
Rank Test ◽  
Survival Curves ◽  
Risk Of Disease

Abstract Purpose To evaluate the effect of delayed start of combination therapy (CT) with dutasteride 0.5 mg and tamsulosin 0.4 mg on the risk of acute urinary retention or benign prostatic hyperplasia (BPH)-related surgery (AUR/S) in patients with moderate-to-severe lower urinary tract symptoms (LUTS) at risk of disease progression. Methods Using a time-to-event model based on pooled data from 10,238 patients from Phase III/IV dutasteride trials, clinical trial simulations (CTS) were performed to assess the risk of AUR/S up to 48 months in moderate-to-severe LUTS/BPH patients following immediate and delayed start of CT for those not responding to tamsulosin monotherapy. Simulation scenarios (1300 subjects/arm) were investigated, including immediate start (reference) and alternative delayed start (six scenarios 1–24 months). AUR/S incidence was described by Kaplan–Meier survival curves and analysed using log-rank test. The cumulative incidence of events as well as the relative and attributable risks were summarised stratified by treatment. Results Survival curves for patients starting CT at month 1 and 3 did not differ from those who initiated CT immediately. By contrast, significant differences (p < 0.001) were observed when switch to CT occurs ≥ 6 months from the initial treatment. At month 48, AUR/S incidence was 4.6% vs 9.5%, 11.0% and 11.3% in patients receiving immediate CT vs. switchers after 6, 12 and 24 months, respectively. Conclusions Start of CT before month 6 appears to significantly reduce the risk of AUR/S compared with delayed start by ≥ 6 months. This has implications for the treatment algorithm for men with LUTS/BPH at risk of disease progression.

scholarly journals Treating COVID-19 With Hydroxychloroquine (TEACH): A Multicenter, Double-Blind Randomized Controlled Trial in Hospitalized Patients

2020 ◽  
Vol 7 (10) ◽  
Author(s):  
Robert J Ulrich ◽  
Andrea B Troxel ◽  
Ellie Carmody ◽  
Jaishvi Eapen ◽  
Martin Bäcker ◽  
...  
Keyword(s):  
Randomized Controlled Trials ◽  
Disease Progression ◽  
Severe Disease ◽  
Small Sample ◽  
Hospitalized Patients ◽  
Controlled Trials ◽  
Double Blind ◽  
Randomized Controlled ◽  
End Point ◽  
Clinical Scores

Abstract Background Effective therapies to combat coronavirus 2019 (COVID-19) are urgently needed. Hydroxychloroquine (HCQ) has in vitro antiviral activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), but the clinical benefit of HCQ in treating COVID-19 is unclear. Randomized controlled trials are needed to determine the safety and efficacy of HCQ for the treatment of hospitalized patients with COVID-19. Methods We conducted a multicenter, double-blind randomized clinical trial of HCQ among patients hospitalized with laboratory-confirmed COVID-19. Subjects were randomized in a 1:1 ratio to HCQ or placebo for 5 days and followed for 30 days. The primary efficacy outcome was a severe disease progression composite end point (death, intensive care unit admission, mechanical ventilation, extracorporeal membrane oxygenation, and/or vasopressor use) at day 14. Results A total of 128 patients were included in the intention-to-treat analysis. Baseline demographic, clinical, and laboratory characteristics were similar between the HCQ (n = 67) and placebo (n = 61) arms. At day 14, 11 (16.4%) subjects assigned to HCQ and 6 (9.8%) subjects assigned to placebo met the severe disease progression end point, but this did not achieve statistical significance (P = .350). There were no significant differences in COVID-19 clinical scores, number of oxygen-free days, SARS-CoV-2 clearance, or adverse events between HCQ and placebo. HCQ was associated with a slight increase in mean corrected QT interval, an increased D-dimer, and a trend toward an increased length of stay. Conclusions In hospitalized patients with COVID-19, our data suggest that HCQ does not prevent severe outcomes or improve clinical scores. However, our conclusions are limited by a relatively small sample size, and larger randomized controlled trials or pooled analyses are needed.

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