scholarly journals Impact of the Addition of Baricitinib to Standard of Care Including Tocilizumab and Corticosteroids on Mortality and Safety in Severe COVID-19

2021 ◽  
Vol 8 ◽  
Author(s):  
Mar Masiá ◽  
Sergio Padilla ◽  
José Alberto García ◽  
Javier García-Abellán ◽  
Andrés Navarro ◽  
...  

Background: Baricitinib is a Janus kinase (JAK) inhibitor with a broader anti-inflammatory activity than tocilizumab and an antiviral potential although no head-to-head trials are available. The benefits of adding baricitinib to patients with COVID-19 experiencing clinical progression despite the standard of care (SOC), including corticosteroids and tocilizumab, are also unknown.Methods: A cohort study included microbiologically confirmed COVID-19 hospitalizations. The primary outcome was 28-day mortality. Secondary outcomes were 60- and 90-day mortality, the composite outcome “28-day invasive mechanical ventilation (IMV) or death” and the safety of the combination. Propensity score (PS) matching was used to identify the association between baricitinib use and the outcomes of interest.Results: Of 1,709 admissions, 994 patients received corticosteroids and tocilizumab and 110 of them received baricitinib after tocilizumab. PS matched 190 (95:95) patients with baricitinib + SOC vs. SOC, of whom 69.5% received remdesivir. No significant effect of baricitinib was observed on 28-day [39 events; adjusted hazard ratio (aHR), 0.76; 95% CI, 0.31–1.86], 60-day (49 events, aHR, 1.17; 95% CI, 0.55–2.52), or 90-day mortality (49 events; aHR, 1.14; 95% CI, 0.53–2.47), or on the composite outcome 28-day IMV/death (aHR, 0.88; 95% CI, 0.45–1.72). Secondary infections during hospitalization were not different between groups (17.9 vs. 10.5%, respectively; p = 0.212) and thromboembolic events were higher with baricitinib (11.6% vs. 3.2%; p = 0.048), but differences vanished after the adjustment [aHR 1.89 (0.31–11.57), p = 0.490].Conclusion: The addition of baricitinib did not substantially reduce mortality in hospitalized patients with COVID-19 having clinical progression despite the therapy with tocilizumab and corticosteroids. The combination of baricitinib and tocilizumab was not associated with an increased risk of secondary infections or thromboembolic events.

Nutrients ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 3381
Author(s):  
Sang Heon Suh ◽  
Tae Ryom Oh ◽  
Hong Sang Choi ◽  
Chang Seong Kim ◽  
Eun Hui Bae ◽  
...  

To investigate the association of body weight variability (BWV) with adverse cardiovascular (CV) outcomes in patient with pre-dialysis chronic kidney disease (CKD), a total of 1867 participants with pre-dialysis CKD from Korean Cohort Study for Outcomes in Patients With Chronic Kidney Disease (KNOW-CKD) were analyzed. BWV was defined as the average absolute difference between successive values. The primary outcome was a composite of non-fatal CV events and all-cause mortality. Secondary outcomes were fatal and non-fatal CV events and all-cause mortality. High BWV was associated with increased risk of the composite outcome (adjusted hazard ratio (HR) 1.745, 95% confidence interval (CI) 1.065 to 2.847) as well as fatal and non-fatal CV events (adjusted HR 1.845, 95% CI 1.136 to 2.996) and all-cause mortality (adjusted HR 1.861, 95% CI 1.101 to 3.145). High BWV was associated with increased risk of fatal and non-fatal CV events, even in subjects without significant body weight gain or loss during follow-up periods (adjusted HR 2.755, 95% CI 1.114 to 6.813). In conclusion, high BWV is associated with adverse CV outcomes in patients with pre-dialysis CKD.


2016 ◽  
Vol 116 (10) ◽  
pp. 687-695 ◽  
Author(s):  
Zohar Nachum ◽  
Israel Gavish ◽  
Shabtai Romano ◽  
Meirav Braverman ◽  
Gali Garmi ◽  
...  

SummaryWomen with thrombophilias and previous placenta-mediated pregnancy complications (PMPC) have an increased risk of both recurrent PMPC and venous thromboembolism (VTE) during subsequent pregnancies. We aimed to examine whether enoxaparin dose adjusted according to anti-factor Xa levels compared to a fixed dose would reduce the risk of PMPC in subsequent pregnancies. In a randomised trial, conducted at a single teaching hospital, pregnant women with thrombophilia and previous PMPC were enrolled in a 1:1 ratio to either a fixed dose of 40 mg daily enoxaparin or adjusted dose according to anti-factor Xa plasma levels. The primary outcome was a composite that included any of the following: pregnancy loss after enrollment, pre-eclampsia, birthweight <10th percentile, placental abruption, or VTE. Overall, 144 women were needed to detect a decrease of 20 % in the incidence of the composite outcome among the adjusted dose group. Between 2009 and 2015, 144 women consented; four in the fixed-dose group were excluded. Overall, 66 and 74 in the fixed- and adjusted-dose groups, respectively, were included. Demographic and obstetric characteristics were comparable. Composite outcome occurred in 12 (18.2 %) and 20 (27.0 %) women in the fixed- and adjusted-dose groups, respectively (p=0.24). Gestational age at delivery, preterm births, and birthweights were similar between the two groups. In conclusion, dose of enoxaparin adjusted according to anti-factor Xa levels compared to fixed dose, does not reduce the risk of PMPC recurrence in thrombophilic women.ClinicalTrial Registration: ClinicalTrials.gov, www.clinicaltrials.gov, NCT01068795.


2021 ◽  
Author(s):  
Sergio Fragoso-Saavedra ◽  
Isaac Núñez ◽  
Belem M. Audelo-Cruz ◽  
Sarahi Arias-Martínez ◽  
Daniel Manzur-Sandoval ◽  
...  

AbstractBackgroundHospitalized patients with severe COVID-19 have an increased risk of developing severe systemic inflammatory response, pulmonary damage, and acute respiratory distress syndrome (ARDS), resulting in end-organ damage and death. Acetylcholine modulates the acute inflammatory response through a neuro-immune mechanism known as the inflammatory reflex. Pyridostigmine, an acetylcholine-esterase inhibitor, increases the half-life of endogenous ACh, chemically stimulating the inflammatory reflex. This trial aimed to evaluate whether pyridostigmine could decrease invasive mechanical ventilation (IMV) and death in patients with severe COVID-19.MethodsWe performed a parallel-group, multicenter, double-blinded, placebo-controlled, randomized clinical trial to evaluate if add-on pyridostigmine to standard treatment reduced the composite outcome of initiation of IMV and 28-day all-cause mortality among hospitalized patients with severe COVID-19.Results188 participants were randomly assigned to placebo (n=94) or pyridostigmine (n=94). The composite outcome occurred in 22 (23.4%) vs. 11 (11.7%) participants, respectively (hazard ratio 0.46, 95% confidence interval 0.22-0.96, p=0.03). Most of the adverse events were mild to moderate, with no serious adverse events related to pyridostigmine; discontinuation of the study drugs was similar in both groups.ConclusionsWe provide evidence indicating that the addition of pyridostigmine to standard treatment resulted in a clinically significant reduction in the composite outcome (IMV/death) among patients hospitalized for severe COVID-19. (Funded by Consejo Nacional de Ciencia y Tecnología, México; ClinicalTrials.gov number: NCT04343963).


Author(s):  
Andrew T. Kuykendall ◽  
Rami S. Komrokji

ABSTRACT Myelofibrosis (MF) is a myeloproliferative neoplasm hallmarked by uncontrolled blood counts, constitutional symptoms, extramedullary hematopoiesis, and an increased risk of developing acute myeloid leukemia. Janus kinase (JAK) inhibitors are the most common treatment for MF due to their ability to reduce spleen size and improve disease-related symptoms; however, JAK inhibitors are not suitable for every patient and their impact on MF is limited in several respects. Novel JAK inhibitors and JAK inhibitor combinations are emerging that aim to enhance the treatment landscape, providing deeper responses to a broader population of patients with the continued hope of providing disease modification and improving long-term outcomes. In this review, we highlight several specific areas of unmet need within MF. Subsequently, we review agents that target those areas of unmet need, focusing specifically on the JAK inhibitors, momelotinib, pacritinib, itacitinib, and NS-018 as well as JAK inhibitor combination approaches using CPI-0610, navitoclax, parsaclisib, and luspatercept.


2020 ◽  
Vol 66 (5) ◽  
pp. 706-717
Author(s):  
Daoxia Guo ◽  
Zhengbao Zhu ◽  
Tan Xu ◽  
Chongke Zhong ◽  
Aili Wang ◽  
...  

Abstract Background S100A8/A9 is implicated in inflammation mechanisms related to atherosclerosis and plaque vulnerability, but it remains unclear whether S100A8/A9 is associated with the prognosis of ischemic stroke. The aim of this study was to investigate these associations in 2 independent multicenter cohorts. Methods Plasma S100A8/A9 concentrations at baseline were measured among 4785 patients with ischemic stroke from 2 independent cohorts: Infectious Factors, Inflammatory Markers, and Prognosis of Acute Ischemic Stroke (IIPAIS) and China Antihypertensive Trial in Acute Ischemic Stroke (CATIS). The primary outcome was a composite outcome of death or major disability at 3 months after ischemic stroke. Secondary outcomes were major disability, death, and a composite outcome of death or vascular events. Results Among the combined participants of IIPAIS and CATIS, the adjusted odds ratios associated with the highest quartile of plasma S100A8/A9 were 2.11 (95% CI, 1.66–2.68) for the primary outcome and 1.62 (95% CI, 1.27–2.07) for the secondary outcome of major disability; adjusted hazard ratios were 4.14 (95% CI, 2.10–8.15) for the secondary outcome of death and 2.08 (95% CI, 1.38–3.13) for the composite outcome of death or vascular events. Each SD increase of log-transformed S100A8/A9 was associated with 28% (95% CI, 18%–39%; P &lt; 0.001) increased risk of the primary outcome. Multivariable-adjusted spline regression analyses showed a linear association between plasma S100A8/A9 concentrations and primary outcome (P &lt; 0.001 for linearity). Subgroup analyses further confirmed these associations. Conclusions High plasma S100A8/A9 concentrations at baseline were independently associated with increased risks of adverse clinical outcomes at 3 months after ischemic stroke, suggesting that S100A8/A9 might have a role as a prognostic marker of ischemic stroke.


2019 ◽  
Vol 40 (25) ◽  
pp. 2032-2043 ◽  
Author(s):  
Michael Böhm ◽  
Helmut Schumacher ◽  
Koon K Teo ◽  
Eva M Lonn ◽  
Felix Mahfoud ◽  
...  

Abstract Aims Studies have shown a non-linear relationship between systolic blood pressure (SBP) and diastolic blood pressure (DBP) and outcomes, with increased risk observed at both low and high blood pressure (BP) levels. We hypothesized that the BP-risk association is different in individuals with and without diabetes at high cardiovascular risk. Methods and results We identified patients with (N = 11 487) or without diabetes (N = 19 450), from 30 937 patients, from 133 centres in 44 countries with a median follow-up of 56 months in the ONTARGET/TRANSCEND studies. Patients had a prior history of stroke, myocardial infarction (MI), peripheral artery disease, or were high-risk diabetics. Patients in ONTARGET had been randomized to ramipril 10 mg daily, telmisartan 80 mg daily, or the combination of both. Patients in TRANSCEND were ACE intolerant and randomized to telmisartan 80 mg daily or matching placebo. We analysed the association of mean achieved in-trial SBP and DBP with the composite outcome of cardiovascular death, MI, stroke and hospitalization for congestive heart failure (CHF), the components of the composite, and all-cause death. Data were analysed by Cox regression and restricted cubic splines, adjusting for risk markers including treatment allocation and accompanying cardiovascular treatments. In patients with diabetes, event rates were higher across the whole spectrum of SBP and DBP compared with those without diabetes (P < 0.0001 for the primary composite outcome, P < 0.01 for all other endpoints). Mean achieved in-trial SBP ≥160 mmHg was associated with increased risk for the primary outcome [diabetes/no diabetes: adjusted hazard ratio (HR) 2.31 (1.93–2.76)/1.66 (1.36–2.02) compared with non-diabetics with SBP 120 to <140 mmHg], with similar findings for all other endpoints in patients with diabetes, and for MI and stroke in patients without diabetes. In-trial SBP <120 mmHg was associated with increased risk for the combined outcome in patients with diabetes [HR 1.53 (1.27–1.85)], and for cardiovascular death and all-cause death in all patients. In-trial DBP ≥90 mmHg was associated with increased risk for the primary outcome [diabetes/no diabetes: HR 2.32 (1.91–2.82)/1.61 (1.35–1.93) compared with non-diabetics with DBP 70 to <80 mmHg], with similar findings for all other endpoints, but not for CHF hospitalizations in patients without diabetes. In-trial DBP <70 mmHg was associated with increased risk for the combined outcome in all patients [diabetes/no diabetes: HR 1.77 (1.51–2.06)/1.30 (1.16–1.46)], and also for all other endpoints except stroke. Conclusion High on treatment BP levels (≥160 or ≥90 mmHg) are associated with increased risk of cardiovascular outcomes and death. Also low levels (<120 or <70 mmHg) are associated with increased cardiovascular outcomes (except stroke) and death. Patients with diabetes have consistently higher risks over the whole BP range, indicating that achieving optimal BP goals is most impactful in this group. These data favour guidelines taking lower BP boundaries into consideration, in particular in diabetes. Clinical trial registration http://clinicaltrials.gov.Unique identifier: NCT00153101.


2021 ◽  
Vol 10 (9) ◽  
pp. 1844
Author(s):  
María Ayala Gutiérrez ◽  
Manuel Rubio-Rivas ◽  
Carlos Romero Gómez ◽  
Abelardo Montero Sáez ◽  
Iván Pérez de Pedro ◽  
...  

(1) Objectives: To describe the clinical characteristics and clinical course of hospitalized patients with COVID-19 and autoimmune diseases (ADs) compared to the general population. (2) Methods: We used information available in the nationwide Spanish SEMI-COVID-19 Registry, which retrospectively compiles data from the first admission of adult patients with COVID-19. We selected all patients with ADs included in the registry and compared them to the remaining patients. The primary outcome was all-cause mortality during admission, readmission, and subsequent admissions, and secondary outcomes were a composite outcome including the need for intensive care unit (ICU) admission, invasive and non-invasive mechanical ventilation (MV), or death, as well as in-hospital complications. (3) Results: A total of 13,940 patients diagnosed with COVID-19 were included, of which 362 (2.6%) had an AD. Patients with ADs were older, more likely to be female, and had greater comorbidity. On the multivariate logistic regression analysis, which involved the inverse propensity score weighting method, AD as a whole was not associated with an increased risk of any of the outcome variables. Habitual treatment with corticosteroids (CSs), age, Barthel Index score, and comorbidity were associated with poor outcomes. Biological disease-modifying anti-rheumatic drugs (bDMARDs) were associated with a decrease in mortality in patients with AD. (4) Conclusions: The analysis of the SEMI-COVID-19 Registry shows that ADs do not lead to a different prognosis, measured by mortality, complications, or the composite outcome. Considered individually, it seems that some diseases entail a different prognosis than that of the general population. Immunosuppressive/immunoregulatory treatments (IST) prior to admission had variable effects.


2021 ◽  
Author(s):  
Hernando Guillermo Gaitan-Duarte ◽  
Carlos alvarez-Moreno ◽  
Carlos Javier Rincon-Rodriguez ◽  
Nancy Yomayusa-Gonzalez ◽  
Jorge Alberto Cortes ◽  
...  

BACKGROUND The effectiveness of rosuvastatin plus colchicine, emtricitabine/tenofovir, and of their combined use in hospitalized patients with coronavirus disease 2019 (Covid-19) pneumonia is unclear. METHODS In each hospital, hospitalized adults with Covid-19 pneumonia, were randomly assigned, in a 1:1 ratio, to receive: a) standard of care; or b) emtricitabine/tenofovir; or c) colchicine + rosuvastatin; or d) emtricitabine/tenofovir + colchicine + rosuvastatin. The primary outcome was all-cause mortality within the first 28 days after randomization. Severe adverse events (SAE) were those with a high probability of being treatment-related. RESULTS 633 patients were randomized in 6 hospitals in Bogota, Colombia. Overall, 98% of the patients received glucocorticoids during hospitalization. The cumulative incidence of death through day 28 was 10.7% in the emtricitabine/tenofovir + colchicine + rosuvastatin arm, 14.4% in the colchicine + rosuvastatin arm, 13.8% in the emtricitabine/tenofovir arm, and 17.4% in the standard of care arm, with adjusted risk differences (aRD) against the standard treatment of -0.07 (95% confidence interval [CI], -0.17 to 0.04), aRD -0.03 (95%CI: -0.11 to 0.05) and aRD: -0.05 (95%CI: -0.15 to 0.05), respectively. Need for invasive mechanical ventilation was lower in the emtricitabine/tenofovir + colchicine + rosuvastatin arm compared to the standard treatment arm, aRD: -0.06 (95%CI: -0.11 to -0,01), but no differences were found between the other comparisons. SAE occurred in 3 patients distributed in the 3 treatment arms. CONCLUSIONS Among patients hospitalized with moderate and severe SARS Covid-19, the use of the emtricitabine/tenofovir + colchicine + rosuvastatin combination emerges as a treatment alternative.


2009 ◽  
Vol 29 (02) ◽  
pp. 193-196 ◽  
Author(s):  
H. Rott ◽  
A. Kruempel ◽  
G. Kappert ◽  
U. Nowak-Göttl ◽  
S. Halimeh

SummaryThe risk of thromboembolic events (TE) is increased by acquired or inherited thrombo -philias (IT). We know that some hormonal contraceptives also increase the risk of thrombosis, thus, the use of such contraceptives are discussed as contraindications in women with IT. TEs are infrequent events in children and adolescents and in the majority of cases are associated with secondary complications from underlying chronic illness. Although adolescents are not typically considered to be at high-risk for TE, this cohort is frequently using hormonal contraception, leading to an increased risk in cases with unknown IT. The risk of TE with pregnancy alone is higher than associated with combined hormonal contra -ception. Progestin-only methods have not been found to increase the risk of TE with only moderate changes of coagulation proteins compared to normal reference values. Conclusion: Thrombophilic women are good candidates for progestin-only contraceptive methods.


2021 ◽  
pp. 1-27
Author(s):  
Chichen Zhang ◽  
Shi Qiu ◽  
Haiyang Bian ◽  
Bowen Tian ◽  
Haoyuan Wang ◽  
...  

Abstract Objective: We evaluate the association between the Dietary Inflammatory Index (DII) and kidney stones. Design: We performed a cross-sectional analysis using data from National Health and Nutrition Examination Survey. Dietary intake information was assessed using first 24-HR dietary recall interviews, and the Kidney Conditions was presented by questionnaire. The primary outcome was to investigate the association between DII and incidence of kidney stones, and the secondary outcome was to assess the association between DII and nephrolithiasis recurrence. Setting: The National Health and Nutrition Examination Survey (NHANES), 2007-2016. Participants: The study included 25984 NHANES participants, whose data on DII and kidney stones were available, of whom 2439 reported a history of kidney stones. Results: For the primary outcome, after fully multivariate adjustment, DII score is positively associated with the risk of kidney stones (OR = 1.07; 95% CI: [1.04–1.10]). Then, compared Q4 with Q1, a significant 38% increased likelihood of nephrolithiasis was observed. (OR=1.38; 95% CI: [1.19–1.60]). For the secondary outcome, the multivariate regression analysis showed that DII score is positively correlated with nephrolithiasis recurrence (OR=1.07; 95% CI: [1.00–1.15]). The results noted that higher DII scores (Q3 and Q4) are positively associated with a significant 48% and 61% increased risk of nephrolithiasis recurrence compared with the reference after fully multivariate adjustment. (OR=1.48; 95% CI: [1.07–2.05]; OR=1.61; 95% CI: [1.12–2.31]). Conclusions: Our findings revealed that increased intake of pro-inflammatory diet, as a higher DII score, is correlated with increased odds of kidney stones incidence and recurrence.


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