scholarly journals Primary and key secondary results from the ROCKET AF trial, and their implications on clinical practice

2016 ◽  
Vol 11 (3) ◽  
pp. 105-120 ◽  
Author(s):  
Rohan Shah ◽  
Manesh R. Patel
Keyword(s):  
High Risk ◽  
Renal Impairment ◽  
Clinical Management ◽  
Dose Adjustment ◽  
East Asian ◽  
Adverse Outcomes ◽  
Moderate Renal Impairment ◽  
Drug Discontinuation ◽  
Management Scenarios ◽  
Concurrent Use

Background: The safety and efficacy of the oral anticoagulant rivaroxaban were studied in the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF trial). A number of subanalyses of the ROCKET AF trial have subsequently analyzed the use of rivaroxaban in special patient populations. Methods: The outcomes of the ROCKET AF trial were reviewed. The use of rivaroxaban in higher risk populations, as determined by the presence of co-morbidities included in the CHADS2 criteria, was analyzed. Requirements for dose adjustment in patients with renal impairment and in East Asian patients were described. Finally, clinical management challenges, including interruptions in therapy, drug discontinuation, management of bleeding events, drug interactions, and management of patients requiring cardioversion/ablation were reviewed. Results: Rivaroxaban is efficacious in high-risk populations, including elderly patients, patients with diabetes, heart failure, history of stroke, prior myocardial infarction, or peripheral arterial disease (PAD). Patients with PAD have a higher risk of bleeding with rivaroxaban compared with warfarin. East Asian populations do not require a dose adjustment for rivaroxaban, while a reduced dose of 15 mg daily is required for patients with moderate renal impairment. Rivaroxaban remains effective with temporary interruptions in therapy and in patients requiring cardioversion/ablation. Rates of major bleeding and subsequent outcomes were similar in patients on warfarin and rivaroxaban, although rates of gastrointestinal bleeding were higher with rivaroxaban. Concurrent use of antiarrhythmic therapy was not associated with adverse outcomes. Conclusions: Rivaroxaban represents an efficacious alternative to warfarin in high-risk patients with AF. Dose adjustment is required for patients with moderate renal impairment. Rivaroxaban can be used safely in a number of challenging clinical management scenarios although the concurrent use of amiodarone requires more study.

1004-P: Oral Semaglutide vs. Placebo in Patients with Type 2 Diabetes and Moderate Renal Impairment: PIONEER 5

Diabetes ◽  
2019 ◽  
Vol 68 (Supplement 1) ◽  
pp. 1004-P ◽  
Author(s):  
OFRI MOSENZON ◽  
SIGNE ROSENLUND ◽  
JAN W. ERIKSSON ◽  
SIMON R. HELLER ◽  
RICHARD E. PRATLEY ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Renal Impairment ◽  
Moderate Renal Impairment

scholarly journals 2021 Update on the Clinical Management and Diagnosis of Kawasaki Disease

2021 ◽  
Vol 23 (3) ◽  
Author(s):  
Frank Zhu ◽  
Jocelyn Y. Ang
Keyword(s):  
High Risk ◽  
Kawasaki Disease ◽  
Corticosteroid Therapy ◽  
Clinical Management ◽  
Treatment Guidelines ◽  
Day Treatment ◽  
Significant Proportion ◽  
Clinical Manifestations ◽  
Heart Association ◽  
Ivig Resistance

Abstract Purpose of Review Provide an updated review of the clinical management and diagnosis of Kawasaki disease with inclusion of potential diagnostic difficulties with multisystem inflammatory syndrome in children (MIS-C) given the ongoing COVID-19 pandemic. Recent Findings Adjunctive corticosteroid therapy has been shown to reduce the rate of coronary artery dilation in children at high risk for IVIG resistance in multiple Japanese clinical studies (most notably RAISE study group). Additional adjunctive therapies (etanercept, infliximab, cyclosporin) may also provide limited benefit, but data is limited to single studies and subgroups of patients with cardiac abnormalities. The efficacy of other agents (atorvastatin, doxycycline) is currently being investigated. MIS-C is a clinically distinct entity from KD with broad clinical manifestations and multiorgan involvement (cardiac, GI, hematologic, dermatologic, respiratory, renal). MIS-C with Kawasaki manifestations is more commonly seen in children < 5 years of age. Summary The 2017 American Heart Association (AHA) treatment guidelines have included changes in aspirin dosing (including both 80–100 mg/kg/day and 30–50 mg/kg/day treatment options), consideration of the use of adjuvant corticosteroid therapy in patients at high risk of IVIG resistance, and the change in steroid regimen for refractory KD to include both pulse-dose IVMP and longer course of prednisolone with an oral taper. A significant proportion of children diagnosed with MIS-C, a post-infectious syndrome of SARS-CoV-2 infection, meet criteria for Kawasaki disease. Further investigation is warranted to further delineate these conditions and optimize treatment of these conditions given the ongoing COVID-19 pandemic.

scholarly journals Interactions between hippocampal activity and striatal dopamine in people at clinical high risk for psychosis: relationship to adverse outcomes

2021 ◽  
Author(s):  
Gemma Modinos ◽  
Anja Richter ◽  
Alice Egerton ◽  
Ilaria Bonoldi ◽  
Matilda Azis ◽  
...  
Keyword(s):  
High Risk ◽  
Functional Outcomes ◽  
Mental States ◽  
Adverse Outcomes ◽  
Striatal Dopamine ◽  
Psychotic Symptoms ◽  
Dopamine Synthesis ◽  
Clinical High Risk ◽  
Hippocampal Activity ◽  
The Relationship

AbstractPreclinical models propose that increased hippocampal activity drives subcortical dopaminergic dysfunction and leads to psychosis-like symptoms and behaviors. Here, we used multimodal neuroimaging to examine the relationship between hippocampal regional cerebral blood flow (rCBF) and striatal dopamine synthesis capacity in people at clinical high risk (CHR) for psychosis and investigated its association with subsequent clinical and functional outcomes. Ninety-five participants (67 CHR and 28 healthy controls) underwent arterial spin labeling MRI and 18F-DOPA PET imaging at baseline. CHR participants were followed up for a median of 15 months to determine functional outcomes with the global assessment of function (GAF) scale and clinical outcomes using the comprehensive assessment of at-risk mental states (CAARMS). CHR participants with poor functional outcomes (follow-up GAF < 65, n = 25) showed higher rCBF in the right hippocampus compared to CHRs with good functional outcomes (GAF ≥ 65, n = 25) (pfwe = 0.026). The relationship between rCBF in this right hippocampal region and striatal dopamine synthesis capacity was also significantly different between groups (pfwe = 0.035); the association was negative in CHR with poor outcomes (pfwe = 0.012), but non-significant in CHR with good outcomes. Furthermore, the correlation between right hippocampal rCBF and striatal dopamine function predicted a longitudinal increase in the severity of positive psychotic symptoms within the total CHR group (p = 0.041). There were no differences in rCBF, dopamine, or their associations in the total CHR group relative to controls. These findings indicate that altered interactions between the hippocampus and the subcortical dopamine system are implicated in the pathophysiology of adverse outcomes in the CHR state.

Moderate renal impairment does not preclude the accuracy of 24‐hour urine normetanephrine measurements for suspected pheochromoctyoma

2020 ◽  
Vol 92 (6) ◽  
pp. 518-524
Author(s):  
Gregory A. Kline ◽  
Jessica Boyd ◽  
Alex A. Leung ◽  
Andrew Tang ◽  
Hossein M. Sadrzadeh
Keyword(s):  
Renal Impairment ◽  
Moderate Renal Impairment

Complex and irregular heart rate dynamics in fetuses compromised by maternal anemia as a high-risk pregnancy

2015 ◽  
Vol 43 (6) ◽  
Author(s):  
Young-Sun Park ◽  
Jeong-Kyu Hoh
Keyword(s):  
Heart Rate ◽  
High Risk ◽  
Approximate Entropy ◽  
Risk Groups ◽  
Adverse Outcomes ◽  
Maternal Anemia ◽  
Risk Pregnancy ◽  
Heart Rate Dynamics ◽  
Study Population ◽  
Normal Controls

AbstractTo examine how complex and irregular fetal heart rate (FHR) dynamics differ between fetuses of normal pregnancies and those of pregnancies complicated by maternal anemia (MA), and to place this in the context of high-risk pregnancies.Our study population consisted of 97 pregnant women affected by MA, 118 affected by pregnancy-induced hypertension (PIH), 88 affected by gestational diabetes mellitus (GDM), 53 with preterm premature rupture of membranes (pPROM), and 356 normal pregnancies as controls. We calculated approximate entropy (ApEn), sample entropy (SampEn), and correlation dimension (CD) to quantify irregularity and the chaotic dynamics of each FHR time series.The ApEn in the fetuses of the MA and PIH groups was significantly lower than that of the normal controls (P<0.05). The SampEn was significantly lower in the high-risk groups, except for the pPROM group, than in the normal controls (P<0.05). The CD in the PIH and severe MA groups was significantly lower than that of the normal controls (P<0.05, respectively). In the MA group, the dynamic indices showed a highly significant positive correlation with hemoglobin (Hb) levels (P<0.0001).The decreased complexity and/or irregularity in the FHR from pregnancies with MA may reflect abnormalities in the complex, integrated cardiovascular control. The irregularity and complexity of the FHR increased together with Hb levels in pregnancies with MA. Our data suggest that the integrity of the nervous system in the fetuses compromised by severe MA might result directly in adverse outcomes.

scholarly journals Pharmacokinetics of lamivudine in human immunodeficiency virus-infected patients with renal dysfunction.

1996 ◽  
Vol 40 (6) ◽  
pp. 1514-1519 ◽  
Author(s):  
A E Heald ◽  
P H Hsyu ◽  
G J Yuen ◽  
P Robinson ◽  
P Mydlow ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Renal Function ◽  
Renal Impairment ◽  
Normal Renal Function ◽  
Severe Renal Impairment ◽  
Moderate Renal Impairment ◽  
Pharmacokinetic Parameters ◽  
Geometric Means ◽  
Immunodeficiency Virus

The purpose of this study was to determine the safety and pharmacokinetics of lamivudine (3TC), a nucleoside analog that has shown potent in vitro and recent in vivo activity against human immunodeficiency virus. Sixteen human immunodeficiency virus-infected patients, six with normal renal function (creatinine clearance [CLCR], > or = 60 ml/min), four with moderate renal impairment (CLCR, 10 to 40 ml/min), and six with severe renal impairment (CLCR, < 10 ml/min), were enrolled in the study. After an overnight fast, patients were administered 300 mg of 3TC orally. Blood was obtained before 3TC administration and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24, 32, 40, and 48 h afterward. Timed urine collections were performed for patients able to produce urine. Serum and urine were assayed for 3TC by reverse-phase high-performance liquid chromatography with UV detection. Pharmacokinetic parameters were calculated by using standard noncompartmental techniques. The peak concentration of 3TC increased with decreasing renal function; geometric means were 2,524, 3,538, and 5,684 ng/ml for patients with normal renal function, moderate renal impairment, and severe renal impairment, respectively. The terminal half-life also increased with decreasing renal function; geometric means were 11.5, 14.1, and 20.7 h for patients with normal renal function, moderate renal impairment, and severe renal impairment, respectively. Both oral and renal clearances were linearly correlated with CLCR. A 300-mg dose of 3TC was well tolerated by all three patient groups. The pharmacokinetics of 3TC is profoundly affected by impaired renal function. Dosage adjustment, by either dose reduction or lengthening of the dosing interval, is warranted.

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