Abstract 17169: The Impact of Renal Function on Outcomes With Edoxaban in the ENGAGE AF-TIMI 48 Trial

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Erin A Bohula ◽  
Robert P Giugliano ◽  
Christian T Ruff ◽  
Julia F Kuder ◽  
Sabina A Murphy ◽  
...  

Background: Edoxaban (edox), an oral factor Xa inhibitor with 50% renal clearance, was non-inferior to warfarin for prevention of thromboembolic events and significantly reduced bleeding in pts with AF. However, a detailed analysis of the impact of creatinine clearance (CrCl) on clinical outcomes with edox has not been described. Purpose: We evaluated the safety, efficacy and net clinical outcome of edox vs warfarin (warf) across the range of baseline CrCl in the ENGAGE AF-TIMI 48 trial. Methods: 14,071 AF pts at moderate-to-high risk of stroke were randomized to edox 60mg QD or warf. Severe renal dysfunction (CrCl<30ml/min) was exclusionary and a CrCl 30-50 resulted in a 50% dose reduction of edox (30mg QD). Endpoints of stroke or systemic embolism (SSE), ISTH major bleeding (MB) and the primary net clinical outcome of SSE/MB and all-cause mortality (ACM) were evaluated by intention-to-treat analysis by the pre-specified singular CrCl cutpoint of 50ml/min and additional exploratory cutpoints. Results: The relative risk of SSE with edox vs warf in the pre-specified analysis in those with CrCl≤50 (HR 0.87, 0.65-1.18) was similar to those with CrCl>50 (HR 0.87, 0.72-1.04; p-int=0.94). Evaluation by more granular, exploratory cutpoints demonstrated higher rates of SSE (Fig 1a; p-int<0.001) and ischemic stroke (p-int=0.05) with edox vs warf in the upper range of CrCl, but lower rates of bleeding were observed at all levels of CrCl with edox (Fig 1a; p-int=0.39). For the net clinical outcome (SSE/MB/ACM), there was no significant difference between edox and warf at higher levels of renal function due to the preserved effect on bleeding and mortality (Fig 1b; p-int 0.17). An on-treatment analysis with plasma drug levels will be shown. Conclusion: While there is a trend towards decreasing efficacy with increasing CrCl for edox compared to well-managed warfarin, the overall safety and net clinical benefit of edox compared to warfarin is consistent across renal function groups.

2020 ◽  
Vol 19 (1) ◽  
Author(s):  
Congjie Wang ◽  
Wenjie Shi ◽  
Jianyang Xu ◽  
Chengbing Huang ◽  
Jiannan Zhu

Abstract Background Although there are some existing data describing the usage of topiramate in patients with antipsychotic-induced obesity, study on its comparison with metformin is limited. This study aimed to explore the effectiveness and safety of concomitant topiramate on antipsychotic-induced obesity as well as its comparison with metformin. Methods 62 stabilized outpatients with antipsychotic-induced obesity were randomized into the topiramate group and the metformin group with 16-week treatment. The patients’ weight, body mass index (BMI), waist–hip ratio, and their side effects were assessed and compared. Intention-to-treat and completer analyses were performed. Meanwhile, covariance analysis was conducted to control the impact of the significant difference in BMI between the two groups. Results The two groups had comparable characteristics, though their difference in baseline BMI was significant. (1) Intention-to-treat analyses: the random missing values were replaced using the last observation carried forward method when intention-to-treat analyses were conducted. Compared with the baseline, the weight, BMI, and waist–hip ratio in the topiramate group markedly decreased at each follow-up, whereas, in the metformin group, only waist–hip ratio significantly decreased at 4 weeks after treatment. Compared with the metformin, only weight and BMI in the topiramate group were significantly decreased at week 4 after treatment, and at week 8–16, weight, BMI and waist–hip ratio were remarkably declined. (2) Completer analyses: compared with the baseline, the weight, BMI, and waist–hip ratio in the topiramate group at week 4–16 were markedly decreased, whereas only waist–hip ratio with metformin was significantly decreased at week 4. Compared with the metformin, all BMI with topiramate were markedly decreased at week 4–16. Moreover, its weight and waist–hip ratio also were notably lowered at week 8. No significant differences in adverse events were found between the two groups. Conclusions Topiramate, similar to metformin in reducing obesity as previously reported, also significantly reduced body weight, BMI, and waist–hip ratio in patients with antipsychotic-induced obesity and demonstrated well tolerance in psychiatric patients. Trialregistration The trial was registered at http://www.chictr.org.cn, and the number was ChiCTR-IPR-17013122.


2020 ◽  
Vol 54 (7) ◽  
pp. 633-643
Author(s):  
Carmen Guadalupe Rodriguez-Gonzalez ◽  
Esther Chamorro-de-Vega ◽  
Cristina Ortega-Navarro ◽  
Roberto Alonso ◽  
Ana Herranz-Alonso ◽  
...  

Background: Real-life data on single-tablet regimen (STR) dolutegravir/abacavir/lamivudine (DTG/ABC/3TC) is scarce, and concerns about DTG neuropsychiatric adverse events (NP-AEs) have recently arisen. Objective: To explore the effectiveness and safety, in particular NP-AEs, of DTG/ABC/3TC in a cohort of HIV-1 adult infected patients. Pill burden, adherence to this STR, and the impact of switching on costs were also evaluated. Methods: This was an observational, retrospective study. The study population included antiretroviral therapy (ART)-naive and treatment-experienced (TE) patients who started DTG/ABC/3TC between February 1, 2016, and October 31, 2016. Effectiveness and safety were analyzed at week 48 (W48) by intention-to-treat analysis. The Cox regression model was used to investigate predictors of DTG/ABC/3TC discontinuation. Results: A total of 253 patients were included (44 ART naïve, 209 TE). At W48, the proportion of patients with virological suppression was 72.7% (95% CI = 58.4-87.0) in ART-naive patients, 85.6% (95% CI = 80.3-90.9) in previously suppressed TE patients, and 86.4% (95% CI = 65.1-97.1) in previously not suppressed TE patients. The rate of protocol-defined virological failure was 4.3%. The incidence of AEs was higher in the subgroup of ART-naive patients (56.1% vs 39.0%), with a rate of interruptions for this reason of 13.6% and 7.6%, respectively. The incidence of NP-AEs was 20.6%, with 3.9% of patients requiring discontinuation. Patients who had switched from a raltegravir-containing regimen discontinued DTG/ABC/3TC because of AEs more frequently (relative risk = 2.83; 95% CI = 1.04-7.72; P = 0.041) in the multivariate analysis. After switching to DTG/ABC/3TC, the median pill burden was reduced from 3 to 1 and the proportion of patients with an adherence <90%, from 20.1% to 12.0%. The annual per-patient ART costs increased by €48 (0.6% increase). Conclusion and Relevance: DTG/ABC/3TC is an effective strategy as first-line and switching ART. Our data suggest a worse tolerance in ART-naive patients, although the rate of discontinuation resulting from NP-AEs was relatively low. In the short-term, the adherence was slightly improved without significant changes in costs.


2019 ◽  
Vol 10 (03) ◽  
pp. 358-366 ◽  
Author(s):  
Anuj K. Dalal ◽  
Patricia Dykes ◽  
Lipika Samal ◽  
Kelly McNally ◽  
Eli Mlaver ◽  
...  

Background Care plan concordance among patients and clinicians during hospitalization is suboptimal. Objective This article determines whether an electronic health record (EHR)-integrated patient portal was associated with increased understanding of the care plan, including the key recovery goal, among patients and clinicians in acute care setting. Methods The intervention included (1) a patient portal configured to solicit a single patient-designated recovery goal and display the care plan from the EHR for participating patients; and (2) an electronic care plan for all unit-based nurses that displays patient-inputted information, accessible to all clinicians via the EHR. Patients admitted to an oncology unit, including their nurses and physicians, were enrolled before and after implementation. Main outcomes included mean concordance scores for the overall care plan and individual care plan elements. Results Of 457 and 283 eligible patients approached during pre- and postintervention periods, 55 and 46 participated in interviews, respectively, including their clinicians. Of 46 postintervention patients, 27 (58.7%) enrolled in the patient portal. The intention-to-treat analysis demonstrated a nonsignificant increase in the mean concordance score for the overall care plan (62.0–67.1, adjusted p = 0.13), and significant increases in mean concordance scores for the recovery goal (30.3–57.7, adjusted p < 0.01) and main reason for hospitalization (58.6–79.2, adjusted p < 0.01). The on-treatment analysis of patient portal enrollees demonstrated significant increases in mean concordance scores for the overall care plan (61.9–70.0, adjusted p < 0.01), the recovery goal (30.4–66.8, adjusted p < 0.01), and main reason for hospitalization (58.3–81.7, adjusted p < 0.01), comparable to the intention-to-treat analysis. Conclusion Implementation of an EHR-integrated patient portal was associated with increased concordance for key care plan components. Future efforts should be directed at improving concordance for other care plan components and conducting larger, randomized studies to evaluate the impact on key outcomes during transitions of care. Clinical Trials Identifier NCT02258594.


2018 ◽  
Vol 40 (3) ◽  
pp. 256-260 ◽  
Author(s):  
Serra Sürmeli Döven ◽  
Ali Delibaş ◽  
Hakan Taşkınlar ◽  
Ali Naycı

ABSTRACT Introduction: Cystinuria is an autosomal recessive disorder due to intestinal and renal transport defects in cystine and dibasic amino acids, which result in recurrent urolithiasis and surgical interventions. This study aimed to assess the impact of surgical interventions on renal function by analyzing estimated glomerular filtration rates. Methods: Thirteen pediatric patients with cystinuria, who were followed-up in a single tertiary institution between 2004 and 2016, were included in the study. Medical records were reviewed to collect data on clinical presentation of patients, urine parameters, stone formation, medical treatment, surgical intervention, stone recurrence after surgical procedure, stone analysis, ultrasonography, 99m-technetium dimercaptosuccinic acid (99mTc-DMSA) radionuclide imaging results, and follow-up time. Creatinine clearances estimated by modified Schwartz (eGFR) formula before and after surgery were used to assess renal function and compared statistically. Results: Nine patients (69.2%) had renal scarring which were detected with 99mTc-DMSA radionuclide imaging. In ten patients (76.9%), open surgical intervention for stones were needed during follow-up. Significant difference was not detected between eGFR before and after surgical intervention (mean 92 versus 106, p = 0.36). Nine of the patients (69.2%) were stone free in the last ultrasonographic examination. Relapses of stone after surgery were seen in 66.6% of patients who underwent surgical intervention. Conclusions: Surgical interventions for urinary stones are commonly required in patients with cystinuria. Renal scarring is a prevalent finding in cystinuric patients. Surgical interventions have no negative impact on eGFR in patients with cystinuria according to the present study.


Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 5579-5579
Author(s):  
Daniel E Ezekwudo ◽  
Rohit Singh ◽  
Bolanle Gbadamosi ◽  
Mark Micale ◽  
Ishmael Jaiyesimi ◽  
...  

Abstract Introduction: In plasma cell myeloma (PCM), tumor burden and activity plays an important role in diagnosis and prognosis (e.g. circulating plasma cells), however very little attention has been directed to the impact of the non-plasma cell component of the bone marrow. The presence of anemia has been used to distinguish PCM from smoldering myeloma; however this can be a non-specific finding as there are many potential causes of anemia besides PCM. We sought to determine if the level of erythropoiesis in bone marrow biopsies may be a more reliable prognostic factor. In the study herein, we assessed the level of bone marrow erythropoiesis in patients with newly diagnosed PCM, and compared those findings with cytogenetic results (CGs), other prognostic factors and overall clinical outcome. We hypothesized that patients with adequate erythropoiesis (AEp) are likely to have favorable cytogenetics and better outcome compared to those with decreased erythropoiesis (DEp). Methods: We retrospectively reviewed pathology database for bone marrow biopsies in patients with diagnosis of plasma cell myeloma (PCM) at Beaumont Hospital, an academic community center from 2012 and 2014. Biopsy cases without anemia were excluded. A total of 91 patients with plasma cell myeloma and anemia were identified. Each biopsy was re-examined to determine the level of erythropoiesis. The level of erythropoiesis was calculated by multiplying erythroid fraction (obtained from M:E ratio) with non-plasma cell bone marrow cellularity. Cases were separated into AEp and DEp using an erythroid compartment cut-off of 7.5% based on already established data. Kaplan-Meier analysis was used to compare survival between groups. Results: Demographic distribution of studied patients were 46 (50.1%) white, 39 (43%) African Americans and 6 (6.6%) others. Out of 91 cases analyzed, 38 (42%) had AEp whereas 53 (58%) had DEp. Among those with AEp, 23 (62%) had favorable CGs (defined as those without t (4, 14), t (14, 16), t (14, 20) or 17 p deletion); 15 (38%) had unfavorable CGs. Among those with DEp, 14 (26%) had favorable CGs whereas 39 (74%) had unfavorable cytogenetics. The vast majority of patients with favorable CGs were alive whether they had AEp (87%) or DEp (79%), thus CGs remained significant even after controlling for erythroid compartment (p = 0.03). Overall, those with AEp were noted to have significantly lower β-2 microglobulin (AEp median =2.42 mg/dL, DEp median = 4.50 mg/dL, p = 0.02). Kaplan-Meier analysis showed a significant difference in survival curves among the four groups (AEp with favorable CGs, AEp with unfavorable CGs, DEp with favorable CGs, DEp with unfavorable CGs, p<.0001). While the two groups with favorable CGs showed no significant difference (p=.6050), the two groups with unfavorable CGs did (p=.0027). Conclusion: Our findings suggest that patients with PCM and anemia are not a homogenous population. Assessment of the erythroid compartment in these patients reveals a population with AEp that has more favorable CGs and lower β-2 microglobulin than patients with DEp. Despite this finding, patients with favorable CGs had a favorable clinical outcome whether they had AEp or not, indicating that current therapies can overcome differences in erythropoiesis in that group. For patients with unfavorable CGs, however, those with AEp had superior survival outcome compared to those with DEp, indicating that there may be some prognostic or diagnostic utility to assessing erythropoiesis in patients who meet current criteria for PCM, and possibly, incorporating erythropoietic activity into diagnostic/prognostic schema. Disclosures No relevant conflicts of interest to declare.


2020 ◽  
Author(s):  
Zhiyong Xie ◽  
Zhilian Li ◽  
Wei Dong ◽  
Yuanhan Chen ◽  
Ruizhao Li ◽  
...  

Abstract Background Idiopathic membranous nephropathy (IMN) is frequently coexisted with diabetes mellitus (DM). Few researches investigate clinical outcomes in IMN patients coexisting diabetes mellitus (DM), including remission rates, renal survival and complications. Concurrent DM also pose therapeutic challenges to IMN patients due to the influence of glucocorticoids and immunosuppressant on metabolic disorders. We performed this study to investigate the impact of DM on clinical outcomes in IMN and the influence of therapeutic regime on metabolic parameters in diabetic IMN patients. Methods Two hundred and six adult hospitalized patients diagnosed with biopsy-proven IMN were retrospectively studied, including 42 patients coexisted with DM. Clinical outcomes including remission rates, renal outcome and complications were compared between groups. Impact of cyclophosphamide and ciclosporin on metabolism and complications were analyzed in IMN patients coexisting DM. Results IMN patients coexisted with DM were presented with advanced age, lower level of eGFR and hemoglobin. Patients coexisted with DM experienced worse renal function deterioration and higher incidence of infection. COX regression analysis showed that DM was an independent risk factor for renal function deterioration in IMN patients. There was no significant difference in remission rates and incidence of venous thromboembolism between two groups. Further exploration on the impact of therapeutic regimens on complications and metabolism showed that cyclophosphamide and ciclosporin had no significant difference in incidence of complications including infection and venous thromboembolism, and posed comparable influences on blood glucose, uric acid and blood lipids in IMN patients coexisted with DM. Conclusion Coexisting DM was an independent risk factor for renal function deterioration in IMN patients but did not influence the remission of proteinuria. Glucocorticoids in combination with cyclophosphamide or ciclosporine had similar impact on complications and metabolic index including blood glucose, uric acid and blood lipids in IMN patients coexisted with DM.


2006 ◽  
Vol 43 (4) ◽  
pp. 275-279
Author(s):  
Eduardo Lorens Braga ◽  
André Castro Lyra ◽  
Lourianne Nascimento ◽  
Eduardo Netto ◽  
Luciano Kalabrik ◽  
...  

BACKGROUD: Studies on hepatitis C virus kinetics showed that serum levels of interferon fall 48 h after drug administration, when viral load is increasing again. Previously to the availability of pegylated interferon, daily induction therapy with standard interferon was under evaluation. AIMS: To evaluate the safety and efficacy of interferon alpha daily induction regimen in combination with ribavirin. PATIENTS AND METHODS: A randomized trial including 93 patients with chronic hepatitis C was carried out. On satisfying all eligibility criteria, patients were randomly allocated to two different treatment groups: 44 individuals in treatment arm A: IFN 3 MU thrice weekly + ribavirin 1.0-1.2 g daily for 48 weeks (IFN TIW) and 49 individuals in treatment arm B: IFN 3 MU daily + ribavirin 1.0-1.2 g daily for 12 weeks followed by IFN 3 MU thrice weekly + ribavirin 1.0-1.2 g daily, until completion of 48 weeks of therapy (IFN QD). HCV genotyping was obtained in 85 subjects. A negative HCV-RNA 6 months after cessation of therapy was considered a sustained virological response RESULTS: Eighty three patients completed treatment, five dropped out (one from IFN TIW and four from IFN QD) and in five patients therapy was discontinued due to medical request (two from IFN TIW and three from IFN QD). There was no statistically significant difference between groups with respect to therapy interruption. The frequency of cirrhosis was 29%, similar in both groups. In the "intention to treat" analysis the overall sustained virological response was 39.8%. There was no significant difference in sustained virological response rate between both treatment strategies (36.4% IFN TIW vs 42.9% IFN QD). In the 83 patients who finished the trial, sustained virological response was 44.6%. Among subjects with HCV genotype-1, the sustained virological response was 42% (40.9% IFN TIW vs 42.9% IFN QD) and among patients with HCV genotype 2 or 3, the sustained virological response was 55.6% (50% IFN TIW vs 63.6% IFN QD) CONCLUSIONS: Combination therapy had an overall sustained virological response rate of 39.8% ("intention to treat analysis"). There was no difference with respect to sustained virological response rates between patients who used daily induction schedule compared to standard regimen. Adverse events, even more frequent in the daily induction group, did not interfere with the treatment strategies.


2018 ◽  
Vol 39 (2) ◽  
pp. 361-370 ◽  
Author(s):  
Zhiwei Li ◽  
Zhenzhen Gao ◽  
Jie Xiang ◽  
Jie Zhou ◽  
Sheng Yan ◽  
...  

2009 ◽  
Vol 4 (2) ◽  
pp. 174
Author(s):  
Jennifer Kelson

A Review of: Mulvaney, Shelagh A., Leonard Bickman, Nunzia B. Giuse, Warren E. Lambert, Nila A. Sathe, and Rebecca N. Jerome." A Randomized Effectiveness Trial of a Clinical Informatics Consult Service: Impact on Evidence-based Decision-making and Knowledge Implementation." Journal of the American Medical Informatics Association 15.2 (2008): 203-11. Objective – To determine whether the provision of synthesized research evidence provided by the Clinical Informatics Consult Service (CICS) affects the clinical decision-making of clinicians working in intensive care units (ICUs). Design – Non-blinded randomized control effectiveness trial. Setting – ICUs in United States-based 658 bed university hospital providing tertiary care for adults and children. Subjects – Clinical staff working within one of four ICUs who submitted a request for clinical information during the study period. Methods – Valid requests submitted by clinical staff from the four clinical ICUs (medical, paediatric, trauma, or neonatal) were randomly allocated to receive information from the CICS (CICS provided) or no information (no CICS provided). Pre-consult forms, completed at the time of the request, examined reasons for the request and the clinical actions clinicians thought might be influenced by the search results. Requestors could opt out of the no CICS provided group either before or after the randomization of their request. Responses to requests, supplied within 0.5 to 7 days as agreed with the requestor, included a search strategy and bibliographic references, a targeted list of full-text articles, and a written synthesis and critique of the relevant research. Clinicians within both groups were free to conduct their own searches and reviews. An online evaluation form, emailed to recipients, was used to assess the impact of the information supplied. The evaluation form asked clinicians to record the time spent on their own searches, sources of information consulted including colleagues, the immediate and future impact of the information provided (either from the CICS or their own searches), what influence the information had on their clinical actions, whether there were any barriers to using the information, and quality and overall satisfaction with the results provided by the CICS. Data was analyzed according to the randomized group assignment using standard intention-to-treat analysis for the main outcomes between the two groups. Statistical adjustments were made to control for possible clustering of responses or multiple ratings from individual clinicians. The data was also analyzed on an efficacy basis depending on who provided the search results. The groups were Clinician only, CICS librarian-only, or Both Clinician and CICS librarian. Results from the Clinician only search group were used as a comparison to the remaining groups. This assessment did not take account of the randomization and therefore constitutes a cohort analysis. Results were analysed by one of two methods using statistical software SAS Proc Mixed (v9) for multi-level quantitative data analysis, e.g., analysis of variance, and SPSS (v14) for all other quantitative data analysis, including descriptive statistics. Main Results – The study period was conducted over 19 months: August 2004 to March 2006. During this time, 299 valid requests were received and 226 post consult evaluation forms were returned giving a response rate of 76%. Post consult forms were returned for 108/146 of the CICS provided group and 118/153 of the no CICS provided group. The 24% of requests that had no post consult evaluation were excluded from further analysis. Statistical tests, conducted to check for potential bias relating to missing data, suggested that the missing data had little impact on the findings. Medical and neonatal ICUs accounted for the majority of completed forms (40.3% and 38.1% respectively). The majority of opt-outs (10.2% overall) were from the medical ICU. No significant difference in outcome variables was found between opt-out and other requests when tested using analysis of variance (ANOVA). Evaluation forms were completed by 89 unique clinicians and over half (49) submitted more than one request. The average requests per clinician was 2.96, SD 3.17, range 1-15, and the average number of requests per clinician who submitted more than one request was 4.57, SD 3.55, range 2-15. Total number of responses, mean, standard deviation, and Cohen’s d effect size were reported for the outcome variables based on intention to treat analysis. Results showed no significant difference between the groups on the immediate impact of the information provided, the number of articles read or the frequency with which clinicians consulted colleagues, either formally or informally. The potential future impact of the information was rated higher in the CICS group (p=


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