scholarly journals Non-vitamin K Oral Anticoagulants and Anti-seizure Medications: A Retrospective Cohort Study

2021 ◽  
Vol 11 ◽  
Author(s):  
Chen-Jui Ho ◽  
Shih-Hsuan Chen ◽  
Chih-Hsiang Lin ◽  
Yan-Ting Lu ◽  
Che-Wei Hsu ◽  
...  

Purpose: Concerns of drug–drug interactions (DDIs) between anti-seizure medications (ASMs) and non-vitamin K oral anticoagulants (NOACs) have emerged in recent case reports and guidelines. Theoretically, the induction of hepatic cytochrome P450 3A4 (CYP3A4) enzyme and permeability glycoprotein (P-GP) efflux transporter protein systems may reduce the effect of NOACs. We aimed to investigate whether such DDIs are clinically relevant in a real-world situation.Methods: We retrospectively reviewed 320 ischemic stroke patients with atrial fibrillation (Af) and grouped them according to different potential interactions with CYP3A4 and P-GP. Ischemic stroke events, transient ischemic attack (TIA) events, follow-up duration, baseline characteristics, concomitant ASMs, and stroke risk factors were collected. Statistical analysis included Kaplan–Meier survival curves and the log-rank test.Results: Overall, 320 ischemic stroke with Af patients received NOACs. Among the NOAC users, 75 also took ASMs, including 56 that have potential DDIs: 43 (13.4%) were categorized as potential CYP and P-GP DDIs and 13 (4.1%) as P-GP-only DDIs. The remaining 264 (82.5%) patients were used as controls including 19 exposed to nonsignificant DDI ASMs and 245 patients without ASM exposure. The incidence rates of recurrent stroke/TIA events in both CYP3A4 and P-GP DDIs, P-GP DDIs only, and no DDIs were 7.5, 2.1, and 8.4/100 person-years, respectively. Kaplan–Meier survival curves and the log-rank test did not show significant differences among the groups.Conclusions: The recurrent stroke rate of NOAC users with potential DDIs was not higher than in those without potential DDIs in this single-institute study. Our results suggest that theoretical interactions between ASMs and NOACs may not be as severe as previously thought in a real-world situation.

2012 ◽  
Vol 33 (2) ◽  
pp. 287-292 ◽  
Author(s):  
Calin I Prodan ◽  
Julie A Stoner ◽  
Linda D Cowan ◽  
George L Dale

Coated-platelets are procoagulant platelets observed upon dual-agonist stimulation with collagen and thrombin. Coated-platelet levels are elevated in patients with nonlacunar (large-vessel) ischemic stroke and decreased in patients with spontaneous intracerebral hemorrhage as compared with controls. The purpose of this study was to investigate a possible relationship between coated-platelet levels and stroke recurrence in patients with nonlacunar ischemic stroke. We assayed coated-platelet levels in 190 consecutive patients with nonlacunar stroke who were followed for up to 12 months; 20 subjects experienced recurrent stroke. Subjects were categorized into tertiles of coated-platelet levels. The distributions of time-to-recurrent stroke were estimated for each tertile using cumulative incidence curves and compared statistically using a log-rank test. The cumulative incidence of recurrent stroke at 12 months differed among the coated-platelet tertiles: 2% for the first tertile (lowest coated-platelet levels), 18% for the second tertile, and 17% for the third tertile (overall log-rank test, P = 0.019). These data suggest that higher levels of coated-platelets, measured shortly after a nonlacunar stroke, are associated with an increased incidence of stroke recurrence. This observation offers an additional tool for identifying patients at highest risk for stroke recurrence following a nonlacunar (large-vessel) infarct.


2009 ◽  
Vol 46 (5) ◽  
pp. 928-933 ◽  
Author(s):  
K. D. McSporran

Local recurrence of marginally excised subcutaneous soft tissue sarcomas is variable and difficult to predict. This study aimed to identify predictors of local recurrence after excisional biopsy. Medical records of 236 dogs from which tumors had been received between 2004 and 2007 were analyzed. Medium- to large-breed dogs, median age 10 years, were most commonly affected. A total of 139 tumors were graded histologically: 71 were grade 1 (51%); 59, grade 2 (42%); and 9, grade 3 (7%). Of these, 34 tumors (25%) were completely excised, and 104 (75%) were marginally excised. None of 30 completely excised tumors with follow-up information recurred. Three of 41 grade 1 tumors (7%), 14 of 41 grade 2 tumors (34%), and 3 out of 4 grade 3 tumors recurred after marginal excision. Kaplan-Meier survival curves were generated to evaluate survival and the tumor-free interval. The log-rank test and log-rank test for trend were used for comparisons. Tumor recurrence-free intervals for dogs with grade 1 and 2 tumors and for those with grade 1 and 3 tumors differed significantly ( P = .0027 and .0001, respectively) and overall were inversely related to tumor grade ( P = .0007). Kaplan-Meier survival curves, regardless of recurrence, for patients with grade 1, 2, or 3 tumors treated by marginal excision did not differ significantly, and none differed from the survival curves of patients treated by complete excision. In conclusion, histologic grade is a strong predictor for recurrence of marginally excised subcutaneous soft tissue sarcomas. Clean margins predict nonrecurrence. Tumor recurrence did not significantly reduce survival time.


Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 2141-2141
Author(s):  
Angela Vitrano ◽  
Giuseppina Calvaruso ◽  
Eliana Lai ◽  
Grazia Colletta ◽  
Alessandra Quota ◽  
...  

Abstract Introduction. In the last few decades, the life expectancy of Thalassemia Major (TM) patients has progressively been increasing. The improvement can be due to several factors, including introduction of chelation treatment (Deferoxamine 1965, Deferiprone 1987, Deferasirox 2006), screening of blood for the most common viral agents, aggressive treatment of infection and improved treatment of cardiac complications. However, no comparative survival curves between TM versus Thalassemia Intermedia (TI) have been so far reported. Moreover, no data on life expectancy, after introduction of chelation treatment have been described. Methods. Data coming from several randomized clinical trials, carried ahead by Campus of Hematology Franco and Piera Cutino-A.O.O.R Villa Sofia-V. Cervello, Palermo (Italy), were retrospectively considered for this study. Primary goal of the study was to provide evidence of possible differences in survival curves between TM versus TI. Survival curves in TM versus TI patients were compared using Kaplan-Meier method and the log-rank test before and after the introduction of Deferoxamine (DFO) (1965). Moreover, Cox regression model was even used to explore risk of death between the two diagnoses. Each dead patient was observed from its birth to its death, and each alive patient was observed from its birth to June 30, 2015. Results. Three hundred seventy-nine patients with TM (n=284, dead 40) and TI (n=95, dead 13) entered into the study. Males were 50.7% of this cohort of patients. Among the cohort of dead patients, 15% (6/40) TM and 76.9% (10/13) TI patients were born before introduction of DFO (1965) . The mean age survival was 50.6 (SE 0.9) and 70.6 (SE 1.7) for TM and TI, respectively. Table 1 shows the main causes of death. In TM patients the most common causes of death were heart damage (16 cases, 40%, Tab. 1), followed by cancer (3 cases, 7.5%, Tab. 1), liver cirrhosis (3 cases, 7.5%, Tab. 1) and infections (3 cases, 7.5%, Tab. 1). In TI patients the most common causes of death were cancer (2 cases, 38.5%, Tab. 1), followed by infections (3 cases, 23.1% , Tab. 1), heart damage (2 case, 15.4%, Tab. 1). Kaplan-Meir curves showed statistically significant difference in TM versus TI survival (log-rank test, p- value<0.0001; Figure 1A). Survival was higher for TI subjects (median age was 73.6 years). Cox regression models of TM versus TI suggested that risk of death for TM patients was 6.8 times higher than TI patients (HR 6.8 (3.3), p- value<0.0001). However, the introduction of chelation treatment (DFO, 1965), changed the Kaplan-Meier curves showing that there was not statistically significant difference between TM versus TI patients in life expectancy ( log-rank test, p- value=0.086; Fig. 1B). Conclusion. These results suggest as TM survival, after the introduction of chelation treatment, improved so much that nowadays it is not different in comparison with TI one's. Moreover, the TM risk of death has been decreased from 6.8 to 2.8 (Cox Model HR 2.8 (1.7), p- value=0.099). These findings, if further confirmed, suggest as, in Western countries, our approach for genetic counselling of "at risk couples" for TM should be reconsidered. Table 1. Causes of death in Thalassemia Major and Thalassemia Intermedia patients. Diagnosis Causes of Death TM n (%) TI n (%) Cancer 3 (7,5) 5 (38,5) Heart Damage 16 (40,0) 2 (15,4) Infection 3 (7,5) 3 (23,1) Multi Organ Failure 1 (2,5) 0 (0,0) Stroke 1 (2,5) 0 (0,0) Liver Failure 3 (7,5) 1 (7,7) Not Available 11 (27,5) 1 (7,7) Other complications not related to Thalassemia 2 (5,0) 1 (7,7) Total 13 40 Figure 1. Kaplan-Meier Survival curves of Thalassemia Major versus Thalassemia Intermedia patients before and after the introduction of chelation treatment (DFO, 1965). Figure 1. Kaplan-Meier Survival curves of Thalassemia Major versus Thalassemia Intermedia patients before and after the introduction of chelation treatment (DFO, 1965). Disclosures Pepe: Chiesi: Speakers Bureau; ApoPharma Inc: Speakers Bureau; Novartis: Speakers Bureau.


2020 ◽  
Vol 26 (3) ◽  
pp. 253-262
Author(s):  
Seung-Hwan Lee ◽  
Eun-Joo Lee

AbstractThis paper proposes a weighted log-rank test that maintains sensitivity to realistic alternatives of two survival curves, such as crossing curves, in the presence of heavy censoring. The new test incorporates a weight function that changes over the censoring level, increasing adaptivity and flexibility of the commonly used weighted log-rank tests. The new statistic is asymptotically normal under the null hypothesis that there is no difference in survival between two groups. The performances of the new test are evaluated via simulations under both proportional and non-proportional alternatives. We illustrate the new method with a real-world application.


2020 ◽  
Vol 3 (3) ◽  
pp. 82-86
Author(s):  
Gede Wirya Kusuma Duarsa ◽  
Oka Udrayana ◽  
Yeni Kandarini ◽  
Raka Widiana ◽  
Marleen

Background. To determine risk factors that influence peritonitis event on patients with Continuous Ambulatory Peritoneal Dialysis (CAPD) in Sanglah Hospital, thus, we can prevent the occurrence of peritonitis in CRF patients with CAPD. Methods. This is a retrospective cohort study, which was conducted at the Sanglah Hospital in Denpasar from August to September 2016. All data are processed using SPSS 17.0 for Windows, data analysis by using the Kaplan Meier (K-M) curves, hypothesis using the log-rank test, while for the survival is by using the median or mean survival. The significance is determined by the value of p < 0.05 with 95% CI. Results. A total of 78 people (46 men and 32 women) who meet the inclusion criteria of this study. Thirteen people (16.7%) are experiencing peritonitis. K-M Survival Curves between in CRF patients with CAPD, with Age ≥ 50 years (51.36 months survival rates, 95% CI 44.79 until 57.93) with < 50 years (56.1 months Survival rates, 95% CI 51.41 until 60.78) with RR 2.54 log-rank p 0.084. K-M Survival Curves between in CRF patients with CAPD, with DM (mean 52.63 months survival rates, 95% CI 47.21 until 58.06) with No DM (56.88 months survival rates, 95% CI 52.89 until 60.88) with RR 4.16 and 0.037 log-rank p. Conclusion. There is a correlation between DM and the incidence of peritonitis in CRF patients with CAPD at Sanglah Hospital. However, age and education level are not related.


2018 ◽  
Vol 23 (3) ◽  
pp. 149-154
Author(s):  
Krisha Desai ◽  
Alexandra M. Vinograd ◽  
Mary Kate F. Abbadessa ◽  
Aaron E. Chen

Abstract Background: Ultrasound-guided peripheral intravenous lines are frequently used in patients with difficult access. We have previously reported on the longevity and complication rates of ultrasound-guided peripheral intravenous lines, but there are limited data comparing outcomes of ultrasound-guided peripheral intravenous lines to traditionally placed peripheral intravenous lines in children. The aim of this study was to compare the longevity and complication rates of ultrasound-guided peripheral intravenous lines to traditionally placed intravenous lines in a pediatric population. Methods: This study analyzed 300 ultrasound-guided peripheral intravenous lines and 552 traditionally placed intravenous lines using patient records to determine the reason and timing for intravenous line removal. A t-test was used to compare overall mean survival times, and a log-rank test was used to compare Kaplan-Meier survival curves. Complication rates were compared using a chi-squared test. Results: The survival times of ultrasound-guided peripheral intravenous lines (mean = 73 hours, SD = 68 hours) were significantly longer than those of traditionally placed intravenous lines (mean = 38 hours, SD = 29.4 hours), t(559) = 8.51, P &lt; .0001. Kaplan-Meier survival analysis yielded a median ultrasound-guided peripheral intravenous line survival time of 143 hours (IQR = 68–246) and a median traditionally placed intravenous line survival time of 100 hours (IQR = 65–106) with a significant difference between the 2 survival curves by the log-rank test. There was also no significant difference in complication rates between ultrasound-guided peripheral intravenous lines (34.8%) compared to traditionally placed intravenous lines (31.8%), x2(1, N = 517) = 0.465, P = .50. Conclusions: Our data suggests that ultrasound-guided peripheral intravenous lines are a viable option for children, including those with a history of difficult access. Survival times were longer for ultrasound-guided peripheral intravenous lines versus traditionally placed intravenous lines, and complication rates of the ultrasound-guided peripheral intravenous lines and traditionally placed intravenous lines were similar.


2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
A Hirata ◽  
Y Sotomi ◽  
T Kobayashi ◽  
R Amiya ◽  
A Hirayama ◽  
...  

Abstract Background Renal dysfunction is one of the high bleeding risk factors in patients with atrial fibrillation as presented in the HAS-BLED score. The impact of renal function on bleeding risk is, however, still to be investigated in the era of direct oral anticoagulants (DOAC). Methods We conducted a single-center prospective observational registry of NVAF patients with DOACs: the DIRECT registry (UMINehz745.112933283). All patients with NVAF (N=2216) who were users of dabigatran (N=648), rivaroxaban (N=538), apixaban (N=599), or edoxaban (N=431) from 2011 to 2017 were enrolled (71.6±10.8 years, mean follow-up duration: 407.2±388.3 days). In the present substudy, all patients were stratified by renal function. Creatinine clearance (CCr) was estimated with the Cockcroft-Gault equations with available creatinine at baseline. Patients were divided into 4 groups based on CCr. (CCr>80, CCr50–80, CCr30–50, and CCr<30). The primary endpoint was major bleeding according to the ISTH criteria. Clinical endpoints were compared between the groups (Kaplan-Meier analysis, Log-rank test). The influence of DOAC type in patients with renal dysfunction was also assessed for the primary endpoints of major bleeding. Results Kaplan-Meier estimated 2-year major bleeding rate significantly increased as renal function decreased (CCr>80 2.5%, CCr50–80 4.2%, CCr30–50 4.2%, CCr<30 7.8%, Log-rank test p<0.001). However, in patients with apixaban (low CCr 59.6±25.9ml), major bleeding does not appear to increase as renal function decreased.(CCr >80 9.2%, CCr 50–80 8.0%, CCr 30–50 10.3%, CCr<30 7.3%, Log-rank test p=0.97). Kaplan-Meier Analysis Conclusions Renal dysfunction increased bleeding risks in NVAS patients with DOACs. Apixaban might be safely used for patients with renal dysfunction.


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