scholarly journals Platelet counts in epileptic children receiving valproic acid

2020 ◽  
Vol 60 (1) ◽  
pp. 13-7
Author(s):  
Lilik Indrayati ◽  
Fadhilah Tia Nur ◽  
Bambang Soebagyo
Keyword(s):  
Valproic Acid ◽  
Epileptic Seizures ◽  
Term Treatment ◽  
Common Adverse Event ◽  
Platelet Counts ◽  
Central Java ◽  
Long Term Treatment ◽  
Epileptic Children ◽  
The Brain

Background Epileptic seizures are a transient occurrence resulting from abnormal, excessive, or synchronous neural activity in the brain. Epilepsy requires long-term treatment, increasingly larger doses, and combination therapy. Anti-epileptic drugs (AEDs), especially valproic acid (VPA), are the main treatment of choice. Thrombocytopenia is the most common adverse event from AEDs. Objective To evaluate platelet counts in epileptic children receiving valproic acid monotherapy vs. polytherapy. Methods This analytic, observational, retrospective cohort study was conducted in children with epilepsy below 18 years of age and treated in Dr. Moewardi Hospital, Surakarta, Central Java. Subjects had received VPA treatment for at least 6 months, either as monotherapy or polytherapy. There were 40 subjects in each group (VPA monotherapy vs. VPA polytherapy). The exclusion criteria were patients who had thrombocytopenia and did not take valproic acid regularly. The data was taken from laboratory and the outcome assessed was decreasing of platelet count. Results  Administration of VPA as monotherapy vs. polytherapy was not significantly associated with incidence of thrombocytopenia. However, duration of VPA use > 2 years was associated with significantly greater proportion of thrombocytopenia, with OR 33.0 (95%CI 4.157 to 261.962; P=0.001) compared to VPA use < 2 years. Similarly, VPA dose of >30 mg/kg/day was significantly associated with greater proportion of thrombocytopenia, with OR 4.081 (95%CI 1.337 to 12.458; P=0.013) compared to <30 mg/kg/day dosage. Conclusion Incidence of thrombocytopenia is not significantly different between VPA as a  monotherapy and polytherapy. However, higher VPA dose and longer VPA duration are associated with higher proportion of thrombocytopenia.

Long-Term Treatment with Romiplostim in Patients with Chronic Immune Thrombocytopenic Purpura (ITP): 3-Year Update from An Open-Label Extension Study

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 402-402 ◽  
Author(s):  
David J Kuter ◽  
James B Bussel ◽  
Adrian Newland ◽  
Joost TM de Wolf ◽  
Troy Guthrie ◽  
...  
Keyword(s):  
Platelet Count ◽  
Term Treatment ◽  
Duration Of Treatment ◽  
Open Label ◽  
Platelet Counts ◽  
Chronic Itp ◽  
Long Term Treatment ◽  
Open Label Extension ◽  
Grade 3

Abstract Chronic ITP is characterized by increased platelet destruction and suboptimal platelet production. Romiplostim is an investigational Fc-peptide fusion protein (peptibody) being studied for its ability to increase platelet counts in patients with chronic ITP. We report data from an open-label extension study of romiplostim in adult patients with chronic ITP. Collection of safety and efficacy data from long-term treatment of these patients is ongoing. Eligible patients had completed a prior romiplostim study and had platelet counts □50×109/L. Romiplostim was administered subcutaneously once weekly with dose adjustments to maintain a platelet count of 50–250×109/L. As of July 13 2007, 142 patients had been treated with romiplostim. Their median time since diagnosis was 6.4 years (range 0.6–46.4 years). Most were female (67%) and had previously undergone a splenectomy (60%). The median baseline platelet count was 17×109/L (range 1–50×109/L). The median duration of treatment was 65 weeks (range 1–156 weeks). Twenty-nine (20%) patients discontinued the study, 10 (7%) due to adverse events (AEs) [2 each of bone marrow reticulin and thrombosis; 1 each of bleeding, pain, cardiac arrest, pneumonia, hepatic and renal failure, and monoclonal gammopathy of undetermined significance]. Different measures of platelet count response were analyzed; any platelet counts within 8 weeks of receiving rescue medications were excluded from these analyses. Platelet counts were increased from baseline by ≥20×109/L more than 80% of the time in 54% of patients and more than 50% of the time in 73% of patients. Platelet counts remained above 20×109/L more than 90% of the time in 67% of patients and more than 50% of the time in 94% of patients. A platelet count &gt;50×109/L and double baseline was achieved by 30% (42/138) of patients after the first dose, by 51% (71/138) of patients after the third dose, and by 87% (124/142) of patients overall. The durability of platelet count increases was analyzed: platelet counts &gt;50×109/L were sustained for ≥10, ≥25, and ≥52 consecutive weeks in 78% (102/131), 54% (66/122), and 35% (29/84) of patients, respectively. The patient incidence of bleeding events both of any severity and of clinical significance (≥Grade 3) declined over time (Table). AEs were reported in 95% of patients, with most mild to moderate in severity. The most common were headache (37%); nasopharyngitis (32%); and contusion, fatigue and epistaxis (each 30%). AE frequency did not increase with time on study (Table). Bone marrow reticulin was present or increased in 8 patients with no evidence of progression to collagen fibrosis or chronic idiopathic myelofibrosis. Thrombotic events were reported in 7 (5%) patients; 6 had pre-existing risk factors for thrombosis. In conclusion, romiplostim increased platelet counts in most patients for most of the time, and clinically relevant bleeding was reduced over time. Romiplostim was well-tolerated and AEs did not increase with longer duration of treatment. Table. Summary of patient incidence of AEs by study period &lt;24 wks (N=142) n (%) 24 to &lt;48 wks (N=126) n (%) 48 to &lt;72 wks (N=97) n (%) 72 to &lt;96 wks (N=65) n (%) 96 to &lt;120 wks (N=29) n (%) 120 to &lt;144 wks (N=25) n (%) AEs 129 (91) 110 (87) 64 (66) 36 (55) 23 (79) 21 (84) Serious AEs 25 (18) 13 (10) 7 (7) 4 (6) 4 (14) 1 (4) Treatment-related AEs 48 (34) 14 (11) 12 (12) 7 (11) 4 (14) 3 (12) Treatment-related serious AEs 6 (4) 3 (2) 1 (1) 2 (3) 1 (3) 1 (4) Study withdrawals due to AEs 4 (3) 5 (4) 0 (0) 0 (0) 0 (0) 1 (4) Bleeding any grade 60 (42) 37 (29) 22 (23) 13 (20) 11 (38) 8 (32) Bleeding ≥ Grade 2 (moderate) 25 (18) 12 (10) 8 (8) 4 (6) 3 (10) 2 (8) Bleeding ≥ Grade 3 difference in thisresponsebetween refractory (severe) 9 (6) 1 (1) 1 (1) 1 (2) 0 (0) 0 (0)

Effects of long-term treatment with antiepileptic drugs on serum lipid levels in epileptic children

1994 ◽  
Vol 11 (2) ◽  
pp. 108-109
Author(s):  
M. Castro-Gago ◽  
I. Novo ◽  
S. Lojo ◽  
M.C. del Río ◽  
M. del Río ◽  
...  
Keyword(s):  
Antiepileptic Drugs ◽  
Serum Lipid ◽  
Term Treatment ◽  
Lipid Levels ◽  
Serum Lipid Levels ◽  
Long Term Treatment ◽  
Epileptic Children

Long-term treatment with clonidine and α-receptors in the brain of Normotensive rats

1984 ◽  
Vol 321 (1) ◽  
pp. 45-54 ◽  
Author(s):  
Franca Cerrito ◽  
Maria Martire ◽  
Paolo Preziosi
Keyword(s):  
Term Treatment ◽  
Long Term Treatment ◽  
The Brain

scholarly journals Spotlight on eltrombopag in pediatric ITP in China: a long-term observational study in real-world practice

2021 ◽  
Vol 5 (19) ◽  
pp. 3799-3806
Author(s):  
Xiaoling Cheng ◽  
LingLing Fu ◽  
Jingyao Ma ◽  
Hao Gu ◽  
Zhenping Chen ◽  
...  
Keyword(s):  
Adverse Events ◽  
Pediatric Patients ◽  
Complete Response ◽  
Term Treatment ◽  
Serious Adverse Events ◽  
Platelet Counts ◽  
Chronic Itp ◽  
Long Term Treatment ◽  
Concomitant Medications

Abstract Immune thrombocytopenia (ITP) is an autoimmune bleeding disorder with isolated thrombocytopenia and risk of hemorrhage. Treatment with eltrombopag increases and maintains hemostatic platelet counts; however, to date, long-term data are lacking on the outcome of children with ITP who are treated with eltrombopag. This prospective, observational, longitudinal cohort study evaluated the efficacy and safety of eltrombopag in pediatric patients with persistent or chronic ITP. For the 116 pediatric patients enrolled, duration of eltrombopag treatment was at least 3 months. Median effective dose was 25 mg/day, 50 mg/day, and 50 mg/day, respectively, for children age 5 years or younger, 6 to 11 years, or 12 years or older. In all, 89 patients (76.7%) achieved overall response, 53 (45.7%) achieved complete response, and 36 (31.0%) achieved response. Median platelet counts increased by week 1 and were sustained throughout the treatment period. During treatment with eltrombopag, the proportion of patients with grade 1 to 4 bleeding symptoms decreased from 83.61% at baseline to 9.88% at 6 months when only grade 1 was reported. Forty-three patients (37.1%) reported using concomitant medications at study entry, which was reduced to 1 patient (2.5%) who needed concomitant medications at 12 months. All adverse events were grade 1 or 2 according to Common Terminology Criteria for Adverse Events. No serious adverse events, cataracts, malignancies, or thromboses were reported during the study. Long-term treatment with eltrombopag was generally safe, well tolerated, and effective in maintaining platelet counts and reducing bleeding in most pediatric patients with persistent or chronic ITP. Combined with future studies, these findings will help establish how eltrombopag should best be used in the management of pediatric patients with East Asian ancestry.

Essential Thrombocythemia: A Prospective Analysis of Efficacy and Safety of Anagrelide for Long Term Treatment in Patients Below and Above the Age of 60 Years.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3561-3561 ◽  
Author(s):  
Heinz Gisslinger
Keyword(s):  
Disease Progression ◽  
Essential Thrombocythemia ◽  
Term Treatment ◽  
Younger Patients ◽  
Platelet Counts ◽  
Patient Cohort ◽  
Long Term Treatment ◽  
History Of

Abstract Thromboembolic complications and less frequently bleeding characterize morbidity and mortality in patients with essential thrombocythemia (ET). The average estimated risk for thrombotic episodes in ET is 6.6% per patient year and platelet counts above 1000G/L, older age (&gt;60 years) and a history of thrombosis were identified as major risk factors for serious complications. Since a direct correlation of platelet numbers with the number of thrombotic events is suggested by numerous prospective trials, it is generally accepted that these patients should receive platelet lowering treatment. Although hydroxyurea is considered as the treatment of choice in ET, there is still major concern about leukemogenicity of this compound. Anagrelide, on the other hand seems to be better tolerated in younger patients, but this has not been proved by prospective studies. It is therefore the aim of the present study to compare tolerability and efficacy of anagrelide (Thromboreductin, a novel non-immediate release formulation of anagrelide) over a prolonged time between ET patients below the age of 60 years with those above the age of 60 years. Among a total of 722 patients with ET on anagrelide who were prospectively documented within a standardized patient registry, 386 patients were previously untreated at the time of initiation of anagrelide therapy and this therapy was prospectively documented up to 5 years. The median age of this previously untrated patient cohort was 58 years (6 to 91 years), 179 (46,4%) patients were older than 60 years and 274 (71%) patients were female. Sixtythree patients (16,3%) had a history of thrombosis. The main inclusion criteria were those defined for qualifying a patient to be at high risk. During the first two years of follow up, the group of younger patients (&lt; 60 years) did receive higher daily doses of anagrelide as compared to the older patient cohort (2,0mg vs.1,5mg). Anagrelide reduced platelet counts from a median baseline value of 920G/L to 581G/L and 382 G/L on month 3 and month 60 respectively. The overall response rate (platelet counts&lt; 600G/L) was 64%. The rate of complete response (platelet counts &lt;450G/L) went up from 58% after one year to 71% after 5 years of treatment. Group comparisons showed that a significant response to anagrelide was achieveable in patients below and above the age of 60 years with no significant difference between the two groups. With regard to safety, there is no evidence that anagrelide gives concern to an increased rate of bleeding (2%) or disease progression. Over the 5 year follow up period an adverse event was recorded in 24% of patients. The rate of treatment discontinuation as a result of adverse events was low (5%), treatment was discontinued when no further response was achieved or a negative risk benefit judgement of the treating physician was made. Only 4 patients of the whole cohort discontinued anagrelide due to disease progression. A small number of patients (12/722), 1,7%) died during the 5 years observation period, all cases were described as not drug related. In summary the data confirm that anagrelide yields comparable response rates in the two age groups during long term treatment.

scholarly journals Imbalanced Dopaminergic Transmission Mediated by Serotonergic Neurons in L-DOPA-Induced Dyskinesia

2012 ◽  
Vol 2012 ◽  
pp. 1-16 ◽  
Author(s):  
Sylvia Navailles ◽  
Philippe De Deurwaerdère
Keyword(s):  
Brain Regions ◽  
Term Treatment ◽  
Serotonergic Neurons ◽  
Brain Areas ◽  
Dopaminergic Transmission ◽  
The Core ◽  
Long Term Treatment ◽  
The Brain ◽  
Serotonergic Innervation

L-DOPA-induced dyskinesias (LIDs) are one of the main motor side effects of L-DOPA therapy in Parkinson's disease. The review will consider the biochemical evidence indicating that the serotonergic neurons are involved in the dopaminergic effects of L-DOPA in the brain. The consequences are an ectopic and aberrant release of dopamine that follows the serotonergic innervation of the brain. After mid- to long-term treatment with L-DOPA, the pattern of L-DOPA-induced dopamine release is modified. In several brain regions, its effect is dramatically reduced while, in the striatum, its effect is quite preserved. LIDs could appear when the dopaminergic effects of L-DOPA fall in brain areas such as the cortex, enhancing the subcortical impact of dopamine and promoting aberrant motor responses. The consideration of the serotonergic system in the core mechanism of action of L-DOPA opens an important reserve of possible strategies to limit LIDs.

Safety of long-term treatment of HAM/TSP patients with valproic acid

Blood ◽  
2011 ◽  
Vol 118 (24) ◽  
pp. 6306-6309 ◽  
Author(s):  
Stéphane Olindo ◽  
Gildas Belrose ◽  
Nicolas Gillet ◽  
Sabrina Rodriguez ◽  
Mathieu Boxus ◽  
...  
Keyword(s):  
Valproic Acid ◽  
Proviral Load ◽  
Spastic Paraparesis ◽  
Term Treatment ◽  
Final Visit ◽  
Open Label ◽  
Long Term Treatment ◽  
Time Test ◽  
Walking Time

Abstract HTLV-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a neurodegenerative disease of the central nervous system induced by human T-lymphotropic virus type 1. As a potential therapeutic approach, we previously suggested reducing the proviral load by modulating lysine deacetylase activity using valproic acid (VPA) and exposing virus-positive cells to the host immune response. We conducted a single-center, 2-year, open-label trial, with 19 HAM/TSP volunteers treated with oral VPA. Proviral load, CD38/HLA-DR expression, and CD8+ lysis efficiency were not significantly affected by VPA. Mean scores of HAM/TSP disability did not differ between baseline and final visit. Walking Time Test increased significantly (> 20%) in 3 patients and was in keeping with minor VPA side effects (drowsiness and tremor). Walking Time Test improved rapidly after VPA discontinuation. We conclude that long-term treatment with VPA is safe in HAM/TSP.

Safety and efficacy of eltrombopag for treatment of chronic immune thrombocytopenia: results of the long-term, open-label EXTEND study

Blood ◽  
2013 ◽  
Vol 121 (3) ◽  
pp. 537-545 ◽  
Author(s):  
Mansoor N. Saleh ◽  
James B. Bussel ◽  
Gregory Cheng ◽  
Oliver Meyer ◽  
Christine K. Bailey ◽  
...  
Keyword(s):  
Immune Thrombocytopenia ◽  
Term Treatment ◽  
World Health ◽  
Concomitant Treatment ◽  
Open Label ◽  
Safety And Efficacy ◽  
Platelet Counts ◽  
Long Term Treatment ◽  
Chronic Immune Thrombocytopenia

Abstract Patients with chronic immune thrombocytopenia may have bleeding resulting from low platelet counts. Eltrombopag increases and maintains hemostatic platelet counts; however, to date, outcome has been reported only for treatment lasting ≤ 6 months. This interim analysis of the ongoing open-label EXTEND (Eltrombopag eXTENded Dosing) study evaluates the safety and efficacy of eltrombopag in 299 patients treated up to 3 years. Splenectomized and nonsplenectomized patients achieved platelets ≥ 50 000/μL at least once (80% and 88%, respectively). Platelets ≥ 50 000/μL and 2 × baseline were maintained for a median of 73 of 104 and 109 of 156 cumulative study weeks, respectively. Bleeding symptoms (World Health Organization Grades 1-4) decreased from 56% of patients at baseline to 20% at 2 years and 11% at 3 years. One hundred (33%) patients were receiving concomitant treatments at study entry, 69 of whom attempted to reduce them; 65% (45 of 69) had a sustained reduction or permanently stopped ≥ 1 concomitant treatment. Thirty-eight patients (13%) experienced ≥ 1 adverse events leading to study withdrawal, including patients meeting protocol-defined withdrawal criteria (11 [4%] thromboembolic events, 5 [2%] exceeding liver enzyme thresholds). No new or increased incidence of safety issues was identified. Long-term treatment with eltrombopag was generally safe, well tolerated, and effective in maintaining platelet counts in the desired range. This study is registered at www.clinicaltrials.gov as NCT00351468.

scholarly journals Safety and efficacy of long-term treatment of chronic/persistent ITP with eltrombopag: final results of the EXTEND study

Blood ◽  
2017 ◽  
Vol 130 (23) ◽  
pp. 2527-2536 ◽  
Author(s):  
Raymond S. M. Wong ◽  
Mansoor N. Saleh ◽  
Abderrahim Khelif ◽  
Abdulgabar Salama ◽  
Maria Socorro O. Portella ◽  
...  
Keyword(s):  
Term Treatment ◽  
Safety And Efficacy ◽  
Platelet Counts ◽  
Key Points ◽  
Long Term Treatment

Key Points Median platelet counts increased to 50 × 109/L or more by week 2 in patients with ITP and were maintained for ≥2 years. Lower platelet counts, more previous therapies, and/or splenectomy resulted in good but somewhat lower responses to eltrombopag.

scholarly journals Long-Term Treatment of Cuban Policosanol Attenuates Abnormal Oxidative Stress and Inflammatory Response via Amyloid Plaques Reduction in 5xFAD Mice

Antioxidants ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1321
Author(s):  
Jin-Ho Kim ◽  
Dong-Kyun Lim ◽  
Yoo-Hun Suh ◽  
Keun-A Chang
Keyword(s):  
Neurodegenerative Disorder ◽  
Lipid Peroxide ◽  
Amyloid Plaques ◽  
Term Treatment ◽  
Number Of Patients ◽  
Tnf Α ◽  
Long Term Treatment ◽  
5Xfad Mice ◽  
The Brain

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder resulting in cognitive decline or dementia, the number of patients with AD is continuously increasing. Although a lot of great progress has been made in research and development of AD therapeutics, there is no fundamental cure for this disease yet. This study demonstrated the memory-improving effects of Cuban policosanol (PCO) in 5xFAD mice, which is an animal model of AD. Following 4-months of treatment with PCO in 5xFAD mice, we found that the number of amyloid plaques decreased in the brain compared to the vehicle-treated 5xFAD mice. Long-term PCO treatment in 5xFAD mice resulted in the reduction of gliosis and abnormal inflammatory cytokines level (interleukin [IL]-1β, IL-6, and tumor necrosis factor [TNF]-α) in the cortex and hippocampus. Levels of lipid peroxide (4-hydroxynonenal [4-HNE]) and superoxide dismutase (SOD1 and SOD2) levels were also recoverd in the brains of PCO-treated 5xFAD mice. Notably, PCO administration reduced memory deficits in the passive avoidance test, as well as synaptic loss (PSD-95, synaptophysin) in 5xFAD mice. Collectively, we identified the potential effects of PCO as a useful supplement to delay or prevent AD progression by inhibiting the formation of Aβ plaques in the brain.

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