scholarly journals Effects of Carbamazepine and Phenytoin on Pharmacokinetics and Pharmacodynamics of Rivaroxaban

Pharmaceutics ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 1040
Author(s):  
Lien Thi Ngo ◽  
Sung-yoon Yang ◽  
Quyen Thi Tran ◽  
Sang Kyum Kim ◽  
Hwi-yeol Yun ◽  
...  
Keyword(s):  
Adverse Events ◽  
Compartmental Model ◽  
Control Group ◽  
Therapeutic Effects ◽  
Pharmacokinetics And Pharmacodynamics ◽  
Elimination Kinetics ◽  
Post Stroke ◽  
Lack Of Information ◽  
Disposition Model ◽  
Model Approach

Rivaroxaban (RIV) is commonly prescribed with carbamazepine or phenytoin (CBZ/PHT) in post-stroke seizure or post-stroke epilepsy patients. Although adverse events have been reported in several previous studies when they are coadministered, there are no studies of the interactions between these drugs. Therefore, our study was conducted to solve this lack of information. The potential effects of CBZ/PHT were investigated by comparing the pharmacokinetic (PK) and pharmacodynamic (PD) parameters of RIV between the control group (RIV alone) and the test groups (RIV administered with CBZ/PHT) in rats using the noncompartmental analysis (NCA) and the compartmental model approach. The NCA results indicate that AUCt of RIV decreased by 57.9% or 89.7% and Cmax of RIV decreased by 43.3% or 70.0% after administration of CBZ/PHT, respectively. In addition, both CBZ and PHT generally reduced the effects of RIV on the prothrombin times of the blood samples. PK profiles of RIV were most properly described by a two-compartment disposition model with a mixed first- and zero-order absorption kinetics and a first-order elimination kinetics. The compartmental model approach showed that a 211% or 1030% increase in CL/F of RIV and a 33.9% or 43.4% increase in D2 of RIV were observed in the test groups by the effects of CBZ/PHT, respectively. In conclusion, CBZ and PHT significantly reduced RIV exposure and therefore reduced the therapeutic effects of RIV. Consequently, this might result in adverse events due to insufficient RIV concentration to attain its therapeutic effects. Further studies are needed to validate this finding.

PP455 Cost-effectiveness Of Ixazomib-Based Regimen Compared With Bortezomib-Based Regimen In Chinese Patients With Relapsed/Refractory Multiple Myeloma: A Retrospective Study

2020 ◽  
Vol 36 (S1) ◽  
pp. 36-37
Author(s):  
Pei Wang ◽  
Jing Li ◽  
Yang Yang ◽  
Peng Liu
Keyword(s):  
Multiple Myeloma ◽  
Adverse Events ◽  
Staging System ◽  
Chinese Patients ◽  
Disease Stage ◽  
Control Group ◽  
Therapeutic Effects ◽  
Lower Grade ◽  
Refractory Multiple Myeloma ◽  
Grade 3

IntroductionThe treatment of relapsed/refractory multiple myeloma (RRMM), a common hematological malignancy, remains a great challenge in China, partially due to the limited accessibility to novel agents and inadequate public health insurance coverage. Ixazomib, a novel oral proteasome inhibitor (PI), was approved by the China Food and Drug Administration (CFDA) for RRMM in 2018. While bortezomib, a traditional PI, is the recommended agent in the clinical guideline for MM. Here, we compared their costs and effectiveness.MethodsRRMM patients who has received an ixazomib-based regimen (at least 2 cycles) were analyzed. Using a propensity score matching method, we generated a control group of RRMM patients who received the bortezomib-based regimen. The criteria included the number of treatment lines, age, and the revised international staging system stage (R-ISS) which representing the disease stage for myeloma, and paired at a ratio of 1:2 (allowing one control to match multiples). The difference in hospitalization stay, grade 3/4 adverse events rates, overall response rate (ORR), mortality during treatment, and treatment costs was then compared.ResultsNineteen patients received ixazomib and twenty-seven that received bortezomib were included. The ixazomib-group demonstrated a shorter hospital stay (9 days versus 27 days, p < 0.001), lower grade 3–4 adverse events rates (42.1% versus 55.6%, p < 0.001), higher ORR (63.2% versus 48.1%, p = 0.228), and lower mortality rate during treatment (0% versus 7.4%, p = 0.169) than that of bortezomib-group. The ixazomib group had lower total costs (127,620CNY versus 156,424CNY [18,033USD versus 22,103USD], p > 0.05), lower drug costs (98,376CNY versus 103,307CNY [13,901USD versus 14,598USD], p > 0.05), and the lower costs of supportive treatment (5,507CNY versus 14,701 CNY [778USD versus 2,077USD], p < 0.001). Only in terms of self-funded costs, the bortezomib-based regimen was significantly lower (37,127CNY versus 11,521CNY [5,246USD versus 1,628USD], p < 0.001).ConclusionsCompared with the bortezomib-based regimen, the ixazomib-based regimen has better therapeutic effects on MM patients while saving costs. Hence, it may be preferable for use in the treatment of RRMM in China.

A Self-Empowered Upper Limb Repetitive Engagement Program to Improve Upper Limb Recovery Early Post-Stroke: Phase II Pilot Randomized Controlled Trial

2021 ◽  
pp. 154596832110329
Author(s):  
Lay Fong Chin ◽  
Kathryn S. Hayward ◽  
Audrey Lik Ming Chai ◽  
Sandra G. Brauer
Keyword(s):  
Adverse Events ◽  
Upper Limb ◽  
Controlled Trial ◽  
Motor Evoked Potential ◽  
Inpatient Rehabilitation ◽  
Dropout Rate ◽  
Potential Effect ◽  
Control Group ◽  
Post Intervention ◽  
Post Stroke

Background. Time outside therapy provides an opportunity to increase upper limb (UL) use during post-stroke hospitalization. Objective. To determine if a self-directed UL program outside therapy (Self-Empowered UL Repetitive Engagement, SURE) was feasible and to explore the potential effect of the SURE program on UL use and recovery. Methods. Twenty-three patients from an inpatient rehabilitation center who were ≤21 days post-stroke and had a Fugl Meyer UL (FMUL) score ≤50 and a positive motor evoked potential (MEP+) response were randomized (stratified by impairment) to either experimental group (SURE: individualized, UL self-exercise and use outside therapy for 6 hours/week for 4 weeks) or control group (education booklet). Feasibility was evaluated by program adherence, dropout rate, adverse events, and satisfaction. Potential effect was measured by paretic UL use via accelerometry weekly during the intervention, FMUL and Action Research Arm Test (ARAT) at baseline (Week 0), post-intervention (Week 4), and follow-up (Week 8 and Week 16). Results. Adherence to SURE was high: 87% program completion (mean 313±75 repetitions/day). There were no dropouts, no adverse events related to SURE, and patient satisfaction averaged 7.8/10. Experimental participants achieved an additional hour of UL use daily (range: .3–1.2 hours/day) compared to control. Significant improvements in FMUL and ARAT were observed in both groups from Week 0 to Week 4 and to Week 8 ( P ≤ .002), which were maintained to Week 16. There were no differences between groups ( P ≥ .119). Conclusions. SURE was a feasible self-directed program that increased UL use in MEP+ individuals with moderate-severe impairment early post-stroke. Further studies with larger sample sizes and potentially higher dose are required to determine efficacy.

scholarly journals Functional electrical stimulation reduces pain and shoulder subluxation in chronic post-stroke patients?

2020 ◽  
pp. 1-5
Author(s):  
Willian Vasconcellos da Silva ◽  
Gabriele Natane de Medeiros Cirne ◽  
Edson Meneses da Silva Filho ◽  
Enio Walker Azevedo Cacho ◽  
Johnnatas Mikael Lopes ◽  
...  
Keyword(s):  
Electrical Stimulation ◽  
Functional Electrical Stimulation ◽  
Total Duration ◽  
Chronic Phase ◽  
Control Group ◽  
Mcgill Pain Questionnaire ◽  
Therapeutic Effects ◽  
Stroke Patients ◽  
Post Stroke ◽  
Scale Scores

Background: Shoulder subluxation is a common complication of cerebral vascular accident (stroke) and the use of Functional Electrical Stimulation (FES) within the rehabilitation process is extremely important. Objective: To analyze the therapeutic effects of FES in the treatment of chronic shoulder subluxation in post-stroke patients. Method: This is a case study of patients with radiologically subluxation confirmed, who were randomly divided into two groups: Control Group (CG) and Treatment Group (TG). Patients were assessed before and after treatment and at the 2-month follow-up. The assessment consisted of the modified Ashworth scale; passive goniometry; Fugl-Meyer scale; McGill pain questionnaire and evaluation of shoulder subluxation by radiography. The CG did not receive physiotherapeutic intervention; and TG underwent 20 sessions of motor kinesiotherapy and FES associated with functional exercises with a total duration of 1 hour, three times a week, for 7 weeks. The data were analyzed descriptively. Results: The mean age of CG participants was 82.5 ± 1.5 years and of the TG was 70.5 ± 13.5 years. All of them were retired, sedentary, non-smokers/alcoholics and had hemiparesis on the left side. There was an approximate increase of 10o for most joint movements of the shoulder, improvement in McGill scale scores and reduction of shoulder subluxation in TG patients. Conclusion: FES associated with functional movements was effective in reducing the degree of subluxation of the shoulder joint and decreased pain in subjectsin the chronic phase of the post-stroke.

scholarly journals The Impact of Voluntary Exercise on Stroke Recovery

2021 ◽  
Vol 15 ◽  
Author(s):  
Klara J. Lohkamp ◽  
Amanda J. Kiliaan ◽  
Justin Shenk ◽  
Vivienne Verweij ◽  
Maximilian Wiesmann
Keyword(s):  
Functional Connectivity ◽  
Voluntary Exercise ◽  
Stroke Recovery ◽  
Control Group ◽  
Therapeutic Effects ◽  
Stroke Treatment ◽  
Post Stroke ◽  
Post Surgery ◽  
Running Wheels ◽  
The Impact

Stroke treatment is limited to time-critical thrombectomy and rehabilitation by physiotherapy. Studies report beneficial effects of exercise; however, a knowledge gap exists regarding underlying mechanisms that benefit recovery of brain networks and cognition. This study aims to unravel therapeutic effects of voluntary exercise in stroke-induced mice to develop better personalized treatments. Male C57Bl6/JOlaHsd mice were subjected to transient middle cerebral artery occlusion. After surgery, the animals were divided in a voluntary exercise group with access to running wheels (RW), and a control group without running wheels (NRW). During 6 days post-stroke, activity/walking patterns were measured 24/7 in digital ventilated cages. Day 7 post-surgery, animals underwent MRI scanning (11.7T) to investigate functional connectivity (rsfMRI) and white matter (WM) integrity (DTI). Additionally, postmortem polarized light imaging (PLI) was performed to quantify WM fiber density and orientation. After MRI the animals were sacrificed and neuroinflammation and cerebral vascularisation studied. Voluntary exercise promoted myelin density recovery corresponding to higher fractional anisotropy. The deteriorating impact of stroke on WM dispersion was detected only in NRW mice. Moreover, rsfMRI revealed increased functional connectivity, cerebral blood flow and vascular quality leading to improved motor skills in the RW group. Furthermore, voluntary exercise showed immunomodulatory properties post-stroke. This study not only helped determining the therapeutic value of voluntary exercise, but also provided understanding of pathological mechanisms involved in stroke.

Assessment of biochemical determinants in Multiple Sclerosis patients following the oral administration of β-D-Mannuronic acid [M2000]

2020 ◽  
Vol 17 ◽  
Author(s):  
Mohamad Reza Nikouei Moghaddam ◽  
Monireh Movahedi ◽  
Maryam Bananej ◽  
Soheil Najafi ◽  
Nahid Beladi Moghadam ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Uric Acid ◽  
Vitamin D3 ◽  
Chronic Inflammatory Disease ◽  
Toxic Effects ◽  
Control Group ◽  
Therapeutic Effects ◽  
Mannuronic Acid ◽  
Anti Inflammatory ◽  
Multiple Sclerosis Patients

Background: Multiple sclerosis is an autoimmune chronic inflammatory disease of the central nervous system that can lead to some serious disabilities. Despite using various immunomodulatory and anti-inflammatory drugs that have therapeutic effects, they cannot reduce its progression completely, and have some unwanted side effects too. The immunomodulatory and anti-inflammatory effects of the β-D-Mannuronic acid [M2000] have been proven in several surveys, and the present research was designed to determine its toxicity and therapeutic effects in MS patients. Methods: This study was performed on 15 MS patients who took 25 mg/kg/day the oral form of the β-D-Mannuronic acid for six months, and 15 healthy people as a control group. Serum levels of Urea, Creatinine, GGT, Vitamin D3, Uric acid, and Anti-Phospholipids were compared to evaluate the therapeutic and possible toxic effects of this drug after this period. Results: Non- toxic effects through the study of Urea, Creatinine, GGT, and non-significant changes in Uric acid and AntiPhospholipids levels, besides a significant rise in Vitamin, D3 levels in the M2000 treated cases were found. Conclusions: Our results suggested that β-D-Mannuronic acid is a safe drug and has no toxicity when administered orally and also has some therapeutic effects in MS patients.

Efficacy and Safety of Non-Steroidal Anti-Androgens in Patients with Metastatic Prostate Cancer: Meta-Analysis of Randomized Controlled Trials

2020 ◽  
Vol 15 (1) ◽  
pp. 34-47 ◽  
Author(s):  
Muhammed Rashid ◽  
Madhan Ramesh ◽  
K. Shamshavali ◽  
Amit Dang ◽  
Himanshu Patel ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Adverse Events ◽  
Randomized Controlled Trials ◽  
Quality Assessment ◽  
Cochrane Library ◽  
Control Group ◽  
Controlled Trials ◽  
Efficacy And Safety ◽  
Randomized Controlled ◽  
Significant Difference

Background: Prostate cancer (PCa) is the sixth primary cause of cancer death. However, conflicts are present about the efficacy and safety of Non-steroidal anti-androgens (NSAA) for its treatment. The aim of this study was to assess the efficacy and safety of NSAAs versus any comparator for the treatment of advanced or metastatic PCa (mPCa). Methodology: MEDLINE and the Cochrane Library were searched. References of included studies and clinicaltrials.gov were also searched for relevant studies. Only English language studies after 1990 were considered for review. Randomized controlled trials (RCTs) examining the efficacy and safety of NSAAs as compared with any other comparator including surgery or chemotherapy in mPCa patients were included. The outcomes include efficacy, safety and the tolerability of the treatment. The Cochrane Risk of Bias Assessment Tool was used for quality assessment. Two authors were independently involved in the selection, extraction and quality assessment of included studies and disagreements were resolved by discussion or by consulting a third reviewer. Results: Fifty-eight out of 1307 non-duplicate RCTs with 29154 patients were considered for the review. NSAA showed significantly better progression-free survival [PFS] (Hazard ratio [HR], 0.60; 95% confidence interval [CI], 0.46-0.78; P=0.0001), time to distant metastasis or death [TTD] (HR, 0.80; 95% CI 0.73-0.91; p<0.0001), objective response (Odds ratio [OR], 1.64; 95% CI 1.06-2.54; P=0.03) and clinical benefits (OR, 1.33; 95% CI 1.08-1.63; P=0.006) as compared to the control group. There was no significant difference observed between the groups in terms of overall survival (HR, 0.95; 95%CI, 0.87-1.03; P=0.18) and time to progression (HR, 0.93; 95% CI 0.77-1.11; P=0.43). Treatment-related adverse events were more with the NSAA group, but the discontinuation due to lack of efficacy reason was 43% significantly lesser than the control group in patients with mPCa. Rest of the outcomes were appeared to be non-significant. Conclusion: Treatment with NSAA was appeared to be better efficacious with respect to PFS, TTD, and response rate with considerable adverse events when compared to the control group in patients with metastatic PCa.

An Internet-based health gateway device for interactive communication and automatic data uploading: Clinical efficacy for type 2 diabetes in a multi-centre trial

2016 ◽  
Vol 23 (6) ◽  
pp. 595-604 ◽  
Author(s):  
Jae Hyoung Cho ◽  
Hun-Sung Kim ◽  
Seung Hyun Yoo ◽  
Chang Hee Jung ◽  
Woo Je Lee ◽  
...  
Keyword(s):  
Adverse Events ◽  
Healthcare System ◽  
Glucose Control ◽  
Large Scale ◽  
Diabetes Management ◽  
Intervention Group ◽  
Diabetes Control ◽  
Control Group ◽  
Anthropometric Parameters ◽  
Automatic Data

Introduction The aim of this study was to improve the quality of diabetes control and evaluate the efficacy of an Internet-based integrated healthcare system for diabetes management and safety. Methods We conducted a large-scale, multi-centre, randomized clinical trial involving 484 patients. Patients in the intervention group ( n = 244) were treated with the Internet-based system for six months, while the control group ( n = 240) received the usual outpatient management over the same period. HbA1c, blood chemistries, anthropometric parameters, and adverse events were assessed at the beginning of the study, after three months, and the end of the study. Results There were no initial significant differences between the groups with respect to demographics and clinical parameters. Upon six-month follow-up, HbA1c levels were significantly decreased from 7.86 ± 0.69% to 7.55 ± 0.86% within the intervention group ( p < 0.001) compared to 7.81 ± 0.66% to 7.70 ± 0.88% within the control group. Postprandial glucose reduction was predominant. A subgroup with baseline HbA1c higher than 8% and good compliance achieved a reduction of HbA1c by 0.8 ± 1.05%. Glucose control and waist circumference reduction were more effective in females and subjects older than 40 years of age. There were no adverse events associated with the intervention. Discussion This e-healthcare system was effective for glucose control and body composition improvement without associated adverse events in a multi-centre trial. This system may be effective in improving diabetes control in the general population.

EXPRESS: Altering the rehabilitation environment to improve stroke survivor activity (AREISSA): a Phase II trial.

2021 ◽  
pp. 174749302110069
Author(s):  
Heidi Janssen ◽  
Louise Ada ◽  
Sandy Middleton ◽  
Michael Pollack ◽  
Michael Nilsson ◽  
...  
Keyword(s):  
Adverse Events ◽  
Clinical Outcomes ◽  
Environmental Enrichment ◽  
Brain Plasticity ◽  
Social Activity ◽  
Stroke Survivor ◽  
Group Differences ◽  
Control Group ◽  
Serious Adverse Events ◽  
Clinical Trial Registration

Background: Environmental enrichment involves organisation of the environment and provision of equipment to facilitate engagement in physical, cognitive and social activity. In animals with stroke, it promotes brain plasticity and recovery. Aims: To assess the feasibility and safety of a patient-driven model of environmental enrichment incorporating access to communal and individual environmental enrichment. Methods: A non-randomised cluster trial with blinded measurement involving people with stroke (n=193) in 4 rehabilitation units was carried out. Feasibility was operationalised as activity 10 days after admission to rehabilitation and availability of environmental enrichment. Safety was measured as falls and serious adverse events. Benefit was measured as clinical outcomes at 3 months, by an assessor blinded to group. Results: The experimental group (n=91) spent 7% (95% CI -14 to 0) less time inactive, 9% (95% CI 0 to 19) more time physically, and 6% (95% CI 2 to 10) more time socially active than the control group (n=102). Communal environmental enrichment was available 100% of the time, but individual environmental enrichment was rarely within reach (24%) or sight (39%). There were no between-group differences in serious adverse events or falls at discharge or 3 months nor in clinical outcomes at 3 months. Conclusions: This patient-driven model of environmental enrichment was feasible and safe. However, the very modest increase in activity by people with stroke, and the lack of benefit in clinical outcomes 3 months after stroke do not provide justification for an efficacy trial. Clinical Trial Registration: ANZCTR 12613000796785 Words: 245

Single Instillation of Hypertonic Saline Immediately Following Transurethral Resection of Bladder Tumor for Recurrence Prevention –A Phase I Study

2021 ◽  
pp. 1-6
Author(s):  
Jonathan Modai ◽  
Alexey Kovalyonok ◽  
Avigdor Scherz ◽  
Dina Preise ◽  
Yuval Avda ◽  
...  
Keyword(s):  
Adverse Events ◽  
Hypertonic Saline ◽  
Serum Sodium ◽  
Transurethral Resection ◽  
Bladder Tumor ◽  
Osmotic Dehydration ◽  
Control Group ◽  
Plasma Sodium ◽  
Pelvic Cavity ◽  
Blue Discoloration

BACKGROUND: Urologic guidelines recommend perioperative instillation of chemotherapy after transurethral resection of bladder tumor (TURBT) to decrease tumor recurrence, yet implementation of this recommendation is partial due to associated morbidity. Hypertonic saline destroys cells by osmotic dehydration and might present a safer alternative. OBJECTIVE: To evaluate the safety of 3% hypertonic saline (Hypersal) intravesical instillation following TURBT in rats and in humans. METHODS: In 8 rats whose bladders were electrically injured, intravesical blue-dyed Hypersal was administered. We measured serum sodium levels before and after instillation and pathologically evaluated their pelvic cavity for signs of inflammation or blue discoloration. Twenty-four patients were recruited to the human trial (NIH-NCT04147182), 15 comprised the interventional and 10 the control group (one patient crossed over). Hypersal was given postoperatively. Serum sodium was measured before, 1 hour and 12–24 hours after instillation. Adverse effects were documented and compared between the groups. RESULTS: In rats, average sodium levels were 140.0 mEq/L and 140.3 mEq/L before and following instillation, respectively. Necropsy revealed no signs of inflammation or blue discoloration. In humans the average plasma sodium levels were 138.6 mEq∖L, 138.8 mEq∖L and 137.7 mEq∖L before, 1 hour and 12–24 hours after instillation, respectively. During the postoperative follow-up there was one case of fever. A month after the surgery, dysuria was reported by 5 patients while urgency and hematuria were reported by one patient each. The most severe adverse events were grade 2 on the Clavien-Dindo scale. Adverse events were similar in the control group. CONCLUSIONS: Hypersal instillation is safe and tolerable immediately after TURBT.

The Effect of Lavender Oil on Perioperative Pain, Anxiety, Depression, and Sleep after Microvascular Breast Reconstruction: A Prospective, Single-Blinded, Randomized, Controlled Trial

2021 ◽  
Author(s):  
Ronnie L. Shammas ◽  
Caitlin E. Marks ◽  
Gloria Broadwater ◽  
Elliot Le ◽  
Adam D. Glener ◽  
...  
Keyword(s):  
Randomized Controlled Trial ◽  
Adverse Events ◽  
Breast Reconstruction ◽  
Controlled Trial ◽  
Depression Scale ◽  
Control Group ◽  
Lavender Oil ◽  
Entire Cohort ◽  
Randomized Controlled ◽  
Anxiety Depression

Abstract Background Psychosocial distress, depression, or anxiety can occur in up to 50% of women after a breast cancer diagnosis and mastectomy. The purpose of this study was to assess the potential benefit of lavender oil as a perioperative adjunct to improve anxiety, depression, pain, and sleep in women undergoing microvascular breast reconstruction. Methods This was a prospective, single-blinded, randomized, controlled trial of 49 patients undergoing microvascular breast reconstruction. Patients were randomized to receive lavender oil or placebo (coconut oil) throughout their hospitalization. The effect of lavender oil on perioperative stress, anxiety, depression, sleep, and pain was measured using the hospital anxiety and depression scale, Richards–Campbell Sleep Questionnaire, and the visual analogue scale. Results Twenty-seven patients were assigned to the lavender group and 22 patients were assigned to the control group. No significant differences were seen in the perioperative setting between the groups with regard to anxiety (p = 0.82), depression (p = 0.21), sleep (p = 0.86), or pain (p = 0.30) scores. No adverse events (i.e., allergic reaction) were captured, and no significant differences in surgery-related complications were observed. When evaluating the entire cohort, postoperative anxiety scores were significantly lower than preoperative scores (p < 0.001), while depression scores were significantly higher postoperatively as compared with preoperatively (p = 0.005). Conclusion In the setting of microvascular breast reconstruction, lavender oil and aromatherapy had no significant adverse events or complications; however, there were no measurable advantages pertaining to metrics of depression, anxiety, sleep, or pain as compared with the control group.

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