scholarly journals Serum lysophosphatidylcholines to phosphatidylcholines ratio is associated with symptomatic responders to symptomatic drugs in knee osteoarthritis patients

2019 ◽  
Vol 21 (1) ◽  
Author(s):  
Guangju Zhai ◽  
Jean-Pierre Pelletier ◽  
Ming Liu ◽  
Edward W. Randell ◽  
Proton Rahman ◽  
...  
Keyword(s):  
Term Treatment ◽  
Serum Samples ◽  
Optimal Cutoff ◽  
Knee Oa ◽  
Symptomatic Knee ◽  
Long Term Treatment ◽  
High Prevalence ◽  
The Difference ◽  
Total Concentrations

Abstract Background Identification of the optimal treatment for a given patient is of paramount importance. This is of particular relevance in osteoarthritis (OA) because of the high prevalence of the disease, extensive heterogeneity of the disease, and need for long-term treatment. The aim of the study was to examine whether serum lysophosphatidylcholines (lysoPCs) to phosphatidylcholines (PCs) ratio can predict clinical response to licofelone and naproxen treatments in symptomatic knee OA patients. Methods One hundred fifty-eight OA patients who completed the study according to protocol (ATP) of a previous 24-month clinical trial cohort comparing the effect of licofelone vs. naproxen in symptomatic knee OA patients were included. Symptomatic responses to either treatments were classified according to the OARSI-OMERACT criteria based on the WOMAC scores at 24 months. Total concentrations of PCs and lysoPCs were measured in the serum samples collected before the initiation of the treatments, and the lysoPCs to PCs ratio was calculated. Student’s t test was utilized to compare the difference in the ratio of lysoPCs to PCs between the symptomatic responders and non-responders. Logistic regression was utilized to adjust for the potential confounders. Receiver operating characteristic (ROC) analysis was performed to identify the optimal cutoff of the ratio for prediction. Results Data showed that 61.4% of the patients symptomatically responded to licofelone and naproxen and 38.6% were deemed as therapeutic failures (non-responders). There was no difference in responders between licofelone and naproxen (p = 0.87). Responders had a significantly higher lysoPCs to PCs ratio than non-responders (0.097 ± 0.003 vs. 0.085 ± 0.003; p = 0.006). Patients with a ratio greater than the optimal cutoff of 0.088 had 2.93 times more likely to respond to licofelone and naproxen (p = 0.002). Conclusions Serum lysoPCs to PCs ratio is a marker for response to licofelone and naproxen and may aid in the personalized treatment to knee OA.

Glucosamine Long-Term Treatment and the Progression of Knee Osteoarthritis: Systematic Review of Randomized Controlled Trials

2005 ◽  
Vol 39 (6) ◽  
pp. 1080-1087 ◽  
Author(s):  
Nalinee Poolsup ◽  
Chutamanee Suthisisang ◽  
Patchareeya Channark ◽  
Wararat Kittikulsuth
Keyword(s):  
Knee Osteoarthritis ◽  
Disease Progression ◽  
Term Treatment ◽  
Glucosamine Sulfate ◽  
Controlled Trials ◽  
Efficacy And Safety ◽  
Knee Oa ◽  
Randomized Controlled ◽  
Long Term Treatment

OBJECTIVE: To investigate the structural and symptomatic efficacy and safety of glucosamine in knee osteoarthritis (OA). DATA SOURCES: Clinical trials of glucosamine were identified through electronic searches (MEDLINE, EMBASE, BIOSIS, EMB review, the Cochrane Library) using the key words glucosamine, osteoarthritis, degenerative joint disease, degenerative arthritis, osteoarthrosis, gonarthrosis, knee, disease progression, and clinical trial. The bibliographic databases were searched from their respective inception dates to August 2004. We also hand-searched reference lists of relevant articles. STUDY SELECTION AND DATA EXTRACTION: Studies were included if they were double-blind, randomized, controlled trials that evaluated oral glucosamine long-term treatment in knee OA; lasting at least one year; and reporting as outcome measures the symptom severity and disease progression as assessed by joint space narrowing. Two authors interpreted data independently. Disagreements were resolved through discussion. DATA SYNTHESIS: Glucosamine sulfate was more effective than placebo in delaying structural progression in knee OA. The risk of disease progression was reduced by 54% (pooled RR 0.46; 95% CI 0.28 to 0.73; p = 0.0011). The number-needed-to-treat was 9 (95% CI 6 to 20). The pooled effect sizes for pain reduction and improvement in physical function were 0.41 (95% CI 0.21 to 0.60; p < 0.0001) and 0.46 (95% CI 0.27 to 0.66; p < 0.0001), respectively, in favor of glucosamine sulfate. Glucosamine sulfate caused no more adverse effects than placebo. CONCLUSIONS: The available evidence suggests that glucosamine sulfate may be effective and safe in delaying the progression and improving the symptoms of knee OA. Due to the sparse data on structural efficacy and safety, further studies are warranted.

A Review of Metabolic Parameters in Quetiapine Studies Across Diagnoses

2009 ◽  
Vol 24 (S1) ◽  
pp. 1-1
Author(s):  
J. Newcomer ◽  
R. Ratner ◽  
M. Åström ◽  
H. Eriksson
Keyword(s):  
Atypical Antipsychotics ◽  
Extended Release ◽  
Term Treatment ◽  
Metabolic Parameters ◽  
Short Term ◽  
Pooled Data ◽  
Long Term Treatment ◽  
Potential Risks ◽  
The Difference

Background:Data pertaining to changes in weight during long-term treatment with quetiapine (QTP) have been published previously (1).Methods:Pooled data are presented from 26 short-term clinical studies (up to 12 weeks) of QTP or quetiapine extended-release (QTP XR)-as monotherapy or adjunct therapy-conducted by AstraZeneca up to November 2007. Studies were conducted in adult patients (18-65 years) across a number of psychiatric diagnoses. Variables were analyzed irrespective of fasting status with similar analyses planned in the fasting subset. LSM changes from baseline for the difference between QTP and placebo are presented.Results:Approximately 10000 patients were included in the analyses, 70% of whom were treated with QTP or QTP XR. Across the entire short-term dataset, the difference in LSM change in weight for QTP vs. placebo was 1.07 kg. Corresponding differences in glucose regulation parameters were 1.39 mg/dL for glucose and 0.04% units for HbA1C. the overall difference in total cholesterol was 5.48 mg/dL, with differences in HDL and LDL cholesterol of -0.62 mg/dL and 1.69 mg/dL. the difference in LSM change in triglycerides was 22.62 mg/dL.Discussion:Within the context of balancing potential risks against the acknowledged benefits of atypical antipsychotics, the degree and significance of variations in metabolic parameters is an area of continued interest. This analysis helps clinicians to better understand changes in important metabolic parameters across trials with QTP and QTP XR, and the size and uniqueness of the dataset permits further analyses within this important area.Supported by funding from AstraZeneca Pharmaceuticals LP.

scholarly journals Comparison of Long-term Ambulatory Function in Patients with Duchenne Muscular Dystrophy Treated with Eteplirsen and Matched Natural History Controls

2021 ◽  
pp. 1-11
Author(s):  
Jerry R. Mendell ◽  
Navid Khan ◽  
Nanshi Sha ◽  
Helen Eliopoulos ◽  
Craig M. McDonald ◽  
...  
Keyword(s):  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Gene Mutations ◽  
Exon Skipping ◽  
Term Treatment ◽  
Long Term Treatment ◽  
The Difference ◽  
Dmd Gene ◽  
6 Minute Walk Test

Background: Duchenne muscular dystrophy (DMD) is a rare, X-linked, fatal, degenerative neuromuscular disease caused by DMD gene mutations. A relationship between exon skipping and dystrophin production in exon 51-amenable patients treated with eteplirsen (EXONDYS 51 ®) is established. Once-weekly eteplirsen significantly increased dystrophin, with slower decline in ambulatory function compared to baseline. Long-term treatment with eteplirsen leads to accumulation of dystrophin over time and observed functional benefits in patients with DMD. Objective: Compare long-term ambulatory function in eteplirsen-treated patients versus controls. Methods: Study 201/202 included 12 eteplirsen-treated patients assessed twice/year for ambulatory function over 4 years. Ambulatory evaluations (6-minute walk test [6MWT], loss of ambulation, and North Star Ambulatory Assessment [NSAA]) were compared with matched controls from Italian Telethon and Leuven registries. Results: At Years 3 and 4, eteplirsen-treated patients demonstrated markedly greater mean 6MWT than controls (difference in change from baseline of 132 m [95%CI (29, 235), p = 0.015] at Year 3 and 159 m [95%CI (66, 253), p = 0.002] at Year 4). At Year 4, a significantly greater proportion of eteplirsen-treated patients were still ambulant versus controls (10/12 vs 3/11; p = 0.020). At Year 3, eteplirsen-treated patients had milder NSAA decline than controls (difference in change from baseline of 2.6, 95%CI [-6, 11]), however, the difference was not statistically significant; Year 4 control NSAA data were not available. Conclusion: In this retrospective matched control study, eteplirsen treatment resulted in attenuation of ambulatory decline over a 4-year observation period, supporting long-term benefit in patients with DMD.

scholarly journals Intramuscular Clodronate in Long-Term Treatment of Symptomatic Knee Osteoarthritis: A Randomized Controlled Study

Drugs in R&D ◽  
2020 ◽  
Vol 20 (1) ◽  
pp. 39-45
Author(s):  
Bruno Frediani ◽  
Carmela Toscano ◽  
Paolo Falsetti ◽  
Antonella Nicosia ◽  
Serena Pierguidi ◽  
...  
Keyword(s):  
Knee Osteoarthritis ◽  
Term Treatment ◽  
Randomized Controlled Study ◽  
Controlled Study ◽  
Randomized Controlled ◽  
Symptomatic Knee Osteoarthritis ◽  
Symptomatic Knee ◽  
Long Term Treatment

scholarly journals The Role of Advanced Imaging in Gout Management

2022 ◽  
Vol 12 ◽  
Author(s):  
Shuangshuang Li ◽  
Guanhua Xu ◽  
Junyu Liang ◽  
Liyan Wan ◽  
Heng Cao ◽  
...  
Keyword(s):  
Scoring Systems ◽  
Term Treatment ◽  
Advanced Imaging ◽  
Non Invasive ◽  
Long Term Treatment ◽  
High Prevalence ◽  
Magnetic Resonance Imaging Mri ◽  
Urate Crystals

Gout is a common form of inflammatory arthritis where urate crystals deposit in joints and surrounding tissues. With the high prevalence of gout, the standardized and effective treatment of gout is very important, but the long-term treatment effect of gout is not satisfied because of the poor adherence in patients to the medicines. Recently, advanced imaging modalities, including ultrasonography (US), dual-energy computed tomography (DECT), and magnetic resonance imaging (MRI), attracted more and more attention for their role on gout as intuitive and non-invasive tools for early gout diagnosis and evaluation of therapeutic effect. This review summarized the role of US, DECT, and MRI in the management of gout from four perspectives: hyperuricemia, gout attacks, chronic gout, and gout complications described the scoring systems currently used to quantify disease severity and discussed the challenges and limitations of using these imaging tools to assess response to the gout treatment.

scholarly journals Renal function in Japanese HIV-1-positive patients who switch to tenofovir alafenamide fumarate after long-term tenofovir disoproxil fumarate

2021 ◽  
Author(s):  
Kensuke Abe ◽  
Taku Obara ◽  
Satomi Kamio ◽  
Asahi Kondo ◽  
Junji Imamura ◽  
...  
Keyword(s):  
Renal Function ◽  
Renal Dysfunction ◽  
Tenofovir Disoproxil Fumarate ◽  
Antiviral Effect ◽  
Term Treatment ◽  
Long Term Treatment ◽  
The Difference ◽  
Tenofovir Alafenamide ◽  
Hiv 1

Abstract BACKGROUND Tenofovir disoproxil fumarate (TDF) has a strong antiviral effect, but TDF is known to cause renal dysfunction. Therefore, we are investigating preventing renal dysfunction by replacing TDF with tenofovir alafenamide fumarate (TAF), which is known to be relatively safe to the kidneys. However, the changes in renal function under long-term use of TAF are not known. In this study, we evaluated renal function in Japanese HIV-1-positive patients switching to TAF after long-term treatment with TDF.METHODS A single-center observational study was conducted in Japanese HIV-1-positive patients. TDF was switched to TAF after at least 48 weeks of treatment so we could evaluate the long-term use of TDF. The primary endpoint was the estimated glomerular filtration rate (eGFR) at 144 weeks of TAF administration. In addition, we predicted the factors that would lead to changes in eGFR after long-term use of TAF.RESULTS Of the 125 HIV-1-positive patients who were prescribed TAF at our hospital during the study period, 70 fulfilled the study criteria. The eGFR at the time of switching from TDF to TAF was 81.4 ± 21.1 mL/min/1.73 m2. eGFR improved significantly after 12 weeks of taking TAF but significantly decreased at 96 and 144 weeks. At 144 weeks of taking TAF, the factors significantly correlated with the difference in eGFR from baseline were the difference in eGFR at 48 weeks of taking TAF and age at the start of TAF.CONCLUSIONS In this study, Japanese HIV-1-positive patients who had been taking TDF for a long period of time showed a decrease in eGFR after switching to long-term use of TAF. Japanese HIV-1-positive patients are expected to take TAF for a long time. Depending on age, laboratory values related to renal function need to be monitored carefully.

The Value of Capillary Thrombotest Method for the Control of Long Term Anticoagulant Therapy

1962 ◽  
Vol 08 (02) ◽  
pp. 333-341
Author(s):  
L Poller ◽  
J. S Woolliff
Keyword(s):  
Marked Reduction ◽  
Coagulation Factors ◽  
Term Treatment ◽  
Quick Test ◽  
Upper Limit ◽  
Long Term Treatment ◽  
Similar Range ◽  
The Difference ◽  
Dilution Curves

SummaryThe capillary form of the Thrombotest gives results similar to the venous Thrombotest technique in patients on long term phenindione and nicoumalone, and can be recommended as a reliable laboratory investigation.The Thrombotest range of 10—30% is a much less marked reduction of coagulability than the similar range with the Quick test. The difference in the results does not appear to be due to the sensitivity of Thrombotest to other additional coagulation factors, but simply because saline dilution curves are usually employed in the Quick test.The upper limit of the Thrombotest therapeutic range on the basis of our studies appears to be about 15%. The lower limit of safety assessed from comparison with the Quick test and by clinical experience in the control of long term treatment appears to be in the region of 5%.

scholarly journals In vivo antithrombotic synergy of oral heparin and arginine: Endothelial thromboresistance without changes in coagulation parameters

2006 ◽  
Vol 95 (05) ◽  
pp. 865-872 ◽  
Author(s):  
Bruce Daniels ◽  
Fuming Zhang ◽  
Wenjun Mao ◽  
Sandra Wice ◽  
Linda Hiebert ◽  
...  
Keyword(s):  
Thrombus Formation ◽  
Anticoagulant Activity ◽  
Term Treatment ◽  
Antithrombotic Activity ◽  
Thrombosis Model ◽  
Long Term Treatment ◽  
Saline Administration ◽  
The Difference

SummaryOn the basis of suggested clinical efficacy in an uncontrolled study in ninety-seven patients with unstable angina, an animal study was conducted to investigate antithrombotic synergy between orally administered heparin and arginine. A rat venous thrombosis model tested the difference in thrombus formation when heparin (7.5 mg/kg) and arginine (113 mg/kg) were administered, alone or in combination, by stomach tube with a minimum of 20 rats/group. Oral heparin, arginine, and heparin plus arginine reduced thrombus formation by 50%, 75%, and 90%, respectively,when compared to saline administration. Heparin was recovered from endothelium, yet there was little or no observable plasma anticoagulant activity. An orally administered lowmolecular-weight anticoagulant glycosaminoglycan mixture, sulodexide (7.5 mg/kg), showed an 88% reduction in stable thrombus formation when administered alone but showed no synergy with oral arginine. A 28-day study with oral sulodexide (2.9 mg/ kg) and arginine (43.9 mg/kg), 20 rats/group, showed antithrombotic activity with minimal anticoagulant activity indicating suitability for long term treatment. These findings suggest the endothelial localization of heparin and a synergistic antithrombotic effect for orally administered heparin and arginine.

scholarly journals Relationships between FSH, inhibin B, anti-Mullerian hormone, and testosterone during long-term treatment with the GnRH-agonist histrelin in patients with prostate cancer

2010 ◽  
Vol 162 (1) ◽  
pp. 177-181 ◽  
Author(s):  
Talia Eldar-Geva ◽  
Gad Liberty ◽  
Boris Chertin ◽  
Alon Fridmans ◽  
Amicur Farkas ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Gnrh Agonist ◽  
Sertoli Cells ◽  
Term Treatment ◽  
Inhibin B ◽  
Serum Samples ◽  
Long Term Treatment ◽  
Long Acting ◽  
Established Treatment

ObjectivesMedical castration with long-acting GnRH-agonist (GnRHa) is a well-established treatment for metastatic prostate cancer. Our aim was to explore the relationships between FSH, inhibin B, anti-Mullerian hormone (AMH), and testosterone during treatment with an implant releasing GnRHa.DesignAnalysis of hormone levels in frozen serum samples.MethodsTen patients aged 77±7 (means±s.e.m.) years with prostate cancer were treated with the GnRHa histrelin for at least a year. Two weeks prior to insertion and for 3–4 months following removal the patients were treated with the antiandrogen flutamide. Serum inhibin B, FSH, testosterone, and AMH levels were measured retrospectively.ResultsFSH, inhibin B, and testosterone increased during antiandrogen administration and levels fell after implant insertion. Four weeks post insertion, FSH gradually increased while inhibin B and testosterone remained fully suppressed. AMH levels did not change during antiandrogen treatment, but increased following implant insertion and remained elevated for the duration of implant use. Following removal, FSH and testosterone increased, inhibin B remained low, while AMH decreased.ConclusionsThe secondary increase in FSH following initial suppression with the implant is probably related to impaired inhibin B secretion. The lack of inhibin B response to the secondary increase in FSH suggests that long-term exposure of Sertoli-cells to GnRHa impairs their function. This effect appears to be selective since unlike inhibin B, AMH increased. In the absence of testosterone, FSH has a role in AMH regulation.

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