scholarly journals Potential Characteristics for Prediction of the Efficacy of Non-Steroid Anti-Inflammatory Drugs for Migraine Treatment: A Retrospective Cohort Study

2021 ◽  
Author(s):  
Heng-Le Wei ◽  
Jin-Jin Wang ◽  
Gang-Ping Zhou ◽  
Yu-Sheng Yu ◽  
Hong Zhang
Keyword(s):  
Logistic Regression ◽  
Area Under The Curve ◽  
Analgesic Efficacy ◽  
Considerable Proportion ◽  
Migraine Treatment ◽  
Inflammatory Drugs ◽  
Auc Value ◽  
Anti Inflammatory ◽  
Headache Impact ◽  
Prediction Capability

Abstract Background: Although several special medications for migraine are currently available, non-steroid anti-inflammatory drugs (NSAIDs) are still the first-line pharmacological option. A considerable proportion of migraineurs still be unresponsive to NSAIDs for reasons that remain unknown. The study aimed to develop significant characteristics to predict the efficacy of NSAIDs for patients with migraine. Methods: In this retrospective study, 567 patients suffering migraine were included and divided into an effective NSAIDs (M-eNSAIDs) group and a noneffective NSAIDs (M-neNSAIDs) group according to the analgesic efficacy at 2 hours after taking NSAIDs. Clinical and neuropsychiatric characteristics were collected and used to build a logistic regression model. And a receiver operating characteristic (ROC) curve was drawn to represent the prediction capability.Results: Five predictors including education, attack duration, headache impact intensity, anxiety and depression scores were identified to build the logistic regression modal. The area under the curve (AUC) values of each predictor were 0.706, 0.639, 0.560, 0.683 and 0.632, respectively, failing to predict the efficacy of NSAIDs. All five predictors-combined method achieved an acceptable AUC value of 0.834 and a sensitivity of 90.9%.Conclusions: Despite the insufficient predictive capability of these predictors when analyzed individually, this study developed an effective and convenient method to accurately predict the efficacy of NSAIDs, which would be helpful for developing individualized therapeutic strategies for treatment of migraine.

scholarly journals Evaluation of the pharmacokinetic interaction and safety of ubrogepant coadministered with acetaminophen or nonsteroidal anti-inflammatory drugs: A randomized trial

2020 ◽  
Vol 3 ◽  
pp. 251581632092118 ◽  
Author(s):  
Abhijeet Jakate ◽  
Ramesh Boinpally ◽  
Matthew Butler ◽  
Kaifeng Lu ◽  
Kristi Womack ◽  
...  
Keyword(s):  
Drug Concentration ◽  
Geometric Mean ◽  
Plasma Drug Concentration ◽  
Migraine Treatment ◽  
Maximum Plasma ◽  
Plasma Drug ◽  
Two Phase ◽  
Inflammatory Drugs ◽  
Anti Inflammatory ◽  
Healthy Participants

Background: Ubrogepant is a novel, oral calcitonin gene–related peptide receptor antagonist approved by the US Food and Drug Administration for acute treatment of migraine with or without aura in adults. Objectives: To assess potential pharmacokinetic (PK) drug–drug interactions in healthy participants and inform the safety and tolerability of ubrogepant alone and in combination with acetaminophen or nonsteroidal anti-inflammatory drugs (NSAIDs) in healthy participants and participants with migraine. Methods: Two phase 1, three-way crossover studies randomized healthy adults to 100 mg ubrogepant alone, 1000 mg acetaminophen or 500 mg naproxen alone, and 100 mg ubrogepant plus 1000 mg acetaminophen or 500 mg naproxen. Geometric mean ratios (GMRs) and 90% confidence intervals were calculated based on statistical comparison of maximum plasma drug concentration ( C max) and area under the plasma drug concentration–time curve (AUC) for treatment in combination versus alone. Two phase 3 randomized trials included adults with migraine. Treatment-emergent adverse events (TEAEs) were evaluated. Results: Time to C max and terminal elimination half-life for all treatments were unchanged when coadministered. Ubrogepant C max and AUC increased by approximately 40% when coadministered with acetaminophen. Acetaminophen C max decreased by 24% (GMR = 0.76) when coadministered with ubrogepant. There were no significant PK interactions between ubrogepant and naproxen. TEAE rates in the acetaminophen and NSAID rescue medication groups were similar to ubrogepant alone. Conclusions: Coadministration of ubrogepant and acetaminophen resulted in a statistically significant increase in ubrogepant exposure and a decrease in acetaminophen C max; however, these changes were not clinically relevant. No statistically or clinically relevant changes in PK were associated with ubrogepant and naproxen coadministration. No safety concerns were identified for ubrogepant alone or in combination with acetaminophen or NSAIDs.

Investigate the Influence of Hydraulic Factors on Landslide Susceptibility of Riverbank for the Chenyulan watershed

2020 ◽  
Author(s):  
Xiao-Zhu Hong ◽  
Po-An Chen ◽  
Hsun-Chuan Chan
Keyword(s):  
Logistic Regression ◽  
Landslide Susceptibility ◽  
Area Under The Curve ◽  
Predictive Performance ◽  
Sediment Supply ◽  
Upstream Region ◽  
Sinuosity Index ◽  
Topographic Slope ◽  
Auc Value ◽  
Lateral Erosion

<p>The riverbank landslide is considered as the major sediment supply in the watershed. It mostly due to the river flows erode the foot of the riverbank, which makes the slope unstable. This study focused on the watershed susceptibility analysis of the riverbank landslide in the Chenyulan watershed. The Logistic regression method was used to establish the landslide susceptibility model not only with the topography, geological and anthropic factors, but also with the hydraulic factors including the hydraulic Sinuosity index, channel gradient, and concave-or-convex bank. The study areas were classified into four regions, according to the river-bed slope and confluence of rivers. The effects of the hydraulic factors on the model results were investigated. In the upstream region with mild topographic slope, the landslides were found to be dominated by the topography factors. The area under the curve (AUC) value of the model was 74.2%. In the upstream region with steep topographic slope, the steep hillslopes and the channel erosion of the concave bank produced a high weight of concave-or-convex bank in the model. The developed model exhibited an increased AUC value of 77.2%. In the downstream region, the lateral erosion of the channel increased the weights of hydraulic sinuosity index and channel gradient in the model. The developed model exhibited high area under the curve (AUC) value of 89.2%. The hydraulic factors increased the predictive performance of the model considerably.</p><p>Keyword: Riverbank, Hydraulic factors, Logistic regression</p>

scholarly journals Analgesic efficacy of non-steroidal anti-inflammatory drugs in experimental pain in humans

1993 ◽  
Vol 36 (5) ◽  
pp. 417-425 ◽  
Author(s):  
JUDITH S. WALKER ◽  
JESUS F. ARROYO ◽  
TUAN NGUYEN ◽  
RICHARD O. DAY
Keyword(s):  
Analgesic Efficacy ◽  
Experimental Pain ◽  
Inflammatory Drugs ◽  
Anti Inflammatory

scholarly journals A Simple Method for Evaluating Analgesic Efficacy of Non-Steroidal Anti-Inflammatory Drugs

1971 ◽  
Vol 19 (7) ◽  
pp. 1506-1508 ◽  
Author(s):  
EIICHI FUJIHIRA ◽  
TOMIZO MORI ◽  
MASAO NAKAZAWA ◽  
HIKARU OZAWA
Keyword(s):  
Analgesic Efficacy ◽  
Simple Method ◽  
Inflammatory Drugs ◽  
Anti Inflammatory

scholarly journals Metamizole (dipyrone) effects on sevoflurane requirements and postoperative hyperalgesia in rats

2016 ◽  
Vol 51 (4) ◽  
pp. 365-375
Author(s):  
Daniel Ruiz-Pérez ◽  
Javier Benito ◽  
Carlota Largo ◽  
Gonzalo Polo ◽  
Susana Canfrán ◽  
...  
Keyword(s):  
Analgesic Efficacy ◽  
Positive Control ◽  
Negative Control ◽  
Controlled Study ◽  
Perioperative Analgesia ◽  
Male Wistar Rats ◽  
Inflammatory Drugs ◽  
Anti Inflammatory ◽  
Sparing Effect ◽  
Prospective Controlled Study

Unlike non-steroidal anti-inflammatory drugs (NSAIDs), metamizole has poor anti-inflammatory effects; and is suitable for models where analgesia, but not anti-inflammatory effects, is desirable. Like opioids, these drugs produce perioperative analgesia while reducing anaesthetic requirements, but it remains unclear whether they may develop tolerance or hyperalgesia, and thus decrease in analgesic efficacy. The aim was to determine whether tolerance or hyperalgesia to metamizole occurred in rats, and whether the sevoflurane minimum alveolar concentration (MAC) was affected. In a randomized, prospective, controlled study, male Wistar rats ( n = 8 per group) were administered metamizole (300 mg/kg, day 4). Previously, the following treatments were provided: daily metamizole for four days (0–3), morphine (10 mg/kg; positive control, day 0 only) or saline (negative control). The main outcome measures were mechanical (MNT) and warm thermal (WNT) nociceptive quantitative sensory thresholds. The baseline sevoflurane MAC and the reduction produced by the treatments were also determined. The mean (SD) baseline MAC [2.4(0.2)%vol] was decreased by morphine and metamizole by 45(11)% and 33(7)% ( P = 0.000, both), respectively. Baseline MNT [35.4(4.5) g] and WNT [13.2(2.4) s] were decreased by morphine and metamizole: MNT reduction of 22(6)% ( P = 0.000) and 22(7)% ( P = 0.001), respectively and WNT reduction of 34(14)% ( P = 0.000) and 24(13)% ( P = 0.001). The baseline MAC on day 4 was neither modified by treatments nor the MAC reduction produced by metamizole (days 0 and 4; P > 0.05). In conclusion, repeated metamizole administration may produce hyperalgesia, although it may not modify its anaesthetic sparing effect. The clinical relevance of this effect in painful research models requiring prolonged analgesic therapy warrants further investigation.

scholarly journals Nonsteroidal Anti-Inflammatory Drugs and Opioids in Postsurgical Dental Pain

2020 ◽  
Vol 99 (7) ◽  
pp. 777-786 ◽  
Author(s):  
E.V. Hersh ◽  
P.A. Moore ◽  
T. Grosser ◽  
R.C. Polomano ◽  
J.T. Farrar ◽  
...  
Keyword(s):  
Naproxen Sodium ◽  
Analgesic Efficacy ◽  
Optimal Dose ◽  
Dental Pain ◽  
Third Molars ◽  
Short Course ◽  
Surgical Extraction ◽  
Inflammatory Drugs ◽  
Anti Inflammatory ◽  
Versus Risk

Postsurgical dental pain is mainly driven by inflammation, particularly through the generation of prostaglandins via the cyclooxygenase system. Thus, it is no surprise that numerous randomized placebo-controlled trials studying acute pain following the surgical extraction of impacted third molars have demonstrated the remarkable efficacy of nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen, naproxen sodium, etodolac, diclofenac, and ketorolac in this prototypic condition of acute inflammatory pain. Combining an optimal dose of an NSAID with an appropriate dose of acetaminophen appears to further enhance analgesic efficacy and potentially reduce the need for opioids. In addition to being on average inferior to NSAIDs as analgesics in postsurgical dental pain, opioids produce a higher incidence of side effects in dental outpatients, including dizziness, drowsiness, psychomotor impairment, nausea/vomiting, and constipation. Unused opioids are also subject to misuse and diversion, and they may cause addiction. Despite these risks, some dental surgical outpatients may benefit from a 1- or 2-d course of opioids added to their NSAID regimen. NSAID use may carry significant risks in certain patient populations, in which a short course of an acetaminophen/opioid combination may provide a more favorable benefit versus risk ratio than an NSAID regimen.

scholarly journals Evaluating the Cardiovascular Safety of Nonsteroidal Anti-Inflammatory Drugs

Circulation ◽  
2017 ◽  
Vol 135 (21) ◽  
pp. 2062-2072 ◽  
Author(s):  
Elliott M. Antman
Keyword(s):  
Medical Condition ◽  
Controlled Trial ◽  
Analgesic Efficacy ◽  
Pharmaceutical Manufacturer ◽  
Safety Signal ◽  
Cardiovascular Safety ◽  
Planning Stage ◽  
General Medical Condition ◽  
Inflammatory Drugs ◽  
Anti Inflammatory

Some drugs used to treat noncardiovascular conditions may adversely impact the cardiovascular status of individuals both with and without known cardiovascular disease. When the US Food and Drug Administration judges the potential cardiovascular safety signal to be of sufficient concern, it may require the pharmaceutical manufacturer of the drug in question to conduct a postmarketing (phase 4) randomized controlled trial (RCT). Although historically many phase 4 RCTs focused on efficacy (using a superiority design), contemporary phase 4 RCTs often are focused on safety and use a noninferiority design. The choices made by investigators during the planning stage of a postmarketing phase 4 RCT dedicated to the evaluation of cardiovascular safety can influence the ability to compare the standard and test agents. Multiple factors reflecting the conduct of a phase 4 RCT for a general medical condition may influence interpretation of a cardiovascular safety signal. The higher the rates of failure to adhere to the protocol and dropout from the study, the greater the risk of bias. Trials evaluating the cardiovascular safety of nonsteroidal anti-inflammatory drugs (NSAIDs) when used for arthritis are difficult to conduct and even more challenging to interpret. Concerns include the comparison of drug regimens that do not provide comparable analgesic efficacy and problems with adherence to the protocol and retention in the study. On the basis of phase 4 RCTs of NSAIDs to date, it appears that a comparatively low dose of celecoxib administered to low-risk subjects is associated with approximately the same cardiovascular risk as NSAIDs with less cyclooxygenase-2 inhibitory activity, but at the cost of not controlling arthritic pain as effectively.

scholarly journals Non-Steroidal Anti-Inflammatory Drugs: Pharmacokinetics and Mitigation of Procedural-Pain in Cattle

Animals ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 282
Author(s):  
Brooklyn K. Wagner ◽  
Emma Nixon ◽  
Ivelisse Robles ◽  
Ronald E. Baynes ◽  
Johann F. Coetzee ◽  
...  
Keyword(s):  
Management Practices ◽  
Production Systems ◽  
Analgesic Efficacy ◽  
The United States ◽  
The Body ◽  
Future Research ◽  
Experimental Conditions ◽  
Flunixin Meglumine ◽  
Inflammatory Drugs ◽  
Anti Inflammatory

Common routine management practices in cattle, such as castration and disbudding, are recognized as being painful. In the United States (U.S.), these procedures are frequently performed without pain mitigation and there are currently no drugs federally approved for such use. Non-steroidal anti-inflammatory drugs, such as meloxicam, flunixin meglumine and aspirin, are the most commonly used analgesics in U.S. food-animal production systems. However, the body of research investigating the effectiveness of these pharmaceuticals to control pain in cattle at castration and disbudding has not been comprehensively evaluated. Therefore, this review examined existing literature to summarize meloxicam, flunixin and aspirin (1) pharmacokinetics (PK) and (2) administration outcome in regard to pain control during castration and disbudding procedures, in cattle. Following systematic searches and screening, 47 PK and 44 publications were extracted for data and are presented. The sample size contained notable variability and a general deficiency of validated and replicated methodologies for assessing pain in cattle remain substantial challenges within this research area. Future research should prioritize replication of pain assessment methodologies across different experimental conditions to close knowledge gaps identified by the present study and facilitate examination of analgesic efficacy.

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