Nonopioid vs opioid analgesics after impacted third-molar extractions: The Opioid Analgesic Reduction Study randomized clinical trial.

Background: Opioids are still being prescribed to manage acute postsurgical pain. Unnecessary opioid prescriptions can lead to addiction and death, as unused tablets are easily diverted.

Methods: To determine whether combination nonopioid analgesics are at least as good as opioid analgesics, a multisite, double-blind, randomized, stratified, noninferiority comparative effectiveness trial was conducted, which examined patient-centered outcomes after impacted mandibular third-molar extraction surgery.

Leveraging the functionality of Research Electronic Data Capture (REDCap) to enhance data collection and quality in the Opioid Analgesic Reduction Study.

Background: The Opioid Analgesic Reduction Study is a double-blind, prospective, clinical trial investigating analgesic effectiveness in the management of acute post-surgical pain after impacted third molar extraction across five clinical sites. Specifically, Opioid Analgesic Reduction Study examines a commonly prescribed opioid combination (hydrocodone/acetaminophen) against a non-opioid combination (ibuprofen/acetaminophen). The Opioid Analgesic Reduction Study employs a novel, electronic infrastructure, leveraging the functionality of its data management system, Research Electronic Data Capture, to not only serve as its data reservoir but also provide the framework for its quality management program.

Research objectives and general considerations for pragmatic clinical trials of pain treatments: IMMPACT statement.

Many questions regarding the clinical management of people experiencing pain and related health policy decision-making may best be answered by pragmatic controlled trials. To generate clinically relevant and widely applicable findings, such trials aim to reproduce elements of routine clinical care or are embedded within clinical workflows. In contrast with traditional efficacy trials, pragmatic trials are intended to address a broader set of external validity questions critical for stakeholders (clinicians, healthcare leaders, policymakers, insurers, and patients) in considering the adoption and use of evidence-based treatments in daily clinical care.

The Opioid Analgesic Reduction Study (OARS)-a comparison of opioid vs. non-opioid combination analgesics for management of post-surgical pain: a double-blind randomized clinical trial.

Background: Everyday people die unnecessarily from opioid overdose-related addiction. Dentists are among the leading prescribers of opioid analgesics. Opioid-seeking behaviors have been linked to receipt of initial opioid prescriptions following the common dental procedure of third molar extraction.

Analgesic efficacy of naproxen sodium versus hydrocodone/acetaminophen in acute postsurgical dental pain: a randomized, double-blind, placebo-controlled trial.

Objectives: Opioid/acetaminophen combinations may be overly prescribed in many post-surgical situations where a non-steroidal anti-inflammatory drug with equal or greater efficacy, fewer central nervous system side effects, and no risk for opioid abuse could be substituted. We compared a single, non-prescription dose of naproxen sodium 440 mg (NapS) against hydrocodone plus acetaminophen 10/650 mg (HYD+APAP) in post-impaction surgery pain.

Methods: Single-center, randomized, double-blind, placebo-controlled study in moderate-severe pain after surgical removal of impacted third molars (ClinicalTrials.

Efficacy and Safety of Two Fixed-Dose Combinations of Tramadol Hydrochloride and Diclofenac Sodium in Postoperative Dental Pain.

Objective: To evaluate the analgesic efficacy and safety of tramadol hydrochloride/diclofenac sodium fixed-dose combination 25 mg/25 mg (FDC 25/25) and 50 mg/50 mg (FDC 50/50) vs tramadol 50 mg (T50) and diclofenac 50 mg (D50) monotherapies in acute postoperative dental pain.

Setting: Eight sites across Mexico.

Subjects: Adults (N = 829) with moderate to severe pain after third molar extraction.

Longer analgesic effect with naproxen sodium than ibuprofen in post-surgical dental pain: a randomized, double-blind, placebo-controlled, single-dose trial.

Non-steroidal anti-inflammatory drugs (NSAIDs) are recommended as first-line medications in mild-to-moderate acute pain. However, comparative data regarding the duration of analgesia for commonly-used NSAIDs at non-prescription doses is lacking. This study evaluated the time to rescue medication following a single dose of naproxen sodium (NAPSO) vs ibuprofen (IBU) and placebo in subjects with moderate-to-severe post-surgical dental pain.

Current methods and challenges for acute pain clinical trials.

Introduction: The clinical setting of acute pain has provided some of the first approaches for the development of analgesic clinical trial methods.

Objectives: This article reviews current methods and challenges and provides recommendations for future design and conduct of clinical trials of interventions to treat acute pain.

Conclusion: Growing knowledge about important diverse patient factors as well as varying pain responses to different acute pain conditions and surgical procedures has highlighted several emerging needs for acute pain trials.

Clinical trial designs and models for analgesic medications for acute pain in neonates, infants, toddlers, children, and adolescents: ACTTION recommendations.

Clinical trials to test the safety and efficacy of analgesics across all pediatric age cohorts are needed to avoid inappropriate extrapolation of adult data to children. However, the selection of acute pain models and trial design attributes to maximize assay sensitivity, by pediatric age cohort, remains problematic. Acute pain models used for drug treatment trials in adults are not directly applicable to the pediatric age cohorts-neonates, infants, toddlers, children, and adolescents.

Exploring the Interplay between Rescue Drugs, Data Imputation, and Study Outcomes: Conceptual Review and Qualitative Analysis of an Acute Pain Data Set.

In placebo-controlled acute surgical pain studies, provisions must be made for study subjects to receive adequate analgesic therapy. As such, most protocols allow study subjects to receive a pre-specified regimen of open-label analgesic drugs (rescue drugs) as needed. The selection of an appropriate rescue regimen is a critical experimental design choice.

The ACTTION-APS-AAPM Pain Taxonomy (AAAPT) Multidimensional Approach to Classifying Acute Pain Conditions.

Objective: With the increasing societal awareness of the prevalence and impact of acute pain, there is a need to develop an acute pain classification system that both reflects contemporary mechanistic insights and helps guide future research and treatment. Existing classifications of acute pain conditions are limiting, with a predominant focus on the sensory experience (eg, pain intensity) and pharmacologic consumption. Consequently, there is a need to more broadly characterize and classify the multidimensional experience of acute pain.

The ACTTION-APS-AAPM Pain Taxonomy (AAAPT) Multidimensional Approach to Classifying Acute Pain Conditions.

Objective: With the increasing societal awareness of the prevalence and impact of acute pain, there is a need to develop an acute pain classification system that both reflects contemporary mechanistic insights and helps guide future research and treatment. Existing classifications of acute pain conditions are limiting, with a predominant focus on the sensory experience (e.g.

Pain intensity rating training: results from an exploratory study of the ACTTION PROTECCT system.

Clinical trial participants often require additional instruction to prevent idiosyncratic interpretations regarding completion of patient-reported outcomes. The Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks (ACTTION) public-private partnership developed a training system with specific, standardized guidance regarding daily average pain intensity ratings. A 3-week exploratory study among participants with low-back pain, osteoarthritis of the knee or hip, and painful diabetic peripheral neuropathy was conducted, randomly assigning participants to 1 of 3 groups: training with human pain assessment (T+); training with automated pain assessment (T); or no training with automated pain assessment (C).

Research design considerations for single-dose analgesic clinical trials in acute pain: IMMPACT recommendations.

This article summarizes the results of a meeting convened by the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) on key considerations and best practices governing the design of acute pain clinical trials. We discuss the role of early phase clinical trials, including pharmacokinetic-pharmacodynamic (PK-PD) trials, and the value of including both placebo and active standards of comparison in acute pain trials. This article focuses on single-dose and short-duration trials with emphasis on the perioperative and study design factors that influence assay sensitivity.

Assay sensitivity of pain intensity versus pain relief in acute pain clinical trials: ACTTION systematic review and meta-analysis.

Unlabelled: The magnitude of the effect size of an analgesic intervention can be influenced by several factors, including research design. A key design component is the choice of the primary endpoint. The purpose of this meta-analysis was to compare the assay sensitivity of 2 efficacy paradigms: pain intensity (calculated using summed pain intensity difference [SPID]) and pain relief (calculated using total pain relief [TOTPAR]).

Reporting of adverse events and statistical details of efficacy estimates in randomized clinical trials of pain in temporomandibular disorders: Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks systematic review.

Background: Statistical methods and adverse events (that is, harms) data affect the accuracy of conclusions about the risk-to-benefit ratio of treatments for temporomandibular disorders (TMDs). The authors reviewed the quality of reporting in TMD clinical trials to highlight practices that are in need of improvement.

Types Of Studies Reviewed: The authors included articles published between 1969 and May 31, 2013, in which the investigators reported randomized clinical trials of TMD treatments with pain as a principal outcome variable.

Quality of pain intensity assessment reporting: ACTTION systematic review and recommendations.

Unlabelled: Pain intensity assessments are used widely in human pain research, and their transparent reporting is crucial to interpreting study results. In this systematic review, we examined reporting of human pain intensity assessments and related elements (eg, administration frequency, time period assessed, type of pain) in all empirical pain studies with adult participants in 3 major pain journals (ie, European Journal of Pain, Journal of Pain, and Pain) between January 2011 and July 2012. Of the 262 articles identified, close to one-quarter (24%) ambiguously reported the pain intensity assessment.

Delayed-onset muscle soreness: a pilot study to assess analgesic study design features.

Based on a thorough review of the available literature in the delayed-onset muscle soreness (DOMS) model, we identified multiple study design characteristics that are considered to be normative in acute pain research but have not been followed in a majority of published DOMS experiments. We designed an analgesic investigation using the DOMS model that both complied with current scientifically accepted standards for the conduct of analgesic studies and demonstrated reasonable assay sensitivity. This randomized, double-blind, placebo-controlled within-subject study compared the efficacy of topical diclofenac sodium 1% with a matching placebo in reducing pain associated with DOMS.

Pharmacokinetic properties and tolerability of low-dose SoluMatrix diclofenac.

Purpose: This study compared the pharmacokinetic properties and safety profile of low-dose (18- and 35-mg) diclofenac capsules manufactured using SoluMatrix Fine Particle Technology (Trademark of iCeutica Inc. (Philadelphia, Pennsylvania), and the technology is licensed to Iroko Pharmaceuticals, LLC (Philadelphia, Pennsylvania) for exclusive use in NSAIDs), which produces submicron-sized drug particles with enhanced dissolution properties, to those of diclofenac potassium immediate-release (IR) 50-mg tablets.

Methods: This Phase 1, single-center, randomized, open-label, single-dose crossover study was conducted in 40 healthy volunteers.

Research designs for proof-of-concept chronic pain clinical trials: IMMPACT recommendations.

Proof-of-concept (POC) clinical trials play an important role in developing novel treatments and determining whether existing treatments may be efficacious in broader populations of patients. The goal of most POC trials is to determine whether a treatment is likely to be efficacious for a given indication and thus whether it is worth investing the financial resources and participant exposure necessary for a confirmatory trial of that intervention. A challenge in designing POC trials is obtaining sufficient information to make this important go/no-go decision in a cost-effective manner.

Expression of astrocytic genes coding for proteins implicated in neural excitation and brain edema is altered after acute liver failure.

In vitro and in vivo studies have suggested that reduced astrocytic uptake of neuronally released glutamate, alterations in expression of glial fibrillary acidic protein (GFAP) and aquaporin-4 (AQP-4) contribute to brain edema in acute liver failure (ALF). However, there is no evidence to date to suggest that these alterations occur in patients with ALF. We analyzed the mRNA expression of excitatory amino acid transporters (EAAT-1, EAAT-2), GFAP, and AQP-4 in the cerebral cortex obtained at autopsy from eight patients with ALF and from seven patients with no evidence of hepatic or neurological disorders by real-time PCR, and protein expression was assessed using immunoblotting and immunohistochemistry.

A comparison of the clinical and experimental characteristics of four acute surgical pain models: dental extraction, bunionectomy, joint replacement, and soft tissue surgery.

When a clinical trial of an analgesic produces a negative finding, it is important to consider the influence (if any) of experimental error on the validity of that result. Although efforts to identify and minimize experimental error in chronic pain investigations have begun in earnest, less work has been performed on the optimization of acute pain methodology. Of the acute surgical pain methodology articles that have been published over the last decade, almost all focus on either the dental or bunion model.