Pain
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Review Meta Analysis
THE PERIOPERATIVE USE OF PREGABALIN FOR ACUTE PAIN- A SYSTEMATIC REVIEW AND META- ANALYSIS.
Evidence supporting postoperative pain management using pregabalin as an adjunct intervention across various surgical pain models is lacking. The objective of this systematic review was to evaluate "model-specific" comparative effectiveness and harms of pregabalin following a previously published systematic review protocol. MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials were searched from inception through August 2013. ⋯ Pregabalin analgesic effectiveness is largely restricted to surgical procedures associated with pronociceptive mechanisms. The clinical significance of observed pregabalin benefits must be weighed against the uncertainties about serious harms and enhanced recovery to inform the careful selection of surgical patients. Recommendations for future research are proposed.
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Randomized Controlled Trial Multicenter Study
Development and Preliminary Validation of an Integrated Efficacy-Tolerability Composite Measure for the Evaluation of Analgesics.
The goal of this analysis was to develop and evaluate integrated measures of benefit and tolerability of analgesic drugs in clinical trials. We evaluated an efficacy-tolerability composite (ETC) measure combining different cutoff values for daily pain reduction (≥20%, ≥30%, or ≥50% pain reduction) and adverse events (AEs) (no AE, no or mild AEs, no or mild drug-related AEs). Nine ETC cutoff values (3 × 3) were tested using data from a randomized double-blind trial comparing tapentadol extended release (ER) (n = 310), oxycodone controlled release (CR) (n = 322), and placebo (n = 314) in subjects with chronic low back pain. ⋯ For all 9 ETC measures, validity was demonstrated by significant correlation of ETC scores with patients' Global Impression of change and with change from baseline in pain scores. Tapentadol ER ETC scores were statistically significantly higher than oxycodone CR ETC scores for 4 of the ETC measures. "No/mild drug-related AE and ≥20% pain reduction" demonstrated the best overall validity (correlation with patients' global impression of change) and responsiveness (discrimination between treatment groups), yielding a higher standardized effect size for tapentadol ER compared with placebo (0.19 [95% confidence interval: 0.031-0.346]) and with oxycodone CR (0.23 [95% confidence interval: 0.070-0.383]) than other cutoff values. Thus, we have identified herein a composite measure that seems to be a valid and responsive measure of the overall efficacy and tolerability of analgesics in clinical trials.
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Review
Research design considerations for chronic pain prevention clinical trials: IMMPACT recommendations.
Although certain risk factors can identify individuals who are most likely to develop chronic pain, few interventions to prevent chronic pain have been identified. To facilitate the identification of preventive interventions, an IMMPACT meeting was convened to discuss research design considerations for clinical trials investigating the prevention of chronic pain. We present general design considerations for prevention trials in populations that are at relatively high risk for developing chronic pain. ⋯ Improvements in the design of chronic pain prevention trials could improve assay sensitivity and thus accelerate the identification of efficacious interventions. Such interventions would have the potential to reduce the prevalence of chronic pain in the population. Additionally, standardization of outcomes in prevention clinical trials will facilitate meta-analyses and systematic reviews and improve detection of preventive strategies emerging from clinical trials.
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Randomized Controlled Trial
Cerebral analgesic response to non-steroidal anti-inflammatory drug ibuprofen.
Nonopioid agents, such as nonsteroidal anti-inflammatory drugs (NSAIDs), are the most commonly used class of analgesics. Increasing evidence suggests that cyclooxygenase (COX) inhibition at both peripheral and central sites can contribute to the antihyperalgesic effects of NSAIDs, with the predominant clinical effect being mediated centrally. In this study, we examined the cerebral response to ibuprofen in presurgical and postsurgical states and looked at the analgesic interaction between surgical state and treatment. ⋯ However, in the postsurgical state, we observed increased activation of top-down modulatory circuits, which was accompanied by decreases in the areas engaged because of ongoing pain. Our findings demonstrate that ibuprofen has a measurable analgesic response in the human brain, with the subjective effects of pain relief reflected in two distinct brain networks. The observed activation of descending modulatory circuits warrants further investigation, as this may provide new insights into the inhibitory mechanisms of analgesia that might be exploited to improve safety and efficacy in pain management.
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The objective of this study was to assess whether migraine and tension-type headache (TTH) are best viewed as discrete entities or points on a severity continuum using taxometric analysis. Historically, classification systems have conceptualized the primary headache disorders of migraine and TTH as fundamentally different disorders that are differentiated by their characteristic symptom profiles and, as such, imply differing pathophysiologies and required treatments. Despite this categorical nosology, findings continue to emerge suggesting that migraine and TTH instead reflect dimensions of severity within the same headache construct. ⋯ Specifically, graphical results revealed that high headache frequency (>15 d/mo) and younger age (<24 years old) were associated with unimodal distributions suggestive of a dimensional construct of primary headache, whereas lower headache frequency and older age were associated with bimodal distributions characteristic of discrete diagnostic entities. Conceptualizing primary headache as a severity continuum was supported for young adults and those with frequent headaches. The distinctions of a categorical classification system were supported for adults (>24 years old) and those with infrequent headache.