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The provision of appropriate discharge analgesia can be challenging and is often prescribed by some of the most junior members of the medical team. Opioid abuse has been considered a growing public health crisis and physician overprescribing is a major contributor. In 2015 an initial audit of discharge analgesia at the Royal Perth Hospital led to the development of discharge analgesia guidelines. Compliance with these guidelines was assessed by a follow-up audit in 2016, which showed improved practice. This audit assesses discharge analgesia prescribing practices two years following guideline implementation. Dispensing data were obtained for analgesic medication over a three-month period from April to July 2017 and 100 unique patients were chosen using computer generated randomisation. Patients' medical records were assessed against the hospital's Postoperative Inpatients Discharge Analgesia Guidelines. The data collected were then compared with equivalent data from the previous 2015 and 2016 audits. Overall 83.4% of the 170 discharge analgesia prescriptions written were compliant with guidelines. The highest overall compliance rates were achieved for paracetamol (100%, up from 95.9% in 2016), celecoxib (96%, down from 100% in 2016), and oxycodone immediate release (IR) (74%, down from 88.9% in 2016). The quantity of oxycodone IR given on discharge complied with quantity guidelines in only 56% of cases. Overall there has been a significant and sustained improvement in appropriateness of discharge analgesia prescribing since 2015, though the results from 2017 show less compliance than 2016 and that achieving compliance with quantity guidelines is an ongoing challenge. This demonstrates the challenge of obtaining high adherence to guidelines over a longer time period.
Learn More >Type-A γ-aminobutyric (GABA) receptors are ligand-gated chloride channels with a very rich pharmacology. Some of their modulators, including benzodiazepines and general anaesthetics, are among the most successful drugs in clinical use and are common substances of abuse. Without reliable structural data, the mechanistic basis for the pharmacological modulation of GABA receptors remains largely unknown. Here we report several high-resolution cryo-electron microscopy structures in which the full-length human α1β3γ2L GABA receptor in lipid nanodiscs is bound to the channel-blocker picrotoxin, the competitive antagonist bicuculline, the agonist GABA (γ-aminobutyric acid), and the classical benzodiazepines alprazolam and diazepam. We describe the binding modes and mechanistic effects of these ligands, the closed and desensitized states of the GABA receptor gating cycle, and the basis for allosteric coupling between the extracellular, agonist-binding region and the transmembrane, pore-forming region. This work provides a structural framework in which to integrate previous physiology and pharmacology research and a rational basis for the development of GABA receptor modulators.
Learn More >Chronic widespread pain (CWP) is one of the most difficult pain conditions to treat due to an unknown etiology and a lack of innovative treatment design and effectiveness. Based upon preliminary findings within the fields of motivational psychology, integrative neuroscience, diaphragmatic breathing, and vagal nerve stimulation, we propose a new treatment intervention, motivational non-directive (ND) resonance breathing, as a means of reducing pain and suffering in patients with CWP. Motivational ND resonance breathing provides patients with a noninvasive means of potentially modulating five psychophysiological mechanisms imperative for endogenously treating pain and increasing overall quality of life.
Learn More >In 2016, a special interest group from the International Forum for the Study of Itch defined sensitive skin (SS) as a syndrome that manifests with the occurrence of unpleasant sensations (stinging, burning, pain, pruritus, and tingling sensations) after stimuli that should not cause a reaction, such as water, cold, heat, or other physical and/or chemical factors. The pathophysiology of sensitive skin is still poorly understood, but the symptoms described suggest inflammation and peripheral innervation. Only two publications have focused on sensitive skin transcriptomics. In the first study, the authors performed a microarray comparison of SS and non-sensitive skin (NSS) samples and showed differences in the expression of numerous genes in SS and NSS samples. Moreover, in the SS samples, two clusters of genes were identified, including upregulated and downregulated genes, compared to NSS samples. These results provide some interesting clues for the understanding of the pathophysiology of SS. The second study compared SS and NSS samples using RNA-seq assays. This method allowed the identification of long non-coding RNAs (lncRNAs) and differentially expressed mRNAs and provided a comprehensive profile in subjects with SS. The results showed that a wide range of genes may be involved in the pathogenesis of SS and suggested pathways that could be associated with them. In this paper, we discuss these two studies in detail and show how transcriptomic studies can help understand the pathophysiology of sensitive skin. We call for new transcriptomic studies on larger populations to be conducted before putative pathogenic mechanisms can be detected and analyzed to achieve a better understanding of this complex condition.
Learn More >This study examined the association between pain characteristics and the incidence of functional disability among community-dwelling older adults. This prospective cohort study included 4,365 older adults (mean age 74.7 years, 53.5% female) living in community settings. Pain characteristics, including severity and duration of pain, were assessed in participants who also underwent monthly follow-up assessment of functional disability for 24 months based on the national long-term care insurance system. Among the 4,365 participants, 2,149 (48.7%) reported pain, regardless of severity and duration. Of the 2,149 participants with pain, 950 (44.2%) reported moderate to severe pain and 1,680 (78.2%) reported chronic pain. Based on the univariate analyses, participants with moderate (hazard ratio [95% confidence interval]: 1.48 [1.05-2.09]) or severe (2.84 [1.89-4.27]) pain and chronic pain (1.50 [1.15-1.95]) showed significantly higher risk of disability incidence than did those without pain. After adjusting for covariates, severe pain remained a significant predictor (hazard ratio [95% confidence interval]: 1.66 [1.05-2.62]), but moderate (1.00 [0.69-1.47]) and chronic pain (1.04 [0.77-1.40]) did not. Our results established that moderate to severe pain or chronic pain affects functional disability; in particular, severe pain was independently associated with the incidence of disability. Subjective complaints of pain do not always correspond to physical causes; however, simplified questions regarding pain characteristics could be useful predictors of functional disability in community-dwelling older people.
Learn More >Despite the notable benefits of physical activity for chronic pain, a large proportion of patients with chronic pain report that they do not receive activity-related recommendations from their providers. Research suggests that patient factors such as weight and gender influence activity-related recommendations for chronic pain. Research also suggests that appraisals of the intensity and cause of pain may explain these weight and gender effects. We investigated the influence of patient weight and gender on observers' likelihood of recommending activity-related treatments for pain. We also explored the mediating effects of observers' ratings of pain severity and the extent to which pain was due to medical and lifestyle factors (pain attribution).
Learn More >The subjective nature of pain assessment and its large variance negatively affect patient-health care provider communication and reduce the assay sensitivity of pain clinical trials. Given the lack of an objective gold standard measure, identifying the source (true or error) of the within-subject variability of pain reports is a challenge. By assessing the within-subjects variability of pain and taste reports, alongside with interoceptive measures, the current study is aimed to investigate if the ability to reliably report bodily sensations is a cross-modal characteristic.
Learn More >Intravenous ketamine is often prescribed in severe neuropathic pain. Oral -methyl-D-aspartate receptor (NMDAR) antagonists might prolong pain relief, reducing the frequency of ketamine infusions and hospital admissions. This clinical trial aimed at assessing whether oral dextromethorphan or memantine might prolong pain relief after intravenous ketamine.
Learn More >Pain perception is associated with priming of the motor system and the orienting of attention in healthy adults. These processes correspond with decreases in alpha and beta power in the sensorimotor and parietal cortices. The goal of the present study was to determine whether these findings extend to individuals with chronic pain. Individuals with chronic jaw pain and pain-free controls anticipated and experienced a low pain or a moderate pain-eliciting heat stimulus. Although stimuli were calibrated for each subject, stimulus temperature was not different between groups. High-density EEG data were collected during the anticipation and heat stimulation periods and were analyzed using independent component analyses, EEG source localization, and measure projection analyses. Direct directed transfer function was also estimated to identify frequency specific effective connectivity between regions. Between group differences were most evident during the heat stimulation period. We report three novel findings. First, the chronic jaw pain group had a relative increase in alpha and beta power and a relative decrease in theta and gamma power in sensorimotor cortex. Second, the chronic jaw pain group had a relative increase in power in the alpha and beta bands in parietal cortex. Third, the chronic jaw pain group had less connectivity strength in the beta and gamma bands between sensorimotor cortex and parietal cortex. Our findings show that the effect of chronic pain attenuates rather than magnifies neural responses to heat stimuli. We interpret these findings in the context of system-level changes in intrinsic sensorimotor and attentional circuits in chronic pain.
Learn More >Despite numerous studies that have investigated clinical, radiological, and biochemical response predictors, the clinical profile of those patients who might benefit from OnabotulinumtoxinA is still missing. The aim of the present study was to identify potential OnabotulinumtoxinA response predictors among several clinical characteristics and confirm OnabotulinumtoxinA efficacy and safety in chronic migraine (CM) prevention. The study was conducted at the Headache Center-Neurology Clinic-Spedali Civili Hospital of Brescia. Eighty-four consecutive CM patients were enrolled, with a mean age of 48 years (SD 9.7) and a mean disease duration of 10.1 years (SD 6.6). The mean reported headache-days frequency was 22.5 (SD 5.9) per month, while the mean number of severe headache-days was 15.2 (SD 8.9) with a mean monthly medication intake of 33.2 (SD 5.6). The clinical characteristics analyzed as potential response predictors were: gender, disease duration, migraine characteristics (location, side constancy, unilateral autonomic and neurovegetative symptoms), previous prophylactic treatments, add-on therapies, withdrawal therapies, psychiatric (anxiety and depression symptoms) comorbidities and medication overuse. A significant reduction from baseline to 3, 6, 9, and 12 month treatment cycles in total headache days, high intensity headache days and triptans consumption per month was found. Depressive symptoms and medication overuse negatively predicted OnabotulinumtoxinA outcome. Our results confirm the efficacy and safety of OnabotulinumtoxinA in CM. Depressive comorbidity and medication overuse, among all clinical variables, were the only significant response predictors. Such findings provide interesting insights regarding patients selection for OnabotulinumtoxinA treatment as, with the introduction of anti calcitonin gene-related (CGRP) monoclonal antibodies, clinicians will have to thoroughly judge and tailor among the many available therapeutic options now available. Future research might be needed to confirm our findings, in particular for its therapeutic implications.
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