Pain
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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 meeting was organized by the Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks (ACTTION) public-private partnership. The consensus process was informed by expert presentations, panel and consensus discussions, and a preparatory systematic review. In the context of pragmatic trials of pain treatments, we present fundamental considerations for the planning phase of pragmatic trials, including the specification of trial objectives, the selection of adequate designs, and methods to enhance internal validity while maintaining the ability to answer pragmatic research questions.
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Paclitaxel-induced peripheral neuropathy (PIPN) is a barrier to effective cancer treatment and impacts quality of life among patients with cancer. We used a translational approach to assess the utility of neurofilament light chain (NFL) as a biomarker of PIPN in a human cell model and in patients with ovarian cancer. We measured NFL in medium from human induced pluripotent stem cell-derived sensory neurons (iPSC-SNs) exposed to paclitaxel. ⋯ The median elimination half-life of sNFL was 43 days (IQR 27-82 days). Neurofilament light chain constitutes an objective biomarker of neurotoxicity in iPSC-SNs and in ovarian cancer patients with high sNFL predicting PIPN-related adverse outcomes. If prospectively validated, NFL can be used to study PIPN and may guide clinical decision making and personalize treatment with paclitaxel.
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Surgery is often advised when conservative treatment fails in musculoskeletal pain conditions, but a substantial proportion still suffers chronic pain after surgery. Somatosensory processing system (SPS) signs were previously studied as potential predictors for chronic postsurgical pain, but results are inconsistent. Therefore, studying the evolution of SPS signs could be of added value. ⋯ On the other hand, dynamic QST mostly improved after surgery. Worthfully mentioning is that worsening of SPS signs was only seen at a follow-up of <3 months after surgery, that conclusions are stronger when evaluating dynamic QST with a follow-up of ≥3 months after surgery, and that pain improvement postsurgery was an important predictor. Future high-quality research should focus on the evolution of SPS signs after nociceptive targeted surgery, accounting for pain improvement groups and focusing on preoperative, perioperative, and postoperative predictors of this evolution.
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Quantitative sensory testing (QST) is increasingly used in pediatric chronic pain; however, assessment in youth with acute musculoskeletal (MSK) pain is limited. This study evaluated the feasibility, reliability, and sources of variability of a brief QST protocol in 2 clinical samples of youth with acute MSK pain. Participants were 277 youth (M age = 14.5 years, SD = 2.0, range = 11-18 years, 59% female, 81% non-Hispanic) across 3 geographic study sites who completed a QST protocol assessing pressure and thermal pain sensitivity, temporal summation of pain, and conditioned pain modulation 8 weeks after MSK surgery (n = 100) or within 4 weeks after an acute MSK injury (n = 177). ⋯ Hispanic youth had higher pressure and heat pain thresholds (d = 0.37-0.45) and pain ratings for cold pain tolerance (d = 0.54) compared with non-Hispanic youth. No significant differences were observed in QST values by sex or personal contextual factors at the time of assessment (momentary pain, menstrual period, use of pain medications). Overall findings demonstrate feasibility of a brief QST protocol with youth with diverse acute MSK pain and data provide initial support for the reliability of this QST protocol for multisite research studies.
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Evidence and gap maps (EGMs) can be used to identify gaps within specific research areas and help guide future research agendas and directions. Currently, there are no EGMs within the broad domain of chronic musculoskeletal (MSK) pain in adults. The aim of this study was to create a contemporary EGM of interventions and outcomes used for research investigating chronic MSK pain. ⋯ Few systematic reviews used interdisciplinary interventions (3%) and economic-related outcomes (2%). This contemporary EGM revealed a low proportion of high-quality evidence within chronic MSK pain. This EGM clearly outlines the lack of high-quality research and the need for increased focus on interventions encompassing the entire biopsychosocial perspective.